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https://f1000research.com/articles/10-778/v1
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09 Aug 21
|
{
"type": "Case Report",
"title": "Case Report: Metachronous bilateral upper tract and bladder urothelial carcinoma: a long-term follow-up",
"authors": [
"Agus Rizal Ardy Hariandy Hamid",
"Fakhri Zuhdian Nasher",
"Meilania Saraswati",
"Sahat Matondang",
"Chaidir Arif Mochtar",
"Agus Rizal Ardy Hariandy Hamid",
"Meilania Saraswati",
"Sahat Matondang",
"Chaidir Arif Mochtar"
],
"abstract": "Background: Upper tract urothelial carcinoma (UTUC) is a malignant disease of the urothelial cell lining the upper urinary tract from renal calyces, pelvises, and ureter down to the ureteral orifice. Urothelial carcinoma is a multifocal malignant tumor which tends to reoccur after treatment. Radical cystectomy shows that upper tract recurrence occurs in 0.75% to 6.4% of patients. The occurrence of contralateral UTUC after nephroureterectomy is rarer with a prevalence of 0.5%. Case presentation: The case of a 43-year-old male with metachronous bilateral UTUC was reported. The patient had undergone gemcitabine-cysplatine neoadjuvant chemotherapy followed by radical cystectomy and orthotopic neobladder for urothelial carcinoma of the bladder cT2N0M0. Left hydronephrosis was discovered three months after the procedure. The patient was diagnosed with left UTUC cT4N0M0 of renal pyelum after a series of examinations. A left open radical nephroureterectomy was conducted to remove the mass followed by adjuvant chemotherapy. This was followed up with routine ultrasound and magnetic resonance imaging (MRI) every three months with a “tumor-free” period of 26 months. Meanwhile, the patient was re-admitted with fever and an increase in creatinine value of 4.3. After further workups, the patient was diagnosed with UTUC cT2N0M0 of the right renal pyelum. A kidney sparring approach with laser evaporation of the tumor was conducted followed by eight cycles of Gemcitabine intracavity antegrade per nephrostomy. After the regimen was finished, an MRI evaluation was conducted to assess treatment results, and the mass had decreased. Conclusions: This report showed a rare case of urothelial cell carcinoma recurrences. From bladder urothelial carcinoma to left UTUC and then to contralateral UTUC. It is important to evaluate the upper tract to reduce the risk of recurrence.",
"keywords": [
"Keywords: Upper Tract Urothelial Carcinoma",
"metachronous bilateral UTUC",
"Urothelial cancer recurrence",
"kidney sparing surgery",
"intracavity chemotherapy"
],
"content": "Introduction\n\nUpper tract urothelial carcinoma (UTUC) is a malignant disease of the urothelial cell lining the upper urinary tract from renal calyces, pelvises, and ureter down to ureteral orifice. UTUC is considered a rare malignancy, representing 5% of urothelial cancer and less than 10% of all renal tumors1 and it occurs 2-3 times more in males than females.2 Urothelial carcinoma is a multifocal disease and tends to reoccur after initial treatment. The incidence of UTUC and collateral recurrency after the first tumor episode are also reported, and it is infrequent.3,4 The overall prevalence after cystectomy ranges from 0.75% to 6.4%. Furthermore, the recurrence can appear at a range of 2.4 to 164 months.5 The incidence of metachronous contralateral UTUC is also rare with a prevalence of 0.6%. This is manifested 9-71 months after the diagnosis of primary unilateral UTUC.4 The occurrence of contralateral UTUC after nephroureterectomy is even rarer with the prevalence of 0.5% developing metachronous UTUC.4 There are some risk factors like smoking and exposure to carcinogen contaminants in foods.6 The metachronous contralateral recurrence also depends on some risk factors such as young age onset, small tumor size, and the history of bladder cancer.4\n\nThis report aims to discuss a rare case of a patient at Ciptomangunkusumo National Hospital with a long history of urothelial carcinoma from the bladder. The patient had a recurrence in the left pyelum and after treatment, the right was affected.\n\n\nCase presentation\n\nThe patient is an Indonesian male born in 1978 who works as a cook. He was admitted to Ciptomangunkusumo National Hospital (RSCM) in November 2017 with gross haematuria as the chief complaint. The patient’s timeline is shown in Figure 1.\n\nThe patient was an active smoker for 20 years and ate roasted meat regularly. From ultrasound and contrast computed tomography (CT) scan evaluation, a mass was discovered in the bladder (Figure 2a). A cystoscopy and an incomplete transurethral resection of bladder tumour (TURBT) was then conducted on the papillary mass in the bladder. Furthermore, a biopsy was conducted, and pathology examination concluded that the tumor was an infiltrative papillar urothelial carcinoma pT1 high grade (Figure 2b). In March 2018, the patient had bilateral hydronephrosis, and bilateral nephrostomy was confirmed. The bladder UCC was clinically diagnosed as cT2N0M1, and the patient was given 6-cycle neoadjuvant gemcitabine-cisplatin chemotherapy. During the chemotherapy phase, the patient was in good condition with a Karnofsky score of 90. In July 2018, a radical cystectomy followed by an orthotopic neobladder was conducted. Meanwhile, the frozen section of the right and left ureter, and urethral punctum showed no tumor. Pathology examination showed chronic inflammation of hyperplastic urothelium, with fibrinoid necrosis (Figure 2c).\n\n(a) Contrast computed tomography (CT) scan in December 2019 showing isodens mass that enhanced after contrast administration in the bladder. (b) Ultrasound in March 2020. An isoechoic lesion with irregular edges, on the left inferolateral bladder wall, and appears to be obstructing the left ureter with its distal part dilated. (c) The initial diagnosis was infiltrative high-grade urothelial carcinoma. The pictures show tumor cells with round/oval nuclei, pleomorphic, coarse chromatin, vesicular with nuclei, Hematoxylin and Eosin (H&E) stain 400×. (d) A follow-up biopsy showing urethra with minimal inflammatory infiltration. The picture showed that no tumor was found, chronic inflammatory, fibrinoid necrosis, H&E stain 100×.\n\nThe patient was scheduled for adjuvant chemotherapy but was delayed due to the complaint of left abdominal fullness two months after the procedure. Ultrasound examination showed bilateral hydronephrosis with the left kidney being more severe. An abdominal MRI with contrast was performed (Figure 3a). Furthermore, left nephrostomy and biopsy were conducted and pathology workup showed papillary arranged tumor mass. From diagnostic workup, the patient was diagnosed with left UTUC cT4N0M1 in renal pyelum (Figure 3b).\n\n(a) Abdominal magnetic resonance imaging (MRI) with Gadobutrol 5 ml contrast, shown hyperintense lesions were seen on T1-T2WI and FS on the left intrapelviocalyceal and extracapsular perirenal, which were enhanced after the contrast was administered. (b) High-grade infiltrative urothelial carcinoma. (c) The picture shows papillary-arranged tumor mass, Hematoxylin and Eosin (H&E) stain 400×.\n\nIn November 2018, a left open radical nephroureterectomy was conducted to remove the mass, followed by six cycles of adjuvant chemotherapy of gemcitabine-cisplatin. Furthermore, a routine ultrasound and MRI were followed up every three months, and the indwelling catheter was replaced every two weeks. During the follow-up, the patient worked as a chef in satay shop and had a “tumor-free” period of 26 months with a Karnofsky score of 90. This continued until the patient was re-admitted with fever and an increase in creatinine value of 4.3 in August 2020. Then MRI was performed, and hyperintense solid mass was seen in the right renal pyelum. This mass measured 2.2 × 2.1 cm with left hydronephrosis grade II-III and surgery was planned for August 2020. In addition, a puncture was made in the right flank to the superior calyx guided by fluoroscopy into the pelvicalyceal system during the surgery. A nephroscope was then inserted, which exposed a tumor on the right pyelum sized about 3 cm (Figure 4a). The tumor was then extracted using forceps for biopsy, and the residue was evaporated using a laser. Furthermore, nephroscope post-laser ablation examination shows some tumor residue (Figure 4b). The biopsy result was a urothelial carcinoma infiltrative high grade.\n\n(a) Nephroscopy examination in pelviocalyceal system inserted through the right flank reveals a tumor sized about 3 cm. (b) Ureter post evaporation using laser shows some tumor residue even after laser procedure. (c) Tissue fragments containing papillary, infiltrative epithelial malignant tumors with fibrovascular stalk Hematoxylin and Eosin stain (H&E) stain 40×.\n\nThe patient was given intracavitary chemotherapy using gemcitabine through nephrostomy. Furthermore, cystoscopy intracavitary instillation of chemotherapy agent using gemcitabine was administered through nephrostomy. The examination conducted in September 2020 showed a normal right kidney with no hydronephrosis, but there was a sign of intraluminal neobladder clotting. The patient then went to a clot evacuation cystoscope, and the last cycle of intracavitary gemcitabine was given in November 2020. Furthermore, an MRI and ureterorenoscopy were conducted and the mass was shown to be decreased. Abdominal MRI in May 2021 showed benign calyx dilatation suspicious due to stricture and heterogeneous renal parenchyma (Figure 5).\n\nAbdominal magnetic resonance imaging (MRI) May 2021 shows benign calyx dilatation suspicious due to stricture, heterogeneous renal parenchyma.\n\n\nDiscussion\n\nUpper tract urothelial carcinoma (UTUC) is a malignant disease of the urothelial cell lining the upper urinary tract from renal calyces, pelvises, and ureter down to ureteral orifice. UTUC is considered a rare malignancy, representing 5% of urothelial cancer and less than 10% of all renal tumors.1 and it occurs 2-3 times more in males than females.2 Generally, cancer has some risk factors that are categorized into endogenous and exogenous. Some endogenous factors are non-modifiable such as biological aging and genetic susceptibility while others are partially modifiable such as inflammation and hormones.6 The example of genetic susceptibility is demonstrated in a meta-analysis by Chen, et al. (2016), where the correlation between HER2 expression and prognosis of UTUC was analyzed. This study showed that HER2 expression is significantly associated with a higher stage of tumor and worse recurrence-free in UTUC patients.7 The exogenous factors are the most modifiable and are often modified to prevent cancer in the long term. These factors include radiation coming from radiologic examinations, chemical carcinogens from burnt food, and lifestyles including smoking, obesity, and lack of exercise.6 Furthermore, urothelial carcinoma is a multifocal disease that may reoccur after initial treatment. This tendency can make a second tumor arise in another site with the urothelial cell as its lining, including the bladder.\n\nIn November 2017, the patient was admitted to Ciptomangunkusumo National Hospital with a chief complaint of gross hematuria, which is a common symptom of bladder tumors. Ultrasound, CT, and pathology confirmed that the patient had a urothelial cell carcinoma of the bladder and in July 2018, a radical cystectomy with an orthotopic neobladder was conducted. The patient had a left abdominal fullness and intrapyelum mass three months after radical cystectomy. With further workup, the patient was diagnosed with UTUC cT4N0M1 of the left pyelum. Furthermore, the odd of this recurrency is rare, especially after a radical cystectomy. A meta-analysis of 27 studies showed that the incidence of UTUC is rare and ranged from 0.75% to 6.4%. This was reported to occur as early as 2.4 to 164 months after cystectomy.5\n\nThe patient is an active smoker and works as a cook in a satay shop. This exposed the patient to smoke and admitted eating roasted meat frequently. Smoking in particular is associated with advanced-stage disease, recurrence, and cancer-specific mortality in a patient treated with radical nephrouretectomy (RNU) for UTUC.8 Furthermore, this also includes inhalation of smoke fume from cooking.9 Cooking fumes are known to contain several mutagens such as 2-naphtylamine and 4-aminobiphenyl that can cause UTUC,9 and consumption of processed meat also increases the occurrence of UTUC.10 In addition, several meat preparations methods such as stewing and roasting can increase the risk of UTUC.10,11 For high-risk UTUC, open RNU with bladder cuff excision is the standard treatment. This can be performed either open or with a laparoscopic approach. Lymph node dissection is also recommended to reduce the risk of local occurrence.12\n\nThe patient was then declared cancer-free for 26 months before returning with fever and an increase in creatinine value of 4.3 in August 2020. Furthermore, abdominal MRI and anterograde evaluation using flexible URS (Ureterorenoscopy) and pathology report confirmed the diagnosis of right UTUC cT2N0M0 of renal pyelum. The biopsy resulted in a high-grade infiltrative urothelial carcinoma, and because of the history of previous radical nephroureterectomy of the left kidney, the sparring strategies were implemented on the patient. The incidence of metachronous contralateral UTUC was rare and according to a cohort study that follows up 23.075 patients with unilateral UTUC, only 144 (0.6%) developed metachronous UTUC. This was manifested after 9-71 months after the diagnosis of primary unilateral UTUC.4 The occurrence of contralateral UTUC after nephroureterectomy was even rarer, and from the 12.382 patients with unilateral UTUC treated with nephroureterectomy, only 63 (0.5%) developed metachronous UTUC.4 This development was not associated with survival outcomes of a patient with UTUC regardless of tumor stage.4\n\nThere are some risk factors in determining the occurrence of metachronous contralateral UTUC. The same study that states the rarity of metachronous contralateral UTUC showed that younger age and smaller tumor size increase the risk of contralateral recurrence. Furthermore, the history of bladder cancer is also an important risk factor.4 The onset is in the younger age range, and the tumor size, which is only 3 cm, and also has a history of bladder cancer and radical cystectomy. The patient remained a cook and was continuously exposed to smoke during the 26 months cancer-free period as well as frequently eating roasted meat, which contributed to the recurrence of UTUC metachronously.\n\nAccording to the EAU (European Association of Urology) guideline for risk stratification, the patient experienced hydronephrosis, had a history of recurrency, and a biopsy showing high-grade infiltrative properties, so the second recurrence was categorized as a high-grade UTUC.12 To the best of our knowledge, no case in the literature discussing the same clinical setting of UTUC recurrences in three different places especially after previous radical cystectomy and nephroureterectomy has been reported. It was then decided that the patient should undergo gemcitabine intracavity instillation eight cycle regiment. This gemcitabine regimen is analog to BCG (Bacillus Calmette–Guérin) or Mitomycin C regiment used intracavitary in low-risk UTUC guideline.12 In addition, the installation of chemotherapy can be conducted through nephrostomy or retrograde through a single J open-ended ureteric stent. These regimens can be used as adjuvant therapy to decrease recurrent rate or as first-line therapy.12 BCG instillation is widely reported in several case reports, but it is only used for low-risk carcinoma such as carcinoma in situ UTUC. A study using BCG instillation for first-line treatment of UTUC carcinoma in situ showed a 90% complete recovery rate.13 Furthermore, a meta-analysis showed that both anterograde and retrograde have the same rate of complete recovery, overall survival, and recurrent rate. A retrospective study of 58 patients with UTUC carcinoma in situ also compares BCG instillation and radical nephroureterectomy as a treatment of choice. There was no difference in progression-free and overall survival between the two groups.14 This is because both BCG and Mitomycin C are not available and, gemcitabine was used instead for a intracavity instillation regimen. A randomized control trial conducted at 23 US centers showed that Gemcitabine therapy decreases four years of recurrent risk from 47% with placebo to 35% in patients with non-muscle invasive urothelial cancer.15 Also, a meta-analysis from 386 subjects and five pooled trials showed that as adjuvant therapy, there were no statistical differences in risk of recurrence and progression in a patient with non-muscle invasive bladder cancer.16 The two studies showed a potential for gemcitabine to replace BCG as an intravesical chemotherapy agent. Histologically, both UTUC and urothelial carcinoma of the bladder consists of a neoplastic urothelial cell. The application of gemcitabine to replace BCG for topical installation can also be applied for UTUC. Meanwhile, no previous study has explained or reported the use of gemcitabine for intracavity installation through nephrostomy.\n\nIn this patient, gemcitabine 8 cycle was applied per antegrade through nephrostomy until November 2020. In addition, MRI evaluation of the post-gemcitabine intracavity regimen showed a decrease of the mass in the right pyelum. Kidney sparring treatment using topical intracavity chemotherapy after laser evaporation is still adequate to clear the tumor even at high-risk UTUK. The surgery is associated with shorter 5-years and 10-years overall survival in grade 3 UTUC.17 Kidney sparring is associated with shorter 5-years and 10-years local recurrence-free survival even though there are no significant differences in 5-year metastasis with RNU. Furthermore, it is associated with an increased risk of upstaging compared to RNU which is particularly visible for grade 2 and 3 UTUC.17\n\n\nConclusion\n\nThis study reported a rare case of urothelial cell carcinoma recurrences. This was manifested in the bladder and left kidney pyelum treated with radical cystectomy and nephroureterectomy respectively. Also, another recurrence was reported contralateral in the right kidney pyelum. Therefore, genetic and risk factor exploration should be considered in young urothelial bladder cancer. This is important to evaluate upper tract in bladder urothelial carcinoma and reduce the risk of recurrency.\n\n\nData availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and clinical images was obtained from the patient and the family of the patient.",
"appendix": "References\n\nSiegel RL, Miller KD, Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1): 7–34. PubMed Abstract | Publisher Full Text\n\nShariat SF, Favaretto RL, Gupta A, et al.: Gender differences in radical nephroureterectomy for upper tract urothelial carcinoma. World J Urol. 2011; 29(4): 481–486. PubMed Abstract | Publisher Full Text\n\nRabbani F, Perrotti M, Russo P, et al.: Upper-tract tumors after an initial diagnosis of bladder cancer: Argument for long-term surveillance. J Clin Oncol. 2001; 19(1): 94–100. PubMed Abstract | Publisher Full Text\n\nWu K, Liang J, Lu Y: Risk factors and survival outcomes of metachronous contralateral upper tract urothelial carcinoma. Sci Rep. 2020; 10(1): 1–7. Publisher Full Text\n\nWu S, Zhu W, Thompson P, et al.: Evaluating intrinsic and non-intrinsic cancer risk factors. Nat Commun. 2018; 9(1). PubMed Abstract | Publisher Full Text | Free Full Text\n\nRouprêt M, Babjuk M, Burger M, et al.: EAU Guidelines on Upper Urinary Tract Urothelial Carcinoma 2021. Eur Assoc Urol Guid. 2019 Ed. 2021; 1–32. Reference Source\n\nChen CH, Tsai YS, Tzai TS: Significance of HER2 expression in patients with upper tract urothelial carcinoma: A meta-analysis. Urol Sci . 2016; 27(4): 238–243. Publisher Full Text\n\nPicozzi S, Ricci C, Gaeta M, et al.: Upper urinary tract recurrence following radical cystectomy for bladder cancer: A meta-analysis on 13,185 patients. J Urol . 2012; 188(6): 2046–2054. PubMed Abstract | Publisher Full Text\n\nRink M, Xylinas E, Margulis V, et al.: Impact of smoking on oncologic outcomes of upper tract urothelial carcinoma after radical nephroureterectomy. Eur Urol. 2013; 63(6): 1082–1090. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChung KT: The etiology of bladder cancer and its prevention. J Cancer Sci Ther. 2013; 5(10): 346–361. Publisher Full Text\n\nAl-Zalabani AH, Stewart KFJ, Wesselius A, et al.: Modifiable risk factors for the prevention of bladder cancer: a systematic review of meta-analyses. Eur J Epidemiol. Springer Netherlands; 2016: 811–851. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDi Maso M, Turati F, Bosetti C, et al.: Food consumption, meat cooking methods and diet diversity and the risk of bladder cancer. Cancer Epidemiol. 2019; 63(April): 101595. PubMed Abstract | Publisher Full Text\n\nTomisaki I, Kubo T, Minato A, et al.: Efficacy and Tolerability of Bacillus Calmette-Guérin Therapy as the First-Line Therapy for Upper Urinary Tract Carcinoma In Situ. Cancer Invest . 2018; 36(2): 152–157. PubMed Abstract | Publisher Full Text\n\nFoerster B, D’Andrea D, Abufaraj M, et al.: Endocavitary treatment for upper tract urothelial carcinoma: A meta-analysis of the current literature. Urol Oncol Semin Orig Investig. 2019; 37(7): 430–436. PubMed Abstract | Publisher Full Text\n\nHoriguchi H, Yoneyama T, Hatakeyama S, et al.: Impact of bacillus Calmette–Guérin therapy of upper urinary tract carcinoma in situ: comparison of oncological outcomes with radical nephroureterectomy. Med Oncol. 2018; 35(4): 1–7. PubMed Abstract | Publisher Full Text\n\nMessing EM, Tangen CM, Lerner SP, et al.: Effect of intravesical instillation of gemcitabine vs saline immediately following resection of suspected low-grade non-muscle-invasive bladder cancer on tumor recurrence SWOG S0337 randomized clinical trial. JAMA - J Am Med Assoc. 2018; 319(18): 1880–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYe Z, Chen J, Hong Y, et al.: The efficacy and safety of intravesical gemcitabine vs bacille calmette-guérin for adjuvant treatment of non-muscle invasive bladder cancer: A meta-analysis. Onco Targets Ther. 2018; 11: 4641–4649. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCutress ML, Stewart GD, Tudor ECG, et al.: Endoscopic versus laparoscopic management of noninvasive upper tract urothelial carcinoma: 20-year single center experience. J Urol . 2013; 189(6): 2054–2061. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "95637",
"date": "04 Nov 2021",
"name": "Alcides Chaux",
"expertise": [
"Reviewer Expertise Pathology",
"genitourinary"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this article, the authors report the clinicopathologic and outcome features of a patient with metachronous bilateral upper tract urothelial carcinoma. Overall, the case is well presented and the authors provide an appropriate background for their findings. A few recommendations are provided below.\nIn the text, please provide the patient’s age instead of his year of birth.\n\nIn Figure 1, please provide a consistent nomenclature for the histopathologic diagnoses. In all cases, the diagnosis should be “invasive urothelial carcinoma”. The use of descriptive terms such as “urothelial high grade” or “papillary, infiltrative epithelial malignant tumor with a fibrovascular stalk” could be confusing. The term “TCC” is also inappropriate. From the microphotographs presented by the authors, the tumor seems to correspond to the usual variant of invasive urothelial carcinoma, so no further specification is required.\n\nIn Figure 1 and in the text, UCC should be UC. I would argue against using UC at all, recommending spelling “urothelial carcinoma” out at all instances to render the text clearer.\n\nIn the text, the description of Figure 2c does not correspond to the actual microphotograph. Figure 2d is not cited in the text. Please revise.\n\nFigures 3c and 4c are not cited in the text. Please revise.\n\nA few typos that need correction (reocurr, UTUK).\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
},
{
"id": "129088",
"date": "12 Apr 2022",
"name": "Mohamed Mohamed Elawdy",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the invitation to review this article. My notes are as follows:\n\"Radical cystectomy shows that upper tract recurrence occurs in 0.75% to 6.4% of patients.\" Please elaborate on this sentence.\n\"Upper tract urothelial carcinoma (UTUC) is a malignant disease of the urothelial cell lining the upper urinary tract from renal calyces, pelvises, and ureter down to ureteral orifice.\" This is a complicated sentence, instead perhaps you can write: \"from the renal calyces or collecting system to the ureteral orifice.\"\nIf the case is a UTUC after bladder cancer, why did you deal with contralateral UTUC after nephroureterectomy to such a degree?\nIf you mention a case with multiple events, it is best practice to start with the most recent, then to mention the past history. Additionally, there is too much focus on the details of the patient’s habits.\n\"An abdominal MRI with contrast was performed (Figure 3a). Furthermore, left nephrostomy and biopsy were conducted and pathology workup showed papillary arranged tumor mass.\" Why left nephrostomy for a biopsy? Why you did not get it with URS?\nFigure 2. \"(a) Contrast computed tomography (CT) scan in December 2019 showing isodens mass that enhanced after contrast administration in the bladder. (b) Ultrasound in March 2020. An isoechoic lesion with irregular edges, on the left inferolateral bladder wall, and appears to be obstructing the left ureter with its distal part dilated.\" Please correct, figure (a) is the ultrasound.\nFigure 3. \"(a) Abdominal magnetic resonance imaging (MRI) with Gadobutrol 5 ml contrast, shown hyper- intense lesions were seen on T1-T2WI and FS on the left intrapelviocalyceal and extracapsular perirenal, which were enhanced after the contrast was administered. (b) High-grade infiltrative urothelial carcinoma.\" Please correct, figure ( b) is the MRI.\nFurthermore, a routine ultrasound and MRI were followed up every three months, and the indwelling catheter was replaced every two weeks.\" Imaging is every 6 months, so why it was done every 3 months? What do you mean by indwelling catheter was replaced every two weeks?\nWhat do you mean by Karnofsky score of 90?\n\"...right renal pyelum\" This should be written as renal pelvis.\n\"In addition, a puncture was made in the right flank to the superior calyx guided by fluoroscopy into the pelvicalyceal system during the surgery. A nephroscope was then inserted, which exposed a tumor on the right pyelum sized about 3 cm.\" Taking a biopsy by puncturing the kidney is not a standard. Why was this done? You can give a rational saying being a tumor in solitary kidney or so.\n\"Furthermore, nephroscope post-laser ablation examination shows some tumor residue (Figure 4b). The biopsy result was a urothelial carcinoma infiltrative high grade.\" Can you mention the pathology clearly, was it non-muscle or muscle invasive?\nOverall, the discussion is very long for a case report, please shorten as much as possible.\nYou should generally have a message from the case report, and the only massage is treating UTUC in a single kidney with resection and BCG. This is the rationale for this case to be accepted. Focus on this point and bring similar studies and make the discussion mainly on this point.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": [
{
"c_id": "9010",
"date": "10 Nov 2022",
"name": "Agus Rizal Ardy Hariandy Hamid",
"role": "Author Response",
"response": "Thank you for the comments, the following are our responses to the review: \"Radical cystectomy shows that upper tract recurrence occurs in 0.75% to 6.4% of patients.\" Please elaborate on this sentence. Upper urinary tract disease may develop in the residual transitional tissue in patients who have radical cystectomy for urothelial carcinoma. The odd of this recurrence is rare, especially after a radical cystectomy. A meta-analysis of 27 studies showed that the incidence of UTUC ranged from 0.75% to 6.4%. Numerous risk factors for upper urinary tract recurrence have been found in previous studies, however, it is still debatable how well each one predicts future occurrences. \"Upper tract urothelial carcinoma (UTUC) is a malignant disease of the urothelial cell lining the upper urinary tract from renal calyces, pelvises, and ureter down to ureteral orifice.\" This is a complicated sentence, instead perhaps you can write: \"from the renal calyces or collecting system to the ureteral orifice.\" Thank you for your constructive feedback. Yes, we will paraphrase to: “Upper tract urothelial carcinoma (UTUC) is a malignant disease of the urothelial cell lining the upper urinary tract from the renal calyces or collecting system to the ureteral orifice.\" If the case is a UTUC after bladder cancer, why did you deal with contralateral UTUC after nephroureterectomy to such a degree? This is the reason why we present this rare case of multiple event recurrence of UTUC which possible to make a second tumor arise in another site with the urothelial cell as its lining If you mention a case with multiple events, it is best practice to start with the most recent, then to mention the past history. Additionally, there is too much focus on the details of the patient’s habits. Well noted, thank you for the feedback \"An abdominal MRI with contrast was performed (Figure 3a). Furthermore, left nephrostomy and biopsy were conducted and pathology workup showed papillary arranged tumor mass.\" Why left nephrostomy for a biopsy? Why did you not get it with URS? Thank you for your question, we would like to clarify that the nephrostomy mentioned in the line above was related to the management of the hydronephrosis of the left kidney that is more severe. The biopsy itself was done via URS Figure 2. \"(a) Contrast computed tomography (CT) scan in December 2019 showing isodens mass that enhanced after contrast administration in the bladder. (b) Ultrasound in March 2020. An isoechoic lesion with irregular edges, on the left inferolateral bladder wall, and appears to be obstructing the left ureter with its distal part dilated.\" Please correct, figure (a) is the ultrasound. Well noted, thank you for the correction, we will swap the picture in Figure 2 Figure 3. \"(a) Abdominal magnetic resonance imaging (MRI) with Gadobutrol 5 ml contrast, shown hyper- intense lesions were seen on T1-T2WI and FS on the left intrapelviocalyceal and extracapsular perirenal, which were enhanced after the contrast was administered. (b) High-grade infiltrative urothelial carcinoma.\" Please correct, figure (b) is the MRI. Both Figure 3 (a) and (b) are the Abdominal MRI with different planes (axial and coronal view) Furthermore, a routine ultrasound and MRI were followed up every three months, and the indwelling catheter was replaced every two weeks.\" Imaging is every 6 months, so why it was done every 3 months? What do you mean by indwelling catheter was replaced every two weeks? After a cystectomy, some patients who are at a higher risk of recurrence might benefit from stricter upper tract surveillance. Early diagnosis of recurrent disease allows for prompt administration of the proper therapy and may even enhance patient outcomes. Regular computerized tomography with urography enables the investigation of the upper urinary system from an oncological and functional perspective as well as the detection of any recurrence. (1) The indwelling catheter is regularly changed to reduce the risk of Ca-UTI. The timing of catheter changes should be individualized. (1) Picozzi S, Ricci C, Gaeta M, Ratti D, Macchi A, Casellato S, Bozzini G, Carmignani L. Upper urinary tract recurrence following radical cystectomy for bladder cancer: a meta-analysis on 13,185 patients. The Journal of urology. 2012 Dec 1;188(6):2046-54. What do you mean by Karnofsky score of 90? According to Crooks et al., The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment. This can be used to compare the effectiveness of different therapies and to assess the prognosis in individual patients. In this setting, Karnofsky Score 90 means the patient is still able to carry on the normal activity with minor signs or symptoms of the disease. (Crooks, V, Waller S, et al. The use of the Karnofsky Performance Scale in determining outcomes and risk in geriatric outpatients. J Gerontol. 1991; 46: M139-M144) \"...right renal pyelum\" This should be written as renal pelvis. Noted, thank you for the correction \"In addition, a puncture was made in the right flank to the superior calyx guided by fluoroscopy into the pelvicalyceal system during the surgery. A nephroscope was then inserted, which exposed a tumor on the right pyelum sized about 3 cm.\" Taking a biopsy by puncturing the kidney is not a standard. Why was this done? You can give a rational saying being a tumor in solitary kidney or so. Thank you for your comment, many recommend the ureteroscopic approach in the case of tumor biopsy. In the case a tumor in solitary kidney or a large tumors that would require long operatory time or even multiple procedures for a complete treatment, the antegrade approach is preferred. In this case, the tumor was then extracted using forceps for biopsy, and the residue was evaporated using a laser. \"Furthermore, nephroscope post-laser ablation examination shows some tumor residue (Figure 4b). The biopsy result was a urothelial carcinoma infiltrative high grade.\" Can you mention the pathology clearly, was it non-muscle or muscle invasive? Muscle invasive Overall, the discussion is very long for a case report, please shorten as much as possible. Well noted, thank you for your kind feedback You should generally have a message from the case report, and the only massage is treating UTUC in a single kidney with resection and BCG. This is the rationale for this case to be accepted. Focus on this point and bring similar studies and make the discussion mainly on this point. Thank you for your constructive feedback related to our article/manuscript"
}
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}
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https://f1000research.com/articles/10-778
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https://f1000research.com/articles/10-382/v1
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13 May 21
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{
"type": "Research Article",
"title": "Patient perspectives on home-based rehabilitation exercise and general physical activity after total hip arthroplasty: A qualitative study (PHETHAS-2)",
"authors": [
"Anne Grøndahl Poulsen",
"Janni Dahlgaard Gravesen",
"Merete Nørgaard Madsen",
"Lone Ramer Mikkelsen",
"Thomas Bandholm",
"Camilla Blach Rossen",
"Janni Dahlgaard Gravesen",
"Merete Nørgaard Madsen",
"Lone Ramer Mikkelsen",
"Thomas Bandholm",
"Camilla Blach Rossen"
],
"abstract": "Background: Home-based rehabilitation exercise following Total Hip Arthroplasty (THA) shows similar outcomes compared to supervised outpatient rehabilitation exercise. Little is known about patients' experiences with home-based rehabilitation, and this study aimed to investigate patient-perceived facilitators and barriers to home-based rehabilitation exercise and general physical activity after THA. Methods: Semi-structured interviews of qualitative design were conducted with 22 patients who had undergone THA and who had performed home-based rehabilitation exercise. The study took place in a regional hospital in Denmark between January 2018 and May 2019. Data was analyzed using an interpretive thematic analysis approach, with theoretical underpinning from the concept ‘conduct of everyday life’. The study is embedded within the Pragmatic Home-Based Exercise Therapy after Total Hip Arthroplasty-Silkeborg trial (PHETHAS-1), which aims to quantitatively investigate recovery outcomes after a home-based rehabilitation exercise program. Results: The main theme, ‘wishing to return to the well-known everyday life’, and the subtheme ‘general physical activity versus rehabilitation exercise’ were identified. Generally, participants found the home-based rehabilitation exercise boring but were motivated by the goal of returning to their habitual conduct of everyday life and performing their usual general physical activities. Participants enrolled in the PHETHAS-1 study used the enrollment as part of their motivation for doing the exercises. Both pain and the absence of pain were identified as barriers for doing home-based rehabilitation exercise. Pain could cause insecurity about possible medical complications, while the absence of pain could lead to the rehabilitation exercise being perceived as pointless. Conclusions: The overall goal for the THA patients was to return to their habitual everyday life. This goal served as a facilitator for undertaking home-based rehabilitation exercise. Being able to perform usual activities paradoxically became a barrier for some participants, as they were more motivated to engage in general physical activity than the rehabilitation exercise.",
"keywords": [
"total hip arthroplasty",
"rehabilitation",
"qualitative research",
"patient perspective"
],
"content": "Introduction\n\nTotal hip arthroplasty (THA) is a common surgical intervention in Western countries. It is often performed as fast-track surgery and the number of THAs has been rising.1,2 Fast-track surgery has proven to be effective in terms of reducing costs, length of hospital stay, morbidity, and convalescence.3,4 In Denmark alone, 11,000 THAs are performed every year,5 with patients routinely being discharged from the hospital within two days of surgery.6\n\nRehabilitation exercise is a customary part of the postoperative program for patients undergoing THA, in the expectation that it will reduce pain and increase mobility.7 This is also the case in Denmark, with each hospital having different procedures. Some hospitals refer patients to supervised rehabilitation exercise in the municipality while others recommend home-based rehabilitation exercise after initial instruction is provided.8\n\nLevel 1a-evidence from systematic reviews show that supervised exercise after THA provides no additional benefit compared to home-based rehabilitation exercise after initial instruction, when considering patient-reported function, pain, health-related quality of life, or performance-based functions.9,10 Additionally, home-based rehabilitation is presumably less expensive than supervised rehabilitation, and with rising healthcare costs, one might expect home-based rehabilitation exercise to become even more prevalent in the future.\n\nThere are indications that adherence to home-based rehabilitation exercise is low which might affect outcome. Jan et al. found that only half of their included participants performed 50% or more of the prescribed home-based rehabilitation exercise.11 They also found that the high compliance group showed greater improvements in muscle strength and functional ability compared to the low compliance group.11 Yet we know little about patients' perspectives on home-based rehabilitation exercise and general physical activity after THA.\n\nThe PHETHAS studies were founded to support and optimize clinical pathways with patients rehabilitating at home after THA. PHETHAS-1 (ClinicalTrials.gov NCT03109821, April 12, 2017) quantitatively investigates the physical outcomes of performing a home-based rehabilitation exercise program,12 while this study, PHETHAS-2, qualitatively investigates patient-perceived facilitators and barriers to home-based rehabilitation exercise and general physical activity after THA.\n\n\nMethods\n\nThe study complies with the declaration of Helsinki13 and was approved by The Ethics Committee of Central Denmark Region and the Danish Data Protection Agency (ref. no: 1-16-02-589-15). The interviewer obtained written informed consent from participants prior to the interviews being conducted. Consent included participation in the interview, and consent for the participant’s data being used in analysis, including publication of anonymized quotations.\n\nThe concept ‘conduct of everyday life’ from critical psychology14,15 was chosen as the theoretical underpinning for this study. ‘Conduct of everyday life’ is an overall concept that embraces the complexity of an individual's everyday life across contexts.14,15 It includes the different aspects of a person's everyday life, which could be working, performing general physical activities, or home-based rehabilitation exercises. According to theory, the individual person will prioritize activities based on what he/she considers will contribute to their subjective understanding of ‘quality of life’.14,15\n\nUsing ‘conduct of everyday life’ as the theoretical underpinning provides the potential to elucidate how patients integrate both general physical activity and home-based rehabilitation exercise into their everyday lives in the rehabilitation period, thereby informing on possible patient perceived barriers and facilitators for performing the rehabilitation exercise.\n\nWe defined home-based rehabilitation exercise as a plan of physical activities designed and prescribed to meet specific therapeutic goals. Its purpose is to restore normal musculoskeletal function or to reduce pain caused by diseases or injuries. This definition is synonymous with the Medical Subject Headings (MeSH) term ‘Exercise therapy’ as defined in the PubMed MeSH database.16 Our definition is also in alignment with the World Health Organization’s description of ‘exercises’ as a subcategory of ‘physical activity’.17 In this study we distinguish this type of prescribed rehabilitation exercise from general physical activity undertaken while working, playing, gardening, and engaging in leisure time activities.\n\nParticipants were recruited from a Danish Regional Hospital in the period January 2018 to September 2019. In terms of study inclusion and exclusion criterion, adults > 18 years who had undergone a primary THA due to osteoarthritis were included, but any patients who had been referred for supervised rehabilitation were excluded. The participants also needed to understand written and spoken Danish. The participants were purposely sampled18 with the aim of reflecting the gender and ages of typical THA patients.19\n\nAs this study was embedded in the PHETHAS-1 study, participants were recruited from participants enrolled in PHETHAS-1 by the researcher responsible for PHETHAS-1 (MNM) in a face-to-face approach. Participants in PHETHAS-1 may have been more motivated to exercise than the average THA patient and hence may have been more adherent than those who decline participation in clinical exercise trials. With this in mind, and to avoid gathering data from participants of PHETHAS-1 only, we recruited an additional eight participants from standard care. Standard care participants were recruited in a face-to-face approach by physiotherapists responsible for the standard care pathway at the hospital (see Figure 1). A total of 22 participants were included. No participants dropped out. All participants were instructed to perform the exact same home-based rehabilitation exercise. Details of this home-based rehabilitation exercise have previously been published,10 see Figure 1 for an overview.\n\n* Pragmatic Home-Based Exercise after Total Hip Arthroplasty – Silkeborg (PHETHAS-1) is a trial investigating the preliminary efficacy of home-based rehabilitation using elastic band exercise on performance-based function after Total Hip Arthroplasty.\n\nThe interviews took place during the period February 2018 to December 2019. Demographic data in terms of age, gender and working status (retired or not) were collected. The demographics of the participants are illustrated in Table 1.\n\nIndividual interviews with the participants were conducted to gain an in-depth knowledge of their experiences with home-based rehabilitation exercise and general physical activity after THA.20 The interviews were guided by a semi-structured interview guide20,21 which is provided in Extended data.22 The interview guide was informed by existing knowledge in the field of THA along with the theoretical concept ‘conduct of everyday life'. The first interviews conducted were planned for pilot testing the interview guide, but since no changes were found necessary regarding interview guide and procedure, these interviews were included for analysis.\n\nData collection and recruitment was guided by a concurrent data analysis.23 The interviews were conducted 10 weeks postoperatively.\n\nParticipants enrolled in PHETHAS-1 were physically tested at the hospital 10 weeks postoperatively and were individually interviewed afterwards in a private meeting room. Participants following standard care were interviewed in their homes (Figure 1). Occasionally a spouse was present when the interview was conducted, but they did not interfere or participate in the interview. Interviews were audio recorded and lasted an average of 43 minutes (20–67 minutes). The interviews were conducted by AG, JG and CR, who are all female researchers. AG and JG, both research assistants holding a master’s degree, are trained in the qualitative field of research and are trained interviewers. They were supervised in between interviews by CR, who is a researcher holding a PhD, and an experienced qualitative researcher and interviewer.\n\nData were thematically analyzed. This is a method for identifying and analyzing patterns of meaning across data.24,25 The audio recordings were transcribed verbatim by assistants. The transcripts were subsequently read and corrected by AG and JG, while listening back on the recordings. Initially, the interviews were manually coded by AG and JG, with supervision and input from CR. The coding process was carried out both deductively and inductively. The deductive part of the analysis was guided by theory e.g. how the participants integrate home-based rehabilitation exercise and general physical activity as part of their everyday life during the rehabilitation period. This included which activities they prioritized and why, along with factors serving as motivators or barriers respectively. The inductive part of analysis added an openness for other themes of importance in the dataset.24,25 After potential themes were identified and discussed with the co-authors, the original data were re-visited to validate the themes using an iterative process.24,25 The analytic process was supported by NVivo version 12 software26 (this can be replicated using Taguette, a free, open source alternative).\n\n\nResults\n\nThe analysis of the data resulted in the identification of the main theme, ‘wishing to return to the well-known everyday life’, which is expanded on below, and includes the subtheme ‘general physical activity versus rehabilitation exercise’.\n\nAll participants wished to be physically active and their overall goal was to return to their habitual everyday life. The following quote came from a male participant who was still working and enjoyed being active through sports.\n\nP04: The goal was to be able to do sports again. Primarily to be pain free. And then leading a more or less ordinary life again with some sports. [...] Aesthetically it is nice to get outside and experience the world with your eyes and ears, as you do when you go outside. First and foremost, the aim of the operation was to get my quality of life back again and then pain free.\n\nThe participants’ goal was to return to their usual everyday life, consisting of activities that contribute to their quality of life. What they perceived as valuable activities were unique to each individual, and they used their own habitual everyday activities as a reference point. Participants found motivation for doing the home-based rehabilitation exercise program in the belief that it would bring them closer to their goal.\n\nWhen asked whether there were times when it was difficult to get the home-based rehabilitation exercise done, a male participant who worked part time in a shop answered:\n\nP07: No. If something came up, I did it in the evening. [...]\n\nI think it is nice you can decide for yourself when you do it, compared to going somewhere to see a physiotherapist.\n\nAnalysis showed that for some participants, flexibility on when and where to include the rehabilitation exercise in their everyday life helped in facilitating their performance of rehabilitation exercise. The flexibility made room for other activities that they considered as contributing to their quality of life. In this sense, the home-based rehabilitation exercises had an advantage compared to supervised rehabilitation.\n\nSome participants missed being in contact with a physiotherapist during the rehabilitation period. One participant, who was retired from an office job, described how she phoned the hospital staff to address certain issues she was worried about. She would prefer participating in group training with a physiotherapist to performing home-based rehabilitation.\n\nP12: Because first of all you could have your exercises corrected. Second you could have been told when to use a tighter elastic band. And talk to the others. And this thing in my head being so afraid of crossing my legs, I think that could have been killed [laughing]. And then I might have been able to talk about pain in the groin, because I did have a lot of pain in the groin. Just being told to go see my own [private] physiotherapist with that problem. That would have been nice.\n\nLack of contact with a physiotherapist during the period of performing the home-based rehabilitation exercise could be identified as a potential barrier for some participants. The quote above reflects the patient’s concerns about missing the possibility to address issues of uncertainty with both a physiotherapist and other THA patients.\n\nOur data showed that most participants experienced a degree of pain that did not affect their performance of the home-based rehabilitation exercise. However, the analysis also revealed that having more intense pain and having no pain affected performance of home-based rehabilitation exercise. A male participant working in academia and who was usually active experienced rather intense pain and described his struggle:\n\nP06: I think the challenge all along has been how much it must hurt. We are instructed to repeat to exhaustion, […]but where is that point when you are in pain?\n\nOther participants felt hardly any pain at all. An active female participant, who was retired from the healthcare sector, explained how having no pain affected her:\n\nP14: When you get out of bed three hours after the surgery and walk and bike and climb stairs and go all the way down the hall and back again and you notice nothing. Then you say to yourself: nothing is wrong with you. […] Then you really have to pull yourself together to do the exercises, because you already feel that you can do everything.\n\nOur data paradoxically showed that both pain and the absence of pain can be seen as barriers in regard to performing the home-based rehabilitation exercise. Pain provided insecurity about how to best perform the exercise, and the absence of pain provided the possibility of simply returning to the patient’s habitual and preferred everyday life, which was more tempting than prioritizing time to do the rehabilitation exercise.\n\nWe identified the subtheme ‘general physical activity versus rehabilitation exercise’ which showed that the participants consistently distinguished between the instructed home-based rehabilitation exercise and the general physical activities they considered part of their habitual everyday life.\n\nThis retired female participant was usually very active with hiking and fitness. She explained:\n\nP001: Well, I would rather do normal activities, long walks or something like that. That’s what I prefer. And I do the exercises to achieve that. I mean, it is quite boring doing those exercises, it depends on what’s on the radio [laughs]. [...] I do them to be able to do the other things.\n\nFor most participants, the rehabilitation exercise was used as a means of regaining their habitual everyday life. Their usual general physical activities contributed to their understanding of quality of life and were considered joyful, while the rehabilitation exercise was perceived as boring and time consuming.\n\nA male participant, who had already restarted work and exercise, explained why he no longer performed the rehabilitation exercise as instructed.\n\nP008: It is going so well [laughing]. I do them, [the exercises] but not...maybe not every day, and there are days where I have forgotten.\n\nAnalysis revealed a difference between the group of standard care participants and participants also enrolled in PHETHAS-1. Standard care participants often modified the home-based rehabilitation exercises as illustrated in the citation above. To this group, as their level of functioning improved and they were able to perform their usual general physical activities, they perceived the rehabilitation exercises as having lost their purpose.\n\nIn contrast, a very active male participant enrolled in PHETHAS-1 explained his motivation for performing the exercises:\n\nInterviewer: [...] As you have resumed all these usual activities, are you still motivated for doing the exercises with the elastic band?\n\nP08: I think so, yes. Absolutely, because it is part of this trial [PHETHAS-1] that I wish to be very loyal to. So I have followed it completely. Otherwise you can’t use it for anything if you don’t know whether one just filled it [the training diary] out as one pleases.\n\nAnalysis showed that for the group of participants enrolled in PHETHAS-1, their enrollment served as a facilitator for performing the rehabilitation exercises exactly as instructed. They referred to an obligation towards the researcher and the study they had signed up for, and they knew that it would supposedly benefit them personally as well.\n\n\nDiscussion\n\nFindings from our study show that participants wished to return to their habitual conduct of everyday life after their THA surgery. Similar results have previously been reported in other studies,27,28 also concluding that patients have little interest in achieving greater levels of physical activity than they had before the hip restricted their functioning.27 In our study, many participants found the home-based rehabilitation exercise boring and preferred performing their usual general physical activities. They generally performed the home-based rehabilitation exercise, believing it would bring them closer to their goal of returning to their usual conduct of everyday life and used this as a motivator to get the exercise done.\n\nFurthermore, we found an important difference between the two groups of participants. Analysis showed that participants also enrolled in PHETHAS-1 were motivated by an obligation towards the study and the researcher, which supports a review with similar findings.29 Other studies also find that contact with a physiotherapist can enhance adherence to rehabilitation exercises, using the concept of therapeutic alliance as a possible explanation.30,31 Therapeutic alliance focuses on the impact of the relationship between the patient and the professional on adherence to rehabilitation exercise.30,31 This knowledge is crucial when assessing results from clinical training studies.\n\nStandard care participants gradually modified the exercises as they were able to return to their habitual everyday life, and performed the usual general physical activities they felt contributed to their quality of life. Modifying therapeutic instructions is well known in other areas,32 but to our knowledge, this is the first time it is described in THA patients.\n\nOverall the participants favored general physical activities where possible, and it would be useful to investigate whether general physical activities could be as effective as home-based rehabilitation exercise, and if so, whether future THA patients could rehabilitate by only doing their preferred physical activities.\n\nA previous study has shown that patients can have a feeling of uncertainty with being left alone to perform the rehabilitation exercise after discharge from the hospital, for example when dealing with pain.33 Our study supports this finding, with some participants also describing a wish to have contact with a physiotherapist who would be able to provide advice. Furthermore, our study adds the knowledge that the absence of pain can be identified as a barrier for performing home-based rehabilitation exercise.\n\nWhile it could be seen as a limitation of the study that we recruited participants from both the PHETHAS-1 study and from standard care, this particular combination of participants revealed an important difference in motivation towards adherence to, and performance of, the home-based rehabilitation program and could therefore be viewed as a strength. Moreover, we note that our findings show no other differences regarding results of the analysis between the two groups of participants.\n\nWe recruited participants from only one hospital, and since the rehabilitation after THA differs between hospitals this might have affected our results, although we made clear what this particular rehabilitation consisted of.\n\nThe participants in our study are considered relatively physically active, which could have influenced the results and it would have been favorable to have included more sedentary patients as well. Additionally, our participants consisted of fewer females compared to males which differs from the group of patients undergoing a THA in general, where more females undergo THA compared to males.18 This might have affected our results.\n\nThere may be additional contributing factors in relation to patients’ perceptions of home-based rehabilitation exercise after THA. These include age, gender, previous training experience, and culture. Further studies are needed to explore this.\n\nScientific rigor is enhanced in this study by using theory throughout the scientific process34 and triangulation in the form of more investigators collaborating on the analysis, is also considered a strength.35\n\n\nConclusion\n\nThis study showed that THA patients' goal was returning to their habitual conduct of everyday life as it was before their hip restricted their functioning, and that this goal generally served as a facilitator for performing the home-based rehabilitation exercise, because it was perceived as a means to achieve their goal. Most participants found the rehabilitation exercises boring and would prefer usual general physical activities. Partly motivated by an obligation towards the researcher, participants enrolled in the PHETHAS-1 trial reportedly performed the home-based rehabilitation program as instructed. In contrast, the participants following standard care often modified the program, as they became able to perform their usual general physical activities, which they found more motivating.\n\nParadoxically both pain and the absence of pain could be identified as barriers to performing the home-based rehabilitation exercise and some participants experiencing barriers towards the home-based rehabilitation exercise missed having contact with a physiotherapist in the rehabilitation period.\n\n\nData availability\n\nAccess to this data is restricted due to ethical reasons. The data cannot be made publicly available as it is not possible to sufficiently de-identify the interview transcripts, which contain information that could compromise research participant privacy and consent. Transcripts can be made available upon reasonable request e.g., for the purpose of reviewing this article. Please contact the corresponding author, Anne Grøndahl Poulsen (anngrora@rm.dk). Please note that transcripts are in Danish.\n\nFigshare: PHETHAS-2. https://doi.org/10.6084/m9.figshare.14101877.v2.22\n\nThis project contains the following extended data:\n\n− Interviewguide.docx (semi-structured interview guide).\n\nFigshare: COREQ checklist for ‘Patient perspectives on home-based rehabilitation exercise and general physical activity after total hip arthroplasty: A qualitative study (PHETHAS-2)’. https://doi.org/10.6084/m9.figshare.14101877.v2.22\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nPabinger C, Geissler A: Utilization rates of hip arthroplasty in OECD countries. Osteoarthritis Cartilage. 2014; 22: 734–741.\n\nSingh JA: Epidemiology of Knee and Hip Arthroplasty: A Systematic Review. Open Orthop J. 2011; 5: 80–85. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBüttner M, Mayer AM, Büchler B, et al.: Economic analysis of fast-track total hip and knee arthroplastry: a systematic review. Eur J Orthop Surg Traumatol. 2020; 30: 67–74. PubMed Abstract | Publisher Full Text\n\nKehlet H: Fast-track hip and knee arthroplasty. Lancet. 2013; 381(9878): 1600–1602. PubMed Abstract | Publisher Full Text\n\nThe Danish Hip Arthroplasty Register (DHR): National Annual Report Web site.2019. Updated June 19, 2019. Reference Source\n\nJung KD, Husted H, Kristensen BB: Total knee and hip arthroplasty within 2 days: The Danish Fast-Track Model. Orthopade. 2019; 49(3): 218–225. 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PubMed Abstract | Publisher Full Text\n\nCoulter CL, Scarvell JM, Neeman TM, et al.: Physiotherapist-directed rehabilitation exercises in the outpatient or home setting improve strength, gait speed and cadence after elective total hip replacement: a systematic review. J Physiother. 2013; 59(4): 219–226. PubMed Abstract | Publisher Full Text\n\nJan M-H, Hung J-Y, Lin JC-H, et al.: Effects of a home program on strength, walking speed, and function after total hip replacement. Arch Phys Med Rehabil. 2004; 85(12): 1943–1951. PubMed Abstract | Publisher Full Text\n\nMikkelsen L, Madsen M, Rathleff M, et al.: Pragmatic Home-Based Exercise after Total Hip Arthroplasty - Silkeborg: Protocol for a prospective cohort study (PHETHAS-1) [version 1; peer review: 3 approved]. F1000Res. 2019; 8(965). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMA declaration of Helsinki - Ethical principles for medical research involving human subjects.World Medical Association; 2013. 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Hans Reitzel: København; 2015.\n\nBrinkmann S: Forskningsdesign i interviewundersøgelser. In: Brinkmann S, editor. Det kvalitative interview. 1st edition. København: Hans Reitzels Forlag; 2014: 67–108.\n\nPoulsen AG, Dahlgaard GJ, Madsen MN: Mikkelsen, Lone Ramer; Bandholm, Thomas Quaade; Rossen, Camilla Blach. PHETHAS-2. figshare. 2021. Reference Source\n\nCharmaz K: Theoretical Sampling, Saturation, and Sorting. In: Charmaz K, editor. Constructing Grounded Theory. 2nd edition. New York: SAGE; 2014: 192–224.\n\nBraun V, Clarke V: Using thematic analysis in psychology. Qual Res Psychol. 2006; 3(2): 77–101. Publisher Full Text\n\nClarke V, Braun V: Thematic Analysis. In: Michalos AC, editor. Encyclopedia of Quality of Life and Well-Being Research. Dordrecht: Springer Netherlands; 2014: 6626–6628.\n\nQSR: NVivo qualitative data analysis software. Version 12. Pty Ltd.2018. Reference Source\n\nSmith TO, Latham S, Maskrey V, et al.: Patients’ perceptions of physical activity before and after joint replacement: a systematic review with meta-ethnographic analysis. Postgrad Med J. 2015; 91(1079): 483. PubMed Abstract | Publisher Full Text\n\nStrickland LH, Kelly L, Hamilton TW, et al.: Early recovery following lower limb arthroplasty: Qualitative interviews with patients undergoing elective hip and knee replacement surgery. Initial phase in the development of a patient-reported outcome measure. J Clin Nurs. 2018; 27(13-14): 2598–2608. PubMed Abstract | Publisher Full Text\n\nDavenport S, Dickinson A, Minns Lowe C: Therapy-based exercise from the perspective of adult patients: a qualitative systematic review conducted using an ethnographic approach. Clin Rehabil. 2019; 33(12): 1963–1977. PubMed Abstract | Publisher Full Text\n\nBabatunde F, McDermid J, MacIntyre N: Characteristics of therapeutic alliance in musculoskeletal physiotherapy and occupational therapy practice: a scoping review of the literature. BMC Health Serv Res. 2017; 17: 375. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKinney M, Seider J, Beaty AF, et al.: The impact of therapeutic alliance in physical therapy for chronic musculoskeletal pain: A systematic review of the literature. Physiother Theory Pract. 2020; 36(8): 886–898. PubMed Abstract | Publisher Full Text\n\nDreyer O: Psychotherapy in everyday life. Cambridge: Cambridge University Press; 2008.\n\nSpecht K, Agerskov H, Kjaersgaard-Andersen P, et al.: Patients’ experiences during the first 12 weeks after discharge in fast-track hip and knee arthroplasty – a qualitative study. Int J Orthop Trauma Nurs. 2018; 31: 13–19. PubMed Abstract | Publisher Full Text\n\nBradbury-Jones C, Taylor J, Herber O: How theory is used and articulated in qualitative research: Developement of a new typology. Soc Sci Med. 2014; 120: 135–141. PubMed Abstract | Publisher Full Text\n\nMiles MB, Huberman M: Saldaña. Qualitative Data Analysis -A Methods Sourcebook. 3rd edition. Thousand oaks, California: SAGE Publications Inc.; 2014."
}
|
[
{
"id": "85349",
"date": "17 Jun 2021",
"name": "Kirsten Specht",
"expertise": [
"Reviewer Expertise Orthopaedics",
"fast-track in hip and knee arthroplasty",
"qualitative studies"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article addresses patients’ perspectives on home-based rehabilitation exercises following total hip arthroplasty (THA). The topic is investigated through a qualitative method using semi-structured interviews. Data were analysed using thematic analysis. The study found the theme: 'wishing to return to the well-known everyday life', and the subtheme 'general physical activity versus rehabilitation exercise'. The topic of the paper is interesting and overall the paper is well-written; however, there are a number of issues throughout the paper.\nIntroduction:\nThe Introduction is a well-written section uncovering the knowledge within THA and home-based rehabilitation exercise.\n\nAim:\nThere are some concerns about the aim as it could reflect the title in a better way. The semi-structured interview guide sets the stage for broader and more open interviews with the patients’ perspectives on the topic in general, including facilitators and barriers. Rewording is wanted for the aim so that it better reflects the title which has a more open approach. A suggestion could be something like this: 'the study aimed to investigate how patients perceived home-based rehabilitation exercise and general physical activity after THA, including facilitators and barriers'.\n\nMethods:\nThe theoretical underpinning with the use of the concept 'conduct of everyday life' fits the topic very well, and the definition of home-based rehabilitation exercise is helpful for the overall understanding of the paper.\n\nThe study investigates home-based rehabilitation exercises, for international readers, it is crucial to understand what it contains in Denmark and Silkeborg. Therefore, there is a need for a detailed description of home-based rehabilitation exercises.\n\nFurthermore, was it the same programme for the two included groups? The authors have reference number 10 to describe the home-based rehabilitation exercise, this is a review, which confuses me. Please elaborate on the details of the programmes and whether they were similar for the two groups.\nRegarding the patients and recruitment, please elaborate on some of the details:\nSample size – how was that determined?\n\nHow many were asked to participate in the study?\n\nDid any refuse to participate?\n\nIncluded participants from the PHETHAS-1 study were 14 – how many were included in the PHETHAS-1 study, as this might be the group of patients where the participants in the PHETHAS-2 study were selected?\n\nResults:\nTaking into account that the interviews lasted an average of 43 minutes and the open questions in the semi-structured interview guide, it is surprising that only one theme, including one under-theme, was generated. There must be huge data material from all these minutes of interviews. During the analysis process, could it be possible to find more valuable results to give more perspectives on the aim?\n\nQuote P12: “Because first of all…\" – Could another interpretation be more like a desire for a contact to the healthcare system because of uncertainty?\n\nTo build upon what is already known, it could be interesting if there were any quotes about the last question in the interview guide: We are considering investigating whether this exercise program works better than general physical activities, what do you think of this idea?\n\nDiscussion:\nThe Discussion section is very short. Further discussion about the meaning of motivation, intrinsic and extrinsic factors could be valuable for the paper.\n\nThe concept 'conduct of everyday life' was chosen as a theoretical framework, it would have been interesting to bring this framework into the discussion. Additionally, topics such as pain and absence of pain and individual expectations alignment could be further discussed.\n\nTo improve the Discussion section, more research and other theories on, for example, the above-mentioned topics could expand on the results and make implications for practice more clear.\n\nPatients from the two groups were interviewed in different places (at the hospital and in their homes), what impact could that have on the results? In addition, patients being a part of another study, what consequences does that have for the transferability of the study?\n\nTwo paragraphs in the Discussion section belong more to the Conclusion or a perspective section: “Overall the participants …” and “There may be additional …”.\n\nConclusion:\nThe conclusion is supported by the results. However, adding a perspective section would be helpful to clarify how the findings can improve clinical practice.\"\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "7750",
"date": "04 Feb 2022",
"name": "Anne Poulsen",
"role": "Author Response",
"response": "Dear Reviewer, Thank you for the thorough review and highly valuable comments, improving the quality of the manuscript Patient perspectives on home-based rehabilitation exercise and general physical activity after total hip arthroplasty: A qualitative study (PHETHAS-2). Please find listed below the reviewer comments, our responses, and subsequent actions taken to improve the manuscript. We find that working with your comments greatly improved the manuscript and we hope you will find that the revisions address the concerns and issues raised in the review. Sincerely, Anne Grøndahl Poulsen, on behalf of the authors No 1. Reviewer comments: There are some concerns about the aim as it could reflect the title in a better way. The semi-structured interview guide sets the stage for broader and more open interviews with the patients’ perspectives on the topic in general, including facilitators and barriers. Rewording is wanted for the aim so that it better reflects the title which has a more open approach. A suggestion could be something like this: 'the study aimed to investigate how patients perceived home-based rehabilitation exercise and general physical activity after THA, including facilitators and barriers'. Author response: Thank you for turning our attention towards a better coherence between title and aim. We have taken your suggestion into consideration and reworded the aim. At the same time (for transparency), we want to stay true to the meaning and wording of the original aim as laid out in the trial protocol (see reference under No.2, Action taken). We feel that the current revision of the aim does that. Action taken: Rewording of the aim into: To investigate how patients perceived home-based rehabilitation exercise and general physical activity after THA, focusing on facilitators and barriers. No 2. Reviewer comments: The study investigates home-based rehabilitation exercises, for international readers, it is crucial to understand what it contains in Denmark and Silkeborg. Therefore, there is a need for a detailed description of home-based rehabilitation exercises. Furthermore, was it the same programme for the two included groups? The authors have reference number 10 to describe the home-based rehabilitation exercise, this is a review, which confuses me. Please elaborate on the details of the programmes and whether they were similar for the two groups. Author response: Thank you for making this point and for your sharp observation towards the wrongly noted reference. We have addressed this comment in two ways. A) Correcting the reference in which a full description of the home-based rehabilitation exercises is included. B) The article already states that the two groups were instructed in the exact same rehabilitation exercises. As a supplement, we have added a passage that describes the rehabilitation exercises in brief terms. Action taken: A) Correction of reference into: Mikkelsen LR, Madsen MN, Rathleff MS, Thorborg K, Rossen CB, Kallemose T, et al. Pragmatic Home-Based Exercise after Total Hip Arthroplasty-Silkeborg: Protocol for a prospective cohort study (PHETHAS-1) 2019. B) The following passage is added: This included an instruction before hospital discharge, where the patients were instructed to perform daily unloaded hip exercises for the first three weeks. At the clinical follow up after three weeks, the patients were instructed to perform strengthening exercises every second day, supplemented with daily balance exercise and stretching of the hip flexor muscles. The strengthening exercises were hip abduction, hip flexion and hip extension with elastic band resistance plus sit-to-stand exercise. No 3. Reviewer comments: Regarding the patients and recruitment, please elaborate on some of the details: Sample size – how was that determined? How many were asked to participate in the study? Did any refuse to participate? Author response: Thank you for these comments regarding the sampling process. The sampling process followed the principles of purposeful sampling and hence the number of participants was not determined ahead of recruitment. We have elaborated the passage describing the recruitment process in more detail and hope it will answer the questions asked. Action taken: The following passage in italics is added: The participants were purposely sampled hence sampling was based on the ongoing analysis including themes that were under continual development and with the aim of reflecting the gender and ages of typical THA patients. All invited patients accepted participation. No 4. Reviewer comments: Included participants from the PHETHAS-1 study were 14 – how many were included in the PHETHAS-1 study, as this might be the group of patients where the participants in the PHETHAS-2 study were selected? Author response: Thank you for this comment. The number of participants in the PHETHAS-1 study is 94. This will of course be stated when the PHETHAS-1 study is published. It is unclear to us how this information could be relevant for the qualitative PHETHAS-2 study. Please do not hesitate to comment on this again and elaborate if you find it needed. Action taken: No action taken. No 5. Reviewer comments: Taking into account that the interviews lasted an average of 43 minutes and the open questions in the semi-structured interview guide, it is surprising that only one theme, including one under-theme, was generated. There must be huge data material from all these minutes of interviews. During the analysis process, could it be possible to find more valuable results to give more perspectives on the aim? Author response: Thank you for this perspective on the relationship between the length of interviews and identified themes. We find the content of the two themes reflects the content of the interviews related to the concept of everyday life, which is a comprehensive concept. In relation to the aim, the identified themes do provide several aspects of the focus on barriers and facilitators towards performing home-based rehabilitation exercises, which might not be stated very clearly. Therefore, we have added a table illustrating facilitators and barriers to home-based rehabilitation exercises. Also, we have added several elaborations in the results section, underpinning analytical findings regarding facilitators and barriers. Action taken: We have added Table 2 illustrating facilitators and barriers towards home-based rehabilitation exercises. We have elaborated on the results section to more clearly present findings regarding facilitators and barriers towards home-based rehabilitation exercises. No 6. Reviewer comments: Quote P12: “Because first of all…\" – Could another interpretation be more like a desire for a contact to the healthcare system because of uncertainty? Reviewer comments: Thank you for suggesting an alternate interpretation of this quote. We believe it would be an overinterpretation to suggest that the participant refers to the healthcare system as a whole since this was said in relation specifically to the performance of the home-based rehabilitation exercises. Of course, we cannot rule out that there could be a connection to the healthcare system as well, but our data do not support this. Action taken: No action taken. No 7. Reviewer comments: To build upon what is already known, it could be interesting if there were any quotes about the last question in the interview guide: We are considering investigating whether this exercise program works better than general physical activities, what do you think of this idea? Author response: Thank you for your careful attention to the interview guide. The specific question was asked as a supplement with the purpose of gaining information regarding a possible future research study. Such a research study is currently being undertaken. Since the replies to the question do not provide answers to the aim of this study, no replies are included in this paper. Action taken: No action taken. No 8. Reviewer comments: The Discussion section is very short. Further discussion about the meaning of motivation, intrinsic and extrinsic factors could be valuable for the paper. Author response: Thank you for your suggestions regarding the discussion section, also including comments No. 9, 10, and 11. We agree that adding a perspective regarding intrinsic and extrinsic motivation could improve the discussion section, and we have added a passage concerning this. Action taken: The discussion section is extended and rewritten to a wide degree, including the perspectives of intrinsic and extrinsic motivation. No 9. Reviewer comments: The concept 'conduct of everyday life' was chosen as a theoretical framework, it would have been interesting to bring this framework into the discussion. Author response: Concerning this suggestion, we have elaborated on how returning to the well-known everyday life is used and described in relation to the concept of everyday life. Action taken: The discussion section is extended and rewritten to a wide degree, including the concepts of 'conduct of everyday life'. No 10. Reviewer comments: Additionally, topics such as pain and absence of pain and individual expectations alignment could be further discussed. Author response: Thank you for this suggestion. We have expanded the discussion regarding pain in the Discussion section. Action taken: The existing passage concerning pain has been extended, and now include the following: Some participants described a wish to have contact with a physiotherapist who would be able to provide guidance and support during the rehabilitation period. Positive impact of being in contact with a therapist during rehabilitation is supported in a review by Davenport et al. In terms of motivation this would serve as an extrinsic motivational factor for performing the home based rehabilitation exercises. Some of the participants in this study wished for contact to a physiotherapist, because they experienced barriers such as doubt of whether the exercises were performed correctly or whether to perform them at all e.g. due to pain. In such a situation the person might be fully motivated for performing the exercises on their own, but choose not to do so due to doubt regarding how to handle pain. According to Davenport et al, this would be accommodated when in contact with a therapist. Specht et al showed that patients can have a feeling of uncertainty when being left alone to perform the rehabilitation exercise after discharge from the hospital, for example when dealing with pain. Our study adds the knowledge that not only pain, but also absence of pain can be identified as a barrier for performing home-based rehabilitation exercise. Standard care participants in this study gradually modified the exercises as they were able to return to their habitual everyday life, and performed the usual general physical activities they felt contributed to their quality of life instead. Modifying the exercises might also be a way of handling the fact that most participants described the exercises as boring. Modifying therapeutic instructions is well known in other areas, but to our knowledge, this is the first time it is described in THA patients. No 11. Reviewer comments: To improve the Discussion section, more research and other theories on, for example, the above-mentioned topics could expand on the results and make implications for practice more clear. Author response: Thank you for the suggestion. We have addressed this by adding a section into the discussion, concerning perspectives on both implications for practice and for future research. Action taken: The following section is added to the discussion: Perspectives Several perspectives grow out of our study both in terms of implications for practice and for further research. Importantly, most participants appreciate the home-based rehabilitation exercise program underscoring the flexibility of deciding for themselves when and where to perform the exercises. Based on this, our study support the use of home-based rehabilitation exercise, but attention should be paid towards patients who might need additional support and easy access to a physiotherapist should be provided. Concerning participants wish to return to their usual everyday lives and this serving as a motivational factor for performing the exercises, it is important that healthcare professionals are in dialogue with the individual patient to identify which activities are preferred in their habitual everyday life, and on that basis decide on relevant goals for the rehabilitation period. Further, physiotherapists working in this area might want to consider how to include general physical exercise into rehabilitation exercise programs, since participants generally favoured this type of exercise over formal exercises. This might also address the finding of home-based rehabilitation exercises perceived as boring and thereby increase motivation and support adherence to the exercise program. Additionally, it would be useful to investigate whether general physical activities could be as effective as home-based rehabilitation exercise, and if so, whether future THA patients could rehabilitate by only doing their preferred physical activities. There may be additional contributing factors in relation to patients’ perceptions of home-based rehabilitation exercise after THA. These could include age, gender, previous training experience, and culture. Further studies are needed to explore this. No 12. Reviewer comments: Patients from the two groups were interviewed in different places (at the hospital and in their homes), what impact could that have on the results? Author response: Thank you for turning our attention to the potential impact of the setting of the interviews. We have added a passage addressing this point in the 'strengths and limitations' section. Action taken: The following passage is added to the section of strengths and limitations: The two groups of participants also differed regarding the location of the interviews. Participants recruited from usual care were interviewed in their homes, while participants recruited from PHETHAS-1 study were interviewed in a hospital setting. This might have affected data e.g. if participants were more comfortable in their homes as well as being in the setting where the home based rehabilitation exercises were performed and therefore would give more open hearted and detailed interviews. Data retrieved from interviews conducted in both types of settings are similar which indicate that this potential limitation is not applicable to this study. No 13. Reviewer comments: In addition, patients being a part of another study, what consequences does that have for the transferability of the study? Author response: We have been transparent throughout the paper about recruiting from two groups of participants. Importantly, the only difference was some participants being part of another study. This recruitment strategy had a positive impact, and we have accounted for potential negative impacts. Meanwhile, we have elaborated on these points in the discussion section. We do view results as transferable to similar settings, although one could argue for a higher degree of transferability regarding findings from participants recruited from usual care. Yet, the only difference in our findings was a higher degree of motivation towards adherence over time and performing exercises as instructed, which is accounted for in the discussion section. Action taken: We have added the following passage in italics to the strengths and limitations section: In this study we recruited participants from both the PHETHAS-1 study and from standard care. This combination of participants revealed an important difference in motivation towards adherence to, and performance of, the home-based rehabilitation program. The PHETHAS-1 participants had a higher degree of motivation towards adherence over time and performing exercises as instructed, but our findings showed no other differences between the two groups of participants. In addition to this specific point, one might argue that findings from the PHETHAS-1participants have a lower degree of transferability to practice compared to the usual care participants. No 14. Reviewer comments: Two paragraphs in the Discussion section belong more to the Conclusion or a perspective section: “Overall the participants …” and “There may be additional …”. Author response: Thank you for this fine suggestion. Action taken: The two paragraphs are moved to the new 'perspectives' section. No 15. Reviewer comments: The conclusion is supported by the results. However, adding a perspective section would be helpful to clarify how the findings can improve clinical practice. Author response: Again, thank you for this suggestion which we have met by adding a 'perspectives' section. Action taken: A 'perspectives' section is added."
}
]
}
] | 1
|
https://f1000research.com/articles/10-382
|
https://f1000research.com/articles/11-1179/v1
|
17 Oct 22
|
{
"type": "Research Article",
"title": "Clinical equivalence of Trusynth fast® and Vicryl rapide® polyglactin 910 fast absorbing sutures on maternal morbidity experienced by women following episiotomy repair: a single-blind, randomized study",
"authors": [
"Dongabanti Hemalatha Devi",
"Chethana Bolanthakodi",
"Prema D’Cunha",
"Mudiki Bheema Bai",
"Ashok Kumar Moharana",
"Deepak TS",
"Dongabanti Hemalatha Devi",
"Prema D’Cunha",
"Mudiki Bheema Bai",
"Ashok Kumar Moharana",
"Deepak TS"
],
"abstract": "Background: Episiotomy procedure enlarges the vaginal outlet to facilitate childbirth. Polyglactin 910 fast-absorbing sutures are widely used for the repair of episiotomy because of their rapid absorption and less inflammatory response. This study was designed for subjective assessment of perineal pain post-episiotomy repair, with Trusynth Fast® and Vicryl Rapide® polyglactin 910 fast-absorbing sutures. Method: This was a single-blind, randomized, prospective study conducted between January 7, 2021 and July 14, 2021 across two centers in India. Primiparous or multiparous women (18—40 years), who required episiotomy during vaginal delivery were included, and either Trusynth Fast® (n=47) or Vicryl Rapide® (n=49) suture was used for their episiotomy repair. The primary endpoint, perineal pain was assessed with visual analogue scale at all follow-up visits. The secondary endpoints, quantity of local anesthesia, number of sutures used, time to repair episiotomy, intraoperative suture handling, analgesics used, early and late wound complications, wound re-suturing, time to complete healing, presence of residual sutures, return to sexual activity, dyspareunia, and adverse events were also recorded. Results: The study showed no significant difference in perineal pain between the two groups at any visit. A statistically significant difference (p<0.05) in total score of episiotomy healing scale on day 2 (0.13±0.34 versus 0.35±0.56) and swelling on day 2 (8.51 versusversus 28.57%) was noted between Trusynth Fast® and Vicryl Rapide® group. Non-significant difference was observed between the groups regarding anesthesia, number of sutures, time to repair episiotomy, intraoperative suture handling, analgesics, puerperal fever, wound infection, dehiscence, hematoma, urinary incontinence, re-suturing, time to complete healing, return to sexual activity and dyspareunia. Conclusion: Trusynth Fast® suture is clinically equivalent to Vicryl Rapide® suture and can be used for episiotomy repair with minimal risk of perineal pain and wound complications. Clinical Trials Registry of India Registration: CTRI/2020/12/029925; Registered on December 18, 2020",
"keywords": [
"Episiotomy healing scale",
"Episiotomy repair",
"Perineal pain",
"Polyglactin 910 fast absorbable suture",
"Vaginal delivery",
"Wound complications"
],
"content": "Introduction\n\nEpisiotomy, the most frequently performed operative procedure enlarges the vaginal outlet in order to facilitate childbirth. It is performed by applying an incision on the perineum. In India, episiotomy is performed in approximately 63% of women during vaginal delivery.1 Generally, episiotomy is associated with wound infection, wound dehiscence, perineal pain and discomfort.2 About 46% of mothers in lower income countries experience some degree of trauma to the perineal area during vaginal delivery.3\n\nAfter performing episiotomy, the incised tissue has to be approximated, which is significantly impacted by the suture material used for tissue approximation, as it may affect perineal pain, discomfort and episiotomy healing.4 Although chromic catgut suture material was most commonly used for episiotomy repair, a higher incidence of short-term morbidity was found after using it in comparison to absorbable synthetic material.5 Furthermore, in comparison to chromic catgut sutures, use of polyglactin 910 sutures reported lower cases of morbidity and perineal pain.6 The fast-absorbing polyglactin 910 sutures accelerate hydrolysis and take 42 days to be absorbed.7 Previous studies compared synthetic absorbable suture materials (both polyglactin-910 and fast-absorbing polyglactin 910) with catgut sutures for episiotomy repair,5,8,9 but comparison between Trusynth Fast® and Vicryl Rapide® fast-absorbing polyglactin 910 sutures for episiotomy repair has not been done yet. Therefore, this study was designed to compare Trusynth Fast® and Vicryl Rapide® fast-absorbing polyglactin 910 sutures for evaluating maternal morbidity experienced by women following episiotomy repair.\n\n\nMethods\n\nThis was a single-blind, randomized, prospective study conducted between January 7, 2021 and July 14, 2021 across two centers in India. The primary objective was subjective assessment of perineal pain post-episiotomy repair, with Trusynth Fast® and Vicryl Rapide® suture. The secondary objectives included assessment of overall intraoperative handling, use of analgesics, wound healing, resumption of sexual activity and dyspareunia, number of sutures utilized and residual suture removal and maternal morbidities post-episiotomy in Trusynth Fast® and Vicryl Rapide® suture groups.\n\nThis trial was registered at Clinical Trials Registry of India (CTRI Reg. No: CTRI/2020/12/029925; December 18, 2020) and the Institutional ethics committee of both participating sites approved the study protocol. Government Victoria Hospital-King George hospital ethics committee, approved the study on 4th December 2020, and Father Muller Institutional ethics committee approved the study on 15th December 2020 with registration number FMIEC/CCM/693/2020. The study is reported as per Consolidated Standards of Reporting Trials (CONSORT), and details regarding the CONSORT check list is present in data availability section.\n\nWritten informed consent was obtained from all participants for participation in the study as well as for publication of their clinical data.\n\nPrimiparous or multiparous women aged 18 to 40 years, with a singleton pregnancy, gestational age of >34 weeks, and good systemic/mental health, who required episiotomy during the course of vaginal delivery, who visited the Department of Obstetrics & Gynecology of both the centers were invited to participate in this research. They were included in this study after obtaining informed consent.\n\nWomen were excluded if they had intrapartum fever, tears (perineal, cervical or vaginal) or extension of the episiotomies, HIV or hepatitis B infection, stillbirth, known allergy to the suture materials and a history of bleeding/coagulation disorders or perineal surgery other than the primary repair after childbirth.\n\nThe women were also excluded if the investigator felt it would be difficult to follow the study procedure and follow-up.\n\nThe study was conducted at two sites: (i) Department of Obstetrics & Gynecology, Government Victoria Hospital, Visakhapatnam-530001, Andhra Pradesh, India, and (ii) Department of Obstetrics & Gynecology, Father Muller Medical College, Mangalore-575002, Karnataka, India.\n\nThe two studied interventions were Trusynth Fast® (Healthium Medtech Limited) and Vicryl Rapide® (Ethicon, Johnson and Johnson) sutures. Both sutures are coated, braided, absorbable sterile polyglactin 910 fast absorbable sutures and indicated for use in soft tissue approximation, where only short-term wound support is required, and rapid absorption of the suture can be beneficial.\n\nOn the day of delivery (Baseline visit or day 0), the episiotomies were repaired as per standard institutional protocol with either Trusynth Fast® or Vicryl Rapide® sutures. The time between giving of the episiotomy and the time of start and completion of suturing was noted. The subjects were followed on day 2 (In-patient visit while in the hospital), day 11 (In-clinic/Telephonic visit), week 6 (In-clinic visit) and week 12 (Telephonic visit).\n\nBaseline demographics including age, ethnicity, smoking and alcohol consumption history, weight, height, vital signs along with period of gestation, parity, history of previous episiotomy, fetal presentation in utero and medical/surgical history were recorded.\n\nPrimary outcome\n\nThe primary outcome, perineal pain following repair of episiotomy at 2 hours, 4 hours, 6 hours, and 12 hours after surgery, and on the day 2, day 11, week 6, and week 12 were noted using the visual analogue scale (VAS). VAS of 0–4 was graded as no pain, 5–44 as mild pain, 45–74 as moderate pain and 75–100 as severe pain.\n\nSecondary outcome\n\nThe secondary endpoints, quantity of local anesthesia, number of sutures used, time to repair episiotomy, intraoperative suture handling, post-episiotomy number and dosage of analgesics, early and late wound complications, viz. puerperal fever (fever caused by uterine infection), swelling, infection (mild to severe discharge requiring treatment), hematoma (wound swelling >1 cm with changing color of skin), wound gaping, disruption or dehiscence (separation of wound edges of ≥1 cm) and urinary incontinence (involuntary loss of urine with coughing, sneezing, laughing, or running), time to complete healing, presence of residual sutures, frequency of wound re-suturing, return to sexual activity, dyspareunia and adverse events were evaluated.\n\nThe intraoperative suture handling was assessed using parameters like ease of passage through tissue, first-throw knot holding, knot tie-down smoothness, knot security, stretch capacity, memory, suture fraying on a five-point scale: 1 poor; 2 fair; 3 good; 4 very good; and 5 excellent. Wound healing was assessed by the standardized and valid REEDA (redness, edema, ecchymosis, discharge, and approximation) scoring scale, with scores ranging from 0 to 15. A lower score indicates better healing at the episiotomy site and higher score shows poor healing processes. Any unanticipated clinical signs, medical condition, disease or injury during the study period, which were already captured as study endpoints were not labeled and reported as adverse events.\n\nOther standard details about the duration of second stage of labor, length of incision, number of layers closed, suture related challenges, perioperative complications, postpartum hemorrhage, outcome of surgery, length of hospital stay, antibiotic prophylaxis, suture loosening, feeling of slight stitches, and suture sent for culture were also recorded. In addition, the prescribed/concomitant medications during the study period were also noted.\n\nThe data from a previous study found that one out of 50 (2%) women in Vicryl Rapide® group had mild discomfort in sitting posture at six weeks, and 98% had no discomfort or pain.9 Following the findings of this study, the proportion of patients experiencing no perineal pain, post-episiotomy repair, in the standard Vicryl Rapide® arm was assumed to be 98% i.e., π1=98%. Assuming type I error as 5% (α=0.05), power as 80% (1-β=0.8) and a difference to be detected as 1% for the proportion of patients experiencing no perineal pain in the Trusynth Fast® arm (π2=97%) with a margin of non-inferiority as 10% of the difference (δ), a minimum sample size was determined approximately as 38 in each arm. Further, considering a drop out of 20% and post-randomization exclusion of 10%, the required sample size was increased to 50 in each arm. So, a total of 100 subjects participated in this trial.\n\nSample size calculation formula:\n\nni: sample size required in each group; Zα: conventional multiplier for alpha; Zβ: conventional multiplier for power; π1: proportion of patients experiencing no perineal pain in the Vicryl Rapide® arm; π2: proportion of patients experiencing no perineal pain in the Trusynth Fast® arm; δ: margin of non-inferiority difference; π1-π2: size of difference of clinical importance.\n\nBefore initiation of the study, a computer-based, automated randomization number was generated by using version 1.0 of Random Allocation Software, using block sizes of 4, 6 or 8 by an independent programmer. The randomization concealment was done by sequentially numbered opaque sealed envelopes (SNOSE) technique. The subjects were allocated randomly in a 1:1 ratio to Trusynth Fast® (n=50) or Vicryl Rapide® (n=50) suture group. This was a single-blind study and the subjects were kept blinded to the device allocation status.\n\nThe per-protocol or PP analysis set was used for statistical analysis using the SPSS version 25.0 (SPSS, Chicago, Illinois, USA). The PP set includes all subjects, who have complete data on the primary effectiveness parameter during 12 weeks follow-up. All continuous variables were expressed as mean±SD (standard deviation) and compared using the t-test for normally distributed data or Mann-Whitney U test for distribution-free data. All qualitative variables were expressed as proportions/percentages, and compared using Chi-squared test or Fisher's Exact test. A p value of < 0.05 was considered statistically significant.\n\n\nResults\n\nA total of 100 women were screened for eligibility between January 7, 2021 and April 21, 2021 and follow-up of the last subject was completed on July 14, 2021. However, four subjects met the exclusion criteria and did not receive the intervention. Therefore, the PP set consisted of 96 subjects, who received the allocated intervention (Trusynth Fast®, n=47; Vicryl Rapide®, n=49) for episiotomy repair and completed the study (Figure 1).\n\nBaseline demographics, vital signs and other relevant characteristics were comparable between the two treatment arms (Table 1). All the subjects who participated in the study were Indians and none of them had a history of alcohol consumption or smoking. The fetus of all the studied women was in vertex position.\n\nThe perineal pain was assessed using VAS scale at 2 hours, 4 hours, 6 hours and 12 hours after childbirth and on all follow-up visits. No significant difference in perineal pain was observed, between the two groups at any time point. The intensity of pain was gradually decreased in subsequent follow-up visits (Figure 3a and b).\n\nIntraoperative profile\n\nAll subjects received 10 mL of local anesthesia (lignocaine) and antibiotic prophylaxis. In all subjects, normal delivery was done with no requirement for instrument use. All the episiotomies were right mediolateral incisions and three layers were closed in both groups. The results relative to the intraoperative handling characteristics are shown in Figure 2. “Excellent” score was higher for ease of passage, first-throw knot holding, knot security, stretch capacity, memory, and degree of fraying in Trusynth Fast® group, and for knot tie-down in Vicryl Rapide® group. Moreover, good outcome of surgery was noted in all subjects, as well as no suture-related challenges and perioperative complications were noted in both groups. The other intraoperative characteristics are summarized in Table 2.\n\nNone of the characteristics had “poor” score.\n\n* p<0.05.\n\nPost-operative profile\n\nThe subjects of Vicryl Rapide® group took comparatively longer time for complete healing after episiotomy repair than Trusynth Fast® group, but the difference was not statistically significant (Table 2). None of the subjects in any group required analgesic during week 6 and week 12 of delivery. A significantly higher (p<0.05) mean score of total episiotomy healing scale at day 2 in Vicryl Rapide® group indicated good healing in Trusynth Fast® group (Figure 3c). At day 2, more subjects with score 0 for REEDA scale were found in Trusynth Fast® group, compared to Vicryl Rapide® group (Figure 3d). The feeling of slight stitches was registered in both Trusynth Fast® and Vicryl Rapide® group at day 2 (mild, 2.13 versus 2.04%; moderate, 40.43 versus 40.82%, p=0.98), day 11 (mild, 31.92 versus 14.29%; moderate, 6.38 versus 8.16%, p=0.09) and week 6 (mild, 17.02 versus 14.29%, moderate 0 versus 0, p=0.71). At week 12, no subjects had the feeling of slight stitches.\n\nhr: Hours, p<0.05 is statistically significant.\n\nNone of the subjects were readmitted to the hospital during any follow-up visits. Incidence of suture loosening, residual suture removal and sent for culture were not recorded during entire study period. The incidence of swelling was observed in subjects of both Trusynth Fast® and Vicryl Rapide® groups at day 2 (8.51 versus 28.57%, p<0.05), that improved at day 11 (2.13 versus 2.04%, p=0.98), and became nil at week 6 and 12. No other wound complications (wound infection, wound dehiscence, hematoma, wound re-suturing, puerperal fever and urinary incontinence) were noted at any follow-up visits. After 6 weeks of delivery, 6 (12.77%) women in the Trusynth Fast® group and 6 (12.24%) women in the Vicryl Rapide® group were able to resume sexual activity (p=0.94). After 12 weeks of surgery, 21 (44.68%) women in Trusynth Fast® group and 17 (34.69%) women in the Vicryl Rapide® group resumed sexual activity (p=0.32). Furthermore, the women who resumed sexual activity did not report incidence of dyspareunia. Other post-operative characteristics are presented in Table 2.\n\nNon-serious adverse events were observed, viz. drug allergy in one (2.13%) subject, mild vaginal discharge in one (2.13%) subject, and fever in 3 (6.38%) subjects of Trusynth Fast® group. In the Vicryl Rapide® group, one (2.04%) subject had general body pains along with vomiting and headache, one (2.04%) subject had fever, one (2.04%) subject had general body pains, and one (2.04%) subject had vomiting. The adverse events were mild in severity and not related to the study device. The prescribed/concomitant medications used during the study period are given in Table 3.\n\n\nDiscussion\n\nIn India, more than 60% of women undergo episiotomy during vaginal delivery.1 Post-episiotomy development of swelling, hemorrhage, hematoma, wound dehiscence and infection along with prolonged hospital stay, perineal pain and delayed resumption of sexual activity is already reported.2 The repair technique and the type of suture material used have a major influence on the outcome of episiotomy repair. According to NICE guidelines, rapidly absorbable synthetic suture is the optimal material for perineal repair.10 Existing literature demonstrated the beneficial effect of synthetic suture over chromic catgut suture material regarding post-episiotomy complications, perineal pain and discomfort.5,6,8,9 However, the comparison of two polyglactin 910 fast absorbing suture brands for episiotomy repair post-vaginal delivery is still not established. Therefore, this study compared Trusynth Fast® and Vicryl Rapide® fast-absorbing polyglactin 910 sutures for evaluating maternal morbidity experienced by women following episiotomy repair.\n\nDifferent aspects of intraoperative suture handling characteristics studied in this study were comparable between the suture groups. Ease of passage, knot security, knot tie-down and stretch capacity were graded as either “very good” or “excellent” in all subjects of Trusynth Fast® group, while only ease of passage was graded either “very good” or “excellent” in all subjects of Vicryl Rapide® group. None of the suture handling characteristics was graded “fair” or “poor” in Trusynth Fast® group, and “poor” in Vicryl Rapide® group. Furthermore, good outcome of surgery along with no suture related challenges indicates the clinical equivalence of both sutures.\n\nPerineal pain for ≥72 hours of episiotomy is the common morbidity in women, for which analgesia can be continued for ≥10 days after delivery.2 Use of a rapidly absorbable form of polyglactin 910 for the repair of perineal trauma offers a significant reduction in pain and analgesic number, when compared to standard absorbable synthetic material.11 Polyglactin 910 elicits minimal tissue reaction as compared to catgut, and is associated with less pain.6 A decrease in perineal pain and analgesic requirement with the use of a rapidly absorbable synthetic suture material was reported in previous studies.9,11 Withstanding the findings of these studies, subjects of present study also showed reduction in perineal pain, from day 2 onwards after using Trusynth Fast® and Vicryl Rapide® fast-absorbing polyglactin 910 suture for episiotomy repair. In both suture arms, similar improvement in pain was evident, with no significant difference at any follow-up visit. In addition, the mean analgesics prescribed were also decreased with each passing visit in both groups, and not required by any subjects at 6–12 weeks.\n\nPostpartum infection is a major cause of maternal mortality and also associated with maternal anxiety and postpartum depression.12 Similarly, wound dehiscence is one of the important causes of re-suturing, and requires hospital re-admissions in the postpartum period, leading to physical and psychological problems.13 The results of the present study depicted no wound infection, wound dehiscence, hematoma, puerperal fever or urinary incontinence. Moreover, re-suturing was not required in any of the subjects. However, a significantly higher incidence of swelling was observed in the Vicryl Rapide® group on day 2, which decreased eventually (within 11 days post-delivery), and no significant differences were found in the subsequent visits. A previous study reported that routine episiotomy resulted in inflammation along with hematoma, infection and dehiscence, pain, extension of the episiotomy incision, and sexual dysfunction.14 However, in this study, comparable number of subjects in both groups resumed sexual activity by week 6 and 12, with no complaint of dyspareunia.\n\nPerineal wound heals by primary closure, with least possible complications within 14 days of suturing.11 Episiotomy repair with polyglactin 910 suture results in more satisfactory wound healing as compared to chromic catgut suture.8 A non-significant, but faster wound healing was noted in Trusynth Fast® group as compared to Vicryl Rapide® group. In addition, no incidence of any suture-related adverse event was observed in this study.\n\nThis study is methodologically robust and appropriately powered to detect a difference in the primary and secondary outcomes; hence the findings of this study can be generalized to the wider population. The clinical equivalence of these two sutures regarding efficacy and safety indicates that Trusynth Fast® suture can be used in all surgeries indicated for Vicryl Rapide® suture. The limitation of the present study is that the surgeons who assessed the intraoperative suture handling characteristics were not blinded, and therefore, a potential bias might have occurred if they favored one suture over the other.\n\n\nConclusion\n\nThe findings demonstrated clinical equivalence of Trusynth Fast® suture to Vicryl Rapide® suture in terms of non-significant differences in primary and secondary endpoints (except swelling and mean score of episiotomy healing scale on day 2). Both the sutures can be used for episiotomy repair with minimal risk for maternal morbidity, viz. perineal pain, early and late wound complications, and re-suturing.\n\n\nData availability\n\nFigshare. Trusynth fast suture study Dataset, https://doi.org/10.6084/m9.figshare.21184411.v1.15\n\nThis project contains the underlying data related to all the data points mentioned below:\n\n• Demographic data, primary and secondary endpoints\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: Trusynth fast study CONSORT checklist, https://doi.org/10.6084/m9.figshare.21184420.v1.16\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgements\n\nThe authors are grateful to WorkSure® India for providing clinical research support.\n\n\nReferences\n\nSingh S, Thakur T, Chandhiok N, et al.: Pattern of episiotomy use & its immediate complications among vaginal deliveries in 18 tertiary care hospitals in India. Indian J. Med. Res. 2016; 143: 474–480. PubMed Abstract | Publisher Full Text\n\nOnonuju C, Ogu R, Nyengidiki T, et al.: Review of episiotomy and the effect of its risk factors on postepisiotomy complications at the University of Port Harcourt Teaching Hospital. Niger Med. J. 2020; 61: 96–101. PubMed Abstract | Publisher Full Text\n\nAguiar M, Farley A, Hope L, et al.: Birth-Related Perineal Trauma in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis. Matern. Child Health J. 2019; 23: 1048–1070. PubMed Abstract | Publisher Full Text\n\nThukral P, Mendiratta S, Bhola G: A comparative study of subcuticular and interrupted stitches for episiotomy. Int. J. Reprod. Contraception, Obstet. Gynecol. 2018; 7(5107): 5107. Publisher Full Text\n\nPerumal D, Selvaraju D: Comparative study of episiotomy repair: absorbable synthetic versus chromic catgut suture material. Int. J. Reprod. Contraception, Obstet. Gynecol. 2017; 6: 2186. Publisher Full Text\n\nGupta K, Gupta T, Dalmia K, et al.: Section: Obstetrics and Gynaecology “A Comparative Study of Vicryl Rapide Versus Chromic Catgut for Episiotomy Repair”.2021; 8: 1–5.\n\nSusmitha DJ, Bidri DSR: A comparative study between fast absorbing polyglactin 910 vs chromic catgut in episiotomy wound repair. Int. J. Clin. Obstet. Gynaecol. 2021; 5: 287–291. Publisher Full Text\n\nHowells IE, Abasi IJ: Episiotomy Repair in Poor Resource Settings, is It Justifiable to Recommend the Fast Absorbing Polyglactin 910 Suture (Vicryl Rapide) as the Suture of Choice ? – A Randomized Controlled Trial.2020; 4: 30–42.\n\nSamant M, Bose E, Ghosh A, et al.: Comparison of impact of polyglactin 910 (Vicryl rapide) and chromic catgut sutures on perineal pain following episiotomy wound repair in eastern Indian patients. J. Sci. Soc. 2013; 40: 95. Publisher Full Text\n\nNational Institute for Health and Clinical Excellence: Intrapartum care for healthy women and babies. Nice. 2014; 33–54.\n\nKettle C, Rk H, Kmk I: Second degree tears (Review).2007. Publisher Full Text\n\nBoushra M, Rahman O: Postpartum Infection Pathophysiology.2013; 1–8.\n\nDudley L, Kettle C, Waterfield J, et al.: Perineal resuturing versus expectant management following vaginal delivery complicated by a dehisced wound (PREVIEW): A nested qualitative study. BMJ Open. 2017; 7: e013008–e013010. Publisher Full Text\n\nGün İ, Doğan B, Özdamar Ö: Long- and short-term complications of episiotomy. Turkish J. Obstet. Gynecol. 2016; 13: 144–148. PubMed Abstract | Publisher Full Text\n\nDevi DH, Bolanthakodi C, D’Cunha P, et al.: Trusynth fast suture study [DATASET]. figshare.2022 [cited 2022Sep22].Reference Source\n\nDevi DH, Bolanthakodi C, D’Cunha P, et al.: Trusynth fast study CONSORT checklist. figshare.2022 [cited 2022Sep22].Reference Source"
}
|
[
{
"id": "171249",
"date": "02 Jun 2023",
"name": "Geetika Kaur",
"expertise": [
"Reviewer Expertise Immunology",
"Cell and Molecular Biology",
"Angiogenesis",
"Pathology",
"Anatomy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript entitled “Clinical equivalence of Trusynth fast® and Vicryl rapide® polyglactin 910 fast absorbing sutures on maternal morbidity experienced by women following episiotomy repair: a single-blind, randomized study” by Devi et al. is quite interesting. The manuscript is well-written and provides additional evidence in the literature on the safe usage of polyglactin sutures. Detailed methodology and results have been provided. However, minor changes are required to improve the manuscript.\nAdditional comments:\nIn the introduction section, provide characteristic features of Trusynth Fast sutures, if any previous studies have been conducted using it; they need not to be randomised but any general studies, suggesting the qualities of the suture.\n\nIn the methodology section, provide IEC no. of Government Victoria Hospital-King George hospital also, if any, similar to other institute’s registration number.\n\nAs mentioned in the result section, 100 females were screened and 4 were excluded. Were 100 consecutive women screened for eligibility? If yes, why were further patients not screened or recruited when four patients met exclusion criteria?\n\nThe study was conducted at two sites. How many patients were recruited from each site?\n\nFigure numbers are not consecutive. Figure 1, 3 and then figure 2. Kindly rectify this.\n\nIn Figure 3, it would be better to mention SD along with mean values of pain score and mean healing score. It is not required to be mentioned for frequency of subjects.\n\nIn the post-operative profile of secondary endpoint analysis, the authors have mentioned that “The subjects of Vicryl Rapide® group took comparatively longer time for complete healing after episiotomy repair than Trusynth Fast® group, but the difference was not statistically significant (Table 2).” On applying two tailed t-test, the difference is found to be statistically significant with p value= 0.026. I would like to know which statistical test was applied to compare the mean values?\n\nHow many in clinic and telephonic follow up visits were conducted on Day 11, as mentioned in methodology? How did you verify the adverse events on telephonic follow-up?\n\nIn the discussion section, I would suggest to add a few studies from the literature to discuss the findings of this study.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9777",
"date": "27 Jun 2023",
"name": "Chethana Bolanthakodi",
"role": "Author Response",
"response": "The manuscript entitled “Clinical equivalence of Trusynth fast® and Vicryl rapide® polyglactin 910 fast absorbing sutures on maternal morbidity experienced by women following episiotomy repair: a single-blind, randomized study” by Devi et al. is quite interesting. The manuscript is well-written and provides additional evidence in the literature on the safe usage of polyglactin sutures. Detailed methodology and results have been provided. However, minor changes are required to improve the manuscript. Authors’ response: We appreciate your valuable time and efforts invested in reviewing this manuscript. Additional comments 1. Comment: In the introduction section, provide characteristic features of Trusynth Fast sutures, if any previous studies have been conducted using it; they need not to be randomised but any general studies, suggesting the qualities of the suture. Response: It is to bring to your attention that no studies are available in the literature on Trusynth Fast® suture. However, we have added studies related to fast-absorbing polyglactin 910 sutures in the introduction. [Page 4]. Further, the characteristic features of both Trusynth Fast® and Vicryl Rapide® sutures are included in the Methodology section [Intervention; Page 6]. 2. Comment: In the methodology section, provide IEC no. of Government Victoria Hospital-King George hospital also, if any, similar to other institute’s registration number. Response: No IEC number was provided on the ethical approval letter of King George Hospital. Therefore, it has not been mentioned in the manuscript. 3. Comment: As mentioned in the result section, 100 females were screened and 4 were excluded. Were 100 consecutive women screened for eligibility? If yes, why were further patients not screened or recruited when four patients met exclusion criteria? Response: Female patients were recruited on the basis of inclusion and exclusion criteria rather than consecutive recruitments. The four females were excluded after randomization and during surgery due to cervical tear, perineal tear, and vulvar hematoma, as shown in the CONSORT flow diagram. As mentioned in the sample size calculation, 76 females were to be included to attain significance. Thus, further recruitments were not conducted. 4. Comment: The study was conducted at two sites. How many patients were recruited from each site? Response: Both sites recruited an equal number of patients i.e., 50 females at each site. 5. Comment: Figure numbers are not consecutive. Figure 1, 3, and then figure 2. Kindly rectify this. Response: As per your suggestion, we have now rectified the same. 6. Comment: In Figure 3, it would be better to mention SD along with mean values of pain score and mean healing score. It is not required to be mentioned for the frequency of subjects. Response: We have now mentioned the same. 7. Comment: In the post-operative profile of secondary endpoint analysis, the authors have mentioned that “The subjects of Vicryl Rapide® group took comparatively longer time for complete healing after episiotomy repair than Trusynth Fast® group, but the difference was not statistically significant (Table 2).” Response: On applying a two-tailed t-test, the difference is found to be statistically significant with p value= 0.026. I would like to know which statistical test was applied to compare the mean values? Primarily, KS test was done to check the normality. The data was not found to be normally distributed thus, non-parametric approach, Mann-Whitney U test was used which resulted in p-value of 0.175. The difference was found to be statistically non-significant. 8. Comment: How many in clinic and telephonic follow up visits were conducted on Day 11, as mentioned in methodology? How did you verify the adverse events on telephonic follow-up? Response: Equivalent numbers of in-clinic and telephonic follow-ups were conducted on Day 11. During telephonic follow-up, the subjects were asked for the occurrence of any disease, injury, or any other signs for assessment of adverse events. In case of severe problems, the patients were asked for in-clinic visit. However, adverse events such as vaginal discharge, fever, general body pains, vomiting, and headache were reported. 9. Comment: In the discussion section, I would suggest to add a few studies from the literature to discuss the findings of this study. Response: Limited studies are available related to complications of episiotomy and post-episiotomy healing with polyglactin 910 sutures. We have included published articles as recent as possible to discuss the findings of the present study as described below: Improvement in perineal pain and a decrease in a number of analgesics with the use of polyglactin 910 suture has been discussed with respect to previous studies by Ononuju et al., 2020; Gupta et al., 2021; Samant et al., 2013 and Kettle et al., 2007 (Reference 2, 6, 9 and 11). Postpartum complications like infection, wound dehiscence and re-suturing, and requirement for hospital re-admissions have been discussed with respect to studies by Boushra and Rahman, 2013, and Dudley et al., 2017 (Reference 12 and 13). In addition, post-episiotomy inflammation, hematoma, infection and dehiscence, pain, extension of the episiotomy incision, and dyspareunia have been discussed after referencing the study of Gun et al., 2016 (Reference 14). Wound healing after episiotomy repair with Trusynth Fast® and Vicryl Rapide® group polyglactin 910 fast-absorbing sutures has been discussed with respect to studies by Howells and Abasi, 2020 and Kettle et al., 2007 (Reference 8 and 11)."
}
]
},
{
"id": "163358",
"date": "12 Jun 2023",
"name": "Shraddha Shetty K",
"expertise": [
"Reviewer Expertise High risk obstetrics and adolescent gynecology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nBrief description of the article: This article aims at describing the type of suture material that can be used to repair the episiotomy. Benefits and complications of using Trusynth Fast and Vicryl Rapide polygactin 910 fast absorbing sutures. Primary outcome analysed was subjective post episiotomy perineal pain with the type of suture material used. Secondary outcomes analysed were quantity of local anesthesia, number of sutures used, time to repair episiotomy, intraoperative suture handling, analgesics used, early and late wound complications, wound re-suturing, time to complete healing, presence of residual sutures, return to sexual activity and dyspareunia. They concluded that Trusynth Fast® suture is clinically equivalent to Vicryl Rapide® suture and can be used for episiotomy repair with minimal risk of perineal pain and wound complications.\nRelevance: Studying the type of suture material used for episiotomy and assessing the complications and side effects will help the clinicians in deciding the type of suture material to be used for episiotomy.\nComments: Dear authors, I read with great interest, which falls within the aim of this journal. In my honest opinion, the topic is of great interest to attract the readers’ attention.\nMajor:\n\nAims and objectives have been mentioned clearly. Review of literature is appropriate for the study. Materials & Methods have been explained in brief. The study area has been defined clearly. Data collection technique is appropriate for the study. Data analysis technique is described in detail. Results have been described and analysed in detail. The discussion has been described clearly and results have been compared with other studies and analysed.\n\nMinor:\nIntroduction to the topic has been mentioned in detail. Conclusions and the summary of the study have been defined which is appropriate.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-1179
|
https://f1000research.com/articles/12-737/v1
|
23 Jun 23
|
{
"type": "Study Protocol",
"title": "Comparative study between therapeutic effects of microneedling versus CO2 laser in acne scars",
"authors": [
"Kunal Gupta",
"Pravin Maheshwari",
"Bhushan Madke",
"Pravin Maheshwari",
"Bhushan Madke"
],
"abstract": "Objectives: To study the clinical aspect of acne scars while grading them on the basis of severity as well as to study and compare the therapeutic effects of CO2 laser and microneedling in their management. Methods: This study used prospective comparison as its method of study. Over the course of two years, from June 2021 to June 2023, 100 patients above 18 years of age having post-acne atrophic scars will be enrolled. Patients will be split into two groups and each group will be selected for fractional CO2 laser (non-ablative) and microneedling respectively. Four treatments will be administered to each group of patients with a four-week gap between each session. All clinical findings will be recorded for data analysis and comparision. “Goodman and Baron’s Qualitative and Quantitative grading system for scars” will be used after each session in order to compare the therapeutic effects for each group. Results: At the end of each session, acne scar grading will be done in each group and data will be compiled to assess and compare the therapeutic effects between CO2 laser and microneedling. Conclusions: The findings of the protocol research will be used to form the conclusions. Trial Registration: Submitted for registration to Clinical Trial Registry of India (CTRI).",
"keywords": [
"CO2 laser",
"microneedling",
"fractional",
"acne scars",
"atrophic scars",
"inflammation"
],
"content": "Introduction\n\nAcne, a common inflammatory condition of the pilosebaceous unit, is characterized by comedones, papulo-pustules, and occasionally nodules. It mostly affects the face, followed by the chest and back. Remaining scarring is a usual adverse effect of acne treatment. Acne scarring can negatively affect quality of life, leading to low self-esteem and unpleasant feelings.1\n\nSeverity of the residual scarring depends on the duration and intensity of the inflammatory response during the active disease. There is weakening of the collagen synthesis caused by an increased ratio of tissue inhibitors of MMPs to matrix metalloproteinases (MMPs) during the extracellular matrix remodeling process.2\n\nA classification system has been described to segregate atrophic scars post acne into three types: icepick, rolling, and boxcar scars. With the help of this classification, treatment options can be better tailored to each individual patient.1Ice pick scars being less than 2 mm in diameter that extend vertically through the whole length of dermis. Boxcar scars are spherical skin depressions with flat bases and sharp edges that could be shallow (0.1-0.5 mm) or deep (>0.5 mm). Lastly, rolling scars are depressions which range in size from 4 to 6 mm and are shallower than boxcar type but have the largest circumference. The aberrant fibrous bands causing these scars pull the dermis down to attach to the subcutaneous layer.2\n\nMicroneedling is a commonly used minimally invasive technique used to treat acne scars. It involves creating skin punctures using sterile micro needles attached to a handheld rolling device which helps in disrupting dermal collagen fibers that connect the scar tissue. Growth factors are regenerated as a result, encouraging the dermal blood vessels to produce collagen and elastin.3 Microneedling works best for healing shallow boxcar and rolling scars since it only reaches the upper dermis.1 Fractional ablative CO2 lasers, which have only recently as of 2003 hit the market, are an efficient method of managing acne scars with least adverse effects. They work on the principle of fractional thermolysis. This refers to the creation of pixilated columnar zones of thermal injury to the dermis also known as micro thermal zones in order to promote collagen formation.4\n\nThe fractional component of the laser makes sure that the tissue injury is spatially well distributed in a precise pattern across the treated area, while retaining the healing function of the epidermis whereas the ablative component ensures fewer side effects, such as erythema, edema, hemorrhage, crusting, infection, and scarring since they target the dermis while leaving the epidermis intact.5\n\nIn carbon lasers, water acts as a chromophore which produces light at a wavelength of 10,600 nm. Due to the significant tissue water absorption of the carbon dioxide beam, depth penetration is limited. However, depths of over 2 mm can be reached by increasing irradiation over a very small region in a fractionated method and employing greater pulse energies. In addition to modifying dermal collagen, development of myofibroblasts and matrix proteins like hyaluronic acid is also aided by carbon dioxide lasers. Matrix metalloproteinases are present at exceptionally high concentrations promoting wound healing (MMPs).6\n\nTherefore, by comparing the outcome between these two commonly used treatment modalities, we can have knowledge as to which intervention would be most effective in acne scar management.\n\n\nProtocol\n\nScarring in post acne lesions is a very common, difficult, and upsetting issue for medical professionals and patients. It may negatively affect the quality of life of the patient. It is necessary to examine the pathophysiology and morphology of each scar in order to address this issue and treatment must be decided accordingly. An early and aggressive approach helps not only in improving cosmesis but also in limiting the further progression of severity.7\n\nAcne scars can be primarily of three types: hypertrophic, atrophic and keloidal, with atrophic scars being associated with collagen loss and affecting 80–90% of patients. Keloids and hypertrophic scars only occur occasionally. It is crucial to further divide atrophic scars into ice pick, rolling, and boxcar categories so that treatment options can be more precisely catered to the needs of each patient.8,9 Rolling and boxcar types of acne scars respond well to fractional CO2 laser therapy and microneedling.1,2 Scar severity is another important aspect to be considered in the management of scars. It helps not only in identifying the treatment most suited to the patient but also in evaluating outcomes. One such grading scale is the “Goodman and Baron Qualitative scar grading system”, which will be used in this study.9\n\nNowadays, a multitude of modalities are available in managing post acne scars. Microneedling and fractional ablative CO2 lasers are very commonly used techniques which are effective and cause fewer side effects when compared to other modalities. In this study, we compare the therapeutic effects between them in different cases of acne scars of varying severity which will help us decide which one is more effective in their management.\n\nTo study and compare the therapeutic effects between CO2 laser and microneedling in acne scars.\n\n\n\n1. To evaluate the characteristics and clinical features of acne scars\n\n2. To grade acne scars on the basis of their severity\n\n3. To evaluate CO2 lasers’ therapeutic effect in post atrophic acne scars\n\n4. To evaulate the therapeutic effects of microneedling in acne scars\n\n5. Comparison between the therapeutic effects of CO2 laser and microneedling in atrophic post acne scars\n\n\nMethods\n\nIn the current study, 100 cases including both males and females with post-acne atrophic scars and age of above 18 years are included presenting in the department of dermatology, venereology and leprosy at AVBRH, Sawangi.\n\nThe method used in this study is prospective comparative.\n\nThe study will be conducted over the course of two years (June 2021 to June 2023).\n\nInclusion criteria\n\na) Patients of both genders above 18 years of age.\n\nb) Patients willing to participate in the study with their informed consent.\n\nc) Patients with clinical diagnosis of post acne atrophic scars will be included.\n\nExclusion criteria\n\na) Patients having any major systemic disease and uncontrolled medical or surgical illness.\n\nb) Patients having any active infection (Viral e.g. Herpes or bacterial/fungal infections).\n\nc) Female patients who are pregnant or lactating.\n\nd) Patients having keloid/hypertrophic scar.\n\ne) Patients on anti-coagulant medications.\n\nf) Patients with immunocompromised conditions e.g. HIV infection.\n\n\n\nn = 99\n\nn = 99 patients needed for the study\n\nWhere,\n\nn = sample size\n\nZα/2 is the level of significance at 5%, that is, 95% confidence interval = 1.96\n\nP = Prevalence of atrophic acne scars = 15% = 0.15\n\nd = Desired error of margin = 7% = 0.07\n\nCases will be defined as any patient above 18 years of age, irrespective of gender, coming to the Department of Dermatology, Venereology and Leprosy and having acne scars.\n\n\nMethods\n\nProspective comparison is used as the method in this study in which 100 patients having acne scars coming to the Department of Dermatology at AVBRH, Wardha, will be enrolled after considering the various exclusion and inclusion criteria’s from June 2021 to June 2023. Institutional Ethical Committee (IEC) clearance will be been obtained. Written and signed informed consent in their vernacular language will be taken from all the participants for voluntary participation. A detailed history including name, age, sex, past history and family history will be taken. A detailed clinical examination will be performed for all patients presenting with post acne atrophic scars.\n\nBased upon the severity of acne scars, patients will be classified into four grades according to the “Goodman and Baron Qualitative scar grading system” (Table 1).9 The patients will be split into two groups with 50 patients each, Group A and Group B. Participants will be randomly assigned to either groups with a 1:1 allocation as per a computer generated randomisation schedule stratified by site and using permuted blocks of random sizes. The block sizes will not be disclosed, to ensure concealment. The group A will be selected for fractional ablative CO2 laser using Futura CO2 Fractional Laser System®. The group B will be selected for microneedling using the Dermapen 4TM. Four treatments will be given to patients in both groups, with a four-week interval between each session. There will be a clinical evaluation of the progress made based on “Goodman and Baron Qualitative scar grading system” at the end of each session by a side by side comparison of pre-operative and post-operative photographs. All patients from both the groups will be prescribed a topical sunscreen and moisturizer post procedure. Additionally, one month following the fourth session, patients will be questioned regarding how scars have improved in order to determine patient satisfaction using the Visual Analogue Score (VAS). In order to improve adherence of patients to the study, patients will be counselled in detail about the procedures and the improvement they can expect with successive therapies. A thorough follow up shall be done using patients contact information collected during the enrollment process along with adjusting dates of treatment according to the patient’s comfort. During the period of the study, patients will not be receiving any concomitant therapy for their acne scars in order to prevent bias in the therapeutic effects of the modalities being compared in the study. Both treatment interventions shall be discontinued in case of any adverse reaction or worsening of existing lesions. The time schedule of enrolment, interventions, assessments, and visits for participants has been explained in the participant timeline figure (Table 2). The progress of the study will be monitored by the departmental committee headed by the Head of the Department of Dermatology.\n\nThis study can help us better understand the response outcome of CO2 lasers and microneedling in acne scars which can further help us decide the most appropriate intervention amongst the two in treatment of acne scars.\n\nAll standard parametric and non-parametric data will be assessed by standard statistical methods.\n\nA ‘p’ value of <0.05 will be considered significant.\n\nLimitation is that this is a hospital based and not a population based study also other types of post acne scars like keloidal and hypertrophic scars are not included in this study.\n\n\nDiscussion\n\nBhalla M, Arora A, in the year 2022, studied the role of fractional CO2 lasers in acne scars and found that fractional carbon dioxide lasers showed effectiveness in skin renewal in atrophic acne scars. They explained the mechanism by which fractional lasers work and the proper treatment protocol to be followed for best results. They concluded that counselling, patient selection with pre and post procedure care guidelines are crucial factors upon which the treatment outcome depends.6 Jordan R, Cummins C et al., in the year 2000, carried out research to determine how laser resurfacing can reduce the appearance of face acne scars. They discovered that the patient efficacy ranged from 25 to 90% for both the carbon dioxide laser and the erbium: YAG laser. Although lasting a few weeks, pigmentation changes as a side effect were experienced by up to 44% of individuals. After receiving the carbon dioxide laser, patients experienced erythema for 1.5 to 4 months before re-epithelialization occurring after 7 to 14 days. Up to 84% of individuals can expect their acne or milia to return. It was discovered that the likelihood of serious consequences, such as hospitalization because of a systemic infection, was quite low. They arrived to the conclusion that high-quality randomized controlled studies with standardized scarring scales and validated patient outcome measures are needed to assess the effectiveness of laser resurfacing.10\n\nIn the year 2012, Levy LL, Zeichner JA, et al. discussed and analyzed the various minimally invasive methods for treating acne scarring with a focus on pharmacologic agents, such as isotretinoin for acne scars that are atrophic and corticosteroids with chemotherapeutic drugs for scars that are hypertrophic. They discuss various in office and minimally invasive techniques like chemical peels, dermabrasion, tissue augmentation, and punch excision. They conclude that no single strategy has emerged as first line as we must individualize the treatment in accordance with the type of acne scars present. Moreover, they emphasize on managing patient expectations and setting realistic goals. They also suggest a combinational approach with lasers in order to achieve best results thereby improving patient’s quality of life.11\n\nZaleski-Larsen LA, Fabi SG et al., in the year 2016, conducted a research to examine the efficacy and safety of combining multiple modalities in the treatment of acne scars. Results of the hyaluronic acid filler were discovered to be evident immediately and to continue to stimulate neocollagenesis for a period of 12 to 24 months. With fat transplantation, optimal effects were typically seen 3 months after the procedure. Treatment options for 45 individuals with atrophic acne scars included skin needling combined with PRP, 100% TCA CROSS, and PRP. Improvement was found in 46.7%, 26.7% and 60% of the patients respectively. Non-ablative fractional lasers with 20% TCA improved atrophic acne scars by 78.27%. Autologous bone marrow stem cells were administered to 14 patients and implanted beneath the acne scars. At six months after the surgery, the acne scars had significantly improved. CONCLUSION: Combining acne scar treatment techniques is safe and leads to optimal patient outcome.12\n\nTo evaluate the efficacy of fractional CO2 laser and fractional radiofrequency microneedling in the treatment of facial acne scars, Reddy KY, Swaroop R et al. did a study in 2020. According to the findings, 20% of patients in the MnRF group had improved by three grades one month following their final session, compared to 13.3% of patients in the fractional CO2 group.13\n\nThis study shall help us decide which intervention amongst CO2 laser and microneedling carries the most therapeutic effectiveness in treating acne scars. It will also reduce the psychological stress brought on by acne scars which shall further improve the patient's quality of life. Knowledge about the best intervention will also help save time and effort for both the patient and the clinician.\n\nAll patients having post acne atrophic scars in both CO2 laser (Group A) and microneedling (Group B) groups have been enrolled and necessary treatment sessions in four-week intervals have been conducted. Pre and post procedure photographs had been taken. Scar grade based upon the severity of acne scars at every four week interval to each patient has been allotted. Patient’s satisfaction one month following the last session using the Visual Analogue Score (VAS) has been recorded. Data compilation has been initiated to assess the comparative effects between the two modalities.\n\nClearance from Institutional Ethics Committee (IEC) and Scientific Scrutiny Committee/Institutional Research Committee has been obtained.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nBoen M, Jacob C: A Review and Update of Treatment Options Using the Acne Scar Classification System. Dermatol. Surg. 2019; 45(3): 411–422. PubMed Abstract | Publisher Full Text\n\nTam C, Khong J, Tam K, et al.: A Comprehensive Review of Non-Energy-Based Treatments for Atrophic Acne Scarring. Clin. Cosmet. Investig. Dermatol. 2022 Mar 14; 15: 455–469. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSitohang IBS, Sirait SAP, Suryanegara J: Microneedling in the treatment of atrophic scars: A systematic review of randomised controlled trials. Int. Wound J. 2021 Oct; 18(5): 577–585.PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcGoldrick RB, Theodorakopoulou E, Azzopardi EA, et al.: Lasers and ancillary treatments for scar management Part 2: Keloid, hypertrophic, pigmented and acne scars. Scars Burn Heal. 2017 Mar 14; 3: 2059513116689805. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSadick NS, Cardona A: Laser treatment for facial acne scars: A review. J. Cosmet. Laser Ther. 2018; 20(7-8): 424–435. PubMed Abstract | Publisher Full Text\n\nBhalla M, Arora A: Fractional carbon dioxide LASER for acne scars. CosmoDerma. 2022; 2: 22. Publisher Full Text\n\nGoodman GJ: Management of post-acne scarring. What are the options for treatment? Am. J. Clin. Dermatol. 2000 Jan-Feb; 1(1): 3–17. PubMed Abstract | Publisher Full Text\n\nConnolly D, Vu HL, Mariwalla K, et al.: Acne Scarring-Pathogenesis, Evaluation, and Treatment Options. J. Clin. Aesthet. Dermatol. 2017 Sep; 10(9): 12–23. Epub 2017 Sep 1. PubMed Abstract | Free Full Text\n\nKravvas G, Al-Niaimi F: A systematic review of treatments for acne scarring. Part 1: Non-energy-based techniques. Scars Burn Heal. 2017 Mar 30; 3: 2059513117695312. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJordan R, Cummins C, Burls A: Laser resurfacing of the skin for the improvement of facial acne scarring: a systematic review of the evidence. Br. J. Dermatol. 2000 Mar; 142(3): 413–423. PubMed Abstract | Publisher Full Text\n\nLevy LL, Zeichner JA: Management of acne scarring, part II: a comparative review of non-laser-based, minimally invasive approaches. Am. J. Clin. Dermatol. 2012 Oct 1; 13(5): 331–340. PubMed Abstract | Publisher Full Text\n\nZaleski-Larsen LA, Fabi SG, McGraw T, et al.: Acne Scar Treatment: A Multimodality Approach Tailored to Scar Type. Dermatol. Surg. 2016 May; 42(Suppl 2): S139–S149. PubMed Abstract | Publisher Full Text\n\nReddy KY, Swaroop R, Mallaya RR, et al.: A comparative study of efficacy of fractional carbondioxide laser and microneedling fractonal radiofrequency in the treatment of acne scars. IP Indian J. Clin. Exp. Dermatol. 2021; 7(1): 47–53. Publisher Full Text"
}
|
[
{
"id": "181677",
"date": "27 Jul 2023",
"name": "Bingrong Zhou",
"expertise": [
"Reviewer Expertise phototherapy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe researchers plan to compare the efficacy of microneedle and CO2 fractional laser in treating acne atrophic scars. The treatment of atrophic scars has always been a hot topic of concern for dermatologists, as traditional lasers and microneedle treatments are difficult to achieve ideal therapeutic effects in limited treatment courses. Which type of scar is more suitable for lasers and microneedles is a concern for clinical doctors.\nCO2 fractional laser is a type of ablative laser, and in the abstract, the author referred to it as non-ablative laser, which is a clerical error.\n\nThe researchers only used the \"Goodman and Baron Qualitative scar grading system\" for efficacy evaluation, which I believe cannot objectively and comprehensively reflect the efficacy evaluation value of multiple aspects of acne scars.\n\nThe efficacy of laser and microneedle therapy varies among different types of acne scars. I suggest researchers compare the efficacy among different types of scars.\n\nGenerally, scars will have a continuous improvement effect within 3-6 months after treatment, and it seems inappropriate for researchers to evaluate the efficacy one month after treatment.\n\nWhile evaluating the efficacy, researchers should also pay attention to the comparison of adverse reactions of these treatments.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Partly\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "10013",
"date": "29 Aug 2023",
"name": "Kunal Gupta",
"role": "Author Response",
"response": "Respected sir, I have read your review and hope to address all your concerns regarding this article: 1. CO2 lasers, as correctly pointed out are traditionally ablative in nature. However, the Futura RF 50 Excited CO2 laser being used in this study is primarily a resurfacing system targeting only the deeper layers, leaving the epidermis intact by delivering a precise wavelength of light inducing a controlled injury, which promotes cellular renewal and the production of collagen making them non-ablative in nature. 2. Goodman and Baron Qualitative scar grading system was used in our study since it is easier to use on a day to day basis considering our study involved a large sample size. Although, quantitative grading system by Goodman and Baron exists, giving a high level of inter-observer reliability, reproducibility and accuracy, it is cumbersome to use on an everyday basis. 3. As correctly stated that efficacy of laser and microneedling varies with different types of scars, in our final completed study, we have studied and compared the efficacy of both the modalities for rolling, ice pick and boxcar type of acne scars indicating which modality would fit best for which type of scar. 4. We have kept the final follow up one month after the last treatment session in order to assess the therapeutic effectiveness at that time. Even though a continuous improvement is seen beyond this time period, due to poor compliance of patients to follow up, we had to limit the follow up period to one month for practical feasibility. 5. In our final completed study, we have studied and compared the adverse reactions to both of these modalities even stated as our secondary outcome. I hope we have adequately addressed your queries to your satisfaction. Regards."
}
]
},
{
"id": "190302",
"date": "10 Aug 2023",
"name": "Chanat Kumtornrut",
"expertise": [
"Reviewer Expertise Acne and rosacea"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study protocol is a prospective analytical design comparing the improvement of acne scars treated by microneedling vs CO2 laser. The protocol should be carefully revised regarding the following comments.\nThe study design reported in the method is an RCT, but the author declared only a prospective comparative study.\n\nThe sample size calculation is based on the prevalence of acne scar, it is not representing the primary objective question of the study.\n\nThe parameters for both laser and microneedling are not mentioned.\n\nThere is no objective measurement of acne scar outcome.\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Partly\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-737
|
https://f1000research.com/articles/12-736/v1
|
23 Jun 23
|
{
"type": "Case Report",
"title": "Case Report: Metachronous urothelial carcinoma of the renal pelvis following radical cystectomy: a rare case report",
"authors": [
"I Putu Gde Fredy Gunawan",
"Rachmat Budi Santoso",
"Edward Usfi Harahap",
"Agus Rizal A. H. Hamid",
"Tato Heryanto",
"Rizky Ifandriani Putri",
"Ikhlas Arief Bramono",
"Rachmat Budi Santoso",
"Edward Usfi Harahap",
"Agus Rizal A. H. Hamid",
"Tato Heryanto",
"Rizky Ifandriani Putri",
"Ikhlas Arief Bramono"
],
"abstract": "Introduction: Bladder carcinoma (BC) is the most common urinary tumor. The most common histologic type of BC is urothelial carcinoma of the bladder (UCB) According to GLOBOCAN 2020 data, there were 573,000 new cases and 213,000 deaths from bladder cancer in 2015. The likelihood of developing upper urinary tract cancer after a bladder tumor were being treated is minimal; nonetheless, such lesions can develop later. Case Report: A 52-year-old man with urothelial carcinoma of the renal pelvis, previously had UCB. Initially, in 2019, he developed hematuria. It was accompanied by dysuria. Every day, the patient smoked 2 packs. The patient denied having a chronic disease. No family history of cancer. At that time, it was discovered that the patient had urothelial bladder cancer following transurethral resection of bladder tumor (TURBT). Histopathology revealed bladder-invasive urothelial carcinoma. The patient then underwent radical cystectomy and ileal conduit. The patient was stable afterward, but during the pandemic period, the follow-up was disturbed. Early in 2021, the patient got hematuria. The patient was referred for a right radical nephrectomy due to a metachronous mass in the right renal pelvis. The histopathological result indicated a high-grade invasive upper urinary urothelial carcinoma. Conclusion: This study reported a case of metachronous urothelial bladder cancer in the upper urinary tract following radical cystectomy. Thorough surveillance in malignancy cases is a mandatory procedure to detect the recurrence of the malignancy and/or the uneventful spreading of the malignancy to other organs. The research regarding the pathophysiology of metachronous malignancy is still being conducted but has shown some promising results.",
"keywords": [
"metachronous cancer",
"radical cystectomy",
"upper tract urothelial carcinoma",
"urothelial carcinoma of the bladder."
],
"content": "Introduction\n\nThe most prevalent tumor of the urinary system is bladder carcinoma (BC). The most prevalent (90%) histologic type of BC is urothelial carcinoma of the bladder (UCB). The invasion of the basement membrane, lamina propria, or deeper by neoplastic cells of urothelial origin is defined as urothelial carcinoma (UC). The term “transitional cell carcinoma” has been replaced by “urothelial carcinoma” by the World Health Organization.1 Bladder cancer is the tenth most often diagnosed cancer worldwide, according to GLOBOCAN 2020 data, with roughly 573,000 new cases and 213,000 deaths. Men are more likely than women to acquire it, with global incidence and mortality rates of 9.5 and 3.3 per 100,000 for men and nearly 4-times those for women.2 Metachronous upper urinary tract carcinoma (UUTC) typically appears in 2 to 9% of bladder cancer patients within 3 years after their cystectomy. Metachronous carcinomas are those that are discovered six months after the main lesion’s surgery and are found in a different location than the primary lesion.3 As a result, when monitoring bladder cancer, it’s appropriate to consider this possibility.3 We reported a rare case of UCB that develops to UUTC after radical cystectomy. The work is documented following the CARE guidelines.4\n\n\nCase report\n\nWe reported a case of 52-year-old male with urothelial carcinoma of the renal pelvis with a previous history of UCB. The patient was diagnosed with UCB in 2019. At first, he was experiencing intermittent hematuria. This was followed by frequent micturition and dysuria. The patient was a frequent smoker, with 2 packs of cigarette consumption a day. The patient denied any history of chronic disease. The patient also denied any history of neoplasm in the family. The patient was a teacher, and he denied any contact with industrial chemical substances or hair dye during his working day. The patient was then referred to the Local General Hospital and was performed transurethral resection of bladder tumor (TURBT) and was diagnosed with muscle invasive bladder cancer (MIBC). After that, the patient was referred to our center and underwent radical cystectomy (RC) with an ileal conduit. The histopathological report revealed a high-grade invasive urothelial carcinoma of the bladder. Two weeks following RC, the patient also underwent below-the-knee amputation of the left leg due to acute limb ischemia. In January 2020, the patient underwent a computed tomography (CT)-scan examination, and there was no sign of malignancy in the urinary tract.\n\nIn early 2021, two years after the radical cystectomy, the patient experienced intermittent hematuria again. However, due to the COVID pandemic, the patient refuses to seek medical treatment. In late December 2021, the hematuria worsened and the patient had to receive a blood transfusion due to severe anemia. A computed tomography scan on January 2022, revealed a mass on the right renal pelvis and upper ureter with suspicion of a newly formed tumor (Figure 1). After the patient’s condition improved, he was referred again to our center and underwent a right radical nephrectomy on February 2022. A macroscopic examination revealed a right kidney with a size of 10×7.5×6 cm. Upon cleavage, a grey-white tumor mass with a size of 5×3×4 cm (Figure 2) was observed. The specimen was fixed in 10% buffered formalin. Microscopic examination of right kidney surgery section showed ureteral and renal parenchyma tissue (Figure 3). The tumor had invaded beyond the muscularis into the peripelvic fat or the renal parenchyma without lymphovascular invasion. The distal margin of the ureter showed no tumor invasion. This finding showed a tumor with histopathology characteristic of high-grade invasive urothelial carcinoma of the upper urinary tract. The patient also experienced hemorrhagic stroke 2 weeks following the radical nephrectomy. The patient was due to receive adjuvant therapy after his stroke-related condition was stable. Recently, the patent has had a routine check-up for urology, oncology, neurosurgery, and palliative care, no progression related to the malignancy was found.\n\n\nDiscussion\n\nUUTC is a cancer of the urothelial cells that line the upper urinary tract, from the renal calyces to the pelvises and the ureter to the ureteral orifice. UUTC is uncommon cancer, accounting for about 5% of all urothelial cancers and fewer than 10% of all renal malignancies. Meanwhile, bladder cancer is common urinary tract carcinoma. The incidence of bladder carcinoma was roughly 500,000 cases with an estimated death of more than 200,000 every year.2 The terms UCB and UUTC are interchangeable. As a result, investigations on UCB are frequently generalized to UUTC. Although UCB and UUTC show some histological similarities and share some risk factors, the most notable of which is tobacco use, there are significant clinical and molecular distinctions between the two entities.5 Within two to three years following their cystectomy, 2 to 9% of bladder cancer patients commonly develop metachronous upper urinary tract carcinoma (UUTC). When a metachronous carcinoma is identified in a different area than the primary lesion, it is usually found six months following the main lesion’s surgery.3\n\nThe molecular pathogenetic framework of UUTC and UCB is the same. As a result, patients with UUTC may have a history of UCB in up to 41% of cases or have contemporaneous UCB in about 20% of instances, which is caused by an epigenetic pan-urothelial “field deficiency”. A small percentage of UCB patients have synchronous UUTC (1.8%) or develop metachronous UUTC (0.7% to 4%). The total risk of metachronous UUTC following RC ranges from 2% to 7%, with the majority of tumors developing within the first 2 to 4 years after RC.6 In our case, the patient developed UUTC 2 years following RC for urothelial bladder carcinoma. This rare finding is relatively in line with what a previous study found in terms of the period it needs to develop metachronous UUTC following UCB.\n\nA study by Doeveren et al. showed that patients who have been diagnosed with urothelial carcinoma of the urinary tract are more likely to develop a tumor throughout the urinary tract.7 Following the first diagnosis of urothelial carcinoma, two explanations have been proposed to explain the increased risk of recurrence in the urinary system. Carcinogenic impacts affect the whole urinary system, resulting in multifocal cancers that form independently of one another. As a result, these tumors aren’t assumed to have the same progenitor cell. In this case report, the patient was an active smoker which can be assumed that the development of metachronous was due to carcinogenic. This, however, does not explain the disparity in UUTC and UCB incidences in general, nor the disparity in the incidence of tumors in the contralateral urinary tract or the bladder after the first diagnosis of UUTC. The other hypothesis proposed is that tumor cells can proliferate and spread through the intraluminal or intraepithelial pathway. Intraluminal seeding occurred due to the implantation of malignant cells on other sites in the urinary tract. Whereas intraepithelial spreading happened due to continuous migration followed by the proliferation of transformed cells on the urinary tract epithelium.8,9\n\nOur patient was a former smoker, hence one of the risks for developing UCB was cigarette smoking. Smoking intensity (cigarettes/day) and duration of smoking had a strong association with BC development. Former smokers had a reduced risk of bladder cancer than current smokers. Unfortunately, former smoker still have a higher risk of BC development than non-smokers.10,11\n\nThere was no clear explanation of the risk of developing UUTC following UCB therapy. However, several studies found patients who develop UUTC after UCB treatment including TURBT, intravesical chemotherapy, and radical cystectomy.12 A study by Lin et al. showed upper tract recurrences in 60 patients who underwent local excision of BC. Compared to Ta lesions, T1 bladder cancer had a 2.5-fold greater probability of recurrence in the upper tract.13 Faba et al. assessed the link between upper tract recurrence and TURBT resection of the intramural area of the distal ureter. UCB in the intramural area of the distal ureter was found in 112 out of 2317 patients who underwent TURBT for NMIBC.14\n\nNishyama et al. conducted a multi-institutional retrospective assessment of 402 patients with bladder cancer who received BCG following TURBT. The researchers discovered 7.5% of recurrences in the upper tract. Upper tract recurrence was predicted by intravesical recurrence and tumor characteristics at TURBT.15 In our case, the patient was diagnosed with muscle-invasive bladder cancer (MIBC). A study by Nuhn et al. showed that MIBC was associated with a high risk of developing metachronous carcinoma. The pathophysiology underlying this occurrence was thought to be similar to NMIBC.16 However studies that emphasize metachronous recurrence is limited and relatively fewer than the NMIBC.\n\nMerrill et al. conducted oncologic monitoring after RC in 1797 patients stratified by pathologic stage. Over a median follow-up of 10.6 years, postoperative monitoring was not standardized. Urine cytology and chest/abdomen/pelvis imaging were performed every 3 months for the first 2 years after surgery, then at 6-month intervals for the next 2 years, followed by yearly imaging. Upper tract recurrence after radical cystectomy was seen in 87 individuals, with an overall recurrence incidence of 8.1%.17\n\nOur patient was also in accordance with the previous studies found about UUTC development following RC. The survival rate for a patient with metachronous urothelial carcinoma is poor. Based on the previous study, the median survival rate was 27 months. At death, the average age was 77 (range 59 to 88).18 This suggested the need for long-term strict surveillance of the patient with bladder cancer regardless of the treatment they received, in order to detect and give an early aggressive treatment of metachronous events. Further studies are needed to get a comprehensive mechanism of UUTC and the development of metachronous UUTC after RC.\n\nStudies on genetic factor contributing to the development of metachronous urothelial carcinoma are also limited. The mechanisms underlying multifocal bladder cancer are still unclear. A previous study observed the loss of heterozygosity (LOH) at 10 microsatellite loci and methylation of the p16INK4 CpG island in numerous tumors and pathologically normal mucosa in bladder cancer patients to see if normal mucosa had already undergone genetic or epigenetic alterations. In 77% of samples of normal epithelium, LOH or methylation was found, and LOH found in normal epithelium samples was typically found in tumor samples. This finding suggested that a population of cells in morphologically normal epithelium shared genetic or epigenetic abnormalities with bladder cancer, which may serve as a basis for the development of numerous tumors.19 Further study about genetic change is needed.\n\nOur study also has limitations, first, the inability to generalize because the data was only available for one patient case and one gender. Second, there is currently no way to demonstrate a cause-and-effect connection. While these limitations are common in case report studies, however, we also hope that this case can add up the available data regarding Metachronous urothelial carcinoma, considering a rare occurrence.\n\n\nConclusion\n\nMetachronous UCB to the upper urinary tract following RC was a rare case. Strict surveillance of patients with UCB is needed to detect the development of metachronous carcinoma events in the urinary tract. Early detection and aggressive treatment are always the best policy in managing malignancy cases. In the future, we hope there will be more studies that can explain comprehensively the mechanism, risk factors, and genetic study of metachronous UUTC following BC surgery.\n\n\nInformed consent\n\nWritten informed consent was received from the patient. The patient and his family agreed to the publication of this article.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nKaseb H, Aeddula NR: Bladder Cancer. StatPearls. Treasure Island (FL): StatPearls Publishing; 2021 Oct 30. 2022 Jan–. PubMed Abstract\n\nSung H, Ferlay J, Siegel RL, et al.: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021 May; 71(3): 209–249. PubMed Abstract | Publisher Full Text\n\nWang P, Luo JD, Wu WF, et al.: Multiple factor analysis of metachronous upper urinary tract transitional cell carcinoma after radical cystectomy. Braz. J. Med. Biol. Res. 2007 Jul; 40(7): 979–984. PubMed Abstract | Publisher Full Text\n\nMillán-Rodríguez F, Chéchile-Toniolo G, Salvador-Bayarri J, et al.: Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups. J. Urol. 2000 Oct; 164(4): 1183–1187. PubMed Abstract | Publisher Full Text\n\nAgha RA, Borrelli MR, Farwana R, et al.: The SCARE 2018 statement: Updating consensus Surgical CAse REport (SCARE) guidelines. Int. J. Surg. 2018; 60: 132–136. PubMed Abstract | Publisher Full Text\n\nSzarvas T, Módos O, Horváth A, et al.: Why are upper tract urothelial carcinoma two different diseases? Transl. Androl. Urol. 2016 Oct; 5(5): 636–647. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSountoulides P, Pyrgidis N, Brookman-May S, et al.: Does Ureteral Stenting Increase the Risk of Metachronous Upper Tract Urothelial Carcinoma in Patients with Bladder Tumors? A Systematic Review and Meta-analysis. J. Urol. 2021 Apr; 205(4): 956–966. PubMed Abstract | Publisher Full Text\n\nvan Doeveren T , van de Werken HJG , van Riet J , et al.: Synchronous and metachronous urothelial carcinoma of the upper urinary tract and the bladder: Are they clonally related? A systematic review. Urol. Oncol. 2020 Jun; 38(6): 590–598. PubMed Abstract | Publisher Full Text\n\nHarris AL, Neal DE: Bladder cancer--field versus clonal origin. N. Engl. J. Med. 1992 Mar 12; 326(11): 759–761. PubMed Abstract | Publisher Full Text\n\nHabuchi T: Origin of multifocal carcinomas of the bladder and upper urinary tract: molecular analysis and clinical implications. Int. J. Urol. 2005 Aug; 12(8): 709–716. PubMed Abstract | Publisher Full Text\n\nLi Y, Tindle HA, Hendryx MS, et al.: Smoking Cessation and the Risk of Bladder Cancer among Postmenopausal Women. Cancer Prev. Res. (Phila.). 2019 May; 12(5): 305–314. PubMed Abstract | Publisher Full Text\n\nAl-Zalabani AH, Stewart KF, Wesselius A, et al.: Modifiable risk factors for the prevention of bladder cancer: a systematic review of meta-analyses. Eur. J. Epidemiol. 2016 Sep; 31(9): 811–851. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLin N, Wu YP, Lin YZ, et al.: Risk factors for upper tract urothelial recurrence following local excision of bladder cancer. Cancer Med. 2018 Aug; 7(8): 4098–4103. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRodriguez Faba O, Gaya JM, Breda A, et al.: Resection of the Intramural Portion of the Distal Ureter during Transurethral Resection of Bladder Tumors: Predictive Factors for Secondary Stenosis and Development of Upper Urinary Tract Recurrence. J. Urol. 2016 Jul; 196(1): 52–56. PubMed Abstract | Publisher Full Text\n\nNishiyama N, Hotta H, Takahashi A, et al.: Upper tract urothelial carcinoma following intravesical bacillus Calmette-Guérin therapy for nonmuscle-invasive bladder cancer: Results from a multi-institutional retrospective study. Urol. Oncol. 2018 Jun; 36(6): 306.e9–306.e15. PubMed Abstract | Publisher Full Text\n\nNuhn P, Novara G, Seitz C, et al.: Prognostic value of prior history of urothelial carcinoma of the bladder in patients with upper urinary tract urothelial carcinoma: results from a retrospective multicenter study. World J. Urol. 2015 Jul; 33(7): 1005–1013. PubMed Abstract | Publisher Full Text\n\nMerrill SB, Boorjian SA, Thompson RH, et al.: Oncologic surveillance following radical cystectomy: an individualized risk-based approach. World J. Urol. 2017 Dec; 35(12): 1863–1869. PubMed Abstract | Publisher Full Text\n\nHolmäng S, Johansson SL: Bilateral metachronous ureteral and renal pelvic carcinomas: incidence, clinical presentation, histopathology, treatment and outcome. J. Urol. 2006 Jan; 175(1): 69–72. discussion 72-3. PubMed Abstract | Publisher Full Text\n\nMuto S, Horie S, Takahashi S, et al.: Genetic and epigenetic alterations in normal bladder epithelium in patients with metachronous bladder cancer. Cancer Res. 2000 Aug 1; 60(15): 4021–4025. PubMed Abstract"
}
|
[
{
"id": "228543",
"date": "23 Dec 2023",
"name": "Pradeep Singh Chauhan",
"expertise": [
"Reviewer Expertise Molecular Biologist"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this case report, authors reported a case of metachronous urothelial bladder cancer developed in the upper urinary tract two years after the radical cystectomy. While the case report is overall well-written, there are some comments needs to be addressed .?\nWhat was the stage of the bladder cancer on the pathology for the patients when undergoes radical cystectomy ?\n\nDid patient received neoadjuvant chemotherapy before radical cystectomy ? Author should mentioned this in the text. Were the tumor were sequenced to see the molecular genetic profile how is it different from the bladder cancer vs UTUC ?\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-736
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https://f1000research.com/articles/9-1089/v1
|
03 Sep 20
|
{
"type": "Research Article",
"title": "Alleviative effects of Fara-darmani Consciousness Field on Triticum aestivum L. under salinity stress",
"authors": [
"Sara Torabi",
"Mohammad Ali Taheri",
"Farid Semsarha",
"Mohammad Ali Taheri"
],
"abstract": "Background: The Fara-darmani Consciousness Field was founded by Mohammad Ali Taheri. It is a novel field and is described similarly to the field of gravity, or the electromagnetic field. This field is neither matter nor energy, and therefore does not possess a quantity. Even though there is no direct scientific evidence for the Consciousness Field, it is possible to investigate its effects on objects through controlled experiments. The aim of the present work was to study the alleviative effects of the Fara-darmani Consciousness Field on common wheat Triticum aestivum L. var Star under salt stress. Methods: Plants were grown under 0 mM NaCl (control) and 150 mM NaCl with or without the influence of Fara-darmani Consciousness Field for 3 weeks. Chlorophyll, hydrogen peroxide (H2O2), malondialdehyde (MDA) content and activity of antioxidant enzymes such as superoxide dismutase (SOD),polyphenol oxidase (PPO), and peroxidase (POX) were measured in all groups of plants. Results: In the salt-treated plants under the influence of the Fara-darmani Consciousness Field, the contents of total chlorophyll, as well as a and b chlorophyll forms, were elevated compared with the salt-treated plants without Fara-darmani CF (34.8%, 17.8%, and 169% respectively). Additionally, Fara-darmani increased H2O2 (57%) and the activity of SOD and PPO by 220% and 168%, respectively, under salinity compared with the salt-treated plants without Fara-darmani CF. MDA content and activity of peroxidase were decreased by 12.5% and 34%, respectively. Conclusion: These results suggest the Fara-darmani Consciousness Field as a qualitative intervention strategy to withstand salt stress in plants, by increasing the contents of chlorophyll, antioxidant enzyme activities, and decreasing MDA content under salinity.",
"keywords": [
"Antioxidant enzymes",
"Fara-darmani",
"Consciousness Field",
"Salt stress",
"Wheat"
],
"content": "Introduction\n\nMost criticism about complementary therapy is the lack of scientific research. In order to be accepted, academic studies using different study designs are necessary. Since one of the critical objections occurring when human beings are treated with complementary therapy is the placebo responses, biochemical plant-based studies can be a suitable method to clarify the phenomenon (Betti et al., 2003). Among the different plant model systems, the wheat plant has been repeatedly selected for homeopathy research Baumgartner et al. (2000) showed that homeopathic drugs improved plant resistance, which exerted their effect through detoxification processes.\n\nIn arid and semi-arid areas of the world, salinity is considered as a major factor in reducing crop productivity (Poonia et al., 1972). Plant growth is adversely affected by multiple environmental stresses, including biotic (e.g. fungi, bacteria, viruses, herbivores) and abiotic (e.g. low temperature, salt, drought, heavy metal toxicity). Among these the salination of arable land is one of the key factors that threatens the sustainability of the agricultural industry. Thus, many studies have attempted to explore processes that contribute to plant survival under salt stress (Ashraf & Harris, 2004) as a strategy to improve productivity and fertility. It is well documented that plants that are exposed to biotic or abiotic stresses have biochemical changes that exert oxidative damage through Reactive Oxygen Species (ROS) (Smirnoff, 1993). These free radicals disrupt cell membrane stability by peroxidation of polyunsaturated fatty acids in the plant cell membranes (Bor et al., 2003; Hernández & Almansa 2002; Shalataetal, 2001) and denature protein and nucleic acids (Chen et al., 1993). To alleviate adverse effects of oxidative stress, plants have developed diverse strategies, which are categorized as enzymatic, such as catalase, superoxide dismutase (SOD), peroxidase (POX), polyphenol oxidase (PPO) and ascorbate peroxidase, and non-enzymatic that directly scavenge ROS, such as glutathione, tocopherol, flavonoids and ascorbates (Agarwal & Pandey, 2004). Plants that have developed an antioxidant system that participates in ROS scavenging have better resistance to oxidative damage (Parida & Das, 2005).\n\nTo date, there have been many studies to explore the relationship between the intangible and physical world, especially the interaction between the human mind and outside physical world. For instance, it has been reported that the mind can affect dice tosses (Rhine, 1944). Researchers have previously focused on probabilistic systems, like tossing coins, using random number generators (RNGs). The first RNG study was conducted by Radin & Nelson (1989), which included 597 experiments and 235 control studies. This type of research was considered as ‘micro-psychokinesis’ (micro-PK) (Jahn et al., 1980; Varvoglis & Bancel, 2015). However, micro-PK is not completely acceptable to science because of the null effects and failure to replicate previous positive results (Jahn et al., 2000). Throughout history, studies can be found that explain the interaction between the human mind and body, such as ‘distant healing’, or the effects of the mind on inanimate physical systems, like morphological changes in a thin strip of metal (Randall & Davis, 1982).\n\nFara-darmani is one of the many Consciousness Field (CFs) founded by Mohammad Ali Taheri. In this theoretical concept, cosmic consciousness is the collection of consciousness, wisdom or intelligence governing the world of existence, which is also called ‘Awareness’. Consciousness, according to Taheri, is one of the three existing elements of the universe apart from matter and energy. By defining Consciousness as neither matter nor energy, we cannot associate a quantity to it. Since consciousness isn’t measurable, its existence can only be known through experience (Taheri, 2013). According to this theory, any living creature, including animals and plants, may be cured via humans by connecting to internet-like facilities called the Cosmic Consciousness Network (CCN). In this type of affection, mind-matter interaction occurs through connecting to the CCN by a Fara-therapist. Fara-darmani establishes a consciousness bond between the ‘whole’ consciousness and the ‘parts’ where all constituents will be scanned and corrected (Taheri, 2013). Although the mechanism of this linkage is not yet definable by science, its consequences can be measured and studied scientifically.\n\nThe aim of this study was to determine the effects of Fara-darmani CF on alleviating the effects of salt stress in a spring wheat variety (Star).\n\n\nMethods\n\nIn Fara-darmani, subjects of study become connected to that Consciousness Field via Fara-therapist by ‘announcement’ which is a process in which Taheri or any Fara-therapist (announcer) declares and sends the information of the subjects under study (e.g. the number of groups) to the CCN. The influence of Consciousness Field begins with the connection between the human mind and the CCN. In other words, the Fara-therapist’s mind acts as an intermediary between the subject of the study and the CCN. The first author of this study is an announcer and at the same time as the seedlings were subjected to salt stress, two groups of treatments became connected to the CCN (group 2: 0 mM NaCl and group 4: 150 mM NaCl). This exposure occurs without any kind of physical intervention, since consciousness according to Taheri’s concepts is neither matter nor energy, receiving this treatment is possible from close and far distances.\n\nThis experiment can easily be repeated by any researcher even from far distances by registering on the COSMOintel website (the Assign Announcement section) COSMOintel is a research center, under the supervision of the innovator of the method (Mohammad Ali Taheri) that has been established to design and implement repeatable and reproducible studies in the world of science1.\n\nIn this research, we used a spring wheat variety Triticum aestivum L. var Star (Seed and Plants Improvement Institute, Karaj, Alborz Province). Seeds were surface sterilized with 2.5% sodium hypochlorite for 10 min and washed thoroughly with sterile distilled water. After sterilization, seeds were soaked in distilled water for 24 hours at room temperature. For each treatment three pots were prepared and six seeds were initially sown in plastic pots (10 × 10 cm) containing perlite soil. After the germination they were thinned to five plants per pot. First, all pots were irrigated daily with 100ml distilled water for four days. Then received 100ml half-strength Hoagland’s nutrient solution (pH= 5.7) (Hoagland & Arnon, 1950) every other day for another 12 days (chemicals purchased from Sigma-Aldrich).\n\nThe sixteen-day-old seedlings were treated with salinity. The salts were added to the nutrient solution. To prevent osmotic shock, salt stress was started gradually on 50 mM NaCl (100ml). Every other day the concentration was increased by 50mM until 150 mM was attained. Salt stress was continued for three weeks (150mM NaCl was added every other day). Initial Fara-darmani connection treatment occurred at the same time as adding the first NaCl solution. Four treatment groups (n=3 pots/group) were performed as follows: group 1, control – grown with no NaCl and did not receive Fara-darmani CF; group 2 –grown with no NaCl and did receive Fara-darmani CF; group 3 – treated with 150 mM NaCl for three weeks and did not receive Fara-darmani CF treatment; group 4 – treated with 150 mM NaCl for three weeks and did receive Fara-darmani CF treatment.\n\nAfter three weeks, four fully expanded leaves were picked per replicate for future analyses. They were frozen in liquid N2 and transferred to -20˚C for imminent bench experiments.\n\nFor measuring photosynthetic pigments, we used the method by Arnon (1949). 0.5 gram of fresh leaf material placed in acetone 80% and homogenized to extract chlorophyll. The resulting solution was filtered through Whatman’s No.1 filter paper. After extracting of photosynthetic pigments in acetone 80%, absorbance of chlorophyll a and b was recorded by UV-visible spectrophotometer (Shimadzu UV-160) at 645 and 663 nm respectively. According to Arnon (1949) chlorophyll concentrations were calculated using the formulas below:\n\nChl.a (mg l-1) = [12.7 (A663) – 2.69 (A645)] * 0.5 ml of extracted sample\n\nChl.b (mg l-1) = [22.9 (A645) – 4.69 (A663)] * 0.5 ml of extracted sample\n\nTotal chlorophyll = Chl a + Chl b\n\nMeasurement of the hydrogen peroxide (H2O2) content was performed according to Velikova et al., (2000). One gram of leaf tissue was homogenized on ice with 5 ml of trichloroacetic acid (TCA; Sigma-Aldrich) 0.1% (w/v) and centrifuged at 12000 rpm for 15 min. Subsequently, 0.5 ml of 10 mM potassium phosphate buffer (pH 7) and 1 ml of 1M potassium iodide was added to 0.5 ml of supernatant. The absorbance of supernatant was determined at 390 nm wavelength.\n\nMalondialdehyde (MDA), which is a product of lipid peroxidation, has been considered as an indicator of membrane destruction. MDA content was determined according to Stewart & Bewley (1980). We added 5 ml of TCA to 0.2 g of fresh leaf. After homogenization, the solution was centrifuged at 13000 × g for 10 min. The mixture of 1 ml of supernatant with 4 ml of 0.5% thiobarbituric acid in 20% TCA was heated for 30 min at 95˚C and quickly placed in an ice bucket. Subsequently, we centrifuged the solution at 10000 × g for 10 minutes and recorded the absorbance of supernatant at 532 and 600 nm. The calculation of MDA was done from the extinction coefficient of 155 mM-1 cm-1.\n\nTo determine enzyme activity, 0.1 g of fresh third leaves were ground in 3 ml of 50 mM Tris-HCl buffer (pH 6.8) at 4˚C. The homogenate was centrifuged at 13000 × g for 20 min at 4˚C. The supernatants were then collected and stored at -70˚C for determination of enzymes activity.\n\nSOD activity was determined using the assay system described by Giannopolitis & Ries (1977). The reaction mixture consisted of 50 mM phosphate buffer pH 7.5, 13 mM methionine, 0.1 mM Na-EDTA, 75µM NBT, 75 µM Riboflavin and 100 µL of enzyme extract in a final volume of 3 ml (all the chemicals were purchased from Sigma-Aldrich). The mixture in glass test tubes was placed 30 cm from 30 W fluorescent lamps. Identical solutions without illumination and enzyme extract were considered as blanks. Since SOD has the ability to inhibit the photochemical reduction of nitroblue tetrazolium (NBT), the amount of inhibition was estimated by reducing the generation of color in the presence of light. One unit of SOD was described as the amount of enzyme that lead to 50% inhibition of NBT reduction. After 16 min, the absorbance at 560 nm was recorded against the blank. SOD activities were calculated as units per milligram of protein.\n\nPOX activity was measured based on the method of Abeles & Biles (1991). The activity of POX was estimated by adding 0.01 ml of enzyme extract to 4 ml of 0.2 M acetate buffer (pH 5), 0.4 ml H2O2 (3%), 0.2 ml 20 mM benzidine. The absorbance was recorded at 530 nm using spectrophotometer and POX activity was expressed as U mg-1 protein.\n\nPPO was assayed according to Raymond et al. (1993). The reaction solution contained 2.5 ml of 200 mM sodium phosphate buffer (pH 6.8), 0.2 ml of 20 mM pyrogallol and 0.01 ml enzyme extract. The temperature of the reaction mixture was 40˚C. The changes in absorbance were recorded at 430 nm.\n\nEach experiment was repeated three times. Data were statistically analyzed using analysis of variance one-way (ANOVA) with SPSS software (version 18). Means were compared by Duncan’s test at the 0.05 level of confidence.\n\n\nResults\n\nSalinity decreased the contents of chlorophyll (Chl) a, Chl b and total Chl (Figure 1a-c). Under the influence of Fara-darmani CF with 150 mM NaCl, the contents of total Chl, Chl a and Chl b were elevated (34.8%, 17.8% and 169%, respectively) compared to the plants treated with 150mM without Fara-darmani CF.\n\nThe effect of NaCl treatment on H2O2 is shown in (Figure 1d). Results of the present study showed that H2O2 content remained unchanged under salinity condition whereas for the Fara-darmani CF treated groups (control and 150mM NaCl) showed significant enhancement 100% and 57.1%, respectively.\n\nMDA content was assessed as an oxidative indicator. Salinity stress caused an increase of 59.5% in MDA content as compared to that of control. The Fara-darmani CF treatment to the salt-stressed plant decreased MDA content by about 12.5% (Figure 2d).\n\nPOX activity was significantly increased by NaCl treatment up to 244 % compared with control while under salinity treatment exposure to Fara-darmani CF decreased the activity of enzyme by 34 % (Fig 2.b).\n\nSOD activity was slightly increased under salinity. However, it was found that with Fara-darmani CF the activity of SOD in salinity condition was about 220 % higher than that in salinity without Fara-darmani CF treatment (Fig 2.c)\n\nSimilarly, PPO activity was not significantly higher than non-saline condition (control). However, the PPO activity showed an increase of 168% under salinity in response to Fara-darmani CF compared to the salinity treated without Fara-darmani CF treatment (Figure 2a).\n\nEffects of Fara-darmani Consciousness Field treatment on (a) chlorophyll a, (b) total chlorophyll, (c) chlorophyll b, (d) hydrogen peroxide (H2O2). Plants were treated with 0 mM NaCl (control) or 150mM NaCl Vertical bars indicate mean ± standard error of three replicates. Means followed by the same letter were not significantly different at P<0.05.\n\n(a) polyphenol oxidase (PPO), (b) peroxidase (POX), (c) superoxide dismutase (SOD) and (d)malondialdehyde (MDA) content. Plants were treated with 0 mM NaCl (control) or 150mM NaCl Vertical bars indicate mean ± standard error of three replicates. Means followed by the same letter were not significantly different at P<0.05.\n\n\nDiscussion\n\nIn this study, chlorophyll a and b, and total chlorophyll contents decreased remarkably under salinity conditions (Figure 1). This is supported by previous data reported in tomato plants (Al-aghabary et al., 2005) and wheat (Ashraf et al., 2002), where salt stress unfavorably affects chlorophyll content. The decrease in chlorophyll content might be due to the formation of ROS in salinity stress that leads to lipid peroxidation and damages thylakoid membranes (Mittler, 2002). There are no previous studies of alleviative effects of Fara-darmani CF on salt-stressed plants to compare to this study. However, observations in the present study showed that under salinity treatment, Fara-darmani CF ameliorated the adverse effects of salt stress, probably by improving antioxidant systems, scavenging ROS and increasing the chlorophyll a and b contents (Figure 1).\n\nVarious abiotic stresses, including salinity, contribute to formation of ROS (Navari-Izzo et al., 1998). Data of this study showed that under salinity conditions there was an increase in H2O2 content with Fara-darmani CF treatment, which coincided with an increase in SOD activity (about 220%). SOD coverts superoxide radicals to H2O2 and molecular oxygen. It is possible that increasing H2O2 could therefore be attributed to Fara-darmani-induced enhancement of SOD activity. This function may have a key role in mitigating oxidative stress. SOD is the first enzyme involved in antioxidative processes (Rubio et al., 2002). Increasing the activity of SOD was observed similarly in the leaves of sugar beet (Bor et al., 2003) and in Lycopersicon (Koca et al., 2006) under salt stress. However, under salinity conditions, Fara-darmani CF decreased POX activity, which decomposes the H2O2 produced by SOD. These results suggest that H2O2 may take part in the signaling networks. It has been reported that seed pretreatment with H2O2 improves salt tolerance of wheat seedlings by alleviation of oxidative damage and expression of stress proteins (Wahid et al., 2007). Additionally, accumulation of H2O2 is thought to be a signal for induction of pathogenesis-related (PR) genes (Chen et al., 1993). Kuźniak & Urbanek (2000) reported that H2O2 contributes to signal transduction, gene expression and cellular defense under oxidative stress conditions.\n\nIn the present study, Fara-darmani CF also induced PPO activity. PPO may play a key role in scavenging H2O2 in salt-stressed plant. Agarwal & Pondey (2004) found that in Cassia angustifolia PPO activity increased under salinity stress. The mechanism of action of Fara-darmani CF as an inducer of antioxidant enzymes activity is not clear; therefore, future studies are needed to gain additional insights on biological and biochemical effects of this CF on various plants under biotic and abiotic stresses.\n\nMDA content, which is a product of lipid peroxidation, reflects membrane destruction under oxidative stresses (Hernández & Almensa, 2002). According to Torabi & Niknam (2011), salinity tolerance of Salicornia persica (salt-tolerant species) is associated with lower MDA content compared to S. europaea (salt-sensitive species). Fara-darmani as a CF decreased MDA content under salinity stress. It seems that decreased MDA content is correlated with increased activity of antioxidant enzymes under the influence of Fara-darmani CF and a strategy developed by plant to withstand salt stress.\n\nFrom these results, it can be concluded that Fara-darmani CF minimizes the negative effects of salt stress in the wheat plant with evidence of increased activity of antioxidant enzymes, increased chlorophyll content and less membrane damage. The main challenge of this study is the fact that Consciousness Field doesn’t possess a quantity and isn’t directly measurable. Therefore, in order to identify its specific effects, we have measured Fara-darmani CF effects indirectly on a plant’s biochemical processes. We suggest that other researchers repeat similar experiment with different plants. It seems that botanical bioassays are suitable for screening the effect of such treatments, and apart from the placebo responses by humans, these assays can be beneficial to save time and resources.\n\n\nData availability\n\nHarvard Dataverse: Alleviative Effects of Fara-darmani Consciousness Field on Triticum aestivum L. under Salinity Stress, https://doi.org/10.7910/DVN/XNMRMV (Torabi, 2020).\n\nThis project contains the following underlying data:\n\nRaw data of chlorophyll a, chlorophyll b, hydrogen peroxide, MDA, POX, PPO, SOD, and total chlorophyll content in control and salinity conditions with and without receiving Fara-darmani consciousness field (separate .tab files).\n\nCharts of chlorophyll a, chlorophyll b, hydrogen peroxide, MDA, POX, PPO, SOD, and total chlorophyll content in control and salinity condition with and without receiving Fara-darmani consciousness field (separate .docx files).\n\nData are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).\n\n\nNotes\n\n1Gaining an announcement: users must register on the COSMOintel Website (free). Once registered, go to the researcher section and fill out the form (the required information is listed below). In order to study at any given time and place, the researchers simply need to introduce the testing center to the guidance center. This means that the exact time of start and finish of the test, the total duration of the test, the number of samples and controls and their contractual name must be specified. It should be noted that registration on the site and also requesting and gaining an announcement is free. We recommend that you contact our center for the definition and selection of the relevant sample in order to obtain a clear and repeatable results (email: researchers@cosmointel.com).\n\nGeneral Condition of Study; Study location; Address; University/center; Research Area: Basic science, Engineering, Medical science, cognitive science, Humanities, others; Sample Name; Number of samples; Control Name; Brief explanation of the experiment; Exact time of research initiation; Exact time of completion of the research",
"appendix": "Acknowledgements\n\nThe authors thank Dr. Noushin Nabavi for revising the English.\n\n\nReferences\n\nAbeles FB, Biles CL: Characterization of peroxidases in lignifying peach fruit endocarp. Plant Physiol. 1991; 95(1): 269–273. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAgarwal S, Pandey V: Antioxidant enzyme responses to NaCl stress in Cassia angustifolia. Biologia Plantarum. 2004; 48(4): 555–560. Publisher Full Text\n\nAl-aghabary K, Zhu Z, Shi Q: Influence of silicon supply on chlorophyll content, chlorophyll fluorescence, and antioxidative enzyme activities in tomato plants under salt stress. J Plant Nutr. 2005; 27(12): 2101–2115. Publisher Full Text\n\nArnon DI: COPPER ENZYMES IN ISOLATED CHLOROPLASTS. POLYPHENOLOXIDASE IN BETA VULGARIS. Plant Physiol. 1949; 24(1): 1. 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New Phytol. 1993; 125(1): 27–58. Publisher Full Text\n\nStewart RR, Bewley JD: Lipid peroxidation associated with accelerated aging of soybean axes. Plant Physiology. 1980; 65(2): 245–248. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTaheri MA: “Human from another outlook” Interuniversal Press; 2nd Edition (September 26, 2013). ISBN-13: 978-1939507006, ISBN-10: 1939507006 2013.\n\nTorabi S: Alleviative Effects of Fara-darmani Consciousness Field on Triticum aestivum L. under Salinity Stress. Harvard Dataverse, V1, UNF:6:C7bIJWJSo6dsQMzfKtpWPQ== [fileUNF] 2020. http://www.doi.org/10.7910/DVN/XNMRMV\n\nTorabi S, Niknam V: Effects of iso-osmotic concentrations of NaCl and mannitol on some metabolic activity in calluses of two salicornia species. In Vitro Cell Dev Biol Plant. 2011; 47(6): 734–742. Publisher Full Text\n\nVarvoglis M, Bancel PA: ‘Micro-Psychokinesis’ In: Parapsychology: A Handbook for the 21st Century, eds E. Cardena, J. Palmer, and D. Marcusson-Clavertz (Jefferson NC: McFarland & Company), 2015; 266–281. Reference Source\n\nVelikova V, Yordanov I, Edreva A: Oxidative stress and some antioxidant systems in acid rain-treated bean plants: Protective role of exogenous polyamines. Plant Sci. 2000; 151(1): 59–66. Publisher Full Text\n\nWahid A, Perveen M, Gelani S, et al.: Pretreatment of seed with H2O2 improves salt tolerance of wheat seedlings by alleviation of oxidative damage and expression of stress proteins. J Plant Physiol. 2007; 164(3): 283–294. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "73503",
"date": "19 Nov 2020",
"name": "Halimeh Hassanpour",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis research investigated effect of Fara-darmani Consciousness Field on alleviation of salt stress. It has some interests for the readers and me. Fara-darmani Consciousness Field increased antioxidant systems in plants against stress. But There are some questions about this art, and need to answer by authors:\nWhy did the authors select just 0 and 150 mM Nacl for this research?\nThe intensity or wavelength are not clear, and isn’t the device regulates for intensity or wave?\nHow Fara-darmani Consciousness Field affect the cell, how is perceived by the cell, what is the effect on organisms? The discussion needs to improve.\nIf there isn’t any research about Fara-darmani Consciousness Field, the author can use some article for the discussion:\n\nImpact of the Static Magnetic Field on Growth, Pigments, Osmolytes, Nitric Oxide, Hydrogen Sulfide Phenylalanine Ammonia-Lyase Activity, Antioxidant Defense System, and Yield in Lettuce.1\n\nEstablishment and assessment of cell suspension cultures of Matricaria chamomilla as a possible source of apigenin under static magnetic field.2\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "6133",
"date": "02 Dec 2020",
"name": "Sara Torabi",
"role": "Author Response",
"response": "Dear Dr. Hassanpour Thank you very much for your kind words about our paper. In the following sections, you will find our responses to each point and suggestions. we have carefully reviewed the comments and have revised the manuscript accordingly. Why did the authors select just 0 and 150 mM Nacl for this research? In the past, various investigations have been made into salinity stresses and attempt to minimize the losses of plant productivity, such as the effects of Coumarin (Saleh and Madany, 2015), Ascorbic acid (Athar et al, 2008, Azzedin et al, 2011, Khan et al, 2006), Oligochitosan (Ma, et al, 2012), Melatonin (Ke, et al, 2018), etc. on the wheat plant. Therefore, based on previous investigations, we screened ameliorative effects of Fara-darmani CF with two similar concentrations of NaCl including 0 and 150 mM. We suggest that the effects of the Fara-darmani CF be investigated with different NaCl concentrations and with different types of plants. Ahmed Mahmoud Saleh, M.M.Y. Madany. Coumarin pretreatment alleviates salinity stress in wheat seedlings, Plant Physiology and Biochemistry, Volume 88, 2015, Pages 27-35, ISSN 0981-9428, https://doi.org/10.1016/j.plaphy.2015.01.005. Habib-ur-Rehman Athar, Ameer Khan, Muhammad Ashraf, Exogenously applied ascorbic acid alleviates salt-induced oxidative stress in wheat, Environmental and Experimental Botany, Volume 63, Issues 1–3, 2008, Pages 224-231, ISSN 0098-8472, https://doi.org/10.1016/j.envexpbot.2007.10.018 Azzedine, F, Gherroucha, H, Baka, M. Improvement of salt tolerance in Durum Wheat by Ascorbic acid application. Journal of Stress Physiology & Biochemistry, Vol. 7, 2011, No. 1, pp. 27-37 ISSN 1997-0838 Khan A, Ahmad MSA, Athar HUR, Ashraf M. Interactive effect of foliarly applied ascorbic acid and salt stress on wheat (Triticum aestivum L.) at the seedling stage. Pakistan Journal of Botany. 2006 Dec;38(5):1407-1414. Ma, L., Li, Y., Yu, C. et al. Alleviation of exogenous oligochitosan on wheat seedlings growth under salt stress. Protoplasma 249, 393–399 (2012). https://doi.org/10.1007/s00709-011-0290-5 Ke Qingbo, Ye Jun, Wang Bomei, Ren Jianhong, Yin Lina, Deng Xiping, Wang Shiwen. Melatonin Mitigates Salt Stress in Wheat Seedlings by Modulating Polyamine Metabolism, Frontiers in Plant Science, VOLUME 9, 2018, PAGES 914. ISSN 1664-462X. DOI: 10.3389/fpls.2018.00914. The intensity or wavelength are not clear, and isn’t the device regulates for intensity or wave? As it was mentioned in the introduction section (paragraph 4, lines 5), according to Taheri, consciousness is one of the three existing elements of the universe apart from matter and energy. By defining consciousness as neither matter nor energy we cannot associate a quantity to it. Therefore, we cannot register it by any device and must be mediated by human mind. How Fara-darmani Consciousness Field affect the cell, how is perceived by the cell, what is the effect on organisms? The discussion needs to improve. As stated in the last paragraph, the main challenge of this study is the fact that Consciousness Field doesn’t possess a quantity and isn’t directly measurable. Therefore, in order to identify its specific effects, we have measured Fara-darmani CF effects indirectly on a plant’s biochemical processes. At this point, more biochemical and histological studies can collaborate to clarify this phenomenon. In addition, more explanation was added in the discussion section (paragraph 2). If there isn’t any research about Fara-darmani Consciousness Field, the author can use some article for the discussion: Thank you for this suggestion. We have put a significant effort in improving the discussion section and these two references were added to the paragraph 1 and 2. In addition, we improved the discussion with more references."
}
]
}
] | 1
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https://f1000research.com/articles/9-1089
|
https://f1000research.com/articles/12-734/v1
|
23 Jun 23
|
{
"type": "Research Article",
"title": "Outcomes from the first dedicated diagnostic and interventional nephrology (DIN) service in a UK renal unit",
"authors": [
"Samuel Morrison",
"Ji Ching Lee",
"Madeline Brazell",
"Haroon Ayub",
"Joanna Marsden",
"Caitlin Pollock",
"Harry Waterman",
"Abbey Smith",
"Simon Davies",
"Sophie Brennan",
"Jennifer Whitehead",
"Debra Sweeney",
"Carol Allan",
"Margaret Dodds",
"Sarah McCloskey",
"James Andrews",
"Rauri Clark",
"Saeed Ahmed",
"Shalabh Srivastava",
"Samuel Morrison",
"Ji Ching Lee",
"Madeline Brazell",
"Haroon Ayub",
"Joanna Marsden",
"Caitlin Pollock",
"Harry Waterman",
"Abbey Smith",
"Simon Davies",
"Sophie Brennan",
"Jennifer Whitehead",
"Debra Sweeney",
"Carol Allan",
"Margaret Dodds",
"Sarah McCloskey",
"James Andrews",
"Rauri Clark",
"Saeed Ahmed"
],
"abstract": "Background: We report the clinical outcomes, operational and training model from the first diagnostic and interventional nephrology (DIN) department in a UK renal unit. Methods: Patient outcomes were evaluated for an array of diagnostic and therapeutic interventional procedures performed at the DIN unit, SDIN (the Sunderland Diagnostic and Intervention Unit), within the first year of its establishment. Data was retrospectively collected for the period beginning 1st October 2019 to 1st October 2020 for patients who underwent the following procedures: ultrasound guided renal biopsy, Tunnelled Dialysis Catheter (TDC) insertion and exchange, Peritoneal Dialysis (PD) catheter insertion/exchange, and Areteriovenous Fistula (AVF) Point of Care Ultrasound (POCUS). These figures were compared to the cohort from the one-year period pre-SDIN, between the 1st October 2018 and 31st September 2019. All results are expressed as mean and percentages unless otherwise specified. Results: Renal Biopsy: 104 biopsies were performed with an improvement in median waiting time from 12 to 7 days with 98.4% being diagnostic. Tunnelled Dialysis Catheters: 99 TDCs were inserted or exchanged with the catheters remaining in place for a mean duration of 156 days. We report an incidence of 2 infections per 1000 catheter days within the 90-day observation period. Peritoneal dialysis catheters: 16 PD catheters were inserted and they remained in place for an average of 153 days. Eleven (69%) catheters had no complications within the 28-day observation period, 3 (19%) catheters required manipulation. AVF POCUS: 279 AVF POCUS scans were performed during the SDIN period. The waiting time from referral to scan was reduced from a mean of 35 days to 2 days. Conclusions: A comprehensive DIN service leads to significant improvements in training, service and patient outcomes and would be an ideal model for wider adaptation across the UK renal units.",
"keywords": [
"Interventional Nephrology",
"Nephrology"
],
"content": "Introduction\n\nDiagnostic and Interventional Nephrology (DIN) forms the core of a unified care service for patients with kidney disease. It is vital in providing rapid diagnoses and treatment for patients presenting to renal units. Diagnostic and interventional procedures are often undertaken exclusively by radiologists, vascular surgeons, or transplant surgeons in the UK. This can lead to fragmented service provision for renal patients, prolonging procedural waiting times, and has resulted in inconsistent and often inadequate exposure to procedural training for renal trainees in this field.\n\nThe development of DIN has been ongoing for the past three decades (Chan, 2013, O’Neill, 2000). We set out to change the regional institutional environment and establish a comprehensive interventional nephrology service at the South Tyneside and Sunderland Foundation Trust (STSFT) renal unit to serve as the test case for other units in the UK. In this paper, we present our service and training model, and data from the first full year of this service.\n\nIn the UK, access-related complications account for around 20% of nephrology bed days. Suboptimal vascular access has mortality and morbidity implications; patients who dialyse via a tunnelled dialysis catheter (TDC) have a seven times higher hospital admission rate with sepsis, and a four times higher mortality rate than patients receiving dialysis via an arteriovenous fistula (AVF) or graft (AVG) (Poinen et al., 2019, Pyart et al., 2020). Unfortunately, catheter-related bacteraemia tends to generate deep-seated infections, such as discitis and endocarditis, which require long hospital admissions and amount to a significant financial burden on the health service. Time spent without functional access puts the patient at risk of hyperkalaemia and pulmonary oedema, frequently necessitates hospital admission, and may require additional invasive procedures such as central venous catheter insertion and emergency dialysis (Niyyar and Chan, 2013).\n\nSuitable vascular access sites are anatomically limited and, even with optimal care, are lost with increasing time spent on dialysis. Ultimately, patients have a higher mortality due to the inability to receive dialysis because of a lack of vascular access. Inevitably, where a service has suboptimal access to endovascular intervention, more patients are exposed to the risks and complications of dialysis via a TDC.\n\nU.S. and Canadian observational literature demonstrate that dialysis patients undergo an average of 1-2 access-related procedures per year. In centres with an access surveillance programme, early intervention reduces the rate of vascular access thrombosis and ensures that dysfunctional access longevity is curtailed, while access without dysfunction is maintained (Salman et al., 2020, Robbin et al., 2018).\n\nVascular access planning, assessment, and intervention is complex and critically important for patients with end-stage renal disease. The nephrologist is in the optimal position to be able to assess the risks, benefits, and cardiovascular impact of each dialysis modality and access type. Balancing these factors with the expected longevity of access, life expectancy, and patient priorities enables the nephrologist to facilitate a shared decision-making process, delivering a truly patient-centred model of care utilising a multi-disciplinary team approach (Vachharajani et al., 2011).\n\nHistorically, nephrology has been a procedural specialty. Senior UK nephrologists were typically trained in peritoneal dialysis (PD) catheter insertion and AVF formation surgery and had experience in maintaining patency of AV shunts (a historic form of vascular access). It remains the case that nephrologists are well-positioned to undergo further training to competently perform the procedures required by our patients and emulate the successes of cardiologists and gastroenterologists in developing a subspecialist, interventional clinical field (Kalloo et al., 2016).\n\nThe current UK renal curriculum only mandates the ability to establish temporary vascular access for dialysis. However, most renal trainees have some experience in performing renal biopsies and tunnelled dialysis catheters. Some trainees also have access to non-surgically inserted PD catheter training, however the access to such training remains variable.\n\nInternationally, DIN training framework has been established by several societies, including the American Society of Diagnostic and Interventional Nephrology (ASDIN), the Association of Vascular Access and InTerventionAl Renal physicians (AVATAR Foundation, India), and the Vascular Access Society of Britain and Ireland (VASBI), to name a few.\n\nTo further develop a rigorous pathway for DIN training in the UK, we have developed a training pyramid that details the proposed stages of progression — this is outlined in Figure 1. The trainees rotating through our unit are trained to stage 1, with those wishing to pursue further training progressing to stage 2 and 3.\n\nThis pyramid details the various stages of training in D&IN. Temporary vascular catheter insertion is the only mandatory skill in the UK training curriculum (below dotted line). Stages 1, 2 and 3 are separated by solid lines and have the associated skills detailed in the figure.\n\n\nService models\n\nThe renal unit at our hospital provides dialysis to 300 patients living in our catchment area in three dialysis centres. The renal ward is a tertiary referral ward, receiving patients from these areas for the diagnosis and management of acute kidney injury and other acute renal diseases. All access-related assessment and procedures are performed in Sunderland Royal Hospital.\n\nRenal biopsies and tunnelled/temporary dialysis access procedures were previously performed after patients were admitted to the renal ward. This led to the recurrent cancellation of procedures due to non-availability of inpatient beds; a service audit previously demonstrated a 62% cancellation rate for renal biopsies due to bed unavailability. AVF and AVG formation procedures and most PD catheter insertions were performed by surgical teams.\n\nThe aim for DIN at our renal unit is a high-quality service that is responsive to patients’ needs and complements the interventional radiology and vascular surgery departments. We have developed a day-case service, providing all the work already undertaken by the nephrology team, whilst expanding our remit to also include work that has previously been performed by these other departments — this model is outlined in Figure 2. The skillset of four nephrologists and two senior nurses at STSFT meant that we were uniquely positioned in the UK to rapidly develop a sustainable multi-professional service.\n\nCurrently, nephrologists have three fluoroscopy lists per week, with capacity to perform up to nine tunnelled haemodialysis or peritoneal dialysis catheter procedures. Nephrologists place almost all PD catheters, with surgeons only doing so in patients with coexistent surgical issues (such as the presence of abdominal hernias). Two days per week are dedicated to non-fluoroscopy work such as renal biopsies, AVF scans and Point of Care Ultrasound (POCUS). These lists operate on a day-case basis with pre-procedural assessment and post-procedural recovery being performed in the day-case IN unit.\n\nPrior to the development of our dedicated DIN unit, a small proportion of vascular ultrasound was also performed by nephrologists, with the majority being performed by the radiology department. In 2017-2018, 280 renal access scans were performed by a vascular ultrasonographer. This includes vein mapping (performed before AVF/AVG surgery), fistula maturation scans, and diagnostic scans in the event of symptoms or dialysis complications, such as poor flow rates or needling difficulty.\n\nHowever, the previously established ‘conventional’ pathway for patients with symptomatic or dysfunctional vascular access was inefficient. Patients typically underwent two stages of assessment: an outpatient vascular ultrasound (wait time two-four weeks), and then fistulography ± fistula angioplasty, performed by an interventional radiologist. Scans also needed to be reported by a radiologist prior to a referral for intervention being made, further lengthening the process. On this conventional pathway, patients with potentially dysfunctional vascular access were subject to waiting times of up to several weeks before a diagnostic scan and radiological intervention were performed. This is a significant time during which stenoses and thromboses can progress, and vascular access may be lost altogether, necessitating the establishment of alternative, temporary access with its associated risks.\n\nSince the implementation of the IN model, most ultrasound scans are now performed by our four interventional nephrologists at the point of care. On this lean pathway, outlined in Figure 3, patients in whom issues have been identified during dialysis sessions can be referred directly from the dialysis unit to the IN department for a same-day scan. Equally, patients can be referred for fistula maturation scans, and assessments of those which have become symptomatic. Patients with positive sonographic findings, such as the presence of a stenosis, are then referred on the same day for intervention. In the case of stenosis, this takes the form of fistulography ± angioplasty, procedures which are also increasingly being performed by interventional nephrologists within the unit.\n\nSince the mid-1990s, Interventional Nephrology has been a recognised subspecialty in the US, and latterly in Canada. Two models exist: a hospital-based service, and a free-standing vascular access clinic. The development of the subspecialty was in response to precisely the same challenges that we experience in the UK (Niyyar and Work, 2009).\n\nWhereas historically a domain of interventional radiology, 40-45% of dialysis angioplasty and thrombectomy procedures performed in the US are now undertaken by Interventional Nephrologists. Unless mandated by co-existing systemic pathology, all procedures are performed on a day-case basis. Patients have access to procedures within 24 hours of referral.\n\nSince the development of Interventional Nephrology, US vascular access-related bed days fell from 1.8 to 0.3 days/patient/year and missed dialysis treatments fell from 0.8 to 0.2 treatments/patient/year (Mishler et al., 2006).\n\nInterventional nephrology has been demonstrated to be safe: a series of 14,000 patients had the highest success rate and lowest complication rate in the medical literature, and a series of 6000 patients also had safe levels of radiation exposure (Beathard, 2015).\n\n\nMethods\n\nThe service provision at our unit was planned after a review of the parameters measured by ongoing, prospective performance measures collected by our institution’s performance audit tool. We submit our data annually, on haemodialysis access, peritoneal dialysis access, and AVF/AVG use to the national UK Renal Registry. The UK Renal Registry is a national registry that receives performance data from all UK renal units.\n\nPatient outcomes were evaluated for an array of diagnostic and therapeutic interventional procedures performed at the IN unit, SDIN (the Sunderland Diagnostic and Intervention Unit), within the first year of its establishment. The data collection was registered with the South Tyneside and Sunderland clinical effectiveness team with the following reference code: CA9545. This was a retrospective collection of data and did not involve diversion from standard care as a result no ethical approval was required. This was confirmed by the research department at the South Tyneside and Sunderland NHS Foundation Trust. Data was retrospectively collected for the period beginning 1st October 2019 to 1st October 2020 for patients who underwent the following procedures: ultrasound guided renal biopsy, TDC insertion and exchange, PD catheter insertion/exchange, and AVF POCUS. These figures were compared to the cohort from the one-year period pre-SDIN, between the 1st of October 2018 and the 31st September 2019. All results are expressed as mean and percentages unless otherwise specified. There were no p value calculations as retrospective observational nature of the study meant that data collection was not powered to calculate significance.\n\n\nResults\n\nWe evaluated the incidence of the following post-procedure complications before and after Sunderland Diagnostic and Interventional Nephrology (SDIN) service was established: pain, peri-nephric haematoma, macroscopic haematuria, bleeding requiring transfusion, bleeding requiring surgical or radiological intervention, and death. These were chosen to enable comparison with a large systematic review and meta-analysis involving 118,000 native kidney biopsies published by Poggio et al. in 2020 (Poggio et al., 2020). We also evaluated biopsy waiting times and biopsy specimen quality. Biopsy specimens with 10 or more glomeruli were deemed adequate, as per the Banff criteria (Roufosse et al., 2018).\n\n104 day-case renal biopsies were performed in the first year of the SDIN service (75 native, 29 transplant) with 18 of those considered urgent (rapidly progressive kidney disease). This was fewer than in the pre-SDIN period, during which 144 biopsies were performed (106 native, 38 transplant), 54 of which were urgent. However, the median waiting time from referral to non-urgent biopsy fell from 12 working days in the pre-SDIN period to seven working days after the implementation of SDIN. The median waiting time for urgent biopsies also fell from three working days to just one working day.\n\nOur data also demonstrates that the overall quality of biopsy specimens improved since the establishment of SDIN, with specimens comprising a greater number of glomeruli on average, and a higher proportion of specimens being adequate and histopathologically diagnostic. This data is outlined in Table 1.\n\nTable 1 lists the post-biopsy complication rates identified at SDIN, and compares these to the pre-SDIN period and those published by Poggio et al. This data demonstrates a higher proportion of patients reporting post-biopsy pain and macroscopic haematuria in the SDIN cohort (11.5% and 13.5% respectively) compared to pre-SDIN (7% and 9.1%) and the published data (4.3% and 11%), an observation which may be partially explained by more intensive patient monitoring and improved documentation implemented during SDIN. However, ongoing prospective data collection is being performed at our unit to ensure these complications are minimised.\n\nConversely, we report a lesser incidence of post-procedure haematomas in SDIN (3.9%) compared to Poggio et al. (11%). Reassuringly, we also report similar incidences at SDIN (difference of <1%) of the three most serious post-biopsy complications — bleeding requiring blood transfusion, bleeding requiring surgical/radiological and intervention, and death from biopsy. In both of our cohorts, there was one patient who required arterial embolization to stem bleeding. There were no deaths within either of our cohorts, and none of the patients required nephrectomy.\n\nWe evaluated the 90-day procedural complication rates from TDC insertion and exchange at our unit, as well as the 30 and 90-day catheter-associated infection (CAI) rates and procedural waiting times. TDC removal reasons at one-year post-insertion were also evaluated for each group. CAI was defined as either a positive catheter line culture, or a positive peripheral blood culture with no other identified source of infection. Catheter-associated sepsis was defined as CAI resulting in sepsis (infection plus systemic inflammatory response syndrome). This data is displayed in Table 1.\n\n99 tunnelled dialysis catheter insertion and exchange procedures were undertaken in the first year of SDIN, as compared to 132 in the pre-SDIN period, with a median waiting time of three days for both cohorts. Catheters inserted during the SDIN period remained in place for a mean duration of 156 days, as compared with 101 days in the pre-SDIN cohort, with no procedural failures within SDIN.\n\n90-day complication rates remained broadly similar for both cohorts, with 66.7% of TDCs having no complications in the SDIN cohort. The most common non-infective complication among both cohorts was minor bleeding during insertion (13.1% SDIN, 14.4% pre-SDIN), all of which were managed successfully during the procedure. 5.1% of catheters developed primary failure within 90 days in the SDIN cohort and required replacement. There were no patients in either cohort who experienced major bleeding and no deaths due to the procedure.\n\nThe one-year TDC removal reasons are also outlined in Table 1. 13.1% of TDCs remained in place after one year in the SDIN cohort, a decrease from 26.5% pre-SDIN. The two most common reasons for removal were infection (21.2%) and definitive alternative access gained (20.1%). We note positively that the proportion of patients whose TDC was removed due to successful renal transplantation increased from 0.8% pre-SDIN to 3% at SDIN, and that 9.5% more patients were offered alternative access modalities, such as AVF/AVG, in line with best practice.\n\nFinally, our 30 and 90-day CAI rates are reported. Within SDIN, 15.2% of patients developed a CAI within 90 days, of which 6.1% developed within 30 days after insertion. 9.1% of patients went on to develop line sepsis within 90 days, however all were successfully treated with antimicrobial therapy, and no patient deaths resulted from this. Further data comparing the pre-SDIN and SDIN cohorts is outlined in Table 1. Infection frequency was also standardised and expressed as number of infections per 1000 catheter days — both cohorts had an incidence of 2 infections per 1000 catheter days within the 90-day observation periods. Published data on CAI rates varies widely between units, but generally ranges between 0.2 and 6.5 infections per 1,000 catheter days for TDCs (Winnicki et al., 2018); our unit therefore reports similar infection rates to those published.\n\nA total of 16 fluoroscopically guided PD catheters were inserted by interventional nephrologists during SDIN, as compared with 12 catheters in the pre-SDIN period.\n\nCatheters remained in place for an average of 153 days. Complication rates were evaluated over a 28-day period between both cohorts. Due to the small sample size, further detailed analysis of outcomes was not undertaken. Overall, a general reduction in complication rates was observed since SDIN was established. 11 (69%) catheters had no complications within the 28-day observation period, 3 (19%) catheters required manipulation by an interventional nephrologist following insertion to reposition in the pelvis due to poor function, and two (12%) catheters required removal; one catheter due to non-function and the other due to intra-abdominal infection. Further comparisons between both cohorts can be found in Table 1.\n\nFigure 3 details the differences between the previously outlined conventional and novel diagnostic imaging pathways for ultrasound assessment of dysfunctional AVFs within our unit. We evaluated the difference in patient waiting times at each stage on both pathways, along with the overall waiting time from imaging being indicated to intervention taking place. We also evaluated the quality of the POCUS scans performed by nephrologists at the unit by comparing the findings from these scans to findings at fistulography — the gold standard imaging modality.\n\n279 AVF POCUS scans were performed during the SDIN period. The waiting time from referral to scan was reduced from a mean of 35 days on the conventional pathway to 2 days on the novel pathway. The mean waiting time from scan to intervention was also reduced from 21 days to 14.8 days. Therefore in total, the time between diagnostic imaging being indicated and intervention occurring was reduced from an average of 56 days on the conventional pathway to 16.8 days after implementation of SDIN, an overall reduction of 39.2 days. When compared to fistulographic findings, the overall sensitivity of the POCUS scans for detecting fistula pathology was 98.4%, with a specificity of 95.8%.\n\n\nDiscussion\n\nIn this paper we report the establishment of a novel diagnostic and interventional nephrology service at a large teaching hospital in the UK. This is a unique service with no similar provision currently available anywhere else in the country. We outline our service model and a selection of patient outcomes after the first full year of this service.\n\nDiagnostic and interventional nephrology is a continually evolving subspecialty of nephrology and remains an exciting area of development. It provides fast and safe access to procedures associated with establishing and maintaining dialysis provision. A day-case model also reduces the reliance on inpatient beds, thereby improving time to access services.\n\nOur data suggests that the delivery of a day-case DIN service is both safe and effective in reducing waiting time for crucial diagnostic and interventional procedures for renal patients. Although fewer renal biopsies and TDC procedures were performed at SDIN, this observation is likely related to the significant impact and service disruption that resulted from the emergence of the COVID-19 pandemic. Though, none of the procedure lists in the SDIN unit were cancelled due to the pandemic. The reduction in numbers is more likely to be reflective of the reduction in patients coming for regular follow up due to the pandemic. Despite this, waiting times for TDCs remained constant, while those for renal biopsies were globally improved. Most encouragingly, we demonstrate that implementing a novel diagnostic POCUS imaging pathway for dysfunctional AVFs resulted in significantly shorter times to diagnosis and intervention, thereby facilitating the preservation of dialysis access. Reassuringly, our data supports the conclusion that the implementation of a dedicated DIN service remains safe, with our unit reporting broadly similar complication rates to those reported pre-SDIN and in the wider medical literature.\n\nDIN reduces the reliance on other specialties, thereby streamlining care for patients. This model also creates wider training opportunities for renal trainees that were hitherto not consistently accessible (Selvaskandan et al., 2022). Data from a recent study in South and Southeast Asia highlighted training as a major barrier for nephrologists performing these procedures (Ramachandran et al., 2021). Training initiatives by the International Society of Nephrology (ISN) play a key part in sharing the learning and experience between centres across the world. Lopez et al. recently published their work in establishing a modular approach to training in DIN with the help of the ISN in Nicaragua (Lopez et al., 2021), and this represents an important example of the value of collaboration in progressing training in this emerging field. Vachharajani et al., have discussed successful models of DIN training in academic medical centres across the USA. This paper discusses a successful collaborative approach between private practice, academic centres and other interventional specialties such as cardiology (Vachharajani et al., 2010).\n\nIn line with the vision of the ISN for developing training in IN, we hosted our first ISN funded fellow in IN from Pakistan. The fellow has since successfully completed his training and returned to Pakistan to establish an interventional nephrology programme there. We aim to continue building our collaborations and have recently started the development of a sister unit at the Kamanga Medics Hospital in Mwanza, Tanzania.\n\nResearch and innovation in DIN remain underfunded and underperformed. The development of IN as a subspecialty interest with robust curricula, well defined training pathways and post graduate training should lend itself to further research in DIN (Roy-Chaudhury et al., 2012). We have lead the development of DIN training in the UK utilizing online webinars at international conferences, and have recently done hands on simulation training in IN at the recently concluded UK Kidney Week conference. We are in the process of launching a post graduate certificate course in association with Newcastle University. The ambition is to develop it as a master’s programme that would include research in DIN as an integral part of training.\n\nWe are acutely aware of the limitations of this data with its small sample size and observational nature. However, we have demonstrated unequivocally that implementing a dedicated DIN unit within our hospital has reduced procedural waiting times, enhanced independence from other interventional specialties, and facilitated the maintenance of definitive vascular dialysis access. We believe that this service serves as a springboard for future innovation and research in developing new service models, improving training, and fostering novel research in interventional nephrology in the UK.",
"appendix": "Data availability\n\nOpen Science Framework: Outcomes from the first dedicated diagnostic and interventional nephrology (IN) service in a UK renal unit, https://doi.org/10.17605/OSF.IO/DY2AN (Srivastava, 2023).\n\nThis project contains the following underlying data:\n\n- FINAL -Renal Biopsy.xlsx\n\n- PD data sheet - 25.9.22.xlsx\n\n- Pre SDIN TNL data.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nBeathard GA: Role of interventional nephrology in the multidisciplinary approach to hemodialysis vascular access care. Kidney Res. Clin. Pract. 2015; 34: 125–131. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChan MR: Interventional nephrology: What the nephrologist needs to know about vascular access. Clin. J. Am. Soc. Nephrol. 2013; 8: 1211–1212. Publisher Full Text\n\nKalloo SD, Mathew RO, Asif A: Is nephrology specialty at risk? Kidney Int. 2016; 90: 31–33. Publisher Full Text\n\nLopez AG, Salgado OJ, Vachharajani TJ: Dialysis Vascular Access Training: A Nicaraguan Experience. Kidney Int. Rep. 2021; 6: 1701–1703. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMishler R, Sands JJ, Ofsthun NJ, et al.: Dedicated outpatient vascular access center decreases hospitalization and missed outpatient dialysis treatments. Kidney Int. 2006; 69: 393–398. PubMed Abstract | Publisher Full Text\n\nNiyyar VD, Chan MR: Interventional nephrology: Catheter dysfunction--prevention and troubleshooting. Clin. J. Am. Soc. Nephrol. 2013; 8: 1234–1243. Publisher Full Text\n\nNiyyar VD, Work J: Interventional nephrology - past, present and future. Int. J. Artif. Organs. 2009; 32: 129–132. Publisher Full Text\n\nO’Neill WC: The New Nephrologist. Am. J. Kidney Dis. 2000; 35: 978–979.\n\nPoggio ED, Mcclelland RL, Blank KN, et al.: Systematic Review and Meta-Analysis of Native Kidney Biopsy Complications. Clin. J. Am. Soc. Nephrol. 2020; 15: 1595–1602. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPoinen K, Quinn RR, Clarke A, et al.: Complications From Tunneled Hemodialysis Catheters: A Canadian Observational Cohort Study. Am. J. Kidney Dis. 2019; 73: 467–475. PubMed Abstract | Publisher Full Text\n\nPyart R, Evans KM, Steenkamp R, et al.: The 21st UK Renal Registry Annual Report: A Summary of Analyses of Adult Data in 2017. Nephron. 2020; 144: 59–66. Publisher Full Text\n\nRamachandran R, Bhargava V, Jasuja S, et al.: Interventional nephrology and vascular access practice: A perspective from South and Southeast Asia. J. Vasc. Access. 2021; 11297298211011375.\n\nRobbin ML, Greene T, Allon M, et al.: Prediction of Arteriovenous Fistula Clinical Maturation from Postoperative Ultrasound Measurements: Findings from the Hemodialysis Fistula Maturation Study. J. Am. Soc. Nephrol. 2018; 29: 2735–2744. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRoufosse C, Simmonds N, Clahsen-Van Groningen M, et al.: A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology. Transplantation. 2018; 102: 1795–1814. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRoy-Chaudhury P, Yevzlin A, Bonventre JV, et al.: Academic interventional nephrology: a model for training, research, and patient care. Clin. J. Am. Soc. Nephrol. 2012; 7: 521–524. Publisher Full Text\n\nSalman L, Rizvi A, Contreras G, et al.: A Multicenter Randomized Clinical Trial of Hemodialysis Access Blood Flow Surveillance Compared to Standard of Care: The Hemodialysis Access Surveillance Evaluation (HASE) Study. Kidney Int. Rep. 2020; 5: 1937–1944. Publisher Full Text\n\nSelvaskandan H, Baharani J, Hamer R: Regional variations in nephrology trainee confidence with clinical skills may relate to the availability of local training opportunities in the UK: results from a national survey. Clin. Exp. Nephrol. 2022; 26: 886–897. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSrivastava S: Outcomes from the first dedicated diagnostic and interventional nephrology (IN) service in a UK renal unit. [Dataset]. 2023. Publisher Full Text\n\nVachharajani TJ, Moossavi S, Salman L, et al.: Dialysis vascular access management by interventional nephrology programs at University Medical Centers in the United States. Semin. Dial. 2011; 24: 564–569. PubMed Abstract | Publisher Full Text\n\nVachharajani TJ, Moossavi S, Salman L, et al.: Successful models of interventional nephrology at academic medical centers. Clin. J. Am. Soc. Nephrol. 2010; 5: 2130–2136. PubMed Abstract | Publisher Full Text\n\nWinnicki W, Herkner H, Lorenz M, et al.: Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters. Kidney Int. 2018; 93: 753–760. Publisher Full Text"
}
|
[
{
"id": "229456",
"date": "05 Feb 2024",
"name": "Carlo Lomonte",
"expertise": [
"Reviewer Expertise Vascular access"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nMy comments:\nIn the Introduction section, the Authors should try to place their experience into a broader context of the worldwide nephrologists shortage and the reduction of the workforce in the next years (https://asndataanalytics.github.io/AY-2020-Nephrology-Match/);(Moura-Neto et al, 2021)[Ref 1]; (Sharif MU et al,2016)[Ref 2] Nephrologists should play a central role as leaders of the multidisciplinary team to optimise the care of dialysis patients (Niyyar VD et al,2020)[Ref 3]. This is a crucial point to emphasis. But how can nephrologists incorporate other competencies into daily clinical practice? What about surveillance of vascular accesses. Can these screening programs reduce the burden of procedures? Can we rethink a screening program in a DIN context? Regarding training in interventional nephrology, a very recent paper described the first European advanced training course in diagnostic and interventional nephrology ( Lomonte et al,2023)[Re4]. Please, comment in the Discussion section.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-734
|
https://f1000research.com/articles/11-1090/v1
|
22 Sep 22
|
{
"type": "Study Protocol",
"title": "Effect of intraoperative PEEP with recruitment maneuvers on the occurrence of postoperative pulmonary complications during general anesthesia––protocol for Bayesian analysis of three randomized clinical trials of intraoperative ventilation",
"authors": [
"Guido Mazzinari",
"Fernando G. Zampieri",
"Lorenzo Ball",
"Niklas S. Campos",
"Thomas Bluth",
"Sabrine N.T. Hemmes",
"Carlos Ferrando",
"Julian Librero",
"Marina Soro",
"Paolo Pelosi",
"Marcelo Gama de Abreu",
"Marcus J. Schultz",
"Ary Serpa Neto",
"PROVHILO investigators",
"iPROVE investigators",
"PROBESE investigators",
"PROVE network investigators",
"Fernando G. Zampieri",
"Lorenzo Ball",
"Niklas S. Campos",
"Thomas Bluth",
"Sabrine N.T. Hemmes",
"Carlos Ferrando",
"Julian Librero",
"Marina Soro",
"Paolo Pelosi",
"Marcelo Gama de Abreu",
"Marcus J. Schultz",
"Ary Serpa Neto"
],
"abstract": "Background: Using the frequentist approach, a recent meta–analysis of three randomized clinical trials in patients undergoing intraoperative ventilation during general anesthesia for major surgery failed to show the benefit of ventilation that uses high positive end–expiratory pressure with recruitment maneuvers when compared to ventilation that uses low positive end–expiratory pressure without recruitment maneuvers. Methods: We designed a protocol for a Bayesian analysis using the pooled dataset. The multilevel Bayesian logistic model will use the individual patient data. Prior distributions will be prespecified to represent a varying level of skepticism for the effect estimate. The primary endpoint will be a composite of postoperative pulmonary complications (PPC) within the first seven postoperative days, which reflects the primary endpoint of the original studies. We preset a range of practical equivalence to assess the futility of the intervention with an interval of odds ratio (OR) between 0.9 and 1.1 and assess how much of the 95% of highest density interval (HDI) falls between the region of practical equivalence. Ethics and dissemination: The used data derive from approved studies that were published in recent years. The findings of this current analysis will be reported in a new manuscript, drafted by the writing committee on behalf of the three research groups. All investigators listed in the original trials will serve as collaborative authors.",
"keywords": [
"Mechanical ventilation",
"intraoperative ventilation",
"PEEP",
"recruitment maneuvers",
"postoperative pulmonary complications",
"Bayesian analysis"
],
"content": "Introduction\n\nMechanical ventilation under general anesthesia and neuromuscular blockade yields a reduction in lung volume that can affect respiratory mechanics and gas exchange,1 especially in specific clinical scenarios such as laparoscopic surgery with pneumoperitoneum insufflation.2 This reduction in volume can lead to a cyclic opening and closing of alveoli during mechanical ventilation, ultimately inducing tissue injury known as atelectrauma.3 Minimizing atelectrauma by applying a ‘lung protective ventilation’ to reopen the closed alveoli with a recruitment maneuver (RM) while sustaining their permeability by applying higher positive end–expiratory pressure (PEEP) is likely associated with a reduction in postoperative pulmonary complications.4 The optimization of intraoperative ventilation and its potential beneficial effects on clinically relevant postoperative outcome measures is of particular importance due to the large number of surgical operations worldwide per year.5\n\nUsing the frequentist statistical approach, a recent meta–analysis of three randomized clinical trials (RCTs) in patients undergoing intraoperative ventilation during general anesthesia for major surgery failed to show the benefit of ventilation that uses high PEEP with RM when compared to ventilation that uses low PEEP without RM.6\n\nTo enhance comprehension of the study data, the Bayesian methodology is beginning to be used in anesthesiology and critical care studies with uncertain frequentist outcomes.7–10 In addition, applying a Bayesian framework in meta–analysis allows to model the heterogeneity estimation directly and to estimate pooled effects more precisely, especially when the number of studies included in the analysis is small.11 Furthermore, Bayesian analysis can produce a full posterior distribution for both the effect estimate and heterogeneity and provide the capability of testing for tailored hypotheses assessing, for instance, if the estimate is smaller or larger than a specified interesting threshold.12,13\n\nWe hypothesize that the intervention effect on the posterior probability distribution will lay outside a predefined region of practical equivalence. To test this hypothesis, we will reanalyze the pooled individual patient dataset of the three largest RCTs of intraoperative ventilation comparing ventilation with high PEEP with RM with ventilation with low PEEP without RM using a Bayesian framework according to previously published recommendations.7,14 The protocol for the Bayesian statistical approach is presented in this paper. The posterior probability for the effect of the intervention on postoperative pulmonary complications will be assessed to better understand the potential benefit or harm of the tested intervention. This could provide a more interpretable probabilistic framework and allows to include preexisting knowledge into the analysis.\n\n\nProtocol\n\nWe will perform a Bayesian analysis of the previously combined dataset named ‘Re–evaluation of the Effects of High PEEP with Recruitment Manoeuvres versus Low PEEP without Recruitment Manoeuvres During General Anaesthesia for Surgery’ (REPEAT),6,15 registered at ClinicalTrials.gov: NCT03937375 on 3rd May 2019. This dataset merged the individual patient data from three RCTs, the ‘High versus low positive end–expiratory pressure during general anesthesia for open abdominal surgery’ (PROVHILO) study (registered with Controlled-Trials.com: ISRCTN70332574),16 the 'Individualized perioperative open–lung approach versus standard protective ventilation in abdominal surgery' (iPROVE) study (registered with ClinicalTrials.gov: NCT02158923)17 and the ‘Effect of intraoperative high positive end–expiratory pressure with recruitment maneuvers vs low PEEP on postoperative pulmonary complications in obese patients’ (PROBESE) study (registered with ClinicalTrials.gov: NCT02148692).18 The study protocols of the original studies were approved by the respective institutional review boards and were published before the start of patient enrolment.19–21 Written informed consent was obtained from all participating individuals before enrolment, and the rules of good clinical practices were followed. All analyses were performed with R version 4.0.1 (R Core Team).\n\nPROVHILO was an international multicenter study comparing intraoperative ventilation with 12 cm H2O PEEP with RM to intraoperative ventilation with 0–2 cm H2O PEEP without RM in non–obese patients scheduled for major abdominal surgery.16 iPROVE was a national multicenter study comparing two intraoperative ventilation strategies and two postoperative ventilatory support strategies in non-obese patients scheduled for major abdominal surgery.17 In this study, intraoperative ventilation with high PEEP titrated to the best respiratory compliance combined with RM was compared to intraoperative ventilation with 5 cm H2O PEEP without RM. Postoperative ventilation was carried out by applying 5 cm H2O PEEP continuous positive airway pressure (CPAP) and supplementary oxygen at 0.5 fraction of inspired oxygen (FiO2) or 0.5 FiO2 alone. PROBESE was an international multicenter study comparing intraoperative ventilation with 12 cm H2O PEEP with RM to intraoperative ventilation with 4 cm H2O PEEP without RM in obese patients scheduled for major surgery.18\n\nThe REPEAT database is harmonized, protected, and does not contain any patient–identifying information. Data are stored at Hospital Israelita Albert Einstein, Sao Paulo, Brazil. The full description of the data harmonization process is published elsewhere in full detail.6,15 Briefly, the level of PEEP considered in the low PEEP group was considered as ≤5 cm H2O and data from iPROVE were used according to the intraoperative ventilation strategy as no significant interaction with postoperative intervention was found.15\n\nThe single primary outcome of this current analysis is a collapsed composite of postoperative pulmonary complications (PPCs) developed during the first seven postoperative days as collected in the REPEAT database. The definitions used in the study are reported in Table 1.\n\n* Bernard GR, Artigas A, Brigham KL, et al. Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination. The Consensus Committee. Intensive Care Med 1994;20:225–232.\n\n** Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012;307:2526–2533.\n\nFor this unplanned analysis, we will use all the available data without any a priori power calculations.\n\nWe will carry out a one–stage approach meta–analysis by fitting a multilevel Bayesian logistic model including the effect of the PEEP and RM strategy as population (fixed) effect and the study and site as a varying (random) effect modeling heterogeneity of effect across different studies.\n\nFor defining priors, we will follow previously published recommendations on Bayesian reanalysis7 and recommendations from studies focusing on Bayesian modelling and meta–analysis.22,23 We will use one skeptical, one pessimistic, and one optimistic prior for the effect of PEEP and RM compared to low PEEP, i.e., a PEEP of 5 cmH2O or less, without RM on PPCs. Previous studies suggested a benefit of PEEP and RM, but many studies were neutral or indeterminate when using a frequentist approach. Therefore, we will consider a moderate belief strength for both the optimistic and neutral prior and a weak pessimistic prior. Following previous recommendations,7 we will define priors as follows:\n\n• The neutral skeptical prior of moderate strength is normally distributed and centered at the absence of effect [OR = 1; log (OR) = 0] with an SD of 0.355, such that 0.95 of the probability falls in the range of 0.5–2. Therefore, our skeptical prior will follow a normal distribution with a mean of 0 and an SD of 0.355 [N(0, 0.355)] (Figure 1);\n\n• The pessimistic and optimistic priors are informed by the averaged effect size estimate from the three original studies (PROVHILO: OR = 0.63; iPROVE: OR = 0.45; PROBESE: OR = 0.44; Mean: OR = 0.51). The standard deviation (SD) of the optimistic prior will be defined to retain a 0.15 probability of harm [Pr (OR > 1)], and the pessimistic prior is chosen to retain a 0.30 probability of benefit [Pr (OR < 1)] (Figure 1);\n\n• The prior for the heterogeneity of the intervention across studies is defined first assuming that at least some between–study variability is present; thus, it should always be more than 0. In the context of log-ORs there are established thresholds of heterogeneity according to the parameter τ that are defined as ‘reasonable’ (0.1 < τ < 0.5), ‘fairly high’ (0.5 < τ < 1.0), ‘fairly extreme’ (τ > 1.0).24 As recommended in a previously published paper23 we assume a prior distribution for heterogeneity as a half-Normal with a mean of 0 and an SD = 0.5, this yields prior probabilities of 52% in the reasonable, 27% in the fairly high and 5% in the extreme category respectively (Figure 2);\n\n• The prior correlation for the correlation matrix will be based on the Lewandowski-Kurowicka–Joe (LKJ) distribution with a η parameter of 2 for the varying effect.22,25 (Figure 3).\n\nDotted lines show the mean estimate for each distribution. The skeptic prior is centered at 0 while optimistic and pessimistic prior are centered at -0.67 and 0.67 respectively.\n\nDotted lines separate heterogeneity categories based on τ values.\n\nThe ROPE measures how much the posterior probability distribution falls between a specific interval of equivalent effect. By assessing how much of the 95% highest density interval (HDI) falls between the ROPE we can quantify the probability of the studied intervention having a benefit or harm.26 We define the ROPE as the interval between 0.9 < OR > 1.1. In addition, we define a threshold for severe harm at OR = 1.25. We will draw samples from the posterior distribution after fitting the models with each of the previously defined priors and determine how much of the mass probability lies in the ROPE interval or exceed the threshold for severe harm and determine the expected predicted posterior probabilities of treatment effect using the emmeans package. Furthermore, we compare the ROPE interval with the 95% HDI as previously recommended to see if the HDI probability mass falls outside the ROPE.26 To illustrate this principle, we simulate data for a binary outcome and a binary dependent variable with four different effect estimates and report the posterior distribution with 95%HDIs and ROPE along with probability masses after fitting logistic models with skeptic priors as previously stated and following a previously published approach7 (Figure 4).\n\nThe black vertical line at 0 represents the point at which the OR is equal to 1 [i.e., log (OR) = 0]. The area to the right (in green) represents the probability that the intervention is harmful. The probability of severe harm [Pr (OR.1.25)] is shown in darker green. Probabilities for each posterior distribution are reported in the upper part of each panel. Values below 0 mean the intervention is beneficial [Pr (log(OR),0); Pr (OR,1.0)] and are shown in light yellow with the probability of benefit again in the upper part of the figure. The ROPE is defined as the OR between 1/1.1 and 1.1 (the segmented area around log (OR) = 0). The 95% High-Density Interval (HDI) is reported as a blue line in each panel. We can see how fitting logistic models with different simulated effect yields to different interpretation for instance there is considerable difference between panel A, where the probability of harm is 63% and the probability that the estimate fall in the ROPE is 68% and the HDI 95% crosses the 0 threshold and panel D, where the probability of benefit is 100% and the 95%HDI and ROPE do not overlap.\n\nTo determine if the relationship between treatment and the primary outcome differs between predetermined, clinically significant subgroups, we will fit the varying effect logistic regression model by adding an interaction term between treatment and subgroup and report the conditional effect of the interaction.\n\nWe will assess the following subgroups:\n\n• Type of surgery, i.e., laparoscopic vs. open surgery;\n\n• Risk for PPCs, i.e., Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score < 45 vs. ≥ 45;\n\n• Body mass index (BMI), used as a continuous variable;\n\n• Type of PEEP selection, i.e., fixed vs. titrated; and\n\n• Use of a postoperative element as part of the tested intervention.\n\nWe plan to perform the following sensitivity analyses:\n\n• We will fit the same prespecified model but use only severe PPCs as the primary outcome, i.e. excluding mild respiratory failure.\n\n• We will perform one analysis including only patients with lung collapse before the intervention; and\n\n• We will fit the model by varying the heterogeneity prior τ to a proper uniform I2 prior.27\n\n\nEthics and dissemination\n\nThe study will be performed according to national and international guidelines. All data derive from clinical trials approved by a competent institutional review board in each participating center according to the applicable legislation. The study Steering Committee will publish the study findings. The writing committee will submit the main manuscript on behalf of the research group. All investigators listed in the original trials will be listed as collaborators in an Appendix in alphabetical order, according to the centre's name. All efforts will be made to link all collaborators to the final publication in indexed databases.\n\n\nStudy status\n\nWe will carry out the analysis on the already locked database after publishing the protocol.\n\n\nDiscussion\n\nWe here describe the protocol and statistical analysis plan for a Bayesian reanalysis of an individual patient data meta–analysis which aim is to compare the effect of intraoperative high PEEP after RM vs. low PEEP without RM on the incidence of postoperative pulmonary complications in patients undergoing surgery with general anesthesia and low tidal volume mechanical ventilation. The optimization of mechanical ventilation during surgery is important since it can potentially improve clinically relevant post-operative outcomes with beneficial effects on patients, families and healthcare systems.\n\nThe present proposed analysis has several strengths. Firstly, we can use the merged dataset of three well–performed multicenter RCTs, that tested the effect of fairly comparable intraoperative ventilation strategies concerning a similar endpoint. Secondly, the Bayesian framework will provide probabilities of harm or benefit associated with the studied intervention, adding further insights to the frequentist interpretations used in the previous analyses of these three RCTs.15 We scrupulously followed the published recommendations, especially concerning prior selection.7 Thirdly, we prespecify subgroups analysis to assess the intervention effect in particularly interesting subpopulations such as patients who underwent laparoscopic surgery, and sensitivity analyses to test the robustness of our methodology, which is crucial in a Bayesian framework.\n\nThe current standard statistical paradigm to analyze RCTs and perform meta–analyses is based on null–hypothesis testing and P–values and is referred to as frequentist approach. P–values indicate how incompatible a data set is with a specified statistical model, but their correct interpretation can be counterintuitive and at times even problematic. For instance, the typical P < 0.05 is defined as the probability that another study would yield a result equal to or more extreme than the one observed, assuming that the null hypothesis is true. This definition can hamper the correct interpretation of the results of different studies, particularly if P > 0.05. When a test returns a P > 0.05, a study is often interpreted as negative, meaning that the intervention had no effect on the outcome of interest, while the rigorous interpretation should be that the available data were insufficient to reject the null hypothesis.28,29\n\nThe results from the REPEAT analysis fall precisely in this category. The effect of a high PEEP after RM maneuvers compared to low PEEP without RM on post-operative pulmonary complications was not statistically significant, with a P value of 0.06, thus yielding an indeterminate result. We plan to leverage the advantages of a Bayesian approach to expand and escape the all-or-nothing simplistic interpretation of the study derived from the null hypothesis testing. Further, a probabilistic framework to attach probabilities to specific estimates has been added to the analysis, thus providing a much more interpretable and intuitive explanation of the results.\n\nBayesian analysis in this context has proven to help gain additional insights and scope and has been increasingly used in recent years. For instance, Bayesian analysis applied to RCTs with indeterminate frequentist in intensive care setting interventions focused on improving mortality30,31 found that the posterior probability of mortality benefit, i.e., relative risk (RR) < 1 or OR <1, ranged between 88% and 99% according to a range of prespecified priors.8,9 Other reports used the same approach7 to investigate further an opposite, i.e. probability of harm, indeterminate result in same clincal setting RCT,32 found that the probability of harm of the intervention was > 90%. Bayesian analysis has also been used to elucidate the effect of interventions in specific subgroups,10 to evaluate the effect of selection bias33 and in meta-analysis.34\n\nThis current analysis has several limitations which need to be addressed. First, some differences between studies concerning how PEEP and RM were used and titrated cannot be unraveled, although we will use a previously harmonized individual patient database. Secondly, we analyze the effect of a broad category, i.e., high PEEP and RM vs. low PEEP and no RM. Defining the optimal PEEP and RM strategy is beyond the scope of the current analysis and must be elucidated in further investigations. Thirdly, the original RCTs did not exclude patients without lung collapse; therefore, a selection bias towards less benefit of the intervention cannot be excluded. Fourthly, although previously published recommendations7 were rigorously followed, there is no unequivocal way to choose a universally correct prior probability distribution. Moreover, although we included all data available from three of the largest RCTs assessing the effect of open lung strategy in the perioperative period, a certain degree of precision bias cannot be excluded should data from other studies be incorporated, although a change in the overall conclusions is unlikely.\n\nIn conclusion, we will use a Bayesian methodology to better interpret data from three large RCTs investigating the potential beneficial role of high PEEP after RM compared to low PEEP without RM during intraoperative low tidal mechanical ventilation to prevent post-operative pulmonary complications and improve clinically relevant outcome measures. Bayesian analysis can be a helpful tool to augment the interpretation of anesthesiology and critical care trials.\n\n\nData availability\n\nThe de-identified database derived from the original studies is stored at Hospital Israelita Einstein, Sao Paulo, Brazil. Data can be requested at the center IRB at: https://www.einstein.br/en/research/clinical-research-center/contact-us. Email address to contact: ary.neto2@einstein.br",
"appendix": "Acknoledgements\n\nThe original trials received the following funds: The PROVHILO trial (a collaboration of the Protective Ventilation Network [PROVENet]) was funded by the European Society of Anaesthesiology (ESA) and the Academical Medical Center (AMC, Amsterdam, The Netherlands). The iPROVE trial was funded by the Instituto de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness (grant PI14/00829, co-financed by the European Regional Development Fund), and the Grants Programme of the European Society of Anaesthesiology. The Clinical Trials Network of the European Society of Anaesthesiology provided financial support for the steering committee meetings, onsite visits to participating sites, for the building of the electronic data capture system, and for the advertising of the PROBESE trial. The Technische Universitat Dresden provided logistical support for the coordinating site.\n\nThe Conselho Nacional de Desenvolvimento Científico e Tecnologico provided financial support for insurance in Brazil. The Association of Anaesthetists of Great Britain and Ireland and the Northern Ireland Society of Anaesthetists provided financial support for the participating sites in the UK.\n\n\nReferences\n\nCulley DJ, Bigatello L, Pesenti A: Respiratory Physiology for the Anesthesiologist. Anesthesiology. 2019 Jun; 130: 1064–1077. Publisher Full Text\n\nMazzinari G, Diaz-Cambronero O, Alonso-Iñigo JM, et al.: Intraabdominal pressure targeted positive end-expiratory pressure during laparoscopic surgery: An open-label, nonrandomized, crossover, clinical trial. Anesthesiology. 2020; 667–677. Publisher Full Text\n\nBall L, Costantino F, Fiorito M, et al.: Respiratory mechanics during general anaesthesia. Ann. Transl. Med. 2018 Oct; 6(19): 379–379. Publisher Full Text\n\nSlutsky AS, Ranieri VM: Ventilator-Induced Lung Injury. N. Engl. J. Med. 2013; 369: 2126–2136. Publisher Full Text\n\nRose J, Weiser TG, Hider P, et al.: Estimated need for surgery worldwide based on prevalence of diseases: a modelling strategy for the WHO Global Health Estimate. Lancet Glob. Health. 2015 Apr 27; 3: S13–S20. Publisher Full Text\n\nCampos NS, Bluth T, Hemmes SNT, et al.: Re–evaluation of the effects of high PEEP with recruitment manoeuvres versus low PEEP without recruitment manoeuvres during general anaesthesia for surgery – Protocol and statistical analysis plan for an individual patient data meta–analysis of PROVHILO, iPROVE and PROBESE. Rev. Esp. Anestesiol. Reanim (English Edition). 2020; 67: 76–89. Publisher Full Text\n\nZampieri FG, Casey JD, Shankar-Hari M, et al.: Using bayesian methods to augment the interpretation of critical care trials. an overview of theory and example reanalysis of the alveolar recruitment for acute respiratory distress syndrome trial. Am. J. Respir. Crit. Care Med. 2021; 203: 543–552. Publisher Full Text\n\nZampieri FG, Damiani LP, Bakker J, et al.: Effects of a Resuscitation Strategy Targeting Peripheral Perfusion Status versus Serum Lactate Levels among Patients with Septic Shock A Bayesian Reanalysis of the ANDROMEDA-SHOCK Trial. Am. J. Respir. Crit. Care Med. 2020 Feb 15; 201(4): 423–429.\n\nGoligher EC, Tomlinson G, Hajage D, et al.: Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome and Posterior Probability of Mortality Benefit in a Post Hoc Bayesian Analysis of a Randomized Clinical Trial. JAMA. 2018 Dec 4; 320: 2251–2259. Publisher Full Text\n\nZampieri FG, Costa EL, Iwashyna TJ, et al.: Heterogeneous effects of alveolar recruitment in acute respiratory distress syndrome: a machine learning reanalysis of the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial. Br. J. Anaesth. 2019; 123: 88–95. Publisher Full Text\n\nHarrer M, Cuijpers P, Furukawa Toshi A, et al.: Doing Meta-Analysis with R: A Hands-On Guide. London:Chapman & Hall CRC Press;2021.\n\nFriede T, Röver C, Wandel S, et al.: Meta-analysis of two studies in the presence of heterogeneity with applications in rare diseases. Biom. J. 2017; 59: 658–671. Publisher Full Text\n\nRhodes KM, Turner RM, White IR, et al.: Implementing informative priors for heterogeneity in meta-analysis using meta-regression and pseudo data. Stat. Med. 2016; 20(35): 5495–5511. Publisher Full Text\n\nSung L, Hayden J, Greenberg ML, et al.: Seven items were identified for inclusion when reporting a Bayesian analysis of a clinical study. J. Clin. Epidemiol. 2005; 58: 261–268. Publisher Full Text\n\nCampos NS, Bluth T, Hemmes SNT, et al.: Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomized clinical trials. Br. J. Anaesth. 2022; 128(6): 1040–1051. Publisher Full Text\n\nPROVE Network Investigators for the Clinical Trial Network of the European Society of AnaesthesiologyHemmes SNT, Gama de Abreu M, et al.: High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): A multicentre randomized controlled trial. Lancet. 2014; 384(9942): 495–503. Publisher Full Text\n\nFerrando C, Soro M, Unzueta C, et al.: Individualized perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomized controlled trial. Lancet Respir. Med. 2018; 6: 193–203. Publisher Full Text\n\nBluth T, Serpa Neto A, Schultz MJ, et al.: Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) with Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial. JAMA. 2019; 321(23): 2292–2305. Publisher Full Text\n\nHemmes SNT, Severgnini P, Jaber S, et al.: Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery. Trials. 2011; 12: 111. Publisher Full Text\n\nFerrando C, Soro M, Canet J, et al.: Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): Study protocol for a randomized controlled trial. Trials. 2015; 16: 193. Publisher Full Text\n\nBluth T, Teichmann R, Kiss T, et al.: Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): Study protocol for a randomized controlled trial. Trials. 2017; 18: 202. Publisher Full Text\n\nMcElreath R: Statistical Rethinking: A Bayesian Course with Examples in R and Stan. 2nd ed.Boca Raton Florida:Chapman & Hall/CRC Texts;2020.\n\nRöver C, Bender R, Dias S, et al.: On weakly informative prior distributions for the heterogeneity parameter in Bayesian random-effects meta-analysis. Res. Synth. Methods. 2021 Jul 1; 12(4): 448–474. Publisher Full Text\n\nSpegelhalter David J, Abrams Keith R, Myles JP: Bayesian Approaches to Clinical Trials and Health-Care Evaluation. Chichester England:Wiley and Sons;2005.\n\nWilliams DR, Rast P, Bürkner PC: Bayesian Meta-Analysis with Weakly Informative Prior Distributions.2018. PsyArXiv Epub ahead of print 10 January 2018. Publisher Full Text\n\nKruschke JK: Rejecting or Accepting Parameter Values in Bayesian Estimation. Adv. Methods Pract. Psychol. Sci. 2018 Jun 1; 1(2): 270–280.\n\nRöver C: Bayesian random-effects meta-analysis using the bayesmeta r package. J. Stat. Softw. 2020; 93: 1–51. Publisher Full Text\n\nWasserstein RL, Lazar NA: The ASA's statement on P-values: Context, process, and purpose. Am. Stat. 2016; 70: 129–133. Publisher Full Text\n\nGreenwald AG, Gonzalez R, Harris RJ, et al.: Effect sizes and p values: What should be reported and what should be replicated? Psychophysiology. 1996 Mar; 33: 175–183. Publisher Full Text\n\nHernández G, Ospina-Tascón GA, Damiani LP, et al.: Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality among Patients with Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019; 321: 654–664. Publisher Full Text\n\nCombes A, Hajage D, Capellier G, et al.: Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N. Engl. J. Med. 2018; 378: 1965–1975. Publisher Full Text\n\nCavalcanti AB, Suzumura ÉA, Laranjeira LN, et al.: Effect of lung recruitment and titrated Positive End-Expiratory Pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome - A randomized clinical trial. JAMA. 2017; 318: 1335–1345. Publisher Full Text\n\nZampieri FG, Machado FR, Biondi RS, et al.: Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults A Secondary Exploratory Analysis of the BaSICS Clinical Trial. Am. J. Respir. Crit. Care Med. 2022; 205: 1419–1428. Publisher Full Text\n\nAlbuquerque AM, Tramujas L, Sewanan LR, et al.: Mortality Rates among Hospitalized Patients with COVID-19 Infection Treated with Tocilizumab and Corticosteroids: A Bayesian Reanalysis of a Previous Meta-analysis. JAMA Netw. Open. 2022; 5: e220548. Publisher Full Text"
}
|
[
{
"id": "173632",
"date": "22 May 2023",
"name": "Andrea Cortegiani",
"expertise": [
"Reviewer Expertise Anaesthesiology and Critical Care Medicine"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors submitted the protocol for a Bayesian analysis of a dataset composed by data from three major RCTc of intraoperative ventilation evaluating high PEEP + recruitment maneuvers vs low PEEP and no recruitment maneuvers. The dataset (REPEAT) has been already used for frequentist analysis and is of high internal and external validity. The authors are expert in the field and are able to provide important insights with this analysis. The methods for this Bayesian analysis, especially the selected prior distributions are reasonable and adequate.\nI fully support the indexing of this protocol and look forward to seeing the results of the analysis.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "9699",
"date": "23 May 2023",
"name": "Guido Mazzinari",
"role": "Author Response",
"response": "Thank you very much for your time and effort to review our protocol."
}
]
},
{
"id": "173633",
"date": "22 May 2023",
"name": "Lukas Gasteiger",
"expertise": [
"Reviewer Expertise Ventilation",
"Right Ventricular Function",
"Circulation"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a very well designed protocol for a Bayesian analysis of three recent RCT's to better understand the effect of intraoperative PEEP on PPCs. By now no RCT was able to clearly show a benefit of a higher PEEP and RM compared to lower PEEP levels and no RM. Therefore the question, if such an intervention is beneficial to our patients, is of high clinical relevance. The chosen model to use a Bayesian protocol seems appropriate and adds the advantage that no new trial and inclusion of patients is needed.\nFurthermore to assess the effect of this intervention is of central interest as it is known, that a higher lever of PEEP may also interact with Right Ventricular Function and therefore may lead to circulatory side-effects such as hypotension. Also, an increased need for vasopressor therapy may be associated.\n\nIs it planned to also assess for circulatory side-effects as secondary outcome?\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "9700",
"date": "23 May 2023",
"name": "Guido Mazzinari",
"role": "Author Response",
"response": "Thank you very much for your time and effort in reviewing our protocol. Regarding your question: - Is it planned to also assess for circulatory side-effects as secondary outcome? We chose to limit this reanalysis to the primary outcome, i.e. occurrence of postoperative pulmonary complications, to keep our aim simple and focused. Moreover, we feel that the prior distribution selection was easier since we followed a previously published approach to this type of outcome. As for hypotension episodes of hemodynamic related side-effects, the longitudinal nature of the data would require a careful planning of the priors, and we are not aware of any already accepted approach in this field. It is certainly worth looking into it in the future."
}
]
},
{
"id": "173629",
"date": "05 Jun 2023",
"name": "Ottokar Stundner",
"expertise": [
"Reviewer Expertise Comparative Effectiveness Research",
"Public Health",
"Regional Anesthesia"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors present a comprehensive protocol for a reanalysis of three RCTs using Bayesian meta-analysis techniques. While the three individual studies had slightly different scopes, the common primary outcome of all is the incidence of postoperative pulmonary complications (PPCs), and the exposure is a different ventilation strategy (“long protective” vs “non-lung protective”; high PEEP + recruitment maneuvers vs. low PEEP and no RMs).\n\nThe authors argue that a recent meta-analysis using classical frequentist methodology (mixed effects logistic regression) yielded “no difference” between the exposure levels (n=1,913 “lung protective” vs. 1,924 “non-lung protective”, raw complication incidence 29.4% vs 32.2% (OR 0.87 (0.75-1.01)), but some differences in secondary endpoints (more frequent desaturations in low PEEP, more intraoperative hypotension in high PEEP, …). The point that Bayesian methodology, providing a more tangible and interpretable effect size for the interventions’ efficacy, would be a suitable analytic approach here, is well taken and there are prominent examples in the literature where a Bayesian re-analysis served to further the understanding of (particularly composite) datasets.\n\nThank you for the opportunity to review your work. The protocol is very well written and the research question is valid, relevant, and succinctly presented.\n\nMy two primary concerns lie (1) in the definition of PCCs, and (2) in the explanation text on how the effect estimate priors will be weighted.\n\nThe PCC definition arguably differs between the three studies. E.g., the pulmonary infection category which is looser in PROVHILO than in the other studies, or bronchospasm, which is looser in PROBESE. The authors duly note the existence of these differences in their limitations section. As they argue, using a wide outcome definition may be sensible, given a relatively broad exposure bandwidth and heterogeneity in practical application of the treatment arms. The reviewer wonders if the authors deliberated adding different complication stages in the analysis or expanding their sensitivity analysis in this regard (they were already planning on excluding “minor” complications for sensitivity analysis). On the other hand, subgrouping may limit statistical power further and lead to model convergence issues.\n\nAs for the prior definition; This important topic is explained at length and is planned according to a comprehensive protocol (Zampieri et al, 2021) and technical description (Röver et al, 2021). The reviewer appreciates the nuanced approach. However, I do believe that some more information / explanation could be conveyed regarding the choice of relative prior weighting.\n\nSpecific comments:\nPlease add a reference to the published results of the frequentist meta-analysis (Campos et al, BJA 2022 1); only the study protocol is referenced.\n\nThe authors will use a half-normal distribution for the heterogeneity prior. Could they briefly explain the rationale to perform a sensitivity analysis with I squared distribution (instead of i.e. Half-Cauchy).\n\n“Previous studies suggested a benefit of PEEP and RM, but many studies were neutral or indeterminate when using a frequentist approach. Therefore, we will consider a moderate belief strength for both the optimistic and neutral prior and a weak pessimistic prior. Following previous recommendations,7 we will define priors as follows….”\n\nWhat exactly does the word “therefore” signify here? It seems sensible to align the means ESs to the preexisting data, the weighting choice for the optimistic vs pessimistic priors could be explained some more (especially with regard to possible pessimistic assumptions, i.e., higher complication incidence). I suggest the authors elaborate a bit more here.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "9784",
"date": "23 Jun 2023",
"name": "Guido Mazzinari",
"role": "Author Response",
"response": "My two primary concerns lie (1) in the definition of PCCs, and (2) in the explanation text on how the effect estimate priors will be weighted. 1. The PCC definition arguably differs between the three studies. E.g., the pulmonary infection category which is looser in PROVHILO than in the other studies, or bronchospasm, which is looser in PROBESE. The authors duly note the existence of these differences in their limitations section. As they argue, using a wide outcome definition may be sensible, given a relatively broad exposure bandwidth and heterogeneity in practical application of the treatment arms. The reviewer wonders if the authors deliberated adding different complication stages in the analysis or expanding their sensitivity analysis in this regard (they were already planning on excluding “minor” complications for sensitivity analysis). On the other hand, subgrouping may limit statistical power further and lead to model convergence issues. Thank you for the interesting remark. Indeed, we used a database where the primary outcome definition where previously harmonised to join the data from the different RCTs. New aspiration pneumonitis, pulmonary infiltrates and cardiogenic pulmonary oedema were not included in the definition of PPC, because they were not recorded in the iPROVE trial. Also, moderate respiratory failure, as defined only in the PROBESE trial was merged in the definition of severe respiratory failure to achieve concordance with the other trials. Still, there is some slight mismatch in some of the definitions, as the reviewer points out, and we already acknowledge in the limitations section of the protocol and in the previous studies. We planned indeed a sensitivity analysis excluding mild respiratory failure from the outcome to test the robustness of our findings. We purposedly tried to design a simple protocol and not overburden with too many secondary analysis because we feel that this would drive the focus away from the main question and could possibly complicate the model estimation as the reviewer correctly pointed out. 2. As for the prior definition, This important topic is explained at length and is planned according to a comprehensive protocol (Zampieri et al, 2021) and technical description (Röver et al, 2021). The reviewer appreciates the nuanced approach. However, I do believe that some more information / explanation could be conveyed regarding the choice of relative prior weighting. We agree that this is a key concept. We, therefore, reworked the paragraph on the prior to be clearer and more explicit. The updated version of the manuscript now reads as follows: “For defining priors, we will follow previously published recommendations on Bayesian reanalysis7 and recommendations from studies focusing on Bayesian modelling and meta–analysis.22,23 The guidelines recommend to consider the full range of possible beliefs. Thus, we will use one skeptical, one pessimistic, and one optimistic prior for the effect of PEEP and RM compared to low PEEP, i.e., a PEEP of 5 cmH2O or less, without RM on PPCs. In other words, we define three distributions to decide where to assign most of the probability mass. The pessimistic and optimistic prior distributions will be centred, on the averaged estimate from the original, whereas the skeptical prior will be centred around the absence of effect, i.e. 0. The variance of the prior distributions is defined according to the clinical belief that we cannot rule out a benefit for the intervention, although we can likely rule out a large effect and we cannot exclude a probability of harm and we set the probability masses accordingly. Therefore, we will consider a moderate belief strength for both the optimistic and neutral prior and a weak pessimistic prior. Following previous recommendations,7 we will define priors as follows: The neutral skeptical prior of moderate strength is normally distributed and centered at the absence of effect [OR = 1; log (OR) = 0] with an SD of 0.355, such that 0.95 of the probability falls in the range of 0.5–2. Therefore, our skeptical prior will follow a normal distribution with a mean of 0 and an SD of 0.355 [N(0, 0.355)] (Figure 1); The pessimistic and optimistic priors are informed by the averaged effect size estimate from the three original studies (PROVHILO:OR= 0.63; iPROVE:OR= 0.45; PROBESE:OR= 0.44; Mean:OR= 0.51). The standard deviation (SD) of the optimistic prior will be defined to retain a 0.15 probability of harm [Pr (OR > 1)], and the pessimistic prior is chosen to retain a 0.30 probability of benefit [Pr (OR < 1)] (Figure 1)” Specific comments: 3. Please add a reference to the published results of the frequentist meta-analysis (Campos et al, BJA 2022 1); only the study protocol is referenced. The mentioned study is already referenced in the manuscript; it is reference #15. If the reviewer is referencing another study, please let us know, and we will add it to the manuscript. 4. The authors will use a half-normal distribution for the heterogeneity prior. Could they briefly explain the rationale to perform a sensitivity analysis with I squared distribution (instead of i.e. Half-Cauchy). We agree. The I2 distribution is used mainly for modelling heterogeneity in conventional Bayesian metanalysis models with aggregate data, as explained in length in Rover et al. Res. Synth. Methods. 2021 Jul 1;12(4): 448–474. Following the reviewer, we changed the distribution of the heterogeneity prior for the sensitivity analysis to a half-Cauchy prior. We changed the manuscript accordingly, which now reads: “We will fit the model by varying the heterogeneity prior τ to a half-Cauchy distribution with location 0 and scale 1.\" 5.“Previous studies suggested a benefit of PEEP and RM, but many studies were neutral or indeterminate when using a frequentist approach. Therefore, we will consider a moderate belief strength for both the optimistic and neutral prior and a weak pessimistic prior. Following previous recommendations,7 we will define priors as follows….”. What exactly does the word “therefore” signify here? It seems sensible to align the means ESs to the preexisting data, the weighting choice for the optimistic vs pessimistic priors could be explained some more (especially with regard to possible pessimistic assumptions, i.e., higher complication incidence). I suggest the authors elaborate a bit more here. Please see our reply to comment #2. We hopefully made the logic behind the priors definition clearer."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1090
|
https://f1000research.com/articles/12-732/v1
|
23 Jun 23
|
{
"type": "Case Report",
"title": "Case Report: Transient complete blindness after coronary angiography",
"authors": [
"Moez Alnazeer",
"Sapna Kher",
"David Ficklen",
"Sapna Kher",
"David Ficklen"
],
"abstract": "Transient cortical blindness is a rare complication that can occur after coronary angiography. We report a case of a 53-year-old Caucasian male with a history of multiple cardiovascular risk factors who presented to the emergency room with chest pressure and shortness of breath. He underwent cardiac catheterization and subsequently developed transient bilateral blindness. His vision gradually improved over the next 72 hours without any intervention. This case highlights the importance of considering transient cortical blindness as a potential complication of coronary angiography and the favorable outcome of this condition.",
"keywords": [
"Keywords: Transient cortical blindness",
"coronary angiography",
"complications",
"case report"
],
"content": "Background\n\nCoronary angiography is a well-established and widely used diagnostic procedure for evaluating the patency of coronary arteries. While the procedure is generally considered safe, there are potential risks associated with it, including bleeding, infection, allergic reactions to the contrast dye, and damage to the artery where the catheter was inserted.1 One rare but potentially serious complication of coronary angiography is transient cortical blindness, which occurs due to the contrast dye used during the procedure.2 As a result, patients may experience a temporary loss of vision that can last from a few minutes to several days. This can be a source of significant stress and anxiety for both patients and healthcare providers. By recognizing and managing this condition, providers can help alleviate patient anxiety and ensure appropriate follow-up care.\n\n\nCase report\n\nA 53-year-old Caucasian male teacher presented to the emergency room with complaints of chest pressure that started two hours after dinner and was associated with shortness of breath. He had a past medical history hyperlipidemia, diabetes mellitus type 2, hypertension, ventricular tachycardia, ventricular fibrillation which had led to defibrillator placement, and of coronary artery disease for which he underwent coronary artery bypass surgery. The patient reported that his mother suffered from a myocardial infarction at age 50 years and his brother died suddenly at age 35 years. Upon arrival at the ER, he was given aspirin, nitroglycerin paste, and enoxaparin. His chest discomfort resolved. The patient underwent cardiac catheterization due to suspicion of acute coronary syndrome.\n\nIopamidol 76% (a nonionic, iso-osmolar iodinated contrast material) was used during the cardiac catheterization. The procedure revealed evidence of three-vessel disease with two of three bypass grafts patent. The left ventricular function was mildly impaired. During the procedure, the patient developed chest pain and significant inferior ST elevation prompting immediate intervention with percutaneous coronary intervention (PCI)/drug-eluting stent of the ostial right coronary artery and PCI/percutaneous transluminal coronary angioplasty (PTCA) of the mid-right posterior descending coronary artery. After recovering from the anesthesia, the patient developed marked bilateral vision loss. MRI of the brain could not be obtained due to the incompatibility of the patient's pacemaker device. A CT scan of the brain without contrast (Figure 1) and a CT angiogram of the head and neck showed no acute intracranial abnormality, aneurysms, or significant stenosis. Ophthalmology evaluation showed significantly reduced visual acuity in the eyes bilaterally of 20/400. The ocular motility was intact. Pupils were 3 mm, equal, and reactive without an afferent pupillary defect. Intraocular pressure with Tono-Pen was 12 mmHg on the right and 15 mmHg on the left. The anterior segment exam was essentially normal. Dilated fundal examination revealed a normal cup/disc ratio of 0.3 in each eye, flat optic nerve and retina, and patent vessels without any hemorrhages or edema. Otherwise, the neurological examination was unremarkable.\n\nThe patient's vision gradually improved without any intervention over 72 hours. His visual acuity returned to normal and he did not experience any further episodes of vision loss.\n\n\nDiscussion\n\nTransient cortical blindness is a rare occurrence following coronary angiography, with an estimated incidence of only 0.05%.2 The differential diagnosis for this condition includes central retinal artery occlusion, amaurosis fugax, or cerebrovascular accident (CVA); however, these are less likely given the normal funduscopic exam of the retina during the episode and lack of ischemic changes on imaging. Transient cortical blindness has been more commonly reported in cases of vertebral artery angiography,3 likely because the occipital cortex receives blood supply from the posterior cerebral artery through the vertebrobasilar system. In the case presented, the patient experienced transient cortical blindness after undergoing coronary angiography, despite having undergone the procedure without complications before undergoing bypass surgery. Reports have suggested that transient cortical blindness after coronary angiography is more prevalent in patients who have undergone coronary artery bypass grafting (CABG).4 It is plausible that direct injection of contrast during angiography may reach the vertebral artery through the internal mammary artery used during CABG. The exact mechanism underlying transient cortical blindness is not yet fully understood, but it has been hypothesized to be related to allergic or immune mediated contrast medium-induced neurotoxicity.5,6 Corticosteroids have been used for the management of some cases, although our patient made a complete recovery without any corticosteroids. The use of hyperosmolar contrast solutions during angiography may increase the permeability of the blood-brain barrier in the occipital cortex, facilitating the entry of contrast agents into the visual cortex area during the procedure. This is particularly common in patients with chronic hypertension.7,8 Unfortunately, using iso-osmolar contrast does not mitigate the risk, as is demonstrated in our case. Re-exposure to contrast material has been reported to be safe.9 However, further research is warranted to better understand the underlying mechanisms and develop strategies for prevention in high-risk patients.\n\nThis case report highlights a rare complication of coronary angiography and is potential occurrence even in patients who underwent the procedure in the past without issues. This serves as a reminder to clinicians to be vigilant and consider the possibility of transient cortical blindness when evaluating patients who develop visual disturbance after coronary angiography. While the case report provides valuable insights, it is important to note that it has limitations. An MRI of the brain which could have provided additional information about potential structural abnormalities or ischemic changes in the brain, could not be obtained due to the patient's pacemaker device which was incompatible with MRI. It is important to note that this represents an individual experience and may not be generalized move to the broader population.\n\nThe patient reported that suddenly losing his vision had caused a feeling confusion, helplessness and fear. During the 72-hour period when his vision gradually improved, he experienced a mix of emotions ranging from hope to uncertainty. The gradual improvement was a relief but he also felt anxious about whether there are vision with fully recovered.\n\nThe patient provided a written informed consent for the publication of this case report, including the use of de-identified clinical data and imaging results. The patient understood that their identity will remain confidential and their participation is voluntary.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nBaim DS, Grossman W: Complications of cardiac catheterization. Cardiac Catheterization, Angiography and Intervention. Baim DS, Grossman W, editors. Baltimore: Williams & Wilkins; 1996; p.17.\n\nFernandes SIL, Carvalho RJR, Santos LMG, et al.: Transient Cor cal Blindness Following Coronary Angiography. JACC Case Rep. 2019; 1(2): 188–191. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMerchut MP, Richie B: Transient Visuospa al Disorder From Angiographic Contrast. Arch. Neurol. 2002; 59(5): 851–854. PubMed Abstract | Publisher Full Text\n\nYazici M, Ozhan H, Kinay O, et al.: Transient cortcal blindness after cardiac catheterization with iobitridol. Tex. Heart Inst. J. 2007; 34: 373–375. PubMed Abstract\n\nMouine N, Ndom MS, Hankari T, et al.: Zbir Transient cortical blindness after coronary angiography: report of 2 cases. Am. J. Mens Health. 2010; 7: 431–433. Publisher Full Text\n\nScherling C, Berkefeld J, Auch-Schwelk W, et al.: Transient bilateral cor cal blindness a er coronary angiography. Lancet. 1998; 351(9102): 570. PubMed Abstract | Publisher Full Text\n\nOktaviono YH, Kawilarang MV, Kawilarang M, et al.: Case Report: Transient cor cal blindness following coronary angiography. F1000Res. 2021 Jun 3; 10: 439. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBorghi C, Saia F, Marzocchi A, et al.: Branzi The conundrum of transient cortical blindness following coronary angiography. J. Cardiovasc. Med. 2008; 9: 1063–1065. PubMed Abstract | Publisher Full Text\n\nBalasingam S, Azman RR, Nazri M: Contrast media induced transient cortical blindness. QJM. February 2016; 109(2): 121–122. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "235569",
"date": "13 Feb 2024",
"name": "Tatsuya Kawasaki",
"expertise": [
"Reviewer Expertise Cardiology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAlnazeer et al. reported a case of transient complete blindness after coronary angiography. This case report highlights the importance of recognizing contrast-induced cortical blindness, which is not well recognized in clinical practice.\nThe reviewer believes that transient blindness due to embolization cannot be completely excluded, and this should be stated in the discussion section.\nThe approach site of the coronary intervention was not shown. Cardiac catheterization via the femoral or left radial artery puts patients at risk for cerebral embolism during the procedure.\nIt would be appreciated if the authors could report the total amount of contrast used during the procedure. I think people would like to know the relationship between contrast dose and the incidence of transient cortical blindness needs to be added.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? No\n\nIs the case presented with sufficient detail to be useful for other practitioners? No",
"responses": []
},
{
"id": "235567",
"date": "27 Feb 2024",
"name": "Toma Spiriev",
"expertise": [
"Reviewer Expertise Neuroanatomy"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI read the paper and I find the case report interesting, with a good level of English, well described case presentation and nice literature review.\nThe case is very well documented, including the patient's history offering valuable insights into a rare but significant complication of coronary angiography.\nThe case reports provides important information about this rare complications increasing the awareness among clinicians about the possibility of transient cortical blindness as a complication of coronary angiography. Such complication has been described in other instances with angiograms of the posterior brain circulation. A major limitation of the case is the lack of MRI data, due to the pacemaker of the patient. MRI could have presented ischemic changes or DWI changes in the occipital lobe, which could provide explanation of transient cortical blindness, as described by other authors citing temporary edema of the occipital lobes.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-732
|
https://f1000research.com/articles/12-730/v1
|
23 Jun 23
|
{
"type": "Research Article",
"title": "Prevalence of and factors associated with depression, anxiety and stress among adolescents in Bangladesh during the COVID-19 pandemic: A population-based study",
"authors": [
"Md Atiqul Haque",
"Afifa Anjum",
"Sabrina Mousum",
"Marium Salwa",
"Zubair Ahmed Ratan",
"Md Maruf Haque Khan",
"Mohammad Tanvir Islam",
"Helal Uddin Ahmed",
"Md Robed Amin",
"Mohammad Abdullah Al Mamun",
"Afifa Anjum",
"Sabrina Mousum",
"Marium Salwa",
"Zubair Ahmed Ratan",
"Md Maruf Haque Khan",
"Mohammad Tanvir Islam",
"Helal Uddin Ahmed",
"Md Robed Amin",
"Mohammad Abdullah Al Mamun"
],
"abstract": "Background: The COVID-19 pandemic has brought significant mental health challenges among adolescents in Bangladesh. This study aimed to investigate the prevalence of and associated factors of depression, anxiety and stress among adolescents of Bangladesh during the COVID-19 pandemic. Methods: This cross-sectional study used a two-stage cluster sampling procedure for collecting the sample. A total of 2030 adolescents were enrolled from urban and rural areas of all eight administrative divisions of Bangladesh. The Depression, Anxiety, and Stress-21 (DASS-21) scale was used to assess depression, anxiety, and stress in adolescents. In addition, data on sociodemographics, parenting style, food insecurity, and anthropometric measures were also obtained. Linear regression was done to measure the risk factors. Results: Depression, anxiety, and stress were identified in 18%, 14%, and 16% of adolescents, respectively. Sociodemographic characteristics such as female sex, higher age, urban resident, food insecurity, and poor parenting were significant risk factors for depression, anxiety, and stress during the COVID-19 pandemic. In addition, inconsistent parenting has been identified as a significant risk factor for depression only. Conclusions: During the COVID-19 pandemic in Bangladesh, depression, anxiety, and stress are found quite common among adolescents. Therefore, necessary action is required to prevent the mental health epidemic from spreading.",
"keywords": [
"COVID-19",
"Depression",
"Anxiety",
"Stress",
"Adolescent",
"Rural",
"Urban",
"Bangladesh"
],
"content": "Introduction\n\nAdolescence is a crucial phase of physical and psychological development, and adolescents are vulnerable to different mental health conditions that are often overlooked (Kieling et al., 2011). Mental health disorders in this population have been recognized as a significant public health challenge given that, according to the World Health Organization (WHO) data, 13% of adolescents worldwide suffer from psychological problems (WHO, 2021). Thus, given the disruption to their daily lives during the COVID-19 pandemic, which has resulted in severe mobility restrictions, including partial or complete lockdowns, it is not surprising that adolescents have experienced an upsurge in psychological problems (Racine et al. 2021). In adolescents already suffering from mental health conditions, sudden closure of academic institutions and extracurricular venues, unexpected bereavements, social isolation, increased screen time, and chronic stress may exacerbate the symptoms (Imran et al., 2020).\n\nDepression, anxiety, and stress have been recognized as the three most common mental health issues among adolescents (Hicks and Heastie, 2008). Globally, depression and anxiety are ranked as the fourth and ninth leading cause of disease and disability in this age group (Reddy, 2010). However, the prevalence of depression and anxiety among adolescents is increasing around the globe (Zhang et al., 2021). In a survey conducted in 2019 in Bangladesh by Anjum et al. (2019) around 37% of participating adolescents reported being affected by depressive disorders. In another study conducted among 622 Bangladeshi adolescents, 30% and 16.4% of participants experienced depression and anxiety, respectively (Moonajilin et al., 2020). Since the COVID-19 outbreak in Bangladesh in March 2020, several preventive nationwide measures have been taken to limit the infection rate, including the closure of educational institutions, as well as episodic lockdowns and travel bans (Hossain et al., 2021). These measures have had an adverse effect on adolescents’ psychological well-being even though this age group was at the lowest risk of infection and fatal outcome.\n\nAs research on the mental health status of Bangladeshi people during the COVID-19 epidemic is limited, data pertaining specifically to adolescents is lacking (Das et al., 2021; Abir et al., 2021; Khatun et al., 2021; Islam et al., 2020). Thus, it is worth noting that through an online-based cross-sectional study involving 10,609 Bangladeshi participants conducted in 2021, Abir et al. (2021) found that 34% of the sample suffered from moderate depression during the COVID-19 pandemic, while in the same year, Das et al. (2021) found that 38% and 64% of 672 participants aged 15−65 years suffered from depression and anxiety, respectively, in Bangladesh. In another study conducted among Bangladeshi university students aged 18−29 years during the pandemic, 35.2%, 40.3%, and 37.7% prevalence of severe depression, anxiety, and stress, respectively, was noted (Islam et al., 2020). This is a marked increase compared to 2020, when Safa et al. (2021) reported 11.8% prevalence of severe anxiety among medical students, while 3.3% of the sample suffered from severe depression.\n\nIn these studies conducted in Bangladesh, different factors have been found to be associated with poor mental health during the COVID-19 pandemic, including female sex, unemployment, living without family, sharing the household with a greater number of family members, urban residence, sedentary lifestyle, greater screen time, and dissatisfaction with the system adopted for remote learning (Das et al., 2021; Islam et al., 2020). Apart from these factors, age, marital status, fear of humiliation, inability to pay attention to studies, and anxiety associated with the risk of being infected by the virus were also linked to the poor mental health status of physicians and medical students (Khatun et al., 2021; Safa et al., 2021). Therefore, the objective of this study was to determine the prevalence of depression, anxiety, and stress symptoms among adolescents during the COVID-19 pandemic in Bangladesh. Its further objective was to assess the factors potentially associated with depression, anxiety, and stress among the study participants.\n\n\nMethods\n\nThis cross-sectional population-based study was carried out among a representative sample of adolescents from rural and urban areas of Bangladesh. A multistage random sampling method was applied for this purpose. Bangladesh is divided into eight administrative divisions, each comprising four to thirteen districts. Within each district, there are several subdistricts known as upazilas, encompassing both rural and urban areas. To ensure representation, we utilized a lottery system to randomly select one district from each division, resulting in a total of eight districts. For urban representation, we specifically chose the Sadar upazilas from the following four districts: Magura, Gazipur, Cumilla, and Mymensingh. Similarly, for rural representation, we included four additional sub-districts: Kamalganj in Moulvibazar district, Sadullapur in Gaibandha district, Banaripara in Barisal district, and Boraigram in Natore district. The municipal territory of the Sadar upazila, which serves as the district headquarters, was designated as the urban area. This municipal area is further divided into several wards, from which we randomly selected one ward from each chosen Sadar upazila as an urban data enumeration area.\n\nIn Bangladesh, each upazila is composed of multiple unions. For the purpose of rural data enumeration areas, we randomly selected one union from each chosen upazila. Additionally, each union consists of several wards, from which we randomly selected one ward for data collection.\n\nRecruitment and training of data collectors took place up to two weeks from 16 May 2021. Afterward, pretesting of the questionnaire was done in the non-sampling area to bring out any discrepancies in the questionnaire as well as the eligibility of the data collectors and based on the findings of that further steps were taken. Finally, data collection was conducted between 26 May 2021 and 6 June 2021. Household mapping was performed in the data enumeration areas before the commencement of the study, and a list of eligible households where adolescents aged 14−19 years lived was prepared. In this study adolescents who were aged 14-19 years and who were residents at the data collection areas were included in this study. The participants who were absent at the time of data collection or were unwilling to participate were excluded from the study.\n\nWith the 13.6% prevalence of mental health disorders among adolescents (NIMH and WHO, 2019), design effect of 1.3, and 5% margin of error, at 95% confidence interval, the approximate sample size was 234. The final sample size was calculated as 257*8 = 2,056 after considering division as the strata and the non-response rate of 10%.\n\nSixteen data collectors and eight field supervisors were recruited and trained on data collection through a two-week intensive training program. Prior to the field data collection, field testing was conducted in order to assess the efficacy of the data collectors and the study instruments. During the data collection, data collectors approached the listed households and invite the potential participant for interview. Face-to-face interviews were conducted in an isolated place at the respondent’s residence, using REDCap (Research Electronic Data Capture) software through Computer Assisted Personal Interviewing (CAPI). During these home visits, participants’ height, weight, and blood pressure (BP) were taken manually using measuring tape, NuLife Plus digital weight scale, and OMRON HEM-7121, respectively. During the height and weight measurements, the participant was asked to stand still, looking forward, having removed any heavy objects, such as a wristwatch. At every step, same-gender data collectors were made available for participants.\n\nA Bengali validated version of the Depression, Anxiety, Stress Scale-21 (DASS-21) was used to measure the level of depression, anxiety, and stress among adolescents (Lovibond and Lovibond, 1995; NIMH and WHO, 2019). It consists of 21 items divided into three self-reported subscales (each with seven items) to assess depression, anxiety, and stress. All items require a response on a 4-point Likert scale (0 = “Did not apply to me at all”, 1 = “Applied to me to some extent, or some of the time”, 2 = “Applied to me to a considerable extent, or a good part of the time”, and 3 = “Applied to me very much, or most of the time”), with participants instructed to consider how they felt during the previous week. Each subscale’s final score was multiplied by two and evaluated based on its severity rating index. The depression, anxiety, and stress scores were determined by summing the values for all items across the three subscales. The findings were interpreted in the manner outlined in Supplementary Table 1.\n\nSociodemographic measures\n\nPertinent sociodemographic data was obtained from the respondents, including age, sex, residential area (urban or rural), parental educational qualifications, parental marital status (currently married vs. separated, widowed, divorced, which were classed under “other”), number of siblings, and number of family members. The number of family members and number of siblings were then further categorized according to the ideal household size and total fertility rate of women in Bangladesh (BBS, 2018).\n\nAlabama Parenting Questionnaire\n\nThe Alabama Parenting Questionnaire (APQ-9) is a nine-item questionnaire that examines three dimensions of parenting behaviors—positive parenting, inconsistent discipline, and poor supervision—with three items related to each dimension (Essau et al., 2006). The responses are given on a 5-point Likert-type scale, anchored at 1 (never) and 5 (always). The three dimensions of this scale were validated in a previous study and were found highly reliable (Elgar et al., 2007). We adapted this questionnaire for use with adolescents. For example, “You threaten to punish your child and then do not actually punish him/her” (inconsistent discipline) was replaced by “Your parents threaten to punish you and then do not actually punish you.” The overall APQ-9 score was calculated by adding the scores from each subscale.\n\nFood insecurity index\n\nThe United Nations Food and Agricultural Organization—Voices of the Hungry initiative (FAO-VoH) developed the Food Insecurity Experience Scale (FIES) in 2014. This scale probes into the self-reported experiences related to food access due to the lack of money or other resources throughout a 12-month recall period, with no regard for frequency of occurrence. As the scale contains eight questions with two response options (yes/no), the total score ranges from 0 to 8, which is subdivided into three categories: food secure (0−3), moderate food insecurity (4−6), and severe food insecurity (7−8). In this study, food security was further dichotomized into food secure (0−3) and food insecure (4−8).\n\nBMI\n\nUsing participants’ weight and height measurements, BMI (kg/m2) was calculated and was categorized based on the ranges provided for south Asian adolescents: <18.5 kg/m2 − underweight, 18.5−22.9 kg/m2 − normal weight, 23−24.99 kg/m2 − overweight and ≥25 kg/m2 – obese (WHO Expert Consultation, 2004).\n\nHypertension\n\nHypertension was defined as having either a systolic BP of 140 mm of Hg or a diastolic BP of 90 mm of Hg, or both.\n\nDescriptive analysis was performed on the sociodemographic data, as well as the anxiety, stress, and depression scores. Frequencies and percentages were calculated as summary measures for the qualitative variables, while arithmetic means and standard deviations (SDs) were used to summarize the quantitative variables. Pearson correlation, independent samples t-test, one-way ANOVA, and multilinear regression model were employed to evaluate the relationships between variables. Independent variables with a p-value ≤ .1 in the bivariate model were entered into the multivariate model. We included adolescents’ sex and age, parental marital status, number of siblings, residential area, food security, positive parenting, inconsistent parenting discipline, and poor parental supervision as independent variables. Three separate multivariate linear regression models were constructed to determine the extent to which the independent variables explained stress, anxiety, and depression, respectively. The associations are reported using unstandardized regression coefficient (B). The sample size was large enough for regression analysis and there was no evidence of multicollinearity among variables. Normal P-P plots of regression-standardized residuals of the dependent variables were acceptable. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 24 for Windows. The raw data can be found under Underlying data (Salwa and Haque, 2023).\n\nEthical clearance was obtained from the Institutional Review Board of BSMMU (Memo no: BSMMU/2021/4408). Prior to data collection, the data collector provided a comprehensive explanation of the study's objectives, as well as the potential benefits and risks involved, to both the parents and the adolescents. Written assent from the adolescents and written consent from their parents were obtained, respectively, in the presence of at least one witness.\n\n\nResults\n\nThe study sample comprised of 2,030 adolescents aged 14−19 years, 41.4% of whom reported having experienced mental health disorders (95% CI = 39.2–43.6%), with a statistically significant female predominance (female vs. male: 66.9% vs. 33.1%, p-value < .001) and no rural−urban difference (40.1% vs. 42.7%, p-value > .05) (Table 1).\n\n¶ Significant at.05 level (independent samples t-test).\n\n† Significant at.05 level (one-way ANOVA).\n\nFigure 1 shows that depressive symptoms were reported by 18% of participating adolescents, while extremely severe depression was noted by 0.4% of the sample. At 16% and 14%, respectively, stress symptoms and anxiety were slightly less prevalent, and reached extremely severe levels in 1.2% and 0.3% of the cases.\n\nTable 3 demonstrates that age (B = 0.575, p-value < .001) and female sex (B = 1.404, p-value < .001) were found to have significant relationships with depressive symptoms in the participating adolescents. Adolescents whose parents were separated, widowed, or divorced (B = 1.664, p-value < .001), who lived in urban regions (B = 1.701, p-value < .001), and who experienced food insecurity (B = 2.437, p-value < .001) showed a higher propensity for depressive symptoms compared to their counterparts. Again, Table 2 and Table 3 exhibit that positive parenting exhibited a substantial negative association with depression (B = -0.247, p-value < .001), whereas poor parental supervision had a significant positive relationship with depression (B = 0.218, p-value < .001).\n\n* Correlation is significant at .01 level.\n\n* At the 10% significance level.\n\nAnxiety was found to be significantly associated with female sex (B = 1.881, p-value ≤ .001), age (B = 0.477, p-value < .001), urban residence (B = 0.795, p-value ≤ .001) and food insecurity (B = 1.357, p-value < .001). Positive parenting had a significant negative relation (B = -0.210, p-value <.001) whereas poor supervision had a significant positive relation (B = 0.093, p-value = .007) with anxiety (Table 3).\n\nStress symptoms among adolescents exhibited a significant relationship with female sex (B = 1.876, p-value ≤ .001), age (B = 0.627, p-value < .001), having separated, widowed, or divorced parents (B = 1.318, p-value = .004), urban residence (B = 2.601, p-value < .001) as well as food insecurity (B = 2.290, p-value < .001). Both positive parenting (B = -0.166, p-value = .008) and inconsistent parental discipline (B = -0.141, p-value = .002) had a significant negative link with stress (Table 3).\n\n\nDiscussion\n\nThe findings obtained in this study indicate 18%, 14%, and 16% prevalence of depression, anxiety, and stress symptoms, respectively, among urban and rural adolescents living in Bangladesh. These percentages exceed those yielded by the 2018−19 Bangladesh's National Mental Health Survey conducted in the pre-pandemic period (National Institute of Mental Health and WHO, 2019), suggesting that the social isolation and worries about contracting COVID-19 have exacerbated these mental health issues. However, a systematic review of the available research on the impact of COVID-19 on the adult population of Bangladesh indicated a much higher prevalence of depression and anxiety in adults (Hossain et al., 2021), likely due to methodological differences, as well as those related to sample characteristics. As no prior research has been conducted on Bangladeshi adolescents’ mental health during the pandemic, it is worth noting that, according to a recent poll in the Latin America and Caribbean region conducted by the United Nations Children's Fund (UNICEF), 27% of the respondents aged 13−29 years experienced anxiety and 15% experienced depression during the COVID-19 pandemic (UNICEF, 2021). Similarly, children and adolescents from European countries have been found to experience a wide range of psychological and behavioral problems during the early stages of the pandemic (Racine et al., 2021). Data yielded by an Australian survey involving 760 adolescents aged 12−18 indicated that about three-quarters reported mental health problems during the COVID-19 pandemic (Li et al., 2021). High prevalence of depression and anxiety was also noted among young adults aged 18−30 years living in the U.S. (Liu et al., 2020). These alarming findings point to the urgent need to provide adequate support to this population to prevent a mental health pandemic that could have devastating long-term repercussions.\n\nIn the cohort analyzed in this study, female sex emerged as a risk factor for depression, anxiety, and stress during the COVID-19 pandemic, concurring with the findings reported by other authors (Qiu et al., 2020; Wang et al., 2020; Alamri et al., 2020). While it is too early to draw any conclusions regarding the causality of this association, it is likely that fluctuations in estrogen and progesterone levels during the menstrual cycle, as well as environmental and hereditary variables, and a variety of physiological, social, and mental health factors play a role (Pigott, 2003; Tambs et al., 2012).\n\nAlthough the present study focused on adolescents, there were still some age-related differences in the prevalence of depression, anxiety, and stress among urban and rural adolescents, with somewhat higher figures noted for those aged 17−19 relative to participants in the 14−16 age group. This finding is supported by a previous comparison of 14−20 vs. 21−35 age cohorts, whereby the former group was found to be more likely to suffer from psychological problems during the pandemic (Liang et al., 2020). However, other authors have noted that depressive and anxiety symptoms are more likely to be observed among older compared to younger adolescents (Xie et al., 2020; Zhou et al., 2020; Chen et al., 2020). Although the relationship between age and depression, anxiety, and stress among adolescents during the pandemic is still unclear, sociodemographic factors and parental mental health have been found to profoundly impact adolescents, and these issues are likely to be exacerbated by the pandemic (Schmidt et al., 2021).\n\nParental marital status was found to have an impact on the mental health of the adolescents that took part in our study, as depression and stress were less prevalent among adolescents whose parents were currently married. In their meta-analysis conducted in 2020, Wahyuningsih et al. (2020) similarly found that parental marital quality could affect the psychological wellbeing of adolescents (Shek, 2010). Available evidence further suggests that adjustment, academic, and behavioral problems, as well as depressed mood, are more likely to be experienced by adolescents whose parents are divorced or separated (Lee and McLanahan, 2015). As the pandemic also posed a risk to physical health, and even survival, it is also noteworthy that the death of one of both parents often leads to mental ill-health and related disorders among adolescents (Bergman et al., 2017). Thus, all these factors combined would likely worsen the mental health of adolescents, especially those living with only one parent.\n\nAccording to our analyses, depression, anxiety, and stress symptoms were more pronounced among adolescents living in urban areas relative to those living in rural areas. These findings are contrasted by the results yielded by the study conducted in China by Zhou et al. in 2020. On the other hand, they concur with the view put forth by Menculini et al. that the urban environment, air pollution, complex social context, and other factors adversely affect the mental health of urban residents (Menculini et al., 2021). These issues are amplified during lockdowns, as urban adolescents would feel the social isolation during lockdowns more acutely than their rural counterparts (Pizarro-Ruiz and Ordóñez-Camblor, 2021).\n\nAs expected, adolescents that had experienced food insecurity throughout the pandemic period were more likely to report depression, anxiety, and stress compared to those who did not have such existential problems. Given that Bangladesh ranks 84th out of 113 countries in the Global Food Security Index 2020, it is evident that food security plays a major role in the mental health status of its residents, and thus adolescents (Shibli, 2021). Similar observations were made by other authors in relation to developed countries, as food insecurity is on the rise across the world and contributes to mental health problems (Rahman et al., 2021; Mishra and Rampal, 2020).\n\nIn the present study, positive parenting style was also found to significantly reduce the level of depression, anxiety, and stress among Bangladeshi adolescents, concurring with the previously reported findings (Kingsbury et al., 2020). Conversely, inconsistent parenting discipline was found to be inversely related to stress, which is counterintuitive and should be examined further. Moreover, according to Tirfeneh and Srahbzu (2020), parental neglect or poor supervision strongly impacts adolescent negative affective emotions.\n\nAs this is the first population-based study to identify the prevalence and risk factors associated with depression, anxiety, and stress among adolescents in Bangladesh, its findings are certainly beneficial, but should be interpreted in light of some limitations. Specifically, owing to the cross-sectional nature of the study, it was not possible to determine causal relationships between any of the examined risk factors and depression, anxiety, and stress among adolescents. Moreover, as all data was self-reported and relied on respondents’ recollection, there is a risk of recall bias. Although the survey was conducted in person and participants could ask for interpretation of unfamiliar terms, there is also a risk of response bias. Finally, type-1 error inflation could have been caused by the use of multiple statistical tests without performing statistical correction of p-values.\n\nWe employed random sampling to collect data from all administrative divisions of Bangladesh, ensuring representation from both urban and rural areas. As a result, the findings from this study can be generalized to the entire population of Bangladesh.\n\n\nConclusions\n\nAccording to this cross-sectional study, a significant percentage of urban and rural adolescents in Bangladesh experienced depression, anxiety, and stress during the COVID-19 pandemic. Age, sex, food insecurity, parenting style, and place of residence emerged as significant risk factors for adolescent mental health. Given that mental health problems during adolescence increase the risk of adult mental distress, responsible authorities must take immediate action if we are to avert a mental health epidemic in the post-COVID era.",
"appendix": "Data availability\n\nMendeley data: Mental Health of Adolescents in Bangladesh. DOI:10.17632/fycfkms359.1. (Salwa and Haque, 2023).\n\nThis project contains the following underlying data:\n\n- Adolescent_Mental health.sav\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nWe would like to express our heartfelt gratitude to the study participants and their parents for their willingness to partake in this investigation and provide thoughtful and responsible responses. We also wish to convey our appreciation towards all the people responsible for field implementation, management, and supervision of this study. We are also grateful for the financial and practical support offered by relevant authorities, especially for the monitoring and supervision of the study.\n\n\nReferences\n\nAbir T, Kalimullah NA, Osuagwu UL, et al.: Prevalence and Factors Associated with Mental Health Impact of COVID-19 Pandemic in Bangladesh: A Survey-Based Cross-Sectional Study. Ann. Glob. Health. 2021; 87(1): 43. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlamri HS, Algarni A, Shehata SF, et al.: Prevalence of depression, anxiety, and stress among the general population in Saudi Arabia during Covid-19 pandemic. Int. J. Environ. Res. Public Health. 2020; 17(24): 9183. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnjum A, Hossain S, Sikder T, et al.: Investigating the prevalence of and factors associated with depressive symptoms among urban and semi-urban school adolescents in Bangladesh: A pilot study. Int. Health. 2019; ihz092. PubMed Abstract | Publisher Full Text\n\nBBS: Report on Bangladesh Sample Vital Statistics 2017. Bangladesh: Bangladesh Bureau of Statistics; 2018.\n\nBergman AS, Axberg U, Hanson E: When a parent dies - a systematic review of the effects of support programs for parentally bereaved children and their caregivers. BMC Palliat. Care. 2017; 16(1): 39. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen F, Zheng D, Liu J, et al.: Depression and anxiety among adolescents during COVID-19: A cross-sectional study. Brain Behav. Immun. 2020; 88: 36–38. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDas R, Hasan MR, Daria S, et al.: Impact of COVID-19 pandemic on mental health among general Bangladeshi population: a cross-sectional study. BMJ Open. 2021; 11(4): e045727. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElgar FJ, Waschbusch DA, Dadds MR, et al.: Development and validation of a short form of the Alabama Parenting Questionnaire. J. Child Fam. Stud. 2007; 16: 243–259. Publisher Full Text\n\nEssau CA, Sasagawa S, Frick PJ: Psychometric properties of the Alabama Parenting Questionnaire. J. Child Fam. Stud. 2006; 15: 595–614. Publisher Full Text\n\nHicks T, Heastie S: High school to college transition: a profile of the stressors, physical and psychological health issues that affect the first-year on-campus college student. J. Cult. Divers. 2008; 15(3): 143–147. PubMed Abstract\n\nHossain MM, Rahman M, Trisha NF, et al.: Prevalence of anxiety and depression in South Asia during COVID-19: A systematic review and meta-analysis. Heliyon. 2021; 7(4): e06677. PubMed Abstract | Publisher Full Text | Free Full Text\n\nImran N, Zeshan M, Pervaiz Z: Mental health considerations for children & adolescents in COVID-19 Pandemic. Pak. J. Med. Sci. 2020; 36(COVID19-S4): S67–S72. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIslam MS, Sujan MSH, Tasnim R, et al.: Psychological responses during the COVID-19 outbreak among university students in Bangladesh. PLoS One. 2020; 15(12): e0245083. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhatun MF, Parvin MF, Rashid MM, et al.: Mental health of physicians during COVID-19 outbreak in Bangladesh: A Web-Based Cross-Sectional Survey. Front. Public Health. 2021; 9: 592058. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKieling C, Baker-Henningham H, Belfer M, et al.: Child and adolescent mental health worldwide: Evidence for action. Lancet. 2011; 378(9801): 1515–1525. PubMed Abstract | Publisher Full Text\n\nKingsbury M, Sucha E, Manion I, et al.: Adolescent mental health following exposure to positive and harsh parenting in childhood. Can. J. Psychiatr. 2020 Jun; 65(6): 392–400. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee D, McLanahan S: Family structure transitions and child development: Instability, selection, and population heterogeneity. Am. Sociol. Rev. 2015; 80(4): 738–763. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi SH, Beames JR, Newby JM, et al.: The impact of COVID-19 on the lives and mental health of Australian adolescents. Eur. Child Adolesc. Psychiatry. 2021; 31: 1465–1477. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiang L, Ren H, Cao R, et al.: The effect of COVID-19 on youth mental health. Psychiatry Q. 2020; 91(3): 841–852. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu CH, Zhang E, Wong GTF, et al.: Factors associated with depression, anxiety, and PTSD symptomatology during the COVID-19 pandemic: Clinical implications for U.S. young adult mental health. Psychiatry Res. 2020; 290: 113172. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLovibond SH, Lovibond PF: Manual for the Depression Anxiety Stress Scales. 2nd ed.Sydney: Psychology Foundation; 1995.\n\nMenculini G, Bernardini F, Attademo L, et al.: The influence of the urban environment on mental health during the COVID-19 Pandemic: Focus on air pollution and migration—A narrative review. Int. J. Environ. Res. Public Health. 2021; 18(8): 3920. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMishra K, Rampal J: The COVID-19 pandemic and food insecurity: A viewpoint on India. World Dev. 2020; 135: 105068. Publisher Full Text\n\nMoonajilin MS, Rahman ME, Islam MS: Relationship between overweight/obesity and mental health disorders among Bangladeshi adolescents: A cross-sectional survey. Obes. Med. 2020; 18: 100216. Publisher Full Text\n\nNational Institute of Mental Health and WHO: National Mental Health Survey of Bangladesh, 2018-19: Provisional Fact Sheet.2019. 21 August, 2021]. Reference Source\n\nPigott TA: Anxiety disorders in women. Psychiatr. Clin. North Am. 2003; 26(3): 621–672. vi-vii. Publisher Full Text\n\nPizarro-Ruiz JP, Ordóñez-Camblor N: Effects of Covid-19 confinement on the mental health of children and adolescents in Spain. Sci. Rep. 2021; 11: 11713. PubMed Abstract | Publisher Full Text | Free Full Text\n\nQiu J, Shen B, Zhao M, et al.: A nationwide survey of psychological distress among Chinese people in the COVID-19 epidemic: Implications and policy recommendations. Gen. Psychiatr. 2020; 33(2): e100213. Erratum in: Gen Psychiatr. 2020;33(2):e100213corr1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRacine N, McArthur BA, Cooke JE, et al.: Global prevalence of depressive and anxiety symptoms in children and adolescents during COVID-19: A meta-analysis. JAMA Pediatr. 2021; 175(11): 1142–1150. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRahman T, Hasnain MDG, Islam A: Food insecurity and mental health of women during COVID-19: Evidence from a developing country. PLoS One. 2021 Jul 29; 16(7): e0255392. PubMed Abstract | Publisher Full Text | Free Full Text\n\nReddy MS: Depression: The disorder and the burden. Indian J. Psychol. Med. 2010; 32(1): 1–2. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSafa F, Anjum A, Hossain S, et al.: Immediate psychological responses during the initial period of the COVID-19 pandemic among Bangladeshi medical students. Child Youth Serv. Rev. 2021; 122: 105912. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSalwa M, Haque MA: Mental Health of Adolescents in Bangladesh. Mendeley Data. 2023; V1. Publisher Full Text\n\nSchmidt SJ, Barblan LP, Lory I, et al.: Age-related effects of the COVID-19 pandemic on mental health of children and adolescents. Eur. J. Psychotraumatol. 2021; 12(1): 1901407. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShek DTL: Parental Marital Quality and Well-Being, Parent-Child Relational Quality, and Chinese Adolescent Adjustment. Am. J. Fam. Ther. 2010; 28(2): 147–162. Publisher Full Text\n\nShibli A: Food insecurity increases amidst the latest Covid-19 spike. The Daily Star. Dhaka: 2021.\n\nTambs K, Kendler KS, Reichborn-Kjennerud T, et al.: Genetic and environmental contributions to the relationship between education and anxiety disorders - a twin study. Acta Psychiatr. Scand. 2012; 125(3): 203–212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTirfeneh E, Srahbzu M: Depression and Its Association with Parental Neglect among Adolescents at Governmental High Schools of Aksum Town, Tigray, Ethiopia, 2019: A Cross Sectional Study. Depress. Res. Treat. 2020; 2020: 1–9. Publisher Full Text\n\nUNICEF: The impact of COVID-19 on the mental health of adolescents and youth.2021 22 August, 2021]. Reference Source\n\nWahyuningsih H, Kusumaningrum FA, Novitasari R: Parental marital quality and adolescent psychological well-being: A meta-analysis. Cogent Psychol. 2020; 7: 1. Publisher Full Text\n\nWang C, Pan R, Wan X, et al.: Immediate psychological responses and associated factors during the initial stage of the 2019 Coronavirus Disease (COVID-19) epidemic among the general population in China. Int. J. Environ. Res. Public Health. 2020; 17(5): 1729. Publisher Full Text\n\nWHO Expert Consultation: Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet (London, England). 2004; 363(9403): 157–163. PubMed Abstract | Publisher Full Text\n\nWHO: Adolescent Mental Health.2021. Reference Source\n\nXie X, Xue Q, Zhou Y, et al.: Mental Health Status Among Children in Home Confinement During the Coronavirus Disease 2019 Outbreak in Hubei Province, China. JAMA Pediatr. 2020; 174(9): 898–900. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang X, Yang H, Zhang JY, et al.: Prevalence of and risk factors for depressive and anxiety symptoms in a large sample of Chinese adolescents in the post-COVID-19 era. Child Adolesc. Psychiatry Ment. Health. 2021; 15(1): 80. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhou SJ, Zhang LG, Wang LL, et al.: Prevalence and socio-demographic correlates of psychological health problems in Chinese adolescents during the outbreak of COVID-19. Eur. Child Adolesc. Psychiatry. 2020; 29(6): 749–758. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "183509",
"date": "20 Jul 2023",
"name": "Minhazur Rahman Rezvi",
"expertise": [
"Reviewer Expertise Public health",
"Public policy",
"Social protection",
"& Politics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you so much for writing an excellent paper. I believe that this paper will bring an additional insight regarding the issue discussed in paper. Despite all the things, this needs some corrections are stated as follows:\nMajor:\nThough authors cited recent literature, authors should also cite papers from 2022 & 2023. There have been published several papers on adolescent mental health & COVID-19 in 2022 & 2023.\n\nThe conclusion part seems not reflect the result part of the paper. The authors should revise the conclusion part again.\n\nAuthors added the food insecurity index in the methodology part. In the result analysis, the authors added an analysis of food insecurity issues but the authors did not make any relation to food insecurity index to mental health impact, as I think. The authors should revise this part.\n\nMinor revision:\nAuthors should revise the abstract part again\n\nIn acknowledgment, authors should add funding sources/organizations or sources of data.\n\nAuthors should revise the introduction part for checking grammatical errors and sentences.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "190939",
"date": "10 Aug 2023",
"name": "Mohammad Meshbahur Rahman",
"expertise": [
"Reviewer Expertise Public Health",
"Global Health",
"Biostatistics",
"Epidemiology and Evidence-Based Research."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI want to thank all authors for conducting this nice research entitled “Prevalence of and factors associated with depression, anxiety and stress among adolescents in Bangladesh during the COVID-19 pandemic: A population-based study”. The manuscript is well-written and important for taking policy of adolescents healthcare.\n\nHowever, the following issues can be addressed to strengthening the study. The point-by-point comments are given below:\nIn abstract, it would be better to present the results in the informative way. For example: for writing statistically significance, give p-value as \"........and poor parenting were significant (p<0.05) risk factors for depression, anxiety....\". For any specific factors, give specific p-value (e.g., inconsistent parenting (p=0.001)).\n\nThere is an inconsistency in the methodology of the study. In abstract, the author (s) reported that the sampling technique was two-stage cluster but, in the full-text article, they mentioned a multistage random sampling technique. Also, in the sample size estimation section, they reported that \"......after considering division as the strata....\" Are the authors applied stratified random sampling?.\n\nThe authors randomly selected 8 districts from 8 administrative divisions where four were from urban and four were from Rural, which does not complete the representative criteria of sampling. It could be more appropriate it they could collect data from both urban and rural areas of eight divisions.\n\nThe authors used several scales in data collection. It could be more interpretable if they could give the cut-off values of these scales (e.g., cut-off values of mild, moderate and severe).\n\nThe authors performed statistical analysis by using various statistical tools like Pearson's correlation, independent samples t-test, one-way ANOVA, and multiple linear regression model. But they did not presented the justification of these statistical tools. The Pearson's correlation test, independent samples t-test, one-way ANOVA, and multiple linear regression analysis are restricted under particular assumptions. Sometimes, we normality, we perform Mann–Whitney U test and Kruskal–Wallis test instead of t-test and ANOVA, due to the fails of normality assumption. The authors' should justified the methodology or in the supplementary file of the study.\n\nIn the result interpretation of Table 3, there is some revision. For example, food insecurity (B=2.437; 95% CI: 1.88-2.99; p=0.001) is more presentable than food insecurity (B = 2.437, p-value < .001).\n\nIn every section where needed, there is a recommendation of writing exact p-value instead of P<0.001.\nIn conclusion, I again thank to the authors for this nice study and recommend to revise the manuscript accordingly.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "190937",
"date": "08 Sep 2023",
"name": "Ridwan Islam Sifat",
"expertise": [
"Reviewer Expertise Health disparities",
"health policy",
"public policy analsysis",
"AI & public policy",
"digital health",
"climate change & health."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe available information regarding the previous study's findings adequately enables readers to comprehend the rationale and procedures of the present study. However, it is important to provide a broader perspective by incorporating insights from other countries in the introduction and background sections. Additionally, the methodology section currently lacks justification for the selection of specific methods, techniques, and sampling procedures. It would be beneficial to clarify the reasons behind these choices. Moreover, it would be beneficial for the authors to provide a detailed description of the methodology used for participant selection, including the criteria for eligibility and the process of randomization. This information would allow readers to assess the potential bias in the sample and the robustness of the study's conclusions. Furthermore, the handling of secondary data remains unclear. It would be helpful to elaborate on the inclusion and exclusion criteria employed for the secondary data analysis. Furthermore, the results paragraph needs to be summarized to provide a more fluent section for the readers. Also, the most relevant study limitations/shortcomings need to be appropriately described as the main caveats have been only partially reported. Finally, what is the take-home message of this manuscript? What are the exact recommendations? You need to rearrange the conclusion part for more analysis. The authors should mention some other perspectives (minority populations). You may cite these articles:\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-730
|
https://f1000research.com/articles/12-729/v1
|
22 Jun 23
|
{
"type": "Research Article",
"title": "Comparative evaluation of the effects of lighting conditions on the shade selection of maxillary central incisor using visual methods",
"authors": [
"Rewa Kawade",
"Seema Sathe",
"Aditee Apte",
"Seema Sathe",
"Aditee Apte"
],
"abstract": "Background: The selection of shade of a tooth is a routine practice for a dentist, especially a prosthodontist, to make esthetically pleasing prostheses. The phenomenon of colour is a matter of perception by the eye. Every opaque object receives light, absorbs some of it and reflects the rest. A tooth being an opaque object, reflects some amount of light. The dominant wavelength of this reflected light is discerned by us as the colour of the tooth. Light has variable properties that influence our perception. Daylight is regarded as the standard source for the selection of the colour of a tooth. Conversely, the lack of optimal circumstances during different times of the day necessitates using artificial illuminants to select shade of a tooth. This study was carried out to compare the accuracy of a shade-matching light (SMILE LINE) to that of standard daylight. Methods: This study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for cross-sectional studies. The study comprised 125 participants of ages ranging from 20 to 30 years. Five observers from the Department of Prosthodontics, Sharad Pawar Dental College (SPDC), Wardha selected the shade of the maxillary central incisor of 125 subjects under sunlight, dental operatory light, and shade-matching light. The statistical analysis was performed using the SPSS software, and Kappa statistics were used to compare the shades selected by the shade-matching light and dental operatory light with sunlight. Results: A strong correlation was discovered between the shades of tooth selected under the shade matching light and shades selected under sunlight for four out of five observers.\nConclusions: The shade correcting device gives shades comparable to those selected under sunlight in ideal conditions making it useful as an alternative to sunlight for shade selection.",
"keywords": [
"Shade selection",
"Shade matching light",
"SMILE LINE",
"esthetic dentistry",
"Shade guide"
],
"content": "Introduction\n\nColour and shade of teeth have gained popularity in cosmetic and esthetic dentistry in the past decades with the increased awareness of the ‘perfect smile’. The advent of the digital age, as well as patient awareness have driven the focus of dentistry to esthetics. Selecting shade is a crucial step for fabricating an aesthetically pleasing prosthesis. Knowledge of colour aids a clinician in this process of selecting a tooth shade. A light source, any object, and the human eye are the factors that interact to create colour.\n\nThe average wavelength of ambient light is known as ‘colour temperature’.1 The temperature of the colour hence associates with the quality of the light source that is expressed in Kelvin (K). As sunlight or daylight is considered the best for selecting tooth colour,2 we must have a light source similar to daylight. Standard daylight is infrequently available as the dominant wavelength of sunlight depends on climate, season, and time of the day. Compared to the daytime, during early hours and sunset the wavelength of incident sunlight is towards the red spectrum. When the light source or the light reflected off an item changes, the perceived colour of the light changes as well.3 This necessitates the use of artificial illuminants for selection of tooth colour as the optimal light conditions are available infrequently. The primary consideration in choosing the light source in this study was how closely it could mimic natural daylight.\n\nThe shade of a prosthesis may not match in shade with the shade of natural tooth due to metamerism, which is a problematic factor. This phenomenon is due to the spectrophotometric changes of the tooth under different light sources.4,5 Two subjects may seem to be of the same colour underneath one light source yet seem to be of varied colour under another light source. Metamerism is attributed to the distribution of spectral energy of a light source. This influences the observer’s perception. Enamel also contains spectrophotometric pigments that differ from the restorative materials used in dentistry.\n\nAs the light source has momentous effect on shade selection and there exists a debate as to which light source other that natural sunlight is accurate enough to reproduce a shade.6 Hence the aim of this study was to evaluate the effect of a light source, which claims to be of the accuracy of sunlight, when compared with sunlight and dental operatory light.\n\nThe aim of this research is to evaluate the effect of different light conditions on shade selection of natural teeth in comparison with daylight.\n\nThe objectives were to evaluate the effect of sunlight on visual shade matching of natural teeth. The first objective was to evaluate the effect of shade matching light (in this case, we have selected SMILE LINE) on visual shade matching of natural teeth. Our second objective was to evaluate the effect of dental operatory chair light on visual shade matching of natural teeth. Finally, we aimed to complete a comparative evaluation of the efficiency of the shade matching light to dental operatory chair light in comparison with sunlight using visual method on shade selection of natural teeth.\n\n\nMethods\n\nThis in-vivo study was conducted in the Department of Prosthodontics, Sharad Pawar Dental College, Sawangi (Meghe), Wardha, and is reported following the STROBE (The Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational studies (see Extended data51).\n\nThe study was conducted from January 2021 to January 2022 during which time the participants were recruited for this single-blinded study. The participants were 1st and 2nd year dental undergraduate students of Sharad Pawar Dental College (recruited via telephone; telephone numbers were obtained with permission from the college). Observers in this study were prosthodontists of the department who were recruited on the basis of their visual acuity. The prosthodontists that qualified the colour deficiency tests were chosen for the shade selection of natural teeth. Data for this study was collected when the prosthodontists indicated the shade of the maxillary central incisors of the subjects. The sample size was calculated for this study that was 125. Each prosthodontist selected shade for only 30 participants per day. One of the five prosthodontists, Dr. Aditee Apte (AA) is author in this study. Data collection was done during the selection of shade under the three illuminants. There was no follow up in this study as the shades were selected by each prosthodontist for the same 125 participants under three different light sources.\n\nEthical approval for this study was obtained from the Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (Previously DMIMS), Deemed to be University (Sawangi, Wardha) with reference number DMIMS (DU)/IEC/2020-21/9393 on 24th December 2020.\n\nInformed written consent was obtained from all the participants and observers for participation in this study and publication of the research data. The permission to use the images of the participants and observers in the presentation of this data was also obtained via a written informed consent.\n\nA summary of the study design is presented in Figure 1. The sample size was calculated with formula for difference between two proportions7:\n\nWhere,\n\nZα is the level of significance at 5% i.e. 95%\n\nConfidence interval = 1.96\n\nZβ = Power of the test = 80% = 0.84%\n\nP1 = 45.8% = 0.458\n\nP2 = 28.9% = 0.289\n\nThis study comprised of 125 subjects that were students in Sharad Pawar Dental College (SPDC) with ages ranging from 20-30 years. Participants with healthy, unrestored maxillary central incisors, without discolouration, prosthesis, fracture, malalignment were included in this study. Participants with fractured, restored, discoloured maxillary central incisors and maxillary incisors with crown prosthesis were not considered in this study. Selection of participants was done over telephone. All the subjects underwent shade selection under the three illuminants of this study. The comparison of variation in selected shades under three illuminants was performed when all the participants selected shade of the same subjects under the three light sources.\n\nFor the purpose of overcoming the eye fatigue for observers, shade selection was done at the rate of only 30 selections per day. The selection of shade was done first under sunlight by all prosthodontists for all 125 subjects. Afterwards, all the five prosthodontists selected shade of the maxillary central incisors of the same 125 subjects under dental chair light and then the shade matching light. The shades indicated by each prosthodontist at each step was blinded from the other prosthodontists to overcome observer bias.\n\nThis study comprised of five experienced prosthodontists as observers from the department and were labelled as observer 1, 2, 3, 4, and 5. One of these observers was author AA. The inclusion criteria for the prosthodontists to be qualified as observers for shade selection was if they passed the Pseudoisochromatic Plates Test (PIP) and Ishihara Tests and were willing to participate in the study. Observers (prosthodontists) that did not pass the PIP and Ishihara tests were excluded from this study. Observers and participants unwilling to participate in this study were excluded.\n\nThe observers were tested using Pseudoisochromatic Test and the Ishihara test for red-green deficiency in vision. These test are efficient in determining the colour deficient individuals that cannot discriminate between the red and green colour.8,9 The tests contained plates with numbers made up of green and red dots of different hue and chroma. The observers were then asked to identify the number made up by the red dots in a green dots containing background.8,10 The significance of carrying out these tests is that the hue of the natural teeth can be reddish-brown, reddish-yellow, grey or greyish red. The red hue is seen for most of these groups and hence testing discrimination of the observers for the red-green colour was essential. The colour blind individuals cannot view the red-green hue and hence cannot select the corresponding shades leading to a mismatch of tooth shade. The colour matching ability of the colour blind individuals is different than that of the normal individuals.11\n\nAll observers passed the tests and hence were qualified for this study. The participants were informed about the process of shade selection and that it would be carried out for a period of about three to six months to avoid the observer bias and observer fatigue. The observers also selected shades of only 30 participants for a day to overcome observer fatigue. Data collection was done by author Dr. Rewa Kawade (RK) and was blinded from the prosthodontists (observers in this study) to remove any source of bias.\n\nFor the selection of shade of subjects, a semi-open grey box was created by covering the portable hospital curtain with a neutral grey sheet. Figure 2 shows one of our observers seated in semi-open grey box. This setup was then moved near a window. The hospital curtain was then bent to create the semi-open grey box. The three sides of the portable hospital curtain would surround the window on three sides. The subjects who were considered for shade selection were seated in this grey box facing the window.\n\nPermission to use the images of the participants and observers in the presentation of this data was obtained via a written informed consent.\n\nPrior to selection of shade, the subjects were asked to remove any makeup. The shade selection under sunlight was carried out during daytime from 11am to 1 pm The shade selection was performed on the maxillary central incisors of the subjects using a VITA Classic Shade guide (VITA classical A1-D4® shade guide Prod. no. G027C).12 The steps of shade selection were explained to the observers as given by Pizzamilglio.13 This arrangement was done first by selecting the maximum hue of the four groups – A4, B4, C4, and D4. This was to be followed by selecting the chroma and value in the respective selected group. For example for group A, they were asked to indicate if the chroma was A1, A2, A3, A3.5 or A4. The shade selection by only one illuminant per day was carried out to remove the observer bias. The artificial illuminants used in this study is the SMILE LINE shade matching device (Figure 3) and the dental chair light. The SMILE LINE shade matching device has the temperature of 6500K which is similar to that considered as ideal or near sunlight.1,4,14–16 Hence this light source was selected to carry out our study which offers an economic option as against the other illuminants. Following protocol was followed when using each illuminant.\n\nShade selection under sunlight\n\nThe observers were to first select shades of the maxillary central incisor under sunlight till they faced observer fatigue. The selection of shade for prolonged periods may lead to fatigue of eyes leading to formation of double images which would affect the results of this study. The subjects were asked to remove any make-up. They were then seated upright on a chair in the semi-open grey box at the eye-level of the observers. They were facing an open window during the shade selection under sunlight. The observers then selected the shade for maxillary central incisors of the subjects (Figure 4). This was carried out during daytime from 11am to 1 pm. All the data was recorded in the form of an excel sheet.\n\nPermission to use the images of the participants and observers in the presentation of this data was obtained via a written informed consent.\n\nShade selection using SMILE LINE shade matching light\n\nThe observers selected the shade using the SMILE LINE with the polarizing filter attached to it that was provided in the kit. The shade matching device was kept at a distance of 15cm as instructed in the manual. The subjects were seated in the grey box with makeup removed. The maxillary central incisor of the subject and the shade tabs were both viewed from the hand-held SMILE LINE shade matching instrument (Figure 5). The shade indicated by the observer for each subject was noted. All the data was recorded in the form of an excel sheet.\n\nPermission to use the images of the participants and observers in the presentation of this data was obtained via a written informed consent.\n\nShade selection using dental chair light\n\nThe grey box was moved to cover the dental chair on three sides at the back and the open end covering the head end of the dental chair. The dental operatory light was switched on and the light was positioned such that it was at a distance of elbow reach from the operator. The VITA Classic shade guide was then used to select the shade of the maxillary central incisor (Figure 6) and the values were again noted in the excel sheet.\n\nPermission to use the images of the participants and observers in the presentation of this data was obtained via a written informed consent.\n\nThere were no drop outs in this study as it was carried out in a period of six months. During this period, for all the participants qualified for the study, shade of maxillary central incisor was selected under the three illuminants on different days. The obtained data in the form of a master chart was then analyzed statistically for comparative evaluation of the shade matching device and dental chair light to sunlight.\n\nStatistical analysis was done in SPSS software using the Kappa (κ) statistics for measuring the intra-observer variation of shade selection under two illuminants. Kappa statistics is the ratio of the number of times there is an agreement between two values. For this case it was the agreement between the shades selected under sunlight and shade selected under shade matching light. The second kappa ratio was for the agreement between the shades selected under sunlight and dental chair light. The agreement of data is complete when the value κ is 1, and no agreement when it is 0. Value more than 0.60 is considered a significant relationship, values less than 0.6 is an indication that the agreement is insufficient.\n\n\nResults\n\nThe number participants that participated in this study were 125 for each prosthodontist. The total of 200 students from 1st BDS and 2nd BDS were examined for their eligibility and hence the 125 participants that satisfied the inclusion criteria were selected. The same 125 participants were then followed up in this study. In case if any participant was not present on the particular day of data collection, the participant was followed up by author RK who made sure the participant shade was selected by all five prosthodontists under three illuminants.\n\nNumber of female participants were 95 and number of male participants were 30. The potential confounders in this study were eliminated during the selection process of the participants and observers. The 125 participants underwent the shade selection process by five prosthodontists. Under each prosthodontist, the participants underwent shade selection by three illuminants. Please see Underlying data50 for the full results.\n\nFollowing the statistical analysis, the κ value for observers 1, 2, 3, 4, and 5 was found to be 0.162, 0.155, 0.087, 0.261, and 0.190 for the tungsten light of dental chair (Table 1). The κ value for the Shade matching device (SMD) for observers were 0.672, 0.298, 0.638, 0.630, and 0.702 calculated for 1, 2, 3, 4, and 5 (Table 1). This κ value is significant for four out of five observers with the highest for observer 5 when compared with the value of significant agreement which is 0.6 (Figure 7).\n\nDCL (Dental chair light), SML (Shade matching light).\n\n\nDiscussion\n\nThe selection of shade is an important step for completion of a restoration as performed by an observer on the subject. In our study, the subjects included were the ones that do not have any abnormality with the maxillary central incisor such as any restoration, crown, fracture or discolouration. Selection of observers was done based on their colour discerning ability tested through the PIP (pseudo-isochromatic test) and Ishihara tests. All observers passed both the PIP test and the Ishihara test and hence were qualified for our study and the above mentioned complication was avoided.\n\nExperience matters in selecting a shade as the ‘eyes’ do not see what the ‘mind’ does not know. The authors Ristic et al,17 Nakhaei et al,18 Sellen et al19 and Sproull4 have suggested that the accuracy of selecting a shade improves when the observer is experienced. Dr. Sproull stated that the study of colour and its perception comes with experience and training. A trained individual would understand the phenomenon of colour, the properties of the tooth, and leading to better selection of shade. In the study by Ristic et al they educated the observers regarding the procedures of shade selection and the appropriate terminologies. This education regarding shade selection proved to be beneficial for the observers as their ability to select shades improved.17 Nakhaei et al stated that the experience did not affect the shade selection when the 3D Master shade guide was used as compared to VITA Classic shade guide.18 The observers in this study were prosthodontists with minimum experience of four years. They were informed about the procedure to be followed for selection of shade.\n\nPerception of the tooth colour is also influenced by the background colour or the colour of the operatory. Several studies have suggested numerous colours to be used for background. The colours black, white, blue, pink, and grey have been reportedly used on various occasions.20–22 The white background enhances the reflections providing an increase in value and the black increases the contrast. Conversely when we stare at a black background the receptors for back colour will fatigue and a white after image is seen when we look away.1,16 The use of pink background was justified for use as it is the colour of the surrounding mucosa.20 The blue background was chosen as it is the complementary colour.20 Use of blue coloured background will then cause the blue receptors to fatigue and the complementary orange colour will be seen in the after images. All these backgrounds in fact, have a disadvantage that they will initiate a change in colour in the retina in their respective complementary shade.1 This is a property of the eye and colour vision that these complementary colours then cause a distortion of the retinal receptors such that the complementary colour perception is affected.1,23 Grey does not have a complementary colour and hence will not cause any change in the perception of other colours.1,16,19,23–26 Hence, the use of a grey background, which is a true neutral colour, was selected.1,19,24–26\n\nThe common mode for selection of a shade is by the means of a shade guide. The VITA 3D Master shade guide and VITA Classic shade guides are popular among dentists. Studies have revealed that the use of VITA Classic shade guide is more reliable, popular, and accurate for selection of shade than 3D Master22,27,28 Although the studies by Paravina29 and Ongul et al30 support the VITA 3D Master shade guide, due to its consistent and systematic shade variation in the colour spectrum, this shade guide is difficult to use especially if the operators are not well versed with the procedure and steps to use it.31 According to the study by Dudea et al, the VITA 3D Master shade guide causes fatigue owing to increased number of shade tabs than the VITA Classic shade guide.22 The time taken to select a shade for any tooth subsequently decreases as the number of shade tabs to choose from decreases. The VITA shade guide was also tested for its reliability when compared to reliability of the 3D Master shade guide by Kim-Pusateri et al and found no difference between the two.27 Considering the popularity of VITA Classic shade guide it was used for this study. The order of the VITA shade guide was rearranged by the value in the present study as suggested by Pizzamiglio.13 This arrangement was done first by selecting the maximum hue of the four groups – A4, B4, C4, and D4. This was to be followed by selecting the chroma and value in the respective selected group. This method of shade selection was used for this study.\n\nFor the elimination of the subjective errors of visual shade matching, various instruments such as spectrophotometers,15,21,26,30,32,33 spectroradiometers,34,35 colourimeter,11,27,36 and photographic methods37 have been used in various studies in literature. However, visual shade selection is the method of choice that is routinely performed by dentists due to its ease as the other methods can be inconsistent.25,32,36,38–41 Lagouvardos et al in their article stated that the L*a*b* values and displayed shades by colourimeter and spectrophotometer were different.42 This concludes that the inter device reliability of the instruments is not sufficient. The study by Kim-Pusateri et al also concluded that the devices have dissimilarity in their shade selection.43 Hence, the visual method was used for the study.\n\nEffect of the incident light has been studied in the past but these experiments have been carried out comparing the shade tabs of shade guides.3,11,26,27,30,32,34,35,44,45 The observers in these studies were asked to select a shade of a blinded shade tab with the shade guide. The detriment of this study design is that the shade tabs are inconsistent in their coverage of tooth shades in the population as mentioned by Ahn46 and Paravina.28,29 The shade tabs are made up of ceramics that have different optic nature when compared with the natural teeth. A difference is also found in the perception of the shade of the shade tab and the natural tooth. Incident light on the surface of ceramics produces optical sensation in the eye that is unlike the tooth.1,26 Studies conducted on the ceramic shade guides cannot validate the accuracy of shade on natural teeth. Perception of the colour of a tooth is affected largely by metamerism and the surface characteristics of a tooth as well.1,4,5 So natural teeth were used for shade selection in our study.\n\nDigitalization in dentistry has given us a range of instruments that will match shades within seconds with precision. These devices however are costly and can be out of reach of a regular dentist.47 The visual method of shade selection remains to be the most popular aid for shade selection.28 The critical appraisal by Paravina justifies the superiority of visual shade matching.28 The observer’s perception is a major influence on the selected shade as it is ultimately the patient himself who will perceive the colour of the restoration with their eyes.\n\nIlluminant plays an important role in selection of the shade. Sunlight is considered as the gold standard for shade selection. The temperature of sunlight is 5000K which is a quality that we look for in an alternative light source.16 This study was conducted to evaluate the effect of two illuminants on shade matching of the maxillary central incisor with the help of experienced Prosthodontists. The illuminants selected were dental chair light (DCL), and Shade Matching Light (SML). Light is a major determining factor for shade matching and there have been various studies regarding the ideal source of light for selection of shade of a tooth. The effect of an illuminant on the shade of a natural tooth changes the accuracy of the selected shade. Shade matching under a light source comparable to sunlight is recommended by many authors. Although the D65, D55 sources are ideal near the daylight, considering the cost it maybe unaffordable for some dentists. A light source needs to be easily available, easy to operate and accurate enough to allow their mass usage. The SMILE LINE shade matching device has the temperature of 6500K which is similar to that considered as ideal or near sunlight.1,4,14–16 Hence this light source was selected to carry out our study which offers an economic option as against the other illuminants.\n\nThis study compared the accuracy of dental chair light to that of sunlight which was taken as the standard illuminant. The kappa statistics for the dental chair light were 0.087, 0.155, 0.162, 0.190, and 0.261 that indicated insufficient agreement for similarity for the observers, which can be referred back to the temperature of these lights. The dental chair light is usually a tungsten-based light in the older dental chairs. The newer LED lights have also been incorporated in the dental chairs that overcome the lower temperatures of the tungsten-based lights. The dental chair light and its inefficiency have been established in the literature in previous studies. These studies stated that these lights are either inclined towards red or blue spectrum.1,4,5,16,48,49 The temperature of the tungsten/incandescent light is lower than that of the ideal conditions and hence it causes a mismatch due to variation in the perception. Thus the shade matching light could not attain similar results in the selected shade when compared with sunlight.\n\nThe shade matching similarity, as calculated using Kappa statistics, between the Shade matching light (SML) and sunlight was found to be significant for all the 5 observers. The Kappa value was found with strong correlation for observers 1, 3, 4, and 5; whereas the agreement was slight for observer 2. These results are in agreement with the studies performed by Curd,44 Gokce,11 Jouhar,45 Berger,5 and Carsten.16 The authors concluded that the shade selection performed under the shade correcting devices used in their respective studies was significantly better than the shades selected under sunlight. These studies were conducted on various shade correcting instruments however, the use of the SMILE LINE shade matching light was not mentioned. Hence this shade correcting light was selected for this study. The authors suggested the use of a light correcting device for selecting colour of teeth as the sunlight is inconsistent in nature. This inconsistent nature of sunlight is attributed to place, time of selection, clouds, and pollution.1,24,47\n\nAlthough the sunlight is considered as the ideal source of light for selecting shades, there are occasions when adequate amount is not available. The selection of shade itself might not be performed during the day. In such conditions, we can opt for a light correcting device for selecting tooth shades and get results that are esthetically pleasing under sunlight.\n\nWithin the constraints of this study the limitations are\n\n1. The means of visual method for shade selection used in this study can be biased due to the lighting conditions, background colour, mood of the observer, and colour perception of the observer himself.\n\n2. Although VITA Classic shade guide is more user friendly, the VITA 3D Master shade guide has been proved to more vastly cover the spectrum of shades which can be taken up for further evaluation.\n\n3. The use of digital devices can be performed to compare the accuracy of shade selection in further studies.\n\nAccording to the results obtained in this study, the shade matching light is comparable to that of sunlight and hence can be used as a substitute of sunlight while selecting shade. The results suggest that shades selected under this light had significant similarity, as calculated by Kappa ratio, to the shades selected under sunlight for four out of five observers. To summarize the findings of this study we can state that there is a strong correlation between the shades selected by the observers under shade matching device and the shades selected under sunlight with the kappa value of 0.5864 (average for the five observers).\n\nThe selected shade for a tooth using shade correcting light is significantly similar to the shade selected under sunlight. Out of five observers considered for shade selection, four had strong correlation between the shades selected under sunlight and shade corrected light suggestive of the same. The shades selected under dental operatory light showed very less correlation with the shades of the tooth selected under sunlight. As quoted correctly, to disguise the art in nature is the supreme form of art. The ideal conditions for selecting a shade should be created for each case that will lead to perfectly matched restorations and prosthesis. This can be achieved using the a shade correcting device.",
"appendix": "Data availability\n\nFigshare: Thesis data.csv, https://doi.org/10.6084/m9.figshare.22650958.v1. 50\n\nThis project contains the following underlying data:\n\n- Thesis data.csv (data sheet of the shades selected by five observers under sunlight, dental chair light, and shade matching light).\n\nZenodo: STROBE guidelines checklist. https://doi.org/10.5281/zenodo.7976827. 51\n\nThis project contains the following extended data:\n\n- STROBE-checklist-v4-cross-sectional.doc.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nFondriest J: Shade matching in restorative dentistry: the science and strategies. J. Prosthet. Dent. 2004 Jun; 91(6): 553. Publisher Full Text\n\nMohammed AO, Mohammed GS, Mathew M, et al.: Shade Selection in Esthetic Dentistry: A Review. Cureus. 2022 Mar 20 [cited 2023 Apr 22]. Publisher Full Text Reference Source\n\nDagg H, O’Connell B, Claffey N, et al.: The influence of some different factors on the accuracy of shade selection. J. Oral Rehabil. 2004 Sep; 31(9): 900–904. PubMed Abstract | Publisher Full Text\n\nSproull RC: Colour matching in dentistry. Part III. Colour control. J. Prosthet. Dent. 1974 Feb; 31(2): 146–154. Publisher Full Text\n\nBergen SF, McCasland J: Dental operatory lighting and tooth colour discrimination. J. Am. Dent. Assoc. 1977 Jan; 94(1): 130–134. PubMed Abstract | Publisher Full Text\n\nKawade R, Kambala SS: Comparative Evaluation of the Effects of Lighting Conditions on the Shade Selection of Ceramics using Visual Method. J. Pharm. Res. Int. 2021 Dec 28; 3771–3775. Publisher Full Text\n\nChadha V: Sample size determination in health studies. Newslett. Natl. Tubercul. Inst. 2006; 42: 55–62.\n\nHaskett MK, Hovis JK: Comparison of the Standard Pseudoisochromatic Plates to the Ishihara Colour Vision Test. Optom. Vis. 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PubMed Abstract | Publisher Full Text\n\nLee YK, Yoon TH, Lim BS, et al.: Effects of colour measuring mode and light source on the colour of shade guides. J. Oral Rehabil. 2002 Nov; 29(11): 1099–1107. PubMed Abstract | Publisher Full Text\n\nCarston DL: Successful shade matching-What does it take? Compend. Contin. Educ. Dent. 2003 Mar; 24(3): 175–188. 180, 182 passim; quiz 188.\n\nRistic I, Stankovic S, Paravina RD: Influence of Colour Education and Training on Shade Matching Skills: Influence of Colour Education and Training. J. Esthet. Restor. Dent. 2016 Sep; 28(5): 287–294. PubMed Abstract | Publisher Full Text\n\nNakhaei M, Ghanbarzadeh J, Alavi S, et al.: The Influence of Dental Shade Guides and Experience on the Accuracy of Shade Matching. J. Contemp. Dent. Pract. 2016 Jan; 17(1): 22–26. PubMed Abstract | Publisher Full Text\n\nSellen PN, Jagger DC, Harrison A: The selection of anterior teeth appropriate for the age and sex of the individual. How variable are dental staff in their choice? J. Oral Rehabil. 2002 Sep; 29(9): 853–857. PubMed Abstract | Publisher Full Text\n\nNajafi-Abrandabadi S, Vahidi F, Janal MN: Effects of a shade-matching light and background colour on reliability in tooth shade selection. Int. J. Esthet. Dent. 2018; 13(3): 198–206.\n\nBraun A, Glockmann A, Krause F: Spectrophotometric evaluation of a novel aesthetic composite resin with respect to different backgrounds in vitro. Odontology. 2013 Jan; 101(1): 60–66. PubMed Abstract | Publisher Full Text\n\nDudea D, Gasparik C, Botos A, et al.: Influence of background/surrounding area on accuracy of visual colour matching. Clin. Oral Investig. 2016 Jul; 20(6): 1167–1173. PubMed Abstract | Publisher Full Text\n\nPensler AV: Shade selection: problems and solutions. Compend. Contin. Educ. Dent. 1998 Apr; 19(4): 387–390. 392–4, 396; quiz 398.\n\nClark EB: An Analysis of Tooth Colour. J. Am. Dent. Assoc. 1931 Nov; 18(11): 2093–2103. Publisher Full Text\n\nSampaio CS, Atria PJ, Hirata R, et al.: Variability of colour matching with different digital photography techniques and a gray reference card. J. Prosthet. Dent. 2019 Feb; 121(2): 333–339. PubMed Abstract | Publisher Full Text\n\nCorcodel N, Helling S, Rammelsberg P, et al.: Metameric effect between natural teeth and the shade tabs of a shade guide: Metameric effect between teeth and tabs. Eur. J. Oral Sci. 2010 May 11; 118(3): 311–316. PubMed Abstract | Publisher Full Text\n\nKim-Pusateri S, Brewer JD, Dunford RG, et al.: In vitro model to evaluate reliability and accuracy of a dental shade-matching instrument. J. Prosthet. Dent. 2007 Nov; 98(5): 353–358. PubMed Abstract | Publisher Full Text\n\nParavina RD, Swift EJ Jr: Colour in Dentistry: Improving the odds of correct shade selection. J. Esthet. Restor. Dent. 2009 Jun; 21(3): 202–208. PubMed Abstract | Publisher Full Text\n\nParavina RD, Majkic G, Imai FH, et al.: Optimization of Tooth Colour and Shade Guide Design. J. Prosthodont. 2007 Jul; 16(4): 269–276. Publisher Full Text\n\nÖngül D, Şermet B, Balkaya MC: Visual and instrumental evaluation of colour match ability of 2 shade guides on a ceramic system. J. Prosthet. Dent. 2012 Jul; 108(1): 9–14. Publisher Full Text\n\nMarcucci B: A shade selection technique. J. Prosthet. Dent. 2003 May; 89(5): 518–521. Publisher Full Text\n\nPark JH, Lee YK, Lim BS: Influence of illuminants on the colour distribution of shade guides. J. Prosthet. Dent. 2006 Dec; 96(6): 402–411. PubMed Abstract | Publisher Full Text\n\nTashkandi E: Consistency in colour parameters of a commonly used shade guide. Saudi Dent. J. 2010 Jan; 22(1): 7–11. Publisher Full Text\n\nLee YK, Yu B, Lim HN: Lightness, chroma, and hue distributions of a shade guide as measured by a spectroradiometer. J. Prosthet. Dent. 2010 Sep; 104(3): 173–181. PubMed Abstract | Publisher Full Text\n\nLee YK, Yu B, Lim JI, et al.: Perceived colour shift of a shade guide according to the change of illuminant. J. Prosthet. Dent. 2011 Feb; 105(2): 91–99. PubMed Abstract | Publisher Full Text\n\nParavina RD, Powers JM, Fay RM: Dental Colour Standards: Shade Tab Arrangement. J. Esthet. Restor. Dent. 2001 Jul; 13(4): 254–263. PubMed Abstract | Publisher Full Text\n\nĐozić A, Kleverlaan CJ, Aartman IHA, et al.: Relation in colour among maxillary incisors and canines. Dent. Mater. J. 2005 Mar; 21(3): 187–191. Publisher Full Text\n\nRagain JC: A Review of Colour Science in Dentistry: Shade Matching in the Contemporary Dental Practice. J. Dent. Health Oral Disord. Ther. 2016 Jul 15; 4(2): 01–05. Publisher Full Text\n\nIshikawa-Nagai S, Yoshida A, Da Silva JD, et al.: Spectrophotometric Analysis of Tooth Colour Reproduction on Anterior All-Ceramic Crowns: Part 1: Analysis and Interpretation of Tooth Colour. J. Esthet. Restor. Dent. 2010 Feb; 22(1): 42–52. PubMed Abstract | Publisher Full Text\n\nVaidya S, Ahuja N, Bajaj P, et al.: Objective measurement of shade colour in age estimation. J. Forensic Dent. Sci. 2015; 7(3): 171–174. PubMed Abstract | Publisher Full Text\n\nMiller L: Shade selection. J. Esthet. Dent. 1994; 6: 47–60. Publisher Full Text\n\nLagouvardos PE, Fougia AG, Diamantopoulou SA, et al.: Repeatability and interdevice reliability of two portable colour selection devices in matching and measuring tooth colour. J. Prosthet. Dent. 2009 Jan; 101(1): 40–45. Publisher Full Text\n\nKim-Pusateri S, Brewer JD, Davis EL, et al.: Reliability and accuracy of four dental shade-matching devices. J. Prosthet. Dent. 2009 Mar; 101(3): 193–199. Publisher Full Text\n\nCurd FM, Jasinevicius TR, Graves A, et al.: Comparison of the shade matching ability of dental students using two light sources. J. Prosthet. Dent. 2006 Dec; 96(6): 391–396. PubMed Abstract | Publisher Full Text\n\nJouhar R: Comparison of Shade Matching Ability among Dental Students under Different Lighting Conditions: A Cross-Sectional Study. Int. J. Environ. Res. Public Health. 2022 Sep 20; 19(19): 11892. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAhn JS, Lee YK: Colour distribution of a shade guide in the value, chroma, and hue scale. J. Prosthet. Dent. 2008 Jul; 100(1): 18–28. PubMed Abstract | Publisher Full Text\n\nBrewer JD, Wee A, Seghi R: Advances in colour matching. Dent. Clin. N. Am. 2004 Apr; 48(2): 341–358. Publisher Full Text\n\nBarna GJ, Taylor JW, King GE, et al.: The influence of selected light intensities on colour perception within the colour range of natural teeth. J. Prosthet. Dent. 1981 Oct; 46(4): 450–453. PubMed Abstract | Publisher Full Text\n\nSproull RC: Colour matching in dentistry. Part II. Practical applications of the organization of colour. J. Prosthet. Dent. 1973; 29(5): 556–566. Publisher Full Text\n\nKawade R: Thesis data.csv. [Dataset]. figshare. 2023. Publisher Full Text\n\nKawade R: STROBE guidelines checklist. [Dataset]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "191792",
"date": "01 Aug 2023",
"name": "Stephen Westland",
"expertise": [
"Reviewer Expertise I am a colour scientist with considerable research experience in dental aesthetics."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an interesting paper that merits indexing. It describes research that has been conducted to compare shade selection in prosthodontics carried out with several different light sources. Generally, the experiment is adequately described and the conclusions that are drawn are justified. However, the review of the literature is a little limited (only six references are reviewed in the Introduction) and there are some misconceptions in the text which I think would be confusing to some readers. The misconceptions are listed below:\n\nPage 3, para 2: The authors state that the average wavelength of ambient light is known as the colour temperature. A reference is provided for this statement but the reference is only a single paragraph that makes no mention of colour temperature so I could not check the source. However, it is definitely not the case that the average wavelength of ambient light is known as the colour temperature. The correlated colour temperature of a whitish light source is the temperature (in K) of a black-body radiator whose perceived colour is most similar to the light source. It therefore defines the colour appearance of the light source but makes no comment on the wavelength distribution of the light source. [Note that there is a similar issue in the Abstract.] The authors should not make reference to the term 'dominant wavelength in this paper because it has no relevance.\n\nPage 3, para 3: The authors state that ‘Two subjects may seem to be of the same colour underneath one light source yet seem to be of varied colour under another light source.’ The term ‘varied’ could be confusing. I suggest this is rewritten as ‘Two objects may seem to be of the same colour when viewed under one light source yet appear to be different in colour under another light source.’\n\nPage 3, para 3: More seriously, the authors write that ‘Metamerism is attributed to the distribution of spectral energy of a light source.’ It is not correct to claim that metamerism is simply a property of the light source. If two samples have identical spectral properties then they will always appear to be a colour match (no matter what the light source) when viewed under the same conditions. However, metamerism can occur when the spectral reflectance factors of two samples are dissimilar; when this is the case, the samples may be a visual match under one light source but then may appear as a mismatch under a different light source.\n\nPage 3, para 8: The authors state that observers were recruited on the basis of their visual acuity but then describe tests of colour vision rather than visual acuity. I would be surprised if observers were selected on the basis of visual acuity. If they were selected on the basis of having good colour vision then this should be stated instead of visual acuity.\n\nPage 9, para 5: In this paragraph the authors discuss their choice of colour of background. I agree that grey was a good choice. However, when discussing the possibility of using black the authors refer to ‘receptors for back colour’. Is this a typo? Do they mean black colour? Anyway, there are no receptors for black. Indeed, the use of black could hardly result in retinal fatigue since it reflects so little light. When discussing blue backgrounds (and perhaps this is nitpicking) there are no blue receptors. Contrary to popular opinion the visual system does not have red, green and blue receptors. Perhaps here the authors could write that ‘the short-wavelength sensitive cones in the retina are fatigued by the short-wavelength light reflected by the blue background.’\nIn addition, I have the following minor comments:\nFigure 7 is unnecessarily confusing with the two sets of bars. The blue bars can be simply replaced by a horizontal line (at kappa = 0.6) to indicate the threshold.\n\nThe authors note that observers only evaluated 30 participants a day. They mentioned this at least three times (once on page 3 and twice on page 5). I am not sure this repetition is required.\n\nTable 1: If I understand it correctly the SML agrees with Sunlight to a greater extent than the DCL agrees with Sunlight. However, the kappa only exceeds 0.6 for 4 of the 6 observers. Also, if I understand it correctly, a kappa of 0.6 means that there are still differences in the selected shade in about 40% of cases. I wonder of the authors should discuss the clinical significance of this.\n\nPage 9: para 7: The term ‘colorimeter’ is spelt without a u even in British English.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "191785",
"date": "03 Aug 2023",
"name": "Kevin George Varghese",
"expertise": [
"Reviewer Expertise Prosthodontics and Implantology"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors have compared the effects of lighting conditions on shade selection. The study has concluded that the shade correcting device has provided comparable results to those done under direct sunlight.\nAlthough the authors have attempted the study, the main objective of the study to compare shade correcting device to the dental operatory light and sunlight does not warranty any novelty.\nVarious articles have already established the importance of shade correcting device for shade selection. This is particularly true when shade selection has to be done at night or in a clinical operatory setting without any sunlight exposure. It is almost impractical to bring the patient under sunlight for shade selection.\nTherefore, the reviewer is of the opinion that this present study does not add any valuable contribution to what is already known in the literature.\n\nAdditionally, although there are lot of questions that can be asked, few points that might improve the manuscript are:\nit is recommended to provide good quality photographs when submitting a manuscript.\n\nLanguage and grammar needs improvement.\n\nInformation regarding the participants under the study that does not directly contribute to the obtained results may be omitted.\n\nAvoid random statements such as VITA classic guide being \"user-friendly\".\n\nHow did the observers confirm their findings? Was spectrophotometer or any other device used to standardize the selected shade?\n\nWhat does \"Selection of participants was done over telephone\" mean? What is its significance in the process of selection?\nStatistical analysis methods need to be further evaluated.\nOverall, the quality of manuscript and the study design is poor and needs further improvement if it is to be considered for indexing.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-729
|
https://f1000research.com/articles/11-155/v1
|
08 Feb 22
|
{
"type": "Research Article",
"title": "Scopus based bibliometric and scientometric analysis of occupational therapy publications from 2001 to 2020",
"authors": [
"Koushik Sau",
"Yogendra Nayak",
"Koushik Sau"
],
"abstract": "Background: Occupational therapy (OT) is one of the allied health professions that had its first journals way back in 1920. The main objective of this study was to find out the publication trend in the field of OT research for the period of 2001-2020 using the principles of bibliometrics and scientometrics. Methods: The data was retrieved from Scopus from the past 20-years (2001-2020). VOSviewer software was used to find year-wise publications in OT-specific and non-OT-specific Journals along with top journals, countries, organisations, authors, cited articles, and highly used keywords. Results: There was a steady growth of OT articles from the past 20-years. Scopus indexes 16 OT-specific journals are identified. American Journal of Occupational Therapy, British Journal of Occupational Therapy Journal, Australian Occupational Therapy Journal, Scandinavian Journal of Occupational Therapy and Canadian Journal of Occupational Therapy are the leading publications and citations. Comparison of OT-specific and non-OT journals inferred that the OT-specific papers are three times more published in non-OT journals. There is a trend in publishing multidisciplinary medical journals than OT journals. The US publishes the highest number of articles, followed by the UK, Australia, Canada, and Germany. Though the US alone produced a considerable number of articles (9517), only five organisations are listed in the top-20, compared to Canada (n=6) and Australia (n=5). Australia represents the highest published authors (n=11/20), and Canada represents a highly cited author from the top-cited publications. The “occupational therapy”, “rehabilitation”, “stroke”, “physical therapy,” and “activities of daily living” are the five common keywords used by OT authors. This study lists top-20 journals along with their CiteScore and Journal Impact Factor. Conclusions: This study will help the budding researchers in OT to select a suitable quality journal for publication and, further, helpful for research promotion, researcher incentivising, grant allocations, and policymakers in the OT field.",
"keywords": [
"Occupational therapy",
"occupational therapy journals",
"core journals",
"citations metrics",
"Scopus",
"VOSviewer"
],
"content": "Introduction\n\nOccupational therapy (OT) is one of the allied health professions practiced globally. Research and research publications are an integral part of the OT profession. “Archives of Occupational Therapy” was the first published OT journal published in 1922 (Cruz et al., 2019). In the 21st century, most of the journals became online web-based after the invention of the internet (Cruz et al., 2019). There are thirty-nine journals published that have contained “occupational therapy” in journal-title available online. Thirty-two among those journals are published in the English language (Cruz et al., 2019). These journals are core OT journal that mainly publishes OT-related articles. With the advancement in electronic databases and the online availability of periodicals, the newer bibliometrics and scientometrics methods of journal evaluation or evaluation of research measures are evolved (Meho and Yang, 2006). Citation analysis and content analysis are two commonly used methods of bibliometric analysis (Wallin 2005; T. Brown, Gutman, Ho, et al., 2018). This method is proven to examine the impact or influence of published articles, journals, researchers, institutions, and countries. Further, this method evaluates the performance in micro-level such as institution/university performance to macro-level such performance of a particular profession in research and country-wise research evaluation (Wallin 2005; T. Brown, Gutman, Ho, et al. 2018).\n\nContent and citation analysis is a common practice in bibliometrics of occupational therapy. In the past, most of the content analysis was performed for specific OT journals such as the American Journal of Occupational Therapy (AJOT) (Ottenbacher and Short, 1982; Ottenbacher and Petersen, 1985), Canadian Journal of Occupational Therapy (CJOT) (Ernest, 1983), Australian Occupational Therapy Journal (AOTJ) (Trevan-Hawke, 1986; Madill et al., 1989), British Journal of Occupational Therapy Journal (BJOT) (Cusick, 1995; Mountain 1997) and Occupational Therapy Journal of Research (OTJR) (G. T. Brown and Brown, 2005). Pearl et al. (2014) evaluated and reported the content of five occupational therapy journals as AJOT, AOTJ, BJOT, CJOT, and Scandinavian Journal of Occupational Therapy (SJOT).\n\nMost of the reported studies were based on the cited journal analysis, that is, analysis of what OT journals articles cited from other journals (Johnson and Leising, 1986; Roberts, 1992; Reed, 1999; Potter, 2010). Recently, Nowrouzi-Kia et al., (2018) evaluated top publications with more than 100-citations in occupational therapy. This study was the first to uncover the highest annual citation rates, randomised control trials, literature reviews, and cross-sectional studies in occupational therapy.\n\nZiviani and colleagues (1984) analysed the content and citation of three OT journals, AJOT, BOTJ, and AOTJ. It was the first bibliometric study examining both content and authority in the OT field. In the recent past, bibliometric studies have become a popular method to know the publication trends, find researchers/authors in a particular topic, and identify research journals where prospective authors select to publish their manuscripts. This type of study helps identify the publication landscape of a specific profession (MacDermid et al., 2015). These data are also used as criteria for research promotion, researcher incentivizing, grant allocations, and policymaking. Further, these data can also be used to benchmark faculty, department, and institute or research organization (T. Brown et al., 2019).\n\nSeveral studies were reported on the performance of OT researchers. Those studies evaluate OT authors' publication output in terms of their content and citations impact. All analyses were conducted for OT authors from specific geographical locations such as Canada (MacDermid et al., 2015), Brazil (Folha et al., 2017), the United Kingdom (T. Brown, Ho et al., 2018), and Australia (T. Brown, Gutman, and Ho, 2018). Recently one study reported the bibliometric analysis for authors of western countries and Asian countries. It includes a total of nine countries among them, United States (US), Canada, the United Kingdom (UK), and Australia were included as countries of the west, and Hong Kong, Japan, Taiwan, Singapore, and South Korea were included as Asian countries (Man et al., 2019). Among those few publications, it was observed that OT authors had published a high number of publications in non-OT journals (MacDermid et al., 2015; T. Brown et al., 2017; T. Brown, Ho, et al., 2018; T. Brown, Gutman, and Ho, 2018). A good percentage of highly cited OT papers, also published in non-OT-specific journals (Man et al., 2019). Another study on OT-publication in non-OT journals for 2004 to 2015 found publication in non-OT journals increased by 173% (Folha et al., 2019). Because there has been an explosion of new online electronic journals with open access options for publications, publishing is a multidisciplinary type of journal that has become the global trend by prospective authors in any discipline.\n\nRecently all bibliometric studies in the field of OT used Journal Citation Report (JCR) matrices and Journal Impact Factor (JIF) for their analysis provided by Web of Science (WOS) (T. Brown, Gutman, Ho, et al., 2018; MacDermid et al., 2015; Gutman et al., 2017; Augusto De Araujo et al., 2017; T. Brown et al., 2017; T. Brown et al., 2019; T. Brown, Gutman, and Ho, 2018; Man et al., 2019). JIF is calculated by a simple mathematical formula, where the total citations will be in the numerator and the citable item as the denominator for the previous two years. The denominator creates confusion because the authors cite anything from the available literature, and journals do not label the publications as citable items in their author guidance. Neither prevents any kind of item for citing (Fernandez-Llimos, 2018). Similar to JIF, Scopus CiteScore also use citation analysis for ranking journals. The Scopus database that provides CiteScore is among the two databases accepted worldwide. The other is Web of Science (WOS), which provides JIF (T. Brown and Gutman, 2019; Fernandez-Llimos 2018; Sau, 2020).\n\nThe CiteScore metrics released in 2017 offer access to citing and citable articles, and it computes all published materials as citable articles (Fernandez-Llimos, 2018). But, there was concern about citable items such as “notes”, “letter to the editor”, “editorials”, “erratum”, “retracted”, and there will be many unidentified items. This error has been fixed in the recently updated version of CiteScore metrics 2020, where they have fixed for the “articles”, “reviews”, “conference papers”, “book chapters” and “data papers” published. Scopus CiteScore has more excellent comprehensive coverage of published research data (Fernandez-Llimos, 2018; Sau, 2020). Both JIF and CiteScore calculations are based on citations received by a journal in a given period for the published citable item in that duration (Fernandez-Llimos, 2018; Sau, 2020). Significant and strong correlations were found between JIF and CiteScore in recent studies comparing 14-OT journals published in English (T. Brown and Gutman, 2019). Hence, both JIF and CiteScore for measuring journal quality are used in our current study.\n\nThus, it indicates a requirement for a comprehensive bibliometric evaluation of OT literature using accurate and accessible matrices, which can be used to understand the global prospect of OT literature. These reasons prompted us to conduct a detailed bibliometric and scientometric analysis of research output in OT using the Scopus database. Hence, the following research questions were proposed.\n\ni) What is the year-wise OT-publications trend in Scopus indexed journals for 2001-2020?\n\nii) What are the trend in OT-specific journals and non-OT-specific journal publications for 2001-2020?\n\niii) Which are the top journals that publish peer-reviewed OT publications between 2001 and 2020?\n\niv) Which are top-performing countries in OT-research publications between 2001 and 2020?\n\nv) What are the collaboration trends in OT for 2001-2020?\n\nvi) Which are the top-performing organisations in OT for the period of 2001-2020?\n\nvii) Which are the top-cited publications in OT for 2001-2020?\n\nviii) Which are the commonly used keywords in OT journals for 2001-2020?\n\n\nMethodology\n\nThis study was conducted based on data retrieved from Scopus between 2001 and 2020. Due to no human subjects involvement, ethical approval was not required.\n\nScopus database was used for the study. Scopus is one of the international scientific committee's best bibliographic databases (Fernandez-Llimos, 2018; Sau, 2020). Scopus covers 70 million items and 1.4 billion cited references since 1970, making it the biggest research publication database. Scopus bibliometric information is expensively used in scientometric analysis.\n\nThe search was conducted in December 2021 and was limited to scientific articles and reviews on OT published from 2001 to 2020. We used the TITLE-ABS-KEY function using the advance search option of the Scopus database. Keywords such as “Occupational Therapy” and “Occupational Therapist” (T. Brown, Gutman, Ho, et al., 2018; Nowrouzi-Kia et al., 2018; T. Brown et al., 2019; T. Brown et al., 2017: Gutman et al., 2017) was used along with multiple Boolean operators such as “AND”, and “OR” to retrieve the maximum number of relevant articles. We excluded non-peer-reviewed documents such as “short survey”, “conference paper”, “editorial”, “notes”, “letter”, “book”, “book chapter”, “erratum” and “retracted papers” (T. Brown, Gutman, Ho, et al., 2018; Nowrouzi-Kia et al., 2018).\n\nThe VOSviewer®, a free software, was used. Microsoft Excel 2016® was used for all the figures and scientometric calculations.\n\nScientometric data was retrieved from Scopus using a comma-separated file (CSV) with complete information. The full details such as citation information, bibliographical information, abstract and keywords, funding details, and other pieces of information were downloaded as CSV-file to analyse the data using VOSviewer.\n\nAll journal titles were screened to identify the OT-specific journals from the Scopus database. The journals with titles that contained the “Occupational therapy” word were categorised as OT-specific journals (Folha et al., 2019). Additionally, we verified all journals' title, which contains either of these three words “Ergotherapia”, “Occupational Therapy”, or “OT” and confirmed the organisation that published those journals. Further, the occupational therapy organisation or association publishing journals were included in the OT-specific journal list. The remaining journals were categorised as non-OT-specific journals. Then year-wise CSV file was imported into VOSviewer to generate year-wise publication of OT-specific, non-OT specific information. We used VOSviewer software citation per source function for this purpose. VOSviewer uses “source” instead of “journal” in software. Citation per publication is used to generate ten-year journal publication output. Then the information is imported to an Excel file to compute year-wise OT publications, year-wise publications in OT-specific journals, and year-wise publications in non-OT specific journals. The cumulative publications for all three categories were calculated separately to identify the growth trend of OT publications.\n\nThe VOSviewer was used to categorise the top twenty journal sources, countries, and 20 organisations based on publication numbers. Similarly, we used twenty-year files to identify the top twenty authors who published a minimum of 25 articles and the top 20 individual articles based on the number of citations. We referred to analysis using CiteScore 2020 from the Scopus database and Journal Citation Report 2020 from WoS Master Journal List respectively to tabulate the Scopus CiteScore and JIF for the top-twenty journals.\n\nA network map on international collaboration about OT publication and author keywords visualisation was generated using VOSviewer software.\n\n\nResults\n\nThe overall OT publication trends revealed a steady growth of (7.72%) each year. In OT-specific and non-OT specific journals publication, growth was 0.29% and 7.44%, respectively (Figure 1). Approximately one-fourth (24.30%) of articles were published in OT-specific journals in the last twenty years, and three-fourths (75.69 %) articles were published in non-OT-specific journals. From 2001 to 2020 the OT publications increased by 165.14 % (n = 1544). Similarly, the overall OT publication in OT-specific journals increased 14.84 % (n=57), whereas non-OT-specific journals overall publication increased 269.85% (n =1487).\n\nA total of 16 OT-specific journals are listed in the Scopus database. Year-wise OT specific journal publication for the period of 2001 to 2020 showed in Figure 2. The top five journals published more than half of OT-specific journal publications. Those journals were American Journal of Occupational Therapy (AJOT) 18.42 %, British Journal of Occupational Therapy (BJOT) 17.56 %, Australian Occupational Therapy Journal (AOTJ) 11.53%, Canadian Journal of Occupational Therapy (CJOT) 7.64 % and Scandinavian Journal of Occupational Therapy (SJOT) 7.64 %, (Table 1). Reaming articles were published in Occupational Therapy in Health Care (OTHC) 6.87 (n=511), Ergotherapie und Rehabilitation (ErgoR) 6.15 % (n=458), Occupational Therapy International (OTI) 5.28 %(n=393), OTJR Occupation, Participation and Health (OTJR) 4.27 % (n=318), Occupational Therapy in Mental Health (OTMH) 3.56% (n=265), Journal of Occupational Therapy, Schools, and Early Intervention (JOTSEI) 3.10 % (n=231), Physical and Occupational Therapy in Pediatrics (POTP) 2.42% (n=180), Physical and Occupational Therapy in Geriatrics (POTG) 2.24% (n = 167), Brazilian Journal of Occupational Therapy (BrJOT) 1.71 % (n=127), Hong Kong Journal of Occupational Therapy (HKJOT)1.32% (n =98), and Irish Journal of Occupational Therapy (IrJOT) 0.28 % (n=21).\n\nThe current analysis found that 14 out of the top-20 journals are OT-specific journals, which published one-fourth of OT articles from 2001 to 2020 (Table 1). Among those journals, the AJOT received more citations (n = 27770), but the Archives of Physical Medicine and Rehabilitation (APMR) received the highest citation per document (37.27). CiteScore of those 20 journals ranges from minimum zero to a maximum of 5.7. Fifteen journals out of the top-20 journals have journal impact factors (JIF) or journal citation indicators (JCI). Six journals were indexed in the Emerging Sources Citation Index (ESCI) of WOS, whereas two journals were not listed in WOS. Impact factors for those 15 journals were rage from 0.03 to 3.966.\n\nAmong the top OT publishing countries, the US published the highest number of articles (n= 9517), followed by the UK, Australia, Canada, and Germany (Table 2). The Netherlands received the highest citation per document (41.84), followed by Denmark, France, Italy, Norway. Furthermore, data revealed the US, UK, Australia, and Australia have solid international collaboration among the best 20 countries published in the past 20 years (Figure 3).\n\nThe top five organisations publishing OT publications in the last 20-years are the department of occupational science and occupational therapy, the University of Toronto, Toronto, Canada, department of health sciences, Lund University, Lund, Sweden, school of rehabilitation science, McMaster University, Hamilton, Canada, school of health and rehabilitation sciences, the University of Queensland, Brisbane, Australia and department of occupational therapy, Colorado state university, Fort Collins, USA (Table 3). Among the Top-20 university of British Columbia, Vancouver, Canada, received the highest citations (cpd = 200.50).\n\nAmong the top researcher, Brown T (n=128) was identified as a leading author with the maximum number of articles in the field of OT, followed by Eklund M (n=88), Kottorp A (n= 41), Rodger S (n=88), Ziviani J. (n=76) and Mackenzie I. (n=67). The top authors' citation per document and lifetime h Indexed are provided in Table 4. Further, the top-20 highly cited publications are listed in Table 5. The article published in 2017, received the 2309 citation was the highly cited article in the lancet. We observed a negative correlation (-0.14278) when comparing citations with the total year after publication.\n\nOur study enlisted 20 author keywords commonly used in OT literature. Overall, the best 20 keywords were identified, with at least 50 occurrences in the OT publications (Figure 4).\n\n\nDiscussion\n\nOver the last twenty years, overall OT publication output steadily increased, indicating the profession's growth in terms of research, and its dissemination is not significantly influencing the modern era of digitalization. Publication in non-OT-specific journals is three times more compared to OT-specific journals. A similar trend was also observed in recent studies (T. Brown et al., 2019; Gutman et al., 2017; Folha et al., 2017; T. Brown, Ho et al., 2018; T. Brown, Gutman, and Ho 2018; Folha et al., 2019). This increase may reflect the growth of research activities in OT across the globe (Folha et al., 2019). Occupational therapy works along with medical and other allied health professionals. It allows occupational therapies to work as a part of the multidisciplinary team. Similarly, it opens the door to interdisciplinary research opportunities. That multidisciplinary research is used to publish in either medical-related or multidisciplinary journals. Those journals have high JIF compared to OT journals (T. Brown et al., 2019; Gutman et al., 2017; Folha et al., 2017; T. Brown, Ho et al., 2018; T. Brown, Gutman, and Ho 2018; Folha et al., 2019). A recent study found that non-OT-specific journals have three times more JIF than OT-specific journals (Folha et al., 2019). These multidisciplinary and medical-oriented journals have more readers than OT-specific journals, giving more visibility and increasing the chance of receiving more citations. It may also encourage OT researchers to publish more in non-OT-specific journals (T. Brown et al., 2019; Gutman et al., 2017; Folha et al., 2017; T. Brown, Ho et al., 2018; T. Brown, Gutman, and Ho 2018; Folha et al., 2019).\n\nA total of five journals, such as AJOT, BJOT, AOTJ, SJOT, and CJOT, published half of the OT-specific journals articles. Previous studies also made similar observations (T. Brown and Gutman 2019; T. Brown, Gutman, and Ho, 2018). These journals are well-known among the OT profession and have a long publishing history (T. Brown and Gutman, 2019). AJOT, BJOT, AOTJ, and CJOT were published by prominent national organizations of OT and recognised by the global OT community (T. Brown and Gutman, 2019). These journals' publication frequencies are more and published many articles per issue compared to other journals. Among these 16 OT journals, two journals, BrJOT and IrJOT, are new in the Scopus database and have data for the past three years. Hence, those journals will have a lower number of articles. According to the previous study, Scopus indexed OT-specific journal numbers was 14 (T. Brown and Gutman, 2019). Among these two new journals, BrJOT published many articles in three years and placed under the best 20 journals that published OT-specific articles. OT-specific journals published one-third of total OT publications. Several OT-specific journals are published globally and have an online publication (Cruz et al., 2019) but are not included in the Scopus database. Including all those OT-specific Journals might change the scenario of citation matrices of occupational therapy journals because occupational therapy journals tend to get more citations in for OT-specific journals.\n\nOut of 20 top journals that produced the maximum articles in occupational therapy, the first eight are OT-specific journals. There is a normal phenomenon because these journals published OT-specific articles. ErgoR received more minor citations among those ten OT-specific journals due to its publication language. This is the only journal listed in the top twenty published in Germany. All other periodicals are published in the English language. AJOT, BJOT, AOTJ, SJOT, and CJOT received more citations in terms of overall citation. It may be due to their large volume of publications (T. Brown and Gutman, 2019; T. Brown, Gutman, Ho, et al., 2018). AJOT, BJOT, AOTJ, SJOT, and CJOT received more than ten citations per document. Archives of Physical Medicine and Rehabilitation received more citations per document than any other journal listed in top-20, and it has the highest CiteScore and JIF. Among the OT-specific journals, POTP had the highest CiteScore (2.9), and AJOT had the highest JIF (2.246).\n\nThe US, Australia, UK, Canada, Germany, Sweden, Netherlands, and Italy are the top most country in terms of numbers of published articles, and this is different from that of the previous study (T. Brown and Gutman 2019; T. Brown, Gutman, Ho, et al., 2018). The US published approximately one-third of total OT publications (n=9517). Other study findings also revealed that the US is the top OT article (T. Brown, Gutman, Ho, et al., 2018). The US received many citations (216810) for the published documents. US is the country where OT originated from and also have a good education and research system in OT, which may be the reason for the huge number of the publication. The US is also the host country for a large number of OT-specific and non-OT-specific journals. This could also be a reason for the huge number of publications in occupational therapy. But citation per document is more minor for US articles than the Netherlands, Denmark, Italy, France, and Norway, with very few publications compared to the US. It may be due to the lack of availability of OT-specific journals in their geographic location, which triggered them to publish their research in non-OT specific journals with higher quality than OT-specific journals.\n\nWe found that the US, Australia, UK, and Canada are the leading countries in international collaborations in OT publications. The size of the level and circle indicate the weightage of collaborative activity. A bigger size represents more collaborations, and smaller size means fewer collaborations. The line between two nodes and their densities represents their link and strength (Figure 3). Colour expressed different clusters levels based on international collaborations (Van Eck and Waltman, 2019).\n\nAmong the top-20 organizations, 18 are either universities or entities of a university. This happens because universities are mainly placed in the urban set up with all necessary support such as research culture among academicians, well-equipped libraries with academic resources, affiliated hospitals, client participation, internal funding, grant office supports (T. Brown et al., 2019). All this is favourable for more research output, which may cause university domination's top twenty organization list. Our study found only one organization in this top list: research institutes from Denmark and one occupational therapy association of USA. Though the US alone produced many OT articles, only five organizations are listed in the top 20, compared to US Canada (n=6) and Australia (n=5). Despite having a high volume of publications, less representation of US organization in the top list was also observed in previous studies (T. Brown, Gutman, Ho, et al., 2018; Man et al., 2019). Other countries that are listed in top organizations are Denmark (n=1), Iran (n=12), Sweden (n=1), and Taiwan (n=1).\n\nAustralia (n=11) has the highest representation in the top author list, followed by Canada (n=1) Sweden (n=4), US (n =3), and Japan (n=1). The US authors are less in the top list instate having high publication volume. UK authors produce more publications after US authors, but there are no authors from the UK listed in the top 20 author list. Law M. from McMaster University, Hamilton, Canada had the highest h indexed (63) and Gitlin L. N from Johns Hopkins University, Baltimore, united states received the highest citation per document (57.51) among top-20 authors. Our study found Brown T as a top author in publication number. The finding of T. Brown, Gutman, Ho, et al. (2018) supported our study.\n\nOut of the top-twenty highly cited articles for 2001 to 2020, four papers were published in 2008, two each in 2005, 2006, 2009, and 2012, one each in 2002, 2003, 2004, 2007, 2013, 2014, 2016, and 2017. Our study does not find any relation with year after with more citations. Our findings opposed previous studies' findings, which observe a long citation window helps an article gather maximum citation (Gutman et al., 2017; T. Brown et al., 2019; T. Brown, Gutman, Ho, et al., 2018; T. Brown et al., 2017). Most of the highly cited papers are published in non-OT-specific journals. Most of the highly cited studies published non-OT-specific journals like earlier studies. Those non-OT journals are generally high-quality medical journals (Gutman et al., 2017; T. Brown, Gutman, Ho, et al., 2018; T. Brown et al., 2019; T. Brown et al., 2017; T. Brown, Ho et al., 2018). It may happen due to the increased pressure to publish in journals with good impact factors or CiteScore. The quality of journals provides more visibility, which helps the author get more readership and citation because it helps in a grant application and promotion (Gutman et al. 2017; T. Brown et al., 2019).\n\nVOSviewer density visualisation (Figure 4), by default, uses blue, green, and yellow to represent the density visualisation (Van Eck and Waltman, 2019). The yellow colour indicates the number of items in the neighbourhood of a point and the higher weights of the neighbouring items. Out of the total best 20 keywords, “occupational therapy”, “rehabilitation,” and “stroke”, “physical therapy” and “activities of daily living” are five common keywords used more frequently in OT research, which are in yellow (Figure 4). Occupational therapy and rehabilitation are commonly used as keywords because these two words are identical terms for the occupational therapy profession. The authors used these two words to make their research visible in the electronic search. Stoke is most probably the oldest and strongest research field, where occupational therapist works across the globe. Physical therapy is a common allied health profession occupational therapists may collaborate and publish together. Activities of daily living are one of the core practice areas of the occupational therapist.\n\n\nConclusion\n\nThis study retrieved scientometric information from the Scopus database and listed 25 journals along with their CiteScore and Journal Impact Factor. It was observed OT articles were published three times more in non-OT-specific journals, indicating that OT research is significantly overlapping with other disciplines of medicine. Hence, the investigation should not conclude a literature search with only OT-specific journals. The SJOT is one of the core OT journals but listed under subject category of “public health, environmental and occupational health” rather than the category of “occupational therapy”.\n\n\n\n1) From Scopus database, twenty Journals were identified, which published a maximum number of occupational therapy articles.\n\n2) Scopus database indexed a total of 16 OT-specific journals. Scopus database also included two OT practice magazines in their database.\n\n3) VOSviewer software is an open-access tool that can be used as a cost-effective method for any scientometric analysis.\n\n4) BJOT, AJOT, AOTJ, SJOT, and CJOT are the leading occupational therapy journals in the number of published items.\n\n\nData availability\n\nMendeley Data: Scopus Based Occupational Therapy Research (2001-2020). https://doi.org/10.17632/yp7xjg4zs3.2 (Sau and Nayak, 2022)\n\nThis project contains the following underlying data:\n\nData File “20 best source which published maximum number of article” contains analysis of the data obtained from Scopus for 2001-2020. The analysis includes 20 best sources, 20 best cited documents, 20 best authors, 20 best countries, 20 best organisations, 20 highest used keywords, year-wise publication analysis, and OT-specific journals details.\n\nData files “Scopus-935-Analyze-Source”, “Scopus-981-Analyze-Source”, “Scopus-984-Analyze-Source”, “Scopus-1029-Analyze-Source”, “Scopus-1038-Analyze-Source”, “Scopus-1186-Analyze-Source”, “Scopus-1365-Analyze-Source”, “Scopus-1287-Analyze-Source”, “Scopus-1366-Analyze-Source”, “Scopus-1400-Analyze-Source”, “Scopus-1508-Analyze-Source”, “Scopus-1657-Analyze-Source”, “Scopus-1784-Analyze-Source”, “Scopus-1785-Analyze-Source”, “Scopus-1819-Analyze-Source”, “Scopus-1776-Analyze-Source”, “Scopus-1868-Analyze-Source”, “Scopus-1962-Analyze-Source”, “Scopus-2234-Analyze-Source”, “Scopus-2479-Analyze-Source” respectively contains the data obtained for the years 2001, 2002, 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, 2014, 2015, 2016, 2017, 2018, 2019 and 2020 respectively with the keywords for search.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nBrown GT, Brown A: Characteristics of the occupational therapy journal of research: the first twenty years. Occupational therapy in health care. 2005; 19(3): 73–92. PubMed Abstract | Publisher Full Text\n\nBrown T, Gutman SA: A comparison of bibliometric indicators in occupational therapy journals published in English. Can. J. Occup. Ther. 2019; 86(2): 125–135. PubMed Abstract | Publisher Full Text\n\nBrown T, Gutman SA, Ho Y-S: Occupational therapy publications by Australian authors: A bibliometric analysis. Aust. Occup. Ther. J. 2018; 65(4): 249–258. PubMed Abstract | Publisher Full Text\n\nBrown T, Gutman SA, Ho Y-S, et al.: Highly Cited Occupational Therapy Articles in the Science Citation Index Expanded and Social Sciences Citation Index: A Bibliometric Analysis. Am. J. Occup. Ther. 2017; 71(6): 7106300010p1–7106300010p11. PubMed Abstract | Publisher Full Text\n\nBrown T, Gutman SA, Ho Y-S, et al.: A bibliometric analysis of occupational therapy publications. Scand. J. Occup. Ther. 2018; 25(1): 1–14. Publisher Full Text\n\nBrown T, Ho Y-S, Gutman SA: A Bibliometric Analysis of Peer-Reviewed Journal Publications by British Occupational Therapy Authors. The Open Journal of Occupational Therapy. 2018; 6(1). Publisher Full Text\n\nBrown T, Ho Y-S, Gutman SA: High Impact and Highly Cited Peer-Reviewed Journal Article Publications by Canadian Occupational Therapy Authors: A Bibliometric Analysis. Occupational therapy in health care. 2019; 33(4): 329–354. PubMed Abstract | Publisher Full Text\n\nda Cruz DMC , Costa JD, Veiga J, et al.: Current electronic journals on occupational therapy: A descriptive study. Revista de la Facultad de Medicina. 2019; 67: 437–442.\n\nCusick A: Australian occupational therapy research: A review of publications 1987–91. Aust. Occup. Ther. J. 1995; 42(2): 67–75. Publisher Full Text\n\nErnest M: Canadian Journal of Occupational Therapy: a reflection of professional growth. Canadian journal of occupational therapy. Revue canadienne d’ergotherapie. 1983; 50(5): 165–169. PubMed Abstract | Publisher Full Text\n\nFernandez-Llimos F: Differences and similarities between Journal Impact Factor and CiteScore. Pharm. Pract. 2018; 16(2): 1282. PubMed Abstract | Publisher Full Text\n\nFolha OAdAC, da Cruz DMC , Emmel, et al.: Identification of articles published by brazilian occupational therapists in journals indexed in databases. Cadernos Brasileiros de Terapia Ocupacional. 2017; 28(3): 358–367. Publisher Full Text\n\nFolha OAdAC, Folha DRdSC, da Cruz DMC , et al.: An overview of occupational therapy publication in non-specific professional journals in the period of 2004 to 20151. Brazilian Journal of Occupational Therapy. 2019; 27(3): 650–662. Publisher Full Text\n\nGutman SA, Brown T, Ho Y-S: A Bibliometric Analysis of Highly Cited and High Impact Occupational Therapy Publications by American Authors. Occupational therapy in health care. 2017; 31(3): 167–187. PubMed Abstract | Publisher Full Text\n\nJohnson KS, Leising DJ: The literature of occupational therapy: a citation analysis study. Am. J. Occup. Ther. 1986; 40(6): 390–396. Publisher Full Text\n\nMacDermid JC, Fung EH, Law M: Bibliometric Analyses of Physical and Occupational Therapy Faculty across Canada Indicate Productivity and Impact of Rehabilitation Research. Physiotherapy Canada. Physiotherapie Canada. 2015; 67(1): 76–84. PubMed Abstract | Publisher Full Text\n\nMadill H, Brintnell S, Stewin L: Professional Literature: One View of a National Perspective. Aust. Occup. Ther. J. 1989; 36(3): 110–119. Publisher Full Text\n\nMan DWK, Tsang WSF, Lu EY, et al.: Bibliometric study of research productivity in occupational therapy and physical therapy/physiotherapy in four Western countries and five Asian countries/regions. Aust. Occup. Ther. J. 2019; 66(6): 690–699. PubMed Abstract | Publisher Full Text\n\nMeho LI, Yang K: A New Era in Citation and Bibliometric Analyses: Web of Science, Scopus, and Google Scholar. Cs/0612132. 2006.\n\nMountain GA: A Review of the Literature in the British Journal of Occupational Therapy, 1989–1996. Br. J. Occup. Ther. 1997; 60(10): 430–435. Publisher Full Text\n\nNowrouzi-Kia B, Chidu C, Carter L, et al.: The top cited articles in occupational therapy: a citation analysis study. Scand. J. Occup. Ther. 2018; 25(1): 15–26. PubMed Abstract | Publisher Full Text\n\nOttenbacher K, Petersen P: Quantitative trends in occupational therapy research: implications for practice and education. Am. J. Occup. Ther. 1985; 39(4): 240–246. PubMed Abstract | Publisher Full Text\n\nOttenbacher K, Short MA: Publication Trends in Occupational Therapy. The Occupational Therapy Journal of Research. 1982; 2(2): 80–88. Publisher Full Text\n\nPotter J: Mapping the literature of occupational therapy: an update. Journal of the Medical Library Association: JMLA. 2010; 98(3): 235–242. PubMed Abstract | Publisher Full Text\n\nReed KL: Mapping the literature of occupational therapy. Bull. Med. Libr. Assoc. 1999; 87(3): 298–304. Reference Source\n\nRoberts D: The Journal Literature of Occupational Therapy: A Comparison of Coverage by Four Bibliographic Information Services. Br. J. Occup. Ther. 1992; 55(4): 143–147. Publisher Full Text\n\nSau K: Punitive provision to tackle predatory journals. Curr. Sci. 2020; (Vol. 118). Manipal. Reference Source\n\nTrevan-Hawke JA: British Journal of Occupational Therapy: Composition and Authorship Patterns 1975–1984. Br. J. Occup. Ther. 1986; 49(9): 301–304. Publisher Full Text\n\nVan Eck NJ, Waltman L: VOSviewer Manual.2019. Reference Source\n\nWallin JA: Bibliometric Methods: Pitfalls and Possibilities. Basic Clin. Pharmacol. Toxicol. 2005; 97(5): 261–275. PubMed Abstract | Publisher Full Text\n\nZiviani J, Behan SUE, Rodger S: Occupational Therapy Journals‐The State of the Art. Aust. Occup. Ther. J. 1984; 31(1): 6–12. Publisher Full Text"
}
|
[
{
"id": "140811",
"date": "20 Jul 2022",
"name": "Sureshkumar Kamalakannan",
"expertise": [
"Reviewer Expertise Disability",
"Public Health and Epidemiology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an important work implying the need for OT (occupational therapy) research development. The primary concern is related to the selection of only one database for this research study and the rationale/importance of this work in the current context. This needs to be justified and details related to the rationale must be added. The other concern is related to the discussion conclusion sections - where the authors highlight several aspects related to the results from this research but fail to connect the findings with implications for OT research, professional development, policies, and practice. Particularly the implications for LMICs (Low and Middle Income Countries). This study highlights OT research developing in 5 high-income nations and misses to include what could be done in the rest of the world to bring OT research to the standards found in those 5 high-income nations. The conclusions are also not directly relevant. These issues require revision. Additionally, the language requires proofreading and revision.\nI congratulate the authors for their efforts and suggestions to revise the manuscript based on my comments.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "9501",
"date": "11 May 2023",
"name": "Yogendra Nayak",
"role": "Author Response",
"response": "Authors are thankful for the reviewer comment. We are writing the following responses with the revision of the manuscript. We have justified why we used one databased for our study in methodology sections under the subheadings “source of data”. Citations vary between databases and it is based on the number of journals indexed in that database. We selected Scopus for this study because it includes more OT-specific journals compared to WOS and overall indexed more journals compared to WOS. The citation count was calculated within the database. Due to extensive coverage, Scopus has a more citable item and a probability of getting more citations to count. The suggestions of LIMC is included in the discussion sections of revised manuscript. Conclusion is modified according to suggestions, incorporation of the implications for further research in the field of occupational therapy. Language proofing taken care and the necessary changes are made in the revised manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/11-155
|
https://f1000research.com/articles/11-1301/v1
|
14 Nov 22
|
{
"type": "Research Article",
"title": "The COVID-19 third wave in Myanmar following the military coup",
"authors": [
"Spring Research Team"
],
"abstract": "Background: COVID-19 seriously hit Myanmar between June and August 2021, a few months after the military coup, though the first and second waves in 2020 were managed effectively by the government. People in Myanmar experienced serious consequences of the COVID-19 pandemic precipitated by the disorganized health system under the military junta. This study aimed to analyse the situation of COVID-19 occurrence and death proportions during its third wave in Myanmar. Methods: An online survey was conducted using a Google form. People with the symptoms of COVID-19 and those who died from COVID-19 between June and August 2021 were eligible to participate. The Google form was extracted into an Excel datasheet and analysed using Stata v16.1. Results: Among the 29,171 participants, 76.7% were over 30 years old and 56.4% were female. A majority of participants were from highly populated regions: Yangon (17,220; 59%) (Business capital), Mandalay (3,740; 12.8%) and Sagaing (1,546; 5.3%). Participants sought health care from telegram/other online services (34%), home care by health care providers (22%), private clinics (13%) and public hospitals run under the military junta (5%). Overall, 15% of participants died, of which, 72% occurred at home and 17% at public hospitals. Significantly higher proportions of deaths were seen among participants over 60 years than other age groups and males (p<0.001). Death proportions at different weeks from June to August 2021 ranged from 12.4% to 17.3%, much higher than the military junta’s reports. Overall, 25% of participants received oxygen therapy. Conclusions: Death proportions in different weeks were consistently over 12%. The majority of participants received tele/online and home treatment services. Most deaths occurred at home. Findings indicated the high COVID-19 case fatality rates with limited access to public hospital care during the third wave. The data suggests that the outcomes were adversely impacted by the military coup.",
"keywords": [
"COVID-19",
"Myanmar",
"mortality",
"third wave"
],
"content": "Introduction\n\nCoronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus and its occurrence was first reported in China in December 2019. The virus spread rapidly inside China and to all parts of the globe. The World Health Organization announced the COVID-19 outbreak as a Public Health Emergency of International Concern on 30th January 2020 and a pandemic on 11th March 2021. As of the end of April 2022, there were over 513 million confirmed cases and over 6.2 million deaths worldwide.1,2\n\nMost COVID-19 cases suffer from mild illness and do not require hospitalization.3 However, those with severe illness may need close monitoring and hospitalization.4 Mortality is generally low. Public healthcare responses, efficiency of treatment, and COVID-19 variants may determine the COVID-19 severity and case fatality rate (CFR),5 which is defined as the number of total deaths divided by the total confirmed cases, shown in per cent. As of July 2020, the global mean and median CFR were 3.31% and 2.19%, respectively, with the highest rate of 27% in Yemen. North Europe and North America also documented a high CFR of more than 10%.6 CFR depends on the policies, responses, and efficiency of local healthcare systems, although its estimation has some flaws.5\n\nMyanmar had its first confirmed COVID-19 cases on 23rd March 2020. Since then, the first wave of COVID-19 in Myanmar lasted for about three months, followed by a second wave in August 2020. Country level coordination, risk communication, and surveillance at point of entry were initiated in January 2020; before the WHO declaration of a global health emergency. In response to the pandemic, an increased number of COVID-19 testing centres, community quarantine sites, fever clinics, contact tracing measures, and guidelines were timely implemented. Confirmed cases were admitted to the COVID-19 designated centres and tertiary care hospitals, which provided comprehensive care to lower the adverse consequences and fatalities (https://www.brookings.edu/blog/future-development/2020/12/01/myanmars-response-to-the-covid-19-pandemic/).7 The “National COVID-19 Call Centre” was established to provide correct and timely COVID related health information to the general community https://dmr.gov.mm/officialannouncement/COVID_19CallCenter.pdf. The CFR during the first and second waves in Myanmar was 2.2%, which was similar to the global CFR.8\n\nThe third wave of COVID-19 seriously hit Myanmar between June and August 2021, a few months after the military coup, which took place in February. People in Myanmar faced serious consequences of the COVID-19 pandemic, added to the disorganized health system impacted by the coup. Health workers in Myanmar have been oppressed by the military for providing medical care to injured protesting civilians and for participating in the Civil Disobedience Movement (CDM). The Insecurity Insight, Physicians for Human Rights (PHR), and John Hopkins University Center for Public Health and Human Rights (CPHHR) reported at least 252 attacks and threats against health workers and facilities during the first six months of the coup (https://phr.org/news/at-least-252-reported-attacks-and-threats-to-health-care-in-myanmar-during-six-months-of-militarys-crackdown/)(https://phr.org/our-work/resources/violence-against-health-care-in-myanmar/). Consequently, people had limited access to healthcare services even when they had severe COVID-19 symptoms. Critical shortages of oxygen and medicines and movement restrictions at night due to curfew further compounded the situation (https://phr.org/our-work/resources/violence-against-health-care-in-myanmar/) (https://crisis24.garda.com/alerts/2021/07/myanmar-authorities-to-implement-stay-home-orders-nationwide-july-17-25-update-38).\n\nTo mitigate the COVID-19 third wave under the impact of military coup and inefficient health care system, Ministry of Health of the National Unity Government (NUG) implemented the online telehealth clinics for treating the COVID-19 patients and established the COVID-19 knowledge centre Facebook page to disseminate the correct and timely health messages to the community.9 The NUG is the interim government formed by elected members of parliament, community leaders, representatives from Ethnic Resistance Organizations and CDM staff, and is recognized by the majority of Myanmar people (https://www.iseas.edu.sg/articles-commentaries/iseas-perspective/2022-8-myanmars-national-unity-government-a-radical-arrangement-to-counteract-the-coup-by-moe-thuzar-and-htet-myet-min-tun/) (https://aseanmp.org/2022/07/18/southeast-asian-mps-urge-asean-special-envoy-to-myanmar-to-meet-national-unity-government/).\n\nMyanmar went through a COVID-19 third wave differently due to the difficult situation following the military coup. Therefore, this current study aimed to document the situation of the COVID-19 third wave in Myanmar, using an online survey.\n\n\nMethods\n\nThis is a cross-sectional descriptive study, based on an online survey using a Google form. The weblink to the Google form was made available to the public through a number of online outlets.\n\nOnline data collection using a Google form was conducted between 1st August 2021 and 30th September 2021. The survey questionnaire was developed in the Myanmar language, after reviewing the literature and discussing with the relevant healthcare specialists. The questionnaire contained 13 questions and it took approximately 5 minutes to complete. Anyone who experienced COVID-19 symptoms themselves or knew someone (family members, relatives or neighbours) who had or died from COVID-19 symptoms, between 1st June 2021 and 31st August 2021 (referring to the study period), could participate in the survey. There was no limitation or exclusion in age, sex, geographical areas of the participants. Efforts were made to minimize the sampling bias and to get the representative samples from the different geographical areas throughout the country by sharing the google form through the community networks from different regions.\n\nQuestions included in the assessment were background characteristics (age, sex, state/region), week of symptom onset, COVID-19 symptoms, COVID-19 testing and result, duration of illness, treatment seeking, oxygen therapy, outcome of disease, place of death (if the patient died).\n\nThe Google form was extracted into an Excel datasheet, which was analysed using Stata v16.1. All the participants (N=29,171) were included in the analysis, reporting subgroups and missing values in detail. Prior calculation of sample size was not done in order to recruit the elgible participants from all regions across the country. The age variable was cleaned for typos and for mixed Myanmar and English entries. The multiple-response variables were re-coded into binary variables for each response for analysis. The categories of the remaining variables were pre-defined. Descriptive analysis was performed to report the participants’ characteristics, by geographical regions; the patterns of COVID-19 symptom presentations, by outcomes such as recovered or death; the use of a healthcare facility for treating COVID-19 symptoms, by oxygen treatment; numbers of symptomatic participants in relation to proportions of death over the study period; and the place of death of the deceased participants. The survey was structured with simple questions for the general public, aiming to report the broad picture of the COVID-19 burden in the population; therefore, it did not allow further complex analysis. No multivariable analysis was done and only bi-variate analyses were applied to describe the overall situation during the third wave.\n\nThe first section of the Google data collection form provided the participants with the information on the survey and asked the participants’ consent to participate in the study. If they agreed to participate, they could continue answering the survey questions. The study strictly ensured the anonymity and confidentiality of the information. Questions focused only on the disease happening and did not include personal information except age, sex and geographic location. Ethical approval was not sought because of the non-functioning of almost all ethical boards in Myanmar due to the country’s political situation, and the low risk, anonymised nature of the data collection.\n\n\nResults\n\nTable 1 shows the COVID-19 symptomatic participant’s characteristics and geographical distribution. A total of 29,171 symptomatic participants were included in the assessment and 77% were from the major cities such as Yangon, Mandalay and Sagaing. Others included the remaining states and regions in Myanmar. The community from all the administrative states and regions participated in the study showing a nationwide coverage of the survey. In general, 76.7% were over 30 years of age and, specifically, the 31–45 years group was most commonly reported (29%). The proportion of females (56.4%) exceeded males (42.8%). Nearly 76% of the participants developed COVID-19 symptoms in the month of July. Over 42% received the COVID-19 test and 90% of their results were positive. Nearly 44% recovered from all symptoms while 15.1% had died at the time of the survey.\n\n^ n=330 (1.13%) missing.\n\n* Other group includes participants who still had COVID-19 symptoms or experienced complications of COVID-19 at the time of survey.\n\nAs mentioned in Table 2, the highest proportion of deaths was reported among the participants over 60 years (38.5%), which was followed by 18.7% between 46 to 60 years. Significant difference was detected in death proportions or case fatality rate according to age (p<0.001). A higher proportion of deaths was seen among males than females (20.1% versus 11.4%), which was significantly different (p<0.001). However, death proportions were not different according to the location.\n\n* n=330 missing (1.13%).\n\nThe pattern of COVID-19 symptom presentation relating to outcomes is described in Table 3. Overall, fever (84.1%), anosmia (68.1%), cough (65.6%), appetite loss (57.1%) and muscle ache (52.6%) were the most common symptoms and generally similar presentations were seen among those who recovered. In contrast, among the deceased, fever (82%), breathlessness (75.7%), fatigue (67.9%), cough (59.7%), and appetite loss (55.8%) were presented most commonly. Symptoms mostly lasted between 11 and 15 days (31%), followed by a longer duration of 16 days or more (30%). Over 25% of participants (15% recovered and 81% in the deceased group) received oxygen treatment during their illness.\n\n^ Multiple response variable.\n\nTable 4 describes the use of healthcare facilities for treating COVID-19 symptoms, shown by oxygen treatment. The participants most commonly used online or telehealth services (34.3%) among different healthcare points. Nearly 22% invited the healthcare provider for a home visit and 13% sought healthcare from private clinics. Very few participants (4.8%) received healthcare from public hospitals. Among those who were treated with oxygen, 43% and 35% were treated with online or telehealth services, respectively. Only 14% were treated at public hospitals.\n\n^ Multiple response variable.\n\n* Oxygen treatment was not necessarily arranged by the treating health facility, except at hospitals, but self-arranged by buying or hiring oxygen cylinders or as such for individual use at home.\n\nOver the period of 1st June 2021 to 31st August 2021, the proportions of death ranged between 12.4% and 17.3%, with less variations throughout, despite the peak occurrence of COVID-19 in July week 2 (Figure 1). The majority of deaths (72%) happened at home and 18.3%, at public hospitals (Figure 2).\n\nNote: Aug w4 is omitted as it includes ‘0’.\n\nTotal N = 4,404.\n\n\nDiscussion\n\nThe current assessment documented the situation of COVID-19 occurrence and death proportions during its third wave in Myanmar, which took place under the impact of the military coup. The data indicated that the peak incidence happened during the 2nd week of July 2021. Over half of the participants sought healthcare from Telegram/other online services and home care from healthcare providers. Significantly higher proportions of deaths were seen among older age groups (46 to 60 years and over 60 years) and males. Death proportions or CFR at different weeks were consistently over 12%. The majority of deaths occurred at home and only a few at public hospitals.\n\nCFR is one informative epidemiologic tool that reflects the effectiveness of health policies, healthcare responses, and efficiency of health systems although its estimation has flaws.5 In the current study, CFR was consistently high at above 12% over the study period, which was, in fact, much higher than the announcement made by the military junta (3.7%).10 This study identified the overall death percent of 15.1%, while the global CFR remained 2.1%, according to the data as of July 2021.5 During the first and second waves, in Myanmar, the CFR showed 2.2% (3,100 deaths among 140,600 COVID-19 confirmed cases), which was comparable to the global CFR.11 This devastating increase in CFR in the third wave appears to be underpinned by the failed healthcare system following the coup.\n\nCOVID-19 deaths were different according to age group and gender. Based on the global data, death among males was 2.8% and that of females was 1.7%. With regards to the age group difference, the death rate was 3.6% in the 60–69 years old age group and 8% in the 70–79 years old group (https://www.worldometers.info/coronavirus/coronavirus-age-sex-demographics/). Age group and gender differences in the current study were observed with much higher differences than that of the global data. Specifically, death among the older age group over 60 years was 38%, and that of males was 20%. This finding reflected an underlying vulnerability like old age had a greater impact of the limited healthcare access that leads to much higher mortality.\n\nThese adverse outcomes reflect the lack of essential healthcare for treating COVID-19 in Myanmar. This study identified that only a few COVID-19 symptomatic participants (4.8%) were treated at public hospitals with essential health facilities. Most participants, including those who received oxygen, were treated at places other than public hospitals. The findings highlighted that communities had limited access to the public hospitals run under the military junta. The data also suggest that the situation was contributed by the attack of the military on the healthcare providers and health facilities, including the diversion of medical supplies to military use. Furthermore, arresting healthcare workers providing COVID-19 treatment outside of junta-run facilities worsened the condition (https://phr.org/our-work/resources/violence-against-health-care-in-myanmar/).\n\nAbout one-quarter of COVID-19 symptomatic participants in the current study received oxygen therapy. Medical oxygen is an essential medicine in the treatment of COVID-19 for cases with hypoxemia and is related to disease severity.12,13 In a Chinese study, about 63% of COVID-19 patients under 65 years old admitted to hospital required oxygen therapy and mortality was 2.9% among the oxygen therapy patients.12 In Myanmar, most COVID-19 cases were cared at home and given oxygen, when required, at home during the third wave. According to the news agencies, there were very high demands for oxygen in the community.14 Worse, the military junta set restrictions on the sale and importation of oxygen cylinders during the period (https://phr.org/our-work/resources/violence-against-health-care-in-myanmar/). Oxygen shortage was so severe that the family members of COVID-19 cases needed to queue for many hours to hire or get the oxygen cylinders filled. The crowded situation further precipitated the risk of disease transmission. Besides the oxygen shortage, rising pharmaceutical prices and shortage of medicines and other essential medical goods, including personal protective equipment (PPE), became a substantial strain on the Myanmar People.14\n\nOur study indicates that online/tele consultation was the most frequently used healthcare service for treating COVID-19. To address the healthcare needs of the community, the Ministry of Health of National Unity Government (NUG) had initiated telehealth free online clinics in June 2021. These telehealth online clinics cover 210 townships throughout the country within three months. Subsequently, COVID-19 specific Telegram channels were established in July. This service has provided consultation and treatment to more than 66,000 COVID-19 suspected and confirmed cases in 298 townships (90.3% of the total townships in Myanmar).9 These telehealth clinics were efficient in providing healthcare services for mild-to-moderate COVID-19 cases during the third wave. It was reflected in the current study as over one-third of the COVID-19 symptomatic participants sought care from the online telehealth services.\n\nThere were both strengths and limitations in the current study. High participation from the community throughout the country making a large sample with nationwide coverage was a key strength of the study. Due to the nature of the online survey, clinical details of the participants could not be collected, neither could verification information, such as COVID-19 test results. As the study was available online only and encouraged voluntary participation of the public, it was unable to estimate the disease prevalence or mortality in the population.\n\n\nConclusion\n\nThe study documented the high COVID-19 case fatality rates with limited access to public hospital care during the third wave (1 June to 31 August 2021) in Myanmar. The majority of participants received tele/online healthcare services and home treatment. CFR at different weeks were consistently much higher than the global data and most deaths occurred at home with little tertiary care. The data from this study suggest that the outcomes of the COVID-19 third wave in Myanmar were adversely impacted by the military coup.\n\n\nData availability\n\nFigshare: Underlying data for “The COVID-19 third wave in Myanmar following the military coup”, https://doi.org/10.6084/m9.figshare.20560017.15\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nCoronavirus: World Health Organization.Reference Source\n\nCoronavirus: World Health Organization.Reference Source\n\nStokes EK, Zambrano LD, Anderson KN, et al.: Coronavirus disease case surveillance—United States, January 22–May 30, 2020. MMWR Morb. Mortal. Wkly Rep. 2019; 69: 759–765. Publisher Full Text Reference Source\n\nCenters for Disease Control and Prevention: Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19).2021. [Accessed 13 Dec 2021].Reference Source\n\nAbou Ghayda R, Lee KH, Han YJ, et al.: The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis. J. Med. Virol. 2022; 94(6): 2402–2413. PubMed Abstract | Publisher Full Text\n\nCao Y, Hiyoshi A, Montgomery S: COVID-19 case-fatality rate and demographic and socioeconomic influencers: worldwide spatial regression analysis based on country-level data. BMJ Open. 2020; 10: e043560. PubMed Abstract | Publisher Full Text\n\nOo MM, Tun NA, Lin X, et al.: COVID-19 in Myanmar: Spread, actions and opportunities for peace and stability. J. Glob. Health. 2020; 10(2): 020374. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: WHO coronavirus disease (COVID-19) dashboard.2020. [Accessed 9 Feb 2021].Reference Source\n\nMinistry of Health, National Unity Government: One year activities by MOH, NUG.Reference Source\n\nMinistry of Health: Coronavirus Disease 2019 (COVID-19), Surveillance Dashboard (Myanmar) Nay Pyi Taw. Myanmar:Ministry of Health;2021. [Accessed 1 Dec 2021].Reference Source\n\nWorld Health Organization: WHO coronavirus disease (COVID-19) dashboard.2020. [Accessed 9 Feb 2021].Reference Source\n\nNi YN, Wang T, Bm L, et al.: The independent factors associated with oxygen therapy in COVID-19 patients under 65 years old. PLoS One. 2021; 16(1): e0245690. PubMed Abstract | Publisher Full Text\n\nYang X, Yu Y, Xu J, et al.: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published correction appears in Lancet Respir Med. 2020 Apr;8(4):e26]. Lancet Respir. Med. 2020; 8(5): 475–481. PubMed Abstract | Publisher Full Text\n\nWorld Vision: Myanmar crisis response 2021: situation report 3.5 August 2021.Reference Source\n\nSpring Research Team: Underlying data for “The COVID-19 third wave in Myanmar following the military coup” [data].2022. Publisher Full Text"
}
|
[
{
"id": "157852",
"date": "05 Jan 2023",
"name": "Su Myat Han",
"expertise": [
"Reviewer Expertise universal health coverage",
"health services",
"humanitarian aids"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe COVID-19 third wave in Myanmar following the military coup\nThe current study added the value of the knowledge gap on the COVID-19 impact at the community level. The available research papers on the COVID-19 were mainly conducted at the hospital level and online people movement. This study particularly highlights the true burden of COVID-19 within the population.\n\nOverall, this is a very good study, highlighting the disrupted health system and its impact on the health care sector response particularly at the pandemic situation of COVID-19. Below are the few comments and suggestions.\nAbstract Background: The first sentence of the background already concluding the severity of impact which is the main objective of the study. Background can be re-structured as “COVID-19 has disrupted health system of many countries including those developed nations. The impact is particularly worse in those resource limited settings including Myanmar. First and second waves in Myanmar during 2020 were effectively managed by the government. However, the momentum was disrupted due to the military coup in early 2021. People in Myanmar experienced serious consequences of the COVID-19 pandemic precipitated by the disorganized health system under the military junta. This study aimed to analyze the situation of COVID-19 occurrence and death proportions during its third wave in Myanmar.”\nConclusion: The conclusion of \" The data suggests that the outcomes were adversely impacted by the military coup.\" is very strong, but the results of the study does not directly refer to this outcome. I would suggest to improve the conclusion as: \"The data suggests that COVID-19 third wave severely hit Myanmar, adverse outcome fueled by the military coup. However, the online Telehealth clinics operated by Ministry of Health (MoH), Myanmar National Unity Government (NUG), offered the alternative accessible solution for the certain population within the country.\"\nIntroduction: Well written and structured.\nMethod: Given the descriptive nature of the study (exploratory), the current method and data analysis are enough for the study. However, given the large number of participants, regression analysis can be performed to see the factors associated with outcomes (recovered/death/complications). It is worthy to investigate risk of death (or) complications in association with cumulative symptoms (having two or more symptoms versus having only one by applying multilevel poisson regression model.\n\nResults: Table (1): For those with outcome of death, who fill in the information in the google form. It would be great if the authors shared the survey google form (English translated version). For the COVID-19 test, what kinds of test the participants are taking (PCR, or rapid antigen test?). Is it included in the survey?\nTable (2): p-value column needs to be corrected (between the age and sex category).\nTable (3): OK , however, I noticed the variables are multiple response variables. It is worthy to investigate risk of death (or) complications in association with cumulative symptoms (having two or more symptoms versus having only one) by applying multilevel poisson regression model.\nTable (4): It is better to recategorize the flow of the health care facility ( for example: others should be the last one).\nDiscussion: Well written and discussed accordingly with the results\nConclusion: The conclusion of \" The data suggests that the outcomes were adversely impacted by the military coup.\" is very strong, but the results of the study does not directly refer to this outcome. I would suggest to improve the conclusion as: \"The data suggests that COVID-19 third wave severely hit Myanmar, adverse outcome fueled by the military coup. However, the online Telehealth clinics operated by Ministry of Health (MoH), Myanmar National Unity Government (NUG), offered the alternative accessible solution for the certain population within the country.\"\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9775",
"date": "22 Jun 2023",
"name": "Spring Research Team",
"role": "Author Response",
"response": "Comment 1 The current study added the value of the knowledge gap on the COVID-19 impact at the community level. The available research papers on the COVID-19 were mainly conducted at the hospital level and online people movement. This study particularly highlights the true burden of COVID-19 within the population. Overall, this is a very good study, highlighting the disrupted health system and its impact on the health care sector response particularly at the pandemic situation of COVID-19. Below are the few comments and suggestions. Response 1: Thanks so much for the comments. Comment 2: Abstract Background: The first sentence of the background already concluding the severity of impact which is the main objective of the study. Background can be re-structured as “COVID-19 has disrupted health system of many countries including those developed nations. The impact is particularly worse in those resource limited settings including Myanmar. First and second waves in Myanmar during 2020 were effectively managed by the government. However, the momentum was disrupted due to the military coup in early 2021. People in Myanmar experienced serious consequences of the COVID-19 pandemic precipitated by the disorganized health system under the military junta. This study aimed to analyze the situation of COVID-19 occurrence and death proportions during its third wave in Myanmar.” Response 2: Thanks. We revise it based on your suggestion and word count limit as follows. “COVID-19 has disrupted health system of many countries, particularly worse in those resource limited settings including Myanmar. First and second waves in Myanmar during 2020 were effectively managed by the government. However, the momentum was disrupted due to the military coup in early 2021. This study aimed to analyse the situation of COVID-19 occurrence and death proportions during its third wave in Myanmar.” Comment 3: Conclusion: The conclusion of \"The data suggests that the outcomes were adversely impacted by the military coup.\" is very strong, but the results of the study does not directly refer to this outcome. I would suggest to improve the conclusion as: \"The data suggests that COVID-19 third wave severely hit Myanmar, adverse outcome fueled by the military coup. However, the online Telehealth clinics operated by Ministry of Health (MoH), Myanmar National Unity Government (NUG), offered the alternative accessible solution for the certain population within the country.\" Response 3: We revise it according to your suggestion. Comment 4: Introduction: Well written and structured. Response 4: Thanks Comment 5: Method: Given the descriptive nature of the study (exploratory), the current method and data analysis are enough for the study. However, given the large number of participants, regression analysis can be performed to see the factors associated with outcomes (recovered/death/complications). It is worthy to investigate risk of death (or) complications in association with cumulative symptoms (having two or more symptoms versus having only one by applying multilevel Poisson regression model. Response 5: Thanks for your suggestion. However, as you also mentioned that the main objective of our study is to highlight the overall burden of the COVID-19 amidst the military coup, our current analysis addresses the main objective of the study. Comment 6: Results: Table (1): For those with outcome of death, who fill in the information in the google form. It would be great if the authors shared the survey google form (English translated version). For the COVID-19 test, what kinds of test the participants are taking (PCR, or rapid antigen test?). Is it included in the survey? Table (2): p-value column needs to be corrected (between the age and sex category). Table (3): OK, however, I noticed the variables are multiple response variables. It is worthy to investigate risk of death (or) complications in association with cumulative symptoms (having two or more symptoms versus having only one) by applying multilevel poisson regression model. Table (4): It is better to recategorize the flow of the health care facility (for example: others should be the last one). Response 6: Table (1): For those with outcome of death, respondent is immediate family member of a deceased who stays together in the same house. Among the respondents, only 42% had received COVID-19 test. Over half of them were diagnosed and treated by the symptoms at that time. For the type of COVID-19 test, we cannot ask whether the test is PCR or RDT since most of them are lay people. Table (3): Thanks for the suggestion. As we’ve explained above, the main objective of our study is to highlight the overall burden of the COVID-19 amidst the military coup, our current analysis addresses the main objective of the study. Table (4): Thanks. We recategorized the flow of health care facility as your suggestion. Comment 7: Discussion: Well written and discussed accordingly with the results Response 7: Thanks Comment 8: Conclusion: The conclusion of \" The data suggests that the outcomes were adversely impacted by the military coup.\" is very strong, but the results of the study does not directly refer to this outcome. I would suggest to improve the conclusion as: \"The data suggests that COVID-19 third wave severely hit Myanmar, adverse outcome fueled by the military coup. However, the online Telehealth clinics operated by Ministry of Health (MoH), Myanmar National Unity Government (NUG), offered the alternative accessible solution for the certain population within the country.\" Response 8: Thanks. We revise according to your suggestion."
}
]
},
{
"id": "174658",
"date": "02 Jun 2023",
"name": "Nikos Kapitsinis",
"expertise": [
"Reviewer Expertise Health geography",
"Geographies of pandemics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn the introduction, second paragraph, I think it would very useful for the reader if the authors added and presented some socio-economic factors that affected the COVID-19 health implications. Several scholars have written about this. Illustrative studies that the authors could include are:\n\nKapitsinis, N. (2021) The underlying factors of excess mortality in 2020: a cross-country analysis of pre-pandemic healthcare conditions and strategies to cope with Covid-19. BMC Health Services Research 21: 11971.\nPana T, Bhattacharya S, Gamble D, Pasdar Z, Szlachetka W, Perdomo-Lampignano J, et al. Country-level determinants of the severity of the first global wave of the COVID-19 pandemic: an ecological study. BMJ Open. 2021;11:e0420342.\nIn the methods, the authors should explain more clearly and detailed how they distributed the online questionnaire, e.g. which online outlets they used. This will offer a more clear picture of methodology adopted.\n\nMoreover, the authors could present and describe whether the questionnaire included a question about the participant's status, i.e. whether he/she experienced COVID-19 or another person he/she knows. This is crucial to be clarified in the methodology section.\n\nThe authors mention that over 42% of participants received the COVID-19 test. What about the others that reported they have been infected? Is there a question about how the participants realised/clarified that they had been infected by COVID-19? I.e. what about testing methods? The authors present it as one of the limitations of the study, in the discussion and they could elaborate a little more on this.\n\nI think the authors could present the questionnaire and its questions in the appendix.\n\nIt would be useful if the authors presented some socio-economic data about Myanmar, in the discussion, and connect them with the capacity of the population to afford the private clinics and healthcare, but also the current status of public hospitals and healthcare in the country (number of doctors and medical beds per capita, for instance).\n\nThey could also highlight the importance of the use of online consultation. What it means for the country, how it can help populations excluded from healthcare or quarantined and whether it could be more applicable in the future healthcare pathways.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9774",
"date": "22 Jun 2023",
"name": "Spring Research Team",
"role": "Author Response",
"response": "Comment 1: In the introduction, second paragraph, I think it would very useful for the reader if the authors added and presented some socio-economic factors that affected the COVID-19 health implications. Several scholars have written about this. Illustrative studies that the authors could include are: Kapitsinis, N. (2021) The underlying factors of excess mortality in 2020: a cross-country analysis of pre-pandemic healthcare conditions and strategies to cope with Covid-19. BMC Health Services Research 21: 11971. Pana T, Bhattacharya S, Gamble D, Pasdar Z, Szlachetka W, Perdomo-Lampignano J, et al. Country-level determinants of the severity of the first global wave of the COVID-19 pandemic: an ecological study. BMJ Open. 2021;11:e0420342. Response 1: Thanks for the suggestion. We added the socio-economic factors as you suggested in the second paragraph of the introduction as follows. “Contextual factors that may reduce the COVID-19 mortality included adequate level of health care resources like doctors, nurses, hospital beds, strong primary health care, low rate of health privatization and wide health coverage (Kapitsinis N, 2021).” Comment 2: In the methods, the authors should explain more clearly and detailed how they distributed the online questionnaire, e.g. which online outlets they used. This will offer a more clear picture of methodology adopted. Moreover, the authors could present and describe whether the questionnaire included a question about the participant's status, i.e. whether he/she experienced COVID-19 or another person he/she knows. This is crucial to be clarified in the methodology section. Response 2: Thanks for the comments. We added more explanation about the distribution of online questionnaire. “The weblink to the Google form was made available to the public through a number of online outlets of Ministry of Health, National Unity Government of Myanmar such as Facebook page, Signal and Telegram.” Regarding the respondent, anyone who experienced COVID-19 themselves or anyone in the family members answered the questionnaire. We edited accordingly in the data collection section. Comment 3: The authors mention that over 42% of participants received the COVID-19 test. What about the others that reported they have been infected? Is there a question about how the participants realised/clarified that they had been infected by COVID-19? I.e. what about testing methods? The authors present it as one of the limitations of the study, in the discussion and they could elaborate a little more on this. I think the authors could present the questionnaire and its questions in the appendix. Response 3: Thanks for the comments. At that time, people from Myanmar had limited access to testing facility. We added more information on that issue in the limitation (last paragraph of the discussion section) as follows. “At that time, people from Myanmar experienced COVID-19 third wave and because of limited testing capacity and situation following the coup, most patients were diagnosed and treated according to the symptoms.” Regarding the questionnaire, we described the questions included in the 2nd paragraph of the data collection section under the method. Journal does not allow to put the appendix. Comment 4: It would be useful if the authors presented some socio-economic data about Myanmar, in the discussion, and connect them with the capacity of the population to afford the private clinics and healthcare, but also the current status of public hospitals and healthcare in the country (number of doctors and medical beds per capita, for instance). They could also highlight the importance of the use of online consultation. What it means for the country, how it can help populations excluded from healthcare or quarantined and whether it could be more applicable in the future healthcare pathways. Response 4: Thanks. We added more information of some socio-economic data in the fourth paragraph of discussion section according to your suggestion as follows. “Before the coup, in 2015-2016, doctor population ratio was one doctor per 1,477 population which was below the WHO recommendation of one per 1,000 population (Saw YM, 2019). Existing weakness in human resources in health was fueled by the attack of the military on the healthcare providers and health facilities, including the diversion of medical supplies to military use.”"
}
]
}
] | 1
|
https://f1000research.com/articles/11-1301
|
https://f1000research.com/articles/11-1021/v1
|
09 Sep 22
|
{
"type": "Systematic Review",
"title": "Prevalence, causes and impacts of human trafficking in Asian countries: A scoping review",
"authors": [
"Zeeshan Khan",
"Mohammad Rahim Kamaluddin",
"Saravanan Meyappan",
"Jamiah Manap",
"Ramalinggam Rajamanickam",
"Zeeshan Khan",
"Saravanan Meyappan",
"Jamiah Manap",
"Ramalinggam Rajamanickam"
],
"abstract": "Background: In Asian countries, human trafficking is often encountered as forced labor, forced marriage, sex trafficking, men, women, and children exploitation. This review points out how human trafficking activities are prevalent in Asian countries and also reveals different causes that are the basis of increasingly human trafficking in Asian countries such as poverty, unemployment, political uncertainty, war, natural disaster, corruption and weak policies. Human trafficking also creates huge health, physical, psychological and social implications on individuals and the overall society. Methods: The purpose of this study is to collect evidence on human trafficking in Asian countries. A scoping review methodology was used to systematically search online databases including Sage Journals Online, Wiley Online, Hein Online, Taylor & Francis Online, Web of Science, and Scopus literature to amalgamate information on this issue. For the purposes of this article, 64 studies met the inclusion criteria after searching and screening a total number of 1,278 studies. Results: The findings of this study were classified under three categories: prevalence of human trafficking in Asia, causes of human trafficking in Asia (poverty and unemployment, environmental and manmade disaster, weak policies and corruption), and impacts of human trafficking including social, health, physical, psychological impacts. Conclusion: Keeping in mind the prevalence and impacts of human trafficking, the author also recommends some meaningful and practical steps for policymakers and researchers to effectively tackle human trafficking in Asian countries.",
"keywords": [
"Human trafficking",
"Asian countries",
"prevalence of human trafficking",
"causes of human trafficking",
"social impacts",
"health impacts"
],
"content": "Introduction\n\nHuman trafficking is one of the hugely intensifying and alarming illicit worldwide trades. It is a process where human victims have been moved either voluntarily or involuntarily i.e., kidnapping, abduction, deception, use of force, fraudulent recruitment or giving and receiving payments to maintain the hegemonic power over others by the traffickers within the nation or across borders for various exploitation purposes.1 Furthermore, exploitation is also meant to include, inter alia prostitution of other persons, or other forms of sexual transgression, forced labour or services, slavery, or practices akin to slavery, servitude, or removal of human organs. In essence, it is apposite to say that human trafficking is a heinous, alarming cross border crime and a bane to humanity as it violates and transgress upon the basic human rights and personal liberties due to its lucrative and rapacious illegal business demand across the globe. There is no doubt that human trafficking is a modern-day form of slavery. The practice of abducting and tricking innocent people for the purpose of money exploitation and servitude is horrific and vile enough to infringe on human rights.2,3 While the effects of human trafficking are diverse, ranging from public health to environmental issues, the spectrum of violence has the biggest impact on the victims.4 In regard to public health, the problems that lie as a result of this crime include both physical and behavioral disturbances, such as the consequences of physical and sexual abuse.5 Living in crowded and cramped conditions often results in the spread of viruses and lethal diseases such as tuberculosis and infectious diarrhea.2 Not only that, sexually transmitted infections are more pronounced in cases where sexual activities are involved.6 Among the victims, there is a high prevalence of mental health issues such as anxiety, depression, trauma, and phobias as a result of physical and emotional abuse.4 Concerning environmental issues, most industries involved in human trafficking are likely to have a negative impact on the environment, which eventually leads to climate change.7 The increase in the number of migrant workers in forced labour activities has been proven as a major contributor to environmental damage.8 The demand for more workers in industries that heavily depend on human labour such as agriculture, fishing, logging, and mining, has increased the exploitation of both people and natural resources.9 Hence, the need to acknowledge that human trafficking can cause many detrimental issues must be taken seriously by many in order to end this crime.\n\nThere are millions of people including men, women and children around the world that are trafficked within the country or across the borders for different purposes i.e., forced labor, sexual exploitation and forced marriages.10 Around 800,000 women cross international borders for sexual exploitation, where 54% send to Central Asia and Europe, 25% to Southeast Asia, 14% to Middle East and Africa and 7% to America. Global Survey Index 2016, noted that nearly 45.8 million victims of human trafficking in 167 countries around the globe.11 It is also reported, that human trafficking has been considered one of the most remunerative methodical crimes, with illegal profit exceeding 150 billion US dollars every year and Asian region recorded the highest profit of 51.8 billion US dollars per year.12,13 Because of these illicit profits, large number of trafficked women, men and children victims had their freedom and basic fundamental human rights subjugated from them.13 It is estimated that every year around 5.5 million children are forced into labor conditions and 1.2 million are trafficked victims.14 However, boys and transgender persons are also trafficked.15 In general, human trafficking is an organized syndicated crime that is considered to be the third-largest illegitimate profiting crime in the world after drugs and weapons.16 Asian countries are the main fertile centers of human trafficking such as Pakistan, India, Bangladesh, Afghanistan, China, Malaysia, Sri Lanka, Philippine, Nepal, Thailand, Myanmar.17 It is to be noted that every year, millions of people become victims of human trafficking in Asian countries.11,17 Asia is considered as a largest continent of the world with a size of about 44 million km2 and with having large number of 4.6 billion population.18 With the inferential movement of people and expansion of population, the natural geography of Asia has widely changed. Because of such geographical and demographic changes, majority of people in Asian countries are facing huge social, economic and political difficulties.19 Apart from that, with the eruption of globalization, with preamble borders and with easy visa requirements, it is very easy for the migrant population to enter into majority of the Asian countries. Through this process, human trafficking and other criminal activities increase tremendously.20 Studies in Malaysia show that it is important to identify the nature of crimes in order to formulate preventive efforts.21–28\n\nThe goal of this review is to mainstream the activities of human trafficking in Asia alongside the violation of national and international human rights. Additionally, this review attempts to tap deeper into the nature of crime and to highlight the incidents of human trafficking in Asia and recommend suggestions to policymakers and practitioners to prioritize the concerned issue based on the findings of this review. The objectives of this review were as follows:\n\n1. To identify the prevalence of human trafficking in Asian countries.\n\n2. To assess the root causes and impacts of human trafficking in Asian countries.\n\n3. To analyse the research gap in the literature of human trafficking in Asian countries.\n\n\nMethods\n\nOne of the prominent features of the scoping review is to widely use all related literature according to the study design. In this review, the preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P) and PRISMA extension for scoping review checklist were used as a guideline.29,30 Consequently, this study consists of empirical, conceptual, and theoretical literature regarding human trafficking. Following are the details of the methods.\n\nFor the purpose of this review, the author only relied upon electronic databases to collect relevant research data. The specific databases that were used for searching the articles include, Sage Journal Online, Wiley Online, Hein Online, Taylor & Francis Online, Web of Science, and Scopus literature. These databases have rich data including, scholarly articles, journals, reports and other scholarly data that can be easily explored for a scoping review. The search for data took place from January 2015 to June 2022, by using different terms and keywords. The search strategy was as follows;\n\n(Human trafficking in Asia, social and economic factors contributing to human trafficking, causes and impacts of human trafficking, and names of Asian countries).\n\nVarious types of studies, reviews, and international professional reports included in the English language that meet the inclusion criteria, addressed the research objectives, full-text articles, and focused on human trafficking are presented in this review. Likewise, studies or reports published before January 2015, did not have a link with human trafficking and illegal migration, and did not focus on Asian countries were excluded from this review.\n\nFor this review, 1,278 sources were found in the online electronic databases. Initially, every article went through the process of screening; based on the title and abstract. Articles unrelated to human trafficking activities and irrelevant to Asian countries, were published before January 2015 and duplicates were removed in the process. After removing these data, a total number of 147 articles were selected for in-depth screening. Next, 83 articles and reports were removed at the eligibility stage because their content and concept did not match and be in tandem with the objectives of the study. Finally, 64 articles were selected and reviewed for this research. Figure 1 describes the flowchart of the scoping review process and identification and Table 1 summarizes the reviewed studies.\n\n\nResult\n\nThe scoping review selection process and summary of quality assessment for all reviewed literature are presented in Figure 1 and Table 1. More specifically, the search strategy for this review was limited to Asian countries, a total number of 64 articles were included in this review and the content of reviewed articles reflated the prevalence of human trafficking, causes of human trafficking and impacts of human trafficking in Asian countries. For the effects and results of the individual sources, the following are the variables obtained by the researchers from the selected articles.\n\nIn the 21st century, international political environment pose different major issues of concern. The most passing issues is the prevalence of trafficking in persons across the globe. The history of human trafficking could be traced back many years ago when slavery and forced servitude were among the said issues. We might think that in the 21st century such forms of trafficking activities have ended, but unfortunately and to the chagrin of mankind, new forms have emerged. This assumption follows the classical phrase; “old wine in new bottle”.31,32 Internationally, the human trafficking is recognized as a crime since year 2000.33 According to the United Nations office of drugs and crime (UNODC) the spread of human trafficking activities increased between year 2003 to year 2016 in the world and specifically in Asian countries.34 12.3 million Victims of these crime were reported in year 2005 which later increased, 21 million victims in year 2012 and eventually 40.3 million victims in year 2016 on multifarious forms such as sexual exploitation, forced labor and forced marriages.35 In these estimations, 30% of human trafficking victims were recorded from south Asia, East Asia and pacific region which are considered to be a large share in total global figure.34 It has also been noted that human trafficking increased in the Asian countries after the invasion of Russia and later in year 2001 by US civil war on Afghanistan. With this fact, majority of Afghan and Pakistani girls are being trafficked to Saudi Arabia and UAE. Likewise, women and children are also trafficked to Pakistan and other Asian countries for forced marriage and forced labor purposes.36 In the last 30 years, more than 30 million of children and women are sexually victimized in Asia. Mostly Asian trafficking victims are sent to Asian countries, i.e., Thailand, Japan, Pakistan, India, Bangladesh, Nepal and Taiwan.37 The latest global survey index indicates that 35.8 million people are suffering due to enslavement. These estimations based on different existing studies and on face to face-to-face interviews conducted by Gallop international in different countries, including Brazil, Pakistan, Nepal, Malaysia, Indonesia, Qatar, Saudi Arabia and Russia.38\n\nLikewise, a report on human rights indicated that in Bangladesh, 10,000 to 20,000 women and men are trafficked internally as well as on international borders to India, Pakistan, Bahrain, Kuwait and many other Asian countries for sexual exploitations.39 Similarly, in India 14 million of human trafficking cases estimated in year 2014, which includes victims of labor trafficking, sex trafficking and forced marriages.40 In year 2016, Global Slavery Index indicated that majority of 58% of human trafficking victims are reported in Asian countries specifically in China, India, Pakistan, Uzbekistan and Bangladesh.11 It is noted that 57% of workers (women and children) are the victims of human trafficking in Thailand. Generally, Thailand also transports human trafficking victims to other countries such as India, Malaysia, Japan, Hong Kong, Germany and Australia for the purpose of sex business.41 Likewise, majority of North Korean women trafficked to Asian countries for sexual exploitations, are being sold to Chinese men especially.42 Malaysia is also one of the targeted countries for the human trafficking activities in Southeast Asia due to its impressive economic growth, strategic location and political stability.43 It is of irresistible truth that on yearly basis, Malaysia has a large influx of migrant workers, be it documented or undocumented working in various fields of economy and being susceptible to human trafficking thereafter.\n\nHuman trafficking is considered a fast-growing crime in the world. It is imperative to know why an individual becomes a victim of trafficking through the use of deception and coercion. The causes of human trafficking vary from region to region and country to country. In Asian countries, many push and pull factors contribute and describe the root causes of human trafficking. In the general contexts, it can be divided into four main categories namely political, economic, environmental and cultural.44 There are several causes as to the occurrence of human trafficking. In this study, the author will focus on some major causes which significantly and prevalently contribute towards human trafficking. These causes are the following:\n\nPoverty and unemployment: Poverty is one of the major causes that contribute to human trafficking.2 It is the reason behind the decision of an individual to become a prostitute or forced labor. It is primarily because of their weak economic duress and fiscal status. The gap between developing and developed countries with poverty and marginalization has fabricated with globalization. Majority of population in Asian countries live in third world conditions with less basic infrastructure and employment opportunities. Traffickers take advantage from these conditions and give false offers to poor people to exploit them.36,38,45 Many individuals leave their families and home because of the financial, educational and job opportunities, but most of them were coerced into trafficking.16 A study indicates, that every year five to seven thousands girls are trafficked to India from Nepal. These girls are sold by the poor parents on the façade of bogus marriages or employment promises. A qualitative study resulted that because of economic troubles, Thai and Filipina women had been trafficked as a sex worker.46 Likewise, many Pakistani and Indian women, men and children migrated to Europe, America and other Asian developed countries for the purpose of low skilled jobs like constrictions and driving. Many of them become the victims of human trafficking.10,12,44 In addition, recently more than 130 Bangladeshis were trafficked to Thailand with fake promises for employment. It is also noted that 200,000 Filipinos became the victims of labor trafficking.47 Large number of people from central Asian countries i.e., Kyrgyzstan and Uzbekistan are trafficked on the promises of better socio-economic conditions and bright future. In addition, 70% of North Korean women are trafficked to China for the purpose of forced marriage and forced labor.47,48 Similarly, because of fraudulent employment offers, many men and women are trafficked from Sri Lanka, Bhutan, Maldives and Afghanistan.39\n\nEnvironmental and manmade disaster: In today’s world, many populations migrated from one place to another place because of a conflict, natural calamity, terrorism and war. The issue of human trafficking burns whenever a disaster strikes.49 The United Nations (UN) environmental program has stated that because of disasters 20% to 30% of human trafficking activities increased.50 It is reported that by the end of 2017, 68.5 million people were forcibly displaced due to conflict and natural disasters. More than two-thirds of them originated from Afghanistan, South Sudan, Somalia, Syria and Myanmar in the form of refuges, IDPs and asylum seekers.51 Similarly, due to militancy and terror, large numbers of Rohingya Muslims trafficked to Bangladesh, Malaysia, Indonesia and other countries of Asia. A number of victims were sexually abused, raped, put to labor by force and killed. Same cases were also noted in Iraq and Libya.52 Furthermore, climate changes and other forms of environmental changes also lead to child labor, domestic abuse and human trafficking.50 During flood in year-2011, approximately 13 million people were affected in Thailand. The consequences of this natural disaster were encountered as economic inequality, political and most importantly human rights violation and human trafficking.53 Likewise, during 2010-flood, the cases of rapes, sexual harassment and trafficking of young girls and women increase in Pakistan and Bangladesh. Same scenario was also reported after 2005 earthquake in Kashmir, Pakistan.54 In addition, after the 2015 earthquake in Nepal, traffickers targeted mostly children in camps and shelters for victimization.50\n\nWeak policies and corruption: In the 21st century the political model of the world changed because of war and political unrest in the Middle East. Majority of traffickers take advantage from these favourable environments.55 Corruption is the main compound of weak policies and law enforcement.56 The irregular migration increases because of the high level corruption and weak policies by the government and political leaders.57 For example, the border of India and Nepal monitored on regular basis. Majority of Indian and Nepali citizen cross the 1850-kilometer-long border without showing any legal documents. The trafficker easily targeted people from Nepal and make heavy dominancy on the corrupt authorities.56 In several Asian countries weak policies of political leaders and the corruption of law enforcing agencies leads to irregular migration and human trafficking.15 Like in Iraq, Libya and Myanmar the government officials and other policy makers involve in the recruitment of human trafficking for the purpose of child soldiers and forced labor in armed forces. Armed military and other political and government policy makers have used trafficking to increase their resources and political power.53 Most of the trafficking victims have not trust on government agencies and did not want to report their cases in police stations. For instance, one female victim told “if we go to the police station for help, I am sure they will not help”.42\n\nHuman trafficking has created hostile social, physical and psychological impacts on individuals. It also has social, economic and political disorders on the system of society.15,31,58 For instance, a study of 14 countries indicates that more than 95% of women victims had suffered by physical and sexual violence. It is also documented that 23% of Nepalese human trafficking victim girls and women were tested HIV positive.37 Likewise, 33% of psychical violence cases of human trafficking victims reported from Cambodia. Similarly, in south Asian countries a large number of men, women and children i.e., 22% to 49% experienced physical and sexual violence.59 It was observed during the collection of data from Cambodia, Thailand and Vietnam, that majority of men victim respondents had experienced physical violence (e.g. Beaten, kike, slapped, dragged and push). While women and children highly observed in sexual violence.58 Furthermore, the victims of human trafficking such as women, men and children are noted in the high risk of psychological wellbeing.60,61 Traffickers use the tactics of threats to control the minds of victims. They usually threaten their families to violence and deaths. Degradation is the most powerful psychological tactic, used by traffickers to control the victim’s behaviour. Likewise, the traffickers insulted and humiliated the victims. They also destroyed their privacy and dignity and treated them like animals. For example, a victim of trafficking told that “it was very difficult, he was treating me like a dog”.61 However, in different studies the trafficking victims commonly documented psychological issues including, stress, anxiety, depression, nightmares, insomnia, personality disorder or chronic. A recent study examined 98% trafficking victims have at least one psychological disorder. It is also reported that because of these psychological problems many of victims commit suicide.62,63 In addition, human trafficking activities also create huge impacts on overall society. In every society, traffickers search for targeted young women and men who are looking for a job or education opportunities. For example, after the victimizations, large numbers of Indian victims do not want to return to their home countries, because of social stigmatization, threat calls of traffickers and bad economic condition.60\n\n\nDiscussion and conclusion\n\nHuman trafficking is a global phenomenon. Its dimensions vary from one country to another, but it usually creates huge vulnerability for individual and communities. This scoping review blended advanced knowledge about the issue of human trafficking in Asian countries, including general overview, the prevalence and its causes and socio-health implications. In a nutshell, during this review it is concluded from the findings that majority of Asian countries i.e., India, Pakistan, Thailand, Myanmar, Burma, Afghanistan, Bangladesh, Nepal, Iraq, Syria, Uzbekistan, North Korea, Bhutan, and Sri Lanka were found to be the most vulnerable ones in the context of sex, forced labor and debt bondage trafficking. It was further discovered that in these countries, different social, economic and political elements contribute to force individuals towards victimization of human trafficking.32 The lives of the victims are always at risk. Likewise, many studies reported that trafficking in persons is a serious infringement of human rights. The main intention of the traffickers is to sexually, physically, psychologically and forcefully exploit the victims. The victims of child trafficking specifically girls, are trafficked into different commercial sex industries, massage centers, hotels and private locations. Because of sexual exploitation, massive number of young girls, women and children are suffering with HIV/AIDS.64–66 Furthermore, after victimization, the process of returning back to the society and living in a normal life situation is a big challenge for human trafficking victims. It is to be noted that many of them commit suicide because of anxiety, stress, depression and fears of societal stigmatization.66 In this article different studies highlight the high level variability of victims in the shape of severe health outcome and violence. In addition, many scholars affirmed that corruption, weak government and political policies are deeply intertwined in the Asian region. Traffickers have organized networks and links. In many Asian countries, even law enforcement officer’s support the traffickers. In this way, many corrupt government officers and traffickers make huge illicit profits.67 Meanwhile, gaps still exist in our understanding of the outcomes to developing future clarity. This still needs more policies and practices in Asian region to increase the identification of victims and expose the underground network of traffickers. It is somehow heartening to note that at the global stage, plethora of international legal framework took birth in the pursuit to combat human trafficking such as the Protocol to Prevent, Suppress, and Punish Trafficking in Persons, Especially Women and Children and the Protocol Against the Smuggling of Migrants by Land, Sea and Air which are part of the United Nations Convention Against Transnational Organized Crimes.34 These legal instruments are the impetus aimed to provide effective action to prevent and combat human trafficking apart from providing protection to the victims and swift punishments to the perpetrators. More recently in year 2015, ASEAN Convention Against Trafficking in Persons was signed by all the ASEAN leaders at the 27th ASEAN Summit in Kuala Lumpur, Malaysia which saw a positive progressive move by the countries in the ASEAN region to address human trafficking issue seriously. This particular Convention inter alia, sets out inter-state cooperation on border control, mutual legal assistance and criminal extradition, law enforcement in the cross-border context and some standards on victim assistance and protection including safe repatriation to the home countries.68\n\nTherefore, premised upon the discussion and analysis above that the author recommends the following suggestions to the government, non-government policy makers. These recommendations also provide directions to academic scholars for future research.\n\n\nLimitations and policy recommendations for future research\n\nThis scoping review has several limitations. Firstly, information gathered regarding the link between human trafficking with prevalence, causes and impacts in Asian countries was only obtained from the Sage Journal Online, Wiley Online, Hein Online, Taylor & Francis Online, Web of Science, and Scopus literature and published from January 2015 to June 2022. Secondly, this review was limited to those articles and international reports which must have a focus on or a link with Asian countries and also have link with human trafficking and illegal migration. Therefore, it is possibility that some high-quality research articles might have been excluded from this scoping review process.\n\nApart from the limitations, there are still gaps in our knowledge and challenges to developing future clarity. Firstly, it is highly important that every Asian country needs to imbue an operative surveillance system to better understanding the essence and immensity of human trafficking and make effective interventions. Furthermore, government officials and policy makers need to understand the seriousness of trafficker’s violations and make a high-level committee to expose the corrupt officials and those who cooperate the traffickers. Likewise, this is still a need that future research should contribute to increase the identification of human trafficking victims. Additionally, every government and non-government agency and academic scholar needs to develop awareness programs on local and international basis regarding the illicit activities of human trafficking. These awareness campaigns must educate the local people of all ages and gender about the risks of traffickers. Besides, empowerment program should be given to the trafficking victims. They need a transit shelter, counselling, and training program to handle trauma and continue their life survival. Finally, human traffickers and individual who abet them deserves severe punishment for violating human rights.\n\n\nData availability\n\nNo data are associated with the article.\n\nFigshare: PRISMA-ScR checklist for “Prevalence, causes and impacts of human trafficking in Asian countries: A scoping review” https://doi.org/10.6084/m9.figshare.20484357.69\n\nData are available under the terms of Creative Common Attribution 4.0 International license (CC BY 4.0)",
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}
|
[
{
"id": "149994",
"date": "14 Sep 2022",
"name": "Haezreena Begum Abdul Hamid",
"expertise": [
"Reviewer Expertise Human trafficking",
"migration",
"smuggling",
"gender",
"victimisation",
"international crimes."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an ambitious piece of research and writing which did not quite hit the mark unfortunately.\nThere seems to be a confusion on what amounts to human trafficking in this paper and the authors tend to conflate human trafficking with illegal migration. Many trafficked victims migrate legally but are later trafficked, many are also smuggled but later trafficked. All these are not properly understood or explained in this paper. The choice of words used such as bane, germane, etc are not appropriate in the context of trafficking.\nThere were multiple grammatical errors throughout the paper which makes it hard to follow at times.\nThe paper also kept referring to human trafficking as a cross border-crime. While many human trafficking activities occurs cross borders, many occur domestically and also internationally. Therefore, trafficking occurs domestically, trans nationally and internationally. The paper appears to present human trafficking as a very straight forward activity and have omitted the complexities that rises within human trafficking. It is vital to explain how the term trafficking is vague and is subject to different interpretations which affects the countries policies and practices.\nTerms such as modern slavery is rampantly used in this paper when this term itself is very contentious. There must be a clear explanation on what slavery is and why this term is being used in this article. There also seems to be a confusion between the lives of some undocumented migrants who lives in cramped spaces and the lives of trafficked victims. The victimisation of trafficked victims are all jumbled up to sound like they are being physically tortured when most harms are caused through psychological and emotional means. This was not explained thoroughly in the paper.\nAnother error in this paper is how South Asia countries are referred to as Asian or Asean countries. South Asia countries include Pakistan, Bangladesh, Nepal and India and are not members of Asean countries. The term Asian is different from Asean and there must be a clear distinction made between Southeast Asian countries and South Asia countries. Asean on the other hand is an association of 10 (+1) Southeast Asian countries that works together to promote political, economic, and cultural growth. In this sense, the title itself is misleading and incorrect.\nOne of the greatest challenges in trafficking is the data obtained from various sources as there's no standard data in assessing human trafficking victims or human trafficking activities. There's been a plethora of literature and critiques on this. Each organization would have its own variables in collating their data and all these were not discussed.\nAlso, human trafficking can be carried out by individuals, groups or organised crime and not just organised crime per se as referred to in this article. I find this troubling and misleading. There's also no mention of the recruiters that could also involve family members, relatives and friends.\nThere is plenty of misleading information in this article particularly on how trafficking activities are carried out. While trafficking could also include involuntariness, many victims voluntarily migrate to other countries but eventually find themselves trafficked. This was not discussed in the article when this is the most prevalent form of deception in trafficking. The term deception would also include under payment or non-payment of wages, poor living conditions or conditions of work that differs from what was promised earlier which does not necessarily mean poor conditions. It can mean different working hours, clients, type of work, places, etc. Although the authors are all from Malaysia or based in Malaysia, there was no mention of the Malaysian Anti Trafficking and Anti Smuggling of Migrants Act 2007, neither were there references made to this Act. The annual US Trafficking in Persons Report was not mentioned in this article when this report forms an integral part of the assessment of trafficking globally.\nThe methodology was vague, clunky, and incomplete. There needs to be more discussion and understanding on what amounts to methodology and methods with regards to conducting document analysis, data analysis, content analysis, thematic analysis and secondary analysis in trafficking. Overall, the paper is rather weak and contains many misleading statements. The article needs to be re-written to reflect the true nature of human trafficking. More research and analysis is needed.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? No\n\nAre sufficient details of the methods and analysis provided to allow replication by others? No\n\nIs the statistical analysis and its interpretation appropriate? No\n\nAre the conclusions drawn adequately supported by the results presented in the review? No",
"responses": []
},
{
"id": "151686",
"date": "19 Oct 2022",
"name": "Farhan Navid Yousaf",
"expertise": [
"Reviewer Expertise Migration",
"human trafficking",
"human rights"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an interesting review article that focuses on a very significant issue of human trafficking in Asia. The authors did a good job in summarizing the available literature highlighting the prevalence, causes, and impacts of various forms of human trafficking in the region. However, I have the following observations:\nThe authors need to articulate their main argument and contribution of the study to the existing body of knowledge. How the information about Asia helps to understand and fight trafficking as a global issue.\n\nWhile discussing the situation of trafficking in Asia and anti-trafficking interventions, the authors need to be careful not to oversimplify or overgeneralize their findings. They also need to discuss regional diversity, and specific forms of trafficking that prevail in particular countries. The authors may consult and cite annual trafficking in persons report issued by the US State Department and UNODC’s Global Report on Trafficking in Persons (2021) that provide an overview of patterns and flows of trafficking in persons at global, regional and national levels\n\nThe section on policy recommendations needs to be further strengthened linking it with the findings of the study. Lack of coordination among countries to counter trafficking is also a serious issue. For example, despite some regional Conventions e.g., ASEAN Convention Against Trafficking in Persons, and SAARC Convention on Prevention and Combating Trafficking of Women and Children for Prostitution, countries have not yet taken concrete steps to mutually address this issue at the regional level.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "149995",
"date": "19 Oct 2022",
"name": "Sunee Kanyajit",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn my opinion, this article is very interesting because the researchers select other academic articles from a variety database. Consequently, this article is reliable. Also, meta-analysis is appropriate with this article. However, I suggest that this article should add data and information as follows.\nIn the methodology section, the article gathers a lot of data from variety database and extract to main issue. So, please explain and clarify the how the methodology was conducted.\nIn result section, the article shall explain data in Table 1. Also, please explain reason 1, reason 2 and reason 3. Especially, the reason 3 must clarify how to find out. The result shall increase more information. Increasing data in result section make this article to be perfect and beneficial for reader.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-1021
|
https://f1000research.com/articles/12-723/v1
|
21 Jun 23
|
{
"type": "Research Article",
"title": "Is metformin the only culprit for cognitive impairment in diabetes?",
"authors": [
"Murali R",
"Archith Boloor",
"Yeshwanth H",
"Murali R",
"Yeshwanth H"
],
"abstract": "Background: As patients with diabetes are conventionally on a long-term prescription for metformin, it is important to identify any increase in their risk for developing cognitive disorders due to metformin. Hence, an attempt was made to study the cognitive impairment by using Montreal Cognitive Assessment test (MoCA) as a possible predictor of development of cognitive impairment in type 2 diabetes patients on metformin therapy. Methods: Four hundred type 2 diabetes patients on metformin were enrolled for this cross-sectional study, and data recorded. Cognitive test MoCA was administered and a score less than 26 was considered abnormal. Results: In this study, the participants on metformin had a statistically significant correlation with age > 65 years, duration of diabetes (>5 years), metformin dose (1 gm and more) and presence of diabetes complications. Ordinal regressions showed significant correlation between abnormal MoCA scores and older age, longer duration of DM, and presence of one of the DM complications. Conclusions: Amongst patients receiving medical therapy for control of type 2 diabetes, participants using metformin showed a very high prevalence rate of abnormal MoCA scores (85%). Increased duration of metformin intake leads to a decline in MoCA performance.",
"keywords": [
"Metformin",
"MoCA",
"diabetes mellitus",
"cognitive impairment."
],
"content": "Introduction\n\nDiabetes mellitus (DM) is a multifactorial disorder which leads to end-organ damage in many of the vital organs of the body, including the nervous system. Dementia and cognitive decline are increasingly being attributed to diabetes complications. Relationship between DM and cognitive decline is due to various diabetes-related factors (macro and micro-vascular complications, chronic inflammatory changes, persistent hyperinsulinemic state, resistance to the action of insulin, impaired metabolism of glucose or free radical mediated damage), cardiovascular related risk factors (elevated blood pressure, atherosclerotic coronary artery disease), and lifestyle related risk factors (dietary habits, smoking, lack of exercise).1–4\n\nTreatment options for DM namely insulin and oral hypoglycaemic agents (OHAs) which can potentially prevent diabetes complications like cognitive decline and decrease the diabetes symptoms are of significant importance. Moreover, these treatment options may halt cognitive decline in diabetes patients through anti-inflammatory effects of the drugs or by targeting the vascular and neurodegenerative complications. Several studies have proven that better glycaemic control leads to improvement in several subjective and objective measures of cognitive performances.5–7\n\nThe frequently used OHA for treatment of diabetes is metformin. The mechanism of action of metformin is to prevent hepatic release of glucose, to improve peripheral utilization of glucose,8,9 to increase the sensitivity of insulin in the peripheral tissues and to restore signalling pathways of insulin.10 Metformin protects against neurodegeneration by decreasing insulin resistance, optimizing blood glucose levels, decreasing adiposity, and decreasing the production of atheromatous plaques. Apart from the peripheral actions, studies have shown that this drug also has neuroprotective properties on the nervous system and anti-inflammatory properties.9 An attempt was made here to study the cognitive impairment by using Montreal Cognitive Assessment test (MoCA)11 as a possible predictor of development of cognitive impairment in patients with type 2 diabetes on metformin therapy.\n\n\nMethods\n\nIn this cross-sectional study, we enrolled 400 type 2 DM patients attending medical outpatient and inpatient departments of teaching hospitals attached to Kasturba Medical College, Mangalore. They were enrolled by consecutive patient selection, and if they satisfied the eligibility criteria demographic data and history were recorded, general physical examination and systemic examination were done and recorded. This study received ethics approval from Institutional Ethics Committee, Kasturba Medical College, Mangalore. The approval number is IEC KMC MLR 09-16/230.\n\nAll type 2 DM patients attending the outpatient and inpatient of teaching hospitals attached to Kasturba Medical College, Mangalore who satisfy inclusion criteria were enrolled in the study. Adults aged above 18 years of age with diabetes (ADA criteria) who were on metformin were included in the study. The patients were included only after obtaining written informed consent. Diagnosed cases of type 1 diabetes, thromboembolic disorders, mood disorder, depression, Alzheimer’s disease (AD) and other dementias were excluded.\n\nThe data collected included demographic details, detailed medical history, history regarding the present event, drugs used by the patients, physical examination findings and Montreal Cognitive Assessment (MoCA) test report.\n\nSeveral factors responsible for decline of cognition which have also been associated with DM were included as covariates in this study. Variables noted like age, gender, educational qualifications, duration of DM, dosage and duration of metformin and other OHAs, and presence of DM complications.\n\nFor cognitive assessment Montreal Cognitive Assessment (MoCA) was used. MoCA is a screening tool for mild cognitive dysfunction. MoCA takes about 10 minutes to administer. It assesses the following domains of cognition: attention and concentration, executive functions, memory, language, visuo-constructional skills, conceptual thinking, calculations, and orientation. Maximum possible score is 30 points. A score of >26 is considered normal. One point was added for an individual who has a formal education of twelve years or lesser, to give a possible maximum score of 30 points.\n\nStatistical analysis for the study was conducted using the IBM SPSS Version 25.0 (RRID:SCR_016479). Subgroup analysis was done according to the dose and duration of metformin therapy, age and sex of the patient, presence or absence of other diabetes complications. The primary endpoint was presented as proportion of patients with cognitive impairment as detected on the MoCA. For the correlation between categorical variables chi-squared test or Fisher’s exact test was used. For the correlation between categorical variable with continuous variable an independent t test or Mann-Whitney U test was used. The variables that showed a significant association were further tested on an ordinal logistic regression. P value <0.05 was considered statistically significant.\n\n\nResults\n\nTable 1 describes characteristics of the study population. The oldest patient in our study was 83 years old and youngest was 34 years old. Majority of the participants in our study were between the age of 50 and 70 years. Our study population was predominantly male. The male to female ratio in the study was 2.1:1.\n\n* Dipeptidyl peptidase 4.\n\n+ Montreal Cognitive Assessment test.\n\nMost of patients included in our study had a duration of DM above 5 years (341), 59 patients who had DM for less than 5 years. Diabetic nephropathy was present in 34 % of the subjects, while retinopathy and neuropathy were present in 12% and 39% of the subjects respectively.\n\nMajority of our study patients were on metformin and sulfonylurea (SU) combination. Forty-two (10.5%) of the subjects were on insulin & metformin while 13.5 % were on insulin, metformin & SU. Twenty-four (6%) were on metformin, SU & DPP4 inhibitors (DPP4I), 3.5% were on metformin, DPP4I & insulin, 8.3% were on metformin, SU, DPP4I & insulin, 2.3% were on metformin & thiazolidinedione, 6.3% were on metformin, SU & thiazolidinedione, 4.5% were on metformin & DPP4I, 2% were on metformin & alpha glucosidase inhibitors (AGI), 0.8% were on metformin, AGI & insulin, 0.5% were on metformin, thiazolidinedione & insulin.\n\nMontreal Cognitive Assessment (MoCA) test was applied to all the subjects. A total MoCA score of twenty-six or more is considered normal.\n\nIn our study, 341 (85%) subjects had abnormal MoCA score i.e., less than 26 and only 15% had score more than or equal to 26. Scores below 26 and 17 indicate mild cognitive impairment (MCI) and dementia, respectively. In our study 124 patients had score below 17.\n\nEighty-five percent of the subjects on metformin had abnormal MoCA scores, 91% of patients on SU drugs had abnormal MoCA scores while it was 78.5% in patients not on SU drugs. This correlation was very highly significant.\n\nNinety-five percent of patients on thiazolidinediones had abnormal MoCA scores while it was 84.5% in patients not on thiazolidinediones. This correlation was not statistically significant. While 98.9% of patients on DPP4I had abnormal MoCA scores it was 81.4% in patients not on DPP4I. This correlation was very highly significant. All patients on AGI had abnormal MoCA scores while it was 85% in patients not on AGI. This correlation was very highly significant. All patients on insulin had abnormal MoCA scores while it was 78.8% in patients not on insulin. This correlation was also very highly significant.\n\nWhen we correlated MoCA with variables Table 2, we found statistically significant correlation with age >65 years, duration of diabetes (>5 years), metformin dose (1 g and more) and presence of complications. Running ordinal regression among the above significant variables we found the results depicted in Table 3 with significant correlation between abnormal MoCA scores and older age, longer duration of DM, and presence of one of the DM complications.\n\n\nDiscussion\n\nSince type 2 diabetes patients are conventionally on a long-term treatment with metformin, any association, if found between metformin use and cognitive impairment multiplies their risk for developing cognitive disorders. Such an association needs to be further evaluated and analysed as cognitive impairment. It is a diagnosable condition which can be monitored if detected early, and further deterioration can be halted.\n\nThe prevalence of abnormal MoCA scores of less than 26 (signifying cognitive impairment) was calculated to be 85% in the metformin users. This shows that those patients prescribed metformin for control of diabetes are at a higher risk for developing dementia. These results corroborate with the results of the case-control study carried out by Imfeld and colleagues12 in UK where amongst the metformin users, those who used 60 or more prescriptions of metformin showed a higher risk for developing AD with an adjusted odds ratio (AOR) = 1.71, 95% CI = 1.12–2.60, while those using anti-diabetic drugs did not show any altered risk for developing AD.\n\nOur study did find a significant association between metformin use and an abnormal MoCA score of <26 (cognitive impairment) with a P-value of 0.006. The latest study done by Murray MD and colleagues was presented in International Alzheimer’s Association Conference. Of the study participants, 150 had used metformin. On follow-up, 87 participants developed dementia. After adjusting for age, gender, BMI, education, and APOE ε4 status, metformin use was associated with a greater risk for incident dementia (hazard ratio 2.28; P =.0152).\n\nLimited evidence exists regarding the association between treatment options for DM and cognitive performance. The results of two longitudinal studies noted similar cognitive performance scores (TICS and a global score) for study participants without DM and for patients in the OHA treatment group.13,14 An Australian study showed that a greater decline in global cognition and executive functioning was observed in participants with diabetes. But, on analysing further, there was no relationship between the type of diabetic treatment (diet control versus OHA) and the fall in global cognitive performance.15 In contrast to this study, using Wechsler Logical Memory story recall Elias et al.16 showed poorer cognitive performance results among patients with DM, however on cognitive assessment using “immediate and delayed verbal memory on the story recall test” and “visual memory” the study group on insulin therapy performed more poorly compared to healthy controls. Notably, analysing the results of the seven neuropsychological tests, the performance of patients on OHA did not differ from the non-diabetic participant group. In the Primary Research in Memory (PRIME) study and the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, Moore et al. studied the effects of DM and metformin use on cognitive performance. Among the study participants, metformin use was associated with worse cognitive performance (after adjusting for gender, age, depression, and educational qualification). However, only MMSE was used to measure cognitive function in this study. Also, this study did not analyse other treatments used along with metformin. This correlation was not significant after adjusting for B12 levels.17 Ng et al.18 in their study included a larger cohort wherein they assessed the effect of metformin on cognitive performance using MMSE. The results of the study (both cross-sectional and longitudinal analyses) showed significant protective effects of the drug metformin. In our study we did not asses vitamin B12 levels due to financial constraints. However, we found significant correlation with increasing age, dose and duration of metformin. Also, in our study we had 57 pure vegans and all of them had abnormal and low MoCA scores.\n\nThe ordinal regression data reveals a positive correlation between abnormal MoCA scores and older age, longer duration of DM, and presence of complications. Longer duration of DM can also signify longer duration of metformin usage. Metformin being the first line treatment, all the subjects in the study have been on metformin since they were diagnosed to have DM. Presence of complication and older age group as a positive correlation may signify that DM and aging are independent risk factors, as has been described in several studies.1–4,13–17\n\nThere are a few limitations in this study. Firstly, lack of a control group without antidiabetic medications, the results of our study can only give preliminary conclusions, which needs to be further proved by larger multi-center clinical trials with higher sample size. The correlation between cognitive impairment in metformin users have been attributed to deficiency of vitamin B12, vitamin D and calcium. We did not assess these deficiencies in our study. Also, cognitive impairment is associated with stroke and other macrovascular diseases. In our study we did not analyse and correlate cognitive impairment with macrovascular complications. Many of our patients were on other anti-diabetic agents. The role of metformin alone causing cognitive decline cannot be ascribed. Also, the score we used for ascertaining cognitive decline, the Montreal Cognitive Assessment (MoCA), which has been earlier used in studies of dementia, but has not been used in diabetic population.\n\n\nConclusion\n\nAs per our study, the participants using metformin showed a very high prevalence rate of abnormal MoCA scores (85%). Participants using metformin had worse performance in MoCA (scores <26). Increased duration of metformin intake leads to a decline in MoCA performance.",
"appendix": "Data availability\n\nDryad: Is metformin the only culprit for cognitive impairment in diabetes?, https://doi.org/10.5061/dryad.wpzgmsbrs. 19\n\nThis project contains the following underlying data:\n\n- Thesis_stats_final.xlsx\n\nDryad: Is metformin the only culprit for cognitive impairment in diabetes?, https://doi.org/10.5061/dryad.wpzgmsbrs. 19\n\nThis project contains the following extended data:\n\n- MoCA_Availability.docx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nThe authors thank the support received from Manipal Academy of Higher Education, Manipal.\n\nWe acknowledge that this article is an updated version of the preprints available at SSRN (DOI: 10.2139/ssrn.3387524) and Research Square (DOI: 10.21203/rs.3.rs-1491947/v1).\n\n\nReferences\n\nCraft S, Watson GS: Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol. 2004 Mar; 3(3): 169–178. Publisher Full Text\n\nStrachan MW, Reynolds RM, Marioni RE, et al.: Cognitive function, dementia and type 2 diabetes mellitus in the elderly. Nat. Rev. Endocrinol. 2011 Feb; 7(2): 108–114. Publisher Full Text\n\nBanks WA, Owen JB, Erickson MA: Insulin in the brain: there and back again. Pharmacol. Ther. 2012 Oct; 136(1): 82–93. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKodl CT, Seaquist ER: Cognitive dysfunction and diabetes mellitus. Endocr. Rev. 2008 Jun; 29(4): 494–511. Publisher Full Text\n\nTesta MA, Simonson DC: Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled, double-blind trial. JAMA. 1998 Nov 4; 280(17): 1490–1496. Publisher Full Text\n\nGradman TJ, Laws A, Thompson LW, et al.: Verbal learning and/or memory improves with glycemic control in older subjects with non-insulin-dependent diabetes mellitus. J. Am. Geriatr. Soc. 1993 Dec; 41(12): 1305–1312. Publisher Full Text\n\nMeneilly GS, Cheung E, Tessier D, et al.: The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes. J. Gerontol. 1993 Jul; 48(4): M117–M121. Publisher Full Text\n\nHe L, Sabet A, Djedjos S, et al.: Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell. 2009 May 15; 137(4): 635–646. PubMed Abstract | Publisher Full Text | Free Full Text\n\nŁabuzek K, Suchy D, Gabryel B, et al.: Quantification of metformin by the HPLC method in brain regions, cerebrospinal fluid and plasma of rats treated with lipopolysaccharide. Pharmacol. Rep. 2010 Sep-Oct; 62(5): 956–965. PubMed Abstract | Publisher Full Text\n\nKirpichnikov D, McFarlane SI, Sowers JR: Metformin: an update. Ann. Intern. Med. 2002 Jul 2; 137(1): 25–33. PubMed Abstract | Publisher Full Text\n\nNasreddine ZS, Phillips NA, Bédirian V, et al.: The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment [published correction appears in J Am Geriatr Soc. 2019 Sep;67(9):1991]. J. Am. Geriatr. Soc. 2005; 53(4): 695–699. Publisher Full Text\n\nImfeld P, Bodmer M, Jick SS, et al.: Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a population-based case-control study. J. Am. Geriatr. Soc. 2012 May; 60(5): 916–921. PubMed Abstract | Publisher Full Text\n\nGrodstein F, Chen J, Wilson RS, et al.: Nurses' Health Study. Type 2 diabetes and cognitive function in community-dwelling elderly women. Diabetes Care. 2001 Jun; 24(6): 1060–1065. Publisher Full Text\n\nLogroscino G, Kang JH, Grodstein F: Prospective study of type 2 diabetes and cognitive decline in women aged 70-81 years. BMJ. 2004 Mar 6; 328(7439): 548. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSamaras K, Lutgers HL, Kochan NA, et al.: The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study. Age (Dordr.). 2014 Apr; 36(2): 977–993. Publisher Full Text\n\nElias PK, Elias MF, D'Agostino RB, et al.: NIDDM and blood pressure as risk factors for poor cognitive performance. The Framingham Study. Diabetes Care. 1997 Sep; 20(9): 1388–1395. PubMed Abstract | Publisher Full Text\n\nMoore EM, Mander AG, Ames D, et al.: Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care. 2013 Oct; 36(10): 2981–2987. Erratum in: Diabetes Care. 2013 Nov; 36(11): 3850. Publisher Full Text\n\nNg TP, Feng L, Yap KB, et al.: Long-term metformin usage and cognitive function among older adults with diabetes. J. Alzheimers Dis. 2014; 41(1): 61–68. PubMed Abstract | Publisher Full Text\n\nMurali R, Boloor A, Yeshwanth H: Is metformin the only culprit for cognitive impairment in diabetes? [Datset]. Dryad. Publisher Full Text"
}
|
[
{
"id": "226505",
"date": "18 Dec 2023",
"name": "Yuzhen Xu",
"expertise": [
"Reviewer Expertise cognitive",
"stroke",
"diabetes",
"rehabitation",
"TCM"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript is a topical study of cognitive impairment in diabetes, in which the role of metformin has been widely reported in recent years.The relationship between metformin and cognitive function in diabetic patients should be analyzed using prospective cohort studies rather than cross-sectional studies. Cross-sectional studies have too many confounding factors and cannot explain the causal relationship between the two.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-723
|
https://f1000research.com/articles/12-721/v1
|
21 Jun 23
|
{
"type": "Study Protocol",
"title": "Identification and quantification of growth factors involved in growth and development of cartilage present in exosomes of lactating mother’s milk of cleft infant as compared to non-cleft infant – a protocol for an analytical observational study",
"authors": [
"Mrudula Shinde",
"Pallavi Daigavane",
"Priyanka Niranjane",
"Nikita Soni"
],
"abstract": "Background: Cleft lip and palate (CLP) have complex etiology and even after successful cleft surgeries in a CLP child, there are chances of relapse as there may be a lack of something at the cellular level. Several growth factors like TGF-β, IGF, and BMP7 are involved in modulating chondrocyte homeostasis and can also induce chondrogenic differentiation in the bone marrow. Objectives: To identify growth factors involved in the growth and development of cartilage present in exosomes of lactating maternal milk of cleft and non-cleft children. Methodology: There will be two groups: GROUP-A: The lactating mother of a CLP child. GROUP-B: The lactating mother of a non-cleft child. Mothers with a CLP child and a non-cleft child between the age of 0–6 months will be selected for the study. The need for the study will be explained to the mothers and consent will be taken. A milk sample of 2ml will be collected in a falcon tube and transported in cold storage facilities to the laboratory. Initially, the isolation of exosomes from milk samples will be done, from which total proteins will be isolated by centrifugation process. This will be followed by an analysis of growth factors from the isolated total proteins (from both exosomes) through immunoblotting. Once the analysis is done, the quality and quantity of growth factors responsible for cartilage growth and development will be compared. Expected results: Isolated maternal exosomes are expected to contain an ample amount of growth factors involved in cartilage growth and development, highlighting its potential for use as a therapy alongside prevalent procedures in CLP. Conclusion: In this study, we expect that maternal exosomes act as a carrier of factors that can have therapeutic significance to the natural compensation of the cartilage to maintain nasal symmetry by naso-alveolar molding.",
"keywords": [
"Exosome",
"Growth Factors",
"cleft lip and palate"
],
"content": "Introduction\n\nThe most prevalent birth abnormality is cleft lip and palate (CLP), which is linked to several inherited genetic diseases that damage the child’s orofacial region. Many variations and combinations of this syndrome can exist. When compared to African populations, Asian and American populations have a far higher prevalence of CLP. A 2009 study found that India, with a population of over 1.1 billion, produces 24.5 million births annually, with a birth prevalence of clefts of between 27,000 and 33,000 per year.1 The incidence of CLP is higher in males than females. This birth defect creates medical, psychological, and social problems which affect both individuals and their families. CLP has a complex etiology with both genetic and environmental factors that act as key factors for the occurrence of CLP.2 The common risk factors leading to CLP are maternal smoking, alcohol consumption, consumption of certain medications such as Topiramate, Valproic acid, etc during the 1st trimester, nutritional deficiency like folic acid deficiency, vitamin A deficiency, low serum folate level, low vitamin B6 and B12 level, chemical exposure like cosmetics, pesticides, psychological factors such as stress, depression, and consanguineous marriage. The genes responsible for non-syndromic CLP are FGFR2, IRF6, FGF8, BMP4, Wnt, etc.2\n\nThe anatomy of CLP highlights abnormal shape and position of the nasal septum and nasal tip cartilage which creates an uneven appearance of the nostril, nasal tip, and nasal dome/contour. This leads to poor esthetics, and difficulty in breathing, speech, and feeding. The deviated nasal cartilage is molded and corrected with the help of various presurgical infant orthopaedics (PSIO) appliances to expand the nasal cartilage pre-surgically. The nasal cartilage is a structure present within the nose that provides form and support to the nasal cavity. This cartilage is made up of hyaline cartilage. Since there is no direct blood supply to the cartilage, it is an avascular connective tissue that obtains its nutrition through diffusion from the environment. The process of diffusion is accelerated by increasing the compressive stresses exerted on the cartilage. Our joints are shielded by this sturdy, pliable tissue, which also serves as a shock absorber.\n\nBecause cartilage is made of highly differentiated, specialised cells, maintaining the stability of the matrix elements is its primary purpose. Extracellular matrix (ECM), which makes up the structure and organisation of cartilage, is crucial to the proper operation of cartilage. Its ability to self-repair is limited when it gets injured. The cartilage consists of a large number of chondrocytes that are embedded in the ECM. Several growth factors like TGF-β, IGF, and BMP7 are involved in modulating chondrocyte homeostasis and can also induce chondrogenic differentiation in the bone marrow.3\n\nEven after successful cleft palate and lip surgeries in CLP children, there are chances of relapse as there may be a lack something on a cellular level. Direct cell-to-cell interaction and the maintenance of homeostasis depend on intercellular communication. Since the last decade, there has been an increased interest in the role of extracellular vesicles, especially exosomes. Recent studies have illustrated that exosomes act as a potential portal for a cell-free drug delivery system with the native characteristic of the parent cell of origin. Exosomes, called extracellular vesicles, are present in almost all cells, tissue and body fluids. It helps in intercellular signaling and maintaining tissue homeostasis in diseased physiology.4 It consists of 9769 proteins, 2838 miRNAs, 3408 mRNAs & 1116 lipids.\n\nThese exosomes can act as a key player in treating a cleft patient. It acts as the drug delivery tool as its characteristics are derived from the parent cell. Almost all cells, blood, tissue, saliva, tear, breast milk, urine, and the gastrointestinal tract (GIT) secrete exosomes. Exosomes have the potential to cross the blood-brain barrier.4 Its lipid-bilayer-coated with extracellular vesicles protect against immune cells and enzymes. It can promote cellular growth and the regeneration of new blood vessels.4\n\nRecently many studies have been done which state that exosome contains many factors:\n\nMengna Duan et al. in 2020 studied the effects of exosomes derived from epidermal stem cells on the rate of wound healing in rat skin. When epidermal stem cells were combined with exosomes, scar formation was found to be reduced and wound healing increased.5 Kan Yin et al. in 2019 found that exosomes derived from mesenchymal cells have many growth factors like TGFβ1, VEGF, HGF, cytokines, and proteins.6\n\nExtracellular vesicles that are secreted are known as exosomes, and they are vital components of cells that also contain growth factors. Exosomes contain signalling growth factors that are responsible for the growth and development of cartilage, and this has therapeutic potential in the management of CLP.\n\nA variety of molecules, including proteins, enzymes, growth hormones, genes, DNA, and RNA, are found in exosomes. Exosomes are believed to include growth factors that are crucial for the growth and development of cartilage, thus it was expected to evaluate their quantity and quality. It was necessary to determine the elements influencing cartilage development in a patient with CLP since the exosome can express the growth of cartilage in a newborn with CLP.\n\nThe following study is one of a kind. It was thereby thought to assess the quality and quantity of growth factors in the mother of a child with CLP and a child with non-cleft and to evaluate the mother’s growth factors, which are genetically passed on to the child and produce a particular type of cartilage with a particular set of properties.\n\nThis literature highlights the current conventional treatment regime for CLP management which is not addressing the cellular aspect and especially the cellular signaling for cartilage molding. This is a rate-limiting factor towards CLP management, which may be overcome by providing cartilage growth and development-triggering growth factors.\n\nThe following study was thereby designed with a hypothesis to assess the quality and quantity of growth factors in lactating mothers of cleft children and non-cleft children.\n\n\n\n1. To identify growth factors involved in the growth and development of cartilage present in exosomes of lactating maternal milk of cleft and non-cleft children.\n\n2. To quantify the identified growth factors in the exosomes of lactating maternal milk of cleft and non-cleft children.\n\n3. To compare the expression of the growth factors between the isolated exosomes and the source of the exosomes (milk) in a cleft and non-cleft child.\n\n\nMethods\n\nEthical approval for the study was obtained from the institutional ethics committee of Datta\n\nMeghe Institute of Higher Education and Research (Deemed to be University) (ref. no: DMIHER (DU)/IEC/2023/571) Date of approval: 06-02-2023. A written participant information sheet will be given regarding the details of the study, and it will be explained to participants and their parents before enrolment to the study. Their involvement benefits and harm will be explained to the participants. Written informed consent from the participants will be obtained before involving them in study.\n\nThis will be a parallel group, analytical observational study.\n\nThe following study will be conducted in the Department of Orthodontics and Dentofacial Orthopedics at Sharad Pawar Dental College in collaboration with Central Research Laboratory (Center of Translation Sciences), Sawangi, Wardha.\n\nInclusion criteria\n\n• Lactating mothers of a child aged 0–6 months.\n\n• Age of mother <35 years.\n\n• No systemic conditions such as diabetes, hypertension, etc.\n\n• Mother with no developmental and congenital disease.\n\nExclusion criteria\n\n• Lactating Mother of child age > 6 months.\n\n• Age of mother >35 years (due to hormonal change).\n\n• Mother with systemic disease such as diabetes, hypertension.\n\n• Mother with developmental and congenital disease.\n\nLactating mothers reporting in the Department of Orthodontics and Dentofacial Orthopedics and Department of Gynecology & Obstetrics fulfilling the inclusion criteria will be included in the study.\n\nThe study will include a total sample size of 30. There will be two groups with 15 patients in each group:\n\nThe patient will be selected from the smile train outpatient department (OPD) of the Orthodontic Department, while the non-cleft patient will be selected from the Department of Gynaecology. Mothers with a CLP child and a non-cleft child between the age of 0–6 months will be selected for the study. The purpose of the study will be explained to mothers, and those who are willing to participate will be given the consent form in a language they can understand, after which their signature will be obtained. The milk sample from the mother with a CLP child will be collected in the breastfeeding room of the smile train unit in the Department of Orthodontic and Dentofacial Orthopaedic, Sharad Pawar Dental College, and from the mother with the non-cleft child it will be collected from the Department of Gynecology. The milk sample of 2 ml will be collected in a falcon tube and transported with cold storage facilities to a laboratory in R&D house (DMIHER) for evaluation. It will be stored at a temperature of -80°C until the experiment is performed. Initially, the isolation of exosomes from the milk sample will be done from which total proteins will be isolated under the centrifugation process. This will be followed by an analysis of growth factors from the isolated total proteins (from both exosomes) through immunoblotting. Once the analysis is done, the quality and quantity of growth factors responsible for cartilage growth and development will be compared for both groups.\n\nImmunoblotting is a technique in which we use host antibodies to identify a target protein via antigen-antibody reaction as it identifies the target protein among the number of unrelated proteins. Proteins are separated by electrophoresis and transferred onto the nitrocellulose membrane. This technique uses three elements which are:\n\n(1) Separation by size\n\n(2) Transfer to the solid support\n\n(3) Marking of a target protein using a primary and secondary antibody to visualize\n\nOutcomes\n\nPrimary outcome\n\nThe proposed study is intended to highlight the therapeutic potential of maternal exosomes which can be genetically identified for their quality and quantity. Results will be highlighting the growth factors in infants with CLP. Likewise, further modalities for the management of the nasal cartilage can be done. In CLP subjects, the availability of maternal growth factors is limiting owing to its deficiency.\n\nSecondary outcome\n\nBecause of this, isolated maternal exosomes are expected to contain ample growth factors involved in cartilage growth and development, highlighting its potential for use as a therapy alongside prevalent procedures in CLP.\n\nThe sample size was calculated by using Daniel’s formula for sample size:\n\nWhere,\n\nZ∝2 is the level of significance at 5% i.e. 95% confidence interval = 1.96\n\nP = Prevalence of cleft lip and palate = 1% = 0.01\n\nd = Desired error of margin = 6% = 0.06\n\nn is the population size\n\nTotal sample size is 30\n\nThere is a total two groups which means 15 patients in each group.\n\nAll the demographic and outcome data will be presented using descriptive statistics for continuous variables can be categorized using mean, standard deviation, and median for discrete variables, and frequency and proportion for continuous variables.\n\nThe outcome variable will be tested for normality using the Kolmogorov-Smirnov test for continuous data. Results will be analysed using SPSS version 27.0.\n\nGrowth factors will be categorized according to the range that will be distributed for analysing the data into the normal range and not in the normal range. The chi-squared test will be used for finding the result of the association of growth factors with milk from the mother of cleft and non-cleft infants.\n\nAn odds ratio will be used to find the risk involved multiple times.\n\nAn independent t-test will be used to find the results of the two groups for outcome variables if data comes under the normal distribution, or a non-parametric test will be used to find the significant difference if data doesn’t come under the normal distribution.\n\nIn this study, we expect that maternal exosomes act as carriers of factors that can have therapeutic significance to the natural compensation of the cartilage to maintain nasal symmetry by naso-alveolar molding. Because of growth factors, which in the first 2–3 months help/enhance cartilage development and growth. However, due to a lack of these growth factors in children, this period declines to 1 month, which can result in the failure of many mechanical appliances like stunts in the 3- to 4-month range getting no results due to a lack of certain factors.\n\nIdentifying the factors like growth factors, estrogen or hormones can enhance the growth and development of cartilage and, by highlighting their therapeutic significance in CLP management as isolated maternal exosomes are expected to contain ample amount of growth factors involved in cartilage growth and development, highlighting its potential for use as a therapy alongside prevalent procedures in CLP.\n\nNot started yet.\n\n\nDiscussion\n\nConsidering the complexity of naso-alveolar cartilage molding, the management of CLP is a great challenge and time-factor is very crucial. According to the literature, the initial 2–3 months of a child’s life is a crucial time for cartilage molding but children with CLP are deprived of important nutrients present in their mother’s milk. Certain developed countries provide fortified milk to CLP children which provides important nutrients necessary for the growth and development of cartilage, but developing countries like India lack that as 90% of the population there provide animal (cow/buffalo/goat) derived milk which has fewer nutrients compared to mother’s milk or fortified milk.\n\nThe importance of the transforming growth factor-β family and the potential for treating osteoarthritis with stem cell-derived exosomes were concluded by Kwang Ho Yoo et al. in their study published in 2022. TGF-β plays an important role in many cellular processes, including cellular proliferation, and the role of exosomes in chondroprotection has also been established.3 In 2015, Qiongqiong Yu et al. investigated the role of the BMP7 gene in nonsyndromic orofacial clefts. Bmp7 plays an important role in the development of the palate and other orofacial structures. Bmp7 promotes cartilage matrix synthesis and inhibits catabolic cytokine activity.7 In 2022, Nathlic G Thielen et al. evaluated the transcription factor responsible for the TGF-β driven hypertrophy-like phenotype in human osteoarthritic chondrocytes. TGF-β induces the expression of a critical hypertrophy factor in chondrocytes.8 In 2021, Mengmeng Duaner et al. studied the effect of TGF-β on cartilage development and disease. TGF-β2 controls all aspects of endochondral ossification and upholds homeostasis.3\n\n\nConclusion\n\nIn this study, we expect that maternal exosomes act as carriers of factors that can have therapeutic significance to the natural compensation of the cartilage in order to maintain the nasal symmetry by naso-alveolar moulding.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nWe would like to thank my institute and my colleagues.\n\n\nReferences\n\nIPDTOC Working Group: Prevalence at birth of cleft lip with or without cleft palate: data from the International Perinatal Database of Typical Oral Clefts (IPDTOC). Cleft Palate Craniofac. J. 2011 Jan; 48(1): 66–81. Publisher Full Text\n\nKawalec A, Nelke K, Pawlas K, et al.: Risk factors involved in orofacial cleft predisposition – review. Open Med (Wars). 2015 Feb 5; 10(1): 163–175. PubMed Abstract | Publisher Full Text\n\nTransforming growth factor-β family and stem cell-derived exosome therapeutic treatment in osteoarthritis (Review).[cited 2023 Feb 28]. Publisher Full Text\n\nMuthu S, Bapat A, Jain R, et al.: Exosomal therapy—a new frontier in regenerative medicine. Stem Cell Investig. 2021 Apr 2; 8: 7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDuan M, Zhang Y, Zhang H, et al.: Epidermal stem cell-derived exosomes promote skin regeneration by downregulating transforming growth factor-β1 in wound healing. Stem Cell Res. Ther. 2020 Oct 23 [cited 2023 Feb 28]; 11: 452. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYin K, Wang S, Zhao RC: Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm. Biomark. Res. 2019 Apr 4 [cited 2023 Feb 28]; 7: 8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYu Q, He S, Zeng N, et al.: BMP7 Gene involved in nonsyndromic orofacial clefts in Western Han Chinese. Med. Oral Patol. Oral Cir. Bucal. 2015 May 1; 20(3): e298–e304. PubMed Abstract | Publisher Full Text\n\nThielen NGM, Neefjes M, Vitters EL, et al.: Identification of Transcription Factors Responsible for a Transforming Growth Factor-β-Driven Hypertrophy-like Phenotype in Human Osteoarthritic Chondrocytes. Cell. 2022 Jan; 11(7): 1232. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "188540",
"date": "01 Sep 2023",
"name": "Māra Pilmane",
"expertise": [
"Reviewer Expertise Morphology",
"facial clefts",
"development",
"paediatry"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nMy main criticism relates to:\nI would recommend that the article is thoroughly copy-edited.\n\nAbstract is superficial, imprecise in all the sections mentioned here and doesn't give impression of the research; results are practically not provable, also the conclusions cannot be proven using all of the obtained data.\n\nIntroduction. Contains different ideas but they are not elaborated on so the meaning is not understand to the reader. There are many more genes, than mentioned here, involved in the pathogenesis of clefts; also the described growth factors are just a small part from those that are responsible for the hard tissue development/differentiation in the clefts.\nMy main concern is about the lack of a provable hypothesis, as the maternal exosomes are supposed to contain systemic factors for all the hard tissue of the child (with or without cleft). These factors work systemically in the child's body. Exosomes in the milk of each mother are systemic, but also individual, as this depends not only on her current health status, but on many other factors, for instance, her underwent diseases during pregnancy and even before it. Thus, it will be very difficult to obtain an equal group of mothers for the research. It is simply not possible to connect maternal milk exosomes with a specific cleft affected nasal cartilage defect in the child due to the many confounding factors in both - maternal and child body.\nAdditionally, the research of the same vesicles should involve the common detection of all the indices responsible for the cartilage defects in child body, including growth factors, remodelation, defence factors and genes/transcriptional factors at least. Even then would not be possible to connect a specific nasal cartilage response with the maternal milk extracellular vesicles with GF. It is also not understandable why there is suddenly information about estrogens.\n\nCommonly, many more factors may influence the hard tissue in cleft-affected and unaffected children.\nFinally, the thesis that \"... mother’s growth factors are genetically passed on to the child...\" is slightly wrong, as there are distinct types of factors that we can receive, and what can't be received by the child from the mother's milk. This is already widely described and it is very important here that all the diseases underwent by mothers of children, including, for instance, the infectious diseases, are not mentioned here by the authors.\nNext, the idea of what is carried by exosomes, is nice, but the article misses the description about the \"fate\" of these structures after they enter the child body, especially when they move through the gastrointestinal tract. This should be considered also as a factor that changes the vesicles.\n\nInclusion/exclusion criteria are not sufficient neither for mothers, nor for children;\n\nResearch groups are not fully elaborated and described on enough good level;\n\nMethods do not seem to be reproducible, and they lack references.\n\nWell, it seams that the author has just filled the separate sections, for instance, the Dissemination/results section is completed with irrelevant information. Also the Discussion is very short and doesn't prove the idea of the forthcoming work. There are few references and it gives the impression that the topic has not been elaborated on.\n\nIs the rationale for, and objectives of, the study clearly described? No\n\nIs the study design appropriate for the research question? No\n\nAre sufficient details of the methods provided to allow replication by others? No\n\nAre the datasets clearly presented in a useable and accessible format? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-721
|
https://f1000research.com/articles/12-436/v1
|
24 Apr 23
|
{
"type": "Research Article",
"title": "Nigella sativa L. seed extracts promote wound healing progress by activating VEGF and PDGF signaling pathways: An in vitro and in silico study",
"authors": [
"Chella Perumal Palanisamy",
"Phaniendra Alugoju",
"Selvaraj Jayaraman",
"Sirilux Poompradub",
"Chella Perumal Palanisamy",
"Phaniendra Alugoju",
"Selvaraj Jayaraman"
],
"abstract": "Background: A significant area of clinical research is the development of natural wound healing products and the management of chronic wounds. Healing wounds with medicinal plants has been a practice of ancient civilizations for centuries. Nigella sativa L (N. sativa) is a medicinal plant that has several pharmacological properties. Methods: The present study evaluated the wound healing properties of Nigella sativa L. (N. sativa) seed extracts using normal cell lines such as normal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs). The expression levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were analyzed through western blot analysis. Furthermore, computational analyses were carried out to screen the potential bioactive compounds for wound healing applications. Results: The results of the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay revealed that, all the tested solvent extracts of N. sativa seeds (including ethanol, ethyl acetate, chloroform, and petroleum ether) did not exert any cytotoxic effects at the tested concentrations. Furthermore, the western blot analysis showed elevated levels of VEGF and PDGF upon treatment with N. sativa seed extracts. Gas chromatography-mass spectrometry (GC-MS) analysis of N. sativa extracts identified 268 phytocompounds. Molecular docking studies revealed that three phytocompounds of N. sativa extracts, including tricyclo[20.8.0.0(7,16)]triacontane, 1(22),7(16)-diepoxy-, adaphostin and obeticholic acid had strong binding affinity with wound healing-related target proteins, showing docking scores ranging from -5.5 to -10.9 Kcal/mol. These compounds had acceptable Absorption, Distribution, Metabolism, and Excretion (ADME) properties. Conclusions: Based on these results, N. sativa seed extracts might possess potential wound healing properties owing to the presence of a wide range of bioactive components.",
"keywords": [
"Nigella sativa L.",
"Wound healing",
"Vascular endothelial growth factor",
"Platelet-derived growth factor"
],
"content": "Introduction\n\nThe management of wounds, especially extensive and full-thickness wounds, has long been a concern in the field of medicine.1 Infection by pathogenic bacteria delay the healing process and increase health risks to the general public. Clinicians exploring effective ways to promote wound healing is a hot topic in research.2 Vigorous development of advanced wound dressings is imperative for accelerating wound healing and achieving closure of wounds quickly.3 Hemostasis, inflammation, proliferation, and tissue remodeling are sequential and timed processes involved in wound healing.4 These complex processes are mediated by released cytokines, chemokines, and growth factors, which are released by neutrophils, macrophages, keratinocytes, and endothelial cells.5 It is important to manage wounds in a timely and comfortable manner in order to facilitate a quick healing process.6 The wound care industry has developed a number of products that are designed to treat wounds (for example MEBO, Calmoseptine®, Boroline). A variety of wound healing techniques have been developed over the years, including traditional (especially herbal) and modern methods.1,7 Traditional herbal wound-healing therapies remain popular among rural populations in developing countries in part due to their availability and affordability, and they have been demonstrated to be effective, clinically accepted, and have few or no side effects.8\n\nThere has been a growing awareness in recent years that many phytocompounds possess medicinal properties that are effective in treating diseases and in healing wounds.9 A chemical scaffold can provide a framework for developing synthetic and/or semi-synthetic analogues of drugs, which can be used in drug development for disease treatment in a wide range of settings.10 As a result of the advent of modern techniques like molecular biology, metabolomics, phytochemical analysis, and drug discovery, natural products chemists have been able to unravel the ancient therapeutic hypotheses and mechanisms of herbal medicines.11–14 It is common to find these types of treatments used in Ayurveda, Traditional Chinese medicine, and Traditional Thai medicine.15\n\nNigella sativa L. (N. sativa) (Family Ranunculaceae) seeds, commonly known as black cumin or black seeds, have a long history of being used as a treatment for a variety of ailments by traditional healers throughout the world, in regions like South-eastern Asia, the Middle East, Africa, and many areas of the Mediterranean.16,17 It is also notable to point out that N. sativa possess a plethora of pharmacological properties. A variety of health-related conditions have been treated with this herb throughout history, including respiratory and digestive disorders, and kidney, liver, and cardiovascular diseases.18 The most important pharmacological effects of N. sativa seeds can be attributed to thymoquinone, according to a previous study.19 The extracts of N. sativa seeds also contain alkaloids, saponins, steroids, terpenoids, p-cymene, limonene, and fatty acids as well as proteins, carbohydrates, vitamins, trace minerals (like iron and zinc) and crude fiber.20\n\nN. sativa seeds are reported to have several pharmacological effects, including analgesic, appetizer, anti-diabetic, antioxidant, anti-inflammatory, and antimicrobial properties.21 Despite extensive research on the phytochemical pharmacological properties of N. sativa seeds, N. sativa seed extracts are not yet completely characterized chemically.22 As people become more aware that natural products can have potential therapeutic effects on wound healing properties and at present do not have any known toxic effects, it is becoming clear that they are seeking out natural products that can work in this regard. As well as providing information regarding the compositional profile and evaluating the medicinal effects of herbal extracts and/or oils, there is a need to re-evaluate their therapeutic properties in addition to providing information regarding their compositional profile.23 Consequently, the primary objective of the present study was to investigate the effects of N. sativa seed extracts and their phytocompounds on wound healing. Normal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs) were used as primary cell lines in the present study to study these issues in vitro. The phytochemicals were also docked with multiple wound healing-related proteins (Tumor necrosis factor α (TNFα), transforming growth factor beta receptor 1 (TGFBR1) kinase, interleukin-1 beta (IL-1β), protein kinase C (PKC)-βII, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)).\n\n\nMethods\n\nThis study was performed at Chulalongkorn University (Thailand) and Saveetha University (India).\n\nBovine serum albumin (BSA) (cat. no. 23209), HUVECs (cat. no. C0035C) and NHDFs (cat. no. C0135C) used in this study were purchased from Thermo Fisher Scientific Inc. Dulbecco’s Modified Eagle Medium (DMEM) (cat. no. D6429), TRIS-buffered saline (TBS) (cat. no. SRE0071) and fetal bovine serum (FBS) (cat. no. F7524) were purchased from Sigma-Aldrich. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) was purchased from BioVision Inc. (cat. no. 2808). Anti-VEGF mouse monoclonal antibody was procured from Santa Cruz Biotechnology, Inc., (cat. no. sc-53462). Anti-PDGF Receptor β polyclonal antibody (produced in rabbit) was purchased from Sigma-Aldrich (cat. no. SAB4502149). Anti-β-actin mouse monoclonal antibody was purchased from Santa Cruz Biotechnology, Inc. (cat. no. sc-69879). Enhanced Chemiluminescence Detection (ECL) kit was obtained from Amersham BioSciences UK Ltd (cat. no. RPN2209).\n\nN. sativa seeds were purchased from a local herbal shop in Bangkok, Thailand. After being cleaned with tab water, they were dried under shade conditions, powdered, and air-tight packaged in a container.\n\nIn order to determine the yield on the plant material, 3,000 mL petroleum ether, chloroform, ethyl acetate, and ethanol were continuously shocked with 600 g plant material in a conical flask for 72 h (during the cold percolation process). After the extracts were collected and filtered using Whatman No. 1 filter paper, a rotary evaporator set at 40°C was used to dry them. In order to preserve the dried extracts until further use, they were stored at 4°C until use.\n\nGas Chromatography-Mass Spectrometer Model Shimadzu GCMS-QP2020 NX (Shimadzu, Japan) equipped with 5 Sil MS 5% diphenyl/95% dimethyl polysiloxane capillary column (measuring 30 mm wide, 0.25 mm diameter, and 0.25 mm thick) was used analyze the extracts of N. sativa seeds. Then, 100 μl of solvent extracts were diluted using 1,400 μl dimethyl sulfoxide (DMSO). Next, 1 μl diluted sample (100/1,400, V/V in DMSO) was injected in the split mode with a split ratio 1:10. Electron impact ionization was used for GC-MS detection with an ionization energy of 70 eV. A low flow rate of 1.0 mL per min of helium at a low pressure was used as the carrier gas in the column. Before the injector temperature was set at 250°C, 60°C was set for 15 min before gradually increasing to 280°C over 3 min. It was conducted at 70 eV with a scanning distance of 0.5 s as well as fragment sizes ranging between 50 Da and 650 Da for the MS analysis, 40 min were spent on the GC operation. Acquisition mode scan ranged from 35 m/z to 500 m/z with scan speed 2,500. Extracts were analyzed for their percentage composition of compounds. NIST20R and Wiley libraries were used to interpret and compare GC-MS data as well as compare retention indices.24\n\nCell lines and culture\n\nA humidified atmosphere containing 5% CO2 was used for HUVEC and NHDF cell lines during the experiment to maintain 37°C for the duration. DMEM supplemented with 10% FBS and 1% antibiotics (100 U/mL penicillin and 100 g/mL streptomycin) was used to grow the cells in T-25 flasks. Trypsinization and passage were performed once the cells reached 70% confluency.\n\nCell viability analysis\n\nIn culture media, 10 mg/mL stock solutions of plant extracts were diluted in DMSO. To determine cell viability, cells were seeded into 96 well plates at a density of 5x103 cells per well and incubated at 37°C and 5% CO2 for 24 h. Fresh DMEM supplemented with various solvent extracts of N. sativa seeds (petroleum ether, chloroform, ethyl acetate and ethanol) (0, 10, 20, 50, 100 g/mL) was added, and incubation was carried out for 24 h. After the incubation with extracts, cells were incubated for 2 h in growth media (DMEM) containing 20% MTS solution to assess viability. Microplate readers were used to measure the absorbance of formazan at 490 nm. The crude extracts were dissolved in 0.5% DMSO, which represents the highest concentration of DMSO used in the vehicle culture medium.\n\nProtein expression analysis by western blotting\n\nLaemmli (1970) described sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as a method for separating proteins.25 Using equal volumes (50 g) of samples and buffer, sample mixtures were heated at 95°C for 4 min, then cooled on ice. The dye front was reached at the bottom of the running gel after separating proteins with a Bio-Rad mini slab gel apparatus at a constant voltage of 100 V. In this experiment, polyvinylidene difluoride (PVDF) membranes were charged at a constant voltage of 100 V for 1 h in order to transfer protein bands. Incubation with primary antibodies (anti-VEGF (mouse monoclonal antibody 200 μg/ml) and anti-PDGF Receptor β (rabbit polyclonal antibody 100 μg/ml); β-actin (mouse monoclonal antibody 100 μg/ml) was used as the control) at appropriate dilutions followed by blocking with 5% BSA blocking solution at room temperature for 1 h. A secondary antibody (goat anti-mouse monoclonal antibody 400 μg/ml), purchased from Santa Cruz Biotechnology, Inc., (cat. no. sc-2005; 1:10,000) was incubated for 1 h after primary antibody incubation. Incubation with secondary antibody was followed by two washes (5 min each) with Tris-buffered saline, Tween (TBS-T) and placement on Saran Wrap™ (protein-side up). After adding detection reagent mixture to the blot, blots were incubated for 30-60 sec and we drained off excess reagent (ECL). Quantity One 1-D Analysis Software (RRID:SCR_014280) (Bio-Rad) was used to quantify the immunoblot signals. Using a probe consisting of β-actin, similar amounts of proteins were loaded onto the membranes.\n\nSelection and preparation of ligands\n\nThrough GC-MS analysis, a total of 268 phytocompounds were identified in four different extracts of N. sativa. The 3D structures of all the identified compounds were extracted from the PubChem database (RRID:SCR_004284).26 A list of phytocompounds identified are provided in Tables 1-4 as Underlying data.42 Using PyRx software (RRID:SCR_018548) with default parameters, energy minimization of each ligand was performed using universal force fields, followed by Gasteiger charges to achieve a good structural conformation for docking.\n\nSelection and preparation of receptors\n\nAs part of this study, six different proteins such as TNFα, TGFBR1 kinase, IL-1β, PKC-βII, VEGF and PDGF that participate in wound healing were selected, and their crystal structures were retrieved from Protein Data Bank (PDB). Using Chimera 1.16 (RRID:SCR_002959), any missing residues in the selected target proteins were modelled, nonstandard hetero atoms were removed, polar hydrogens and Gasteiger charges were added, and then energy minimization of each protein performed with 100 steepest descent gradient steps using amber force field (Amber ff14SB). Finally, the energy minimized protein was converted into pdbqt format for molecular docking.\n\nProtein-ligand docking\n\nThe Autodock Vina (RRID:SCR_011958) was used for the molecular docking of phytocompounds of N. sativa with selected wound healing target proteins. If the ligand binding site is represented, it will be located at the center of the grid box. A value of eight is set for the exhaustiveness of the model. A configuration file was created based on the dimensions of the XYZ axis determined by Discovery studio’s visualizer. In Autodock Vina 1.1.2, this configuration file was used for docking using the command line. To dock ligands with a degree of flexibility, Autodock Vina uses the Monte Carlo algorithm. Monte Carlo algorithm used in Autodock Vina is relatively faster than other docking programs.27 In addition to the results file, the binding modes were generated as a single file (PDBQT format) in a log format. BIOVIA Discovery Studio (RRID:SCR_015651) visualizer was used to analyze the binding interactions between best docked ligands and receptors. Strong hydrogen bonds (2.2 to 2.5), moderate hydrogen bonds (2.5 to 3.2), and weak hydrogen bonds (up to 3.6) were measured with respect to the hydrogen atom of the heavy atom.\n\nADME properties prediction\n\nQikProp (RRID:SCR_014906) module was used to predict ADME properties (Schrodinger Suite 2022). To determine a ligand’s pharmacokinetics and pharmacodynamics, the QikProp module analyses its properties, which are resembling those of a drug. Several ADME properties were considered significant, including the molecular weight (MW), H-bond donor, H-bond acceptor, and logarithm of n-octanol/water partition coefficient (log P (O/W)).\n\nData were analyzed using GraphPad Prism (RRID:SCR_002798) version 5 software to assess the significance of individual variations between the control and treatment groups by one-way analysis of variance (ANOVA) and Duncan’s multiple range test. Approximately P<0.05 was considered significant in Duncan’s test.\n\n\nResults\n\nGC-MS analysis identified a total of 268 phytocompounds in N. sativa seed extracts (Figure 1).42 Petroleum ether, chloroform, ethyl acetate and ethanolic extracts showed 65, 70, 67 and 66 peaks, respectively, which are indicating the presence of phytocompounds (Tables 1-4 in Underlying data42). Among these, the highest peak levels were observed such as, 66.81% linoleic acid (PubChem CID: 5280450) at 33.908 min retention time (petroleum ether extract), 42% cis-vaccenic acid (PubChem CID: 5282761) at 33.343 min retention time (chloroform extract), 29.24% ethyl palmitate (PubChem CID: 12366) at 30.050 min retention time (petroleum ether extract), 20.09% oleic acid (PubChem CID: 445639) at 34.550 min retention time (petroleum ether extract), 16.72% palmitic acid (PubChem CID: 985) at 29.904 min retention time (chloroform extract), 16.57% tetradecanoic acid (PubChem CID: 11005) at 25.974 min retention time (petroleum ether extract), 16.37% 3-(3-Chlorophenyl)imidazolidine-2,4-dione (PubChem CID: 285803) at 31.375 min retention time (ethanolic extract), 15.83% methyl linoleate (PubChem CID: 5284421) at 32.22 min retention time (chloroform extract), 15.34% adaphostin (PubChem CID: 387042) at 30.733 min retention time (ethanolic extract), 14.07% glyceryl diacetate 2-oleate (PubChem CID: 5363238) at 31.897 min retention time (ethanolic extract), 12.62% 2-linoleoylglycerol (PubChem CID: 5365676) at 31.502 min retention time (ethanolic extract), 11.34% monopalmitin (PubChem CID: 14900) at 28.131 min retention time (ethyl acetate extract), 11.14% (z)-tetradec-7-enal (PubChem CID: 5364468) at 2.3 min retention time (ethyl acetate extract), 10.54% glycerol, 2-octadecanoate, diacetate (PubChem CID: 539925) at 33.703 min retention time (ethanolic extract), 10.52% glyceryl diacetate 1-linolenate (PubChem CID: 6434505) at 35.075 min retention time (ethanolic extract), 10.45% olealdehyde (PubChem CID: 5364492) at 36.797 min retention time (ethyl acetate extract), 10.25% 2,3-dihydroxypropyl acetate (PubChem CID: 33510) at 10.419 min retention time (ethyl acetate extract), 10.23% 16-trimethylsilyloxy-9-octadecenoic acid, methyl ester (PubChem CID: 6421149) at 34.547 min retention time (chloroform extract), 10.08% propyl ester (PubChem CID: 221069) at 34.71 min retention time (ethyl acetate extract).\n\nTo check the cytotoxicity of N. sativa seed extracts, two different normal cell lines (NHDF and HUVECs) were used at the different concentrations of crude extracts. Cell viability percentages were plotted against extracts treatment concentrations to obtain treatment-response curves. A concentration-dependent increase in cell viability was observed with N. sativa seed extracts (Figures 2 and 3). In response to 25-50 μg/mL of ethanolic and chloroform extract on both cell lines, the viability of cells were increased by 60-68% following 48 h treatment (Figures 2 and 3).\n\nCells were cultured in DMEM supplemented with 10% FBS were incubated with indicated concentrations of extracts (0–100 μg) for 48 h. Each bar represents the mean ± SEM of six independent observations. Significance was considered as the levels of p < 0.05 level using Duncan’s multiple range test. a - compared to control; b - compared to DMSO control; c - compared with 10 μg treated cells; d - compared with 25 μg treated cells.\n\nCells cultured in DMEM supplemented with 10% FBS were incubated with indicated concentrations of extracts (0–100 μg) of 48 h. Each bar represents the mean ± SEM of six independent observations. Significance was considered at p < 0.05 level using Duncan’s multiple range test. a - compared to control; b - compared to DMSO control; c - compared with 10 μg treated cells; d - compared with 25 μg treated cells.\n\nEffect of crude seed extracts on VEGF and PDGF protein expression in NHDF cell lines\n\nThe effect of different solvent extracts of N. sativa seeds on VEGF and PDGF protein expression in NHDF cell lines were investigated. Incubation for 24 h with extracts of indicated concentrations was conducted in DMEM supplemented with 10% FBS using NHDF cells. Densitometry analysis was used to calculate protein expression, which is expressed in relative intensity. Internal control was performed using β-Actin. Based on six independent observations, each bar represents the mean and standard error of the mean. The significance level was determined by using Duncan’s multiple range test at p < 0.05. VEGF and PDGF expression levels were comparatively increased at 25 μg/mL by both ethanolic and chloroform extracts (Figure 4).\n\nProtein expression was analyzed by western blotting using specific antibodies. Each bar represents the mean ± SEM of six independent observations. Significance was considered as the levels of p < 0.05 level using Duncan’s multiple range test. a, compared with control; b, compared with ethanolic extract (25 μg) treated cells; c, compared with chloroform extract (25 μg) treated cells; N. sativa, Nigella sativa L.; VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor; NHDF, normal human dermal fibroblast; P. E, Petroleum Ether extract; CHLO, Chloroform extract; E. A, Ethyl Acetate extract; ETOH, Ethanolic extract.\n\nEffect of crude seed extracts on VEGF and PDGF protein expression in HUVEC lines\n\nEffect of different solvent extracts on VEGF and PDGF protein expression in HUVEC lines. Incubation of HUVECs with indicated concentrations of extracts for 24 h was performed in DMEM supplemented with 10% FBS. Densitometry analysis was used to quantify protein expression, which is expressed as relative intensity. An internal control was performed using β-actin. Six independent observations are represented by a bar with a mean and standard error of measurement. The Duncan’s multiple range test was used to determine significance at p < 0.05. At a concentration of 25 μg/mL, ethanolic and chloroform extracts of N. sativa seed led to comparatively significant increases in the expression levels of VEGF and PDGF proteins (Figure 5).\n\nProtein expression was analyzed by western blotting using specific antibodies. Each bar represents the mean ± SEM of six independent observations. Significance was considered as the levels of p < 0.05 level using Duncan’s multiple range test. a, compared with control; b, compared with ethanolic extract (25 μg) treated cells; c, compared with chloroform extract (25 μg) treated cells; N. sativa, Nigella sativa L.; VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor; HUVEC, human umbilical vein endothelial cell; P. E, Petroleum Ether extract; CHLO, Chloroform extract; E. A, Ethyl Acetate extract; ETOH, Ethanolic extract.\n\nIn the present study, Autodock Vina was used to predict the binding affinity of a total of 268 selected phytocompounds of N. sativa with the target proteins of wound healing process such as TNFα (PDB ID: 2AZ5), TGFBR1 kinase (PDB ID: 6B8Y), IL-1β (PDB ID: 6Y8M), PKC-βII (PDB: 2I0E), VEGF-A (PDB ID: 3QTK) and platelet-derived growth factor receptor alpha (PDGFRA) (PDB ID: 6JOL). The binding energies of 10 ligands that showed the highest binding affinities are indicated in the heatmap (Figure 6). It is clear from Figure 6, three compounds (1, 2, and 3) namely tricyclo[20.8.0.0(7,16)]triacontane, 1(22),7(16)-diepoxy- (PubChem CID: 543764), adaphostin (PubChem CID: 387042), and obeticholic acid (PubChem CID: 447715), respectively, showed highest binding affinity with all the tested target proteins. The best docked protein ligand interactions are shown in Table 1 and Table 2. The 2D and 3D structures of the top docked complexes are shown in Figures 7-9. ADME properties of those compounds were under the acceptable range (Table 3).\n\nMolecular docking analysis of tricyclo[20.8.0.0(7,16)]triacontane, 1(22),7(16)-diepoxy- complexed with targeted proteins of A) PKC-βII, B) TNFα, C) IL-1β, D) PDGFRA, E) VEGF-A and F) TGFBR1.\n\nMolecular docking analysis of adaphostin complexed with targeted proteins of A) PKC-βII, B) TNFα, C) IL-1β, D) PDGFRA, E) VEGF-A and F) TGFBR1.\n\nMolecular docking analysis of obeticholic acid complexed with targeted proteins of A) PKC-βII, B) TNFα, C) IL-1β, D) PDGFRA, E) VEGF-A and F) TGFBR1.\n\n\nDiscussion\n\nA wound is defined as a disruption of anatomical integrity of any biological tissue by physical, mechanical, chemical, or microbial factors. The wound healing process starts following the wound formation and repairs the injured or damaged tissues.28 Development of natural wound healing agents is of current interest to mitigate the side effects of wound care products.29 Nature has gifted us with a diverse range of medicinal plants to treat various ailments including wound healing.30 It has been reported that N. sativa has a wide range of pharmaceutical properties.31 The complete extracts and their phytocompounds from N. sativa seeds have not been investigated for their wound healing properties. Therefore, this study has been conducted to determine wound healing activity of various solvent extracts of N. sativa seeds by in vitro and in silico analyses. Cells, cellular components, and chemical mediators interact to heal wounds in a complex way.32 The process of wound healing is broadly divided into four phases, namely coagulation and hemostasis, inflammation, proliferation, and scar tissue formation (maturation). The process of angiogenesis involves the formation of new blood vessels, and it is one of the most important steps in wound healing.33 In the wound area, angiogenic signals from the macrophage-derived factors stimulate the proliferation, migration and differentiation of endothelial cells, and subsequent increase in blood vessel formation.34 During the wound healing process, the new capillaries develop into the fibrin clots, which subsequently form a microvascular network that is a critical for the formation tissue formation. HUVECs are primary endothelial cells from umbilical cord and are widely used for in vitro investigation of angiogenesis.35 In order to determine whether different crude extracts of N. sativa are cytotoxic, this study first carried out MTS tests on HUVECs. As shown in the Figure 2, all tested crude extracts did not exert any cytotoxic activity on the HUVECs. Notably, ethanol and chloroform extracts significantly enhanced the viability of HUVECs. Angiogenesis involves a complex series of molecular events mediated by several factors. In the wound healing process, there are a number of growth factors that play key roles, including PDGF, TGF-β1, EGF, VEGF and bFGF.36 Proangiogenic factors, such as VEGF, promote the survival, migration, differentiation, self-assembly, and self-repair of endothelial cells. As soon as VEGF binds to the VEGF receptor, multiple downstream protein kinase pathways are activated and new blood vessels are formed.37 The wound healing process is also affected by PDGF, another important growth factor. Additionally, PDGF stimulates the formation of new blood vessels by acting as a pro-angiogenic factor.38 Thus, the onset of angiogenesis is positively regulated by both PDGF and VEGF. Therefore, this study has analyzed the expression levels of VEGF and PDGF in both tested cell lines. As seen in Figures 4 and 5, both ethanol and chloroform extracts increased the expression levels of VEGF and PDGF in both NHDFs as well as HUVECs. This indicates that the N. sativa seed extracts might promote the cell survival and self-repair of cells, and subsequent wound healing efficacy.\n\nWounds are characterized by excessive inflammation due to increased local and systemic levels of TNFα.39 Evidence suggests that inhibition of TNFα is critical for the treatment of wounds. It plays an important role in wound healing by re-epithelializing, inducing inflammation, stimulating angiogenesis, and forming new skin tissue.40 The docking studies were used to predict the possible therapeutic effects of phytocompounds of N. sativa against wound healing related molecular targets including TNFα, TGFBR1 kinase, IL-1β, PKC-βII, VEGF and PDGF. Based on the docking studies, it was predicted that bioactive compounds N. sativa showed strong binding affinity to select the wound healing related targets. Together, the current study results suggest that N. sativa seeds might exert wound healing effects mainly through the modulation of proangiogenic factors.\n\n\nConclusions\n\nManagement of chronic wounds and the development of natural wound healing products is of critical importance in the area of clinical research. Medicinal plants have long served as a potential source of wound healing medications since ancient times, with their use going as far back as 3,000 BC).41 N. sativa is one such medicinal herb that has been shown to possess a wide range of pharmacological properties. In this aspect, this study investigated the wound healing properties of different solvent extracts of N. sativa seeds. Both ethanolic and chloroform extracts significantly improved the viability in NHDF and HUVEC cell lines. Besides, both ethanolic and chloroform extracts increased the expression levels of VEGF and PDGF proteins indicating N. sativa can have significant impact on the rate of wound healing by promoting the angiogenesis and cell proliferation. The computational analysis of identified phytocompounds from the GC-MS spectrum showed potent binding affinity towards the wound healing-associated target proteins such as PKC-βII, TNFα, IL-1β, PDGFRA, VEGF-A, and TGFBR1 kinase. Based on the current findings, N. sativa seed extracts can exert potent wound healing activity via activating the VEGF and PDGF signaling pathways. However, further in vitro and in vivo studies are still required to confirm the current findings.",
"appendix": "Data availability\n\nZenodo: Nigella sativa L. seed extracts promotes wound healing progress by activating VEGF and PDGF signalling pathways: An in vitro and in silico study, https://doi.org/10.5281/zenodo.7712528. 42\n\nThis project contains the following data:\n\n• Cell viability assay.zip\n\n• Docking results.zip\n\n• GC-MS identified Compounds from N. sativa seed extracts.zip\n\n• Protein structures.zip\n\n• Westernblot raw data.pptx\n\n• List of tables.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nThe authors are thankful to Second Century Fund (C2F), Chulalongkorn University, Center of Excellence in Green Materials for Industrial Application, Ratchedaphiseksomphot endowment fund, Faculty of Science, Chulalongkorn University and Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospital, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai 600077, India to complete this research work in fine fulfillment.\n\n\nReferences\n\nZhang W, Guan X, Qiu X, et al.: Bioactive composite Janus nanofibrous membranes loading Ciprofloxacin and Astaxanthin for enhanced healing of full-thickness skin defect wounds. 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Publisher Full Text\n\nDu Cheyne C, Tay H, De Spiegelaere W: The complex TIE between macrophages and angiogenesis. Anat. Histol. Embryol. 2020; 49(5): 585–596. PubMed Abstract | Publisher Full Text\n\nNaito H, Iba T, Takakura N: Mechanisms of new blood-vessel formation and proliferative heterogeneity of endothelial cells. Int. Immunol. 2020; 32(5): 295–305. PubMed Abstract | Publisher Full Text\n\nDeng S, Lei T, Chen H, et al.: Metformin pre-treatment of stem cells from human exfoliated deciduous teeth promotes migration and angiogenesis of human umbilical vein endothelial cells for tissue engineering. Cytotherapy. 2022; 24(11): 1095–1104. PubMed Abstract | Publisher Full Text\n\nLee J-H, Parthiban P, Jin G-Z, et al.: Materials roles for promoting angiogenesis in tissue regeneration. Prog. Mater. Sci. 2021; 117: 100732. Publisher Full Text\n\nDhavalikar P, Robinson A, Lan Z, et al.: Review of Integrin-Targeting Biomaterials in Tissue Engineering. Adv. Healthc. Mater. 2020; 9(23): 2000795. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMariotti V, Fiorotto R, Cadamuro M, et al.: New insights on the role of vascular endothelial growth factor in biliary pathophysiology. JHEP Reports. 2021; 3(3): 100251. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRuder B, Atreya R, Becker C: Tumour necrosis factor alpha in intestinal homeostasis and gut related diseases. Int. J. Mol. Sci. 2019; 20(8): 1887. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAhmed SR, Mostafa EM, Musa A, et al.: Wound Healing and Antioxidant Properties of Launaea procumbens Supported by Metabolomic Profiling and Molecular Docking. Antioxidants. 2022; 11(11): 2258. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaver T, Kurečič M, Smrke DM, et al.: Herbal Medicine. Chapter 8: Plant-Derived Medicines with Potential Use in Wound Treatment. IntechOpen; 2018; pp. 121–150. Publisher Full Text\n\nPalanisamy CP, Alugoju P, Jayaraman S, et al.: Nigella sativa L. seed extracts promotes wound healing progress by activating VEGF and PDGF signalling pathways: An in vitro and in silico study.Publisher Full Text"
}
|
[
{
"id": "171686",
"date": "16 May 2023",
"name": "Balasubramani Ravindran",
"expertise": [
"Reviewer Expertise Plants"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nPalanisamy et al., have demonstrated the role of Nigella sativa L. (N. sativa) seed extracts for wound healing potential using two different cell lines and with computational work in order to show the mechanisms via regulates VEGF and PDGF signalling. This research work has scientific merit and sounds enough to be considered in the F1000Research journal.\nHowever, the authors should justify the following:\nWhether the authors have done phytochemical screening analysis in all the extracts?\n\nWhat was the dilution of primary antibody? Please mention.\n\nThe plant name should be in italic style, please check it throughout the manuscript.\n\nThe author may continue these findings in in vivo experimental animal model.\n\nHow can the authors conclude N. sativa seed extracts possess wound healing properties with basic experiments? Please justify.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9745",
"date": "20 Jul 2023",
"name": "Chella Perumal Palanisamy",
"role": "Author Response",
"response": "Dear Reviewer, Thank you very much for your valuable comments and suggestions on our submitted research manuscript entitled “Nigella sativa L. seed extracts promote wound healing progress by activating VEGF and PDGF signaling pathways: An in vitro and in silico study” I given below the responses to the reviewer comments; Reviewer comments: Whether the authors have done phytochemical screening analysis in all the extracts? Response: Yes, we done the phytochemical screening of all the extracts and given the phytochemicals details in this manuscript (Underlying data) Reviewer comments: What was the dilution of primary antibody? Please mention. Response: The dilution of primary antibody was 100 μg/ml which was mentioned in ‘Materials and methods’ section of the manuscript. Reviewer comments: The plant name should be in italic style, please check it throughout the manuscript. Response: As per the reviewer comments, the plant name was changed as italic style in throughout the manuscript. Reviewer comments: The author may continue these findings in in vivo experimental animal model. Response: Yes, we will continue these studies in animal model to evaluate the current findings. Reviewer comments: How can the authors conclude N. sativa seed extracts possess wound healing properties with basic experiments? Please justify. Response: N. sativa seed extracts significantly improved the viability in NHDF and HUVEC cell lines. Protein expression analysis (western blot) revealed that, the increased expression levels of VEGF and PDGF proteins indicating N. sativa can have significant impact on the rate of wound healing by promoting the angiogenesis and cell proliferation. Moreover, N. sativa seed extracts possess variety of phytochemicals which many compounds have significant binding affinity with wound healing target proteins of PKC-βII, TNFα, IL-1β, PDGFRA, VEGF-A, and TGFBR1 kinase. Therefore, based on the results, this study can be conclude that, VEGF and PDGF signalling pathways are activated by N. sativa seed extracts, which can induce wound healing. However, further in vitro and in vivo studies are still required to confirm the current findings."
}
]
},
{
"id": "171685",
"date": "18 May 2023",
"name": "Monica Mironescu",
"expertise": [
"Reviewer Expertise microbiology",
"antimicrobials"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nNigella sativa is native to Southeast Asia and its seed extract has been used for many centuries to treat diseases and more recently, the main active compound - thymoquinone has been tested for its effectiveness against diseases such as cancer. There are numerous researches and reviews that evaluate the medicinal use of Nigella sativa in various conditions. A series of preclinical and clinical studies describe multiple effects of Nigella sativa in animal or cellular models such as bronchodilator, antihistaminic, anti-inflammatory, anti-leukotriene and immunomodulatory effects.\nThis research is investigating the action of Nigella sativa seed extracts on wound healing and its progress by activating VEGF and PDGF signaling pathways. In vitro and in silico studies are realized. The research is very complex and well done.\nStill, there are two aspects to be improved by the authors: 1. There is not enough discussion of the results obtained by the authors in comparison with other researches. 2. Some spelling mistakes are given below:\nTo connect the time of the verb with the subject in the proposition: Infection by pathogenic bacteria delay the healing process and increase health risks to the general public; 'Aliments' instead of 'ailments'; 'Tap water' instead of 'tab water'; To finish the proposition: A humidified atmosphere containing 5% CO 2 was used for HUVEC and NHDF cell lines during the experiment to maintain 37°C for the duration …; Comma in the phrase \"…as the control)\" has to be removed.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9746",
"date": "20 Jul 2023",
"name": "Chella Perumal Palanisamy",
"role": "Author Response",
"response": "Dear Reviewer, Thank you very much for your comments and suggestions. Now, our research manuscript entitled “Nigella sativa L. seed extracts promote wound healing progress by activating VEGF and PDGF signaling pathways: An in vitro and in silico study” was greatly improved by your valuable comments and suggestions. I have given below the responses to the reviewer comments; Reviewer comments: Still, there are two aspects to be improved by the authors: 1. There is not enough discussion of the results obtained by the authors in comparison with other researches. 2. Some spelling mistakes are given below: To connect the time of the verb with the subject in the proposition: Infection by pathogenic bacteria delay the healing process and increase health risks to the general public; 'Aliments' instead of 'ailments'; 'Tap water' instead of 'tab water'; To finish the proposition: A humidified atmosphere containing 5% CO 2 was used for HUVEC and NHDF cell lines during the experiment to maintain 37°C for the duration …; Comma in the phrase \"…as the control)\" has to be removed. Response: As per the reviewer's comments, the author’s given enough discussion of the results in the submitted revised manuscript. Moreover, we carried out all the spelling mistakes mentioned by the reviewer."
}
]
},
{
"id": "171688",
"date": "30 May 2023",
"name": "Viji Rajendran",
"expertise": [
"Reviewer Expertise Environmental Science"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this study, the authors examined the wound healing properties of Nigella sativa seed extracts using normal cell lines such as normal human dermal fibroblasts (NHDFs) and normal human umbilical vein endothelia cells (HUVECs). An analysis of western blots was performed to determine VEGF and PDGF expression. Moreover, computational analysis was conducted to screen the potential bioactive compounds for wound healing. The overall quality of the research work and its clarity are excellent. The figures are clear and of good quality; in fact, they are intended to improve the reader's experience with the paper. The work is sufficiently scientifically interesting and technically sound to merit indexing.\nAlthough there are many minor corrections that need to be made, the authors should take time to revise the manuscript carefully.\nProvide a detailed description of the incubation period, treatment period of the cells, and concentration of the extracts used in the cell viability analysis.\n\nThe international unit system should be checked and corrected throughout the manuscript.\n\nThe author stated that each bar represented the mean + SEM of six independent observations, but the figure only shows five independent bars. The author should correct the figures.\n\nThere is a need for the author to clarify whether the treatment period was 24 or 48 hours.\n\n‘Effect of crude seed extracts on VEGF and PDGF protein expression in HUVEC lines’ it should be ‘Effect of crude seed extracts on VEGF and PDGF protein expression in HUVEC cell line’.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9747",
"date": "20 Jul 2023",
"name": "Chella Perumal Palanisamy",
"role": "Author Response",
"response": "Dear Reviewer, Based on your comments and suggestions, our research manuscript was greatly improved. Thank you very much for your valuable time and consideration on our submitted research manuscript. I given below the responses to the reviewer's comments; Reviewer comments: Provide a detailed description of the incubation period, treatment period of the cells, and concentration of the extracts used in the cell viability analysis. Response: As per the reviewer's comments, the authors described clearly the incubation period, treatment period of the cells, and concentration of the extracts used in the cell viability analysis. Reviewer comments: The international unit system should be checked and corrected throughout the manuscript. Response: According to the international unit system, the measurements were corrected throughout the manuscript. Reviewer comments: The author stated that each bar represented the mean + SEM of six independent observations, but the figure only shows five independent bars. The author should correct the figures. Response: As per the reviewer's comments, the authors corrected the + SEM independent observations both figures and the main text in the manuscript. Reviewer comments: There is a need for the author to clarify whether the treatment period was 24 or 48 hours. Response: The treatment period of extracts was 24 hours which was corrected in the submitted manuscript. Reviewer comments: ‘Effect of crude seed extracts on VEGF and PDGF protein expression in HUVEC lines’ it should be ‘Effect of crude seed extracts on VEGF and PDGF protein expression in HUVEC cell line’. Response: As per the reviewer's comments, the above-mentioned mistakes were corrected in the submitted manuscript."
}
]
},
{
"id": "171687",
"date": "20 Jun 2023",
"name": "Vinothkannan Ravichandran",
"expertise": [
"Reviewer Expertise Chromatography",
"Cell line studies",
"Docking"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nHere the authors found that Nigella sativa L. seed extracts promote wound healing progress by activating VEGF and PDGF signaling pathways.\nN. sativa seeds were purchased from a local herbal shop in Bangkok, Thailand. But was it authenticated? If yes, that detail has to be included.\n\nHUVEC and NHDF cell lines were used, explain why they have been chosen.\n\nYield of the extraction was not mentioned anywhere; it has to be mentioned.\n\nChromatogram image is not clear. Update the image.\n\nEffect of extracts on HUVEC viability figure is a little confusing because of the comparison. Explain what extracts in legend (NSE something like that).\n\nDocking data Table 1 has to include chemical structure of the compound.\n\nDiscussion has to be elaborated on.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-436
|
https://f1000research.com/articles/12-716/v1
|
20 Jun 23
|
{
"type": "Case Report",
"title": "Case Report: Case report: Effect of intraovarian platelet-rich plasma therapy on latent female genital tuberculosis patient",
"authors": [
"Shilpa Dutta",
"Akash More",
"Namrata Choudhari",
"Deepti Shrivastava",
"Vaibhav Anjankar",
"Shilpa Dutta",
"Namrata Choudhari",
"Deepti Shrivastava",
"Vaibhav Anjankar"
],
"abstract": "Latent female genital tuberculosis (FGTB) has been gaining attention in the world of assisted reproductive technology due to its adverse effect on the female reproductive system, which is becoming a cause of concern in the pathway of fulfilling the dream of children in infertile couples. It has been known to severely affect the ovarian reserve, which is one of the prime causes of infertility in females nowadays. Intraovarian plasma-rich platelet therapy (IOPRP) has been known to improve diminished ovarian reserve (DOR); however, its effect on DOR caused due to latent FGTB is not known. A 34-year-old middle-aged South Asian woman was unable to get pregnant due to being a victim of latent female genital tuberculosis. The patient also had a history of four failed IUI (intra-uterine insemination) cycles prior to their visit to Wardha Test Tube Baby Centre, Sawangi, Maharashtra, in January 2021. The patient had reported having improved ovarian reserve, thereby having positive clinical pregnancy upon the administration of IOPRP at our centre. This case report throws light on the aspect that the use of IOPRP on patient suffering from DOR caused due to latent FGTB may lead to significant positive pregnancy outcomes.",
"keywords": [
"Endometrium",
"Poor ovarian reserve",
"Dilation and Curettage",
"Oocyte",
"Embryo."
],
"content": "Introduction\n\nAssisted reproductive techniques have long addressed the ongoing problems in regards to infertility in the world. We have come across various methodologies to strategically handle the root cause of infertility and provide a suitable solution to it. Worldwide, it has been reported that more than 180 million couples are suffering from infertility.1 Several factors, like thin endometrium, poor ovarian reserve, uterine polyps, etc., are responsible for causing infertility.2 Out of all the problems, the current trending factor is female genital tuberculosis (FGTB). FGTB is a type of extrapulmonary tuberculosis that has been seeing an increase in trend in young females globally, especially in developing countries.3 As per the global tuberculosis report, it has been estimated that around 25% of the world’s populace suffers from latent TB, which means they’re asymptomatic despite exposure to the TB pathogen Mycobacterium tuberculosis.3 Endometrial development has reportedly been affected due to the manifestation of TB, which is known to increase harmful cytokines in the decidual layer of the uterus. The descending order of damage caused in the female genital system by FGTB is oviduct (90–100%), hystera (70%), ovaries (30%), cervix (10%) and rarely in the vagina and valvular region (<1%).3 This is known to cause a decrease in ovarian reserve, which decreases AFC (antral follicular count), followed by low AMH (anti-Mullerian hormone) value, an endometrial lining aberration in the female reproductive region, which leads to infertility.4\n\nInstillation of intraovarian platelet-rich plasma therapy (IOPRP) in ovaries has been reported to improve ovarian reserve and enhance AFC and AMH levels, promoting the chances of a successful pregnancy.5 This case report has been made to highlight the effect of IOPRP on a patient suffering from latent FGTB.\n\n\nCase presentation\n\nThis case study is based on a middle-aged South Asian couple who selected Wardha Test Tube Baby Centre, Sawangi (M), India, in January 2021 to fulfil their pregnancy dream, hindered by infertility. A 34-year-old middle-aged South Asian woman suffering from secondary infertility for two years out of three years of married life was enrolled for three in vitro fertilisation (IVF) cycles at WTTBC, Wardha. The couple was vividly counselled about the procedure, and duly informed consent was taken from them. The husband was a lecturer by profession, and the wife was a staff nurse. Both parties have no history of smoking, drinking or any addictions.\n\nThis study gyrates around a woman who was nulligravida. They had no sexual complications in their three years of marital life. She was suffering from secondary infecundity for two years. Semen analysis of the male partner revealed the total sperm count to be 13 million/mL, which is below the lower reference limit as mentioned in WHO 2021 Guidelines.6 The male partner was diagnosed with mild oligospermia. The normal morphology of sperm was reported to be 10%.\n\nThe patient was diagnosed with a left ovarian cyst in 2019 and suffered from extrapulmonary tuberculosis, validated by a positive Z.N. Stain report in 2021. Tuberculosis mainly affected her endometrium, causing adhesions along with a milder effect on her ovaries. She also had a history of hypothyroidism for the past year. She was under regular medication of thyroid tablet of 125 μg for the last year. In 2022, between the IVF treatment at WTTBC, Wardha, she also suffered from asymptomatic Covid-19, diagnosed by taking an RT-PCR test, which came to be positive. The couple’s family pedigree was also reported to have hypertension.\n\nThe couple also had a history of undergoing IUI (intra-uterine insemination) treatment four times before visiting WTTBC, Wardha. All attempts of IUI failed prior to their IVF treatment at WTTBC, Wardha.\n\nAMH (anti-Mullerian hormone) is an essential biomarker to gauge the ovarian reserve present in women.7 The usual range of serum AMH to predict a healthy ovarian reserve is 2 to 6.8 ng/mL.7 In our case study, the value of the serum AMH of the patient was 0.4, which is indicative of a meagre ovarian reserve. The patient's hormonal profile was found to be TSH (thyroid stimulating hormone) 18.09 mIU/L; FSH (follicle stimulating hormone) 4.99 mIU/mL; estrogen 99.319 pg/mL; and LH (luteinizing hormone) 8.97 IU/mL. Upon the use of thyroid supplement tablet of 125 μg for a year, the TSH value was brought down to 3.69 mIU/L. She also had a history of undergoing a diagnostic procedure, dilation and curettage (D&C), with histopathology of the endometrium two years ago to understand the endometrial pathology.\n\nIn the first cycle of IVF Treatment, we tried to do a fresh embryo transfer using the self-oocytes of the patient. Gonadotrophin releasing hormone (GnRH) antagonist protocol was followed for the patient. Post this, we administered 10.000 IU of human chorionic gonadotrophin (HCG) injection subcutaneously to the patient, which is responsible for oocyte maturation. We tried to do transvaginal ovum pick-up 36 hours after the injection application. However, no oocytes were found during the procedure.\n\nThe couple was counselled on the following condition, and they were prepared for a second round of IVF treatment. Antral follicular count (AFC) is an effective parameter for analysing ovarian health. The patient reported having 1–2 follicular counts in both ovaries. Lower AFC indicates poor ovarian reserve.5 We planned to administer IOPRP on both the ovaries for the second round of treatment. We advised the patient to have coenzyme Q10, dehydroepiandrosterone and melatonin combined tablet once a day, and alfacalcidol 0.5 μg and astaxanthin 8 mg combined pill once a day. From day 2 of the menstrual cycle, we started administering minimal ovarian stimulation protocol using 100 mg of clomiphene citrate till day 6. From day 3, 150–225 units of hMG (human menopausal gonadotrophin) were administered to the patient until one follicle reached 17–18 mm in size. On ovulation day, we performed oocyte retrieval on the patient. We prepared the IOPRP sample by withdrawing 15 mL of venous blood from the patient in a conical tube. At first, we centrifuge the sample for 10 minutes under 1200 rpm (190×g). The blood is segregated into three layers. The supernatant and the buffy coat (which is believed to have concentrated platelets) were pipetted into a different conical tube and centrifuged for 10 mins under 2000 rpm (535×g). 4 mL of supernatant, which is our PRP sample was collected with the plan of instilling 1–1.5 mL of the sample per ovary. The aspiration procedure was undertaken transvaginally using guided ultrasound by administering mild anaesthesia to the patient. After removing the dominant follicle, we instilled IOPRP in the collapsed follicle for around 45 seconds. We used 1–1.5 mL of PRP for both ovaries. AFC was recorded as 1 in the right ovary and 2 in the left. Upon subsequent follow-up, we performed the oocyte aspiration procedure again, and IOPRP was followed for round 2. Upon the final aspiration procedure, we were able to retrieve 5 MII Oocytes from the patient. We planned to do a fresh embryo transfer with two embryos and freeze the rest of the embryos for frozen embryo transfer. We performed a fresh embryo transfer on the patient. β-HCG report performed after two weeks of the transfer resulted in negative. The couple was counselled and prepared for a frozen embryo transfer.\n\nDuring the subsequent visit to our centre, we analysed the thickness of the endometrium. The usual range of endometrium is above 7 mm for the transfer of embryos.8 She was started with oestradiol 2 mg tablet twice daily, vitamin supplements and thyroxine 125 μg as a part of pre-medication.\n\nA globally approved thawing kit was used to thaw the embryo and was stored in a benchtop incubator for around 130 mins for the blastocyst to expand. Once the agenda was achieved, we transferred one embryo of 4AA grade (Figure 1) into the uterus. The patient had no discomfort using the procedure in August 2022.\n\nAfter the successful transfer of the embryo, the patient was discharged with the advice of follow-up. The patient was advised to have ofloxacin and ornidazole combined tablet twice daily, omeprazole 40 mg on an empty stomach daily, vitamin E supplement once a day, arginine tablet once a day, vitamin supplements, oestradiol 2 mg tablet twice a day and progesterone 400 mg once a day. She was also advised to injectables of human chorionic gonadotrophin (HCG), hydroxyprogesterone 500 mg and intralipid injection. After two weeks from the day of embryo transfer, we drew a syringe of blood from the patient and sent it for a β-HCG test at our laboratory centre in ABVRH, Sawangi Wardha. The report came to be positive. The level of β-HCG was reported to be 1050 mIU/mL.\n\n\nDiscussion\n\nFarimani et al. (2021) did a retrospective study on the effect of oocyte variables upon the administration of IOPRP on patients affected by DOR (diminished ovarian reserve) and reportedly found significant positive results.9 On a similar line, Parikh et al. (2022) conducted a prospective cohort study to analyse the effect on pregnancy outcome on the instillation of IOPRP in young Indian women suffering from infertility due to poor ovarian reserve (POR) and found a significant positive effect.5 This research formed the basis of our application of IOPRP in our case. The limitation of this case report is that it is performed on a single patient, and the result of this report cannot be generalised in the population. This requires further validation via RCTs (randomised clinical trials) to form baseline treatment in latent FGTB patients seeking IVF treatment.\n\nDue to extrapolating frequency of increase in infertility across the world, it has become a matter of great importance for scientists to research its reasons and fight back with suitable outcomes to continue the human race. There are several reported reasons for infertility found in both males and females, such as low sperm count, sexual dysfunction, aspermia, teratozoospermia etc for men and uterine adhesions, hostile uterine environment, cystic ovary, blocked fallopian tubes etc for females.2,10 Latent FGTB has been reported as one of the factors of infertility and caught an upward rising trend for affecting the dreams of several infertile couples desiring for a child.3 In our case study, the patient was suffering from secondary infertility due to being affected by latent FGTB. Hence, we instigated a venture to study the effect of latent FGTB on the fertility of females and find a possible solution for it. Our patient was in her middle age and was nulligravida; therefore, chances of a normal pregnancy using her own gametes seem to be a feasible option. Latent FGTB is an external form of tuberculosis. It is found to affect the fallopian tube majorly, followed by the uterus, cervix, vagina and slight chances of the valvular region.3 In our patient, latent FGTB was found to affect her ovarian reserve, thereby causing a diminished ovarian content as well as uterine adhesions presented in the case upon histopathological examination of the endometrium. We discovered several studies which show significantly positive improvement of the ovarian reserve upon the administration of IOPRP in case of poor ovarian response patients.5 However, there were no studies available on the application of IOPRP in DOR cases which was caused by latent FGTB. It has been reported in some literature that there are several growth factors in PRP that play a vital role in regulating vascular activation and neoangiogenesis by either activating the latent oocytes or stimulating the dormant ovarian stem cells to differentiate and develop into active oocytes.5 Growth factors (GFs) like VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) are important angiogenesis molecules present in PRP, which helps in the vascularisation of granulosa, thereby developing the pioneer corpus luteum into its functionality.5 Other GFs like BMP-2, BMP-4 and GDF-5 also play an essential role in developing oocyte competency by stimulating the mesenchymal and progenitor stem cells. This is believed to improve the pregnancy rate.5\n\nIt is also hypothesised by some literature that follicular rupture causes injury to the ovarian epithelium, which activates the stem cells in this region to promote healing. Administration of IOPRP by the needle is thought to be activating a similar effect in the ovaries which improves the AFC in further ovum pick-up.5\n\nIn our case report, we found that the instillation of IOPRP does improve the AFC in our patient suffering from DOR. We were able to retrieve healthy 5 MII oocytes, which led to a fruitful, positive clinical pregnancy outcome for the patient. This was validated by a positive β-HCG report.\n\n\nConclusion\n\nThis case report outlines the upbeat sequel of the instillation of IOPRP in the case of a patient suffering from secondary infertility due to the adverse effects of latent female genital tuberculosis on her endometrium and ovaries, thereby resulting in successful clinical pregnancy with the assistance of in vitro fertilisation (IVF) procedure at WTTBC, Wardha, India. This case also throws light on the fact that IOPRP may have a significant positive effect on the utilisation on patients suffering from genital tuberculosis.\n\n\nConsent\n\nWritten informed consent was obtained from the patient and her partner for the publication of their clinical details and clinical images.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article, and no additional source data are required.\n\n\nReferences\n\nOmbelet W: Global access to infertility care in developing countries: a case of human rights, equity and social justice. Facts Views Vis. ObGyn. 2011; 3(4): 257–266. PubMed Abstract\n\nWalker M, Tobler K: Female Infertility. [Updated 2022 Dec 19]. Treasure Island (FL): StatPearls; 2023. Reference Source\n\nKesharwani H, Mohammad S, Pathak P: Tuberculosis in the Female Genital Tract. Cureus. 2022 Sep 2 [cited 2023 May 21]; 14: e28708. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nJirge PR, Chougule SM, Keni A, et al.: Latent genital tuberculosis adversely affects the ovarian reserve in infertile women. Hum. Reprod. 2018 Jul 1 [cited 2023 May 21]; 33(7): 1262–1269. PubMed Abstract | Publisher Full Text Reference Source\n\nParikh FR, Sawkar SG, Agarwal S, et al.: A novel method of intraovarian instillation of platelet rich plasma to improve reproductive outcome in young Indian women with diminished ovarian reserve. Glob. Reprod. Health. 2022 [cited 2023 May 21]; 7(2): e59–e59. Publisher Full Text\n\nChiu YH, Edifor R, Rosner BA, et al.: What Does a Single Semen Sample Tell You? Implications for Male Factor Infertility Research. Am. J. Epidemiol. 2017 Oct 15; 186(8): 918–926. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDayal M, Sagar S, Chaurasia A, et al.: Anti-Mullerian Hormone: A New Marker of Ovarian Function. J. Obstet. Gynecol. India. 2014 Apr [cited 2023 May 21]; 64(2): 130–133. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang Y, Zhu Y, Sun Y, et al.: Ideal embryo transfer position and endometrial thickness in IVF embryo transfer treatment. Int. J. Gynecol. Obstet. 2018 Dec [cited 2023 May 21]; 143(3): 282–288. PubMed Abstract | Publisher Full Text\n\nFarimani M, Nazari A, Mohammadi S, et al.: Evaluation of intra-ovarian platelet-rich plasma administration on oocytes-dependent variables in patients with poor ovarian response: A retrospective study according to the POSEIDON criteria. Reprod. Biol. Endocrinol. 2021 Dec [cited 2023 May 21]; 19(1): 137. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLeslie SW, Soon-Sutton TL, Khan MA: Male Infertility. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 May 21]. Reference Source"
}
|
[
{
"id": "203100",
"date": "30 Oct 2023",
"name": "Yogita Dogra",
"expertise": [
"Reviewer Expertise Reproductive Medicine"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe present case report has highlighted the effect of TB on ovarian reserve and the effect of IOPRP in improving the same. The patient is a 38 year old woman with low AMH and low AFC with previous history of extrapulmonary TB and four failed IUI cycles. The ovarian reserve improved after two subsequent rounds of IOPRP instillation. Subsequently patient conceived in FET cycle.\nThe background of case history and the progression should be made more clearer. The nature of cyst diagnosed in 2019 is not mentioned e.g. endometriotic cysts are known to decrease the ovarian reserve. The authors have mentioned that FGTB has led to decrease in ovarian reserve in this case. However it is difficult to reach this conclusion keeping in mind the age of the patient and the presence of ovarian cyst.\nWhether patient took ATT for Extrapulmonary TB diagnosed in 2021 needs to be mentioned.\n\nWhat was the AFC in first IVF cycle? Any supplements were advised before IVF to improve the ovarian reserve? Please elaborate.\nPlease provide the reference for IOPRP instillation in a stimulated cycle. Can it be instilled in a natural cycle?\nIt has also not been mentioned whether again ovarian stimulation was done for second round of IOPRP.\nBefore final aspiration, please mention the AFC. Whether IVF protocol was used and which protocol in which 5 MII oocytes were retrieved.\n\nWhat was the ET during FET cycle as uterine adhesions have also been mentioned? Did the patient receive any treatment or hysteroscopy advised for adhesions? The detailed methodology in step wise manner would be more helpful for the readers and the other practitioners to understand the positive effect of IOPRP in improving the ovarian reserve.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
},
{
"id": "267756",
"date": "02 May 2024",
"name": "Johnbosco Mamah",
"expertise": [
"Reviewer Expertise Benign Gynaecology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis was a very interesting case report highlighting the role of IOPRP treatment in the management of DOR in subfertile individuals whose infertility may have been caused by genital tuberculosis. The use of platelet-rich plasma in medical practice remains an evolving area of medical research, and it is gratifying to see its use being expanded into new areas.\n\nI find that the patient's medical history was not detailed enough, thereby leaving a few unanswered questions. For instance, the diminished Ovarian reserve in the patient could have been caused by many factors, including the Ovarian cyst the patient had. It is not clear the nature of the cyst and any treatment received for the cyst. Cystectomies may lead to diminished ovarian reserve, which can impact fertility. If there was no treatment, the authors should clarify.\n\nThe authors state that the patient had secondary infertility, yet she is described as nulligravida. This is confusing. What was the nature of the infertility? Has she ever been pregnant or had a child in the past?\n\nIt is not clear which came first: endometrial adhesions or D/C. D/C is a risk factor for endometrial adhesions, so it may not have been due to genital TB. The authors did not clarify if the tuberculosis was treated. How did we establish that the patient had TB of the ovary? Was ovarian fluid aspirate/tissue tested for M-TB? How did the authors establish a cause-and-effect relationship between DOR and genital TB?\nThe patient was significantly hypothyroid, was the treatment she had contributory to the positive outcome?\nAlthough the patient had a positive pregnancy test in the end, what was the final outcome of the pregnancy?\n\nThe authors used many unconventional terms/words, which is not typical of scientific writing.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? No\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-716
|
https://f1000research.com/articles/12-715/v1
|
20 Jun 23
|
{
"type": "Research Article",
"title": "Measuring behaviour in hens using an ethogram to assess analgesia during further refinement of a high welfare, on-hen, poultry red mite feeding device",
"authors": [
"F. G. Nunn",
"D. A. Ewing",
"K. Bartley",
"Javier Palarea-Albaladejo",
"W. Chen",
"D. R. G. Price",
"A. J. Nisbet",
"D. A. Ewing",
"K. Bartley",
"Javier Palarea-Albaladejo",
"W. Chen",
"D. R. G. Price",
"A. J. Nisbet"
],
"abstract": "Background: To refine an on-hen mite feeding device, an ethogram was employed to measure the reactions of hens during a routine experimental procedure (feather plucking) and to assess effects of analgesic cream on those reactions. Methods: Three experimental groups were used; one treated with EMLA 5% before plucking (“EMLA group”); one with aqueous cream (“placebo group”) and a “no treatment” group. Behaviours were measured and compared on three days: ‘dummy handling day’ i.e. no plucking; ‘plucking day’, plucking the left thigh; and ‘treatment day’ i.e with right thighs plucked post-treatment. Poultry red mite feeding assays were performed to examine effect of creams on mite feeding rates, mortality and fecundity. All data were analysed using generalised linear (mixed) modelling approaches. Results: Use of the ethogram demonstrated no significant difference in hen behaviours in the EMLA group between dummy handling day and treatment day (p = 0.949) alongside a significant reduction in measured behaviours between plucking day and treatment day in the same group (p = 0.028). There was a statistically significant increase in measured behaviours from the dummy handling day to the plucking day in both placebo (p = 0.011) and no treatment group (p < 0.001). Effect sizes and directions were similar between dummy handling and treatment days in the ‘placebo’ and ‘no treatment’ groups, though not statistically significant (placebo, p = 0.064; no treatment p = 0.069). Mite feeding in the EMLA group was significantly lower than in the no treatment group in feeding assay 1 (p = 0.029) only. Mite mortality and fertility were unaffected. Conclusions: The ethogram successfully measured changes in observed behaviours between the dummy handling session and procedures. No adverse effects of EMLA cream on hens were demonstrated at 3mg/kg in hens. Use of analgesia for this routine procedure improves hens’ experiences during experimental trials.",
"keywords": [
"ethogram",
"poultry",
"EMLA",
"mite",
"refinement",
"behaviours",
"welfare"
],
"content": "Introduction\n\nPoultry red mite (PRM) is a major pest of laying hens with a worldwide distribution (Sigognault Flochlay et al., 2017) and a major welfare concern. The mite has a simple life cycle (Figure 1) and infestations cause stress behaviours, a decrease in egg production, egg quality and an increase in mortality (Sigognault Flochlay et al., 2017). Research approaches include vaccine development and systemic acaricides which require testing on-hen, using various hen infestation models (Bartley et al., 2017; Mul et al., 2015). In 2019, we reported the development of a high-welfare, on-hen mite feeding device (Nunn et al., 2019) that allowed all hematophagous PRM life stages to feed on-hen. This is an important refinement on other methods of testing and allows a reduction in the number of birds needed to test a novel control product (Nunn et al., 2019). The device has now been used to assess several PRM vaccine candidates (Price et al., 2019; Lima-Barbero et al., 2019a, b).\n\nBlood feeding stages are indicated with the red arrows, with both protonymphs and deutonymphs requiring a feed in order to moult into the next life stage.\n\nUse of this device requires plucking of the hens’ thighs because close attachment of the feeding mesh to the skin facilitates mite feeding. Plucking causes transient pain/distress. The use of analgesic cream may relieve this pain/distress but there is a paucity of published information on the effectiveness of such creams on birds (Machin, 2005; Hocking et al., 1997). Equally, there is little published information on the assessment of pain in birds. Flecknell (1994) argues that instead of focusing on detection of pain, we should strive to alleviate both pain and distress due to the difficulty in differentiating between the two in animals.\n\nThe purpose of the current study was to ascertain if an ethogram used to measure behaviours could gauge discomfort and/or distress in hens during a routine procedure and to assess whether the use of EMLA cream afforded any measurable relief from pain/distress during the same procedure. In addition, respiration rate was assessed as a measurable effect of discomfort/distress. PRM feeding assays were performed on the three days following treatment to assess any increased mortality or reduced feeding rates of mites fed on hens treated with EMLA and placebo creams.\n\nAll efforts were made to ameliorate any suffering of hens used in this study. Staff were experienced with the feeding assays and procedures and the veterinary grade bandages and tape have been previously used with no harm caused. Hens were kept in floor pens in groups with pens divided by wire so that each group could see all the other groups and all treatments were carried out in a different room where birds could not see the other birds. Birds always had access to pellets and water, with nest boxes and perches available. The pens were based within animal accommodation with clear panels in the ceiling allowing for natural light. Birds were monitored several times daily and constantly throughout ‘treatment day’ for any adverse signs of EMLA cream. Potential adverse signs included ataxia, distress or recumbency which would result in veterinary intervention, although were understood from the available literature to be transient. No humane endpoints were anticipated from the mite feeding assays outside any sudden ill-health.\n\nAll experimental procedures described here were reviewed and approved by the Moredun Research Institute Animal Welfare Ethical Review Body (7/04/2021) and were conducted under the legislation of UK Home Office Project License (reference P46F495BD) in accordance with the Animals (Scientific Procedures) Act of 1986. The manuscript was written in adherence with the ARRIVE 2.0 guidelines (Percie du Sert et al., 2020; Nunn, Francesca, 2023).\n\n\nMethods\n\nBovans Hyline pullets (n=15, 17 weeks old) were purchased from a commercial hatchery and haphazardly assigned to floor pens (3×4 hens and 1×3 hens) by animal care staff. Pens contained perches, nest boxes, substrate in the form of wood shavings and straw and ad libitum pellets and water. Hens were permitted to acclimatise for 7 days before the start of procedures.\n\nPoultry red mites were collected and pre-conditioned as previously described (Nunn et al., 2019, 2020). In short, mites were collected from farms by gently scraping mite aggregations with a spatula into a weigh boat and then transferring these into a 75 cm3 tissue flask. Mites were then stored in 75 cm3 tissue flasks (Corning, New York, USA) with vented caps and stored at room temperature (RT) for 7 days before being kept at 5°C for three weeks. Adult female mites were isolated on ice as described in Nunn et al. (2020) for use in this trial. Briefly, flasks containing mites were placed at RT for 15 minutes. Mites that crawled up into the cap during this time were tapped out onto a glass petri dish and the dish was then placed on a weigh boat containing wet ice. Females were identified using size under light microscopy, counted and placed into pouches using fine detail paint brushes.\n\nTrial\n\nA timetable of the experiment can be seen in Table 1. Three experimental groups consisted of; the “EMLA group” which had EMLA (5%) cream applied on treatment day, the “placebo group” which had aqueous cream (Lloyds Pharmacy Aqueous cream B.P.) applied on treatment day (to facilitate blinding of the groups to the plucker and ethogram scorer) and the “no treatment group”, which had no creams applied on treatment day. The no treatment group existed to facilitate a real-time mite feeding control group to enable comparisons of feeding, mortality and fecundity of mites not exposed to EMLA or aqueous cream. No a priori exclusion criteria were set for this study.\n\nDay 1 began seven days after hens were acquired to allow for acclimatisation. Hen handling was carried out by experienced researchers throughout. All hens (n=15) were habituated to handling and a one-minute restraint on day 1 and day 2 in the treatment room. On day 3 all hens (n=15) were handled, with baseline behavioural ethogram recordings, respiratory rates and hen weight recorded. On day 6, all hens (n=15) were taken into the treatment room, restrained and a respiratory rate taken prior to having a 2×2 cm area of their left thigh plucked and behaviour scores were taken. A further respiratory rate was taken straight after plucking was finished. On day 7, hens either had EMLA cream (n=5) or aqueous cream (n=5) applied to a 2×3 cm area on their right thigh with bandages put on top or bandages only (n=5), before being returned to their pens. Hens were then retrieved, bandages removed, respiration rate taken and an area of 2×2 cm plucked with behaviour scores recorded. Respiratory rate was taken immediately after plucking was finished. On days 8, 9 and 10, each hen had a pouch containing 50 female mites attached to their right thigh with medical tape for three hours before its removal.\n\nEthogram behaviours and respiration rates were measured on three days as follows; dummy handling day (i.e. with no plucking), plucking day (all left thighs plucked with no treatment) and treatment day (right thighs plucked with treatments in the EMLA and placebo group). Poultry red mite feeding assays took place on the three days after the treatment day.\n\nThe trial was designed so that both ‘plucker’/ethogram scorer and bird handler were blinded to the EMLA and placebo groups throughout the trial including recording of mite feeding rates and mite mortality monitoring. The ethogram scorer also applied the treatments, wearing gloves (Protech), changing pairs between each bird.\n\nThe behavioural ethogram (see the Underlying data, Nunn, 2023) was designed by handlers experienced in the procedure and included all observed reactions to plucking from previous trials. Presence or absence of each behaviour in response to plucking or handling was recorded by scoring 1 (reaction observed) or 0 (no reaction observed), respectively. The behaviours included in the ethogram were; blinking corresponding with plucking, looking at leg, trying to move leg, bodily resistance (wing), vocalisation (once), vocalisation (repeated), vocalisation (loud), and trying to stand/flee. Vocalisation was only scored if it occurred in response to a feather being manipulated (as in ‘dummy handling’) or to a feather being plucked, which is distinct from general background vocalisation.\n\nAfter the acclimatisation period, hens were habituated to handling by removal from pens, being carried to the treatment room and then restrained in the same way as they would during procedures, for one minute for two consecutive days (Table 1, days 1 and 2). All raw behavioural data, respiration data and information on bird weights, doses, treatment groups and pen distribution can be found in the Underlying data (Nunn, 2023).\n\nOn day 3, baseline recordings were made during a ‘dummy handling’ session. Individually, each hen was taken from their pen to the treatment room and given one minute to recognise their surroundings. Hens were then restrained on their side and respirations recorded for 30s. Respirations were recorded by gently laying a finger on the keel bone and the number of times the finger was raised was counted within the 30s. To take behaviour and respiratory measurements that were related to hen handling but not plucking, a 60s period of gentle feather manipulation was then used to score behaviours according to the ethogram. This was immediately followed by a second respiratory rate taken over 30s. Hens were then assigned a pre-numbered leg ring and the number recorded next to their behaviour and respiration rate recordings and returned to their pen.\n\nOn day 6 (“plucking day”), hens were again selected from each pen, taken to the treatment room and respiratory rate measured. Leg ring numbers were obscured from plucker and scorer by turning the number away from the handlers. A section of thigh approximately 3 cm×3 cm on the left leg of each hen was then plucked and the behaviour for each bird was scored. A second respiration rate was then recorded and birds were then weighed and returned to their pen.\n\nOn day 7 (“treatment day”), hens were assigned a treatment group with treatment groups being intermingled across the four pens and with birds chosen to be as close to the average weight of the group as possible. Doses of EMLA cream for each bird were calculated by weight and placebo cream (aqueous cream) doses were the equivalent of the EMLA cream doses by weight. Hens were selected from each pen, taken to the treatment room and respiratory rate measured. Treatments were applied using a child’s interdental brush (Microbrush® Plus Micro Applicator regular size, PR400GR, Microbrush Corporation, USA) to gently apply cream around the base of the feathers on the hens’ right thighs until the cream was uniformly distributed in the 3×3 cm area where the feeding device would be subsequently attached (days 8–10). A cotton gauze swab (Covetrus 10 cm×10 cm) was placed on top and was then bandaged with a cohesive bandage (Steroban Cohesive, 2.5 cm×4.5 m). The no treatment group had the cotton swab and bandage applied only. Hens were then placed back in their respective pens. So that all treatments could be left on the birds for a set period, an electronic timer was set at time = 0 when the first bird had a treatment and the pens were completed to facilitate plucking at around 45mins after treatment application. There was no evidence to suggest a difference between application periods across the treatment groups based on Tukey’s multiple comparisons of means, with the following estimated differences (in minutes) between groups; “no treatment – EMLA” 2.0 (-3.0, 7.0), “placebo – EMLA” 0.6 (-4.4; 5.6) and “placebo – No Treatment” -1.4 (-6.4; 3.6). Birds were continually monitored during this application period for any adverse effects such as loss of balance or distress (none were observed). Hens were then brought into the treatment room in order of treatment application, respiratory rate was measured and bandages removed, right thighs plucked and behaviour recorded before the respiratory rate was then measured again.1\n\nFeeding assays were carried out as previously reported (Nunn et al., 2019, 2020). Briefly, each hen was haphazardly allocated a feeding device on each of the three days after treatment day. Pouches containing 50 adult female PRM were applied to the hens’ right thighs and attached with medical tape for three hours. At the end of the feeding period, hens were haphazardly selected for removal of the feeding devices. Pouches were then removed with “fed” and “unfed” mites recovered and counted to assess feeding rates. Fed mites were kept for observing mortality and fecundity by counting eggs laid per fed female, over a 6-day period.\n\nPower calculations were based on simulation from a binomial generalised linear mixed model (GLMM) for mortality and feeding rates over time as described below and included in the Underlying data (Nunn, 2023).\n\nMortality rates. We assumed a mortality rate of 2% as baseline and increases of 5% and 7% that would be considered biologically meaningful differences in mortality rates after the application of topical analgesia, three time points, 50 mites per feeding pouch, and normally distributed random effects for time (SD=0.35) and bird (SD=0.14). Model parameters were based on previous data from PRMs in all life stages fed on hens of the same age (Nunn et al., 2020).\n\nFeeding rates. We assumed a feeding rate of 65% as baseline and reductions to 60% and 55% that would be considered biological meaningful reductions after the application of topical analgesia, three time points, 50 mites per feeding pouch, and normally distributed random effects for time (SD=0.23) and bird (SD=0.11). Model parameters were based on previous data (see the Underlying data (Nunn 2023); Data: Obj 2 18 weeks data for Power Calcs) from PRMs in all life stages.\n\nThe results indicated that five birds per experimental group was the minimum required to reach the standard 80% statistical power threshold at a 5% significance level for both mortality rates and feeding rates under those conditions.\n\nNo power calculations were performed for the behaviour/ethogram analyses or for respiration rates. Due to the nature of mixed model analysis reference to experimental units are not made, as mixed models have multiple random components with affects assessed against appropriate levels in the random hierarchy.\n\nThe behaviour scores were analysed using Firth’s bias-reduced logistic regression (Firth, 1993), to allow for combinations of treatment and timepoint with entirely zero responses, with the binary response variable denoting whether a behaviour was observed or not. A 3-way interaction between the treatment group, behaviour type (as described above) and the day was considered, alongside all 2-way interactions and main effects. There was little evidence of variability between birds or pens, so random effects were not included in the model.\n\nRespiration rates were analysed using generalised linear mixed models (GLMMs) with a Poisson response and logarithmic link function fitted by maximum likelihood to the respiration counts. A 3-way interaction between the treatment group, whether the measurement was pre- or post-treatment, and the day was considered, alongside all 2-way interactions and main effects. Random effects were included for each bird but there was no evidence to support a more complex structure (e.g. random effects for pen or day nested within bird).\n\nAnalysis of mite feeding rates was conducted using GLMMs, with a binomial response and a logit link function, fitted by maximum likelihood to the number fed out of total mites per feeding pouch (i.e. per bird by assay) including treatment group and assay number and the interaction between these two terms as fixed effects and bird as a random effect (there was no evidence of a pen effect). Equivalent models were considered for the mite mortality rates, however no variance was attributed to bird or pen so generalised linear models (GLMs) with the same fixed effects structure were fitted to the number dead after 6 days out of total fed mites. Fertility rates of mites (i.e. total offspring per fed mite), were analysed using a zero-inflated Poisson GLMM fitted to the number of offspring per pouch with a logarithmic link function, including an offset (on logarithmic scale) to account for total number of fed mites recorded per pouch, with the interaction between treatment group and assay number as a fixed effect and bird as a random effect.\n\nAssessment of the statistical significance of fixed effects was conducted using likelihood ratio tests. The use of mixed models ensures that fixed effects were assessed against appropriate variances in the random hierarchy. Post hoc pairwise tests of differences in means were conducted based on the predicted marginal means from the model estimates. The resultant p-values were adjusted to account for multiple testing using the multivariate t-distribution. Results show contrast effect sizes (es) and standard errors (SE) on the transformed scales (e.g. log, logit). Means and 95% confidence intervals (LCL, UCL lower and upper limits of the 95% confidence interval, respectively) estimated from the above models back transformed onto the original scale (e.g. proportions) are also shown to aid interpretation. Significance tests were assessed at the standard 5% significance level. All analyses were conducted using R (4.1.3., R Core Team, 2022) with the lme4 package for GLMMs (Bates et al., 2015), the glmmTMB package for zero-inflated models (Brooks et al., 2017), the brglm package for Firth’s bias-reduced logistic regression (Kosmidis, 2021), the car package for likelihood ratio tests (Fox and Weisberg, 2019) and the emmeans package for pairwise comparisons and multiple testing adjustments (Lenth, 2022).\n\n\nResults\n\nSummaries of the dose rates, application duration and weights of birds are shown in Table 2. Raw data for behaviour and respiration scores, experimental groupings, dose weights etc are in the Underlying data (Nunn, 2023).\n\nThe standard deviations are given in brackets for each group.\n\nWhen analysing the ethogram scores the best fitting model included 2-way interactions between the behaviour type and the day (p<0.001) and between the treatment and day (p=0.053) alongside main effects for each of the terms. Averaged over behaviours (Table 3a and Figure 2b), no statistically significant differences between any of the three treatment groups were observed on either the dummy handling or plucking days (Table 3b). There was evidence of a statistically significant decrease in the probability of observing a pain-related behaviour in the EMLA group compared to either the placebo (es=-2.41, p=0.040) or no treatment (es=-2.62, p=0.020) groups on the treatment day (Table 3b). Figure 2a shows that these differences appear to be driven primarily by a subset of the measured behaviours; namely blinking, looking at the leg and vocalisations.\n\n“SE”, “LCL” and “UCL” are the standard error, and the lower and upper limits of the 95% confidence interval, respectively.\n\nPlots in the top panel (a) show the estimated probability of each behaviour being displayed with 95% CI for each combination of day and treatment group. The bottom panel (b) shows the estimated probability with 95% CI of observing a pain related behaviour averaged across behaviour types for each treatment group on each day (generating estimates in Table 3a and comparisons in Tables 3b and 3c).\n\nThere was a statistically significantly lower probability of exhibiting a pain related behaviour in the EMLA group on treatment day than on plucking day (es=2.75, p=0.03) and no statistically significant evidence of a difference between treatment day and the dummy handling day (es=0.85, p=0.95) (Table 3c). In the other two treatment groups there was a statistically significant increase in the probability of recording a behaviour on plucking day compared to dummy handling day (placebo; es=3.01, p=0.011, no treatment; es=3.48, p<0.001) but no statistically significant difference between the response probabilities on the other days. Nonetheless, it should be noted that there were fairly similar differences between the dummy handing and treatment days as between the dummy handling and plucking days but these were marginally statistically insignificant at the 5% level (Table 3c).\n\nThe respiration rates and percentage changes in respirations following handling summarised by treatment group and day are shown in Table 4. Following model selection there was no evidence of a statistically significant effect of the treatment group on the respiration rate before or after treatment, with the significant term being the effect of day (p=0.018), which stemmed from a statistically significantly higher respiration rate on the plucking day than on the dummy day (es (log respiration rate)=0.18, p=0.013).\n\nRaw data is in the Underlying data (Nunn, 2023). For feeding rates, there were statistically significant main effects of treatment group (p=0.017) and assay number (p<0.001) and a statistically significant interaction between these effects (p<0.001). The estimated mean mite feeding rate (Figure 3a and Table 5a) was always lowest in the EMLA group, irrespective of assay and was statistically significantly lower (Table 5b) in the EMLA group than in the group with no treatment applied in the first assay (es=0.88, p=0.029). The estimate of the difference between the EMLA group and the placebo group was similar to the difference between the EMLA group and no treatment group in assay 1, though not statistically significant at the 5% level (es=0.78, p=0.070). There was no evidence of a statistically significant difference between the groups in assay 2. In assay 3 the feeding rate was statistically significantly higher in the placebo group than in either the EMLA group (es=1.21, p=0.001) or the group which received no treatment (es=0.90, p=0.031), however there was no difference between the EMLA group and the group which received no treatment (es=0.32, p=0.879).\n\nPlots in the top panel show the estimated proportion of mites fed with 95% CI for each combination of treatment group and feeding assay (generating estimates in Table 5a and comparisons in Tables 5b). The bottom panel (b) shows estimated mite mortality rates with 95% CI of fed mites for each combination of treatment group and feeding assay (generating estimates in Table 6a and comparisons in Table 6b).\n\n“SE”, “LCL” and “UCL” are the standard error, and the lower and upper limits of the 95% confidence interval, respectively.\n\nThe assay number was found to have a statistically significant effect on the mite mortality at the 5% level (p<0.001), however there was no statistically significant effect of either the main effect of treatment group (p=0.100) or the interaction between assay and treatment group (p=0.230). The mite mortality rate (Figure 3b and Table 6a) was statistically significantly lower (Table 6b) in the first assay than in either the second (p=0.001) or the third (p<0.001) assays, however there was no statistically significant difference between the second and third assays (p=0.278).\n\n“SE”, “LCL” and “UCL” are the standard error, and the lower and upper limits of the 95% confidence interval, respectively.\n\nThere was no evidence of a statistically significant effect of treatment on mite fertility. There was no statistically significant effect of either treatment group or assay number or the interaction between these two terms in either the conditional or the zero-inflation part of the GLMM of mite fertility.\n\n\nDiscussion\n\nThe purposes of this study were to assess whether an ethogram could be used to measure behaviours indicative of pain/distress in hens undergoing a routine experimental procedure, assess any analgesic effect of EMLA 5% Cream on pain related behaviour using the ethogram and whether the use of EMLA cream affected poultry red mite feeding, mortality and fecundity data collected during a trial.\n\nWith regards to mite feeding, the mites fed on hens in the EMLA group showed the lowest mean feeding rates on all days although this was only statistically significantly lower than the no treatment group in the first feeding assay. The effect of the EMLA cream on mites could be physical or chemical and may decrease with time. Its effect on mite feeding on hens that have had a longer period between treatment and feeding assays should be evaluated as well as its effect on the other blood-feeding life stages of the mite. Variation in mite feeding is an issue with ‘farm-collected’ mites with mite fitness dependent on an array of factors not yet understood (Nunn et al., 2020).\n\nThe behaviour categories in the ethogram were based on observations from two scientists with experience of the procedure over the course of several trials including four published trials (Lima-Barbero et al., 2019a, b; Nunn et al., 2019, 2020). The highest behaviour scores were demonstrated on plucking day, when no hens received treatments and all hens had their left thighs plucked. On treatment day, decreased probabilities of displaying pain-related behaviours were demonstrated in all three experimental groups when compared to plucking day, although this was largest and only statistically significant for the EMLA group, suggesting successful analgesia in this group. Progressive removal of feathers has previously been shown to lead to a decrease in the type of agitated behaviour observed during the first feather removal (Gentle and Hunter, 1991) and is a reminder that indicators of pain differ between species. A decrease in a certain behaviour does not necessarily mean a decrease in pain/distress if all other factors remain constant and care must be taken in interpretation of results.\n\nChickens have a range of vocalisations (Bright, 2008) and the ones scored in this trial were those directly associated with the plucking of feathers and were distinct from the background, low vocalisations witnessed during dummy handling and when the hens were removed from the other hens. Vocalisations were classed on whether they corresponded to having a feather pulled, whether this was repeated more than once or whether it was a distinctive loud squawk. No vocalisations other than the background vocalisations were recorded during the dummy handling session although all birds vocalised on plucking day with 14/15 repeatedly vocalising and 3/15 giving additional single loud vocalisations demonstrating this as a useful measure of pain/distress in birds.\n\nThe behaviours that showed the most pronounced increases in estimated probability of occurrence from dummy handling day to the plucking day were blinking and vocalisations. Conversely there was a slight decrease in the estimated probability of moving the leg from the dummy handling day to the plucking and treatment days. The largest estimated differences between treatment groups within a particular day stemmed from lower behaviour counts in the EMLA group on the treatment day.\n\nTo allow respiratory rates of the hens to recover from being caught by a handler, sessions were carried out to habituate hens to being caught and taken to a different place away from the rest of the birds. There was no evidence to support a relationship between treatment group and the change in respiration rate before and after the procedure in our data. Nonetheless, the use of respiratory rates in monitoring pain in mammals under anaesthesia is routine practice in some species although there is a lack of published data on respiratory rates on birds and pain. An online respiration guide from The International Veterinary Academy of Pain Management exists, though there are no metadata detailing its development. This scale of 0–3 indicates that a 10% increase in respirations equals a score of zero, with a 10–50% increase leading to a scale of 1, a 2 being 50–100% increase and 3 more than 100% increase. By this scale and using the percentage change in respirations that were demonstrated in this study, all the birds in this study would have scored a zero during dummy handling day, 10 of the birds used would have had a pain score of 1 during plucking day and five birds a pain score of 1 on treatment day. Only birds in the EMLA group (4/5) scored a zero-percentage change in respiratory rate during treatment day. Heart rate monitoring to monitor pain was considered for this trial but is skilled and takes practice (Smith et al., 2014). Respirations were judged to be a more attainable measurement for those not skilled in auscultation and their assessment as an effective tool in monitoring pain/distress would be useful for other researchers. It is likely that this study did not possess sufficient power to detect an effect of treatment on change in respiration rate if such an effect did exist, particularly as the respiration rate can be affected by outside noise.\n\nOverall significant differences were observed by behavioural scores, indication that use of an ethogram to measure behaviour is useful during experimental procedures. Further work is required to evaluate if learned helplessness occurs across repeated procedures in longitudinal trials and the usefulness of this ethogram to measure behaviour over time. The results presented here indicate measurable differences in behaviour during ‘benign’ procedures such as the dummy handling session in this trial and the regulated procedures in both plucking sessions and that pain relief during the latter is useful in mitigating distress. Previously published studies (Flecknell et al., 1990; Keating et al., 2012) in the use of EMLA cream as an analgesic in the pain management of laboratory animals exist for small animals (rats, rabbits and dogs) during procedures such as venepuncture and tattooing. It is helpful to think of the alleviation of distress in birds rather than pain given the difficulties in recognising signs of pain across classes, species and in individuals as reviewed by Flecknell (1994). Both the EMLA cream and aqueous cream were easily absorbed, to the point that on removal of bandages, handlers could not tell which birds were in the no treatment group or the EMLA and placebo groups. The creams were easily applied around the feathers using the interdental brushes. The dosage leads to a small volume of product that would not cover a larger surface area (i.e. > 3×4 cm) although it would be enough to use in minor procedures such as blood sampling etc. No adverse effects were demonstrated suggesting that it could be safely used at that dose for other procedures.\n\nCurrently there are four active research teams in Europe working in early-stage vaccine development with further groups in Japan that this research may benefit. There are also groups in Europe who have adapted the device for other uses in the study of PRM such as mite genetic studies and behavioural studies that use mite feeding. Research groups using the on-hen mite feeding device will typically use between 4–5 birds per experimental group (Nunn et al., 2019; Lima-Barbero et al., 2019a, b) leading to a refinement in the procedure for each of those birds.\n\nThe study provides a reference point of EMLA use for plucking and potentially other minor procedures in hens used in other experimental settings. Of 1.73 million experimental procedures in 2021, 14% were carried out on birds, although a breakdown of species is not available (U.K. Government Home Office, 2022) the use of respiratory rates for other species may also prove useful.\n\nBackyard hens are a popular pet species, with an estimated 1.4 million in 2021–2022 (Bedford, 2022) with ‘chicken friendly’ veterinary practices across the UK that have specialist knowledge of chicken care. The use of EMLA cream in this study provides a reference point for clinicians who may want to provide hens with local analgesia for certain procedures.\n\nIn summary, the ethogram used to measure behaviour, demonstrated a significant increase in stress-related behaviours when used during the plucking of feathers from hens’ thighs compared with the benign ‘dummy handling‘session. EMLA cream did significantly reduce the ethogram scores when plucking treated hens, with no adverse effects on hen behaviour during the incubation period.\n\nApplication of EMLA cream is an easy, non-invasive method to use and its incorporation in experimental procedures should be encouraged, though effects on other measurements, such as mite feeding on the treated area need to be considered.",
"appendix": "Data availability\n\nFigshare: Measuring behaviour in hens using an ethogram to assess analgesia during further refinement of a high welfare, on-hen, poultry red mite feeding device. https://doi.org/10.6084/m9.figshare.22183009 (Nunn, 2023).\n\nThis project contains the following underlying data:\n\n• Feeding and mortality data_DE.xlsx (raw feeding, mortality and fecundity data collected at timepoints.)\n\n• Obj 2 18week Data for Power Calcs.xlsx (feeding data from previous trial use to perfom power calculations for hens of a same age for this trial)\n\n• PowerCalculationsNewProject_Feb2021.pdf (power calculation reports)\n\n• raw ethogram scores FINAL docx.docx (raw data collected from trial)\n\n• Raw Respiration rates.docx.docx (raw data collected from trial)\n\n• Supp. File 1 (ethogram).docx (ethogram table listing behaviours)\n\nFigshare: ARRIVE checklist for ‘Measuring behaviour in hens using an ethogram to assess analgesia during further refinement of a high welfare, on-hen, poultry red mite feeding device’. https://doi.org/10.6084/m9.figshare.22183009 (Nunn, 2023).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nWe thank the Bioservices Group at Moredun Research Institute for their ongoing help and expertise and to Sarah Brocklehurst of Biomathematics & Statistics Scotland for her work reviewing the manuscript.\n\n\nReferences\n\nBartley K, Turnbull F, Wright HW, et al.: Field evaluation of poultry red mite (Dermanyssus gallinae) native and recombinant prototype vaccines. Vet. Parasitol. 2017; 244: 25–34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBates D, Mächler M, Bolker B, et al.: Fitting Linear Mixed-Effects Models Using lme4. J. Stat. Softw. 2015; 67(1): 1–48.\n\nBedford E: Domestic fowl population in the United Kingdom (UK) 2010-2022.Reference Source\n\nBright A: Vocalisations and acoustic parameters of flock noise from feather pecking and non-feather pecking laying flocks. Br. Poult. Sci. 2008; 49: 241–249. PubMed Abstract | Publisher Full Text\n\nBrooks ME, Kristensen K, van Benthem KJ , et al.: glmmTMB Balances Speed and Flexibility Among Packages for Zero-inflated Generalized Linear Mixed Modeling. The R Journal. 2017; 9(2): 378–400. Publisher Full Text Reference Source\n\nFirth D: Bias Reduction of Maximum Likelihood Estimates. Biometrika. 1993; 80: 27–38. Publisher Full Text\n\nFlecknell PA, Liles JH, Williamson HA: The use of lignocaine-prilocaine local anaesthetic cream for pain-free venepuncture in laboratory animals. Lab. Anim. 1990; Apr; 24(2): 142–146. PubMed Abstract | Publisher Full Text\n\nFlecknell PA: Refinement of animal use--assessment and alleviation of pain and distress. Lab. Anim. 1994; Jul; 28(3): 222–231. PubMed Abstract | Publisher Full Text\n\nFox J, Weisberg S: An R Companion to Applied Regression. Third ed.Thousand Oaks CA: Sage; 2019. Reference Source\n\nGentle MJ, Hunter LN: Physiological and behavioural responses associated with feather removal in Gallus gallus var domesticus. Res. Vet. Sci. 1991; Jan; 50(1): 95–101. PubMed Abstract | Publisher Full Text\n\nHocking PM, Gentle MJ, Bernard L, et al.: Evaluation of a protocol for determining the effectiveness of pretreatment with local analgesics for reducing experimentally induced articular pain in domestic fowl. Res. Vet. Sci. 1997; 63: 263–267. PubMed Abstract | Publisher Full Text\n\nKeating SC, Thomas AA, Flecknell PA, et al.: Evaluation of EMLA cream for preventing pain during tattooing of rabbits: changes in physiological, behavioural and facial expression responses. PLoS One. 2012; 7(9): e44437. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKosmidis I: brglm: Bias Reduction in Binary-Response Generalized Linear Models. R package version 0.7.2.2021. Reference Source\n\nLenth RV: emmeans: Estimated Marginal Means, aka Least-Squares Means. R package version 1.7.3.2022. Reference Source\n\nLima-Barbero JF, Contreras M, Mateos-Hernández L, et al.: A vaccinology Approach to the Identification and Characterization of Dermanyssus Gallinae Candidate Protective Antigens for the Control of Poultry Red Mite Infestations. Vaccines (Basel). 2019a Nov 20; 7(4): 190. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLima-Barbero JF, Contreras M, Bartley K, et al.: Reduction in Oviposition of Poultry Red Mite (Dermanyssus gallinae) in Hens Vaccinated with Recombinant Akirin. Vaccines (Basel). 2019b; Sep 19; 7(3): 121. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMachin KL: Avian Analgesia, Seminars in Avian and Exotic Pet Medicine.2005; Volume 14(4): Pages 236–242.1055-937X.\n\nMul MF, van Riel JW , Meerburg BG, et al.: Validation of an automated mite counter for Dermanyssus gallinae in experimental laying hen cages. Exp. Appl. Acarol. 2015 Aug; 66(4): 589–603. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNunn F, Bartley K, Palarea-Albaladejo J, et al.: Nisbet.AJ.A novel, high-welfare methodology for evaluating poultry red mite interventions in vivo. Vet. Parasitol. 2019; 267: 42–46. PubMed Abstract | Publisher Full Text\n\nNunn F, Bartley K, Palarea-Albaladejo J, et al.: The evaluation of feeding, mortality and oviposition of poultry red mite (Dermanyssus gallinae) on aging hens using a high welfare on-hen feeding device. F1000Res. 2020; Oct 22; 9: 1266. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNunn F: Measuring behaviour in hens using an ethogram to assess analgesia during further refinement of a high welfare, on-hen, poultry red mite feeding device. [Dataset]. figshare. 2023. Publisher Full Text\n\nPercie du Sert N, Hurst V, Ahluwalia A, et al.: The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020; Jul 14; 18(7). Publisher Full Text\n\nPrice DRG, Küster T, Øivind Øines E, et al.: Evaluation of vaccine delivery systems for inducing long-lived antibody responses to Dermanyssus gallinae antigen in laying hens. Avian Pathol. 2019; Sep; 48(sup1): S60–S74. PubMed Abstract | Publisher Full Text\n\nR Core Team: R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2022. Reference Source\n\nSigognault Flochlay A, Thomas E, Sparagano O: Poultry red mite (Dermanyssus gallinae) infestation: a broad impact parasitological disease that still remains a significant challenge for the egg-laying industry in Europe. Parasit. Vectors. 2017; 10: 357. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSmith CF, Gavaghan BJ, McSweeney D, et al.: Comparison of the measurement of heart rate in adult free-range chickens (Gallus domesticus) by auscultation and electrocardiography. Aust. Vet. J. 2014; Dec; 92(12): 509–511. PubMed Abstract | Publisher Full Text\n\nU.K. Government Home Office: Annual statistics of scientific procedures on living animals. Great Britain. 2022; 2022. Reference Source\n\n\nFootnotes\n\n1 On ‘treatment day’ an error reading leg rings meant that two birds had to be reassigned experimental groups. As the birds had already been kept in their groups for over a week, the decision was made to keep them in the same pen hence the uneven distribution of experimental groups in the last pen."
}
|
[
{
"id": "196063",
"date": "22 Jan 2024",
"name": "Jan Perner",
"expertise": [
"Reviewer Expertise Molecular Biology of ticks and mites."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe aim of the study by Nunn et al. is to evaluate an ethogram as a proxy for discomfort/distress/pain in hens during procedures, such as feather plucking (for example, before on-animal poultry red mite feeding assays), and to evaluate whether the application of a commercially available short-term local anaesthesia cream EMLA provides any observable relief from pain/distress during routine experimental procedures. Additionally, poultry red mite feeding assays were performed, and the effects of the anaesthesia cream on mite feeding rates, mite mortality, and mite fertility were evaluated.\nIn general, the study is interesting and all the conclusions are supported by the presented results.\nSuggestions for improvement of the research article:\nAbstract, the methods section:\nThe description of the three days, when hens’ behaviours were measured, is rather confusing. It is clearly described only later in the text and Table 1. Please consider increasing clarity.\n\nI recommend replacing 'in the same group' with 'in the EMLA group' to improve understanding.\n\nIntroduction:\nI miss a mention of an artificial membrane feeding system for D.gallinae mites, which is suitable, at least for screening and initial testing of acaricides, and represents a possibility for a partial replacement of experimental animals.\n\nResults:\nBodily resistance has zero observations across groups. Possibly consider removing this criterion. The applied statistics also skews slightly the first-hand impression, where not every zero is plotted equally.\n\nDiscussion:\nEven though it was not the purpose of this study, I would appreciate if there were more comments on Figure 3 in the discussion. What is the explanation for lower rates in the first feeding of EMLA(Lidocaine and Prilocaine)-treated group? Is it a common observation that feeding rates decline during subsequent feedings (applies for the 'placebo' and 'none' groups). Strikingly, the Aqueous Cream B.P. seems to significantly enhance the third feeding, despite being neglected both in results and discussion. Possibly rectify this overlook if you think it deserves attention. Can this be attributed to enhanced skin physicality?\n\nRaw ethogram scores are difficult to read as there is no indication of the belonging of particular hens to individual experimental groups. I suggest changing the row order according to experimental groups rather than according to the number on the hens’ label. Furthermore, this table could be moved to supplementary data.\n\nTitle:\nThe title implicates a combination of ethogram and D. gallinae feeding. While the authors define well the former, and then describe the latter, ie the D. gallinae feeding as a function of feeding repetition and +/- analgetics or lotion application, the application of ethogram on the variances of D. gallinae feeding is a sad miss in this work.\n\nAre a suitable application and appropriate end-users identified? Yes\n\nAre the 3Rs implications of the work described accurately? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "205055",
"date": "08 Apr 2024",
"name": "Mike J. McGrew",
"expertise": [
"Reviewer Expertise Genetic modification"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article by Nunn et al. addressing the reduction pain after feather plucking is an interesting, well written article that address an important welfare question. The authors design an ethogram to examine behaviour after feather plucking. Breathing rates were monitored and the effect of the analgesic on red mite feeding rates and fertility rates were measured.\nThe authors find that using analgesic cream reduced the probability of observing a pain related behaviour after plucking a 3 cm area on the leg.\nMy comment is that the plucking/analgesic analysis is focused on red mite and may have broader experimental uses for birds. Feather plucking is also used as a method to obtain feather pulp which is cultured in vitro to obtain fibroblasts from adult birds of many species (Kjelland and Kraemer, 20121). The results here indicate that an analgesic cream would be useful in reducing indications of pain after feather plucking. My question is if the cream can be delivered after the procedure to alleviate pain related behaviour would mean the bird needs to be handled twice which might increase bird distress, i.e. the cream needs to be delivered before plucking, and the manufacturer states that the cream be placed under a dressing. Perhaps the authors could further comment on the other uses of feather plucking in the discussion.\nSpecific comment:\nI am confused by the Methods section, page 6 (PDF version) and the conditions that occurred on the plucking day, right leg (day 6) and on the treatment day, left leg (day 7). From the Methods’ text, it appears no analgesic was used on day 6, analgesic was only used on day 7 for the right leg. Yet in Figure 2, there are three conditions listed for the plucking group (day 6): none, EMLA, placebo as well as three conditions for the treatment group (day 7): none, EMLA, placebo. How is this possible?\n\nAre a suitable application and appropriate end-users identified? Yes\n\nAre the 3Rs implications of the work described accurately? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-715
|
https://f1000research.com/articles/10-1135/v1
|
10 Nov 21
|
{
"type": "Systematic Review",
"title": "The Ideal Diet for Humans to Sustainably Feed The Growing Population – Review, Meta-Analyses, and Policies for Change",
"authors": [
"Galit Goldfarb",
"Yaron Sela",
"Yaron Sela"
],
"abstract": "INTRODUCTION:\n\nAs of now, no study has combined research from different sciences to determine the most suitable diet for humans. This issue is urgent due to the predicted population growth, the effect of this on the environment, and the deterioration of human health and associated costs.\nMETHODS:\n\nA literature review determined whether an optimal diet for humans exists and what such a diet is, followed by six meta-analyses. The standard criteria for conducting meta-analyses of observational studies were followed. A review of literature reporting Hazard Ratios with a 95% confidence interval for red meat intake, dairy intake, plant-based diet, fiber intake, and serum IGF-1 levels were extracted to calculate effect sizes.\nRESULTS:\n\nResults calculated using NCSS software show that high meat consumption increases mortality probability by 18% on average and increases diabetes risk by 50%. Plant-based and high-fiber diets decrease mortality by 15% and 20% respectively (p < .001). Plant-based diets decreased diabetes risk by 27%, and dairy consumption (measured by increased IGF-1 levels) increased cancer probability by 48% (p < 0.01). A vegetarian or Mediterranean diet was not found to decrease the probability of heart disease. A vegetarian diet can be healthy or not, depending on the foods consumed. A Mediterranean diet with high quantities of meat and dairy products will not produce the health effects desired. The main limitations of the study were that observational studies were heterogeneous and limited by potential confounders.\nDISCUSSION:\n\nThe literature and meta-analyses point to an optimal diet for humans that has followed our species from the beginnings of humankind. The optimal diet is a whole food, high fiber, low-fat, 90+% plant-based diet. This diet allowed humans to become the most developed species on Earth.\nTo ensure people’s nutritional needs are met healthily and sustainably, governmental dietary interventions are necessary.",
"keywords": [
"Optimal nutrition",
"optimal diet",
"diet for health",
"early human diet",
"human evolution and diet",
"nutrition",
"nutrition and disease",
"diet for health",
"nutrition for health"
],
"content": "Introduction\n\nAs of now, there has not been a study that combines research from all of the available sciences to conclude what is the most suitable diet for humans that can heal and also prevent chronic disease and at the same time be sustainable for the environment. It is essential to address this issue urgently due to the predicted growing human population, increasing healthcare costs, and lessening agricultural land to grow foods due to global warming.\n\nThis research aims to determine whether there is one ideal diet for all humans. And if so, to examine how individuals and governments can use this knowledge to create policies that ensure the growing global population is fed healthily and sustainably without causing further environmental destruction.\n\nResearch shows that 95% of the global population is living in poor health.1–3 The obesity epidemic has led to higher incidences of noncommunicable diseases (NCDs) including heart disease, type 2 diabetes, and specific cancers.4–9\n\nCurrently, individuals are confused as to what diet is ideal for promoting health and longevity.\n\nIndividuals need to have a set standard for healthy food based on human needs, to enable them to improve health and require less healthcare in the future.\n\nAn extensive literature review combining data from different scientific fields helped determine underlying factors relating to the ideal diet for humans. A look at human evolutionary research was necessary for a thorough approach to this subject.\n\nThe literature review points to a major change within the hominin lineage (Australopithecus) occurring about 5 million years ago with the evolution of bipedalism.\n\nThis locomotive change came to hominin benefit about 2 million years ago, following a global change in weather conditions when the earth entered the Ice Age.\n\nThe North African tropical rain forest began receding and the savanna grasslands expanded. Bipedalism gave hominins the ability to leave the shrinking rainforest where food resources were dwindling as a result of the ice age, for the growing savannas.10 Skull fossils show that hominins living in the rainforest had a brain size of 320-380 cm3 in volume.11–13\n\nUpon moving to the savanna grasslands, hominins needed to change dietary practices to survive. Herbaceous leaves that were plentiful in the rain forests were sparse on the savanna, forcing hominins to start feeding on other foods. Dental microwear and stable isotope analysis show evidence of C4 resources, mainly underground storage organs (USOs) (tubers, roots, and bulbs), as a significant component of hominin diets on the savanna.14–22\n\nThe next hominin fossils found of the genus Homo, Homo habilis, demonstrate a steady process of brain growth to 400-600 cc.\n\nThe dry savanna habitat was also rich in sedge and grass grains, rich in carbohydrates, perfect to nutritionally support hominin brain growth.20–28\n\nA larger brain requires more energy to fuel. It is a metabolically expensive organ, and therefore requires a stable, high-energy, nutrient-dense food source to support its growth under natural selection.16,20,29\n\nFossils of the next ancestor of the genus Homo, Homo ergaster, who lived exclusively on the savanna, show a brain size 50% larger than their predecessor Homo habilis (800–1200 cc).30,31 The larger more advanced brain allowed Homo ergaster to thrive in the hostile savanna environment. Homo ergaster had a jaw and tooth size closely resembling that of modern humans, and fossils show that their digestive tracts grew smaller.\n\nDue to the vast number of animals on the savanna, it would seem obvious to suggest that the change in diet was towards a meat-based diet, however, to be dependent on meat as a stable food source on the savanna, hominins would have needed to hunt big game that roamed the savanna. To hunt successfully, hominins would have needed to master the skills of hunting. Research suggests that hunting skills have a very long learning curve.32–34\n\nEvidence also suggests that big game roaming the savanna were a poor food source for hominins. Their meat was lean, with almost no fat, and the protein levels were too high to consume in abundance, rendering them an inefficient source of calories.\n\nDietary protein, when consumed in excess, becomes toxic to the human body. Humans can metabolize about 250 grams of protein per day; exceeding this level produces toxic waste that the body has difficulty eliminating. Furthermore, some of the protein consumed is required for cellular growth and repair and would not be available for energy. In fact, 250g of protein provides only 1000 calories, not nearly enough to sustain a modern-day sedentary adult, let alone an active hunter-gatherer on the harsh African savanna. It is well documented that those who consume excessive amounts of lean protein, without sufficient fat, develop a condition called “mal de caribou,”35 whereby ammonia builds up in the blood. If this diet persists, the person will suffer from diarrhea and mineral losses and will eventually die.36–39\n\nResearch shows that modern hunter-gatherer groups such as the Hadza and San, with modern sized brains, fail to catch meat on 97% of their hunts, and share the meat mainly with their co-hunters. Furthermore, hunting is usually practiced when staple foods are available in abundance.40–46 It is suggested that hunting occurred primarily for rituals and shows of courage rather than solely for dietary necessity.46–48\n\nIn 1993, more than 1,000 researchers participated in a study titled The Lost Crops of Africa, examining ancient crops of Africa. The report comes to a clear conclusion: “Grass seeds have sustained humans throughout time.”49,50\n\nIn 1984, anthropologists found the nearly complete skeleton of a Homo ergaster child assumed to be 1.7 million years old. The skeleton, referred to as Nariokotome Boy,51,52 had a brain size of 880 cm3 in volume. In the fossil remains we see evidence from the shape of the ribcage, that at this stage, hominin gut size shrunk to the size of a modern human gut. This shrinkage of gut size allowed the available energy to be directed to feed the growing brain.\n\nThe brain is an incredibly energy expensive organ using 22% of human basal metabolic energy. To accommodate the increase in brain size, humanity’s forebears needed a good, high-quality, readily available food source.53\n\nSuch food sources grew readily all year round on the savanna and include legumes, grains, plants with USOs, seeds and fruits.54–76\n\nThe switch to starchy foods, very different from the dietary habits in the rainforests, allowed early humans to thrive on the savanna with shorter guts which required less energy to maintain. The excess energy became available for brain tissue growth77 because hominin survival depended on intelligence.\n\nEnzyme inhibitors in plants stop enzymatic reactions. As a result, enzyme inhibitors can have an anti-nutritional effect.77–79\n\nCooking deactivates these anti-nutrients. But when cooking was still unavailable, anti-nutrients could easily be deactivated by a simple soaking in water61,79,80 causing enzyme inhibitors to stop functioning. Also, an adapted gut microbiota helps the breakdown of such starches.79 Furthermore, young grass grains do not have enzyme inhibitors.\n\nThe probable low bio-accessibility of nutrients from legumes and grains is less relevant due to the wealth of legumes, grains and tubers available on the savanna.79–83\n\nUSOs, by contrast, have a physical defense mechanism by being located underground or covered in thick outer layer. USO-bearing plants are edible in raw form.74\n\nFossil dental calculus, accepted as a significant pool of dietary data, show that Neanderthals 400,000 years ago ate a wide variety of plant matter especially USOs and grass seeds. Neither geographic region, species, nor known stone tool technology had a significant impact on the number of plant species consumed.84 Fossilized Neanderthal feces was also found to have large amounts of plant matter.85 Other research has also revealed that plant foods had a leading role in early human diets.84,86–91 In later fossils, evidence of damaged grass seeds in dental calculus are a sign of cooking.84,92–94\n\nThe control of fire by hominins began sometime between 400,000-700,000 years ago. At this time, another major brain growth spurt in hominin fossils is observed (from 800 cm3 to 1,100 cm3 in volume).86,95–100 Fire enabled a reduction in the need for chewing and detoxification of anti-nutrients, making more energy and nutrients available for the brain and the body.101,102\n\nApproximately 195,000 (±100,000) years ago evidence shows that the first Homo sapiens (modern humans) appeared and replaced other Homo species in Africa. Omo, the oldest fossil remains of modern humans, show that they had the same anatomical build as we have today.103,104\n\n12,000 years ago, agriculture began at the geographic corridor through which humans left Africa. The first foods chosen to be grown through agriculture were grains, emphasizing their significance for humans during the hunting-gathering period.\n\nGrains and legumes were easily domesticated from their wild ancestors because they required very little genetic change to domesticate.105\n\nAnimals were domesticated 6000 years ago only in a few areas on earth, principally in Asia, and Europe. Animals were rarely domesticated in America. Animals were not domesticated in tropical Africa or Australia.106–108 This lack of domestication is probably due to the abundance and variety of grains, legumes and USOs found in these places, reducing the need to domesticate animals for food.\n\nThe domestication of animals for food resulted in increased meat consumption beyond previous consumption patterns of hunter-gatherers who ate meat sparsely when available.109–112\n\nHuman brain size decreased after the dawn of agriculture.112,113\n\nPrevious to agriculture, life expectancy was past the age of menopause in women. When agriculture was introduced, life expectancy dropped to 40 years because human eating habits changed dramatically.112,114 Only certain crops were grown, exposing farmers to many risks and leading people to suffer from severe nutrient deficiencies, shortening lifespans.105,112,115–117\n\nAfter the industrial revolution, life expectancy increased, but quality of life did not necessarily follow suit.118–124\n\nThe awe for meat and processed grain consumption increased with the industrial revolution when food processing became popular for storage and transport. Grains that could originally supply a wealth of nutrients, were stripped of their healthy bran and germ layers becoming nutritionally deplete. This move to processed grains caused large populations to develop nutrient deficiencies including protein deficiency which led to the discovery of a disease named Kwashiorkor. Kwashiorkor was caused by consumption of nutrient and protein depleted dried grains that were ground into flour for children as food. Kwashiorkor sometimes healed with animal protein consumption.125,126\n\nHowever, nutrient and protein shortage were never a problem for humans until grain processing began.127–130\n\nA whole-food, mostly plant-based diet, from varied plant sources, as ancient humans consumed, easily incorporates all of the nine essential amino acids for humans.\n\nProtein content in human breast milk is lowest in comparison with other lactating mammals and is higher in carbohydrates, and mono- and polyunsaturated fats.131,132\n\nThis suggests that although protein is necessary for human health, consuming large quantities of protein carries a considerable price on human health.\n\nIn recent decades, the world has seen a rise in NCDs such as heart disease, cancer, and diabetes. Seven out of every ten deaths are due to NCDs.133\n\nNowadays domesticated animals are rich in fat. The fatty deposits among muscle fibers soften the cooked meat and improve their flavor.\n\nThe fat composition of domesticated meat has also changed over time. Previously, animal fat had equal amounts of ω-6 and ω-3 fatty acids (FAs). Nowadays animal fat is rich in inflammatory ω-6 FAs and low in health promoting ω-3 FAs because of the intensive rearing methods.134,135 The levels of ω-3 FAs in meats 100 years ago were 170 mg/100 g of meat. Now they are 20 mg/100 g of meat.134,136\n\nAnimal milk is also less suitable for human consumption. Milking animals only began around 6000 years ago.137\n\nMost of the current world population (75%) is lactose intolerant, leading to side effects such as mineral losses, diarrhea, cramping, bloating, and gas.\n\nIt is also common for only about 25% of dairy calcium from milk to be absorbed. The remaining unabsorbed 75% may end up deposited around the body, leading to atherosclerosis, gout and kidney stones.\n\n\nMethods\n\nA will to bring to the table valid results that prove the literature review formed the reasoning behind the following meta-analyses, since meta-analysis is considered by many to be the platinum standard of evidence.\n\nA look at mortality statistics for people following different diets as well as a look at different dietary patterns and the most common diseases in the world today (cancer, heart disease and diabetes, were examined through a collection of studies performed in the last decade only. The results were calculated using NCSS 2019 software available for free at: https://www.ncss.com/download/ncss/free-trial/. Furthermore, other meta-analyses that were performed in this time period were used as a comparison between results received with the meta-analysis results received in this research.\n\nThe standard criteria for conducting and reporting of meta-analyses of observational studies was followed (Stroup et al, 2000). Studies were identified through a systematic review of the literature by using the PubMed and Google Scholar databases against a list of pre-defined comprehensive search terms on 17 March 2019 and updated on 28 March 2019 to search for more recent papers. Searches were run independently in each database because of their different set-ups, different thesaurus terms such as Medical Subject Headings (MeSH), and other relevant subject heading searching, and keywords. Exclusion criteria were (a) reviews, protocols, conference abstracts, practice guidelines, opinions, discussion pieces, editorials, commentaries, book chapters, and case reviews. (b) No limits were applied for language and foreign papers were translated (c) publication dates before December 2008, and after December 2018, except meta-analyses which were accepted.\n\nSeven different meta-analyses combining the results of multiple studies were performed to support the argument that this ideal diet for humans can prove itself as the optimal diet also in our day and age. Each meta-analysis had its own hypothesis. The probability factor (p = value) was calculated to see if the null hypothesis was rejected or not. If the probability was small (less than 5% or less than 1 in 20 chance of being wrong), then the null hypothesis was rejected, and I could safely conclude that there was a connection between the independent explanatory variable and the dependent variable.\n\nThe search terms used for all studies included keywords, and subject headings, for example “meat,” “beef,” “red meat”, processed meat”, “unprocessed red meat”, “pork,” “veal,” “lamb,” “steak,” “hamburger,” “ham,” “bacon,” or “sausage,” “IGF-1,” “dairy,” “milk,” “Plant-based,” “vegan,” “vegetarian,” “fiber,” “Mediterranean diet,” “healthy diet” in combination with “mortality,” or “death”, or “heart disease,” or “diabetes,” or “cancer.” In addition, the reference lists of relevant publications were also searched for more studies. The search is archived at: https://doi.org/10.17605/OSF.IO/64NAM.\n\nPapers were selected if they met the followed inclusion criteria (a) Prospective studies performed only in the last ten years, between December 2008 and December 2018 (as required by OUS university), (b) studies that reported relative risks and Hazard Ratios with 95% confidence intervals for the associations of unprocessed red meat, processed meat, total red meat consumption, dairy, high fiber, plant-based, vegan, vegetarian, with all-cause mortality, diabetes, cancer and heart disease. (c) Meta-analyses that were performed in the last ten years but included also studies performed from beforehand, were added to each meta-analysis performed for every subject so that the aggregated HR derived from the analysis could be compared and thus, the results would have a more holistic nature.\n\nThe search strategy retrieved 91 articles. After removing the duplicates, the title/abstract screening process identified 88 studies. After a further full-text assessment for sufficient statistics, 44 articles were excluded from the systematic review and 37 met the inclusion criteria for all studies, (please see search strategy in data availability section). No additional publications were found through reference lists and hand searching.\n\nFrom each publication, the first author's last name, year of publication, study location, gender, age, sample size (total number of participants and number of deaths or disease), relative risks and Hazard Ratios with a 95% confidence interval for each category of red meat intake, dairy intake, plant-based diet, fiber intake, serum IGF-1 levels, and covariates adjusted for in the analysis were extracted.\n\nThe primary goal of meta-analysis was to compute the aggregative effect of specific food group consumption on mortality/disease, taking into consideration standalone and heterogeneous results. In order to examine the aggregate effect size, individual studies were gathered estimating mortality of people consuming a specific food group (e.g. red meat/high-fiber/plant-based), in comparison with people who do not consume this specific food group. Each individual study calculated Hazard Ratio (HR), the event rate corresponding to the conditions (dead/alive; disease/no disease) described by two levels of an explanatory variable (red meat vs. no red meat; vegetarian vs. non-vegetarian; high fiber vs. low fiber).\n\nThe main function of the meta-analysis was to estimate effects in the population by combining the effect sizes from a variety of studies. Specifically, the estimate is a weighted mean of the effect sizes. The ‘weight’ that is used is usually a value reflecting the sampling accuracy of the effect size, which is typically a function of sample size. The final goal of the meta-analysis was to determine the aggregative effect size beyond all effects that were gathered, its significance, 95% confidence interval and possible moderators for the results (variables that could explain non-random variance between effects).\n\nFor the final effect, the HR as effect-size estimate; a confidence interval (lower limit [LL] and upper limit [UL]); Q statistic; and its p value were reported. Q, a chi-square statistic, reflects variability among effect estimates due to true heterogeneity, rather than sampling error. The null hypothesis is that all studies used to calculate each effect, shared the same effect size. Under the null hypothesis, Q should follow a central chi square distribution with degrees of freedom equal to k − 1. When the p value is less than 0.05, the null hypothesis is rejected, and it can be concluded that there is true variance in the studies' common effect size.139\n\nThe random-effects model which assumes that variance between effects is basically random, was applied, and therefore any variance was not attributed to specific moderators. Forest plots, which depicts the effects on a single figure, and also the aggregated effect and its confidence interval, were produced.\n\nSeven separate meta-analysis were performed:\n\n• Meat consumption and mortality\n\n• Plant-based nutrition and mortality\n\n• High fiber diet and mortality\n\n• Plant-based nutrition and diabetes\n\n• Vegetarian/Mediterranean diet and heart disease\n\n• IGF-1 in dairy products and cancer\n\n• Meat consumption and diabetes\n\nThe results were calculated using NCSS 2019 software which has a statistical package for calculating aggregated hazard ratio (HR). The input included individual HR from each study, variance for each HR (calculated as SE2, and SE (standard error that was calculated manually using CI with the following calculation:\n\nOutputs included the following figures:\n\n1. A forest plot which shows individual HR and its CI, in addition to aggregated HR and CI.\n\n2. A radial plot which shows the study bias for aggregated HR according to heterogeneity.\n\nThe results are as follows:\n\n1. Meat Consumption and Mortality\n\nTo assess aggregative Hazard Ratio (HR) of meat consumption and mortality, two individual studies were used yielding three effect sizes (see Table 1).\n\nResults of meta-analysis (n = 666,995) showed that the aggregated effect size between meat consumption and mortality is HR = 1.18 (HR S.E. = 0.03, 95% CI [1.12,1.24]) (see Figure 1). This result is significant χ2 (DF = 2) = 3737.16, p < 0.001 and means that people consuming meat at any time point during the study period were 18% more likely to die than people that were not consuming meat, and we are 95% confident that people consuming meat are between 12% and 24% more likely to die at any given age than people not consuming meat.\n\nNo heterogeneity was found between studies, meaning there are no potential moderators which could bias this effect, Q (2) = 3.80, p = 0.09. Hence, differences between individual studies are not significant and considered as homogeneous (see Figure 2, all studies are within the CI borders).\n\nTo conclude, consuming red meat significantly increases death probability by about 20% on average in comparison with not consuming red meat. This effect size is larger compared with effect size received by Wang et al.142 (HR = 1.15). In addition, it is important to note that in a similar meta-analysis conducted by Larsson and Orsini,143 no significant consistent effect was found between meat consumption and mortality.\n\n2. Plant-Based Nutrition and Mortality\n\nTo assess aggregative Hazard Ratio (HR) of plant-based nutrition and mortality, four individual studies were used yielding four effect sizes (see Table 2).\n\nResults of the meta-analysis (n = 218,712 people) showed that the aggregated effect size between plant-based nutrition and mortality is HR = 0.85 (HR S.E. = 0.04, 95% CI [0.77,0.94]) (see Figure 3). This result is significant χ2 (4) = 3497.7, p < 0.001 and means that people consuming a plant-based diet at any time point during the study periods were 15% less likely to die than people that were not consuming a plant-based diet, and we are 95% confident that the true value is lying between 6%-23% (we are 95% sure that people consuming a plant-based diet are between 6% and 23% less likely to die at any period of time than people not consuming a plant-based diet).\n\nA significant heterogeneity was found between studies, meaning that the studies included in this analysis were different by several methodological aspects which could bias the aggregated HR effect, Q (3) = 20.70, p < 0.01. Differences between individual studies are significant and considered heterogeneous (see Figure 4, result of 4 - Kim, Caulfield, & Rebholz,147 exceeds CI borders), in this study among Seventh-day Adventists, vegetarians were healthier than non-vegetarians but this cannot be ascribed only to the absence of meat.\n\nTo conclude, plant-based nutrition significantly decreases death probability by about 15% on average, in comparison with non-plant-based nutrition.\n\n3. High Fiber Diet and Mortality\n\nTo assess aggregative Hazard Ratio (HR) of a high fiber diet and mortality, six individual studies were used yielding six effect sizes. In addition, two meta-analyses were gathered in order to compare aggregated HR derived from our analysis. These meta-analyses were documented in order to compare results between independent meta-analysis and published meta-analyses (see Table 3).\n\nResults of meta-analysis (n = 978,380) showed that the aggregated effect size between fiber diet and mortality is HR = 0.80 (HR S.E. = 0.03, 95% CI [0.74,0.86]). See Figure 5). This result is significant χ2 (5) = 8155.70, p < 0.001. and means that people consuming a high fiber diet at any time point during the study period were 20% less likely to die than people that were not consuming a high fiber diet, and we are 95% confident that the true value is lying between 14%-26% (we are 95% sure that people not consuming meat are between 14% and 26% less likely to die at a given age than people consuming a high fiber diet).\n\nA significant heterogeneity was found between studies, meaning that the studies included in this analysis are different by several methodological aspects which could bias the aggregated effect, Q (5) = 21.44, p < 0.01. Hence, differences between individual studies are significant and considered heterogeneous (see Figure 6, result of 3. Dominguez et al.,150 exceeds CI borders).\n\nTo conclude, a high fiber diet significantly decreases death probability by about 20% on average, in comparison with non-fiber diet. This effect size is in line with effect size received by Yang et al.155 (HR = 0.84), and by Kim & Je154 (HR = 0.77).\n\n4. Plant-Based Nutrition and Diabetes\n\nTo assess aggregative effect size of plant-based nutrition and diabetes, three individual studies were used yielding three effect sizes. These effects were based on random control trial designs in which individuals in a diet group were compared to individuals in a control group. These designs yielded effect size of difference between means. In addition, a single meta-analysis was found which computed Hazard Ratio between plant-based nutrition and diabetes (see Table 4).\n\nResults of meta-analysis (n = 133) showed that the aggregated effect size between plant-based nutrition and diabetes is Cohen’s d = −0.17 (S.E. = 0.06, 95% CI [−0.30, −0.03]) (see Figure 7). When translated to HR = 0.73 (95% CI [0.58, 0.94]. This result is significant χ2 (2) = 6.24, p < 0.05 and means that people consuming a plant-based diet at the end of the trial (dietary change to PBD) showed 27% improvement in their diabetic status.\n\nNo heterogeneity was found between studies, meaning there are no potential moderators which could bias this effect, Q (2) = 1.06, p = 0.50. Hence, differences between individual studies are not significant and considered as homogeneous (see Figure 8, all studies are within the CI borders).\n\nTo conclude, individuals who keep plant-based have decreased risk of diabetes in comparison with individuals who do not keep this type of diet. This result is stronger in when translated to HR = 0.73, in comparison with effect size for of 0.51.159\n\n5. Vegetarian or Mediterranean Diet and Heart Disease\n\nTo assess aggregative Hazard Ratio (HR) of Healthy diet and heart disease, two individual studies were used yielding two effect sizes. In addition, a single meta-analysis examining this effect was found (see Table 5).\n\nResults of meta-analysis (n = 19,580) showed that the aggregated effect size between vegetarian or Mediterranean diet and heart disease is HR = 0.86 (HR S.E. = 0.10, 95% CI [0.67,1.06]) (see Figure 9). This result is not significant χ2 (1) = 25.10, p = 0.413.\n\nThese effects were homogenous between two studies, meaning, studies included in this analysis were not different by methodological aspects which could bias the aggregated effect, Q (1) = 3.34, p = 0.07 (see Figure 10).\n\nTo conclude, a vegetarian or Mediterranean diet was not found to decrease probability for heart disease. Although non-significant, effect size found in this meta-analysis is similar to effect size received by Kwok et al.162 (HR = 0.84). They come to the conclusion that there is modest cardiovascular benefit, but no clear reduction in overall mortality associated with a vegetarian diet.\n\nA vegetarian diet can be healthy or not, depending on the foods consumed in this diet. A vegetarian diet that is rich in processed foods, or a Mediterranean diet that has high quantities of meat and dairy products will not produce the health effects desired. Furthermore, only two studies were found that met all the criteria for inclusion.\n\n6. IGF-1 and Cancer\n\nInsulin-like growth factor 1 (IGF-1) is a protein produced in the liver, encoded by the IGF-1 gene which stimulates growth in cells throughout the body. Protein intake increases IGF-1 levels in humans under age 65, independent of total calorie consumption.\n\nIGF-1 has a role in regulating lifespan by controlling longevity in mammals and resisting oxidative stress, a known determinant of aging. IGF-1 also plays a role in assisting growth hormones in their anabolic function. It plays several roles in human physiology including tissue growth and development, especially at a young age where it promotes growth in children and ensures that they grow tall.163 IGF-1 is also found in breast milk.\n\nResearch shows that IGF-1 continues to have anabolic effects as the person gets older where increased levels of IGF-1 seem to have several adverse effects on health, as people reach adulthood and age.\n\nStudies have implicated IGF-1 with a few forms of cancer including colon, pancreas, endometrium, prostate, breast, lung, and colorectal cancer,164-174 as IGF-1 exerts strong mitogenic actions and triggers a signaling cascade leading to increased proliferation and differentiation of cells and has an anti-apoptotic effect. Certain drug companies are working on medications that reduce the level of IGF-1 in a means to protect from cancer.175 However, there is no definitive association between IGF-1 and cancer in the Japanese population.183,184 This may be due to the fact that IGF-1 which can also be attained through the diet, is not found in foods regularly consumed as part of the Japanese diet. When examining dairy products and the Japanese population, we will see the same results as with the rest of the population.185\n\nEpidemiological evidence shows that dairy food consumption significantly increases circulating IGF-1 levels, and dairy consumption after the weaning period maintains high levels of IGF-1 signaling.176-181 A study showed that when insulin-like growth factor-1 is taken in through the diet, further to the added exogenous dose of IGF-1 in the body, there is also increased stimulation of IGF-1 production in the body,182 which promotes the proliferation of certain cancers.\n\nTo assess the aggregative Hazard Ratio (HR) of dairy products (IGF-1) and cancer, thirteen individual studies were used yielding thirteen effect sizes.164,166-169,171,181,183,186-190 In addition, a single meta-analysis examining this effect was found (see Table 6).191\n\nResults of meta-analysis (n = 26,909) of these studies showed that the aggregated effect size between IGF-1 and cancer is HR = 1.48 (HR S.E. = 0.09, 95% CI [1.31,1.65]) (see Figure 11). This result is significant χ2 (12) = 914.23, p < 0.001 and means that people consuming high IGF-1 products (dairy products) at any time point during the study period were 48% more likely to be diagnosed with cancer than people that were not consuming a high IGF-1 diet, and we are 95% confident that the true value is lying between 31%-65% (we are 95% sure that people consuming dairy are between 31% and 65% more likely to be diagnosed with cancer than people consuming a low/no dairy diet).\n\nA significant heterogeneity was found between studies, meaning that the studies included in this analysis are different by several methodological aspects which could bias the aggregated effect, Q (12) = 25.67, p < 0.01. Hence, differences between individual studies are significant and considered heterogeneous (see Figures 11 and 12, result of Annekatrin et al.,166 exceeds CI borders).\n\nTo conclude, high IGF-1 levels were found to increase probability for cancer diagnosis by about 48% in comparison with patients with low IGF-1 levels. This finding was larger in comparison with effect size derived from the meta-analysis of Shi et al.191 (HR = 1.05). This suggests that reduced dairy product consumption will lead improved health in the long term.\n\nTo assess aggregative Hazard Ratio (HR) of meat consumption and diabetes, two individual studies were used yielding 3 effect sizes (see Table 7).\n\nResults of meta-analysis of these studies (n = 353,300) showed that the aggregated effect size between meat consumption and diabetes is HR = 1.52 (HR S.E. = 0.43, 95% CI [1.17, 2.37]) (see Figure 13). This result is significant χ2 (1) = 3194.10, p < 0.001.\n\nA significant heterogeneity was found between two studies, meaning, studies included in this analysis are different by several methodological aspects which could bias the aggregated effect, Q (1) = 13.61, p < 0.01 (see Figure 14, results of Pan et al.,216 exceeds CI borders).\n\nTo conclude, meat consumption significantly increases probability for diabetes by about 50% on average, in comparison with vegetarian nutrition. This effect size is larger in comparison with effect size received by Aune et al.218 (HR = 1.17), and by Micha et al.219 (HR = 1.16).\n\n\nResults\n\nThe results from these meta-analyses presented, which involved 2,264,009 people (9,600,738 including previous meta-analyses for which there may be overlap), of which 220,906 (734,711 including previous meta-analyses for which there may be overlap) became sick or died during the studies, aimed to assess aggregate effect sizes of several nutrition types with both mortality and diseases.\n\nTo conclude, all meta-analyses conducted to assess mortality showed highly significant results. Specifically, meat consumption increased mortality probability by 18% on average, a plant-based diet and a high fiber diet decreased mortality in 15% and 20% respectively. In addition, dietary diary consumption (as measured by IGF-1) was found to increase probability for cancer by about 48%, while plant-based nutrition reduced diabetes by about 27% and meat consumption increased probability for diabetes by about 50% on average. No significant effects were indicated for meat consumption or vegetarian or Mediterranean diet on diabetes or heart disease (see Table 8).\n\nThe possible limitations of these meta-analysis should be taken into consideration. Although the combination of results from different studies will increase statistical power in detecting significant associations because of the increased sample size, however, this often results in heterogeneity. Heterogeneity is expected as the studies took place in different geographic locations, used different dietary assessment methods, and included participants who are in different gender and age groups. In general, there was significant heterogeneity in many of the meta-analyses, as can be seen in the redial plots.\n\nPublication bias is another concern. The statistical tests did not suggest the presence of publication bias in these meta-analyses, although some may have had limited statistical power due to the sometime low number of studies, but on the other hand, very large numbers of participants do reduce this bias.\n\nCompletely ruling out the possibility of residual confounding or a temporal bias cannot be done, but if the associations found are real, then it is safe to say that a whole food plant-based diet can reduce the risk for common diseases and increase longevity.\n\nThe evidence from this research component suggests that the most suitable diet for human consumption for health and longevity is a natural, whole food, high-fiber and 90+% plant-based diet, with small amounts of lean meat. This diet leads to health for our species, reducing the need for and costs of healthcare, especially for the growing elderly population.\n\nIn order to produce change and have more of the population follow this type of diet, governments and individuals need practical methods and health policies that improve health, with a smaller carbon footprint.\n\nThe consumption of animal products not only influences personal health, but also environmental health. The current situation shows that the rearing of livestock and meat consumption on a commodity-basis, accounts for the highest greenhouse gas (GHG) emissions, respectively, producing 41% and 20% of the sector’s overall GHG output.192 Rearing of livestock is also the single greatest anthropogenic source of methane, a GHG about 25 times more powerful at trapping heat in the atmosphere than CO2, (from raising cattle for food) and nitrous oxide emissions (from fertilizer and manure usage), two very potent GHGs.\n\nRearing of livestock is responsible for approximately 37% of anthropogenic methane emissions and approximately 65% of human nitrous oxide emissions globally.193\n\nFurthermore, animal agriculture is a notable contributor to global warming due to the quantities of fossil fuels used, together with deforestation. Worldwide, energy from fossil fuels are responsible for 40% of human GHG emissions, which does not include deforestation at about 18%, and animal agriculture 18%. In fact, most deforestation is done for the purpose of rearing animals and to expand pastures and arable land used to grow crops for feeding livestock. Thus, of the 91-97% human induced GHG emissions, 60% is due to animal agriculture.\n\nManufacturing beef demands significantly higher resources. Beef production needs 28 times more land, six times more fertilizer and 11 times more water than the production of chicken or pork. Furthermore, producing beef releases four times more GHGs than the same amount of pork on a calorie basis, and five times more than poultry.194\n\nThe consumption of plant-based foods produces very low GHG emissions.195 It is more economical to grow crops for food than to grow crops for animal feed, necessitating the build-up of muscle mass and bone tissue.\n\nOverall, the goal of agriculture and governments must be to build a sustainable future and to support the health of the population. This means finding solutions that will continue to meet human food and energy requirements in cheap, safe, and high-quality ways even for a growing human population, while leaving little or no negative effects on our planet, along with disease control and caring for animal welfare, in a way that is profitable for the farmer.\n\nTo ensure that every person on the planet would be able to meet their nutritional needs in the future, we would need to (1) build stable national relationships between different countries for consistent import and export of agricultural goods for food security, (2) establish domestic and global policies including meat and dairy taxes to be implemented to ensure that a price is paid for the destruction of the earth and its resources, and (3) make agricultural policies and trade rules compatible with global food security and sustainability.\n\nWe also need to improve dietary habits. The number of men and women existing in sub-optimum health is a dramatic 95% of the global population, and this number is estimated to grow in the upcoming years.196-198\n\nIf there is no change in prevailing dietary habit trends, GHG emissions in 2050 connected with food systems will rise by 51% compared with current levels.\n\nIf the global population followed a 90% plant-based diet, with meat and animal products forming 10% of the diet, GHG emissions would decrease by 55%. These statistics show a clear and simple way to effect change. By reducing meat and dairy products from the diet to twice a week and changing the composition of the common diet to mostly vegetables, nuts, fruits, whole grains, nuts and legumes, we can immensely influence global GHG emissions, slow deforestation, and prevent many diseases.\n\nGovernments and civil society are profoundly unwilling of to intrude into people’s diets and tell them what to eat. But we will soon understand that this is the only way to go.\n\nAlthough reducing overall meat and dairy product consumption will help, the type of meat chosen also has an immense effect on our planet and the future of food. Some animal products are more sustainably produced than others. A way of comparing species is to look at how efficiently an animal converts feed into biomass for human nutrition.\n\nOne needs only 1.1 kg of pellet food to get 1 kg of fish meat.199-201\n\nChickens also use feed efficiently, where 1.7 kg of feed produces 1 kg of chicken because they are grown quickly and slaughtered at a young age.\n\nBy comparison, 2.9 kg of feed is needed for the making of 1 kg of pig meat, and 6.8 kg of feed is needed for the making of 1 kg of cow meat.\n\nA reduction in animal consumption would have major effects on life on Earth:\n\n• Of the available 12 billion acres of agricultural land available on earth, 68% is currently used for livestock.202 Some of this land could be restored for grasslands and forests, to help capture carbon further reducing carbon emissions or be diverted to growing plants for human consumption.\n\n• People previously involved in the livestock industry, (about one-seventh of the global population), would require help making the shift towards a different career, whether in plant-based agriculture, in reforestation, in the biofuel industry from the byproducts of crops now used as food for livestock, or in caring for the animals (re) introduced into the wild or into sanctuaries and zoos.\n\n• About one-third of the planet's land is arid to semi-arid rangeland only able to support livestock agriculture. In these areas, land could be used to house the growing African population, for vertical farming facilities, for growing native trees found to be of medicinal value (e.g., moringa or shea) and for growing livestock for wool for populations such as the Mongols and Berbers, who would otherwise lose their cultural identity, causing them to settle permanently in cities or towns. Solar farms could also be located on this land, providing sustainable sources of energy to local communities.\n\nApart from the myriad reasons to lower meat consumption, meat has an important role in tradition and cultural identity. Giving up meat has impact on the culture of many societies, so governments and people have personally failed to reduce meat consumption.\n\nThis indifference can be combated by increasing the price of meat so that farmers can raise fewer animals and earn the same. This shift in production would make meat take the form of a treat rather than a staple food, as it is today.\n\nGovernments can subsidize fresh vegetables and fruits, making them more affordable and more widely accessible to all populations, instead of subsidizing meat and dairy products.\n\nThe environmental issue may also be solved with meat coming from the use of technology, such as lab-grown meat and fish.203-205\n\nThe current problem is that newly rich societies are increasing their demand for animal products. As people’s incomes increase, they start buying more dairy, poultry and meat and fish.\n\nTherefore, to improve people’s eating habits, a whole food mostly plant-based diet should be encouraged and taught in schools including medical school. Just as teaching first aid is common practice all over the world, the same should be done with regard to plant-based food choices.\n\n\nDiscussion\n\nAs we see, food choices are very dependent on prices, and can therefore be influenced by prices.\n\nDifficulties also arise in making healthy food choices in food swamps, where affordable, fresh and healthy foods are accessible, but where there is an overabundance of energy dense, low-nutrient foods as well. Here, unhealthy food choices are much easier to make than healthy food choice, due to their cheaper prices. This is where education is critical.\n\nSince sodas are not a necessary element of a wholesome diet, soda is a welcome candidate for taxation. We see that if a tax of about 20% is introduced, it has a serious effect on the buying behavior of consumers producing many health benefits.\n\nIn Mexico, a sugar tax on soft drinks has been successful due to the fact that the funds were spent providing free drinking water in schools.206-208\n\nThe price of animal products must match their real cost to society, including their carbon footprint. A meat tax puts a specific price on the harm they cause the environment. Currently, there are no consequences for the raising of livestock, even though these industries are proven to be detrimental to health and the environment. There must be a financial deterrent such as taxes, fines, or penalties to discourage their production and usage. To date, no economic incentives are in place for industries or individuals to move away from the generation and consumption of animal goods. Taxing meat and dairy products will put economic pressure on people and these industries to make change.\n\nThis tax money can then be given back to meat farmers as government support.\n\nPeople will still buy meat, but more as a treat rather than as a staple.\n\nA meat tax will lead to a major reduction in GHG emissions and preserve over 500,000 lives per year through healthier diets.\n\nIf we add a 35% meat and dairy tax and encourage sellers to sell meat and dairy products at 50% higher prices, people will make different choices.\n\nFood stamps:\n\nFor 40 years, the food stamps program has been a very significant domestic hunger safety net that helps provide economic well-being, access to proper nutrition, food security and accessibility, and a reduction of child poverty and money for food spending that benefits those most in need. Food stamps are also good for the economy.209\n\nThere is one major drawback of such programs, namely the foods they include.\n\nPeople can use food stamps to purchase any food item for human consumption, including candy, soft drinks, ice-cream, crackers, cookies, and cakes.210\n\nFood stamp policy should change to allow the purchase of only natural foods, without options for foods that are the leading causes of illness and chronic diseases.\n\nFood stamps can thus help guide populations using them towards making healthy food choices by default. In this way, the government will target the poorest, most needy families first and this will lead the way for agriculture to follow suit.\n\nSubsidies\n\nIn the current US food pyramid, (see Figure 15), the USDA suggests that meat, poultry, fish, eggs and legumes together should comprise 10% of our diet and that dairy products should comprise 23% of our diet. When putting these foods together and reducing intake of legumes, the pyramid suggest we should be consuming about 30% of our calories from animal-based products.211,212 However, the meat and dairy industries get 74% of USDA subsidies. Vegetables and fruits, according to the USDA food pyramid, are to form 38% of total calories. However, these industries get under 3% of the subsidies.213\n\nGrains receive 13% of subsidies, with most going to feed livestock; sugar, oil, starch and alcohol, 11%; nuts and legumes, 1.9%; and fruits and vegetables, 0.4% of subsidies.\n\nIn order to improve health, subsidies should become more similar in percentages to the USDA’s tiers in the food pyramid.\n\nThe Recommended Food Pyramid Based on This Research:\n\nAccording to this research into the ideal diet for humans the optimal food pyramid would reflect the following breakdown (see Figure 16):\n\n• grain consumption (27%), recommending that all grains should be consumed as whole grains.\n\n• vegetables (26%), highlighting a variety of dark green vegetables, as well as root vegetables.\n\n• legumes (20%), peas, lentils and beans, and their spreads.\n\n• fruits (15%), emphasizing variety and deemphasizing fruit juices.\n\n• meat (7%), emphasizing lean meats such as fish, and chicken.\n\n• oils, nuts, seeds (5%), recommending nuts and seeds and their pastes as sandwich toppings.\n\n• honey, emphasizing whole natural honey (0-0.5%).\n\nTo conclude, a whole-food, high-fiber, plant-based diet consisting mainly of whole grass grains, legumes, USOs, nuts, seeds and fruits, with reduced quantities of meat and dairy products has been statistically proven to not only prevent most modern-day diseases but may also reverse them while supporting the growing population in a healthy and sustainable way.\n\nIndividuals and governments should aim to use this knowledge through policies, to feed the growing global population in a healthy and sustainable way without causing further environmental destruction.\n\nIn developed countries, interventions can include increased income-earning opportunities, changes in the food pyramid, meat, dairy, and sugar taxes, a change in food stamp guidelines, subsidies for farmers, support for excess food sharing, supermarket availability for all communities, and school feeding and education programs in all countries. In developing countries, this effort could include local markets for food producers, improved infrastructure, secured purchasing power through governmental prevention of price fluctuations, securing land ownership, easier access to credit, knowledge-sharing through demonstration farms and websites, and legal structures supporting private investors.\n\n\nConclusions\n\nAll meta-analyses conducted to assess mortality showed highly significant results. Specifically, meat consumption increased mortality probability by 18% on average, plant-based diets and fiber-rich diets decreased mortality by 15% and 20%, respectively.\n\nIn addition, dairy consumption (as measured by IGF1) was found to increase the probability of cancer by about 50%, while plant-based nutrition reduced diabetes by about 27%.\n\nTo conclude the findings, a whole-food, high-fiber, plant-based diet consisting mainly of whole grass grains, legumes, USOs, nuts, seeds, and fruits, with reduced quantities of meat and dairy products, has been statistically proven to prevent most modern-day diseases while supporting the growing population healthily and sustainably.\n\nIndividuals and governments should use this knowledge and begin the process of change to support, through policies, the feeding of the growing global population healthily and sustainably without causing further environmental destruction. Future research should examine different aspects of whole food plant-based diets and their effects on health and mortality, such as nut and seed consumption and disease. Also, research into dietary recommendation strategies is necessary to translate the findings of this study to influence a wider population.\n\nZ Statistic, standardized score that indicates a higher probability for a significant result; Hazard ratio (log), the ratio of the hazard rates corresponding to the conditions described by two levels of an explanatory variable that explain the outcome in survival analysis; Forest plot, a graphical display of estimated results from a number of scientific studies addressing the same correlation in a meta-analysis. The forest plot depicts the relationship between an independent variable and the outcome across several similar correlations; Radial plot, a graphical display of heterogeneity in the data in a meta-analytic context. For a fixed-effects model, the plot shows the inverse of the standard errors (1/standard error) on the horizontal axis against the observed effect sizes or outcomes standardized by their corresponding standard errors on the vertical axis\n\n\nData availability statement\n\nOpen Science Framework: Manuscript - The Ideal Diet for Humans. https://doi.org/10.17605/OSF.IO/64NAM.215\n\nThis project contains the following underlying data:\n\n• Research Findings Galit Goldfarb.pdf (the search strategy and results)\n\nThe reporting of this systematic review was guided by the standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement openly available in Open Science Framework at https://doi.org/10.17605/OSF.IO/64NAM.\n\nThis repository includes the following files:\n\n• PRISMA 2009 flow diagram Galit Goldfarb.pdf\n\n• PRISMA 2009 checklist.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
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Publisher Full Text Reference Source\n\nTonstad S, Butler T, Yan R, et al.: Type of vegetarian diet, body weight, and prevalence of type 2 diabetes. Diabetes Care. 2009 May; 32(5): 791–6. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nLi S, Chiuve SE, Flint A, et al.: Better diet quality and decreased mortality among myocardial infarction survivors. JAMA Intern. Med. 2013; 173: 1808–18. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nStewart RA, Wallentin L, Benatar J, et al.: Dietary patterns and the risk of major adverse cardiovascular events in a global study of high-risk patients with stable coronary heart disease. Eur. Heart J. 2016; 37(25): 1993–2001. Publisher Full Text | Free Full Text PubMed Abstract | Reference Source\n\nKwok CS, Umar S, Myint PK, et al.: Vegetarian diet, Seventh Day Adventists and risk of cardiovascular mortality: a systematic review and meta-analysis. Int. J. Cardiol. 2014 Oct 20; 176(3): 680–6. PubMed Abstract | Publisher Full Text Reference Source\n\nLaron Z: Insulin-like growth factor 1 (IGF-1): a growth hormone. Mol. Pathol. 2001 Oct; 54(5): 311–6. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nRenehan AG, et al.: Circulating insulin-like growth factor II and colorectal adenomas. J. Clin. Endocrinol. Metab. 2000; 85(9): 3402–8. PubMed Abstract | Publisher Full Text\n\nYu H, Rohan T: Role of the insulin-like growth factor family in cancer development and progression. J. Natl. Cancer Inst. 2000 Sep 20; 92(18): 1472–89. PubMed Abstract | Publisher Full Text\n\nAnnekatrin L, et al.: Circulating levels of insulin-like growth factor-I and risk of ovarian cancer. Int. J. Cancer. 2002; 101(6): 549–54. PubMed Abstract | Publisher Full Text\n\nRenehan AG, et al.: Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004; 363(9418): 1346–53. PubMed Abstract | Publisher Full Text Reference Source\n\nAllen NE, et al.: Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol. Biomark. Prev. 2007; 16(6): 1121–7. PubMed Abstract Reference Source\n\nRoddam AW, et al.: Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann. Intern. Med. 2008; 149(7): 461–71. W83–8. Publisher Full Text | PubMed Abstract | Free Full Text Reference Source\n\nKey TJ, et al.: Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol. 2010; 11(6): 530–42. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nRinaldi S, et al.: Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies. Int. J. Cancer. 2010; 126(7): 1702–15. PubMed Abstract | Publisher Full Text\n\nClayton PE, Banerjee I, Murray PG, et al.: Growth hormone, the insulin- like growth factor axis, insulin and cancer risk. Nat. Rev. Endocrinol. 2011; 7: 11–24. PubMed Abstract | Publisher Full Text Reference Source\n\nYang Y, Yee D: Targeting insulin and insulin-like growth factor signaling in breast cancer. J. Mammary Gland Biol. Neoplasia. 2012 Dec; 17(3-4): 251–61. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nChristopoulos PF, Msaouel P, Koutsilieris M: The role of the insulin-like growth factor-1 system in breast cancer. Mol. Cancer. 2015; 14: 43. Publisher Full Text | PubMed Abstract | Free Full Text Reference Source\n\nPollak M: Insulin and insulin-like growth factor signalling in neoplasia. Nat. Rev. Cancer. 2008; 8: 915–28. PubMed Abstract | Publisher Full Text Reference Source\n\nHoppe C, Molgaard C, Michaelsen KF: Cow's milk and linear growth in industrialized and developing countries. Annu. Rev. Nutr. 2006; 26: 131–73. PubMed Abstract | Publisher Full Text Reference Source\n\nRogers I, Emmett P, Gunnell D, et al.: Milk as a food for growth? The insulin-like growth factors link. Public Health Nutr. 2006 May; 9(3): 359–68. PubMed Abstract | Publisher Full Text Reference Source\n\nRich-Edwards JW, Ganmaa D, Pollak MN, et al.: Milk consumption and the prepubertal somatotropic axis. Nutr. J. 2007; 6: 28. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nCrowe FL, Key TJ, Allen NE, et al.: The association between diet and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol. Biomark. Prev. 2009; 18: 1333–1340. Publisher Full Text Reference Source\n\nQin LQ, He K, Xu JY: Milk consumption and circulating insulin-like growth factor-I level: a systematic literature review. Int. J. Food Sci. Nutr. 2009; 60(Suppl 7): 330–40. Publisher Full Text\n\nMajor JM, Laughlin GA, Kritz-Silverstein D, et al.: Insulin-like growth factor-I and cancer mortality in older men. American Goiter Association Transactions of the American Goiter Association. 2010; 95: 1054–9. Publisher Full Text | PubMed Abstract | Free Full Text Reference Source\n\nAllen NE, Appleby PN, Davey GK, et al.: The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans. Cancer Epidemiol. Biomark. Prev. 2002 Nov; 11(11): 1441–8. PubMed Abstract Reference Source\n\nMikami K, et al.: Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan. Asian Pac. J. Cancer Prev. 2009; 10(Suppl): 57–61. PubMed Abstract Reference Source\n\nSuzuki S, et al.: Insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein-3, and risk of colorectal cancer: a nested case-control study in the Japan Collaborative Cohort study. Asian Pac. J. Cancer Prev. 2009; 10(Suppl): 45–9. PubMed Abstract Reference Source\n\nAkter S, Kurotani K, Nanri A, et al.: Dairy consumption is associated with decreased insulin resistance among the Japanese. Nutr. Res. 2013 Apr; 33(4): 286–92. PubMed Abstract | Publisher Full Text Reference Source\n\nHankinson SE, Willett WC, Colditz GA, et al.: Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998; 351: 1393–6. Publisher Full Text Reference Source\n\nYu H, Spitz MR, Mistry J, et al.: Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis. J. Natl. Cancer Inst. 1999 Jan 20; 91(2): 151–6. PubMed Abstract | Publisher Full Text Reference Source\n\nSpitz MR, et al.: Serum insulin-like growth factor (IGF) and IGF-binding protein levels and risk of lung cancer: a case-control study nested in the beta-Carotene and Retinol Efficacy Trial Cohort. Cancer Epidemiol. Biomark. Prev. 2002; 11(11): 1413–8. PubMed Abstract Reference Source\n\nGunter MJ, Hoover DR, Yu H, et al.: Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J. Natl. Cancer Inst. 2009; 101: 48–60. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nEndogenous Hormones and Breast Cancer Collaborative Group:Key TJ, Appleby PN, et al.: Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol. 2010; 11(6): 530–42. Publisher Full Text | PubMed Abstract | Free Full Text Reference Source\n\nShi R, Yu H, McLarty J, et al.: IGF-I and breast cancer: a meta-analysis. Int. J. Cancer. 2004; 111: 418–23. PubMed Abstract | Publisher Full Text Reference Source\n\nFood And Agriculture Organization Of The United Nations: Tackling Climate Change Through Livestock - A Global Assessment Of Emissions And Mitigation Opportunities.2013.Reference Source\n\nFood and Agriculture Organization of the United Nations: Key facts and findings. By the numbers: GHG emissions by livestock.2018.Reference Source\n\nEshel G, Shepon A, Makov T, et al.: Land, irrigation water, greenhouse gas, and reactive nitrogen burdens of meat, eggs, and dairy production in the United States. Environmental costs of animal-based categories. PNAS. 2014; 111(33): 11996–12001. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEnvironmental Working Group: A meat-eaters guide to climate change - climate and environmental impacts.2011.Reference Source\n\nGBD - Global Burden of Disease Study 2013 Collaborators: Global Burden of Disease Study Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 386(9995): 743–800. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGBD - Global Burden of Disease Study Collaborators, 2017: Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10; 392(10159): 1789–858. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nMurray CJ, Barber RM, Foreman KJ, et al.: Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: quantifying the epidemiological transition. Lancet. 2015; 386(10009): 2145–91. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMelo MC, Andersson E, Fjelldal PG, et al.: Salinity and photoperiod modulate pubertal development in Atlantic salmon (Salmo salar). J. Endocrinol. 2014; 220(3): 319–32. PubMed Abstract | Publisher Full Text\n\nDe Ridder D, Wauben M, Voesenek R: Unravelling solutions for Future Food problems. Utrecht:Utrecht University. Production limiting factors;2018.Reference Source\n\nThe Farm Animal Welfare Council: Report on the welfare of farmed fish.2018.Reference Source\n\nGood C, Davidson J: A Review of Factors In uencing Maturation of Atlantic Salmon, Salmo salar, with Focus on Water Recirculation Aquaculture System Environments. J. World Aquacult. Soc. 2016; 47: 605–32. Publisher Full Text\n\nKupferschmidt K: Here It Comes … The $375,000 Lab-Grown Beef Burger. Sci. Mag. Aug 2, 2013. Reference Source\n\nWilks M, Phillips CJV: Attitudes to in vitro meat: A survey of potential consumers in the United States. PLoS One. 2017; 12(2): e0171904. PubMed Abstract | Publisher Full Text | Free Full Text\n\nServick K: As lab-grown meat advances, U.S. lawmakers call for regulation. Sci. Mag. May 10, 2018. Publisher Full Text Reference Source\n\nSmith A: An Inquiry into the Nature and Causes of the Wealth of Nations. London:W. Strahan;1776; vol. 1. . 1st ed.\n\nBoseley S: Mexican soda tax cuts sales of sugary soft drinks by 6% in first year. The Guardian. Jun 18, 2015.Reference Source\n\nBoseley S: Mexico enacts soda tax in effort to combat world's highest obesity rate. The Guardian. Jan 16, 2014. Reference Source\n\nHanson K: USDA - Economic Research Service - Economic Research Report No. (ERR-103) The Food Assistance National Input-Output Multiplier (FANIOM) Model and Stimulus Effects of SNAP.2010.Reference Source\n\nEconomic Research Service: United States Department of Agriculture (USDA) - Economic Linkages - Supplemental Nutrition Assistance Program (SNAP) Linkages with the General Economy.2018.Reference Source\n\nBritten P, Marcoe K, Yamini S, et al.: Food Guide Pyramid- Development of Food Intake Patterns for the MyPyramid Food Guidance System. J. Nutr. Educ. Behav. 2006; 38: S78–92.\n\nUSDA - United States Department of Agriculture - Economic Research Service: Agricultural Subsidies.2019.Reference Source\n\nUSDA - United States Department of Agriculture - Economic Research Service: U.S. dairy policy.2018.Reference Source\n\nU.S. Department of Health and Human Services, U.S. Department of Agriculture: 2015–2020 Dietary Guidelines for Americans.8th Edition.December 2015.Reference Source\n\nGoldfarb G: Manuscript - the Ideal Diet for Humans. OSF. 2021. September 12.Publisher Full Text\n\nPan A, Sun Q, Bernstein AM, et al.: Red meat consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis. Am J Clin Nutr. 2011; 94(4): 1088–96.Publisher Full Text\n\nPan A, Sun Q, Bernstein AM, et al.: Changes in red meat consumption and subsequent risk of type 2 diabetes mellitus: Three cohorts of US men and women. JAMA Intern Med. 2013; 173(14): 1328–35.Publisher Full Text\n\nAune D, Ursin G, Veierød MB, et al.: Meat consumption and the risk of type 2 diabetes: A systematic review and meta-analysis of cohort studies. Diabetologia 2009; 52: 2277–87.Publisher Full Text\n\nMicha R, Wallace SK, Mozaffarian D, et al.: Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: A systematic review and meta-analysis. Circulation. 2010; 121(21): 2271–83.Publisher Full Text"
}
|
[
{
"id": "145030",
"date": "29 Sep 2022",
"name": "Katherine Curi Quinto",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nComplement the introduction with background and rationality regarding the “Current Ideal dietary patterns” The historical track of changes of the human diet, is ok. But what about the current recommended dietary patterns such the one from the EAT Lancet commission, flexitarian diet, etc.?\n\nBe clear in the methods section. The first two lines do not contribute with the clarity of the explanation of the methods, I suggest to drop it.\n\nExplain the rationality to make the research using terms regarding food groups instead of looking the impact of a dietary pattern which includes all the components of the diet.\n\nInclude in the methods the quality control for the selection/identification of the paper included in the review, as well as the quality of the papers itself.\n\nIt would be helpful to explain the different dietary patterns included in the review, because you want to recommend an “ideal diet”. Eg. What is the “Plant based diet” or “plant based nutrition” as the author mentions.\n\nIn the discussion the authors include some recommendation for policy such as taxes for meat, it would be important to discuss about population that eat low amounts of meat due to low economical access, this population is vulnerable to important nutritional deficiencies that are caused of mortality and morbidity in early years. Remember that the main nutritional problem in developing countries is the malnutrition with the coexistence of excess weight.\n\nDiscuss how representative are the review in geographical terms. The results could be transferable to low-income countries.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": [
{
"c_id": "9627",
"date": "28 Nov 2023",
"name": "Galit Goldfarb",
"role": "Author Response",
"response": "Dear Dr. Katherine Curi Quinto, Thank you for your constructive feedback on my research paper about the ideal diet for humans. I appreciate your efforts in providing specific points that require further clarification. In response to your first comment, I agree that it is important to complement the introduction with background and rationality regarding the \"Current Ideal Dietary patterns,\" such as the ones recommended by the EAT-Lancet Commission and the flexitarian diet. I have revised the introduction to include a discussion on the rationale behind these dietary patterns. Thank you for your feedback on the methods section. I have removed the first two lines to ensure clarity and conciseness. Regarding your third comment, I understand your concern about using food groups instead of a dietary pattern that includes all diet components. I have revised the manuscript to explain the rationale behind this approach better. In response to your fourth comment, I have included all studies with sufficient analytical data in the review. I have addressed your comment in the “study selection” category. I appreciate your suggestion to explain the different dietary patterns included in the review, particularly the \"Plant-based diet.” I have revised the manuscript to provide a more detailed explanation of this dietary pattern to help readers better understand these concepts. In response to your sixth comment, I understand the importance of discussing the potential impact of policy recommendations such as taxes for meat on vulnerable populations who may have limited access to other sources of nutrients. I have revised the discussion to include a more thorough exploration of the potential benefits and drawbacks of such policies on different populations. Finally, I acknowledge your concern about the geographical representation of the review and how transferable the results are to low-income countries. I have revised the manuscript to include a more comprehensive discussion of opportunities available as well as the potential limitations of the study in terms of geographical representation and the applicability of the findings to different populations. Thank you again for your valuable feedback. I hope the revisions will address your concerns, and I look forward to hearing from you soon. Best regards, Dr. Galit Goldfarb"
}
]
},
{
"id": "163444",
"date": "22 Mar 2023",
"name": "Aysha Karim Kiani",
"expertise": [
"Reviewer Expertise Human genetics",
"Molecular Biology",
"Immunology",
"Diabetes",
"nutrigenomics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis review plus meta-analysis has discussed effect of different food components on the quantity/longevity as well as quality of life. Introduction is well written and gives comprehensive picture of evolutionary changes in the dietary habits of man. Although, introduction should also include some information about current dietary habits and type of foods options available such as processed food to give.\nThe objectives and rationales of this systemic review are stated but they should be written under proper headings. Methodology is well explained and results are supported by the conclusions of previous studies.\nThis review elaborated that more consumption of plant based diet including vegetables, grains and fruits, increases the life span and prevent diseases while the over consumption of meat and dairy product decreases the life span as well as effects the health of people around the world. In addition to the facts stated in this review it will be encouraged to also analyze the effect of these food components in relation with the geographical distribution and highlight the difference in the food or caloric requirements among people from different geographical regions. The policies suggested are valid and conclusions drawn are significant to consider.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required.\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": [
{
"c_id": "9628",
"date": "28 Nov 2023",
"name": "Galit Goldfarb",
"role": "Author Response",
"response": "Dear Dr. Aysha Karim Kiani, I appreciate your thoughtful and constructive feedback on my research paper about the ideal diet for humans. Thank you for taking the time to provide me with your valuable insights, which have helped me to improve the quality of my work. I would like to address the specific points you have raised. Firstly, regarding the introduction, I agree with your suggestion to include information about current dietary habits and types of food options available, including processed foods. I have made the necessary changes to the manuscript to reflect this. Secondly, I appreciate your suggestion to include proper headings for the objectives and rationales of the review. I have reorganized the manuscript to ensure that the objectives and rationales are clearly stated and presented under proper headings. Finally, I agree with your suggestion to analyze the effect of food components in relation to geographical distribution and highlight the differences in food or caloric requirements among people from different regions. I believe that this is an important consideration, and I have addressed this in the revision of the manuscript. Overall, I am grateful for your feedback, which has helped me to improve the quality and clarity of my research paper. I hope that the changes I have made are satisfactory, and I look forward to hearing from you. Sincerely, Dr. Galit Goldfarb"
}
]
}
] | 1
|
https://f1000research.com/articles/10-1135
|
https://f1000research.com/articles/12-277/v1
|
14 Mar 23
|
{
"type": "Data Note",
"title": "The identification of high-performing antibodies for TDP-43 for use in Western Blot, immunoprecipitation and immunofluorescence",
"authors": [
"Donovan Worrall",
"Riham Ayoubi",
"Maryam Fotouhi",
"Kathleen Southern",
"Peter S. McPherson",
"Carl Laflamme",
"NeuroSGC/YCharOS/EDDU collaborative group",
"ABIF Consortium",
"Donovan Worrall",
"Riham Ayoubi",
"Maryam Fotouhi",
"Kathleen Southern",
"Peter S. McPherson"
],
"abstract": "TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA binding protein playing a critical role in the regulation of transcription, splicing and RNA stability. Mutations in TARDBP leading to aggregation, are suspected to be a characteristic feature of various neurogenerative diseases. The lack of well-characterized anti- TDP-43 antibodies acts as a barrier to establish reproducible TDP-43 research. In this study, we characterized eighteen TDP-43 commercial antibodies for Western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many well-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.",
"keywords": [
"Uniprot ID Q13148",
"TARDBP",
"TDP-43",
"antibody characterization",
"antibody validation",
"Western Blot",
"immunoprecipitation",
"immunofluorescence"
],
"content": "Introduction\n\nTDP-43, encoded by the TARDBP gene, is a DNA/RNA-binding protein implicated in RNA metabolism and processing.1 Belonging to the heterogeneous nuclear ribonucleoprotein (hnRNP) family of proteins that bind to RNA via highly conserved RNA recognition motifs, TDP-43 binds to UG-repeats with high specificity.1,2\n\nMutations in TARDBP that result in TDP-43 aggregation and neuropathology have been observed in distinct neurodegenerative diseases, known as TDP-43 proteinopathies.3,4 Various studies have identified a subset of amyotrophic lateral sclerosis (ALS) patients that possess TARDBP mutations, suggesting that TDP-43 gain of toxic function or loss of function is a causative factor in sporadic and/or familial ALS.4–6 Mechanistic studies would be greatly facilitated by the availability of high-quality antibodies.\n\nHere, we compared the performance of a range of commercially available antibodies for TDP-43 and characterized high-quality antibodies for Western blot, immunoprecipitation and immunofluorescence, enabling biochemical and cellular assessment of TDP-43 properties and function.\n\n\nResults and discussion\n\nOur standard protocol involved comparing readouts from wild-type (WT) and TARDBP knockout (KO) cells.7,8 The first step was to identify a cell line(s) that expresses sufficient levels of TDP-43 to generate a measurable signal. To this end, we examined the DepMap transcriptomics database to identify all cell lines that express the target at levels greater than 2.5 log2 (transcripts per million “TPM” +1), which we have found to be a suitable cut-off (Cancer Dependency Map Portal, RRID: SCR_017655). Commercially available HAP1 cells expressed the TARDBP transcript at RNA levels above the average range of cancer cells analyzed. Parental and TARDBP knockout HAP1 cells were obtained from Horizon Discovery (Table 1).\n\nFor Western Blot experiments, we resolved proteins from WT and TARDBP KO cell extracts and probed them side-by-side with all antibodies in parallel (Figure 1).\n\nLysates of HAP1 (WT and TARDBP KO) were prepared and 50 μg of protein were processed for Western blot with the indicated TDP-43 antibodies. The Ponceau stained transfers of each blot are shown. Antibody dilutions were chosen according to the recommendations of the antibody supplier. Exceptions were given for antibody 80001-1-RR**, which was titrated to 1/1000 as the signal was too weak when following the supplier’s recommendations. When the concentration was not indicated by the supplier, which was the case for antibody 80002-1-RR**, we tested the antibody at 1/1000. Antibody dilution used: 10782-2-AP at 1/5000, 12892-1-AP at 1/1000, 800001-1-RR** at 1/1000, 80002-1-RR** at 1/1000, MAB7778* at 1/500, NBP1-92695* at 1/1000, 711051** at 1/1000, MA5-27828* at 1/1000, MA5-32627** at 1/1000, A19123** at 1/1000, 89789** at 1/1000, 89718** at 1/1000, GTX630196* at 1/500, GTX630197* at 1/500, ab109535** at 1/2000, ab133547** at 1/1000, ab190963** at 1/1000, ab254166** at 1/1000. Predicted band size: 45 kDa. *Monoclonal antibody, **Recombinant antibody.\n\nFor immunoprecipitation experiments, we used the antibodies to immunopurify TDP-43 from HAP1 cell extracts. The performance of each antibody was evaluated by detecting the TDP-43 protein in extracts, in the immunodepleted extracts and in the immunoprecipitates (Figure 2).\n\nHAP1 lysates were prepared, and IP was performed using 2.0 μg of the indicated TDP-43 antibodies pre-coupled to Dynabeads protein G or protein A. Samples were washed and processed for Western blot with the indicated TDP-43 antibody. For Western blot, 80002-1-RR** was used at 1/1000. The Ponceau stained transfers of each blot are shown for similar reasons as in Figure 1. SM=4% starting material; UB=4% unbound fraction; IP=immunoprecipitate. *Monoclonal antibody, **Recombinant antibody.\n\nFor immunofluorescence, as described previously, antibodies were screened using a mosaic strategy.9 In brief, we plated WT and KO cells together in the same well and imaged both cell types in the same field of view to reduce staining, imaging and image analysis bias (Figure 3).\n\nHAP1 WT and TARDBP KO cells were labelled with a green or a far-red fluorescent dye, respectively. WT and KO cells were mixed and plated to a 1:1 ratio in a 96-well plate with a glass bottom. Cells were stained with the indicated TDP-43 antibodies and with the corresponding Alexa-fluor 555 coupled secondary antibody including DAPI. Acquisition of the blue (nucleus-DAPI), green (identification of WT cells), red (antibody staining) and far-red (identification of KO cells) channels was performed. Representative images of the merged blue and red (grayscale) channels are shown. WT and KO cells are outlined on both channels with green and magenta dashed lines, respectively. Antibody dilutions were chosen according to the recommendations of the antibody supplier. Exceptions were given for antibodies 12892-1-AP, MA5-32627**, A19123**, 89789**, 89718** and ab133547** which were titrated to 1/400, 1/1000, 1/900, 1/30, 1/10 and 1/700, respectively, as the signals were too weak when following the supplier’s recommendations When the concentration was not indicated by the supplier, which was the case for antibodies 80001-1-RR**, GTX630196* and ab254166**, we tested antibodies at 1/700, 1/1000 and 1/500, respectively. At these concentrations, the signal from each antibody was in the range of detection of the microscope used. Antibody dilution used: 10782-2-AP at 1/400, 12892-1-AP at 1/250, 800001-1-RR** at 1/700, 80002-1-RR** at 1/250, MAB7778* at 1/500, NBP1-92695* at 1/1000, 711051** at 1/500, MA5-27828* at 1/1000, MA5-32627** at 1/1000, A19123** at 1/900, 89789** at 1/30, 89718** at 1/10, GTX630196* at 1/1000, GTX630197* at 1/1000, ab109535** at 1/30, ab133547** at 1/700, ab190963** at 1/800, ab254166** at 1/500. Bars = 10 μm. *Monoclonal antibody, **Recombinant antibody.\n\nIn conclusion, we have screened TDP-43 commercial antibodies by Western Blot, immunoprecipitation and immunofluorescence and identified several high-performing antibodies under our standardized experimental conditions.\n\n\nMethods\n\nAll TDP-43 antibodies are listed in Table 2, together with their corresponding Research Resource Identifiers (RRID), to ensure the antibodies are cited properly.10 Peroxidase-conjugated goat anti-mouse and anti-rabbit antibodies are from Thermo Fisher Scientific (cat. number 62-6520 and 65-6120). Alexa-555-conjugated goat anti-mouse and anti-rabbit secondary antibodies are from Thermo Fisher Scientific (cat. number A21424 and A21429).\n\n* Monoclonal antibody.\n\n** Recombinant antibody.\n\n1 Refer to RRID recently added to the Antibody Registry (on January 2023), they will be available on the Registry website in coming weeks.\n\nBoth HAP1 WT and TARDBP KO cell lines used are listed in Table 1, together with their corresponding RRID, to ensure the cell lines are cited properly.11 Cells were cultured in DMEM high glucose (GE Healthcare cat. number SH30081.01) containing 10% fetal bovine serum (Wisent, cat. number 080450), 2 mM L-glutamate (Wisent, cat. number 609065), 100 IU penicillin and 100 μg/ml streptomycin (Wisent cat. number 450201).\n\nWestern blots were performed as described in our standard operating procedure.12 HAP1 WT and TARDBP KO were collected in RIPA buffer (25mM Tris-HCl pH 7.6, 150mM NaCl, 1% NP-40, 1% sodium deoxycholate, 0.1% SDS) from Thermo Fisher Scientific (cat. number 0089901), supplemented with protease inhibitor from MilliporeSigma (cat. number P8340). Lysates were sonicated briefly and incubated for 30 min on ice. Lysates were spun at ~110,000 x g for 15 min at 4°C and equal protein aliquots of the supernatants were analyzed by SDS-PAGE and Western blot. BLUelf prestained protein ladder from GeneDireX (cat. number PM008-0500) was used.\n\nWestern blots were performed with precast midi 4-20% Tris-Glycine polyacrylamide gels from Thermo Fisher Scientific (cat. number WXP42012BOX) and transferred on nitrocellulose membranes. Proteins on the blots were visualized with Ponceau staining which is scanned to show together with individual Western blots. Blots were blocked with 5% milk for 1 hr, and antibodies were incubated overnight at 4°C with 5% bovine serum albumin (BSA) (Wisent, cat number 800-095) in TBS with 0,1% Tween 20 (TBST) (Cell Signaling Technology, cat. number 9997). Following three washes with TBST, the peroxidase conjugated secondary antibody was incubated at a dilution of ~0.2 μg/ml in TBST with 5% milk for 1 hr at room temperature followed by three washes with TBST. Membranes were incubated with ECL (Thermo Fisher Scientific, cat. number 32106) prior to detection with the iBright™ CL1500 Imaging System (Thermo Fisher Scientific, cat. number A44240).\n\nImmunoprecipitation was performed as described in our standard operating procedure.13 Antibody-bead conjugates were prepared by adding 2 μg to 500 μl of Pierce IP Lysis Buffer from Thermo Fisher Scientific (cat. number 87788) in a 1.5 ml microcentrifuge tube, together with 30 μl of Dynabeads protein A- (for rabbit antibodies) or protein G- (for mouse antibodies) from Thermo Fisher Scientific (cat. number 10002D and 10004D, respectively). Tubes were rocked for ~2 hrs at 4°C followed by two washes to remove unbound antibodies.\n\nHAP1 WT were collected in Pierce IP buffer (25 mM Tris-HCl pH 7.4, 150 mM NaCl, 1 mM EDTA, 1% NP-40 and 5% glycerol) (Thermo Fisher Scientific, cat. number 87788), supplemented with protease inhibitor (Millipore Sigma, cat. number P8340). Lysates were rocked for 30 min at 4°C and spun at 110,000× g for 15 min at 4°C. 0.5 ml aliquots at 2.0 mg/ml of lysate were incubated with an antibody-bead conjugate for ~2 hrs at 4°C. The unbound fractions were collected, and beads were subsequently washed three times with 1.0 ml of IP lysis buffer and processed for SDS-PAGE and Western blot on precast midi 4-20% Tris-Glycine polyacrylamide gels. Prot-A: HRP (MilliporeSigma, cat. number P8651) was used as a secondary detection system at a dilution of 0.4 μg/ml for an experiment where a rabbit antibody was used for both immunoprecipitation and its corresponding Western blot.\n\nImmunofluorescence was performed as described in our standard operating procedure.9 HAP1 WT and TARDBP KO were labelled with CellTrackerTM green (Thermo Fisher Scientific, cat. number C2925) or CellTrackerTM deep red (Thermo Fisher Scientific, cat. number C34565) fluorescence dye, respectively. The nuclei were labelled with DAPI (Thermo Fisher Scientific, cat. number D3571) fluorescent stain. WT and KO cells were plated on glass coverslips as a mosaic and incubated for 24 hrs in a cell culture incubator at 37oC, 5% CO2. Cells were fixed in 4% paraformaldehyde (PFA) (Beantown chemical, cat. number 140770-10ml) in phosphate buffered saline (PBS) (Wisent, cat. number 311-010-CL) for 15 min at room temperature and then washed 3 times with PBS. Cells were permeabilized in PBS with 0,1% Triton X-100 (Thermo Fisher Scientific, cat. number BP151-500) for 10 min at room temperature and blocked with PBS with 5% BSA, 5% goat serum (Gibco, cat. no 16210-064) and 0.01% Triton X-100 for 30 min at room temperature. Cells were incubated with IF buffer (PBS, 5% BSA, 0,01% Triton X-100) containing the primary TDP-43 antibodies overnight at 4°C. Cells were then washed 3 × 10 min with IF buffer and incubated with corresponding Alexa Fluor 555-conjugated secondary antibodies in IF buffer at a dilution of 1.0 μg/ml for 1 hr at room temperature with DAPI. Cells were washed 3 × 10 min with IF buffer and once with PBS.\n\nImages were acquired on an ImageXpress micro widefield high-content microscopy system (Molecular Devices), using a 20×/0.45 NA air objective lens and scientific CMOS camera (16-bit, 1.97mm field of view), equipped with 395, 475, 555 and 635 nm solid state LED lights (Lumencor Aura III light engine) and bandpass emission filters (432/36 nm, 520/35 nm, 600/37 nm and 692/40 nm) to excite and capture fluorescence emission for DAPI, CellTrackerTM Green, Alexa fluor 555 and CellTrackerTM Red, respectively. Images had pixel sizes of 0.68 × 0.68 microns. Exposure time was set with maximal (relevant) pixel intensity ~80% of dynamic range and verified on multiple wells before acquisition. Since the IF staining varied depending on the primary antibody used, the exposure time was set using the most intensely stained well as reference. Frequently, the focal plane varied slightly within a single field of view. To remedy this issue, a stack of three images per channel was acquired at a z-interval of 4 microns per field and best focus projections were generated during the acquisition (MetaExpress v6.7.1, Molecular Devices). Segmentation was carried out on the projections of CellTrackerTM channels using CellPose v1.0 on green (WT) and far-red (KO) channels, using as parameters the ‘cyto’ model to detect whole cells, and using an estimated diameter tested for each cell type, between 15 and 20 microns.14 Masks were used to generate cell outlines for intensity quantification. Figures were assembled with Adobe Illustrator.",
"appendix": "Data availability\n\nZenodo: Antibody Characterization Report for TDP-43, https://doi.org/10.5281/zenodo.7249802. 15\n\nZenodo: Dataset for the TDP-43 antibody screening study, https://doi.org/10.5281/zenodo.7665963. 16\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nWe would like to thank the NeuroSGC/YCharOS/EDDU collaborative group for their important contribution to the creation of an open scientific ecosystem of antibody manufacturers and knockout cell line suppliers, for the development of community-agreed protocols, and for their shared ideas, resources and collaboration. We would also like to thank the Advanced BioImaging Facility (ABIF) consortium for their image analysis pipeline development and conduction (RRID:SCR_017697). Members of each group can be found below.\n\nNeuroSGC/YCharOS/EDDU collaborative group: Riham Ayoubi, Thomas M. Durcan, Aled M. Edwards, Carl Laflamme, Peter S. McPherson, Chetan Raina, Wolfgang Reintsch, Kathleen Southern and Donovan Worrall.\n\nABIF consortium: Claire M. Brown and Joel Ryan.\n\nAn earlier version of this article can be found on Zenodo (https://doi.org/10.5281/zenodo.7249802).\n\n\nReferences\n\nBhardwaj A, Myers MP, Buratti E, et al.: Characterizing TDP-43 interaction with its RNA targets. Nucleic Acids Res. 2013; 41(9): 5062–5074. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSephton CF, Good SK, Atkin S, et al.: TDP-43 is a developmentally regulated protein essential for early embryonic development. J. Biol. Chem. 2010; 285(9): 6826–6834. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLagier-Tourenne C, Polymenidou M, Cleveland DW: TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum. Mol. Genet. 2010; 19(R1): R46–R64. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPesiridis GS, Lee VM, Trojanowski JQ: Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis. Hum. Mol. Genet. 2009; 18(R2): R156–R162. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNeumann M, Sampathu DM, Kwong LK, et al.: Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006; 314(5796): 130–133. Publisher Full Text\n\nArai T, Hasegawa M, Akiyama H, et al.: TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 2006; 351(3): 602–611. Publisher Full Text\n\nLaflamme C, McKeever PM, Kumar R, et al.: Implementation of an antibody characterization procedure and application to the major ALS/FTD disease gene C9ORF72. elife. 2019; 8.\n\nAlshafie W, Fotouhi M, Shlaifer I, et al.: Identification of highly specific antibodies for Serine/threonine-protein kinase TBK1 for use in immunoblot, immunoprecipitation and immunofluorescence. F1000Res. 2022; 11: 977. Publisher Full Text\n\nAlshafie W, McPherson P, Laflamme C: Antibody screening by Immunofluorescence.2021.\n\nBandrowski A, Pairish M, Eckmann P, et al.: The Antibody Registry: ten years of registering antibodies. Nucleic Acids Res. 2023; 51(D1): D358–D367. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBairoch A: The Cellosaurus, a Cell-Line Knowledge Resource. J. Biomol. Tech. 2018; 29(2): 25–38. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAyoubi R, McPherson PS, Laflamme C: Antibody Screening by Immunoblot.2021.\n\nAyoubi R, Fotouhi M, McPherson P, et al.: Antibody screening by Immunoprecitation.2021.\n\nStringer C, Wang T, Michaelos M, et al.: Cellpose: a generalist algorithm for cellular segmentation. Nat. Methods. 2021; 18(1): 100–106. PubMed Abstract | Publisher Full Text\n\nWorrall D, Ryan J, Fotouhi M, et al.: Antibody Characterization Report for TDP-43. [Dataset]. 2022. Publisher Full Text\n\nLaflamme C: Dataset for the TDP-43 antibody screening study. [Dataset]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "166439",
"date": "20 Mar 2023",
"name": "Makoto Urushitani",
"expertise": [
"Reviewer Expertise Motor neuron disease",
"protein misfolding",
"antibody generation"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDue to the continuing significance of morphological assay to clarify TDP-43 proteinopathy, the characteristics of the antibody are crucial to drawing convincing and replicable results. Numerous antibodies against TDP-43 are commercially available to meet the needs. As is often the case, however, the results could be misleading unless the antibodies are used with a sufficient understanding of their properties. However, such information is hardly accessible until our use.\nIn this work, the authors comprehensively investigated the specificity and affinity of commercially available antibodies against TDP-43 by analyzing Western blotting, immunoprecipitation, and immunofluorescence. Another advantage of their work is adopting HAP1 cells through careful screening from transcription levels and TARDBP-KO cells. They successfully suggested several antibodies, which are conformation- and sequence-specific with high reactivity. Experimental protocols are clearly written, and the data presentation is compelling. This work deserves considerable attention because such information may help researchers minimize the time for optimization and acquire solid and replicable results. The weak points of their work is a lack of experiments using ALS-linked TDP-43 mutations or immunohistochemistry of ALS patients. However, those are beyond their scope, which awaits future validation.\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "9490",
"date": "22 Mar 2023",
"name": "Kathleen Southern",
"role": "Author Response",
"response": "Thank you to Makoto Urushitani for your review of our publication. Although there is an abundance of commercial antibodies available for TDP-43, there lacks guidance to help researchers find the appropriate antibody for their experimental need. Accordingly, we too agree that the characterization of antibodies is a determinant factor when drawing convincing and replicable results. As such, the YCharOS initiative has set out to solve the antibody reproducibility crisis by characterizing commercially available antibodies for human proteins. In terms of scoring the antibodies based on performance, we have found that for the most part, scientists interested in our reports have the expertise to interpret the antibody characterization data. Moreover, because we tested the antibodies under one set of conditions, and the scoring/recommendation would be valid only under this precise experimental setup and in the cell line used. That said, YCharOS reports serve as an invaluable guide pointing scientists to appropriate antibodies for their experimental needs. In the future, we hope to study the ALS protein-network in ALS patients, using the YCharOS reports as a guide to select the appropriate antibodies. As for now, our aim for this publication is to assist researchers in selecting high-quality TDP-43 antibodies for studying TDP-43 proteinopathies."
}
]
},
{
"id": "178389",
"date": "14 Jun 2023",
"name": "Seiji Watanabe",
"expertise": [
"Reviewer Expertise Amyotrophic Lateral Sclerosis",
"Protein Aggregation",
"Organelle Contact"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nVarious antibodies against TDP-43 are now commercially available from several companies, but their validation is still insufficient. This study comprehensively validated the performance of various antibodies, which will provide important information for researchers when they select TDP-43 antibodies for their studies. The procedures are detailed and carefully described, and together with the references, are well reproducible.\nPathological TDP-43 is generally aggregated, fragmented, and hyperphosphorylated, which may affect antibody recognition. Thus, although it would be beyond the scope of this study, future validation using human patients’ samples, as recommended by the reviewer #1, or of the recognition sites of each antibody would make this data even more valuable.\nThe references 9, 12, and 13 were found to be available on Zendo, but it is difficult to reach them because of a lack of direct links. It is recommended that the DOI be appended.\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-277
|
https://f1000research.com/articles/12-704/v1
|
20 Jun 23
|
{
"type": "Research Article",
"title": "A cross-sectional survey measuring effectiveness of fuel subsidy restructure in Malaysia",
"authors": [
"Yuen Yee Yen",
"Lai Jing Wen",
"Suganthi Ramasamy",
"Eka Puspitawati",
"Lai Jing Wen",
"Suganthi Ramasamy",
"Eka Puspitawati"
],
"abstract": "Background: Out of the MYR 14 billion of fuel subsidy, the top 20% households (T20) in the country enjoy MYR 8 billion compared to MYR 6 billion of the fuel subsidy restructure enjoyed by the low income (B40) households. As the Malaysian government has started to restructure the fuel subsidy scheme in December 2022 when the national economy began to recover post coronavirus 2019 (COVID-19) pandemic, this study is in need as it highlights the key concerns of B40 and middle 40% (M40) households to the government. This research aims to determine key factors affecting fuel subsidy restructure effectiveness from the perspective of B40 and M40 households in Malaysia post COVID-19 pandemic. Methods: A total of 150 questionnaires were disseminated to Malaysia B40 and M40 households. The questionnaire was completed by 105 households with no missing value. This paper utilized cross-sectional design to examine factors that contribute to fuel subsidy restructure in Malaysia post COVID-19 pandemic. Results: Efficient targeting and social protection were the most important factor that contribute to the effectiveness of fuel subsidy restructure in Malaysia. Conclusions: This research serves as the pioneer research to provide valuable insights to the Malaysian government to effectively restructure fuel subsidy initiative towards creating greater social protection, efficient targeting and better governance and administrative capacity in improving the quality of life of the B40 and M40 households.",
"keywords": [
"B40",
"M40",
"Fuel subsidy restructuring",
"Efficient targeting",
"Malaysia"
],
"content": "Introduction\n\nAccording to Ministry of Finance of Malaysia (2022), the Malaysian government spent substantial amount of MYR 14 billion to subsidize fuel in response to the surge in global commodity prices. The government has decided to subsidize fuel to maintain the price of RON 95 and diesel at affordable price of MYR 2.05 per L and MYR 2.15 per L respectively (Ministry of Finance, 2022). The government strives to support this increased spending on fuel subsidy to maintain the well-being of the low income (B40) people and the continuity of small businesses in the country (Ministry of Finance, 2022).\n\nUnfortunately, out of the 14 billion of fuel subsidy, the top 20% households (T20) in the country, was enjoying MYR 8 billion compared to MYR 6 billion of the fuel subsidy restructure enjoyed by the low income households (Ministry of Finance, 2022). As revealed by the finance minister, under today’s blanket fuel subsidy, where everyone in the country enjoys the same flat rate, for every MYR 1 of fuel subsidy, MYR 53 cents go to the T20, while only MYR 15 cents benefit the B40 (Ministry of Finance, 2022).\n\nThis study is timely and important as Malaysia’s government is currently revising fuel subsidy mechanism before its implementation. As of today, there is lack of specific research in Malaysia to determine key factors affecting fuel subsidy restructure from the perspective of B40 and M40 households. As the Malaysian government has started to restructure the fuel subsidy scheme in December 2022 when the national economy begins to recover post COVID-19 pandemic (Ministry of Finance, 2022), this study is in need as it highlights the key concerns of B40 and M40 households to the government. As Malaysia government has recently promised that final decision of fuel subsidy restructure will only take place after majority of the people from B40 and M40 households are comfortable with the mechanism or the platform to execute it, this study is timely to propose valuable insights to the government from the perspectives of B40 and M40 households.\n\n\nLiterature review\n\nFuel subsidy restructure effectiveness refers the successflness of government adminstration in where a fraction of the price that consumers are supposed to pay to enjoy the use of petroleum products is no longer paid by government to ease the price burden of the consumers, particularly high income households (Aleksandrova & Costella, 2021). The Malaysian government proposes to gradually rationalize fuel subsidy to narrow the spending gap between high income (T20), middle incone (M40) and low income (B40) households in the 2010–2015 Malaysia Plan. This fuel subsidy restructure is motivated by rising national budget deficit, increasing national debt and dwindling current account surplus (Institute for Sustainable Development [IISD], 2014).\n\nGiven the fact that out of the MYR 14 billion of fuel subsidy, the T20 households enjoyed MYR 8 billion while B40 households enjoyed less than RM6 billion of the fuel subsidy (Ministry of Finance, 2022), it is timely to investigate how B40 and M40 households think about fuel subsidy restructure and factors affecting the effectiveness of fuel subsidy restructure implementation.\n\nSocial protection is an important determinant of fuel subsidy restructure effectiveness. Social protection refers to adequate housing, food, medical care, and financial assistance for daily life (Feltenstein, 2017). Fuel subsidy restructure are considered to be effective if it allows poor households to strive decent standard of living amid the rising of the global fuel prices (Dennis, 2016; Fuje, 2019). The middle income and the low income households are bound to suffer more loss to social protection when fuel subsidy restructure is not provided (Ilyas, Hussain, Ullah, & Xue, 2022). High income households with an average expenditure of MYR 3849.8 will lose MYR 269.5 in social protection when fuel subsidy restructure is implemented while the low income households with MYR 931 of average expenditure, will lose MYR 65.2 of the social protection due to fuel subsidy restructure (Couharde & Mouhoud, 2020). The lowest income household will obviously have substantial difficulties absorbing such a large social protection loss (Hunt, Weber, & Dordi, 2017).\n\nMalaysia has been facing a lot of new challenges post coronavirus 2019 (COVID-19) pandemic in its developmental journey of moving away from the middle income trap (Ministry of Finance, 2022). To propel away from the middle income trap and advances into a high income nation, effective fuel restructure mechanism should be incorporated in the Government Transformation Programme and the New Economic Model, which are premised on bringing the nation towards a high income nation with great inclusiveness and effectiveness in term of social protection (Ministry of Finance, 2022). Adequate social protection should be provided to ensure that all layers in Malaysia society are able to unleash productivity-led growth and sustain inclusive and innovative development post COVID-19 pandemic (Khalid & Salman, 2020). Hence, the following hypothesis is formed and tested in this study:\n\nH1: Social protection positively influences fuel subsidy restructure effectiveness\n\nGovernance and administrative capacity is another important indicator in measuring the effectiveness of fuel subsidy restructure. According to Lin and Xu (2019), fuel subsidy restructure is considered as ineffective if governments are able to improve governance and administrative capacity on the infrastructure, education and health services of the nation. If governments can invest more on the infrastructure, education and health development of the nation by utilizing saving from the fuel subsidy restructure, then the fuel subsidy restructure are considered to be effective (Kyle, 2018).\n\nAccording to Kojima (2016), governance and administrative capacity refers to the government’s continuous efforts in monitoring, evaluation and reflection of expenditure on public infrastructure to maintain the effectiveness of the fuel subsidy restructure. One example of governance and administrative capacity is to carefully plan massive transportation expansion projects while implementing fuel subsidy restructure among high income households (Li, Shi, & Su, 2017). Good governance and administration is the key capacity, which lower the cost-of-living of the low income households are most likely to enhance the effectiveness of the fuel subsidy restructure in the country (Institute for Sustainable Development [IISD], 2014).\n\nImproving governance and administrative capacity is essential for economic transformation of the nation, as fuel subsidy needs to be restructured for high income households and well targeted for low income households who need fuel frequently to survive and to improve their well-beings (Ilyas, Hussain, Ullah, & Xu, 2022). For example, fossil fuel subsidy is more important in improving the living conditions of the poor as low income people use fossil fuel more frequently in daily life for cooking and heating (McCulloch, Moerenhout, & Yang, 2021). Good governance and administrative capacity is needed to ensure the standard of living of the low income people while phasing out fuel subsidy gradually in the country. Good governance and administrative capacity can also ensure less environmental pollution and more opportunity for education and economical productive activities following fuel subsidy restructure (McCulloch, Moerenhout, & Yang, 2021). Hence, the following hypothesis is formed and tested in this study:\n\nH2: Governance and administrative capacity positively influences fuel subsidy restructure effectiveness\n\nPublicity campaigns aim to educate and promote understanding of the rationale for fuel subsidy restructure to Malaysian households (Couharde & Mouhoud, 2020). The more frequent the publicity campaigns are held, the more effective and transparent is the fuel subsidy restructure (Feltenstein, 2017). A significant barrier to fuel subsidy restructure can be a lack of understanding of fuel subsidy restructure and the inefficiency to promote the benefits of it to Malaysian households (Mundaca, 2017). Educating the citizens about the benefits of fuel subsidy restructure has been an important factor affecting the effectiveness of it in developing countries (Umar & Umar, 2013). Ilyas et al. (2022) discovered that one of the reasons for the failure to implement fuel subsidy restructure in Senegal was the lack of publicity campaigns.\n\nRentschler and Bazilian (2020) discovered that publicity campaigns create wider trust in government and enhance fuel subsidy restructure effectiveness. Ilyas et al. (2022) suggested establishing a publicity committee to promote legitimacy and trust in the fuel subsidy restructure is crucial for the success of the fuel subsidy in the nation. By communicating fuel subsidy restructure plans effectively to the public, governments can reduce the social pressure associated with the rising domestic fuel-price due to subsidy restructure. Public trust can also be improved if fuel subsidy restructure is tied with economic transformation of the country to establish a more rational structure of energy welfare (McCulloch, Moerenhout, & Yang, 2021). Hence, the following hypothesis is formed and tested in this study:\n\nH3: Publicity campaigns positively influence fuel subsidy restructure effectiveness\n\nEfficient targeting is important for fuel subsidy restructure effectiveness since it allows existing subsidized arrangements to be targeted to the neediest population. According to Loo and Mukaramah (2019), transferring the revenue received from the sales tax on fuel refinery products to the subsidy of the low income population to offset the increase in fuel price serves a great help to reduce the financial burden of the vulnerable populations. In addition, the government may also consider imposing a fuel tax on those with higher incomes, given that consumption rates among those with higher incomes are higher than those with lower incomes (Rentschler & Bazilian, 2020). Efficient targeting for the needy and taxing for the rich approach should be considered to preserve the government from fiscal imbalance (McCulloch, Moerenhout, & Yang, 2021).\n\nFuel subsidy in Malaysia are targeted to all citizens irrespective of their income. Inefficient targeting has led to wealthy families and organizations consume fuel more frequent than poor families (McCulloch, Moerenhout, & Yang, 2021). As high income households received more than half of the total subsidies (Schaffitzel, Jakob, Soria, Vogt-Schilb, & Ward, 2020), fuel subsidy in the country needs to be strategized.\n\nSchaffitzel et al. (2020) discover that many countries have switched their subsidy systems from providing subsidy to the fuel distributor to providing a direct transfer to the targeted beneficiary. For instance, India adopted Aadhaar, a scheme based on a user database that can directly link fuel subsidy restructure to targeted recipients’ bank accounts (Kojima, 2016). According to Clarke (2016), fuel subsidy restructure must be carefully assessed to make sure that the targeted recipient can receive affordable, inexpensive and efficient fuel subsidy restructure. Hence, the following hypothesis is formed and tested in this study:\n\nH4: Efficient targeting positively influences fuel subsidy restructure effectiveness\n\nIn Malaysia, there is a lack of public poll inquiring the Malaysian viewpoint on fuel subsidy restructure effectiveness. One of the most recent polls conducted by the government 10 years ago showed that 61% of the Malaysia public supported fuel subsidy restructure (Institute for Sustainable Development [IISD], 2014). As the Malaysian government has started to restructure the fuel subsidy scheme in December 2022 when the national economy begins to recover post COVID-19 pandemic (Ministry of Finance, 2022), this study is in need as it highlights the key concerns of B40 and M40 households to the government.\n\n\nMethods\n\nThis research was conducted by a group of researchers who have sound experience in approaching 150 B40 and M40 households at a specific point in time from January 2022 to July 2022. According to World Food Programme (2023), based on experience from many subsidy-related surveys, a sample size of 150 households is considered to be sufficient and representable. The respondents were approached face-to-face, door-to-door to ensure the purpose of this study is clearly communicated to the respondents prior to the data collection.\n\nEthical approval was obtained for this project from the Research Ethics Committee (REC) Multimedia University (Ethical Approval Number: EA1312021). Written informed consent was obtained from participants for participation and the use of and publication of their anonymized data. A written consent statement was printed on the survey. Respondents were required to tick the written consent form before they started the survey.\n\nThis is a quantitative research using primary survey dataset to explore fuel subsidy restructure effectiveness in Malaysia post COVID-19 pandemic (Figure 1).\n\nIn this research, purposive sampling was used to recruit suitable survey respondents. Purposive sampling refers to selecting target respondents based on characteristics of a population and the objective of the study. Purposive sampling was used to select suitable B40 and M40 households. The target household for this study must have households with income less than MYR 4850 (B40 households) and between MYR 4850 and MYR 10959 (M40 households). B40 and M40 households are targeted in this study as they are the most affected households of fuel subsidy restructure. From January 2022 to July 2022, a questionnaire was developed and distributed face-to-face to 150 B40 and M40 households of three states that have the largest population of fuel subsidy beneficiaries in Malaysia: Selangor, Johor and Kuala Lumpur, according to Ministry of Finance (2022). In order to address survey bias, the questionnaire was meticulously checked by one independent academic and two independent industry experts, who have no personal relationship with any of the authors, to avoid leading questions, ambiguous questions and double-barrel questions. Researchers has no conflict of interest with any of the survey participants. Ethical clearance is applied before the data collection and clearly explained to the respondents prior to the data collection.\n\nPre-testing validation was conducted face-to-face to ensure that the target respondents are originated from B40 and M40 households. By collecting data face-to-face, it results in lower error as all doubts can be explained at the first place. When error and survey bias are low, the data will be reliable and generalizable.\n\nA total of 150 questionnaires were disseminated to households. The target household for this study must have households with income less than MYR 4850 (B40 households) and between MYR 4850 and MYR 10959 (M40 households).\n\nData collection period of this study was from September 2021 to November 2022. The data was collected through a self-administered questionnaire. Data was collected face-to-face from B40 and M40 households of three states that have the largest population of fuel subsidy beneficiaries in Malaysia: Selangor, Johor and Kuala Lumpur immediately after they have answered the questionnaire. Questionnaires with incomplete responses were discarded from the data analysis.\n\nQuestionnaire consists of 30 questions measuring fuel subsidy restructure, social protection, governance and administrative capacity, public campaign and efficient targeting. Respondents were requested to rate each question using on a five Likert scale basis, with 1-strongly disagree, 2-disagree, 3-moderate, 4-agree and 5-strongly agree. Please refer to the underlying data and extended data for the details of the questionnaire (Yuen, 2023a, 2023b).\n\nThis study used statistical software package, IBM SPSS Statistics version 23.0 to process and analyze the data, IBM SPSS Statistics Version 23.0 was employed for data screening for Common Method Variance (CMV) was used in data screening to eliminate bias caused by the variations in responses to the questionnaire. IBM SPSS Statistics Version 23.0 was also utilized to perform multiple linear regression analysis to examine the most important factors affecting the effectiveness of fuel subsidy reform in Malaysia. The open source alternative to IBM SPSS Statistics is PSPP, which provides equivalent analytical capability.\n\nThe R-square value of the multiple linear regression analysis is a statistical measure used to determine how close the data are to the fitted regression. The higher the R-squared, the better the model.\n\n\nResults\n\nDescriptive statistics in Table 1 indicates that one hundred and five B40 and M40 households completed the questionnaire with no missing value. Out of 105, 56 were M40 households and 49 were B40 households. The dataset for this study can be found in the underlying data (Yuen, 2023a). B40 households with income less than MYR 4850 and M40 households earn income between MYR 4850 and MYR 10959.\n\nInferential statistics in Table 2 indicate that M40 households were more likely to welcome fuel subsidy restructure in Malaysia (mean rating=4.04) compared to B40 households (mean rating=3.89). There was a significant difference in terms of the perception of subsidy restructure effectiveness. M40 households perceive the current government effort to rationalize fuel subsidy as significantly more effective compared to B40 households.\n\n** Significant at 0.05 level.\n\nCompared to B40 households (mean rating=3.84), M40 households (mean rating=4.01) gave significantly higher rating on the importance of efficient targeting in influencing the effectiveness of fuel subsidy restructure. M40 households were also more inclined to think social protection is more significantly important (mean rating=3.97) in influencing the effectiveness of the fuel subsidy restructure.\n\nB40 and M40 households are equally concerned about the importance of governance and administrative capacity in influencing the effectiveness of the fuel subsidy restructure.\n\nMultiple linear regression analysis was conducted to determine the predictive influence of the key factors affecting fuel subsidy restructure effectiveness. Multiple linear regression is more powerful than correlational analysis as it analyses the correlation and directionality of all tested factors before proposing a comprehensive model. From the perspectives of both M40 and B40 households, multiple linear regression results in Table 3 show that efficient targeting was the most important factor (Standardized Beta Coefficient=0.368) that contributes to the effectiveness of fuel subsidy restructure in Malaysia. Social protection was the second most important factor (Standardized Beta Coefficient=0.314) that contributes to the effectiveness of fuel subsidy restructure. Governance and administrative capacity was the third most important factor (Standardized Beta Coefficient=0.128) while publicity campaign was the fourth most important factor (Standardized Beta Coefficient=0.115) that contributes to the effectiveness of fuel subsidy restructure. All four factors studied in this research are found to be significantly influence the effectiveness of fuel subsidy restructure. All these four factors explain 62.3% of the variance in fuel subsidy restructure effectiveness. Hence, H1 to H4 are supported.\n\n*** Significant at 0.01 level.\n\n** Significant at 0.05 level.\n\n\nDiscussion and recommendation\n\nThis study aims to determine key factors affecting fuel subsidy restructure effectiveness from the perspective of B40 and M40 households in Malaysia post COVID-19 pandemic. Efficient targeting was perceive the most important factor affecting the effectiveness of fuel subsidy restructure post COVID-19 pandemic because the high income households continue to enjoy fuel subsidy while B40 and M40 families are losing jobs and income due to the pandemic (Ilyas et al., 2022). The middle income (M40) households were the most significantly affected households of fuel subsidy restructure as this households of household receive the least financial and economic assistance from the government and society, especially post COVID-19 pandemic (Kyle, 2018; Ministry of Finance, 2022). This explains why M40 households express greater concern on the importance of efficient targeting in determining the effectiveness of fuel subsidy restructure compared to the low income households.\n\nSocial protection was the second most important factor affecting the effectiveness of fuel subsidy restructure in Malaysia from the perspective of B40 and M40 households. The Malaysian government should provide social protection measures such as cash transfers to manage the adverse risks of fuel subsidy restructure for vulnerable households to increase B40 and M40 households’ acceptance of restructure. The effectiveness of fuel subsidy restructure depends on social protection mechanisms for fuel pricing (Lin & Xu, 2019). Lump-sum transfers, which are paid uniformly to B40 and M40 households every year funded by fuel subsidy restructure revenues, are a significantly more equitable and efficient way of social protection (Khalid & Salman, 2020). Besides reducing poverty rates, universal transfer can also enhance the resilience of B40 and M40 households towards coping the economic challenges post COVID-19 pandemic (Schaffitzel et al., 2020).\n\nGovernance and administrative capacity was the third most important factor affecting the effectiveness of fuel subsidy restructure in Malaysia from the perspective of B40 and M40 households. Government should strengthen fuel subsidy governance and administrative capacity by introducing post COVID-19 relief measures that incentivize B40 and M40 households to reduce their fuel consumption. Good governance and administrative is in need to support fuel usage to households to compensate fossil-fuel heating cost (Mundaca, 2017). Potential savings in fuel restructure subsidy should not be whittled away and discriminated in favour of car owners, as opposed to motorcycle owners (Fuje, 2019). Good governance and administrative capacity is also important to ensure that B40 and M40 consumers reap benefits from the saving relocation of fuel subsidy restructure to cope with higher fuel prices successfully in the long run.\n\nPublicity campaign was the fourth most important factor affecting the effectiveness of fuel subsidy restructure in Malaysia from the perspective of B40 and M40 households. The government needs to ensure public trust in the fuel subsidy restructure through clear and broad public communication before deciding the appropriate timing of subsidy restructure. Explaining the need for change and the compensating measures clearly to the public through mass media and social media before the fuel subsidy restructure is introduced. Clear communication to the poor and middle income households who will be most affected by the subsidy restructure can help minimize public opposition to fuel subsidy restructure because B40 and M40 households who receive subsidized fuel are often not even aware that government in fact subsidizes their consumption (Kojima, 2016; McCulloch, Moerenhout, & Yang, 2021).\n\nThis research is the pioneer research in Malaysia that provides comprehensive information and valuable recommendations that contribute to the effectiveness of petrol subsidy restructure post COVID-19 pandemic. This research helps Malaysia government to effectively restructure fuel subsidy initiative towards creating greater social protection, efficient targeting and better governance and administrative capacity in improving the quality of life of the B40 and M40 households. Comprehensive insights and recommendations are provided to assist the Malaysian government to analyze their impact of fuel subsidy restructure on B40 and M40 households to effectively plan and communicate the fuel subsidy restructure mechanism in the next few years.",
"appendix": "Data availability\n\nFigshare: Fuel Subsidy Restructure Effectiveness. https://doi.org/10.6084/m9.figshare.22144838 (Yuen, 2023a).\n\nThis project contains the following underlying data:\n\n- FuelSubsidyRestructuredata.xlsx (Survey data)\n\nFigshare: FuelSubsidyRestuctureQuestionnaire.doc. https://doi.org/10.6084/m9.figshare.22492720 (Yuen 2023b).\n\nThis project contains the following extended data:\n\n- Questionnaire.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAleksandrova M, Costella C: Reaching the poorest and most vulnerable: addressing loss and damage through social protection. Curr. Opin. Environ. Sustain. 2021; 50: 121–128. Publisher Full Text\n\nClarke K: Estimating the Impact of Price Reforms on Kerosene Subsidy Expenditure in India. 2016. Reference Source\n\nCouharde C, Mouhoud S: Fossil fuel subsidy, income inequality, and poverty: Evidence from developing countries. J. Econ. Surv. 2020; 34: 981–1006. Publisher Full Text\n\nDennis A: Social protection implications of fossil fuel subsidy restructure in developing countries. Energy Policy. 2016; 96: 597–606. Publisher Full Text\n\nFeltenstein A: Subsidy restructure and implications for social protection: An analysis of IMF advice on food and fuel subsidy. IEO Background Paper No. BP/17-01/02 (Washington: International Monetary Fund). 2017.\n\nFuje H: Fossil fuel subsidy reforms, spatial market integration, and welfare: evidence from a natural experiment in Ethiopia. Am. J. Agric. Econ. 2019; 101: 270–290. Publisher Full Text\n\nHunt C, Weber O, Dordi T: A comparative analysis of the anti-Apartheid and fossil fuel divestment campaign. J. Sustain. Finance Invest. 2017; 7: 64–81. Publisher Full Text\n\nIlyas R, Hussain K, Ullah MZ, et al.: Distributional impact of phasing out residential electricity subsidy on household welfare. Energy Policy. 2022; 163: 112825. Publisher Full Text\n\nInstitute for Sustainable Development [IISD]: Lessons Learned: Malaysia’s 2013 Fuel Subsidy Reform. 2014. Reference Source\n\nKhalid SA, Salman V: Welfare impact of electricity subsidy restructure in Pakistan: a micro model study. Energy Policy. 2020; 137: 111097. Publisher Full Text\n\nKojima M: Fossil fuel subsidy and pricing policies: recent developing country experience. World Bank Policy Research Working Paper. 2016; 7531. Publisher Full Text\n\nKyle J: Local corruption and popular support for fuel subsidy restructure in Indonesia. Comp. Pol. Stud. 2018; 51: 1472–1503. Publisher Full Text\n\nLi Y, Shi X, Su B: Economic, social and environmental impacts of fuel subsidy: A revisit of Malaysia. Energy Policy. 2017; 110: 51–61. Publisher Full Text\n\nLin B, Xu M: Good subsidies or bad subsidies? Evidence from low-carbon transition in China’s metallurgical industry. Energy Econ. 2019; 83: 52–60. Publisher Full Text\n\nLoo SY, Mukaramah L: Fuel subsidy abolition and performance of the sectors in Malaysia: A computable general equilibrium approach. Malays. J. Econ. Stud. 2019; 56(2): 303–326. Publisher Full Text\n\nMcCulloch N, Moerenhout T, Yang J: Fuel subsidy reform and the social contract in Nigeria: A micro-economic analysis. Energy Policy. 2021; 156: 112336. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMinistry of Finance: Largest ever Subsidy of RM77.3 bln for 2022 to Reduce Cost of Living for the People. 2022. Reference Source\n\nMundaca G: Energy subsidy, public investment and endogenous growth. Energy Policy. 2017; 110: 693–709. Publisher Full Text\n\nRentschler J, Bazilian M: Policy monitor—principles for designing effective fossil fuel subsidy restructure. Rev. Environ. Econ. Policy. 2020; 11: 138–155. Publisher Full Text\n\nSchaffitzel F, Jakob M, Soria R, et al.: Can government transfers make energy subsidy restructure socially acceptable? A case study on Ecuador. Energy Policy. 2020; 137: 111120. Publisher Full Text\n\nWorld Food Programme: Selection of Households or Individuals within Locations. 2023. Reference Source\n\nUmar HM, Umar MS: An assessment of the direct welfare impact of fuel subsidy restructure in Nigeria. Am. J. Econ. 2013; 3: 23–26.\n\nYuen YY: Fuel Subsidy Restructure Effectiveness. [Dataset]. Figshare. 2023a. Publisher Full Text\n\nYuen YY: FuelSubsidyRestuctureQuestionnaire. [Dataset]. Figshare. 2023b. Publisher Full Text"
}
|
[
{
"id": "206492",
"date": "03 Oct 2023",
"name": "Muhammad Safwan Ibrahim",
"expertise": [
"Reviewer Expertise Time series and statistical modelling"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript shows a lot of promise but requires several revisions to improve clarity and overall quality before publication. The detailed comments and suggestions for enhancing the paper are given below:\nIntroduction\nParagraph 1, line 3: Writing the full word \"liter\" in academic writing is better. This makes the writing more formal and easier to read.\nParagraph 1-3: I noticed that you only used one reference in the introduction. It is generally recommended to use multiple references in the introduction to support your claims and show that you understand the current state of knowledge on the topic.\nI found the introduction to be somewhat lacking in clarity. The main objective of the paper is not immediately apparent, and the reader is left wondering what the paper is trying to achieve. I recommend that you revise the introduction by clearly stating the objectives and providing a concise overview of the research problem and key challenges.\nLiterature review\n(Fuel subsidy restructure effectiveness) Paragraph 1, Lines 3 -5: It is better if you can provide the reference. Maybe the author can cite the 2010-2015 Malaysia Plan report.\n(Governance and administrative capacity) Paragraph 3, Lines 3-5: Are you sure that fossil fuel is used for cooking? Is this situation referred to as the Malaysia situation?\nMethods\nParagraph 1, Line 3: I think you need to have more references to justify your sample size, or you need to determine by yourself the number of sample sizes. You must also explain how you distribute the questionnaire to each state accordingly.\n(Sampling and pre-testing) Paragraph 2, Lines 1-3: How many samples do you use for pre-testing validation? How can collecting data face-to-face, it can result in lower errors? Which references do you refer to that say that when error and survey bias are low, the data will be reliable and generalizable? (Data collection) Paragraphs 1-2: Redundant paragraph. In paragraph 2, you say the study was conducted from September 2021 to November 2022. However, in paragraph 1 (under section Method), you say that the research was conducted from January 2022 to July 2022. So which one is true? (Analysis) Paragraph 2: Please elaborate further on how you analyse it using multiple linear regression. The current paragraph is too short and lacks clarity.\nResults\nParagraph 1, line 1: I noticed that you sometimes write numbers in numerals (e.g., 105) and sometimes in words (e.g., one hundred and five). I recommend that you be consistent in your use of numbers throughout the manuscript.\nParagraph 1, line 3: Redundant sentence.\nTable 1 does not show full information about the demographics of the respondents. For example, there is no information about the number of respondents from each state (Selangor, Johor, Kuala Lumpur). I think the household size, gender and race also should be included in the respondents' demographic. Table 3: No P-value for social protection and efficient targeting. If the p-value is too small, you can write it as <0.01. Paragraph 4, Last line: What justification do you use to say that H1-H4 are supported? I think you should elaborate in more detail.\n\nDiscussion and recommendation\nThe discussion can be further improved by more clearly explaining the implications of the findings towards Malaysia.\nConclusion\nThe conclusion could be made clearer by summarizing the main findings of the study and reiterating the implications of the findings.\nIn summary, this paper has the potential to make a valuable contribution to the field but requires significant revisions to improve clarity, coherence, and depth. Addressing the reviewer's comments and suggestions will enhance the quality and impact of the paper.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "212289",
"date": "19 Oct 2023",
"name": "Theresia Betty Sumarno",
"expertise": [
"Reviewer Expertise Fossil fuel subsidy policy (reforms)",
"carbon tax",
"energy taxation",
"energy fiscal policies",
"energy economics",
"climate change and sustainability",
"global business."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThere are some typos in the current work. The work needs a good proofread (for example succesflness, adminstration, incone, etc.). The way some statements being phrased could have been made clear. For example the last paragraph on the Introduction:\n\"Given the fact that out of the MYR 14 billion of fuel subsidy, the T20 households enjoyed MYR 8 billion while B40 households enjoyed less than RM6 billion of the fuel subsidy (Ministry of Finance, 2022), it is timely to investigate how B40 and M40 households think about fuel subsidy restructure and factors affecting the effectiveness of fuel subsidy restructure\".\n\"The middle income and the low income households are bound to suffer more loss to social protection when fuel subsidy restructure is not provided\" --> this statement is unclear. what fuel subsidy restructure? Do you mean the social protection? Proofreading will help to prevent this type of unclear statement.\n\nI will also highlight the value of the subsidy - it would have been better to have a USD equivalent to add more understanding for people from other countries.\nThe statistical result analysis could have been more in-depth by having some more literature study to support the discussion.\n\nThe justification of the cities being selected in the sample is needed. Why did the authors only do the three cities?\n\nThe implementation of the current fossil fuel subsidy needs to be explained further. As for now, I am not sure if the Government of Malaysia applies one price for all cities in the country, or if they could be different from one to another.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "212307",
"date": "30 Oct 2023",
"name": "Ronald Steenblik",
"expertise": [
"Reviewer Expertise My areas of expertise include subsidy analysis and subsidy reforms. I previously served as the OECD's Special Counsellor for Fossil Fuel Subsidy Reform. I am now a non-resident Senior Technical Advisor to the Sustainable and Just Economic Systems programme of the Quaker United Nations Office (QUNO) in Geneva."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe type of analysis provided by the paper is useful for informing the reform of fuel subsidies in Malaysia (and elsewhere), but the paper over-stresses the point. The authors certainly should not repeat the claim themselves (as they do several times). Is suffices to confine such self-evaluation to the last section (\"Unique contributions of this research\").\nIn general, the paper could benefit from a substantial edit, both to improve the English and to make it much more concise. The paper is marred by considerable repetition. With judicious editing its length could be reduced by at least one-third, possibly by one half.\nI would suggest that the authors speak of \"fossil fuel subsidy reform\" rather than \"fossil fuel subsidy restructure\" or \"... restructuring\". The former terminology is much more common and more likely to be located by searches on the topic.\nIntroduction\nThroughout the document, beginning with the Introduction, I would suggest providing USD equivalents within parentheses following the amount in Malaysian Ringgit (MYR), such as \"MYR 14 billion (USD 3.4 billion)\". In the first sentence, the year in which the MYR 14 billion was spent (2021? 2022?) needs to be specified. The currency (MYR) should be specified everywhere; it is missing, for example, in the opening sentence of the second paragraph.\nI would suggest also spelling out abbreviations the first time they occur, including RON 95, which stands for \"premium petrol or gasoline with a research octane number of 95\".\nThe first sentence if the third paragraph is redundant and can be deleted.\nLiterature review\nThis section is not so much a literature review as a restating of earlier points. Moreover, it is unclear to this reader why a an observation made in a paper from 2014 is used to explain the motivation behind the recent (post-Covid-19) fuel price reforms.\nSocial protection\nThe authors seem to use the term \"social protection\" both with respect to assurance of the necessities of life (2nd sentence of first paragraph in this section) and the amount of fuel-subsidy benefits (5th sentence of the same paragraph). That sows confusion later on in the paper. The authors should also avoid too many significant digits when citing statistics that are unlikely to be precise — e.g., they should round the average expenditure of high-income households from MYR 3849.8 to MYR 3850.\nGovernance and administrative capacity\nI find this section confusing, likely because some of the words are misused. The second sentence (\"According to Lin and Xu ...\") makes no sense to me. I think the authors mean \"unable\" not \"able\". But in any case, if the governance (of what?) and \"administrative capacity on\" (?) the infrastructure, education and health services of the nation are neither improved nor made worse as a result of fuel-subsidy reform, how does that render the reform ineffective? I am equally unsure of the point the authors are trying to make in the opening sentence of the 2nd paragraph.\nIn the third paragraph, the authors assert that \"fossil fuel subsidy is more important in improving the living conditions of the poor as low income people use fossil fuel more frequently in daily life for cooking and heating\". Are they referring to Malaysia? Because in the section on Efficient Targeting, the authors state, citing the same source, that \"Inefficient targeting has led to wealthy families and organizations consum[ing] fuel more frequent than poor families.\" I can understand that fuel costs likely constitute a larger share of a poor household's expenditure than of a wealthy household's, but that in terms of total benefits (in MYR), the more wealthy households benefit more. But if that is the case then the point needs to be made more clearly, ideally backing it up with actual data specific to Malaysia.\nEfficient targeting\nThe penultimate sentence in this section needs rewording. Currently it ends with \"the targeted recipient can receive affordable, inexpensive and efficient fuel subsidy restructure\". Come again?\nKnowledge gaps\nThis section provides very little information. It speaks of a \"recent poll\" but cites a source that is now nine years old. And then it ends with a sentence that simply repeats information about the reform programme already provided earlier.\nMethods\nThe opening sentence of this section needs rewriting for clarity. I think the authors mean something like \"This research was conducted by an experienced group of researchers, who approached 150 B40 and M40 households between January and July 2022.\"\nSampling and pre-testing\nI would add in parentheses after the first mention of purposive sampling: \"(also known as judgment, selective or subjective sampling)\". The time period of the cited houshold income categories — annual, I presume — needs to be specified.\nIn the last paragraph in this section, I would recommend changing the first sentence to \"Pre-testing validation was conducted face-to-face to ensure that the target respondents belonged to B40 or M40 households\", instead of \"... originated from B40 and M40 households\". In the last sentence, I'd change \"... the data will be reliable and generalizable\" to \"... the data will more likely be reliable and generalisable\".\n\nData collection\nThis section is characterised by considerable repetition of previous statements.\nResults\nAgain, there is a fair amount of repetition in this section.\n\nOften what were the questions in the questionnaire that respondents were asked to respond to is hard to discern in the English-language version (https://figshare.com/articles/dataset/FuelSubsidyRestuctureQuestionnaire/22492720), which has been roughly translated at best. Because of the rough translation it is hard for me to judge whether in many cases the questions were appropriate and would lead to unambiguous results. In the case of \"Section C: Governance and Administrative Capacity\", for example, some of the questions bear little relation to the discussion earlier in the text under the heading of \"Governance and administrative capacity\", and some of the questions seem more pertinent to social protection than governance or administrative capacity.\nDiscussion and recommendation\nWhile the findings seem logical, apart from the ranking of importance of general factors (Table 3), I find it difficult to relate the detailed recommendations to the numerical results, which seem to rely as much or more more on findings in other studies.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-704
|
https://f1000research.com/articles/11-1537/v2
|
20 Jun 23
|
{
"type": "Case Report",
"title": "Case Report: Rehabilitation of bilateral below-knee and partial-hand amputations in a developing country",
"authors": [
"Astika Cahya Noviana",
"I Putu Alit Pawana",
"Martha Kurnia Kusumawardani",
"I Putu Alit Pawana",
"Martha Kurnia Kusumawardani"
],
"abstract": "Limb ischemia is a complication of peripheral artery disease (PAD)which can lead to amputation. Amputation occurs in approximately 3-4% of PAD patients. In Indonesia, post-amputation patients are only hospitalized for the acute phase and the post-amputation rehabilitation programs must be done as an outpatient. This could be a barrier to the continuity of rehabilitation programs. A solution is the application of home-based rehabilitation programs. A 57-year-old female was referred from the Cardiothoracic Surgery Outpatient Clinic post-amputation with bilateral below-knees and partial-hands amputation after being diagnosed with PAD. On initial examination, all her elbows, wrists, thumbs, hips, and knees showed weakness. The patient received neuromuscular electrical stimulations (NMES) as well as a home-based rehabilitation programs. On the second examination, after considering the data from the clinical finding and supporting examination, the patient received bilateral below-knee prostheses and bilateral functional partial-hand prostheses, created using 3D printing technology with polylactic acid material. After a few months, she was able to do most of her activities of daily living (ADLs) independently, work as a shopkeeper in her store, and feel more confident interacting with others. A comprehensive rehabilitation programs, patient adherence to exercise, and caregiver support are critical to improving functional capacity and the quality of life in a patient with bilateral below-knee and bilateral partial-hand amputation caused by PAD.",
"keywords": [
"amputation",
"below-knee",
"partial-hand",
"peripheral arterial disease",
"prosthesis",
"3D printing technology"
],
"content": "Introduction\n\nPeripheral artery disease (PAD) is defined as arteriosclerotic occlusion disease of the extremities when one or more peripheral arteries become blocked, resulting in a decrease in blood flow to the peripheral area.1,2 In developed countries, the prevalence of PAD is comparable between men and women, and the incidence rises steadily with age, from 5% in the population aged 45-49 years to 18% in the population over the age of 85 years. However, in developing countries, women have a higher prevalence than men, with 6.3% and 2.9% at 45-49 years old and 12.3% and 10.1% at 75-79 years old, respectively.3 Between 2000 and 2010, the prevalence of PAD increased by about 200 million cases, with developing countries (29%) having a higher prevalence than developed countries (13%), and Southeast Asia and Western Pacific countries having the highest prevalence.3\n\nIntermittent claudication, caused by the insufficient blood supply to the legs, is the most common symptom experienced by PAD patients.1 Some patients with PAD, including those with moderate to severe cases, are frequently asymptomatic. A complication of this disease is limb ischemia, which can lead to amputation, which occurs in approximately 3–4% of PAD patients.4–6\n\nIn Indonesia, post-amputation patients are only hospitalized for the acute phase, which lasts less than a month. They must visit the rehabilitation center on a regular basis to receive the post-amputation rehabilitation programs. A barrier to implementing the rehabilitation programs is that the distance between the center and the patient’s home is sometimes great, requiring a significant amount of time and money to travel to the hospital. The solution to this problem is to create a home-based rehabilitation programs.\n\n\nCase presentation\n\nIn September 2019, a 57-year-old female Javanese was referred from the Cardiothoracic Surgery Outpatient Clinic post- bilateral below-knee and partial-hand amputations. In May 2019, she felt a tingling sensation on both of her soles, and a week later, she was numb and unable to walk. One week later, her second, third, and fifth tips of her toes had turned black, as had the left tip of her fifth finger. At that time, she also felt her right hand heavy and could not move it. In June 2019, she had ulcers on the tips of her toes. She was taken to the hospital by her family and diagnosed with PAD. The doctor amputated both of her lower legs and both of her second to fifth fingers. According to the July 2019 Doppler ultrasound examination, she still has non-significant stenosis on her right brachial artery and radial artery. She had also had hypertension for over ten years but did not routinely take the antihypertensive drug. Before she suffered from this condition, she had worked as a kindergarten teacher and participated in community activities. She hoped that she would be able to perform her activities of daily living (ADLs) independently and participate in social activities as before.\n\nThe muscle strength was measured using the manual muscle testing (MMT) method, and it was scored on a five-point scale.7 After examination, the muscles of her elbows, wrists, thumbs, hips, and knees were all weak, with the right wrist and thumb muscle strength remaining zero. Table 1 shows the detailed muscle strength examination results. Her right hand had a 20% sensory deficit. The condition of the partial-hands and below-knees stumps was quite good, except that there were still phantom sensations, and the pulse of the right radial artery was slightly weaker than the left side. For mobility, she still required the assistance of others with the wheelchair. The Barthel Index (BI) was 30 out 100, indicating that the patient was severely dependent8 As part of the rehabilitation programs, the patient received NMES on her right wrist and thumb with intensity until visible muscle contraction, ROM exercise for upper and lower extremities, sensory re-sensitization of the right hand, and pre-prosthesis preparation, namely gentle tapping on the stump, stump shaping using elastic bandage with figure of eight method, upper and lower extremities muscle strengthening, transfer exercise from bed to the wheelchair and vice versa, standing exercise with the knee and the forearm as the support, ADLs exercise and modification. Because the patient's home was far from the hospital, she underwent a home-based rehabilitation programs. She did the exercise for about 1-2 hours every day with the help of her family. The doctor would oversee the exercise via telephone and instant massage weekly. The weekly evaluation included adherence to exercise, complaints felt before and after exercise and evaluating the patient's ability to carry out daily activities. The patient would visit the Physical Medicine and Rehabilitation (PMR) outpatient clinic monthly to check her condition and evaluate the rehabilitation programs. Figure 1 depicts the rehabilitation timeline.\n\nIn November 2019, she had a Doppler ultrasound re-examination, and there was no occlusion on the artery in both her legs and arms (Table 2). Her muscle power in her upper and lower extremities improved significantly (Table 1). The patient met the requirements of the prostheses after considering the data from the clinical finding and supporting examination. The patient was fitted with bilateral below-knee prostheses as well as bilateral functional partial-hand prostheses. The hand prostheses were created using 3D printing technology with polylactic acid material. She was the first patient in our center to receive 3D-printed hand prostheses. The patient continued the pre-prostheses rehabilitation programs, which included standing balance exercises (while the patient held a chair), and the NMES was discontinued because it was no longer required since the MMT was satisfactory. She continued to do the home-based pre-prosthetics rehabilitation programs for about 1-2 hours per day.\n\nUnfortunately, due to the COVID-19 pandemic, the prostheses programs were delayed, but the patient continued to participate in the pre-prostheses home rehabilitation programs. In July 2020, the patient received her prostheses and began the prostheses rehabilitation programs. Standing balance exercises and gait training were added during this rehabilitation phase. To help with the gait training program, the patient’s family built a parallel bar in their home. She was able to do the gait training intensively for about two hours per day. In October 2020, the patient was able to walk with a walker and perform the majority of her ADLs independently, and her BI had improved (Figure 2). She could also work as a shopkeeper in her store and gained confidence in interacting with others.\n\n\nDiscussions\n\nAlthough amputation of the lower limb would impair the patients’ functional mobility, not all patients require a prosthesis. Some of them may get better mobility from using a wheelchair or crutches.9 Giving a prosthesis to the patient was challenging because the post-prosthetic outcome had to be predicted based on pre-prosthetic ability. Amputee Mobility Predictor (AMP) was used to measure the patient’s capability without prostheses and to predict her ambulation ability using prostheses.10,11 It is made up of 29 variables that could affect prosthetic use. Based on this tool, the patient was categorized as K1 level, a potentially good candidate for lower limb prostheses. The below-knee prosthesis comprises a foot unit, shank, socket, and suspension.12 The foot unit allows the amputee to stand and aids in the stance phase. The solid ankle cushioned heel (SACH) foot is the most commonly used foot prosthetic. It was chosen for this patient because of its durability and the foot unit choice for the K1 classification. The shank is a prosthesis component that is located above the foot. The patient was fitted with an endoskeletal shank. This shank type was chosen because it allows for minor adjustment after the prosthesis has been fabricated, and it is lighter than the exoskeletal shank, making it suitable for patients who require bilateral below-knee prostheses.12 To support the load in the patellar tendon, the patellar tendon bearing (PTB) socket was used, and the suspension was brim suspension (suprapatellar supracondylar suspension) to increase the stability when the patient stands and walks.\n\nAfter receiving bilateral below-knee prostheses, the patient began gait training in accordance with the International Committee of the Red Cross (ICRC) recommendations.13 The first step was to begin gait training on the parallel bar, starting with partial weight-bearing and partial weight-shifting training. After the patient was able to do it, she began to perform the prosthetic-leg step forward, backward, and through. The last gait training was walking between parallel bars. Because she was unable to attend the rehabilitation center on a regular basis, her family assisted the rehabilitation programs by constructing the parallel bars in their home. The patient diligently completed the gait training program while being monitored by the doctor via phone. She was able to return to the rehabilitation center after three months, and according to the evaluation, she was able to train to walk with a walker. The walker was chosen because it would assist the patient in maintaining her balance while walking. The patient was unable to use the crutches due to her hand condition. Initially, the patient used four-footed walkers. The patient stated that moving the walker was still challenging because she has difficulty grasping and lifting the walker while ambulating. The walker was converted to two-wheeled walker to accommodate the patient’s needs. The patient was satisfied after the modification. She was able to walk faster while remaining safe. This was similar to previous research that compared the use of four-footed and two-wheeled walkers in people with lower-limb amputation. The researchers concluded that the two-wheeled walker allowed people wearing lower-limb prostheses to walk faster and with less interruption, but it was no less safe than the four-footed walker.14\n\nThe bilateral functional partial-hand prostheses for this patient were created using 3D printing technology with polylactic acid material. She was the first patient in our center to receive 3D-printed hand prostheses. The scan of the extremity from various angles was required to create the computerized model for the 3D-printed prostheses. When compared to traditional prostheses, 3D-printed prostheses have advantages and disadvantages. The advantages of the 3D method are that it is less expensive because it requires less material and labor than the traditional one. Another advantage of this method is that the device is highly customizable. Because the 3D files were saved digitally, they were simple to modify to meet the needs and comfort of the patient. The disadvantages of 3D-printed prostheses include decreased grip strength, durability, fine motor skill, and difficulty lifting heavy objects.15 This patient found the hand prostheses to be uncomfortable and found it difficult to use them on a daily basis. She broke the first-hand prosthetic models. To accommodate the patient’s needs, the prostheses were revised, using more sturdy models and the robotic hand 3D prostheses model. Unfortunately, she chose not to use the hand prostheses, but she could perform the majority of her ADLs independently. Overall, after the rehabilitation programs, the patient felt satisfied, and her confidence increased. Apart from being able to perform most of her ADLs independently, the patient began to feel confident in running her grocery shop at home as a cashier.\n\nThe home-based rehabilitation programs applied in this case study have advantages but also some limitations. The home programs could reduce contact between the doctor or physiotherapist (PT) and the patients, which was essential to address, especially during the COVID-19 pandemic. It also gave the patient flexibility to choose the exercise time, reduced physical barrier (because the patient home was far from the rehabilitation center), reduced transportation fee for car rental, and reduced the caregiver's absence from work caused by accompanying the patient to the hospital. The limitations of the home-based rehabilitation programs are that the doctor and PT cannot supervise the exercise directly. In order to overcome this limitation, before the home programs started, the doctor would explain it to the patient and caregiver. Once a week, the doctor will evaluate the exercise by phone: the symptom that the patient felt before and after exercise, to ensure that the patient exercises regularly and rehabilitation program adjustments if needed.\n\n\nConclusions\n\nA patient who has had PAD and amputation must undergo rehabilitation programs as soon as possible. The key to improving functional capacity and the quality of life in a patient with bilateral below-knee and bilateral partial-hand amputation caused by PAD is a comprehensive rehabilitation programs, patient adherence to exercise, and caregiver support. Prostheses and walking aids also played an essential role in assisting them in achieving their functional abilities.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and/or clinical images was obtained from the patient.\n\n\nAuthor roles\n\nNoviana AC: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Software, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Pawana IP: Conceptualization, Data Curation, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Review & Editing; Kusumawardani MK: Data Curation, Investigation, Resources, Writing – Review & Editing",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nCriqui MH, Aboyans V: Epidemiology of Peripheral Artery Disease. Circ. Res. 2015; 116(9): 1509–1526. Publisher Full Text\n\nTreat-Jacobson D, McDermott MM, Beckman JA, et al.: Implementation of supervised exercise therapy for patients with symptomatic peripheral artery disease a science advisory from the American Heart Association. Circulation 2019; 140(13): e700–e710. PubMed Abstract | Publisher Full Text\n\nFowkes FGR, Aboyans V, Fowkes FJI, et al.: Peripheral artery disease: Epidemiology and global perspectives. Nat. Rev. Cardiol. 2016; 14: 156–170. PubMed Abstract | Publisher Full Text\n\nSteffen LM, Duprez DA, Boucher JL, et al.: Management of Peripheral Arterial Disease. Diabetes Spectr. 2008; 21(3): 171–177. Publisher Full Text\n\nWrobel JS, Mayfield JA, Reiber GE: Geographic Variation of Lower- Extremity Major Amputation in Individuals With and Without Diabetes. Diabetes Care 2001; 24(5): 860–864. PubMed Abstract | Publisher Full Text\n\nFirnhaber JM, Powell CS: Lower Extremity Peripheral Artery Disease: Diagnosis and Treatment. Am. Fam. Physician 2019; 99(6): 362–369. PubMed Abstract Reference Source\n\nAvers D, Brown M: Daniels and Worthingham’s Muscle Testing: Techniques of Manual Examination and Performance Testing . Elsevier Inc.; 2018; vol. 416. .\n\nSchulte OJ, Stephens J: Ann J. Aging, Dementia, and Disorders of Cognition. Umphred’s Neurological Rehabilitation Missouri: Elsevier; 6th Edition. 6th Editio.2013; p. 835–861.\n\nCondie ME, McFadyen AK, Treweek S, et al.: The trans-femoral fitting predictor: A functional measure to predict prosthetic fitting in transfemoral amputees-validity and reliability. Arch. Phys. Med. Rehabil. 2011; 92(8): 1293–1297. PubMed Abstract | Publisher Full Text\n\nGailey RS: Predictive Outcome Measures Versus Functional Outcome Measures in the Lower Limb Amputee. J. Prosthet. Orthot. 2006; 18(2): P51–P60. Publisher Full Text\n\nMduzana LL, Visagie S, Mji G: Suitability of ‘Guidelines for Screening of Prosthetic Candidates: Lower Limb’ for the Eastern Cape, South Africa: A qualitative study. South African J Physiother. 2018; 74(1): 1–9. Publisher Full Text\n\nMoroz A, Flanagan S, Zaretsky H: Medical Aspects of Disability for the Rehabilitation Professional New York: Springer Publishing Company; Fifth ed2016.\n\nICRC: Exercises for Lower-Limb Amputees International Committee of the Red Cross; 2008. Reference Source\n\nTsai HA, Kirby RL, MacLeod DA, et al.: Aided gait of people with lower-limb amputations: Comparison of 4-footed and 2-wheeled walkers. Arch. Phys. Med. Rehabil. 2003; 84(4): 584–591. PubMed Abstract | Publisher Full Text\n\nRibeiro D, Cimino SR, Mayo AL, et al.: 3D printing and amputation: a scoping review. Disabil. Rehabil. Assist. Technol. 2019; 16: 221–240. Publisher Full Text"
}
|
[
{
"id": "186911",
"date": "21 Aug 2023",
"name": "Jie Hao",
"expertise": [
"Reviewer Expertise Physical therapy",
"rehabilitation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis case study reports the post-amputation rehabilitation of a patient with bilateral below-knee and partial-hand amputations. Due to the limited healthcare resource and the barriers for the patient to attend outpatient rehabilitation, home-based rehabilitation programs were created and customized to the patient’s conditions. The home-based rehabilitation programs were supervised by a physician with monthly office visits and telephone/message communication throughout the process. The rehabilitation included pre-prosthetic and post-prosthetic phases. The patient demonstrated increased muscle strength, improved balance and gait abilities, restored functional mobility and independence, and finally was able to return to work as a shopkeeper.\nThe case study was overall well written and has good implications for the delivery of amputation rehabilitation in developing countries where barriers often exist for patients to access in-person rehabilitation in facilities. This manuscript can be improved by adding more details to the rehabilitation interventions, particularly, the home-based rehabilitation programs. As the patient was on her own with the assistance of family while performing these exercises and activities, it would be important to have detailed instructions for exercises and activities including frequency, intensity, type, and duration. In addition, including the range of motion measurements of the bilateral knee throughout the course of rehabilitation is warranted because one of the goals for below-knee amputation rehabilitation should be to achieve full knee extension and restore hip extension. Adding the score of the Amputee Mobility Predictor will provide readers with a better understanding of the patient’s mobility function prognosis after amputation.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
},
{
"id": "241947",
"date": "15 Feb 2024",
"name": "Huthaifa Atallah",
"expertise": [
"Reviewer Expertise prosthetics and orthotics",
"biomechanics",
"gait. outcome measures",
"rehabilitation"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTitle: Case Report: Rehabilitation of bilateral below-knee and partial-hand amputations in a developing country Reviewer’s comments: Thank you for your submission and the opportunity to review your work! Below are the comments that I’m recommending to be considered: - Amputee Mobility Predictor (AMP) was not mentioned with the other tools under the case presentation. - \"(SACH) foot is the most commonly used foot prosthetic\": This is not correct, or be more precise about the area/country\n\n- \"The shank is a prosthesis component that is located above the foot\": No need to mention the functions of prosthetic components. - be simple: PTB socket design was used. no need for extra explanation. - mention some possible reasons for rejecting (not using) the upper limb prostheses\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 2
|
https://f1000research.com/articles/11-1537
|
https://f1000research.com/articles/12-374/v1
|
06 Apr 23
|
{
"type": "Software Tool Article",
"title": "CRUMB: a shiny-based app to analyze rhythmic feeding in Drosophila using the FLIC system",
"authors": [
"Sergio Hidalgo",
"Joanna C Chiu"
],
"abstract": "Rhythmic feeding activity has become an important research area for circadian biologists as it is now clear that metabolic input is critical for regulating circadian rhythms, and chrononutrition has been shown to promote health span. In contrast to locomotor activity rhythm, studies conducting high throughput analysis of Drosophila rhythmic food intake have been limited and few monitoring system options are available. One monitoring system, the Fly Liquid-Food Interaction Counter (FLIC) has become popular, but there is a lack of efficient analysis toolkits to facilitate scalability and ensure reproducibility by using unified parameters for data analysis. Here, we developed Circadian Rhythm Using Mealtime Behavior (CRUMB), a user-friendly Shiny app to analyze data collected using the FLIC system. CRUMB leverages the ‘plotly’ and ‘DT’ packages to enable interactive raw data review as well as the generation of easily manipulable graphs and data tables. We used the main features of the FLIC master code provided with the system to retrieve feeding events and provide a simplified pipeline to conduct circadian analysis. We also replaced the use of base functions in time-consuming processes such as ‘rle’ and ‘read.csv’ with faster versions available from other packages to optimize computing time. We expect CRUMB to facilitate analysis of feeding-fasting rhythm as a robust output of the circadian clock.",
"keywords": [
"Feeding-fasting rhythm",
"FLIC",
"Shiny",
"Drosophila",
"Circadian clock",
"chrononutrition",
"time-restricted eating"
],
"content": "Introduction\n\nThe fly Drosophila melanogaster has been used for several decades to understand the molecular and neuronal basis of behavior.1,2 This animal has been instrumental in the description of the circadian clock,3–10 the machinery that allows animals to maintain daily rhythms in physiology and behavior. A common behavioral output used to assess circadian rhythmicity is locomotor activity, which is considered by many as a gold standard. Commercial options such as the Trikinetics Drosophila Activity Monitoring System (DAMS) have made it possible to conduct high throughput screening of clock mutants11–13 and functional experiments to dissect molecular and cellular mechanisms regulating circadian rhythms.14,15 Nonetheless, this behavior is only one example of circadian clock behavioral output. Feeding-fasting rhythm is also strongly regulated by the clock, although mechanisms required for maintaining food intake rhythm differ from those used in the regulation of circadian locomotion.16–20\n\nIn contrast to locomotor activity rhythms, technical advances to assay feeding rhythms have lagged. A popular option is the Capillary Feeder (CAFE) assay, which allows for the quantification of the amount of feeding by means of measuring the movement of a meniscus along a capillary tube.21 This assay has proven useful in capturing the feeding rhythms of groups of flies; however, the distance of the meniscus is only evident when a significant amount of liquid food has been consumed and thus its temporal resolution is limited. In 2014, Scott Pletcher’s lab developed FLIC (Fly Liquid-Food Interaction Counter), a new system to assess feeding which allows for continuous monitoring (millisecond scale) and scalability, promising high throughput recordings.22 Since then, several other groups have adopted the system and used it to address different biological questions including rhythmic feeding and metabolic homeostasis.18,23–32\n\nAvailable options of software to analyze locomotor activity from DAMS have multiplied over the years, offering different user interphases and developed in different coding languages33–37 (summarized in Cai et al.15). In contrast, due to its recent implementation, user-friendly tools to analyze FLIC data are still scarce,23 and available scripts require the user to understand and use R coding syntax. Here we present CRUMB (Circadian Rhythm Using Mealtime Behavior), a shiny app based on the popular DAMS Shiny app Shiny-R DAM combined with the core FLIC code master scripts provided with the equipment (GitHub FLIC R code). CRUMB leverages features from several packages including ‘plotly’ and ‘DT’, to generate easily manipulable graphs and data tables. CRUMB also uses some of the versatile tools offered by the ‘zeitgebr’ package35 to enable easy and comprehensive circadian analysis—all of this wrapped in a simple Graphical user interface (GUI) provided by the ‘shiny’ package.\n\n\nMethods\n\nInitialization\n\nInitialization of the app must be conducted from the ‘app.R’ script. On the first usage, if ‘shiny’ or any other package is not installed, running this script will prompt a message indicating the list of missing packages and asking for installation. Following this process, CRUMB will be started and ready to run. The tabs on this app are organized in the required order of use, meaning that processes in the tab ‘File loading & QC’ are required for the subsequent tab ‘Initial Survey’, which then is required for subsequent tabs and so forth.\n\nInput files\n\nThe current version of CRUMB supports the original, unedited CSV files from the FLIC-MCU-2 system (Sable Systems International, NV). Further testing is needed to determine its suitability for other versions of the FLIC-MCU system. Given that the time resolution provided by FLIC monitors is in the scale of milliseconds, file sizes are correlated to the length of the recordings. For a full day of recordings, the file size is 44.4 MB. Although CRUMB is designed to analyze the data of several consecutive days, shorter recordings/files can be used as input but some functionalities (i.e., circadian analysis) will not be available.\n\nTo load the files, use the ‘Browse’ button. Select the file or files, from one or several different monitors. After loading, use ‘Cache data & Populate dates’ to engage the files and populate the dates of the experiments and monitor numbers (Figure 1A).\n\n(A) Raw data files and dates of the experiment are loaded in step 1. In step 2, the user can select parameters to baseline the raw data by choosing (i) a baseline function and time duration window for the Running Median option. Additional parameters including (ii) a binning interval and (iii) a binning function can be indicated for visualization purposes. (B) Baselined data are visualized using ‘plotly’ interactive graphs, allowing individual inspection of data. Data can be downloaded as CSV files.\n\nBaseline data & QC\n\nFeeding events are calculated from the baselined data obtained from FLIC monitors. In CRUMB, this baseline can be calculated using one of two functions: running median or asymmetric least squares. The running median is the original method used in the FLIC master code, adopted by CRUMB, and requires a window in minutes to calculate the median for subtraction. If desired, data can be trimmed by choosing the start and end date. This trimming is made to the raw data, preventing unnecessary processing, and therefore reducing computation time. For visualization purposes, a binning interval and a binning function are needed. By default, these values are set to ‘1 hour’ and ‘Sum’, respectively (Figure 1A). Note that if recordings are shorter than this interval, the data will be represented as a unique point. Once these parameters are set, press ‘Baseline data!’. Graphs are compiled using the ‘plotly’ package, an interactive interface that permits easy inspection of the graphs, allowing the selection of individual points and areas within the plots (Figure 1B). The isolation of tracks in ‘plotly’ graphs can thus be used to visualize individual flies to look for anomalies or drifting in the baseline due to liquid food overfill.\n\nInitial survey\n\nThe tab in Figure 2A (‘Initial Survey’) allows assigning names and colors to the different conditions present in the experiment. Given that CRUMB allows input from several FLIC monitors, an option to choose the monitor is available. This is populated with the monitor number extracted from the filenames. We recommend that the users use two or more conditions per monitor to account for variability between monitors. Because of this, CRUMB allows assigning wells from the same monitor to different conditions. Use the boxes on the right to check or uncheck the wells. If the same condition is repeated in different monitors (i.e., flies from the same genotype in two or three monitors), adding another condition with the same name will allow the pooling of the data in subsequent analyses (Figure 2A). If no names are assigned, fields will be populated automatically with the default name “Condition”.\n\n(A) In step 1, users can define conditions per monitor and/or wells. Step 2 allows the selection of the parameters required to calculate feeding events based on the baseline data. The ‘Parameter Description’ image (modified from FLIC code master) provides definitions for these factors. (B) After the calculation, the summary section displays the processed data as individual events per fly/well (top left), average events per group (top right and bottom left), and the number of events across days for each fly (bottom right). The feeding activity of each well can be scaled to the highest value of that well throughout the duration of the experiment by using the normalization switch. This selection is inheritable, meaning that the rest of the analysis will be conducted with the normalized data. Additionally, users can select outliers from the ‘Individual Stats’ table to exclude them from the rest of the analysis.\n\nThe FLIC system is designed so events that meet certain criteria can be considered feeding events (Figure 2A). These parameters correspond to the feeding minimum (minimum value of the baselined signal to consider an interaction), feeding threshold (threshold value that consecutive interactions need to pass to consider the event as feeding), number of consecutive licks (minimum number of interactions required to define a feeding event) and gap (time between events to consider consecutive events as one single event). The setting of these parameters can be tuned and tailored to each monitor and need to be determined empirically.\n\nOnce parameters are defined, clicking ‘Get Events!’ will initiate the calculations. This process is the most machine-demanding of the entire analysis, and the time spent on it correlates with the length of the input files. Additionally, permissive parameters will result in more events being considered, increasing the processing time.\n\nThe output summary is composed of four main elements that allow the inspection of the data (Figure 2B). First, an ‘Individual Stats’ table and a ‘Group Stats’ table are displayed to show the total number of events per fly and the average, standard deviation (SD), and standard error of the mean (SEM) for the groups indicated in the previous step, respectively. Second, two graphs are displayed, a boxplot of the total events per condition showing individual points and a graph of events per day throughout the duration of the experiment. Given the variability of the data, it is possible to enable or disable normalization, which divides the binned events of each fly by the sum of all the events per fly. This will impact the display of the feeding events and average event profiles in the next tab, ‘Feeding Analysis’, and the calculations in the ‘Circadian Analysis’ tab.\n\nThe function of this summary is two-fold: 1) it allows for inspection of the data for each individual fly and pooled data and 2) allows for the exclusion of dead flies. The criterion to consider dead individuals may vary but data from this section can provide guidance. For example, from the ‘Individual Stats’ table, flies that fail to show any events above a threshold defined by the experimenter can be excluded. Also, the boxplot of total events facilitates the determination of outliers as they will be marked by a black dot next to the data point. Finally, flies that do not survive for the entire experiment can be excluded. This information can be extracted from the ‘Events per day’ graph. To exclude individuals from the rest of the analyses, simply select them in the ‘Individual Stats’ table by clicking them.\n\nFeeding analysis\n\nThe ‘Feeding Analysis’ tab (Figure 3) displays binned events across several days of recordings and average daily events (feeding profile). To access these, the user must indicate a binning interval (1 min, 30 min, or 1 hour), binning function (Sum or Mean), and descriptive statistic represented by the error bars (SEM, SD, or None) (Figure 3). The generated graphs are also interactive and allow the resizing of the axis and zoom of particular windows within the graph.\n\nUsers can access and visualize the feeding events across the duration of the experiment (top graph) with the time resolution defined by (i) a binning interval and (ii) a binning function. The daily feeding events are averaged and displayed as an activity profile graph (middle graph) with gray backgrounds indicating when the lights are off. The duration of day and night can be selected under ‘Light Transition’ from the left panel where the region between the two sliders is when the light is on (red line). This selection also serves to calculate the daytime feeding events (bottom left graph and table) and nighttime feeding events (bottom right graph and table) per well. Error bars for the top two graphs can be defined by the user as Standard Error of the Mean (SEM), Standard Deviation (SD), or can be omitted if desired, by selecting ‘None’. Additionally, data are available as CSV files for download using the download buttons below each graph.\n\nThe user can indicate the time of lights on and off using the light transition feature. This information is used to determine which events occurred during the day and which events occurred during the night. This information is summarized in data tables and in boxplots (Figure 3).\n\nCircadian analysis\n\nThe circadian analysis is carried out in the ‘Circadian Analysis’ tab, and the current version of CRUMB allows the setting of the start and end date of the constant darkness (DD) period and a slider to choose the range of periods (in hours) that are included in the circadian analysis (Figure 4). CRUMB uses the autocorrelation function estimation to get the period and power for rhythmicity from the ‘stats’ package wrapped in the periodogram function from the ‘zeitgebr’ package.\n\nIn this tab, users can calculate the rhythmicity of feeding events from data collected under constant darkness using autocorrelation analysis. A range of possible period lengths can be specified for this calculation. An average periodogram (top left) and a graph of the maximum power values per well (top right) are displayed. Dotted lines indicate the threshold for the significance of periods and error bars are displayed as SEM. A summary table with this information is also provided (bottom) and can be downloaded as a CSV file.\n\nThe output of this analysis is a periodogram graph, showing the period over the power from the autocorrelation function and a boxplot of the highest power for each condition. Finally, a table (exportable as CSV) is obtained with the period, the highest power for each fly, and the p-value for that period estimation. The significant threshold (signif_threshold) is also shown in the table and is displayed as dotted lines in the periodogram and the power graphs (Figure 4).\n\nOperation (minimal system requirements needed to run the software)\n\nCRUMB was developed with R version 4.0.3 using the FLIC master code version 4.0 from the Pletcher lab as a backbone, modified and wrapped in a shiny app to manage the GUI using Shiny version 1.7.4. No internet connection is required to run the app but if any required package is missing, the user will be prompted with the option to download and install them from CRAN, and the completion of these actions requires internet access. Output graphs can be obtained from ‘plotly’ features as PNG files.\n\nOutput tables are in CSV format and can be opened using any compatible spreadsheet application including Microsoft Excel, Apple Numbers, or any other spreadsheet application.\n\nDefault: determining rhythmicity\n\nCRUMB can be used to determine differences in the number of feeding events as a means to understand the motivation and innate status of flies or survey rhythmic feeding behavior to understand circadian control of feeding. Here we show one example of CRUMB used to determine feeding rhythmicity in a control strain (w1118) compared with mutant flies with a defective circadian clock (w1118; clkout; annotated as clkout).38 In this example, CSV files collected from FLIC Monitor 1 across 7 full days were used as input. Wells from 1 to 6 correspond to clkout flies while wells 7 to 12 correspond to w1118 flies. Further, default settings for all parameters for baseline calculation and for feeding event detection was used; a threshold of 5 was set as the minimum and 15 was chosen as the top limit. Flies were kept in 12 hours light:12 hours dark (12:12 LD) cycles for three days, with lights on at 09:00 am and lights off at 09:00 pm, and then changed to constant darkness for four days. As expected, feeding events for w1118 flies peak close to the light transition (Figure 5A), both at dawn and dusk. Although this is different from reports showing only a single peak at dawn using the CAFE assay,20,39,40 this result is consistent with other articles using the FLIC assay.18,22,32 This discrepancy highlights the advantage of using an assay with high time resolution such as FLIC. Consistent with previous studies,39 while w1118 flies show a circa 24 period in feeding behavior (Figure 5B; black line) clkout mutants display arrhythmic feeding behavior (Figure 5B; red line). This is not due to a reduction in feeding events as no differences are found in the average number of daytime events or the average number of nighttime events (Figure 5C and D, respectively).\n\n(A) Feeding activity was recorded for 2 days under 12:12 light-dark cycles followed by 4 days in constant darkness (DD) for a circadian mutant (clkout, red) and control flies (w1118, black). Average activity across days for control flies shows increased feeding activity anticipating lights on (09:00, blue arrow) and lights off (21:00, blue arrow), which is absent in mutant flies. (B) Control flies show a 24 h period of feeding activity as seen in the periodogram (black lines, blue arrow), a feature that is not observed for the mutant flies (red line). The dotted line represents the threshold for significance in the autocorrelation analysis. Analysis of average daytime (C) and nighttime (D) feeding events shows no difference between mutant (red) and control (black) flies. Error bars in A and B are displayed as SEM.\n\n\nConclusions\n\nThe development of FLIC offers a new, high throughput option for continuous measurement of feeding events.22 In contrast to DAMS for locomotor activity, FLIC system lacks easy-to-use options for data analysis. Here, we addressed this gap by developing CRUMB, a Shiny-based app for FLIC data analysis. Our platform offers a pipeline to analyze feeding events over several days and extract key rhythmic data such as day and night feeding events and feeding rhythmicity.\n\nCRUMB uses the FLIC master code backbone, which offers compatibility with previous analysis. Also, we increased calculation speed by dropping some collected data, such as the number of licks or time of feeding events. We believe that this trade-off is crucial when analyzing long recordings necessary for circadian rhythm analysis, which require longer computing time. Although these parameters have been used in other studies,31,32 obtaining the number of events allows for the extraction of key circadian features of the feeding behavior, such as period and rhythmicity. Future versions could include these data points as selectable options, to adjust to the experimenters’ needs.\n\nAlthough our app offers in-site statistical analysis, output files can be obtained from all the analysis, allowing the export of processed data to other statistical software such as GraphPad Prism or Matlab. This could be particularly useful if in-depth statistical analysis is required, a feat that CRUMB is unable to achieve.\n\nFinally, CRUMB is open-access, and the code is freely available, which hopefully will promote the use of this tool as a backbone for other functions required for the community. Although CRUMB was initially conceived with circadian analysis of feeding in mind, the app can be expanded to include analysis of food choices, also available in the FLIC system.",
"appendix": "Data availability\n\nExample data used in this paper are available as part of the CRUMB app on GitHub (CRUMB GitHub).\n\nZenodo: ClockLabX/CRUMB: Version 1.0 (v1.0.0), https://doi.org/10.5281/zenodo.7738298. 41\n\nData are available under the terms of the Creative Commons Attribution 4.0 International License (CC-BY-04).\n\nSource code available from: https://github.com/ClockLabX/CRUMB.git\n\nArchived source code at time of publication: https://doi.org/10.5281/zenodo.7738298. 41\n\nLicense: MIT license.\n\n\nAcknowledgments\n\nWe thank members of the Chiu Lab for their valuable comments on the development of this work, especially Christine Tabuloc and Kyle Lewald.\n\n\nReferences\n\nKasture AS, Hummel T, Sucic S, et al.: Big Lessons from Tiny Flies: Drosophila melanogaster as a Model to Explore Dysfunction of Dopaminergic and Serotonergic Neurotransmitter Systems. Int. J. Mol. Sci. 2018; 19: 1788. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nFulgham CV, Dreyer AP, Nasseri A, et al.: Central and Peripheral Clock Control of Circadian Feeding Rhythms. J. Biol. Rhythm. 2021; 36: 548–566. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchmid B, Helfrich-Förster C, Yoshii T: A new ImageJ plug-in “actogramJ” for chronobiological analyses. J. Biol. Rhythm. 2011; 26: 464–467. PubMed Abstract | Publisher Full Text\n\nGilestro GF, Cirelli C: pySolo: a complete suite for sleep analysis in Drosophila. Bioinformatics. 2009; 25: 1466–1467. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGeissmann Q, Rodriguez LG, Beckwith EJ, et al.: Rethomics: An R framework to analyse high-throughput behavioural data. PLoS One. 2019; 14: e0209331. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDonelson N, Kim EZ, Slawson JB, et al.: High-resolution positional tracking for long-term analysis of Drosophila sleep and locomotion using the “tracker” program. PLoS One. 2012; 7: e37250. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCichewicz K, Hirsh J: ShinyR-DAM: a program analyzing Drosophila activity, sleep and circadian rhythms. Commun. Biol. 2018; 1: 25. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMahesh G, Jeong E, Ng FS, et al.: Phosphorylation of the Transcription Activator CLOCK Regulates Progression through a ∼24-h Feedback Loop to Influence the Circadian Period in Drosophila. J. Biol. Chem. 2014; 289: 19681–19693. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi YH, Liu X, Vanselow JT, et al.: O-GlcNAcylation of PERIOD regulates its interaction with CLOCK and timing of circadian transcriptional repression. PLoS Genet. 2019; 15: e1007953. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu X, Blaženović I, Contreras AJ, et al.: Hexosamine biosynthetic pathway and O-GlcNAc-processing enzymes regulate daily rhythms in protein O-GlcNAcylation. Nat. Commun. 2021; 12: 4116–4173. 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}
|
[
{
"id": "168914",
"date": "21 Apr 2023",
"name": "Abhilash Lakshman",
"expertise": [
"Reviewer Expertise organismal biology",
"chronobiology",
"animal behavior",
"neuroscience",
"computational biology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript by Hidalgo and Chiu is an important and timely contribution to the Drosophila rhythms community and describes a very useful and easy to implement application to analyze feeding rhythms in flies. The application allows users to analyze data from the FLIC system and from what I understand the FLIC assay from Scott Pletcher’s lab is becoming a more popular tool to assay long-term feeding in flies, and therefore, this application will be an asset to the field. I feel like the strengths of the application lay in, (i) the availability of several options for analyses, downloads, (ii) the ability to analyze multiple conditions simultaneously, (iii) the use of plotly which makes it easy for dynamic visualization of data, and (iv) that it is a freely available tool.\nHere are my specific comments that I feel may improve the manuscript:\nIn the Introduction, the authors talk about several software options to analyze Drosophila locomotor activity rhythms, but do not cite several of the new and some old programs too. It is important to have them cited here.\n\nMany of the packages used by the authors such as DT, plotly and shiny (and others) are lacking appropriate citations, which must be provided.\n\nBaseline data and QC section: If I understand correctly, due to some constraints imposed by the detection system, some baselining is required. The authors talk about two ways of baselining the raw data, i.e., running median and asymmetric least squares. It is important for the authors to describe how these two are different and under what circumstances one should choose one or the other method. For this manuscript to be a standalone resource for analyzing FLIC data, such clarification is critical. Also, in my opinion while the binning interval is intuitive and obvious, it may not be particularly clear as to when using ‘mean’ binning function would be biologically meaningful/relevant. The authors are requested to clarify these and provide examples of when one choice would make more sense than the other.\n\nIn the parameter selection section, the authors talk about how the minimum threshold, feeding threshold, number of consecutive licks and gaps must be tailored to each monitor and need to be determined empirically. This is not clear to me. Based on what should one determine what is an acceptable parameter value? Are there example citations? The authors should cite and/or describe the influence of these settings on outcomes of the analyses and how this could affect downstream interpretations. Maybe some examples would help. For a reader coming across this paper, that would be crucial information.\n\nIn the third section (Figure 3), there is an additional tab for binning length and binning function. I don’t see any description of how this is different from the same input in section 1. For example, can the binning length and function be different in sections 1 and 3? Either way, it is important for the authors to state it explicitly.\n\nAlso, the daytime and nighttime feature is great. But how is the computation carried out for subjective day and nighttime under constant conditions if the users have provided long-term DD recording? If this is not possible at the moment, a cautionary note would be important.\n\nIn the ‘Use Case’ section, I am assuming that the autocorrelation period analysis is being performed for the four days in DD. This is not clearly described in the text. If this is indeed the case, the authors must clarify, while adding a disclaimer that four days is anyway too short for using time-series methods robustly. If the authors have long-term (7-day) recording and they can use it, that would be great. But it’s absolutely fine if they don’t have that.\n\nAlso, in panels C and D, is the data considered only from LD? If so, there is some other interesting thing going on here: if this is in LD, and there is no difference between day and nighttime feeding events in the clock mutant; does that mean that feeding rhythms, unlike locomotor activity, does not mask to light/dark transitions? I think this may be worth pointing out because this adds a new dimension to the behavior that you have been able to identify using your new tool. Also, I think showing the time-course of feeding activity over the entire duration of seven days may be useful to the reader.\n\nThere also seems to be some discrepancy between the text and figure legend. The text says three days in LD and four days in DD, and the legend says two days in LD and four days in DD. Please clarify.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Partly\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Partly\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "9755",
"date": "29 Nov 2023",
"name": "Joanna Chiu",
"role": "Author Response",
"response": "Response to Reviewer 1- Abhilash Lakshman (Our responses are in italics) This manuscript by Hidalgo and Chiu is an important and timely contribution to the Drosophila rhythms community and describes a very useful and easy to implement application to analyze feeding rhythms in flies. The application allows users to analyze data from the FLIC system and from what I understand the FLIC assay from Scott Pletcher’s lab is becoming a more popular tool to assay long-term feeding in flies, and therefore, this application will be an asset to the field. I feel like the strengths of the application lay in, (i) the availability of several options for analyses, downloads, (ii) the ability to analyze multiple conditions simultaneously, (iii) the use of plotly which makes it easy for dynamic visualization of data, and (iv) that it is a freely available tool. We thank the reviewer for taking the time and effort to thoroughly review this manuscript and for giving such insightful comments. The manuscript has been modified to address all the comments. Here are my specific comments that I feel may improve the manuscript: In the Introduction, the authors talk about several software options to analyze Drosophila locomotor activity rhythms, but do not cite several of the new and some old programs too. It is important to have them cited here. We apologize for this oversight. Although we referenced some software for DAMS data analysis, not all were included. We have now updated the references in the introduction to include the following: Gosh and Sheeba, 2022; Persons et al., 2022; Sisobhan et al., 2022; Abhilash & Shebaa, 2019; Gierke and Cornelissen, 2016. Many of the packages used by the authors such as DT, plotly and shiny (and others) are lacking appropriate citations, which must be provided. Although references to the GitHub pages to the respective packages and related articles were included, the citations to the CRAN repositories were not included. We have now included appropriate citations for the packages used when first mentioned in the article. Baseline data and QC section: If I understand correctly, due to some constraints imposed by the detection system, some baselining is required. The authors talk about two ways of baselining the raw data, i.e., running median and asymmetric least squares. It is important for the authors to describe how these two are different and under what circumstances one should choose one or the other method. For this manuscript to be a standalone resource for analyzing FLIC data, such clarification is critical. Also, in my opinion while the binning interval is intuitive and obvious, it may not be particularly clear as to when using ‘mean’ binning function would be biologically meaningful/relevant. The authors are requested to clarify these and provide examples of when one choice would make more sense than the other. Indeed, due to some constraints relative to the FLIC detection system, such as food evaporation or well flooding, the baseline signal drifts and shifts considerably. Because of this, baseline correction is required. The standard running median is recommended and has advantages, including that it is extremely fast. However, it requires the selection of a time window to run iterative calculations. Here we use Asymmetric Least Squares (ALS) as an alternative given that it does not require user input, thus automatizing the baselining and promoting reproducibility in data analysis. This is an important point we omitted initially from the article, but it is now included. Additionally, suggestions on the use of the binning intervals are described in the “Feeding analysis” section. In the parameter selection section, the authors talk about how the minimum threshold, feeding threshold, number of consecutive licks and gaps must be tailored to each monitor and need to be determined empirically. This is not clear to me. Based on what should one determine what is an acceptable parameter value? Are there example citations? The authors should cite and/or describe the influence of these settings on outcomes of the analyses and how this could affect downstream interpretations. Maybe some examples would help. For a reader coming across this paper, that would be crucial information. As the reviewer noted, this is a crucial point. Nonetheless, it is not possible to give “acceptable” parameters. As we mentioned, and supported by Dr. Cavanaugh's review point 2, these parameters can indeed be quite variable across monitors. We believe that the best practice is to tune these parameters and then report them while presenting the processed data. We will, however, include a new feature to better define these parameters in each experiment. Leveraging the 'ploltly' graphs, we will give the option to browse the unbinned, baselined data so users can accurately identify feeding events and defined the best parameters for their condition. Additionally, we are working on new tools to automatize this process so no user input is required, a challenging task so far. In the third section (Figure 3), there is an additional tab for binning length and binning function. I don’t see any description of how this is different from the same input in section 1. For example, can the binning length and function be different in sections 1 and 3? Either way, it is important for the authors to state it explicitly. We thank the reviewer for raising this point. This is a really important difference that we did not clarify in the text. The binning used in the first section is for graphing purposes only. This allows the survey of the baseline data to detect any possible abnormalities (e.g., dead flies). While the binning in the next section takes the feeding events instead to produce all other graphs and analyses. This information has now been included in the Methods section, Implementation, under the Baseline Data and QC section. We apologize for this omission. Also, the daytime and nighttime feature is great. But how is the computation carried out for subjective day and nighttime under constant conditions if the users have provided long-term DD recording? If this is not possible at the moment, a cautionary note would be important. It is important to notice that the current version of CRUMB calculates the day and night events from the entire recording, without differentiation between LD and DD. The dissection between these two conditions can be achieved by trimming the data during the baselining step. We thank the reviewer for this comment. We have added a note to help users decide how to use this feature until the release of the next version when we plan to include a dissection feature, among other updates. In the ‘Use Case’ section, I am assuming that the autocorrelation period analysis is being performed for the four days in DD. This is not clearly described in the text. If this is indeed the case, the authors must clarify, while adding a disclaimer that four days is anyway too short for using time-series methods robustly. If the authors have long-term (7-day) recording and they can use it, that would be great. But it’s absolutely fine if they don’t have that. The analysis is indeed conducted on the DD data. We agree with the reviewer that this is a short time to get robust rhythmicity statistics. We added a note to data interpretation including a suggestion on the experimental conditions to use. Additionally, we are now providing the data used to generate figures 1 to 4. These are w1118 flies subjected to 2 full days of 12:12 LD cycles followed by 8 days in DD. A circa 24-hour rhythmicity is observed providing further evidence for the use of CRUMB in circadian analysis. Figure 3 has also been changed accordingly to include only DD days. Also, in panels C and D, is the data considered only from LD? If so, there is some other interesting thing going on here: if this is in LD, and there is no difference between day and nighttime feeding events in the clock mutant; does that mean that feeding rhythms, unlike locomotor activity, does not mask to light/dark transitions? I think this may be worth pointing out because this adds a new dimension to the behavior that you have been able to identify using your new tool. Also, I think showing the time-course of feeding activity over the entire duration of seven days may be useful to the reader. Panels C and D show data from LD and DD days combined thus we were not able to make such conclusions from these graphs, unfortunately. To get a better answer to this interesting point, we have analyzed data on LD and DD separately. Under LD, an increase in nighttime events is observed in the clk mutant, which is consistent with locomotor activity data (Lee et al., PLoS Genet. 2014 Aug 14;10(8):e1004545; Lee et al., Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):E4904-13). We have included additional discussion of this data in the manuscript. We agree with the reviewer that showing 7 days might be useful, thus we have included this graph in the updated figure. Non-normalized data are presented, as opposed to the normalized data shown in the first iteration of this manuscript thus resulting in a slightly different graph. There also seems to be some discrepancy between the text and figure legend. The text says three days in LD and four days in DD, and the legend says two days in LD and four days in DD. Please clarify. We apologize for this mistake. The data are for 3 days of LD and 4 days of DD. We have now corrected this in the figure legend."
}
]
},
{
"id": "168915",
"date": "21 Apr 2023",
"name": "Daniel J. Cavanaugh",
"expertise": [
"Reviewer Expertise Circadian neurobiology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article by Hidalgo and Chiu discusses the development of CRUMB, a novel software tool for analysis of data obtained with the Fly Liquid-Food Interaction Counter (FLIC) system. FLIC was developed for real-time monitoring of Drosophila interactions with a liquid food source. These interactions have previously been demonstrated to be highly correlated with feeding events, which allows for an automated assessment of feeding behavior over extended periods of time. The FLIC system therefore provides the opportunity to uncover the genetic and cellular underpinnings of circadian control of feeding behavior. This is important as it is becoming increasingly clear that circadian rhythms of feeding and metabolism have tremendous impact on overall organismal health and wellbeing.\nA current limitation of the FLIC system is the absence of user-friendly analysis tools. Existing analysis tools for the FLIC system require knowledge of the R programming language. Hidalgo and Chiu have therefore created CRUMB, a Shiny app that provides an easy-to-use Graphical user interface that performs standard FLIC analysis to identify feeding events and apply statistical methods to determine whether the data exhibit circadian patterns. This program will be extremely useful to the growing community of researchers using the FLIC system to monitor for circadian feeding patterns. CRUMB does an excellent job of producing intuitive data output files and graphs for data visualization. It also provides a streamlined pipeline that should enable speedier data processing compared with existing FLIC analysis programs. CRUMB could also serve to standardize data analysis, which will facilitate comparison of results across labs. A few small changes, detailed below, could make CRUMB even more useful:\nData are extracted as feeding ‘events’ occurring within a user-defined bin length. As defined, events can be quite variable in length, potentially obscuring differences in total feeding time across the day. I recommend extracting ‘lick’ data in addition to events, and allowing the option to use binned ‘lick’ data in subsequent circadian analysis, as this will better capture dynamic changes in overall feeding throughout the day.\n\nOne argument for the use of CRUMB is to standardize analysis across labs. It should be noted that the parameters shown in Figure 2A under “Select threshold for feeding events” are extremely important for accurate identification of feeding events. We found that parameter settings had to be determined empirically for our setup—for example, these differed significantly when moving from the original FLIC-MCU-1 to the FLIC-MCU-2. Although this would entail significant additional work on the authors’ part, it would be beneficial to build in an analysis that allows users to compare raw data to identified feeding events, to make sure that most apparent events are being captured with the parameter settings.\n\nCurrently, statistical analysis of circadian rhythmicity is limited to autocorrelation testing. To allow for more direct comparison with locomotor activity data, it would be helpful to also offer chi-square periodogram, since the vast majority of papers reporting locomotor activity rhythms in Drosophila use this test. This would be beneficial but not essential, as the authors already note that data output files are available as CSV files, which can then be used for circadian analysis with other programs that offer more extensive circadian statistics.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Yes\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Yes\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes",
"responses": [
{
"c_id": "9756",
"date": "29 Nov 2023",
"name": "Joanna Chiu",
"role": "Author Response",
"response": "Response to Reviewer 2 - Daniel J. Cavanaugh (Our responses are in italics) This article by Hidalgo and Chiu discusses the development of CRUMB, a novel software tool for analysis of data obtained with the Fly Liquid-Food Interaction Counter (FLIC) system. FLIC was developed for real-time monitoring of Drosophila interactions with a liquid food source. These interactions have previously been demonstrated to be highly correlated with feeding events, which allows for an automated assessment of feeding behavior over extended periods of time. The FLIC system therefore provides the opportunity to uncover the genetic and cellular underpinnings of circadian control of feeding behavior. This is important as it is becoming increasingly clear that circadian rhythms of feeding and metabolism have tremendous impact on overall organismal health and wellbeing. A current limitation of the FLIC system is the absence of user-friendly analysis tools. Existing analysis tools for the FLIC system require knowledge of the R programming language. Hidalgo and Chiu have therefore created CRUMB, a Shiny app that provides an easy-to-use Graphical user interface that performs standard FLIC analysis to identify feeding events and apply statistical methods to determine whether the data exhibit circadian patterns. This program will be extremely useful to the growing community of researchers using the FLIC system to monitor for circadian feeding patterns. CRUMB does an excellent job of producing intuitive data output files and graphs for data visualization. It also provides a streamlined pipeline that should enable speedier data processing compared with existing FLIC analysis programs. CRUMB could also serve to standardize data analysis, which will facilitate comparison of results across labs. A few small changes, detailed below, could make CRUMB even more useful: First, we thank the reviewer for the support and shared enthusiasm for this new tool. We hope this could be a starting point for establishing a shared pipeline for data analysis that labs working in feeding and fasting rhythms could use. Additionally, we thank the reviewer for his invaluable suggestions that we currently are working to implement as soon as possible. Data are extracted as feeding ‘events’ occurring within a user-defined bin length. As defined, events can be quite variable in length, potentially obscuring differences in total feeding time across the day. I recommend extracting ‘lick’ data in addition to events, and allowing the option to use binned ‘lick’ data in subsequent circadian analysis, as this will better capture dynamic changes in overall feeding throughout the day. We thank the reviewer for this important comment. We agree that the ‘events’ measurement might be quite variable. Adding the licks as another output would greatly benefit the consistency across experiments. An option to choose between ‘events’ and ‘licks’ is currently in progress and will be provided in the next version of CRUMB. One argument for the use of CRUMB is to standardize analysis across labs. It should be noted that the parameters shown in Figure 2A under “Select threshold for feeding events” are extremely important for accurate identification of feeding events. We found that parameter settings had to be determined empirically for our setup—for example, these differed significantly when moving from the original FLIC-MCU-1 to the FLIC-MCU-2. Although this would entail significant additional work on the authors’ part, it would be beneficial to build in an analysis that allows users to compare raw data to identified feeding events, to make sure that most apparent events are being captured with the parameter settings. Variation across monitors seems to be a key factor in the determining the parameters as noted by the reviewer. Empirical tunning is thus required to achieve comparable measurements. We completely agree with the reviewer as this would be an extremely useful feature. Currently, we are working on developing this option to be available in the next CRUMB update. Currently, statistical analysis of circadian rhythmicity is limited to autocorrelation testing. To allow for more direct comparison with locomotor activity data, it would be helpful to also offer chi-square periodogram, since the vast majority of papers reporting locomotor activity rhythms in Drosophila use this test. This would be beneficial but not essential, as the authors already note that data output files are available as CSV files, which can then be used for circadian analysis with other programs that offer more extensive circadian statistics. We thank the reviewer for this suggestion. The new update will include other popular rhythmicity statistics including chi-square analysis and Lomb-Scargle, among others."
}
]
}
] | 1
|
https://f1000research.com/articles/12-374
|
https://f1000research.com/articles/12-699/v1
|
19 Jun 23
|
{
"type": "Research Article",
"title": "The effectiveness of minimally-invasive corticotomy-assisted orthodontic treatment of palatally impacted canines compared to the traditional traction method in terms of treatment duration, velocity of traction movement and the associated dentoalveolar changes: A randomized controlled trial",
"authors": [
"Mahran R. Mousa",
"Mohammad Younis Hajeer",
"Ahmad S. Burhan",
"Omar Heshmeh",
"Mohammad Khursheed Alam",
"Mahran R. Mousa",
"Ahmad S. Burhan",
"Omar Heshmeh",
"Mohammad Khursheed Alam"
],
"abstract": "Objective: To evaluate the effectiveness of a minimally-invasive corticotomy-assisted treatment of palatally impacted canines (PICs) compared with the traditional method by evaluating treatment time, the velocity of movement, and the associated dentoalveolar changes. Materials and methods: Forty-six patients with palatally or mid-alveolar upper impacted canines were recruited and distributed into two groups: the corticotomy-assisted traction group (CAT group, mean age: 20.39±2.27 years) and the traditional treatment group (TT group, mean age: 20.26±2.17 years). The closed surgical approach was used in both study groups. The velocity of traction movement, traction duration and overall treatment duration were evaluated clinically. In addition, the bone support ratios and the amount of root resorption were assessed on cone-beam computed tomography (CBCT) images. Results: At the end of treatment, significant differences were found between the two groups regarding the velocity of traction movement, traction time, and overall treatment time (P<0.05). The mean velocity of traction movement in the CAT group was greater than the TT group (x velocity =1.15±0.35 mm/month; 0.70±0.33 mm/month, P=0.027, respectively). The duration of the active traction and the overall orthodontic treatment in the CAT group were significantly shorter than the TT group by 36% and 29%, respectively. The mean bone support ratios of the aligned canines did not differ significantly between the two groups (88% vs. 89% in the CAT and TT groups, respectively). No significant differences were found between the two groups regarding the mean amount of root resorption on the adjacent laterals (x resorption = 1.30±1.18 mm; 1.22±1.02 mm, P=0.612, in CAT and TT groups, respectively). Conclusions: The traction movement velocity of the palatally impacted canines can be increased using minimally-invasive corticotomy-assisted orthodontic treatment. The side effects of the acceleration procedure were minimal and almost similar to those of the traditional technique.",
"keywords": [
"Upper impacted canine",
"palatally impacted canine",
"unerupted canine",
"forced eruption",
"orthodontic",
"treatment",
"acceleration",
"corticotomy",
"piezosurgery",
"CBCT imaging"
],
"content": "Introduction\n\nThere are several approaches to treat the impacted maxillary canines, including no treatment,1 interceptive treatment,2 extraction,3 auto transplantation,4 and orthodontic traction after surgical exposure.5 According to clinical experience, the surgical/orthodontic approach is a highly successful treatment method, especially in cooperating patients.6 The time required for orthodontic traction of impacted canines is a particularly troubling clinical problem because it prolongs the orthodontic treatment duration.7\n\nThe duration of the surgical/orthodontic treatment ranged between 18-30 months.8,9 This is related to many factors, including: the patients’ age, the severity of dental crowding, the initial inclination of the impacted canines, the bucco-lingual impacted canine’s position, the distance from the occlusal plan and the periodontal health.10\n\nStewart et al.,11 in a retrospective study, identified the factors that could affect the duration of treatment in patients with palatally impacted maxillary canines by age, sex, severity of impaction, amount of crowding, and unilateral or bilateral impaction. They found that the duration of treatment was 25.8 months for unilateral impaction cases, and in bilateral cases, the duration of treatment was 32.3 months. They showed that if the impacted canine was less than 14 mm away from the occlusal plan, the average treatment duration was 23.8 months, while the average treatment duration in cases of impaction of more than 14 mm was about 31.1 months.11\n\nAccording to the comparative prospective study by Parkin et al.,12 the effective traction period is defined as the period from the first application of the orthodontic traction force until the possibility of applying the first rectangular archwire. While the total treatment duration is defined as the period between the bonding of orthodontic brackets and to the removal of the orthodontic appliance. They demonstrated that focusing on the duration of active treatment is more important than the total duration of treatment that focuses on correcting other factors associated with malocclusion.12\n\nBecker and Chaushu13 in a comparative retrospective study compared a group of adult patients (mean age 28.8 years) with a group of young patients (mean age of 13.7 years) who had palatally impacted canines. They found a significant increase in the treatment duration in the adult patients group (22.3±10.7 months and 19.6±9.1 months, in the adult and young patient groups, respectively) and a decrease in the success rate of treatment. On the other hand, Zuccati et al.14 concluded that patients with palatally impacted canines over the age of 25 years required an average of 30 more visits than those who were under 25 years of age (the mean number of visits was about 40).\n\nThe type of surgical exposure technique may affect the treatment duration of impacted canines,14 with conflicting evidence available.12,15–17 The results of a systematic review by Mousa et al.18 showed that the duration of orthodontic treatment of palatally impacted canines could be reduced when the open traction technique was combined with either superelastic wires or elastic traction elements. This review also concluded that the use of mini screws as a direct anchorage means can reduce the treatment duration and that the use of acceleration techniques (surgical and non-surgical) can increase the velocity of traction movement.18\n\nThe use of various techniques to accelerate tooth movement during orthodontic treatment of different types of malocclusion, such as retraction of upper canines,19–21 decrowding of lower anterior teeth,22–24 retraction of maxillary anterior teeth,25,26 the intrusion of posterior teeth,27 and relieving upper dental crowding,28 has recently been gaining more and more attention. In contrast, a few articles have been published on accelerating the traction movement of the maxillary impacted canines either by surgical or non-surgical accelerating methods.29–31\n\nThe preliminary split-mouth design study conducted by Fischer29 concluded that there was an acceleration in the traction movement of the palatally impacted canines by 28% to 33% when using the corticotomy-assisted technique compared to the conventional traction method. However, the results of this study remain not fully reliable due to the small sample size (only six patients).\n\nFerguson et al.,30 in their retrospective cohort study, evaluated the effectiveness of the ostectomy-decortication technique in the forced-eruption duration of palatally impacted canines. They found that the impacted canines moved about 3.2 times faster in the surgical intervention group than in the conventional traction group, but the acceleration technique used in this study was invasive and involved the removal of a large amount of bone, which in turn could have affected the level of bone support around the aligned canines and their adjacent teeth.\n\nHowever, the potential effects of such surgical interventions on the root resorption and bone support of the canines and their adjacent teeth have not been evaluated in these previous two studies. Finally, Yussif et al.,31 in a randomized controlled trial, used a non-surgical acceleration method that involved repeated local injections of vitamin C into the impaction area during orthodontic traction of the palatally impacted canines. They found that the rate of movement of the impacted canines in the acceleration group was 2-2.5 mm/month compared to 0.5-1.5 mm/month in the control group. Despite the effectiveness of this method in accelerating the withdrawal movement, the acceleration procedure used may be associated with significant levels of discomfort and patient’s dissatisfaction. The main aim of the current study was to evaluate the effectiveness of corticotomy, applied at the exposure operation time and in a flapless manner two months post-operatively, on accelerating canine withdrawal in cases with unilateral maxillary canine impactions. The secondary objectives were to evaluate the ratios of bone support of the aligned canine, the adjacent lateral incisor and first premolar, as well as the root resorption status of the adjacent lateral incisor.\n\n\nMethods\n\nThe current study was designed as a randomized, controlled, two-parallel group clinical trial to investigate the efficacy of the corticotomy technique accompanying surgical exposure enhanced by a subsequent flapless corticotomy in accelerating traction movement of the palatally impacted canines (PICs) and to evaluate the associated dentoalveolar changes compared with traditional traction method. The study sample was compiled by reviewing the lists of patients recorded in the archives of the Orthodontics Department at the Faculty of Dentistry, Damascus University. The patients who were referred to the Orthodontic Department for treatment of impacted upper canines diagnosed in other departments were also examined. The approval of the Local Research Ethics Committee of Damascus University was obtaining before conducting this study (UDDS-499-01022020/SRC-2195). This study was registered at ClinicalTrials.gov and was funded by the Postgraduate Research Budget of Damascus University (Ref no: 83005751015DEN).\n\nThe desired sample size was established using Minitab® version 17 software (Minitab Inc., State College, Pennsylvania, USA). A proprietary free alternative is G*Power 3.1.9.7 program (the Heinrich-Heine University, Dusseldorf, Germany). It was believed that 0.25 mm/month would be the least clinically meaningful difference requiring detection in the impacted canine’s movement velocity between the two study groups. The standard deviation of this variable, based on a comparable prior study, was 0.278.29 An independent-samples t-test (significance level 5%, power 80%) revealed that each group needed a minimum of 21 patients. To account for the possibility of patient withdrawal, each group’s patient count was increased to 23.\n\nAlong with contacting and recalling 75 individuals listed in the Orthodontics Department’s archives, 52 referred patients with upper impacted canines were also examined. It was found that 66 of them satisfied the inclusion requirements. Fifty-eight patients were accepted to participate in the study after the treatment plan and the orthodontic/surgical procedures were explained to all patients. Forty-six patients were then chosen at random to enter this study (Figure 1). The selected patient group received information sheets, and their written informed consent was obtained.\n\nThe following definitions represent the inclusion criteria: (1) patients aged 18 to 28; (2) unilateral palatally or mid-alveolar upper impaction; (3) distally placement of the impacted canine crown to the lateral incisor root midline; (4) no use of any medications that may affect the orthodontic movement. The following conditions were excluded: (1) bilateral or buccal canine impaction cases; (2) more than 45-degree angle between the canine’s longitudinal axis and the vertical facial plane; (3) presence of lateral incisors root resorption; (4) presence of contact between the canine crown and the lateral incisor root; (5) previous orthodontic treatment; (6) any medical condition that prevents oral surgery; (7) oral structural abnormality that is inherited or congenital.\n\nThe participant patients were randomly assigned to the two study groups based on a list of random numbers created using Minitab® software version 17 (Minitab Inc., State College, Pennsylvania, USA), with a 1:1 allocation ratio. With the use of this randomization process, patients were distributed to the two study groups in an equal numbers: the traditional traction group (TT), which consisted of 23 patients, and the corticotomy-assisted traction group (CAT), which also consisted of 23 patients. Using sequentially numbered, opaque, sealed envelopes, a researcher from the Orthodontic Department who was not involved in this study concealed the allocation.\n\nThe principal researcher (MRM) and the patients could not have been blinded during the surgical interventions. Blinding, however, was only achievable during the data analysis stage. In other words, the outcome assessors were blinded and unable to determine to which group the patients belonged.\n\nThe aligning and leveling of the maxillary dental arch were performed using the fixed orthodontic appliance (MBT prescription; 0.022-in slot, Votion™, Ortho Technology®, Florida, USA) in both study groups. The following wire sequence was used: (1) 0.012\"- or 0.014\" nickel-titanium (NiTi); (2) 0.016 × 0.022\" NiTi; (3) 0.017 × 0.025\" NiTi (NT3® SE NiTi Wire, American Orthodontics, Sheboygan, USA); (4) 0.019 × 0.025\" stainless steel (American Orthodontics, Sheboygan, WI, USA). This preparatory stage aimed to open sufficient space for aligning the impacted canine within the dental arch. A NiTi open-coil spring (made of 0.010\" wire with an inner diameter of 0.030\", American Orthodontics, Sheboygan, WI, USA) was used to gain additional space between the lateral incisor and the first premolar, if that distance was not sufficient to accommodate the impacted canine (Figure 2A). Finally, in order to maintain the opened distance, a stainless steel closed-coil spring (made of 0.010\" wire with an inner diameter of 0.030\", American Orthodontics, Sheboygan, WI, USA) was inserted (Figure 2B).\n\nIn both study groups, the impacted canines were surgically exposed using the closed flap approaches. Under the direction of one of the co-authors (OH), the same surgeon from the Department of Oral and Maxillofacial Surgery at Damascus University, Faculty of Dentistry, carried out all surgical procedures.\n\nTraditional traction group (TT)\n\nUnder local anaesthesia (lidocaine HCL 2% - epinephrine 1:80000), a full-thickness palatal flap was raised (Figure 3A) and the bone overlying the impacted canine crown was removed to reveal a suitable area for attachment bonding, without exposing the cemento-enamel junction (CEJ). An eyelet attachment with a hand-made twisted ligature wire was then bonded to the exposed canine crown (Figure 3B). The flap was sutured back with the twisted ligature wire extending under the gingival mucosa towards the buccal side. A prescription of an antibiotic (Clavulanic Acid + Amoxicillin, 1000 mg, twice daily for 5 days) and a painkiller (Paracetamol 500 mg, three times daily for 4 days) was given to patients. Patients received guidelines about postoperative oral health care.\n\nCorticotomy-assisted traction group (CAT)\n\nDuring the surgical exposure phase, patients in this group underwent a corticotomy procedure by drilling a series of circular holes (1 mm in diameter, 1-2 mm deep and spaced about 1.5 mm apart) in the cortical bone. These holes drilled at the area where the impacted canine would be moved towards as well as in the mesial and distal sides of the canine crown (Figure 4A).\n\n(A) The first corticotomy procedure involved drilling a series of circular holes (1 mm in diameter, 1-2 mm deep and spaced about 1.5 mm apart) in the cortical bone. (B) The second corticotomy procedure performed using piezosurgery. Two to three vertical gingival incisions with a height of 8 mm were made at the buccal side of the impaction area using a surgical scalpel. Then, the cortical cuts were created using BS1 tip with a cutting depth of 2 to 3 mm and 2-mm spaces between the cuts. Each cut was 1-mm width.\n\nTwo months after the first corticotomy intervention, the second flapless corticotomy procedure was performed using piezosurgery (Mectron PIEZOSURGERY®, Carasco, Genova, Italy). Using a surgical scalpel, 2-3 vertical gingival incisions with a height of 8 mm were made during this intervention at the buccal side of the impaction area. Then, the cortical cuts were created using BS1 tip with a cutting depth of 2-3 mm, a 2 mm space between cuts, and a 1 mm cut width (Figure 4B).\n\nThe traction force was applied for the first time two weeks after the surgical exposure using active power chain tied on one end to the twisted ligature wire and on the other end to the first molar band hook on the impaction side. The intensity of the applied traction force was 60 g29 measured using intraoral force gauge (Dentaurum, Ispringen, Germany). Re-activation was done every 2 weeks31 until the appearance of half of the clinical crown of the impacted canine; this moment was considered as the end of the active traction phase. Then, the canine bracket was bonded to start its alignment and levelling stage. Once this stage was complete, the fixed orthodontic appliance was removed, and a vacuum-formed retainer was placed.\n\nFor all patients, two cone-beam computed tomography (CBCT) images of the maxillary jaw were obtained. The first CBCT image was obtained two weeks before the beginning of treatment while the second image was obtained right on the day the fixed appliance was removed. The CBCT system was a CBCT Picasso® Pro (Vatech, Seoul, South Korea) with a voxel size of 0.25 mm (FOV 70 × 120 mm), tube voltage of 70 kV, current of 6 mA, and an exposure time of 10 s.\n\nThe principal researcher (MRM) performed the measurements and evaluated all variables. The primary outcomes were (1) traction duration, (2) total treatment duration, and (3) the velocity of traction movement. The traction duration is measured as the interval between the onset of orthodontic traction on the impacted canine and the emergence of half of its clinical crown. The total treatment duration calculated as the time between the bonding of the fixed orthodontic appliance until it is removed. The velocity of traction movement is determined by dividing the depth of impaction, which is defined as the distance from the impacted canine cusp tip to the occlusal plane, by the traction duration.\n\nThe secondary outcomes were (1) bone support of the aligned canine (BS-IC), (2) bone support of the contralateral naturally erupting canine (BS-CON), (3) bone support of the adjacent lateral incisor (BS-LI), (4) bone support of the adjacent first premolar (BS-PR), and (5) root resorption of the adjacent lateral incisor (RR-LI). Bone support was evaluated on the posttreatment CBCT scans. It was assessed on the mesial, distal, buccal, and palatal aspects of the canines, lateral incisors and first premolar. The total bone support ratio was calculated by averaging the four measurements made on each tooth. The alveolar bone level was measured from the root apex of the evaluated tooth to the alveolar crest, whereas the root length of the evaluated tooth was measured from root apex to the midpoint of a line connecting the mesial and distal points on the cemento-enamel junction of this tooth. The ratio of alveolar bone level to the root length was considered the percentage of bone support.32 The amount of root resorption of the adjacent lateral incisor was evaluated by comparing the root length measured in millimetres before and after treatment.\n\nThe method error was assessed by repeating the CBCT measurements for twenty patients selected by random (ten from each group) thirty days after the first measurement. The interclass correlation coefficients (ICCs) were used to determine the presence of any random error, and the paired sample t-tests were used to determine the presence of any systematic error.\n\nMinitab® statistical package (version 17, State College, Pennsylvania, USA) was used to analyse data. Using Anderson-Darling normality tests, normal distributions were confirmed. Therefore, the two-sample t-test was employed for inter-group comparisons, while the paired sample t-test was used for intra-group comparisons. The two-sample t-tests were used to detect the homogeneity between the two study groups at baseline in terms of age, impaction depth, mesio-distal and buccal-palatal inclinations of the impacted canine longitudinal axis, while the chi-square test was used for gender and impaction site.\n\n\nResults\n\nThe baseline characteristics of the sample are shown in Table 1. The study sample consisted 46 patients (13 male and 33 female). There were 39 palatally impacted canines and 7 mid-alveolar impacted canines. There were 23 patients in each group, with a mean age of 20.26±2.17 years and 20.39±2.27 years, in TT and CAT group, respectively. The two study groups did not significantly differ in terms of the initial characteristics of the impacted canine’s position, and they were homogeneous concerning the patient’s age and gender.\n\na Employing two-sample t-test.\n\nb Employing chi-square test.\n\nThe ICCs were in the 0.989 to 0.996 range, demonstrating the high reliability of the measurement method. The Paired-sample t-tests results showed that there was no significant difference between the two measurements, indicating the minor and insignificant systematic errors (Table 2).\n\n* Paired t-tests were used to detect significant differences.\n\n** Intraclass correlation coefficients; P<0.05 was considered statistically significant.\n\nThe mean duration of active traction was 9.68±3.24 months in the TT group and 6.13±1.81 months in the CAT group with a significant difference between the two groups (P=0.015, Table 3). The mean duration of total orthodontic treatment was 19.98±3.55 months in the TT group and 14.23±1.95 months in the CAT group with a significant difference between the two groups (P=0.001, Table 3). The mean velocity of traction movement was 0.70±0.33 mm/month in the TT group, while it was 1.15±0.35 mm/month in the CAT group with a significant difference between the two groups (P=0.027, Table 3). The duration of active traction decreased by 36%, while the duration of total orthodontic treatment decreased by 29% in the CAT group compared with the TT group. The velocity of traction movement was 39.21% greater in the CAT group than the TT group.\n\n* Two-sample t-test was used.\n\nRegarding the bone support ratio, the differences between the aligned and contralateral canines were non-significant in both study groups (P≈1.000; P=0.559, in the TT and CAT group, respectively; Table 4). No significant differences were found between the two groups when comparing the posttreatment bone support ratios of the aligned canines (P=0.512, Table 5), the adjacent lateral incisors (P=0.379, Table 5), and the adjacent first premolars (P=0.622, Table 5).\n\n* Paired t-test was used to detect the statistically significant differences. P<0.05 was considered statistically significant;\n\n* Two-sample t-test was used. P<0.05 was considered statistically significant.\n\nThe mean bone support ratio of the aligned canines in the TT group was 89% (SD: 0.04), while it was 88% (SD: 0.03) in the CAT group. As for the mean bone support ratio of the contralateral canines, the mean bone support ratio was 90% (SD: 0.03) and 89% (SD: 0.02), in the TT and the CAT group, respectively (Table 4). The posttreatment values of the bone support ratio of the adjacent laterals was 85% (SD: 0.03), in the TT group and 86% (SD: 0.03), in the CAT group, while it was 87% (SD: 0.04) and 87% (SD: 0.03) for the adjacent first premolars in the TT and the CAT group, respectively (Table 5).\n\nThe mean amount of root resorption of the adjacent laterals was 1.22±1.02 mm in the TT group and 1.30±1.18 mm in the CAT group, with no significant differences between the two study groups (P=0.612, Table 5).\n\n\nDiscussion\n\nThere is little published data on the effect of the corticotomy techniques on the acceleration of palatally impacted canine traction movement, even though these techniques have been shown to be effective in accelerating several orthodontic movements.33,34 With the exception of the preliminary study conducted by Fischer,29 this randomized controlled trial appears to be the first study that evaluates the efficacy of minimally-invasive corticotomy-assisted orthodontic treatment in accelerating the traction movement of palatally impacted maxillary canines and the associated dento-alveolar changes compared with the traditional surgical/orthodontic treatment. The homogeneity of the patient sample and the initial positioning of the impacted canines enabled such a comparison.\n\nOur study findings showed that both the duration of active traction and the total treatment duration were significantly shorter in the CAT group compared to the TT group. In other words, the velocity of traction movement in the CAT group was significantly greater. This can be attributed to the fact that the corticotomy interventions decreased the cortical bone mass and its resistance to the impacted canine forced eruption movement due to its weakening by cortical cuts.29 Furthermore, the stimulation of the regional acceleration phenomenon (RAP) caused by corticotomy interventions may have stimulated the expression of inflammatory markers and cytokines which led to increased osteoclast activity, stimulated bone remodelling and reinforced blood circulation in the alveolar bone, which led to acceleration of the orthodontic traction movement.35,36\n\nThe results of the current study were in line with the previous studies that compared the acceleration and the conventional traction methods in terms of the incidence of acceleration but were inconsistent with those studies’ results regarding the amount of acceleration obtained. The mean traction movement velocity in the current study was greater (0.37 mm/wk.) than that of Fischer (0.26 mm/wk.).29 This difference might be attributed to the corticotomy procedure performed twice from both the buccal and palatal sides in the current study, which further weakened the resistance of the cortical bone to the forced eruption movement, In addition to the occurrence of additional stimulation of the RAP.\n\nIn contrast, Ferguson et al.30 reported a larger movement acceleration ratio (about 65%) than the current study (about 36%). This can be explained by the difference in the acceleration technique used, the mean ages of the participants and the removal of a greater amount of bone surrounding the impacted canine in that study compared to the current study. Moreover, Ferguson et al.30 included cases of unilateral and bilateral PICs and both surgical exposure approaches (open and closed traction methods) were used in that study. Although the results of the current study were consistent with those of Yussif et al.,31 a direct comparison with that study was not possible due to the difference in the acceleration method that was used, i.e., local injections of vitamin C.\n\nThis study showed that the posttreatment bone support ratios of the aligned canines did not differ significantly between the TT and CAT groups as well as when compared to the contralateral canines in both study groups. In addition, the results of the inter-group comparison showed that there were no significant differences in the mean bone support ratios of the adjacent lateral incisors and the first premolars. These results can be explained by the use of the same orthodontic traction techniques in both study groups, the use of light traction force in a direction that resembles the normal eruption path, and the fact that the amount of bone removed during surgical interventions was minimal. The results of the current study were in agreement with those of Fischer29 who found a non-significant difference in bone level of the PICs treated by the corticotomy-assisted withdrawal method compared to the traditional traction method.\n\nNo clinical trials have been published in the medical literature evaluating the level of bone support of the teeth adjacent to the PICs underwent corticotomy-assisted orthodontic treatment until now. Therefore, the results of the CAT group in the current work cannot be compared with others due to the lack of similar studies.\n\nThe mean amount of root resorption of the adjacent laterals was almost similar in the two study groups with no significant differences. The light traction force used and its direction that from the beginning of its application was away from the root of the lateral incisors, could explain the presence of the low percentage and mild degree of root resorption of the adjacent laterals. Due to the lack of similar studies, the results obtained in the current study are only compared with the results of studies that used the traditional traction methods.\n\nThe results of the current study were consistent with those of Arriola-Guillén et al.,37 who found that the amount of root resorption of adjacent laterals did not exceed 2 mm after the treatment of unilateral vs. bilateral palatally impacted canine cases by the closed traction method. Our results were also in agreement with those of Lempesi et al.38 who evaluated the root resorption of maxillary incisors induced by the orthodontic treatment for patients with upper impacted canines and found a range of 0.86-1.17 mm of root resorption of adjacent laterals.\n\nThe current study included a specific type of upper canine impactions. Therefore, the effects of different probabilities of the initial location, mesiodistal and bucco-lingual angulation of the impacted canines on the traction movement velocity were not evaluated. Secondly, only one type of mechanical traction means was used and the effectiveness of other traction techniques were not evaluated. Thirdly, this trial did not assess the effects of gender and age on the traction movement rate, for which a larger sample size would be necessary.\n\nAs the present study included particular impaction conditions with particular impacted canine’s locations and conducted on a specific patient group treated with specific mechanical orthodontic and surgical techniques in only one teaching hospital, the results of the current study can be limitedly generalized. In order to acquire results that are more generalizable, more randomized controlled trials with larger sample sizes should be carried out in diverse populations with various types of canine impaction.\n\n\nConclusions\n\nOrthodontic traction assisted with minimally-invasive corticotomy was effective in increasing the rate of traction movement of the palatally impacted canines, thereby decreasing the traction duration and the overall treatment duration. The acceleration surgical interventions used did not cause significant changes in the bone support ratios of the aligned canines and the adjacent teeth compared with the traditional traction method. Finally, the acceleration procedure did not result in any significant difference regarding the amount of root resorption of adjacent laterals compared with the traditional treatment methods.\n\n\nEthical statement\n\nThe approval of the Local Research Ethics Committee of Damascus University was obtaining before conducting this study (UDDS-499-01022020/SRC-2195). This study was registered at ClinicalTrials.gov and was funded by the Postgraduate Research Budget of Damascus University (Ref no: 83005751015DEN). The selected patient group received information sheets, and their written informed consent was obtained.",
"appendix": "Data availability\n\nFigshare. Accelerated Traction of Impacted Canines. DOI: https://doi.org/10.6084/m9.figshare.22926152.v1. 39\n\nThis project contains the following underlying data:\n\n• 01 Baseline Sample Characteristics.xlsx. (This file contains the data used to summarize the characteristics of the include patients in this study).\n\n• 02 Duration of treatment.xlsx (This file contains the variables used to measure the duration of the provided treatment for each patient).\n\n• 03 Bone Support and Root Resorption.xlsx (This file contains the variables used to evaluate the percentages of bone support and the amount of root resorption observed on the lateral incisors adjacent to the impacted canines)\n\n• Information Sheet.pdf (This is the information sheet distributed to the candidate patients for inclusion in this study)\n\n• CONSORT2010 checklist v01.pdf (This checklist contains the 25 items of the CONSORT guidelines and the pages where these items can be found).\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nReferences\n\nBishara SE: Clinical management of impacted maxillary canines. Semin. Orthod. Jun 1998; 4(2): 87–98. Publisher Full Text\n\nBaccetti T, Mucedero M, Leonardi M, et al.: Interceptive treatment of palatal impaction of maxillary canines with rapid maxillary expansion: a randomized clinical trial. Am. J. Orthod. Dentofac. Orthop. Nov 2009; 136(5): 657–661. PubMed Abstract | Publisher Full Text\n\nD’Amico RM, Bjerklin K, Kurol J, et al.: Long-term results of orthodontic treatment of impacted maxillary canines. Angle Orthod. Jun 2003; 73: 231–238. PubMed Abstract\n\nKallu R, Vinckier F, Politis C, et al.: Tooth transplantations: a descriptive retrospective study. Int. J. Oral Maxillofac. Surg. Oct 2005; 34(7): 745–755. PubMed Abstract | Publisher Full Text\n\nBjörksved M, Arnrup K, Lindsten R, et al.: Closed vs open surgical exposure of palatally displaced canines: surgery time, postoperative complications, and patients’ perceptions: a multicentre, randomized, controlled trial. Eur. J. Orthod. Nov 2018; 40(6): 626–635. PubMed Abstract | Publisher Full Text\n\nHusain J, Burden D, McSherry P, et al.: Clinical Standards Committee of the Faculty of Dental Surgery, Royal College of Surgeons of England. National clinical guidelines for management of the palatally ectopic maxillary canine. Br. Dent. J. Aug 2012; 213(4): 171–176. PubMed Abstract | Publisher Full Text\n\nCruz RM: Orthodontic traction of impacted canines: Concepts and clinical application. Dental Press. J. Orthod. Jan-Feb 2019; 24(1): 74–87. Publisher Full Text\n\nIramaneerat S, Cunningham SJ, Horrocks EN: The effect of two alternative methods of canine exposure upon subsequent duration of orthodontic treatment. Int. J. Paediatr. Dent. Jun 1998; 8: 123–129. PubMed Abstract | Publisher Full Text\n\nPearson MH, Robinson SN, Reed R, et al.: Management of palatally impacted canines: the findings of a collaborative study. Eur. J. Orthod. Oct 1997; 19: 511–515. PubMed Abstract | Publisher Full Text\n\nNieri M, Crescini A, Rotundo R, et al.: Factors affecting the clinical approach to impacted maxillary canines: A Bayesian network analysis. Am. J. Orthod. Dentofac. Orthop. Jun 2010; 137(6): 755–762. PubMed Abstract | Publisher Full Text\n\nStewart JA, Heo G, Glover KE, et al.: Factors that relate to treatment duration for patients with palatally impacted maxillary canines. Am. J. Orthod. Dentofac. Orthop. Mar 2001; 119(3): 216–225. PubMed Abstract | Publisher Full Text\n\nParkin NA, Almutairi S, Benson PE: Surgical exposure and orthodontic alignment of palatally displaced canines: can we shorten treatment time? J. Orthod. Jun 2019; 46(1_suppl): 54–59. PubMed Abstract | Publisher Full Text\n\nBecker A, Chaushu S: Success rate and duration of orthodontic treatment for adult patients with palatally impacted maxillary canines. Am. J. Orthod. Dentofac. Orthop. Nov 2003; 124(5): 509–514. PubMed Abstract | Publisher Full Text\n\nZuccati G, Ghobadlu J, Nieri M, et al.: Factors associated with the duration of forced eruption of impacted maxillary canines: a retrospective study. Am. J. Orthod. Dentofac. Orthop. Sep 2006; 130(3): 349–356. PubMed Abstract | Publisher Full Text\n\nQuirynen M, Op Heij DG, Adriansens A, et al.: Periodontal health of orthodontically extruded impacted teeth. A split-mouth, long-term clinical evaluation. J. Periodontol. Nov 2000; 71(11): 1708–1714. PubMed Abstract | Publisher Full Text\n\nSmailiene D, Kavaliauskiene A, Pacauskiene I, et al.: Palatally impacted maxillary canines: choice of surgical-orthodontic treatment method does not influence post-treatment periodontal status. A controlled prospective study. Eur. J. Orthod. Dec 2013; 35(6): 803–810. Publisher Full Text\n\nNaoumova J, Rahbar E, Hansen K: Glass-ionomer open exposure (GOPEX) versus closed exposure of palatally impacted canines: a retrospective study of treatment outcome and orthodontists’ preferences. Eur. J. Orthod. Nov 2018; 40(6): 617–625. PubMed Abstract | Publisher Full Text\n\nMousa MR, Hajeer MY, Burhan AS, et al.: The Effectiveness of Conventional and Accelerated Methods of Orthodontic Traction and Alignment of Palatally Impacted Canines in Terms of Treatment Time, Velocity of Tooth Movement, Periodontal, and Patient-Reported Outcomes: A Systematic Review. Cureus. May 2022; 14(5): e24888. PubMed Abstract | Publisher Full Text\n\nAl-Naoum F, Hajeer MY, Al-Jundi A: Does alveolar corticotomy accelerate orthodontic tooth movement when retracting upper canines? A split-mouth design randomized controlled trial. J. Oral Maxillofac. Surg. Oct 2014; 72(10): 1880–1889. PubMed Abstract | Publisher Full Text\n\nAlfawal AMH, Hajeer MY, Ajaj MA, et al.: Evaluation of piezocision and laser-assisted flapless corticotomy in the acceleration of canine retraction: a randomized controlled trial. Head Face Med. Feb 2018; 14(1): 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJaber ST, Al-Sabbagh R, Hajeer MY: Evaluation of the efficacy of laser-assisted flapless corticotomy in accelerating canine retraction: a split-mouth randomized controlled clinical trial. Oral Maxillofac. Surg. Mar 2022; 26(1): 81–89. PubMed Abstract | Publisher Full Text\n\nGibreal O, Hajeer MY, Brad B: Efficacy of piezocision-based flapless corticotomy in the orthodontic correction of severely crowded lower anterior teeth: a randomized controlled trial. Eur. J. Orthod. Mar 2019; 41(2): 188–195. PubMed Abstract | Publisher Full Text\n\nAlsino HI, Hajeer MY, Alkhouri I, et al.: Evaluation of the Levels of Pain, Discomfort, Functional Impairments and Satisfaction With the Periodontally Accelerated Osteogenic Orthodontics (PAOO) When Leveling and Aligning Crowded Teeth: A Prospective Cohort Study. Cureus. Feb 2022; 14(2): e22623. PubMed Abstract | Publisher Full Text\n\nSirri MR, Burhan AS, Hajeer MY, et al.: Efficiency of Corticision in Accelerating Leveling and Alignment of Crowded Lower Anterior Teeth in Young Adult Patients: A Randomised Controlled Clinical Trial. J. Clin. Diagn. Res. Oct 2020; 14(10): ZC26–ZC31. Publisher Full Text\n\nKhlef HN, Hajeer MY, Ajaj MA, et al.: The effectiveness of traditional corticotomy vs flapless corticotomy in miniscrew-supported en-masse retraction of maxillary anterior teeth in patients with Class II Division 1 malocclusion: A single-centered, randomized controlled clinical trial. Am. J. Orthod. Dentofac. Orthop. Dec 2020; 158(6): e111–e120. PubMed Abstract | Publisher Full Text\n\nAl-Imam GMF, Ajaj MA, Hajeer MY, et al.: Evaluation of the effectiveness of piezocision-assisted flapless corticotomy in the retraction of four upper incisors: A randomized controlled clinical trial. Dent. Med. Probl. Oct-Dec 2019; 56(4): 385–394. PubMed Abstract | Publisher Full Text\n\nHasan AA, Rajeh N, Hajeer MY, et al.: Evaluation of the acceleration, skeletal and dentoalveolar effects of low-level laser therapy combined with fixed posterior bite blocks in children with skeletal anterior open bite: A three-arm randomised controlled trial. Int. Orthod. Mar 2022; 20(1): 100597. PubMed Abstract | Publisher Full Text\n\nAl-Ibrahim HM, Hajeer MY, Alkhouri I, et al.: Leveling and alignment time and the periodontal status in patients with severe upper crowding treated by corticotomy-assisted self-ligating brackets in comparison with conventional or self-ligating brackets only: a 3-arm randomized controlled clinical trial. J. World Fed. Orthod. Feb 2022; 11(1): 3–11. PubMed Abstract | Publisher Full Text\n\nFischer TJ: Orthodontic Treatment Acceleration with Corticotomy-assisted Exposure of Palatally Impacted Canines: A Preliminary Study. Angle Orthod. May 2007; 77(3): 417–420. PubMed Abstract | Publisher Full Text\n\nFerguson DJ, Rossais DA, Wilcko MT, et al.: Forced-eruption time for palatally impacted canines treated with and without ostectomy-decortication technique. Angle Orthod. Sep 2019; 89(5): 697–704. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYussif NMA, Dehis HM, Rahman ARA, et al.: Efficacy and safety of locally injectable Vitamin C on accelerating the orthodontic movement of maxillary canine impaction (oral mesotherapy technique): Prospective study. Clinical Cases in Mineral and Bone. Metabolism. April 2019; 15(2): 280–287.\n\nBecker A, Kohavi D, Zilberman Y: Periodontal status following the alignment of palatally impacted canine teeth. Am. J. Orthod. Oct 1983; 84(4): 332–336. PubMed Abstract | Publisher Full Text\n\nAlfawal AM, Hajeer MY, Ajaj MA, et al.: Effectiveness of minimally invasive surgical procedures in the acceleration of tooth movement: a systematic review and meta-analysis. Prog. Orthod. Dec 2016; 17(1): 33. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlfailany DT, Hajeer MY, Aljabban O, et al.: The Effectiveness of Repetition or Multiplicity of Different Surgical and Non-Surgical Procedures Compared to a Single Procedure Application in Accelerating Orthodontic Tooth Movement: A Systematic Review and Meta-Analysis. Cureus. Mar 2022; 14(3): e23105. PubMed Abstract | Publisher Full Text\n\nKim SJ, Park YG, Kang SG: Effects of corticision on paradental remodeling in orthodontic tooth movement. Angle Orthod. Mar 2009; 79(2): 284–291. PubMed Abstract | Publisher Full Text\n\nBaloul SS, Gerstenfeld LC, Morgan EF, et al.: Mechanism of action and morphologic changes in the alveolar bone in response to selective alveolar decortication-facilitated tooth movement. Am. J. Orthod. Dentofac. Orthop. Apr 2011; 139: S83–S101. PubMed Abstract | Publisher Full Text\n\nArriola-Guillén LE, Ruíz-Mora GA, Rodríguez-Cárdenas YA, et al.: Root resorption of maxillary incisors after traction of unilateral vs bilateral impacted canines with reinforced anchorage. Am. J. Orthod. Dentofac. Orthop. Nov 2018; 154(5): 645–656. PubMed Abstract | Publisher Full Text\n\nLempesi E, Pandis N, Fleming PS, et al.: A comparison of apical root resorption after orthodontic treatment with surgical exposure and traction of maxillary impacted canines versus that without impactions. Eur. J. Orthod. Dec 2014; 36(6): 690–697. PubMed Abstract | Publisher Full Text\n\nHajeer MY, Mousa MR, Burhan AS: Accelerated Traction of Impacted Canines. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "179863",
"date": "18 Jul 2023",
"name": "Iyad K. Al-Omari",
"expertise": [
"Reviewer Expertise Orthodontic treatment",
"cleft lip and palate",
"Oral health ralted quality of life"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe effectiveness of minimally-invasive corticotomy-assisted orthodontic treatment of palatally impacted canines compared to the traditional traction method in terms of treatment duration, velocity of traction movement and the associated dentoalveolar changes: A randomized controlled trial.\nThis is an interesting study that is investigating the effectiveness of minimally-invasive corticotomy-assisted orthodontic treatment of palatally impacted canines compared to the traditional traction method. The RCT design of this manuscript as well as the layout is nicely written. There are, however, few minor modifications that need to be addressed by the authors. My recommendation is to accept this manuscript.\nTitle:\nThe title is too long, please consider rewriting the title to indicate the main key factors that are investigated in this study, it could be shortened as follows: The effectiveness of minimally-invasive corticotomy-assisted orthodontic treatment of palatally impacted canines compared to the traditional traction method: A randomized controlled trial.\nIntroduction:\nThe literature review is too long and the authors provide a detailed review of several similar key studies (page 2: 2nd, 5th and 9th paragraphs). Please consider critically reviewing these studies in a summarized concise manner and highlighting any shortcoming of these studies.\n\nConsider replacing the word “troubling” with “challenging” in the text: “The time required for orthodontic traction of impacted canines is a particularly troubling clinical problem because it prolongs the orthodontic treatment duration.”\n\nMethods:\nThe authors need to justify and discuss why they considered the use of a closed surgical technique to align the palatally impacted canines. The literature supports the use of open surgical technique to align impacted canines that are palatally positioned.\nResults:\nThis section could be modified in order to avoid repeating the reported results in different format. The authors could describe the general trends of the results in text and refer the reader to tables and figures instead of reporting the same numbers, values and percentages in text and tables.\nFigures and Tables:\nFigure 1 and 2: please consider removing these figures as it does not illustrate any details relevant to the investigated variables\nFigure 4B: there is a confusion with regards to the description of procedure on the buccal side of the impaction while the photographs depict a palatal view of the impaction. Please consider replacing the photograph with an appropriate illustration of the procedure performed in the buccal side of the impaction.\nTable 2: no need to include this table as the results are reported in full in text. Please consider removing this table\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "179862",
"date": "31 Oct 2023",
"name": "Ashraf Ayoub",
"expertise": [
"Reviewer Expertise Orthognathic surgery",
"3D image analysis",
"bone bioengineering."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an excellent piece of research which is based on randomized control trial at the top of the hierarchy of scientific evidence in the literature. The study was well conducted, the results are comprehensive and answers the research question. I have recommended the indexing of the manuscript, with minor corrections, in recognition of its high quality. The following minor corrections may be considered:\nI suggest the \"velocity\" of tooth movement should be replaced by the the \"average rate\".\n\nWhat is (BS1)?\n\nA new photo (4B) showing the buccal gingival cuts and the cortctotomy would be ideal.\n\nPlease add a sentence regarding the hypothesis that was tested in this study.\n\nPlease add a sentence regarding future studies.\nCongratulations for this excellent piece of research.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "215289",
"date": "15 Dec 2023",
"name": "Huang Li",
"expertise": [
"Reviewer Expertise orthodontics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study was to evaluate the effectiveness of a minimally-invasive corticotomy-assisted treatment of palatally impacted canines (PICs) compared with the traditional method by evaluating treatment time, the velocity of movement, and the associated dentoalveolar changes. It was an interesting study, but still needs to address the following questions- 1. For palatally impacted canines, the traditional treatment during surgical procedure was to remove some bone and reduce some obstacle. Therefore, the corticotomy seems not very necessary from this point. 2. The duration time was closely related to impaction distance. it is very important to analyze the detailed result. 3. The literature showed \"They found that the duration of treatment was 25.8 months for unilateral impaction cases, and in bilateral cases, the duration of treatment was 32.3 months.\" Actually, the treatment time in this study was too short compared to the previous study. 4. The author should simplify the introduction, not like a review to show all studies. 5. Figure 3B and Figure 4B look like the same picture. Please clarify it.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-699
|
https://f1000research.com/articles/12-698/v1
|
19 Jun 23
|
{
"type": "Research Article",
"title": "Patient’s attitudes and perceptions around attending oncology consultations following surgery for colorectal cancer: A qualitative study",
"authors": [
"Yoshan Moodley",
"Shona Bhadree",
"Laura Stopforth",
"Shakeel Kader",
"Steven Wexner",
"Jacqueline van Wyk",
"Alfred Neugut",
"Ravi Kiran",
"Shona Bhadree",
"Laura Stopforth",
"Shakeel Kader",
"Steven Wexner",
"Jacqueline van Wyk",
"Alfred Neugut",
"Ravi Kiran"
],
"abstract": "Background: The oncology consultation following surgery for colorectal cancer (CRC) is usually the first step in the receipt of chemotherapy. Non-compliance with this consultation results in non-receipt of recommended chemotherapy, when appropriate, and worse clinical outcomes. This study sought to explore South African patients’ attitudes and perceptions around attending scheduled oncology consultations following their CRC surgery. Methods: Semi-structured qualitative interviews were conducted with patients who had surgery for CRC at a quaternary South African hospital and who had to decide whether they would return for an oncology consultation. The “Model of health services use” informed the design of the interview guide, which included questions on factors that impact health seeking behavior. Demographics of participants, CRC disease stage, and compliance with scheduled oncology consultations were also collected. Descriptive statistics were used to analyse the quantitative data, while deductive thematic analysis was used to analyse the qualitative data. Results: Seven participants were interviewed. The median age was 60.0 years and four participants (57.1%) were female. Black African, White, and Asian participants accounted for 85.7% of the study sample. Most participants had stage III CRC (71.4%). The oncology consultation no-show rate was 14.3%. Participant’s knowledge and beliefs around CRC proved to be an important predisposing factor that influenced follow-up decisions. Family support and religion were cited as important enabling factors. Travel costs to the hospital and frustrations related to the clinic appointment booking/scheduling process were cited as important disabling factors. Lastly, the participant’s self-perceived need for additional oncology care also appeared to influence their decision to return for ongoing oncology consultation after the initial surgery. Conclusion: Several contextual factors can potentially influence a patient’s compliance with a scheduled oncology consultation following CRC surgery. A multipronged approach which addresses these factors is required to improve compliance with oncology consultations.",
"keywords": [
"Attitudes",
"Perceptions",
"Post-procedural",
"Consult",
"Surgery",
"Colorectal cancer."
],
"content": "Introduction\n\nColorectal cancer (CRC) incidence has steadily increased in South Africa, and it is now one of the most significant causes of cancer-related morbidity and mortality in the country.1 The initial recommended treatment for CRC is surgery; however, adjuvant chemotherapy might also be necessary in the context of advanced CRC.2 Evidence from clinical trials demonstrates the benefits of receiving adjuvant chemotherapy, notably improved disease-free survival and improved overall survival rates.3 The initiation of chemotherapy is preceded by an oncology consultation, at which a patient is assessed as a possible candidate for treatment by an oncologist.4 A treatment plan might also be communicated by the oncologist to patients who are deemed good candidates for adjuvant chemotherapy.4 Therefore, the oncology consultation is seen as a crucial step to the possible receipt of chemotherapy. The published literature reports that 15-34% of eligible CRC patients will not participate in a scheduled oncology consultation,5,6 and, therefore, will likely not end up receiving their recommended chemotherapy. Given the growing public health problem posed by CRC in South Africa and the implications if patients do not access and discuss treatment options with an oncologist, this study sought to explore South African patients’ attitudes and perceptions around attending scheduled oncology consultations following surgery for CRC.\n\n\nMethods\n\nThis was an exploratory, qualitative study. The theoretical framework adopted for this study was the “Model of health services use”.7 As outlined in Figure 1, this model proposes that an individual’s use of healthcare services is based on the interaction of factors which predispose him/her to use healthcare services, factors which facilitate or hinder the use of healthcare services, and factors that drive the need for care. This study was conducted at the Inkosi Albert Luthuli Central Hospital (IALCH) in Durban, South Africa. The hospital is a government-funded facility which offers specialist healthcare services, including oncology care, to the population of the KwaZulu-Natal Province on the eastern seaboard of South Africa. IALCH is the only quaternary-level hospital in the province, and patients predominantly access health care services at the facility after being referred from lower-level healthcare facilities.\n\nThe study population included adult (aged >18 years old) CRC patients with stage III/IV disease who had undergone surgery at IALCH during the period 13 April 2022-12 June 2022, and who needed to decide on whether they would return for their scheduled oncology clinic consultation. A convenience sampling strategy was used to identify and invite eligible patients to participate in this study. Informed consent was obtained from all study participants. Participants were enrolled in this study (hereafter referred to as “the study sample”) until data saturation was reached and no new information was collected for the qualitative analysis.\n\nInformation on each participant’s age, gender, and race was collected directly from their medical records and entered on a Microsoft Excel spreadsheet. A trained research assistant conducted semi-structured qualitative interviews at the bedside, just before the participants were discharged from hospital after their surgery. The interview questions, shown in Table 1, explored the three main components of the “Model of health services use” – predisposing factors, enabling or disabling factors, and factors which drive the need to access healthcare services.7 Interviews were conducted in English or the local isiZulu Language, where appropriate. Predisposing factors can include patient demographics and health beliefs. Given the qualitative nature of this research, a decision was made to restrict the interview questioning around “predisposing factors” to the participant’s health beliefs. Broadly, enabling factors include patient socioeconomic factors (high level of education, being employed), social factors (psychosocial support mechanisms in place), and health system-related factors (access to healthcare information and efficient delivery of healthcare). Disabling factors encompass the converse of enabling factors. The need for care can be considered as perceived (patient) or evaluated (healthcare provider). Since the recommended treatment for stage III/IV CRC usually involves a combination of surgery followed by adjuvant chemotherapy,8 it was assumed that all healthcare providers would consider there to be a need amongst CRC patients for an oncology consultation following their cancer surgery. As such, the interview questioning around factors which drive the need to access healthcare was restricted to the participant’s perspective (perceived need for care) rather than the healthcare provider’s perspective (evaluated need for care). All interviews were recorded electronically and took about 30 minutes to complete. The content from the interviews was transcribed shortly after the interview was completed and entered onto a Microsoft Excel spreadsheet for coding and the subsequent data analysis. In addition, the medical records of participants were screened to establish compliance with instructions to return for an oncology consultation at IALCH.\n\n\n\n• Tell me about your beliefs about this cancer?\n\n\n\n• What factors will make it difficult or easier for you to come back to the oncology clinic for your consultation with the oncologist?\n\n• Are any of the factors more important to you and your family?\n\n• How will each factor influence your decision to continue with your treatment?\n\n• In what way can the doctor/nurse or other professional(s) at the hospital help to ensure that you come for your next treatment opportunity?\n\n\n\n• Do you think that you will come back for oncology care?\n\nDescriptive statistics were used to summarize the key characteristics of the study sample. The results of the descriptive statistical analysis are presented as medians (interquartile range) or as frequencies (%). Deductive thematic analysis was used to analyse the data from the semi-structured qualitative interviews.9 The deductive thematic analysis followed six steps10: familiarisation with the data (listening to the recorded interviews), coding of the data (generating broad labels for important features of the data), generating themes (collating the coded data under similar themes), reviewing themes (assessing the relevance of individual themes and whether some themes might need to be collapse together or split into two or more themes), defining themes (conducting and writing a detailed analysis of each theme), and writing up the findings from the qualitative analysis (integrating the analytic narrative and the data extracts from the interviews). Both the descriptive statistics and the deductive thematic analysis were performed using Microsoft Excel.\n\n\nResults\n\nA total of seven participants were interviewed. An overall description of the study sample is provided in Table 2. The median age of the study sample was 60.0 years, and there were four female participants (57.1%). There were similar numbers of Black African, White, and Asian participants (two participants from each of these demographic groups, accounting for 85.7% of the study sample). Two participants had stage IV CRC (28.6%), while the remaining five participants had stage III CRC (71.4%). There was one participant who was a no-show for the oncology consultation (14.3%).\n\nInformation on the characteristics of the individual participants that comprised the study sample is provided in Table 3. The findings of the deductive thematic analysis are reported as three core themes based on the “Model of health services use” - predisposing factors, enabling or disabling factors, and factors driving the need for care.7\n\nSome participants possessed knowledge that informed their understanding and beliefs around CRC, as indicated below. Some knew that cure was possible and were able to identify more complex risk factors for CRC, such as genetics and pre-cancerous colonic polyps. The need for timely treatment of pre-cancerous colonic polyps was also acknowledged by one patient.\n\nP1: “I know it is curable. I really don’t have specific beliefs but since I always had constipation all my life, so maybe it has something to do with constipation. Well, I won’t say it is related to my family genes since I don’t know my family history.” [48; Female; Asian]\n\nP4: “Yes, there are beliefs that I have, what I know is they say if you have small polyps, they might predispose you into developing colon cancer if they are not removed.” [60; Female; Black African]\n\nOn the other hand, when asked about what their beliefs were regarding CRC, there were also some participants who did not have a clear understanding (or no understanding at all in some instances) of how CRC develops, the disease process, and its associated risk factors.\n\nP5: “I don’t know, I really have no idea. However, they say it can pass from one person to another - my mother had skin cancer, my grandmother had either breast cancer or bone marrow cancer, either than that my father had no cancer, my brothers and sisters have no cancer and none of our children have cancer. Um, I don’t know.” [72; Male; White]\n\nP2: “I would be lying if I say I have any belief that is associated with cancer, but I normally hear people saying you can develop cancer from smoking, and I don’t know how true it is.” [53; Female; Black African]\n\nP6: “No, I have no idea.” [62; Male; Mixed race]\n\nFamily support and religion were cited by several participants as important enabling factors. Family members were a source of strength and psychosocial support for some study participants.\n\nP4: “Family support, I think it’s best for my family to know what I am going through so that I can get all the support I need from them.” [60; Female; Black African]\n\nP5: “Regarding my family, it is all the love I am receiving from them that keeps me going.” [72; Male; White]\n\nP6: “The family support influence will be very strong for me in such a way that they will make sure I come for my appointments.” [62; Male; Mixed race]\n\nP7: “My daughter works in Durban, so she makes sure she drops and pick me up at the hospital, so there is not much of an inconvenience. She pays for my medical bills.” [48; Female; White]\n\nParticipants were motivated by prayer, religion, and words of encouragement from their local religious leaders.\n\nP3: “Religion is very important; it is important in everyday life. Yesterday I could not pray following surgery as I was still in pain.” [66; Male; Asian]\n\nP5: “It’s my God that opened the doors for me to be here. If he did not want me to be here, he would have closed the doors.” [72; Male; White]\n\nP7: “Well, my pastor in church believes that I should be spokesperson for people with cancer, of which I would like to do when but once I am healed or fully recovered. Maybe I can be a volunteer in at a hospital well, I will see. I would like to give back.” [48; Female; White]\n\nAll but one of the study participants did not attend their scheduled oncology consultation. Travel costs to the hospital for the oncology consultation were cited as an important disabling factor by one of the participants. She stated that she was the only breadwinner in her family, and that she had to balance the need to seek treatment for her CRC against possible unpaid leave from her employment.\n\nP2: “The cost of getting here. The main issue is the money for transport since I only work for certain days, and the most difficult part is that I only earn R2000 which is not enough to support my family. If I can have enough money that will make my situation easy. Money is the main issue. Money is the most important factor since I am the only one who is working, everyone is relying on me. Since I am here in hospital, I must make sure that I ask for the letter of attendance otherwise I won’t even get paid. I work as a cleaner, so my money is not enough, as I end up borrowing money to make it to the hospital for my appointments.” [53; Female; Black African]\n\nAnother participant, who resided a great distance away from IALCH also cited transportation costs as a disabling factor. He also stated that besides the costs associated with his transport to IALCH, he would have to seek financial assistance from his family to secure accommodation in Durban while he waited for his return trip home.\n\nP3: “The cost of getting to Durban from Newcastle. My family supports me financially to get accommodation in Durban.” [66; Male; Asian]\n\nSome participants felt that healthcare providers could do more to facilitate their compliance with scheduled oncology consultations. These frustrations were mostly related to the clinic appointment booking/scheduling process.\n\nP1: “They must make sure that we are registered (at the hospital admissions desk) for our consultation. It happens every time when I get to the clinic by 5 am, to find out that I am not registered and had to go back to register and to the clinic and wait again.” [48; Female; Asian]\n\nP2: “Maybe if they can book my appointments towards month end, when I have money for transport, that will help me not to have stress of borrowing money from people.” [53; Female; Black African]\n\nP3: “I am not sure, maybe they can send me reminder few days before my appointment.” [66; Male; Asian]\n\nThere were certain participants who merely required encouragement to come back for a scheduled oncology consultation, such as in the case below.\n\nP6: “Well, they can encourage me. For example - if you come, we will do this for you and we going to clear this.” [62; Male; Mixed race]\n\nOther participants requested honest conversations with their healthcare providers regarding their care and reasons for why the oncology appointments were being scheduled.\n\nP4: “They must tell you why it is important to come for the follow-up.” [60; Female; Black African]\n\nP5: “They must be straight forward; in other words, the healthcare professionals must let you know if there are greater or lesser chances of surviving.” [72; Male; White]\n\nThe most important factor driving the need for care was the self-perceived need for additional oncology care following surgery. Two participants appeared to perceive themselves as still being at risk for CRC following surgery (and hence requiring the recommended additional oncology treatment).\n\nP2: “I will make sure I come for ongoing care, because at the end of the day I need help.” [53; Female; Black African]\n\nP7: “I will come back, even the doctors told me that I will definitely be coming back here for ongoing care.” [48; Female; White]\n\nThere was one participant who, due to misconceptions around the aggressiveness of this cancer, perceived that he was no longer at further risk following surgery, and did not require additional treatment.\n\nP3: “I don’t think so, because once they have removed the cancer, I should be fine. This cancer is not aggressive.” [66; Male; Asian]\n\n\nDiscussion\n\nAlthough it is based on a small sample size, the observed oncology consultation no-show rate in this South African study was comparable with the range of no-show rates reported in the published literature from high-income countries,5,6 suggesting that non-compliance with scheduled oncology consultations amongst CRC patients is indeed a global problem. However, this finding takes on added significance in the South African context for two reasons: Firstly, CRC is an emerging public health concern in South Africa, even amongst younger populations,1,11 and the expectation is that there would also be a growing trend in the number of individuals who require surgery and additional oncologic treatment for CRC. Secondly, the South African public healthcare sector is resource-constrained when compared with public health systems in high-income countries,12,13 and missed oncology consultations would have implications for efficient utilisation of clinical oncology services, as well the downstream consequences of incomplete CRC treatment on patient clinical outcomes.\n\nThe published literature reports that a large portion of cancer patients do not receive oncology care due to their refusal of treatment,14 highlighting the importance of patient-centered research in this population. The current study improves our understanding of context-specific factors that influence a patient’s decision to default on a scheduled oncology consultation. The study has identified several key contextual factors of interest, all of which fall within the scope of the established “Model of health services use” and are amenable to modification. These factors must be considered by South African public health specialists when tailoring a response to this challenge.\n\nA clear understanding of CRC and its treatment is required to enable patients to make informed decisions regarding their subsequent oncology care.15,16 Public health campaigns targeting CRC are generally lacking in African countries.17 Therefore, South African CRC patients have limited access to vetted educational materials on the subject. Most patients in the current setting will likely receive information about their disease via a direct conversation with the healthcare workers who are also treating them, or their information will be based on discussions with their friends and family. In the current study, several participants expressed misconceptions around the causes of CRC and how the disease progresses. Not only does this finding emphasize the shortcomings in how healthcare workers communicate information on CRC to afflicted patients, but it also questions the quality of information delivered through other traditional sources. There is much scope to improve patient information to the general public through the well-designed educational materials on CRC. As per the characteristics of the study sample, the CRC population of KwaZulu-Natal Province is racially and culturally diverse.11 Accordingly, any new educational materials or awareness campaigns for CRC will need to be culturally relevant and accessible in isiZulu, the most common dialect in the region. Knowledge and awareness campaigns have proven to be effective at increasing the use of CRC disease screening,18 and this approach will likely have a similar impact on other aspects of the cancer treatment pathway, including oncology consultation attendance.\n\nThe perceived need for healthcare can be an important factor which prompts patients to seek healthcare services.19,20 While it is encouraging that most study participants had still perceived themselves as being at risk for CRC following surgery (and there still being a need for additional oncology care), patient educational materials on CRC would also be of benefit in raising awareness around the consequences of incomplete oncology treatment in those who do not feel the need for further oncology care due to misconceptions related to the seriousness of the disease.\n\nCommunication of CRC information between healthcare workers and patients, particularly information regarding the importance of oncology care, can be improved through educational interventions for healthcare workers. In-person workshops to improve physician’s communication practices with cancer patients have been well-received.21,22 Formal training in communication practices would also ensure that relevant information on CRC treatments is communicated to patients and delivered in a standardised manner.\n\nUp to 80% of cancer patients desire a qualitative prognosis (i.e. “Will I die from this disease”) from their attending physician.23 This conversation can be difficult for the physician for several reasons: news of a poor prognosis can be depressing for a patient and could lower their motivation for additional care; the misconception that involvement of Hospice care will reduce patient survival; fear that the prognosis may be incorrect, and the possible medicolegal implications thereof; whether it is culturally appropriate to deliver news of a poor prognosis to some patients; and the stress that delivering this news places on the physician himself/herself.24 Approaches to assist physicians having this complex and difficult discussion with their patients have been reported.25 The first step in this process involves establishing whether the patient wants to know more on their prognosis, and how much they would like to know. For patients who do request more information on their prognosis, the content of the discussion is then negotiated; information is provided; the patient’s (and family’s) response to the news is acknowledged; and the patient’s understanding of the discussion should be assessed.25\n\nThe important role played by family in providing motivational support to a cancer patient during their treatment journey has long been acknowledged. A recent systematic review reported that being married (versus being unmarried) was associated with a significantly lower odds of treatment refusal amongst CRC patients.26 In addition to motivational support, participants in the current study also stated that family members were crucial in providing financial support or directly facilitating their attendance to hospital visits. These important roles played by family members should be encouraged and strengthened. However, there might be instances where a patient does not have any family members to support them during their cancer treatment journey. In such instances, close friends or peers may assume this supportive role. Peers are cancer survivors who have been cured of cancer, and are thus well-placed to provide motivation, advice, and information to other cancer patients who are just beginning their treatment journeys.27\n\nSpirituality is considered a fundamental component of holistic person-centered care.28 The published literature demonstrates the benefits of religion and spirituality in the context of cancer, empowering patients to accept their illness and allowing them to deal with it in a way that is both positive and purposeful.29,30 This notion was indeed confirmed in the current study, with many participants citing religion as a source of strength and a coping mechanism as they battle their disease. It is therefore crucial that the spiritual needs of CRC patients be assessed and addressed throughout the cancer treatment journey. There are existing tools that have been used to assess the spiritual needs of cancer patients,30 however these originate in populations which are culturally and racially different from the South African population. The existing tools may, however, be less accurate in assessing the spiritual needs of CRC patients in the South African setting, thereby necessitating the development of a locally relevant tool for this purpose. Oncology units should also look to work closely with community-based religious groups, to ensure that patients who do require spiritual support are able to draw on support from community-based resources.\n\nEven in settings where efficient transportation networks exist, distance to a healthcare facility is known to impact compliance with cancer treatment.31 It is therefore unsurprising that transportation costs were cited by participants in this study as a barrier to attending an oncology consultation. This barrier could potentially be addressed in one of two ways: Firstly, transportation to the hospital on the day of the oncology consultation could be arranged through provision of a dedicated hospital bus service to patients.32 Secondly, it might be possible to decentralise the oncology consultation to a lower-level healthcare facility which is closer to a patient’s place of residence,33 thereby facilitating attendance of the consultation. Both proposed solutions are likely to have financial implications for the resource-constrained South African public healthcare system. However, this would be worthwhile in the long term as patients with CRC would be linked to care more efficiently, thereby averting some of the undesired clinical outcomes associated with this disease.34\n\nForgetting or being completely unaware of a scheduled clinic appointment are common reasons for missed clinic appointments and are not unique to oncology care.35 Many participants in this study expressed the need to be reminded about their oncology consultation. Ownership of mobile phones amongst the South African population is high when compared with other African countries,36 and the opportunity exists to leverage this technology to reduce the possibility of missed oncology appointments in CRC patients. Pre-appointment short message service (SMS) alerts have been used with much success (reduced the “did not attend” response by nearly 50%) in the United Kingdom at a breast cancer clinic.37 However, there are several factors which must be considered before a similar intervention for CRC patients can be implemented in South Africa. These factors include illiteracy, patient confidentiality, and loss or theft of mobile phones.38 Allowing for flexibility in the patient appointment scheduling system might be appreciated by patients who are employed and who may not be able to take time off from work on their initially scheduled appointment date.39 Lastly, identifying gaps in the patient admission system and addressing these gaps would help alleviate the frustrations around patient workflow between the hospital admissions department and the oncology clinic.40\n\nThis research was not without limitations. The sample size was small, and the quantitative findings on oncology consultation no-shows should be interpreted with caution. Although the study participants were representative of the CRC population in KwaZulu-Natal Province,11 they are likely to differ from CRC patients in other South African provinces and the findings of this research might therefore not be entirely applicable to CRC patients across all the South African provinces. This study did not include CRC patients from the South African private healthcare sector, who might also have different attitudes and perceptions around attending oncology consultations following their surgery. In addition, this study enrolled participants over a short time period and it is also possible that there might be seasonal differences in oncology consult no-show rates or patient responses as to why they would possibly not attend an oncology consultation.\n\nIn conclusion, this study has identified several contextual factors based on the “Model of health services use” which can potentially influence a patient’s compliance with a scheduled oncology consultation following CRC surgery. Bearing in mind that these contextual factors are unlikely to occur in isolation, a multipronged approach which addresses these factors is required to improve CRC patient’s compliance with oncology consultations. Despite the useful information yielded by this study, the findings should be confirmed with additional research which attempts to address some of the limitations that have been declared.",
"appendix": "Data availability\n\nOpen Science Framework: Patient’s attitudes and perceptions around attending oncology consultations following surgery for colorectal cancer, https://doi.org/10.17605/OSF.IO/9T5BV. 41\n\nThis project contains the following underlying data:\n\n• Dataset.xlsx\n\n• Interview transcripts: Interview_transcripts.xlsx\n\nOpen Science Framework: ‘SRQR’ checklist for ‘Patient’s attitudes and perceptions around attending oncology consultations following surgery for colorectal cancer’, https://doi.org/10.17605/OSF.IO/9T5BV. 41\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nThe authors thank Ms. Sphe Sikhahlane for assisting with the participant interviews for this study.\n\n\nReferences\n\nMotsuku L, Chen WC, Muchengeti MM, et al.: Colorectal cancer incidence and mortality trends by sex and population group in South Africa: 2002-2014. BMC Cancer. 2021; 21(1): 129. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSahakyan AM, Aleksanyan A, Batikyan H, et al.: Lymph Node Status and Long-Term Oncologic Outcomes After Colon Resection in Locally Advanced Colon Cancer. Indian J. Surg. 2022; 84(1): 79–85. Publisher Full Text\n\nSargent D, Sobrero A, Grothey A, et al.: Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J. Clin. Oncol. 2009; 27(6): 872–877. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGarcia-Alonso A: Improving the chemotherapy process and service to cancer patients. Risk Manag. Healthc. Policy. 2011; 4: 41–45. Publisher Full Text\n\nOng S, Watters JM, Grunfeld E, et al.: Predictors of referral for adjuvant therapy for colorectal cancer. Can. J. Surg. 2005; 48(3): 225–229.\n\nOliveria SA, Yood MU, Campbell UB, et al.: Treatment and referral patterns for colorectal cancer. Med. Care. 2004; 42(9): 901–906. Publisher Full Text\n\nAndersen R: A Behavioral Model of Families’ Use of Health Services. Chicago: Center for Health Administration Studies, University of Chicago; 1968.\n\nWerner J, Heinemann V: Standards and Challenges of Care for Colorectal Cancer Today. Visc. Med. 2016; 32(3): 156–157. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBraun V, Clarke V: Using thematic analysis in psychology. Qual. Res. Psychol. 2006; 3(2): 77–101. Publisher Full Text\n\nClarke V, Braun V: Teaching thematic analysis: Overcoming challenges and developing strategies for effective learning. Psychologist. 2013; 26(2): 120–123.\n\nMadiba T, Moodley Y, Sartorius B, et al.: Clinicopathological spectrum of colorectal cancer among the population of the KwaZulu-Natal Province in South Africa. Pan. Afr. Med. J. 2020; 37: 74. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaphumulo WT, Bhengu BR: Challenges of quality improvement in the healthcare of South Africa post-apartheid: A critical review. Curationis. 2019; 42(1): e1–e9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMalakoane B, Heunis JC, Chikobvu P, et al.: Public health system challenges in the Free State, South Africa: a situation appraisal to inform health system strengthening. BMC Health Serv. Res. 2020; 20(1): 58. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLandrum MB, Keating NL, Lamont EB, et al.: Reasons for underuse of recommended therapies for colorectal and lung cancer in the Veterans Health Administration. Cancer. 2012; 118(13): 3345–3355. PubMed Abstract | Publisher Full Text\n\nHolden CE, Wheelwright S, Harle A, et al.: The role of health literacy in cancer care: A mixed studies systematic review. PLoS One. 2021; 16(11): e0259815. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nFeyisa BB, Deyaso SF, Tefera GM: Self-Reported Morbidity and Health-Seeking Behavior and its Predictors Among a Geriatric Population in Western Ethiopia: Community-Based Cross-Sectional Study. Int. J. Gen. Med. 2020; 13: 1381–1393. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaile WF, Lenzi R, Kudelka AP, et al.: Improving physician-patient communication in cancer care: outcome of a workshop for oncologists. J. Cancer Educ. 1997; 12(3): 166–173. Publisher Full Text\n\nDelvaux N, Merckaert I, Marchal S, et al.: Physicians’ communication with a cancer patient and a relative: a randomized study assessing the efficacy of consolidation workshops. Cancer. 2005; 103(11): 2397–2411. PubMed Abstract | Publisher Full Text\n\nKaplowitz SA, Campo S, Chiu WT: Cancer patients’ desires for communication of prognosis information. Health Commun. 2002; 14(2): 221–241. Publisher Full Text\n\nMack JW, Smith TJ: Reasons why physicians do not have discussions about poor prognosis, why it matters, and what can be improved. J. Clin. Oncol. 2012; 30(22): 2715–2717. PubMed Abstract | Publisher Full Text\n\nBack AL, Arnold RM: Discussing prognosis: “how much do you want to know?” talking to patients who are prepared for explicit information. J. Clin. Oncol. 2006; 24(25): 4209–4213. PubMed Abstract | Publisher Full Text\n\nMoodley Y, Govender K, van Wyk J , et al.: Predictors of treatment refusal in patients with colorectal cancer: A systematic review. Semin. Oncol. 2022; 49(6): 456–464. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZiegler E, Hill J, Lieske B, et al.: Empowerment in cancer patients: Does peer support make a difference? A systematic review. Psychooncology. 2022; 31(5): 683–704. PubMed Abstract | Publisher Full Text\n\nNathan R, Zuercher D, Eveland S, et al.: Spirituality as an Essential Element of Person-Centered Care. Innov. Aging. 2021; 5(Suppl 1): 878–879. Publisher Full Text\n\nWeaver AJ, Flannelly KJ: The role of religion/spirituality for cancer patients and their caregivers. South. Med. J. 2004; 97(12): 1210–1214. PubMed Abstract | Publisher Full Text\n\nLee YH: Spiritual Care for Cancer Patients. Asia Pac. J. Oncol. Nurs. 2019; 6(2): 101–103. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmbroggi M, Biasini C, Del Giovane C, et al.: Distance as a Barrier to Cancer Diagnosis and Treatment: Review of the Literature. Oncologist. 2015; 20(12): 1378–1385. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKulshrestha A, Singh J: Inter-hospital and intra-hospital patient transfer: Recent concepts. Indian J. Anaesth. 2016; 60(7): 451–457. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChitha W, Jafta Z, Mnyaka OR, et al.: Protocol of mixed-methods assessment of demographic, epidemiological and clinical profile of decentralised patients with cancer at Nelson Mandela Academic Hospital and Rob Ferreira Hospital, South Africa. BMJ Open. 2022; 12(4): e054983. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVan Cutsem E, Borràs JM, Castells A, et al.: Improving outcomes in colorectal cancer: where do we go from here? Eur. J. Cancer. 2013; 49(11): 2476–2485. PubMed Abstract | Publisher Full Text\n\nWilson R, Winnard Y: Causes, impacts and possible mitigation of non-attendance of appointments within the National Health Service: a literature review. J. Health Organ. Manag. 2022; 36(7): 892–911. PubMed Abstract | Publisher Full Text\n\nAker JC, Mbiti IM: Mobile Phones and Economic Development in Africa. J. Econ. Perspect. 2010; 24(3): 207–232. Publisher Full Text\n\nKiruparan P, Kiruparan N, Debnath D: Impact of pre-appointment contact and short message service alerts in reducing ‘Did Not Attend’ (DNA) rate on rapid access new patient breast clinics: a DGH perspective. BMC Health Serv. Res. 2020; 20(1): 757. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDemsash AW, Tegegne MD, Walle AD, et al.: Understanding barriers of receiving short message service appointment reminders across African regions: a systematic review. BMJ Health Care Inform. 2022; 29(1): e100671. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGupta D, Denton B: Appointment scheduling in health care: Challenges and opportunities. IIE Trans. 2008; 40(9): 800–819. Publisher Full Text\n\nLeviner S, Debbie T: Patient Flow Within Hospitals: A Conceptual Model. Nurs. Sci. Q. 2020; 33(1): 29–34. Publisher Full Text\n\nMoodley Y: Patient’s attitudes and perceptions around attending oncology consultations following surgery for colorectal cancer. [Dataset]. Open Science Framework. 2023, May 20. Publisher Full Text"
}
|
[
{
"id": "204249",
"date": "14 Sep 2023",
"name": "Shanaz Ghuman",
"expertise": [
"Reviewer Expertise epidemiology",
"risk behaviours",
"public/community health",
"medicinal plants",
"community development",
"administration/management",
"microbiology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the opportunity to review the manuscript on patients attitudes and perceptions around attending oncology consultations following surgery for colorectal cancer: a qualitative study. The paper is well written, and despite a small sample size of 7 participants the results align with previously published studies/research. The Health Services Use Model is appropriate, and 3 components were presented namely predisposing factors, enabling or disabling factors for compliance with oncology consultation and need for care. The results are presented and reported in tables for qualitative data; thematic analysis for qualitative data define the participants interview responses. The authors conclude that in order to improve oncology consultations, multifaceted approaches are integral to support patients with CRC.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "229113",
"date": "02 Jan 2024",
"name": "Haniee Chung",
"expertise": [
"Reviewer Expertise Colorectal cancer outcomes",
"Global surgery education"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nA simple study design to answer a very practical and important question. This study highlights the universal discrepancy that exists between providers' understanding and patients' perception of appropriate cancer care. No amount of evidence based clinical service will make up for cultural/social/economic hurdles that act as barriers to care if a patient is unwilling or unable to overcome them. Studies like this begin to close this gap.\n\nA particularly interesting and consideration is the recognizable global phenomenon in the rise in CRC in LMICs where previously CRC rates were low or unknown. This, in conjunction with the rise in young CRC in HICs raise very thought provoking questions regarding not only the pathophysiology underlying CRC development, but also the barriers to care that lead to higher stage at diagnosis.\n\nTo emphasize the urgency and importance of adjuvant systemic treatment, please consider including language and findings of studies that have established the importance of initiating treatment within 8-12 weeks postoperatively. In clinical practice, patients may no-show, but also present late- after this recommended window of treatment. Adding this to the suggested improvement in patient education may also be useful.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "229118",
"date": "19 Jan 2024",
"name": "Rajesh Balkrishnan",
"expertise": [
"Reviewer Expertise Cancer epidemiology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a qualitative study assessing perceptions around getting oncologic consultations following colorectal cancer surgery in a group of South African patients. Overall the study is well conducted and detailed in the report. The paper will be enhanced if the authors can spend more time in introduction and discussion discussing the importance of follow up care after CRC surgery and what type of interventions may be needed to increase post operation follow up rates.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-698
|
https://f1000research.com/articles/12-694/v1
|
16 Jun 23
|
{
"type": "Systematic Review",
"title": "Mapping inspiration in human resources: A systematic review of themes and approaches",
"authors": [
"Vagisha .",
"James P S",
"Vishwanathan Iyer",
"James P S",
"Vishwanathan Iyer"
],
"abstract": "Background: This study was motivated by the need to invigorate research on inspiration, especially within the domain of management. The authors’ objective was to devise a unifying structure for theory building and provide an overview of emergent constructs on inspiration research. Thus, the incremental contribution of the study is that the authors reviewed extant relevant literature and enhanced the focus on research on inspiration in management. Methods: We performed a literature search on empirical studies on inspiration from 15 June to 31 August 2022. We retrieved English articles published between 2003 and 2022. The information sources were Ebscohost, ProQuest, Science Direct, and Scopus. Risk of bias was assessed regarding review methods and the relevance of review to the research questions. We developed a data extraction sheet for the data collection process, considering the systematic review goals to ensure that all the pertinent data was retrieved. Results: Six out of 224 articles were identified for the final review. The excluded articles did not meet the either one or all of the inclusion criteria. The results revealed that there is a vast knowledge gap awaiting empirical research which can have a far-reaching impact on society and management; for instance, the impact of inspiration on performance and the role of moderators such as spirituality, visioning capability, gender variation, and linguistic proficiency. Conclusion: This study recommends that research on inspiration focuses to crystallize inspiration as a construct, identify various dimensions of inspiration, and then firm up a general theory of inspiration with robust empirical evidence. There is a need to expand the scope of the IS by developing and trying out newer competing scales.",
"keywords": [
"inspiration",
"human resource management",
"systematic literature review"
],
"content": "Introduction\n\nInspiration plays a vital role in the life of people and organizations. In the organizational context, inspiration is the responsibility of leadership. The role of leaders to motivate and inspire people is often considered the key to productivity (Conger, 1991). The era of managing by inspiration is gradually replacing the era of managing by control (Conger, 1991). Inspirational leadership (Molenberghs, 2015) is considered the appropriate leadership style when workers are worried, production is tenuous, and business is unstable. Therefore, inspirational leadership is needed most during economic downturns, uncertainties in world affairs, or in case of unexpected natural disasters (e.g., a tornado or an earthquake) or acts of terrorism (e.g., 9/11) (Angelo, 2020).\n\nThe role of inspiration is even more crucial when organizations must embark upon change and handle ambiguity in times such as COVID-19 (Joly, 2020) which underscored the importance of inspiring people to ensure high productivity (Tabrizi, 2020) and has tested leaders on all fronts on how they lead their employees (Joly, 2020; Goffee and Jones, 2000). Despite the hardships and risks, millions of frontline workers continued to do their jobs well in sub-optimal conditions, and COVID-like situations, Monkeypox, or wars/threats of war continue to loom large not to speak of contemporary challenges such as quiet quitting. These call for the best practices (Tomer and Kane, 2020), and inspiration could be an important influencer of such practices.\n\nA detailed search on inspiration from various sites such as (Ebsco, Proquest, and Science Direct), suggests that the concept of inspiration has been theorized sparsely. However, the term is referred to frequently in the domains of religion, creativity, interpersonal relationship, and leadership and often as a loose term to describe things that evoke something special in us; for example, we use terms such as inspired by a painting, a person, a waterfall, a writing, celestial beauty, etc. The initial discourses of inspiration find their place in theology as an extension of revelation. The term ‘revelation’ refers to the declaration of divine knowledge to the individual, whereas inspiration refers to transmitting the revelation into written form with invariable truths (Aquinas, 1950). This theological account of inspiration is a typical precursor of the tripartite conceptualization of inspiration (Thrash and Elliot, 2003) which consists of transcendence, evocation, and motivation. Inspiration implies motivation, which is to say that inspiration involves the energization and direction of behaviour (Elliot, 1997); however, inspiration is evoked, rather than initiated directly through an act of will. Though the trigger of inspiration is often invisible, perhaps because research has not unravelled it, the result of inspiration involves a transcendence of the ordinary preoccupations or limitations of human agency (Thrash and Elliot, 2003).\n\nThe word inspiration has its roots in biology where the term means drawing of breath and is metaphorically equivalent to energizing (Thrash and Elliot, 2003). A semblance of use of the term in academic literature may be found in the work of Bakker which refers to vigour, which is one of the dimensions of employee engagement, other two being dedication and absorption Bakker (2008). While vigour implies energy for action, absorption, is considered to lead to enduring motivation and focus, and energization for a course of behaviour (Thrash and Elliot, 2003; Elliot, 1997). Prior to the work of Thrash and Elliot (2003), Bass had coined the term ‘inspirational motivation’ in the leadership context (Bass, 1999). Inspirational motivation is one of the components of transformational leadership, others being idealized influence, intellectual stimulation, and individualized consideration (Bass, 1999). Inspirational motivation stands out as a unique component of transformational leadership, suggesting that the role of a leader goes beyond the well-researched concept of motivation. Literature around transformational leadership suggests that such leaders can beat resistance by inspiring people (Edmondson, 2002; Faupel and Süß, 2019; Lam, 2002; Joshi et al., 2009). Bass (1988) further suggested that an inspirational leader “employs persuasive appeals and arouses emotional acceptance” (p. 22). Such inspirational appeal aims to “generate enthusiasm and develop commitment” (Yukl, 1999), which is a major role in leadership. Although Bass (1998, 1999), Yukl (1999), Cho and Dansereau (2010) and several other authors have contributed to inspiration through the prism of transformational leadership (Gilley and Maycunich, 2000; Popper and Lipshitz, 2000; Tichy and DeVanna, 1990), none of them have explained what inspiration is. Rather, they preferred to combine the word ‘motivation’ with ‘inspiration’, perhaps because motivation was a well-established construct by the time Bass and others embarked upon research on transformational leadership, whereas inspiration was not.\n\nInspirational motivation leads to extra effort beyond what motivation can achieve (Densten, 2002). Inspirational motivation uses vision of the leader (Bass and Avolio, 1990) and helps organizations need to seize opportunities for growth and development (Conger, 1991). Inspirational motivation has been empirically linked not only to extra effort as discussed above, but also to ethical behaviour (Bass and Steidlmeier, 1999), learning orientation, and project success (Banerji and Krishnan, 2000; Coad and Berry, 1998; Thite, 1999). However, extra effort is the true differentiation of inspirational motivation and is central to the discriminant validity of inspirational motivation (Densten, 2002). This is because the extra effort leads to the ‘augmentation effect’ of inspirational motivation (Waldman et al., 1990). This augmentation effect accounts for the unique variance over and above what is accounted for by transactional leadership. Studies that show a high correlation between inspirational motivation and extra effort also exist (Bass and Avolio, 1990; Hater and Bass, 1988; Howell and Avolio, 1993). Despite the importance of inspirational motivation, the construct validity of inspirational motivation has been questioned (Densten, 2002). The basic question has been whether inspirational motivation is uni-dimensional (Hinkin and Tracey, 1999) as inspirational motivation has been found to be loading on three items including motivating elements and future-oriented theme that is based on open, verbal communication (Grant and Hofmann, 2011) in factor analysis (Hinkin and Tracey, 1999).\n\nOne approach to address the uni-dimensionality issue has been to explore inspirational motivation as image-based concept. This has been attempted by Lord and Emrich (2000) using ‘Martindale’s Regressive Imagery Dictionary’ (Martindale, 1975). Another approach has been to explore inspirational motivation as the result of using concept-based language such as alternative, commitment, work, and so on (Lord and Emrich, 2000). In sum, understanding the idea of inspirational motivation as a unique construct or establishing its uni-dimensionality has been difficult. Despite this challenge, efforts to separate inspiration and motivation and study inspiration as a separate construct has not been attempted in leadership literature and it is the work of Thrash and Elliot (2003) that has become foundational to explore inspiration as a construct.\n\nBroad audience literature uses the word inspiration rather than inspirational motivation. Anecdotal evidence of the role of inspiration in the performance of an individual is rich in the business world; for instance, job interviewers frequently ask the interviewee ‘what inspires you?’, and citations for awards suggest the inspirational action of an individual as the rationale for the award. Inspiration in its many manifestations is not limited to the domain of personal life (e.g., inspiration by a religious or political leader), but transcends to organizational settings (Avramenko, 2014), which is perhaps the reason why business leaders such as Steve Jobs had been given the tag of inspiring leaders.\n\nFrom the above discourse, it emerges that inspirational motivation is not a construct good enough to replace inspiration. Therefore, it is imperative to have a unified understanding of the concept of inspiration differentiated from inspirational motivation. This research addresses the above-mentioned gap by providing a unifying structure for theory building and research on inspiration and provides an overview of emergent constructs and approaches in inspiration research. The incremental contribution of this paper is that 1) the study brings a better understanding of inspiration through a systemic literature review (SLR), and 2) aids to decouple inspiration and motivation and makes a case to augment study inspiration as a separate construct. The authors reviewed extant literature on inspiration between 2003 and 2022 and enhanced the focus of research on inspiration in the organizational context.\n\n\nMethods\n\nThis systematic review was conducted using the PRISMA (Preferred Reporting Items for Systematic reviews and MetaAnalyses) methodology, which is a recognised approach from Liberati et al. (2017). The review was conducted on papers published from 2003 to 2022 to ensure that we had compiled a list of relevant papers that was as complete as possible. The PRISMA Checklist and Abstract Checklist have been reported by the authors under the reporting guidelines (Vagisha, 2023).\n\nFor the selection of the documents for the systematic review, the following inclusion criteria were determined:\n\n• Regarding the language, only studies that were in English were accepted. Studies that were in other languages were excluded, even if the abstract was in English.\n\n• Regarding the format, only articles that came from specialized management journals were accepted. Articles published on nonspecialized web pages, blogs, or digital newspapers, as well as books, book chapters, or doctoral theses, among others, were excluded.\n\n• Regarding the type of research, only empirical studies were accepted. Theoretical and reflective articles were excluded.\n\n• To adequately address the research questions asked, experimental studies that did not specify their sample were also excluded.\n\nTo compile the studies analyzed in the systematic review, a search protocol was carried out. The databases used to carry out the intended bibliographic review were Ebscohost, ProQuest, Science Direct, and Scopus and the search was carried out from 15 June to 31 August 2022 on all databases. The analyzed period corresponded to the last nineteen years (2003-2022) and the search string used was: ‘inspiration’ OR ‘inspirational leadership’, OR ‘inspirational communication’ OR ‘inspire’ OR ‘inspirational’ OR ‘inspiring’, OR ‘inspired’ in English. The search was run by title, abstract, and keywords. The chosen descriptors were selected to characterize the research in the field of inspiration.\n\nBased on the previously defined parameters, various documents were selected and exported to a specific folder in the Endnote software, which allowed duplicate documents to be identified based on the digital object identifier (DOI) and the bibliographic reference of the source. Subsequently, the articles whose title, keywords, abstract, and content were not directly related to the research questions or did not meet all the inclusion criteria previously described were refined.\n\nFor every retrieved paper, the title, abstract, and keywords were confronted with the eligibility criteria. This phase evolved the reading of each abstract of the retrieved papers in an unblinded standardized manner by two researchers, independently. In cases where there was no consensus, the articles were retained for more careful analysis in the phase of full-text analysis.\n\nWe developed a data extraction sheet for the data collection process, considering the Systematic Review goals to ensure that all the pertinent data was retrieved. We The considered variables that started to be collected were the Article Data: type of publication, year, keywords and study variables. The study variables contributed significantly to identifying the emergent themes in the literature. To specifically understand the advancement in the methodological approaches in the literature, we also recorded instruments used, sample characteristics, and selection in the retrieved papers.\n\nThe assessment of Risk of Bias of the retrieved papers is done using ROBIS Tool. It assesses both the risk of bias in a review and (where appropriate) the relevance of a review to the research question at hand. Specifically, it addresses 1) the degree to which the review methods minimised the risk of bias in the summary estimates and review conclusions, and 2) the extent to which the research question addressed by the review matches the research question being addressed by its user (e.g. an overview author or guideline developer). Bias occurs if systematic flaws or limitations in the design, conduct or analysis of a review distort the results. Evidence from a review may have limited relevance if the review question did not match the overview/guidelines question.\n\n\nResults\n\nThe initial data search yielded a total of 224 articles. Based on the inclusion criteria and screening process, 26 articles were included in the review. Table 1 provides the overview of the journals and articles.\n\nAlthough inspiration appears to be a conversant term, it has received little sustained attention in academia. It has been conceptualized narrowly within certain content domains (e.g., religious, creative, and interpersonal) or theoretical frameworks, as the authors indicated earlier in this study. The concept of inspiration has been employed in many disciplines including psychology (Thrash and Elliot, 2003), anthropology (Leavitt, 1997), theology (Aquinas, 1950; Canale,1994a, 1994b), education (Tjas et al., 1996), art and literature (Bowra, 1955; Harvey, 1999), engineering (Beer et al., 1997), management (Bass and Avolio, 1994; Dess and Picken, 2000), and communication (Frese et al., 2003; Rafferty and Griffin, 2004).\n\nThe year 2003 saw a seminal contribution in empirical research on inspiration. The significant section of empirical works on inspiration is ruled by two scholastic spaces: psychology and leadership. The three essential qualities of the state of inspiration are evocation, transcendence, and motivation, according to the tripartite conceptualization (Thrash and Elliot, 2003). Evocation suggests that inspiration is aroused by an external source and is involuntary. Inspiration involves the energization and direction of behavior. Transcendence suggests that inspiration attunes one toward something that is beyond one’s habitual limits enabling one to see better possibilities (Thrash and Elliot, 2003).\n\nAlthough the tripartite conceptualization provides a useful characterization of the state of inspiration, important questions remain regarding the processes that give rise to these characteristics. Thrash and Elliot (2004) proposed that inspiration is a hybrid construct that emerges from the juxtaposition of two component processes. The first component involves an appreciation of and accommodation or adaptation to an evocative object which is referred to as ‘inspired by’. The second component involves a drive to imbibe the qualities demonstrated in the evocative object/person (referred to as ‘inspired to’).\n\nThe broad concept of inspiration discussed earlier can be directly extended to the sphere of creative action (Thrash and Elliot, 2003). Thrash and Elliot’s (2003) research related general trait inspiration to creativity. Even when creative self-concept was controlled, trait inspiration still predicted mean levels of self-reported creativity in daily life. Additionally, among a sample of inventors, the frequency of inspiration predicted the number of U.S. patents received. This latter finding is crucial since patents are a concrete measure of creative achievement (Thrash and Elliot, 2004). Thrash and Elliot (2003) reported inspiration could be an antecedent of creativity and that people’s creativity tends to depend on inspiration. Self-reported creativity and general state inspiration fluctuate within individuals, over time. This suggests that people could be more creative on days when they feel more inspired. In other words, inspiration could be studied as an antecedent of creativity.\n\nTrait assessment scale of inspiration\n\nInspiration is both a state and a personality attribute (Thrash and Elliot, 2004). These are thought to vary between and among individuals. Thrash and Elliot (2004) developed the inspiration scale (IS) as a trait assessment of inspiration. Even if the term ‘trait’ has many meanings, it relates to personal differences in the tendency to experience the condition of inspiration. The IS has two internally consistent four-item subscales: inspiration frequency and intensity. Both subscales have Cronbach’s coefficients of 0.90 or above, indicating that they are internally consistent. The IS demonstrates measurement invariance across time (two months) and demographics (patent holders and university grads), implying that the basic latent components have similar meaning across time and groups. Both subscales exhibit strong test-retest reliabilities of two months (r = 0.77). In a nutshell, the IS has outstanding psychometric properties. The intensity subscale was created as a status indicator (Thrash and Elliot, 2004; Thrash, Elliot et al., 2010).\n\nWellbeing\n\nThrash, Elliot et al. (2010) posited that inspiration promotes different forms of wellbeing, including ‘hedonic wellbeing’ (e.g., activated positive affect), which is ‘pleasure-oriented’, and ‘eudemonic wellbeing’ (e.g., self-actualization), which is ‘growth-oriented’. The component processes of being inspired by and to were theorized to foster gratitude and purpose in life, respectively, and gratitude and purpose were posited to mediate effects on a variety of wellbeing. Inspiration consistently resulted in enhancements in activated “positive affect, life satisfaction, vitality, and self-actualization” throughout a series of research designed for causal inference, including an experiment, two cross-lagged longitudinal studies, and a diary study (Thrash et al., 2010).\n\nIn a more recent study, Milyavskaya et al. (2012) found that inspiration predicts achievements of individual goals. They also highlighted that goal progress may act as an additional mediator of the impact of inspiration on wellbeing. According to Straume and Vittersø (2012), inspiration is a sign of eudemonic wellbeing in and of itself.\n\nRole models\n\nLockwood et al. (2002) investigated inspiration in terms of good and negative role models using three experiments with three different populations. They used regulatory focus questionnaires, role model adjustment ratings, and motivation ratings. Hoyt and Simon (2011) looked at whether upward social comparisons to high-level female leaders had a detrimental impact on women’s self-perception and aspiration and discovered those female role models who contradicted the negative stereotype had a much more positive impact. People are motivated to compare themselves to superior role models to seek inspiration and hope (Hoyt and Simon, 2011). Role models at any level can be inspiring to the extent that individuals identify with them, consider their success as achievable, and “successfully disconfirm, at an explicit level, gender-stereotypical beliefs” (Hoyt and Simon, 2011).\n\nLeadership\n\nMolenberghs et al. (2015) and Waldman et al. (2011) studied the role of neuroscience in inspirational leadership and provided information on underlying brain processes associated with inspirational communication. Searle and Hanrahan (2011) used a phenomenological approach to study the lived and personal experiences of leaders, looking at inspiration as a psychological concept in the context of leadership. According to Rafferty and Griffin (2004), inspiring communication is one of the subdimensions of transformational leadership, in which leaders use inspirational appeals and emotive rhetoric to elicit followers’ motivation to move beyond self-interest for the good of the team Boies et al. (2015). Frese et al. (2003) presented and evaluated a management action training program that included inspirational vision communication as part of charismatic leadership training. They observed being inspirational as one aspect of charismatic leadership. Salas-Vallina and Fernandez (2017) investigated the relationship between inspirational leadership, participatory decision-making, and happiness at work. They found that participatory decision-making acts as a complete intermediary in the relation between inspired leadership and happiness at work. According to Mitchell and Boyle (2019), followers’ good moods tend to mediate the path between inspirational leadership and innovation, which could explain its various benefits. Inspiring leaders boost the team’s morale, which leads to more creative and flexible thinking. Mitchell and Boyle (2019) found that professional salience acts as a critical boundary condition in this relationship, with inspirational leaders increasing multidisciplinary team innovation through positive mood when a profession is salient. Salas-Vallina et al. (2020) looked at how inspirational leaders influence followers’ personality attributes and, as a result, their job happiness. Followers are motivated to actively learn by the intellectual stimulation provided by charismatic leaders. Leaders that instill a sense of responsibility and authority in their followers improve their employees’ quality of life (Salas-Vallina et al., 2020).\n\nSocial comparison\n\nBurleson et al. (2005) and Lockwood et al. (2012) looked at the role of social comparison in understanding changes in a teen’s creative self-concept when looking at inspiration. They assessed unfavorable comparisons that created a sense of inferiority, as well as favorable parallels that instilled a sense of inspiration. They connected comparisons of inferiority to negative changes in self-esteem. They linked improvements in self-esteem to inspirational comparisons made during the training. Upward comparisons inspire people to make the transition to a new cultural setting, according to Lockwood et al. (2012).\n\nSocial learning\n\nXia and Li (2022) introduced a new pasture of the role of inspiration in facilitating people’s social learning and communication across settings. To advance the understanding of how people share what they know, they examined the association between the inspiring level of a given message and its likelihood of being shared. The researchers reported a positive association between them.\n\nInstruments used\n\nThrash and Elliot (2003) developed the IS for their study. Subsequently, other authors (Thrash and Elliot, 2004; Thrash, Elliot et al., 2010; Thrash, Maruskin et al., 2010) used the IS for the research. Most authors (Hoyt, 2013; Hoyt and Simon, 2011; Lockwood et al., 2002, 2012; Parr et al., 2013; Souitaris et al., 2007; Stephan et al., 2015; Thrash et al., 2010; Van Kleef et al., 2015) used self-reported five-point scale to measure inspiration. Molenberghs et al. (2015) used the 204-item battery for visionary leadership (Kahan, 2002). Visionary leadership is transformative and based on the power of inspiration. Sosik and Dinger (2007) used Crowne and Marlowe’s (1960) social desirability scale-personal attributes shortened Reynolds’ (1982). Sosik and Dinger (2007) also used Good and Good’s (1972) 28-item dichotomously score to investigate inspiration through social power motivation. They also used Snyder and Gangestad’s 18-item scale to study the relationship between leaders’ personal attributes, leadership style, and inspirational vision themes. Table 2 offers an overview of the measurements used.\n\n* Overlapping of the codable studies is attributed to the use of multiple instruments in the same study.\n\nSample characteristics and selection\n\nThe authors reviewed the characteristics of the sample to determine the commonalities and differences in the target respondents and the extent to which these were generalisable to populations of interest. They reviewed 26 papers, out of which 18 papers comprehensively discussed sample characteristics. Seven (of 26) papers did not indicate the gender of the respondents and two (out of 26) did not indicate the occupation of the sample. Table 3 provides an overview of sample criteria and characteristics.\n\n* Research setting: U.S. East Coast, Southeast U.S. or Western U.S.\n\nGender of the sample. The authors coded the gender information in the studies as female-only, male-only, mainly female, mainly male, and gender-balanced. Of the 26 studies, 18 studies were codable and the remaining five studies did not indicate any information about the gender of the sample. Three studies used only female samples; 10 studies used mainly females as the sample; four studies used mainly males, and only one study was gender balanced.\n\nOccupation of the sample. 23 studies were codable as per the information indicated regarding the occupation. 12 (out of 23) studies where the occupation was coded indicated students were predominant in the sample selection. The researchers sub-coded the category of students as high school students and undergraduates wherein the latter was predominant. The sample of undergraduates included students of liberal arts, introductory psychology, personality psychology, science, and engineering. Two studies were based on a mixed sample. Six studies were coded as midlevel managers, fundraisers, customer service employees, public sector employees, focal leaders, and mixed. The sampling frames of the two studies were made up of allergy specialists from Spanish public hospitals and multidisciplinary healthcare teams based in the United Kingdom. Frontline banking personnel at Italian and Spanish banks were considered in one study.\n\nGeographic region. 14 out of the 26 studies were codable for geographic regions. Seven (out of 14) were conducted in the United States, two studies each in Canada, Europe, India, and Australia, and one study in the United Kingdom.\n\nThe findings of the study are:\n\n• 26 out of 224 articles were identified for the final review. The excluded articles did not meet the either one or all of the inclusion criteria.\n\n• Inspiration has been well understood intuitively for centuries but is nascent as an academic construct (Thrash and Elliot, 2004).\n\n• Inspiration as a term has been used in leadership literature widely to depict a distinct type of leadership that is superior to other forms, but the construct of inspiration itself has received little attention in conceptual or empirical research till this century (Thrash and Elliot, 2003).\n\n• The term has been used to denote higher order motivation and is distinct enough from motivation to demand theory building (Locke, 1982).\n\n• The term has been used in theology (Canale, 1994a, 1994b), literature (Bowra, 1955; Harvey, 1999), art (Bowra, 1955; Harvey, 1999), management (Bass and Avolio, 1994; Dess and Picken, 2000), and several other areas (Beer, et al., 1997; Hart, 1998; Kris, 1952; Lockwood and Kunda, 1997), which suggests that there is a need to have research that led to a general theory of inspiration.\n\n• Inspiration, as a construct, is recent (Thrash and Elliot, 2003) and has been emerging through a series of studies between 2003 and 2022.\n\n• Robust instruments have been developed to measure inspiration and this is likely to make an impetus in the research on inspiration, but more research in scale building is required (Thrash and Elliot, 2003; Hoyt, 2013; Hoyt and Simon, 2011; Lockwood et al., 2002; Lockwood et al., 2012; Parr et al., 2013; Souitaris et al., 2007; Stephan et al., 2015; Thrash et al., 2010; Van Kleef et al., 2015; Molenberghs et al., 2015; Crowne and Marlowe, 1960; Good and Good, 1972; Snyder and Gangestad, 1986).\n\n• There have been several avenues for studying inspiration: Antecedents of creativity, a component of charismatic leadership (Frese et al., 2003), dimension of transformational leadership (Rafferty and Griffin, 2004), its role in social learning (Xia and Li, 2022), social comparison (Burleson et al., 2005; Lockwood et al., 2012), well-being (Thrash et al., 2010), and role model (Hoyt and Simon, 2011; Lockwood et al., 2002).\n\n• Empirical studies on inspiration are emerging and are poised to fill a key knowledge gap on how people respond to inspiration and go on to achieve exceptional performance.\n\n• A detailed search of the literature revealed that there is a vast knowledge gap awaiting empirical research which can have a far-reaching impact on society and management; for instance, the impact of inspiration on performance and the role of moderators such as spirituality, visioning capability, gender variation, and linguistic proficiency.\n\n\nDiscussion\n\nInspiration has been well understood intuitively for centuries but is nascent as an academic construct (Thrash and Elliot, 2004). Inspiration as a term has been used in leadership literature widely to depict a distinct type of leadership that is superior to other forms, but the construct of inspiration itself has received little attention in conceptual or empirical research till this century (Thrash and Elliot, 2003). The term has been used to denote higher order motivation and is distinct enough from motivation to demand theory building (Locke, 1982). The term has been used in theology (Canale, 1994a, 1994b), literature (Bowra, 1955; Harvey, 1999), art (Bowra, 1955; Harvey, 1999), management (Bass and Avolio, 1994; Dess and Picken, 2000), and several other areas ((Beer, et al., 1997; Hart, 1998; Kris, 1952; Lockwood and Kunda, 1997), which suggests that there is a need to have research that led to a general theory of inspiration. Inspiration, as a construct, is recent (Thrash and Elliot, 2003) and has been emerging through a series of studies between 2003 and 2022. Robust instruments have been developed to measure inspiration and this is likely to make an impetus in the research on inspiration, but more research in scale building is required (Thrash and Elliot, 2003; Hoyt, 2013; Hoyt and Simon, 2011; Lockwood et al., 2002; Lockwood et al., 2012; Parr et al., 2013; Souitaris et al., 2007; Stephan et al., 2015; Thrash et al., 2010; Van Kleef et al., 2015; Molenberghs et al., 2015; Crowne and Marlowe, 1960; Good and Good, 1972; Snyder and Gangestad, 1986).\n\nThere have been several avenues for studying inspiration: Antecedents of creativity, a component of charismatic leadership (Frese et al., 2003), dimension of transformational leadership (Rafferty and Griffin, 2004), its role in social learning (Xia and Li, 2022), social comparison (Burleson et al., 2005; Lockwood et al., 2012), well-being (Thrash et al., 2010), and role model (Hoyt and Simon, 2011; Lockwood et al., 2002). Empirical studies on inspiration are emerging and are poised to fill a key knowledge gap on how people respond to inspiration and go on to achieve exceptional performance. A detailed search of the literature revealed that there is a vast knowledge gap awaiting empirical research which can have a far-reaching impact on society and management; for instance, the impact of inspiration on performance and the role of moderators such as spirituality, visioning capability, gender variation, and linguistic proficiency.\n\nDespite being a concept of long-established interest in varied disciplines, inspiration has gained little empirical attention. There is an absence of systematic analysis of conceptualization as well as of various approaches to research methods across inspiration literature. It is evident from the review that research on inspiration is flourishing but is fragmented. It is indicative that inspiration scholarship needs to bring definitional and conceptual concurrence, so that the foundation for research and theory building becomes robust.\n\nThis paper brings together the emergent constructs of inspiration from the literature and methodological approaches of the studies. There is a scope for a different selection criterion for the target respondents, as the present study indicates that most of the research targets undergraduates, majorly. It seems appropriate to include working professionals and corporate and social leaders. The findings have substantial implications for understanding and taking forward the contemporary inspiration literature by laying down a comprehensive overview of the extant scholarship of inspiration and identifying various gaps.\n\nIt is observed that a significant number of articles revolves around the theme of leadership, which could be attributed to use of inspiration by the leaders to achieve exceptional outcomes. This underscores the importance of knowing about inspiration so that everyone could use the tools of inspiration to achieve exceptional outcomes.\n\nThough this study includes all factors utilised in the study of inspiration, it is limited to journal articles and does not include published books, conference papers or other referred or non-refereed sources. The study had an “empirical articles” focus, and the inclusion of non-empirical studies could enhance the knowledge in this area.\n\nThe current literature on inspiration stops with a few empirical studies and tools, and this study recommends that research on inspiration focuses to crystallize inspiration as a construct, identify various dimensions of inspiration, and then firm up a general theory of inspiration with robust empirical evidence. There is a need to expand the scope of the IS by developing and trying out newer competing scales.",
"appendix": "Data availability\n\nDANS EASY: Mapping inspiration in human resources: A systematic review of themes and approaches. https://doi.org/10.17026/dans-zr5-73km (MAHE, 2022).\n\nThe project contains the following underlying data:\n\n• Data.pdf (Inspiration SLR Data in Tables 1, 2, and 3)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nFIGSHARE: PRISMA and PRISMA abstracts checklists for Mapping inspiration in human resources: A systematic review of themes and approaches’. https://doi.org/10.6084/m9.figshare.21947957.\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nReferences\n\nAngelo P: Inspirational leadership in a crisis. EHS Today; 2020, August 19. Reference Source\n\nAquinas T: Summa theologica. Stanford University Press; 1950.\n\nAvramenko A: Inspiration at work: Is it an oxymoron? Balt. J. Manag. 2014; 9(1): 113–130.\n\nBakker AB, Schaufeli WB, Leiter MP, et al.: Work engagement: An emerging concept in occupational health psychology. Work Stress. 2008; 22(3): 187–200. Publisher Full Text\n\nBanerji P, Krishnan VR: Ethical preferences of transformational leaders: An empirical investigation. Leadersh. Organ. Dev. J.2000; 21: 405–413. Publisher Full Text\n\nBass B: The inspirational processes of leadership. J. Manag. Dev.1988; 7(5):21–31. Publisher Full Text\n\nBass BM: Transformational leadership: Industrial, military, and educational impact. Lawrence Erlbaum Associates Publishers; 1998.\n\nBass BM: Two decades of research and development in transformational leadership. Eur. J. Work Organ. Psy. 1999; 8: 9–32. Publisher Full Text\n\nBass BM, Avolio BJ: Transformational leadership development: Manual for the multifactor leadership questionnaire. Consulting Psychologists Press; 1990.\n\nBass BM, Avolio BJ: Improving organisational effectiveness through transformational leadership. Sage; 1994.\n\nBass BM, Steidlmeier P: Ethics, character, and authentic transformational leadership behavior. Leadersh. Q. 1999; 10(2): 181–217. Publisher Full Text\n\nBeer RD, Quinn RD, Chiel HJ, et al.: Biologically inspired approaches to robotics: What can we learn from insects? Commun. ACM. 1997; 40: 30–38. Publisher Full Text\n\nBoies K, Fiset J, Gill H: Communication and trust are key: Unlocking the relationship between leadership and team performance and creativity. Leadersh. Q. 2015; 26(6): 1080–1094. Publisher Full Text\n\nBowra CM: Inspiration and poetry. Macmillan; 1955.\n\nBurleson K, Leach CW, Harrington DM: Upward social comparison and self-concept: Inspiration and inferiority among art students in an advanced programme. Br. J. Soc. Psychol. 2005; 44(1): 109–123. Publisher Full Text\n\nCanale FL: Revelation and inspiration: The classical model. Andrews University Seminary Studies. 1994a; 32: 7–28.\n\nCanale FL: Revelation and inspiration: The liberal model. Andrews University Seminary Studies. 1994b; 32: 169–195.\n\nCho J, Dansereau F: Are transformational leaders fair? A multi-level study of transformational leadership, justice perceptions, and organizational citizenship behaviors. Leadersh. Q. 2010; 21(3): 409–421. Publisher Full Text\n\nCoad AF, Berry AJ: Transformational leadership and learning orientation. Leadersh. Organ. Dev. J.1998; 19(3):164–172. Publisher Full Text\n\nConger JA: Inspiring others: The language of leadership. Executive. 1991; 5(1): 31–45.\n\nCrowne DP, Marlowe D: A new scale of social desirability independent of psychopathology. J. Consult. Psychol. 1960; 24(4): 349–354. PubMed Abstract | Publisher Full Text\n\nDensten IL: Clarifying inspirational motivation and its relationship to extra effort. Leadersh. Org. Dev. J. 2002; 23: 40–44. Publisher Full Text\n\nDess GG, Picken JC: Changing roles: Leadership in the 21st.2000.\n\nEdmondson AC: The local and variegated nature of learning in organizations: A group-level perspective. Organ. Sci. 2002; 13: 128–146. Publisher Full Text\n\nElliot AJ: Integrating the “classic” and “contemporary” approaches to achievement motivation: A hierarchical model of approach and avoidance achievement motivation.Maehr ML, Pintrich PR, editors. Advances in motivation and achievement. 1997; (pp. 143–179).\n\nFaupel S, Süß S: The effect of transformational leadership on employees during organizational change: An empirical analysis. J. Chang. Manag. 2019; 19: 145–166. Publisher Full Text\n\nFrese M, Beimel S, Schoenborn S: Action training for charismatic leadership: Two evaluations of studies of a commercial training module on inspirational communication of a vision. Psychol. Women Q. 2003; 56(3): 671–698. Publisher Full Text\n\nGilley J, Maycunich A: Organizational learning, performance, and change: An introduction to strategic human resource development. Perseus; 2000.\n\nGoffee R, Jones G: Why should anyone be led by you. Harvard Business Review; 2000, September-October. Reference Source\n\nGood LR, Good KC: An objective measure of the motive to attain social power. Psychol. Rep. 1972; 30: 247–251. Publisher Full Text\n\nGrant AM, Hofmann DA: Outsourcing inspiration: The performance effects of ideological messages from leaders and beneficiaries. Organ. Behav. Hum. Decis. Process. 2011; 116(2): 173–187. Publisher Full Text\n\nHart T: Inspiration: Exploring the experience and its meaning. J. Humanist. Psychol.1998; 38(3):7–35. Publisher Full Text\n\nHarvey J: Music and inspiration. Faber and Faber; 1999.\n\nHater JJ, Bass BM: Superiors' evaluations and subordinates' perceptions of transformational and transactional leadership. J. Appl. Psychol.1988; 73(4):695–702. Publisher Full Text\n\nHinkin TR, Tracey JB : The relevance of charisma for transformational leadership in stable organizations. J. Organ. Change Manag. 1999; 12(2): 105–119. Publisher Full Text\n\nHowell JM, Avolio BJ: Transformational leadership, transactional leadership, locus of control, and support for innovation: Key predictors of consolidated-business-unit performance. J. Appl. Psychol.1993; 78: 891–902. Publisher Full Text\n\nHoyt CL: Inspirational or self-deflating the role of self-efficacy in elite role model effectiveness. Soc. Psychol. Personal. Sci. 2013; 4(3): 290–298. Publisher Full Text\n\nHoyt CL, Simon S: Female leaders injurious or inspiring role models for women? Psychol. Women Q. 2011; 35(1): 143–157. Publisher Full Text\n\nJoly H: Lead your team into post-pandemic world. Harvard Business Review; 2020, May 8. Reference Source\n\nJoshi A, et al.: Getting everyone on board: The role of inspirational leadership in geographically dispersed teams. Organ. Sci. 2009; 20(1): 240–252. Publisher Full Text\n\nKahan S : Visionary Leadership. Executive Update. 2002 April.\n\nLam JYL: Defining the effects of transformational leadership on organisational learning: A cross-cultural comparison. School Leadership and Management. 2002; 22(4): 439–452. Publisher Full Text\n\nLeavitt J: Poetry and prophecy: The anthropology of inspiration. University of Michigan Press; 1997.\n\nLiberati EG, Ruggiero F, Galuppo L, et al.: What hinders the uptake of computerized decision support systems in hospitals? A qualitative study and framework for implementation. Implement. Sci. 2017; 12(1): 113. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLockwood P, Jordan CH, Kunda Z: Motivation by positive or negative role models: Regulatory focus determines who will best inspire us. J. Pers. Soc. Psychol. 2002; 83(4): 854–864. Publisher Full Text\n\nLockwood P, Kunda Z: Superstars and me: Predicting the impact of role models on the self. J. Pers. Soc. Psychol. 1997; 73(1): 91–103. Publisher Full Text\n\nLockwood P, Shaughnessy F, Fortune JL, et al.: Social comparisons in novel situations: Finding inspiration during life transitions. Personal. Soc. Psychol. Bull. 2012; 38(8): 985–996. Publisher Full Text\n\nLord RG, Emrich CG: Thinking outside the box by looking inside the box: Extending the cognitive revolution in leadership research. Leadersh. Q.2000; 11(4):551–579. Publisher Full Text\n\nManipal Academy of Higher Organization: Inspiration SLR Data. Dataset. DANS. 2022. Publisher Full Text\n\nMartindale C: Romantic progression: The psychology of literary history.Washington, D.C.: Hemisphere; 1975.\n\nMilyavskaya M, Ianakieva I, Foxen-Craft E, et al.: Inspired to get there: The effects of trait and goal inspiration on goal progress. Personal. Individ. Differ. 2012; 52(1): 56–60. Publisher Full Text\n\nMitchell R, Boyle B: Inspirational leadership, positive mood, and team innovation: A moderated mediation investigation into the pivotal role of professional salience. Hum. Resour. Manag. 2019; 58(3): 269–283. Publisher Full Text\n\nMolenberghs P: The neuroscience of inspirational leadership: The importance of collective-oriented language and shared group membership. J. Manag. 2015.\n\nParr AD, Hunter ST, Ligon GS: Questioning universal applicability of transformational leadership: Examining employees with autism spectrum disorder. Leadersh. Q.2013; 24(4):608–622. Publisher Full Text\n\nPopper M, Lipshitz R: Organizational learning: Mechanisms, culture, and feasibility. Manag. Learn. 2000; 31(2): 181–196. Publisher Full Text\n\nRafferty AE, Griffin MA: Dimensions of transformational leadership: Conceptual and empirical extensions. Leadersh. Q. 2004; 15(3): 329–354. Publisher Full Text\n\nReynolds WM: Development of reliable and valid short forms of the Marlowe-Crowne Social Desirability Scale. J. Clin. Psychol. 1982; 38(1): 119–125. Publisher Full Text\n\nSalas-Vallina A, Fernandez R: The HRM-performance relationship revisited. Empl. Relat. 2017; 39: 626–642. Publisher Full Text\n\nSalas-Vallina A, Simone C, Fernández-Guerrero R: The human side of leadership: Inspirational leadership effects on follower characteristics and happiness at work (HAW). J. Bus. Res. 2020; 107: 162–171. Publisher Full Text\n\nSearle GD, Hanrahan SJ: Leading to inspire others: Charismatic influence or hard work? Leadersh. Org. Dev. J. 2011; 32(7): 736–754. Publisher Full Text\n\nSnyder M, Gangestad S: On the nature of self-monitoring: Matters of assessment, matters of validity. J. Pers. Soc. Psychol. 1986; 51(1): 125–139. PubMed Abstract | Publisher Full Text\n\nSosik JJ, Dinger SL: Relationships between leadership style and vision content: The moderating role of need for social approval, self-monitoring, and need for social power. Leadersh. Q. 2007; 18(2): 134–153. Publisher Full Text\n\nSouitaris V, Zerbinati, Al-laham: Do entrepreneurship programmes raise entrepreneurial intention of science and engineering students? The effect of learning, inspiration and resources. J. Bus. Ventur. 2007; 22(4): 566–591. Publisher Full Text\n\nStephan E, Sedikides C, Wildschut T, et al.: Nostalgia-evoked inspiration mediating mechanisms and motivational implications. Personal. Soc. Psychol. Bull. 2015; 014616721559698.\n\nStraume LV, Vittersø J: Happiness, inspiration and the fully functioning person: Separating hedonic and eudaimonic well-being in the workplace. J. Posit. Psychol. 2012; 7: 387–398. Publisher Full Text\n\nTabrizi B: Put employees at the centre of your post-pandemic digital strategy. Harvard Business Review; 2020, October 15. Reference Source\n\nThite M: Identifying key characteristics of technical project leadership. Leadersh. Organ. Dev. J.1999; 20(5):253–261. Publisher Full Text\n\nThrash TM, Elliot AJ: Inspiration as a psychological construct. J. Pers. Soc. Psychol. 2003; 84(4): 871–889. Publisher Full Text\n\nThrash TM, Elliot AJ: Inspiration: Core characteristics, component processes, antecedents, and function. J. Pers. Soc. Psychol. 2004; 87(6): 957–973. PubMed Abstract | Publisher Full Text\n\nThrash TM, Elliot AJ, Maruskin LA, et al.: Inspiration and the promotion of well-being: Tests of causality and mediation. J. Pers. Soc. Psychol. 2010; 98(3): 488–506. PubMed Abstract | Publisher Full Text\n\nThrash TM, Maruskin LA, Cassidy SE, et al.: Mediating between the muse and the masses: Inspiration and the actualisation of creative ideas. J. Pers. Soc. Psychol. 2010; 98(3): 469–487. 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Publisher Full Text\n\nWaldman DA, Bass BM, Yammarino FJ: Adding to contingent-reward behavior: The augmenting effect of charismatic leadership. Group Organ. Stud.1990; 15(4):381–394. Publisher Full Text\n\nXia W, Wai Li LM: When and how to share? The role of inspiration. J. Soc. Psychol. 2022; 1–15. Publisher Full Text\n\nYukl G: An evaluation of conceptual weaknesses in transformational and charismatic leadership theories. Leadersh. Q.1999; 10(2):285–305. Publisher Full Text"
}
|
[
{
"id": "181652",
"date": "19 Jul 2023",
"name": "Ashish Bollimbala",
"expertise": [
"Reviewer Expertise Behavioral science."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study fills a major gap in inspirational literature which is sparse and has the potential to kick start deliberate and scientific studies in the concept of inspiration which is highly valued, at least in general literature. The work has the potential to make research in inspiration valuable and so, it is an important contribution to the knowledge on inspiration. However, the authors could address the following issues to enhance the value of this paper.\nAbstract – The authors are advised to revise the abstract to revise the findings/conclusions so that a reader can get a clearer picture of the value of the study. This is important to attract readership to the article and consequently to the journal. For instance, the findings could highlight the themes that have emerged from the analysis of literature.\n\nKey Words – More attention could be given to the key words which enables finding the article against search. For example, a key word such a ‘review’ may be too general to be of much use.\n\nRather than state that various sites have been searched, it is preferable to be more specific and clarify the number of electronic databases used.\n\nIt is important to distinguish between inspiration and motivation. Mere statements that inspirational motivation is different from inspiration is not sufficient to justify that inspiration and motivation are or at the least possibly different constructs. This assertion with literature support is crucial for progression of research in inspiration using it as a distinct construct different from motivation. This is an important aspect the authors should address.\n\nWhile the authors state “From the above discourse, it emerges that inspirational motivation is not a construct good enough to replace inspiration”, it is recommended that some examples of broad audience literature with reference is used. Though this might be intuitive or even correct, referencing is the key to a good research article.\n\nThe authors state “The researchers obtained the abstract from the databases of EbscoHost or ProQuest or Science Direct”. Is it that they procured it using all these databases? The word ‘or’ could be confusing. If they authors have used all of them, the conjunction ‘and’ would be more appropriate than ‘or’.\n\nThe period of inclusion is from 2003 to 2022. While 2022 needs no justification, reason for using 2003 as the start point for the database search needs some elaboration. At the moment it looks a little arbitrary.\n\nPara 3.1, Conceptualization of Inspiration should be rewritten to improve the flow. Thereafter, the emergent themes included in 3.2 are well addressed.\n\nFrom a plain reading of Para 3.3, and the articles in general, it appears that Thrash and Elliot makes a significant contribution and there is an important landmark in inspiration research. It will help the reader if the authors elucidate this instrument a little more and even include some of the qualitative strengths of the instrument such as reliability and validity so that it helps future research.\n\nThough minor, changing the language such as ‘gender of the sample’ or ‘occupation of the sample’ can have a salutary effect on the quality of the paper.\n\nThe findings are comprehensive and well addressed.\n\nThe last para addresses future areas of study. Since the authors have done so much study and are suggesting the importance of addressing the concept more empirically, even though such suggestion may be tacit, could the authors consider suggesting the general direction of empirical studies with some examples so that research in inspiration can be invigorated?\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": []
},
{
"id": "194563",
"date": "18 Aug 2023",
"name": "Hussam Ali Mhaibes",
"expertise": [
"Reviewer Expertise General specialization in public administrationSpecialization in strategic management and organization theory"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI commend the researchers for their diligent work, as their study delves into a significant subject matter in an intriguing manner, offering a unique scientific contribution to an area already explored by scholars.\nWhile the research is commendable, I have a few observations that, if addressed, could further enhance the quality of the study:\nThe research objective, although present, could benefit from greater clarity in its expression. It appears that the researchers may have slightly underestimated the significance of their research objective, warranting a more comprehensive portrayal.\n\nThe mention of the sources originating from Ebscohost, ProQuest, Direct Science, and Scopus might not be necessary. The research itself is lucid, and there's no need to reiterate that the selected sources were of quality. Rather, it would be sufficient to state that the research selected for review was well-chosen.\n\nGiven that a substantial number of sources cited by the researchers pertain to \"Inspirational Leadership,\" it might be advisable to consider incorporating this term into the research title. This approach could effectively encapsulate the research's essence and its focus on this particular area.\n\nThe introduction contains solid theoretical groundwork, yet it lacks certain fundamental elements typically expected in an introduction. Specifically, the final paragraph of the introduction seems to leave room for further elaboration and development.\n\nIn conclusion, the results and conclusions of the study are commendable and have been thoughtfully discussed. Moreover, the selection and formatting of references have been executed with precision.\nThank you for considering these observations. I believe that addressing these points could contribute to refining the research and enhancing its impact. I appreciate the opportunity to engage with this scholarly work and contribute to its improvement.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "194564",
"date": "23 Aug 2023",
"name": "Idris Idris",
"expertise": [
"Reviewer Expertise My research interest includes but is not limited to Organizational behavior",
"leadership",
"and tourism and hospitality."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIntroduction: An overview of leadership literature, the sentence “none of them have explained what inspiration is” should be compared to other previous literature, at least what they were conducted in terms of inspiration that emerged in their studies. In addition, the research question in a systematic literature review is compulsory.\nMethod: The research procedure was presented in detail. But, this manuscript failed to follow the one crucial step in SLR, formulating the research question. This step will specify what type of studies can best address that question and set out criteria for including such studies in the review (inclusion criteria or eligibility criteria). Any research question has ideological and theoretical assumptions around the meanings and processes it is focused on. A systematic review should either specify definitions and boundaries around these elements at the outset or be clear about which elements are undefined, including in the search string used and broken down from the research questions. Another issue is about data analysis used in the review. It is crucial for this study to enhance and formulate the data extraction and analysis and draw the findings of the study.\n\nResults: In the results, the authors should present the PRISMA figure mentioned in the study, such as how many articles in total were obtained based on the search string and excluded based on the eligibility criteria.\nDiscussion: What is presented in the discussion section is better to follow the research goals or research questions.\nConclusion: No conclusion is presented in the manuscript.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Partly\n\nAre the conclusions drawn adequately supported by the results presented in the review? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-694
|
https://f1000research.com/articles/12-690/v1
|
16 Jun 23
|
{
"type": "Research Article",
"title": "Analyzing the relationship between pricing strategy and customer retention in hotels: A study in Albania",
"authors": [
"Brunela Trebicka",
"AZETA TARTARAJ",
"Ariola Harizi",
"AZETA TARTARAJ",
"Ariola Harizi"
],
"abstract": "Background: In the consumer-centric global economy of the 21st century, customer retention is a vital concept in the hospitality industry for building and sustaining long-term relationships. Recognizing the challenges of acquiring new customers, the industry acknowledges the significance of retaining existing ones. To achieve their goals, hospitality businesses need a comprehensive strategy that extends beyond price targets, emphasizing the development of effective pricing strategies from the outset. Methods: Data collection took place between June 2022 and January 2023, involving a random sample of seven international hotels located in Tirana, Durres, and Vlora. Quantitative data was collected through surveys utilizing Likert-scale questions. Statistical analysis, including crosstab tests, was employed to explore the relationship between economy pricing strategies and customer retention. Results: The study encompassed 572 participants representing diverse demographic characteristics. Analysis revealed a statistically significant positive relationship between economy pricing strategies and customer retention in international hotels in Albania. These findings underscore the importance of implementing effective pricing strategies to enhance customer loyalty and guide the development of improved strategies within the hotel industry. Conclusions: This study provides empirical evidence of a significant positive relationship between economy pricing strategies and customer retention in international hotels in Albania. Effective pricing strategies play a crucial role in fostering customer loyalty. However, the study's limitations, primarily its focus on specific hotels in Albania, call for further research to validate the generalizability of these findings. The insights gained from this study inform policymakers and industry stakeholders in formulating strategies to enhance customer retention within the hospitality sector.",
"keywords": [
"Economy Pricing",
"pricing strategies",
"Customer retention",
"Hospitality industry",
"Relationship marketing"
],
"content": "Introduction\n\nOver the past decade, international hotels have undergone significant development, making it challenging for them to gain a competitive advantage in the highly competitive market environment. As a result, hotels have to adopt new strategies to achieve their long-term goals. One of the most significant changes has occurred in international hotel pricing, with the implementation of various pricing strategies. Pricing strategy is critical for the success of international hotels. The price must be competitive, accurate, and consistent (Gao, Wang, and Fang, 2020).\n\nAn effective pricing strategy can improve business performance and lead to positive outcomes such as customer satisfaction, loyalty, and customer retention, especially for business entities (Zakaria, Abdullah, and Ali, 2019). A pricing strategy is an essential part of creating a sustainable competitive advantage that helps businesses build customer loyalty and increase satisfaction. An effective pricing strategy gives a business an edge over competitors by delivering more value to customers at lower cost or higher price, where additional benefits and services are added. When a business spends less than its competitors, it can use lower prices to attract customers. Therefore, pricing is critical to business leadership. Moreover, companies use price reductions as a strategy to increase or maintain their market share. Customers often use price as an indicator of product quality, especially when they have limited information to make a judgment (Rizov, 2019).\n\nThere are many studies on pricing strategies and customer retention in the hospitality industry, but little attention has been given to the impact of economy pricing strategies on hotel customer retention, especially in Albania. Therefore, this study aims to investigate the impact of economy pricing strategies on customer retention in selected international hotels in Albania.\n\nThe research aims to assess the level of use of economy pricing strategies and their impact on customer retention in the international hotel industry in Albania, with the aim of improving the development of hotel services in a competitive market environment.\n\nThis study will provide valuable insights into the effectiveness of cost-effective pricing strategies that comparable hotels can use to retain guests. The results will help hoteliers evaluate their current pricing strategies and make any necessary adjustments to improve guest retention.\n\nAdditionally, this research will help business leaders identify effective retention techniques and areas for improving customer retention policies.\n\nThe main research objectives of this study are:\n\n1. Investigate the relationship between economy pricing strategy and customer retention of international hotels in Albania.\n\n2. Identify the most effective economy pricing strategy to achieve and increase customer retention of international hotels in Albania.\n\nThe following research questions will guide this study:\n\nResearch question one (RQ1): Is there a relationship between economic pricing strategies and customer retention in international hotels in Albania?\n\nResearch question two (RQ2): What is the impact of economy pricing strategies on customer retention in selected international hotels in Albania?\n\nThis study aims to investigate the relationship between economy pricing strategies and customer retention rates in selected international hotels in Albania. Economy pricing strategy is considered as the independent variable, while customer retention is the dependent variable. The conceptual framework in the Figure 1, below illustrates the relationship between the two variables:\n\nBased on the relationship between the independent and dependent variables, the research hypothesis are as follow:\n\nNull hypothesis (H0): There is no significant relationship between economy pricing strategies and customer retention in international hotels in Albania.\n\nHypothesis one (H1): There is a significant positive relationship between economy pricing strategies and customer retention in international hotels in Albania.\n\nThe importance of pricing is an important part of the marketing mix that generates revenue for a company (Asamoah and Chovancová, 2011). It is a flexible variable that can be adjusted based on market demand (Zhang et al., 2017) states that price determines the amount buyers are willing to pay for a product or service based on their decision. Price is one of the four P’s of the marketing mix that consumers consider before making a purchase decision (Kotler et al., 2022a). When determining the pricing strategy, it is essential to consider three critical factors, including the perception of the product’s value by buyers, the number of buyers in the market, and their price sensitivity (Azad and Subrahmanyam, 2022).\n\nFurthermore, understanding how buyers will respond to prices requires research and analysis. Price elasticity, or the sensitivity of buyers to price changes, impacts the demand for products. The degree of change in demand in response to a change in price is known as price elasticity. According to Agwu (2018), when buyers are highly sensitive to price changes, they buy more of a product at lower prices and less of it when the price is higher. This indicates that the demand for the product is elastic with respect to price. Buyers are more likely to purchase products when their prices decrease and less likely to purchase them when their prices increase. In contrast, when demand for a product remains relatively stable and buyers are not sensitive to price changes, the demand is price inelastic (Collado et al., 2017).\n\nThe pricing strategy is an important aspect of marketing as it affects both revenue and consumer behavior. The pricing environment is evaluated from the viewpoint of the firm and its strategies, as well as from the consumer’s perspective, with consideration of external influences such as government policies and competition (Kotler et al., 2022b). Buyers may be individuals or firms who purchase the entire product or only parts of it, aiming to satisfy their needs or requirements (Subramanian and Azad, 2021). To meet these requirements, customers use various parameters such as price and quality to determine their purchasing decisions.\n\nDifferent pricing models are analyzed after considering these factors, and considerations are given to their effective implementation, balancing price levels, and their impact on consumer behavior (Geng et al., 2018). Despite efforts of financial experts to understand pricing and estimation methods, reliable pricing models remain elusive (Chen et al., 2016).\n\nPricing strategy\n\nPricing strategy is an important part of a company’s marketing mix as it directly affects the company’s profitability and its competitiveness in the market. Before choosing an appropriate pricing strategy for its product or service, a company must consider several factors such as customer demand, production costs, and competition (Kotler et al., 2022a).\n\nBusinesses can use a variety of pricing strategies, including cost-plus pricing, value-based pricing, and penetration pricing. Cost-plus pricing involves adding a price to the cost of producing a product to determine the selling price. On the other hand, value-based pricing focuses on the perceived value of a product in the eyes of customers rather than the cost of production. Penetration pricing is often used to enter a new market, where a company sets a low price to attract customers and gain market share (Kotler et al., 2022a).\n\nThe choice of pricing strategy depends on the company’s objectives, the target market, and the competitive environment. For example, a hotel company can use a dynamic pricing strategy to adjust room rates based on occupancy levels and demand fluctuations (Xiang et al., 2017). Alternatively, luxury hotels may adopt a premium pricing strategy, charging high prices to reflect the exclusivity and quality of their services (Luo et al., 2019).\n\nIn summary, pricing strategy plays a vital role in a company’s marketing efforts, and a well-designed pricing strategy can help a company achieve its sales and revenue targets. However, market conditions, customer behavior and competition should be considered when selecting an appropriate pricing strategy for a product or service.\n\nEconomy pricing\n\nAccording to Papatla and Zhang (2021), economic pricing is a pricing strategy when a product or service is offered at a lower price than competitors. Companies often use this tactic to attract price-sensitive customers and increase their market share. The success of economy pricing depends on several factors such as the company’s cost structure, elasticity of demand, and competition. Additionally, research by Papatla and Zhang (2021) highlights that economy pricing has a positive impact on customer satisfaction and loyalty, which can lead to long-term profitability for the business. In the hotel industry, according to Dai and Zhang (2017), economy pricing is used to balance room rates and room demand for future dates. The pricing strategies are influenced by the principles of supply and demand, with lower prices when the demand is low and higher prices when the demand is high. Neubert (2017) also noted that for pre-orders further from the arrival date, the probability of return is generally greater and prices tend to increase as the arrival date approaches.\n\nIn general, economy pricing is a widely used pricing strategy in various industries, including food retail and hospitality. The success of this pricing strategy depends on several factors, such as elasticity of demand, competition, and cost structure, and can have a significant impact on customer satisfaction and loyalty.\n\nEffective customer retention management has become essential for businesses, especially in the hospitality industry. According to Ascarza et al. (2018), if the main objective of hotels is to attract customers, retaining them has become equally important. Research by Del Rio Olivares et al. (2018) shows that a 5% increase in customer retention can lead to increase of profit of 20% to 90%.\n\nTherefore, companies need to manage their customers throughout their lifecycle, from suspect to partner or defender, as explained from Han and Hwang (2018).\n\nIn the past, many hotels did not prioritize guest satisfaction, leading to high churn, known as the ‘broken barrel’ hypothesis. As Hanaysha (2018) pointed out, this approach leads to a constant influx of new customers and the loss of existing customers. However, reducing churn can significantly improve profits. For example, Razzaq et al. (2018) found that a 5% reduction in churn can increase profits by 20% to 100%.\n\nSeveral factors influence guest retention in the hospitality industry. According to Kung and Zhong (2017), adaptability and consistency in the decision-making process can affect customer loyalty patterns. Lee and Fay (2017) also highlight the importance of adaptability in the decision-making process as it shapes hotel strategy and processes. Moreover, the passive behavior of hotel staff greatly affects the level of customer loyalty (Luo et al., 2018). Luo et al. (2018) found that the best hotel staff do not always fully understand the importance and consequences of customer retention, as they often view it as just another characteristic of the hotel. Therefore, customer retention should be integrated into organizational goals and practices, and employees should be trained accordingly (Reen et al., 2017).\n\nLeadership should also provide employees with control checks and learning opportunities to motivate them to prioritize customer retention (Subrahmanyam, 2018). A combination of various strategies, including promotional offers, is the best way to retain customers in the hospitality industry (Ferdous Azam and Karim, 2017).\n\nGuest satisfaction and loyalty are key to improving hotel guest retention. Highly satisfied customers tend to remain loyal and contribute significantly to a hotel’s revenue by repeat purchases and recommending the hotel to others (Kang and Kim, 2017). Additionally, satisfied customers are less likely to switch to competitors and are easier and cheaper to maintain, requiring less training and marketing effort (Subrahmanyam and Azad, 2019).\n\nWith changing demographics, economics and competitive factors, the cost of acquiring new guests is increasing, forcing hotels to focus on profitable guest retention and building lasting relationships with them. Therefore, hotels must prioritize guest satisfaction and value to ensure guest retention and loyalty.\n\n\nMethods\n\nThis study received retroactive ethical approval from the council of ethics of University “Aleksander Moisiu” as this was a low-risk study. Written informed consent was obtained from all participants prior to completing the survey.\n\nThis study uses a quantitative strategy because it uses statistics as a time-saving tool and requires less effort and resources. Moreover, using this method is the best way to quantify and analyze the relationship between variables. In this study, an attempt was made to quantify the economy pricing strategy as an independent variable to determine the relationship with customer loyalty in selected international hotels in Albania.\n\nData collection took place from June 2022 to January 2023 in the cities of Tirana, Durres, and Vlora, where a purposive sampling strategy was employed to select seven international hotels as participants. Inclusion criteria for hotel selection were based on their international status and availability to accommodate data collection. The sample size was determined using the number of rooms in each hotel to ensure representation and diversity. Randomization was achieved by assigning a unique identification number to each hotel and using a random number generator to select the participating hotels. The method of random sampling aimed to provide equal opportunities for all customers to contribute to the study.\n\nThe selected hotels included Rogner, Sheraton, and Hilton in Tirana; Adriatik, Tropikal, and Palace in Durres; and Vlora International Hotel in Vlora. These hotels were chosen based on their relevance and representation within the international hotel sector in Albania.\n\nBy employing a purposive sampling strategy, randomization, and sample saturation, this study ensured the inclusion of diverse international hotels in the sample, increasing the generalizability of the findings. The rationale behind these methodological choices was to obtain a comprehensive understanding of the relationship between economy pricing strategies and customer retention in the international hotel industry in Albania.\n\nAs mentioned in the previous section, the study examines the relationship between economy pricing strategies of international hotels and customer loyalty in Albania using quantitative techniques and questionnaires. A survey consists of several questions asked of respondents based on their opinions and past experiences at a particular hotel. The study used surveys based on various scientific sources. The questionnaire was adapted from reliable academic work published in reliable international publications modified from Njeru and Karega (2017) and Rao and Kartono (2009). To ensure the survey’s suitability for the study’s context, the modified version was piloted prior to the main data collection. The pilot study involved a small group of participants who completed the survey and provided feedback on its clarity, relevance, and comprehensibility. Based on the pilot study’s findings, necessary revisions were made to enhance the questionnaire’s overall quality and ensure its alignment with the research objectives. The participants completed the survey and provided feedback on the aspects such as clarify, relevance and comprehensibility of the questions. The pilot study served as an iterative process to refine and improve the questionnaire. This iterative process allowed for the identification and resolution of any potential issues or ambiguities in the survey instrument, ensuring its effectiveness in collecting the desired data.\n\nThe language used in the modified questionnaire was Albanian for Albanian citizens and English for the foreigners. By adapting the survey to the local language, it was possible to better understanding and improve response rates among the Albanian population. And the questionnaire in English language gave the better understanding for the non-Albanian participants (Trebicka and Tartaraj, 2023).\n\nThe survey was distributed in English language and Albanian language, to ensure maximum participation and understanding among the respondents. Language translation was carried out by bilingual experts to maintain the accuracy and integrity of the survey items.\n\nTo distribute the questionnaires, a systematic approach was adopted. The hotels were personally visited and selected international hotels in Tirana, Durres, and Vlora and the questionnaire were distributed to eligible respondents. The hotel management and staff were informed about the research objectives and provided support in ensuring the questionnaires reached the target participants. The survey administration followed ethical guidelines, ensuring voluntary participation and maintaining respondent confidentiality.\n\nBy modifying and piloting the survey instrument, utilizing established academic sources, employing a suitable language for distribution, and adopting a systematic approach to questionnaire administration, this study aimed to gather reliable and relevant data on the relationship between economy pricing strategies and customer loyalty in international hotels in Albania.\n\nEach question in the questionnaire was rated using a Likert scale. The scale goes from 1 (totally disagree) to 5 (totally agree).\n\nThe study attempted to collect personal information about respondents in the first half of the survey, such as their age, level of education, gender and marital status. The second part of the survey included questions on economy pricing strategies and customer retention. The data collected from survey questionnaires were compiled into a consolidated dataset to facilitate efficient data management and analysis. In order to protect the privacy and confidentiality of the respondents, steps were taken to anonymize the data. Personal identifying information, such as names, addresses, and contact details, were removed or replaced with unique identifiers to ensure that individual participants could not be identified. After this, for the closed-ended questions, coding was applied to transform the responses into categorical values for analysis. This coding process involved assigning specific codes or categories to different response options to facilitate data analysis and interpretation.\n\nThe collected data, whether in electronic or paper format, were entered into a spreadsheet for further analysis. During the data entry phase, careful attention was paid to minimizing errors by implementing double-entry techniques. The data were securely stored and managed throughout the study. Backup copies of the data were created to prevent data loss or corruption. To ensure the accuracy and reliability of the data, a process of data validation and verification was carried out. This involved cross-checking the entered data against the original survey responses to identify any discrepancies or errors. Data cleaning techniques were employed to address missing or inconsistent data.\n\nSeveral statistical tests were performed using IBM SPSS Statistics software (version 27.0) to examine the relationships and test the research hypotheses. The reliability of the survey questions was assessed using the built-in reliability analysis test in SPSS. This test calculates various reliability measures, such as Cronbach’s alpha coefficient, to evaluate the internal consistency of the questionnaire items. The reliability analysis provides information on the reliability and consistency of the questions used in the study.\n\nCosstab and chi-square analysis: To explore the relationship between variables, crosstabulation (crosstab) and chi-square tests were conducted. These tests allow for the examination of associations and dependencies between categorical variables. The crosstab analysis provides a contingency table, and the chi-square test determines whether there is a statistically significant association between the variables.\n\nModel summary: In the multiple regression analysis, the model summary provides information on the overall goodness of fit of the regression model. It includes measures such as R-squared, adjusted R-squared, and the F-test statistic, which indicate the proportion of variance explained by the independent variables and the overall significance of the regression model.\n\nANOVA tests were performed to assess the significance of differences among group means. In the context of the study, ANOVA could be used to examine differences in customer loyalty based on different levels of the independent variable (economy pricing strategy). It helps determine whether these differences are statistically significant.\n\nBy utilizing these statistical tests in SPSS, the study aimed to evaluate the reliability of the questionnaire, explore associations and dependencies between variables using crosstab and chi-square analysis, examine the overall goodness of fit of the regression model through model summary, and assess the significance of differences among group means using ANOVA. These analyses contribute to the understanding of the research hypotheses and provide insights into the relationships between variables.\n\n\nResults\n\nThe study involved a total of 572 participants from various demographic backgrounds, including age, gender, education, and marital status. Reliability analysis was used to assess the reliability of the questions used in this study, while relationship analysis was used to determine the correlation between the independent and dependent variables. Economy pricing strategy was used as the independent variable, while customer loyalty was the dependent variable. A multiple regression analysis was then performed to measure each developed research hypothesis based on the research model.\n\nThis section includes an analysis of demographic data collected from participants who participated in the study, such as age, education level, marital status, and gender.\n\nDistribution of clients by gender\n\nTable 1 and Figure 2 illustrate the distribution by gender of clients participating in this study. Data was collected from seven international hotels in Albania. Of the 572 participants, there were 378 men and 194 women. As can be seen, most of the participants were men (Trebicka and Tartaraj, 2023).\n\nCustomer age\n\nFrom the data in Table 2 and Figure 3, we find that customer age has a significant effect. The study included participants staying at seven international hotels in Albania, covering a wide range of ages. Specifically, there are 39 people aged 18-23, 79 people aged 24-29, 78 people aged 30-35, 98 people aged 36-41, 104 people aged 42-47, 118 people between the ages of 48 and 53 and 56 participants aged 53 and over.\n\nIt is particularly important to note that the majority of respondents were between 48 and 53 years old. This finding suggests that this age group may be particularly important for hoteliers to meet the needs and preferences of their guests.\n\nFrom Table 3 and Figure 4, it can be seen that the visitor’s marital status plays a certain role in this study. A total of 389 married guests from seven international hotels in Albania participated in the study, 171 single guests from seven international hotels in Albania participated in the study, and 5 divorced guests from seven international hotels in Albania participated in the study. Married clients made up the majority of study participants.\n\nAccording to Table 4 and Figure 5, it can be seen that customers’ educational backgrounds played a role in this research. A total of nine customers with high school diplomas from seven international hotels in Albania participated in the current research, 34 customers with vocational school certificates from the same hotels participated in the current study, and 371 customers with university degrees participated in the current study. Also, 126 guests with graduate degrees from seven international hotels in Albania participated, and 32 guests with certificates other than those listed participated. It may be concluded that the majority of participants were university graduates.\n\nIn this section, data obtained through questionnaires from seven different international hotels in Albania are analyzed. As stated in the conceptual framework, the study aims to quantify and assess the resulting research hypotheses. The test of each research hypothesis are done with the use of reliability analysis to assess the dependability of the independent and dependent variables, a relationship method to evaluate the relationship between the independent and dependent variables, and multiple regression analysis to assess the developed research hypothesis.\n\nBased on Table 5, the reliability test used to examine the four questions related to economy pricing shows that the first question, asked whether the specific international hotel is setting prices low to attract more customers to stay at their hotels, had an Alpha value of.842. The second question asks if a particular international hotel offers continuous discounts to its customers, with an alpha value of 0.851, considered a reliable economy pricing element to measure the relationship with customer loyalty for the survey in international hotels in Albania. The third question related to economy pricing asks whether a particular international hotel employs a pricing strategy that allows it to compete with other international hotels to attract more customers. It has an alpha value of 0.846, indicating that it is a reliable measurement. The fourth question asks if an international hotel has lowered the price of rooms by offering fewer services, such as rooms without breakfast. It has an alpha value of 0.847, which is also considered a reliable economy pricing element to study the relationship with customer retention rates in international hotels in Albania.\n\nThis section presents the findings of the relationship analysis conducted between the independent variable (economy pricing strategy) and the dependent variable (customer retention) (Figure 6).\n\nH1: There is a significant and positive relationship between economy pricing strategy and customer retention. Examining the relationship between the variables using a Crosstab as shown in Table 6 shows that out of 572 customers surveyed, 73 customers rated low concerning the relationship between economy pricing strategy and customer loyalty, 201 customers rated as fair concerning the relation between economy pricing strategy and customer retention at selected international hotels in Albania, and 298 customers rated high concerning the relation between economy pricing strategy and customer retention at selected international hotels in Albania. Based on the above results, we can conclude that the majority of customers rated high concerning the relationship between economy pricing strategy and customer retention at selected international hotels in Albania.\n\nAs the Table 7 shows, the chi-square statistic appears in the value column of the chi-square test table, just to the right of ‘Pearson chi-square’. The results show that the chi-square statistical value is 115.897. The p-values are in the same row of the Asymptotic Significance (2-sided) column (.000).\n\nThis result is significant because the P value is less than 0.05. This demonstrates a significant relationship between economy pricing strategies and customer retention rates in selected international hotels in Albania.\n\nThis section presents the results of multiple regression analysis to measure the research hypothesis developed according to the research model.\n\nModel Summary Based on the model summary is shown in the Table 8, the value of Adjusted R Square for the regression analysis is.690. This suggests that 69% of the changes in the dependent variable can be explained by the changes of independent variables included in the model.\n\nAs presented in Table 9, the ANOVA analysis was conducted and it revealed that the F-value was 162.876, and the significance level was .000. Since the p-value is less than .05, it can be concluded that there is a statistically significant positive association between each pricing variable and customer retention at selected international hotels in Albania.\n\nMultiple regression tests were performed between economy pricing strategy as an independent variable and customer loyalty as a dependent variable to test the research hypotheses previously developed for selected international hotels in Albania. As shown in Table 10, multiple regression analysis revealed a significant relationship between economy pricing strategies and customer retention. The B value is 0.238, the Beta value is 0.116, and the significance level is.000.\n\nThis result suggests a positive relationship between economy pricing strategies and customer loyalty. The results support the research hypothesis that there is a positive and significant relationship between economy pricing strategies and customer loyalty in Albania.\n\n\nDiscussion\n\nMany external factors can affect customer retention in the hotel industry in Albania. Pricing is a critical step in building loyalty and retention of hotel guests. Effective pricing strategies have been developed to facilitate the development of international hotel services in a competitive environment. Therefore, this study aims to investigate the existing economy pricing strategies to determine the level of usage and its impact on customer retention in the international hotel sector in Albania. The results of this study will provide valuable information to scholars and researchers interested in conducting research in similar areas.\n\nThe research findings will be significant for the hotel industry in Albania as they will be able to use the insights to develop better pricing strategies to retain customers\n\nThe results of this study will guide how the hospitality industry in Albania can use pricing strategies as a retention strategy, identifying any gaps that may prevent retention and working towards improving customer retention. Business leaders will also have more insight into which retention strategies are being used well and which are not. The findings of this study will help business leaders take the right steps to maintain market share to improve their performance.\n\nIn this study, the independent variable is economic pricing and the dependent variable is customer retention.\n\nAccording to the research hypothesis, there is a significant positive relationship between economy pricing strategies and customer retention. To know the relationship between the economy price of international hotels in Albania and the rate of customer retention, the Crosstab test was used.\n\nThe results are of great importance for the hotel sector in Albania, as they will be able to use this information to develop better pricing strategies to retain customers. Furthermore, the findings of the study are valuable for Albania’s tourism industry, which is an important sector of the country’s economy. The government can use the results to formulate policies that improve sector performance, leading to increase of economic growth.\n\nUltimately, the findings have important implications for the hotel industry and the Albanian tourism industry as a whole. The study will provide valuable insights into the effectiveness of economy pricing strategies in retaining customers in the Albanian international hotels. Based on the results, the hotel industry can develop better pricing strategies to improve customer retention and increase market share.\n\nDespite the valuable insights gained from this study, several limitations should be acknowledged. Firstly, the research focused solely on international hotels in Albania, limiting the generalizability of the findings to other regions or types of accommodations. Secondly, the study relied on self-reported data collected through surveys, which may be subject to response bias or inaccuracies. Future research could employ a longitudinal approach to examine the long-term effects of pricing strategies on customer loyalty. Furthermore, incorporating qualitative methods or interviews could provide deeper insights into customers’ perceptions and experiences. Despite these limitations, the findings of this study contribute valuable knowledge to the field and offer a foundation for further investigations in pricing strategies and customer retention in the hotel industry.\n\n\nConclusion\n\nIn conclusion, this study examines the impact of economy pricing strategies on customer retention in the international hospitality industry in Albania. The results show that a considerable number of customers perceive the relationship between economy pricing strategies and customer retention to be fair. Moreover, the statistical analysis revealed a significant positive relationship between economy pricing strategies and customer retention, which supports the research hypothesis.\n\nThese results provide valuable insights for business owners and hotel managers in Albania to use economy pricing strategies as a retention strategy and improve customer retention. Additionally, the study provides guidance on identifying gaps in pricing strategies that may prevent retention and working towards improving customer retention.\n\nFurthermore, the study contributes to the existing literature on pricing strategies in the hotel industry and provides raw data for scholars and researchers interested in conducting research in similar areas. It should be noted that similar results have been found in previous studies using economy pricing in other industries.\n\nIn conclusion, the findings of the study have important implications for the international hotel industry in Albania, particularly in a highly competitive market environment. Using economy pricing strategies as a retention strategy can boost hotel services and improve their performance. The study also forms the basis for future research in the areas of pricing strategies and customer retention in the Albanian hotel industry.",
"appendix": "Data availability\n\nFigshare: Analyzing the Relationship Between Pricing Strategy and Customer Retention in Hotels: A study in Albania. https://doi.org/10.6084/m9.figshare.22814129.v1 (Trebicka and Tartaraj, 2023).\n\nThe project contains the following underlying data:\n\n• Dataset.xlsx. (Anonymised data collected from questionnaires with coded responses).\n\n• Dataset.xlsx. (Anonymised data collected from questionnaires with written responses).\n\nFigshare: Analyzing the Relationship Between Pricing Strategy and Customer Retention in Hotels: A study in Albania. https://doi.org/10.6084/m9.figshare.22814129.v1 (Trebicka and Tartaraj, 2023).\n\nThis project contains the following extended data:\n\n• Questionnaire English and albanian.docx. (Questionnaire in English and Albanian language).\n\nFigshare: SRQR checklist for Analyzing the Relationship Between Pricing Strategy and Customer Retention in Hotels: A study in Albania. https://doi.org/10.6084/m9.figshare.22814129.v1 (Trebicka and Tartaraj, 2023).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAgwu ME: Price elasticity and consumer behavior. International Journal of Marketing and Business Communication. 2018; 7(2): 43–50.\n\nAsamoah K, Chovancová M: Pricing strategies: A marketing mix approach. Econ. Manag. 2011; 16: 1207–1212.\n\nAscarza E, Neslin SA, Netzer O, et al.: In pursuit of enhanced customer retention management: Review, key issues, and future directions. Cust. Needs Solut. 2018; 5(1-2): 65–81. Publisher Full Text\n\nAzad AK, Subrahmanyam R: Customer retention and pricing strategies in the hotel industry. J. Revenue Pricing Manag. 2022; 1–21.\n\nChen Y, Ma Y, Zhang Y: Research on the Price Strategy of E-Commerce Based on the Analysis of the Consumer Behavior. J. Ind. Eng. Manag. 2016; 9(5): 1269–1283.\n\nCollado VM, Fernandez PR, Saura IG: Analysis of price sensitivity and elasticity of demand in the Spanish hotel sector. J. Tour. Res. 2017; 20(1): 32–46.\n\nDai B, Zhang H: Pricing and inventory control for hotel rooms. J. Revenue Pricing Manag. 2017; 16(3): 226–235.\n\nDel Rio Olivares D, De la Cruz Ríos R, Cardoso-Mendoza A: Hotel customer retention and net present value. Tour. Manag. 2018; 68: 470–479.\n\nFerdous Azam SM, Karim KS: Factors influencing customers’ satisfaction on Bangladeshi telecommunication service providers. Eur. J. Manag. Marketing Stud. 2017; 2. Publisher Full Text\n\nGao J, Wang X, Fang J: Study on pricing strategy for international hotels. Int. J. Contemp. Hosp. Manag. 2020; 32(8): 2406–2418.\n\nGeng R, Wang H, Wu S: An Empirical Study on the Pricing Strategy of Mobile Payment under the Perspective of Consumer Behavior. J. Econ. Bus. Manag. 2018; 6(2): 45–50.\n\nHan H, Hwang J: How do value co-creation practices improve customer retention in the hotel industry? Int. J. Hosp. Manag. 2018; 72: 47–56.\n\nHanaysha JR: Customer retention and customer loyalty: A case of hotel industry. J. Tour. Herit. Serv. Mark. 2018; 4(1): 20–25.\n\nKang J-YM, Kim J: Online customer relationship marketing tactics through social media and perceived customer retention orientation of the green retailer. J. Fash. Mark. Manag. 2017; 21: 298–316.\n\nKotler P, Armstrong G, Harris LC, et al.: Principles of Marketing. Pearson Education Limited; 2022a.\n\nKotler P, Keller KL, Koshy A, et al.: Marketing Management: A South Asian Perspective. 15th ed.Pearson; 2022b.\n\nKung L-C, Zhong G-Y: The Optimal Pricing Strategy for Two-Sided Platform Delivery In the Sharing Economy. Transp. Res. Part E. February 15, 2017; 101: 1–12. Reference Source\n\nLee SHS, Fay S: Why offer lower prices to past customers? Inducing favorable social price comparisons to enhance customer retention. Quant. Mark. Econ. 2017; 15(2): 123–163.\n\nLuo C, Huang YF, Gupta V: Dynamic Pricing and Energy Management Strategy for EV Charging Stations under Uncertainties.2018; arkiv preprint arXiv:1801.02783.\n\nLuo X, Li H, Zhang J, et al.: Luxury hotel pricing strategies: The role of perceived quality and customer value. Int. J. Hosp. Manag. 2019; 83: 130–138.\n\nNeubert M: Revenue management and pricing: Case studies and applications. Springer; 2017.\n\nNjeru L, Karega L: Youth in Agriculture; Perceptions and Challenges for Enhanced Participation in Kajiado North Sub-County, Kenya. Greener J. Agric. Sci. 2017; 7: 203–209.\n\nPapatla P, Zhang J: The economics of pricing. Routledge; 2021.\n\nRao VR, Kartono B: Pricing objectives and strategies: A cross-country survey. Handbook of Pricing Research in Marketing. 2009; pp. 9–36.\n\nRazzaq S, Aslam MS, Imran MK, et al.: Customer retention: The case of hospitality sector. Eur. J. Bus. Manag. 2018; 3(1): 16–20.\n\nReen N, Hellström M, Wikström K, et al.: Towards value-driven strategies in pricing IT solutions. J. Revenue Pricing Manag. 2017; 16(1): 91–105.\n\nRizov M: The price-quality relationship in the global hospitality industry. J. Tour. Hosp. Manag. 2019; 7(1): 27–38.\n\nSubrahmanyam S: Corporate Leadership: A Study of Interpersonal Skills in Growing in the Corporate World. International Journal of Trend in Scientific Research and Development (IJTSRD). 2018; 2(4): 2054–2066. Reference Source\n\nSubrahmanyam S, Azad FA: Carrefour’s Competitive Strategy- Cost Leadership and Differentiation: A Case Study. Pac. Bus. Rev. Int. 2019; 11(8): 137–145. Publisher Full Text\n\nSubramanian R, Azad MAK: A review of consumer behavior models and the way forward. J. Consum. Mark. 2021; 38(1): 4–22.\n\nTrebicka B, Tartaraj A: Analyzing the Relationship Between Pricing Strategy and Customer Retention in Hotels: A study in Albania. Dataset. figshare. 2023. Publisher Full Text\n\nXiang Z, Du Q, Ma Y, et al.: A comparative analysis of major online review platforms: Implications for social media analytics in hospitality and tourism. Tour. Manag. 2017; 58: 51–65. Publisher Full Text\n\nZakaria N, Abdullah AM, Ali F: The impact of pricing strategy on customer retention in the hotel industry. Journal of Tourism, Hospitality and Culinary Arts. 2019; 11(1): 35–45.\n\nZhang X, Zhang Z, Chen X, et al.: The impact of pricing strategies on consumer purchasing intention: A conceptual framework and empirical study. Journal of Marketing and Consumer Research. 2017; 36: 55–63."
}
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[
{
"id": "183898",
"date": "26 Jul 2023",
"name": "Satya Subrahmanyam",
"expertise": [
"Reviewer Expertise H.R. Practices",
"Leadership",
"Management",
"Soft Skills & Human Resources Analytics."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAbstract: This review aims to comprehensively analyze the various strategies employed by hotels to enhance customer retention. The study investigates the effectiveness of these strategies using analytical tools while also incorporating a conceptual framework to provide a broader understanding. A slight mention of the theoretical framework that underpins the research is also included. The significance of this study lies in its contribution to the hospitality industry by shedding light on successful customer retention strategies. However, it should be noted that the literature review is somewhat concise and would benefit from the addition of more references. Furthermore, the authors' use of a systematic approach to distribute questionnaires to hotel customers raises some doubts, considering the transient nature of hostel customers who are typically travelers with specific purposes. Nevertheless, the data analysis approaches employed are deemed adequate and in line with the objectives of the study. However, there are resemblances to a previously published article titled \"Economy Pricing Strategy and Customer Retention – An Analysis,\" which should be acknowledged and addressed.\nIntroduction: The introduction provides a comprehensive overview of the importance of customer retention strategies in the hospitality industry, setting the stage for the study's objectives and scope. A conceptual framework is outlined to guide the research, emphasizing the factors that influence customer retention.\nLiterature Review: While the literature review provides a brief and straightforward overview of existing studies on hotel customer retention strategies, it lacks depth and the inclusion of additional relevant references. To strengthen this section, the authors should consider incorporating more recent research and diverse perspectives.\nTheoretical Framework: The study briefly touches upon the theoretical framework that informs the research. A more comprehensive discussion of the underpinning theories, models, or concepts would enhance the clarity of the study's theoretical foundation.\nMethodology: The authors describe the systematic approach used to distribute questionnaires to hotel customers. However, the suitability of this approach is questionable, considering that hotel customers are typically transient and may not be inclined to participate in lengthy surveys due to their purposeful travel nature. Addressing this limitation and offering a justification for the chosen methodology would enhance the study's credibility.\nData Analysis: The approaches used for data analysis are well-defined and appropriate for addressing the research objectives. By utilizing analytical tools, the study provides valuable insights into the effectiveness of various hotel customer retention strategies.\nSignificance of the Study: While the abstract provides an overview of the study's scope, it lacks a clear statement on the significance of the research. The authors should emphasize how their findings can contribute to the hospitality industry and its implications for hotel management.\nSimilarities with Previous Publication: It has come to light that the present study bears resemblances to a previously published article titled \"Economy Pricing Strategy and Customer Retention – An Analysis.\" To maintain academic integrity, the authors must acknowledge this similarity and provide a clear distinction between their work and the referenced article.\nConclusion: The conclusion provides a concise summary of the study's findings, emphasizing the importance of implementing effective customer retention strategies in the hospitality industry. However, it would benefit from a discussion of the study's limitations and avenues for future research.\nOverall, the review offers valuable insights into hotel customer retention strategies using analytical tools and a conceptual framework. To strengthen the manuscript, the authors should expand the literature review, provide a clear theoretical framework, highlight the significance of the study, and address concerns regarding the methodology and similarities with a previously published article. With these improvements, the study will be better positioned to contribute to the existing body of knowledge in the field of hospitality management.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "189929",
"date": "26 Jul 2023",
"name": "Pratap Chandra Mandal",
"expertise": [
"Reviewer Expertise Marketing",
"Marketing Intelligence",
"Marketing Communications",
"Services Marketing",
"Sustainable Marketing",
"Qualitative Methods in Marketing",
"Product Innovation and Management"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nOnly seven hotels from three regions of Albania are studied. Can the results of the study be extended to other locations of Albania?\n\nHow is the questionnaire developed?\n\nIt is obvious that lower prices will improve customer retention. So, what are the contributions of the authors?\n\nThe model in Figure 1 is too simplistic. Kindly develop an in-depth model for analysis.\n\nThe study lacks in novelty.\n\nThe authors should highlight the research limitations, research contributions, research implications, and the avenues of future research.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "189945",
"date": "08 Sep 2023",
"name": "Visar Rustemi",
"expertise": [],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI recently had the opportunity to read the article titled \"Analyzing: A study in Albania by Authors; Trebicka B, TARTARAJ A and Harizi A. I would like to share my positive impressions and highlight the valuable contributions made by this research.\nThe article presents a comprehensive analysis of the relationship between pricing strategy and customer retention in the service sector – hotels mainly. The findings are significant and stresses the light on customer retention as a main and vital concept in the hospitality industry for building and sustaining long-term relationships.\n\nThe authors' choice of methodology and research design is commendable. The study is well-structured and employs rigorous methods, ensuring the reliability and validity of the results. Statistical analysis, including crosstab tests, employed to explore the relationship between economy pricing strategies and customer retention enhance the reliability of the research design.\n\nThis article stands out due to its originality and the unique perspective it brings to the field. The research addresses an important gap in the existing literature and provides valuable insights that contribute to the advancement of knowledge in existing a statistically significant positive relationship between economy pricing strategies and customer retention in international hotels in Albania. These findings underscore the importance of implementing effective pricing strategies to enhance customer loyalty and guide the development of improved strategies within the hotel industry. Effective pricing strategies play a crucial role in fostering customer loyalty.\n\nThe article is exceptionally well-written, with clear and concise language that makes it accessible to a wide range of readers. The logical flow of ideas and the organization of the content further enhance the overall readability.\n\nThe authors have done an excellent job of incorporating relevant and up-to-date references, which strengthens the credibility of their arguments and demonstrates a thorough understanding of the subject matter.\n\nHowever, the study's limitations, primarily its focus on specific hotels in Albania, call for further research to validate the generalizability of these findings. The insights gained from this study inform policymakers and industry stakeholders in formulating strategies to enhance customer retention within the hospitality sector. I highly recommend this article to fellow researchers and scholars in the field. The research presented in this article is of great value and contributes significantly to the existing body of knowledge.\nThank you to the authors for their valuable contribution and for sharing their research with the academic community. I look forward to future publications from this team.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-690
|
https://f1000research.com/articles/12-689/v1
|
16 Jun 23
|
{
"type": "Method Article",
"title": "Development of dish-based population-specific food frequency questionnaire for dietary assessments in Afghanistan",
"authors": [
"Muhammad Reza Joya",
"Ahmad Mujtaba Barekzai",
"Ahmad Esmaillzadeh",
"Muhammad Reza Joya",
"Ahmad Mujtaba Barekzai"
],
"abstract": "Purpose: Dietary intake assessment has an essential role in chronic disease studies and general public health outcomes. To measure dietary intakes in epidemiologic studies, various dietary assessment methods are used. Among them, food frequency questionnaires (FFQs) can provide useful measures of dietary intake. This study aimed to report the development of a population-specific dish-based food frequency questionnaire (DFQ) to assess long-term usual dietary intakes in Afghanistan. Design/Methodology/Approach: We considered the Willet format and followed these steps; listing commonly consumed Afghani foods, determining food groups, defining portion sizes, and determining the frequency response options for each food item. We prepared a comprehensive list of foods and dishes commonly used in Afghanistan. We categorized dishes and food items in the questionnaire into eight major groups. Portion sizes for food items and mixed dishes were defined based on the most commonly consumed and understandable portion sizes for each item among the Afghan general population. The frequency response options for each food item were defined separately in a row against the food list. Findings: We developed a new population-specific DFQ in Afghanistan containing 103 food items or dishes, which can be used as an instrument for the assessment of long-term dietary intakes as well as diet-disease associations in Afghanistan. Originality/Value: This is the first ever-developed dietary assessment tool in Afghanistan.",
"keywords": [
"Food frequency questionnaire",
"Afghanistan",
"diet",
"epidemiologic studies",
"national nutrition surveys",
"nutrition assessment tool"
],
"content": "Introduction\n\nDietary intake assessment has an essential role in chronic disease studies and general public health outcomes.1–3 Improving dietary habits along with environmental and lifestyle factors, is a major target in the prevention of non-communicable diseases (NCDs), such as cancer, cardiovascular diseases, diabetes and chronic kidney diseases.3,4 NCDs are rapidly increasing in low-income and low-middle income countries.5 The potential causes of this rising burden need more investigations and taking preventative policies by the governments.\n\nIt has been demonstrated that long-term dietary intakes affect the risk of chronic conditions.3 To measure dietary intakes in epidemiologic studies, various dietary assessment methods are used such as 24-hour recalls, food records or diaries and food frequency questionnaires (FFQs).6,7 Methods such as 24-hour recalls and food records are associated with high subject burden.8 FFQs can provide useful measures of dietary intakes.7 It has widely been used in investigating the association between diet and chronic diseases in large population-based studies.9–13 The advantage of this method includes its easy application, low respondent burden, self-administered method of use, less training of research staff and assessment of diet for long-term.12,14 Besides providing information on usual intakes of a particular food or a food group of interest, FFQs are particularly useful in identifying dietary patterns at the population level.14 Measurement errors, which refer to the difference between reported dietary intake over a specified time period and true usual dietary intake, that might result in participants’ misclassification in terms of dietary intakes is a big concern in FFQ.11 These errors can arise from the incomplete list of foods included in the questionnaire as well as inaccurate portion sizes.\n\nDespite the availability of many FFQs in the world, there is a great variability in the foods consumed and in dietary culture in diverse populations.15–17 A FFQ which is valid for one population may not be valid when applied to a second population.18 On the other hand, most information on diet-disease association came from western and developed countries and such information is scarce in developing countries19 and to the best of our knowledge almost nothing in Afghanistan.\n\nAs the burden of chronic diseases is increasing worldwide,20 the contribution of dietary intakes to such increasing trend is important.20 To examine diet-disease associations in Afghanistan, development of a FFQ to measure long-term dietary intakes is mandatory. This study is therefore aimed to report the development process of a population-specific DFFQ to assess long-term usual dietary intakes in Afghanistan.\n\n\nMethods\n\nThis study was approved by Tehran University of Medical Sciences (TUMS) ethical committee with approval ID: IR.TUMS.VCR.REC.1399.567 on March 17, 2020. Written informed consent was obtained from all study participants. The Helsinki Declaration is considered through all stages of this study and all methods were carried out in its accordance.\n\nDevelopment of the DFFQ: In the current study, the Willett format was applied to develop a population-specific DFFQ for Afghanistan.14 Commonly, FFQs are used for the purpose of ranking individuals according to food or nutrient intake rather than for estimating absolute amounts of intake.15 Meanwhile Willett’s FFQ, using a close-ended format, was developed with the primary objective of ranking individuals according to their usual dietary intake21 but Block’s instrument was developed in the open-ended format to rank individuals as well as to estimate the absolute intake of several nutrients.21 Therefore we preferred Willett format rather than Block Format for development of current DFFQ. This effort was done to develop a suitable dietary assessment tool to examine usual dietary intakes in adult people in Afghanistan. The questionnaire was developed by taking the following steps. First, we listed commonly consumed Afghani foods. Then, food groups were determined and definition of portion sizes was done. Finally, frequency response options for each food item were defined. The development process of this DFQ is summarized in Figure 1. Here, we describe each step in detail:\n\nFood list construction: First, we created a comprehensive list of foods and dishes commonly used in Afghanistan, based on the information we took from local people. Twenty adult volunteers (18-60 years old), including women, were selected from various regions of Kabul City. We requested that they sign an informed consent letter and provide a list of their usual consumed foods at different meals (breakfast, lunch, dinner and snacks) throughout the year. This was an informal survey based on convenience sampling. Paper forms were given to the participants. The form had a consent statement and 30 blank spaces for writing the names of the foods. They took the forms to their homes and then returned them within three days. The survey was conducted in February 2021. We collected the forms within two weeks. After collecting the forms, all food items and dishes based on this informal survey were listed. This method was done in order to prevent missing major food items in different meals. Based on this listing of foods, we found that Afghanistan populations mostly consume mixed dishes. For example, Afghans consume meat in the form of several mixed dishes such as Kebab, Kofteh (meat balls), Manto, Dopiazeh, Qabli etc. Indeed, it is too difficult to estimate total meat intake of a person in the preceding 12 months, because the frequency consumption of meat in such a long period of time is extremely hard for participants to remember. Estimating the usual intake of meat from various origins would be very difficult for a person and might confuse participants. In addition, it is likely that some dishes containing meat will be neglected. On the other hand, estimating the quantity and frequency of consumption of each dish is rather easy. Therefore, we aimed to design a dish-based FFQ rather than a food-item based questionnaire because it is difficult for people to assess their usual intake of ingredients in mixed dishes. Previous studies showed that questionnaire length has an important role in the survey response rate, as lengthy questionnaires may cause exhaustion and decrease the cooperation of participants.13,22,23 As Afghanistan people consume different mixed dishes, including all ingredients of these dishes would make the questionnaire too lengthy. Therefore, in order to shorten the DFFQ and facilitate responding, we have included dishes and collapsed together some other dishes that have the same ingredients.\n\nFoods and dishes that were nutrient-rich were included in the food list. In other words, nutritious food and dishes were included in the list. In addition, foods and dishes that had considerable contribution to between-person variation were also included. To find such foods and dishes, we discussed all foods and dishes in our prior comprehensive list and then selected the ones that might be different in different regions of the country. Then, a group of health specialists from Afghanistan discussed all the items and the foods rarely consumed were not included in the questionnaire. Finally, 103 food items or dishes were selected (Table 1).\n\nDetermination of food groups: To simplify the questionnaire, we divided the dishes and food items into eight main categories: 1. Prepared or canned mixed dishes, 2. cereals 3. Dairy products, 4. Sweets, 5. Fruits, 6. Vegetables, 7. Beverages, and 8. Miscellaneous food items.\n\nPortion size determination: After determination of food groups, we discussed the portion size section. There was much diversity observed in food and dishes portion sizes common among Afghanistan people. In addition, common portion sizes may vary from one region to another. However, portion size estimation does not make significant contributions to between-person variation in food intake and may not serve to a more accurate ranking of individuals based on their dietary intakes, several well-designed FFQs in the world have portion size section.22 The current DFFQ defines portion sizes for each food item and mixed dish based on the portion sizes most frequently used and understood by the Afghanistan general population. Common portion sizes for each food item and a certain dish was discussed by a group of local health specialists. To make sure that public people understand the units and portion sizes in the questionnaire, we administered the preliminary DFFQ to a group of volunteers in Kabul, Afghanistan as a pilot test before its finalizations.\n\nFrequency response options: According to FFQ of Harvard,24 we introduced multiple choice frequency response options to facilitate responding. Each food item’s frequency response options were defined separately in a row against the food list, rather than mentioning them in a column at the top of the page. Although this is different from the one used in Harvard FFQ,13 we believe that this can result in reducing errors in estimating frequency of foods and dishes consumed. The categories we used in this questionnaire varied from “never or less than once a month” to “6 or more times per day”. Participants should indicate their average frequency of consumption by checking 1 of the 9 frequency categories. The number of frequency response categories is not constant for all foods. For frequently consumed foods, we included 6-9 options and for infrequently consumed foods, we omitted options of high frequency.\n\nFood and nutrient intakes calculation: As mentioned above, the developed DFFQ consisted of foods and dishes with standard portion sizes, usually consumed by Afghanistan people. To compute nutrient intakes from this newly developed DFFQ, we will convert all reported consumption frequencies of foods into grams per day by using household measures. To convert dishes into grams, first we listed the ingredients of the dishes listed in our DFFQ. The ingredients of the dishes were discussed in a group of 3-4 local housewives and their consensus on ingredients was considered as the final ingredients of that specific dish in Afghanistan. To identify nutrient intakes for each individual, we converted all foods and dishes in the questionnaire to 103 individual foods. Then, using Nutritionist IV software, we computed total calories, macronutrients and micronutrients for each individual by summing up nutrients from all foods.\n\n\nResults\n\nIn the current study, we reported the strategies used to develop a new population-specific DFFQ in Afghanistan (Figure 2). FFQs are used to assess long-term dietary intakes in epidemiological studies, and they should be population- and culture-specific. Therefore, a FFQ from one country cannot be used in another due to the difference in dietary intakes and food cultures. Given the lack of any FFQ in Afghanistan, we developed this DFFQ, which can be used for any epidemiological research focusing on diet and nutrition, particularly when the study objective is to evaluate the long-term dietary intakes of the Afghanistan population and when investigating the relationship between diet and disease. However, it must be kept in mind that the current study reports only the development of this DFFQ, and currently there is no data on its validity. The validation study of this new DFFQ is underway, and the findings of the validation study will be reported in the near future.\n\n\nDiscussion\n\nMany culture-specific FFQs have been developed to evaluate the dietary habits of culturally diverse population groups.25–29 Designing a culture-specific FFQ includes some main steps, namely development of a complete and precise food list, determination of culture-specific food groups, and the definition of culturally appropriate portion sizes. Therefore, considering other studies,25,26,30,31 our methodology was based on the above-mentioned guideline. The questionnaire was designed based on Willett-format,13 included 103 food items and mixed dishes along with appropriate portion sizes.\n\nThe FFQ has widely been used in investigating the association between diet and chronic diseases in large population-based studies.9–11,13 It is easily applicable and can reflect long-term usual dietary intakes. Although the accuracy of data from this type of dietary assessment method is lower than other methods, its low cost and easy-to-use format along with reflecting usual long-term dietary intakes has made this dietary assessment tool as an appropriate method in epidemiologic studies.14 It is also useful in identifying dietary patterns at the population level.14 Measurement errors, incomplete list of foods and inaccurate portion sizes have been considered as potential disadvantages of FFQs.11\n\nThe primary objective of this study was to report the development process of a population-specific easy-to-use comprehensive DFFQ for assessment of dietary patterns and diet-disease association in epidemiological studies in Afghanistan. Considering the use of several mixed dishes in Afghanistan and low literacy of public in the country, we decided to design a dish-based questionnaire because most people, in particular men, are not aware of ingredients of the dishes.\n\nFurthermore, accuracy and precision of data collection may be improved by inclusion of dishes in the list of FFQ food items due to the following two reasons.32 First, Non-communicable diseases (NCDs) are related to culture-specific cooking methods and ingredients.32–34 Second, people may not report invisible components of a mixed dish in the FFQs without dishes because they are neither contributed in their cooking process nor can see the ingredients of different recipes. As a result, they cannot remember the consumption of mentioned foods.35\n\nEarlier studies in Iran, with a very close culture to Afghanistan, have also reported the development of a dish-based FFQ for assessment of dietary intakes. The same activity was also done in Korea, Bangladesh and Iran.15,23,35–37 Almost all available studies have shown that DFFQs can facilitate the evaluation of dietary intakes over a long period at populations with a high consumption of mixed dishes.23,35 The DFFQ we developed in the current study contained 103 items (28 mixed dishes and 75 food items), while the one in Iran had 106 and 142 items.15,35 Number of foods and dishes in the DFFQs developed in Bangladeshi and Korean was 42 and 112 items, respectively.23,36 We tried to develop a comprehensive questionnaire for assessment of dietary intakes. This is also the same for the questionnaires developed in Iran. However, the variability in the number of food items might be due to the cultural difference in the consumption of varied foods and dishes in a specific country as well as the main purpose of the investigators.\n\nIn the present DFFQ, we followed the Willett format.13 However, the frequency response options in this DFFQ were included in a row against each food item which is in contrary to Harvard Format.21 The Willet format is widely used in FFQs developed in other parts of the world due to its easy application. The same approach has also been used in Iranian Dish-based FFQs with cultural similarity to Afghanistan.35 However, it provides categorical data, which might not provide enhanced precision in reporting dietary intakes.13 The main limitation of this DFFQ is that it has not been validated yet, and we are currently working on its validation.\n\n\nConclusion\n\nWe developed a new population-specific DFFQ in Afghanistan, which can be used as an instrument for assessment of long-term dietary intakes as well as diet-disease associations in Afghanistan. The next step should be assessment of validity and reproducibility of this questionnaire before using it in large scale studies among Afghanistan population.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nZenodo: Dish-based Food Frequency Questionnaire for Afghanistan, https://doi.org/10.5281/zenodo.7820762. 38\n\nThis project contains the following extended data:\n\n- Population-specific DFQ\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nThis article has already been submitted to and published as a preprint by Research Square. It is available through this link: https://doi.org/10.21203/rs.3.rs-1592326/v1.\n\n\nReferences\n\nOrganization WH: Global action plan for the prevention and control of noncommunicable diseases 2013-2020. World Health Organization; 2013.\n\nAssmann KE, Lassale C, Andreeva VA, et al.: A healthy dietary pattern at midlife, combined with a regulated energy intake, is related to increased odds for healthy aging. J. Nutr. 2015; 145(9): 2139–2145. PubMed Abstract | Publisher Full Text\n\nRegassa IF, Endris BS, Habtemariam E, et al.: Development and validation of food frequency questionnaire for food and nutrient intakes of adults in Butajira, southern Ethiopia. J. Nutr. Sci. 2021; 10: 10. Publisher Full Text\n\nOjo O: Nutrition and chronic conditions. Vol. 11. .2019; p. 459. Multidisciplinary Digital Publishing Institute. Publisher Full Text\n\nSharkey L, Loring B, Cowan M, et al.: National palliative care capacities around the world: results from the World Health Organization Noncommunicable Disease Country Capacity Survey. Palliat. Med. 2018; 32(1): 106–113. PubMed Abstract | Publisher Full Text\n\nBurrows TL, Martin RJ, Collins CE: A systematic review of the validity of dietary assessment methods in children when compared with the method of doubly labeled water. J. Am. Diet. Assoc. 2010; 110(10): 1501–1510. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nKim YO, Kim MK, Lee S-A, et al.: A study testing the usefulness of a dish-based food-frequency questionnaire developed for epidemiological studies in Korea. Br. J. Nutr. 2008; 101(8): 1218–1227. PubMed Abstract | Publisher Full Text\n\nAung WP, Bjertness E, Htet AS, et al.: Fatty acid profiles of various vegetable oils and the association between the use of palm oil vs. peanut oil and risk factors for non-communicable diseases in Yangon Region, Myanmar. Nutrients. 2018; 10(9): 1193. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOnyango EM, Onyango BM: The rise of noncommunicable diseases in Kenya: an examination of the time trends and contribution of the changes in diet and physical inactivity. J. Epidemiol. Glob. Health. 2018; 8(1-2): 1–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKeshteli AH, Esmaillzadeh A, Rajaie S, et al.: A dish-based semi-quantitative food frequency questionnaire for assessment of dietary intakes in epidemiologic studies in Iran: design and development. Int. J. Prev. Med. 2014; 5(1): 29–36. PubMed Abstract\n\nPark MK, Kim DW, Kim J, et al.: Development of a dish-based, semi-quantitative FFQ for the Korean diet and cancer research using a database approach. Br. J. Nutr. 2011; 105(7): 1065–1072. PubMed Abstract | Publisher Full Text\n\nKim M-K, Yun Y-M, Kim Y-O: Developing dish-based food frequency questionnaire for the epidemiology study of hypertension among Korean. Korean J. Community Nutr. 2008; 13(5): 701–712.\n\nJoya MR, Esmaillzadeh A, Barekzai AM: Dish-based Food Frequency Questionnaire for Afghanistan. [dataset]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "179243",
"date": "03 Jul 2023",
"name": "Samira Pourmoradian",
"expertise": [
"Reviewer Expertise Community nutrition and food policy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for giving me the opportunity to read this paper. The article is about the developing population-specific dish-based food frequency questionnaire (DFQ) for Afghanistan. The researcher categorized food items and dishes in 8 subgroups and assessed and calculated the gram of nutrients, using Nutritionist IV software. The paper is well written. Authors have provided full explanations in each section specially methods. Some minor revisions are suggested and hopefully it will improve the quality of the paper.\nThe paper is reasonably well written, but will need editing for English language and grammar.\n\nAbbreviation for dish-based food frequency questionnaire is different in abstract section which was written as DFQ, while for other section it was written as DFFQ. This should be the same.\n\nIn the last paragraph of INTRODUCTION section, the word “mandatory” does not make sense and seems strange. It is better to be replaced by the word “essential”.\n\nIn last paragraph of FOOD LIST CONSTRUCTION section, “Foods and dishes that were nutrient-rich were included in the food list. In other words, nutritious food and dishes were included in the list.” These two sentences are claiming the same points. They can be merged together.\n\nMore discussion of the literature would be helpful in discussion section.\n\nLimitations and strengths can be written in detail.\n\nPlease check carefully that all references are appropriately quoted in the core manuscript.\n\nIs the rationale for developing the new method (or application) clearly explained? Yes\n\nIs the description of the method technically sound? Yes\n\nAre sufficient details provided to allow replication of the method development and its use by others? Yes\n\nIf any results are presented, are all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Yes",
"responses": []
},
{
"id": "197517",
"date": "20 Nov 2023",
"name": "Maryam Amini",
"expertise": [
"Reviewer Expertise Nutritionist"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study aimed to report the development process of a population-specific DFFQ to assess long-term usual dietary intakes in Afghanistan. As far as I understood it is the first FFQ designed in Afghanistan and in this sense, it is commendable and very valuable.\nHowever, there are some ambiguities that need to be clarified:\nPlease explain about the qualification(s) of local people in developing the food list.\n\nFigure 1, in first step, please add it: “a group of health specialists from Afghanistan discussed all the items and finalized the questionnaire”.\n\nConclusion: You claimed that you developed a new population-specific DFFQ in Afghanistan, which can be used as an instrument for assessment of long-term dietary intakes as well as disease-diet associations in Afghanistan, however, unless you validate it, you cannot speak about any diet-disease association.\n\nIs the rationale for developing the new method (or application) clearly explained? Yes\n\nIs the description of the method technically sound? Partly\n\nAre sufficient details provided to allow replication of the method development and its use by others? Partly\n\nIf any results are presented, are all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-689
|
https://f1000research.com/articles/12-680/v1
|
15 Jun 23
|
{
"type": "Research Article",
"title": "Anti-inflammatory effects of oral cannabidiol in rat models",
"authors": [
"Sitthiphon Bunman",
"Sombat Muengtaweepongsa",
"Dilok Piyayotai",
"Ratthaphol Charlermroj",
"Korawit Kanjana",
"Sudtida Kaew-amdee",
"Manlika Makornwattana",
"Sanghyun Kim",
"Sitthiphon Bunman",
"Dilok Piyayotai",
"Ratthaphol Charlermroj",
"Korawit Kanjana",
"Sudtida Kaew-amdee",
"Manlika Makornwattana",
"Sanghyun Kim"
],
"abstract": "Background: Cannabidiol (CBD), a non-psychoactive compound in cannabis, has various pharmacological advantages associated with clinical use, especially for reducing inflammatory arthritis and paw edema in animal models. This study evaluated the anti-inflammatory effects of various oral CBD doses (5-40 mg/kg) in rats after injecting 0.1 mL of carrageenan. Methods: Rats were orally administered various CBD doses an hour before the carrageenan-induced inflammation to observe the anti-inflammatory effects of CBD. Paw edema was measured at 0, 1, 2, 3, 4, and 5 h after carrageenan induction. Following a six-hour induction of carrageenan, histological analysis employing hematoxylin and eosin staining was performed to investigate inflammatory cell infiltration at paw edema. In addition, blood samples were taken and used for cytokine detection using ELISA and bead-base assays. Results: We found that the efficacy of all oral CBD doses decreased paw edema and was comparable to or had greater efficacy than an anti-inflammatory agent (Diclofenac 10 mg/kg), especially at 2, 3, 4, and 5 h after induced paw edema. Moreover, a high dose (40 mg/kg) of CBD suppressed chemokine productions, including monocyte chemoattractant protein (MCP)-1 and MCP-3, compared to diclofenac and placebo. In addition, serotonin levels, a pro-inflammatory-like neurotransmitter, were drastically decreased in rats treated with either CBD or diclofenac. Conclusions: Oral CBD is an interesting anti-inflammatory agent for use in the clinical setting. However, more information regarding drug safety and efficacy in a large population of human studies is needed.",
"keywords": [
"Cannabis",
"CBD",
"Cannabidiol",
"Anti-inflammatory",
"Immunosuppressant"
],
"content": "Introduction\n\nCannabis sativa (Cannabaceae) has been one of the most used herbaceous plants in traditional medicine for decades. There are many bioactive compounds in this plant: around 750 compounds have been identified, such as cannabinoids, flavonoids, terpenoids, alkaloids, among others.1 Among its bioactive compounds, cannabinoids are the main pharmacological phytocannabinoid compounds and include cannabidiol (CBD), cannabinol (CBN), Δ9-tetrahydrocannabinol (Δ9-THC), and Δ8-tetrahydrocannabinol (Δ8-THC). These compounds have been studied in cannabinoid-based medicine. CBD and THC interact in the endocannabinoid system (ECS), but they have different effects. THC compound has psychoactive properties, mediated by activating cannabinoid receptor type 1 (CB1).2 Unlike THC, CBD, a non-intoxicating cannabinoid, has pharmacological anti-inflammatory properties, and lacks psychoactive characteristics because of the low binding affinity of cannabinoid receptors.3 Therefore, CBD exhibits more beneficial properties than THC. Due to the complex mechanism action of CBD, pharmacological studies are required for use in clinical practice. CBD has been studied in animal models for anti-inflammatory effects such as reduced inflammation in arthritis and paw edema.4 Anti-inflammatory properties can be found in CBD, as well as antioxidant activity.5 The pharmacodynamics of CBD probably involve the interaction with host molecular molecules, including PPARγ, GPR3/6/12/18/55, TRPV1/2, TRPA1, 5-hydroxytryptamine receptor, and mitochondrial proteins.6–9 A report has confirmed that CBD is able to reduce arthritis by raising intracellular calcium levels, reducing cell viability, and producing IL-6/IL-8/MMP-3 rheumatoid arthritis synovial fibroblasts.10 In addition, CBD can also minimize inflammation in carrageenan-induced paw inflammation in rat models. Costa et al. demonstrated that CBD could be used for the reduction of paw edema and inflammatory biomarkers levels. However, the study still lacks information on pro-inflammatory cytokine levels.11 Regarding pharmacology dosing titration, CBD is well tolerated even when given in high doses-concentration in the long-term, according to clinical studies.12,13 Recently, a research group also provided evidence that CBD allowed improvements in pain physical function and sleep quality.14 However, no one reported a study of systemic immune changes in an acute inflammatory response during short-term oral CBD administration in an animal model. Conversely, CBD use in animal species is an area of growing interest, especially for its anti-inflammatory and immune modulation effects, even though all its biological effects are still not fully understood.15\n\nIn the present study, we therefore, studied an acute inflammation response by monitoring information regarding the degree of edema, pathophysiology, prostaglandin E2 (PGE2), serotonin, cyclooxygenase (COX) 1 and 2 activities, chemokines, and cytokines at baseline and during 6 hours of various oral CBD administrating doses (5, 10, 20, and 40 mg/kg) in a carrageenan-induced edema rat model.\n\n\nMethods\n\nA total of 48 male Sprague Dawley rats (300-320 g, Nomura Siam International, Thailand) were used. The animals were housed in the Laboratory Animal Canter Thammasat University under standard conditions of strict hygienic conventional temperature (22±1°C), relative humidity (30-70%), light (130-325 Lux), and a light/dark cycle (12 h/12 h). Rats were kept under laboratory conditions for one week prior to the experiments. The protocols and methods used in this study were approved by the Institutional Animal Care and Use Committee of Thammasat University, Thailand (Protocol Approval No. 010/2021).\n\nWe complied with the standard practices and guidelines to treat rats respectfully and compassionately. After six hours post-carrageenan injection, rats were sacrificed with isoflurane and confirmed with cardiac puncture. All tissues and blood samples were collected after being sacrificed with isoflurane by veterinarian staff at Animal Laboratory Animal Center, Thammasat University, Thailand. The center employs trained veterinarians knowledgeable about animal behavior and welfare to ensure the sacrifice is conducted efficiently and with minimal stress to the rat.\n\nCannabidiol powder was purchased from Suranaree University of Technology, Thailand, and was dissolved in sunflower oil. Lambda-carrageenan, hematoxylin and eosin (H&E) staining solution, absolute ethanol, acetic acid, and ethylenediaminetetraacetic acid were purchased from Sigma-Aldrich, Milano, Italy. Diclofenac and formaldehyde were purchased from Tokyo Chemical Industry, Tokyo, Japan.\n\nCarrageenan-induced edema was conducted using the procedure by Morris (2003).16 The original protocol of Morris (2003) used a mouse animal model, and indomethacin (Non-steroidal anti-inflammatory drugs; NSAIDs) was used as a positive control in the experiment. However, we modified the Morris (2003) protocol to use a rat animal model and diclofenac (Non-steroidal anti-inflammatory drugs; NSAIDs) as a positive control. Rats were orally administered with either olive oil placebo (olive oil) (10 mg/kg), diclofenac (10 mg/kg), or CBD (5, 10, 20, and 40 mg/kg). Paw edema was induced by injection of 0.1 mL carrageenan (1% w/v in saline) into the plantar of the right hind paw. Paw edema was measured using a plethysmometer (Ugo Basile, Varese, Italy). After carrageenan injection, the volume of paws was recorded at 0, 1, 2, 3, 4, 5, and 6 h. Paw volume was expressed as the difference in volume between before and after carrageenan induces inflammation.\n\nAfter six hours post-carrageenan injection, rats were sacrificed with isoflurane and confirmed with cardiac puncture. The right hind paw of each rat was cut and fixed in a 10% neutral buffered formalin solution for 12 h. Each sample was decalcified with 10% EDTA solution, dehydrated with ethanol, and embedded in paraffin. Each sample was cut into 2 μm thick sections and stained with H&E. A senior pathologist performed the histologic analysis with a light microscope.\n\nThe degree of inflammation was assessed by choosing the area of maximal infiltration with inflammatory cells in each case and grading the density of inflammatory cells into three tier grades 1, 2, and 3. The criteria for grading inflammation started from grade 1, showing sparse inflammatory cells. In contrast, grade 3 shows distinct high cellularity of inflammatory cells, and in grade 2, the number of inflammatory cells lies between these two grades. The assessment was performed blindly without knowing the information regarding each specimen.\n\nPlasma samples were used for serotonin, prostaglandin E2, chemokine, and cytokine assays, whereas tissue samples were used for cyclooxygenase activity assay. Samples were collected after rats were euthanized using isoflurane. Blood samples (6 mL) were collected in EDTA K2/gel tubes (BD Vacutainer BD Diagnostic, Milan, Italy) via cardiac puncture. Plasma samples were collected by centrifugation for 5 min at 10,000 revolutions per minute. The rats’ plasma samples were stored at -20°C until used. For tissue samples preparation, samples were prepared according to the COX activity assay kit instructions. Briefly, the claws of rat paws were cut and then washed three times with phosphate-buffered saline buffer (PBS). Tissue samples were ground in liquid nitrogen and then homogenized in a lysis buffer with protease inhibitors using a pestle. The supernatant was collected after centrifugation at 12,000×g for 3 min at 4°C.\n\nSerotonin levels in serum samples were measured by a competitive enzyme-linked immunosorbent assay (ELISA) using a commercial test kit (Abcam, UK #ab133053) following the manufacturer’s instruction. Briefly, serum samples or serotonin standards were prepared and mixed into an alkaline phosphatase (AP)-conjugated serotonin solution. A specific antibody to serotonin was then added to each well of the 96-well plate, which was pre-coated with goat anti-rabbit antibody. A mixture solution was incubated at room temperature (RT) for two hours with plate shaking before washing three times with washing buffer. A substrate solution for AP (n p-nitrophenyl phosphate disodium salt; pNpp) was added and incubated for one hour. Followed by a stop reaction step by adding a stop solution before measuring absorbance at 405 nm using a microplate reader (SpectraMax M5 microplate reader, Molecular device). The concentrations of serotonin in samples were calculated from the standard curve.\n\nProstaglandin E2 in serum samples was tested using a competitive ELISA kit (Abcam, UK, #ab133021). Briefly, samples or standards were mixed with alkaline phosphatase-conjugated PGE2 in each well of the 96-well plate. A specific antibody to PGE2 was added and incubated at RT for two hours with shaking. Then, the plate was washed with washing solution three times. An enzyme (pNpp substrate) was added and incubated for 45 min before stopping the reaction with the kit’s stop solution reagent. Absorbance at 405 nm was measured using a microplate reader. The concentrations of PGE2 in samples were calculated from the standard curve.\n\nTo understand an immune response after carrageenan-induced edema, serum 14 cytokines (namely G-CDF/CSF-3, GM-CSF, IFN-gamma, IL-10, IL-12p70, IL-13, IL-17A, IL-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, and TNF-alpha) and eight chemokines (namely Eotaxin, Gro-alpha/KC, IP-10, MCP-1, MCP-3, MIP-1alpha, MIP-2, and RANTES) were measured using the commercial bead array assay (ThermoFisher Scientific, #EPX220-30122-901). Samples were prepared and tested according to manual instructions. Briefly, samples or standards were added to each well of the 96-well plate. Then, a mixture of antibodies-coated beads was added and incubated at RT for two hours. After incubation, the unbound beads were removed, and beads were washed twice with a washing buffer. Next, a rat anti-cytokine/chemokine detecting antibodies cocktail was added. The reaction was incubated at RT for one hour. The washing was repeated before phycoerythrin-conjugated streptavidin was added and incubated for 30 min. Then, beads were washed twice before readout the signal using a MAGPIX detector (Luminex, Austin, TX).\n\nThe cyclooxygenase (COX) activity in tissue serum samples was quantitated using a commercial test kit (Abcam, UK, #ab204699). Samples were tested following the manufacturer’s instructions. Briefly, samples were mixed with a COX probe and COX factor. Then, the mixture solution was added to celecoxib or SC560 solution to measure COX-1 or COX-2 activity, respectively. After that, the arachidonic acid solution was added to each mixture solution and immediately measured fluorescence (Excitation at 535 nm and Emission at 587 nm) in a kinetic mode (15-s interval, 30 min). The protein concentration of each sample was measured by a Bradford protein assay method. The amount of resorufin in samples was calculated from the standard curve. The COX reactivities were calculated from the amount of resorufin per reaction time and the amount of protein in the sample. The COX reactivity was reported in pmol/min/mg or μU/mg.\n\nEach group was constituted of at least eight rats. All results were expressed as mean ± standard deviation (SD) or standard error of the mean (SEM) using Graphpad Prism version 9 (Graphpad Software, San Diego, CA). The experiments were compared using analysis of variance (ANOVA) and Tukey’s post hoc test for multiple comparisons. The correlation between data sets was analyzed using the Spearman r-test and plotted by simple linear regression. The Mann-Whitney U test used analysis of the variance. A p-value of < 0.05 was considered to indicate a statistically significant difference.\n\n\nResults\n\nThe carrageenan-induced paw edema is the most common method for evaluating anti-inflammatory activity, as previously shown in a rat model study of acute inflammation.17 The inflammation was induced by localized paw edema with carrageenan that immediately increased paw edema and severity up to 6 h after carrageen injection. After the carrageen injection, all rats were orally administered a single different dose and evaluated paw volume. All doses of oral Diclofenac (10 mg/kg) and CBD (5, 10, 20, and 40 mg/kg) significantly decreased paw edema compared with placebo (10 mg/kg) at two, three, four, and five hours after induced paw edema (Figure 1, panel A). CBD doses at 10 and 20 mg/kg significantly decreased paw edema compared with diclofenac (p < 0.01; p < 0.01) and CBD doses at 5 mg/kg (p < 0.05; p < 0.01) at two hours, respectively. Moreover, the highest dose of CBD (40 mg/kg) was greater and decreased paw edema more than the dose of 5 mg/kg at two, three, and four hours (p < 0.01; p < 0.05; p < 0.05), respectively. The anti-edema effect of CBD and diclofenac remained until five hours, while treatments did not significantly decrease paw edema at six hours (Figure 1, panel A). In addition, we found that the anti-inflammatory effect of 20 mg/kg for oral CBD five hours after the induced paw edema was correlated with the efficacy of diclofenac (r = 0.753, p < 0.005: Figure 2). Paw edema figures at six hours after the carrageenan induction in different doses and controls were shown in Figure 1, panel B.\n\nPanel A: Paw edema was measured with a plethysmometer and evaluated at 1, 2, 3, 4, 5, and 6 h after induced paw edema. Each bar represents the mean±SD and values obtained from eight animals per group. (one-way ANOVA followed by Tukey’s post-test). *p < 0.05 vs. control, **p < 0.01 vs. control, # p < 0.05 vs. diclofenac 10 mg/kg, ##p < 0.01 vs. diclofenac 10 mg/kg, $ p < 0.05 vs. CBD 5 mg/kg, and $$ p < 0.05 vs. CBD 5 mg/kg for all does of CBD. Panel B: The effect on paw edema six hours after carrageenan-induced paw edema. A is before inducing paw edema (baseline). Rats were treated with a Placebo of 10 mg/kg (B); Diclofenac 10 mg/kg (C); CBD 5 mg/kg (D); CBD 10 mg/kg (E); CBD 20 mg/kg (F), and CBD 40 mg/kg (G).\n\nThe degree of paw edema between both treatments is shown in each rat (A). Moreover, the correlation between both treatments is provided by the Spearman r- test and plotted by simple linear regression analysis (B).\n\nHistological examination consisted in an assessment of the hind paw tissues and revealed that sub-plantar injection of carrageenan. The site of carrageenan injection showed edema, congestion of vessels, and infiltration of inflammatory cells, such as neutrophils and lymphocytes, into the site of inflammation. The degree of inflammation graded the density of inflammatory cells into three tiers (Figure 3A). The degree of inflammation shows that all the treatments had a lower degree of inflammation than the placebo group. The degree of inflammation was highest in the placebo group (grading between 2 and 3) but also the lowest in the oral CBD (40 mg/kg) group (grading between 1 to 2). While diclofenac and oral CBD (5 and 10 mg/kg) groups had similar degrees of inflammation (grading between 2 to 3). The result of the histopathological study was in accordance with the paw edema results at six after carrageenan injection (Figure 3B).\n\nThe COX enzymes, a catalyzer for converting arachidonic acid to prostaglandin, have two isoforms: COX-1 and COX-2. The enzymes also are a common target for anti-inflammatory drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs).18 To determine COX activity, after six hours of the carrageenan induction, tissue samples from oral CBD (40 mg/kg) and control groups were collected, and COX-1 and COX-2 levels were determined by the ELISA method. The results showed that COX-1 (Figure 4A) and COX-2 (Figure 4B) activity were not significantly different among placebo, diclofenac, and the treated-CBD groups. The COX-1 and COX-2 activity results agreed with the level of PGE2 (Figure 4C). Serotonin, a pro-inflammatory-like neurotransmitter,19 in serum isolated from the same group of samples and controls was also measured after six hours of carrageenan injection. Serotonin levels in the diclofenac and oral CBD (40 mg/kg) groups were significantly lower than the placebo (p < 0.01; p < 0.001), respectively. Moreover, the results between the diclofenac and oral CBD groups were not different, indicating that the anti-inflammatory efficacy of CBD is probably equal to that of diclofenac (Figure 4D).\n\nOne-way ANOVA tested these analyses of variance following the Tukey post hoc test (**p < 0.01; ***p < 0.001, ns; not significant).\n\nThe level of serum cytokines and chemokines from rats that received different interventions, including placebo, diclofenac, and oral CBD (40 mg/kg), were determined using a bead array technique. As the results (Figure 5), four out of 18 cytokines and chemokines showed significantly different levels between CBD and either placebo or Diclofenac which were MCP-1 (Figure 5N), MCP-3 (Figure 5O), MIP-2 (Figure 5Q), and RANTES (Figure 5R). The others were not significantly different between the compared groups. However, the IL-17A level of the CBD group had a trend of lowered IL-17A when compared with placebo (Figure 5I).\n\nThose serum cytokines and chemokines were collected from the cardiac at six hours and detected by bead-based flow cytometry. The Mann performed comparisons between the groups–Whitney U test, p-value < 0.05 would be considered statistical significance.\n\n\nDiscussion\n\nCarrageenan-induced inflammation is a well-known model for screening anti-inflammatory activity. This model could predict the dose of anti-inflammatory activity in human inflammation diseases and correlates well with an effective dose in patients.20 In carrageenan-induced paw edema, the inflammation response is time-dependent and biphasic with various mediators.21,22 The first phase (0-2 h after carrageenan injection) increased vascular permeability and release chemical mediators such as COX, bradykinin, histamine, and serotonin products.23–26 The second phase (3-4 h after carrageenan injection) is attributed to the infiltration of leukocytes and released inflammatory mediators such as kinin, PGE2, leukotrienes, platelet-activating factor (PAF), free radicals of oxygen-derivatives and pro-inflammatory cytokines.27–29 Histopathological evaluation of the inflamed right hind paw also supported the anti-inflammatory effect of oral CBD. The oral CBD reduced paw edema and infiltration of inflammatory cells such as neutrophils and lymphocytes into the site of inflammation. This study demonstrated that oral CBD might be anti-inflammatory in both phases of carrageenan-induced inflammation.\n\nCosta et al. (2004) also reported that the administration of oral CBD has a beneficial action that reduces carrageenan-induced paw edema. CBD had a time, and dose-dependent effect after a single carrageenan injection. Paw edema following the carrageenan injection had a maximum peak at three hours. The lower dose of oral CBD (5 mg/kg) had a significant anti-inflammatory activity. However, lower doses of oral CBD did not reduce lipoperoxide production or COX system overactivity. However, it significantly inhibited the increased expression of eNOS in paw tissue.29\n\nOverall, cytokine and chemokine levels of the received oral CBD group were lower than the placebo group. For example, significantly lower levels of MCP-1, MCP-3, MIP-2, and RANTES were seen in those rats treated with CBD (Figure 4). Those MCP-1 (also known as CCL2), MCP-3 (CCL7), and MIP-2 (CCL4) promote inflammatory proteins and are mainly produced by monocyte and macrophage. These chemokines are also expressed in blood cells, fibroblasts, epithelial cells, and vascular smooth muscle cells. Also, they act as a chemoattractant of eosinophils, basophils, dendritic cells (DCs), neutrophils, NK cells, and activated T lymphocytes.30–32 RANTES (CCL5) is usually expressed and secreted by T cells and monocytes. However, CCL5 can also work as a chemoattractant for several leukocytes, but mainly involves T cell activation and regulation process.33 Together, those chemokines are crucial for immune responses and inflammation. In addition, the lowest IL-17A level was seen for CBD usage, and even the statistical comparison was not significantly different compared to the placebo and diclofenac groups (Figure 5I). However, the trend indicated that CBD probably decreased the IL-17A level. The IL-17A is well-known as a pro-inflammatory cytokine secreted by activated T helper cells, especially for Th17.34 This cytokine stimulates the transcriptional factor NF-kappa B and enhances the production of IL-6, which promotes more inflammation. Importantly, high levels of IL-17A are associated with various chronic inflammation and autoimmune diseases.35\n\nThis study demonstrated that oral CBD could reduce cytokine and chemokine levels in rats treated with CBD at 40 mg/kg compared to either placebo or diclofenac (10 mg/kg) group. This finding is consistent with other research groups, revealing that CBD decreases pro-inflammatory cytokines and suppresses immune responses by several mechanisms.36 A report demonstrated that CBD reduced CCL2, CCL5, eotaxin, IL-1ra, and IL-2.37 Another study also showed that CBD could reduce IL-4, IL-5, and eotaxin levels.38 We also demonstrated that the levels of those three cytokines in the CBD group were lower than for the placebo but not significantly different regarding the statistical analysis (Figure 5E, F, and K).\n\nThe possible mechanisms of CBD for immune suppression include CBD acting as an allosteric modulator of CB1 or CB2 receptors, which might work as a CB1 or CB2 antagonist. Also, CBD probably inhibits fatty acid amide hydrolase (FAAH), interrupting CB1 and CB2 receptors.37 Another mechanism of cytokine suppression might be related to the transient receptor potential V1 or the vanilloid receptor (TRPV1) because the TRPV1 antagonist reduces the cytokine-suppressing function of CBD in human tissue.39 According to the CBD intervention, the reduced serum cytokine and chemokine were seen in rats treated with oral CBD rather than placebo in this study. It is also related to localized edema (Figure 1), which decreased in rats treated with a high dose of CBD. This suggests that CBD is a potential immunosuppressant and has a potential role as an anti-inflammatory in the clinical setting.\n\n\nConclusions\n\nIn conclusion, the oral administration of CBD had a potentially beneficial anti-inflammatory effect on carrageenan-induced paw edema. However, the mechanism of the therapeutic effect of CBD has remained controversial. CBD may also be a good candidate for the treatment of inflammatory diseases. Further safety investigations of CBD in clinical use are required.",
"appendix": "Data availability\n\nZenodo: Raw data oral CBD, https://doi.org/10.5281/zenodo.7852520. 40\n\nThis project contains the following underlying data:\n\nCytokine Chemokinecsv\n\n- Serotonin.csv\n\n- PGE2.csv\n\n- COXI.csv\n\n- COXII.csv\n\n- Degree of inflammation.csv\n\n- Paw volume.csv\n\nZenodo: ARRIVE Essential 10 checklist for “Anti-inflammatory effects of oral cannabidiol in rat models”, https://doi.org/10.5281/zenodo.7960633. 41\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nThe research could not have been completed without assistance from a senior pathologist. The author would like to thank Professor Vorachai Sirikulchayanonta, MD, Faculty of Science, Rangsit University, Pathum Thani, Thailand, for his intensive guidance and advice in the part of histopathology analysis.\n\n\nReferences\n\nLiu Y, Liu H-Y, Li S-H, et al.: Cannabis sativa bioactive compounds and their extraction, separation, purification, and identification technologies: An updated review. TrAC Trends Anal. Chem. 2022; 149: 116554. Publisher Full Text\n\nSantana S, Brach C, Harris L, et al.: Updating Health Literacy for Healthy People 2030: Defining Its Importance for a New Decade in Public Health. J. Public Health Manag. Pract. 2021; 27(Suppl 6): S258–s264. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nBurstein S: Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorg. Med. Chem. 2015; 23(7): 1377–1385. PubMed Abstract | Publisher Full Text\n\nHammell DC, Zhang LP, Ma F, et al.: Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur. J. Pain. 2016; 20(6): 936–948. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nAtalay S, Jarocka-Karpowicz I, Skrzydlewska E: Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants (Basel). 2019; 9(1): 21. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nSonego AB, Prado DS, Vale GT, et al.: Cannabidiol prevents haloperidol-induced vacuos chewing movements and inflammatory changes in mice via PPARγ receptors. Brain Behav. Immun. 2018; 74: 241–251. (In eng). PubMed Abstract | Publisher Full Text\n\nMiller S, Daily L, Leishman E, et al.: Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2018; 59(15): 5904–5911. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nLaun AS, Shrader SH, Brown KJ, et al.: GPR3, GPR6, and GPR12 as novel molecular targets: their biological functions and interaction with cannabidiol. Acta Pharmacol. Sin. 2019; 40(3): 300–308. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nIannotti FA, Hill CL, Leo A, et al.: Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem. Neurosci. 2014; 5(11): 1131–1141. (In eng). PubMed Abstract | Publisher Full Text\n\nLowin T, Tingting R, Zurmahr J, et al.: Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. Cell Death Dis. 2020; 11: 714. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCosta B, Colleoni M, Conti S, et al.: Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn Schmiedeberg’s Arch. Pharmacol. 2004; 369(3): 294–299. (In eng). PubMed Abstract | Publisher Full Text\n\nMillar SA, Stone NL, Bellman ZD, et al.: A systematic review of cannabidiol dosing in clinical populations. Br. J. Clin. Pharmacol. 2019; 85(9): 1888–1900. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nLaux LC, Bebin EM, Checketts D, et al.: Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results. Epilepsy Res. 2019; 154: 13–20. (In eng). PubMed Abstract | Publisher Full Text\n\nFrane N, Stapleton E, Iturriaga C, et al.: Cannabidiol as a treatment for arthritis and joint pain: an exploratory cross-sectional study. J. Cannabis Res. 2022; 4(1): 47. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nGugliandolo E, Licata P, Peritore AF, et al.: Effect of Cannabidiol (CBD) on Canine Inflammatory Response: An ex vivo Study on LPS Stimulated Whole Blood. Vet. Sci. 2021; 8: 8(9). (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMorris CJ: Carrageenan-induced paw edema in the rat and mouse. Methods Mol. Biol. 2003; 225: 115–121. (In eng). Publisher Full Text\n\nSukkasem K, Itharat A, Thisayakorn K, et al.: Anti-inflammatory Activity of Kheaw-Hom Remedy in Lipopolysaccharide-stimulated Macrophage Cells and Carrageenan-induced Paw Edema in Rats. Asian Medical Journal and Alternative Medicine. 2022; 22: S108. Publisher Full Text\n\nFitzpatrick FA: Cyclooxygenase enzymes: regulation and function. Curr. Pharm. Des. 2004; 10(6): 577–588. (In eng). Publisher Full Text\n\nPelletier M, Siegel RM: Wishing away inflammation? New links between serotonin and TNF signaling. Mol. Interv. 2009; 9(6): 299–301. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang H, Gao J, Kou J, et al.: Anti-inflammatory activities of triterpenoid saponins from Polygala japonica. Phytomedicine. 2008; 15(5): 321–326. (In eng). PubMed Abstract | Publisher Full Text\n\nBarua CC, Pal SK, Roy JD, et al.: Studies on the anti-inflammatory properties of Plantago erosa leaf extract in rodents. J. Ethnopharmacol. 2011; 134(1): 62–66. (In eng). PubMed Abstract | Publisher Full Text\n\nVinegar R, Schreiber W, Hugo R: Biphasic development of carrageenin edema in rats. J. Pharmacol. Exp. Ther. 1969; 166(1): 96–103. (In eng). PubMed Abstract\n\nSadeghi H, Parishani M, Akbartabar Touri M, et al.: Pramipexole reduces inflammation in the experimental animal models of inflammation. Immunopharmacol. Immunotoxicol. 2017; 39(2): 80–86. (In eng). PubMed Abstract | Publisher Full Text\n\nSalvemini D, Wang ZQ, Wyatt PS, et al.: Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br. J. Pharmacol. 1996; 118(4): 829–838. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nSadeghi H, Hajhashemi V, Minaiyan M, et al.: A study on the mechanisms involving the anti-inflammatory effect of amitriptyline in carrageenan-induced paw edema in rats. Eur. J. Pharmacol. 2011; 667(1-3): 396–401. (In eng). PubMed Abstract | Publisher Full Text\n\nHajhashemi V, Minaiyan M, Banafshe HR, et al.: The anti-inflammatory effects of venlafaxine in the rat model of carrageenan-induced paw edema. Iran. J. Basic Med. Sci. 2015; 18(7): 654–658. (In eng). PubMed Abstract\n\nDi Rosa M, Giroud JP, Willoughby DA: Studies on the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J. Pathol. 1971; 104(1): 15–29. (In eng). PubMed Abstract | Publisher Full Text\n\nGilligan JP, Lovato SJ, Erion MD, et al.: Modulation of carrageenan-induced hind paw edema by substance P. Inflammation. 1994; 18(3): 285–292. (In eng). PubMed Abstract | Publisher Full Text\n\nHalici Z, Dengiz GO, Odabasoglu F, et al.: Amiodarone has anti-inflammatory and anti-oxidative properties: an experimental study in rats with carrageenan-induced paw edema. Eur. J. Pharmacol. 2007; 566(1-3): 215–221. (In eng). PubMed Abstract | Publisher Full Text\n\nMenten P, Wuyts A, Van Damme J: Macrophage inflammatory protein-1. Cytokine Growth Factor Rev. 2002; 13(6): 455–481. Publisher Full Text\n\nCarr MW, Roth SJ, Luther E, et al.: Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc. Natl. Acad. Sci. 1994; 91(9): 3652–3656. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXu LL, Warren MK, Rose WL, et al.: Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro. J. Leukoc. Biol. 1996; 60(3): 365–371. (In eng). PubMed Abstract | Publisher Full Text\n\nAppay V, Rowland-Jones SL: RANTES: a versatile and controversial chemokine. Trends Immunol. 2001; 22(2): 83–87. PubMed Abstract | Publisher Full Text\n\nMathur AN, Chang HC, Zisoulis DG, et al.: Stat3 and Stat4 direct development of IL-17-secreting Th cells. J. Immunol. 2007; 178(8): 4901–4907. (In eng). PubMed Abstract | Publisher Full Text\n\nMcGeachy MJ, Cua DJ, Gaffen SL: The IL-17 Family of Cytokines in Health and Disease. Immunity. 2019; 50(4): 892–906. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNichols JM, Kaplan BLF: Immune Responses Regulated by Cannabidiol. Cannabis Cannabinoid Res. 2020; 5(1): 12–31. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMuthumalage T, Rahman I: Cannabidiol differentially regulates basal and LPS-induced inflammatory responses in macrophages, lung epithelial cells, and fibroblasts. Toxicol. Appl. Pharmacol. 2019; 382: 114713. (In eng). PubMed Abstract | Publisher Full Text | Free Full Text\n\nVuolo F, Abreu SC, Michels M, et al.: Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma. Eur. J. Pharmacol. 2019; 843: 251–259. PubMed Abstract | Publisher Full Text\n\nCouch Daniel G, Tasker C, Theophilidou E, et al.: Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon. Clin. Sci. 2017; 131(21): 2611–2626. PubMed Abstract | Publisher Full Text\n\nMuengtaweepongsa S: Raw data Oral CBD animal. [Data set]. Zenodo. 2023. Publisher Full Text\n\nMuengtaweepongsa S: Oral Cannabis ARRIVE Essential 10 checklist. [Data set]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "181559",
"date": "11 Jul 2023",
"name": "Marco Biagi",
"expertise": [
"Reviewer Expertise Pharmacology of natural products and phytochemical analyses."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI read with interest the study of Sitthiphon Bunmanand and co-authors and I find this is a confirmation on the anti-inflammatory activity of CBD administered per os.\nIn the current version the work has poor novelty and it do not add valuable information for the scientific community, but it has been performed by using a validated in vivo inflammatory model and authors have been able to assess a dose/activity relationship and the comparison with placebo and a positive control (despite the negative control -not stimulated rats- is missing!)\n\nTherefore, I believe that, despite the current version is not acceptable (in my opinion) for indexing, the paper may represent the first part of a more sounding work, worthy to be deeply enlarged and revised, at least as a form of respect for sacrificed animals.\nIn detail: authors did not investigate the mechanism of action at all, and this is not acceptable in a high quality publication. As you evaluated a cannabinoid such as CBD, it would be useful to dose endocannabinoids and/or cannabinoids metabolism signaling, as well as at least some downstream PPAR/TRPV/GPR markers.\nAnother major point: if you look at cytokines/chemokines dosages, you can find that data are a little bit weird (differences between placebo and treated groups seem very small; here the absence of negative control don't allow to make a wise discussion) and results need to be explained in a clearer way. Actually, the used multiparametric assay seems to be not suitable for these analyses as data do not correlate with paw inflammation grading.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "202311",
"date": "15 Sep 2023",
"name": "Gökhan Arslan",
"expertise": [
"Reviewer Expertise Neurophysiology",
"Pain",
"Cannabinoids",
"Nitric oxide",
"Anti-inflammatory mechanism."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study includes evidence of anti-inflammatory effects of oral cannabidiol on carrageenan-induced inflammation. The results are fair, however, there are so many writing and verbal mistakes. I suggest some corrections:\nTitle The title does not reflect the content of the study. It must be added which method is being worked on.\nAbstract Background:\nIn 1st sentence, there is no connection between clinical use and animal research. These are separate.\nResults:\n“We found that the efficacy of all oral CBD doses decreased paw edema and was comparable to or had greater efficacy than an anti-inflammatory agent (Diclofenac 10 mg/kg), especially at 2, 3, 4, and 5 h after induced paw edema”. This sentence is not correct. Please check it by inspecting Figure 1.\n\n40 mg/kg cannabidiol suppressed all chemokine levels?\nConclusions:\n\nAuthors should discuss their results in this section. It is known that cannabidiol is an anti-inflamatuar agent.\nIntroduction\nWith cannabinoids, there is no need for so much information. It is necessary to focus on the anti-inflammatory effect.\n\nWhy didn’t the authors mention the carrageenan-induced inflammation in this section? What is the effect of the carrageenan?\nFigures\nFigure 2: Why did the authors use 20 mg/kg CBD in this correlation?\n\nFigure 3: What is the magnification of the histological images? Isn't there some significance here? CBD 40 mg/kg was reduced by half compared to the control. Please check.\n\nFigure 5: Authors use the Mann-Whitney U test for the comparisons. However, there are 3 groups. Please check your statistical analysis.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-680
|
https://f1000research.com/articles/12-676/v1
|
15 Jun 23
|
{
"type": "Systematic Review",
"title": "The doctor-patient relationship and barriers in non-verbal communication during teleconsultation in the era of COVID-19: A scoping review",
"authors": [
"Isabel Pinedo-Torres",
"Eilhart Jorge Garcia-Villasante",
"Claudia Cecilia Gutierrez-Ortiz",
"Carlos Quispe-Sarria",
"Kevin Morales-Pocco",
"Jamil Cedillo-Balcázar",
"Cristian Moran-Mariños",
"Victor Baca-Carrasco",
"Eilhart Jorge Garcia-Villasante",
"Claudia Cecilia Gutierrez-Ortiz",
"Carlos Quispe-Sarria",
"Kevin Morales-Pocco",
"Jamil Cedillo-Balcázar",
"Cristian Moran-Mariños",
"Victor Baca-Carrasco"
],
"abstract": "Background: Telemedicine is increasingly being used to provide virtual medical care. However, the transition to virtual consultations presents challenges for non-verbal communication. This scoping review aimed to identify and summarize studies that present data on barriers to non-verbal communication during teleconsultation. Methods: We searched MEDLINE/Pubmed, Ovid, APA, EBSCO, Web of Science and Scielo, without language or region restrictions. Our study included case series, cross-sectional, retrospective, and prospective cohorts that addressed barriers in any aspect of the non-verbal communication during teleconsultation. The quality of the evidence was assessed by the New Castle-Ottawa and Murad tools, and a thematic analysis was used for the qualitative synthesis of results. Results: We included 18 studies that reported qualitative findings related to the dimensions of non-verbal communication in telemedicine, which include ‘head and face’, ‘voice and speech’, ‘body language’, and ‘technical aspects’. The most reported barriers were facial gestures, looks, and body posture. Conclusions: Our study identified several dimensions of non-verbal communication that may pose barriers during teleconsultation. These findings may help guide the development of strategies to address these barriers and improve the quality of telemedicine services.",
"keywords": [
"teleconsultation",
"barriers",
"strategies",
"non-verbal communication"
],
"content": "Introduction\n\nThe coronavirus disease 2019 (COVID-19) pandemic has changed the way we live. The need to maintain social distancing to avoid contagion restricts face-to-face medical care, especially in serious cases, and encourages remote care in stable patients, as it has been seen with other diseases.1 Telemedicine uses information and communication technologies (ICT) to perform virtual medical care providing accessibility to a specialized medical service.2\n\nThe correct development of the teleconsultation process depends on a basic organizational strategy to establish an adequate relationship between health personnel and patients.3 The doctor- patient relationship is a determining component in the optimal health care process.4 In virtual care, maintaining an adequate doctor-patient relationship poses a greater challenge due to limitations such as the absence of physical contact, limited non-verbal cues, and potential technical interruptions.4 Any inconvenience during communication could lead to erroneous interpretations of the information, affecting the certainty of the diagnosis and compliance with the proposed treatment.5\n\nThe communication process has several channels: the verbal or linguistic channel that includes the words expressed in the conversation, paralinguistics channel such as intonation and pauses; and the non-verbal or non-linguistic channel that includes eye contact, gestures (nods, winks, smiles, frowns), postures, signs of restlessness, appearance, and lip reading.6 The information exchange process is mainly through a verbal channel; but the interpersonal contact is wider than it seems, with the non-verbal channel being a determining factor to the good understanding,7 in which every participant transmits their own psychological and emotional state being able to give different meanings to the information.8\n\nIn the medical consultation the non-verbal communication elements could have difficulties that have become more evident during the transition from face-to-face to virtual consultations as a solution to the lack of medical service during COVID 19 pandemic. It was found that the level of patient satisfaction seen by teleconsultation is acceptable as well as in face-to-face consultations but not optimal,9 therefore it is becoming necessary to perfect all aspects of the language in the virtual consultation. In the present review we seek to identify and summarize all the studies that present data on barriers in non-verbal communication during teleconsultation and to compile the proposed solutions.\n\nThe research question for this scoping review is: What are the reported barriers to non-verbal communication in telemedicine? Additionally, the review aims to explore the strategies proposed in the literature to overcome these barriers, including recommendations for improving communication technology, providing training to physicians and patients, or implementing changes in healthcare processes.\n\n\nMethods\n\nThis scoping review was conducted according to Joanna Briggs Institute (JBI) methodology.10\n\nThe World Health Organization (WHO) mentions that telemedicine serves to “Provide health services, where distance is a critical factor, by any health professional, using new communication technologies for the valid exchange of information in diagnosis, treatment and prevention of disease or injury, research and evaluation; and continuing education of health providers, all in the interest of improving the health of individuals and their communities”.11 Telemedicine emerges to fight against geographical barriers.12 In the evolution of both medicine and telecommunication technologies, various types of telemedicine have been developed, such as teleconsultation (interaction that occurs between a doctor and a patient in order to provide diagnostic or therapeutic advice through electronic means),13 tele-education (distance training that uses information and communication technologies so that people advance in their training process),14,15 telemonitoring (set of actions carried out by a health professional through use technologies, to provide the patient with advice and counseling with fines for health promotion, prevention, recovery or rehabilitation of diseases)16 and telesurgery (involves a surgeon operating from a remote location, either the next room, another hospital, another location or another continent).17,18\n\nOn the other hand, in non-verbal communication, aspects of the communicative exchange other than words that are capable of conveying meaning are understood. These include aspects of body language such as hand and arm gestures, facial expressions or body posture, and other related aspects such as accent, tone, volume, or speed of speech. The importance lies in the fact that it allows the patient to express her feelings through body and facial manifestations, which constitute a crucial component in the doctor-patient relationship. It should not only serve to obtain information that the doctor needs in the performance of his duties, it should also be used so that the patient feels listened to, to fully understand the meaning of his illness and so that he feels a co-participant in his care.19\n\nOur study was developed according to the recommendations according to the ‘Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA)’, the checklist is in Reporting guidelines.54 Because PROSPERO does not accept the registration of Scoping Review protocols, we opted to register it in the open access repository Figshare with the identifier of digital object (DOI) 10.6084/m9.figshare.13670362.\n\nA systematic search was carried out considering data from the beginning of time until February 2021 in the following electronic databases: MEDLINE/Pubmed, Ovid, APA, EBSCO, Web of Science and SciELO. No restriction was applied by language type or region. Additionally, the references of the included studies were evaluated to collect more bibliographic material. The search strategy included Medical Subject Title (MeSH) terms for “telemedicine”, “telehealth” and “teleconsultation” and related terms is available at the Extended data.52\n\nEligibility criteria\n\nThe participants considered in this scoping review included adult patients with chronic diseases who received care through telemedicine. Case series, cross-sectional studies, retrospective, and prospective cohorts that addressed barriers in any aspect of non-verbal communication in teleconsultation were included; but if it didn’t mention the doctor - patient interaction, these were excluded. We also excluded review articles, clinical trials, abstracts of congresses, letters to the editor, editorials, and systematic reviews.\n\nThe electronic search results were imported into the EndNote 20 reference management program; then, duplicate studies were removed according to the procedures described by Bramer et al.20 After that, we filter by titles and abstracts according to the inclusion criteria and finally potential documents were evaluated in full text to assess the eligibility. Two authors (JGV and CGO) assessed the eligibility of the studies independently using the selection criteria. The results were reviewed by a third investigator (IPT), who resolved any disagreements. The flow chart from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement was used to inform study selection.21,54\n\nThe data extraction was carried out by two researchers independently (JGV and CGO) and they were added to a Microsoft Excel document. by name of the first author, year of publication, country, study design, sample size, sex, dimensions, and aspects of non-verbal communication reported, barriers to an adequate understanding of the message, proposed strategies, among others. If it was necessary, we sent an email to the corresponding author to collect additional information.\n\nTwo authors (JGV and CGO) independently assessed the quality of the studies using the Newcastle-Ottawa scale (NOS)10 for cohorts and its adapted version for cross-sectional studies. It is a validated tool used to assess the methodological quality of non-randomized studies in systematic reviews and meta-analyses. The tool assesses the risk of bias based on three domains: selection of study groups, comparability of groups, and ascertainment of exposure or outcome of interest. Each study is assigned a score based on these criteria, with higher scores indicating lower risk of bias. It was considered as ‘good methodological quality’ if there were 3 or 4 stars in the selection domain, 1 or 2 stars in the comparability domain and 2 or 3 stars in the results domain/exposure; as ‘fair methodological quality’ for 2 stars in the selection domain, 1 or 2 stars in the comparability domain and 2 or 3 stars in the results domain/exposure; and as ‘poor methodological quality’ for 0 or 1 star in the selection domain, 0 stars in the comparability domain or 0 to 1 stars in the result domain/exposition.\n\nFor clinical cases, case series, and studies with fewer than 10 participants we used the Murad tool11 which consists of 8 questions divided into 4 domains (selection, verification, causality, and reporting) and a score greater than 5 was considered acceptable.\n\nAs the objective of this research is to explore the strategies proposed to address barriers in nonverbal communication during virtual medical care, we do not present quantitative results, but rather the results are grouped into each of the dimensions of nonverbal communication according to a classification proposed by the authors.\n\n\nResults\n\nWe found 388 studies in the different databases evaluated, after eliminating duplicates and making the assessment by title and abstract and in full text 18 studies were included (see Figure 1). The general characteristics of the included studies are listed in Underlying data51 and the list of articles excluded at the full text stage is available at the Extended data.53\n\nThe studies predominantly were of the cross-sectional type with a total of 13 studies, followed by reports or series of cases (n = 5).\n\nThe documents were from United States (n = 5), Australia (n = 3), Netherlands (n = 2) and the rest contributed with a single study. One study was from Latin America (Brazil). The total number of participants was 1,404 of which there were reports of 670 females and 303 men. Regarding the age of the patients, it varied in a range from 10 years to over 65 years.\n\nBarriers in non-verbal communication in teleconsultation\n\nIn this review we suggest a systematization scheme of the dimensions and aspects of non-verbal communication (see Figure 2). Based on that, on the dimension of head and face which include vision, gestures, head, and face movements, 16 of the 18 studies13–28 reported barriers of this dimension, being the most registered the decreased eye contact and difficulty recognizing facial expressions.\n\nIn the dimension of voice and speech, 4 of the 18 studies13,14,16,29 covered this topic and treated aspects about loss of tone or volume, dilation when responding by both participants (doctor and patient) and correspondence during the talk.\n\nIn the field of corporal language, 9 of the 18 studies13–15,19,21,23,25,27,29 addressed barriers in this appearance, mainly posture (described in patients with chronic pain, depression disorders, discomfort in front of relatives) and hand movement.\n\nThe technical dimension was assessed in 9 of the18 studies,13,18,21,24–26,28–30 mainly the aspects related to camera focus and lighting from both places involved, as well as the quality of the video. Other points related to this dimension are poor access to the network or ignorance in its use.\n\nStrategies to improve non-verbal communication aspects in teleconsultation\n\nOf the included studies, 7 of 18 mention strategies to improve eye contact and facial expressions.13,15,20,24,26,28,29 Among them, posing the angulation of the camera in 7 degrees and widening the field of vision with the use of multiple cameras was proposed to improve focus, observation of the gait when the participant enters and sits, and the position of the patient and companions.\n\nAchieving empathy with the patient has been addressed in 3 studies13,25,29 and it is mentioned that starting with casual conversations (i.e., telling own experiences) could be effective to gain patient's trust. Adapting to the needs and preferences of the patient in the use of video camera or only audio was mentioned in 1 study.19 In the dimension of voice and speech, 1 study14 reported that using an appropriate tone and pausing to wait for answers improve nonverbal communication. For older adults, 1 study21 mentions that a personal caregiver is beneficial to ensure the telecommunication process.\n\nDaily telepractice trainings to improve skills in non-verbal communication in the doctor are addressed in 2 studies,18,22 3 studies13,16,17 recommend the use of training softwares, and 1 study23 suggests the elaboration of flowcharts of care for telemedicine. In addition, ensuring adequate connectivity to the internet for the participants is widely cited. For a complete list of the proposed barriers and strategies, see Figure 2.\n\nFor the cross-sectional studies (n = 13), it was found that most of them had poor quality (9/18) followed by studies of fair quality (4/18), we did not find any study with good methodological quality. For the case reports, 4/5 obtained an adequate quality categorization (see Tables 1 and 2).\n\n\n\n• Representative sample\n\n\n\n• Sample size\n\n\n\n• Non-respondents\n\n\n\n• Ascertainment of the exposure\n\n\n\n• Comparability subjects\n\n\n\n• Assessment of the outcome\n\n\n\n• Statistical test\n\n\nDiscussion\n\nWe found that most of the barriers in non-verbal communication in teleconsultation reported in the studies were concerning to facial gestures, gaze, and body posture.\n\nHead and face: Vision, gestures, movements of the head and face\n\nIn person, the gaze and eye contact are used more when speaking than when listening,28 while during video call they are used to the same extent in both processes. This overuse of the visual channel in a digital medium increases the cognitive load and difficulties the process of interpreting verbal messages.31 Furthermore, many times during teleconsultation, the doctor is in the situation of reviewing and documenting the clinical records while must empathize and collect additional information from the patient. In this process, the directionality of the gaze does not always go towards the patient, and this can be interpreted as lack of interest to them.\n\nFacial expressions or gestures are useful because they reflect the patient´s internal state32; as well as their preferences. For example, a smile can tell us that the patient agrees, and a sigh can signify a desire or something that teleconsultant cannot reach.33\n\nBody language: Posture, limb movements, clothing and additions and physical self-contact\n\nAn individual's posture and dress can be used as a source of information about personalities and moods. But in video conferencing systems the screens are too small to provide this information. During the teleconsultation the physician only observes the face and perhaps the shoulders of the patients; this diminished visual field prevents us from obtaining useful information about this aspect of non-verbal communication.34 Although there are electronic devices incorporated into gloves that attempt to identify sequences of movements based on the position and angles of the joints these are difficult to use.35 Patients who use gestures to communicate, such as in sign language, involving rapid movements of the upper limbs (temporal features) and hand shapes (spatial features) are those that are most affected in the current covid19 pandemic.35 Finally, self-contact, touching either by crossing arms or holding hair or face reflects emotional alterations during medical care.36\n\nVoice and speech: Intonation, volume, response time and correspondence\n\nThe tone and volume of the voice make it possible to identify which of the interlocutors dominates the conversation. It has been reported during teleconsultations in which physicians had high conversation dominance there is less correspondence and speaking time for patients, resulting in poor information gathering.37 Patient intervention is less when they are not allowed to speak, do not feel empathy during the consultation or do not receive kind words. In addition, health personnel tend to complete the consultation faster when patient responses are very short. This would explain poor patient-doctor interaction and poor collection of information for the clinical records.38\n\nAlso, video call conversations are more disruptive compared to via phone consultations, especially when the streaming is slow. The secondary channel or backchannel during a remote conversation occurs when a participant is speaking, and the other participant responds by interrupting the speaker. The dialogues get more troubles when there is backchannel.\n\nTechnical aspects: Camera focus, video quality and lighting\n\nThe technical aspects of image and video can influence non-verbal communication during teleconsultations. The low video quality of both participants does not allow them to see the facial expressions or the full body of patients.39 Such drawbacks are described as barriers to creating a relationship of empathy with another person or rapport.24\n\nSome patients may not be familiar with ICTs or may not have the components necessary for an adequate exchange of information (microphone, webcam, high speed internet). As a last resort, health personnel could select the communication mode that the patient feels most comfortable with, not being the ideal way to obtain information in several cases.31\n\nThe strategies identified to improve the quality of care during virtual consultations cover multicomponent aspects. At the head, we have those aimed at the practical improvement of non- verbal communication skills such as the use of training software and setting training hours.29 It is necessary because health personnel are afraid of losing the patient information if they fail to observe accurately, moreover when they must watch the screen and write information from the patient at the same time.38\n\nBefore starting the teleconsultation, it is important to check out the audio and video components to ensure that the doctor's image is in the middle of the screen and enlarged so that it is clearly visible. In addition, it has been described that the use of technology must be in optimal conditions to guarantee a better process, therefore correct internet connectivity and high-quality images and videos are essential.\n\nApplications, such as Emopain dataset,40 analyze facial recognition and generate interpretations of the patient's emotions,41 mitigating the further confusion of the effect of acting with the camera.33 The applications would also serve to control specific diseases promoting their self-care and self- monitoring.42 Laptop’s image readers have increased considerably the availability of facial images as a data source about the status of an individual. The large touch screens of the current devices have provided more visual methods and interactive tools to assess patients.43 Although, there are no systems based on smartphones designed to detect facial expressions and only a few smartphone systems identify facial expressions.\n\nEmpathy and creating a friendly environment for the patient can be achieved in multiple ways. Introduce yourself and greet both patients and their family members and saying goodbye at the end is basic. It should be explained that the query face-to-face will be covered in the video consultation and that the level of service will be the same. In the first consultation it is important to spend some time talking about family, home and other social issues to build a good relationship (as you would face-to-face consultations). To maintain visual contact with the patient it is necessary to place the patient's image as close to the webcam as possible so that the patient feels that they are face to face. Additionally, the camera can be zoomed in and out to capture non-verbal signals.\n\nMake sure the patient has an adequate understanding of their diagnosis and treatment is essential to transfer effective information. The use of visual aids such as images and/or drawing on whiteboards can support verbal explanations.44 Summarize the information given and check with small questions to patients can evaluate the understanding process, especially when dealing with older adults. If the consultation involves the discussion of sensitive issues, we recommend considering doubling the evaluation time, this is helpful for aging and terminal patients. Before completing the query, please suggest opportunities to address future concerns by providing contact details from local healthcare providers and other specialists.45\n\nThe physical distance between the participants of the teleconsultation compromises the visual and auditory information. Lack of physical contact (hand shaking and physical examination) affects the emotional and psychological bond between physicians and patients. Therefore, teleconsultation requires greater patient participation since doctors cannot perform the same physical examination as in an encounter face to face.46 It is recommended to advise patients to participate in the consultation virtual with a close relative who can help report data on their physical status.\n\nPrivacy in the use of telemedicine involves three aspects: the patient, the platform and provider. In a video call, we suggest analyzing or imagining the surroundings and who is listening to the teleconsultation even if the camera is off, to maximize similarity to a face-to-face encounter. The patient should describe where they are and if they have privacy, as well as to confirm that the time for talking is enough. To ask a question, try to use the names frequently to address to the appropriate person. Minimize distractions, using a predictable location and decreasing electronic distractions by blocking Windows pop-ups or notifications, divert incoming calls or notifications directly to voicemail.47 Consider that the patient's environment can have its own distractions, which may not be directly apparent. If there are technical failures during the beginning of the conversation, it is recommended to move to a telephone conversation. If the encounter with the patient includes another healthcare professional, it is beneficial for both professionals to be in the same physical space, to create normality, greater comfort in the patient and avoid another source of distraction.33\n\nTeleconsultation is a two-way relationship where it is fundamental to provide the optimal conditions for the best care. Because of the COVID-19 pandemic, great challenges are presented to optimize this service, especially in Peru, which is one of the countries with the highest infected number, higher mortality, less access to health and with projections of worse results than most countries.48,49\n\nCurrently, despite the return of healthcare workers to in-person care, there has been a significant increase in demand for telemedicine in both public and private sectors. The National Telehealth Network of the Ministry of Health (MINSA for its acronym in Spanish), which previously provided a maximum of 250 monthly services prior to the health emergency, now registers one million monthly services across its various modalities. Social Security has also conducted over 2 million teleconsultations in the past year and a half. Despite these achievements, a large portion of the Peruvian population still lacks access to telemedicine and continues to rely on traditional forms of care.50\n\nWe must consider that the processes of adaptation to changes in behavior or customs in the population take time and often generate resistance in people, because of the comfort that represented their close past. The presence of a threat is not recognized and in some sectors the benefit of the vaccine is doubted. Health professionals must recognize that this context is not the best to begin a type of medical attention that was previously prohibited in the country.\n\nThe fear that occurs mainly in the most vulnerable populations generates resistance to any type of information. Distrust of the state is structural, and survival efforts have been always far from any state program that may include them. Our results provide various techniques to optimize teleconsultation; However, digital media, for some people, will be a disadvantage rather than an opportunity, due to the gaps in infrastructure, education, and market access in large sectors of the population, even in the capital itself. For health professionals, a useful strategy would be the development of guidelines based on patient’s profile, considering their degree academic, marital status, comorbidities, and disabilities; with that, it is hoped that the doctor can better adapt to the context of teleconsultation and provide better attention to the patient.\n\nThe generation of empathy is one of the important values that must be incorporated between the doctor and the patient to break that barrier that prevents establishing the trusted connection for healthcare. This requires a lot of practice, and it is important that medical schools include in their undergraduate courses for distance medical care incorporating the strategies mentioned in this review. In addition, the use of language according to the patient's social context is also an essential manner to build trust when engaging a conversation with tolerance, use of simple words and examples.\n\nThe studies included in this systematic review have been observational (cross-sections and case series), ideally, we would have wanted cohort-type studies that will assess exposure to non-verbal communication barriers in telemedicine and measured the results in the transmission of the information and the clinical improvement of the patient; but despite doing a search exhaustive, no studies with this design were found. Only one study corresponds to Latin America (Brazil) and the others come from populations with greater economic solvency, which implies that the technological limitations reported and levels of education of patients are not the same as in our country. Also, strategies to overcome barriers in non-verbal communication in telemedicine should be evaluated in controlled clinical trials.\n\n\nConclusions and recommendations\n\nBarriers in non-verbal communication during telemedicine can be classified in four dimensions: head and face, voice and speech, body language and aspects technicians. Within them, the greatest barriers were reported in the interpretation of facial gestures, appearance, and body posture. We recommend that health professionals who carry out teleconsultations, must consider the various barriers mentioned in this review as well as the proposed strategies. We also suggest that all modalities of the telemedicine training could be part of the undergraduate courses of the different faculties of medicine and, for doctors already graduated from health institutions, provide training courses for virtual care with the use of software and trainers.",
"appendix": "Data availability\n\nFigshare: Tables. https://doi.org/10.6084/m9.figshare.22180012.v2. 51\n\nThis project contains the following underlying data:\n\n‐ Table 1. xlsx (general characteristics of the included studies).\n\nFigshare: Search Strategy. https://doi.org/10.6084/m9.figshare.22180042.v1. 52\n\nThis project contains the following extended data:\n\n- Search strategy.docx\n\nFigshare: The list of articles excluded at the full text stage. https://doi.org/10.6084/m9.figshare.22180045.v1. 53\n\nThis project contains the following extended data:\n\n‐ The list of articles excluded at the full text stage.docx\n\nFigshare: PRISMA checklist for ‘The doctor-patient relationship and barriers in non-verbal communication during teleconsultation in the era of COVID-19: A Scoping Review’. https://doi.org/10.6084/m9.figshare.22180051.v2. 54\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAhmed F, Zviedrite N, Uzicanin A: Effectiveness of workplace social distancing measures in reducing influenza transmission: a systematic review. BMC Public Health. 2018; 18(1): 518. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMá L: Telemedicina en el Minsa, Telemedicina Perú.[citado el 11 de octubre del 2020]. Reference Source\n\nLockamy A, Smith D: Telemedicine: A process enabler for enhanced healthcare delivery systems. Bus. Process. Manag. J. 2009; 15: 5–19. Publisher Full Text\n\nHjelm NM: Benefits and drawbacks of telemedicine. J. Telemed. Telecare. 2005; 11(2): 60–70. Publisher Full Text\n\nDa Luz P: Telemedicine and the Doctor/Patient Relationship. Arq. Bras. Cardiol. 2019; 113: 100–102. PubMed Abstract | Publisher Full Text\n\nFussell SR, Benimoff NI: Social and cognitive processes in interpersonal communication: implications for advanced telecommunications technologies. Hum. Factors. 1995; 37(2): 228–250. PubMed Abstract | Publisher Full Text\n\nCukor P, Baer L, Willis BS, et al.: Use of videophones and low-cost standard telephone lines to provide a social presence in telepsychiatry. Telemed. 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Publisher Full Text\n\nPeters MDJ, Godfrey C, McInerney P, et al.: Chapter 11: Scoping Reviews.Aromataris E, Munn Z, editors. JBI Manual for Evidence Synthesis. JBI; 2020. Publisher Full Text\n\nWHO (World Health Organization): Telemedicine. Opportunities and developments in member states. Report on the second global survey on eHealth. Global Observatory for Health series. World Health Organization; 2010 [access 8 Feb 2022]; Volume 2. . 9789241564144ISSN2220-5462Reference Source\n\nCasado-García ME, Santervás-Sanz A: Estado del arte de la Telemedicina en España y Europa. Sistemas de Telecomunicación.[access 8 Feb 2022]. Reference Source\n\nRuiz C, Zuluaga A, Trujillo A: Telemedicina: Introducción, aplicación y principios de desarrollo. Rev CES Med. 2007; 21(1): 77–93.\n\nOrganización Panamericana de la Salud/Organización Mundial de la Salud: Teleconsulta durante una pandemia. [Access 11 feb 2022]. Reference Source\n\nDel Aguilar-Gordon F : aprendizaje en escenarios presenciales al aprendizaje virtual en tiempos de pandemia. Estud. Pedagóg. 2020; 46(3): 213–223. Publisher Full Text\n\nViloria-Nuñez C, Cardona-Pena J, Saavedra-Antolinez I: Telemonitoreo de datos cardiacos y respiratorios a través de un sistema Web con JSP. Ing. Desarro. 2014; 32(1): 102–114. Publisher Full Text\n\nGordillo F, López RM, Mestas L, et al.: Comunicación no verbal en la negociación: La importancia de saber expresar lo que se dice. Revista Electrónica de Psicología Iztacala. 2014; 17(2): 646–666.\n\nBramer WM, Giustini D, de Jonge GB , et al.: De-duplication of database search results for systematic reviews in EndNote. J. Med. Libr. Assoc. 2016; 104(3): 240–243. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTricco AC, Lillie E, Zarin W, et al.: PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann. Intern. Med. 2018; 169(7): 467–473. PubMed Abstract | Publisher Full Text\n\nAggarwal D, Ploderer B, Vetere F, et al.: Acm. Doctor, Can You See My Squats? Understanding Bodily Communication in Video Consultations for Physiotherapy. ACM Conference on Designing Interactive Systems. DIS. 2016; 1197–1208\n\nBulik RJ: Human factors in primary care telemedicine encounters. J. Telemed. Telecare. 2008; 14(4): 169–172. Publisher Full Text\n\nHenry BW, Ames LJ, Block DE, et al.: Experienced Practitioners' Views on Interpersonal Skills in Telehealth Delivery. Internet J. Allied Health Sci. Pract. 2018; 16(2). Publisher Full Text\n\nLiu C, Scott KM, Lim RL, et al.: EQClinic: a platform for learning communication skills in clinical consultations. Med. Educ. Online. 2016; 21: 31801. Publisher Full Text\n\nLucas GM, Gratch J, Scherer S, et al.: Ieee. Towards an Affective Interface for Assessment of Psychological Distress. 2015 International Conference on Affective Computing and Intelligent Interaction. Interaction (ACII). pp. 539–545. Publisher Full Text\n\nOverby MS, Baft-Neff A: Perceptions of telepractice pedagogy in speech-language pathology: A quantitative analysis. J. Telemed. Telecare. 2017; 23(5): 550–557. PubMed Abstract | Publisher Full Text\n\nPetersson NB, Jorgensen AL, Danbjorg DB, et al.: Video-consulted rounds with caregivers: The experience of patients with cancer. Eur. J. Oncol. Nurs. 2020; 46: 1–8.\n\nPostma-Nilsenova M, Postma E, Tates K: Automatic detection of confusion in elderly users of a web-based health instruction video. Telemed. J. E Health. 2015; 21(6): 514–519. PubMed Abstract | Publisher Full Text\n\nSävenstedt S, Zingmark K, Hydén L-C, et al.: Establishing joint attention in remote talks with the elderly about health: a study of nurses' conversation with elderly persons in teleconsultations. Scand. J. Caring Sci. 2005; 19(4): 317–324. PubMed Abstract | Publisher Full Text\n\nTorppa MA, Timonen O, Keinänen-Kiukaanniemi S, et al.: Patient-nurse-doctor interaction in general practice teleconsultations--a qualitative analysis. J. Telemed. Telecare. 2006; 12(6): 306–310. PubMed Abstract | Publisher Full Text\n\nvan Gurp J , van Selm M , Vissers K, et al.: How outpatient palliative care teleconsultation facilitates empathic patient-professional relationships: a qualitative study. PLoS One. 2015; 10(4): e0124387. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZilliacus E, Meiser B, Lobb E, et al.: The virtual consultation: practitioners' experiences of genetic counseling by videoconferencing in Australia. Telemed. J. E Health. 2010; 16(3): 350–357. Publisher Full Text\n\nBarbosa IA, Silva M: Nursing care by telehealth: what is the influence of distance on communication? Rev. Bras. Enferm. 2017; 70(5): 928–934. PubMed Abstract | Publisher Full Text\n\nSuzuki T, Murase S, Kitano A, et al.: Eye contact in medical examinations using videophones. Telemed. J. E Health. 2006; 12(5): 535–541. PubMed Abstract | Publisher Full Text\n\nManchanda M, McLaren P: Cognitive behaviour therapy via interactive video. J. Telemed. Telecare. 1998; 4 Suppl 1: 53–55. PubMed Abstract | Publisher Full Text\n\nTam T, Cafazzo JA, Seto E, et al.: Perception of eye contact in video teleconsultation. J. Telemed. Telecare. 2007; 13(1): 35–39. Publisher Full Text\n\nNewcomb AB, Duval M, Bachman SL, et al.: Building Rapport and Earning the Surgical Patient's Trust in the Era of Social Distancing: Teaching Patient-Centered Communication During Video Conference Encounters to Medical Students. J. Surg. Educ. 2021; 78(1): 336–341. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEgede JO, Song S, Olugbade TA, et al.: EMOPAIN. Challenge 2020: Multimodal Pain Evaluation from Facial and Bodily Expressions. CoRR.2020. abs/2001.07739.\n\nAung MSH, Kaltwang S, Romera-Paredes B, et al.: The Automatic Detection of Chronic Pain-Related Expression: Requirements, Challenges and the Multimodal EmoPain Dataset. IEEE Trans. Affect. Comput. 2016; 7(4): 435–451. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaptista S, Wadley G, Bird D, et al.: Acceptability of an Embodied Conversational Agent for Type 2 Diabetes Self-Management Education and Support via a Smartphone App: Mixed Methods Study. JMIR Mhealth Uhealth. 2020; 8(7): e17038. 1-12. Publisher Full Text\n\nAung MSH, Alquaddoomi F, Hsieh CK, et al.: Leveraging Multi-Modal Sensing for Mobile Health: A Case Review in Chronic Pain. IEEE J. Sel. Top. Signal Process. 2016; 10(5): 962–974. PubMed Abstract | Publisher Full Text | Free Full Text\n\nColeman C: Health Literacy and Clear Communication. Best Practices for Telemedicine. 2020; 4(4): 224–229.\n\nSabesan S, Allen D, Caldwell P, et al.: Practical aspects of telehealth: doctor-patient relationship and communication. Intern. Med. J. 2014; 44(1): 101–103. PubMed Abstract | Publisher Full Text\n\nMiller EA: The technical and interpersonal aspects of telemedicine: effects on doctor-patient communication. J. Telemed. Telecare. 2003; 9(1): 1–7. PubMed Abstract | Publisher Full Text\n\nAlmathami HKY, Win KT, Vlahu-Gjorgievska E: Barriers and Facilitators That Influence Telemedicine-Based, Real-Time, Online Consultation at Patients' Homes: Systematic Literature Review. J. Med. Internet Res. 2020; 22(2): e16407. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRahman S: Country-by-country COVID-19 projections - evolution, peak and saturation.2020. Reference Source\n\nWorld Health Organization. (November 28th: WHO Coronavirus (COVID-19) Dashboard.2021. Reference Source\n\nFORBES Perú: February 26th 2023. Telemedicina en Perú: ¿Cómo cambió el servicio con la pandemia y qué le depara?Reference Source\n\nPinedo Torres I: Tables. [Dataset]. figshare. 2023. Publisher Full Text\n\nPinedo Torres I: Search Strategy. [Dataset]. figshare. 2023. Publisher Full Text\n\nPinedo Torres I: The list of articles excluded at the full text stage. [Dataset]. figshare. 2023. Publisher Full Text\n\nPinedo Torres I: PRISMA checklist. [Dataset]. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "188449",
"date": "20 Jul 2023",
"name": "Ani Orchanian-Cheff",
"expertise": [
"Reviewer Expertise Systematic Review and Scoping review methodology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the privilege of reviewing your scoping review on non-verbal communication during teleconsultation. I have some concerns regarding your search reporting.\nPlease follow PRISMA for searching http://prisma-statement.org/Extensions/Searching\n\nIn terms of databases searched, Ovid, APA, EBSCO are not databases but vendors. You should indicate both the database and the vendor, such as Embase (Ovid), PsycINFO (Ovid). What database did you search on EBSCO? Was it CINAHL or something else?\n\nIn terms of your search strategy you should be using both subject headings and key words. For Embase for example, you should be using exp nonverbal communication/ as well as exp telemedicine/. These would not be the same subject headings in PsycINFO, so you would need to search that database separately rather than at the same time. In PsycINFO the subject headings are exp nonverbal communication/ and mobile health/ or exp telemedicine/ For Ebsco this would depend on what specific database you are searching.\n\nFor your key words, I would suggest adding virtual consult* OR virtual appointment* OR virtual care.\n\nFor your searches in methods you should list the exact date searched. Database results vary depending upon what day you searched.\n\nFebruary 2021 for your search is outdated. Please update your search so that it is current.\n\nFor your search you list that is was searched \"from the beginning of time\". This is not accurate. The start date of a search is dependent on the database and varies. I would omit this and simply put the date searched.\n\nWhy did you exclude \"review articles, clinical trials, abstracts of congresses, letters to the editor, editorials, and systematic reviews\" Systematic reviews and clinical trials about non-verbal communication would have been relevant to your question.\n\nThere are some grammatical errors. Please review the paper carefully for errors.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? No\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "178893",
"date": "16 Aug 2023",
"name": "Udoka Okpalauwaekwe",
"expertise": [
"Reviewer Expertise Primary care",
"family medicine",
"participatory research",
"health promotion"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt was a pleasure reviewing your work. I find the study inquiry relevant to research and practice considering the current trends post-COVID. My major gripe was with the language and tense. I don't know when this was written but you wrote in the present tense mixing it with the past tense thus making it difficult to logically follow your chain of thought. This was rife in all sections of this article. Perhaps may benefit from professional reviewing if language translation may have played into the lack of logical fluidity.\nThe methods and methodology were aptly described and showed rigor and reliability.\nThe discussion could be improved to engage the practical implications of the study findings to practice in the context of the research objectives and external validity.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-676
|
https://f1000research.com/articles/11-853/v1
|
28 Jul 22
|
{
"type": "Research Article",
"title": "The role of oncogenes and tumor suppressor genes in determining survival rates of lung cancer patients in the population of North Sumatra, Indonesia",
"authors": [
"Noni Novisari Soeroso",
"Fannie Rizki Ananda",
"Johan Samuel Sitanggang",
"Noverita Sprinse Vinolina",
"Fannie Rizki Ananda",
"Noverita Sprinse Vinolina"
],
"abstract": "Background: Gaining a better understanding of molecular alterations in the pathogenesis of lung cancer reveals a significant change in approach to the management and prognosis of lung cancer. Several oncogenes and tumor suppressor genes have been identified and have different roles related to survival rates in lung cancer patients. This study aims to determine the role of KRAS, EGFR, and TP53 mutations in the survival rate of lung cancer patients in the population of North Sumatra.\nMethods: This is a retrospective cohort study involving 108 subjects diagnosed with lung cancer from histopathology specimens. DNA extractions were performed using FFPE followed by PCR examinations for assessing the expressions of EGFR, RAS, and TP53 protein. Sequencing analysis was carried out to determine the mutations of EGFR exon 19 and 21, RAS protein exon 2, and TP53 exon 5-6 and 8-9. Data input and analysis were conducted using statistical analysis software for Windows. The survival rate analysis was presented with Kaplan Meier.\nResults: 52 subjects completed all procedures in this study. Most of the subjects are male (75%), above 60 years old (53.8%), heavy smokers (75%), and suffer from adenocarcinoma type of lung cancer (69.2%). No subjects showed KRAS exon 2 mutations. Overall survival rates increased in patients with EGFR mutations (15 months compared to 8 months; p=0.001) and decreased in patients with TP53 mutations (7 months compared to 9 months; p=0.148). Also, there was increasing Progression-Free Survival in patients with EGFR mutations (6 months compared to 3 months) (p=0.19) and decreasing PFS in patients with TP53 mutations (3 months compared to 6 months) (p=0.07).\nConclusions: There were no KRAS mutations in this study. EGFR mutations showed a higher survival rate, while TP53 mutations showed a lower survival rate in overall survival and progression-free survival.",
"keywords": [
"lung cancer",
"EGFR",
"KRAS",
"TP53",
"survival rate."
],
"content": "Background\n\nRecent molecular studies have focused on the genetic alterations and epigenetic impacts in the pathogenesis of lung cancer.1 Several tumor suppressor genes and oncogenes have been identified and altered the micro and macro environment related to lung carcinogenesis.2 This was a multistep process where the oncogenes mutation initiates and triggers conversions of the normal epithelium to cancer cells due to environmental factors, particularly cigarette smoke.1 P53 and KRAS genes play crucial roles in maintaining cells integrity that affects the early stage of lung carcinogenesis, particularly in lung cancer-related tobacco exposure.3 Recent studies showed the mutations of KRAS and TP53 mutations have been related to shorter overall survival and progression-free survival rates in lung cancer patients, whether in early or advanced stages.4,5 In contrast, EGFR mutations, as one of the most common oncogenic mutations together with targeted therapy management, gives longer survival times than for subjects with wild-type mutations who received systemic chemotherapy.6–8\n\nHowever, there has been a surge of EGFR resistance around the world. The concurring mutations with other oncogenes and tumor suppressor genes have been identified as the cause of EGFR resistance.3–5,9,10 Unfortunately, there is still limited data regarding oncogenes and tumor suppressor gene mutations in Indonesia. This study aimed to assess the role of oncogenes and tumor suppressor genes in determining the survival rate of lung cancer patients in the population of North Sumatra.\n\n\nMethods\n\nThis was a retrospective cohort study conducted in the Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sumatra Utara during the period of 2017–2020. All subjects were enrolled in the study via several cancer-referral hospitals in North Sumatra in collaboration with the Faculty of Medicine, Universitas Sumatra Utara. The criteria for inclusion in this study were subjects aged 18 or over and diagnosed with lung cancer confirmed by histopathology preparations from bronchoscopy, open biopsy, thoracotomy, and trans-thoracal lung biopsy. The number of cells in one section of the paraffin block must be a minimum of 50 cells. All medical records were then observed to assess the demographic and clinical characteristics and followed the progressivity of disease based on RECIST criteria.11 Subjects’ deaths were recorded in their medical records in the case of subjects who passed away in hospital, while others were assessed based on phone calls from the subjects’ relatives addressed in medical records. The exclusion criteria of this study were an inadequate amount of cancer cells in a paraffin block, incomplete medical records, and difficulties in assessing the subjects’ relatives.\n\nAll the procedures of this study were approved by the Ethics Committee of the Faculty of Medicine, Universitas Sumatra Utara with reference number 124/KEP/USU/2020. Written informed consent was obtained from all the subjects or their relatives. All the pathology specimens received permission for genetic analysis from the Pathology Department at each collection site.\n\nDNA was extracted from Formalin-Fixed Paraffin-Embedded using Quick-DNA FFPE mini prep (Zymo Research, USA) and sliced using microtome in 1–2 slices and 4 μm thickness. After being deparaffinized, digested, and purified, the DNA was eluted by a DNA elution buffer. The PCR was performed using MyTaq HS Red Mix (Bioline, UK) with the following process: denaturation, annealing, and elongation. DNA was then amplified using certain primers (Table 1) and run in 2% agarose electrophoresis in Tris Buffer EDTA pH 8.0. Sequencing analysis was carried out via two different methods. EGFR and KRAS were converted to reverse complement and analysed using ClustalW in BioEdit Sequence Alignment Editor 7.2.5. The reverse sequence was also compared to human reference genome NG_007524.2 (LRG_433) using BLASTn NCBI. The BLASTn results were also aligned with corresponding Coding Sequences (CDS). Lastly, the sequence was analysed using FinchTv 1.4 Software using reverse complement views. Meanwhile, TP53 genes were analysed using Unipro Ugene v. 38.1 software (RRID: SCR_005579) and compared with standard reference NG-017013.2. Samples in which there was a change in protein base analysed using Nucleotide Basic Local Alignment Search Tool (BLASTn) were then compared with several TP53-specific databases including SNP (dbSNP), Cosmic (assessing somatic mutation), ClinVar (Clinical variations, assessing the correlation of mutations with clinical profile).\n\n\nResults\n\nAs shown in Figure 1, a total of 52 subjects completed the procedures of this study with most of the subjects being male (75%), aged over 60 years (53.8%), heavy smokers (75%), with adenocarcinoma type lung cancer (69.2%) stage IVA (71.25%). Further characteristics were as described in Table 2. From sequencing analysis results no KRAS exon 2 mutations were detected, while EGFR mutations were detected in 6 subjects, consisting of 5 subjects who had exon 19 mutations, 1 subject with intron 19 mutations, and 2 subjects with exon 21 mutations. TP53 mutations were seen in 5 subjects, of which 2 subjects had missense mutations of exon 5, 1 subject showed silent mutations, 1 subject with missense exon 8mutations, and 1 subject had nonsense exon 8 mutations.\n\nSurvival analysis for EGFR mutations is depicted in Figure 2. EGFR mutations showed a significant increase in both overall survival (OS) and progression-free survival (PFS) with p=0.001 for OS and p=0.018 for PFS (Log-Rank Test). Five of six subjects showed mutations in exon 19 and 2 subjects showed double mutations in exon 19 and exon 21. Further analysis also showed significant improvements in OS and PFS of both single and double mutations of EGFR while double mutations showed higher OS and PFS compared with single mutations. Detailed comparisons of EGFR mutations are described in Table 3.\n\na. Overall Survival (OS) with and without EGFR mutations. b. Progression-free Survival (PFS) with and without EGFR mutations. c. OS with different types of EGFR mutations. d. PFS with different types of EGFR mutations.\n\n* p-value < 0.05 considered significant.\n\nSurvival analysis was presented in OS and PFS curve in Figure 3. Generally, subjects with TP53 mutations had a lower survival rate including OS and PFS compared with non-mutations. Subjects with TP53 mutations had 7 months of OS, 2 months less than subjects without TP53 mutations (p=0.148). This study also compared median survival rates for different types of TP53 mutation including non-mutations, missense mutations, nonsense mutations, and silent mutations as follows; 9 months, 7 months, 9 months, and 5 months. Nevertheless, the association between median survival rates and different types of TP53 mutation was not significant in statistical analysis with a p-value of 0.245. Patients with TP53 mutations also had a three months’ shorter PFS compared to those with non-mutations (3 months vs 6 months; p=0.07). After further analysis according to different types of mutation, the PFS of subjects with missense mutations and silent mutations was 3 months, while for subjects with non-mutations and nonsense mutations it was 6 months. These different mutations were also insignificant in relation to median PFS with a p-value of 0.107.\n\na. OS between subjects with and without TP53 mutations. b. OS with different types of TP53 mutation. c. PFS between subjects with and without TP53 mutations. d. PFS with different types of TP53 mutation.\n\nThe survival rates assessed in this study were overall survival (OS) and progression-free survival (PFS) and Table 3 shows the comparisons of OS and PFS in subjects with EGFR, TP53, and no mutations. EGFR mutations showed a significant increase in both OS and PFS compared with no mutations, while TP53 was a poor predictor of lung cancer patients with shorter survival rates.\n\n\nDiscussion\n\nKRAS mutation is one of the common oncogenes mutations that are related to poor prognosis of lung cancer and is strongly associated with smoking.12–19 This study follows on from a study by Soeroso et al. which analyzed KRAS mutations in the population of North Sumatra.20 However, there were no KRAS exon 2 mutations among the subjects of this study. The scanty population of KRAS mutations in Asia is not completely understood, although recent data has shown that Asia has a lower prevalence of KRAS mutations compared with worldwide data.21,22 In Asian populations, KRAS mutations were present in 4.3%–10.5% of the population, while data shows that KRAS mutations were present in 30–40% of populations worldwide.23 In addition, Syahruddin et al., as the first study to identify KRAS mutations in lung cancer in Indonesia, showed a lower incidence of KRAS mutations compared with populations worldwide (7% vs 31%).24,25 The occurrence of KRAS mutations also often coincides with mutations in other oncogenes or tumor suppressor genes. Co-mutations between KRAS and TP53 were the most prevalent and were related to the poorest outcomes in all pharmacological approaches including targeted therapy, chemotherapy, and radiotherapy.25 However, studies by Fang et al. and Dong et al. showed a better outcome in administering immune checkpoint inhibitors in a patient with KRAS and TP53 mutations compared with KRAS mutations alone or with no mutations at all.26,27 On the other hand, KRAS mutations were among the most common factors related to EGFR-TKI resistance. Several studies reported the concurring EGFR-KRAS mutations in 15–20% populations28–31 while KRAS mutations were presumed to be independent factors in resistance to EGFR-TKI treatment. The absence of KRAS mutations in this study directs the pulmonologists to analyze other factors which might contribute to resistance to EGFR-TKI treatment in the population of North Sumatra and other populations with a low prevalence of KRAS mutations, despite the limitations of facilities in detecting KRAS mutations in certain populations.\n\nKRAS mutations can be detected in cytology and histopathology examinations following the RT-PCR or DNA Sequencing method.32 The type of KRAS mutation will be identified using the DNA-Sequencing method where a change in GGT to TTG is addressed as G12C,33 the most common mutation of KRAS related to longer survival rate compared with other mutations.25 The second most common KRAS mutation type is in codon 12 changes in GGT to GTT, referred to as G12V mutations.33 In this study, we examined the histopathology preparations from the paraffin block for all subjects diagnosed with lung cancer, and from the PCR test it was found that almost all subjects showed expressions of RAS protein in exon 2 codon 12-13. Nevertheless, there was no change in protein base with DNA sequences showing GGT-GGC known as normal RAS protein expressions. This finding showed that the Sanger sequencing method carried out in this study is still reliable in identifying the KRAS mutations, although the variations in North Sumatra populations showed no mutations.\n\nRole of the EGFR mutations in lung cancer has been described in previous studies.8,34,35 EGFR mutations treated with EGFR-TKI-targeted therapy showed a significantly improved survival rate with lung adenocarcinoma.7,35,36 However, the multiple mutations are not completely understood. The various studies tried to identify the impact of double mutations or triple mutations of EGFR in clinicopathology characteristics in lung cancer patients.37,38 All previous studies showed poorer outcomes with multiple mutations compared with single EGFR mutations.37,38 Nevertheless, in this study, double mutations of exon 19 and exon 21 showed a better outcome in both OS and PFS compared with single mutations of exon 19. Unfortunately, this study was a small size study, so it is still difficult to draw general conclusions concerning the wider population. In the previous studies, the double mutations consisted of exon 20 T790M, which has been identified as primary factors in 1st and 2nd EGFR TKI-resistance.38 Barnet et al. also showed shorter PFS in a patient with co-mutations of exon 19 with noncommon EGFR mutations including exon 20, T90M, and PIK3CA.39 This differs from the current study, which looked at exon 19 and exon 21 mutations. A larger scale of genetic studies is needed to evaluate the impact of double mutations in the treatment of lung adenocarcinoma, both in receiving targeted therapy and systemic chemotherapy.\n\nIn addition to the oncogenes mutations mentioned above, mutations of TP53 as one of the most common tumor suppressor gene mutations associated with resistance to cancer therapy.40,41 Having a role as the guardian of the genome, the TP53 gene maintains the integrity of the genome by modifying, stabilizing, and preventing cell proliferation in response to cellular stress.42–45 This study found five subjects with TP53 mutations and showed a shorter survival rate in both OS and PFS. When different kinds of mutation were analyzed in depth, missense and silent mutations showed shorter OS and PFS compared with nonsense mutations. However, the small number of subjects analyzed in this study might bias the effect due to individual variations. On a larger scale of different types of TP53, a missense mutation is the most common TP53 mutation,46 particularly in tobacco-related lung cancer.46,47 According to the latest evidence, missense mutation has a “gain-of-functions” effect, leading to an increase in the expression of cancer cells.48,49 In contrast, Halvorsen found that missense mutations showed higher OS compared with other types of TP53 mutations although, in general, TP53 mutations showed a higher Hazard Ratio (HR) compared with no mutations.46\n\nAs oncogene activations occur, TP53 activates and arrests the cell cycle in both G1 and G2, allowing sufficient time for DNA repair.50,51 Along with RAS mutations, p53 is a multifunctional protein which alters cell regulations, cancer cell transformations, and vascular invasion in all solid cancers including lung cancers. Therefore, oncogenic activations and over-expressions of p53 genes are independent predictors of poor prognosis in NSCLC. In this study, there were no co-mutations of TP53 with any of EGFR or RAS mutations meaning it is difficult to evaluate the interactions of concurring mutations, whether they have mutual or opposite effects.\n\nOther data highlighted in this study is the lower number of mutations of oncogene and tumor suppressor gene in North Sumatra. A large cohort study in Norway showed 38% of subjects had positive mutations of KRAS in non-small cell lung cancer patients, while in Chen’s study involving a lower number of subjects KRAS mutations accounted for 11% of all mutations with a higher prevalence among smokers (20–30%) compared with those who never smoked (7–13%).52 This is in contrast this to study which found no KRAS mutations in subjects diagnosed with lung cancer. EGFR was the most common oncogene mutation, particularly in Asia. The median global prevalence of EGFR in the advanced stage of NSCLC was 33.07%53 while 47% of Asians showed EGFR mutations.52 The latest data on EGFR mutations in Indonesia also revealed EGFR mutations in 44.4% of 1874 cytological specimens diagnosed with EGFR. In this study, just 11.5% of subjects were positive with EGFR mutations with allele-specific for exon 19 and 21 and DNA sequencing. Furthermore, TP53, as the common tumor suppressor gene accounted for more than 50% in NSCLC40,52,54 was only detected in 9.6% of the subjects in this study. A definite mechanism explaining the lower prevalence of both oncogenes and tumor suppressor genes may not be understood yet. Lung carcinogenesis is a complex process characterized by the after-effects of genetic variations as the individual process works synergistically with environmental exposure.55,56 Long durations of exposure to carcinogens might alter DNA methylation, resulting in the conversion of normal cells to cancer cells. Therefore, a better understanding of genetic variations and individual vulnerability of lung carcinogenesis may provide better anti-cancer research.\n\nAlthough this study has several limitations including the small samples size and the limited survival aspect, this is the first study to identify TP53 mutations in lung cancer patients in Indonesia and the first study to identify the DNA sequencing of common oncogenes and tumor suppressor genes in the population of Sumatra. Further multi-center study involving larger sample size is needed to identify the prevalence of oncogenes and tumor suppressor genes to actualized personal therapeutic approach for cancer patients, particularly in a developing country such as Indonesia.\n\n\nData availability\n\nFigshare: Underlying data for “The role of oncogenes and tumor suppressor genes in determining survival rates of lung cancer patients in the population of North Sumatra, Indonesia”, https://doi.org/10.6084/m9.figshare.19522468.57\n\nIn addition, this study adds Research Resource Identifiers (RRIDs) from these research resources including the following software tools and data:\n\n1. Human lung carcinoma (RRID:CVCL_5791)\n\nhttps://web.expasy.org/cellosaurus/CVCL_5791\n\n2. FFPE/Formalin-Fixed Paraffin-Embedded (RRID:SCR_001307)\n\nhttp://www.bioconductor.org/packages/release/bioc/html/ffpe.html\n\n3. FinchTV (RRID:SCR_005584)\n\nhttp://www.geospiza.com/Products/finchtv.shtml\n\n4. ClustalW (RRID:SCR_017277)\n\nhttp://clustalw.ddbj.nig.ac.jp/index.php\n\n5. BLASTn (RRID:SCR_001598)\n\nhttp://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastn&BLAST_PROGRAMS=megaBlast&PAGE_TYPE=BlastSearch\n\n6. Unipro UGENE (RRID:SCR_005579)\n\nhttp://ugene.unipro.ru/",
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}
|
[
{
"id": "145779",
"date": "11 Aug 2022",
"name": "Fariz Nurwidya",
"expertise": [
"Reviewer Expertise Thoracic oncology."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this study, the author determined the role of KRAS, EGFR, and TP53 mutations in the survival rate of lung cancer patients in the population of North Sumatra, Indonesia. They assessed the expressions of EGFR, RAS, and TP53 protein from lung cancer specimens. Furthermore, they performed sequencing analysis to detect the mutations of EGFR exon 19 and 21, RAS protein exon 2, and TP53 exon 5-6 and 8-9. Finally, survival rate analysis was presented with Kaplan Meier. They found that EGFR mutations showed a higher survival rate, while TP53 mutations showed a lower survival rate in overall survival and progression-free survival.\nThis is a well-written manuscript and provides data on oncogenes and tumor suppressor gene mutations in Indonesia and the relationship with the survival rate.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "151763",
"date": "17 Nov 2022",
"name": "Darren Wan-Teck Lim",
"expertise": [
"Reviewer Expertise Lung cancer"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors have completed a manuscript that describes common oncogenes found in lung cancer patients in North Sumatra.\nIt is a descriptive and retrospective study.\nSome comments on the data presented have to be made:\nOnly TP53 and EGFR mutations were found in the study. Were the TP53 and EGFR mutations co-mutant in the same patient tumor? And if so how many of them demonstrated co-mutation? Populations with co-mutations of EGFR/p53 do worse than EGFR alone populations and has been described before in other literature. It would be good for the authors here to look into this.\n\nWere the Stage IV EGFR mt patients treated with EGFR TKI? If so with which generation of drug and for how long? In other words what is the median OS for the pts who were treated with EGFR TKI vs those who did not receive EGFR TKI?\n\nIf 71.25% of the patients were stage IVA, how were the other stages of disease treated? Did stage IIIB vs IIIC vs IV survive differently? and what were the proportion of pts in each stage who were treated with EGFR TKI?\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "9157",
"date": "03 Jan 2023",
"name": "Johan Samuel Sitanggang",
"role": "Author Response",
"response": "Dear reviewer, Thank you for the reviews that have been submitted to us. Meanwhile, we also would like to convey a number of things related to several reviews and questions that have been made by the reviewer as follows. 1. Were the TP53 and EGFR mutations co-mutant in the same patient tumor? And if so how many of them demonstrated co-mutation? In this study, there were no samples with co-mutation P53 and EGFR at the same time. Only co-mutations of exon-19 and exon-21 were found in the EGFR found in 2 individuals. This has also been discussed in the discussion column of this study, precisely in paragraph 2 page 6 of this study, where based on previous studies, a higher number of mutations in EGFR is associated with a worse prognosis. However, in this study, better overall survival and progression free survival were found in patients with double mutations compared to single mutations. This might happen because the number of samples with double-mutation in the study was very small. It is known that the co-mutation of P53 and EGFR is associated with a worse patient prognosis, this has been found based on the available literature, we may add this to the discussion of this paper. 2. Were the Stage IV EGFR mt patients treated with EGFR TKI? If so with which generation of drug and for how long? In other words what is the median OS for the pts who were treated with EGFR TKI vs those who did not receive EGFR TKI? Because of the objectives of this study did not cover this, accompanied by limited data regarding patients and also the lack of research samples so we could not present the information that reviewer asked. Based on previous studies, it was found that there was an increase in the prognostic parameters of EGFR mt patients with treatment with EGFR-TKI, with KRAS mutations found playing a major role in the existence of resistance to this drug. In our next study, we are going to make a research in this regard. Thank you for the advice that has been given. 3. If 71.25% of the patients were stage IVA, how were the other stages of disease treated? Did stage IIIB vs IIIC vs IV survive differently? and what were the proportion of pts in each stage who were treated with EGFR TKI? This study focuses only on assessing the role of oncogenes and tumor suppressor genes from lung cancer on survival rates of lung cancer patients in North Sumatra, Indonesia, so that in this paper we do not include data on the management of each patient. Previous studies have indeed mentioned several specific treatments for different mutations. However, we will probably consider this in the implementation of our next research. We would probably publish a second version soon adding some of the suggestions you have provided. Thank you for the review you have given."
}
]
}
] | 1
|
https://f1000research.com/articles/11-853
|
https://f1000research.com/articles/12-673/v1
|
14 Jun 23
|
{
"type": "Research Article",
"title": "Heart rate variability as a prognostic marker in critically ill patients",
"authors": [
"Yogesh Kakde",
"Shilpa Bawankule",
"Satish Mahajan",
"Sourya Acharya",
"Sunil Kumar",
"Abhay Gaidhane",
"Shilpa Bawankule",
"Satish Mahajan",
"Sourya Acharya",
"Sunil Kumar",
"Abhay Gaidhane"
],
"abstract": "Background: Heart rate variability (HRV) can be used to assess cardiac autonomic activity in critically ill patients. Heart rate variability is termed as fluctuation in the time interval between adjacent heartbeats. The equilibrium among the sympathetic and parasympathetic subgroups of the autonomic nervous system (ANS) is essential for the maintenance of systemic homeostasis and effective response to external stressors. Hence we aimed this study to determine whether heart rate variability can be used as a prognostic marker in critically ill patients. Methods: A cross-sectional study was conducted among 225 consecutive critically ill patients admitted to the medicine Intensive care unit (ICU) of AVBRH, Sawangi (Meghe) based on the inclusion and exclusion criteria. The selected participants were evaluated for 24 hours Heart Rate Variability (HRV) and APACHE 4 score. Outcomes like mortality and survival were corelated with 24 hours Heart Rate Variability and APACHE 4 score. Results: The variables were significantly associated (p<0.05) with Standard deviation of the average Normal-to normal HRV intervals (SDANN) and Standard deviation of the NN intervals (SDNN). The variables were also significantly associated (p<0.05) with the variable High frequency (HF), High frequency/Low frequency (LF/HF) ratio. LF/HF parameter was abnormal in 86% of patients who died as compared to 54% of the patients who survived (p-value <0.001). Conclusions: Out of the 225 participants, 20% died during the study period. APACHE 4, Glasgow coma scale (GCS) score, and LF were significantly and independently associated with mortality. Decrease in Low frequency parameter of 24 hours Heart Rate Variability identified mortality with accuracy of 74% with 81.2% specificity, and 46.7 % sensitivity",
"keywords": [
"Apache 4",
"Critical Care Medicine",
"Heart rate variability",
"Intensive Care Unit."
],
"content": "Introduction\n\nThe fluctuation in the time between contiguous heartbeats is referred to as heart rate variability. For the maintaining of systemic homeostasis and an adequate response to external stimuli, the sympathetic and parasympathetic subgroups of the autonomic nervous system (ANS) must be in balance.1 The autonomic nervous system (ANS) is a part of the peripheral nervous system (PNS) that is responsible for coordinating involuntary physiological functions that include respiration, heart rate, blood pressure, digestion, etc. These functions are further controlled by the sympathetic and parasympathetic systems. Dysfunction of ANS (one or more subdivisions) along with a pre-existing disease has been seen to be been associated with a poor outcome of the disease. Cardiac autonomic dysfunction can result from any disease that affects any of the various components of the ANS.2\n\nDisorders such as sepsis, coronary artery disease, strokes, chronic liver disease, chronic kidney disease, malignancy, hypertension, diabetes mellitus, etc, with autonomic dysfunction, often require management in intensive care units (ICUs). In the ICU, prompt and proper assessment of patients’ prognosis, outcome, and mortality risk is of the most importance. It has been speculated that early recognition of autonomic dysfunction can help predict prognosis and direct appropriate and timely treatment. The available scoring systems such as APACHE 4, though competent, lack feasibility of application in the ICU setting due to lack of required information for scoring.3 Therefore, over the years, many methods have been used in assessing autonomic function such as the baroreflex sensitivity, cardiac-chemoreflex sensitivity, and the heart rate variability (HRV).4\n\nHeart rate variability calculation is one of popular approaches to estimate autonomic nervous system (ANS) dysregulation. It is the variability between heart beats or more scientifically, variability between successive R waves on electrocardiogram (ECG) or the R-R interval (RR). It is a non-invasive method increasingly used in medicine.3 The clinical potential of HRV recognized by Hon and Lee in 1965, when they discovered that the acute changes in HRV was linked to foetal distress and foetal hypoxia could be predicted from it before any appreciable changes occurred in the heart rate itself.5 This finding was paramount in the development of the standard of care in monitoring fetal distress and therefore, significantly reduced incidences of morbidity and mortality.6 Further, in the survivors of myocardial infarction, an association of reduced HRV with increased risk of mortality and subsequent events of arrhythmic events was noted.7\n\nIn recent times, it has been found that reduced variability of the heart rate could prove to be an indicator of risks of adverse events and mortality in patients with several diseases that affects the autonomic nervous system more so in the critically ill.8,9 A healthy individual with normal functioning autonomic nervous system usually has a high variability in the heart rate whereas a lower variability often indicates dysfunction and inadequate adaptability of the autonomic nervous system.10 Patients who are critically ill may experience an altered sympathetic-parasympathetic balance and a key task of the ANS is to regulate the cardio-respiratory interaction to ensure an optimal oxygen supply.4 Loss of this balance results in variability of the heart rate. It has been suggested that in the ICU and emergency settings, the heart rate variability analysis can help predict at risk patients and those who can be benefitted from early admissions and management.11,12\n\nLike many other physiological phenomena, HRV demonstrates intricate relationships between organs, tissues, and cells. The phenomena of HRV is based on the concept that the state of organs, tissues, and cells and the strength of interaction among them are affected by illness and treatment which in turn affects the HRV in an individual.13 Heart rate variability can arise from both cardiac and noncardiac events, frequently reflecting overall/global rather than local processes.\n\nMany methods for HRV analysis have been developed, some more accurate than others. All the methods essentially are derived from three general domains, namely, the time domain, frequency domain, the regularity domain. Continuous ECG recordings that are digitally processed at a frequency of at least 125 Hertz (Hz) are the source of HRV data. Several more adult studies have demonstrated that decreases in HRV are correlated with clinical outcomes and precede clinical decline.11 As a result, HRV can be useful in the ICU as a gauge of clinical prospects. It is not yet possible to translate these findings into useful information that emergency room doctors can use right now. Use of heart rate variability is an uncommon clinical practice due to its limited applicability in acute care. Determining the function of heart rate variability as a predictive factor in critically ill patients admitted to the ICU was the goal of this study. The additional goals were to determine the mortality rate, the length of ICU/hospital stays, and how those factors are related to HRV.\n\n\nMethods\n\nThis cross-sectional study took place at the Department of Medicine at a rural tertiary care teaching hospital in Maharashtra, India. After receiving approval from the Institutional Ethics Committee of Datta Meghe Institute of Medical Sciences, the study was started. Studying took place from December 2020 until November 2022 with IEC number DMIMS (DU)/IEC/2022/1231. Dated 08/07/2022.\n\nOn admission all consenting patients/patient relatives were asked to sign a written informed consent form (in the language best understood by them). The information regarding each patient was kept confidential & was not revealed at any point in time.\n\nThe study participants were critically ill patients admitted to the Medicine intensive care unit (ICU) of Acharya Vinoba Bhave rural hospital of Jawaharlal Nehru Medical College Sawangi, Wardha.\n\nInclusion criteria were\n\n• Patient admitted to the Intensive Care Units (ICUs) for more than 24 hours\n\n• Patients or their relatives who gave consent to participate in study.\n\nExclusion criteria were as follows:\n\n• Patients who did not give consent\n\n• Patients who were on any sedative medications, drowsy state, or disoriented at a time of admission\n\n• Individuals who were currently taking medications that may interact with the HRV analysis. drugs like beta blockers\n\n• Age < 18 years\n\nThe minimum total sample size needed was calculated to be 215 using the below equation. We used a sample size of 225 for our study considering a drop out of 5%.\n\nSpecificity of Low frequency of HRV = 0.61\n\nPrevalence of positive character (Prev) = 0.128\n\nEstimation error = 7%\n\nn = 215\n\nThe selected participants were evaluated for 24 hours. The principle investigator carried out all measures. Heart Rate Variability analysis was assessed for 24 hours and the APACHE 4 score was calculated within 48 hours of admission. The following data were collected using structure pilot tested study proforma which includes demographic profile, co-morbidity status, Glasgow coma scale score, vitals (Systolic and Diastolic blood pressure: Blood pressure was measured twice using mercury sphygmomanometer, 5 minutes apart and average of both the reading was taken. Mean arterial pressure: It was calculated by formula Diastolic pressure + 1/3 (Systolic blood pressure - Diastolic blood pressure), Respiratory rate), biochemical parameters (Total leucocytes count, Hematocrit, Sodium, Creatinine, Urea, Serum lactate, Fasting blood sugar, Post-meal blood sugar, Hba1c, Albumin, Bilirubin, Total cholesterol, Low density lipid, High density lipid, Triglycerides) was processed in automated chemical analyzer (VITROS 5600) and heart rate variability parameters.\n\nHolter machine: Holter system helps to record, analyze, display ECG signal, edit and create HRV analysis. The recorder was used under the direction of be doctors and trained healthcare professionals. The analysis result is for clinical reference only and the final diagnosis must be made by physicians.\n\nOn the first day of enrolment, each participant in the research was assessed with a 3-channel Holter (Cardios® CardioLight model, So Paulo, Brazil). The 24-hour measure was implemented without interfering with ICU care as usual. Using a system created especially for this purpose (Cardios®), data analysis to determine HRV was carried out. This system automatically produces the following indices of HRV in the time domain: Normal-to-Normal (NN) average interval, standard deviation of the NN interval (SDNN), square root of the squared mean of the difference between subsequent NN-intervals (r-MSSD), and percentage of NN intervals that deviated by more than 50 ms from adjacent NN-intervals (pNN50); frequency domain with fast Fourier Transform (FFT) method: Power in total, Very Low Frequency (VLF) power, Low Frequency (LF) power, and High Frequency (HF) power.\n\nAPACHE score was calculated with the help of clinical history, vitals and biochemical analysis within 48 hours of admission. After assessing HRV and APACHE4 Score, participants were moniterd till the discharge from hospital and death. Participants were also monitored for use of vasopressor, Ventilator.\n\nWe performed statistical analysis using the Statistical Software STATA MP Version 14.0. For categorical variables, descriptive statistics, frequency analysis, and percentage analysis were used to describe the data, while mean and SD were used for continuous variables. The Chi-square test was used to determine the significance of categorical data (that is, to test the difference in proportions between two groups). The probability value of 0.05 is used as the significance level in all of the above statistical tools.\n\n\nResults\n\nFigure 1 shows the patients flow diagram. The total number of ICU patients admitted during the study was N = 1640. Individuals were excluded from the study for the following reasons: patients who are currently taking medications that may interact with HRV analysis drugs like beta blocker (N = 330), patients who are on sedatives (N = 490), patients who are drowsy and disoriented at the time of admission (N = 550), patients who did not give consent (N = 6) and due to technical error of hrv analysis (N = 19) and loss to follow up due to leaving against medical advice (N = 20) excluded from the study. A total of 225 subjects were eligible for study.21\n\nTable 1 shows a mean age of 54.0 years (16.3), systolic blood pressure of 124.4 mmHg (16.9), diastolic blood pressure of 83.2 mmHg (14.7), and respiratory rate of 26.6 (6.2) respectively. The most common co-morbidity affecting the study population was hypertension which was seen in 146 (64.9%) patients. The other co-morbidities were sepsis 82 (36.4), stroke 63 (28.4), diabetes 67 (29.8), chronic liver disease 20 (8.9). Male study participants had significantly higher no. of sepsis 65 (43.0%) as compared to in females 17(23.0%) and Chronic liver disease was seen in more males 18 (11.9%) as compared to females 2 (2.7%). 40% of female participants had a stroke which was significantly higher than males 21.9%.\n\nTable 2 shows the distribution of biochemical parameters among the study population. There was no significant difference between males and females in biomedical parameters.\n\nTable 3 shows the mean duration of hospital stay was 11.4 (10.2%) days among the study population. 42 patients died during hospital stay amounting to an 18.7 % mortality. 183 (81.3%) patients were discharged during the study period. The number of patients who required ventilatory support was 48 (±21.3), male 37 (±24.5), females 11 (±14.9). Vasopressor support 61 (±27.1), male 44 (±29.1), and females 17 (±23.0).\n\nTable 4 shows the variables High frequency, Low frequency/High frequency ratio were significantly associated (p < 0.05) with SDANN and SDNN.\n\nTable 5 shows the variables High frequency, Low frequency/High frequency ratio and Outcome were significantly associated (p < 0.05) with APACHE 4 score. HF parameter was abnormal in 83% of patients who died as compared to 44% of the survived group (p-value < 0.001). LF/HF parameter was abnormal in 86% of patients who died as compared to 54% of the survived group (p-value < 0.001).\n\nTable 6 shows the variables low frequency, High frequency, Low frequency/High frequency ratio, APACHE 4 score, GCS score were significantly associated (p < 0.05) with the variable’s outcome.\n\nTable 7 shows the variables Urea, Low density lipid, Use of mechanical Ventilator, FiO2, PaO2 significantly associated with survival were (p < 0.05) with the Sepsis, SDANN, and SDNN, APACHE 4, GCS score, LF, HF, and LF/HF ratio.\n\nTable 8 shows diagnostic accuracy of heart rate variability shows at a cutoff of SDANN Index was ≤15 by ROC to predict mortality: Death with a sensitivity of 86% and specificity of 31%. At a cutoff of SDANN Index was ≤15 by ROC it predicts mortality: Death with a sensitivity of 86%, and specificity of 31%. At a cutoff of RMSSD was ≥31 by ROC it predicts mortality: Death with a sensitivity of 67%, and as and specificity of 44%. At a cutoff of LF ≤9.2 by ROC it predicts mortality: Death with a sensitivity of 47%, and Specificity of 81%. At a cutoff of HF ≤39.5 by ROC it predicts mortality: Death with a sensitivity of 47%, and a specificity of 69%. At a cutoff of LF/HF ≤0.3 by ROC it predicts mortality: Death with a sensitivity of 60%, and a specificity of 64%. At a cutoff of APACHE 4 score was ≥71 by ROC it predicts mortality: Death with a sensitivity of 98% and specificity of 88%.\n\nTable 9 shows the coefficients representing the log-odds of the outcome variable for each predictor variable. APACHE 4 score shows the increase in score with the odds of the outcome variable while age and LF shows negative association.\n\n\nDiscussion\n\nIn this study, we show that heart rate variability is clinically useful for critically ill patients’ severity rating (APACHE 4) and prognosis. When compared to patients who failed to improve and had to be brought to the ICU, individuals whose critical illness stabilised tended to have larger heart rate variability and showed bigger hour-by-hour rises. Mean and hourly heart rate variability also predicted variations in survival.\n\nThe gold standard for clinical HRV measurement is HRV recordings, which are influenced by circadian rhythms, core body temperature, metabolism, the sleep cycle, and the renin-angiotensin system.14 varying heart rate The quantity of HRV that was detected during monitoring intervals that could last from 1 min to >24 hours is quantified by time domain indices. Included in the measures are the SDNN, SDANN, RMSSD, LF, HF, and LF/HF.\n\nLow HRV has been previously described as a marker of greater illness and worse outcomes.15 In the prospective cohort of Castilho FM et al.15 the values reported in the 20 minutes Holter among the survivor group vs non- survivor group were: LF power 18.0 vs 2.0, HF power 9.0 vs 6.5 and LF/HF 1.29 vs 0.40. In our study as per the 24-hour Holter HRV among the survivor group vs non- survivor group were: LF was 211.3 ± 268.7 while HF was 241.5 ± 366.1 and the mean LF/HF ratio was 1.4 ± 1.3, SDANN index was recorded as 18.3 ±40.0 while the mean SDNN was evaluated as 39.6 ± 36.1. RMSSD was 37.8 ± 21.4. The mean analyzed beats were observed to be 1358 ± 714.9 while the mean analyzed units were 17.1 ± 4.6. HF parameter was abnormal in 83 % of patients who succumbed as compared to 44 % of those who survived. LF/HF parameter was abnormal in 89 % of patients who died as compared to 44 % of those who survived.\n\nAmongst the ICU population, the mean APACHE 4 score of 225 study participants was 58.9 ± 23.0 and a significant association was observed between the outcome and the APACHE 4 score. A mean score of 92.1 ± 15.2 was observed for participants who died which were significantly higher than the other group of discharged participants (51.3 ± 16.9). In the prospective cohort of Castilho FM et al.15 the mean APACHE 4 score among survivors was 14.15 ± 5.93 while among non- survivors it was 21.94 ± 8.45.\n\nIn the cohort study by Salahuddin N et al.16 on heart rate variability during rapid response team consultations on 91 patients. The Mean age was 49.9 ± 22.3 years and 54.9% of the participants were male. The reasons for admission at the hospital included liver cirrhosis patients (10%), chronic respiratory disease patients (9%), renal disease patients (9%), malignancy cases (32%), chronic multiorgan dysfunction cases (12%) and other cases (13%). In our study Hypertensive patients (64.9%), sepsis (36.4%), diabetes patients (29.8%), acute stroke (28.0%), coronary artery disease (22.7%), chronic liver disease (8.9%), malignancy (2.7%), chronic kidney disease (2.2%).\n\nIn the prospective, observational cohort study conducted by Bishop DG et al.,17 out of the total 55 patients, 35 required invasive ventilation (55%), 19 required inotropic support (35%) and 2 needed renal replacement therapy (4%). The median duration of stay in the ICU was 2.6 days (1-22 days). In the retrospective cohort study conducted by Liu N et al.18 on 342 patients, 19% had 30 days of in-house mortality and the remaining 81% survived. In our study 225 patients, mean duration of hospital stay. 10.5 % died, 10.1% discharged. A significant association was observed between GCS score and patient outcome as the mean GCS score was significantly higher for the group who got discharged (13.7 ± 2.8) in comparison to the group who died (7.4 ± 1.4).\n\nStudies by Maheshwari A et al.,19 Graff B et al.,20 Hadase M et al.21 and Ong ME et al.22 also reported an association between low heart rate variability with sudden cardiac death, stroke outcome, prognosis in heart failure and risk of cardiac arrest respectively. In our study, factors associated with mortality were low HF, low LF, low LF/HF ratio, high APACHE IV Score and low GCS score.\n\nTakase et al.23 demonstrated that SDANN lower than 30 ms had greater sensitivity and specificity (92%) than SDANN higher than 20 ms (31% sensitivity and 100% specificity) to detect autonomic dysfunction and cardiac events in cardiac autonomic neuropathy. In our study diagnostic accuracy of HRV was analyzed and it was higher in APACHE 4 (89.8%) and LF (74.1%).\n\nThis was a single centre study. Results from multi centre studies will help in generalizing the results. The results would have been more robust with a larger cohort. All the HRV were not taken into consideration.\n\n\nConclusion\n\nOut of the 225 participants, 20% died during the study period. APACHE 4, Glasgow coma scale (GCS) score, and LF were significantly and independently associated with mortality. Decrease in Low frequency parameter of 24 hours Heart Rate Variability identified mortality with accuracy of 74% with 81.2% specificity, and 46.7% sensitivity.",
"appendix": "Data availability\n\nZenodo: Heart rate variability as a prognostic marker in critically ill patients. https://doi.org/10.5281/zenodo.7858390. 24\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nKakde YK, Gaidhane S, Acharya S, et al.: A Study Protocol on Assessment of Heart Rate Variability as a Prognostic Marker in Critically Ill Patients. J. Pharm. Res. Int. 2021 Dec 27; 33(60B): 2851–2857. Publisher Full Text\n\nSánchez-Manso JC, Gujarathi R, Varacallo M, et al.: Autonomic Dysfunction.Reference Source\n\nJohnston BW, Barrett-Jolley R, Krige A, et al.: Heart rate variability: Measurement and emerging use in critical care medicine. J. Intensive Care Soc. 2020 May; 21(2): 148–157. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchmidt HB, Werdan K, Müller-Werdan U, et al.: Autonomic dysfunction in the ICU patient. Curr. Opin. Crit. Care. 2001 Oct 1; 7(5): 314–322. Publisher Full Text\n\nHon EH, et al.: Electronic evaluations of the fetal heart rate patterns preceding fetal death, further observations. Am. J. Obstet. Gynecol. 1965; 87: 814–826.\n\nKamath MV, Watanabe MA, Upton AR, et al.: Heart rate variability: A historical perspective. Heart. 1990; 1981: 1991–2000.\n\nKleiger RE, Miller JP, Bigger JT Jr, et al.: Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am. J. Cardiol. 1987 Feb 1; 59(4): 256–262. Publisher Full Text\n\nChen WL, Chen JH, Huang CC, et al.: Heart rate variability measures as predictors of in-hospital mortality in ED patients with sepsis. Am. J. Emerg. Med. 2008 May 1; 26(4): 395–401. PubMed Abstract | Publisher Full Text\n\nKarmali SN, Sciusco A, May SM, et al.: Heart rate variability in critical care medicine: a systematic review. Intensive Care Med. Exp. 2017 Dec; 5(1): 33–35. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPumprla J, Howorka K, Groves D, et al.: Functional assessment of heart rate variability: physiological basis and practical applications. Int. J. Cardiol. 2002 Jul 1; 84(1): 1–4. PubMed Abstract | Publisher Full Text\n\nMazzeo AT, La Monaca E, Di Leo R, et al.: Heart rate variability: a diagnostic and prognostic tool in anesthesia and intensive care. Acta Anaesthesiol. Scand. 2011 Aug; 55(7): 797–811. PubMed Abstract | Publisher Full Text\n\nMarsillio LE, Manghi T, Carroll MS, et al.: Heart rate variability as a marker of recovery from critical illness in children. PLoS One. 2019; 14(5): e0215930. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBuchman TG, Stein PK, Goldstein B, et al.: Heart rate variability in critical illness and critical care. Curr. Opin. Crit. Care. 2002; 8(4): 311–315. Publisher Full Text\n\nShaffer F, McCraty R, Zerr CL: A healthy heart is not a metronome: an integrative review of the heart’s anatomy and heart rate variability. Front. Psychol. 2014; 5: 1040. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Castilho FM , Ribeiro AL, da Silva JL , et al.: Heart rate variability as predictor of mortality in sepsis: a prospective cohort study. PLoS One. 2017 Jun 27; 12(6): e0180060. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSalahuddin N, Shafquat A, Marashly Q, et al.: Increases in heart rate variability signal improved outcomes in rapid response team consultations: a cohort study. Cardiol. Res. Pract. 2018 Mar 1; 2018: 1–8. Publisher Full Text\n\nBishop DG, Wise RD, Lee C, et al.: Heart rate variability predicts 30-day all-cause mortality in intensive care units. Southern African J. Anesth. Analg. 2016 Aug 5; 22(4): 125–128. Publisher Full Text\n\nLiu N, Chee ML, Foo MZ, et al.: Heart rate n-variability (HRnV) measures for prediction of mortality in sepsis patients presenting at the emergency department. PLos One. 2021 Aug 30; 16(8): e0249868. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaheshwari A, Norby FL, Soliman EZ, et al.: Low heart rate variability in a 2-minute electrocardiogram recording is associated with an increased risk of sudden cardiac death in the general population: the atherosclerosis risk in communities study. PLoS One. 2016 Aug 23; 11(8): e0161648. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGraff B, Gasecki D, Rojek A, et al.: Heart rate variability and functional outcome in ischemic stroke: a multiparameter approach. J. Hypertens. 2013 Aug 1; 31(8): 1629–1636. Publisher Full Text\n\nHadase M, Azuma A, Zen K, et al.: Very low frequency power of heart rate variability is a powerful predictor of clinical prognosis in patients with congestive heart failure. Circ. J. 2004; 68(4): 343–347. PubMed Abstract | Publisher Full Text\n\nOng ME, Lee Ng CH, Goh K, et al.: Prediction of cardiac arrest in critically ill patients presenting to the emergency department using a machine learning score incorporating heart rate variability compared with the modified early warning score. Critical Care. 2012 Jun; 16(3): R108. Publisher Full Text\n\nTakase B, Kurita A, Noritake M, et al.: Heart rate variability in patients with diabetes mellitus, ischemic heart disease, and congestive heart failure. J. Electrocardiol. 1992; 25(2): 79–88. Publisher Full Text\n\nKakde YK: Heart rate variability as a prognostic marker in critically ill patients. [Dataset]. 2023. Publisher Full Text"
}
|
[
{
"id": "196956",
"date": "20 Sep 2023",
"name": "Kishore K. Deepak",
"expertise": [
"Reviewer Expertise Autonomic function testing HRV"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGrammar, throughout the article, e.g. last line in Procedure, the paragraph starting with Holter Machine. The whole paper requires re-writing.\n\nThe authors should have depicted total power.\n\nJustify the use of \"125 Hertz (Hz) are the source of HRV data.\" Current recommendation for HRV is at least 500 Hz or more. (See Task Force paper 1996).\n\nJustify the statement \"Several more adult studies have demonstrated that decreases in HRV are correlated with clinical outcomes and precede clinical decline.11\". You have cited only one paper.\n\nPoor HRV analysis detail.\n\nThe authors need to discuss how ventilator support influenced the results (48 patients were on a ventilator. The ventilatory frequency will certainly affect HRV).\n\nThe blood pressure measurement protocol is not clear.\n\nThe normal range of LF/HF is reported as 4.61. It is not clear how the authors got it; they need to justify.\n\nSurprisingly the weight is not reported. Looking at the data at Zenodo papers, the patients were obese or on the higher side.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "226063",
"date": "04 Dec 2023",
"name": "Eitaro Kodani",
"expertise": [
"Reviewer Expertise Atrial fibrillation",
"anticoagulation"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript by Kakde et al. focused on the association between heart rate variability (HRV) and mortality in critically ill patients admitted to intensive care unit (ICU). Authors evaluated several parameters of HRV and compared them between survivors and dead patients. Then, authors demonstrated that APACHE 4 score, age, and LF were independently associated with mortality. As authors mentioned, several parameters of HRV are reportedly associated with disease outcomes and patient prognosis. Therefore, the concept of this manuscript to clarify these issues is valuable and the contents seem reasonable. Although this manuscript seems written well, authors may want to resolve several issues as follows.\nMajor comments:\nAlthough authors described that Glasgow coma scale (GCS) score was independently associated with mortality, GCS was not significant in Table 9. Therefore, your interpretation of the present results seems inappropriate.\n\nIn Table 9, coefficient should be calculated for mortality (not for survival). In addition, logistic regression analysis with the results expressed by odds ratios seems better to be adopted.\n\nExplain about APACHE4 score briefly.\n\nMinor comments:\nIn abstract, once heart rate variability was abbreviated to HRV, use it throughout the abstract. What is AVBRH?\n\nOnce abbreviations of ANS and HRV were defined, use them throughout the manuscript.\n\nIn Table 1, the name of 3 groups should be described.\n\nIn Table 6, is there any difference between “non-survived” in this table and “death” in other tables? Unify these descriptions. Then, p-value of >0.832 is inappropriate.\n\nIt should be clarified how authors dealt with patients with atrial fibrillation.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "226056",
"date": "05 Sep 2024",
"name": "Ali R Mani",
"expertise": [
"Reviewer Expertise Network physiology",
"Computational physiology",
"Sepsis",
"Heart rate variability analysis"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors examined the relationship between classical linear HRV indices and outcomes in 225 critically ill patients admitted to the ICU. The results indicated that the low-frequency HRV index can predict mortality in this patient population. The study aligns with previous reports on the relationship between reduced HRV and mortality in critically ill patients. My overall assessment of this manuscript is that it does not investigate any novel ideas. It is not clear what the main question of this study is in comparison with previous reports. It is also unclear what aspect of this study is going to help researchers in the field fill the gap in knowledge about the relationship between HRV and mortality in the ICU. There are even well-conducted systematic reviews and meta-analyses on this topic (e.g., please see doi: 10.1371/journal.pone.0203487). In addition to this general comment, I have the following queries/suggestions, and I hope these comments will help the authors in their future research:\n1. Abstract: The definition of HRV is not precise. The authors stated that \"Heart rate variability is termed as fluctuation in the time interval between adjacent heartbeats.\" This only refers to short-term HRV. Many important HRV indices rely on the long-term trend of changes in inter-beat intervals and not only the difference between adjacent heartbeats. This is particularly important as the authors used 24-hour Holter monitoring and were able to examine ultralow HRV indices. In the results section of the abstract, it is not clear what the authors mean when they say \"the variable.\" The conclusion section is more suitable as part of the results section. 2. Introduction: After providing background information and citing previous reports, it is expected to discuss the gap in knowledge and the research questions/objectives. It is not clear what aspect of this study is novel. 3. Method: I suggest addressing the following queries: A. Please justify why 24 hours recording is used. Many HRV indices such as LF and HF, used in this study, can be calculated using a 10-minute recording. B. Sample size calculation is not clear. Where did the expected values of Specificity of Low frequency of HRV = 0.61, Prevalence of positive character (Prev) = 0.128, and Estimation error = 7% come from? C. It appears that data were collected from December 2020 until November 2022, during the COVID-19 pandemic. The expectation is to have many patients with COVID-19 in the ICU. However, nothing is mentioned about the number of included patients with COVID-19. D. It is not justified why patients who were on any sedative medications, in a drowsy state, or disoriented at the time of admission were excluded. Most patients in the ICU have delirium or are on multiple medications such as sedatives. Please justify why this large group of patients is sedated. This may cause bias and limit the generalizability of these results to a typical ICU patient. E. The SOFA score is commonly used in the ICU. Please justify why it is not considered as a covariate in this study. F. I recommend using multivariate Cox regression analysis for statistical analysis. The time-to-event analysis and the independence of covariates such as APACHE or SOFA score and HRV is important, and it can be assessed using multivariate Cox regression methods. G. It is not clear why non-linear indices of HRV are not used in this study.\nResults: A. It is mentioned that the ROC curve is used to find the cut-off value for the estimation of sensitivity and specificity. However, details of the ROC curve, such as the Area Under the Curve (AUC) and its p-value, are not mentioned. This information is important for the assessment and interpretation of data. B. Out of 1640 patients, only 225 were included in this study. The authors need to discuss the chance of bias or re-evaluate their inclusion/exclusion criteria. C. Mortality seems to be the main outcome in this study. However, it is not known in which time frame mortality is assessed. Most studies on critically ill patients use 28-day mortality as the main outcome. It would be difficult to compare the effect of HRV on the survival of patients who died 1 week after admission with another group of patients who died 2 months later. I suggest providing more clarification on the time-frame used for assessing mortality. D. It is not clear where the data from the age/gender-matched control (healthy) group in Table 3 came from. Discussion: The discussion needs to be more comprehensive, with a focus on the novel aspects and limitations of this study.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-673
|
https://f1000research.com/articles/12-672/v1
|
14 Jun 23
|
{
"type": "Research Article",
"title": "Comparative evaluation of the forces produced by tongue on circummaxillary sutures in skeletal Class III malocclusion with maxillary hypoplasia using tongue crib with that of facemask therapy - A FEM study",
"authors": [
"Jeni Ann Mathew",
"Ranjit H Kamble",
"Sunita Shrivastav",
"Pallavi S Daigavane",
"Ranjit H Kamble",
"Sunita Shrivastav",
"Pallavi S Daigavane"
],
"abstract": "Background: Class III malocclusion has the lowest incidence when compared to other malocclusions. Class III malocclusion can be present in retrognathic maxilla, prognathic mandible or a combination. Various modalities have been used in treatment. Facemask with expansion is an effective appliance used for protraction in case of retrognathic mandible; although it is effective, dentists have to deal with patient compliance. Efforts have been directed to simplify the design of appliance to redirect growth. The finite element method can be used to simulate conditions to check various hypothesis. Methods: A finite element method (FEM) study was performed in two important steps: generation of model and model analysis. A tongue force of 4-6 pounds was applied to cribs (Group I) based on the frequency of swallowing per day (minimum to maximum). In facemask therapy (Group II), a downward force at 30 degrees along with transverse expansion of 1N was applied. Mean values of both sides were considered. Results: Von-Mises stresses in Group I and Group II showed a non-significant difference (p=0.535). Displacement in Group I and Group II showed a significant difference (p=0.0001). Maximum amount of displacement was seen in maxillary dentition on canines and incisors, and minimum stress was seen on posterior teeth in both interventional therapies, even though the Von-Mises stresses generated were different in both groups. Overall displacement in both Group I and Group II was similar. Conclusions: Both modalities were effective in the treatment of Class III malocclusion. The force transmission varied and overall displacement was similar in both modalities, which implies both modalities are effective in treating Class III malocclusion.",
"keywords": [
"Class III malocclusion",
"Finite element method",
"Nasomaxillary complex",
"Tongue crib",
"Facemask",
"force",
"Von-Mises stresses",
"displacement"
],
"content": "Introduction\n\nSkeletal and dental anomalies have been mentioned in the literature as early as the 18th century when Bourdet had noticed protruding chin in children. In the 19th century, Delbarre termed this condition as edge to edge or under-bite.1,2 Across the world, Class III malocclusion has the lowest frequency among malocclusions. The incidence of Class III malocclusion is 5.93%, and its prevalence in permanent dentition is greater than mixed dentition. Its prevalence was 1.19% when the prevalence in the Indian population was validated against the world population.3\n\nIt is recognized among the public and dental professionals that early treatment is crucial. The time for intervention may vary from prepubertal to pubertal phase. Treatment approaches vary from orthopaedics in the earlier phase, to orthodontic intervention to combined orthodontic and orthognathic management in later phases. Treatment appliances range from protraction facemask, Class III Bionator, Frankel’s FR-III appliance, comprehensive orthodontic treatment using Class III biomechanics, orthognathic surgery, among others. After growth completion, surgery is the best option to correct Class III malocclusion.4\n\nClass III malocclusion has a greater genetic predisposition; for controlling expression, it needs intervention at an early age. Class III malocclusion needs a longer retention period as it has a greater chance of relapse as mandibular growth continues till later ages. Not only are the treatment appliances bulky and complex, but so is the retention appliance. Hence there is a need to develop a simpler appliance.\n\nThe finite element method (FEM) is a modality where simulations are used to study impact. Forces on biological structures like bone and soft tissue can also be evaluated. In FEM, mathematical calculations are inbuilt into software to simplify calculations while doing the analysis. FEM has been used in various orthodontic studies.5,6 Forces exerted on the craniofacial complex can be studied by simulation analysis like the finite element analysis.\n\nThe aim of our study was to compare and evaluate the effect of forces produced by the tongue on circummaxillary sutures in skeletal Class III malocclusion with maxillary hypoplasia using a tongue crib (Group I), with that of facemask therapy with expansion (Group II) using FEM. The objectives of our study were to evaluate stress and displacement patterns in Group I and Group II and compare them.7\n\n\nMethods\n\nThe present study was carried out in the Department of Orthodontics and Dentofacial Orthopaedics, Sharad Pawar Dental College, Datta Meghe Instiute of Medical Sciences, Wardha, Maharashtra. The study was approved from the ethical committee of Datta Meghe Institute of Medical Sciences. Ref No-DMIMS (DU)/IEC/2020-21/9401.\n\nThree-dimensional finite element model of skull with circummaxillary suture and teeth, periodontal ligament and bone of maxilla was built. Tongue crib and facemask therapy with expansion were modelled and forces were incorporated in the model. Simulations were run to analyze stress exerted and displacement produced. Finite element modelling and analysis was performed at DICUL AM Private Limited, Nagpur. The computational devices used for this study included a PC workstation having a AMDRyzen 7 2700X Eight-Core Processor with 32GB RAM 1 TB secondary storage graphics accelerator. The operating system used for this study was Windows 10. Initial modelling was done using the Dassault Systèmes 3D Experience Platform software.\n\nThe study was performed in two stages:\n\nI - Generation of model\n\nII - Model analysis\n\n\n\n1. Geometric model construction: According to the measurements and morphology of a dried model of human skull, an analytical model of the human skull was created for this investigation.\n\n2. Geometric model conversion to a finite element model was done: The Geometric Model (x_t) Parasolid extension file was converted to a.stl extension file for the analysis. The Dassault Système’s 3D experience platform (Digitized shape to preparation) was used to generate the finite element model. The solid tetrahedral element shape with 6 degrees of freedom that the model specified. Through a process known as meshing, these elements were joined to nearby elements with the aid of triangles using Dassault Système’s: Structural Model Creation. Our model had 11,119,347 elements and 248,464 nodes.\n\n3. Assignment of material property data: Material property was assigned to structure. The skull finite element model consisted of circummaxillary suture and bone. The material properties of structures were assigned on the basis of values quoted in the literature in Table 1.\n\n4. Boundary condition definition: The engineer validated the final model. Important elements of FEM are the nature of modelling and accuracy depend upon modelling and the number of elements used.\n\nThe model of the skull comprised circummaxillary suture, maxillary teeth and bone. The model was analyzed.\n\nApplication of force\n\nThe efficacy of two modalities were compared in our study:\n\nGroup I - Tongue crib\n\nGroup II - Facemask therapy with expansion\n\nApplication of forces in this study was in conjunction with the range of tongue forces for Class III malocclusion patients during rest and swallowing. Tongue forces applied on cribs based on the frequency of swallowing per day (minimum to maximum) were a frequency of 500 to 1200 times and a pressure of 4-6 pounds per swallow. This intermittent force was transferred through the tongue appliance to the nasomaxillary complex.8 In facemask therapy, the force exerted ranged from 180 to 800 g per side and was angulated from 20 and 30 degree to occlusal plane and ranged from 10 to 24 hours of wear per day.9 The criteria followed in our study are depicted in Table 2.\n\nSolution of linear algebraic equation\n\nThe above-mentioned steps were followed sequentially leading to a system of algebraic equation where nodal displacement was not known. The equations were solved by Dassault Système’s Mechanial Scenario Creation and final analysis was done by SIMULIA.\n\n\nResults\n\nThe aim of the present study was to evaluate and compare the stress distribution pattern following tongue forces in antero-posterior direction on the tongue crib placed on the anterior region, and facemask with expansion to quantify the stresses and deformation produced at the circummaxillary sutures and the maxillary dentition using FEM.\n\nVon-Mises stresses were seen in all the circummaxillary sutures and maxillary dentition and compared as represented graphically in Figure 1. Amongst circummaxillary sutures in tongue crib therapy, maximum stress was seen in mid-palatine suture (11.55) and minimum in zygomatico-frontal suture (0.5715). Amongst circummaxillary sutures in facemask therapy with expansion, maximum stress was seen in transverse-palatine suture (8.93) and minimum in zygomatico-temporal suture (0.224). Maximum amount of Von-Mises stresses was seen in maxillary dentition at canines, incisors, and minimum stress was seen on posterior teeth in both interventional therapies. Von-Mises stresses in tongue forces applied on the tongue crib appliance and facemask therapy with expansion showed non-significant differences (p=0.535).\n\nDisplacement was seen in all the circummaxillary sutures and maxillary dentition and compared as represented graphically in Figure 2. Amongst circummaxillary sutures in tongue crib therapy, maximum displacement was seen in inter-maxillary suture (0.00116) and minimum in pterygomaxillary suture (0.000316). Amongst circummaxillary sutures in facemask therapy with expansion, maximum displacement was seen in mid-palatine suture (0.0003725) and minimum in zygomatico-frontal suture (0.00005895). Displacement in tongue forces applied on the tongue crib appliance in second rugae area and facemask therapy with expansion was significant (p=0.0001).\n\nMaximum amount of displacement was seen in maxillary dentition at canine, incisors and minimum stress was seen on posterior teeth in both interventional therapies as depicted in Figures 3 and 4 and Table 3. Von-Mises stresses generated were different in both groups. Overall displacement in both Group I and Group II was similar.\n\n\nDiscussion\n\nIn the literature, the timing of functional treatment in orthodontics in various malocclusion has been discussed. There have been various studies assessing treatment during mixed and permanent dentition. However,most of the clinicians prefer intervening during the pubertal growth period rather than post-pubertal period.10 Various modalities are used in the correction of Class III malocclusion; appliances used in clinical practice include facemask, protraction with RME, chin cup, Class III Bionator, fixed orthodontics with Class III elastics, etc. After growth completion, orthognathic surgery is the last alternative.11\n\nThough it has been found that facemask with expansion is an effective modality in Class III malocclusion, appliance bulk affects compliance among the subjects treated. Studies done by Jamilian and Showkatbaksh showed that forces exerted by the tongue through tongue crib had a considerable effect on the maxillary dentition and circummaxillary sutures. In our study, Von-Mises stresses seen on the maxillary dentition were greater as compared to stresses seen on circummaxillary sutures. Our study’s findings were supported by those of Jamilian and Showkatbaksh, who claimed that tongue crib appliances harnessed tongue forces—intermittent and continuous tongue resting forces—to push the maxilla forward. Tongue forces are efficient in skeletal Class III patients with retrusive maxilla to correct the maxilla in the antero-posterior plane as well as generate a downward movement of the maxilla in the vertical plane.8,12\n\nAhrari treated Class III malocclusion with a retrusive maxilla. Tongue appliance to correct deficient maxilla was the intervention used in transmission of force exerted by tongue through tongue crib to protract the maxilla. Positive overjet was attained at the conclusion of the procedure. It was found that tongue crib was an effective treatment modality in Class III malocclusion. The author claimed that tongue crib appliance in a Class III patient causes the maxilla to shift forward and lower, as shown by a rise in SNA (the angle between the sella/nasion plane and the nasion/A plane) and N-A-Pog (Angle of convexity). Tongue crib appliance is efficient in treating protraction of deficient maxilla in Class III cases that are mild to moderate. In Class III patients, tongue guard appliance is an effective substitute for face mask therapy.13\n\nBy using X-ray cephalometric analysis, Zhao assessed the effectiveness of the tongue crib treatment in the correction of severe skeletal Angle Class III malocclusion in mixed dentition. Every patient received a good facial profile. The relationships between the upper and lower first molars as well as the anterior and posterior crossbite were improved. The maxillary skeletal component had considerable modifications as measured by cephalometry. By promoting maxillary growth and regulating mandibular growth, the tongue crib combo is a useful tool for patients with skeletal Angle Class III malocclusion who are still growing.14\n\nThe difference amongst the modalities was direction of the exertion of force. The force exerted by the tongue through the tongue crib was push force. Facemask therapy with expansion exerted pull force. Both modalities were effective in the treatment of Class III malocclusion. The force transmission varied and Von-Mises stresses and displacement were different at various sutures, but overall displacement was similiar in both modalities.13\n\nThe following conclusions were drawn from the study: Circummaxillary suture responded in different ways when push force was exerted by tongue crib and pull force was exerted by facemask therapy with expansion.\n\n1. When the tongue is positioned in the second rugae area, forces are applied that cause Von-Mises stress in the maxillary dentition and circummaxillary sutures. Amongst circummaxillary sutures in tongue crib therapy, maximum stress was seen in mid-palatine suture and minimum in zygomatico-temporal suture. The effect was substantial in the dentition. Tongue crib therapy exerted push force, maximum displacement was seen in inter-maxillary suture and minimum displacement in pterygomaxillary suture.\n\n2. In contrast, in facemask therapy with expansion, pull force was exerted amongst circummaxillary sutures in facemask therapy with expansion; maximum stress was seen in transverse-palatine suture and minimum in zygomatico-temporal suture. Maximum displacement was seen in mid-palatine suture and minimum in zygomatico-frontal suture. When facemask therapy with expansion was simulated in the model, the effect was substantial in the sutures. When facemask therapy with expansion was used, it caused more displacement on circummaxillary sutures than dentition, whereas in tongue crib therapy more displacement was seen in dentition.\n\n3. Overall displacement was similar in both tongue crib and facemask therapy with expansion in response to stress generated.\n\nSimulation studies like finite element studies are effective in testing the effectiveness of treatment modalities, but clinical trials aid in understanding the stability of the results, which is not possible in finite element studies.\n\nFEM can serve as a foundation for evaluating and comparing the biomechanical efficiency of modalities. The study serves as a theoretical basis for understanding the efficiency of tongue crib. The simplification of appliance design in dentofacial orthopaedics would encourage cooperation from patients. The use of tongue crib in mild to moderate skeletal Class III cases would encourage correction amongst children. It would decrease the length of orthodontic treatment and the probability of surgical intervention later.\n\n\n\n1. FEM can serve as a foundation for evaluating and comparing the efficiency of modalities and comparison. Patients should be included as study subjects in further investigations to determine the movements in all three planes and evaluate the efficiency of modalities.\n\n2. It would be beneficial to compare Class III and Class I with anterior open bite groups, since this would help us understand the differences in morphology in all three planes.\n\n3. To learn more about the intricate function of the tongue and tongue crib device in dentofacial morphology, further clinical research is indicated.\n\nThe study was approved from the ethical committee of Datta Meghe Institute of Medical Sciences. Ref No-DMIMS (DU)/IEC/2020-21/9401.",
"appendix": "Data availability\n\nZenodo: Comparative evaluation of the forces produced by tongue on circummaxillary sutures in skeletal Class III malocclusion with maxillary hypoplasia using tongue crib with that of facemask therapy - A FEM study, https://doi.org/10.5281/zenodo.7840856 . 15\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nSanborn RT: Differences between the facial skeletal patterns of Class III malocclusion and normal occlusion. Angle Orthod. 1955 Oct; 25(4): 208–222.\n\nAngle EH: Classification of malocclusion. Dent. Cosmos. 1899; 41: 350–375.\n\nEllis E III, McNamara JA Jr: Components of adult Class III malocclusion. J. Oral Maxillofac. Surg. 1984 May 1; 42(5): 295–305. Publisher Full Text\n\nProffit WR, Fields HW: Contemporary Orthodontics. 4th ed.St. Louis: Mosby; 2007.\n\nSung SJ, Baik HS, Moon YS, et al.: A comparative evaluation of different compensating curves in the lingual and labial techniques using 3D FEM. Am. J. Orthod. Dentofac. Orthop. 2003 Apr 1; 123(4): 441–450. PubMed Abstract | Publisher Full Text\n\nMao JJ, Wang X, Kopher RA: Biomechanics of craniofacial sutures: orthopedic implications. Angle Orthod. 2003 Apr; 73(2): 128–135. PubMed Abstract\n\nMathew JA, Kamble RH, Shrivastava SS, et al.: Comparative Evaluation of the Forces Produced by Tongue on Circummaxillary Sutures in Skeletal Class-III Malocclusion with Maxillary Hypoplasia Using Tongue Crib with that of Facemask Therapy: A FEM Study. J. Pharm. Res. Int. 2021; 33(61B): 125–129. Publisher Full Text\n\nJamilian A, Showkatbakhsh R, Boushehry MB: The effect of tongue appliance on the nasomaxillary complex in growing cleft lip and palate patients. J. Indian Soc. Pedod. Prev. Dent. 2006 Jul 1; 24(3): 136–139. PubMed Abstract | Publisher Full Text\n\nYepes E, Quintero P, Rueda ZV, et al.: Optimal force for maxillary protraction facemask therapy in the early treatment of class III malocclusion. Eur. J. Orthod. 2014 Oct 1; 36(5): 586–594. PubMed Abstract | Publisher Full Text\n\nPerinetti G, Franchi L, Contardo L: Determination of timing of functional and interceptive orthodontic treatment: A critical approach to growth indicators. J. World Fed. Orthod. 2017 Sep 1; 6(3): 93–97. Publisher Full Text\n\nZere E, Chaudhari PK, Sharan J, et al.: Developing Class III malocclusions: challenges and solutions. Clin. Cosmet. Investig. Dent. 2018; 10: 99–116. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJamilian A, Showkatbakhsh R: The effect of tongue appliance on the maxilla in Class III malocclusion due to maxillary deficiency. Int. J. Orthod. Milwaukee. 2009 Jan 1; 20(3): 11–14. PubMed Abstract\n\nAhrari F, Eslami N: Nonsurgical treatment of maxillary deficiency using tongue guard appliance: a case report. J. Dent. Res. Dent. Clin. Dent. Prospects. 2011; 5(4): 136–140. PubMed Abstract\n\nZhao W, Chen Y, Kyung HM, et al.: Effectiveness of Tongue Crib Combination Treating Severe Skeletal Angle Class III Malocclusion in Mixed Dentition. Int. J. Clin. Pediatr. Dent. 2020 Nov; 13(6): 668–676. PubMed Abstract | Publisher Full Text\n\nMathew JA: Comparative evaluation of the forces produced by tongue on circummaxillary sutures in skeletal Class III malocclusion with maxillary hypoplasia using tongue crib with that of facemask therapy - A FEM study (Version V1). [Data set]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "181625",
"date": "18 Jul 2023",
"name": "Huang Li",
"expertise": [
"Reviewer Expertise orthodontic"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n\"The aim of our study was to compare and evaluate the effect of forces produced by the tongue on circummaxillary sutures in skeletal Class III malocclusion with maxillary hypoplasia using a tongue crib (Group I), with that of facemask therapy with expansion (Group II) using FEM. The objectives of our study were to evaluate stress and displacement patterns in Group I and Group II and compare them.\" However, the manuscript had some siginificant flaws which cannot be overcome.\n1. Please clarify what kind of patient you chose? Skeletal class III or class I, and what age?\n2. \"Tongue forces applied on cribs based on the frequency of swallowing per day (minimum to maximum) were a frequency of 500 to 1200 times and a pressure of 4-6 pounds per swallow. This intermittent force was transferred through the tongue appliance to the nasomaxillary complex. In facemask therapy, the force exerted ranged from 180 to 800 g per side and was angulated from 20 and 30 degree to occlusal plane and ranged from 10 to 24 hours of wear per day.\" It is not clear how the authors established this model? How much force exactly were on maxilla in FEM study? It is very important what direction the force was on the maxilla. I do not think the intermittent force can transfer on the maxilla. Based on this information, the result from this FEM study was not reliable.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "206010",
"date": "28 Sep 2023",
"name": "Cinzia Maspero",
"expertise": [
"Reviewer Expertise Orthodontics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn general, the idea of this study regarding the analysis of the finite element method performed in two generations of model and model analysis is interesting. The aim of this study was to compare and evaluate the effect of forces produced by the tongue on circummaxillary sutures in skeletal Class III malocclusion with maxillary hypoplasia using a tongue crib (Group I), with that of facemask therapy with expansion (Group II) using FEM. The objectives of this study were to evaluate stress and displacement patterns in Group I and Group II and compare them.\nThe role of these aspects in medicine needs further studies that could open a creative matter of debate in literature by adding new information.\nEthical committee approval was obtained.\nThe study was well conducted by the authors; however, there are some concerns to revise that are described below:\nBetter to formulate the abstract section by better describing the aim of the study.\n\nThe introduction section resumes the existing knowledge regarding this topic but authors should better specify, at the end of the introduction section, the rationale of the study.\n\nIn the central section, the authors should better clarify the inclusion and exclusion criteria of the selected sample.\n\nThe discussion section appears well organized. Please add a specific sentence that clarifies the results obtained in the first part of the discussion.\n\nThe conclusion should be reinforced in light of the discussions.\n\nAdd the strengths of the study.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "196202",
"date": "28 Sep 2023",
"name": "Tarulatha R. Shyagali",
"expertise": [
"Reviewer Expertise Orthodontics and Dentofacial Orthopedics"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article seems to be novel as none of the previous FEM studies have compared the effect of the tongue pressure on the forward movement of maxilla in class III malocclusion cases. Although the effect of tongue pressure on the suture is negligible but it is effective in correcting mild class III malocclusions.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-672
|
https://f1000research.com/articles/8-1441/v1
|
15 Aug 19
|
{
"type": "Research Article",
"title": "Willingness-to-pay for a hypothetical Ebola vaccine in Indonesia: A cross-sectional study in Aceh",
"authors": [
"Mudatsir Mudatsir",
"Samsul Anwar",
"Jonny Karunia Fajar",
"Amanda Yufika",
"Muhammad N. Ferdian",
"Salwiyadi Salwiyadi",
"Aga S. Imanda",
"Roully Azhars",
"Darul Ilham",
"Arya U. Timur",
"Juwita Sahputri",
"Ricky Yordani",
"Setia Pramana",
"Yogambigai Rajamoorthy",
"Abram L. Wagner",
"Kurnia F. Jamil",
"Harapan Harapan",
"Samsul Anwar",
"Jonny Karunia Fajar",
"Amanda Yufika",
"Muhammad N. Ferdian",
"Salwiyadi Salwiyadi",
"Aga S. Imanda",
"Roully Azhars",
"Darul Ilham",
"Arya U. Timur",
"Juwita Sahputri",
"Ricky Yordani",
"Setia Pramana",
"Yogambigai Rajamoorthy",
"Abram L. Wagner",
"Kurnia F. Jamil"
],
"abstract": "Background: Some Ebola vaccines have been developed and tested in phase III clinical trials. However, assessment of whether public have willingness to purchase or not, especially in unaffected areas, is lacking. The aim of this study was to determine willingness to pay (WTP) for a hypothetical Ebola vaccine in Indonesia. Methods: A cross-sectional study was conducted from 1 August to 30 December 2015 in five cities in Aceh province of Indonesia. Patients’ family members who visited outpatient departments were approached and interviewed about their sociodemographic characteristics, knowledge of Ebola, attitude towards vaccination practice and their WTP for a hypothetical Ebola vaccine. A multivariable linear regression model assessed the relationship between these explanatory variables and WTP. Results: During the study, 500 participants were approached and interviewed. There were 424 (84.8%) respondents who completed the interview and 74% (311/424) expressed their acceptance for an Ebola vaccine. There were 288 participants who were willing to pay for an Ebola vaccine (92.6% out of 311). The mean of WTP was US$2.08 (95% CI: 1.75-2.42). The final multivariable model indicated that young age, high educational attainment, working as a private employee, entrepreneur or civil servant (compared to farmers), being unmarried, and residing in a suburb (compared to a city) were associated with higher WTP. Conclusions: Although the proportion of the participants who would accept the Ebola vaccine was relatively high, the amount they were willing to pay for Ebola vaccine was very low. This finding would indicate the need of subsidies for Ebola vaccine in the country.",
"keywords": [
"Ebola vaccine",
"Ebola virus disease",
"Indonesia",
"vaccine acceptance",
"willingness-to-pay"
],
"content": "Introduction\n\nEbola virus disease (EVD), formerly called as Ebola hemorrhagic fever, is a disease characterized by high mortality in human populations1. EVD is caused by Ebola virus (EBOV) which is an enveloped, filamentous, and non-segmented negative-strand RNA virus2. EBOV first emerged in tropical areas of Africa – in the countries now known as the Democratic Republic of the Congo and South Sudan – in 1976, and was recognized as a new viral hemorrhagic fever3. Since then, EVD outbreaks have been reported intermittently. Recently there was an outbreak of almost 28,610 cases and 11,308 deaths, mostly affecting West Africa, but also spreading to Europe, North America, and Asia4,5. In Asia, EVD cases were reported in the Philippines6. Although no cases have yet been reported in Indonesia, many travelers pass through the country. Since 2017, several outbreaks of EVD have impacted the Democratic Republic of the Congo, with over 2,000 reported cases as of June 20197.\n\nEVD is a highly fatal disease and can be economically burdensome in affected countries. The case fatality rate of EVD ranges from 25% to 100%, with an average of approximately 68%8,9. The highest rates of mortality are in infants and children10. It is estimated that between $2.8 and $32.6 billion was spent to control the EVD outbreaks of 2014–201611. Accordingly, the World Health Organization (WHO) declared EVD outbreak as a Public Health Emergency of International Concern with severe global economic burden in August 201412. There is no specific treatment for EVD beyond supportive care.\n\nDevelopment of a safe and effective Ebola vaccine is a key component to future programs to control EVD13. Several vaccines have been developed and tested in phase III clinical trials, such as rVSV-EBOV and the combination of Ad26-ZEBOV and MVA-BN Filo14. The trials demonstrated that these vaccines have good effectiveness and provide robust protection against EVD; no EVD case have been reported among vaccinated individuals14. Vaccine development will be beneficial for people living in West Africa and other regions affected by Ebola outbreaks. The vaccine has had some use in the current outbreaks in the Democratic Republic of the Congo15. However, the problem with any new vaccine, particularly vaccines that require payment, is the public response, and whether members of the general population are willing to purchase the vaccine. A previous study reported high willlingness to pay (WTP) for an Ebola vaccine in West Africa16. However, in areas not yet affected, the results might differ because community members might lower perceptions of risk. This present study therefore aimed to investigate community WTP for Ebola vaccine in Indonesia, a currently unaffected EVD country.\n\n\nMethods\n\nApproximately 16 months after the Ministry of Health of the Republic of Indonesia raised an alert for EVD in Indonesia, a cross-sectional study was conducted to assess acceptance and WTP for a hypothetical Ebola vaccine among family members of patients with any illness admitted to eight health facilities (hospitals or Community Health Centres [Puskesmas]) in four regencies (Nagan Raya, Aceh Selatan, Langsa and Banda Aceh) of Aceh province from 1 August to 30 December 2015. The study was conducted in. Aceh is located in the westernmost part of the Indonesian archipelago with a total population approximately 4,906,800 in 201417.\n\nStudy participants were patients’ family members who visited infection and non-infection outpatient departments. Based on the population size of Aceh in 2014, the minimum sample size required was 38518. To recruit the samples, four regencies were selected randomly, and both urban and suburban areas were included. The number of participants from each study site was gathered proportionally to the size of regency’s population. To avoid repetitive field visits and to minimize the study design effect, the number of participants was increased for each study site. Family members who had resided in the specified regency for more than 3 months, were ≥17 years old, and were able to communicate in Bahasa Indonesia (the national language) were considered to be eligible for inclusion.\n\nTo facilitate the interviews a set of a structured questionnaire, adapted from previous studies19,20, was used. Prior to use in the actual study, a pilot study was conducted to measure reliability of questionnaires among 25 participants in Lhokseumawe regency. For this pilot study, a Cronbach’s alpha score of ≥0.7 was considered good internal consistency. Edits were made to the questionnaire based on findings from the pilot study; the questionnaire is available in Indonesian and English as Extended data21.\n\nResponse variable. The response variable was WTP for a hypothetical Ebola vaccine. Prior to assessing their WTP, participants were provided with an introduction to the Ebola disease including the symptoms and modes of transmission. They were also informed of the following points: (a) infected patients need to be isolated and health care workers need to use special protection equipment while providing healthcare to the patients; (b) currently there is no available treatment for EVD; (c) the mortality rate of EVD is up to 90%; and (d) an Ebola vaccine would be safe and protective against EVD.\n\nTo assess the amount of money that participants would be willing to pay for a hypothetical Ebola vaccine, participants were asked whether they would be willing to pay for the vaccine using a list of Ebola vaccine prices: Indonesian Rupiah (IDR) 5.000, 10,000, 17.500, 37.500, 87.500, 150.000, and 300.000 (equivalent to US$ 0.37, 1.29, 2.78, 4.63, 6.48, 11.12, and 22.24). The possible responses were “very likely”, “likely”, “undecided”, “unlikely” or “very unlikely”. The WTP was defined as the highest price the participants said they were still “very likely” or “likely” willing to pay.\n\nExplanatory variables. Sociodemographic data: Sociodemographic factors such as age, gender, educational attainment, type of occupation, marital status, monthly income and urbanicity were collected from participants. The date of birth was recorded, converted into actual age and then collapsed into three groups. Educational attainment, defined as the highest level of formal education completed by respondents, was grouped into: (a) less than junior high school (year 9); (b) senior high school (year 12); (c) diploma certificate; and (d) university graduate. Participants were grouped into five types of occupation: (a) farmer; (b) private sector employee; (c) housewife; (d) entrepreneur (owned a small-scale business, or traders in a market); and (e) civil servant. Monthly income was grouped into: (a) less than 1 million Indonesian Rupiah (IDR) (equivalent to US$ 74.1); (b) 1 –2 million IDR (equivalent to US$ 74.1 - US$ 148.2); and (c) more than 2 million IDR (equivalent to US$ 148.2). Urbanicity included cities and suburbs.\n\nSocioeconomic status (SES): SES was assessed based on 15 household assets owned by participants such as radio, landline phone, refrigerator, motorcycles, car, other electronics and house characteristics. Details of the full list of the household assets have been published previously20,22. The ownership of those assets was used to construct an asset index based on principal component analysis23. SES classified into three tertiles, with the 1st tertile the poorest and the 3rd tertile the wealthiest.\n\nAttitude towards vaccination practice: To measure attitude towards vaccination practice, five questions adopted from a previous study20 was used. The questions included the attitude towards the safety and importance of vaccines, and previous experiences regarding vaccination practices. Participants responded to each statement on a five-point Likert-like scale ranging from “1=strongly disagree” to “5=strongly agree” with a higher score indicating a more positive attitude. The summed scores for this domain ranged from 5 to 25. Participants were classified as having a ”good” or ”poor” attitude based on a 75% cut-off point of the maximum score achieved by participants.\n\nKnowledge regarding Ebola: To assess knowledge regarding Ebola, a set of six questions on transmission and prevention methods of EVD, adapted from a previous study19, was used. Each valid response was given a score of one, whereas an incorrect response was given a score of zero. The summed scores for this domain ranged from 0 to 6, and knowledge of each participant was also classified into ”good” or ”poor” based on a 75% cut-off point.\n\nTo assess the relationship between explanatory variables and WTP, a multivariable linear regression model was employed24,25. Various diagnostic assessments were used to check how well the data met the assumptions of linear regression. The variance inflation factor (VIF)26, Glejser test27 and Kolmogorov-Smirnov test28 were employed to assess multicollinearity, heteroscedasticity and residual normality of the data, respectively. A VIF value of lower than 10 was used to define no multicollinearity between variables. A P-value greater than 0.05 in the Glejser test, and Kolmogorov-Smirnov test was applied to indicate no heteroscedasticity, and normal distribution of residuals, respectively24.\n\nInitial assessment indicated that the data violated all three assumptions and WTP values were then transformed using a natural logarithm function (Ln). After transformation, data showed better adherence to assumptions and therefore the transformed WTP values were used in linear regression model. In the initial multivariable model, all explanatory variables were included. Then, all explanatory variables that had P > 0.25 in this model were excluded from final linear regression model. Significance in the final model was assessed at an alpha level of 0.05. All associations between an explanatory factor and WTP were interpreted in relation to a reference category.\n\nBecause the outcome had been log-transformed, the mean estimated WTP in US$ and its 95% CI were calculated as Exp(Xβ^+σ^2/2) where β^ was the estimated regression coefficients (B) and σ^2 was the mean squared error (MSE) of the multivariate model24,29,30. All analyses were performed using SPSS (version 15, Chicago, USA).\n\nThe protocol of this study was approved by Institutional Review Board of the School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia (Approval 315/KE/FK/2015). Prior to enrolment, the aims of the study were explained to the participants and they signed written consent forms. Participation in this study was voluntary and participants received no financial compensation.\n\n\nResults\n\nThe raw data for this study are available as Underlying data on Figshare31.\n\nIn this study, 500 participants were approached, all agreed to participate, but 76 were excluded due to incomplete data. Among those with completed data (424 or 84.8%), approximately 74% (311/424) of participants would accept an Ebola vaccine. There were 288 participants (92.6%, 288/311, of those who would accept an Ebola vaccine, or 67.9%, 288/424, of all participants with completed data), willing to pay for Ebola vaccine. The characteristics of the participants who were willing to pay for Ebola vaccine are presented in Table 1.\n\nCI, confidence interval; IDR, Indonesia rupiah; US$, American dollar; SE, standard error; Ref, reference group.\n\nMore than half (51.0%) of those who willing to pay for the vaccine were aged 30–44 years old, and 52.4% were female. A majority (75.7%) of them had finished their senior high school (year 12) and none of them had no formal education. The most frequent type of occupation was farmer, followed by entrepreneur, housewife, civil servant and private employee. A vast majority (96.5%) of the respondents who willing to pay were married and approximately 44% of the them were living under the poverty line, i.e. <1 million IDR (equivalent to US$74.1). Overall, 52.1% of them had good attitude towards vaccination and almost 70% had poor knowledge about transmission and prevention of EVD.\n\nAmong 288 participants who were willing to pay for Ebola vaccine, 114 (39.6%) of them expressed their WTP at US$ 1.29 and this decreased to 28.1%, 14.6% and 3.1% as the price for Ebola vaccine increased to US$2.78, US$4.63, and US$6.48, respectively (Figure 1). Only 7 out of 288 respondents agreed to pay the highest price (US$22.24). The mean of WTP was US$2.08 (95% CI: 1.75-2.42).\n\nOnly those who were willing to pay for Ebola vaccine were included in this analysis.\n\nThe initial multivariable model showed that age, educational attainment, type of occupation, marital status, type of residence and having good knowledge of Ebola were associated with WTP with a P-value under 0.25. (Table 1). The final multivariable model indicated that age, educational attainment, type of occupation, marital status and urbanicity were significantly associated with WTP (Table 2). Knowledge of Ebola had no association with WTP. Compared to the youngest age group (17–29-year-olds), participants who were between 30–44 years old and those older than 45 years had lower WTP, at approximately US$ 1. Respondents who finished senior high school (year 12) and graduated from university had higher WTP – approximately US$1.7 and US$2.3, respectively, compared to those who had an education less than junior high school (year 9). Compared to farmers, participants who were working as employees in private companies, entrepreneurs and civil servants were willing to pay US$2.6, US$1.8 and US$2.3 more, respectively. In addition, this study found that participants who were married and those who were living in the city had lower WTP compared to unmarried participants and those who were living in the suburbs (Table 2).\n\nCI, confidence interval; IDR, Indonesia rupiah; US$, American dollar; SE, standard error; Ref, reference group.\n\n\nDiscussion\n\nThis study was conducted to assess the WTP for a hypothetical Ebola vaccine and its associated determinants among community members in Aceh province, Indonesia. We found that age, educational attainment, type of occupation, marital status and urbanicity were all associated with WTP. Better understanding of which groups have greater WTP for the vaccine and what this amount would be are important to consider if the vaccine were to be introduced into Indonesia in the future.\n\nAge was related to WTP, with younger participants having higher WTP compared to older participants. This corresponds to another study in Indonesia that also showed older participants had lower WTP for a vaccine compared to their younger counterparts20. In Indonesia, this association could arise for several reasons. First, in general, the older generation tends to have lower education levels. In the context of health-related knowledge and WTP, it has been shown that higher education was associated with better health-related knowledge32,33 and WTP for vaccines against infectious diseases34,35 although some studies found educational attainment had no association or had no consistent association with WTP20,24,36,37. Second, older community members may have had less exposure to information regarding Ebola, resulting in lower knowledge and awareness of the disease. In addition, many older people work as farmers, have less income and therefore are less willing to pay for vaccination. This could also explain why participants who were working in other sectors had higher WTP compared to farmers.\n\nWe also found that participants with higher educational attainment had higher WTP. Higher education level has a positive association with higher WTP in interventions related to infectious diseases34,35. And it could be that education relates to WTP because of knowledge related to Ebola. However, we found no relationship between knowledge and WTP. It is interesting to discuss why knowledge on Ebola was not significantly associated with WTP in this present study, but higher education was. This is understandable since Ebola, as the new re-emerging infectious disease, was not taught in Indonesia’s curriculum. However, education does increase people’s awareness of infectious diseases and vaccination in general38,39. Therefore, even though people do not have much knowledge of Ebola, they still have better awareness of the importance to keep themselves protected from infectious diseases, resulting in higher WTP for vaccination as found in this study. Therefore, it is important for the government to target groups with lower education levels during vaccination campaigns to raise their awareness of a specific disease.\n\nOur study found there was no association between income or SES and WTP. However, previous studies have consistently found that income or economic status is one of the most robust predictors for WTP20,25,34,36,37,40, i.e., individuals with a higher income can afford a more expensive vaccine. However, one previous study found that income could had negative association with WTP in Nigeria41. The diversity of these findings may serve as an indication that socioeconomic variables behave differently across countries. We note that the vaccine prices that were provided in this present study were substantially lower than the WTP of the respondents. Nevertheless, few respondents (less than 3%) were willing to pay for the vaccine at the highest price (US$22.24) indicating that the provided vaccine prices were not significantly lower than participants’ WTP. According to the theory of goods classification in microeconomics, a negative relationship between income and WTP label the products as inferior goods42. This happen when the consumers have low knowledge and awareness of that particular product and leads the low WTP even though very important.\n\nThere are some limitations of this study that need to be discussed. There were no Ebola cases reported in Indonesia and therefore the respondents were provided with brief information related to Ebola infection prior to assess their WTP. Social desirability bias is inevitable in which participants might tend to give favorable answer in some questions given included in WTP section. Finally, a hypothetical bias might exist in which respondents misstate their actual WTP as this study was conducted when no Ebola vaccine had been approved and licensed.\n\n\nConclusions\n\nIn this study, the mean of WTP for a hypothetical Ebola vaccine was US$2.08 (95% CI: 1.75-2.42) and the proportion of respondents who were willing to pay for the vaccine decreased with increase of vaccine price. Younger and unmarried participants, those with higher educational attainment and those who were living in the suburbs had higher WTP. In addition, compared to farmers, private employee, entrepreneurs and civil servants also had higher WTP. Better understanding which groups are more willing to pay for the vaccine and what this amount are important to consider if the vaccine were to be introduced into Indonesia in the future.\n\n\nData availability\n\nFigshare: Willingness-to-pay for a hypothetical Ebola vaccine in Indonesia: A cross-sectional study in Aceh. https://doi.org/10.6084/m9.figshare.925603731.\n\nThis project contains answers given to each question by each participant.\n\nFigshare: Willingness-to-pay for a hypothetical Ebola vaccine in Indonesia: A cross-sectional study in Aceh (Questionnaire). https://doi.org/10.6084/m9.figshare.9293378.v121.\n\nThis project contains the questionnaire in Indonesian (original) and English.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
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}
|
[
{
"id": "52546",
"date": "28 Aug 2019",
"name": "Roger Chun-Man Ho",
"expertise": [
"Reviewer Expertise Willingness to pay on vaccine"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for inviting me to reviewing the paper “Willingness-to-pay for a hypothetical Ebola vaccine in Indonesia: A cross-sectional study in Ace”. This is an important and well written paper with sound methodology. I have the following recommendations to improve this paper.\nUnder discussion, the authors stated that, “However, we found no relationship between knowledge and WTP. It is interesting to discuss why knowledge on Ebola was not significantly associated with WTP in this present study, but higher education was.” The authors should state that knowledge on an infectious disease provided health professional was found to be associated with WTP. Please add the following statement:\n…. but higher education was. It could due to the observation that only knowledge on an infectious disease provided health professional was found to be associated with WTP for vaccine.1\n\nUnder limitation, the authors should state that this study did not explore on the effect of insurance on WTP. Please add the following statement under limitation:\n….. some questions given included in WTP section. This study did not explore the effect of health insurance on WTP as previous study found that having health insurance were associated with WTP for vaccine.2\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "61990",
"date": "21 Apr 2020",
"name": "Jing-Xin Li",
"expertise": [
"Reviewer Expertise Vaccine Clinical Evaluation"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nFor novel vaccines (e.g., Ebola vaccines), WTP was often considered as a major factor of vaccine policy and innovation1,2. Several studies have examined WTP for an Ebola vaccine in Ebola-affected countries (e.g., West Africa3,4,5 and America6. This study in Indonesia helped to supplement and enrich WTP for an Ebola vaccine in non-Ebola- affected countries.\n\nHowever, there are several significant omissions in study design from this manuscript.\n\nAlthough this study aimed to investigate community WTP for Ebola vaccine in Indonesia, the selection of respondents (patients’ family members who visited outpatient departments) caused selection bias.\n\nThis study was conducted in Aceh province, Indonesia. Aceh comprises predominantly rural areas7, which might result in the skewed distribution of participants’ characteristics, including Education (Senior high school: 47.2%), Occupation (Farmer: 26.7%) and (Suburb: 85.8%). As a result, some conclusions that high educational attainment, working as a private employee, entrepreneur or civil servant (compared to farmers) and residing in a suburb (compared to a city) were associated with higher WTP could not exclude the influence of these skewness distributions.\n\nThe authors stated that, “Prior to assessing their WTP, participants were provided with an introduction to the Ebola disease including the symptoms and modes of transmission.” Although there were no Ebola cases reported in Indonesia, some respondents were still likely to learn about Ebola and Ebola vaccines in a variety of ways, such as the Internet or newspapers. In addition, knowledge of vaccines had proven to be one of the crucial variables affecting WTP7. Therefore, this intervention would bias the outcome of WTP, which did not reflect the real WTP of respondents.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "62583",
"date": "30 Apr 2020",
"name": "Trung Quang Vo",
"expertise": [
"Reviewer Expertise Health economic",
"Public health and Pharmacy Administration"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nFirstly, I give you a big praise for all the efforts you made in the paper. This is a well-designed study with appropriate methods and explicit results so this paper should be accepted. However, there are minor points that should be clarify to improve your paper. The following are my comments on your manuscript:\nThe manuscript needs the use of a language editing service. Mistakes in grammar were made, in some cases, even the meaning got lost.\n\nThe Introduction should be strengthened. I did not see the importance of getting vaccine against Ebola in this part.\n\nAlthough the aim of the study was to “investigate community WTP of Ebola”, only patients’ family members were recruited. I think the study subjects did not consistent with its objective. Perhaps, you should consider to change the term “community WTP” into more suitable one.\n\nI know you used contingent valuation method to investigate the WTP even though no information provided. I think you should name the method and the technique used for a better understanding.\n\nPlease give more explanation: how did you set the range of vaccine price?\n\nPlease give more explanation: why did you collapse participant into three groups of age? Did they have any significance?\n\nI do not think you should define all the variables in the section “Explanatory variables”. Readers can find the groups of each variable in the Table. Please be shortened.\n\nPlease give more explanation: why did you set the cut-off point of 75% to divide attitude and knowledge into “good” and “poor”?\n\nPlease cite the reference for this information: “all explanatory variables that had P > 0.25 in this model were excluded from final linear regression model.\n\nYou said that you had provided information to the Ebola disease prior to assess WTP. I wonder if this step would affect questions regarding the knowledge about Ebola, therefore affect the WTP. Please consider carefully if you still want to state this step on the paper.\n\nOne of your finding is that higher education associated with higher WTP but the knowledge did not. I think you should give more discussion on this interesting finding.\n\nIn discussion section, you should state more about benefits of WTP assessment on the economic evaluation. Please add this statement on your discussion: “…WTP is a commonly used method in economic evaluation pf healthcare interventions. In cost-benefit analysis, the WTP method can value both the indirect and intangible aspects of a disease or condition. In cost-effectiveness or cost-utility analysis, WTP is consider to be a reference value to assess if an intervention is cost-effective or not1. It is important to be aware of methodology and interpretation of results because of affecting to decision of policy maker and also affecting in national expanded program in immunization on adding new good vaccines2.”\n\nIn limitation, you should state that this study did not explore the effects of vaccine efficacy on WTP values. Please add this statement under limitation: “This study did not explore the WTP difference between two or more scenarios of vaccine with different efficacy. As could be seen in previous study, higher efficacy of vaccines resulted in higher value of WTP3,4,5”\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "62295",
"date": "14 May 2020",
"name": "Brian Godman",
"expertise": [
"Reviewer Expertise My areas of interest including enhancing the quality and efficiency of the use of medicines across countries including LMICs. This includes WTP for medicines including vaccines. I have published to date over 250 papers - many of which are listed in PubMed"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for submitting this interesting paper. However, I am not sure regarding the rationale - although you have highlighted this at the beginning of the paper - but even more unlikely currently with travel bans, etc., as a result of COVID-19. This is because I believe Ebola is currently confined to the Congo (and hopefully now reducing) with ongoing steps in the neighbouring countries to prevent the infection spreading. I am not sure therefore of the hypothetical situation regarding Ebola in Indonesia - so good to discuss this more to put the findings into context.\nThis is because we have seen similar WTP approaches in Brazil for hypothetical and potential vaccines in key infectious disease areas (different to the situation in Indonesia currently with Ebola), with the need to balance the availability of the vaccine against other protective measures - so good to expand on this in the Introduction. Refs include: (i) Godoi IP et al. Consumer Willingness to Pay for Dengue Vaccine (CYD-TDV, Dengvaxia(R)) in Brazil; Implications for Future Pricing Considerations1; Muniz Júnior RL et al. Consumer willingness to pay for a hypothetical Zika vaccine in Brazil and the implications. Expert review of pharmacoeconomics & outcomes research2 and Sarmento TTR et al. Consumer willingness to pay for a hypothetical chikungunya vaccine in Brazil and the implications. Expert review of pharmacoeconomics & outcomes research3. This builds also on studies discussing the economic impact, etc., of infectious diseases such as dengue - Godoi IP et al. Economic and epidemiological impact of dengue illness over 16 years from a public health system perspective in Brazil to inform future health policies including the adoption of a dengue vaccine. Expert review of vaccines4.\nIn addition - good to compare the findings and differences in WTP between different groups for the Ebola vaccine in Indonesia and Brazil as both middle income countries. This can include difference in WTP for a vaccine and any potential rationale. This is very different to just concentrating on e.g. US nationals in West Africa - with very different income levels in Brazil - more akin to Indonesia.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/8-1441
|
https://f1000research.com/articles/12-668/v1
|
14 Jun 23
|
{
"type": "Research Article",
"title": "Association of PD-L1 immunoexpression with the clinicopathological characteristics and its prognostic significance in OPMD and OSCC: A cross-sectional study",
"authors": [
"Shelley Rajendra Durge",
"Alka Hande",
"Samiha Khan",
"Madhuri Nitin Gawande",
"Swati K Patil",
"Archana Sonone",
"Aayushi Pakhale",
"Alka Hande",
"Samiha Khan",
"Madhuri Nitin Gawande",
"Swati K Patil",
"Archana Sonone",
"Aayushi Pakhale"
],
"abstract": "Background: Head and neck cancers stands on eighth most prevalent tumor in Oral and Maxillofacial region among which the most frequent malignant tumor is Oral Squamous Cell Carcinoma (OSCC). Worldwide 880,000 patients suffer with head and neck cancer each year, and around 440,000 die due to it. Every day the number of clinical trials is increasing and many research focuses on improved surgery, radiotherapy and also chemotherapy. The immune system, under normal conditions, functions for the protection of the host against various infectious diseases and tumours. Cell surface proteins known as \"programmed cell death 1\" (PD-1) and \"programmed cell death ligand 1\" (PD-L1) are essential for the proper functioning of immunological checkpoints. The expression of “PD-L1” positive cells has a direct correlation with poorer prognostic outcome and its correlation is inversed with CD8+T cells infiltrating tumor. This study focuses on association of “PD-L1\" immunoexpression to clinicopathological characteristics and its prognostic importance in Oral Premalignant Disorder (OPMD) and OSCC. Methods: The study included surgical tissue samples from individuals who underwent surgery for OSCC. Cases altogether, including OPMD and OSCC were chosen. Examination of sections stained with “PD-L1” antibody was done under Leica DMLB2 (Leica microscope). Results: The present study showed significant correlation between PD-L1 immunoexpression with the clinicopathological characteristics of OPMD and OSCC cases. Conclusions: The premalignant lesions show the intermediate “PD-L1” expression which lie between the normal or hyperplastic lesions to the OSCC. This shows a condition where there are biological adaptations has been confirmed already which directed towards malignant transformation. So, there is a crucial role of “PD-L1’ in the progression of tumor.",
"keywords": [
"Oral squamous cell carcinoma",
"Oral potentially premalignant disorder",
"programmed cell death - ligand 1",
"Programmed cell death – 1",
"Cytotoxic T lymphocyte-associated protein 4",
"Disease-specific survival rate",
"Tumor-proportion score",
"Combined-positive score."
],
"content": "Introduction\n\nHead and neck cancer are the world’s eighth most prevalent tumour in the oral and maxillofacial region, among which the most frequent malignant tumour is oral squamous cell carcinoma (OSCC).1,2 About 880,000 patients suffer with OSCC each year worldwide and approximately half the patients die due to it.2 The lifestyle habits such as tobacco eating, smoking, alcohol drinking, and chewing betel nuts develops the OSCC. Many researchers believe that there are approximately 25 % patients who are positive for OSCC are also positive for HPV so showing high correlation between OSCC and HPV infection.3 Globally there are 3.90 per 100 000 of OSCC cases and the mortality of them is 1.94 per 100,000 globally.4,5\n\nThe early staged OSCC cases are treated with surgery only while the rest OSCC cases requires a multi-modal approach that is the chemotherapy and radiotherapy. There is day to day increasing in clinical trials in many researches on improved surgery, radiotherapy and also chemotherapy. It is because there is very high incidence and mortality rate in many countries worldwide. Also there is complex and economic impact for patients which manage to survive this highly disabling disease.6\n\nThe contradiction of the OSCC is its simplicity to diagnose it with the routine clinical and histological examination in most of the cases. However very large number of cases are diagnosed at advanced stages. There is impact on prognosis of diseases due to late diagnosis in many cases which hampers the quality of life of patients and financial burden for healthcare systems worldwide.7 In present decades, there have been pivotal advancement in the therapeutic management of OSCC. For efficient strategy to battle with the advanced and metastatic OSCC the immunotherapy is the example.8\n\nMost OSCCs are preceded by oral precursor lesions or conditions (OPMDs). These lesions mainly include “oral leukoplakia, erythroplakia, oral lichen planus, and OSMF”. Histopathological spectrum of these OPMD’s ranges from hyperkeratosis/hyperplasia to different grades of “epithelial dysplasia”, to “carcinoma in situ”, and eventually “invasive squamous cell carcinoma”. The morbidity and mortality of the disease can be decreased by early diagnosis at the premalignant stage. Further histological assessment of OED with various grades helps in the prediction of malignant transformation.9\n\nThe immune system, under normal conditions, functions for the protection of the host against various infectious diseases and tumor. Additionally, it helps in clearing the unhealthy and ailing cells. Immune checkpoints, which are the inhibitory regulators of immune system, play a vital role in maintaining self-tolerance. They aid in regulating immune response latency, intensity, and extent, limiting autoimmunity and decreasing collateral tissue damage. Among them is “cytotoxic T lymphocyte-associated protein 4” (CTLA-4). Its expression is significantly higher in regulatory T cells (Tregs) and upregulated in activated conventional T cells. CTLA4 is similar to CD28 which is a T-cell co-stimulatory protein. Both of these molecules compete in binding to CD80 (B7). When triggered by CD80, CTLA4 sends a signal to T cells that is inhibitory. CD28 transmits a stimulatory signal. Cell surface proteins known as “programmed cell death 1” (PD-1) and “programmed cell death ligand 1” (PD-L1) are essential for the proper functioning of immunological checkpoints.10 The expression of “PD-L1” positive cells has a direct correlation with poorer prognostic outcome and its correlation is inversed with CD8+T cells infiltrating tumor.11\n\nDevelopment of tumor, “immune privilege” regions, viral persistence, and immune evasion are some important roles of “PD-L1”. “PD-L1” ligation on tumor cell surface protects the tumor from cell death. Therefore, dysfunctional or exhausted T cells are reactivated by blockade of the “PD-1/PD-L1” axis by restoring tumor-specific immunity that eliminates the cancer cells. Nivolumab is a commercially available human monoclonal anti-programmed death-1 antibody. It is clinically approved in several countries after undergoing a successful phase III clinical trial and it is reportedly active against recurrent/metastatic head and neck cancers.12\n\nPositive tumor “PD-L1” expression is determined by immunohistochemistry (IHC), which predicts the clinical response. Nivolumab and pembrolizumab are the PD-1/PD-L1 checkpoint inhibitors which have shown clinical effectiveness in advanced treatment of head and neck cancer.13\n\nThe presence of expression “PD-L1” is seen in the cell membrane and cytoplasm of tumor cells and infiltrating lymphocytes. Physiologically, it is seen in the placenta, pancreatic islet cells and mesenchymal stem cells. Higher expression of “PD-L1” is corresponds with the poorly differentiated tumor, advanced cancer staging, nodal as well as distant metastasis.14\n\nIn HNSCC, the degree of inter-observer variability in “PD-L1” assessment represents an obstacle even after the preliminary analysis. This is owing to the variety of scoring systems available for “PD-L1”, like the “tumor-proportion score” (TPS), the immune-cell (IC) score, and the “combined-positive score” (CPS), which is recommended in the HNSCC.15\n\nIn 2016, new medications that target the immune checkpoint “PD-1/PD-L1” were being evaluated for the treatment of instances of advanced HNSCC. A new immunotherapy treatment approach was launched, and early studies on select patients revealed encouraging outcomes. Due to the fact that it is expressed in various malignancies, including HNSCC, PD-L1 has become a frequently investigated biomarker for immune checkpoint therapy.16\n\nExpression of “PD-1/PD-L1” differs in numerous cancers and OPMDs. The function of expression of “PD-1 and PD-L1” has explored in OPMDs. The over- expression of “PD-1/PD-L1” was seen higher in cases of actinic cheilitis as compared to healthy individuals but lower in cases of OSCC.17 This investigation was performed with the aim of identifying the immunological checkpoint molecules that are the target before OPMDs proceed to OSCC.18\n\nThis study focuses on correlating “PD-L1” immunoexpression to clinicopathological characteristics and its prognostic importance in OPMD and OSCC, a new role for “PDL1” has been discovered.\n\n\nMethods\n\nThis study was conducted in “Department of Oral and Maxillofacial Pathology and Microbiology”, “Sharad Pawar Dental College and Hospital”, Datta Meghe Institute of Higher Education and Research (DMIHER), Sawangi (M), Wardha, Maharashtra, India. Prior to the study, ethical approval was obtained from the Institutional Ethical Committee of Datta Meghe Institute of Medical Sciences. (DMIMS (DU)/IEC/2020-21/9425). The informed written consent was obtained from the participants before the study.\n\nThe study included surgical tissue samples from patients by taking consent who underwent surgery for OSCC from 2003 to 2019 retrospectively at the same facility. The tissue specimens were retrieved from the department’s archives. 62 cases altogether, including 31 OPMD cases and 31 OSCC cases were chosen. The histopathological grading of OSCC followed the Broder’s grading system as well differentiated, moderately differentiated and poorly differentiated squamous cell carcinoma.\n\nIn this cross-sectional study, a total of 62 samples divided into three groups: The groups are as follows:\n\nGroup I: 31 samples with Oral Potentially Premalignant Disorders\n\nGroup II: 31 samples with Oral Squamous Cell Carcinoma\n\nFor OPMD group, 31 cases of hyperkeratosis and oral sub mucous fibrosis (OSMF) were selected. The study’s inclusion criteria took into account instances with OSCC that had been clinically and histopathologically diagnosed and were largely operated surgically.\n\nThe cases that were excluded from the study were those with head neck cancer history in the past, recurrent or distant disease and also patients who had undergone pre-operative treatments except biopsy.\n\nThe IHC for PD-L1 monoclonal antibody, which is a nuclear proliferative marker was carried out in the “Department of Oral and Maxillofacial Pathology & Microbiology”, “Sharad Pawar Dental College”, DMIHER, Sawangi (Meghe), Wardha. Sections were hydrated with increasing grades of alcohol and brought to distilled water and treated with hydrogen peroxide (H2O2) to eliminate endogenous peroxidase activity. The tissues were then incubated sequentially with:\n\n• Primary antibody, which binds to specific tissue antigens.\n\n• Secondary antibody, which binds to the primary antibody; it is a polyvalent antibody that will bind to primary antibodies derived from rabbit, mouse, rat and guinea pig.\n\nA coloured precipitate is formed by adding peroxidase substrate (hydrogen peroxidase) to chromogen at the tissue antigen sites. Counter staining with hematoxylin aided in visualization.\n\n\n\n1. Fixation of tissues was done by using 10% formalin (neutral buffered) for 24 hours which were later routinely processed and embedded in paraffin wax.\n\n2. Silane coated slides provided proper adherence of tissue sections to the glass slides. Sections were floated on silane-coated slides in a 45°C water bath. Air drying of sections was done overnight at 37°C which were heated at 56°C for one hour.\n\n3. Sections were dewaxed thoroughly in xylene and hydrated through descending grades of alcohol to water as seen in Table 1.\n\nSections were kept in running tap water for 5 minutes and were later rinsed in distilled water.\n\nM sodium citrate buffer (pH 6.0) was used to heat the slides in the microwave oven for 12 mins for antigen retrieval which was then bench cooled for 20 mins. The same cycle was repeated again. Then sections were washed thrice by shaking gently in TBS for 5 mins each.\n\nIndividual sections were outlined by NCL-Pen. Sections were incubated in Peroxidase block (0.3% H2O2 in methanol) for 20 mins. This is to inactivate the “endogenous peroxidise” activity to avoid false positive reactions when using the same or similar enzyme as label. These sections were then washed with TBS 3 times each for 5 mins.\n\nBlocking serum was poured off and wiped gently around each section. Covering of sections was done using prediluted polyclonal antibody and incubation was done in a humidifying chamber for 1 hour at room temperature. Wash buffer was later used for washing the sections 3 times for 10 mins each.\n\nWash buffer was wiped gently from around each section. Addition and incubation of biotinylated secondary antibody was done at room temperature for 60 minutes in a humidifying chamber. Then these slides were washed with TBS 3 times each for 10 minutes.\n\nSlides were cleaned (wiped) as before. Application of substrate chromogen solution was done which should be enough for covering the section. Incubation was done at room temperature for twenty minutes. Preparation of DAB chromogen working solution was done by mixing 5ul of concentrated DAB in 50ml of substrate buffer.\n\nSections were washed for 2 mins in water and were later counterstained with Harris’s hematoxylin for 30 sec. Dehydration of sections was done Sections were dehydrated through ascending grades of alcohol, cleared in xylene and mounted in DPX.\n\nExamination of sections stained with “PD-L1” antibody was done under Leica DMLB2 (Leica microscope) at 40×.\n\nAt the site of the target antigen (DAB chromogen brown end product), examination of the sections was done for the presence of a coloured end product. This indicated a positive staining result and proper performance of kit reagents.\n\nThe cells which showed the presence of brown colour (membranous staining) were considered positive for the “PD-L1.”The positive score of the stained cells was regardless of the intensity of staining. Cells that did not show a clear staining were excluded. Each section had a minimum of 1000 cells. Evaluation of tissue sections positive for “PD-L1” was done by locating the epithelial linings and was labelled by scanning the sections at 10X. The cells were counted at 40× under Leica DMLB2 (Leica microscope) in 5 different fields. “PD-L1” labelled cells counting was done.\n\nFive randomly chosen fields from the representative areas were evaluated at a 40× magnification. Each field’s membranous/cytoplasmic cell positive was recorded, regardless of its level. Cells that were positive for “PD-1” and “PD-L1” in the sub-epithelial region were counted up to sixty micrometres from the basement membrane. This was carried out in accordance with the oral mucosa’s superficial lamina propria. In each example, the basal and spinous layer were evaluated for “PD-L1” expression. The proportion of positively labelled cells to all cells was calculated.\n\nThe evaluation and tracing was done with the help of computer aided analysis system Leica Q-Win ProV3.5.0, Leica Microsystems (Switzerland) Ltd.\n\nTonsils showing expression of “PD-L1” were used as positive control. For negative control, one section was taken from each positive control and primary antibody were excluded. It was then incubated with serum. The rinsing was done 3 times for 10 mins in PBS after primary reaction of antigen and antibody. Incubation of the HRP-labelled anti-mouse polymer was done for 30 mins at room temperature in a humidifying chamber. There were antigen-antibody reactions in the chromogen buffer solution of “3,3′ diaminobenzidine”. Final counterstaining was done using “Mayer’s Hematoxylin”.\n\nThen the assessment of “PD-L1” immunoexpression was done manually by 3 different observers in blinded manner.\n\nThe evaluation was done into 4 categories according to percentages stained for malignant cells (0 = negative; 1 = 1-33%; 2 = 34-66%; 3 = 67-100%). More than 10% “PD-L1” expression show poor survival outcomes. So even 1% PD-L1 expressed cancer cells were considered as positive.\n\nConsidering the prevalence of Oral Potentially Malignant Disorder as 2% in outpatient department of Oral Medicine and Radiology, using Single Proportion Formula, sample size was calculated by using the formula:\n\nWhere,\n\nAnd Zα/2 is the critical value of the Normal distribution at a/2 (e.g. for a confidence level of 95%, a is 0.05 and the critical value is 1.96), MOE is the margin of error, p is the sample proportion, and N is the population size.\n\nThe sample size was calculated to be 31. There are total 2 groups, hence, total 62 samples were required.\n\nThe Chi-square test will be used to analyse differences in categorical variables. Survival analysis will be done by Kaplan-Meier method, and the log-rank test will be used to test for significant differences by SPSS 17.0 version 8, SPSS Inc., Chicago, IL.\n\n\nResults\n\nFigure 1 representing the hematoxylin and eosinophilic stained tissue section showing well differentiated squamous cell carcinoma and thereby Figure 2 showing transmembranous PD-L1 immunostaining in it. Figure 3 represents haematoxylin and eosin stained tissue section at 400× magnification and Figure 4 represents transmembranous PD-L1 immunostaining at 400× in oral squamous cell carcinoma.\n\nEvaluation of 31 OPMD and 31 OSCC cases were done and results were obtained as follows.\n\nOPMD and OSCC was more prevalent in 4th and 5th decade of life. In OPMD, the age range of patient was 27-60yrs with the mean age of 44.83 ± 10.83. Whereas, In OSCC the age ranging from 27-75 years with the mean age of 48.80 ± 12.1. There was no significant Correlation between PD-L1 score with age of OPMD cases (χ2-value 3.68; P = 0.45) (Table 2) and OSCC cases (χ2-value = 0.009 and P = 0.99) (Table 4).\n\nMales were more frequently affected than female with OPMD and OSCC. In OPMD cases, there were 24(77.4%) males and 7(22.6%) females. In OSCC cases, there were 25(80.6%) males and 6(19.4%) females. However, we found no significant correlation between PD-L1 score and gender of OPMD cases (χ2-value = 3.88 and P value = 0.14) (Table 3) and OSCC cases (χ2-value = 0.07 and P = 0.79) (Table 5).\n\nWe further evaluated the clinical diagnosis of OPMD and OSCC cases. Among 31 OPMD, 23(74.2%) cases were Leukoplakia and 8(25.8%) were OSMF. A significant correlation was seen between PD-L1 score with clinical Diagnosis of OPMD patients with the χ2-value = 26.08 and P = 0.0001 (Table 6). We have classified the tumor into four categories according to AJCC classification for TNM: stage I, stage II, stage III, stage IV and among 31 cases we found 2(6.5%), 5(16.1%), 7(22.6%), 17(54.8%) patients respectively. Among 31 OSCC patients, in stage I, 2(14.29%) patient showed score 2. In stage II, 3(21.43%) showed score 2 and 2(11.76%) showed score 3. In stage III, 6(42.86%) patients showed score 2 and 1(5.88%) patients showed score 3. In stage IV, 3(21.43%) patients showed score 2 and 14(82.35%) showed score 3. There was significantly positive correlation between PD-L1 score with TNM Staging of OSCC patients with χ2-value = 12.74 and P = 0.005 (Table 7).\n\nIn OPMD, we histologically divided the patients into 5 categories i.e. hyperkeratosis, no dysplasia, mild dysplasia, moderate dysplasia and severe dysplasia having 14(45.16%), 8(25.81%), 2(6.45%), 3(9.68%), 4(12.9%) patients in each category respectively. In leukoplakia, 16(94.12%) patients showed score 1 and 7(22.58%) patients showed score 2. In OSMF, 7(22.58%) patients showed Score 0 and 1(5.88%) patients showed score 1. We corelate PD-L1 score with histopathological diagnosis of OPMD and observed, there were 14(82.35%) patients in hyperkeratosis showing score 1. 7(100%) patients showed no dysplasia with score 0 and 1(5.88%) were with score 1. Patients showing mild dysplasia were 2(11.76%) with score 1. In moderate dysplasia there were 3(9.68%) patients in score 2. In severe dysplasia, 4(57.14%) patients showed score 2. A remarkable correlation was observed between PD-L1 score with Histopathological diagnosis of OPMD patients with χ2-value of 56.52 and P-value = 0.0001 (Table 8).\n\nAmong 31 OSCC patients, in WDSCC, 5(35.71%) patients showed score 2 and only 1(5.88%) patient showed score 3. In MDSCC, 9(64.29%) patients showed score 2 and majority of patients i.e. 12(70.59%) showed score 3. In PDSCC, all the patients i.e. 4(23.53%) showed score 3. So, we found significantly positive Correlation between PD-L1 score with histopathological diagnosis of OSCC patients with the χ2-value = 6.96 and P = 0.032) (Table 9).\n\nAccording to percentages of stained tumor cells we evaluate PD-L1 score into four categories. (0 = negative; 1 = 1-33%; 2 = 34-66%; 3 = 67-100%). In OPMD cases, we observed 7(22.6%), 17(54.8%), 7(22.6%) showing score 0,1 and 2 respectively. There were 0 cases showing score 3. However, in OSCC cases, we observed 14(45.2%) and 17(54.8%) showing score 2 and 3 respectively. Whereas there were no cases showing score 0 and 1. The χ2 value was 43.33 and both the groups showing significantly positive correlation (P = 0.00001) (Table 10).\n\n\nDiscussion\n\nCarcinomas represent the commonest form of human cancer. Worldwide, oral carcinomas rank from 6th to 8th as the most prevalent cancers.19 Despite advanced treatment modalities, the overall five-year survival rate of OSCC patients remains unchanged. The prognosis of a tumor does not depend upon a single factor, rather it is multifactorial. The contribution of various factors to the tumor progression decides the outcome of the tumor. Therefore, it is of prime importance to evaluate multiple factors (tumor markers) for correct assessment of the tumor prognosis. A thorough literature review showed a rarity of such a study on OSCC. Hence, this study was designed keeping in mind this need.20\n\nOPMDs are proportionately common with a global prevalence rate of 1–5% showing similar age, site and gender predilections as OSCC. It is observed that oral leukoplakia (OL) is often associated with OSCC. However, the exact rate of malignant transformation of OMPDs is unknown. In the present study, a similar pattern was seen in 77% cases. Surveillance directed to OPMDs could have been an important factor in early detection and diagnosis of OSCC in the population of this study. These results show the importance of considering the chances of development of OSCC in cases of leukoplakia and OSMF. This adds to the need of obtaining biopsy specimens from all lesions from this group.20\n\nIn OPMD, the age range of patient was 27-60 yrs with the mean age of 44.83 ± 10.83. According to Graham R. Ogden21 the age range of occurrence of OPMD in population was 11 to ≥50 years and 40% of OPMD cases were seen in 21–30 years of age group. Whereas, In OSCC the age ranging from 27-75 years with the mean age of 48.80 ± 12.12 (χ2-value 0.11; P = 0.94 NS) was there. Our results are similar with that of Hong zhi Quan et al.22 who stated that, OSCC patients were in age range of 33 to 78 years with the mean age of 56 years. The OPMD cases at an earlier age occurrence are more as compared to OSCC and it may convert into OSCC.23 In context to the gender predilection in patients with OPMD and OSCC, the male predominance was observed. These results were in accordance with previous study by Preeti Sharma et al.24 and Shenoi et al.25 Age was not related to “PD-L1” positive (P > 0.05). This outcome was consistent with research by Hui Tang et al.,26 who found no connection between PD-L1 expression and age. On correlation of gender of patents with the “PD-L1” score we found no significant correlation between “PD-L1” score and gender of OPMD cases (χ2-value = 3.88, P = 0.14). “PD-L1” expression was independent of gender of OPMD and OSCC group. Same as our results, Hui Tang et al.27 also found no significant correlation between “PD-L1” expression with age and gender in HNSCC (OR = 1.09, 95% CI: 0.51-2.34; OR = 0.87, 95% CI: 0.56-1.36; OR = 1.23, 95% CI: 0.96–1.56).\n\nWe evaluated the Clinical presentation and site of the lesion of OPMD and OSCC patients. In OPMD, 23 (74.2%) cases were Leukoplakia and 8(25.8%) were OSMF, predominantly involving buccal mucosa. In OSCC, the most common involved site was the gingivobuccal sulcus 15(48.38%) followed by buccal mucosa 11(35.48%), alveolar mucosa 4(12.90%) and labial mucosa 1(3.22%). Juana Maria García-Pedrero et al.20 noted that most common involved site was the tongue. In regions like America and Europe, the most common site of OSCC is considered to be the border of tongue.28 In southern Asian countries, the habit of areca nut and tobacco chewing makes the buccal mucosa as an occasional site for OSCC. In a study done by Jainkittivong et al.,29 it was reported that around 50% of their total cases of OSCC were of gingival and alveolar ridge. This could be justified by the association of different etiologic factors and OSCC development in their specific population. In their research done in Nigeria, observed that the most commonly affected sites of OSCC are upper and lower gingiva, followed by the tongue. The most commonly affected OSCC sites were border of tongue and floor of mouth, as reported by majority of the studies which focused on Brazilian and other countries of the west populations.20 The clinical staging of OSCC is determined by the tumor’s size, the involvement of nearby lymph nodes, and the presence or absence of metastases, which is referred to as TNM tumour staging. We have further divided the tumor into 4 main categories according to AJCC classification for TNM: stage I-IV and observed that 2(6.5%) cases were in stage I, 5(16.1%) in stage II, 7(22.6%) in stage III, 17(54.8%) in stage IV. There was significantly positive correlation between “PD-L1” score with TNM Staging of OSCC patients (χ2-value = 12.74; P = 0.005, S). This result is in accordance with Jing He et al.,30 a significant positive correlation was found between expression of “PD-L1” and the TNM staging.\n\nWe found significantly positive correlation between “PD-L1” score with histopathological diagnosis of OSCC patients. (χ2-value = 6.96; P = 0.032, S). Similarly, Chen et al.31 found that “PD-L1” was significantly associated with the OSCC pathological grade.\n\nThe management of OPMD is related to the histopathological diagnosis which may be range from hyperkeratosis and further with various grades of dysplasia. In OPMD, we observed that 14(45.16%) showed hyperkeratosis, 8(25.81%) showed no dysplasia, 2(6.45%) showed mild dysplasia, 3(9.68%) showed moderate dysplasia and 4(12.9%) showed severe dysplasia. Erythroplakias having histopathologic features of severe dysplasia or carcinoma in situ (Ca in situ), should be excised with a clear margin. The malignant transforming rate of oral leukoplakia (OL) ranges between 1 and 17.5% per year. It is generally managed either by patient follow up or excision of lesion depending on the histopathological evaluation and severity of dysplasia. It is still unclear whether the excision of leukoplakia or erythroplakia prevents the development of OSCC. However, a study done on leukoplakia has documented that 20% cases regress due to the elimination of risk factors. A retrospective study was done comprising of 94 cases of surgically resected leukoplakia and erythroplakia with a mean 6.8 years follow up, along with 175 cases which did not undergo surgical resection of the lesion with mean 5.5 years follow up. The study revealed that 12% cases with surgical resection and 4% cases without resection developed OSCC. This led to a conclusion that surgery does not provide protection against malignant transformation of leukoplakia. In a meta-analysis and study on surgical treatment of leukoplakia (with dysplasia), it was revealed that the risk of developing OSCC reduces by surgical intervention by does not eliminate it completely. Efforts should be made to modify habits leading to OSCC and patient counselling should be done at earliest to reduce the risk of transformation of leukoplakia into malignancy. Cases with risk of malignant transformation should be kept on a regular follow-up. The follow up intervals are however entirely based on clinicians’ subjective assessment of clinical appearance of the disease and reported dysplasia and not evidence based. The first 2 years carry the greatest risk of malignant transformation and around 1% may transform on annual basis. Patients should remain on regular follow-up and re-biopsy of suspected lesions should be done by experienced clinicians if clinically indicated.32,33\n\nIn the present study, the histopathologic features of epithelial dysplasia were seen in 30% cases of OPMDs. Mello et al.34 has reported a high proportion of epithelial dysplasia (73%) in OPMDs. Prevention of malignant transformation of the lesion is the main goal for identifying oral pre-cancerous lesions. Regular surveillance of the lesion, change of lifestyle like use of tobacco and alcohol, retinoid or antioxidant treatment and surgery are some of the treatment options for oral precancerous lesions. However, none of these options have shown significance in reducing the malignant transformation in the long-term follow-up studies.\n\nIn present study of OSCC patients most of the cases were of moderately differentiated tumors, and around 50% cases were in late cancer stages (stage III/IV). In all patients, 6(19.4%) were WDSCC, 21(67.7%) were MDSCC and 4 (12.9%) were PDSCC.\n\nThis study concluded that the host immune system by “PD-L1” expression may be escaped by OPMD lesions on dysplastic cells of epithelium as well as the recruited subepithelial cells. This results in the development of invasive SCC. So to prevent their malignant transformation and to inhibit the “PD-L1’ pathways there are immunological approaches which gives new treatment modalities.35\n\nSo according to our results, there is a crucial role of “PD-L1’ in the progression of tumor, the only limitation of the study is the sample size.\n\nWe interpreted that there is propensity of OPMD lesions showing more prevalence of “PD-L1” positive expression when we compared it to the normal mucosa. But in contrast it shows lower PD-L1 positivity than OSCC. This shows a condition where there are biological adaptations has been confirmed already which directed towards malignant transformation. Though there is still control of the immune the system. So, we can note that the premalignant lesions show the intermediate “PD-L1” expression which lie between the normal or hyperplastic lesions to the OSCC. As expected, researches which very clearly differentiate between the hyperplastic lesion, low grade dysplasia and high grade dysplastic lesions had not evaluated any significant difference amongst all these kind of lesions.30,36",
"appendix": "Data availability\n\nZenodo: Association of PD-L1 immunoexpression with the clinicopathological characteristics and its prognostic significance in OPMD and OSCC, https://doi.org/10.5281/zenodo.7765551. 37\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nI acknowledge the support of Research House Team, Dr. S.Z. Quazi, Director Research and Development, DMIHER.\n\n\nReferences\n\nGhapanchi J, Ranjbar Z, Mokhtari MJ, et al.: The LncRNA H19 rs217727 Polymorphism Is Associated with Oral Squamous Cell Carcinoma Susceptibility in Iranian Population. Biomed. Res. Int. 2020 Apr 2; 2020: 1–6. Publisher Full Text\n\nSung H, Ferlay J, Siegel RL, et al.: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021 May; 71(3): 209–249. PubMed Abstract | Publisher Full Text\n\nChai AWY, Lim KP, Cheong SC: Translational genomics and recent advances in oral squamous cell carcinoma. Semin. Cancer Biol. 2020 Apr; 61: 71–83. PubMed Abstract | Publisher Full Text\n\nGlobal Burden of Disease Cancer CollaborationFitzmaurice C, Abate D, et al.: Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2019 Dec 1; 5(12): 1749–1768. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLing Z, Cheng B, Tao X: Epithelial-to-mesenchymal transition in oral squamous cell carcinoma: Challenges and opportunities. Int. J. Cancer. 2021 Apr 1; 148(7): 1548–1561. PubMed Abstract | Publisher Full Text\n\nCaruntu A, Caruntu C: Recent Advances in Oral Squamous Cell Carcinoma. J. Clin. Med. 2022 Oct 29; 11(21): 6406. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGrafton-Clarke C, Chen KW, Wilcock J: Diagnosis and referral delays in primary care for oral squamous cell cancer: a systematic review. Br. J. Gen. Pract. 2019 Feb; 69(679): e112–e126. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCaruntu A, Scheau C, Tampa M, et al.: Complex Interaction Among Immune, Inflammatory, and Carcinogenic Mechanisms in the Head and Neck Squamous Cell Carcinoma. Adv. Exp. Med. Biol. 2021; 1335: 11–35. PubMed Abstract | Publisher Full Text\n\nAittiwarapoj A, Juengsomjit R, Kitkumthorn N, et al.: Oral Potentially Malignant Disorders and Squamous Cell Carcinoma at the Tongue: Clinicopathological Analysis in a Thai Population. Eur. J. Dent. 2019 Jul; 13(3): 376–382. PubMed Abstract | Publisher Full Text\n\nAkhtar M, Rashid S, Al-Bozom IA: PD− L1 immunostaining: what pathologists need to know. Diagn. Pathol. 2021 Dec; 16(1): 1–2. Publisher Full Text\n\nTekade SA, Chaudhary MS, Tekade SS, et al.: Early Stage Oral Submucous Fibrosis is Characterized by Increased Vascularity as Opposed to Advanced Stages. J. Clin. Diagn. Res. JCDR. 2017 May; 11(5): ZC92–ZC96. PubMed Abstract | Publisher Full Text\n\nPlanes-Laine G, Rochigneux P, Bertucci F, et al.: PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences are Emerging—A Literature Review. Cancers. 2019 Jul 22; 11(7): 1033. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Vicente JC , Rodríguez-Santamarta T, Rodrigo JP, et al.: PD-L1 Expression in Tumor Cells Is an Independent Unfavorable Prognostic Factor in Oral Squamous Cell Carcinoma. Cancer Epidemiol. Biomark. Prev. Publ. Am. Assoc. Cancer Res. Cosponsored Am. Soc. Prev. Oncol. 2019 Mar; 28(3): 546–554. PubMed Abstract | Publisher Full Text\n\nDeliverska E, Forghani P, Parusheva S: Evaluation of programmed death 1 (PD-1) and programmed death ligand-1 (PD-L1) as tumor biomarkers an in patients with head and neck squamous cell carcinoma. J. Med. Dent. Pract. 2020 Jun 4; 7(2): 1198–1202. Publisher Full Text\n\nCrosta S, Boldorini R, Bono F, et al.: PD-L1 testing and squamous cell carcinoma of the head and neck: a multicenter study on the diagnostic reproducibility of different protocols. Cancers. 2021 Jan 14; 13(2): 292. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLenouvel D, González-Moles MÁ, Talbaoui A, et al.: An update of knowledge on PD-L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives. Oral Dis. 2020 Apr; 26(3): 511–526. PubMed Abstract | Publisher Full Text\n\nMeng X, Huang Z, Teng F, et al.: Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat. Rev. 2015 Dec; 41(10): 868–876. Publisher Full Text\n\nKujan O, van Schaijik B , Farah CS: Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review. Cancers. 2020 Jul 17; 12(7): 1937. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMarocchio LS, Lima J, Sperandio FF, et al.: Oral squamous cell carcinoma: an analysis of 1,564 cases showing advances in early detection. J. Oral Sci. 2010 Jun; 52(2): 267–273. PubMed Abstract | Publisher Full Text\n\nGarcía-Pedrero JM, Martínez-Camblor P, Diaz-Coto S, et al.: Tumor programmed cell death ligand 1 expression correlates with nodal metastasis in patients with cutaneous squamous cell carcinoma of the head and neck. J. Am. Acad. Dermatol. 2017 Sep; 77(3): 527–533. PubMed Abstract | Publisher Full Text\n\nOgden GR: Alcohol and oral cancer. Alcohol Fayettev N. 2005 Apr; 35(3): 169–173. Publisher Full Text\n\nQuan H, Liu S, Shan Z, et al.: Differential expression of programmed death-1 and its ligand, programmed death ligand-1 in oral squamous cell carcinoma with and without oral submucous fibrosis. Arch. Oral Biol. 2020 Nov; 119: 104916. PubMed Abstract | Publisher Full Text\n\nKadashetti V, Shivakumar KM, Chaudhary M, et al.: Influence of risk factors on patients suffering from potentially malignant disorders and oral cancer: A case-control study. J. Oral Maxillofac. Pathol. JOMFP. 2017; 21(3): 455–456. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSharma P, Saxena S, Aggarwal P: Trends in the epidemiology of oral squamous cell carcinoma in Western UP: an institutional study. Indian J. Dent. Res. Off. Publ. Indian Soc. Dent. Res. 2010; 21(3): 316–319. Publisher Full Text\n\nShenoi R, Devrukhkar V, Chaudhuri, et al.: Demographic and clinical profile of oral squamous cell carcinoma patients: a retrospective study. Indian J. Cancer. 2012; 49(1): 21–26. Publisher Full Text\n\nTang H, Zhou X, Ye Y, et al.: The different role of PD-L1 in head and neck squamous cell carcinomas: A meta-analysis. Pathol. Res. Pract. 2020 Jan; 216(1): 152768. PubMed Abstract | Publisher Full Text\n\nLin YM, Sung WW, Hsieh MJ, et al.: High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma. PLoS One. 2015; 10(11): e0142656. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOhaegbulam KC, Assal A, Lazar-Molnar E, et al.: Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol. Med. 2015 Jan 1; 21(1): 24–33. Publisher Full Text\n\nJainkittivong A, Swasdison S, Thangpisityotin M, et al.: Oral Squamous Cell Carcinoma: A Clinicopathological Study of 342 Thai Cases. J. Contemp. Dent. Pract. 2009 Sep 1; 10: 33–41. Publisher Full Text\n\nHe J, Chen XF, Xu MG, et al.: Relationship of programmed death ligand-1 expression with clinicopathological features and prognosis in patients with oral squamous cell carcinoma: A meta-analysis. Arch. Oral Biol. 2020 Jun; 114: 104717. PubMed Abstract | Publisher Full Text\n\nChen XJ, Tan YQ, Zhang N, et al.: Expression of programmed cell death-ligand 1 in oral squamous cell carcinoma and oral leukoplakia is associated with disease progress and CD8+ tumor-infiltrating lymphocytes. Pathol. Res. Pract. 2019 Jun; 215(6): 152418. Publisher Full Text\n\nSathiyasekar AC, Chandrasekar P, Pakash A, et al.: Overview of immunology of oral squamous cell carcinoma. J. Pharm. Bioallied Sci. 2016 Oct; 8(Suppl 1): 8–12. Publisher Full Text\n\nGatti RA, Good RA: Aging, immunity, and malignancy. Geriatrics. 1970 Sep; 25(9): 158–168. PubMed Abstract\n\nMello FW, Miguel AFP, Dutra KL, et al.: Prevalence of oral potentially malignant disorders: A systematic review and meta-analysis. J. Oral Pathol. Med. Off. Publ. Int. Assoc. Oral Pathol. Am. Acad. Oral Pathol. 2018 Aug; 47(7): 633–640. Publisher Full Text\n\nDeshmukh V, Shekar K: Oral Squamous Cell Carcinoma: Diagnosis and Treatment Planning. Oral Maxillofac. Surg. Clin. 2021; 1853–1867. Publisher Full Text\n\nYoshida S, Nagatsuka H, Nakano K, et al.: Significance of PD-L1 Expression in Tongue Cancer Development. Int. J. Med. Sci. 2018 Nov 22; 15(14): 1723–1730. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDurge S: Association of PD-L1 immunoexpression with the clinicopathological characteristics and its prognostic significance in OPMD and OSCC. [Data set]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "191542",
"date": "21 Aug 2023",
"name": "Simin Li",
"expertise": [
"Reviewer Expertise Tumor immunity",
"oncology",
"oral cancer."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript by Durge et al. investigates the association between PD-L1 expression and clinicopathological features in oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). The authors evaluated PD-L1 immunohistochemistry on 62 samples - 31 OPMDs and 31 OSCCs. They found that PD-L1 expression correlated significantly with clinical diagnosis, histopathological diagnosis, and TNM stage in OPMDs and OSCCs respectively. The results suggest PD-L1 could play a role in malignant transformation from OPMDs to OSCC.\nOverall, this is an interesting preliminary study examining PD-L1 as a prognostic biomarker in oral cancers. I recommend the following changes for the manuscript to be acceptable for indexing after minor revision.\nThe sample size of 62 seems quite small to draw definitive conclusions from the analysis. Expanding the sample size could strengthen the results.\n\nProvide more details on the patient population - demographic information, risk factors, comorbidities etc. This context helps interpret the results.\n\nInclude a table summarizing the PD-L1 expression patterns seen in the different histopathological grades of OPMDs and OSCC. This would help visualize the progression of PD-L1 levels.\n\nDiscuss the potential mechanisms by which PD-L1 could promote malignant transformation and tumor progression.\n\nElaborate on the prognostic ability of PD-L1 expression. Does it predict outcomes like recurrence or survival? Correlating PD-L1 levels with clinical outcomes would be informative.\n\nProvide some more background on PD-L1 biology and its significance as a biomarker in the introduction section.\n\nIn the methodology, include details about the PD-L1 antibody clone, dilution, scoring system etc.\n\nSpecify the statistical tests used for correlation analyses.\n\nAvoid excessive use of abbreviations - spell out terms when first introduced.\n\nCarefully proofread the manuscript - there are some minor grammar, spelling and style errors.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "11075",
"date": "13 Apr 2024",
"name": "shelley Durge",
"role": "Author Response",
"response": "The information needed is already shared ."
}
]
},
{
"id": "283658",
"date": "25 Jun 2024",
"name": "Baris Ertugrul",
"expertise": [
"Reviewer Expertise cancer genetic"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study entitled “Association of PD-L1 immunoexpression with the clinicopathological characteristics and its prognostic significance in OPMD and OSCC: A cross-sectional study” investigates the prognostic significance of PD-L1 immunoexpression in OPMD and OSCC. The study is well-designed and included 31 OPMDs and 31 OSCC patients. The authors claim that PD-L1 could play a significant role in the progression from OPMDs to OSCC.\nThe authors have given the sample size calculation formula, but I wonder if the authors used power analysis by using the effect size from similar studies or not.\nInclusion and exclusion criteria should be explained in more detail in the material and method section or better in a table format.\nHow the authors explain that the study is different from others. There are similar tumor marker analyses on already known markers in different studies.\nHead and neck cancer, OPMD, and OSCC are known to be a tumor composed of a heterogeneous population. What do the authors think that only PD-L1 levels are adequate to contribute to this progression?\nSome grammar and spelling errors should be corrected over the whole manuscript. The abbreviation for HNSCC is not included in the Introduction and discussion, the authors should use the abbreviations and they should spell out where it is first used.\nAt the end of the introduction section; “This study focuses on correlating “PD-L1” immunoexpression to clinicopathological characteristics and its prognostic importance in OPMD and OSCC, a new role for “PDL1” has been discovered.” The authors underlined that a new role of PDL1 has been discovered, but one can see there are similar studies in the literature.\nMy decision is; Minor revision.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-668
|
https://f1000research.com/articles/11-1562/v2
|
14 Jun 23
|
{
"type": "Systematic Review",
"title": "Trends of research topics related to Halal meat as a commodity between Scopus and Web of Science: A systematic review",
"authors": [
"Muhammad Nafik Hadi Ryandono",
"Imron Mawardi",
"Lina Nugraha Rani",
"Tika Widiastuti",
"Ririn Tri Ratnasari",
"Akhmad Kusuma Wardhana",
"Muhammad Nafik Hadi Ryandono",
"Imron Mawardi",
"Lina Nugraha Rani",
"Ririn Tri Ratnasari",
"Akhmad Kusuma Wardhana"
],
"abstract": "Background: People are more aware of halal products in commodity markets. Halal meat is an essential commodity for society in the Islamic commodity market in particular. The objective of this study was to analyze differences in research trends related to halal meat in published papers indexed by Scopus and Web of Science. The objective is to observe how was halal meat as commodity become the trend of research written by Indonesian authors, as well as what was the novelty of the research trend related to such tiopic. Methods: This study used purposive sampling with a bibliometric approach in collecting the samples. The samples were published papers from the Scopus and Web of Science (SCI) databases from 2006 to 25th October 2021. The were 154 samples found from cSopus and 50 samples in Web of Science (SCI). Analysis was performed by VOSviewer and biblioshiny. Results: Overall, 154 papers from Scopus and 50 from SCI were analyzed. Scopus and SCI exhibited different research trends. Moreover, papers from Scopus were dominated by Indonesian authors; those from SCI were not. The source growth of published papers in SCI was more dynamic than that in Scopus. The research trends in papers from SCI were more focused on the types of meat and the source itself. This was different to papers in Scopus, which placed greater emphasis on the supply chain. Conclusions: This paper can act as a reference for continued research into halal meat in commodity markets, especially in Islamic countries. This paper is the first to compare the research trends in halal meat in the commodity market by comparing the differences in two major indexes, Scopus and SCI.",
"keywords": [
"Bibliometric",
"COVID-19",
"halal",
"Islamic commodity market",
"meat",
"Scopus"
],
"content": "Introduction\n\nHalal meat has become a popular product globally for which there is rising demand. The number of Muslims across the world has significantly increased in recent decades (Lever and Miele, 2012). Moreover, advancements in technology, especially the appearance of social media, have increased global awareness of the importance of halal products, especially for meat in the commodity market Lever and Miele, 2012. Meat that is labeled as halal must undergo several steps to meet the standardization determined by the Islamic committees in each country. Meeting the required standardization ensures the meat is free from disease and safe to be consumed by humans (Yazid et al., 2020).\n\nHalal meat has become more important since COVID-19 impacted the world, especially in Muslim society. Muslims are only permitted to consume food that is considered halal (Zulfakar et al., 2011). Meat is important for supplying nutrition to the body, especially for the recovery of the human tissues inside the body that have been damaged by the SARS-CoV-2 virus (Naja and Hamadeh, 2020). Without adequate nutrition, the progress of recovery will be impeded, and it may be difficult to survive the SARS-CoV-2 disease (Iftekhar and Cui, 2021). The study of halal meat and its associated supply chains has been enacted by researchers around the world to identify the best solution for sustaining the supply of halal meat. According to a study by Fuseini et al. (2021), halal meat can be considered as the main driving force of local industries in the Muslim world for development in the pandemic era.\n\nIn addition to studies about the supply chain and demand for halal meat in commodity markets, the criteria for halal meat, the process of meat packaging, types of meat, as well as nutritional information are considered to be equally important as the supply and demand factors (Ayyub et al., 2021). Halal products are associated not only with religious beliefs and regulations but also with the impacts and benefits of consuming them. To achieve a better understanding of halal meat as a major area of study, global collaboration of researchers can achieve new breakthroughs in insight related to halal meat (Othman et al., 2021).\n\nInternational indexing of papers may become the way for global academics or researchers to collaborate on research regarding halal meat. A paper is a public format in which results can be reported after a study has been conducted successfully to allow another person or group to continue the study (Afeyan and Cooney, 2020). Papers are often written by a single author to create greater novelty for a study as well as to cover the expenses in conducting a study (Khiste, 2017). Moreover, because of the advancement in digital technology, people could discuss the matter of collaborative research anytime and anywhere. Such advancements in technology have accelerated the publication of scientific papers published each year. There have been an increasing number of innovations reported in papers each year. There are also many international indexes for papers.\n\nStudies which compared halal meat as topic of research from different indexing institutions to journals globally were still few. Moreover, the topic of halal meat as a commodity in the market were minimal, both in Scopus, as well as Web of Science. This study also used the papers that were related to Indonesia as a country with the biggest Muslim community in the world. Within this novelty, this study could give a new insight about the halal meat as a commodity.\n\nMany number of scientific papers can facilitate research activities because they act as a comprehensive source of references as guidance in conducting research processes (Djoussé et al., 2012). It needs a study which could observe the development of the trend topic to understand the novelty that still remains if further research want to conduct research with the same topic. Moreover, it is sessential to conduct study to know how many citations papers raised intended topic. According to the study by Jing, Qiu, Tian, and Hao (2022), number of citation showed that the cited papers observed intended topic are interesting to read and to be used as reference for their own study. Moreover, citation also plays an important role in the indexing of the journal (Mafruchati, Wardhana, and Ismail, 2022). It needs a study to obsreve the development of citation and the development of certain topic of papers that cited many times by academicians. Based on this background, there was a need to observe how the topic of halal products is included in publications. The purpose of this study was to observe the trends in how the topic of halal meat is addressed in published papers indexed by Scopus and Web of Science. The research questions of this paper are as follows:\n\n1. Which indexed institutions had more paper related to the halal meat as commodity?\n\n2. Were Islamic institutions pblished more papers than general institutions?\n\n3. How was halal meat as commodity depicted as research trend in Scopus and SCI?\n\n4. What was the novelty that could be found using bibliometric analysis related to the halal meat as commodity?\n\nCommodity exchange is the trading of goods in the form of commodities between sellers and buyers. There are two types of commodity traded in the market—hard commodities such as raw materials and financial derivatives such as stock. The Islamic commodity market is a commodity exchange that runs according to the principles of Maqasid Sharia.\n\nCommodities themselves are defined as the main merchandize or commercial objects. A commodity can also be defined as a real object that is relatively easy to trade and can be preserved over time. The characteristics of the commodity are that the price is determined by market supply and demand, and not by the supplier or seller. The price of the commodity on the market is based on the calculation of real prices based on the commodity type. Examples are agricultural products, such as coffee, cocoa, sugar, meat, fish, and grains, which are relatively lower than the price of mining-type commodities such as crude oil, gas, coal, and precious metals such as gold and silver.\n\nThe Islamic commodity market is quite different from conventional markets because the market follows the application of Sharia principles. According to the study by Kalimullina and Orlov (2020), there are a few Sharia parameters that must be met for the commodity to be accepted to the market. These were implemented to prevent mutual benefit for all. First, the commodities have to be halal and not illegal goods such as cocaine. Second, the type, quality, and quantity of traded commodities have to be transparent and not fraudulent. Traded commodities should have a clear price from the beginning to the end of the sales according to the contract. The contract itself has to be thoroughly observed and agreed upon by the parties conducting trading of commodities. Commodities have to be clearly owned by the sellers. If there was a time to deliver commodities, the time of delivery has to be clear. The buyer has an obligation to pay the seller for the purchased commodity by the agreed procedure and time based on the agreement (Kalimullina and Orlov, 2020).\n\nAgricultural commodities that are usually traded on the commodity exchange include coffee, sugar, cocoa, soybeans, and corn. In addition, forestry product commodities, such as various types of wood, can also be traded on the commodity markets, both Sharia and conventional. No less important are commodities from livestock products, namely, various types of raw meat, which are differentiated according to the source of the carcass (Kalimullina and Orlov, 2020). Mining commodities such as gold, platinum, and silver actually have a much more expensive price than renewable commodities such as agricultural, forestry, and livestock products (Ahmed and Sarkodie, 2021).\n\nDe Smet and Vossen (2016) stated that meat is a source of protein needed for growth. Moreover, meat is considered as a main ingredient besides staple foods such as grains or corn. Without meat, staple food to be eaten will lose flavor. Lose its flavor means that the staple food would taste bland, and needs some savory things to make the appetite of a person who consume it rise (Ivanović et al., 2016). A lack of protein can also lead to malnutrition, as was seen in children from Yemen or Ethiopia because of civil wars. Meat is rich in protein, fat, and iron, which are needed for the recovery of injured tissues. (De Smet and Vossen, 2016).\n\nThe world has entered the fourth Industrial Revolution, in which digital technology has become immersed in every aspect of human life. Globally, society can access almost all information through the internet. The use of social media in conjunction with the available multimedia technologies can help people become more aware of the importance of halal products, especially in Muslim countries (I Vanany et al., 2021).\n\nA study by Maulidizen (2019) stated that halal products are considered as healthy because Islam prohibits gharar or high-risk economic practices. In economic practice, Islams are prohibited to do any transaction with uncertainty that could lead to a high loss because the risk of the transaction was high. Islam emphasizes the mutual prosperity in economic activities, so that there would not be any parties which suffer great loss.\n\nMeat in commodity markets have to undergo several procedures to be accepted as ‘halal’ or ‘allowed to be consumed’ according to the principle of Sharia (Herianingrum and Shofawati, 2019). The demand for halal meat in the commodity market has become a new trend in the industry, especially for halal certification as a means to develop the industry, so that it can meet the required quantity (Asfia et al., 2021).\n\n\nMethods\n\nThis study used a bibliometric method with a purposive sampling technique, collecting secondary data as the sample for this systematic review. The data were collected from Scopus and Web of Science (SCI) databases, which offer a comprehensive dataset of global publications. For this study, data from Scopus and SCI were selected because these two institutions were the most popular and most demanded for journal indexing in the world (Sa’ed and Al-Jabi, 2020).\n\nAccording to the study conducted by Gretsch, Salzmann, and Kock (2019), Scopus is used as one of the indicator in deciding ranking of university globally. The number of publication, citation, and collaboration with overseas academicians when publishig a paper in Scopus indexed journal are the deciding factor involving publication iinto ranking system. Ranking system such as QS World Ranking used database from Scopus as well as Web of Science. Another ranking institution such as Webometric used Web of Science as one of factor in deciding ranking ofn universities (Mendo et al., 2023).\n\nJournals indexed in scopus and Web of science must passed strict procedure to do so to ensure the quality of the journals. Papers published in journals must be in balance with each issue of those journals published every period (Okagbue et al., 2020). Scopus and Web of Science also demand journals to avoid unethical publication and poor reviewing system in accepting papers. Those two indexing institutions always updated the index of all journals quarterly to maintain the quality of journals as long as removing journals which violatig the ethic of publication and research (Martín-Martín, Orduna-Malea, Thelwall, and López-Cózar, 2018).\n\nThe samples were papers containing the keywords ‘halal’ and ‘meat’ from the Scopus and SCI databases. The typed queries were (TITLE-ABS KEY (“halal”)) AND (((“meat”)) AND (“Indonesia”)) AND (“market”). There were 154 samples found in Scopus and 10 samples in SCI. No samples were removed from either the Scopus or SCI search results. The data were saved in CSV format file and analyzed in three steps (Fahimnia, Sarkis, and Davarzani, 2015).\n\nThe first and second steps were analyzed using VOSviewer. The first step was to analyze the search results to determine the organizations/institutions and countries of the authors who have written papers on the intended topic. The data were presented in Table 1. This study took 13 papers from both Scopus and SCI website with highest citations into the tables according to the study by Prasojo et al. (2019). The data that used for bibliometric were 154 from Scopus and 10 from SCI without being eliminated as long as the abstract, title, or keyword contained queries halal, meat, market, and Indonesia in those papers.\n\nThe second step was analyzing the topics that were closely related to ‘halal’ and ‘meat’ and to determine if there was a significant change over time (Mafruchati, 2020). In the second step, the data were analyzed by Vosviewer using author’s keywords. The data were also analyzed by Vosviewer using index keywords.\n\nThe third step was to analyze the source growth of the topic. Source growth here means that the journals that published papers related to the topic of the source used here was the journals where papers with the intended topic was published. Data for this third step were analyzed using the biblioshiny package version 4.0.0, provided by Studio software (Özdemir and Selçuk, 2021).\n\nVOSviewer is used to showed the subtopics along with the major topic related to the halal meat commodity inside sample papers. Thus, it can showed the affiliation of authors with most cited. However, this study also need biblioshiny from R Studio because VOSviewer cannot depicted the source of growth of sample papers. According to the study by Rogers, Szomszor, and Adams (2020), biblioshiny complemented the analysis in bibliometric combined with other software of bibliometric analysis.\n\n\nResults\n\nTable 1 shows that Indonesia was dominant in the number of papers published. Tenth November Institute of Technology/Institut Teknologi Sepuluh Nopember (ITS) was the institution with the highest number of citations of their papers related to halal and meat. There are only two non-Indonesian universities included in the list. Indonesia has the potential to become the center of the halal industry, especially in the meat industry because it has the largest number of Muslims in the world. Moreover, Indonesia has an abundance of natural resources, both renewable and non-renewable in nature (Mangunjaya and McKay, 2012).\n\nTable 1 showed the 13 papers according to the study by Prasojo et al. (2019) with their affiliations. The paper with the highest affiliations was from Tenth of November Surabaya Institute (ITS), followed by Gadjah Mada University and University of Indonesia. It could be concluded that the technical specialized institution like ITS had more publications about halal meat rather than universities with emphasized Islamic major. Ironically, there was no Islamic universities in those Table 1, means that those Islamic universities had not enough papers with high citations which were related with halal meat.\n\nA study by Ismoyowati (2015) stated that unlike Middle Eastern countries, which are countries that have an Islamic majority and barren lands but an abundant oil and gas supply in commodity markets, Indonesia has both rich land and an abundance of non-renewable resources. Indonesia’s rich soil and abundant mining resources could supply commodity markets with more agricultural products than most Middle Eastern countries, as well as mining commodities. Moreover, there has been no serious conflict or civil war, as has occurred in the Middle East, which has made Indonesia more prosperous in the commodity market (Ismoyowati, 2015).\n\nAnother factor supporting Indonesia’s potential as the center of halal industry is the presence of many Islamic boarding schools that run agricultural businesses and small and medium enterprises (SMEs) that can support the national gross domestic product (Aisyah, 2016). Islamic boarding schools in Indonesia, or so called ‘pesantren’, have a pre-determined set of rules for the people who live there to adhere to in daily life (Huda, 2018). Consequently, they are well disciplined when maintaining the business assigned by pesantren. Pesantren also implements the Sharia principles for conducting business activity with the focus of mutual prosperity, rather than for individual interest (Winarsih, Masrifah, and Umam, 2019).\n\nFigure 2 shows that Indonesia emerged as a trend in index keywords related to halal and meat in 2018. Index keywords in Figure 2 were depicted by using Vosviewer and choosing the feature to ‘create a map based on bibliographic data’ – ‘read data from bibliographic data files’ – select ‘scopus’ – select ‘co-occurences’ – select ‘index keywords’ – select ‘finish’. Then vosviewer would started to extract the index keywords related to the topic of this study automatically. There were 18 index keywords with the highest relation with the topic of this study.\n\nSource: Data processed by Vosviewer.\n\nThe index keyword in Vosviewer were developed by Nees Jan van Eck and Ludo Waltman. It was emphasized on the keywords that were made by the indexing website of journals, such as Scopus, SCI, PubMed, Copernicus, etc. The index keyword was developed based on the content of the paper, so that the keywords represented in a paper would reflect the content of the paper. Keywords of a paper also needed to increase reputation of the paper through search engine optimization (SEO), by using the highest trending word in a field of research, so that the paper would receive more attention from readers and aimed to be cited more. The more a paper is cited by the shcolars, the better the reputation of a journal which published that paper (Van Eck and Waltman, 2014).\n\nFigure 2 showed that there was no sub topic related to technology, especially AI which could help in maintaining the condition of the meat itself. it could be means that p [aper with AI and halal meat as commodity would likely had high novety. Topic related to environment also had phigh novelty if it was correlated with halal meat as commodity. Those two topics would likely had novelty if a paper would be submitted into any journals indexed by scopus.\n\n‘Indonesia’ as an index keyword as shown in Figure 2 is closely related to the topics of ‘food safety’ and ‘animals’. According to the study by Silalahi et al. (2021), food safety is a requirement for halal meat; it is related to the Sharia principles in which the economic activities have to be free from riba/usury, maysir/gambling and speculation, and gharar/high uncertainty that may result in injustice or deceit among any of the parties. Food safety is necessary to reduce the risk that consumers will become sick or poisoned as a result of consuming the meat products (Muslimin, 2019).\n\nOther index keywords such as ‘halal product’ and ‘meat’, which were initially related to the topic ‘halal meat’, were smaller-sized dots than other major index keywords such as ‘Indonesia’, ‘article’, ‘humans’, and ‘animals’. There were fewer papers that discussed meat as a popular topic included in index keywords. ‘Meats’ as an index keyword here was related to other index keywords such as ‘halal products’, ‘supply chain’, ‘food safety’, ‘Indonesia’, and ‘animals’. Meat that is considered as a halal product must be maintained in supply to meet demand (Lever and Miele, 2012), so that market equilibrium can be achieved.\n\nThe supply chain is closely related to the commodity market, especially Islamic markets, because the price of commodities is heavily dependent on supply chains. Without a good supply chain system, the price of certain commodities is unlikely to be cheap and the supply will be scarce. Meat, as a commodity of the Islamic commodity market, also requires a good supply chain process to maintain high quality and to ensure that the criteria for halal certification has been met.\n\nAs for the index keyword ‘animals’, meat was closely related to the animal itself as the source of meat. The type of animal, their health, how they were raised, and the methods of processing the animal carcass were very important considerations for maintaining meat quality. The lower the meat quality, the lower the price; moreover, it would affect to the demand.\n\nIt is shown in Figure 3 that ‘meat industry’ as an author keyword was closely related to the keyword ‘risk’. Here, ‘risk’ could encompass not only the risks that need to be avoided for meat to be labeled as halal but also the risk of business processes involved with halal meat supply chains. The risk of profit loss during the COVID-19 pandemic has become higher since several restrictions have been implemented by each government of several countries. Restrictions such as closing international trade borders to stop dissemination of the virus could lead to a decreased demand for halal meat, which would result in profit loss for the industry. The color of dots of author keywords of ‘risk’, ‘meat industry’, and ‘downstream’ in Figure 3 is evidence that 2020 was a year of downturn in the halal industry.\n\nSource: Data processed by Vosviewer.\n\nFigure 3 also shows the that the author keyword ‘halal supply chain’ is connected to the other keywords of ‘meat industry’ alongside ‘risk’ as noted above. In the Islamic commodity market, especially for raw materials traded on the market, safety procedures for consuming the product are obligations that need to be fulfilled. A common method for preserving meat as a commodity is to freeze it, allowing it to withstand decomposition for a certain period of time. This is the way that the commodity of ‘meat’ can be prevented from carrying the risk of being decomposed and causing health issues for consumers.\n\nAwal Fuseini et al. (2017) explained that in Muslim countries, frozen meat is considered as a healthy halal commodity. After the meat was cut and packed from the carcass, the package then was put in a blast freezer. Frozen meat can last longer than the packages of fresh meat and help sustain the supply chain in the meat industry. By maintaining the supply of meat through storage of frozen material, the prices of meat can be stabilized. Moreover, the industry also benefits because the raw materials are stable and safe for consumption when entering the commodity market.\n\nWith the presence of frozen meat, standardization of the quality of processed products can also be achieved. Frozen meat industries could meet the quota of demand from culinary and tourism industries with intended quality (Awal Fuseini et al., 2017). Supply chains, especially by providing good storage for keeping frozen meat, has the major responsibility for preparing and maintaining the quality of meat so that it is suitable for public consumption. One is by increasing the supply of frozen beef stock, because beef can cater to the demand for halal meat in the commodity market to a greater extent than can other types of halal meat, such as mutton, veal, or poultry (Lever and Miele, 2012).\n\nAs shown in Figure 4, the Journal of Islamic Marketing has been published more papers than other journals related to the topic of ‘halal meat’. IOP Conference Series: Earth and Environmental Science also kept developing until 2021, but to a lesser extent than the Journal of Islamic Marketing. Several other journals increased their productivity in 2020 but decreased it in 2021. It can be concluded that halal meat was a very important topic of analysis for papers published by the Journal of Islamic Marketing.\n\nA study by Ence et al. (2016) stated that the more the study with more specialized major poublish papers, the more insight could be dug from papers by the scholars that needed references. Figure 4 showed that Journal of Islamic Marketing published more paper about halal meat. By publishing paper more with the topic that have been become trends, a journal could gain more reputation by citations.\n\nSource: Data processed by Biblioshiny of R studio.\n\nAs shown in Table 2, papers with the topic of ‘halal meat’ in Web of Science (SCI) are completely different in terms of varieties of affiliation than those in Scopus. There are no Indonesian universities included. However, Malaysian institutions are also included in Table 2. There are also a different number of citations in Table 2, several times higher than that in Scopus. It can be concluded that papers related to ‘halal meat’ in SCI were more commonly cited than those in Scopus. Most of these were universities from non-Muslim countries. This was different from Scopus in that most of the papers related to ‘halal meat’ were affiliated to Indonesian universities.\n\nAs shown in Figure 5, the keyword ‘slaughter’ has become a major keyword that was also connected by dots to ‘cattle’, ‘products’, ‘challenges’, and ‘identity’. ‘Slaughter’ refers to how to correctly slaughter cattle in accordance with Sharia regulations. The keyword ‘products’ refers to the meat from cattle. The keywords above mean that ‘cattle’, ‘slaughter’, and ‘product’ were important considerations to preserve the quality of halal meat. These keywords were popular during 2018, as shown by the color of their dots. The major keywords in Figure 5 are different from those in Figure 1, indicating that papers in Scopus related to halal meat had different popular keywords than papers in SCI.\n\nSource: Data processed by Vosviewer.\n\nIn addition, Figure 5 shows that the dominant keywords in 2020 were “cattle,” “meat quality,” “species identification,” “origin,” and “food.” These keywords showed that the trends of research in SCI were focused more on the types of meat and the source itself. These were different from keywords in Scopus (Figure 2), which were more focused on “supply chain.” The keyword “origin” itself also means the source/animals of the meat. It is essential to know the “origin” of the meat before it is traded in the Islamic commodity market, because only verified halal products can enter the market.\n\nFigure 5 also showed that there was no subtopic related to technology and digitalization. There was also no subtopic related to environment. It means that those subtopics also had higher novelty if it was implemented as a topic of the paper and submitted into any journal indexed by SCI.\n\nAs shown in Figure 6, the major author keywords in SCI were different from those in Scopus. While author keywords related to halal meat were related to risk and supply chain, author keywords from SCI related to ‘meat consumer’, ‘supermarket’, ‘livestock’, and ‘self–identity’. The keywords in Figure 6 were more connected to the target market and included ‘consumer’ and ‘supermarket’. Furthermore, the keyword ‘halal meat’ was also connected to the keyword ‘religion’.\n\nSource: Data processed by VOSviewer.\n\nKabir (2015) stated that people prefer to eat halal meat for religious reasons. As the population of Muslims increases worldwide, the demand for halal meat is also growing. Haroon Latif of Dinar Standards, a company that researches the United States of America (US) halal market, said that there were several reasons behind the consumption of halal meat. The consumption of halal meat is increasing because of the large Muslim population of the world increasing as well (Kabir, 2015). Moreover, many non-Muslims also eat halal meat. There is a growing awareness of what halal meat is among society worldwide, but it has also been proposed that delicious halal food should be made more available in restaurants and at halal food festivals to introduce less familiar products (Masudin, Jie, and Widayat, 2020).\n\nFor meat to be acceptable to Muslim consumers, it must pass the halal certification and food inspection. The label halal itself means that a consumer who buys the product should not be exposed to any risk related to the product they bought (A Fuseini et al., 2021). The meat must also not consist of any parts of a pig. Pork is forbidden to be consumed, even a small piece of fat or the essence of meat itself (Vanany et al., 2019). It is said in the Holy Qur’an that halal products should be consumed and non-halal products should be avoided.\n\nيٰٓاَيُّهَا الَّذِيْنَ اٰمَنُوْا كُلُوْا مِنْ طَيِّبٰتِ مَا رَزَقْنٰكُمْ وَاشْكُرُوْا لِلّٰهِ اِنْ كُنْتُمْ اِيَّاهُ تَعْبُدُوْنَ\n\nO you who have believed, eat from the good things which We have provided for you and be grateful to Allah if it is [indeed] Him that you worship (QS Baqarah: 172).\n\nAs shown in Figure 7, journals related to halal meat from SCI were more dynamic than journals from Scopus with similar topics from 2006 to 2021. Moreover, Figure 7 also shows the prediction of source growth in 2022, which did not exist in Scopus. The most dynamic journals were the Italian Journal of Food Safety and Meat Science. All the papers in the figure show smaller source growth in 2020; despite an increase during 2021, it is projected that they will decrease again in 2022.\n\nSource: Data processed by the biblioshiny package in R studio.\n\nHowever, although the journals shown in Figure 7 were more dynamic, their growth rates were less than those in Scopus. The Italian Journal of Food Safety only grew by 30% in one year, whereas a journal in Scopus grew by more than 75% in one year. The number of journals shown in Figure 7 was also less than in Scopus. As Scopus and SCI have their own market pace for academics who wish to publish papers, the trends in topics would also be different (Martín-Martín, Orduna-Malea, and López-Cózar, 2018).\n\n\nConclusion\n\nBased on the results, it can be concluded that the trending topics in papers related to halal meat were different in Scopus and SCI. However, papers in both Scopus and SCI increased in terms of source growth in 2021. Another finding from our results is that the affiliations of authors who wrote the papers in Scopus were mostly Indonesia, whereas in SCI, authors’ affiliations were more diverse and there were no Indonesian authors. The results also showed that the trends in research in papers in SCI were more focused on the types of meat and the source itself, whereas those in Scopus were more focused on ‘supply chain’. Moreover, the results above showed that novelty was found that no subtopic relaed between halal meat as commodity and digital technology. There was also novelty between the subtopic of environment and halal meat as a commodity. It means that a paper with those topics would likely had novelty if it would be submitted into any journals indexed by Scopus or SCI.\n\nFurther research should focus on the role of frozen meat and frozen storage in maintaining the supply of halal meat in the Islamic commodity market. This could be enhanced with further studies also exploring other raw food materials that need to be put in frozen storage to maintain their condition before entering the commodity market. Moreover, as the Islamic commodity market operates in ways different from those of the conventional market, both should be compared to determine which is better in maintaining the supply of commodities, especially meat products.",
"appendix": "Data availability\n\nZenodo: samples data of publications related to halal meat. https://doi.org/10.5281/zenodo.7260213. (Ratnasari and Wardhana, 2022).\n\nThis project contains the following underlying data:\n\n• Savedrecs.txt (List of papers from Web of Science (SCI) and Scopus reviewed in this study).\n\n• Scopus (3).csv (list of papers from Scopus included in this study)\n\n• SCI - halal meat as commodity.xlsx. (List of papers from Web of Science (SCI) included in this study)\n\nZenodo: PRISMA checklist for ‘Trends of research topics related to Halal meat as a commodity between Scopus and Web of Science: A systematic review’. https://doi.org/10.5281/zenodo.7260213. (Ratnasari and Wardhana, 2022).\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nReferences\n\nAfeyan NB, Cooney CL: Professor Daniel IC Wang: A Legacy of Education, Innovation, Publication, and Leadership. 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PubMed Abstract | Publisher Full Text\n\nKhiste GP: Publication productivity of “consortia” by scopus during 1989-2016. International Journal of Current Innovation Research. 2017; 3(11): 879–882.\n\nLever J, Miele M: The growth of halal meat markets in Europe: An exploration of the supply side theory of religion. J. Rural. Stud. 2012; 28(4): 528–537. Publisher Full Text\n\nMafruchati M: Beef, pork, or lamb? Comparative study between 3 kinds of red meat consumption in the USA toward the number of COVID cases. Systematic Reviews in Pharmacy. 2020; 11(9): 808–812. Publisher Full Text\n\nMafruchati M, Wardhana AK, Ismail WIW: Disease and viruses as negative factor prohibiting the growth of broiler chicken embryo as research topic trend: a bibliometric review. F1000Research.2022; 11(1124): 1124. Publisher Full Text\n\nMangunjaya FM, McKay JE: Reviving an Islamic approach for environmental conservation in Indonesia. Worldviews: Global Religions, Culture, and Ecology. 2012; 16(3): 286–305. Publisher Full Text\n\nMartín-Martín A, Orduna-Malea E, López-Cózar ED: Coverage of highly-cited documents in Google Scholar, Web of Science, and Scopus: a multidisciplinary comparison. Scientometrics. 2018; 116(3): 2175–2188. Publisher Full Text\n\nMasudin I, Jie F, Widayat W: Impact of halal supplier service quality and staff readiness to adopt halal technology on halal logistics performance: A study of Indonesian halal meat supply chain. International Journal of Agile Systems and Management. 2020; 13(3): 315–338. Publisher Full Text\n\nMaulidizen A: Ibn Khaldun’s Economic Thought; The Fair Tax And Its Relevance To The Modern Economy. International Journal of Islamic Business and Economics (IJIBEC). 2019; 3(2): 73–89. Publisher Full Text\n\nMendo AY, Singh SK, Yantu I, et al.: Entrepreneurial leadership and global management of COVID-19: A bibliometric study. F1000Research.2023; 12(31): 31. Publisher Full Text\n\nMuslimin JM: Society, Law and Economy: Contextualizing Ibn Khaldun’s Thought. Al-Iqtishad: Jurnal Ilmu Ekonomi Syariah (Journal of Islamic Economics). 2019; 11: 167–180.\n\nNaja F, Hamadeh R: Nutrition amid the COVID-19 pandemic: a multi-level framework for action. Eur. J. Clin. Nutr. 2020; 74(8): 1117–1121. PubMed Abstract | Publisher Full Text\n\nOkagbue HI, da Silva JAT , Opanuga AA, et al.: Disparities in document indexation in two databases (Scopus and Web of Science) among six subject domains, and the impact on journal-based metrics. Scientometrics. 2020; 125(3): 2821–2825. Publisher Full Text\n\nOthman P, Sungkar I, Bulletin WH-AE, et al.: Malaysia as an international halal food hub: competitiveness and potential of meat-based industries. JSTOR. 2021. Retrieved November 29, 2021. Reference Source\n\nÖzdemir M, Selçuk M: A bibliometric analysis of the International Journal of Islamic and Middle Eastern Finance and Management. International Journal of Islamic and Middle Eastern Finance and Management. 2021; 14(4): 767–791. Publisher Full Text\n\nPrasojo LD, Fatmasari R, Nurhayati E, et al.: Indonesian state educational universities’ bibliometric dataset. Data Brief. 2019; 22: 30–40. PubMed Abstract | Publisher Full Text\n\nRatnasari RT, Wardhana AK: samples data of publications related to halal meat. [Data set]. Zenodo. 2022. Publisher Full Text\n\nSa’ed HZ, Al-Jabi SW: Mapping the situation of research on coronavirus disease-19 (COVID-19): a preliminary bibliometric analysis during the early stage of the outbreak. BMC Infect. Dis. 2020; 20(1): 561–568. PubMed Abstract | Publisher Full Text\n\nSilalahi S, Fachrurazi F; Marketing, A. F.-J. of I et al.: Factors affecting intention to adopt halal practices: case study of Indonesian small and medium enterprises.2021. Retrieved October 5, 2021. Publisher Full Text Reference Source\n\nVan Eck NJ, Waltman L: Visualizing bibliometric networks. Measuring scholarly impact. Springer; 2014; (pp. 285–320).\n\nVanany I, Maarif GA, Soon JM: Application of multi-based quality function deployment (QFD) model to improve halal meat industry. Journal of Islamic Marketing. 2019; 10(1): 97–124. Publisher Full Text\n\nVanany I, Maarif G; Marketing, J. S.-J. of I et al.: Application of multi-based quality function deployment (QFD) model to improve halal meat industry.2021. Retrieved November 29, 2021. Publisher Full Text Reference Source\n\nWinarsih R, Masrifah AR, Umam K: The Integration Of Islamic Commercial And Social Economy Through Productive Waqf To Promote Pesantren Welfare. Journal of Islamic Monetary Economics and Finance. 2019; 5(2): 321–340. Publisher Full Text\n\nYazid F, Kamello T, Nasution Y, et al.: Strengthening Sharia Economy Through Halal Industry Development in Indonesia. International Conference on Law, Governance and Islamic Society (ICOLGIS 2019). 2020; 86–89.\n\nZulfakar M, Jie F; Operations, C. C.-10th A., Supply, undefined, & 2012, undefined: Halal food supply chain integrity: from a literature review to a conceptual framework.2011. Reference SourceReference Source"
}
|
[
{
"id": "180207",
"date": "29 Aug 2023",
"name": "Fadzila Azni Ahmad",
"expertise": [
"Reviewer Expertise Management",
"Islamic Institutions",
"Halal",
"Quality Management and Standards",
"Islamic Epistemology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAbstract:\nSpelling error - cSopus\n\nFrom the abstract, it could be determined that this paper is actually doing the bibliometric analysis and not so much on Systematic Review.\nIntroduction:\nLine 2 - statement related to 'recent decades' should not be based on more than 10 years' reference\n\nLine 4 - reference/citation formatting\n\nPara 2 Line 1 & 2 - The very basics of halal requirements should be based on primary sources in Islam.\n\nPara 6 Line 7 - spelling mistake obsreve\n\nRQ1 - what is meant by 'indexed institutions'?\n\nRQ4 - The authors clearly mentioned that this article used bibliometric analysis and not a systematic review. Authors should be advised to change the title, the objective, and the method from Systematic Review to Bibliometric Analysis. Systematic Review has specific methods and reporting to be included. All of those are not mentioned or discussed in this paper.\n\nPara 1 and 2 under \"Halal products in Islamic commodity markets\" sub-topic should include citations / be supported by references\n\nPara 3 under the above sub-topic - These were implemented to prevent mutual benefit for all: What is meant by this statement?\n\nNo discussion in the Introduction on why 'to observe the trends in how the topic of halal meat is addressed in published papers indexed by Scopus and Web of Science'. What are the justifications for studying the trends of such a topic?\nMethods\nAs mentioned above, this article is not a systematic review article. No reviews were done on the selected articles. In the first paragraph of the Methods section, the authors mentioned that they use the bibliometric method. Suggestion: Change / revise the term systematic review to bibliometric analysis in the title, objective, abstract etc. A systematic review method should have (among others): a PICO template, Inclusion/Exclusion Criteria, Review Matrix, PRISMA flow diagram/checklist - which are not included in the existing article\n\nPara 1 Line 3 - Scopus and WoS are academic databases, not institutions nor journal indexing\n\nThe information on the number of documents from WoS is not consistent between the abstract (50) and the method section (10). Which is the correct one?\n\nThe author should merge the analysis of the 2 databases (Scopus and WoS) instead of doing the bibliometric separately. There are papers that have done bibliometric analysis using both Scopus and WoS, and the analyses were merged together, not done separately.\nResults\nPara 1 & 2 - The countries mentioned in Scopus and WoS are the countries relating to the affiliation of the authors who produced the papers/documents. The author should correct the description of this data/result.\n\n(Subsequent paragraphs)The discussions related to the above point are also misleading\n\nResults and discussions on keywords network using Vosviewer are acceptable\n\nFor figure 4 - source growth: the keywords used by authors on the search strategy specifically focus on Indonesia. This should be mentioned in the discussion. The statement: \"Journal of Islamic Marketing has published more papers than other journals related to the topic of ‘halal meat’\" - is not accurate. Same as the other findings - should highlight that these are actually researches done by authors affiliated with the country of Indonesia.\nConclusion\nLine 1 - As commented earlier, the authors should mention that the findings are for papers produced by authors from Indonesia.\n\nLines 2 & 3 - statement: Another finding from our results is that the affiliations of authors who wrote the papers in Scopus were mostly Indonesia - This is because the authors of this article specifically searched for the key term Indonesia.\nOverall\nAuthors should proofread as there are numerous spelling mistakes\n\nThe method of this article is not a systematic review. The authors should revise.\n\nThe results and discussion should be done accurately and accordingly. There are many inaccurate and misleading conclusions.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": []
},
{
"id": "200435",
"date": "12 Sep 2023",
"name": "Aisyah As-Salafiyah",
"expertise": [
"Reviewer Expertise Islamic Economics",
"Fiqh Muamalah",
"Bibliometrics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article presents several notable points and areas for improvement.\n\nTypographical Errors: The manuscript contains numerous typographical errors, such as \"obsreve,\" \"csopus,\" and \"pblished,\" which should be corrected to enhance the overall quality of the work.\nData Sources: One of the strengths of this article is its use of data from reputable sources; Scopus and Web of Science. This adds credibility to the research.\nOutdated References: The article relies on references that appear to be outdated. This is problematic, especially when making statements that are intended to reflect the current state of knowledge. Updating the references is essential for maintaining the accuracy of the content.\nRelevance of Sentences: There are sentences within the manuscript that do not contribute significantly to the overall discussion. For example, the statement about papers often being written by a single author for novelty or covering study expenses seems extraneous to the main focus of the research.\nResearch Gap and Urgency: While the research gap is identified, the sense of urgency regarding why this research is important is not adequately conveyed. Clarifying the significance and timeliness of the study is crucial.\nResearch Questions: It is advisable to present the research questions in a structured paragraph format to enhance clarity and organization.\nLiterature Review: The literature review appears to lack fundamental and foundational references. Incorporating seminal works related to the topic would provide a stronger theoretical foundation for the study.\nIrrelevant Sentences: Certain sentences, such as the one about malnutrition in children from Yemen or Ethiopia due to civil wars, appear to be unrelated to the main topic and should be omitted.\nMeat and Halal Connection: While the importance of meat is discussed, the link to the concept of \"halal\" is not adequately explored. Expanding on the connection between meat consumption and its compliance with halal principles would be beneficial.\nMethodology References: The article lacks well-known and foundational references in the methodology section. Incorporating references related to the chosen research methods can enhance the rigor of the study.\nDiscussion and Analysis: The manuscript primarily describes the results of bibliometric analysis without engaging in a thorough discussion or analysis. It would be valuable to discuss differences between Scopus and Web of Science, their implications, and potential future research directions.\nWhile the article exhibits strengths in data sourcing, it requires substantial revisions to address typographical errors, update references, improve relevance, strengthen the literature review, and enhance the discussion and analysis sections. Ensuring a clear and scholarly presentation of the research findings is essential for its overall quality and impact.\nThank you!\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? No\n\nIs the statistical analysis and its interpretation appropriate? Partly\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": []
},
{
"id": "200420",
"date": "19 Sep 2023",
"name": "Mohammad Naqib Hamdan",
"expertise": [
"Reviewer Expertise Halal research",
"islamic studies",
"islamic medical ethics",
"islamic bioethics"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral comments:\nI would like to suggest the author(s) send the article to the proofreader or copy editor even better to improvise the sentences.\n\nThere are several words that need to be corrected in term of spelling and terminology\nIntroduction:\nHow much the article that published both on scopus and SCI? How do you differentiate between both index?\n“Halal meat has become more important since COVID-19 impacted the world, especially in Muslim society”. What is the basis/reference and the reason to that?\n“...especially for the recovery of the human tissues inside the body that have been damaged by the SARS-CoV-2 virus”. Is this statement correct? Did the SARS virus attack and damage the human tissues? As far as I know, the virus will cause the respiratory systems, and even the is no ‘tissue’ word in the cited article. Please discuss with someone that has the medical or biology background. Then, if the SARS do not damage the tissue, is it necessary to relate meat with SARS?\nIs it necessary to include this paragraph because it is a common knowledge among researchers? From “International indexing of papers may become the way...” to “also many international indexes for papers.”.\nThese sentences need to be rephrased: “Many number of scientific papers can facilitate research activities because they act as a comprehensive source of references as guidance in conducting research processes (Djoussé et al., 2012). It needs a study which could observe the development of the trend topic to understand the novelty that still remains if further research wants to conduct research with the same topic.”.\nRegularly, author(s) state the research objectives, not research questions because this is the academic article, not a thesis.\nResearch Questions 2: What do you mean by ‘general institution’? What is the purpose to differentiate between the paper that published by Islamic Institute and ‘general institute’?\nThe subtopic “Halal products in Islamic commodity markets” is very general and far compared to the title. I suggest it is more suitable if author(s) did a discussion on ‘halal meat’ rather than ‘halal products’ generally. For example, ‘halal meat in current market’ to show that ‘halal meat’ as one of the major commodity and it’s contribution to food market. Then, you can discuss about what is halal meat, how bigger is halal meat compare to other meat, some statistic related to halal meat.\nWhat is the relation of this paragraph “Agricultural commodities that are usually traded” until “and livestock products” with the subtopic “Meat as an important source of nutrition”? I think that it is too far to be and introduction for the subtopic and it’s better to not include it here.\nThis statement “Without meat, staple food to be eaten will lose flavor. Lose its flavor means that the staple food would taste bland, and needs some savory things to make the appetite of a person who consume it rise” may not accurate compare to the cited reference discussion in the article. Futhermore, the flavor of the food is not necessary depend on the meat. What about vegetarian that dont even eat meat? Supposedly they have the way to flavour the food without meat.\nThe 3rd, 4th and 5th paragraphs in subtopic “Meat as an important source of nutrition” is not match with the subtopic title. Even the connection between these three paragraph also not clear.\nThe elaboration of 4th Industrial revolution and its connection with social media is not well discussed here. If author(s) straightly discuss the use of social media in boost the meat market is more suitable.\nWhat is the connection between ‘healthy’ and ‘gharar’ in this sentence “... stated that halal products are considered as healthy because Islam prohibits gharar or high risk economic practices.”?\nThe relation of this statement “In economic practice, Islam are prohibited to do any transaction with uncertainty that could lead to a high loss because the risk of the transaction was high. Islam emphasizes the mutual prosperity in economic activities, so that there would not be any parties which suffer great loss.” Is not clear. Either you remove it or add the elaboration to show its relationship with the commodity or halal supply chain.\nMethods:\nThe method used in this article is not a systematic review.\nThis study will be focusing on Indonesian scholars but the is no discussion about it in literature review. Besides, what is the purpose of the word ‘Indonesia’? Did the author(s) want to focus on the article published by Indonesia authors only?\nResult:\nIs this statement needed? “Table 1 shows that Indonesia was dominant in the number of papers published”. Author(s) already uses ‘Indonesia’ to filter the output and this word lead to only Indonesia auhtor(s).\nIs this statement “Moreover, Indonesia has an abundance of natural resources, both renewable and non-renewable in nature” need to be elaborated to show the relation with ‘meat industry in Indonesia”.\nTable 1: If you already use ‘Indonesia’ and want to focus on Indonesia authors, why dont you exclude organisation from Australia and Malaysia from the beginning?\nWhy do you use other researcher result in Table 1 and not from your finding? “Table 1 showed the 13 papers according to the study by Prasojo et al. (2019) with their affiliations.”?\nWhat is the connection between this statement with the halal industry in Indonesia? “Islamic boarding schools in Indonesia, or so called ‘pesantren’, have a pre-determined set of rules for the people who live there to adhere to in daily life (Huda, 2018). Consequently, they are well disciplined when maintaining the business assigned by pesantren. Pesantren also implements the Sharia principles for conducting business activity with the focus of mutual prosperity, rather than for individual interest”.\nThis is several detail comments but overall the author(s) need to be more help from copy editor to paraphrase the sentences and align the paragraph accordingly.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? No\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Partly\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": []
}
] | 2
|
https://f1000research.com/articles/11-1562
|
https://f1000research.com/articles/12-665/v1
|
13 Jun 23
|
{
"type": "Systematic Review",
"title": "Innovation in entrepreneurship during the time of COVID-19: a scoping review of the scientific evidence from Peru",
"authors": [
"Víctor Hugo Fernández-Bedoya",
"Monica Elisa Meneses-La-Riva",
"Josefina Amanda Suyo-Vega",
"Rosario Violeta Grijalva-Salazar",
"Johanna de Jesús Stephanie Gago-Chávez",
"Hitler Giovanni Ocupa-Cabrera",
"Sofía Almendra Alvarado-Suyo",
"Giovanni Di Deus Ocupa-Meneses",
"Johanna de Jesús Stephanie Gago-Chávez",
"Hitler Giovanni Ocupa-Cabrera",
"Sofía Almendra Alvarado-Suyo",
"Giovanni Di Deus Ocupa-Meneses"
],
"abstract": "Background: Entrepreneurship involves the actions of designing, launching and managing a business that initially starts small and grows along with the human structure that integrates it. The health crisis caused by coronavirus disease 2019 (COVID-19) had negative effects on health, but also on business; many ventures had to innovate in order to survive in this uncertain environment. Peru is a country located in Latin America, recognized for its high levels of entrepreneurial self-efficacy, so this scooping review sought to identify the experiences of innovation in entrepreneurship in times of COVID-19 in that country. Methods: We explored the Scopus and Scielo databases for records detailing innovation in entrepreneurship in both English and Spanish. Inclusion and exclusion criteria were: published between March 11, 2020, to May 5, 2023; English, Spanish, and Portuguese language; original articles that present both quantitative and qualitative results; within Peru; articles with an assigned issue and volume number. The search results identified 5 Peruvian experiences that met the research objectives. Results: The records identified deal with innovations in social entrepreneurship, women's entrepreneurship, entrepreneurship in the educational sector, and new business tools applied during the COVID-19 pandemic. The sources where these records were disclosed were South American journals (3 cases) and conference proceedings (2 cases). The language of the articles was recorded, identifying that most of them are written in Spanish (official language of Peru). Conclusions: We recommend the regional scientific community to disseminate the results of their research in scientific journals indexed in high-level databases in order to have greater visibility.",
"keywords": [
"Innovation",
"Entrepreneurship",
"COVID-19",
"Peru",
"Review"
],
"content": "Introduction\n\nEntrepreneurship is known as the action involved in the process of designing, launching and managing a business.1,2 Such a business usually starts as a very small enterprise that makes available to customers the sale of a product, service or process.\n\nOn the other hand, the health crisis caused by the coronavirus disease 2019 (COVID-19) pandemic had diverse effects not only on people’s health, but also on the economy.3 Some businesses, due to their nature, had to stop, such as those related to leisure and travel.4 Even businesses related to gastronomy were able to operate with limited seating capacity.5,6 However, many other businesses had to innovate and look for new alternatives to stay in operation.\n\nAccording to information from the Pan American Health Organization, on March 11, 2020, the World Health Organization declared a COVID-19 pandemic, due to the high number of cases in 112 countries outside China.7\n\nIn Peru, on March 5, 2020, the first imported case of COVID-19 was confirmed in a person with a history of travel to Spain, France and the Czech Republic. From that date until July 31, 2022, samples have been processed for 33,131,204 people with COVID-19, resulting in 3,909,870 confirmed cases, 29,221,334 negative cases and 214,303 deaths.7\n\nDuring COVID-19 in Peru, many businesses sought to reinvent themselves through innovation, adopting strategies that allowed them to survive the pandemic and even improve their services in the post-COVID-19 scenario and thus innovating.8–11\n\nInnovation in the business field is known as the strategic process through which a company introduces new products, services or ways of doing things.12 This innovation can be radical (creating something new) or incremental (improving something that already exists).13–15 Business innovation is essential to a company’s long-term growth and survival as it helps maintain a competitive advantage and meet changing customer needs.16,17\n\nIn this sense, it is necessary to identify the experiences of innovation in entrepreneurship in times of COVID-19 in Peru. This country is located in South America, a region known to have high levels of entrepreneurial effectiveness.18,19\n\nThe objective of this scooping review was to identify the experiences of innovation in entrepreneurship in times of COVID-19 in Peru. In addition, we sought to identify the language in which it was written. Finally, we sought to identify the conclusions of each experience explored.\n\n\nMethods\n\nIn order to achieve the research objectives, a scooping review (also known as mapping reviews) was conducted, which aims to identify nature and extent of research evidence (usually including ongoing research).20 We followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist21 to ensure comprehensive and transparent reporting of our scoping review methodology and findings (see Reporting guidelines section below27).\n\nWe scanned the Scopus database, and performed the search equation TITLE-ABS-KEY (“entrepreneurship” “COVID-19” “innovation”) AND (LIMIT-TO (AFFILCOUNTRY, “Peru”)). This means that we searched only for articles with the words entrepreneurship, COVID-19, and innovation in the title, abstract or keywords. Based on the articles found, an additional filter was performed, this time by country, identifying only articles registered in the metadata as coming from Peru. This same procedure was used for searches in Spanish, which is one of the official languages of Peru, by means of the search TITLE-ABS-KEY (“emprendimiento” “COVID-19” “innovación”) AND (LIMIT-TO (AFFILCOUNTRY, “Peru”)).\n\nNext, we set out to explore the Scielo database, which is a Brazilian initiative that facilitates the scientific dissemination of research in South America. We searched in English (entrepreneurship AND innovation AND COVID-19) and Spanish (emprendimiento AND innovación AND COVID-19), and then selected Peruvian experiences.\n\nAfter identifying the accessible articles, we proceeded to define the eligibility criteria, taking the following into consideration:\n\na) Temporality: Due to the recognition of the COVID-19 virus as a pandemic by the WHO from March 11, 2020, to May 5, 2023, we considered these publication dates.\n\nb) Language: We considered papers written in English, Spanish, and Portuguese, as these are the most commonly used languages for scientific dissemination in Latin America, and particularly in Peru.\n\nc) Article type: We considered original articles that present both quantitative and qualitative results on specific innovation experiences in entrepreneurship.\n\nd) Temporal context: Our objective was to identify experiences of innovation in entrepreneurship in times of COVID-19 in Peru, so we only included articles that detail experiences in Peru.\n\ne) Publication status: We only considered completed articles with assigned issue and volume numbers.\n\nThe initial results allowed us to identify 11 records extracted from Scopus and 2 from Scielo, totaling 13 in all. This can be seen in Table 1.\n\nSubsequently, we proceeded to download the records to which we had access. In the case of the Scopus database, the documents were downloaded directly from the platform or through the publisher; if possible (we used the institutional access granted by Universidad César Vallejo). On the other hand, for Scielo, which is a database that provides open access articles, all the identified articles were downloaded directly from its platform. Subsequently, the articles were coded, and the extracted data was processed using Microsoft Excel 2021. Finally, 9 records were successfully downloaded.\n\nThen, 2 records were removed due to exclusion criteria: even though the metadata reported it was located in Peru, the content of them didn’t mention any experience from there.\n\nAdditionally, because 4 different searches were used, 2 duplicate records were identified, leaving a total of 5 articles included in the scooping review.\n\nFinally, each of the final records identified was reviewed. The process followed can be seen in Figure 1, which shows the PRISMA flow chart.\n\nData extraction: A systematic search was conducted in databases such as Scopus and Scielo, utilizing specific search equations and filters. Relevant articles were identified based on the inclusion criteria aligned with the research objectives.\n\nDocument download: Following the identification of accessible articles, the records were downloaded. In the case of Scopus, downloads were obtained directly from the platform or through the publisher, utilizing institutional access provided by Universidad César Vallejo. For Scielo, an open-access database, all identified articles were downloaded directly from the platform.\n\nData coding and processing: The downloaded articles underwent coding, and the extracted data was processed using Microsoft Excel 2021. A customized template was developed to ensure systematic extraction and organization of pertinent data from the articles. Please refer to the additional data file for details.\n\nData verification and confirmation: The analysis and findings were based on the information presented within the articles themselves. The focus of the study was on identifying and synthesizing the articles that met the predefined inclusion criteria, rather than conducting primary data collection or additional verification processes. We relied on the data and information provided by the authors in the articles to conduct our analysis and draw conclusions.\n\n\nResults\n\nIn order to identify the experiences of innovation in entrepreneurship in times of COVID-19 in Peru, we explored the Scopus and Scielo databases.\n\nThe 5 records that responded to the research objective were identified. They are “Innovación y emprendimiento social como estrategia para afrontar la Pandemia COVID-19,22 “Peruana del bicentenario: promotora del emprendimiento en tiempos de crisis”,23 “Post COVID-19 Global Macrotrends in the pedagogical practice to achieve Student Outcomes-ICACIT”,24 “Experience In A Training Program To Strengthen Technological Entrepreneurship Through Technological Tools During The Covid-19”,25 and “Generation of New Ventures in the Face of the New Normality: Approaches from its Ethical-Social Dimension”.26 Their code, title and source can be seen in Table 2.\n\nIn order to identify the experiences of innovation in entrepreneurship in times of COVID-19 in Peru, we explored the Scopus and Scielo databates.\n\nIt was also important to identify the language in which each experience was written. Peru is a country whose mainly official language are Spanish, so it was surprising to find that 2 of the 5 records identified were written in English, considered a foreign language. This is shown in Table 3 and Figure 2.\n\nFinally, the results of each of the experiences identified as records are presented in Table 4.\n\n\nDiscussion\n\nOnly 5 records were identified that met the research objectives. It is important to point out that although it is true that the scientific literature reinforces the fact that Latin America is one of the regions with the highest entrepreneurial self-efficacy, there is not much scientific information detailing experiences of innovation in entrepreneurship in Peru.\n\nAs for the sources from which the information was extracted, it is worth noting that 60% (3 cases) come from Latin American journals, while the rest (40%, 2 cases) were the result of scientific dissemination in conference proceedings format. This reinforces what was said in the previous paragraph, in relation to the low visibility of Latin American authors specialized in this subject.\n\nThe language in which the scientific article was written was also identified. Although it is true that 3 records were written in Spanish and 2 in English, 100% of them had abstract and keywords written in English (even if the remaining content was in Spanish), this shows the will of the authors to obtain more visibility by the international public in search engines. Finally, as for the conclusions of each of the records evaluated, all of them detail limitations due to the “new normality” to which both suppliers of goods/services and consumers had to adapt.\n\nAt the national level, the emergence of social entrepreneurship based on social innovation stands out.22 In the case of women entrepreneurs, it is recognized that the social distancing measures and thus running their businesses from home gave them the opportunity to learn new techniques and apply them to add greater value to their ventures.23\n\nA similar case occurred in education. The third register24 details 10 megatrends employed by this type of institutions at the national level; again, innovation in entrepreneurship is present through the implementation of new good practices. The fourth record25 illustrates the case of a Peruvian university that found it necessary to give virtual classes for more than two years, where to break the monotony, they used digital tools such as social networks, videoconferences, and virtual rooms (Habbo).\n\nThe latest record26 details how entrepreneurs were forced to take their businesses to the next level through innovation, ventured into new sales channels such as e-commerce, trained their employees virtually for the first time, and ventured into online advertising. All this contributed to their survival and consolidation as a company in that difficult moment of uncertainty.\n\nThis study employed a comprehensive search strategy utilizing the Scopus and Scielo databases to identify relevant articles on the topic of innovation in entrepreneurship during the COVID-19 pandemic in Peru. The search equation used specific keywords and filters, ensuring a focused and targeted approach. Additionally, English, Portuguese and Spanish languages were considered, which are widely used for scientific dissemination in Latin America and Peru.\n\nWhile the selected databases provide a wealth of information, it is important to acknowledge that this research may not have captured every possible relevant article. However, the chosen databases are reputable and widely recognized sources of scholarly literature, increasing the credibility and validity of the findings.\n\nThe eligibility criteria were carefully designed to include original articles presenting both quantitative and qualitative results on innovation experiences in entrepreneurship. This rigorous approach ensured that only high-quality, completed articles with assigned issue and volume numbers were considered, minimizing the risk of biased or incomplete data.\n\nThe temporal context of the study encompassed the period from March 11, 2020, to May 5, 2023, aligning with the official declaration of COVID-19 as a pandemic by the World Health Organization. This timeframe provided a comprehensive overview of the innovative efforts in entrepreneurship during this challenging period.\n\nWhile the study focused specifically on Peru, it is important to note that the findings may have implications for other regions facing similar circumstances. The experiences and insights gained from the Peruvian context can serve as valuable references for policymakers, entrepreneurs, and researchers globally.\n\nWe recommend that Latin American researchers contribute to the bibliographic collection detailing experiences of innovation in entrepreneurship, especially in the Peruvian case. Very little specific information on these cases was identified in the Scopus and Scielo databases. We make available to the international community the findings of this article. On occasions, the literature (particularly that written in Spanish) is overlooked and not considered; therefore, we have seen fit to present the conclusions of each record identified in the results section. Finally, we encourage a greater number of review articles on this subject, using new search equations, or exploring other local databases that are not very visible at the international level.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nZenodo: PRISMA-ScR Checklist for ‘Innovation in entrepreneurship during the time of COVID-19: a scoping review of the scientific evidence from Peru’. https://doi.org/10.5281/zenodo.7996424. 27\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nBraun M, Cannatelli B, Molteni M: Risk-managing the business model: locating tripwires at the start. J. Bus. Strategy. Mar. 2022; 43(2): 115–121. Publisher Full Text\n\nWalzer NC, Blanke AS: Business starts in the Midwest: potential entrepreneurial groups. Community Dev. Jul. 2013; 44(3): 336–349. Publisher Full Text\n\nNicola M, et al.: The socio-economic implications of the coronavirus pandemic (COVID-19): A review. Int. J. Surg. Jun. 2020; 78: 185–193. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFernández-Bedoya VH, Meneses-La-Riva ME, Suyo-Vega JA: Ecotourism in Times of Covid-19: A Systematic Review from the Five Continents on How This Activity is Being Carried Out and What Proposals They Have for the Near Future. Acad. J. Interdiscip. Stud. Nov. 2021; 10(6): 1. Publisher Full Text\n\nBilal U, Gullón P, Padilla-Bernáldez J: Evidencia epidemiológica acerca del rol de la hostelería en la transmisión de la COVID-19: una revisión rápida de la literatura. Gac. Sanit. Mar. 2022; 36(2): 160–165. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMessabia N, Fomi P-R, Kooli C: Managing restaurants during the COVID-19 crisis: Innovating to survive and prosper. J. Innov. Knowl. Oct. 2022; 7(4): 100234. Publisher Full Text\n\nThe Pan American Health Organization: Respuesta a la emergencia por COVID-19 en Perú.2022. Reference Source\n\nSharma GD, Kraus S, Srivastava M, et al.: The changing role of innovation for crisis management in times of COVID-19: An integrative literature review. J. Innov. Knowl. Oct. 2022; 7(4): 100281. Publisher Full Text\n\nLim KY, Morris D: Business optimism and the innovation-profitability nexus: Introducing the COVID-19 adaptable capacity framework. Res. Policy. Jan. 2023; 52(1): 104623. Publisher Full Text\n\nGreco M, Campagna M, Cricelli L, et al.: COVID-19-related innovations: A study on underlying motivations and inter-organizational collaboration. Ind. Mark. Manag. Oct. 2022; 106: 58–70. Publisher Full Text\n\nAl-Omoush KS, Ribeiro-Navarrete S, Lassala C, et al.: Networking and knowledge creation: Social capital and collaborative innovation in responding to the COVID-19 crisis. J. Innov. Knowl. Apr. 2022; 7(2): 100181. Publisher Full Text\n\nVecchi VC: Made to Measure & Advanced Manufacturing Toward a New Integration between Tradition and Innovation. Res. J. Text. Appar. Nov. 2012; 16(4): 23–30. Publisher Full Text\n\nYusof N, Kamal EM, Lou ECW, et al.: Effects of innovation capability on radical and incremental innovations and business performance relationships. J. Eng. Technol. Manag. Jan. 2023; 67: 101726. Publisher Full Text\n\nSheehan M, Garavan TN, Morley MJ: The Microfoundations of Dynamic Capabilities for Incremental and Radical Innovation in Knowledge-Intensive Businesses. Br. J. Manag. Jan. 2023; 34(1): 220–240. Publisher Full Text\n\nLennon NJ: Balancing incremental and radical innovation through performance measurement and incentivization. J. High Technol. Managem. Res. Nov. 2022; 33(2): 100439. Publisher Full Text\n\nYusuf M, Surya B, Menne F, et al.: Business Agility and Competitive Advantage of SMEs in Makassar City, Indonesia. Sustainability. Dec. 2022; 15(1): 627. Publisher Full Text\n\nLima Rua O, Musiello-Neto F, Arias-Oliva M: Linking open innovation and competitive advantage: the roles of corporate risk management and organisational strategy. Balt. J. Manag. Jan. 2023; 18(1): 104–121. Publisher Full Text\n\nZapata-Huamaní GA, Fernández-López S: Venture Capital and Technology Entrepreneurship in Latin America: A Comparative Approach. Contributions to Management Science. 2022; pp. 9–26. Publisher Full Text\n\nPrado AM, Robinson JA, Shapira Z: Serving rural low-income markets through a social entrepreneurship approach: Venture creation and growth. Strateg. Entrep. J. Dec. 2022; 16(4): 826–852. Publisher Full Text\n\nGrant MJ, Booth A: A typology of reviews: an analysis of 14 review types and associated methodologies. Heal. Inf. Libr. J. Jun. 2009; 26(2): 91–108. PubMed Abstract | Publisher Full Text\n\nTricco AC, et al.: PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann. Intern. Med. Oct. 2018; 169(7): 467–473. PubMed Abstract | Publisher Full Text\n\nCalanchez Urribarri Á, Ríos Cubas MA, Zevallos Aquino RL, et al.: Innovación y emprendimiento social como estrategia para afrontar la Pandemia COVID-19. Rev. Ciencias Soc. 2022; 28(1): 275–287.\n\nMendoza Aranzamendi JA, Villar YMP, Marquina MCG: Peruana del bicentenario: promotora del emprendimiento en tiempos de crisis. Comuni@cción Rev. Investig. en Comun. y Desarro. Dec. 2021; 12(4): 332–342. Publisher Full Text\n\nAldana C, Revilla M, Saavedra Y, et al.: Post COVID-19 Global Macrotrends in the pedagogical practice to achieve Student Outcomes-‘ICACIT,’. 2020 IEEE International Symposium on Accreditation of Engineering and Computing Education (ICACIT). 2020; pp. 1–4.\n\nEsquicha-Tejada J, Calatayud-Rosado L, Cornejo-Paredes A, et al.: Experience In A Training Program To Strengthen Technological Entrepreneurship Through Technological Tools During The Covid-19. Proceedings of the 19th LACCEI International Multi-Conference for Engineering, Education, and Technology. 2021.\n\nPeña WS: Generation of New Ventures in the Face of the New Normality: Approaches from its Ethical-Social Dimension. Rev. Filos. 2022; 39(1): 391–402.\n\nFernández-Bedoya VH, Meneses-La-Riva ME, Suyo-Vega JA, et al.: PRISMA-ScR Checklist for Innovation in entrepreneurship during the time of COVID-19: a scoping review of the scientific evidence from Peru. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "178661",
"date": "23 Jun 2023",
"name": "Patricia Haas",
"expertise": [
"Reviewer Expertise Public health"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article entitled \"Innovation in entrepreneurship during the time of COVID-19: a scoping review of the scientific evidence from Peru\", a systematic review, presents attributes of scientific cooperation and has indications of strengthening the contribution of informative data regarding the pandemic.\n\nThe review is appropriate for publication and within the expected scope for this type of research.\n\nIt includes enough information and discussions, constructed in a meaningful way so that the article can be accepted. The Objective is aligned with the title and discussion and the finalization contemplates the content of the study. The references used are sufficient and current.\nThe research reinforces and helps clarify the health crisis caused by the coronavirus disease 2019 (COVID-19) with evidence of negative effects on health and business, which reflects the need for innovation to remain in the market. Peru is a country located in Latin America, recognized for its high levels of entrepreneurial self-efficacy, so this Scoping Review sought to identify innovation experiences in entrepreneurship in times of COVID-19 in that country.\nThe research reflects the reality of Peru, located in Latin America, but also contributes to the post-pandemic reality of countries of the same size, thus highlighting experiences of innovation in entrepreneurship in times of COVID-19.\nIt is noteworthy that the research responds to current questions, is elaborated in the recommended protocols and presents a relevant scientific contribution.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "225120",
"date": "27 Jan 2024",
"name": "Mercy Ejovwokeoghene Ogbari",
"expertise": [
"Reviewer Expertise Entrepreneurship and entrepreneurship education",
"business strategy",
"strategic mgt",
"General Business & Management",
"Innovation and technology."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study titled Innovation in Entrepreneurship during the Time of COVID-19: A Scoping Review of the scientific evidence from Peru is contemporary and gives the view that locales are opening up to the realities of the present times. the study is commendable. the objectives are well stated. the study is a short paper however, there were no details of concepts regarding the major constructs. the authors did not specifically underpin any theoretical inclination to the study, and neither was emphasis made to prove that such studies have been expanciated upon. on the methodology aspect, it's quite clear it's a semantic review, I didn't see much of the evidence on the discussion as it relates to the innovation/ technological entrepreneurship being dealt with in the article. the discussions were not detailed, I was wondering what exactly the issues of innovativeness as unveiled at Peru were as regards the highlights of the discussion. its summary is not in-depth as the essence of the study is still hidden. it would be nice if the authors critically revealed the innovative entrepreneurship engaged at during the COVID-19 in Peru. the communication is clear, and the language technicality is ok.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": []
},
{
"id": "350225",
"date": "16 Jan 2025",
"name": "Muzaffar Asad",
"expertise": [
"Reviewer Expertise Entrepreneurship"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Researchers, I appreciate your efforts, you have conducted research on a very interesting topic related to micro small and medium enterprises post COVID because during COVID several firms have faced closure or have faced severe losses which has jeopardized the survival and contribution of the sector. Moreover, you have focused on the green practices which is another major contribution. However, I have realized that while developing the introduction section and justification of the study to show the need for research you have overlooked some important research works which I believe that you must consult to make the paper equipped with more current research in the field. The inclusion of the suggested papers will not only help you to stress over the gaps that calls for further research but also may help you in understanding about the argument that you have built over the topic. Thus, in the introduction and especially, in the Literature where you have written the writeup for the Hypothesis, it is too brief, its better to increase by reviewing more literature and adding detailed discussion over the topic. I strongly recommend you to read and cite and especially criticize the below mentioned studies.\nAsad M, et al., 2024 (Ref 1) Kanaan O, et al., 2024 (Ref 2) Satar M, et al., 2024 (Ref 3) Ta’Amnha M, et al., 2024 (Ref 4)\nAdditionally, in the discussions and conclusions section if you link your findings with the latest research and show separately the practical as well as theoretical contribution of the study, it gives a better impression to the reader and improves the readability of the study. Finally, a good research is one that opens the horizons for new research. Thus, you are suggested to add a separate subheading for limitations faced and recommendations for the future researchers in the same field.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-665
|
https://f1000research.com/articles/12-664/v1
|
13 Jun 23
|
{
"type": "Case Report",
"title": "Case Report: A rare case of mucinous adenocarcinoma of the female urethra",
"authors": [
"Mohamad Rheza Firmansyah",
"Ikhlas Arief Bramono",
"Rachmat Budi Santoso",
"Edward Usfie Harahap",
"Farilaila Rayhani",
"Fielda Djuita",
"Rosalina Rosalina",
"Chaidir Mochtar",
"Mohamad Rheza Firmansyah",
"Rachmat Budi Santoso",
"Edward Usfie Harahap",
"Farilaila Rayhani",
"Fielda Djuita",
"Rosalina Rosalina",
"Chaidir Mochtar"
],
"abstract": "Background: Urethral adenocarcinoma is a very uncommon problem in women, with a prevalence of 0.02%. Due to the disease's rarity, there is very little information available about it. Treatment for cancer can have a significant negative influence on a patient's condition. Mucinous adenocarcinomas are a very uncommon type of cancer that is poorly studied. These cancers almost invariably have a worse outcome compared to conventional adenocarcinomas. Case Presentation: A 67 year old woman presented with hematuria and stranguria. A computerised tomography (CT) scan of this patient revealed an urethral tumor. In her histopathologic report we found the tumor cells were arranged in small clusters and single cells were scattered among extracellular mucin and signet ring cell picture, which is consistent with mucionous adenocarcinoma. We then performed partial urethrectomy with negative surgical resection, but the tumor reappeared 18 months later with no symptoms. The patient then decided to undergo radiotherapy for 33 sessions. From a recent MRI follow up the patient remains recurrence free. Conclusions: Early surgical treatment with or without adjuvant radiotherapy appears to be the best option in cases of small, organ-confined disease of urethral mucinous adenocarcinoma. Partial urethrectomy can be performed in this type of cases, which can prevent the use of permanent urinary catheters and further improve the patient's quality of life.",
"keywords": [
"Mucinous adenocarcinoma",
"partial urethrectomy",
"urethral neoplasm",
"radiotherapy"
],
"content": "Introduction\n\nUrethral adenocarcinoma is a rare neoplasm that makes up for 0.02% of malignant tumors in females.1 There are only a few reports about this neoplasm in Indonesia. Mucinous adenocarcinomas are an extremely rare and poorly understood kind of cancer. These tumors have traits in common with a different class of tumors known as signet ring cell adenocarcinomas, which express mucin inside their cells. Compared to other adenocarcinomas, urethral adenocarcinoma frequently has a poor prognosis.2 The objective of this study was to share our experiences managing a female patient with mucinous adenocarcinoma of the urethra who had been monitored for four years.\n\n\nCase presentation\n\nA 67-year-old, retired single female patient from Indonesia presented with blood and clot gushing out from her urethra. She came with stranguria and hematuria. There was no previous history of urinary retention. The patient had a hysterectomy due to fibroids in 1991 and cholecystectomy in 2017. There was no previous history of cervical cancer in her family. She often consumed red meat and drank coffee. Her menarche history began at 12 years old and menopause was at 51 years old.\n\nWe performed a computerised tomography (CT) scan of the abdomen and suspected a urethral tumor, which was followed by a biopsy. We saw a tissue partially lined with locally hyperplastic transitional epithelial cells showing hyperplastic growth, forming a tumor mass with infiltrative growth from our histological examination. Tumor cells are arranged in small clusters and single cells are scattered among extracellular mucin, some of which form glandular structures. Tumor cells with round-oval nuclei, pleomorphic, hyperchromatic, vesicular, some with nucleolus, eosinophilic cytoplasm, some vacuolated. Tumor cells appear with a “signet ring cell” picture (Figure 1). The stroma is filled with mild to moderate acute and chronic inflammatory cells, with areas of bleeding. No tumor emboli were found in the vessels. It is consistent with mucinous adenocarcinoma.\n\nSubsequently we performed an urethrocystoscopy examination. From our examination we can distinguish between healthy tissue and tumor border. We decided to perform a partial urethrectomy. From the resected tumor, it was found that the surgical resection margins were negative from neoplastic involvement, no lymphovascular invasion was identified. After the procedure the patient had been in remission. However, after 18 months, from Magnetic Resonance Imaging (MRI) examination, recurrence had appeared. From our physical examination, it showed a mass in the urethral area, The patient did not feel any symptoms. Then the patient underwent radiotherapy for 33 sessions. Currently, she remains free of recurrence for 22 months of follow-up (Figure 2). The MRI examination showed no residual mass was seen in the urethral area. No paraaortic, parailiac, and obturator lymphadenopathy was seen. No abnormalities were seen in other intra-abdominal and pelvic organs (Figure 3).\n\nWritten informed consent was obtained from the patient for the use and publication of this clinical image.\n\n\nDiscussion\n\nFemale urethral carcinoma is a condition with a modest prevalence, accounting for 5% of female urological tumor cases and 0.02% of all instances of malignant tumors in women.1,3 Mucinous adenocarcinomas are an extremely rare and poorly understood kind of cancer. These tumors resemble a different class of tumors known as signet ring cell adenocarcinomas, which exhibit mucin inside their cells and nearly always have a poorer prognosis than ordinary adenocarcinomas.2 Our case had the chief complaint of blood coming out of the urethra. Other symptoms that are found in urethral cancer include dysuria, dyspareunia, haematuria, perineal pain, urine retention, overflow incontinence, urethral mass, or a projecting meatal mass. It expands locally into the periurethral tissue, vagina, and vulva before spreading proximally to the bladder neck.3 Patients may present with a wide range of symptoms, the majority of which include dysuria, urine frequency, and a palpable mass. These three symptoms account for 50% of all presenting symptoms.4 Because of the shorter length of the female urethra, local spread tends to be more destructive.4\n\nAccording to research by Neto et al., their patient was hospitalized with stranguria, urine retention, and sero-bloody discharge with stoppers of mucopurulent material in addition to discomfort and burning in the urethra. The patient received surgery therapy such as extended radical vulvectomy and urethrectomy, progressing with the use of indwelling urinary catheter, as well as two sessions of radiotherapy.3 In this case, partial urethrectomy seems adequate not only because of the clear ability to distinguish healthy tissue and tumor tissue, but also to maintain the integrity and function of the lower urinary tract. Another study from Satyanarayan et al. reported a case with mucinous urethral adenocarcinoma. They performed a wide local excision of the tumor and underwent radical cystectomy with ileal conduit. The patient had normal postoperative physical examination results and imaging studies. But during the cystectomy she had persistent microscopic invasive adenocarcinoma in the residual urethra. A recurrence could be avoided with early detection and surgical intervention.4\n\nOne recent study from Baffigo et al. reported a patient with mucinous adenocarcinoma of the bladder. The patient underwent anterior pelvectomy. Six months after surgery, bilateral inguinal lymph node dissection was performed because of bilateral palpable masses and the patient also received external radiotherapy of the inguinal area. After 22-months the patient appears healthy.5\n\nA more recent study from Ndiaye M et al. reported a patient with urethra adenocarcinoma underwent partial urethrectomy. After 16 month follow up, the patient was continent without local and metastatic recurrence.6\n\nFrom this case, with long term follow up we assessed response of urethral adenocarcinoma treated with radiotherapy. A limitation of this study is that the primary cause of the adenocarcinoma is still uncertain. In this case, we learned that performing partial urethrectomy is possible and able to maintain continence. Recurrence had appeared in this patient, but after radiotherapy, the patient currently remains clear from tumor.\n\n\nConclusion\n\nMucinous adenocarcinoma of female urethra is rare and there is no consensus on the optimal therapy due to the scarcity of cases. Early surgical treatment with or without adjuvant radiotherapy appears to be the best option in cases of small, organ-confined disease. Partial urethrectomy can be performed in patients with mucinous urethral adenocarcinoma, which can prevent the use of permanent urinary catheters and further improve the patient's quality of life.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and clinical images was obtained from the patient.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nThyavihally YB, Wuntkal R, Bakshi G, et al.: Primary carcinoma of the female urethra: single center experience of 18 cases. Jpn. J. Clin. Oncol. 2005 Feb 1; 35(2): 84–87. Publisher Full Text\n\nBenesch MGK, Mathieson A: Epidemiology of Mucinous Adenocarcinomas. Cancers (Basel). 2020 Oct 30; 12(11): 3193. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCarvalho Neto JD, Leão SC, Fakhouri R, et al.: Adenocarcinoma of the female urethra: a case report. J. Bras. Patol. Med. Lab. 2016 Sep; 52(4): 266–269. Publisher Full Text\n\nSatyanarayan A, Redd L, Dyer A, et al.: Adenocarcinoma of the urethra with mucinous features. Rev. Urol. 2015; 17(1): 38–41.\n\nBaffigo G, Delicato G, Bianchi D, et al.: Mucinous adenocarcinoma of the urinary bladder. Am. J. Case Rep. 2012; 13: 99–101. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNdiaye M, et al.: Primary urethra adenocarcinoma in women: case report and review of the literature. PAMJ Clin. Med. 2020; 4: 38. Publisher Full Text"
}
|
[
{
"id": "185106",
"date": "14 Jul 2023",
"name": "Ivan Putrantyo",
"expertise": [
"Reviewer Expertise Urology",
"Oncology",
"Nanotechnology",
"Biomaterials",
"Tissue Engineering",
"Pediatric",
"Reconstructive Surgery",
"Stone Surgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper is well written in a good English. The explanation about the patient clinical condition maybe missing some details, but enough for the reader to understand the big picture. Magnetic Resonance Imaging should have been performed in the first place instead of MRI, but it is understandable since the reader was not know at first that it was a urethral tumor. The author may suspect it was bladder tumor so I can understand. I would like the authors to provide the CT Scan and urethroscopy finding in this manuscript so the reader could relate with the author point of view. If the author could not provide those two due to some reasoning, at least the authors should elaborate those finding in a few sentences.\nI would like to ask a question about the clinical reasoning on why the patient was not given a chemotherapy. If the histopathological finding was adenocarcinoma, what is the consideration of the writer to not give the patient chemotherapy regimen for adenocarcinoma like Folfox or Folfiri regimen.\nI think, the author should also emphasize that there is no fistulae when performing urethroscopy to exclude tumor infiltration from other organs.\nThat is my suggestion to improve this manuscript. Overall, this manuscript is good enough. However, there is a lot of room for improvement for this manuscript\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
},
{
"id": "236919",
"date": "12 Mar 2024",
"name": "Ting Zhao",
"expertise": [],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAuthors reported a rare case of mucinous adenocarcinoma of the female urethra. A few comments and suggestions are listed below:\nAuthors stated that “There are only a few reports about this neoplasm in Indonesia” in the Introduction. Please provide a comprehensive overview of global literature regarding mucinous adenocarcinoma of the urethra, including relevant studies, findings, and key insights.\n\nAny immunohistochemical stains performed to help confirm the diagnosis?\n\nThe extracelluar mucin pools are not well presented in Figure 1. Please add a lower power of the H&E photo.\n\nAre there variations in tumor characteristics, aggressiveness, or prognosis between male and female cases of mucinous adenocarcinoma of the urethra?\nOverall, mucinous adenocarcinoma of the urethra is rare. However, several case series have been published (listed below).\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-664
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https://f1000research.com/articles/12-663/v1
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13 Jun 23
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{
"type": "Research Article",
"title": "Vertical jump performance and the relationship with sprint speed at 20 m and 50 m in professional soccer players.",
"authors": [
"Carlos Wheeler Botero",
"Brayan Esneider Patiño Palma",
"Carlos Ramos Parrací",
"Alejandro Gómez Rodas",
"Diego Fernando Afanador Restrepo",
"José Armando Vidarte Claros",
"Carlos Wheeler Botero",
"Carlos Ramos Parrací",
"Alejandro Gómez Rodas",
"Diego Fernando Afanador Restrepo",
"José Armando Vidarte Claros"
],
"abstract": "Background: Jumping and sprinting are essential skills for several sports, especially for soccer, since they allow to determine neuromuscular function and maximum power of the lower extremities in athletes. This study aimed to establish the relationship between vertical jump performance and sprint speed at 20 m and 50 m in professional soccer players. Methods: This study took place from June 2020 to November 2021 with participants from the U20 category of the Colombian professional team Fortaleza CEIF, and the U18 category of the Brazilian professional team Boston City. The vertical jump was assessed with the countermovement jump (CMJ), squat jump (SJ), and rebound jump (RJ) variants using the WheelerJump jump sensor while the sprint was measured using the Winlaborat horizontal encoder. Results: 200 participants from the selected teams were included in this study. Almost perfect correlations (p < 0,05 – r: 0.97) and excellent coefficients of determination (R2: 0.95 – 0.93) were observed between the reactive force index with the mean height of the different jump protocols and the 50-meter sprint speed, indicating that the higher the altitude and/or the higher the reactive force index, the higher the 50-meter sprint speed. The same behavior was found with the 20-meter race, but the correlation levels (p <0,05, r: 0.63-0.62) and the determination coefficients were lower (0.40). Conclusions: The results of this study suggest that, in professional soccer players, long sprint performance like 50 m is strongly correlated and could be accuracy explained by the average height reached in SJ, CMJ, and RJ and by the ability to perform repeated jumps using short contact times, thus increasing the ground reaction forces, which translates into a similar behavior during successive contacts of the player's feet against the ground during the race.",
"keywords": [
"Muscle Strength",
"Jogging",
"Sport psychology",
"Plyometric exercise."
],
"content": "Introduction\n\nSprinting is one of the most used skills in professional soccer; Faude et al. (2012), described that short distance sprinting, with or without the ball is one of the most frequent actions in goal situations; for this reason, power and speed skills are important in decisive moments in professional soccer. Therefore, sprinting should be included in the assessment and training of soccer players. Sprinting is generally performed at distances between 20 m and 50 m and is performed up to 60 times per match, which can change according to the competitive level and playing position (Barnes et al., 2014; Varley and Aughey, 2013).\n\nThe ability to quickly generate and apply force has a dominant role in sprint performance (Slawinski et al., 2017). Different authors reported strong relationships between different neuromuscular capacities and sprint performance in different sports (Cronin and Hansen, 2005; Harris et al., 2008; Loturco et al., 2019). Moreover, different experimental studies described those improvements in muscular power resulted in significant improvements in speed, which may suggest a causal relationship between these variables (Loturco et al., 2015, 2018). In this sense, Morin et al. (2011) proposed that the technical capacity to apply force against the ground has more relevance for sprinting performance than for jumping performance itself (Loturco et al., 2015).\n\nJumping is commonly used to assess muscular power in athletes (Bishop et al., 2021; Carling et al., 2009; Read et al., 2016; Wake et al., 2013), especially in soccer. Different technological devices helped evaluate this capacity and its relationship with sports performance, in the case of soccer, mainly the sprint (Tejada and Suarez, 2013).\n\nIn soccer and several sports, sprinting and jumping are fundamental skills. The former is a cyclic motor task that relies on the mechanical capabilities of the neuromuscular system (Samozino et al., 2016); The second is a form of ballistic pushing movement in which the mechanical function of the neuromuscular system of the lower extremities depends on the maximal power capabilities and each athlete’s optimal force-velocity (F-v) profile (Jiménez-Reyes et al., 2017). Therefore, running and jumping can represent the ability of the athletes' neuromuscular system to produce high levels of strength, which can be transmitted to the ground and maintained through high contraction velocities (Morin and Samozino, 2016).\n\nPrevious evidence suggest that the kinematic and kinetic parameters of the runners’ center of mass (CM) during sprinting and jumping reflects a relationship between the F-v profile and the power-velocity profile (P-v) of both motor tasks (Jiménez-Reyes et al., 2018). Based on the differences in the force vector between sprinting (horizontal) and jumping (vertical), this study aimed to determine the relationship between vertical jumping performance and sprinting speed at 20 m and 50 m in soccer players from two professional teams. We hypothesized a moderate and/or strong relationship between the study variables.\n\n\nMethods\n\nThe research was carried out in accordance with the Declaration of Helsinki, Resolution 008430 of 1993 of the Ministry of Health and Social Protection of Colombia and Resolution 196 of October 10, 1996 of the National Health Council of Brazil and was approved by the committee of ethics of the Santiago de Cali University (CEB-USC-08). Each participant accepted and signed the informed consent, in addition to the informed assent for minors, through which they expressed their voluntary desire to be part of the research project.\n\nThis study was cross-sectional with a quantitative approach and a correlational scope. The sample consisted of 200 soccer players, of which 100 were from the under 20 years old (U20) category of the Colombian professional team Fortaleza CEIF, and another 100 were from the under 18 years old (U18) category of the Brazilian professional team Boston City.\n\nFootball players under the age of 20 were recruited who willingly wanted to participate in this research. Therefore, the sample was constituted at convenience. The players studied had more than six years of sports history, of which the last ones were specifically in soccer. They did not present any medical condition that could prevent them from participating in the testing sessions.\n\nData collection started in June 2020 and ended in November 2021. Before the testing session, the participants performed a standardized warm-up of 20 minutes. The warm-up consisted of an aerobic activity with an intensity of 75% of the maximum heart rate measured by heart rate monitor (Polar Monitor, H10); then, the participants executed a neuromuscular activation through short and explosive movements of high intensity (sprint, multi jumps, changes of rhythm). The participants performed five repetitions of sprint in 5m with one minute rest, five repetitions of zigzag running in 10m, with the same rest time, and four series of five vertical jumps with knee elevation with one minute rest between each series, based on the protocol applied by Patiño-Palma et al. (2022).\n\nThe jump assessment was performed with the WheelerJump photoelectric sensor (Version 2-3, Wheeler Sports Tech, Tampa Florida), which has reported concurrent validity (Rho 0.92-0.99) and reliability (ICC 0.91-0.98) in athletes from different sports (Patiño-Palma et al., 2022). The squat jump (SJ), countermovement jump (CMJ), and rebound jump (RJ) were used to determine lower limb power. For the SJ, the participants performed a vertical jump starting from the half squat position (knees bent at 90°), with the trunk upright and with the hands placed at the waist. For the CMJ, the participants performed a vertical jump starting from a two-legged position with an upright trunk and hands on the waist, then performed a quick downward movement and immediately after a quick upward countermovement to achieve the highest possible height. Finally, for the RJ, participants used the same technique as the CMJ and executed the highest number of successive jumps in 10s with the shortest contact time and the highest height in each jump. The average height RJ in 10s was calculated, and the RJ allowed us to calculate the Reactive Strength Index (RSI) by dividing the flight time over the contact time and then averaging the RSI of each jump performed in the test (Jarvis et al., 2022). The elastic percentage (% elastic) was determined from the percentage difference between the SJ and the CMJ (Kozinc et al., 2022).\n\nThe technique of each jump was explained to the participants. Two practice jumps were performed for each protocol to achieve the correct technique for each jump. Knee angle was monitored in the sagittal plane using real-time video digitizing software (Simi Motion® 2D). We developed sprint assessments at 20 m and 50 m in which the participants covered the distance of 20 m and 50 m in the shortest time possible. The best time in seconds of two trials was recorded. The participants had two minutes to rest between each trial. The evaluation was performed with a horizontal encoder (Winlaborat, Buenos Aires, Argentina) with a sampling capacity of 100/1000 Hz and a maximum evaluation distance of up to 110 m.\n\nThe statistical analysis was performed with R version 4.1.3 under the R Studio interface R; we reported means, standard deviations (SD), and 95% confidence intervals (CI) for each variable. We tested if the variables had a normal distribution using the Crawley's graphical methodology, which is a tool that compares the behavior of observed data with those expected in a normal distribution (Crawley, 2015) (Figure 1) and the Shapiro-Wilk test, which is recommended with large sample sizes (Seier, 2011). Since the data was non-parametric, we performed a correlation analysis using the Spearman's correlation coefficient.\n\nWe categorized the correlations based on the following thresholds for the effect sizes: <0.1 trivial; 0.1-0.3 small; 0.3-0.5 moderate; 0.5-0.7 large; 0.7-0.9 very large; and >0.9 almost perfect (Hopkins et al., 2009). Finally, the coefficient of determination was applied to define the coincident pattern not explained by chance between the study variables.\n\n\nResults\n\nA total of 200 soccer players from two professional soccer teams were evaluated (age: 17.45±2.3 years). Table 1 shows the descriptive data of the performance of the different jumps executed and the 20 m and 50 m sprint tests.\n\nA mean SJ height of 34.88±3.31 cm, CMJ of 41.08±4.24 cm, and an average of 34.95±4.54 cm for the RJ. For the RSI evaluated in 10 s a mean value of 2.37 was determined, being a result between moderate to high as established in the work of Healy et al., 2018. Regarding the speed, in the evaluated soccer players, a better performance is evidenced in the sprint at 50 m compared to the sprint at 20 m (7.06±0.62 m*s-1 vs. 6.32±0.40 m*s-1).\n\nFigure 2 shows the correlation coefficients between time and sprint of the different distances evaluated with the variables resulting from the different jumping protocols. Average jump height in absolute terms was significantly correlated with running performance in 20-m and 50-m sprints. The strength of these correlations were moderate to strong. (average height vs Speed 20 m: P<0.05; r: 0.63; IC: 0.55-0.72; average height vs Speed 50 m: P<0.05; r: 0.97; IC: 0.96-0.98).\n\nA positive correlation between moderate and high was found between the RSI in 10 s and the sprint speed at 20 m and 50 m (RSI vs Speed 20 m: P <0.05; r: 0.62; IC: 0.51-0.69; RSI vs Speed 50 m: P<0.05; r: 0.97; IC: 0.89-0.98). Meanwhile, the elastic percentage had a positive and moderate correlation with CMJ (P<0.05, r: 0.54; IC: 0.51-0.68) and a negative and small correlation with SJ (P<0.05; r: -0.47; IC: -0.62 to -0.42).\n\nGiven the strong correlation between jump height and RSI with 50 m sprint performance, the coefficient of determination was applied to explain the coincident pattern between these variables (Figure 3). These coefficients varied between 0.4 and 0.9, showing an intensity between moderate and strong.\n\n\nDiscussion\n\nThe study aimed to determine the relationship between vertical jump performance in SJ and CMJ variants and sprint speed at 20 m and 50 m in professional soccer players. We found a strong and positive correlation between the sprint speed at 50 m with the average height RJ in 10 s (0.97) and the RSI in 10 s (0.97), while a moderate positive relationship was found between elastic % and CMJ (0.6) and an inverse and negative correlation was established with SJ (-0.53). This means that average jump RJ in 10 s and the reactive force are linked to performance in 50 m sprint and that a higher CMJ the better elastic % was developed. Furthermore, the elastic percentage was not found to be linked to SJ performance since this jumping variant precisely eliminates the elastic energy input in its execution. The last is related to the shortening-stretching cycle, a common phenomena that reveal how elastic energy enhance motor performance and the specific contribution of contractil and elastic components of muscles in explosive elastic motor tasks like CMJ (Turner and Jeffreys, 2010).\n\nIn relation to jump height and its association with sprint performance, our findings are consistent with that evidenced by Köklü et al. (2015); Rodríguez-Rosell et al. (2017) and Zileli and Söyler (2021) who also reported strong relationships between vertical jump and sprint performance. However, these authors evidenced this strong relationship in short sprint like 20 m and 30 m. Moreover, we found strong correlation between RSI in 10 s and 50 m sprint performance, which agree with the substantial relation stablished between these two variables in other studies (Jarvis et al., 2022). However, in the case of the present study, this relationship was solid with long sprinting type 50 m.\n\nWe observed a moderate correlation coefficient between average jump height RJ in 10 s and RSI in 10 s with speed sprint in 20 m (0.63 and 0.62). Considering that the correlation between RSI 10s and sprint in 20 m is lower than the correlation between RSI and sprint in 50 m, the hypothesis that RSI correlates better with long sprints than for short distances sprints is supported. Thus, the capacity to sustain high levels of muscular power in very short contact times with high rates of explosive force development is better explained by the RSI (Barker et al., 2018), especially for long-distance sprints. The last is reinforced by the highest goodness of fit between the RSI in 10 s and the sprint performance in 50 m evidenced by the coefficient of determination in this study (0.937).\n\nOur data are particularly relevant in the sense that, even though jump height has been the most used and functional variable to represent the explosive and elastic components of strength using the SJ and CMJ, respectively, the RSI by normalizing jump height or flight time with ground contact time, has been reported as a more accurate variable to quantify jump performance and reflects to a better way the mechanicals phenomena during these movement patterns (Barker et al., 2018).\n\nOur findings in regards to a strong correlation between average jump height RJ in 10s with long distances sprints like 50 m (0.97) are in agreement with Shalfawi et al. (2011). Who evaluated professional basketball players finding progressively higher correlations between sprint speeds at 10, 20, and 40 m with jump height in SJ (0.53, 0.57 and 0.74, P<0.05) and CMJ (0.45, 0.49 and 0.74, P<0.05), suggesting that sprint performance depends on a substantial variation and combination of muscle performance factors. Similarly, Barr and Nolte (2011) found progressively higher correlations for both SJ and CMJ in female rugby players as fractional sprint distance increased from 0-10 m, 10-30 m, and 30-60 m (-0.53 to -0.74, P<0.05); however, they did not find a significant association between sprint performance and RSI.\n\nContrary to our results, Healy et al. (2019) evaluated male and female sprint athletes and did not find significant correlations between RSI and fractional sprint performance of 0-10 m, 10-20 m, 20-30 m, and 30-40 m, possibly due to prolonged contact times related to the measurement method with the vertical jump variant drop jump (DJ). Moreover, Jones et al. (2016) reported low to moderate correlations in female rugby players between sprinting at 5, 10, 15, 15, 20, 30, and 40 m and jump height in SJ and CMJ (-0.41 to - 0.61, P<0.05), however, they only found a significant correlation between RSI and sprint speed at 30 m also using DJ as measurement protocol.\n\nIn contrast, in accordance with our findings, Loturco et al. (2019) evidenced moderate to high correlations in elite field and track athletes between sprint speed and vertical jump performance in SJ (-0.79 to - 0.83, P<0.05) and CMJ (-0.76 to - 0.80, P<0.05) that became stronger as sprint distance increased from 10 to 60 m. However, did not find significant correlations between sprint distance and RSI using DJ as the measurement protocol. In addition, Smirniotou et al. (2008) also using DJ, found a significant correlation between sprint distances at 10, 30, 60, and 100 m with RSI increasing in strength of association as sprint length increased in regional level sprint athletes.\n\nFollowing what we suggest, Lockie et al. (2014) when evaluating recreational field athletes, found moderate correlations between fractional sprint distances of 0-10, 0-20, and 0.40 m for both CMJ (- 0.721 to -0.629, P<0.05) and RSI (-0.53 to - 0.68, P<0.05) using DJ as the measurement protocol. Likewise, Furlong et al. (2021) after evaluating semi-professional Rugby players, found moderate correlations between sprint time at 30 m with SJ (-0.695, P<0.01), CMJ (-0.665, P < 0.01) and RSI assessed with DJ protocol (-0.685, P<0.01) demonstrating the relevance of the evaluation of these variables in the control and monitoring of sprint performance.\n\nConcerning the RSI, all the studies mentioned above used the DJ vertical jump variant for its calculation, but only some studies have used repeated vertical jumps (RJ) for its estimation. In this sense, Nagahara et al. (2014) determined the relationship between the 60 m sprint in athletes specialized in 100 m flat distance with the performance in SJ, CMJ, and RJ using the six repeated jumps method for the latter and using the best RSI of the five available bounces between jumps as the final data. Although they found moderate correlations between the 60 m sprint with SJ (-0.55, P<0.05) and CMJ (-0.52, P<0.05), no significant correlations were found with RSI (-0.07). Likewise, Kariyama and Zushi (2016) determined the relationship between the 60-m sprint with kinetic parameters of torque and power using a force platform and sagittal plane motion data captured by a high-speed video camera during the execution of five repeated jumps, finding moderate correlations between 60 m sprinting with knee and ankle torque in both concentric (0.736 - 0.674, P<0.05) and eccentric (0.616-0.719, P<0.05) phases without finding significant correlations with RSI (0.295).\n\nAll of these considerations regarding our findings show contradictory and diverse results that may be associated with the type of athletes assessed, the evaluation methods and protocols used, and how we calculated the reactive strength indexes. In this regard, this study has some limitations. First, due to the cross-sectional nature of this study, it is impossible to establish causality. Second, using the RSI calculation based on the mean of repeated jumps over time did not favor the comparison with other studies. Third, the specific physical characteristics of the soccer players evaluated, who are in the training process, not only affected the results of the variables addressed in this study but also their comparison with other groups of athletes. For these reasons, the implications of our findings must be contextualized, verified, and replicated in future research.\n\n\nConclusions\n\nThe ability to sprint over long distances such as 50 m is essential for athletic performance and success in soccer. The results of this study suggest that, in professional soccer players, performance in this type of sprint is strongly associated with the ability to perform repeated jumps using short contact times, thus increasing ground reaction forces, which results in similar behavior during successive contacts of the soccer player's feet against the ground during running in typical strategic offensive and defensive tasks in this sport. Furthermore, considering the strong correlation between the RSI in 10s and the 50 m linear sprint suggested by our results, it is also convenient to recommend its inclusion to monitor and control of curved sprint performance as pointed out by Loturco et al. (2020); therefore, its relationship with other manifestations of motor performance should also be addressed.\n\nThe practical applications inferred from our findings are related to optimal monitoring, planning, and control training in soccer players. First, given the strong correlations between long sprinting and RSI in 10 s is relevant to suggest that the RJ performance in 10 s may be an easy and saved time way to infer and explain the 50 m sprint performance in soccer players and its inclusion in future research in other sports and performance conditions that involve the use of high-power production in a short time. Second, this assessment method can be used to plan, control, and program the training process with particular focus on the reactive strength performance and its impact on quick technical skills used in soccer and other sports with similar characteristics. Third, in this context, the periodic evaluation by this method can reflect the velocity-based movements in soccer and bring out the capacity to support long-distance linear sprints in these athletes used frequently in offensive and defensive strategic movements. Finally, concerning elastic percentage, namely the SJ and CMJ difference, since this variable explains the contribution of the series and parallel elastic components of the muscles during the jump performance, it is highly useful to identify by separate the unique biomechanics characteristics of these two components and their contribution to explosive strength profile in these athletes. However, these considerations must be interpreted with caution because the changing behavior of these same variables in other studies.",
"appendix": "Data availability\n\nMendeley Data: Vertical jump performance and the relationship with sprint speed al 20 m and 50 m in professional soccer players, https://doi.org/10.17632/z727frmfdw.1 (Wheeler et al., 2023).\n\nThe project contains the following underlying data:\n\n• base datos.xlsx (Anonymized results from jumps, average height, and speed).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nBarker LA, Harry JR, Mercer JA: Relationships between countermovement jump ground reaction forces and jump height, reactive strength index, and jump time. J. Strength Cond. Res. 2018; 32(1): 248–254. PubMed Abstract | Publisher Full Text\n\nBarnes C, Archer DT, Hogg B, et al.: The evolution of physical and technical performance parameters in the english premier league. Int. J. Sports Med. 2014; 35(13): 1095–1100. 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PubMed Abstract\n\nPatiño-Palma BE, Wheeler-Botero CA, Ramos-Parrací CA: Validación y fiabilidad del sensor Wheeler Jump para la ejecución del salto con contramovimiento. Apunts Educación Física y Deportes. 2022; 149: 37–44. Publisher Full Text\n\nRead PJ, Oliver JL, Croix MBDS, et al.: Consistency of Field-Based Measures of Neuromuscular Control Using Force-Plate Diagnostics in Elite Male Youth Soccer Players. J. Strength Cond. Res. 2016; 30(12): 3304–3311. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRodríguez-Rosell D, Mora-Custodio R, Franco-Márquez F, et al.: Traditional vs. Sport-specific vertical jump tests: Reliability, validity, and relationship with the legs strength and sprint performance in adult and teen soccer and basketball players. J. Strength Cond. Res. 2017; 31(1): 196–206. PubMed Abstract | Publisher Full Text\n\nSamozino P, Rabita G, Dorel S, et al.: A simple method for measuring power, force, velocity properties, and mechanical effectiveness in sprint running. Scand. J. Med. Sci. Sports. 2016; 26(6): 648–658. PubMed Abstract | Publisher Full Text\n\nSeier E: Normality Tests: Power Comparison. International Encyclopedia of Statistical Science. Springer Berlin Heidelberg; 2011; (pp. 1000–1003). Publisher Full Text\n\nShalfawi SAI, Sabbah A, Kailani G, et al.: The relationship between running speed and measures of vertical jump in professional basketball players: A field-test approach. J. Strength Cond. Res. 2011; 25(11): 3088–3092. Publisher Full Text\n\nSlawinski J, Termoz N, Rabita G, et al.: How 100-m event analyses improve our understanding of world-class men’s and women’s sprint performance. Scand. J. Med. Sci. Sports. 2017; 27(1): 45–54. PubMed Abstract | Publisher Full Text\n\nSmirniotou A, Katsikas C, Paradisis G, et al.: Strength-power parameters as predictors of sprinting performance. J. Sports Med. Phys. Fitness. 2008; 48(4): 447–454. PubMed Abstract\n\nTejada C, Suarez G: Correlación entre la potencia en miembros inferiores (altura de despegue del salto) medida con protocolo de Bosco y la velocidad frecuencial (medida con el test de 30 y 60 metros planos) de la selección Colombia femenina y masculina de ultimate frisbe. Revista de Educación Física. 2013; 2(1): 147–162.\n\nTurner AN, Jeffreys I: The stretch-shortening cycle: Proposed mechanisms and methods for enhancement. Strength and Conditioning Journal. 2010; 32(4): 87–99. Publisher Full Text\n\nVarley MC, Aughey RJ: Acceleration profiles in elite Australian soccer. Int. J. Sports Med. 2013; 34(1): 34–39. PubMed Abstract | Publisher Full Text\n\nWake M, Lycett K, Clifford SA, et al.: Shared care obesity management in 3-10 year old children: 12 month outcomes of HopSCOTCH randomised trial. BMJ (Online). 2013; 346(7913) PubMed Abstract | Publisher Full Text | Free Full Text\n\nWheeler Botero C, Patiño-Palma BE, Ramos Parraci CA, et al.: Vertical jump performance and the relationship with sprint speed at 20 m and 50 m in professional soccer players. Dataset. Mendeley Data. 2023; V1. Publisher Full Text\n\nZileli R, Söyler M: The Examination of the Relationship between Sprint and Vertical Jump in Soccer Players. MANAS Sosyal Araştırmalar Dergisi. 2021; 10(1): 485–491. Publisher Full Text"
}
|
[
{
"id": "199174",
"date": "31 Aug 2023",
"name": "Elena Mainer-Pardos",
"expertise": [
"Reviewer Expertise Sport sciences"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the opportunity to review this article. The paper addresses a novel under-researched area, which has the potential to provide useful recommendations for coaches. However, there are some questions that need to be addressed to the manuscript.\nSpecific comments are provided below:\nINTRODUCTION\nCenter the introduction around soccer. There is an extensive bibliography available to develop it in line with the chosen topic.\n\nWhile you have mentioned several studies, it would be helpful to briefly explain why these studies are relevant or significant to your introduction. This will help the readers understand the context and importance of these studies in relation to your topic. (Paragraph 2, 3 and 4)\n\nThere is some repetition of points. For example, you have mentioned that sprinting is frequently used in soccer and that power and speed skills are important in decisive moments. You can consolidate these points to avoid redundancy.\n\nWhen introducing technical terms like \"force-velocity (F-v) profile\" or \"power-velocity (P-v) profile,\" consider providing brief definitions or explanations to ensure that all readers. (Paragraph 4 and 5).\n\nAdd examples of different sports (“Different authors reported strong relationships between different neuromuscular capacities and sprint performance in different sports”)\n\nAdd references related to “especially in soccer”\n\nAdd examples of “technological devices”\nMETHODS\n1. Ethical statement\nWhile you have e mentioned informed consent and assent, you can briefly explain what this mean. Informed consent signifies the participants' understanding of the research's purpose and their voluntary agreement to participate. Informed assent for minors involves their understanding and agreement to the extent they are capable.\n\nIncorporate the signature of parents or legal guardians for minors.\n2. Study design\nProvide more context about why you chose a sample of 200 soccer players, specifically 100 from the under 20 years old category of the Colombian professional team Fortaleza CEIF, and another 100 from the under 18 years old category of the Brazilian professional team Boston City. Explain how this sample size and composition were relevant to your research goals.\n\nDescribe the recruitment process in more detail. How were the football players under the age of 20 recruited? Did you have any inclusion or exclusion criteria for participation? Also, clarify whether this convenience sample was used due to specific practical reasons or limitations.\n\nIncorporate the number of training days and minutes per week for each professional team.\n3. Data collection\nWhy were data collected for more than one season?\n\nWhat were the temperature and humidity levels during the tests?\n\nWhere were the tests conducted? On a soccer field? If so, was it natural or artificial turf?\n\nWhat type of trainers were utilized by the players?\nRESULTS\nWhy was not the sample divided into two groups based on age (U18 and U20), considering the substantial sample size? This would have allowed for a comparison between the two groups.\nDISCUSSION\nInsert \"r\" (correlation) before the numerical values: 0.97, 0.6, and 0.53. Review the entire discussion for this correction.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-663
|
https://f1000research.com/articles/12-659/v1
|
13 Jun 23
|
{
"type": "Research Article",
"title": "Outcomes of a fixed-dose combination of sucralfate, metronidazole, and lidocaine in patients undergoing anorectal surgery: Results from a prospective, single-centre study",
"authors": [
"Niranjan Agarwal"
],
"abstract": "Background: Various topical applications provide varying pain control outcomes among patients undergoing surgery for anorectal conditions like haemorrhoids, anal fissures, and anal fistulae with varying outcomes. We evaluated the outcomes of a fixed-dose combination of sucralfate, metronidazole, and lidocaine as a local application following anorectal surgery. Methods: This was a prospective, single-arm, single-centre study with 50 patients who underwent anorectal surgery. Coprimary endpoints were 1) proportion of patients with minimal clinically important difference (MCID) defined as 10-point reduction in 100-mm visual analogue scale (VAS) score and 2) mean reduction in anal pain on VAS, from baseline to 3 and 6 weeks after surgery. Proportion of patients with complete wound healing and reduction in symptoms of itching, bleeding, and burning and incidence of adverse events (AEs) and tolerability were also assessed. Results: Of 50 patients, 18.0%, 26.0%, and 56.0% underwent haemorrhoidectomy, fissurectomy, and fistulectomy, respectively. All patients achieved MCID at week 3, which was maintained at 6 weeks. The mean VAS score for anal pain reduced significantly from 68.6 at baseline to weeks 3 and 6, respectively (p<0.001). The pain score reduced significantly by 36.5 and by 59.4 at weeks 3 and 6, respectively, in patients who underwent haemorrhoidectomy, by 43.5 and 71.7 at weeks 3 and 6, respectively, in patients who underwent fissurectomy, and by 37.6 and 61.2 at week 3 and 6, respectively, in those who underwent fistulectomy. The mean changes in itching, bleeding, and burning scores at weeks 3 and 6 reduced significantly in the total cohort and in the subgroups. Complete wound healing was achieved in 40.0% of patients by week 6. No AEs were reported and the study medication was well tolerated. Conclusion: The topical FDC was effective, with a good safety and tolerability profile, in patients undergoing surgery for anorectal conditions. Clinical trial registration: CTRI/2020/11/029298.",
"keywords": [
"Anorectal surgery",
"postoperative pain",
"wound healing",
"haemorrhoids",
"fistula",
"anal fissures"
],
"content": "Introduction\n\nAnorectal conditions are commonly seen in clinical settings and patients usually present with rectal pain, rectal bleeding, or purulent discharge.1 Common anorectal conditions include haemorrhoids, anal fissures, and anal fistulae. About 10 million people suffer from haemorrhoids every year. A study estimated that >50% of the US population aged above 50 years has experienced haemorrhoids. The common symptoms of haemorrhoids include painless rectal bleeding, itching, soiling, perianal irritation, or mucus discharge. Patients with grade 4 haemorrhoids or those in whom conservative treatment has failed require surgery.2 The overall prevalence of haemorrhoids is estimated to be 38.9%, with grades III and IV occurring in 8.16% and 0.53% of people, respectively.3 An anal fissure is an elongated ulcer in the longitudinal axis of the lower anal canal. Symptoms of anal fissure include pain on defecation, bright red bleeding, mucus discharge, and constipation. The pain causes contraction of the internal anal sphincter, which leads to further pain, especially during defecation.4 Many patients do not respond to conservative management, and surgery is necessary.5 A fistula-in-ano is a tract lined by epithelium, connecting the anal canal to the perianal skin. It usually occurs following an anorectal abscess. It requires surgical treatment in the majority of cases.6\n\nAmong patients undergoing anorectal surgeries, postoperative pain is common, which can be quite severe and delay return to daily activities. The causes of postoperative pain include internal anal sphincter spasm, inflammation, and bacterial contamination of the operative site; the cause of pain can also depend on the type of surgery.3,7 Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) used for pain control have short duration of action and several adverse effects.3 Topical preparations are preferable because of better bioavailability and fewer adverse effects.7 Various topical applications have been used for pain control following anorectal surgery, e.g., botulinum toxin, calcium channel blockers, glyceryl trinitrate, local anaesthetics, metronidazole, opioids, sucralfate, and others, but their reported outcomes are variable.8 Metronidazole acts against enteric anaerobes, which can colonize the wound after haemorrhoidectomy leading to inflammatory pain. Sucralfate is the aluminium hydroxide salt of the disaccharide sucrose octasulphate. It has been used as a cytoprotective agent for the treatment of gastrointestinal ulcers. It has antimicrobial and antioxidant activity and stimulates prostaglandin E2 (PGE2) secretion leading to increased blood flow and mucus formation. It also enhances the production of epidermal growth factor (EGF), leading to increased angiogenesis.8 Lidocaine, a local anaesthetic agent, has analgesic and anti-inflammatory properties.10 While there are individual studies on the efficacy and safety of sucralfate, metronidazole, and lidocaine local applications in the management of postoperative symptoms after anorectal surgery, there are no studies on the outcomes using all the three drugs together as a single local application.\n\nWe evaluated the effectiveness and safety of a topical fixed-dose combination (FDC) of sucralfate 7% w/w, metronidazole 1% w/w, and lignocaine hydrochloride 4% w/w in the management of postoperative pain, itching, bleeding, burning and improving wound healing, following surgery for anorectal disorders (haemorrhoids, fistula, and anal fissures).\n\n\nMethods\n\nThis was a prospective, single-arm, single-centre study (CTRI/2020/11/029298) conducted between December 2020 and December 2021 at the Salasar Nursing Home, Thane, Maharashtra, India. The study was conducted as per good clinical practices (GCP) and the applicable national regulations to ensure that the rights, safety, and well-being of all participants were protected, and in accordance with the ethical principles in the Declaration of Helsinki. The study protocol and the informed consent form were reviewed and approved by Suraksha Institutional Ethics Committee before the initiation of the study. The study has been registered in Cinical Trials Registry of India (CTRI) on 23 November 2020 (registration number: CTRI/2020/11/029298; https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49047&EncHid=&userName=CTRI/2020/11/029298). All patients provided written informed consent for participation in the study.\n\nThe total duration of the study was 6 weeks (± 5 days). Patients enrolled were prescribed topical FDC of sucralfate 7% w/w, metronidazole 1% w/w, and lignocaine hydrochloride 4% w/w (Cremagel Ano, Abbott India Limited), following surgery for anorectal disorders (haemorrhoids, fistula, and anal fissures), for a period of 6 weeks post-surgery. The ointment was to be applied with a special applicator after cleaning the affected area with mild soap and warm water, rinsing thoroughly, and pat drying. The number of applications of study medication was per physician discretion depending on the condition of the patient. Patients were followed up at weeks 3 and 6.\n\nMales and females aged 18-64 years undergoing surgery for haemorrhoids, fistulae, and/or anal fissures were recruited. All subjects provided signed informed consent for participation in the study.\n\nThe exclusion criteria were history of inflammatory bowel disease, multiple fistulae, perianal dermatitis, proctitis, pulmonary or cardiovascular complications, poorly controlled diabetes mellitus; presence of anal fistulae or fissures due to causes such as Crohn’s disease, anal suppuration, and abscesses; <2 weeks of chemotherapy history; diagnosis of active cancer, severe anaemia, hypoalbuminemia, immunocompromised status; and history of hypersensitivity to any of the ingredients of the study product, namely, metronidazole, lignocaine hydrochloride, sucralfate, or any other ingredient in the study formulation. Additionally, patients with conditions/diseases that the investigator considered inappropriate for a patient to participate in the study, those on class I anti-arrhythmic drugs or anticoagulant treatment, pregnant and lactating females, patients unwilling to undergo an examination of anal wounds and/or patients with the inability or unwillingness to comply with the study protocol were excluded from the study.\n\nThe primary effectiveness endpoints of the study were 1) proportion of patients achieving minimal clinically important difference (MCID), defined as ≥10-point reduction on a 100 mm visual analogue scale (VAS), and 2) mean reduction in anal pain intensity as measured by the 100 mm VAS (0 = absence of pain to 10 = worst possible pain), from baseline to 3 and 6 weeks after surgery.\n\nThe secondary effectiveness endpoints were 1) proportion of patients achieving complete wound healing (defined as fully epithelialized wounds with no discharge), at 3 and 6 weeks after surgery; and 2) mean reduction in the intensity of itching sensation (evaluated on a 5-point scale from 1 = absent to 5 = unbearable), burning sensation (evaluated on a 4-point scale from 0 = no symptoms to 3 = severe symptoms), and bleeding score (calculated as the sum of frequency score [ranging from <1 episode in 2 weeks to >5 episodes in 1 week] and amount of bleeding score [ranging from 1 = non-existent to 4 = severe]), at 3 and 6 weeks after surgery.\n\nSafety endpoints included incidence of all treatment-emergent adverse events (AEs), serious AEs, and AEs leading to treatment discontinuation throughout the study and global tolerability as assessed by patients and investigators at 3 and 6 weeks after surgery.\n\nAs this was a pilot study, no formal sample size calculation was performed. The intention-to-treat (ITT) population included all patients who were enrolled and assigned to the study medication. The safety population consisted of all patients who received at least 1 dose of the FDC. The per-protocol (PP) population included all patients who completed all the study visits as per protocol without major protocol deviations. Qualitative and quantitative variables are presented using descriptive statistics. Qualitative data are presented as numbers (n) and percentages (%) and quantitative data as n, mean and standard deviation (SD). Quantitative variables were further evaluated using paired t-test at a 5% level of significance. Data were analysed using R-studio (version: 4.2.1; RRID:SCR_000432; https://scicrunch.org/resolver/SCR_000432). The software was used for data analysis tabulation and primarily for modelling and hypothesis testing.\n\n\nResults\n\nOf 52 screened patients, 50 (males:females = 29:21) with a mean (SD) age of 41.8 (10.93) years, who underwent surgery for anorectal disorders at our hospital, were enrolled in the study. All patients completed the study as per protocol and were included in the ITT, safety, and PP populations. Of the 50 patients, 9 (18.0%) underwent haemorrhoidectomy, 13 (26.0%) underwent surgery for anal fissure, and 28 (56.0%) underwent fistulectomy. The demographic and baseline characteristics of enrolled patients are summarized in Table 1.\n\nAll patients achieved MCID i.e. at least 10-point reduction in VAS score at week 3 itself, and it was maintained till the end of the study visit at 6 weeks. Mean anal pain scores at postoperative weeks 3 and 6 in the total cohort and according to the type of surgery are presented in Figure 1. Compared to the baseline mean (SD) VAS score of 68.6 (14.2), there was a significant reduction by 38.9 (15.3; p < .001) and by 63.6 (14.1; p < .001) at weeks 3 and 6, respectively. Among patients who underwent haemorrhoidectomy, the mean (SD) anal pain score also reduced significantly by 36.5 (18.8; p < .001) and by 59.4 (20.3; p < .001) at weeks 3 and 6, respectively. It reduced by 43.5 (15.9; p < .001) and by 71.7 (9.3; p < .001) at weeks 3 and 6, respectively, in patients who underwent surgery for anal fissures. In patients who underwent fistulectomy, the mean (SD) pain score reduced by 37.6 (14.0; p < .001) and by 61.2 (12.6; p < .001) at weeks 3 and 6, respectively.\n\nMean (SD) anal pain intensity score on VAS at baseline and weeks 3 and 6 following treatment in overall cohort and by type of anorectal surgery.\n\n*** indicates p < 0.001 by paired t-test at week 3 or week 6 versus baseline.\n\nITT, intention to treat; SD, standard deviation.\n\nThe mean scores for itching, bleeding, and burning also reduced significantly in the total cohort and in the subgroups at week 3 and 6 post-surgery (Table 2). Compared to the baseline mean (SD) score of 3.0 (0.99), the itching score reduced significantly (p < .001) by 1.1 (1.06) and 1.8 (1.07) at weeks 3 and 6, respectively. In patients who underwent haemorrhoidectomy, the mean (SD) itching score reduced significantly by 1.0 (1.22; p < .05) and 1.4 (1.24; p < .01); in those who underwent fissurectomy, the score reduced by 1.6 (0.96; p < .001) and 2.5 (0.88; p < .001) and in those who underwent fistulectomy, it reduced by 0.8 (0.98; p < .001) and 1.6 (0.96; p < .001) at weeks 3 and 6, respectively.\n\na Analyzed using paired t-test at 5% level of significance.\n\nThe mean (SD) bleeding score at baseline was 5.9 (1.87), which decreased significantly (p < .001) by 3.1 (1.76) at week 3 and by 3.9 (1.88) at week 6. Compared to the baseline score, the mean (SD) bleeding score at weeks 3 and 6 reduced significantly (p < .001) by 4.9 (1.36) and 5.4 (1.24) in patients who underwent haemorrhoidectomy, by 3.5 (1.56) and 4.3 (1.70) in those who underwent fissurectomy, and by 2.4 (1.52) and 3.2 (1.81) in those who underwent fistulectomy, at weeks 3 and 6, respectively (Table 2).\n\nThe mean (SD) burning score also reduced significantly (p < .001) by 1.2 (0.98) at week 3 and by 1.6 (0.90) at week 6, compared to the baseline score of 2.8 (0.90). The mean (SD) burning score decreased by 0.6 (1.24; p > .05) at week 3 and by 1.3 (1.00; p < .01) at week 6 in patients who underwent haemorrhoidectomy. The score also reduced significantly (p < .001) in those who underwent fissurectomy by 1.8 (0.73) and 2.3 (0.63) and in those who underwent fistulectomy by 1.1 (0.86) and 1.3 (0.46), at weeks 3 and 6, respectively (Table 2).\n\nWound healing was evaluated at weeks 3 and 6. Two (4.0%) patients had complete wound healing at week 3 and this number increased to 20 (40.0%) patients at end of 6 weeks (Table 3).\n\nNo adverse events were reported, and the study medication was well tolerated, by all patients. The global tolerability was rated as good in 100% of patients by the patients themselves as well as by the investigator at 3 and 6 weeks after surgery.\n\n\nDiscussion\n\nThe results of our study showed a significant decrease in postoperative anal pain score at weeks 3 and 6 with a topical application of an FDC of sucralfate 7% w/w, metronidazole 1% w/w, and lignocaine hydrochloride 4% w/w in patients undergoing anorectal surgery. The decrease in pain score was seen in the total cohort as well as in subgroups of patients undergoing haemorrhoidectomy, fistulectomy, and surgery for anal fissures. All 50 patients enrolled in the study achieved MCID at week 3.\n\nThe topical application of sucralfate ointment once or twice daily for two weeks post-haemorrhoidectomy has been reported to significantly reduce pain and decrease the time to wound healing compared with a placebo ointment.9 A study in 2017 compared outcomes of topical 8% sucralfate cream versus placebo in patients undergoing haemorrhoidectomy. On postoperative day 1, the mean VAS score in the sucralfate group was significantly lower than that in the placebo group (5.72 vs. 8.20; p < 0.001). The mean VAS after first defecation was significantly lower in the sucralfate group than in the placebo group (5.92 vs. 8.64).11 Another study reported that in patients undergoing haemorrhoidectomy, those in the sucralfate group had significantly less pain and consumed fewer analgesics (narcotic and nonsteroidal) on postoperative days 1, 7 and 14 than patients in the control group (p < 0.001).3 Similarly, results from another study found that patients in the sucralfate group had significantly less pain than those in the placebo group at 24 h and the 48 h after haemorrhoidectomy, and patients in the sucralfate group required a lesser amount of analgesics during the same period.12 A comparison of topical applications of sucralfate, lidocaine, and placebo in patients undergoing haemorrhoidectomy showed that the pain outcomes on postoperative days 1, 3, 7, 14, 21, and 28 were best with sucralfate followed by lidocaine. Despite being inferior to sucralfate, lidocaine ointment did reduce pain intensity compared with the placebo group.8 Another study compared the outcomes of topical cream containing lidocaine 2.5% and prilocaine 2.5% (EMLA group) versus placebo in patients undergoing haemorrhoidectomy. The VAS score and frequency and dosage of meperidine injections as rescue medication for uncontrolled pain were significantly lower in the EMLA group than in the placebo group (p < 0.01). The voiding time was significantly delayed in the placebo group (p = 0.04). Furthermore, the frequency of single catheterization was significantly lower in the EMLA group than in the control group (p = 0.03), and patient satisfaction with postoperative pain control was significantly higher in the EMLA.13\n\nA systematic review and meta-analysis of four RCTs including 149 patients (76 treated with 10% metronidazole ointment and the others with placebo) reported that metronidazole significantly reduced post-haemorrhoidectomy pain throughout the first two weeks postoperatively. The mean difference in the VAS score for pain between the groups was -2 to -1.9 Results of a review of 13 studies in which oral or topical metronidazole was used after haemorrhoidectomy revealed that pain score decreased at all time points with both oral and topical metronidazole. However, postoperative pain score and analgesic consumption were lower in the topical metronidazole group.14 In another study, it was reported that topical application of metronidazole 10% significantly reduced discomfort after haemorrhoidectomy up to 14 days and eased postoperative pain during defecation compared with placebo.15 A significant reduction of post-haemorrhoidectomy discomfort and edema after using topical metronidazole 10% has also been reported.16 A study in which topical metronidazole was used in patients with “fissurectomy” wounds reported good results.17 However, studies conducted in the last two decades on the topical use of sucralfate, metronidazole, or lidocaine post fissurectomy are scarce.\n\nThe itching, bleeding, and burning scores in our study also reduced significantly in the overall cohort and in the three subgroups. The decrease in burning score at week 3 in patients who underwent haemorrhoidectomy was not statistically significant; however, it was statistically significant at week 6. We were unable to find studies that have reported the outcomes of these symptoms with local applications of sucralfate, metronidazole, or lidocaine except one, in which the authors reported that application of topical metronidazole in postoperative anorectal wounds after haemorrhoidectomy and fistulectomy increased the risk of bleeding. Though most of the episodes were controlled with conservative management, they caused considerable patient anxiety and apprehension.18\n\nOut of our total cohort of 50 patients, 9 (18.0%) underwent haemorrhoidectomy, 13 (26.0%) underwent surgery for anal fissures, and 28 (56.0%) underwent fistulectomy. There are few studies on the efficacy of topical sucralfate, metronidazole, or lidocaine post-fistulectomy; most studies have been conducted in patients undergoing haemorrhoidectomy. A study in 2011 evaluated the effectiveness and safety of topical sucralfate in wound healing after anal fistulectomy. At 6-week follow-up, mucosal coverage of the wound was significantly greater with sucralfate than with placebo (p = 0.01). Postoperative pain scores were significantly lower with sucralfate than with placebo at 2 and 4 weeks.19 Similarly, a study in 2016 reported that in patients undergoing fistulectomy, patients in the sucralfate group had significantly less pain at rest and on defecation than those in the placebo group from weeks 1 to 5.20\n\nIn our study two (4.0%) patients had complete wound healing at week 3 and this number increased to 20 (40.0%) at the end of 6 weeks. However, this is lower than that in the study by Gupta et al. who reported complete wound healing after fistulectomy in 95% of patients in the sucralfate group and 73% in the placebo group (p = 0.009) at 6 weeks.19 Another study also reported a wound healing rate of 82.2% at 28 days with topical sucralfate in patients undergoing haemorrhoidectomy.3 Yet another study reported complete wound healing in 5.9 (0.8) weeks in the sucralfate group in patients undergoing fistulectomy.20 The lower rate of wound healing in our study might be explained by the varying frequency of application of the treatment in different patients. It has been reported that a 6-hourly application has better outcomes compared to those with a 12-hourly application.8\n\nThere are some limitations to our study. The sample size of the study was small. Additionally, we had no comparative groups. Furthermore, we captured outcomes only at 3 and 6 weeks. Capturing outcomes early after surgery might have provided insights on the effect of this FDC in the acute postoperative phase. Lastly, the number of applications per day were variable, which might have affected the outcomes. Hence, further studies with larger sample sizes and addressing the above limitations are necessary. Nevertheless, considering that there are few studies on the effect of topical applications of drugs in this FDC in patients undergoing fissurectomy or fistulectomy, our study makes a valuable contribution to the literature.",
"appendix": "Data availability\n\nFigshare: [Agarwal N_FDC study in anorectal surgery pain_Underlying data]. https://doi.org/10.6084/m9.figshare.22091816.v1. 21\n\nThe project contains the following underlying data:\n\n- [Agarwal N_2023] (patient data listings)\n\nFigshare: STROBE checklist for [Outcomes of a fixed-dose combination of sucralfate, metronidazole, and lidocaine in patients undergoing anorectal surgery: Results from a prospective, single-centre study], https://doi.org/10.6084/m9.figshare.22091876.v1. 22\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nWriting support for the manuscript was provided by Dr. Sangeeta Dhanuka on behalf of medONE Pharma Solutions, Delhi, India.\n\n\nReferences\n\nHegde R, Trombold JM, Dominguez JM: Colorectal Surgery Review for Primary Care Providers. Mo. Med. 2020; 117: 154–158.\n\nFoxx-Orenstein AE, Umar SB, Crowell MD: Common anorectal disorders. Gastroenterol. Hepatol (N Y). 2014; 10: 294–301.\n\nAlbatanony AA: Sucralfate ointment reduces pain and improves healing following haemorrhoidectomy: a prospective, randomized, controlled and double-blinded study. Egypt. J. Surg. 2016; 35: 102–105. Publisher Full Text\n\nSarla G: Prevalence of Benign Anorectal Diseases in Patients Consulting a General Surgeon. Research & Reviews: Journal of Surgery. 2019; 8: 19–24.\n\nTuran A, Nihan A, Feyyaz G, et al.: Treatment of chronic anal fissure: Is open lateral internal sphincterotomy (LIS) a safe and adequate option? Asian J. Surg. 2019; 42: 628–633.\n\nCarr S, Velasco AL: Fistula In Ano. [Updated 2022 May 15]. StatPearls. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Reference Source\n\nShamssa MSM: Topical Metronidazole for Post-Anal Surgery Pain. Int. J. Sci. Res. 2018; 7: 1606–1610.\n\nAlkhateep Y, Abdelmieniem F: Double blinded randomized placebo-controlled comparative study between sucralfate ointment and lidocaine ointment after Milligan Morgan hemorrhoidectomy. Int. J. Surg. 2017; 4: 3822–3826. Publisher Full Text\n\nLohsiriwat V, Jitmungngan R: Strategies to Reduce Post-Hemorrhoidectomy Pain: A Systematic Review. Medicina. 2022; 58: 418. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLinares-Gil MJ, Valls J, Hereu-Boher P, et al.: Topical Analgesia with Lidocaine Plus Diclofenac Decreases Pain in Benign Anorectal Surgery: Randomized, Double- blind, and Controlled Clinical Trial. Clin. Transl. Gastroenterol. 2019; 9: e210.\n\nAl Khateeb YM, Abdel Sattar AM, Al Batanony AA: Evaluation of the role of sucralfate cream in decreasing pain intensity and improving healing following open hemorrhoidectomy: a randomized controlled study. Menoufia Med. J. 2019; 32: 506–510. Publisher Full Text\n\nMirani AJ, Maroof SM, Raza A, et al.: The role of 10 % Sucralfate Ointment in the Reduction of Acute Postoperative Pain aft er Open Hemorrhoidectomy. Pak. J. Surg. 2015; 31: 153–157.\n\nShiau JM, Su HP, Chen HS, et al.: Use of a topical anesthetic cream (EMLA) to reduce pain after hemorrhoidectomy. Reg. Anesth. Pain Med. 2008; 33: 30–35. Publisher Full Text\n\nGhazala MJ, El-Said MM, Abdalhaffez AY, et al.: Relief of pain after surgery of benign anorectal conditions: topical versus oral metronidazole. Mans. Med. J. 2021; 50: 149–154.\n\nAla S, Saeedi M, Eshghi F, et al.: Topical metronidazole can reduce pain after surgery and pain on defecation in postoperative hemorrhoidectomy. Dis. Colon Rectum. 2008; 51: 235–238. Publisher Full Text\n\nNicholson TJ, Armstrong D: Topical metronidazole (10 percent) decreases posthemorrhoidectomy pain and improves healing. Dis. Colon Rectum. 2004; 47: 711–718. PubMed Abstract | Publisher Full Text\n\nPelta AE, Davis KG, Armstrong DN: Subcutaneous fissurotomy: A novel procedure for chronic fissure-in-ano. a review of 109 cases. Dis. Colon Rectum. 2007; 50: 1662–1667. PubMed Abstract\n\nGarg P, Yagnik VD, Kaur G: Increased Risk of Bleeding with Topical Metronidazole in a Postoperative Wound after Anal Fistula and Hemorrhoid Surgery: A Propensity Score-Matched Case–Control Study. Clin. Pract. 2022; 12: 133–139. Publisher Full Text\n\nGupta PJ, Heda PS, Shrirao SA, et al.: Topical sucralfate treatment of anal fistulotomy wounds: a randomized placebo-controlled trial. Dis. Colon Rectum. 2011; 54: 699–704. PubMed Abstract | Publisher Full Text\n\nAlvandipour M, Ala S, Tavakoli H, et al.: Efficacy of 10% sucralfate ointment after anal fistulotomy: A prospective, double-blind, randomized, placebo-controlled trial. Int. J. Surg. 2016; 36: 13–17. PubMed Abstract | Publisher Full Text\n\nAgarwal N: Agarwal N_FDC study in anorectal surgery pain_Underlying data.xlsx. [Dataset]. figshare. 2023. Publisher Full Text\n\nAgarwal N: STROBE Checklist. figshare. Journal Contribution. 2023. Publisher Full Text"
}
|
[
{
"id": "179224",
"date": "03 Jul 2023",
"name": "Surendra Mantoo",
"expertise": [
"Reviewer Expertise Colorectal surgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a prospective, single-arm, single-centre study with no control group. It is hard to draw any conclusions that whether the perceived benefit of the investigated topical application is a placebo effect or a real benefit to the patient. Most patients after anorectal surgery will have reduced pain at 3 weeks and much reduced pain and discomfort at 6 weeks even without any treatment. Since it is a prospective study, it would have been easy to have a control group.\nI would suggest to add a prospective control group or a historical control group where traditional standard treatment has been used.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "10104",
"date": "25 Aug 2023",
"name": "Niranjan Agarwal",
"role": "Author Response",
"response": "We agree with the reviewer that patients will experience reduced discomfort as time progresses in the post-operative period. While there are individual studies on the efficacy and safety of sucralfate, metronidazole, and lidocaine local applications in the management of postoperative symptoms after anorectal surgery, there are no studies on the outcomes using all the three drugs together as a single local application. Thus, it was decided to have a smaller pilot study in 50 patients receiving this fixed-dose combination initially before doing a larger study with a control arm. Additionally, the results of the study, such as, reduction in post-operative anal pain, and wound healing, has been compared with the results of other similar studies in existing literature in the discussion section of the article. Nevertheless, we respect the reviewer’s opinion and we will consider incorporating a control arm when designing future prospective studies."
}
]
},
{
"id": "192772",
"date": "31 Aug 2023",
"name": "Reno Rudiman",
"expertise": [
"Reviewer Expertise Digestive surgery",
"anorectal surgery",
"colorectal surgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nBeing a single study with no comparative group, the main flaw of the study is whether the outcome variables are resulting solely on the effects of the experimental drug, or it may also results from naturally healed anorectal surgery wounds.\nThere are several articles that has addressed the effects of aforementioned drug, with placebo comparison, which are more prominent in showing clinical efficacy. It has been mentioned in the discussion. So although this study limitation is the biggest weakness of the issue, the authors are well aware of this.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-659
|
https://f1000research.com/articles/12-658/v1
|
13 Jun 23
|
{
"type": "Research Article",
"title": "Happiness and satisfaction research pre and during the COVID-19 pandemic: a bibliometric analysis of global scientific literature",
"authors": [
"Nicholas Tze Ping Pang",
"Assis Kamu",
"Teik Ee Guan",
"Agnis Sombuling",
"Chong Mun Ho",
"Noor Hassline Mohamad",
"Walton Wider",
"Muhammad Ashraf Fauzi",
"Nicholas Tze Ping Pang",
"Teik Ee Guan",
"Agnis Sombuling",
"Chong Mun Ho",
"Noor Hassline Mohamad",
"Muhammad Ashraf Fauzi"
],
"abstract": "Background: The study provides a comprehensive analysis of trends of global scientific research, comparing pre-coronavirus disease (COVID 19) and during COVID-19 research in happiness and satisfaction, from 2014 up to 2021. Methods: The study period of the current research was divided into two phases, before the COVID-19 pandemic (1998 documents) and during COVID-19 (2020 until December 18, 2021). The Scopus database was comprehensively searched on relevant publications on Happiness and Satisfaction. Only articles published in English were retrieved. Bibliometric indicators were analyzed using Bibliometrix, an R package, and VOSviewer. Var1.6.6. Bibliometric indicators include the year of publications, authors, region, subject areas, countries, institutions, journals, country collaboration. Authorship productivity was presented in the final analysis. Results: A total of 3069 documents were extracted from Scopus. Overall, articles retrieved were written by 5220 authors before COVID-19 (2014-2019) and 3520 authors during COVID-19 (2020-2022), published in 2593 journals, with 83 counties represented before COVID-19 and 84 during COVID-19, and 21.66 average citations per document before COVID-19 and 30.4 average citations per document during COVID-19. Journal of Happiness Studies led in the number of articles produced. University of California was the most productive institution both before (number of publications [NP] = 42) and during (NP = 19) the COVID-19 pandemic. The US was the most productive country on multiple metrices; firstly, based on the most productive country both before (NP = 341) and during the pandemic (NP = 145), and secondly, based on the multiple country publications metric both before (NP = 34) and during the pandemic (NP = 34). Conclusions: This bibliometric study demonstrates that the COVID-19 pandemic has not significantly affected the productivity of happiness and satisfaction researchers; however, there are subtle changes in thematic evolution that will probably inform the direction of happiness research in the coming decade.",
"keywords": [
"happiness",
"satisfaction",
"COVID-19",
"bibliometrics analysis",
"publications"
],
"content": "Introduction\n\nHappiness and satisfaction are increasingly influencing a growing movement of quality-of-life studies, and are no longer a single metric, or overly tied to infrastructural development. Rather, they are more holistic, biopsychosocial constructs that look into quality of life, satisfaction, psychological wellness, and salient features of the landscape, of city design, and of spaces in which people interact at work and play. However, the coronavirus disease (COVID-19) pandemic has potentially resulted in shifts among the general population in terms of how happiness and satisfaction are perceived (O’Donnell, Wilson, Bosch, & Borrows, 2020). Such a change is multifactorial and does not merely result from the physical infection and the fear that ensues. More structurally, there have been ripple effects from the psychological consequences of multiple lockdowns, movement restrictions, and quarantine orders imposed across varying degrees in various parts of the world. These have resulted in stagnant or declining economic growth and high levels of opportunities lost, inevitably increasing unemployment rates globally (Mele & Magazzino, 2021). Employment aside, such measures have resulted in high levels of isolation, reduced social interaction with family and friends, and detachment from society, which have been demonstrated to have a detrimental effect on the population. This is especially so in two crucial sectors – the young, for whom the inalienable right to receiving a quality universal education has been impaired by online schooling and connectivity issues; and the elderly, who become increasingly isolated by COVID-19 lockdowns and have more physical susceptibility to the adverse consequences of the pandemic per se.\n\nHence, it is crucial that we quantify and collate the research work performed by institutions around the world during the COVID-19 pandemic that focus on effect of COVID-19 lockdowns on happiness and satisfaction, as evidence-based policies are crucial to provide scientifically sound recommendations that inform governmental policies on this issue. This is even more so as economies and countries gradually open up. As countries transform post-pandemic and continue creating spaces for individuals in cities to work, play, and conduct their business, it is crucial that we can keep our pulse on trends in quality of life, urban design, connectedness, happiness, and psychological wellbeing. Individual studies, though with good reliability and validity, are less generalizable; hence bibliometric analysis has emerged as a new tool to perform big picture analysis on the evidence at large.\n\nBibliometric analysis is crucial as a new analytical technique to map existing literature that revolves around a particular theme of research, and can be important in assessing trends (Deng, Wang, Chen, & Wang, 2020; Derviş, 2019; Kawuki, Yu, & Musa, 2020b; Kutluk & Danis, 2021; Musa, El-Sharief, Musa, Musa, & Akintunde, 2021; Odone et al., 2020; Sun & Yuan, 2020). It identifies suitable research hotspots based on historical trends which can encompass diverse domains both quantitatively and qualitatively. Also, bibliometric analysis can assist with research retrospection (Falagas, Karavasiou, & Bliziotis, 2006; Zhang et al., 2021), allowing analysis, visualization and evaluation of scientific research teams. Hence, connections can be established more clearly between authors, frameworks, methodologies, and translational practice. (Song et al., 2019). Moreover, research trends, topics, and relative importance on publication in particular areas can be ascertained (Ellegaard & Wallin, 2015; Herrera-Viedma et al., 2020). Bibliometric tools have assisted greatly in looking at research trends in various fields across the spectrum including Ebola (Kawuki, Yu, & Musa, 2020b; Yi, Yang, & Sheng, 2016), timeframe-specific COVID-19 research (Furstenau et al., 2021; Lou et al., 2020), malaria (Fu et al., 2015), and childhood obesity (Kawuki et al., 2020a). As the pandemic has shifted global priorities drastically, however, there has been no bibliometric research that examines trends before and after, and does a suitable comparison.\n\nThus, this analysis’s specific objectives include identifying the scientific research growth, publication, and citation trends across time for COVID- 19 affecting happiness and satisfaction. This study looks at these bibliometric parameters pre- and during COVID-19 to identify if there have been disruptions in research output or shifts in research priorities given the cataclysmic changes the world has experienced (Zambrano, Alvarez, & Caballero, 2021). Hence, this bibliometric analysis aims to shine the spotlight on the most active authors, journals, the highest-contributing countries and institutions, and the most proactive funding organizations involved in the field of happiness and satisfaction. Word-cloud and conceptual structure map methods allow more illustrative depictions of the research corpus of happiness and satisfaction research both prior to and in the light of the COVID-19 pandemic, allowing us to make comparisons and contrasts parsimoniously.\n\n\nMethods\n\nThe study adopted the bibliometric method to quantitatively and qualitatively analyze documents indexed in the Scopus database. The study period of the current research was divided into two phases, before the COVID-19 pandemic (covering 1998 documents) and during COVID-19 (2020 until December 18, 2021).\n\nOn December 18, 2021, the Scopus database was comprehensively searched for relevant publications on happiness and satisfaction (search query used: TITLE-ABS-KEY “happiness” AND “satisfaction”). Only articles published in English were retrieved. A total of 3069 documents were extracted from Scopus. Bibliometric indicators include the year of publications, authors, region, subject areas, countries, institutions, journals, country collaboration. Authorship productivity was presented in the final analysis.\n\nThe metadata on the effects of the COVID-19 Pandemic on happiness and satisfaction was exported from Scopus. Bibliometrix, with an R package was used to perform comprehensive science mapping analysis (Aria & Cuccurullo, 2017) and VOSviewer.Var1.6.6 was used to developed bibliometric maps between documents to examine their characteristics (Van Eck & Waltman, 2010).\n\n\nResults\n\nThe data search result included 1998 articles before COVID-19 and 1071 during COVID-19, with 21.66 and 30.4 average citations per document, respectively. The types of documents included were 2593 articles (84.50%) and 129 conference papers (4.20%), among others (refer to Table 1).\n\nThe annual scientific production included the number of articles before the COVID-19 period (year 2019) 449 (14.63%) and during the COVID-19 period (year 2021) 541 (17.63%) (refer to Table 2).\n\n* During the COVID-19 pandemic\n\nThere was a range of 2.06-16.01 mean total citations per year (2015-2019) before the COVID-19 period (21.06%) and 39.06 mean total citations per year in 2020 during the COVID-19 period (refer to Table 3).\n\n* During the COVID-19 pandemic.\n\nThe source local impact was computed by the H index before the COVID-19 pandemic (refer to Figure 1). Advances in Intelligent Systems and Computing had a h-index of 7, followed by a h-index of 5 in Lecture Notes in Computer Science, and h=4 in ACM International Conference Proceeding Series.\n\nThe source local impact was computed by H index for the period during the COVID-19 pandemic (refer to Figure 2). The h-index was 4 for Proceedings of the International Conference on Industrial Engineering and Operations Management, followed by 3 in Pervasive Health, whereby the others ranged between 1 and 2.\n\nA total of 1,139 sources contributed to happiness and satisfaction research before the COVID-19 period. The topmost influential publications are listed in Table 4. Journal of Happiness Studies had 102 articles, followed by Social Indicators Research which had 77 articles.\n\nA total of 643 sources contributed to happiness and satisfaction research during the COVID-19 period. The topmost influential publications are listed in Table 5. Journal of Happiness Studies had 53 articles followed by International Journal of Environmental Research and Public Health with 46 articles.\n\nTable 6 lists the top 10 most influential publications before the COVID-19 pandemic, including their TC per Year and Normalized TC. Table 7 displayed the top ten most influential publications during to the COVID-19 pandemic, including their TC per Year and Normalized TC, as shown in Table 5.\n\nA total of 5220 authors contributed to happiness and satisfaction research before the COVID-19 period. The topmost relevant authors are listed in Table 8. Veenhoven R contributed 15 articles, with 9.92 articles fractionalized, followed by Diener E who contributed 14 articles, with 4.79 articles fractionalized.\n\nA total of 3520 authors contributed to happiness and satisfaction research during COVID-19. The topmost relevant authors are listed in Table 9. Veenhoven R contributed 8 articles, with 3.12 articles fractionalized, followed by Ravina-Ripoll R who contributed 7 articles, with 2.00 articles fractionalized.\n\nUniversity of California was the most relevant affiliation before the COVID-19 pandemic (number of publications [NP] = 42), followed by University of Michigan (NP = 32) and Erasmus University Rotterdam (NP = 26) (refer to Figure 3).\n\nUniversity of California was the most relevant affiliation during the COVID-19 pandemic (NP = 19), followed by University of Toronto (NP = 18) and both University of Pennsylvania and Zhejiang University (NP = 14) (refer to Figure 4).\n\nThe USA was the most productive country (NP = 341), followed by the United Kingdom (NP = 119), China (NP = 79), and Korea (NP = 73) as the most influential countries before the COVID-19 pandemic. Meanwhile, the US was the most productive country based on the multiple country publications metric (NP = 54), followed by the United Kingdom (NP = 47) and Netherlands (NP = 29) (refer to Table 10).\n\nThe USA was the most productive country (NP = 145), followed by China (NP = 81), Spain (NP = 52), and Korea (NP = 47) as the most influential countries during the COVID-19 pandemic. Meanwhile, the US was the most productive country based on the multiple country publications metric (NP = 34), followed by Spain (NP = 21) and China (NP = 19) (refer to Table 11).\n\nUsing a multiple correspondence analysis (MCA) pre- and post-COVID 19, as shown in Figure 5, a total of 39 keywords were divided into one color, hence explaining the concept of research effects of pre-COVID-19 on happiness and satisfaction. This contrasts with Figure 6, where 42 keywords were divided into two colors: red, with 23 keywords; and blue, with 19 keywords. This hence explaining the concept of research effects of during COVID-19 on happiness and satisfaction. Both groups demonstrated different keywords that explain the concept/s of research on happiness and satisfaction pre- and during COVID-19.\n\nThe relation between affiliations, countries, and “keywords plus” occurrence on the effects of the COVID-19 pandemic on happiness and satisfaction are presented in the three fields plot in Figure 7. The keyword visualization is seen in Figure 7a and Figure 7b, with the word cloud in Figure 8a and 8b. Before the COVID-19 pandemic, “female” is the most frequent keyword with 2430 instances, followed by “male” with 2340, then “happiness” with 2290. During the COVID-19 pandemic, “happiness” is the most frequent keyword with 1230 instances, followed by “female” with 1220, then “male” with 1080.\n\nThe analysis of social networks between researchers before the COVID-19 pandemic with three or more publications was considered and had 140 authors; only network maps with 11 items are shown in four clusters with links (links = 18 and total link strength = 42) as shown in Figure 9(a). Figure 9(b) demonstrates collaborative ties among countries during the COVID-19 pandemic and mental health research. Authors who published at least three articles in the dataset (n = 61) were included. Overall collaboration is presented in nine different clusters with distinct colors, and the thickness of the line between two countries that contributed to happiness and satisfaction research represents the strength of research collaboration. The distance between the two countries reflects how much the two countries are closely related to the research field. For example, the top three countries were the USA (links = 52 and total link strength = 300), followed by United Kingdom (links = 42, total link strength = 171) and Australia (links = 33 and total link strength = 114). Figure 9(c) showcased which organizations were related, and 26 organizations that meet the thresholds presented in 2 cluster with links (links = 4 and total link strength = 10).\n\nThe analysis of social networks between researchers during COVID-19 pandemic with three or more publications was considered and had 68 authors; only network maps with 14 items are shown in 11 clusters with links (links = 17 and total link strength = 20) as shown in Figure 10(a). Figure 10(b) demonstrates collaborative ties among countries during the COVID-19 pandemic and mental health research. Authors who published at least three articles in the dataset (n = 62) were included. Overall collaboration is presented in 37 different clusters with distinct colors, and the thickness of the line between two countries that contributed to happiness and satisfaction research represents the strength of research collaboration. The distance between the two countries reflects how much the two countries are closely related to the research field. For example, the top three countries were the USA (links = 43 and total link strength = 164), followed by Spain (links = 30, total link strength = 81) and Germany (links = 32 and total link strength = 63). Figure 10(c) showcased which organizations were related, and 14 organizations that meet the thresholds presented in one cluster with links (links = 6 and total link strength = 18).\n\nThere was a wider range of trend topics pre-COVID 19. Topics ranged across the dimensions, from economic (poverty; productivity) to mental health (suicide; psychological resilience; depression) to general quality of life studies (life satisfaction; happiness; wellbeing); hence no one theme predominated (refer to Figure 11). Post-COVID 19, the topics were more circumscribed, with 2021 topics being relevant to the times (China; patient satisfaction; controlled clinical study) reflecting global anxieties and research priorities (refer to Figure 12). Observing the thematic evolution using author’s keywords pre- and post-COVID 19, some trends emerged out of the literature. Pre-COVID, the themes ranged across the spectrum, from adolescents, social media, to China (refer to Figure 13). Post-COVID-19, the themes coalesced into a few broad keywords, and various themes expanded into separate strands. For instance, the “mental health” keyword evolved into two separate strands of “mental health” and “social support.” The “happiness” keyword evolved into two strands of “subjective well-being” and “happiness” (refer to Figure 14).\n\n\nDiscussion\n\nThis study presents a bibliometric overview of the COVID-19 pandemic and publications related to happiness and satisfaction. Overall, the analysis suggests that themes have become more concise and more wellbeing-related in the post-pandemic landscape. It is interesting to note though that the three articles with the highest citation numbers were all related to happiness and satisfaction in an engineering or technical setting, and they were all from 2021. Due to the usual life cycle of research publication in journals, it is most certain that all three articles were submitted pre-COVID, so are more reflective of the earlier research landscape. The article with the highest impact was a conference series paper focusing primarily on urban quality of life as a response to various urban issues and challenges; however, it was not specific to COVID-19. The article with the second highest level of impact focuses on an elucidation of a human facial expression classification system to test video games using the K-Nearest Neighbor (KNN) classification method and using the Indonesia Mixed Emotion Dataset (IMED) as training data and trial data, incorporating several processes, namely preprocessing, feature extraction, and classification of facial expressions. Again, this research article did not have any correlations with COVID-19 either. The third article with the highest number of citations is a book chapter focusing on psychological impact of design, namely on empirical case studies in city regeneration of post-industrial sites. Notably it is interesting that two of the three top-cited articles focus on the latest evidence in regenerating the urban landscape, despite not being pandemic-specific. Hence, in the new post-COVID urban landscape, it is imperative that cities are replanned and designed smartly to allow for suitable ventilation, physical distancing, increased cyclist, and pedestrian mobility, and higher environmental efficiency and sustainability, as would be suitable in a post-COVID urban landscape.\n\nWe can observe too that there are very little differences in author productivity pre- and during COVID-19. The most productive authors were the same ten people pre- and during COVID-19, with roughly similar numbers of articles. This suggests that the during COVID-19 productivity most probably reflects work performed prior to the commencement of the pandemic; hence it will possibly take a few more years for the literature on happiness and satisfaction directly pertaining to the pandemic to be reflected in the bibliometric analysis. Another postulation is that due to this ten authors’ primacy in this field, they would still accrue similar numbers of authorship during the pandemic as they would be in advisory or consultancy rather than main authorship roles for papers produced by their happiness or satisfaction research units.\n\nThe best place to hence observe a difference is in thematic transformation keywords pre- and during COVID. Pre-COVID, the themes ranged across the spectrum, from adolescents, social media, to China. During COVID-19, the themes coalesced into a few broad keywords. The mental health keyword evolved into two separate strands of mental health and social support.\n\nThis suggested that the latter is a key component of preservation of good mental health. The “happiness” keyword evolved into two strands of “subjective well-being” and “happiness,” suggesting that in the pandemic, individuals’ experiences of happiness and unhappiness were very individualized as different nations and regions were subjected to widely varying levels of lockdown despite having similar epidemiological characteristics. It would be interesting to further perform bibliometric analyses on particular topics within the overall ambit of happiness and see if different trends emerged.\n\nThis research is crucial in that it is the first study utilizing novel bibliometric methodologies examining the relationship between both the pre- and during the COVID-19 period regarding happiness and satisfaction. No doubt limitations are inherent in bibliometric methodology; only English publications were able to be extracted in this project, and other databases, such as Google Scholar, PubMed, Web of Science, and Chinese databases were not included. Nevertheless, Scopus nevertheless retains primacy as one of the largest peer reviewed databases extant and is a highly valid primary search source. Also, bibliometric analyses cannot adequately take into account false-positive and false-negative results. Moreover, top-cited articles in this bibliometric analysis were ranked based on the total citation score. No doubt this metric is accepted in publishing and research as a reasonable judge of a paper’s impact; however, self-citation may be a mechanism that artificially inflates the overall citation numbers and the h-index.\n\n\nConclusion\n\nThis bibliometric study uniquely allows us to observe, with comparisons pre- and during the pandemic, the state of affairs in happiness and satisfaction research across a designated time period, and casts light on the prominent articles, authors, publishing journals, countries, and funding agencies in happiness and satisfaction research. This study demonstrates how themes have evolved over the pandemic, despite the static nature of authors involved, and signals a potential paradigm shift in the priorities of the research community involved in happiness and satisfaction, away from the multifarious foci, towards more focused research addressing the recovery of the world at large from the calamitous economic, social, and psychological consequences of COVID-19. To this end, it is hence crucial that international agencies and research units with expertise or interest in this field offer grants to academicians and researchers who can expedite practical solutions to improve happiness and satisfaction across all strata of society. This bibliometric analysis also underscores the importance of multinational and multiagency collaborations in resolving issues of our times. Despite its precipitous consequences, the sudden shift to universal online working has significantly loosened the barriers to international collaboration, allowing agencies, universities, governments, and individuals to collaborate real-time to share knowledge and expertise in solving the greatest and most pressing issues of our pandemic times, one of which indubitably will be the promotion of higher levels of happiness and satisfaction.",
"appendix": "Data availability\n\nZenodo: Happiness and satisfaction research pre and during COVID-19 pandemic: A Bibliometric analysis of global scientific literature. https://doi.org/10.5281/zenodo.7607045 (Wider, 2023).\n\nThis project contains the following underlying data:\n\n• scopus 2020-2022.bib\n\n• scopus before 2020.bib\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAria M, Cuccurullo C: bibliometrix: An R-tool for comprehensive science mapping analysis. J. Informet. 2017; 11(4): 959–975. Publisher Full Text\n\nDeng Z, Wang H, Chen Z, et al.: Bibliometric analysis of dendritic epidermal T cell (DETC) research from 1983 to 2019. Front. Immunol. 2020; 11: 259. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDerviş H: Bibliometric analysis using Bibliometrix an R Package. J. Sci. Res. 2019; 8(3): 156–160. Publisher Full Text\n\nEllegaard O, Wallin JA: The bibliometric analysis of scholarly production: How great is the impact? Scientometrics . 2015; 105(3): 1809–1831. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFalagas ME, Karavasiou AI, Bliziotis IA: A bibliometric analysis of global trends of research productivity in tropical medicine. Acta Trop. 2006; 99(2-3): 155–159. PubMed Abstract | Publisher Full Text\n\nFu H, Hu T, Wang J, et al.: A bibliometric analysis of malaria research in China during 2004–2014. Malar. J. 2015; 14(1): 1–7. Publisher Full Text\n\nFurstenau LB, Rabaioli B, Sott MK, et al.: A bibliometric network analysis of coronavirus during the first eight months of COVID-19 in 2020. Int. J. Environ. Res. Public Health . 2021; 18(3): 952. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHerrera-Viedma E, López-Robles J-R, Guallar J, et al.: Global trends in coronavirus research at the time of Covid-19: A general bibliometric approach and content analysis using SciMAT. El profesional de la información (EPI) . 2020; 29(3): e290322. Publisher Full Text\n\nKawuki J, Ghimire U, Papabathini SS, et al.: A bibliometric analysis of childhood obesity research from China indexed in Web of Science. Journal of Public Health and Emergency . 2020a; 5(3): 1–11. Publisher Full Text\n\nKawuki J, Yu X, Musa TH: Bibliometric Analysis of Ebola Research Indexed in Web of Science and Scopus (2010-2020). Biomed. Res. Int. 2020b; 2020: 1–12. Publisher Full Text\n\nKutluk MG, Danis A: Bibliometric analysis of publications on pediatric epilepsy between 1980 and 2018. Childs Nerv. Syst. 2021; 37(2): 617–626. PubMed Abstract | Publisher Full Text\n\nLou J, Tian S-J, Niu S-M, et al.: Coronavirus disease 2019: a bibliometric analysis and review. Eur. Rev. Med. Pharmacol. Sci. 2020; 24(6): 3411–3421. PubMed Abstract | Publisher Full Text\n\nMele M, Magazzino C: Pollution, economic growth, and COVID-19 deaths in India: a machine learning evidence. Environ. Sci. Pollut. Res. 2021; 28(3): 2669–2677. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMusa HH, El-Sharief M, Musa IH, et al.: Global scientific research output on sickle cell disease: A comprehensive bibliometric analysis of web of science publication. Scientific African . 2021; 12: e00774. Publisher Full Text\n\nO’Donnell A, Wilson L, Bosch JA, et al.: Life satisfaction and happiness in patients shielding from the COVID-19 global pandemic: A randomised controlled study of the ‘mood as information’theory. PLoS One . 2020; 15(12): e0243278. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOdone A, Salvati S, Bellini L, et al.: The runaway science: a bibliometric analysis of the COVID-19 scientific literature. Acta Bio Medica: Atenei Parmensis . 2020; 91(9-S): 34.\n\nSong Y, Chen X, Hao T, et al.: Exploring two decades of research on classroom dialogue by using bibliometric analysis. Comput. Educ. 2019; 137: 12–31. Publisher Full Text\n\nSun J, Yuan B-Z: Bibliometric mapping of top papers in Library and Information Science based on the Essential Science Indicators Database. Malays. J. Libr. Inf. Sci. 2020; 25(2): 61–76. Publisher Full Text\n\nVan Eck N, Waltman L: Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics . 2010; 84(2): 523–538. PubMed Abstract | Publisher Full Text\n\nWider W: Happiness and satisfaction research pre and during COVID-19 pandemic: A Bibliometric analysis of global scientific literature. [Dataset]. 2023. Publisher Full Text\n\nYi F, Yang P, Sheng H: Tracing the scientific outputs in the field of Ebola research based on publications in the Web of Science. BMC. Res. Notes . 2016; 9(1): 1–7. Publisher Full Text\n\nZambrano D, Serrato Alvarez D, Galindo Caballero OJ: Publications in psychology related to the covid-19: a bibliometric analysis. Psicología desde el Caribe . 2021; 38(1): 11–28.\n\nZhang H, Zhao X, Yin K, et al.: Dynamic estimation of epidemiological parameters of COVID-19 outbreak and effects of interventions on its spread. J. Public Health Res. 2021; 10(1): jphr.2021.1906. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "190917",
"date": "07 Aug 2023",
"name": "Gustaf Nelhans",
"expertise": [
"Reviewer Expertise Scientometrics",
"bibliometric visualisation",
"theory of science",
"research policy studies."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nUnfortunately, this study is already flawed at the study design level and in the inclusion of studies to do a bibliometric study on. A Scopus search on “TITLE-ABS-KEY “happiness” AND “satisfaction”)” does not identify a quality-controlled sample of research on happiness studies. As argued elsewhere, especially the ‘satisfaction’ term is not specific enough—the same with happiness. One can mention both terms without relating to either happiness or [life] satisfaction _research_ (measured or evaluated quantitatively or qualitatively).\nAs discussed further below, since research takes time to conceive, perform, and publish, studies published in the scholarly literature on a general topic, such as Happiness studies, will not have had time to be applied for, funded, performed and published during the pandemic years 2020-2021. Additionally, there is little way of identifying causal links between the pandemic and the research content, even when this research has been performed and published.\nThe rest of the review will give some points to other issues requiring serious revision, but it does not cover all flaws. A resubmission will need a complete reworking of the data sample used, as well as a well-thought-out structure of what bibliometric indicators to include and for what purpose.\nGeneral issues:\nThere is very little scientometric research or theoretical assumption about scientometric research besides references to two articles that describe the software packages used to do the analyses.\nBut no claims other than that bibliometrics is suitable for macro studies or meta-studies of research are made, and these don’t build on scientometric domain knowledge but on studies applying bibliometric techniques to various topics.\nIt is unclear how the author’s expertise is linked to either scientometrics or the subject areas they perform bibliometric studies for. The example of relating happiness and satisfaction, instead of (i.e. ‘life’ satisfaction) not mentioning subjective well-being or other terms closely related to the field (see https://worlddatabaseofhappiness.eur.nl), seems to put the domain knowledge of the authors of the study into question.\nSpecific comments:\nIntroduction:\nThe terminology of the research area is not distinct, and some assertions are not grounded in domain knowledge in either bibliometrics or happiness research.\n“Happiness and satisfaction”: Shouldn’t it be ‘life satisfaction’?\n”and are no longer a single metric”: This statement supposes that it once were a single metric, but when was happiness or satisfaction a single metric?\n“biopsychosocial constructs”: This relates to systems theory, a pretty outdated model of scientific knowledge. Why have the authors chosen this mode of scientific discourse? See Weiner (1994)1; also, see Borrell-Carrió, Suchman & Epstein (2004)2 for a defence from a practitioner position.\nThe upshot of the manuscript is somewhat flawed: “coronavirus disease (COVID-19) pandemic has potentially resulted in shifts among the general population in terms of how happiness and satisfaction are perceived”. But articles published during 2020 and 2021 were probably submitted in the year before and, even more probably, performed and conceived many years before being put into a manuscript, which means that we probably will not see research affected by the COVID-19 pandemic for some years to come.\nThen the manuscript continues to describe the situation and effects on the general problem and especially in two sectors, the young and the elderly, who have missed out on education and are being alienated, in turn. This is used as a background to state that it is “crucial that we quantify and collate the research work performed by institutions worldwide during the COVID-19 pandemic that focuses on the effect of COVID-19 lockdowns on happiness and satisfaction”. But researchers are neither young nor old, but rather in between. And the study does not focus on happiness research on COVID-19 effects but instead on Happiness research during COVID-19. As stated before, the research done during COVID-19 has most likely not yet been published, and certainly not during 2020, the first year of the pandemic.\nRegarding references to earlier bibliometric studies on the topic, few bibliometric studies are performed on happiness studies. But the following is relevant, based on the fact that visualisations of bibliometric networks on happiness studies are used: Kullenberg & Nelhans (2015)3. This paper was published in one of the leading journals in the field, Scientometrics.\nThe authors argue that “has been no bibliometric research that examines trends before and after, and makes a suitable comparison.” How did they come to that conclusion? A simple Scopus search on ‘bibliometric AND before AND after AND COVID-19’ into Scopus and search within article titles, abstracts and keywords. This search results in 159 documents (per Aug. 6, 2023), of which many are candidates for describing research on various phenomena before, during and after the pandemic. Or do they mean particularly Happiness studies? Then, the argument is not very convincing.\n“cataclysmic”: this word is exaggerated. Additionally, it is used in conjunction with a reference to Zambrano D, Serrato Alvarez D, Galindo Caballero OJ: Publications in psychology related to the covid-19: a bibliometric analysis. Psicología desde el Caribe . 2021; 38(1): 11–28. They don’t use that term in that study.\nSearch strategy:\nAs mentioned in the introduction, the terms happiness and satisfaction are too vague to isolate research on these areas. In the 2015 study on the emergence of happiness research referred to above, there was one order of magnitude more publication on “Happiness studies” defined broadly. Since the data set for that study was created in early 2014, there would probably be two to three times as many studies now. Why combine happiness and satisfaction with an AND operator? I would suggest using an OR operator and searching for more specific terms that distinguish various terminology related to the research area in focus.\nResults:\nComparing citation counts for two different cohorts covering documents of varying ages is very problematic. Also, since the scientific literature often expands very quickly (even exponentially (De Solla Price, 19634), comparisons of citation counts for cohorts from different time periods should be avoided.\nIn Table 1, one column is labelled “During COVID-19 (2020-2022)”, but the data set only covers 2020 to Dec. 18 2021. Which is correct?\nIn table 1 it also shows that many different categories (editorials, erratas, notes and conference reviews) are found. These are not research papers. Please argue for their inclusion in the study.\nThe data in Table 1 is more or less taken verbatim from one of the Bibliometrix functions. While many of these measures are interesting in themselves, why are they included here? For instance, the Collaboration index. It was 3.1 before and 3.75 in the COVID sample. But the authors do not relate to the data in the study? Please only present information that is pertinent to the study. Other information could (but why? Be included in an appendix).\nMost of the data shown in the pair-wise tables/figures are incomparable. As mentioned, differences between two cohorts in following time samples cannot say much about the content. For instance: Ed Diener was emeritus during the start of the pandemic and died in 2021. Of course, he could not have been very productive at this time. It is unclear what the tables of different top lists can say about the field of happiness studies during the two periods.\nAdditionally, some data are not comparable because of the different time periods of the groups compared. E.g. Figures 1 and 2 are not comparable.\nIn Figure 1, the outlets’ H-Index is calculated over a five-year period; in Figure 2, it is calculated over a two (three?)-year period. Why is this metric chosen?\nIn Table 6, there is an error: the column Total citations include the publication year.\nThe following study is stated to be the most cited in the table. In fact, it has zero (0) citations: Fobelov D, 2019, Aip Conf Proc 10.1063/1.5137988. Please check: DOI (10.1063/1.5137988). Also, the first author’s name is Fobelová.\nThe following paper has 56 citations, the third has zero. Please do some quality control of the tables. Also, look at the journal titles: Petroleum engineering, Signal processing. Is this where the authors expect to find happiness research?\nFigure 5: there is a blue cluster containing two terms in the top NE corner that should be mentioned.\nFigure 6 seems to show two different conceptual structures focusing on each of the two terms that were used in the original search. Here is food for a conceptual analysis of the content of the research. No such analysis is attempted.\nThen Keywords Plus™ are mentioned regarding Figure 7. But it is a construct created by Clarivate, the competitor of Elsevier for citation data. Did the authors also use Web of Science data? Figure 7 is incomprehensive.\nFigure 8, why include a word cloud? It is not considered a very relevant bibliometric visualisation technique. The information contained, that happiness, male and female, in various order are the most used terms, is not very relevant.\nMany visualisations made with VOSviewer are presented, but it is not based on any idea that there is a relationship between, for instance, co-authorship and content in the two cohorts.\nIn the discussion, the following argument is entirely false: “The “happiness” keyword evolved into two strands of “subjective well-being” and “happiness,” suggesting that in the pandemic, individuals’ experiences of happiness and unhappiness were very individualized as different nations and regions were subjected to widely varying levels of lockdown despite having similar epidemiological characteristics.” There is no way one could make such a far-fetched argument. Subjective well-being has been studied in its own right, evolving exponentially since the early eighties. See https://worlddatabaseofhappiness.eur.nl/search-the-database/bibliography/\nIn conclusion, this study provides no relevant information on the study of happiness research before and during the COVID-19 pandemic.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "224872",
"date": "16 May 2024",
"name": "Solomon Giwa",
"expertise": [
"Reviewer Expertise My field of study is mechanical engineering and I have published extensively using bibliometric analysis in different areas of my field of study."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe work is interesting and worth investigating. The hotspot and future research are missing along with the co-occurrence in the abstract. The introduction section is shallow. The use of cluster references should be avoided. Previous studies using bibliometric analysis in other fields of study and this field of study should be well reviewed and individually relay the results.\n\nThese articles can be of serious help in improving the various sections of the manuscript. 1. [Ref1] 2. [Ref2] 3. [Ref 3] 4. [Ref 4] Methodology The duration of data used in the study should be spelled out by the authors. The raw data must be filtered and scrutinized and not just used the way it is. The types of articles retrieved were not mentioned. The procedure for the use of this software is missing. The authors should provide a detailed procedure of how the software is used and also provide a flow chart for this study. In Table 1, are these \"sources\" (journals, books, etc.) not the same as documents? Why the change in values? Results The values in the third and fourth columns of Tables 3 and 6 should be in one or two decimal places. Same as Tables 10 and 11. The third column of Table 7 should be the year and not the total citations. Figure 7 is not legible. Discussion This section is very critical to this study. As it is, it is shallow. The values in the figures and tables with some mentioned in the manuscript text under the \"results section\" should be discussed for their significance and implications. Each of the obtained values under different analyses should be well explained even with references using previously published works. Also, the authors failed to discuss emerging and future studies in relation to the focus of this manuscript.\n\nConclusion This section should be a summary of the obtained results. The authors are to provide key results with numerical values and the implication of the obtained results. Recommendations, emerging research, and future studies are to be included in this section.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-658
|
https://f1000research.com/articles/11-328/v1
|
18 Mar 22
|
{
"type": "Research Article",
"title": "Evaluating the effectiveness of integrating digital technology into orthodontic cephalometric measurement teaching",
"authors": [
"Xin Yu",
"Yu Tian",
"Dandan Li",
"Wen Sun",
"Hua Wang",
"Siyang Yuan",
"Bin Yan",
"Lin Wang",
"Yongchu Pan",
"Xin Yu",
"Yu Tian",
"Dandan Li",
"Wen Sun",
"Hua Wang",
"Siyang Yuan",
"Lin Wang"
],
"abstract": "Background: This study aimed to evaluate the effectiveness of integrating digital technology into cephalometric measurement teaching. Methods: In total, 94 undergraduates of stomatology were recruited and randomly allocated to two groups. According to the cross-over design, both groups completed cephalometric measurements by the traditional hand-drawn method and digital technology (the Dolphin software) in different order. In the traditional hand-drawn method, students depicted the outline of the craniofacial anatomical structures on sulfuric transfer paper first, then marked the measurement points and completed the measurement of line spacings and angles; by digital technology, they marked the points in the software and adjust the automatically generated outlines of the structures to obtain the results. Two professional orthodontists were invited as instructors and their measurements were set as standards. An online questionnaire was also used to investigate students' attitudes toward digital technology being used in the cephalometric teaching process. Results: There were significant differences of students’ measurements (P1-SNA<0.01, P1-SNB=0.01 and P1-L1-NB (mm)<0.01; SNA: sella-nasion-subspinale angle, SNB: sella-nasion-supramental angle, L1-NB (mm): the distance from the lower central incisor tip to the nasion-supramental plane) between the traditional method and digital technology. Besides, the results of most items by digital technology were closer to the standards than those by the traditional method, including five items with statistical significance (P2-SNB<0.05, P2-L1-NB (mm)<0.01, P2-FMA<0.05, P2-FMIA<0.05, P2-IMPA<0.01), while three items were the opposite (P2-SNA<0.05, P2-ANB (mm)<0.01, P2-NA-PA<0.01). The questionnaire showed more students preferred digital technology (33%) as a better teaching method than the traditional method (2%) and 72% of participants thought they had mastered 50-80% of cephalometric knowledge after the course. Conclusions: This study demonstrated effectiveness and acceptance of the course applying digital technology during the cephalometric teaching process.",
"keywords": [
"orthodontic teaching",
"cephalometric measurement",
"traditional hand-drawn method",
"digital technology",
"the Dolphin software"
],
"content": "Introduction\n\nOrthodontics, as a subdiscipline of stomatology, aims to study various kinds of malocclusion, including deformities of teeth, jaws and the craniofacial region.1 Diagnosis is the most important part of orthodontic clinical work, among which cephalometric measurement is an essential procedure.2 Nevertheless, cephalometric measurement indicators are numerous and complicated. In the past, the traditional hand-drawn method was applied, which required reading lamps, sulfuric acid transfer paper, dividers and so on. In addition, previous studies suggested that undergraduates tended to show less confidence in reading and measuring lateral cranial radiographs.3 These factors may not only affect accuracy of measurements, but also contribute to destruction of students’ enthusiasm for further learning.\n\nAs continuous developments are seen in digital technology, such technology has been applied in the education for undergraduates in recent decades. Digital technology possesses vivid images and operable processes, making it more intuitive, interactive and understandable than simply imparting theoretical knowledge to students, which may help improve the effect of teaching practice.4–6 Buchanan JA et al. found that before starting clinical work, students could better master theoretical knowledge through simulated operation or computer-aided learning method.7,8 It was also reported that students' attitudes towards computer-aided learning and digital technique were positive.9–13 Digital technology has offered great potential for dental education as well.14 For instance, Nagy ZA et al. reported that the Dental Teacher software could help students more efficiently learn the preparation technique of onlay restorations and facilitate their individual performances.15 Liu L et al. also found the digital training system might be a good alternative to the traditional training method in the preclinical practice of tooth preparation.16\n\nThe digital cephalometric analysis system, widely incorporated in intelligent software, was developed to computerize the manual tasks and output the specific results automatically. It was reported to be more time-saving than traditional measurement method and helpful for reducing unnecessary errors during the measurement process.17 Farooq et al. also found that the accuracy of cephalometric measurement by digital tracing with FACAD® was similar with the manual method. Furthermore, its advantages of digital imaging, such as quality improvement, file transmission and archiving made digitalized cephalometric analysis preferrable in daily use.18\n\nThe Dolphin software® (Dolphin Imaging & management solution, America) is widely applied in the field of orthodontics, possessing functions like storage and management of patients’ information and images. After users upload computerized tomography photographs, it can also achieve three-dimensional imaging, cephalometric measurement and treatment effect prediction. It incorporates more than 400 cephalometric analytical methods. This software has been reported to have the potential as an animation textbook for medical college students.19 Although it was assumed to exert some positive effects in the teaching process, there is still lack of research investigating the effectiveness of applying it in orthodontic cephalometric teaching process. Thus, the aim of this study was to examine the effectiveness of applying digital technology (the Dolphin software®) in teaching cephalometric measurement.\n\n\nMethods\n\nThis study followed the guidelines of the Nanjing Medical University ethics review committee and received the approval of the committee (approval number: PJ2019-053-001). All participants gave written informed consent.\n\nG*Power software version 3.1.9.7 (RRID:SCR_013726) was used to estimate the required sample size for this study. This study used two independent t tests to calculate the number of students needed. The study power was set at 90% and alpha value set at 0.05. Based on these, a minimum sample of 86 subjects was required.\n\nThis study approached fourth-year undergraduate students of Stomatology in Nanjing Medical University by inviting them to attend this course, followed by their voluntary registration. All the students, consisting of 63 female and 31 male students (around 21-23 years old), agreed to participate in this pedagogical experiment and signed the informed consent form. There were no exclusion criteria. We also invited two orthodontist faculty members with over 5 years of clinical experience as instructors.\n\nThis study was conducted from May 12, 2020 to June 16, 2020. The flow diagram of this pedagogical study, as shown in Figure 1, was generally divided into anatomical points calibration, pre-test instruction, cephalometric measurement, questionnaire survey and data analysis. Firstly, two instructors unified the standard of the anatomical markers on lateral cranial radiograph, and then gave theoretical lessons and practical guidance to 94 students. According to the cross-over design, students were randomly divided into two groups, and completed cephalometric measurements by the traditional method and digital technology in a different order. The instructors also measured the same lateral radiograph by two methods and repeated the measurement a week later. After the lecture, an online questionnaire survey was conducted to investigate students' attitudes towards the cephalometric measurement course applying digital technology. Finally, we collected information and data for statistical analysis.\n\nAnatomical points calibration\n\nBefore the course, the standard of anatomical markers on lateral cranial radiographs were calibrated. Firstly, two orthodontists reviewed the basic definitions and meanings of common anatomical points and items. Then, they measured a lateral cranial radiograph on paper and by software, followed by discussing and unifying the anatomical position standard. Subsequently, they respectively completed cephalometric measurement of another lateral cranial radiograph. The intraclass correlation coefficient (ICC) was greater than 90%, showing consistency of cephalometric measurement between them.\n\nPre-test instruction\n\nThe total teaching period consisted of 7 credit hours, including 4 credit hours of theoretical class and 3 credit hours for practical instruction. During the theoretical class, one instructor imparted relevant knowledge to the students in detail, including the positions of anatomical markers and the meanings of commonly used measurement items.\n\nIn the practical instruction class, another instructor guided 94 students to review the basic knowledge and showed them how to complete cephalometric measurement by the traditional method and digital technology (the Dolphin software®). For the traditional method, the sulfuric acid transfer paper was fixed to the radiograph with a clip. Then, the patient’s soft tissue profile and hard tissue anatomical structures were depicted on the reading lamp. Finally, the commonly used anatomical points were identified on the sulfuric acid transfer paper and the measurement was completed with the ruler and protractor.\n\nWhile using digital technology, the instructor adjusted results of line spacing on the lateral cranial radiograph to their actual size at first. Then, the instructor accomplished the measurement by adjusting the gray contrast value and other auxiliary methods. After learning the relevant knowledge of commonly used cephalometric measurement points and items, students were encouraged to review relevant contents after class.\n\nCephalometric measurement\n\nOne week after the end of the pre-test instruction, 94 students were randomly allocated into two groups through the RAND function in Excel software (Microsoft® Excel® 2019MSO (2201 Build 16.0.14827.20198 version for 64 bit) and were required to complete cephalometric measurement by both traditional method and digital technology (the Dolphin Imaging® 11.8). Two instructors also measured the same lateral cranial radiograph by two methods.\n\nAccording to the cross-over design, one group took the traditional method first to complete the measurement and then used the Dolphin software®, while the other group completed in the opposite order. Two instructors measured the same lateral cranial radiograph using two methods. A total of 15 cephalometric items (Figure 2) were measured, such as the angle between Sella-Nasion plane and the Nasion-Subspinale plane (SNA), the angle between Sella-Nasion plane and the Nasion-Supramental plane (SNB), the angle between the Nasion-Subspinale plane and the Nasion-Supramental plane (ANB). The measurements of the traditional method and Dolphin software® were recorded, respectively. The collection and input of these data were completed by three postgraduates, with two postgraduates responsible for the inputting and the third one in charge of checking.\n\n1. SNA: the angle between the sella-nasion plane and the nasion-subspinale plane; 2. SNB: the angle between sella-nasion plane and the nasion-supramental plane; 3. ANB: the angle between the nasion-subspinale plane and the nasion-supramental plane; 4. NP-FH: the posterior-inferior angle between the facial plane and the Frankfort horizontal plane; 5. NA-PA: the angle between the nasion-subspinale plane and the pogonion-subspinale plane; 6. U1-NA (mm): the distance from the upper central incisor tip to the nasion-subspinale plane; 7. U1-NA: the angle between the upper central incisor and the nasion-subspinale plane; 8. L1-NB (mm): the distance from the lower central incisor tip to the nasion-supramental plane; 9. L1-NB: the angle between the lower central incisor and the nasion-supramental plane; 10. U1-L1: the angle between the upper central incisor and the lower central incisor; 11.Y axis angle: the anterior-inferior angle between the Frankfort horizontal plane and the sella-pogonion plane; 12. Po-NB (mm): the distance from the pogonion point to the nasion-supramental plane; 13. FMA: the angle between the Frankfort horizontal plane and the mandibular plane; 14. FMIA: the angle between the Frankfort horizontal plane and the long axis of the lower central incisor; 15. IMPA: the angle between the long axis of the lower central incisor and the mandibular plane.\n\nIn order to survey the effectiveness of applying the digital software in cephalometric teaching and students’ attitudes toward it (the Dolphin software®), we designed an online questionnaire and collected results by Wenjuanxing. For example, to investigate how difficult students considered cephalometry is, we set three options ranging from “very difficult”, “kind of tough” to “easy”. As to the mastery degree of students after the course, the options were “50-80%”, “20-50%” to “0-20%”. Gender of the participants was recorded from the university records. The detailed questionnaire list and corresponding options are shown in Table 1.\n\nThe quantitative data of cephalometric measurements were analyzed by the statistical software SPSS 18.0 (IBM Corporation, Armonk, NY, RRID:SCR_016479). The measurements of students by two methods were compared using the independent sample t test, as well as comparing them with corresponding standards, respectively, with the level of significance set as P<0.05.\n\nAs for questionnaire data, we obtained the statistical data through the built-in function on the online questionnaire platform, as it provided the constituent ratio of each option and participants list. Then we performed a descriptive analysis of these results.\n\n\nResults\n\nThe ICC of two instructors’ measurements with one-week interval surpassed 90%, thus the means of two instructors’ measurements of each method were set as the standards, respectively.26\n\nStatistically significant differences were observed in measurements of SNA, SNB and the distance from the lower central incisor tip to the nasion-supramental plane (L1-NB (mm)) between the traditional method and digital technology (P1-SNA<0.01, P1-SNB=0.01, P1-L1-NB (mm)<0.01) (Table 2), while other items showed no significant differences. There were no statistically significant differences of measurements between different genders (P>0.05, ranging from 0.07 to 0.99) (Extended data, Supplementary table 1.26). Besides, the measurements by digital technology were closer to the standard values than those by the traditional method. The accuracy of five items measurements using digital technology was significantly higher, including SNB, L1-NB (mm), the angle between the Frankfort horizontal plane and the mandibular plane (FMA), the angle between the Frankfort horizontal plane and the long axis of the lower central incisor (FMIA), and the angle between the long axis of the lower central incisor and the mandibular plane (IMPA) (P2-SNB<0.05, P2-L1-NB (mm)<0.01, P2-FMA<0.05, P2-FMIA<0.05, P2-IMPA<0.01). However, five items presented the opposite result, among which three items were statistically significant (SNA, ANB and the angle between the Nasion-Subspinale plane and the pogonion-subspinale plane (NA-PA) (P2-SNA<0.05, P2-ANB<0.01, P2-NA-PA<0.01).\n\nWe assigned the questionnaires to all the participants with 82 of 94 students filling out the questionnaire and the response rate was 87%. The statistical results of the questionnaire are shown in Table 1. Among the respondents, 66% thought studying cephalometry was very difficult and 21% thought it was kind of tough. After instruction, review and practice, 72% of them considered they had mastered 50-80% of relevant knowledge and a few students thought they had mastered 20-50%. About 33% of students preferred the digital technology than traditional method (2%) as a better teaching method and 65% held that both were acceptable, which indicated good acceptance by students of digital technology applied in the teaching process. In addition, 98% of participants expressed their interest in studying cephalometry and considered cephalometric analysis helpful to diagnosis of malocclusion.\n\n\nDiscussion\n\nCephalometric measurement is essential for diagnosis and treatment plan design of patients with malocclusions, which are the most significant procedures in orthodontic clinical work. Orthodontic educators put forward that orthodontic teaching for undergraduates should focus on diagnosis and recognition of problems.20 However, there is not a generally accepted teaching method, and a wide variation of course durations and contents exist in different dental colleges and faculties.21 How to arouse students’ interest and achieve better teaching effects is a major problem faced by orthodontic educators. Since only a few reports explored this aspect, we designed this didactical experiment.\n\nIn our study, three cephalometric items measured by two methods were statistically different, while other items were basically similar. These results implied that digital technology could achieve similar results to the traditional method during cephalometric measurement. Additionally, the majority of items measured by digital technology were closer to the standards, including five statistically significant items, which suggested students could achieve more accurate results by digital technology. This may be attributed to the function of digital software to adjust the gray contrast value of X-ray films (Extended data, Supplementary figure 1.26), making it easier to identify the unclear points on the printed paper. In addition, the automatic generation of results also helped to avoid evitable errors during manual measurement. These results were in accordance with previous studies, which suggested that the accuracy of digital measurement on 3-dimensional cone beam computed tomography images was basically similar to or even higher than that of manual measurement.22,23\n\nHowever, in spite of the convenience it provided, the digital technology may lead to a lack of deep understanding of corresponding contents, such as definitions and meanings of these measurement items. The traditional method could better cultivate practical abilities of students and enhance their memory of relevant knowledge. Besides, although the accuracy of some items obtained by digital technology were significantly higher, a few items showed the opposite result (SNA, ANB and NA-PA). The subspinale point (the A point) was associated with these three items, which suggested that the traditional method was more accurate than digital technology in positioning the subspinale point on the lateral cranial radiograph. The subspinale point is the most concave point of the arc from the anterior nasal spine point (the ANS point) to the superior prosthion point (the Spr point). Compared with digital measurement, the advantage of manual measurement is that the arc can be traced on paper, and some auxiliary instruments like ruler and protractor can help to locate the subspinale point (Extended data, Supplementary figure 2.26). These results indicated abundant experience was required to identify the subspinale point, reminding both orthodontic educators and students to devote more time and energy to deep learning it.\n\nBefore the course, the majority of students showed fear towards abstract and complex concepts, assuming cephalometric measurement was difficult to master. However, with instruction and practice, most students could master 50-80% of relevant knowledge, which could result from digital technology realizing visualization of numerous and complicated anatomical markers. Previous studies found that visualization was extremely attractive to young students, and significantly aroused their interest and sense of participation.24,25 Our survey confirmed that more students preferred digital technology (33%) as a better teaching method than the traditional method. As a result, the application of digital technology in teaching cephalometric measurement was widely accepted by students and contributed to favorable teaching results.\n\nThis study still had some limitations. For example, the sample size could be further enlarged. Secondly, the measurement time for students were not strictly required, which may have resulted in the underperformances or supernormal performances of students. Thirdly, exploration of student’s attitudes towards digital technology being applied in this course was not sufficient. The mentioned issues needed to be improved may interrupt us from to accurately assessing the real advantages and disadvantages of the appliance of this digital technology. These findings could guide and encourage university orthodontic teachers to apply this technology in cephalometric teaching and pay more attention to considering the position identification of the subspinale point.\n\n\nConclusion\n\nThis study investigated the effectiveness of applying the digital technology (the Dolphin software®) in cephalometric teaching, demonstrating good effectiveness and acceptance of this technology.\n\n\nData availability\n\nFigshare: Evaluating the effectiveness of integrating digital technology into orthodontic cephalometric measurement teaching. https://doi.org/10.6084/m9.figshare.19270952.26\n\nThis project contains the following underlying data:\n\n- The consistency of two instructors.docx\n\n- The results of students’ measurements.xlsx\n\n- Statistical results of the questionnaire.xlsx\n\nFigshare: Evaluating the effectiveness of integrating digital technology into orthodontic cephalometric measurement teaching. https://doi.org/10.6084/m9.figshare.19270952.26\n\nThis project contains the following extended data:\n\n- Supplementary File.docx (Supplementary table 1; Supplementary figure 1, 2)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nDitmarov A: Orthodontics: Orthodontics vs orthodontiya. Br. Dent. J. Jul 13 2018; 225(1): 2. PubMed Abstract | Publisher Full Text\n\nJheon AH, Oberoi S, Solem RC, et al.: Moving towards precision orthodontics: An evolving paradigm shift in the planning and delivery of customized orthodontic therapy. Orthod. Craniofac. Res. Jun 2017; 20(Suppl 1): 106–113. PubMed Abstract | Publisher Full Text\n\nDrage NA, Atkin PA, Farnell DJJ: Dental and maxillofacial radiology: confidence, knowledge and skills in the newly graduated dentist. Br. Dent. J. Apr 2020; 228(7): 546–550. Publisher Full Text\n\nZitzmann NU, Matthisson L, Ohla H, et al.: Digital Undergraduate Education in Dentistry: A Systematic Review. Int. J. Environ. Res. Public Health. May 7 2020; 17(9). PubMed Abstract | Publisher Full Text\n\nInquimbert C, Tramini P, Romieu O, et al.: Pedagogical Evaluation of Digital Technology to Enhance Dental Student Learning. Eur. J. Dent. Feb 2019; 13(1): 053–057. PubMed Abstract | Publisher Full Text\n\nSilveira MS, Cogo ALP: The contributions of digital technologies in the teaching of nursing skills: an integrative review. Rev. Gaucha Enferm. Jul 13 2017; 38(2): e66204. Contribuições das tecnologias educacionais digitais no ensino de habilidades de enfermagem: revisão integrativa. PubMed Abstract | Publisher Full Text\n\nBuchanan JA: Use of simulation technology in dental education. J. Dent. Educ. Nov 2001; 65(11): 1225–1231. Publisher Full Text\n\nUrbankova A: Impact of computerized dental simulation training on preclinical operative dentistry examination scores. J. Dent. Educ. Apr 2010; 74(4): 402–409. PubMed Abstract | Publisher Full Text\n\nAl-Jewair TS, Qutub AF, Malkhassian G, et al.: A systematic review of computer-assisted learning in endodontics education. J. Dent. Educ. Jun 2010; 74(6): 601–611. Publisher Full Text\n\nAbbey LM, Arnold P, Halunko L, et al.: CASE STUDIES for Dentistry: development of a tool to author interactive, multimedia, computer-based patient simulations. J. Dent. Educ. Dec 2003; 67(12): 1345–54.\n\nAl-Jewair TS, Azarpazhooh A, Suri S, et al.: Computer-assisted learning in orthodontic education: a systematic review and meta-analysis. J. Dent. Educ. Jun 2009; 73(6): 730–739. PubMed Abstract | Publisher Full Text\n\nRosenberg H, Grad HA, Matear DW: The effectiveness of computer-aided, self-instructional programs in dental education: a systematic review of the literature. J. Dent. Educ. May 2003; 67(5): 524–532. PubMed Abstract | Publisher Full Text\n\nSchott TC, Arsalan R, Weimer K: Students' perspectives on the use of digital versus conventional dental impression techniques in orthodontics. BMC Med. Educ. Mar 12 2019; 19(1): 81. PubMed Abstract | Publisher Full Text\n\nRen Q, Wang Y, Zheng Q, et al.: Survey of student attitudes towards digital simulation technologies at a dental school in China. Eur. J. Dent. Educ. Aug 2017; 21(3): 180–186. Publisher Full Text\n\nNagy ZA, Simon B, Tóth Z, et al.: Evaluating the efficiency of the Dental Teacher system as a digital preclinical teaching tool. Eur. J. Dent. Educ. Aug 2018; 22(3): e619–e623. PubMed Abstract | Publisher Full Text\n\nLiu L, Li J, Yuan S, et al.: Evaluating the effectiveness of a preclinical practice of tooth preparation using digital training system: A randomised controlled trial. Eur. J. Dent. Educ. Nov 2018; 22(4): e679–e686. PubMed Abstract | Publisher Full Text\n\nChen SK, Chen YJ, Yao CC, et al.: Enhanced speed and precision of measurement in a computer-assisted digital cephalometric analysis system. Angle Orthod. Aug 2004; 74(4): 501–507. Publisher Full Text\n\nFarooq MU, Khan MA, Imran S, et al.: Assessing the Reliability of Digitalized Cephalometric Analysis in Comparison with Manual Cephalometric Analysis. J. Clin. Diagn. Res. Oct 2016; 10(10): Zc20–zc23. PubMed Abstract | Publisher Full Text\n\nHongyu Chen CW: Wenli Lai The introduction of Dolphin software and its clinical application in orthodontics. Journal of Chinese Physician. 2015; 17(04): 611–613.\n\nRock WP, O'Brien KD, Stephens CD: Orthodontic teaching practice and undergraduate knowledge in British dental schools. Br. Dent. J. Mar 23 2002; 192(6): 347–351. PubMed Abstract | Publisher Full Text\n\nDerringer KA: Undergraduate orthodontic teaching in UK dental schools. Br. Dent. J. Aug 27 2005; 199(4): 224–232. PubMed Abstract | Publisher Full Text\n\nShahidi S, Oshagh M, Gozin F, et al.: Accuracy of computerized automatic identification of cephalometric landmarks by a designed software. Dentomaxillofac. Radiol. 2013; 42(1): 20110187. PubMed Abstract | Publisher Full Text\n\nGupta A, Kharbanda OP, Sardana V, et al.: Accuracy of 3D cephalometric measurements based on an automatic knowledge-based landmark detection algorithm. Int. J. Comput. Assist. Radiol. Surg. Jul 2016; 11(7): 1297–1309. PubMed Abstract | Publisher Full Text\n\nTriepels CPR, Smeets CFA, Notten KJB, et al.: Does three-dimensional anatomy improve student understanding?. Clin. Anat. Jan 2020; 33(1): 25–33. PubMed Abstract | Publisher Full Text\n\nAmer RS, Denehy GE, Cobb DS, et al.: Development and evaluation of an interactive dental video game to teach dentin bonding. J. Dent. Educ. Jun 2011; 75(6): 823–831. PubMed Abstract | Publisher Full Text\n\nTian, Pan Y: Evaluating the effectiveness of integrating digital technology into orthodontic cephalometric measurement teaching. figshare. Dataset. 2022. Publisher Full Text"
}
|
[
{
"id": "148740",
"date": "07 Sep 2022",
"name": "Cinzia Maspero",
"expertise": [
"Reviewer Expertise Orthodontic",
"Orthognati surgery",
"cephalometic",
"maxillary expansion",
"interceptive orthodontics",
"fixed appliances",
"clear aligners",
"pediatric dentistry"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for submitting your research. The manuscript is interesting but some changes are necessary before taking it into consideration for publication. Here are my concerns:\nABSTRACT: \"Besides, the results of most items by digital technology were closer to the standards than those by the traditional method\" What do you mean with standards?\n\nINTRODUCTION: replace the word subdiscipline with discipline.\n\n\"These factors may not only affect accuracy of measurements, but also contribute to destruction of students’ enthusiasm for further learning.\" Are you sure with this sentence?\n\nSTUDY DESIGN: pre-test instruction. Please better explain what do you mean and what instruction have been given.\n\nFLOW CHART: anatomical point calibration: calibrated their standard. What do you mean? Specify which standard.\n\nCEFALOMETRIC MEASUREMENTS: it is not clear if the same lateral teleradiography have been used for all the students. Better specify.\n\nIllustration of 15 commonly used measurement items: which kind of tracing have been used?\n\nPlease better specify the aim of this study.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "8992",
"date": "12 Dec 2022",
"name": "Yu Tian",
"role": "Author Response",
"response": "Thank you for submitting your research. The manuscript is interesting but some changes are necessary before taking it into consideration for publication. Here are my concerns: Response: We are grateful for the reviewer’s helpful suggestions. As shown below, we have addressed the reviewer’s concerns, and provided point-by-point responses. We hope that the changes meet your approval. 1. ABSTRACT: \"Besides, the results of most items by digital technology were closer to the standards than those by the traditional method\" What do you mean with standards? Response: Thank you for your valuable suggestion. The means of two instructors’ measurements were set as the standards, and we’ve added this in the abstract (line 4 in Results, page 2). 2. INTRODUCTION: replace the word subdiscipline with discipline. Response: Thank you for your suggestion. According to your advice, we’ve used the word “discipline” in line 1, page3. 3. \"These factors may not only affect accuracy of measurements, but also contribute to destruction of students’ enthusiasm for further learning.\" Are you sure with this sentence? Response: Thank you for your advice. We’ve deleted the sentence. 4. STUDY DESIGN: pre-test instruction. Please better explain what do you mean and what instruction have been given. Response: Thank you for your suggestion. We’ve checked the manuscript, and described the pre-test instruction in detail in page 6, which included 7 credit hours and let students learn about the 15 cephalometric items and two measurement methods. 5. FLOW CHART: anatomical point calibration: calibrated their standard. What do you mean? Specify which standard. Response: Thank you for your valuable suggestions. We revised the subtitle and described in detail that “Before the course, the inter- and intra-class correlation coefficient of two instructors’ measurements were tested. Firstly, two orthodontists reviewed and discussed the locations of anatomical points. Then, they measured a lateral cranial radiograph by traditional and software methods. One week later, they measured the same radiograph by two methods again. The measurements by one instructor at one-week’s interval were used for calculating intra-class correlation coefficient (ICC intra), and measurements by two instructors were used for calculating inter-class correlation coefficient (ICC inter)” in Inter- and intra-class correlation coefficient of two instructors’ measurements section. 6. CEFALOMETRIC MEASUREMENTS: it is not clear if the same lateral teleradiography have been used for all the students. Better specify. Response: Thank you for your suggestion. We’ve added in line 2, page 7 that “One week after the end of the pre-test instruction, 94 students were randomly allocated into two groups through the RAND function in Excel software (Microsoft® Excel® 2019MSO (2201 Build 16.0.14827.20198 version for 64 bit) and were required to complete cephalometric measurement of the same lateral cranial radiograph by both traditional method and digital technology (the Dolphin Imaging® 11.8).”. 7. Illustration of 15 commonly used measurement items: which kind of tracing have been used? Response: Thank you for your question. The tracing was completed with the Uceph software, and we’ve added “The profile tracing was completed with the Uceph software (Uceph, Chengdu, China).” in the illustration of Figure 2. 8. Please better specify the aim of this study. Response: Thank you for your suggestion. We’ve revised in abstract and introduction section that “This study aimed to evaluate the effect of applying digital technology in cephalometric measurement teaching and students’ acceptance towards it”."
}
]
},
{
"id": "135780",
"date": "07 Sep 2022",
"name": "Ana Corte-Real",
"expertise": [
"Reviewer Expertise Medical and Dentistry Higher Education and Health Quality"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe topic is interesting for assessing learning from the student's perspective, but the title does not correspond to the content. The methodology section is the weakest part of the work. The authors should adjust the study design, including the analysis of intra and inter-observer accuracy and monitoring activities during the study. The selection of participants should include the inclusion and exclusion criteria as the previous use of digital technology for cephalometric measurements impacts the students' skills.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "8993",
"date": "12 Dec 2022",
"name": "Yu Tian",
"role": "Author Response",
"response": "Response: We are grateful for the reviewer’s helpful suggestions. As shown below, we have addressed the reviewer’s concerns, and provided point-by-point responses. We hope that the changes meet your approval. 1. The topic is interesting for assessing learning from the student's perspective, but the title does not correspond to the content. Response: Thank you for your valuable suggestions. We fully understand and agree with your suggestion about the relationship between the title and content of this article. We’ve revised the title to make it more suitable for this study “Evaluating the effect of digital technology on the learning of orthodontic cephalometric measurement”. 2. The methodology section is the weakest part of the work. The authors should adjust the study design, including the analysis of intra and inter-observer accuracy and monitoring activities during the study. Response: Thank you for your valuable suggestion. We added in Methods section that “The measurements by one instructor at one-week’s interval were used for calculating intra-class correlation coefficient (ICC intra), and measurements by two instructors were used for calculating inter-class correlation coefficient (ICC inter).”, and in Standards of cephalometric measurement section that “The inter- and intra-ICC were all surpassed 90%, and there were no significant differences between two instructors’ measurements, and the measurements by two methods”. As regard to the monitoring activity, we’ve added that “During this pedagogical experiments, two instructors took responsibility for guiding students with cephalometric measurements, assuring the measurement order of two student groups, monitoring the process of giving out and recollecting the questionnaire, as well as assistance in the data analysis.” in the Monitoring activity section in page 8. 3. The selection of participants should include the inclusion and exclusion criteria as the previous use of digital technology for cephalometric measurements impacts the students' skills. Response: Thank you for your suggestions. We agree with your advice on the selection of participant students. We’ve added in “Participants” section in line 5, page 6 that “…All the students did not learn about the method of measuring the lateral cranial radiographs and used the Dolphin software before”."
}
]
}
] | 1
|
https://f1000research.com/articles/11-328
|
https://f1000research.com/articles/12-642/v1
|
12 Jun 23
|
{
"type": "Research Article",
"title": "Validity and reliability of the questionnaire of academic knowledge of teachers of basic general education",
"authors": [
"Andrea Basantes-Andrade",
"Juan Carlos López-Gutiérrez",
"Milton Mora Grijalva",
"Yenney Ricardo",
"Juan Carlos López-Gutiérrez",
"Milton Mora Grijalva",
"Yenney Ricardo"
],
"abstract": "Background: The concern and analysis about the knowledge possessed by teachers of basic general education persists in academic debate and professional practice. It is noteworthy that in the studies consulted, there is no precise evidence that determines with accuracy the configurations of these knowledge factors that function as the basis of the teaching profession. Therefore, the objective of this study is to establish the construct validity and reliability of the questionnaire on the nature or origin of the academic knowledge of teachers of basic general education, adapted from the Pedagogical Content Knowledge (PCK) Competence Model. Methods: A methodological study was established that applies a test to the processes of reliability and internal consistency. The construct validity was performed through (n = 8) expert judges, using Cohen's Kappa. An exploratory factor analysis was performed following the criteria of the Kaiser-Meyer-Olkin Coefficient (KMO), the Bartlett sphericity test and the principal components extraction method in the factor analysis with varimax rotation. The sample consisted of (n = 27) teachers of basic general education of the Ibarra Canton. Results: The results show a reliability analysis for the instrument obtained a Cronbach’s alpha (α = 0.901), estimated to be an excellent level. Conclusions: The questionnaire is relevant, valid and reliable, adapting to the needs of teachers of basic general education to determine the nature or origin of the academic knowledge in a fast and reliable manner.",
"keywords": [
"Academic knowledge",
"validity",
"reliability",
"prior knowledge",
"questionnaire",
"factor analysis",
"Kaiser-Meyer-Olkin coefficient."
],
"content": "Introduction\n\nThe concern and analysis about the knowledge possessed by teachers in general, and in particular those of basic general education, persists within the academic debate and in professional practice.1–3 The nature of teachers’ education has become an important field of study considering the role it has in society.\n\nIn Ecuador, studies on the subject are scarce. For this reason, the need arose to carry out this research, with the intention of proposing a questionnaire to determine the origin of the academic knowledge of teachers of basic general education. In the bibliographic review, the absence of instruments to understand the configuration of the knowledge that a teacher puts into practice in the classroom was determined. From the perspective of this research, this fact is decisive for the quality of education.\n\nIn recent years, several studies have addressed the impact of teachers’ professional knowledge on the quality of teaching. There is a prevalence towards the analysis of pedagogical knowledge of the content,4 which can be associated with a traditional conception of education.\n\nAt the same time, the academic community recognizes that a teacher’s level of knowledge is an indicator of the quality of their behaviour in the classroom.5 This implies understanding this fact in terms of relational categories. It is worth mentioning that Shulman6 was a precursor in considering that a teacher’s knowledge affects the student’s assessment of his capacity and with it of quality. This criterion becomes an important conceptual support for the analysis that occupies this work.\n\nAdditionally, it is striking that in the studies consulted,7,8 there is no evidence that accurately determines the factors that make up the knowledge of a teacher, which function as support for the profession of teacher. It is possible that this is due to the multiplicity of ways in which knowledge is manifested and reached.\n\nHowever, in mainstream literature, several authors have shown interest not only in the analysis of knowledge of the teacher,9–11 but also in its implementation by designing tools that allow them to identify student´s learning styles and their pedagogical usefulness.12,13\n\nBuilding on this, it can be added that academic knowledge and its relationship with the teaching praxis are characterized firstly by being integrated into practice, which implies a continuous process of assimilation and organization of knowledge by the individuals involved. Secondly, they are situated within a temporal category that recognizes their emergence and evolution within a specific historical context and are related to a variety of knowledge.14 The combination of theoretical and practical knowledge that a teacher possesses is a result of their academic training and professional experience in the corresponding field.15\n\nIn other words, academic knowledge is considered an active, dynamic, and transformative relationship which is used to apprehend, understand and act on an environment. These relationships have the peculiarity of manifesting, reconfiguring and being open to debate. That is to say, these gradual development characteristics are the result of different processes, which are related to the teacher’s academic training in a specific disciplinary area, as well as their professional, affective, cultural, and social experiences that the teacher assumes.\n\nWithin this order of ideas, it should be considered that academic knowledge has been the center of attention when proposing new didactic strategies that the educator must consider according to the changes that are taking place in society. Likewise, several educational reforms that have been carried out from the point of view of teacher training take this knowledge as a starting point.\n\nIn Ecuador it is observed that in basic education, the role of the teacher is focused on the realization of micro-curricular plans and the incorporation of methodological strategies that involve the student at the center of the educational process. Additionally, it is noticeable that the teacher must develop appropriate resources and the types of evaluation to be carried out. Precisely, one of the aspects indicated to comply with the above comes from the combination of the teacher’s knowledge and professional skills.10 To achieve this goal, they must achieve an innovation of educational work with flexibility in different contexts, as well as the exercise of a systematic pedagogical praxis.\n\nIt is also linked to certain performances developed by the teacher. Important knowledges are identified: to know the area of knowledge that teaches; to know how to teach the subject; to know how to teach in general; and to know how people learn.\n\nThe work “The seven necessary knowledges for the education of the future” by Edgar Morín16 published by the United Nations Educational, Scientific and Cultural Organization (UNESCO), opened a space for reflection on education and the implications for the future of the quality of academic knowledge. In this regard, it has been possible to identify a variety of knowledge that teachers must possess (Table 1).\n\nThe aspects presented in Table 1 are based on the vision of reconfiguring the training of future teachers of basic education based on the paradigm shift of educational processes from teaching to learning. In this way, we proceed to solve those problems of praxis and those that directly affect the integral development of the student. This determines important adjustments not only of teachers, but of students and educational institutions. The former must act as true leaders and agents of change and transformation of didactic praxis.17\n\nAnother important aspect to consider is given by the notions of implicit theories,18 which configure the knowledge indicated. A review of several studies,19 reports that teachers face difficulties in practice motivated by the way they perceive the teaching of a discipline, especially in the use of strategies loaded with values for which they are not prepared.\n\nIt shifts from focusing on what teachers know about the practice to their perceptions of its possibilities. This approach changes the understanding of the social context as an important influence on the way teachers make decisions about their practice. The role of previous experiences is fundamental in teachers’ perception of specific teaching situations.20\n\nThe teachers’ perception of their practice refers to how teachers interpret and view their own work in the classroom; that is, how they understand and value their own performance in teaching. This includes the understanding of their role as educators, the pedagogical strategies they possess, their relationships with students, as well as their ability to respond to unforeseen situations, among other aspects. The teachers’ perception of their practice can influence their decisions and actions in the classroom, as well as their ability to improve and adapt to new situations.\n\nA question arises before the proposal of this systematic construction carried out by teachers: why is it necessary to understand the experience of the profession, as well as the disciplinary structure of which it was formed and its concretion in practice? The answer may be oriented to the lack or weak mastery that this can exercise on knowledge of the subject, in addition to the curriculum and vocational training dictated or oriented in a fragmented and institutional way.\n\nA second answer can be given by the specific disposition of the pedagogical situation through the educator that implies simplifications and exemplifications that allow learning on the part of the student.13,21\n\nRegardless of the historical period in which they were carried out, the studies do not respond to the need to break a pre-established disposition of disciplinary knowledge as a structuring mechanism of teaching and therefore of training. It is considered vital to reconfigure the vision that the teaching profession presents in practice.\n\nGiven these dilemmas and fragmentations, it is essential to determine the nature or origin of this knowledge oriented by personal identity, the work context and the experience accumulated by teachers.\n\nThese elements constitute an argument to conduct a new study that develops the construct of academic knowledge as a central theoretical core, which contributes to a better understanding of the factors that interact with the knowledge raised and that are expressed in the development of teaching practice.\n\nTeachers need to identify academic knowledge to plan, teach and reflect effectively on instruction22; for this purpose, measurement instruments are limited.23 In the literature review, no studies or research were identified that analyse the knowledge of teachers in the conditions of the Ecuadorian territory and even more so in the educational units of the Ibarra Canton; nor the nature or origin of these.\n\nIt is recognized that there is a significant interest in determining the configurations of knowledge; however, evidence of its validity is still lacking. It is precisely this aspect that this proposal seeks to resolve. The objective of the study is to establish the construct validity and reliability of the questionnaire on the nature or origin of the academic knowledge of teachers of basic general education.\n\nThis knowledge has a broad, plural, integrating connotation, linked to social aspects. The proposed conceptual delimitation limits an academic knowledge closely linked to the exercise of reflection on knowledge. In this sense, basic education teachers do not limit themselves to teaching a pre-established curriculum, but develop their didactic activity based on practical knowledge, including their values and beliefs.24\n\nThis last aspect is determined by macro and micro contextual factors, in addition to national educational policies and personal experiences.25 In this way, the orientation of the present research towards the daily practices that interrelate praxis, the tradition of the trade and the disciplinary structure in which the teacher has been trained is established.\n\n\nMethods\n\nA methodological study was established with the objective of developing tests for validity, reliability and internal consistency processes.26,27 The study consisted of education teachers working in educational units in the Ibarra Canton. The sample selection was convenience-based.28,29\n\nThe study took place during the academic period from March to August 2022, starting in the fourth week of this cycle with three 45-minute training sessions. These sessions were conducted for 27 fifth-semester students who were undertaking their pre-professional internships in 27 educational units in the Ibarra Canton as part of the project.\n\nIn the fifth week, the researchers contacted 27 Basic Education teachers, with prior approval from the authorities of their educational units. In this action, the students played a fundamental role in facilitating closer contact with the institutions. Immediately, the “Questionnaire on the nature or origin of academic knowledge of Basic Education teachers” was distributed to all teachers, with the objective of determining its validity, reliability, and internal consistency.\n\nAlthough the educational units were selected by non-probabilistic methods, the data presented30 in their study show a high correspondence in the results between nationally representative samples and convenience samples at the local level. Therefore, it is considered valid to use this type of sample for the current research.\n\nAs inclusion criteria, the level of teaching of the teachers, specifically Basic Education, was established, as well as availability to participate in the study. The teachers participated voluntarily, giving their informed consent to ensure confidentiality and anonymity of the participants. In addition, the confidentiality of the data was maintained by storing and processing them in an exclusive database with access only by the authors of the study. Expert judgment was used to determine the validity of the instrument.\n\nAll work was approved by the Honorable Board of Directors of the Faculty of Education, Science, and Technology of the Universidad Técnica del Norte (Resolution No. 239-2021-HCD). Approval for the study was dated March 26, 2022, as part of the research project: Didactic Transposition and Academic Knowledge of Basic Education Teachers in the Ibarra Canton. This work was carried out in accordance with the guidelines of the university’s code of ethics.31 Finally, each participating educational unit was provided with a report containing information on the overall results of their unit as well as the total sample. This report explains the most significant findings as well as future guidelines for action based on scientific evidence, based on the results obtained.\n\nThe literature review was carried out considering the following assumed research question: How to establish the construct validity and reliability of the questionnaire on the nature or origin of academic knowledge of basic education teachers? The identified keywords for the search were: construct validity and reliability, academic knowledge of teachers, basic education.\n\nThe inclusion criteria were: 1) studies focused on basic education; 2) studies in education that report the construction of questionnaires; 3) empirical or primary studies; 4) studies in French, English, Portuguese, and Spanish. The aspects considered for exclusion generally reflected studies focused on populations other than basic education or that did not include teachers in their samples. Additionally, other analyses that showed viewpoints and opinions, such as editorials, letters to the editor, comments, or perspectives, were excluded.\n\nTo meet these criteria, a search was conducted in the databases Web of Science, Scopus, Taylor & Francis, Science Direct, Springer, and Scielo. As a result of the initial analysis, documents that did not meet the inclusion criteria were eliminated, including studies focused on populations other than basic education or that did not include teachers in their samples. In addition, other analyses that showed points of view and opinions, such as editorials, letters to the editor, commentaries or perspectives, were excluded. In addition, the search was complemented with a manual review of the most relevant journals on the subject.\n\nFrom the total number of identified articles, duplicate articles were eliminated, then a selection was made considering the title, abstract, and finally reviewing the full text, thus eliminating irrelevant research based on the inclusion and exclusion criteria. From the remaining articles, a backward citation searching was performed. This technique was especially useful in finding classic or fundamental studies in the field of quantitative studies in education.\n\nOnce the final number of selected articles was obtained, they were exported to the reference manager Zotero. The process of selecting articles was carried out independently by two researchers, with the mediation of a third researcher in case of differences of opinion.\n\nThe questionnaire is an adaptation of the Pedagogical Content Knowledge (PCK) Competence Model for physics teachers in initial training.32 Several steps were defined for the adaptation process of the questionnaire.\n\nThe first step involved an initial translation into Spanish by the authors of this research, which was later reviewed by subject matter experts. Then, the original questionnaire was evaluated to determine its suitability for the target population and context. The referenced model is based on the refined consensus of PCK, which is defined as a set of knowledge that teachers need to teach their subject matter in a way that is understandable for students. The authors identified three essential components of PCK: 1. Content Knowledge, 2. Pedagogical Knowledge, and 3. Pedagogical Content Knowledge.\n\nSubsequently, in order to identify the understanding of the translated version of the questionnaire, it was sent to a group of judges (n=8), who were experts in the field of education. The selection criteria were people who had graduated in Basic Education and were working in educational units in Cantón Ibarra. This was done to evaluate the quality of the translation and ensure that it was accurate and culturally appropriate.\n\nThe questionnaire was then adjusted to make it relevant and appropriate to the culture of the target population and to meet the proposed objective. After this initial analysis, one team member proposed the first draft of the instrument. It had four variables with a total of 17 indicators: Disciplinary Knowledge (5 indicators), Experience-Based Knowledge (4 indicators), Theory-Based Knowledge (3 indicators), and Script and Routine-Based Knowledge (5 indicators).\n\nThe first draft, agreed upon by the other team members, underwent validation to ensure that it was valid and reliable for the target population. The process was carried out by the expert judges (n=8).\n\nOnce this validation process was completed, one team member drafted the second version of the instrument. It was based on the percentage of agreement obtained in the assignment of scores, and the wording of those where at least 80% agreement had not been reached was modified. A second version of the questionnaire with seven items and a high degree of agreement was obtained. The new proposal had eliminated one variable (Script and Routine-Based Knowledge: 5 indicators). Additionally, several indicators from each of the variables were excluded: Disciplinary Knowledge (3) and Theory-Based Knowledge (2).\n\nThe proposal was discussed and accepted. The final version of the instrument, “Questionnaire on the nature or origin of academic knowledge of elementary education teachers,” consists of seven indicators that respond to three variables. The suggested response scale is a Likert-type scale,34,35 with five levels that range from Completely Disagree (1), Disagree (2), Neither Agree nor Disagree (3), Agree (4), and Completely Agree (5).\n\nThe first phase involved estimating the content validity36,37 based on the assessment of expert judges (n=8) in the field of education.38,39 These judges were selected and contacted from a list of teachers who act as supervisors for pre-professional practices in different educational units where students of the Basic Education career collaborate. This requires a mastery of institutional educational development and teacher training in particular. They hold fourth-level degrees in the specialties of Curriculum Design, Educational Technology, and Educational Innovation. None of them are associated with the researchers of this study, so they express no conflict of interest.\n\nThese expert judges were provided with a guide to the objectives of the study and the second draft of the instrument virtually. They were asked to rate each item in terms of sufficiency, clarity, and coherence. Each indicator was scored using a scale with 1 (Totally Disagree), 3 (Neither Agree nor Disagree), and 5 (Totally Agree). The kappa index,40 was applied to measure the stability of the tool. It was weighted for the established indicators (standard: > 0.41: moderate).\n\nThe second phase focused on validating the “Questionnaire on the nature or origin of academic knowledge of basic education teachers” through the determination of its validity, reliability and internal consistency by the general basic education teachers who participated in the research (n=27).\n\nThe obtained results were loaded into Excel (version 26.0) and incorporated into the Statistical Package for Social Sciences (SPSS) package (version 25.0) for descriptive and inferential analysis.\n\nAn exploratory factorial analysis,41 was performed on principal components using the varimax rotation method. Indicators with communalities >0.3 were considered valid. The internal consistency of the entire instrument was estimated using the Cronbach’s alpha coefficient, with a minimum acceptable value of (α≥0.70) estimated.\n\n\nResults\n\nOf the 27 teachers of basic general education who participated in the research, 81% were female and 19% were male. The median age was 40 years (range: 24-57 years). An important factor has to do with years of teaching experience, which averages 12.37 years (range: 1-30 years). 68% of teachers have degrees in Education Sciences.\n\nTable 2 reports the knowledge of the teachers. Table 3 reports the reliability between the different evaluators (Cohen’s Kappa) (n=8), where the result obtained was substantial (range: κ=0.61- κ=0.80) for two aspects (sufficiency and clarity) and moderate (range: κ=0.41- κ=0.60) for the remaining (coherence). The sufficiency has obtained the highest values, allowing us to consider that the different indicators belong to the same dimension considered as the academic knowledge of the teachers.\n\nAs for the descriptive analysis, it presents an average response that goes between 4 and 5, which assigns values between “Agree” and “Totally agree”, where 87% belongs to the latter value (Table 4).\n\nTable 5 presents the analysis of global reliability of the instrument. Cronbach’s alpha is 0.901, and it is estimated as an excellent level.42 For the principal components analysis, a validation analysis of assumptions was developed using the Bartlett statistic and the KMO value. Bartlett’s sphericity test was used to show if there were significant correlations in the data. The values <0.05 support that the technique is adequate (165,591; gl=21; p<0.000),43 the model is appropriate and does not present sphericity. The KMO sample adequacy measure was 0.778, which is considered medium.\n\nIt was considered that the recommended ratio of commonalities should be ≥ 0.40.44 Of the 7 indicators that are part of the questionnaire, all are considered useful, and have adequate factorial weights. The interval obtained was (=6.15 and =0.96) (Table 5).\n\nThe results of the application of the principal components extraction method in the factor analysis with varix rotation indicate the retention of two factors for presenting an eigenvalue greater than 145; see Table 6.\n\nWhen considering both, an explained variance of 82.74% is obtained. Figure 1 presents the eigenvalue scatter plot of each of the factors; 2 factors have eigenvalues higher than (>1).\n\nThus, the first indicator called “In the preparation of the categories I pay more attention to the knowledge of the disciplines” that retains 65.28%; and a second indicator “I evaluate the concepts of everyday life and in this way I structure the contents” with 17.46%.\n\n\nDiscussion and conclusions\n\nThe possibilities of academic knowledge in education have not been fully explored.45 None of the previous studies has yet explored this knowledge, and the different configurations that support them. Although other studies have addressed the issue,46,47 they have only done so from the perspective of teachers’ content knowledge. That is, the studies have focused particularly on teachers’ professional knowledge for effective teaching.45\n\nThe original instrument from which this questionnaire was adapted was an important measure that can be used to determine the nature or origin of teachers’ academic knowledge. It includes several indicators that in the context of Ecuadorian basic general education have not been recognized or valued by experts previously. Previous studies have described the importance of teachers’ application of their knowledge in the classroom, which allows complex reasoning processes to be involved, selectively identifying those most relevant, from their perspective, to put them in context in a particular situation.48\n\nHowever, the relationship of the implicit theories of the teachers, in addition to the different ways that they teach their classes, have been ignored or not understood their true consequence in didactic practice. The proposal presented also shows differences with respect to the “competence model for teachers’ pedagogical content knowledge.”.49 The reliability analysis obtained an excellent level. These values are consistent with,50 authors who in their research obtained (α=0.981), with values greater than (α=0.80) in all indicators. This reveals a good internal consistency of the instrument, similar to Monroy.49\n\nIn line with Şimşek,49 the idea of considering academic knowledge as a coherent and plausible construct is supported. This makes it possible for the validated questionnaire to become an excellent candidate to identify the nature or origin of the academic knowledge of teachers of basic general education without the need to reduce or eliminate indicators from the instrument.51 Currently, there are few scales that meet these conditions: fast administration, no need to delete items, and high values of Cronbach’s alpha. It is shown that the instrument has high values of internal consistency, measured by Cronbach’s coefficient, as well as by its reliability.52 The scale presented constitutes a reliable tool,53 to assess the nature or origin of the academic knowledge of teachers of general basic education.\n\nAccording to the results of the exploratory factor analysis, the Kaiser-Meyer-Olkin value fits with other studies conducted in the area of education.49,54 In some of these,55 different items were removed from the scales for a factorial load value less than 0.50; however, in the current analysis the values obtained are above the standardized threshold,56 indicating that the correlations between questions are statistically significant and sufficiently strong57 for the analysis of questions. These considerations are strengthened by studies that support the presence of values on a scale between =0.70 and =0.95.58 The principal components analysis using the varimax rotation method to explore the factorial structure of the teachers’ academic knowledge scale was based on the criterion (eigenvalue>1).59 From the 7 initial indicators the procedure of reduction. That is, the questionnaire on the nature or origin of academic knowledge of teachers of basic general education represents a robust and valid framework to understand certain notions of implicit theories and the role of experiences as the basis and support of academic knowledge. In reference to the different indicators that make up the scale, they have adequate factorial weights and no item presented commonality <0.55 (ranges=0.553 and =0.795).60 This has been supported by published and reviewed studies.61,62 which demonstrate the usefulness and saturation of the scale through its different items in order to constitute a theoretical construct and that it allows the identification of the nature or origin of the academic knowledge of teachers quickly and reliably with an instrument composed of 7 indicators.\n\nThe present study examined the validity and reliability of a scale on the nature or origin of the academic knowledge of teachers of basic general education, which can facilitate research in this field and provides a conceptual framework to understand certain notions of implicit theories and the role of experiences as the basis and sustenance of academic knowledge. The ‘Questionnaire on the nature or origin of academic knowledge of teachers of basic general education’ presents an advantage over other instruments since it focuses on the beliefs and implicit theories that are part of the teacher’s thinking. To this end, it determines the role played by disciplinary knowledge and its didactic treatment; the definition of the sources that contribute most to the teaching exercise. In addition, it can demonstrate reflection and change during their professional life.\n\nThe levels of reliability between the different evaluators show an excellent intraobserver correlation. Evidence related to reliability analysis was collected for the entire instrument with a Cronbach’s alpha value (α=0.901), considering the 7 indicators, which is estimated as an excellent level. Bartlett’s sphericity test showed that, if there are significant correlations in the data, this supports that the technique is adequate and that the model is appropriate and does not present sphericity. Of the 7 indicators that are part of the questionnaire, all are considered useful and have adequate factorial weights. The usefulness and saturation of each of these to constitute the theoretical construct related to the academic knowledge of teachers of basic general education is demonstrated. This constitutes a relevant, valid and reliable instrument to determine the nature or origin of the academic knowledge of teachers in a fast and reliable manner.\n\nThe present study has some limitations, which are not related to the fulfilment of the proposed objective; however, it is necessary to mention them. The first is related to the absence of other questionnaires as a standard with which to compare the results obtained. We have reported on the non-existence of measures that serve as a standard. In light of this, the strategy adopted was based on the review of bibliographic material that reflected studies on the construction of similar tools from the methodological point of view and their application to education. A second limitation of the present study considers that the extrapolation of the results obtained for use in other educational units that did not participate in the sample is based on the participation of (n=27), teachers from the same number of institutions. However, this can be minimized considering the responsibility.\n\nThe Questionnaire on the Nature or Origin of Academic Knowledge of Basic General Education Teachers focuses on the implicit beliefs and theories of basic education teachers. It determines the role of disciplinary knowledge and its didactic treatment, as well as the sources that contribute the most to teaching practice and reflection during their professional life. The reliability test showed that the questionnaire is acceptable with a Cronbach’s alpha of =0.704, standard deviation values between =0.76 and =0.97, and appropriate factorial weights for each item. The questionnaire is relevant, valid, and reliable, tailored to the needs of basic general education teachers, and confirming the construct validity and reliability of the questionnaire.\n\nThe entire study was approved by the Honourable Board of Directors of the Faculty of Education, Science and Technology of the Technical University of the North (Resolution No. 239-2021-HCD), as part of the research project: Didactic transposition and academic knowledge of teachers of basic general education of the Ibarra canton. This work was carried out in accordance with the guidelines of the university code of ethics 2012. Those who voluntarily decided to collaborate in this research signed a written informed consent to ensure the confidentiality and anonymity of the participants.",
"appendix": "Data availability\n\nOpen Science Framework: Validity and reliability of the questionnaire, https://doi.org/10.17605/OSF.IO/WBNKC. 63\n\nThis project contains the following underlying data:\n\n- Data_knowledge.sav contains the primary data of the sample that participated in the study (27 basic education teachers) related to gender, age and years of experience, as well as the assessment of the 7 items of the “Questionnaire on the nature or origin of the academic knowledge of basic general education teachers”.\n\n- Data_judges.sav contains the primary data of evaluations by experts (n=8) on the indicators of adequacy, clarity, and coherence of the questionnaire. This served as a basis to determine the reliability among the different evaluators (Cohen’s Kappa).\n\nOpen Science Framework: Validity and reliability of the questionnaire, https://doi.org/10.17605/OSF.IO/WBNKC. 63\n\nThis project contains the following underlying data:\n\n- Results_knowledge.htm, contains the findings from the analysis and comparison of various statistics necessary to fulfil the objective of testing the validity, reliability, and internal consistency processes, as assessed by the study participants.\n\n- Results_knowledge.spv contains the SPSS output.\n\n- Instrument.pdf, the instrument that was given to teachers for validation.\n\n- Table 2. List of knowledge and indicators.xlsx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nThe authors are grateful for the support of the Universidad Técnica del Norte and the different educational units of the Ibarra canton that participated in the research.\n\n\nReferences\n\nTriviño PG, et al.: Comunidades de práctica en educación médica: relación con la enseñanza clínica. Educación Médica. 2021; 22: 509–513. Publisher Full Text\n\nAyala-Villamil LA, Fúquene AA: Saberes que movilizan los docentes de biología en el temprano ejercicio profesional. Profesorado, Revista de Currículum y Formación del Profesorado. 2022; 26(1): 395–414. Publisher Full Text\n\nIivari N, Sharma S, Ventä-Olkkonen L: Digital transformation of everyday life–How COVID-19 pandemic transformed the basic education of the young generation and why information management research should care? Int. J. Inf. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nCelik I: Towards Intelligent-TPACK: An empirical study on teachers’ professional knowledge to ethically integrate artificial intelligence (AI)-based tools into education. Comput. Hum. Behav. 2023; 138: 107468. Publisher Full Text\n\nBerry S: Professional development for online faculty: Instructors’ perspectives on cultivating technical, pedagogical and content knowledge in a distance program. J. Comput. High. Educ. 2019; 31: 121–136. Publisher Full Text\n\nTorbeyns J, Verbruggen S, Depaepe F: Pedagogical content knowledge in preservice preschool teachers and its association with opportunities to learn during teacher training. ZDM. 2020; 52: 269–280. Publisher Full Text\n\nKulgemeyer C, Riese J: From professional knowledge to professional performance: The impact of CK and PCK on teaching quality in explaining situations. J. Res. Sci. Teach. 2018; 55(10): 1393–1418. Publisher Full Text\n\nYilmaz AE, Demirhan H: Weighted kappa measures for ordinal multi-class classification performance. Appl. Soft Comput. 2023; 134: 110020. Publisher Full Text\n\nSchiering D, et al.: A proficiency model for pre-service physics teachers pedagogical content knowledge (PCK)—What constitutes high-level PCK? J. Res. Sci. Teach. 2023; 60(1): 136–163. Publisher Full Text\n\nLimon MR: Assessing knowledge and skills retention of junior high school students on food safety lessons using modified Kirkpatrick’s model. Food Control. 2022; 135: 108814. Publisher Full Text\n\nCaceffo R, et al.: Children’s social interactions within a socioenactive scenario. Comput. Educ. 2022; 176: 104324. Publisher Full Text\n\nJagadeesh N, et al.: Bone Ninja application is reliable alternative to PACS in measuring preoperative and postoperative alignment parameters of total knee arthroplasty. J. Orthop. 2022; 34: 132–136. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBandeira A, Witt RR: Desarrollo de un instrumento de evaluación formativa del agente comunitario de salud. Aten. Primaria. 2022; 54(3): 102275. Publisher Full Text\n\nMonroy AM, et al.: Validación de la escala de convivencia con artrosis en la población española. Aten. Primaria. 2021; 53(6): 102044. PubMed Abstract | Publisher Full Text | Free Full Text\n\nŞimşek P, et al.: Development and psychometric testing of perceived preoperative nursing care competence scale for nursing students (PPreCC-NS). Nurse Educ. Today. 2023; 120: 105632. Publisher Full Text\n\nCamargo L, et al.: Escala de ansiedad generalizada GAD-7 en profesionales médicos colombianos durante pandemia de COVID-19: validez de constructo y confiabilidad. Revista Colombiana de Psiquiatría. 2021. PubMed Abstract | Publisher Full Text | Free Full Text\n\nArquero JL, et al.: Developing teamwork skills in accounting students: is communication apprehension a potential barrier? Desarrollo de capacidades de trabajo en grupo en estudiantes de contabilidad: ¿es la aprensión comunicativa una barrera potencial? Revista de Contabilidad-Spanish Accounting Review. 2023; 26(1): 97–110. Publisher Full Text\n\nShakeel SI, Haolader MFA, Sultana MS: Exploring dimensions of blended learning readiness: Validation of scale and assessing blended learning readiness in the context of TVET Bangladesh. Heliyon. 2023; e12766. Publisher Full Text\n\nKnezek G, et al.: Strategies for developing digital competencies in teachers: Towards a multidimensional Synthesis of Qualitative Data (SQD) survey instrument. Comput. Educ. 2023; 193: 104674. Publisher Full Text\n\nJordan P, Shedden-Mora MC, Löwe B: Psychometric analysis of the Generalized Anxiety Disorder scale (GAD-7) in primary care using modern item response theory. PLoS One. 2017; 12(8): e0182162. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCamargo L, et al.: Escala de ansiedad generalizada GAD-7 en profesionales médicos colombianos durante pandemia de COVID-19: validez de constructo y confiabilidad. Revista Colombiana de Psiquiatría. 2021. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBasantes-Andrade A, López JC, Mora M, et al.: Validity and reliability of the questionnaire. [Dataset]. 2023, May 23. Publisher Full Text"
}
|
[
{
"id": "259132",
"date": "22 Apr 2024",
"name": "Kezang Sherab",
"expertise": [
"Reviewer Expertise teacher education",
"non-cognitive skills",
"student engagement",
"TPACK",
"values education"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript reports a research on testing the validity and reliability of the questionnaire on academic knowledge of basic general education teachers in Ecuador. The study was mainly focused on establishing the construct validity and reliability of the questionnaire designed to check the nature or origin of the academic knowledge of the basic general education teachers. The study conducted with 27 basic general education teachers showed excellent reliability of the questionnaire and the authors suggest it to be used to determine the nature or origin of the academic knowledge. The literature used are fairly recent and the data analytical approach used is quite robust. However, there are a few minor comments for the authors to consider. First, the title could be rephrased to avoid some of the 'of'. Currently there are four 'of' in the title. Secondly, the term 'teachers of basic general education' may not be understood by all readers, especially from other contexts. So it would be useful for the authors to make this term clear with appropriate explanation right from the introduction section. Thirdly, it has been observed that the Cronbach's Alpha level is reported in three decimal places. As far as I am concerned, it should be reported in two decimal places. Similarly, in Table 5 standard deviation should be reported in two decimal places. Fourthly, In the title of Table 6, the phrase varix rotation should be varimax rotation I think. Lastly, the limitations of the study are presented along with the discussion and conclusion section, thought it would provide clarity if the limitations of the study is presented in a separate section.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "212266",
"date": "22 May 2024",
"name": "Laura Guerra",
"expertise": [
"Reviewer Expertise Technology",
"education and society"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nWhy did you say that “The sample selection was convenience-based”? Please, explain this point more.\nThe period considered for the review of the literature is not mentioned.\nAll the articles reviewed coincided with the constructs/variables considered in the questionnaire chosen to translate and adapt it to your research? You said that the questionnaire is an adaptation of the Pedagogical Content Knowledge (PCK) Competence Model for physics teachers in initial training.\nI understand that 27 basic education institutions in Ibarra were considered. Therefore, it is not clear if you worked with only one professor from each institution. It was presented in the results, institutions = teachers?\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-642
|
https://f1000research.com/articles/10-1273/v1
|
13 Dec 21
|
{
"type": "Research Article",
"title": "Gastronot: a pilot project for promoting healthy eating habits using mixed-method study design",
"authors": [
"Titik Respati",
"Susan Fitriyana",
"Nurul Romadhona",
"Ganang Ibnusantosa",
"Rio Frederrico",
"Fajar Awalia Yulianto",
"Aughya Shandriasti",
"Eko Nugroho",
"Susan Fitriyana",
"Nurul Romadhona",
"Ganang Ibnusantosa",
"Rio Frederrico",
"Fajar Awalia Yulianto",
"Aughya Shandriasti",
"Eko Nugroho"
],
"abstract": "Background: Eating habits are formed from childhood and develop into adulthood. Unhealthy eating habits will persist into adulthood and can lead to various diseases. Healthy eating and behaviour should be taught using engaging tools. The study aims to pilot nutrition education using the game-based learning approach, implementing a specially designed learning board game entitled \"Gastronot\". Methods: A mixed-method study was used in two stages. The first stage was an FGD with 14 informants and in-depth interviews with six informants to develop the game. The second stage was the game's development, and a pre and post-test were conducted on 88 children to evaluate the game—the study was conducted from August 2019 to July 2020. Results: Results showed almost half the children (49%) never heard about Balanced Nutrition Diet Pyramid. There was a significant difference between respondents' knowledge before and after playing the game with a p-value of 0.021. The game was able to engage participants in the active learning process. Conclusions: We concluded that the game-based learning utilizing the Gastronot board game demonstrated good results as a method for teaching primary school students about food and healthy eating habits.",
"keywords": [
"Healthy eating habits",
"Children",
"Gamification",
"Game-Based Learning",
"Education."
],
"content": "Introduction\n\nMalnutrition in children is a serious public health problem that can affect child growth and development, leading to a variety of disorders and even death.1–3 Malnutrition is common in developing countries, including Indonesia.4 Malnutrition is a deficiency, excess, or nutritional imbalance resulting from inadequate nutrient intake.5,6 Indonesia is currently experiencing a double burden of malnutrition, that is, an increase in cases of overweight/obesity, and still having unresolved undernutrition problems.4,7 About one in three children under five years old experience stunting, and one in ten children experience wasting.1 Wasting defined as low weight-for-height which indicates recent and severe weight loss. Stunting defined as low height-for-age as a result of chronic or recurrent undernutrition.8 Micronutrient insufficiency is also on the rise in Indonesia.9 Malnutrition in children, especially throughout their growing stage, cannot be isolated from children's eating habits, according to empirical data collected in the field and in academia.6,10,11 Numerous studies have been carried out to establish why children are prone to developing bad eating habits.12,13 For instance, children who suffer from overnutrition risk noncommunicable diseases (NCD), including obesity, hypertension, type 2 diabetes, and cardiovascular diseases.14–16 Therefore, modifying a child's eating habits into healthier ones can lower the risk of developing a diet-related illness in the following years into adulthood.17,18\n\nIn order to combat malnutrition, the Indonesian government has undertaken communication, information, and education programs centered balanced nutrition. It was visualised with Tumpeng Gizi Seimbang or Balanced Nutrition Diet Pyramid and Isi Piringku or My filled Plate.19–21 The method used is direct delivery, such as social marketing, competitions, and the appointment of ambassadors for a balanced nutrition diet. In addition, there was indirect delivery, such as training and teaching in various health institutions and schools, workshops, and role play. The media used are electronic, printed, online, and audio media.22 However, these efforts are still ineffective in increasing public knowledge about balanced nutrition. In Indonesia, the prevention of malnutrition problems has been centered on the policy, with adults or parents as the primary target. Since the messages are aimed at children, it is required to use a particular or distinct intervention method on children in order to encourage them to eat healthier. An approach engaged in delivering messages is using the gamification method or game-based learning approach.23\n\nGame-Based Learning is part of a serious game developed to bring participants engaging and immersive learning experiences to meet expected learning goals. Game-based Learning enhances participants' cognitive and affective aspects to achieve expected learning goals used in different areas.14,24 Game-Based Learning designs learning activities that gradually introduce learning concepts to increase participants' knowledge. A well-designed game can engage and motivate participants by satisfying the participants' basic psychological needs.25 Games also offer challenges that match the player's current abilities. For example, the independence of in-game decision-making reflects autonomy in real life so that the game creates a space that motivates participants to make behavioural changes.26,27\n\nA systematic review regarding game-based Learning and gamification to improve diet and nutritional habits concluded that gamification positively influenced dietary behaviour and nutritional knowledge.28 Some research conducted on elementary school students shows that the game-based learning approach in nutrition education increases nutrition knowledge, improves eating and drinking habits, and has a positive attitude towards gaming.14 As well, serious games can improve eating habits by enhancing nutrition knowledge and attitudes, according to other studies.29 Games can also increase children's courage to explore new healthy foods and reduce eating unhealthy snacks. Game-Based Learning is a new approach that can improve children's knowledge about nutrition and induce healthier eating habits.\n\nTo the best of our knowledge, there is a scarcity of game-based approaches for raising children's awareness of good eating habits in Indonesia. This paper will describe the program to deliver the campaign of balanced nutrition using a game-based learning approach. We proposed a pilot project to explore how an interactive (game-based) learning and gamification program can be designed, optimised, and implemented.\n\n\nMethods\n\nThe study comprised of two parts using a mixed-method study design. The first step was a qualitative one based on individual interviews and a focus group discussion. The second part was the development of the board game based on the findings from the first part.\n\nIn the first part, in-depth interviews were conducted with six informants ranging from health officers responsible for the nutrition programs to understand government targets and available programs, nutritionist specialists, and healthy food practitioners for information regarding ideal healthy food. We also interviewed mothers to understand the nutrition knowledge and skills needed to make nutritious food. In-depth interviews were conducted in the informants' workplaces or homes. Time used for interviews ranged from 30 minutes to 2.5 hours. The instruments used were an in-depth interview guide with notes and a tape recorder to record data.\n\nTo develop the game, we conducted a Focus Group Discussion (FGD) attended by 14 people. They were involved in nutrition programs from the Health Office Bandung and the Office of Bandung City. Also attended Public health expert, Health promotion expert, Family Health and Nutrition expert, Game designer, Nutritionist Association, Nutrition Specialist association, organic farmer, organic farm community representatives, and community representatives (housewives). The FGD lasted for three hours. All participants for the interview and FGD gave their written consent.\n\nThe instruments used in the FGD and interviewed were unstructured interview guides developed in the discussion as needed. Unstructured interviews were chosen because they provide an opportunity to get the best in-depth data compared to other interviewing techniques.30 Informed consent was obtained from all individual participants included in the study. Data were recorded by notes and with a tape recorder. We tested the validity of the data and its analysis to establish its credibility. We used triangulation and assessing its transferability, dependability, and confirmability.\n\nThe focus group discussion and in-depth interview recording results were transcribed ad verbatim (precisely as spoken): the thematic analysis method used to identify and analyse's themes. The study constructs the themes from the data collected. They were objectively and systematically computed to produce descriptive descriptions of the text content. Thematic analysis was chosen because the central theme was already known (nutrition campaign). This analysis is used to summarise many details into concepts, models, or a more general picture. The guideline in data management is inductive study served to search for themes, patterns, and categories for the source analysis in the data.\n\nThe second stage was developing the game using information from the analysis. Authors engaged professional game developers to assist with the development of the game. The process from the idea to the board game development took around three months. Finally, the board game was tested on 88 children aged 10-13 years old through gameplay sessions using a convenience sampling method through a voluntary approach. Before the activities, consent was given by parents verbally.\n\nTo evaluate the ability of the board game to deliver the messages, we conducted pre and post-test to the children. Knowledge of balanced nutrition was measured using a questionnaire of 10 questions. A questionnaire of 10 questions was used to assess attitude variables, while five questions were used to assess behavioral variables. With a cut point as follows, if the score is >80% means good; 60-80% is sufficient, and not sufficient is less than 60%. Software STATA MP 16 from Stata Corp used for data analysis to determine differences in respondents' knowledge, behaviour, and attitudes about balanced nutrition before and after gameplay sessions. Meanwhile, to find out the differences in knowledge, attitudes, and behaviour between the groups involved in gameplay, the Independent T-Test and Mann Whitney test was used as alternatives with an error rate of 5%. The study was conducted from August 2019 until June 2020.\n\nThis study has obtained ethical approval No. 389/Komite Etik FK/VIII/2019 from the Health Research Ethics Committee of Faculty of Medicine Universitas Islam Bandung.\n\n\nResults\n\nThe findings are organized around the themes identified by the research focus group discussion, which are based on elements that have a significant impact on the nutrition campaign. Much of this is reported in the present tense, as that was the way it was articulated. In order of presentation, the themes were challenged to deliver the campaign, environment and provide fun and exciting messages. The themes are further described below.\n\nInformants from the FGD are in the table below.\n\nWe found three emerging themes that were Nutrition Campaign Challenges, Environment, and Campaign messages.\n\nAccording to the data, the Indonesian government has already supported certain programmes aimed at improving children's nutritional status. For example, at the National level, the Nutrition Campaign of Piramida Gizi Seimbang or Balanced Nutrition Diet Pyramid and a guidance campaign of si Piringku or My Filled Plate have been implemented since 2014. Beas Bereum (Bekal Anak Sekolah Bergizi, Enak, dan Murah or Nutritious, Tasty, and Affordable School Lunch Box) was the regional campaign by the Health Office Bandung City. All programs are utilising Puskesmas (Health Centre) and schools. The primary objectives were to convey the campaign's content, focusing on the four pillars of the Balanced Diet Pyramid (food types and recommended portions, hygiene, and the advantages of regular exercise) and the food composition of My Filled Plate. Each school and the District Health Centers have already begun implementing the campaign through lectures and other activities. However, the program still struggles in delivering the content in the best way possible and requires continuous improvement in its method and delivery media.\n\nWe recognised that the biggest challenge lies in school-age children. They rarely eat breakfast. It could be since their family's lack of resources or time to feed them and skipping breakfast affected their school performance. The school environment also promotes unhealthy foods, such as selling ultra-processed foods and sugar-sweetened beverages in school cafeterias, convenience stores, and street stalls outside schools. It was found that controlling the external food environment was very difficult.\n\nIn these themes, some sub-themes emerge, such as the knowledge of nutrition that needs to be delivered. There was the concept of My Filled Plate, the proportion of food to fill each plate at every meal, the concept of eating various foods, and the idea of the recommended number of meals per day. It should also incorporate the concept of nutritional deficiencies and overload. It should include an understanding of the division of nutrients into carbohydrates, protein, fat, vitamins, and minerals. Also noteworthy was the concept of the number of calories needed by the body to meet the recommended calorie requirements (not far above or less than the required, ideal calorie).\n\nThe second stage was the development of Gastronot using the game-based approach. Gastronot, a board game created by the author, is based on the same concept. This game-based approach used Balanced Diet Journal, Balanced Nutrition Pyramid, and My Filled Plate as the main message and content. Players' main goal is to collect foods and arrange them to fulfil the nutritional needs based on the suggested composition and proportion in the above messages.\n\nTo accommodate the prioritised contents of knowledge, the two main messages of the program are translated into the game scoring mechanic. Using the Balanced Nutrition Journal as the primary reference, the game scoring mechanics will consist of several components: - Balanced Nutrition Pyramid presented as a part of the whole scoring system. In addition, each Food Ingredients Card will contain several Nutrition components (based on the data by Health Office), and players can gain scores by collecting these components within the appropriate suggested amount. Five types of nutrition to be collected during the game are Carbohydrates, Protein, Fat, vitamins & minerals, and Water. The actual values of nutrition on each food ingredient are scaled and modified accordingly for gameplay purposes but still represent the good and correct information.\n\nBelow is the tool used in the board game and the reward system (see Figures 1-3).\n\nMy Filled Plate is translated as the second part of the scoring system. Collected foods are to be arranged in 3 lines representing the three main meals during a day. Based on the My Filled Plate campaign information, players can get more scores by setting the cards in correct compositions. The game focused on ensuring that each meal consists of various types of food (Staple Food - Side - Vegetables - Fruits). The scoring system/mechanic will be presented on the player boards to remind the players of their main goals and objectives constantly.\n\nWe also want to make sure that the participants are aware of the many types of dietary ingredients. For that purpose, players can get additional scores at the end of the game by collecting as many unique food ingredients as possible (more variety of foods = more scores assets of the board game). In two elementary schools, 88 children participated in a gameplay trial.\n\nFor the analysis, two data sets were excluded since they were not complete. The children were accompanied by their teachers, who were also involved in the gameplay sessions. Informed consent was given by the parents or guardians of the children before the intervention. Table 1 lists the characteristics of the participants in the focus group discussion. Table 2 shows respondent's characteristics and Table 3 shows the results of the pre- and post-test results.\n\n* Mann Whitney\n\nThe result from the pre and post-test can be seen in Table 3.\n\nTable 3 above shows that the average score of respondents' knowledge about balanced nutrition before playing was 37.94, then increased to 41.13 after. Based on the Wilcoxon test, the z-value is −2.302, and the p-value is 0.021. There is a significant difference between respondents' knowledge before and after playing the game.\n\nOn the attitude variable, the average score of respondents about balanced nutrition before the game session was 79.94, then decreased to 79.30 after playing the game. However, there is no significant difference between respondents' attitudes before and after the gameplay session.\n\nIn the behavioural variable, the average score of respondents before playing the games was 72.33. It decreases to 70.47 after the game. Based on the Wilcoxon test, the z-value is −0.825, and the p-value is 0.410. There was no significant difference between the behaviour of respondents before and after the gameplay session.\n\n\nDiscussion\n\nBehaviours that can last for life are usually gained during the childhood period.1–4 Knowledge delivery was the first and foremost step in bringing the children toward a balanced diet and healthy eating habits. Therefore, education about nutrition is essential to improve the quality of life and health for the children to have better adulthood. Whenever nutritional education and information are given to children, they can build their awareness in choosing healthy food. This study engages game-based learning/gamification design to ensure that participants learn essential information with motivation and engagement. This factor is significant in Learning.23\n\nIn our study, the campaign to improve nutrition was implemented in various schools using lectures and other activities initiated by each school and District Health Centers. However, the program still struggles in delivering the content in the best way possible and requires continuous improvement in its method and delivery media. It is clear since our study showed that almost half of the students (49%) never heard about Balanced Nutrition Diet Pyramid as the main message in the campaign.\n\nThe main goal of our study was to develop the board game to deliver the contents of the campaign, mainly focusing on four pillars of a Balanced Nutrition Diet such as food types and suggested portions, hygiene, and the benefits of regular exercises. It also incorporated the food composition of My Filled Plate. The understanding needs to be appropriately delivered to children since children should consume the proper quantity and a variety of food for an adequate, healthy, and balanced diet. Based on the theme from the FGD, the game content focus aligned with an ongoing campaign that incorporated the national program Balanced Nutrition Diet Pyramid and a guidance campaign of My Filled Plate.20\n\nWe chose Gastronot as the game's name since we were inspired by the daring character of space exploration. It combined the word Astronaut (or Astronot in Bahasa Indonesia) with Gastronomy. The name is also served as a reminder for children to be more adventurous in choosing food ingredients. As in several studies, children tend to choose only one of two types of food. The board game Gastronot aims to show that food comes in wide varieties.\n\nThe findings revealed that there has been a significant rise in participants' awareness of information on the Balanced Nutrition Diet, particularly about a complete meal proportion (i.e., the Fill My Plate campaign). A statistically significant difference between respondents' knowledge before and after playing the game was found. The findings were similar to some studies that found that students tend to have better post-intervention scores after education about nutrition.14,18,32\n\nThe game-based learning session was engaging for the participants. According to the data analysis of the post-questionnaire, it had a positive impact on the level of awareness regarding balanced nutrition knowledge. As per our observations, the majority of the children were engaged and participated in the game throughout the session. They could reiterate the information from the game during the debriefing session. The game-based learning approach in this study strengthened the findings from other studies that concluded that game-based Learning and gamification effectively improve nutrition knowledge.14,28,33\n\nAlthough not statistically significant, we observed a decline in attitude and practice score following the gameplay sessions. It could be because the children were still unfamiliar with the game-based approach. This finding contradicts the prior study on the nutrition game.33,34 In this study, some children were not acquainted with a quantitative measurement tool (using questionnaires) and were confused about filling it out. To them, it was more like an exam and they were striving to find the right answer rather than filling it out based on their knowledge.\n\nThe author saw that schools are vital to education about nutrition, which correlates with some studies.17,22 However, education methods through traditional ways that only provide information should be limited. Instead, active participation in nutrition education becomes very important to teach an exciting and effective method of knowledge transfer. Using game-based learning methods to deliver the information will help children acquire healthy eating habits and, ideally, improve their quality of life.\n\n\nConclusions\n\nThe game-based learning approach with the Gastronot board game showed promising results in promoting sustainable diet and healthy eating habits among elementary school children. Most children showed engagement and participated in the game for the whole session. They could reiterate the information from the game during the debriefing session, and results showed a significant increase in participants' awareness of the information about the Balanced Nutrition Diet. Our findings from implementing the game-based learning approach to promote a healthy diet shed some light on how we can incorporate games (and gamification) to motivate an effective learning process and public participation to overcome some public health issues.\n\n\nData availability\n\nFigshare: Balance Nutrition Dataset EN, https://doi.org/10.6084/m9.figshare.16945744.v1.\n\nThis project contains the following underlying data:\n\n- Balanced Nutrition Diet Pyramid Raw Data.xlsx (This dataset contains the following: Characteristic of respondents, knowledge, attitude and behaviour)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgement\n\nThe author acknowledged the support from Ms, Slivana Paath, Mr. M. Rianto Utama, Hivos South East Asia, Ludenara Foundation, House the House Studio and Bandung District Health Office.\n\n\nReferences\n\nUNICEF: State of the World’s Children 2019: Children, food and nutrition.2019; 4 p.\n\nAmine EK, Baba NH, Belhadj M, et al.: Diet, nutrition and the prevention of chronic diseases. World Heal Organ - Tech Rep Ser. 2003; 916.\n\nArif S, Isdijoso W, Fatah AR, et al.: Strategic Review of Food Security and Nutrition in Indonesia.2020; 38–41 p.\n\nRah JH, Melse-Boonstra A, Agustina R, et al.: The Triple Burden of Malnutrition Among Adolescents in Indonesia. Food Nutr Bull. 2021; 42: S4–S8. PubMed Abstract | Publisher Full Text\n\nUlfah E, Rahayuningsih SE, Herman H, et al.: Asuhan Nutrisi dan Stimulasi dengan Status Pertumbuhan dan Perkembangan Balita Usia 12 – 36 Bulan. Glob Med Heal Commun. 2018; 6(38): 12–20.\n\nThow A, Farrell P, Helble M, et al.: Eating in Developing Asia: Trends, Consequences and Policies. AdbOrg; 2020. Reference Source\n\nMaehara M, Rah JH, Roshita A, et al.: Patterns and risk factors of double burden of malnutrition among adolescent girls and boys in Indonesia. PLoS One. 2019; 14(8): 15–18. Publisher Full Text\n\nWorld Health Organization (WHO): Malnutrition.2020. Reference Source\n\nvan Zutphen KG , Kraemer K, Melse-Boonstra A: Knowledge Gaps in Understanding the Etiology of Anemia in Indonesian Adolescents. Food Nutr Bull. 2021; 42(1_suppl): S39–S58. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWHO, UNICEF: Child growth standards and the identification of severe acute malnutrition in infants and children: A Joint Statement by the World Health Organization and the United Nations Children’s Fund. WHO Press; 2009. Reference Source\n\nUNICEF: Children, food and nutrition: growing well in a changing world.2019; 4 p. Reference Source\n\nHoque KE, Kamaluddin MA, Razak AZA, et al.: Building healthy eating habits in childhood: A study of the attitudes, knowledge and dietary habits of schoolchildren in Malaysia. PeerJ. 2016; 4(11): e2651. Publisher Full Text\n\nScaglioni S, De Cosmi V, Ciappolino V, et al.: Factors influencing children’s eating behaviours. Nutrients. 2018; 10(6): 1–17. Publisher Full Text\n\nChow CY, Riantiningtyas RR, Kanstrup MB, et al.: Can games change children’s eating behaviour? A review of gamification and serious games. Food Qual Prefer. October 2019; 80: 103823. Publisher Full Text\n\nMahgoub HM, Fadlelseed OE, Khamis AH, et al.: Nutritional and micronutrient status of adolescent schoolgirls in eastern Sudan: A cross-sectional study. F1000Res. 2017; 6: 1831. Publisher Full Text\n\nMahmudiono T, Nindya TS, Andrias DR, et al.: The effectiveness of nutrition education for overweight/obese mothers with stunted children (NEO-MOM) in reducing the double burden of malnutrition in Indonesia: Study protocol for a randomized controlled trial. BMC Public Health. 2016; 16(1): 486. PubMed Abstract | Publisher Full Text | Free Full Text\n\nViggiano A, Viggiano E, Di Costanzo A, et al.: Kaledo, a board game for nutrition education of children and adolescents at school: cluster randomized controlled trial of healthy lifestyle promotion. Eur J Pediatr. 2015; 174(2): 217–228. PubMed Abstract | Publisher Full Text\n\nDominguez-Rodriguez A, Oliver E, Cebolla A, et al.: Serious games to teach nutrition education to children between 9 to 12 years old. Pickit! and cookit! Lect Notes Inst Comput Sci Soc Telecommun Eng LNICST. 2017; 181 LNICST: 143–147.\n\nKementerian Kesehatan RI: LEAFLET-ISI-PIRINGKU-ilovepdf-compressed_1011.pdf.2017. Reference Source\n\nKementerian Kesehatan Republik Indonesia: Peraturan Menteri Kesehatan RI No 44 Tahun 2016 Tentang Pedoman Manajemen Puskesmas. Jakarta.2016; 1–88. Reference Source\n\nDirjen Bina Gizi dan KIA: Pedoman Pelayanan Kesehatan Reproduksi Terpadu di Tingkat Pelayanan Kesehatan Dasar. Jakarta: Kemenkes RI; 2015 [cited 2018 Apr 8]; 65. Reference Source\n\nMaghfiroh LH, Arif Tsani AF, Dieny FF, et al.: the Effectiveness of Nutrition Education Through Socio-Dramatic Method To Vegetable & Fruit Knowledge and Consumption in 5-6 Years Old Children. Media Gizi Indones. 2021; 16(1): 1. Publisher Full Text\n\nDichev C, Dicheva D, Angelova G, et al.: From gamification to gameful design and gameful experience in learning. Cybern Inf Technol. 2014; 14(4): 80–100.\n\nNurhayati E: Initial gamification project to increase mental health awareness for Indonesian youth. Gafar A, Abdullah WI, Abdullah CU, editors. Bandung: 1st ed.2020; 0–3 p. Reference Source\n\nRespati T, Nugroho E, Setijono GW: Promoting health and brand awareness - An overview of integrated gamification approach on corporate sector. Pertanika J Soc Sci Humanit. 2018; 26(T): 113–124.\n\nWartella EA, Jennings N: Children and computers: New technology - Old concerns. Futur Child. 2000; 10(2): 31–43. PubMed Abstract | Publisher Full Text\n\nMarache-Francisco C, Brangier E: Redefining gamification. Proc IADIS Int Conf Interfaces Hum Comput Interact 2012, IHCI 2012, Proc IADIS Int Conf Game Entertain Technol 2012. 2012; 227–31.\n\nSuleiman-Martos N, García-Lara RA, Martos-Cabrera MB, et al.: Gamification for the Improvement of Diet, Nutritional Habits, and Body Composition in Children and Adolescents: A Systematic Review and Meta-Analysis. Nutrients. 2021; 13: 2478. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nSharma M: Dietary education in school-based childhood obesity prevention programs. Adv Nutr. 2011; 2(2): 207S–216S. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCreswell JW, Creswell JD: Research design: Qualitative, quantitative, and mixed methods approaches. Sage Publication Inc; 5th edition.2018. Reference Source\n\nRespati T, Fitriyana S, Romadhona N, et al.: Balance Nutrition Diet Raw Data. Bandung: 2021. Publisher Full Text\n\nYien JM, Hung CM, Hwang GJ, et al.: A game-based learning approach to improving students’ learning achievements in a nutrition course. Turkish Online J Educ Technol. 2011; 10(2): 1–10.\n\nUzşen H, Didar BZ: A Game-based Nutrition Education: Teaching Healthy Eating to Primary School Students. J Pediatr Res. 2019; 6(1): 18–23. Publisher Full Text\n\nFolkvord F, Laguna-Camacho A: The effect of a memory-game with images of vegetables on children’s vegetable intake: An experimental study. Appetite. 2019; 134(September 2018): 120–124. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "124145",
"date": "22 Feb 2022",
"name": "Tom Baranowski",
"expertise": [
"Reviewer Expertise games for health in general and for diet change in particular"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article is a report of the development and preliminary evaluation of a nutrition education board game to promote healthy eating among Indonesian children. Ordinarily, this would be two papers: 1) focus groups/interviews and 2) design and preliminary pilot testing/feasibility study of implementing the game. The manuscript lacks an enormous amount of detail as indicated by the questions I have raised for the authors. The measures appear to have been ad hoc, rather than standardized or validated.\nThe authors need to provide more detail on their methods of conducting the focus groups and interviews, and of analyzing this qualitative data. How were triangulation, transferability, dependability, and confirmability assessed?\nWhy did the authors elect to study 10-13 yo?\nHow were they recruited? Of whom/what are they representative?\nWhat were the inclusionary/exclusionary criteria?\nIn the evaluation part of the study, what measures of knowledge, attitude and practice were used? Are there validity coefficients associated with each?\nWhy didn’t the authors ever conduct focus groups and/or interviews with the targeted age group to find out their knowledge, attitudes and preferences, and how they might respond to different intervention elements? How were the cutpoints determined?\nWhy wasn’t there a control group? Any pre-post differences could have been influenced by the other components of the national nutrition program?\nIt would help for the authors to add a table that lists in one column each of the specific concepts that were attempted to be communicated and in a second column list the methods/procedures in the game designed to achieve that communication. It would help if this table also clearly specified what each of the constructs for knowledge entailed.\nIt is not clear where students were supposed to obtain the information to answer the questions raised in the game?\nA game usually has rules and a player can win or lose, usually with an opportunity to play the game to do better if s/he fails on early tries. In what way(s) is Gastronot a game?\nHow many sessions was the game played between pre and post over what time?\nThe Figures are not self-evident and should be explained.\nThis preliminary evaluation of the game should be a pilot/feasibility study, as indicated by the authors’ use of the word “pilot” in the title. A pilot/feasibility study answers questions of Can children be recruited? Will they play the game? Do they like it? What problems occurred that need correction?\nWhat did the authors learn from the focus groups and early interviews?\nThe authors make an overly positive spin on what was learned/achieved in the study. There was a very small increase in knowledge, but that did not translate into a change in attitude or behavior. This is unfortunate but should be stated realistically. In contrast to the apparent positive findings cited by the authors in other nutrition education studies, at least one review found limited evidence of success from nutrition games, mostly just small knowledge increases, which usually did not convert to behavior change. See T Baranowski et al. Games for Health Journal. 2019;8(3):153-176.\nIf the intervention was conducted in schools, then this is a cluster analysis. The authors must account for school/cluster in their analysis of change from pre to post. A high intraclass correlation could vitiate the power assumed in the current analysis.\n\nDid the authors conduct interviews with the children at post to assess their evaluation of the game? Why not?\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "138749",
"date": "22 Jun 2022",
"name": "Oluwatosin Leshi",
"expertise": [
"Reviewer Expertise Nutrition Education",
"Maternal and Child Nutrition"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIntroduction:\nThe definition of malnutrition as \"Malnutrition is a deficiency, excess, or nutritional imbalance resulting from inadequate nutrient intake.\" should be revisited - malnutrition does not only result from inadequate nutrient intake, it also arises from excessive intake.\nAfter the sentence \"Indonesia is currently experiencing a double burden of malnutrition, that is, an increase in cases of overweight/obesity, and still having unresolved undernutrition problems.\", the author did not provide any narrative on overnutrition after claiming an increase in the double burden of malnutrition.\nMethods:\nThe age group of the participants in the FGD should be indicated.\nIn the paragraph, \"To develop the game, we conducted a Focus Group Discussion (FGD) attended by 14 people. They were involved in nutrition programs from the Health Office Bandung and the Office of Bandung City. Also attended Public health expert, Health promotion expert, Family Health and Nutrition expert, Game designer, Nutritionist Association, Nutrition Specialist association, organic farmer, organic farm community representatives, and community representatives (housewives). The FGD lasted for three hours. All participants for the interview and FGD gave their written consent.\":\nWho were the participants for the FGD?\n\nWhat commonality do the participants have together?\n\nWho were the participants for the interview?\n\nClearly indicate if the 10 different people listed were for FGD (but they ought not) or interview.\n\nWhy was the interview conducted?\n\nThe aim or the scope of the interview needs to be indicated.\n\nInformed assent is given on behalf of children and not consent.\nFor the cut off point; the term good and sufficient denotes almost the same. Kindly consider >80% to be excellent; 60-89%good/sufficient and <60% insufficient.\nIn the sentence, \"Meanwhile, to find out the differences in knowledge, attitudes, and behaviour between the groups involved in gameplay,\":\nNothing until now indicated that you are assessing attitudes and behaviour.\n\nWhat were the tools and how were they assessed?\nResults:\nWith only a glimpse of the aims of the FGD, it may be difficult to appreciate the emerging themes.\nDiscussion:\nThe sentence, \"In our study, the campaign to improve nutrition was implemented in various schools using lectures and other activities initiated by each school and District Health Centers.\" is confusing. Was there any form of lecture for the students? This was not indicated in the methodology.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "9319",
"date": "07 Mar 2023",
"name": "Titik Respati",
"role": "Author Response",
"response": "Dear Dr. Leshi, Thank you so much for the valuable input, I will revise them accordingly. Regards, Titik Respati"
},
{
"c_id": "9749",
"date": "13 Jun 2023",
"name": "Titik Respati",
"role": "Author Response",
"response": "Introduction: The definition of malnutrition has already been revised A narrative on overnutrition was added. Methods: The age group of the participants in the FGD is already stated in Table 1. All explanations regarding informants for the interviews are in the method section, paragraph two The cut-off point is revised to >80% to be excellent, 60-89%good/sufficient, and <60% insufficient. The method for assessing knowledge, attitudes, and behavior is stated in paragraph 7 of this section. Discussion: The sentence, \"In our study, the campaign to improve nutrition was implemented in various schools using lectures and other activities initiated by each school and District Health Center.\" is deleted. Thank you for your valuable review."
}
]
}
] | 1
|
https://f1000research.com/articles/10-1273
|
https://f1000research.com/articles/12-637/v1
|
12 Jun 23
|
{
"type": "Research Article",
"title": "Clinical characteristics and long-term consequences of COVID-19 patients in a dedicated COVID unit of a tertiary care hospital: an 8-month follow-up study",
"authors": [
"Utshab Roy",
"Najeeb Mahiyuddin",
"Syeda Kalam",
"Tarek Ahmed",
"Utshab Roy",
"Syeda Kalam",
"Tarek Ahmed"
],
"abstract": "Background: Aim of the study was to assess the demographic, clinical characteristics, long term consequences of Bangladeshi coronavirus disease 2019 (COVID-19) patients and to see any association with severity of COVID-19 and post COVID-19 functional status (PCFS).\nMethods: This prospective cohort study was performed in the COVID-19 unit of Cumilla Medical College and Hospital, Cumilla, Bangladesh. Fifty-eight patients were consecutively selected. Data were collected by direct interview and from hospital archives. All patients were followed up at 6 and 8-months intervals over telephone calls. Data regarding age, gender, contact history with COVID-19 patients, travel history, smoking history, comorbidities, symptoms, severity of COVID-19, post COVID-19 symptoms and functional status were recorded\nResults: About 44 (75.9%) patients recovered with residual damage and one patient died. The common symptoms at admission were fever, cough, dyspnea and fatigue while at follow-up, fatigue, poor memory, dyspnea and insomnia were observed, which persisted after recovery but improved over time. There were 30 (51.7%) patients with severe COVID-19 disease and 11 (21.2%) patients suffered from functional limitation. After multivariate adjustment, patients with severe COVID-19 had an odds ratio (OR) of 1.08 (1.02-1.16) for age and patients with post-COVID-19 functional limitation showed OR of 1.05 (1.00-1.11) for age, OR of 10.83 (2.08-56.35) for female and OR of 27.48 (4.30-175.61) for smoking.\n\nConclusion: Majority of the patients recovered but with persistence of post COVID-19 symptoms, and few patients even developed functional limitation. Age was a significant independent predictor for severe disease whereas higher age, female gender and smokers were at increased odds of developing post COVID-19 functional limitation.",
"keywords": [
"characteristics",
"consequences",
"COVID-19",
"follow-up",
"functional status"
],
"content": "Introduction\n\nThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), has continued to pose a fatal threat causing substantial mortality and morbidity worldwide, resulting in more than 188 million confirmed cases and more than 4 million deaths worldwide.1 Since the first detection of COVID-19 on 8th March, 2020 in Bangladesh, a total of 1,071,774 cases were identified with 17,278 deaths till the writing of this article.1 The clinical spectrum of COVID-19 ranges from asymptomatic infection to critical illness.2 In most of the patients, the presentation is mild but hospitalization is needed in around 20% of patients, and around 5% require critical care with non-invasive or mechanical ventilation.3 A significant percentage of patients who recovered from the acute COVID-19, develop new or continue to have previous symptoms lasting weeks to months. Additionally, delayed resolution of symptoms has been seen even in patients with mild symptoms who did not require any hospitalization.4,5 This emerging condition has been given a variety of terms such as long COVID, post-acute COVID-19, chronic COVID-19, post-COVID syndrome or post-acute sequelae of SARS-CoV-2 infection (PASC).6 This new condition is posing a significant effect on people’s quality of life.\n\nTo understand the “Long COVID”, long-term follow-up studies are necessary. Few studies have looked into the persistent symptoms, functional limitations and lung functions of discharged patients with the longest follow-up duration being 6 months.7–11 Huang et al. found fatigue or muscle weakness, sleep difficulties and anxiety or depression as the most common symptoms 6 months following COVID-19 infection.8\n\nAs there is inadequacy of data on this new emerging condition in Bangladesh, we aimed to follow-up the COVID-19 patients for a longer period to describe the long-term consequences after hospital discharge and describe the functional limitation and potential risk factors.\n\n\nMethods\n\nThis was a prospective cohort study performed in the COVID-19 unit of Cumilla Medical College and Hospital, Cumilla, Bangladesh. Fifty-eight reverse transcriptase polymerase chain reaction (RT-PCR) positive patients from nasopharyngeal sample were consecutively selected 18th to 25th July 2020, excluding those that denied to take part in the study. Data regarding demographic characteristics (age, gender, contact history with COVID-19 patients, travel history, smoking history) and clinical characteristics (comorbidities, symptoms, severity of COVID-19) were collected by direct interview using a preformed data collection form. Information regarding treatment, duration of hospital stay and patient outcome were taken from hospital archives. All patients were followed up at 6-month and 8-month from their date of admission. Follow-up was done over telephone call and data regarding post COVID-19 symptoms and functional status were recorded. Informed written consent was taken from all patients and ethical clearance of the study was taken from the institutional review board (registry number 2407).\n\nThe outcome of the patients was classified as recovered without residual damage (patients that were discharged and had no persistent symptoms), recovered with residual damage (discharged patients having persistent post COVID-19 symptoms) and death. Severity of COVID-19 was determined according to WHO severity definitions. Patients with oxygen saturation (SpO2) < 90%, respiratory rate >30 breaths/min and signs of respiratory distress were classified as severe COVID-19 while those patients not meeting the above criteria were categorized as non-severe COVID-19.12 The functional status of patients at follow-up was assessed using the post COVID-19 functional status scale (PCFS). Klok et al proposed the PCFS as an ordinal tool to measure the functional outcome of COVID-19 patients.13 The construct validity of the scale was demonstrated by Machado et al.14 Centers for Disease Control and Prevention (CDC) has also proposed PCFS as a tool for the assessment of functional outcome of patients with post COVID-19 conditions.15 According to post COVID-19 symptoms, daily activities and lifestyle, the PCFS scale is divided into 6 categories. Briefly, Grade 0 are patients with no post COVID-19 symptoms, Grade 1 are patients with post COVID-19 symptoms and negligible functional impairment, Grade 2 are patients with mild functional impairment, Grade 3 are patients with moderate functional impairment, Grade 4 are patients with severe functional impairment and Grade D are patients that died. For the purpose of this study, PCFS was combined into three groups: PCFS Grade 0 (patients with no post COVID-19 symptoms), PCFS Grade 1 (patients with post COVID-19 symptoms but negligible functional impairment) and PCFS Grades 2-4 (patients with functional impairment or limitation).\n\nAll data were analyzed using Statistical Packages for Social Sciences (SPSS) software version 23. Qualitative data were presented as frequency and percentages and analyzed using Pearson’s chi square test, likelihood ratio, Fisher’s exact test where appropriate while quantitative data were presented as mean ± standard deviation and analyzed using t-test for demographic and clinical variables. Comparison of post COVID-19 symptoms between 6-month and 8-month follow up was done using McNemar test. Analysis of factors associated with severe COVID-19 and PCFS was done by binary and ordinal logistic regression respectively. Multivariate analysis was adjusted for age, gender, smoking and co-morbidities. A p value < 0.05 was considered statistically significant.\n\n\nResults\n\nA total of 58 patients were included in the study. About 57 (98.3%) patients were discharged from the hospital. Among them, 10 (17.2%) patients recovered without residual damage and 47 (81.0%) recovered with residual damage. There was one case of death during hospital stay and one case of death after 6 months of discharge. Four patients were lost to follow-up.\n\nThe demographic and clinical characteristics of the study population are shown in Table 1. Twenty eight (48.3%) patients had non-severe disease and 30 (51.7%) patients suffered from severe COVID-19. The mean age of the study population was 47.79 ± 15.99 years and 53.4% were male. Around 38 (65.5%) patients had co-morbidities, which were diabetes mellitus (41.4%), hypertension (36.2%), ischaemic heart disease (20.7%), obesity (13.8%) and bronchial asthma (13.8%). The mean duration from symptom onset to hospital admission was 4.78 ± 2.73 days and mean duration of hospital stay was 15.37 ± 8.57 days. The common symptoms at admission were fever (87.9%), cough (72.4%), dyspnea (69.0%), fatigue (69.0%), anosmia (46.6%) and headache (36.2%). Severe COVID-19 patients received more oxygen, intravenous fluids, anticoagulant therapy, antiviral therapy and corticosteroid therapy than non-severe COVID-19 patients. Higher age, male gender, smoking, co-morbidities, diabetes mellitus, obesity, fever, cough, dyspnea at admission and increased duration of hospital stay were significantly associated with severe COVID-19 disease. Headache at admission was found more in non-severe COVID-19 patients.\n\n* p value < 0.05 is significant.\n\nAbout 43 (82.7%) patients had at least one symptom at 6-month follow-up which was significantly reduced (p = 0.001) to 29 (55.8%) patients at 8-month follow-up (Figure 1A). The common post COVID-19 symptoms were fatigue, poor memory, dyspnea, insomnia, chest pain, alopecia, depression, anxiety, joint pain and among them, the former 7 symptoms were significantly reduced from 6-month to 8-month follow-up (57.5% to 40.4% for fatigue, 40.4% to 15.4% for poor memory, 28.8% to 13.5% for dyspnea, 26.9% to 13.5% for insomnia, 21.2% to 9.69% for chest pain, 19.2% to 3.8% for alopecia, 17.3% to 3.8% for depression, all p < 0.05). There was a statistically significant increase in PCFS Grade 0 (17.3% to 44.2%, p < 0.05) and decrease in PCFS Grade 1 (50.0% to 34.6%, p = 0.039) from 6-month to 8-month follow-up (Figure 1B). The 4 patients that were lost to follow-up and the 2 patients that died during hospital stay and 6 months following discharge were excluded from the statistical analysis.\n\n(A) Post COVID-19 symptoms; (B) Post COVID-19 Functional Status Scale (PCFS).\n\nWhen the follow-up symptoms were further subdivided according to the severity of COVID-19, cough (23.1%) and visual blurriness (11.5%) were significantly associated with severe COVID-19 at 6 months while fatigue (56.0%) and insomnia (24.0%) were significantly associated with severe COVID-19 at 8 months (Table 2).\n\n* p value < 0.05 is significant.\n\nTable 3 shows the association of post COVID-19 functional status scale (PCFS) at 8-month follow-up with demographic and clinical characteristics of the study population. There were 23 (44.2%) patients with no post COVID-19 symptoms (PCFS grade 0), 18 (34.6%) patients having post COVID-19 symptoms with negligible functional impairment (PCFS grade 1) and 11 (21.2%) patients had some form of functional limitation (PCFS grade 2-4) even at 8 months. Patients with PCFS grades 2-4 showed significant association with severe COVID-19 diagnosis at admission, higher age, dyspnea, ageusia, diarrhea at admission and post COVID-19 fatigue, dyspnea, joint pain, insomnia, poor memory at 8-month follow-up when compared to patients with PCFS grade 0 and with higher age, increased duration of hospital stay, dyspnea and diarrhea at admission when compared to patients with PCFS grade 1. Post COVID-19 fatigue and poor memory were significantly associated with PCFS grade 1 when compared to PCFS grade 0.\n\n* p-value < 0.05 is significant.\n\nUnivariate analysis showed age (OR: 1.13; 95% CI: 1.07-1.21), male gender (OR: 5.81; 95% CI: 1.87-18.03), smoking (OR: 7.53; 95% CI: 1.49-37.99) and co-morbidities (OR: 13.91; 95% CI: 3.38-57.17) as predictors for severe COVID-19 but multivariate analysis showed only age (OR: 1.08; 95% CI: 1.02-1.16) as the significant factor for severe COVID-19. Age (OR: 1.04; 95% CI: 1.01-1.08) and smoking (OR: 9.38; 95% CI: 2.33-37.69) were predictors associated with PCFS grade 2-4 on univariate analysis but on multivariate analysis increased age (OR: 1.05; 95% CI: 1.00-1.11), female sex (OR: 10.83; 95% CI: 2.08-56.35) and smoking (OR: 27.48; 95% CI: 4.30-175.61) were at increased odds for developing post COVID-19 functional impairment (Table 4).\n\n* p-value < 0.05 is significant.\n\n** Reference comparison is male gender.\n\n\nDiscussion\n\nIn this prospective cohort study, the demographic and clinical characteristics of COVID-19 patients at admission, at 6-month and 8-month follow-up was assessed and their association was seen according to severity of COVID-19 and PCFS.\n\nThe mean age of the current study population was 47.79 ± 15.99 years with higher male preponderance. The common symptoms at admission were fever, cough, dyspnea and fatigue. These findings are similar to other previous studies.16–19 The increased male predilection to COVID-19 maybe explained by increased expression of angiotensin converting enzyme receptor-2 (ACE-2) in male, increased resistance to infection by females due to sex hormones and irresponsible attitude of men towards preventive measures.20 Much like in this study, diabetes mellitus and hypertension were the common co-morbidities also in studies in Pakistan, China and France.17,18,21 About 98.3% patients were discharged from the hospital while 1.7% patient(s) died during hospital stay in the current study. Initial study from China reported 1.4% deaths17 but other studies have shown larger number of deaths, 25.1% in a Netherlands study,22 14% in a British study23 and 10.9% in a United States study.24 Lower proportion of deaths may be attributed to smaller sample size in the current study and lower co-morbidities in the Chinese study.\n\nThis study found severe COVID-19 patients had higher mean age, male majority, more smokers, more co-morbidities, greater presentations of fever, cough, dyspnea at admission and increased duration of hospital stay than non-severe COVID-19 patients. Patients with severe illness were older, predominantly male and likely to have co-morbidities in other studies as well.17,22,25–30 Elderly people had reduced immune response due to immunosenescence, inflammaging, alteration of T-cell diversity, epigenetic changes and dysregulation of renin-angiotensin system (RAS) and also are prone to cytokine storm, specially due to age-related decline of oxidized nicotinamide dinucleotide, resulting in increased risk of severe infection.31 An Ethiopian study revealed cough, dyspnea, myalgia, headache, fever, chest pain and anosmia as common symptoms of severe COVID-1925 while a Chinese study reported increased expectoration, dyspnea, anorexia and confusion in the severe COVID-19.28 A study of 101 patients in Wuhan found no association of smoking with severity of COVID-1926 but a meta-analysis showed smoking to be significantly associated with severe disease.32 Smoking may result in upregulation of ACE-2 gene regulation, which may be the cause of increased severity of COVID-19 infection.33 The current study found age as the only significant independent predictor for severe COVID-19. Other studies reported older age, co-morbidities, increased white blood cell count, increased C-reactive protein and higher D-dimer at increased risk of developing severe disease.21,25–27,29,30\n\nThe persistent post COVID-19 symptoms at follow-up of this study were fatigue, poor memory, dyspnea, insomnia, chest pain, alopecia, depression, anxiety and joint pain with 82.7% and 55.8% patients having at least one symptom at 6 and 8 months respectively. A large cohort study in Wuhan, China found 76% of patients had at least one post COVID-19 symptom at 6 months with females getting more affected than males. The common symptoms were fatigue or muscle weakness and sleep difficulties.8 Another Nigerian study found most common post COVID-19 symptoms to be fatigue, headache, chest pain and insomnia.9 The pathophysiology behind persistence of symptoms is still unknown but probable mechanisms maybe vascular inflammation, massive inflammatory response from cytokine storm and endothelial dysfunction by the coronavirus.9 Our study also revealed that over time, the post COVID-19 symptoms significantly reduced in frequency. Furthermore, patients with PCFS grade 0 increased and those with PCFS grade 1 decreased in frequency from 6 to 8-month follow-up. Hence, it can be postulated that the post-COVID 19 symptoms may improve with time. An article by O’Sullivan O, demonstrated that previous coronavirus outbreak, severe acute respiratory syndrome (SARS) and Middle-Eastern respiratory syndrome (MERS) coronavirus, also lead to long-term sequelae after recovery from disease and problems like fatigue, shortness of breath, reduced quality of life and mental health issues reduced with time and rehabilitation but still persisted even after 1 year from disease onset.34\n\nPatients with functional impairment (PCFS grade 2-4) at 8 months were found to have higher age, increased symptoms of dyspnea, ageusia and diarrhea at admission, severe COVID-19 infection at admission and more post COVID-19 symptoms of fatigue, dyspnea, joint pain, insomnia and poor memory when compared to patient with no post COVID-19 sequelae (PCFS grade 0). PCFS grade 2-4 were found to be associated with female sex, age, duration of hospital stay, mechanical ventilation and admission to ICU by Taboada M et al.10 and de Graaf M et al. reported that patients with functional limitation were more likely to have longer period of hospital stay, needed mechanical ventilation, depression and cognitive impairments.7 After adjusting for confounding variables, our study found increasing age, female sex and smoking at higher odds of developing post COVID-19 functional limitation. A Spanish study demonstrated that age and duration of hospital stay were linked to higher functional impairment10 while another study reported that increased age, male gender, duration and need for mechanical ventilation during admission, length of hospital and ICU stay were associated with PCFS grade 2-4 at 6 months in patients who recovered from COVID-19 associated ARDS.11\n\nThere were, however, some limitations to the study. The study population was small, which led to smaller sample size of sub-groups, limiting the power of statistical analysis. The single center study may not be representative of the whole population. Four patients who were lost to follow-up, resulting in missing data and preventing detailed analysis of factors associated with the risk of severe COVID-19 and functional status of patients. Most of the patients belonged to a low- income group so few investigations were done; as a result, adequate data regarding investigation could not be taken. Due to the nature of telephone call follow-up, some information may be less accurate and subjected to memory bias. Our data was also lacking in baseline functional status scale scores, which could have provided a better picture of functional outcomes.\n\n\nConclusion\n\nDespite the limitations, this paper provided some important information about the demographic, clinical characteristics and long-term follow up of Bangladeshi COVID-19 patients. To our knowledge, this is the first study to use PCFS as a tool to follow-up patients at two points of time after recovering from COVID-19, namely at 6 and 8 months. The demographic and clinical characteristics of the Bangladesh population were similar to those of other countries. Age was a significant independent predictor for severe COVID-19 disease. Majority of the patients recovered with persistent symptoms up to 6 months; symptoms improved with time but were still present even at 8 months. Patients with higher age, female gender and smoking history were more prone to develop functional impairment after recovery. Therefore, strategies should be aimed at rehabilitation of these patients to improve their outcome. A multi-centered prospective study of larger sample size and longer follow-up period with demographic, clinical, investigational and treatment data, including assessment of physical, functional, psychiatric and cognitive domain of recovered COVID-19 patients would provide a much more comprehensive health spectrum of the COVID-19 infection that can be representative of the whole population.",
"appendix": "Data availability statement\n\nHarvard Dataverse: Clinical characteristics and long-term consequences of COVID-19 patients in dedicated COVID unit of a tertiary care hospital: an 8-month follow-up study, https://doi.org/10.7910/DVN/AIWPTL. 35\n\nThis project contains the following underlying data:\n\n• covid fup.tab (The aim was to assess the demographic, clinical characteristics, long term consequences of Bangladeshi COVID-19 patients and to see any association with severity of COVID-19 and post COVID-19 functional status)\n\n• strobe checklist (checklist of items included in the manuscript)\n\n• Figure 1 (Follow up of COVID-19 patients at 6-month and 8-month)\n\n• COVID patient record form (The questionnaire used to collect data from study participants)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nThe authors wish to acknowledge the staff of COVID-19 unit of Cumilla Medical College & Hospital, Cumilla, Bangladesh.\n\n\nReferences\n\nWHO coronavirus disease (COVID-19) dashboard. Geneva: World Health Organization; 2021. Reference Source\n\nSollini M, Ciccarelli M, Cecconi M, et al.: Vasculitis changes in COVID-19 survivors with persistent symptoms: an [18 F] FDG-PET/CT study. Eur. J. Nucl. Med. Mol. Imaging. 2021; 48(5): 1460–1466. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWu Z, McGoogan JM: Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13): 1239–1242. Publisher Full Text\n\nOuthoff KO: Sick and tired of COVID-19: long haulers and post viral (fatigue) syndromes. S. Afr. Gen. Pract. 2020; 1(4): 132–133. Publisher Full Text\n\nNath A: Long-haul COVID. AAN Enterprises. 2020; 95(13): 559–560. Publisher Full Text\n\nCenters for Disease Control and Prevention: Post-COVID Conditions: Information for Healthcare Providers.2021. Reference Source\n\nde Graaf M , Antoni M, Ter Kuile M, et al.: Short-term outpatient follow-up of COVID-19 patients: A multidisciplinary approach. EClinicalMedicine. 2021; 32: 100731. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuang C, Huang L, Wang Y, et al.: 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021; 397(10270): 220–232. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOsikomaiya B, Erinoso O, Wright KO, et al.: ‘Long COVID’: persistent COVID-19 symptoms in survivors managed in Lagos State, Nigeria. BMC Infect. Dis. 2021; 21(1): 1–7.\n\nTaboada M, Cariñena A, Moreno E, et al.: Post-COVID-19 functional status six-months after hospitalization. J. Infect. 2020; 82(4): e31–e33. PubMed Abstract | Publisher Full Text\n\nTaboada M, Moreno E, Cariñena A, et al.: Quality of life, functional status, and persistent symptoms after intensive care of COVID-19 patients. Br. J. Anaesth. 2021; 126(3): e110–e113. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTherapeutics and COVID-19: living guideline. Geneva: World Health Organization; 2021. Reference Source\n\nKlok FA, Boon GJ, Barco S, et al.: The Post-COVID-19 Functional Status scale: a tool to measure functional status over time after COVID-19. Eur. Respir. J. 2020; 56(1): 2001494.\n\nMachado FV, Meys R, Delbressine JM, et al.: Construct validity of the Post-COVID-19 Functional Status Scale in adult subjects with COVID-19. Health Qual. Life Outcomes. 2021; 19(1): 1–10.\n\nCenters for Disease Control and Prevention: Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance.2021. Reference Source\n\nZhong Z-F, Huang J, Yang X, et al.: Epidemiological and clinical characteristics of COVID-19 patients in Hengyang, Hunan Province, China. World J. Clin. Cases. 2020; 8(12): 2554–2565. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGuan W-j, Ni Z-y, Hu Y, et al.: Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020; 382(18): 1708–1720. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAsghar MS, Kazmi SJH, Khan NA, et al.: Clinical profiles, characteristics, and outcomes of the first 100 admitted COVID-19 patients in Pakistan: a single-center retrospective study in a tertiary care hospital of Karachi. Cureus. 2020; 12(6): e8712. PubMed Abstract | Publisher Full Text\n\nBoddington NL, Charlett A, Elgohari S, et al.: Epidemiological and clinical characteristics of early COVID-19 cases, United Kingdom of Great Britain and Northern Ireland. Bull. World Health Organ. 2021; 99(3): 178–189. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBwire GM: Coronavirus: why men are more vulnerable to Covid-19 than women? SN Compr. Clin. Med. 2020; 2(7): 874–876. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaeuffer C, Le Hyaric C, Fabacher T, et al.: Clinical characteristics and risk factors associated with severe COVID-19: prospective analysis of 1,045 hospitalised cases in North-Eastern France, March 2020. Eurosurveillance. 2020; 25(48): 2000895. Publisher Full Text\n\nPouw N, van de Maat J , Veerman K, et al.: Clinical characteristics and outcomes of 952 hospitalized COVID-19 patients in The Netherlands: A retrospective cohort study. PLoS One. 2021; 16(3): e0248713. PubMed Abstract | Publisher Full Text | Free Full Text\n\nConway J, Gould A, Westley R, et al.: Clinical characteristics and progression of COVID-19 confirmed cases admitted to a single British clinical centre—A brief case series report. Int. J. Clin. Pract. 2021; 75(3): e13807. Publisher Full Text\n\nKhan MS, Dogra R, Miriyala LK, et al.: Clinical characteristics and outcomes of patients with Corona Virus Disease 2019 (COVID-19) at Mercy Health Hospitals, Toledo, Ohio. PLoS One. 2021; 16(4): e0250400. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbraha HE, Gessesse Z, Gebrecherkos T, et al.: Clinical features and risk factors associated with morbidity and mortality among patients with COVID-19 in northern Ethiopia. Int. J. Infect. Dis. 2021; 105: 776–783. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu X-q, Xue S, Xu J-b, et al.: Clinical characteristics and related risk factors of disease severity in 101 COVID-19 patients hospitalized in Wuhan, China. Acta Pharmacol. Sin. 2021; 43: 64–75. Publisher Full Text\n\nLiu S, Luo H, Wang Y, et al.: Clinical characteristics and risk factors of patients with severe COVID-19 in Jiangsu province, China: a retrospective multicentre cohort study. BMC Infect. Dis. 2020; 20(1): 1–9.\n\nCao Z, Li T, Liang L, et al.: Clinical characteristics of coronavirus disease 2019 patients in Beijing, China. PLoS One. 2020; 15(6): e0234764. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYegorov S, Goremykina M, Ivanova R, et al.: Epidemiology, clinical characteristics, and virologic features of COVID-19 patients in Kazakhstan: A nation-wide retrospective cohort study. Lancet Reg. Health Eur. 2021; 4: 100096. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHu J, Wang Y: The clinical characteristics and risk factors of severe COVID-19. Gerontology. 2021; 67(3): 255–266. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMueller AL, McNamara MS, Sinclair DA: Why does COVID-19 disproportionately affect older people? Aging (Albany NY). 2020; 12(10): 9959–9981. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGülsen A, Yigitbas BA, Uslu B, et al.: The effect of smoking on COVID-19 symptom severity: Systematic review and meta-analysis. Pulm. Med. 2020; 2020: 1–11. Publisher Full Text\n\nLeung JM, Yang CX, Tam A, et al.: ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. Eur. Respir. J. 2020; 55(5): 2000688. PubMed Abstract | Publisher Full Text | Free Full Text\n\nO’Sullivan O: Long-term sequelae following previous coronavirus epidemics. Clin. Med. 2021; 21(1): e68–e70. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRoy U, Mahiyuddin N, Kalam S, et al.: Clinical characteristics and long term consequences of COVID-19 patients in dedicated COVID unit of a tertiary care hospital: an 8-month follow-up study. [DATASET]. Harvard Dataverse. 2022; V3. UNF:6:LS4ilRS2GPTdf8fuFDXXcQ== [fileUNF]. Publisher Full Text"
}
|
[
{
"id": "187110",
"date": "24 Jul 2023",
"name": "Olayinka Rasheed Ibrahim",
"expertise": [
"Reviewer Expertise Pediatric infectious disease",
"COVID-19"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nRE: Clinical characteristics and long-term consequences of COVID-19 patients in a dedicated COVID unit of a tertiary care hospital: an 8-month follow-up study\nGeneral comments This is well written manuscript and a few on data on possible long-term consequences of COVID-19. Hence, it will benefit scientific community and world at large.\nFind below the specific comments\nAbstract:\n\nResults:\n\"Multivariate\" should read 'multivariable'.\nIntroduction:\n\"substantial mortality and morbidity worldwide, resulting in more than 188 million confirmed cases and more than 4 million deaths worldwide.1 Since the first detection of COVID-19 on 8th March, 2020 in Bangladesh, a total of 1,071,774 cases were identified with 17,278 deaths till the writing of this article\". - This data should be quoted with real time update due to the dynamic nature of COVID-19 data. Writing till writing of this article is unspecific and ambiguous\nMethods\nHow was the sample size estimated and at what power?\n\nWhich part of the data was analysed with “ordinal logistic regression”?\n\n\"Multivariate\" - change to 'multivariable'.\n\n\"The 4 patients that were lost to follow-up and the 2 patients that died during hospital stay and 6 months following discharge were excluded from the statistical analysis\" - Any potential impact of this on the analysis; and this should be stated in the exclusion criteria as those with incomplete data or lost to follow up.\nTable 4:\nMultivariate- change to 'multivariable'.\n\nAge: Specify the reference.\n\n\"Univariate analysis showed age (OR: 1.13; 95% CI: 1.07-1.21), male gender (OR: 5.81; 95% CI: 1.87-18.03), smoking (OR: 7.53; 95% CI: 1.49-37.99) and co-morbidities (OR: 13.91; 95% CI: 3.38-57.17) as predictors for severe COVID-19 but multivariate analysis showed only age\" - Can univariate give a predictor where there are multiple independent variables?\n\n\"were predictors associated with PCFS grade 2-4 on univariate analysis\" - see above comment.\nDiscussion\n\"Our study also revealed that over time, the post COVID-19 symptoms significantly reduced in frequency. Furthermore, patients with PCFS grade 0 increased and those with PCFS grade 1 decreased in frequency from 6 to 8-month follow-up\" - this statement appears contradictory and unclear\nConclusion\n\"Despite the limitations, this paper provided some important information about the demographic, clinical characteristics and long-term follow up of Bangladeshi COVID-19 patients. To our knowledge, this is the first study to use PCFS as a tool to follow-up patients at two points of time after recovering from COVID-19, namely at 6 and 8 months\" - delete. This is like justification and not conclusion.\n\n\"as a tool to follow-up patients at two points of time after recovering from COVID-19, namely at 6 and 8 months. demographic and clinical characteristics of the Bangladesh population were similar to those of other countries. Age was a significant independent predictor for severe COVID-19 disease\" - delete: discussion and results respectively.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "215220",
"date": "30 Oct 2023",
"name": "Alex BUOITE STELLA",
"expertise": [
"Reviewer Expertise Physiology",
"pathophysiology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI would like to thank the authors for the interesting work and the topic of long COVID remains important, despite a favourable amount of papers have discussed the relationship with the severity of the acute symptoms in relation to the severity and frequency of the long COVID symptoms.\nI think that the manuscript is well written, clear, and despite the small sample size (that the authors cite as a limitation), considering the importance to have a clear monitoring of the effects of the infection in different countries, and being Bangladesh under-represented.\nMaybe, I would like to see some more discussion around the possible pathophysiological mechanisms, as it is true that the hypothesis of \"vascular inflammation, massive inflammatory response from cytokine storm and endothelial dysfunction by the coronavirus\" exists, but it has been postulated already some years ago, and meanwhile authors have provided some measurements confirming such hypothesis, as for example altered cortical excitability (Versace et al., 2023)1, perfusion (Ajcevic et al., 2023)2 and metabolism (Guedj et al., 2021)3.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-637
|
https://f1000research.com/articles/11-24/v1
|
11 Jan 22
|
{
"type": "Research Article",
"title": "Hesitancy towards the COVID-19 vaccine among health care practitioners in the Kingdom of Saudi Arabia: a cross-sectional study",
"authors": [
"Abdullah A. Almojaibel",
"Khalid Ansari",
"Yahya A. Alzahrani",
"Saleh A. Alessy",
"Faraz A. Farooqi",
"Yousef D. Alqurashi",
"Khalid Ansari",
"Yahya A. Alzahrani",
"Saleh A. Alessy",
"Faraz A. Farooqi",
"Yousef D. Alqurashi"
],
"abstract": "Background: The coronavirus disease 2019 (COVID-19) pandemic is a major public health crisis worldwide. In less than 12 months since the World Health Organization declared the outbreak, several different COVID-19 vaccines have been approved and deployed mostly in developed countries since January 2021. However, hesitancy to accept the newly developed vaccines is a well-known public health challenge that needs to be addressed. The aim of this study was to measure willingness and hesitancy toward COVID-19 vaccines among health care practitioners' (HCPs) in Saudi Arabia.\n\nMethods: A cross-sectional study using an online self-reported survey was conducted among HCPs in Saudi Arabia between April 4th to April 25th 2021 using snowball sampling. Multivariate logistic regression was employed to identify the possible factors affecting HCPs’ willingness and hesitancy to receive COVID-19 vaccines.\n\nResults: Out of 776 participants who started the survey, 505 (65%) completed it and were included in the results. Among all HCPs, 47 (9.3%) either said “no” to receive the vaccine [20 (4%)] or were hesitant to receive it [27 (5.3%)]. Of the total number of the HCPs, 376 (74.5%) already received the COVID-19 vaccine, and 48 (9.50%) were registered to receive it. The main reason of agreement to receive the COVID-19 vaccine was “wanting to protect self and others from getting the infection” (24%).\n\nConclusion: Our findings have shown that hesitancy toward receiving COVID-19 vaccines among HCPs in Saudi Arabia is limited and therefore may not be a serious issue. The outcomes of this study may help to understand factors that lead to vaccine hesitancy in Saudi Arabia and help public health authorities to design targeted health education interventions aiming to increase uptake of these vaccines.",
"keywords": [
"vaccine acceptance",
"COVID-19 vaccine",
"coronavirus",
"Saudi Arabia",
"vaccine hesitancy"
],
"content": "Introduction\n\nThe coronavirus disease 2019 (COVID-19) pandemic is a major public health concern worldwide. Since the beginning of the COVID-19 pandemic, over 236 million confirmed incidences and over 4.8 million deaths were registered worldwide.1 In less than 12 months since the World Health Organization (WHO) declared the outbreak, several numbers of COVID-19 vaccines have been approved and deployed mostly in developed countries since January 2021. In the Kingdom of Saudi Arabia (KSA), four vaccines have been approved by the health regulatory bodies (i.e., Oxford-AstraZeneca, Johnson & Johnson’s Janssen, Moderna, and Pfizer/BioNTech),2 with a priority to vaccinate health care practitioners (HCPs) alongside other groups who are at a higher risk of COVID-19.3\n\nAchieving a high vaccination coverage level among HCPs across KSA will ensure the presence of an adequate number of protected workforces to deal with the pandemic more effectively and efficiently.4 However, hesitancy to accept the newly developed vaccine is a well-known public health challenge,5 which might be exaggerated after documenting rare thromboembolic events among vaccinated individuals.6\n\nArguably, several studies have sought to determine the level of willingness to receive the vaccine as well as the factors influencing vaccine acceptance.7,8 To examine this further, a study was conducted recently in KSA prior to the development of the vaccines, demonstrated that only 50% of the HCPs were willing to receive the vaccine.9 In addition, another study carried out in the United States showed that concerns about vaccine efficacy, adverse effects, and rapidity of the production were the most important factors affecting hesitancy or reluctance to receive the COVID-19 vaccine.10\n\nThere has been no research conducted after the approval of the COVID-19 vaccines in KSA. Therefore, this study aimed to measure willingness and hesitancy toward COVID-19 vaccines among HCPs in Saudi Arabia.\n\n\nMethods\n\nWe conducted a cross-sectional study to assess willingness and hesitancy toward COVID-19 vaccines among HCPs in KSA. We created an online self-reported survey using the Question Pro survey tool hosted at Imam Abdulrahman Bin Faisal University (IAU). The survey was offered only in English because most of the HCPs in Saudi speak and understand English. The questions asked in the survey are available as part of the underlying data.26 Responses were collected anonymously and no personally identifying information was collected. This study was approved by the IAU’s Institutional Review Board (IRB-2021-03-149).\n\nWe utilized convenience sampling method to recruit participants. The survey was distributed via online links posted on social media platforms (e.g., Twitter, LinkedIn, and WhatsApp) to reach responses from various HCPs groups in KSA. Participants were encouraged to further distribute the survey among other HCPs groups. Data were collected from April 4th to April 25th 2021.\n\nAll adults (>18 years of age) currently working in healthcare facilities in KSA, regardless of the level of patient contact and their clinical role, were eligible to participate in the study. Informed consent was obtained from all the participants prior to starting the survey. A participation consent statement was added on the study information page as follows: “If you are a health care practitioner in Saudi Arabia and consent to participate in this survey, please proceed to the next page to start the survey.” Only those who agreed to participate where allowed to complete the survey. Proceeding to the survey page was therefore taken as consent to participate.\n\nThe survey collected participants’ demographics and health information and assessed HCPs’ attitude and perception of COVID-19 and COVID-19 vaccines. Furthermore, the survey assessed the HCPs’ willingness to receive COVID-19 vaccines as well as hesitancy level as measured by the vaccine hesitancy scale (VHS). The VHS includes 10 items measured on a 5-point Likert scale ranging from strongly disagree to strongly agree. The VHS is developed by the WHO Strategic Advisory Group of Experts (SAGE) to capture parental attitudes, beliefs, and behaviors surrounding vaccination.11 The COVID-19 vaccines hesitancy scale,7 which was adopted in this study, is a modified version of the VHS. The validity and reliability of the COVID-19 VHS was established in another study.7 However, we piloted the survey with nine HCPs currently practicing in KSA to assure the clarity of the questions and to evaluate the face and content validity of the scale on the targeted population.\n\nFor descriptive analyses, univariate analyses were used to evaluate the associations between HCPs’ willingness to receive COVID-19 vaccines and their demographic characteristics, awareness, and health status. The differences in the VHS between participants who reported their willingness to receive the vaccine and those who had no intention to receive the vaccine were determined by t tests. Subsequently, we employed multivariate logistic regression to identify the possible factors affecting HCPs’ willingness to receive the COVID-19 vaccines. Based on multiple previous studies that explored vaccines’ acceptance,8,9,12 several sociodemographic factors (e.g., age, residency province, and health profession), health status, and perception of COVID-19 and COVID-19 vaccines were included in the multivariable regression model. For the above regression, odds ratio (OR) and the respective 95% CI were estimated. All analyses were performed using SPSS 26.0 (IBM Corporation, New York, NY, United States). The level of statistical significance was set at p < 0.05 for this analysis.\n\n\nResults\n\nOut of 776 participants who started the survey, 505 (65.1%) completed it and were included in the analysis. The remaining 271 did not complete the survey fully; therefore, they were excluded. The demographical characteristics of the participants are presented in Table 1. Among 505 HCPs who completed the survey, 47 (9.3%) either said “no” to receive the vaccine [20 (4%)] or were hesitant to receive it [27 (5.3%)]. Of the total number of the HCPs, 376 (74.5%) had already received the COVID-19 vaccine, and 48 (9.5%) were registered to receive it. Out of the 34 participants (6.7%) who wanted to receive the vaccine, the majority of them [20 (59%)] preferred the Pfizer-BioNTech vaccine because they believed it had fewer side effects and was more effective than AstraZeneca vaccine.\n\nThe associations between the demographic characteristics of the HCPs and their willingness to receive COVID-19 vaccines is presented in Table 2. Women were more hesitant to receive the vaccine (47.3%) compared to men. However, no statistically significant association was found between gender and willingness to receive the vaccine (p = 0.26). Significant association was only found between having excellent or good health condition and the willingness to receive the COVID-19 vaccine (p = 0.03).\n\nTable 3 represents the bivariate analysis of hesitancy scale items for the HCPs who agreed to receive the COVID-19 vaccine. The majority of the participants who agreed to receive the vaccine were found to agree (53.7%) or strongly disagree (34.6%) that “the COVID-19 vaccine is important for my health”. Also, most of the participants were found to agree (33.1%) or strongly agree (48.6%) that “COVID-19 vaccines will be very effective in preventing COVID-19”. Only 21.2% of the HCPs doubt the safety of COVID-19 vaccines, and 28.9% were neutral about the vaccine’s safety.\n\nFigure 1 shows the reasons of accepting to receive the COVID-19 vaccine; wanting to protect self and others from getting the infection was the main reason (24%). Figure 2, however, shows the reasons for not accepting COVID-19 vaccines. Most of the HCPs were lacking the trust in this vaccine because it is new (20%).\n\n\nDiscussion\n\nThe main finding of this study was that 9.3% of the HCPs either didn’t want to receive the vaccine or were hesitant to receive it. This indicates that the vaccine hesitancy among the HCPs in our sample from Saudi Arabia may not be of a serious issue. Although there are few studies assessed the hesitancy toward vaccination, our results are consistent with the current literature.13,14 Civelek et al. (2021) found that 68.4% of physicians in Turkey were willing to get vaccinated.13 Robertson et al. (2021) reported that 82% of UK population were willing to get vaccinated.14 However, willingness level to receive the vaccine may differ between countries and communities. In a recent study, sampled from 19 countries with more than 13,000 participants, the acceptance of COVID-19 vaccines ranged from 54.8% in Russia to 88.6% in China.15 Data collected from Saudi Arabia before the vaccination campaign showed that the COVID-19 vaccines’ acceptance level among the population was 64.7%.16\n\nThe results of this study showed that 76.6% of the Saudi HCPs were willing to receive COVID-19 vaccines. A previous study on HCPs in Saudi Arabia, prior to the vaccination campaign, showed that the COVID-19 vaccines’ acceptance level was reported to be 50.5%.9 This surge in the acceptancy level by more than 26% following the vaccine campaign can be attributed to several factors, but one major factor was that the government of Saudi Arabia prohibited unvaccinated people from traveling, entering private establishments and government buildings, or performing Hajj and Umrah.17\n\nOur study showed that the majority of those who agreed to receive the vaccine were young, up to 24 years. This result is similar to a study conducted by Al-Mohaithef et al. (2020) in which they found that the majority of those who agree to receive the vaccine were from the age group between 26 to 35.16 Qattan et al. in 2021 measured Saudi HCPs’ acceptance of the COVID-19 vaccine and found that the majority of those who agreed to receive the vaccine were from the age group between 30 to 39 years.9 However, several other studies showed that the willingness to receive COVID-19 vaccines were higher in old ages (50 years and above) for HCPs,10 and for the general population.18 One justification for this contradiction between Saudi HCPs and others can be attributed to the youth population of Saudi Arabia compared to the western countries. In total, 37% of the Saudi population are between the age of 15 to 34 years.\n\nInterestingly, our study results showed that the factors that influenced the HCPs willingness to receive the vaccine were:\n\n1) Perceived their health status as excellent or very good; and\n\n2) Believed that vaccines will relieve the pandemic.\n\nThese findings supports the conclusions of several previous studies20–22 that showed health issues such as mental illness, chronic health problems or physical health problems may lead to both vulnerability and inequality.20 Therefore, even if the vaccines uptake falls short in some high-risk groups, a trivial increase in vaccines uptake will have significant health benefits.22\n\nWe also determined the reasons for accepting or rejecting to receive COVID-19 vaccines as reported by the HCPs. Our findings contradict the results from Verger et al. (2021) about the safety concerns of COVID-19 vaccines.8 Verger and colleagues concluded that concerns about the safety of the COVID-19 vaccines was, by far, the most important factor for hesitancy or reluctance and for moderate acceptance.8 Contrarily, Shekhar et al. (2021) found that most HCPs (86%) believe that the COVID-19 vaccine is safe. However, Qattan et al. (2021) study showed that 16.82% of the HCPs in KSA have safety and efficacy concerns about COVID-19 vaccines, and 26.73% have fear of the adverse side effects of the vaccines.9 Even though our study was conducted after the beginning of the vaccine campaigns, we found that 21% of the HCPs doubt the safety of the vaccines, and 39.5% were worried about the possible side effects of COVID-19 vaccines. The increased percentage of HCPs with concerns regarding the COVID-19 vaccines in our study could be explained by the recent reports about the possible vaccine’s adverse effects, such as the formation of blood clots in large arteries.23\n\nPrevious studies suggested that believing in the conspiracy theory behind COVID-19 was a factor of rejection.9,24,25 This is similar to our findings which suggested that 5% of the HCPs rejected the vaccine because they believed rumors about the vaccines such as the “chip theory”. Although 5% seems low, it may reflect the fact that our population only included HCPs and this percentage could rise if we conducted the study in the general population and amongst those who do not trust any source of information on COVID-19 vaccines. However, Qattan et al. reported that only 0.6% of the HCPs believed that COVID-19 does not exists.9\n\nThis study has some limitations. First, although the sample size in our study was objectively determined, we used a snowball sampling method to distribute the survey link among HCPs in the KSA. This method may have caused a selection bias since most of our sample were from the eastern province of KSA. Therefore, our sample may not be representative of all HCPs in KSA, which can limit the generalizability of the findings. In addition, this was a cross-sectional study. Therefore, we could not draw causal relationships between the factors and COVID-19 vaccine acceptance. Finally, the study's questionnaire was published online in the English language only, which produced a selection bias favoring English-literate HCPs only and those who have Internet connections.\n\nDespite the limitations, our study was able to explore some of the unknown factors associated with COVID-19 vaccine acceptance and rejection which were not explored in previous studies. Also, given the representative sample size across KSA, the findings comprehensively demonstrated health care practitioners’ intention to uptake the COVID-19 vaccine. Future research is therefore needed to assess this study’s findings and to examine additional challenges around vaccinations in the Saudi population. Further investigations of the vaccine’s safety awareness and promotion strategies to encourage individuals to get the vaccine, as well as exploring key barriers towards receiving the COVID-19 vaccination are needed.\n\n\nConclusion\n\nOur findings have shown that hesitancy toward receiving COVID-19 vaccines among HCPs in Saudi Arabia is limited and therefore may not be of a serious issue. Also, the outcomes of this study help to understand factors that lead to vaccine hesitancy in Saudi Arabia and help public health authorities to design targeted health education interventions aiming to increase vaccine’s acceptance and uptake.\n\n\nData availability\n\nHarvard Dataverse: Hesitancy of COVID-19 vaccine among health care practitioners in the Kingdom of Saudi Arabia, https://doi.org/10.7910/DVN/E90NQL26\n\nThe project contains the following underlying data:\n\n- SurveyReport-8303281-04-22-2021-T042516.666.tab (raw data from questionnaire).\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nCompeting interests\n\nNo competing interests were disclosed.\n\n\nGrant information\n\nThe authors declare that no grants were involved in supporting this work.",
"appendix": "References\n\nWHO Coronavirus (COVID-19) Dashboard|WHO Coronavirus (COVID-19) Dashboard With Vaccination Data. http\n\nE-Services - Request for Vaccine Approval in the Kingdom. http\n\nMOH News - MOH Announces Priority Groups for COVID-19 Vaccination. http\n\nAlshammari TM, Yusuff KB, Aziz MM, et al.: Healthcare professionals’ knowledge, attitude and acceptance of influenza vaccination in Saudi Arabia: a multicenter cross-sectional study. BMC Health Serv. Res. 2019 Apr; 19(1): 229. PubMed Abstract | Publisher Full Text\n\nChevallier C, Hacquin A-S, Mercier H: COVID-19 Vaccine Hesitancy: Shortening the Last Mile. Trends Cogn. Sci. 2021/02/09. 2021 May; 25(5): 331–333. PubMed Abstract | Publisher Full Text Reference Source\n\nØstergaard SD, Schmidt M, Horváth-Puhó E, et al.: Thromboembolism and the Oxford–AstraZeneca COVID-19 vaccine: side-effect or coincidence?. Lancet. 2021; 397(10283): 1441–1443. PubMed Abstract | Publisher Full Text\n\nChen M, Li Y, Chen J, et al.: An online survey of the attitude and willingness of Chinese adults to receive COVID-19 vaccination. Hum. Vaccin. Immunother. 2021 Jan; 17: 2279–2288. Publisher Full Text\n\nVerger P, Scronias D, Dauby N, et al.: Attitudes of healthcare workers towards COVID-19 vaccination: a survey in France and French-speaking parts of Belgium and Canada, 2020. Euro Surveill Bull Eur sur les Mal Transm = Eur Commun Dis Bull. 2021 Jan; 26(3). Publisher Full Text\n\nQattan AMN, Alshareef N, Alsharqi O, et al.: Acceptability of a COVID-19 Vaccine Among Healthcare Workers in the Kingdom of Saudi Arabia. Front Med. 2021 Mar 1; 8: 644300. PubMed Abstract | Publisher Full Text Reference Source\n\nShekhar R, Sheikh AB, Upadhyay S, et al.: COVID-19 vaccine acceptance among health care workers in the united states. Vaccines. 2021; 9(2): 1–18. Publisher Full Text\n\nLarson HJ, Jarrett C, Schulz WS, et al.: Measuring vaccine hesitancy: The development of a survey tool. Vaccine. 2015; 33(34): 4165–4175. PubMed Abstract | Publisher Full Text Reference Source\n\nKwok KO, Li K-K, Wei WI, et al.: Influenza vaccine uptake, COVID-19 vaccination intention and vaccine hesitancy among nurses: A survey. Int. J. Nurs. Stud. 2021; 114. Publisher Full Text PubMed Abstract | Reference Source\n\nCivelek B, Yazici O, Ozdemir N, et al.: Attitudes of physicians towards COVID-19 vaccines and reasons of vaccine hesitancy in Turkey. Int. J. Clin. Pract. 2021 May; e14399.\n\nRobertson E, Reeve KS, Niedzwiedz CL, et al.: Predictors of COVID-19 vaccine hesitancy in the UK Household Longitudinal Study. medRxiv. 2021 Jan 1. 2020.12.27.20248899. Reference Source\n\nLazarus JV, Ratzan SC, Palayew A, et al.: Author Correction: A global survey of potential acceptance of a COVID-19 vaccine (Nature Medicine, (2021), 27, 2, (225-228), 10.1038/s41591-020-1124-9). Nat. Med. 2021; 27(2): 354. PubMed Abstract | Publisher Full Text\n\nAl-Mohaithef M, Padhi BK: Determinants of covid-19 vaccine acceptance in saudi arabia: A web-based national survey. J. Multidiscip. Healthc. 2020; Volume 13: 1657–1663. PubMed Abstract | Publisher Full Text\n\nSaudi Arabia to require vaccination to enter governmental, private establishments - SPA|Reuters.[cited 2021 Jul 2]. Reference Source\n\nMalik AA, McFadden SM, Elharake J, et al.: Determinants of COVID-19 vaccine acceptance in the US. EClinicalMedicine. 2020 Sep; 26: 100495. PubMed Abstract | Publisher Full Text\n\nSaudi Arabia: population distribution by age group 2020|Statista.[cited 2021 Jul 2]. Reference Source\n\nCovid-19 vaccination programme: where do people with mental health difficulties lie within the order of priority? - The BMJ. http\n\nAnnex A: COVID-19 vaccine and health inequalities: considerations for prioritisation and implementation - GOV.UK. http\n\nHungerford D, Vivancos R, Read JM, et al.: Rotavirus vaccine impact and socioeconomic deprivation: An interrupted time-series analysis of gastrointestinal disease outcomes across primary and secondary care in the UK. BMC Med. 2018; 16(1): 10. PubMed Abstract | Publisher Full Text\n\nFirst reported cases of clots in large arteries causing stroke following covid-19 vaccination. BMJ [cited 2021 Jul 4]. Reference Source\n\nCOVID-19 vaccine deployment: behaviour, ethics, misinformation and policy strategies.2020. Reference Source\n\nDuffy B: Coronavirus: vaccine misinformation and the role of social media.Reference Source\n\nHesitancy of COVID-19 vaccine among health care practitioners in the Kingdom of Saudi Arabia. DOI: 10.7910/DVN/E90NQL"
}
|
[
{
"id": "119369",
"date": "24 Jan 2022",
"name": "Mohammad Al-bsheish",
"expertise": [
"Reviewer Expertise Healthcare Administration",
"Occupational Safety and Quality Management",
"Nursing Science"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear authors,\n\nThank you for your submission of your article entitled “Hesitancy towards the COVID-19 vaccine among health care practitioners in the Kingdom of Saudi Arabia: a cross-sectional study” for F1000Research.\nHere are some comments for improvement. I hope these comments are useful!\nTitle: your study aims to measure willingness and hesitancy toward COVID-19 vaccines among health care practitioners (HCPs) in Saudi Arabia. However, \"willingness\" is conspicuously absent from the title; I suggest adding the willingness to the title.\nIntroduction\n\nDue to massive changes in the number of cases every day, mentioning the date you got the statistics increases the accuracy for the readers. The problem statement in the introduction needs to be enriching more by mentioning:\n\nThe impact of COVID-19 on HCPs by presenting governmental statistics and previous studies\n\nMore international and national literature on hesitancy and willingness of receiving the vaccine\n\nThe motive to conduct this study in particular if we consider the high percentage vaccination rate in Saudi Arabia and how the compensation mechanism of HCPs who are declining to receive the vaccine is affected, as they are able and trained to protect patients by using the safety compliance behaviours and adhering to PPE. Please see “Al-Bsheish, M., Jarrar, M. T., & Scarbrough, A. (2021). A Public Safety Compliance Model of Safety Behaviors in the Age of the COVID-19 Pandemic. INQUIRY: The Journal of Health Care Organization, Provision, and Financing, 58, 1–6”.\n\nMethods\n\nIn the Participant's part, you mentioned “All adults (>18 years of age) currently working in healthcare facilities in KSA” while your investigation is among HCPs! …This may confuse the readers. In the Measures part, you wrote “we piloted the survey with nine HCPs currently practicing in KSA to assure the clarity of the questions and to evaluate the face and content validity of the scale on the targeted population”, did you mean pre-test? Because you examined the face and content validity, however, the pilot study investigates the reliability of the scale by Cronbach's alpha, and the minimal size to conduct it is 30 participants. Please See “Sekaran, U., & Bougie, R. (2016). Research methods for business: A skill-building approach. John Wiley & Sons”.\n\nResults\n\nYou wrote “Women were more hesitant to receive the vaccine (47.3%) compared to men”. While Table 2 shows the willingness to receive the COVID-19 vaccines. There is a difference between willingness and hesitancy. I would change this to \"Women were less willing to receive the vaccine\".\n\nDiscussion\n\nWell written and interesting, however, it is better to focus on the conspiracy theories in your introduction to enrich your problem statement in this study.\n\nIt is better to add the limitations and future studies in separate parts after the discussion.\n\nLastly, please revise the manuscript for flow and English language edits and update any references\n\nAgain, thank you for your work, and good luck.\n\nMAG\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9021",
"date": "15 Nov 2022",
"name": "Abdullah Almojaibel",
"role": "Author Response",
"response": "Dear reviewer, We would like to thank you for your valuable feedback. We have modified the manuscript based on your suggestions. The introduction section is now modified with more literature about COVID-19 from KSA and other countries presenting the issues, and more statistics. All other valuable comments from the reviewer were also addressed/corrected in this version. Based on the additional citations, the reference list is now modified too. Regards,"
}
]
},
{
"id": "148319",
"date": "06 Sep 2022",
"name": "Sun Caijun",
"expertise": [
"Reviewer Expertise Vaccine",
"infectious diseases",
"antiviral drugs"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript mainly investigated the COVID-19 vaccine acceptance and intentions among healthcare workers in Saudi Arabia. There have been many similar investigations, so the authors should compare their work with the published data and provide explanation of possible discrepancy.\nOnly 505 valid participants were investigated in this survey. Please state how to calculate the minimum sample size of participants in this survey.\nPlease also state the inclusion and exclusion criteria for these participants in this survey. Selection bias may exist if the participants with small sample size were recruited without reasonable inclusion and exclusion criteria.\nThe study was conducted in April, 2021, but the pandemic situation and vaccination policies changed greatly during this year. This change always influenced people’s attitudes towards COVID-19 vaccination, and therefore the conclusion might be changed.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "9608",
"date": "28 Apr 2023",
"name": "Abdullah Almojaibel",
"role": "Author Response",
"response": "Dear Reviewer, Thanks for the feedback. 1- This manuscript mainly investigated the COVID-19 vaccine acceptance and intentions among healthcare workers in Saudi Arabia. There have been many similar investigations, so the authors should compare their work with the published data and provide explanation of possible discrepancy. In the discussion section we compared our findings with the other studies conducted in Saudi Arabia and other countries and explained the differences. 2- Only 505 valid participants were investigated in this survey. Please state how to calculate the minimum sample size of participants in this survey. There was no calculation of the minimum sample size in this study since we used a simplified-snowball sampling technique. The invited participants were requested to share the invitation link with their WhatsApp contacts and other social media platforms. Our data collection period was predetermined by certain dates. We stopped the data collection once we reach the predetermined date and reached a sample size close to a previous study conducted in Saudi Arabia by Qattan et al. in 2021 where they received 673 completed responses. 3- Please also state the inclusion and exclusion criteria for these participants in this survey. Selection bias may exist if the participants with small sample size were recruited without reasonable inclusion and exclusion criteria. We have mentioned the inclusion criteria for this study in the Participants section “All HCPs currently working in healthcare facilities in KSA, regardless of the level of patient contact and their clinical role, were eligible to participate in the study.” No exclusion criteria were stated. 4- The study was conducted in April, 2021, but the pandemic situation and vaccination policies changed greatly during this year. This change always influenced people’s attitudes towards COVID-19 vaccination, and therefore the conclusion might be changed. Yes, agree. We aimed to investigate vaccine acceptance in Saudi Arabia wright after the approval of the COVID-19 vaccines. Prior studies were already conducted before this milestone which provided different prospective and conclusion. However, more studies need to be conducted after the changes in the pandemic situation and the policies which have influenced HCPs’ attitude toward the vaccines. Thank You."
}
]
}
] | 1
|
https://f1000research.com/articles/11-24
|
https://f1000research.com/articles/11-730/v1
|
01 Jul 22
|
{
"type": "Research Article",
"title": "Performance evaluation of the smartphone-based AI cough monitoring app - Hyfe Cough Tracker against solicited respiratory sounds",
"authors": [
"Mindaugas Galvosas",
"Juan C. Gabaldón-Figueira",
"Eric M. Keen",
"Virginia Orrillo",
"Isabel Blavia",
"Juliane Chaccour",
"Peter M. Small",
"Gerard Giménez",
"Simon Grandjean Lapierre",
"Carlos Chaccour",
"Juan C. Gabaldón-Figueira",
"Eric M. Keen",
"Virginia Orrillo",
"Isabel Blavia",
"Juliane Chaccour",
"Peter M. Small",
"Gerard Giménez",
"Simon Grandjean Lapierre",
"Carlos Chaccour"
],
"abstract": "Background: Emerging technologies to remotely monitor patients’ cough show promise for various clinical applications. Currently available cough detection systems all represent a trade-off between convenience and performance. The accuracy of such technologies is highly contingent on the clinical settings in which they are intended to be used. Moreover, establishing gold standards to measure this accuracy is challenging. Objectives: We present the first performance evaluation study of the Hyfe Cough Tracker app, a passive cough monitoring smartphone application. We evaluate performance for cough detection using continuous audio recordings and cough counting by trained individuals as the gold standard. We propose standard procedures to use multi-observer cough sound annotation from continuous audio recordings as the gold standard for evaluating automated cough detection devices. Methods: This study was embedded in a larger digital acoustic surveillance study (clinicaltrial.gov NCT04762693). Forty-nine participants were included and instructed to produce a diverse series of solicited sounds in 10-minute sessions. Simultaneously, continuous audio recording was performed using a MP3 recorder and two smartphones running Hyfe Cough Tracker app monitored and identified cough events. All continuous audio recordings were independently labeled by three medically-trained researchers. Results: Hyfe Cough Tracker app showed sensitivity of 91% and specificity of 98% with a very high correlation between the cough rate measured by Hyfe and that of human annotators (Pearson correlation of 0.968). A standardized approach to establish an acoustic gold standard for identifying cough sounds with multiple observers is presented. Conclusion: This is the first performance evaluation of a new smartphone-based cough monitoring system. Hyfe Cough Tracker can detect, record and count coughs from solicited cough-like explosive sounds in controlled acoustic environments with very high accuracy. Additional steps are required to validate the system in clinical and community settings.",
"keywords": [
"cough",
"artificial intelligence",
"cough monitoring",
"cough counting",
"hyfe",
"hyfe cough tracker"
],
"content": "Introduction\n\nCough is consistently ranked as one of the most common reasons for seeking medical attention.1,2 Acute cough frequently indicates new-onset and potentially contagious respiratory infection,3 while chronic cough can be an important cause of discomfort and disability affecting quality of life.4,5 In current medical practice, objective cough assessment can only occur during face to face interaction with the patient in the context of in- or outpatient visits, effectively making the symptom invisible to the health care provider outside the medical settings. To assess cough in ambulatory settings, health care providers rely on questionnaires and patient-reported outcomes, which are subject to patients’ self-perception, cough tolerance and recall bias.6,7 While different systems for automated cough detection have been developed in the last decade,8,9 they depend on wearable microphones, or spirometers,10 and their adoption is limited by cost, portability and privacy concerns given the need for continuous sound recording. Recent advances in artificial intelligence (AI) allow the monitoring of cough in a non-obtrusive way using smartphones or other wearable digital devices.6,11–14 Unobtrusive and privacy preserving passive cough monitors could revolutionize clinical practice and research in the field of respiratory diseases.\n\nLongitudinal monitoring of cough is particularly attractive for the evaluation of disease progression, or treatment response, as well as in clinical trials where trends in cough rates is an outcome of interest. Longitudinal cough monitoring also opens the door to population-wide capture of cough-signals as a surrogate marker of respiratory diseases epidemiology.14\n\nEvaluating cough and its patterns with limited recording periods (e.g., 24 h) can be misleading, in particular, if only small changes in cough frequency are captured over the limited 24 h recording and in cases that have high variance of cough counts.12 However, the nature and volume of data generated with protracted monitoring raises new challenges in technology validation. A central challenge in this work is establishing a gold standard against which automated devices’ performance can be evaluated.\n\nIn this study, we present the accuracy of Hyfe Cough Tracker app (henceforth referred to as Hyfe), a smartphone-based automated cough monitor that uses a convolutional neural network (CNN) to differentiate coughs from other explosive sounds.13 In this “in-vitro” performance evaluation, we use solicited sounds in a controlled acoustic environment as the first step towards clinical validation. We also propose a standard operating procedure (SOP) to appropriately label cough sounds from continuous audio recording.\n\n\nMethods\n\nHyfe is a software application for patient use, freely available for use on Android and iOS smartphones. It continuously monitors ambient sound and employs a two-step process to (1) detect explosive cough-like sounds, record a 0.5 second sound snippet which is sent to a cloud server where (2) a CNN assigns a cough prediction score (0 to 1) to each sound. For this study, a minimal score threshold of 0.85 was used for classifying a peak sound as a cough. Within this study, Hyfe (Version acl 1.24.4) was installed on smartphones (Motorola G30, Motorola, Inc, Chicago, IL, USA) running Android operating system version 11 (Google, LLC, Mountainview, CA, USA).\n\nTo assess the accuracy of Hyfe, continuous recording using a MP3 recorder (Sony ICD-PX470, Sony, Tokyo, Japan) and manual labeling of cough by medically trained listeners was used as the gold standard.\n\nThis performance evaluation study was conducted at the University of Navarra, Spain, between September to November 2021 and was nested in a larger cohort study (Clinicaltrials.org NCT04762693).12 Both the main and the nested study received approval by the Medical Research Ethics Committee of the chartered community of Navarra (PI_2020/107). Students and staff from the university of Navarra were invited to participate via email. All participants were aged 18 or older and signed informed consent. Baseline respiratory symptoms were not considered for inclusion. Participants were asked to produce a series of solicited sounds by reading a provided script, while being recorded with an MP3 recorder and monitored by Hyfe on two identical smartphones. The phones and recorder were placed on a table at approximately 50 cm from the participants, with microphones oriented towards them.\n\nA pre-generated computer script instructed participants to produce a series of 46 sounds, of which 18 were coughs, the rest consisted of solicited sneezes, throat clearings, spoken letters or words in the same 10 minutes. Some sounds were requested while reading out loud a literary text (in Spanish). Outside the reading, solicited sounds were separated from one another by at least five seconds of ambient silence. There were five different versions of the script, each one presenting a different sequence of instructions, and the version shown to each participant was randomly selected using a computer-generated sequence at the beginning of each session. Recording sessions occurred in a quiet room and lasted approximately 10 minutes. The time at which individual sounds were produced was automatically recorded in every session.\n\nThree medically trained researchers listened to individual recording sessions using Audacity (Audacity team (2021). Audacity(R): Free Audio Editor and Recorder [Computer application]. Version 3.1.3).15 Coughs were manually annotated using digital audio recordings and visual audio wave representation. It was previously shown that ambulatory cough counts from audio recordings have great agreement with patient video recordings, and that digital audio recordings could hence be considered as the gold standard in validating novel cough monitoring tools.16,17 Each sound was labeled using a 4-tier system defined in the SOP, which was developed for cough annotation in continuous audio recordings. In brief, sounds were classified as 0 = definitely not a cough, 1 = disputable cough (i.e., someone could consider the sound as a cough), 2 = definite cough but distant/muffled/obstructed, 3 = definite cough. Labels were made using Audacity and exported as text files for analysis. Labellers were blinded to the classification made by Hyfe and other listeners but knew a participant’s age and gender. Sounds labeled unanimously as a number 3 (“definite cough”) by all the human listeners were considered true coughs.\n\nWe estimated that at least 385 sounds would be required to observe a 90% sensitivity and 85% specificity, with a cough prevalence of 40% (39% of solicited sounds in the script were coughs), a precision of 5%, and a dropout rate of 10%.18,19\n\nLabels created by listeners (in Audacity) and Hyfe detected coughs were manually synchronized to within two seconds of each other. Synchronization was carried out for each phone and each session separately by identifying the time offset that would align Hyfe detections with the labels and adjusting the Hyfe detection timestamps accordingly. Offsets were estimated first using a subroutine in R that iteratively tests the offset-error produced by a wide variety of values, then manually reviewing and adjusting those automatic offsets as needed.\n\nFor the performance analysis, each recording session was divided into seconds. Seconds in which at least one explosive cough-like sound was labeled by a human listener (categories 1, 2, or 3) were pooled and defined as “cough-like-seconds”. Individual labels, which were annotated by the listeners, occurring within one second of each other were treated as a single label, and included as a single “cough-second”. Similarly, seconds in which only non-cough sounds occurred (category 0), were identified as “non-cough seconds”.\n\nHyfe detections on each phone were also pooled into cough-seconds using a similar method: all detected explosive sounds occurring within a one-second period were treated as a single detection; if multiple explosive sounds occurred within a cough-second, the highest cough prediction score among all explosive phases was used as the prediction score for the cough-second.\n\nAll recording seconds were considered as distinct analysis units. Seconds for which there was disagreement between the three human listeners were excluded from the final analysis. Similarly, 10-minute sessions in which less than 10 cough-seconds were unanimously labeled as such by human listeners were considered of inadequate quality and excluded. (Figure 1) True positives (TP) assessments were defined as those cough-seconds detected by Hyfe, and unanimously classified as category 3 by all human listeners. False positives (FP) were defined as seconds in which coughs did not actually occur, but were incorrectly detected by Hyfe. A pooled sensitivity and specificity value for each phone was obtained by aggregating the cough- and non-cough seconds labeled and detected by each phone throughout all sessions included in the analysis. The fraction of TP among cough-seconds was calculated (sensitivity), as well as the fraction of FP among all non-cough seconds, which was used to calculate the specificity, using the following formula: 1 - (FP/non-coughs) = Specificity.\n\nGiven inter-participant variation in ability to generate coughs and other sounds, the performance characteristics of Hyfe for each combination of phone and session were individually assessed and then used to calculate an average sensitivity and specificity in an exploratory sub-analysis.\n\nAll data processing and analysis was performed in R version 4.02 (R Core Team 2020) and the code used is available from GitHub and is archived with Zenodo.23\n\nThis analysis further informed the SOP used by Hyfe to annotate coughs and cough-like sounds (sneezes and throat clears), leading to the most recent version - the 6-tier SOP for cough labeling in continuous audio recordings, which now also instructs to label the complete duration of target sounds.\n\nBecause the utility of a cough monitor is not in noting individual coughs but rather in tracking cough rates, we further analyzed these results to look at the overall performance of Hyfe to the human annotated gold standard. We cut the entire observation period for all participants into one-minute segments, then compared the gold standard (the number of coughs during that minute per the human annotator) against the tool (the number of cough detections per Hyfe).\n\n\nResults\n\nIn total, 49 recording sessions with individual participants of approximately 10 minutes each were carried out. Two sessions did not have enough labels or detections to allow adequate timestamp synchronization and were excluded. Ten sessions did not have at least 10 sounds unanimously labeled as coughs and were also excluded, leaving 37 sessions, with 672 unanimously-labeled cough-seconds, and 1,007 non-cough seconds for the final performance evaluation (Figure 1).\n\nThe performance of Hyfe using both phones was similar in the pooled analysis, and is presented in Figure 2. Phone 1 yielded a sensitivity of 91.5% (95% CI: 89.2%-93.5%) and a specificity of 99.3% (95%CI: 98.6%-99.7%, Table 1), while phone 2 yielded a sensitivity of 92.55% (95% CI: 90.3%-94.4%) and a specificity of 98.7% (95% CI: 97.8%-99.3%, Table 1). The performance of both phones in individual sessions was also evaluated - the average sensitivity of the system in both phones and through the 37 sessions was 90.8% (SD = 11.6%). Specificity was high in both phones (range 93%-100% for phone 1, and 89%-100% for phone 2), with the mean specificity being 99.1% (SD = 1.9%).\n\nSensitivity and specificity of Hyfe Cough Tracker assessed using solicited coughs.\n\nIn three recording sessions, Hyfe had a sensitivity around 55%: sessions 2, 17 and 38 (Figure 3). These sessions met the quality criteria of more than 10 sounds unanimously classified as coughs. Potential explanations for this performance include the acoustic characteristics of the solicited coughs from these particular participants and the level of background noise. Coughs in session 2 and 17 had uncommon acoustic characteristics, such as biphasic decibel peaks, and different spectrographic features. Session 38 had significantly more background noise than the others. Sensitivity for the Session 20 was not evaluated because this was a patient with refractory chronic cough that generated hundreds of out-of-script, making timestamping impossible. We found the Pearson correlation of Hyfe to the gold standard to be 0.968 (Figure 4).\n\nPoints are intentionally jittered by up to 0.3 values so as to provide more visibility on high density areas. The diagonal line (slope = 1, intercept = 0) represents where each point would fall in the hypothetical case of a perfect monitor.\n\nThe major limitation was that this study of performance evaluation was done in a laboratory “in-vitro” environment, not community or a clinical setting. During this study, phone microphones were oriented towards and phones were placed at 50 cm from the participant, however, these settings would vary in real life clinical scenarios with coughing patients which could have longer distances and obstructing objects in between.\n\n\nDiscussion\n\nThe ability to unobtrusively monitor cough has the potential to greatly improve patient care, public health and drug development. The uptake of cough monitoring technologies will be determined by their usability, their clinical performance and the increasing evidence that they can provide actionable information for clinical decision making. Hyfe has advantages over existing cough monitors as it can run in the background of a smartphone and passively monitor coughs for longer than 24h of recordings. Rather than using special equipment and limited time windows for continuous cough monitoring, the use of this novel system improves the efficiency of monitoring and reduces the monitoring costs.\n\nThere are many ways to assess cough detectors accuracy. The intrinsic, or analytical, performance of AI-based cough monitors directly results from their algorithm’s sensitivity and specificity for labeling recorded sounds. However, those same monitoring technologies may perform differently when deployed in various clinical settings where the acquisition of such sounds may represent a challenge in the first place, leading to either unrecorded coughs or recorded and misclassified non-cough sounds. We previously reported on the analytical performance of Hyfe.13 Here we report on its pre-clinical performance using scripted solicited coughs in a controlled environment.\n\nDefining a gold standard for the performance evaluation of passive cough monitors represents a challenge which we addressed with standardized procedures ensuring human listener inter-observer consensus. This process and our results highlight three important issues related to evaluating cough monitors. Firstly, it is critical to have a precise method of aligning different data streams. Our failure to have this resulted in the exclusion of two sessions. Going forward, we propose the use of a distinct auditory signal, or “coda”, that can be played at the beginning of each session so both the continuous audio recorder and the smartphone running the app will have a series of characteristic peak sounds that can be used for timestamping and alignment. The coda currently used for Hyfe-related studies is available on YouTube. Secondly, although solicited coughs have been used to validate cough-counting devices in the past20 and previous literature reports that spontaneous and solicited coughs have similar acoustic characteristics,21 we found significant differences in the sound of solicited coughs from different study participants. When asked to voluntarily cough, ten of the 49 research subjects generated sounds that were not unanimously recognized as coughs by human annotators. This observation raises questions about the utility of solicited coughs for diagnostic purposes. Finally, there are interpersonal differences in how sounds are classified by annotators. Because of this we had to exclude 88 sounds from the analysis. This has prompted additional efforts to minimize interobserver variability by developing clear operating procedures and training programs for cough annotators. We propose that protocols such as these be shared, and that consensus be sought so as to facilitate comparison of monitoring technology.\n\nAfter this study, we believe that labeling cough duration rather than just its beginning has more value in further training Hyfe’s AI model, also in analyzing agreement between human listeners, and agreement with Hyfe (Figure 5). Therefore, the updated 6-tier version SOP was proposed, which is currently being used for cough labeling in continuous audio recordings.\n\nPurple arrows indicate labels placed in this study, according to the 4-tier SOP. The gray arrow indicates how this audio segment would be annotated using the updated 6-tier SOP.\n\nEnvironmental sounds may interfere with capturing coughs in real life, as seen in the sensitivity of session 38 (Figure 3), however, continuous improvements of the AI peak detection models and the cough classifiers, may address this potential issue in the near future. Even though we have not observed any significant differences in the quality of smartphones used in this trial, there might be cases when the version of smartphone operating system plays some role in smartphone’s general usability and experience for the user.\n\nOvercoming these challenges, we were able to evaluate Hyfe’s accuracy using 1679 solicited sounds generated by a total of 37 subjects. Hyfe’s overall sensitivity and specificity were respectively 91% and 98% and did not differ significantly between two phones. Importantly, we feel the more relevant parameter of performance to be the Pearson correlation of the cough rates as measured by the device and the gold standard (human annotation), which was 0.968. We propose that going forward, analysis of cough monitors should use correlation in rates (gold standard vs monitor detections) as the primary metric of their performance. Though we used a minute (due to the highly condensed nature of the study), in most continuous monitoring use cases, coughs per hour is likely to be the most clear and useful period of observation.\n\nOf note, the performance was lower in four subjects, presumably due to the intrinsic acoustic characteristics of solicited coughs and the level of background noise.\n\nFurther validation studies will need to be conducted in the specific clinical settings in which Hyfe is intended to be used. To better contextualize and design such trials, target product performance specifications will be required and are expected to differ significantly between use cases. Lessons can be learned from other types of monitors such as fitness trackers, whose results can differ from each other by up to 30%.22 Whereas, regulated medical devices used in clinical practice will require greater precision. The presented data here is encouraging, suggesting that Hyfe’s performance is adequate to be used in most clinical and research contexts. Taken together, these results show that AI-enabled systems might provide a valuable tool for objectively, and unobtrusively monitoring cough.\n\n\nData availability\n\nGithub: ericmkeen/navarra: Hyfe performance evaluation, https://doi.org/10.5281/zenodo.6710562.23\n\nThis project contains the following underlying data:\n\n• 01.results. R (takes pre-formatted datasets and carries out performance evaluation, plots results)\n\n• detections.csv (Hyfe detections data)\n\n• hyfe_performance.R (analysis of Hyfe performance)\n\n• labels.csv (human labeled data)\n\n• offsets_emk.csv (automatic and manual offsets made to the data)\n\n\nSoftware\n\nSoftware available from:\n\nR version 2.04 (RStudio Team, 2020), available from https://cran.r-project.org/bin/windows/base/old/4.0.2/\n\nHyfe, version acl 1.24.4, available from https://www.hyfe.ai/\n\nAudacity | Free, open source, cross-platform audio software for multi-track recording and editing, available from https://www.audacityteam.org/",
"appendix": "References\n\nCornford CS: Why patients consult when they cough: a comparison of consulting and non-consulting patients. Br. J. Gen. Pract. [Internet] Royal College of General Practitioners;1998 [cited 2022 Jan 19]; 48: 1751–1754. PubMed Abstract | Free Full Text\n\nMotulsky A, Weir DL, Liang MQ, et al.: Patient-initiated consultations in community pharmacies. Res. Soc. Adm. Pharm. 2021 [cited 2022 Jan 19]; 17: 428–440. Elsevier Inc. PubMed Abstract\n\nWorld Health Organization (WHO): WHO operational handbook on tuberculosis. Module 2: screening - systematic screening for tuberculosis disease. Modul. 3 Diagnosis Rapid diagnotics Tuberc. diagnosis.2021 [cited 2022 Jan 19].Reference Source\n\nTashkin DP, Volkmann ER, Tseng CH, et al.: Improved Cough and Cough-Specific Quality of Life in Patients Treated for Scleroderma-Related Interstitial Lung Disease: Results of Scleroderma Lung Study II. Chest. 2017; 151: 813–820. Elsevier Inc. PubMed Abstract | Publisher Full Text\n\nMcCallion P, De Soyza A: Cough and bronchiectasis. Pulm. Pharmacol. Ther. Pulm Pharmacol Ther. 2017 [cited 2022 Jan 19]; 47: 77–83. Publisher Full Text Reference Source\n\nKvapilova L, Boza V, Dubec P, et al.: Continuous Sound Collection Using Smartphones and Machine Learning to Measure Cough. Digit. Biomarkers. 2019; 3: 166–175. S. Karger AG. PubMed Abstract | Publisher Full Text\n\nIrwin RS: Assessing cough severity and efficacy of therapy in clinical research: ACCP evidence-based clinical practice guidelines. Chest. 2006 [cited 2022 Jan 19]; 129: 232S–237S. PubMed Abstract | Publisher Full Text\n\nBirring SS, Fleming T, Matos S, et al.: The Leicester Cough Monitor: Preliminary validation of an automated cough detection system in chronic cough. Eur. Respir. J. 2008 [cited 2021 Dec 22]; 31: 1013–1018. Publisher Full Text Reference Source\n\nCrooks MG, Hayman Y, Innes A, et al.: Objective Measurement of Cough Frequency During COPD Exacerbation Convalescence. Lung. 2016 [cited 2021 Dec 22]; 194: 117–120. PubMed Abstract | Publisher Full Text\n\nSoliński M, Łepek M, Kołtowski Ł: Automatic cough detection based on airflow signals for portable spirometry system. Informatics Med. Unlocked. 2020; 18: 100313. Elsevier. Publisher Full Text\n\nPorter P, Abeyratne U, Swarnkar V, et al.: A prospective multicentre study testing the diagnostic accuracy of an automated cough sound centred analytic system for the identification of common respiratory disorders in children. Respir. Res. 2019 [cited 2022 Jan 19]; 20: 81. PubMed Abstract | Publisher Full Text\n\nGabaldón-Figueira JC, Keen E, Rudd M, et al.: Longitudinal passive cough monitoring and its implications for detecting changes in clinical status. ERJ Open Res. 2022 May 16; 8(2): 00001–02022. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGabaldon-Figueira JC, Brew J, Doré DH, et al.: Digital acoustic surveillance for early detection of respiratory disease outbreaks in Spain: A protocol for an observational study. BMJ Open. 2021 [cited 2022 Jan 19]; 11: 51278. PubMed Abstract | Publisher Full Text\n\nGabaldón-Figueira JC, Keen E, Giménez G, et al.: Acoustic surveillance of cough for detecting respiratory disease using artificial intelligence. ERJ Open Res. 2022; 8: 00053–02022. in press. PubMed Abstract | Publisher Full Text\n\nAudacity®|Free, open source, cross-platform audio software for multi-track recording and editing: [cited 2022 Jan 24].Reference Source\n\nSmith JA, Earis JE, Woodcock AA: Establishing a gold standard for manual cough counting: video versus digital audio recordings. Cough. 2006 Aug 3; 2: 6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLake C, Briffa P, Munoz P, et al.: Documentation of cough provoked during a mannitol challenge using acoustic respiratory monitoring compared to video surveillance monitoring [Conference Abstract]. Respirology. 2012; 17: 1.\n\nHajian-Tilaki K: Sample size estimation in diagnostic test studies of biomedical informatics. J. Biomed. Inform. 2014; 48: 193–204. Academic Press. PubMed Abstract | Publisher Full Text\n\nArfin WN: wnarifin.github.io > Sample size calculator. Sample size Calc. 2021 [cited 2022 Jan 19].Reference Source\n\nVizel E, Yigla M, Goryachev Y, et al.: Validation of an ambulatory cough detection and counting application using voluntary cough under different conditions. Cough Bio. Med. Central. 2010 [cited 2022 Jan 19]; 6: 1–8. Publisher Full Text\n\nKorpáš J, Sadloňová J, Vrabec M: Analysis of the cough sound: An overview. Pulm. Pharmacol. Pulm Pharmacol. 1996 [cited 2022 Jan 19]; 9: 261–268. Publisher Full Text Reference Source\n\nJagim AR, Koch-Gallup N, Camic CL, et al.: The accuracy of fitness watches for the measurement of heart rate and energy expenditure during moderate intensity exercise. J. Sports Med. Phys. Fitness. 2021 [cited 2022 Jan 19]; 61: 205–211. Publisher Full Text Reference Source\n\nKeen E: ericmkeen/navarra: Hyfe performance evaluation (Hyfe). Zenodo. 2022. Publisher Full Text"
}
|
[
{
"id": "146174",
"date": "16 Aug 2022",
"name": "Vasileios Papapanagiotou",
"expertise": [
"Reviewer Expertise digital signal processing",
"machine learning",
"wearables",
"eating behaviour"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper presents an evaluation study for Hyfe. Hyfe is a smartphone app that captures audio and automatically detects coughs using machine learning methods. In this work, authors captured audio using 3 sources (an mp3 recorder for ground truth and two phones running Hyfe). Then, 3 annotators created ground truth annotations, against which Hyfe detections were compared.\nThe dataset includes 10-minute recordings were multiple sounds were performed in randomized sequences. The recordings were performed in complete silence. Evaluation results show high effectiveness, in particular 91% sensitivity and 98% specificity on 1,679 1-second windows.\nQuestions:\nIn section “Methods”, subsection “Automated cough detection system”: it is mentioned that 0.5 second sound snippets are extracted and analyzed. Why was this not followed for the study and 1-second windows were used instead?\n\nIn section “Methods”, subsection “study design” (last paragraph): how exactly were the coughs annotated? Is it with start & stop timestamp per cough? If so, please state clearly. Figure 5 is helpful and perhaps should be presented much earlier in the manuscript. Also, did each of the 3 medically trained researchers perform this process? Also, what is a “sound” in this paragraph?\n\nInter-annotator agreement would be very interesting to know.\n\nIn section “Methods”, subsection “Data processing and analysis”: what does the “within two seconds of each other” mean? Was the maximum allowed offset between the two recordings limited by 2 seconds? If so, why? Please clarify.\n\nIn section “Methods”, subsection “Data processing and analysis”: authors mention “if multiple explosive sounds occurred within a cough-second”. Given that Hyfe uses 0.5 second snippets and authors used 1-second windows, exactly 2 Hyfe predictions should always “fall” within one 1-second window. If so, why do the authors phrase this this way?\n\nSection “Methods”, subsection “Data processing and analysis”: was the 6-tier SOP used after all? If not, why is it mentioned? (mentioning it while it's not being used in the work can be confusing to the reader).\n\nSection “Methods”, subsection “Data processing and analysis” (last paragraph): authors mention that cough rates are of high interest in such applications. However, the data collection protocol forces some strict limitations, e.g., a 5-second silence between each activity.\n\nIn section “Methods”, subsection “Sample size”: authors mention that “at least 385 sounds…” What is a sound in this context? Is it a 1-second window?\n\nIn section “Results”, authors mention that in total 37 sessions were used, each being a 10-minute recording. This corresponds to 370 minutes, i.e., 22,200 seconds. However, authors also mention that the 37 sessions resulted in 672 + 1,007 = 1,679 seconds were used in the evaluation. It is not clear how the discrepancy from 22,200 to 1,679 seconds happens.\n\nFigure 2: what is the unit and scale for the x-axis (for both subfigures)?\n\nFigure 3: image quality should be improved.\n\nFigure 4: Authors mention that 5 seconds of silence were required (at least) between each activity. Given at least 1 second for cough, this yields a pattern of 6 seconds, and this yields a maximum of 10 coughs per minute. If so, how are values larger than 10 obtained in this plot?\n\nDiscussion: continuous 24-hour audio recording can have a significant effect on battery consumption, this is an important limitation of the method. Also, the audio caused by the user when holding and using the phone (while it is recording audio) is also critical in evaluation of the Hyfe effectiveness.\n\nDiscussion: \"we believe that labeling cough duration rather than just its beginning has more value in further training Hyfe’s AI model\". Since there is no description of the Hyfe's algorithm in the paper or any relevant experiment, this argument could be debated.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "9611",
"date": "09 Jun 2023",
"name": "Mindaugas Galvosas",
"role": "Author Response",
"response": "1.1 Comment: In section “Methods”, subsection “Automated cough detection system”: it is mentioned that 0.5 second sound snippets are extracted and analyzed. Why was this not followed for the study and 1-second windows were used instead? Answer: Thank you for taking the time to review this paper and provide comments. Our algorithm at the time of this study was trained on a database of more than 200M of 0.5s sound snippets that are cough and cough-like sounds, collected in real life environments. Therefore, this performance evaluation also evaluated 0.5s sound snippets. Continuing our work, we are exploring the capture and analysis of 1s sound snippets, however, it was not the scope of the work described in this manuscript. Actions: None taken. 1.2 Comment: In section “Methods”, subsection “study design” (last paragraph): how exactly were the coughs annotated? Is it with start & stop timestamp per cough? If so, please state clearly. Figure 5 is helpful and perhaps should be presented much earlier in the manuscript. Also, did each of the 3 medically trained researchers perform this process? Also, what is a “sound” in this paragraph? Answer: In the performance evaluation study described in this manuscript, coughs were annotated following the 4-tier SOP – which instructed to indicate just the beginning of the cough sound. Further work led to developing a 6-tier and most recently – a multi-tier SOP which instructs cough and other respiratory sound annotation from the beginning to the end, taking both audio and visual (spectrogram) inputs to determine those marks. For this study – each of the 3 medically trained researchers annotated every cough and cough-like sound following the 4-tier SOP. Actions: Added a linear analysis (Figure 6) plot and a percentage error Bland-Altman plot (Figure 7) to the section “Results”. 1.3 Comment: Inter-annotator agreement would be very interesting to know. Answer: Thank you. We agree this is an interesting point to look at. There is a separate full paper in preparation looking specifically at this with a whole different dataset. Actions: None taken. 1.4 Comment: In section “Methods”, subsection “Data processing and analysis”: what does the “within two seconds of each other” mean? Was the maximum allowed offset between the two recordings limited by 2 seconds? If so, why? Please clarify. Answer: The manual offset was made to align the data annotation by different labelers (in an mp3 audio recording) and Hyfe timestamps on the smartphones. Due to the automated script setting, which had five second gaps between every solicited sound, two second differences were not outside the five second gap. Actions: Added “(as this was within the silent time of five seconds between the solicited sounds in the automated script)” in the “Data processing and analysis” subsection to clarify the manual offset of the two-second time frame. 1.5 Comment: In section “Methods”, subsection “Data processing and analysis”: authors mention “if multiple explosive sounds occurred within a cough-second”. Given that Hyfe uses 0.5 second snippets and authors used 1-second windows, exactly 2 Hyfe predictions should always “fall” within one 1-second window. If so, why do the authors phrase this this way Answer: 2 Hyfe predictions will always be found within 1 second window but 'multiple explosive sounds' refers to a prediction of a 0.5sec snippet that contains at least 1 cough, which doesn't happen every time. Therefore, the phrasing is appropriate. Actions: None taken. 1.6 Comment: Section “Methods”, subsection “Data processing and analysis”: was the 6-tier SOP used after all? If not, why is it mentioned? (mentioning it while it's not being used in the work can be confusing to the reader). Answer: The text states “This analysis further informed the SOP… leading to the most recent version – the 6-tier SOP…” and we believe there should be no confusion here. Actions: None taken. 1.7 Comment: Section “Methods”, subsection “Data processing and analysis” (last paragraph): authors mention that cough rates are of high interest in such applications. However, the data collection protocol forces some strict limitations, e.g., a 5-second silence between each activity. Answer: While rates indeed remain interesting, calculating them was outside the scope of this performance evaluation, nor is it possible with the methodology that was followed. The main purpose of this work was to evaluate the performance of the system capturing and recording solicited coughs and cough-like sounds in controlled environments. Actions: None taken. 1.8 Comment: In section “Methods”, subsection “Sample size”: authors mention that “at least 385 sounds…” What is a sound in this context? Is it a 1-second window? Answer: Sound refers to any cough or other sound produced by the study participants according to the script provided. Actions: None taken. 1.9 Comment: In section “Results”, authors mention that in total 37 sessions were used, each being a 10-minute recording. This corresponds to 370 minutes, i.e., 22,200 seconds. However, authors also mention that the 37 sessions resulted in 672 + 1,007 = 1,679 seconds were used in the evaluation. It is not clear how the discrepancy from 22,200 to 1,679 seconds happens. Answer: 1,679 was the number of solicited sounds that were evaluated, not the total number of seconds of recording for all participants. Further explanation is provided in the “Study design” section. Actions: Improved “Study design” section: “Participants were asked to produce a series of solicited sounds by reading a provided script, while being recorded with an MP3 recorder and monitored by Hyfe on two identical smartphones. The phones and recorder were placed on a table at approximately 50 cm from the participants, with microphones oriented towards them. A pre-generated computer script instructed participants to produce a series of 46 sounds, of which 18 were coughs, the rest consisted of solicited sneezes, throat clearings, spoken letters or words in the same 10 minutes. Participants were instructed to cough once every time they were prompted by the script to do so. In total for each participant, the script included instructions to cough 20 (18 as individual coughs and 2 in the literary text) times, sneeze 10 times, clear throat 5 times and produce 15 sounds (explosive words, for example, “paella” and numbers as “93”). “ 1.10 Comment: Figure 2: what is the unit and scale for the x-axis (for both subfigures)? Answer: The name of the x-axis in this version is called “frequency of observation”, however, after another review with our data science team, we have agreed to change this Figure 2 to a new visual - newly submitted histograms in Figure 2, which convey the same information on specificity and sensitivity for both phones more clearly and, in our opinion, more efficiently. Actions: “Figure 2” updated to a new visual. The “Figure 2” is also now accompanied by the “Table 2: Summary statistics on sensitivity and specificity for both phones used”. 1.11 Comment: Figure 3: image quality should be improved. Answer: Thank you for noting, the image will be replaced with a better quality file. Actions: New image generated and uploaded (Figure 3). 1.12 Comment: Figure 4: Authors mention that 5 seconds of silence were required (at least) between each activity. Given at least 1 second for cough, this yields a pattern of 6 seconds, and this yields a maximum of 10 coughs per minute. If so, how are values larger than 10 obtained in this plot? Answer: Some participants were instructed to cough once, however, they produced two coughs. These coughs were annotated by the labelers and also picked up by Hyfe, when they happened with at least 0.5s of separation. Actions: None taken. 1.13 Comment: Discussion: continuous 24-hour audio recording can have a significant effect on battery consumption, this is an important limitation of the method. Also, the audio caused by the user when holding and using the phone (while it is recording audio) is also critical in evaluation of the Hyfe effectiveness. Answer: This is a valid point; however, this performance evaluation was done in laboratory settings and was not meant to evaluate battery usage and performance. Additionally, directionality of the audio source was not evaluated by this study and is being evaluated with the continued studies. Actions: None taken. 1.14 Comment: Discussion: \"we believe that labeling cough duration rather than just its beginning has more value in further training Hyfe’s AI model\". Since there is no description of the Hyfe's algorithm in the paper or any relevant experiment, this argument could be debated. Answer: For model training purposes we have seen that labeling the full duration of the sound is a better way of annotating data, ensuring that the algorithm is being trained on the full duration of cough sound. As convolutional neural networks are employed by Hyfe - they learn by example. As long as the training data is relatively unbiased and representative, a neural net can identify a “feature” (such as the acoustic signature of a cough) in a myriad of samples, even if those samples do not resemble each other. Actions: Added to the “Discussion”: “As convolutional neural networks are employed by Hyfe - they learn by example. As long as the training data is relatively unbiased and representative, a neural net can identify a “feature” (such as the acoustic signature of a cough) in a myriad of samples, even if those samples do not resemble each other.” 1.15 Comment: Are all the source data underlying the results available to ensure full reproducibility? – replied “No”. Answer: All source data is updated and made available to reproduce all the analysis presented in the manuscript. Actions: None taken. 1.16 Comment: Are the conclusions drawn adequately supported by the results? – replied “Partly” Answer: We believe that the proposed changes will strengthen the conclusions drawn from the results, thank you for your input and feedback. Actions: None taken."
}
]
},
{
"id": "148456",
"date": "08 Sep 2022",
"name": "Terence E. Taylor",
"expertise": [
"Reviewer Expertise audio signal processing",
"cough sound analysis",
"artificial intelligence",
"telehealth",
"respiratory diseases"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nEditorial note [4th May 2023]: A potential conflict of interest has come to light and so we have added this to the report to ensure full transparency.\nThe aim of the Hyfe app is to provide a portable and high performing system for measuring cough rate. The authors describe an evaluation of the Hyfe app using 10-minute audio recordings consisting of cough and speech obtained from participants in a controlled environment. Audio data were collected using two identical smartphones and an additional MP3 recorder placed 50cm to participants. While I find this area of research quite interesting, I have several major concerns with this study from the data collection to how the evaluation was measured. The type and amount of data does not reflect how the app would be used in real-life settings. In my opinion, this study does not provide sufficient evidence that the Hyfe system can perform adequately in real-life clinical research, particularly over longer periods of time (24 hours or above). Furthermore, I believe this study lacks novelty compared to other audio-based cough detection studies and represents more of a pilot study than an evaluation of the system. Please see further comments below.\nAbstract:\nIn Objectives, please change the relevant sentence to “We evaluate performance of cough detection using continuous audio recordings obtained within a controlled environment and cough counting by trained individuals as the gold standard.”\n\nIntroduction:\nMAJOR: In ref 13, it is noted that participants in this other study complained of increased battery consumption. And so, the evaluation there was constrained to 6-hour windows. Has this app been ever evaluated over at least 24-hour periods? According to the authors, one of the advantages of Hyfe is the ability to passively record for extended periods of time (i.e. greater than 24 hours). Has there been analysis done on the battery consumption effects over longer periods? In my opinion, this study should have monitored cough over at least 24 hours to show a more realistic evaluation of the system.\n\nMINOR: Privacy concerns are mentioned in the introduction. How does Hyfe preserve privacy exactly? If this information has already been published elsewhere, please cite the relevant literature and give a brief explanation on how privacy preservation is achieved.\n\nMethods:\nMINOR: What versions of iOS/Android has the Hyfe app been tested on?\n\nMINOR: Why were baseline respiratory symptoms not considered for participants? Cough sounds can vary in terms of acoustic properties across different respiratory disease types. The data reported here have no mention of being evaluated on any respiratory disease cough sounds.\n\nMINOR: Regarding the CNN model, was it trained on sufficient data across different smartphones, microphone locations, disease types? Please comment on this.\n\nMAJOR: Why place the smartphone 50cm away from the participant? What is the approximate distance between a user’s mouth and a smartphone mic when they are interacting with their smartphone in front of them with smartphone-in-hand? Was this thought of to replicate real-life use? I would have thought that in many real-life cases also, a lot of the audio that Hyfe would capture would be when the smartphone is located inside the user’s pocket or bag. Why not place one smartphone in the participant’s pocket and have one in their hand to try replicate real-life use? Why constrain the recording protocol so heavily? Also, why use two of the same identical smartphones? It would have been useful to compare different smartphones with different builds, battery consumption properties, microphone designs etc. Was the gain/dynamic range of the microphones taken into account? All these points significantly limit the interpretability of this evaluation in relation to how Hyfe could perform in clinical settings in my opinion. The data collection is not representative of real-life use.\n\nMINOR: What is the sampling rate and bit depth of the audio recordings? Please report this.\n\nMINOR: It would be useful to have an English language version of the pre-generated computer script also available to the reader.\n\nMINOR: How were participants instructed to cough exactly? Was it for a certain amount of time? For a certain number of explosive cough sounds? Please explain briefly.\n\nMAJOR: Recording sessions occurred in a quiet room as reported. What does “quiet” mean here? Were there sound intensity levels recorded? Was the room acoustically insulated? What were the signal-to-noise ratio (SNR) values of the different sessions? Please provide this information to help the reader understand the environment the recordings were obtained in.\n\nMAJOR: What were the kappa agreement scores to show inter-rater agreement for the manual labeling? Why do you need a 4-tier labeling system when users were prompted to perform specific sounds? Do you not already know when a user coughed as they were prompted to do so at specific points within the 10min session? I understand the prompts were randomized, but was this not recorded internally for post-analysis? Therefore, why is there a need for labels 1 and 2 if you have a log of what the participants were doing during each part of the recordings?\n\nMINOR: How many sounds were labeled 0, 1, 2 and 3? Please report this information. How many explosive cough sounds on average were there in each cough audio segment? Were participants prompted to perform a certain number of explosive cough sounds?\n\nMINOR: Why does the Hyfe system classify every 0.5 seconds, but labeling was done every 1 second?\n\nMAJOR: Multiple coughs may occur within a 1 second window. Why label a full 1 second window as a single true positive cough even if there could be multiple single manually labeled coughs within the 1 second? In my opinion, cough rate estimation would be more accurate if all coughs were considered rather than labeling a 1 second window of coughing as a single cough event (when estimating app performance). Is there reasoning for this in the literature? If so, please add relevant citations. If I understand correctly, it means technically you could miss all but one cough in a given 1sec window and still have very high sensitivity/specificity based on your labeling system? If this is the case, this is a major limitation. How coughs are grouped together in peals or bouts can have a significant impact on cough rate estimation. I think this discrepancy would become more evident had the system been evaluated on a cough-by-cough basis and over longer periods on patients with respiratory disease as they may tend to cough in groups in quick succession (within 1 second in many cases).\n\nMINOR: Was there any overlap in the labeling of 1 second windows i.e. 50% overlap between consecutive windows for labeling?\n\nMAJOR: Sample Size: “385 sounds” – are you referring to cough sounds here, or a mix of both cough and non-cough? How did you determine the balance of data between cough and non-cough (speech, throat clear, noise etc.)? It seems a balance of approximately 1:2 (coughs to non-coughs) was employed. In real-life settings, over the course of a 24-hour period for example, the number of non-cough segments will far outweigh the number of cough segments if Hyfe was to continuously record audio. This does not seem to be considered here. If the data were to be more realistically balanced in this way, it may have a significant effect on the positive predictive value (PPV) of the algorithm (PPV needs to be reported). One of the biggest challenges of longer term (24 hours or more) audio-based cough monitoring is the PPV performance measure.\n\nMAJOR: One of the advantages of Hyfe, reported by the authors, is that it can monitor cough rate over longer periods (>24 hours). But this study looked at 10-minute recording windows. Even taking into account that no respiratory symptoms were not noted from participants (which I think is a major limitation), I think the balance of data here are not truly representative of real-life settings especially if the authors suggest Hyfe can monitor cough rate over 24-hour periods. This is a major limitation to this evaluation study. This system needs to be evaluated over at least 24-hour periods before it can be suggested that it may perform strongly for longer term analysis in clinical settings.\n\nMINOR: Synchronization of labels - Please provide a clearer explanation for this. Why synchronize to within 2 seconds? This seems like a long duration considering multiple explosive cough sounds may occur within 2 seconds.\n\nMINOR: Data were discarded if they had less than 10 cough seconds of agreement. How often did that occur? How much data were discarded overall? – from Figure 1 it seems 20-25% of data were discarded due to inadequate quality. How would this reflect real-life evaluation then? The app would be unsure of about 20% of coughs at best? That seems to be a potential large margin of error. Please comment on this.\n\nMAJOR: Was the 4-tier or 6-tier labeling SOP used? This is quite confusing for the reader. If 6-tier is superior in the opinion of the authors, why not revert and apply it to all data and re-run the analysis? I understand it may mean re-training the CNN but if it will be beneficial as mentioned by the others, then it should be reported here.\n\nMINOR: “Because the utility of a cough monitor is not in noting individual coughs but rather in tracking cough rates…”. Surely identifying singular coughs should be the goal to obtain the most accurate estimation of cough rate? If not, you could hypothetically be detecting false positives and false negatives, but still hit the correct cough rate. This could affect the analysis of how cough rate changes over time throughout a 24-hour period, for example, if it were of interest. Please provide a stronger argument for this.\n\nResults:\n\nMAJOR: Please report SNR for audio sessions in comparison to cough. It may help the reader understand the poor performance of sessions 2, 17 and 38. Real-life recordings will be full of different types and levels of noise. If it is only possible to evaluate on audio within controlled environments, then the authors should augment the data by adding various different types and levels of noise to the data to replicate real-life use.\n\nMINOR: What were the uncommon acoustic characteristics associated with Sessions 2 and 17? An additional figure with time domain plot as well as a spectrogram plot of coughs from these participants would be useful here for the reader to understand why the system did not perform as well for these participants.\n\nMINOR: Figure 3 image quality should be improved.\n\nMINOR: “Sensitivity for the Session 20 was not evaluated because this was a patient with refractory chronic cough that generated hundreds of out-of-script, making timestamping impossible.” – Please elaborate further. Were there too many coughs? One would assume the data from this participant would have been very interesting to analyze and run through the Hyfe system?\n\nMINOR: Limitations: I agree with the limitations mentioned. So why evaluate the Hyfe system in a way it will rarely if not never be used in? Please comment on this.\n\nMAJOR: Please give details of the effect the Hyfe app has on battery life. One would think a continuous audio recording will significantly drain a smartphone battery. It seems to be mentioned in a previous study (ref 13). Were there experiments done on this? If not, this analysis needs to be performed and reported in this evaluation study.\n\nMAJOR: A Bland Altman plot analyzing cough rate between Hyfe and manual labels is required here. Correlation analysis is not enough to convince the reader that the Hyfe system can accurately estimate cough rate (unless you were to use the linear regression equation to map Hyfe estimation to manual estimation which I don’t think is the goal here). While strong correlation is interesting to observe, simply showing the equal line on Figure 4 does not highlight if there is any bias in cough rate estimation. Please add the linear regression line and equation in Figure 4. Please also add an additional panel for a Bland Altman plot comparing the mean cough rate between manual and Hyfe to the difference in cough rate between manual and Hyfe.\n\nDiscussion:\nMAJOR: Where does the score threshold of 0.85 come from? Can you report the distribution of CNN output probability scores for all label categories as supplementary material? A histogram, for example, of probability scores for each label category would be interesting to see and could enhance the reader’s understanding of the challenges in labeling category 1 and 2 sounds.\n\nMINOR: The discussion on inter-participant variability and the debate on using solicitated voluntary coughs as a diagnostic tool is quite interesting. Does this suggest these are most likely voluntary throat clears rather than involuntary coughs? As a result, why then prompt the user to record a voluntary cough when first using the app?\n\nMINOR: What difference will the 6-tier SOP make for training the CNN model? I assume fixed 0.5sec segments are employed for training the model so how will the duration markers be more beneficial than just the onset markers used in the 4-tier SOP labeling system?\n\nMAJOR: The Pearson correlation is interesting, but I disagree that it should be the primary metric of performance. I think the authors should perform a linear regression analysis also to analyze the slope of the regression line. Only using Pearson correlation does not disclose information regarding how many coughs are missed in detection. For example, you could theoretically have a Pearson coefficient of 1 but you are missing 1 cough in every 2 or 3 coughs consistently in your detection model (this would be reflected in the slope of the regression analysis). The Pearson correlation metric is one of a group of metrics that should be considered in my opinion. I would like to see linear regression analysis, absolute percentage error according to the total number of coughs per participant and a Bland Altman analysis.\n\nMAJOR: “…Hyfe’s performance is adequate to be used in most clinical and research contexts.” This study does not suggest this in my opinion if the data were collected in controlled environments, was not evaluated on real respiratory patients and the smartphones were not evaluated in multiple different positions/locations.\n\nOther Comments:\nMAJOR: While I understand the data were obtained in controlled environments, in my opinion, more data are required to obtain a more realistic measure of performance in order to suggest Hyfe could be used in clinical settings. This includes more data using different smartphone locations (in user’s pocket, bag etc.), more realistic data with different types and levels of noise (including muffled coughs due to hand/mask covering) and I think it should be evaluated on a cough-by-cough basis rather 1 second windows as a form of cough rate.\n\nMINOR: How does the app know if it is the user who coughed and not a person beside them in a crowded area? Has this been taken into account within the CNN training data? Please comment on this.\n\nMINOR: Does the Hyfe app still record audio when the user is on a phone call or sending voice messages?\n\nMINOR: Does the app work without internet connectivity?\n\nMINOR: SOP4 Supplementary Document: Page 4, Section 3, bullet 3 – should that read as “…at the end of the expulsive phase..”?\n\nMINOR: SOP4 Supplementary Document: I think reporting a cough as having one sound or two sounds is a little confusing. Consider moving Fig. 5 and the paragraph above it to before Fig. 3. Start with showing the sound, explaining the three phases of the cough sound event and then describe in more detail the physiology behind it. Fig. 3 panel B needs to highlight that the voiced phase is missing. It is a little confusing to just say A has a “double” sound and B has a “single sound”.\n\nMAJOR: SOP4 Supplementary Document: Page 8, Table 1 – according to the 4-tier process, the label 2 may be due to the phone located in the user’s pocket which, I assume, will be a vastly common occurrence if this app were to be used in cough clinical applications. In this study label 2 coughs weren’t considered in the app evaluation. Why not? I think it is essential particularly for an app-based cough monitoring system to be evaluated on recordings when the phone is in the user’s pocket or bag for example.\n\nMINOR: SOP4 Supplementary Document: Page 8, Labeling Tips – I think the label 2 may highlight a potential limitation of the Hyfe system. It is indicating to the reader that the smartphone needs to be in close proximity to the user. Coughs may sound “distant” even if the user is coughing. Please elaborate what “distant” means here. Is this related to the audio amplitude of the cough sound? Certain types of coughs may have lower amplitudes, particularly if a very ill patient has exhausted their respiratory strength.\n\nMAJOR: The smartphone can be located on a table with many other people in the user’s vicinity. How do you know it is the user’s cough? This could be a major limitation. Particularly if the intention is to detect subtle changes in cough rate. There are many external factors when using an app-based audio cough detection system that can affect cough rate estimation. I don’t think the authors make it clear how they will evaluate this or can overcome such challenges using this system.\n\nMINOR: If possible, it would be very beneficial to have examples of the sounds that were recorded in the controlled environment for readers to listen to.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "9612",
"date": "09 Jun 2023",
"name": "Mindaugas Galvosas",
"role": "Author Response",
"response": "2.1 Comment: While I find this area of research quite interesting, I have several major concerns with this study from the data collection to how the evaluation was measured. The type and amount of data does not reflect how the app would be used in real-life settings. In my opinion, this study does not provide sufficient evidence that the Hyfe system can perform adequately in real-life clinical research, particularly over longer periods of time (24 hours or above). Furthermore, I believe this study lacks novelty compared to other audio-based cough detection studies and represents more of a pilot study than an evaluation of the system. Please see further comments below. Answer: Firstly we want to raise a serious issue with this review. Terence Taylor is a Senior Clinical Data Scientist working for Vitalograph Ireland Ltd, a for profit company that manufactures the Vitalojak, a device used to quantify cough in 24 hour windows in the context of clinical trials. This product could be affected by the emergence of new technologies capable of monitoring cough for longer periods of time. There is a clear economic conflict of interest and the reviewer should have either recused himself or clearly disclosed it. None of these potential remedial actions were taken. We find it equally appalling that the editorial team of F1000 research has failed to act on this after the issue was raised. Here we provide point by point answers to the reviewer´s comments assuming good will, even when the repeated demands for experiments and data outside the scope of this manuscript clearly suggest otherwise. This was the laboratory evaluation of our algorithm, and this manuscript is not meant to demonstrate how it performs in real world environments. Such evaluation, which is a necessary next step, is being done and will be provided as a separate manuscript showing real-world validation of the technology. The scope of this manuscript did not include real-life scenarios and long-term monitoring. The novelty of this study is purely in evaluating the performance of novel fully automated sound capture, cough detection and cough quantification system. Actions: None taken. 2.2 Comment: Abstract: In Objectives, please change the relevant sentence to “We evaluate performance of cough detection using continuous audio recordings obtained within a controlled environment and cough counting by trained individuals as the gold standard.” Answer: Abstract edited as per reviewer recommendation. Actions: Abstract edited as per reviewer recommendation. 2.3 Comment: Introduction: MAJOR: In ref 13, it is noted that participants in this other study complained of increased battery consumption. And so, the evaluation there was constrained to 6-hour windows. Has this app been ever evaluated over at least 24-hour periods? According to the authors, one of the advantages of Hyfe is the ability to passively record for extended periods of time (i.e. greater than 24 hours). Has there been analysis done on the battery consumption effects over longer periods? In my opinion, this study should have monitored cough over at least 24 hours to show a more realistic evaluation of the system Answer: This question is not related to the experiment described in the manuscript, which was purely evaluating the performance of the algorithm. “…one of the advantages of Hyfe is the ability to passively record for extended periods of time (i.e. greater than 24 hours).” – we have conducted separate works that followed-up for long periods of time (months) and that is available: (reference 12, doi: 10.1183/23120541.00001-2022; also reference 14, https://doi.org/10.1183/23120541.00053-2022 ) Actions: References of long-term monitoring are reflected (12, 14). 2.4 Comment: Introduction: MINOR: Privacy concerns are mentioned in the introduction. How does Hyfe preserve privacy exactly? If this information has already been published elsewhere, please cite the relevant literature and give a brief explanation on how privacy preservation is achieved. Answer: Privacy concerns are described in previous publications (references of this manuscript 12-14) that include real patients and monitoring in real world environments. The scope of this manuscript was not to overview the whole monitoring process, but to evaluate the performance of the technology in controlled environments with solicited coughs. Actions: Manuscript references 12-14 address privacy concerns and describe privacy preserving in detail. 2.5 Comment: Methods: MINOR: What versions of iOS/Android has the Hyfe app been tested on? Answer: This study was done with Android phones only and all used Android version 11. Actions: Android version 11 is mentioned in the manuscript. 2.6 Comment: Methods: MINOR: Why were baseline respiratory symptoms not considered for participants? Cough sounds can vary in terms of acoustic properties across different respiratory disease types. The data reported here have no mention of being evaluated on any respiratory disease cough sounds. Answer: Here again, the objective of this work was to evaluate the performance on solicited coughs. There is ongoing work validating the algorithm in clinical patients in real-life environments. Actions: None taken. 2.7 Comment: Methods: MINOR: Regarding the CNN model, was it trained on sufficient data across different smartphones, microphone locations, disease types? Please comment on this. Answer: It was done with a broad range of microphones and collected from various locations and it has been added to the manuscript. Actions: Added to “Methods”: “Hyfe’s CNN model, at the time of this analysis, was trained on more than 200M real-world cough and cough-like samples, collected from multiple countries and multiple devices.” 2.8 Comment: Methods: MAJOR: Why place the smartphone 50cm away from the participant? What is the approximate distance between a user’s mouth and a smartphone mic when they are interacting with their smartphone in front of them with smartphone-in-hand? Was this thought of to replicate real-life use? I would have thought that in many real-life cases also, a lot of the audio that Hyfe would capture would be when the smartphone is located inside the user’s pocket or bag. Why not place one smartphone in the participant’s pocket and have one in their hand to try replicate real-life use? Why constrain the recording protocol so heavily? Also, why use two of the same identical smartphones? It would have been useful to compare different smartphones with different builds, battery consumption properties, microphone designs etc. Was the gain/dynamic range of the microphones taken into account? All these points significantly limit the interpretability of this evaluation in relation to how Hyfe could perform in clinical settings in my opinion. The data collection is not representative of real-life use. Answer: Here again, you are requesting information which goes beyond the scope of the work described in the manuscript. The main objective of this work was to evaluate the performance (sound capture, cough detection and quantification) of the AI model on solicited coughs in a controlled environment. Actions: None taken. 2.9 Comment: Methods: MINOR: What is the sampling rate and bit depth of the audio recordings? Please report this. Answer: The sampling rate was 44.1 Hz and the files are 16-bit. Actions: Added to study design: “The sampling rate was 44.1 Hz and the files are 16-bit.” 2.10 Comment: Methods: MINOR: It would be useful to have an English language version of the pre-generated computer script also available to the reader. Answer: We fail to see the additional value of a translation, given that the Spanish words were chosen based on their pronunciation and cough-like sounding. Actions: None taken. 2.11 Comment: Methods: MINOR: How were participants instructed to cough exactly? Was it for a certain amount of time? For a certain number of explosive cough sounds? Please explain briefly. Answer: This is a valid comment. Participants were instructed to cough once every time they were prompted by the script to do so. Actions: Added “Participants were instructed to cough once every time they were prompted by the script to do so.” to “Study design”. 2.12 Comment: Methods: MAJOR: Recording sessions occurred in a quiet room as reported. What does “quiet” mean here? Were there sound intensity levels recorded? Was the room acoustically insulated? What were the signal-to-noise ratio (SNR) values of the different sessions? Please provide this information to help the reader understand the environment the recordings were obtained in. Answer: This is a valid comment. Sound intensity levels were monitored using https://meters.uni-trend.com/product/ut353-ut353bt/ and never exceeded 110dB. The room was not acoustically insulated. Actions: Added to the “Study design”: “Sound intensity levels in the room were also monitored using UNI-T mini sound level meter. The room was not acoustically insulated”. Added to the “Results”: “Sound levels in the room during the study were never above 110dB.” 2.13 Comment: Methods: MAJOR: What were the kappa agreement scores to show inter-rater agreement for the manual labeling? Why do you need a 4-tier labeling system when users were prompted to perform specific sounds? Do you not already know when a user coughed as they were prompted to do so at specific points within the 10min session? I understand the prompts were randomized, but was this not recorded internally for post-analysis? Therefore, why is there a need for labels 1 and 2 if you have a log of what the participants were doing during each part of the recordings? Answer: The sounds were indeed randomized and triple-human labeling was used as the gold standard. The nature of an elicited sound, even though the instruction is to produce a cough, varies depending on the person (some may get confused and do throat clears when asked to cough, etc). We agree that inter-rater agreement is an interesting point to look at. There is a separate full paper in preparation looking specifically at this with a whole different dataset. Actions: Added a linear analysis plot and Bland-Altman plot in the “Results” section. 2.14 Comment: Methods: MINOR: How many sounds were labeled 0, 1, 2 and 3? Please report this information. How many explosive cough sounds on average were there in each cough audio segment? Were participants prompted to perform a certain number of explosive cough sounds? Answer: the dataset has been made public with this manuscript. The number of sounds instructed was the same for all participants, as prompted by the script. Actions: Added to “Study design”: “In total for each participant, the script included instructions to cough 20 times, sneeze 10 times, clear throat 5 times and produce 15 sounds (explosive words, for example, “paella” and numbers as “93”).” 2.15 Comment: Methods: MINOR: Why does the Hyfe system classify every 0.5 seconds, but labeling was done every 1 second? Answer: This is a misinterpretation. Hyfe uses 0.5s snippets to classify explosive sounds. Labelers were instructed to label every beginning of a cough sound, and the unit of analysis chosen was cough seconds. Actions: None taken. 2.16 Comment: Methods: MAJOR: Multiple coughs may occur within a 1 second window. Why label a full 1 second window as a single true positive cough even if there could be multiple single manually labeled coughs within the 1 second? In my opinion, cough rate estimation would be more accurate if all coughs were considered rather than labeling a 1 second window of coughing as a single cough event (when estimating app performance). Is there reasoning for this in the literature? If so, please add relevant citations. If I understand correctly, it means technically you could miss all but one cough in a given 1sec window and still have very high sensitivity/specificity based on your labeling system? If this is the case, this is a major limitation. How coughs are grouped together in peals or bouts can have a significant impact on cough rate estimation. I think this discrepancy would become more evident had the system been evaluated on a cough-by-cough basis and over longer periods on patients with respiratory disease as they may tend to cough in groups in quick succession (within 1 second in many cases). Answer: Our own data from more than 400hrs monitoring multiple patients with respiratory diseases in real-world environments shows a clear correlation between total coughs and cough seconds – this work is being prepared for publication. We are also analysing cough-seconds and the notion of bouts in the continued work. In the meantime, the objective of this work was to analyse the performance in detecting sounds, capturing and classifying coughs from solicited sounds in a controlled environment. Actions: Added to the “Discussion”: “Our own data from more than 400hrs monitoring multiple patients with respiratory diseases in real-world environments shows a clear correlation between total coughs and cough seconds – this work is being prepared for publication. We are also analysing cough-seconds and the notion of bouts in the continued work. In the meantime, the objective of this work was to analyse the performance in detecting sounds, capturing and classifying coughs from solicited sounds in a controlled environment.” 2.17 Comment: Methods: MINOR: Was there any overlap in the labeling of 1 second windows i.e. 50% overlap between consecutive windows for labeling? Answer: No, there was not. Actions: None taken. 2.18 Comment: Methods: MAJOR: Sample Size: “385 sounds” – are you referring to cough sounds here, or a mix of both cough and non-cough? How did you determine the balance of data between cough and non-cough (speech, throat clear, noise etc.)? It seems a balance of approximately 1:2 (coughs to non-coughs) was employed. In real-life settings, over the course of a 24-hour period for example, the number of non-cough segments will far outweigh the number of cough segments if Hyfe was to continuously record audio. This does not seem to be considered here. If the data were to be more realistically balanced in this way, it may have a significant effect on the positive predictive value (PPV) of the algorithm (PPV needs to be reported). One of the biggest challenges of longer term (24 hours or more) audio-based cough monitoring is the PPV performance measure. Answer: As the text states, this refers to the total number of sounds. Once more, this study did not evaluate the balance of cough and non-cough segments over a long period of time, as the objective was to only evaluate the performance of automated listening to elicited sounds, capturing and quantifying elicited coughs in controlled environments, which we achieved and described in detail. Actions: None taken. 2.19 Comment: Methods: MAJOR: One of the advantages of Hyfe, reported by the authors, is that it can monitor cough rate over longer periods (>24 hours). But this study looked at 10-minute recording windows. Even taking into account that no respiratory symptoms were not noted from participants (which I think is a major limitation), I think the balance of data here are not truly representative of real-life settings especially if the authors suggest Hyfe can monitor cough rate over 24-hour periods. This is a major limitation to this evaluation study. This system needs to be evaluated over at least 24-hour periods before it can be suggested that it may perform strongly for longer term analysis in clinical settings Answer: Here again, you are requesting data that exceeds the scope of this work, which was to evaluate the performance of the Hyfe system in controlled environments with solicited coughs. There is published data about the capacity of Hyfe to monitor patients for periods of months (references 12-14). Actions: None taken. 2.20 Comment: Methods: MINOR: Synchronization of labels - Please provide a clearer explanation for this. Why synchronize to within 2 seconds? This seems like a long duration considering multiple explosive cough sounds may occur within 2 seconds. Answer: We clarify that synchronization was done to the exact time of the sound. The text has been modified to reflect the sequential nature of changes. Actions: Edits in capitalized letters: “Labels created by listeners (in Audacity) and Hyfe detected coughs were FIRST manually synchronized to within two seconds of each other. Synchronization was THEN carried out for each phone and each session separately by identifying the time offset that would align Hyfe detections with the labels and adjusting the Hyfe detection timestamps accordingly.” 2.21 Comment: Methods: MINOR: Data were discarded if they had less than 10 cough seconds of agreement. How often did that occur? How much data were discarded overall? – from Figure 1 it seems 20-25% of data were discarded due to inadequate quality. How would this reflect real-life evaluation then? The app would be unsure of about 20% of coughs at best? That seems to be a potential large margin of error. Please comment on this. Answer: See the third sentence of the “Results” section for clarification: “Ten sessions did not have at least 10 sounds unanimously labeled as coughs and were also excluded, leaving 37 sessions, with 672 unanimously-labeled cough-seconds, and 1,007 non-cough seconds for the final performance evaluation.” Additionally, the goal of this work was not to evaluate the app in real-life and a separate work - app’s evaluation publication is in progress. Actions: None taken. 2.22 Comment: Methods: MAJOR: Was the 4-tier or 6-tier labeling SOP used? This is quite confusing for the reader. If 6-tier is superior in the opinion of the authors, why not revert and apply it to all data and re-run the analysis? I understand it may mean re-training the CNN but if it will be beneficial as mentioned by the others, then it should be reported here. Answer: 4-tier SOP was used in this study. The findings presented here informed further changes to the SOP, resulting in the 6-tier SOP. This work was described as performance evaluation of the app and its result was also the updated SOP. We will be presenting 6-tier SOP results and further updates to the SOP in other soon upcoming publications, as it was applied in multiple studies done afterwards. Actions: None taken. 2.23 Comment: Methods: MINOR: “Because the utility of a cough monitor is not in noting individual coughs but rather in tracking cough rates…”. Surely identifying singular coughs should be the goal to obtain the most accurate estimation of cough rate? If not, you could hypothetically be detecting false positives and false negatives, but still hit the correct cough rate. This could affect the analysis of how cough rate changes over time throughout a 24-hour period, for example, if it were of interest. Please provide a stronger argument for this. Answer: The Hyfe Cough Monitoring System recognizes and timestamps users’ coughs as they occur. To manage the challenges of distinguishing coughs that happen in rapid succession (bouts), these timestamps are converted into cough-seconds as the basic unit of analysis; a cough-second is a second during which at least one cough occurs. The endpoint of our validation trial consists of hourly tabulations of these cough-seconds for each subject. Actions: None taken. 2.24 Comment: Results: MAJOR: Please report SNR for audio sessions in comparison to cough. It may help the reader understand the poor performance of sessions 2, 17 and 38. Real-life recordings will be full of different types and levels of noise. If it is only possible to evaluate on audio within controlled environments, then the authors should augment the data by adding various different types and levels of noise to the data to replicate real-life use. Answer: The goal of this study was not to evaluate Hyfe in real life environments. Ongoing studies validate the technology in real-life environments and publications will prove that in the near future. Actions: None taken. 2.25 Comment: Results: MINOR: What were the uncommon acoustic characteristics associated with Sessions 2 and 17? An additional figure with time domain plot as well as a spectrogram plot of coughs from these participants would be useful here for the reader to understand why the system did not perform as well for these participants. Answer: It is mentioned in the manuscript that sessions 2 and 17 had biphasic decibel peaks and different spectrogram features. This was a result of, for example, multiple solicited coughs being produced and the nature of the solicited sound, even though the script instructed a single cough. Actions: None taken. 2.26 Comment: Results: MINOR: Figure 3 image quality should be improved. Answer: “Figure 3” quality is improved. Actions: “Figure 3” is replaced with a better quality image. 2.27 Comment: Results: MINOR: “Sensitivity for the Session 20 was not evaluated because this was a patient with refractory chronic cough that generated hundreds of out-of-script, making timestamping impossible.” – Please elaborate further. Were there too many coughs? One would assume the data from this participant would have been very interesting to analyze and run through the Hyfe system? Answer: The cough pattern of this participant has been analyzed and is described elsewhere (Reference 13). She made an attempt to collaborate in this particular experiment as well but her chronic cough resulted in hundreds of observations outside the script. Actions: None taken. 2.28 Comment: Results: MINOR: Limitations: I agree with the limitations mentioned. So why evaluate the Hyfe system in a way it will rarely if not never be used in? Please comment on this. Answer: Because this was not an evaluation of the system in real world environments, but of the performance of the algorithm in a controlled environment. Actions: None taken. 2.29 Comment: Results: MAJOR: Please give details of the effect the Hyfe app has on battery life. One would think a continuous audio recording will significantly drain a smartphone battery. It seems to be mentioned in a previous study (ref 13). Were there experiments done on this? If not, this analysis needs to be performed and reported in this evaluation study. Answer: These details are outside the scope of this manuscript. Hyfe was successfully used by hundreds of participants in a cohort study described elsewhere with no major complaints about the battery life REF 14 in the manuscript (DOI: 10.1183/23120541.00053-2022). Actions: None taken. 2.30 Comment: Results: MAJOR: A Bland Altman plot analyzing cough rate between Hyfe and manual labels is required here. Correlation analysis is not enough to convince the reader that the Hyfe system can accurately estimate cough rate (unless you were to use the linear regression equation to map Hyfe estimation to manual estimation which I don’t think is the goal here). While strong correlation is interesting to observe, simply showing the equal line on Figure 4 does not highlight if there is any bias in cough rate estimation. Please add the linear regression line and equation in Figure 4. Please also add an additional panel for a Bland Altman plot comparing the mean cough rate between manual and Hyfe to the difference in cough rate between manual and Hyfe. Answer: Bland-Altman plot analyzing cough rate between Hyfe and human annotators is presented as Figure 6, also Figure 5 shows the linear analysis. Actions: Added “Figure 5” and “Figure 6” to the “Results” section for linear analysis and Bland-Altman plots. 2.31 Comment: Discussion: MAJOR: Where does the score threshold of 0.85 come from? Can you report the distribution of CNN output probability scores for all label categories as supplementary material? A histogram, for example, of probability scores for each label category would be interesting to see and could enhance the reader’s understanding of the challenges in labeling category 1 and 2 sounds. Answer: The threshold of 0.85 was chosen as the cut-off point as it correlates well with the cough second measure while minimizing false-positives, results from the early ROC curves have been published (REF 13 in the manuscript). Actions: A separate manuscript presenting a broad range of thresholds and their impact on correlation with cough seconds and true cough counts is in preparation. 2.32 Comment: Discussion: MINOR: The discussion on inter-participant variability and the debate on using solicitated voluntary coughs as a diagnostic tool is quite interesting. Does this suggest these are most likely voluntary throat clears rather than involuntary coughs? As a result, why then prompt the user to record a voluntary cough when first using the app? Answer: The discussion does not discuss throat clears and our publication does not suggest that solicited coughs are not suitable for diagnostic purposes - more research is needed in this field, and that was not the scope of this study. Actions: None taken. 2.33 Comment: Discussion: MINOR: What difference will the 6-tier SOP make for training the CNN model? I assume fixed 0.5sec segments are employed for training the model so how will the duration markers be more beneficial than just the onset markers used in the 4-tier SOP labeling system? Answer: The labeling by segment, rather than by peak provides the CNN with a breadth of data around the expulsive phase. Actions: None taken. 2.34 Comment: Discussion: MAJOR: The Pearson correlation is interesting, but I disagree that it should be the primary metric of performance. I think the authors should perform a linear regression analysis also to analyze the slope of the regression line. Only using Pearson correlation does not disclose information regarding how many coughs are missed in detection. For example, you could theoretically have a Pearson coefficient of 1 but you are missing 1 cough in every 2 or 3 coughs consistently in your detection model (this would be reflected in the slope of the regression analysis). The Pearson correlation metric is one of a group of metrics that should be considered in my opinion. I would like to see linear regression analysis, absolute percentage error according to the total number of coughs per participant and a Bland Altman analysis. Answer: We are adding “Table 3” to cover linear model parameter estimates: Pearson correlation, intercept and slope for both phones used. Actions: \"Table 3” added to show the linear analysis on model parameter estimates for both phones used. 2.35 Comment: Discussion: MAJOR: “…Hyfe’s performance is adequate to be used in most clinical and research contexts.” This study does not suggest this in my opinion if the data were collected in controlled environments, was not evaluated on real respiratory patients and the smartphones were not evaluated in multiple different positions/locations. Answer: We agree, this phrase was overstated. Editing the manuscript. Actions: Last paragraph of the “Discussion” was edited to: “Hyfe’s performance is adequate to proceed to validation in clinical context”. 2.36 Comment: Other Comments: MAJOR: While I understand the data were obtained in controlled environments, in my opinion, more data are required to obtain a more realistic measure of performance in order to suggest Hyfe could be used in clinical settings. This includes more data using different smartphone locations (in user’s pocket, bag etc.), more realistic data with different types and levels of noise (including muffled coughs due to hand/mask covering) and I think it should be evaluated on a cough-by-cough basis rather 1 second windows as a form of cough rate. Answer: This was not the scope of this study and we have changed the overstated “adequate in..clinical context” to “adequate to proceed to validation…”. All the points mentioned in this comment are being addressed in a separate clinical validation study. Actions: None taken. 2.37 Comment: Other Comments: MINOR: How does the app know if it is the user who coughed and not a person beside them in a crowded area? Has this been taken into account within the CNN training data? Please comment on this. Answer: This was not evaluated in this study, as the scope was just to evaluate the algorithm in detecting and recording solicited coughs in a controlled environment. Actions: None taken. 2.38 Comment: Other Comments: MINOR: Does the Hyfe app still record audio when the user is on a phone call or sending voice messages? Answer: This was not evaluated and not the scope of this study and the manuscript. Just for the interest - the version of the app tested in this study would have not recorded coughs on a call/voice message. Actions: None taken. 2.39 Comment: Other Comments: MINOR: Does the app work without internet connectivity? Answer: The connectivity details were not in the scope of this study, therefore, no information provided in the manuscript. Just for the interest - the version of the app tested in this study works without internet connectivity to capture the sounds, but not analyze them (internet connectivity was needed). The most recent version works fully on-device, with no connectivity needed to both capture and analyze the sounds. Actions: None taken. 2.40 Comment: Other Comments: MINOR: SOP4 Supplementary Document: Page 4, Section 3, bullet 3 – should that read as “…at the end of the expulsive phase..”? Answer: This is correct, a spelling mistake was made in “expulsive”. Actions: Correcting the spelling mistake. 2.41 Comment: Other Comments: MINOR: SOP4 Supplementary Document: I think reporting a cough as having one sound or two sounds is a little confusing. Consider moving Fig. 5 and the paragraph above it to before Fig. 3. Start with showing the sound, explaining the three phases of the cough sound event and then describe in more detail the physiology behind it. Fig. 3 panel B needs to highlight that the voiced phase is missing. It is a little confusing to just say A has a “double” sound and B has a “single sound”. Answer: We appreciate your feedback. With the SOP being updated, confusing parts have been addressed in newer editions. Actions: None taken. 2.42 Comment: Other Comments: MAJOR: SOP4 Supplementary Document: Page 8, Table 1 – according to the 4-tier process, the label 2 may be due to the phone located in the user’s pocket which, I assume, will be a vastly common occurrence if this app were to be used in cough clinical applications. In this study label 2 coughs weren’t considered in the app evaluation. Why not? I think it is essential particularly for an app-based cough monitoring system to be evaluated on recordings when the phone is in the user’s pocket or bag for example. Answer: The scope of this research was not to evaluate the app in real-world environments, just the performance of the algorithm with solicited sounds in controlled environments. Further studies and validation of the system address these concerns mentioned in your comment. Actions: None taken. 2.43 Comment: Other Comments: MINOR: SOP4 Supplementary Document: Page 8, Labeling Tips – I think the label 2 may highlight a potential limitation of the Hyfe system. It is indicating to the reader that the smartphone needs to be in close proximity to the user. Coughs may sound “distant” even if the user is coughing. Please elaborate what “distant” means here. Is this related to the audio amplitude of the cough sound? Certain types of coughs may have lower amplitudes, particularly if a very ill patient has exhausted their respiratory strength. Answer: “Distant” in the 4-tier SOP meant subjectively distant sound (compared to surrounding sound levels both audibly and visually in the recording that is being analysed). This study was not meant to evaluate the system in clinical settings, we will be reporting on system performance with low amplitude coughs in the upcoming publications from our validation studies. Actions: None taken. 2.44 Comment: Other Comments: MAJOR: The smartphone can be located on a table with many other people in the user’s vicinity. How do you know it is the user’s cough? This could be a major limitation. Particularly if the intention is to detect subtle changes in cough rate. There are many external factors when using an app-based audio cough detection system that can affect cough rate estimation. I don’t think the authors make it clear how they will evaluate this or can overcome such challenges using this system. Answer: Differentiating a cougher from the next one was not the scope of this study - this study was to evaluate the performance of the algorithm in very controlled environments - when a script is followed and the sound-producing person is known. In our validation studies and publications concerning real-world environments, all details will be provided. Actions: None taken. 2.45 Comment: Other Comments: MINOR: If possible, it would be very beneficial to have examples of the sounds that were recorded in the controlled environment for readers to listen to. Answer: You are requesting the sharing of recordings from participants in a trial. Following good practices, the informed consent form states that “only the study personnel will have access to the recordings”. This will not be possible. Actions: None taken. 2.46 Comment: Is the work clearly and accurately presented and does it cite the current literature? No Answer: It would be important for the reviewer to back this assessment with specific examples of where the literature was not cited or done so inappropriately. 2.47 Comment: Is the study design appropriate and is the work technically sound? No Answer: The vast majority of the comments by this reviewer were for broader scope than the primary objective of the study described in the manuscript. 2.48 Comment: Are sufficient details of methods and analysis provided to allow replication by others? No Answer: The Methodology section is now updated and the full dataset and code are publicly available. 2.49 Comment: If applicable, is the statistical analysis and its interpretation appropriate? Partly Answer: Many of the comments by this reviewer were for broader scope than the primary objective of this study described in the manuscript. 2.50 Comment: Are all the source data underlying the results available to ensure full reproducibility? No Answer: The full data has been made available with the original version. 2.51 Comment: Are the conclusions drawn adequately supported by the results? Partly Answer: Many of the comments by this reviewer were for broader scope than the primary objective of this study described in the manuscript. 2.52 Comment: Competing Interests. No competing interests were disclosed by the reviewer. Answer: This is outrageous and akin to reviewer misconduct as stated above. Please provide a full disclosure of your economic CoI or recuse."
}
]
}
] | 1
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https://f1000research.com/articles/11-730
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https://f1000research.com/articles/12-636/v1
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09 Jun 23
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{
"type": "Research Article",
"title": "Perceived ease of use on visual learning application for mathematics using holography display for the topic on shape and space",
"authors": [
"Khoo Shiang Tyng",
"Halimah Badioze Zaman",
"Ummul Hanan Mohamad",
"Azlina Ahmad",
"Halimah Badioze Zaman",
"Ummul Hanan Mohamad",
"Azlina Ahmad"
],
"abstract": "Background: A person's life is built on a solid foundation of mathematics. Common causes of learning difficulties in mathematics include abstract ideas, a lack of imagination, and a lack of comprehension of the concepts being studied. Because 3D shapes are abstract concepts, the aim of this study is to better understand how to recognize them in primary school students. Methods: The development of the Mathematics E-Learning Visual application MEL-VIS(MEL-VIS) application involves the design of the Visual Learning Application Iteration-Evolution Development Model, MEL-VIS (PIEMEL-VIS), the MEL-VIS ID Model, and the MEL-VIS Application Module. The development methodology and ID model are built based on the application of various components such as learning theory, a visualization approach, a play-while-learning approach based on scaffolding techniques, as well as interaction and interface based on various touch technologies using tablet computers. The study's contributions are: (i) an iterative-evolutionary development model of the Visual Learning Application, MEL-VIS (PIEMEL-VIS); (ii) a MEL-VIS ID model; (iii) a MEL-VIS application prototype; and (iv) a usability testing instrument for the ease of use of the MEL-VIS application. Results: The usability testing of the MEL-VIS application was carried out through a case study involving 80 students at a primary school in Putrajaya. A task-based, semi-experimental approach was used to assess the ease-of-use construct. Research instruments such as questionnaires and observation checklists are used in this test. The results of the study found that MEL-VIS has a positive impact on students after using the application. Conclusions: Based on the test conducted, primary school students have given positive feedback to the prototype of the E-Visual MEL-VIS application. Thus, it can be concluded that the prototype of the E-Visual MEL-VIS application as a whole is effective, easy to learn and easy to use for student use for primary school mathematics subjects.",
"keywords": [
"Tablet Technology",
"Visual-Electronic Application",
"Mathematic",
"Pyramid Holography",
"Visual Learning",
"Shape and Space",
"E-learning"
],
"content": "Introduction\n\nShape and space in mathematics are widely used in engineering, architecture, science, and technology. The most significant application of form and space can be found in building design and layout. Because of this clear demand, the theme of space and form has been adopted in the Malaysian national school curriculum from pre-school to higher education, particularly in the fields of design and architecture.1\n\nLearning about space and shape entails not only learning about the meaning or notions of geometric concepts, but also learning how to analyse two-dimensional (2D) and three-dimensional (3D) shape characteristics in geometric shapes.2 Furthermore, students can debate geometric relationships to identify position and space in geometric relationships, then change and use symmetry, visualisation, spatial thinking, and geometric models to solve problems.3 Geometry is defined by Bassarear and Moss (2015) as “the study of shapes, relationships, and properties.” According to Aulia,4 geometry is the study of space and form, and better reasoning skills are required to understand these concepts well.\n\nAmong the difficulties encountered when learning and teaching the topic of shape and space are difficulty identifying and confusing the names of 2D and 3D shapes, difficulty referring to the figure’s location, difficulty understanding the figure’s characteristics, and difficulty imagining the layout of the 3D shape.5–7\n\nThe development of the visual-electronic applications in this study was based on a multi-touch tablet, considering several factors that are suitable for students who prefer visual and auditory learning styles, such as the suitability of the navigation button position, the position of the menu and module interface, the level of interactivity, user-friendliness, assistance, and multimedia-fusion elements such as text, colour, and animation. Built electronic-visual, or E-visuals, applications use strategic teaching and learning processes based on the constructivist approach, the 5E learning approach, and the mastery learning method; they use the concept of scaffolding in the process of guiding students, the method of learning while playing, and active learning. All of this is intended to make primary school students’ learning more effective and enjoyable. All the implications of the teaching and learning strategies, approaches, methods, and concepts used in the built visual-electronic or E-visual applications have also been discussed, considering previous studies and reforms implemented in the studies.\n\nThe development of an E-visual application for teaching and learning based on holographic displays. The development of the Mathematics E-learning visual application (MEL-VIS), is a prototype application for learning mathematics for primary school students. The prototype of the E-visual application can create a more effective learning environment where the instructor acts as a guide to the students. Instructors introduce how to use the MEL-VIS application to students, and students can conduct their learning independently based on the concept of self-pace and self-learning. The MEL-VIS Prototype application development process involves several phases based on an agile model called the MEL-VIS Application Iteration-Evolution Development Model (PIEMEL-VIS) which is systematic taking into account the SDLC-Waterfall Model, the Prototype Process Model8 and Content Prototype Iteration Model.9 Figure 1 shows the iterative-evolution development model of mathematical E-visual application (PIEMEL-VIS).\n\nThe design of the E-visual MEL-VIS application was inspired by the skeuominimalist design. Skeuominimalismis a term that combines skeuomorphism and minimalism.10 A skeuominimalist design reduces app usage from human error and allows users to have more interactive experiences with apps.11–13\n\nAs shown in Figure 2, the MEL-VIS visual-electronic learning application is comprised of three (3) primary modules: the ‘Let’s Read Module’, the ‘Let’s Recognize Shapes Module’, and the ‘Let’s Learn Shapes Module’. Students must finish the ‘Let’s Practice’ submodule and the ‘Let’s Play’ submodule for each module indicated. Overall, the MEL-VIS modules’ learning method is founded on the 5E Approach, learning while playing, and digital exploration via serious games. According to few researchers,14–16 learning via gaming increases learning interest.\n\nTo attract primary school students to the E-visual application, MEL-VIS, an introductory montage of the MEL-VIS application is broadcast when the application starts. The montage consists of form elements and the introduction of cartoon characters that appear in the application. The MEL-VIS montage was developed using Adobe Flash CS6 authoring software and loaded with 2D and 3D vector animation elements. The purpose of introducing the application through montage is to allow primary school students to better remember this application and stimulate their instinct for curiosity by revealing various basic forms of visual animation at the beginning of the E-visual application MEL-VIS for learning mathematics. Figure 3 shows the introductory montage interface of the E-visual application, MEL-VIS.\n\nVarious basic shapes and colourful numbers can be seen to create excitement for primary school students before they start learning. The 3D shape animation in the montage is relevant to the topic of shape and space. Through the montage display, students can recall what they learned in their long-term memory. Figure 4 shows the interface of the learning E-visual application, which is called E-visual application for primary school mathematics subjects, MEL-VIS. Animations of cartoon characters and objects are created to attract the attention of primary school students before starting mathematics subjects using the application. The application also introduces characters that appear to attract students’ attention. The screen is accompanied by music, animation, text, and colour combinations to attract students’ interest, create curiosity, and increase their willingness to continue learning. This is in line with pattern recognition-cognitive theory: a template based on pattern recognition theory introduced by Reed17 and a cognitive approach emphasising the use of curiosity and individual achievement as motivation in the learning process.18\n\nThe main menu interface has three (3) main modules and two (2) sub-modules: the Let’s Read module, the Let’s Recognize Shapes module, the Let’s Learn Shapes module, the Let’s Practice sub-module, and the Let’s Play sub-module, as can be seen in Figure 5. In the main menu, soft and entertaining background music is played, aiming to attract primary school students to explore each module and sub-module available in the application. Graphic buttons with labels are used as navigation buttons for the E-visual MEL-VIS application prototype interface. According to few researchers,19–21 the use of both graphic and text navigation icons makes it easier for novice users to explore new applications as compared to using only graphic navigation icons or text navigation only. Using interactive icons that function as elements, students can build knowledge through independent exploration (constructivist theory) and active learning (active learning).\n\nThe Let’s Read module of the prototype E-visual application, MEL-VIS, aims to teach primary school students to recognise 3D shapes, which is one of the important syllabuses in primary school mathematics subjects. Through the Let’s Read Module, students learn 3D shapes such as cones, spheres, cuboids, cubes, cylinders, and pyramids through reading poems and watching interesting animations. All the 3D shapes introduced in the poem are closely related to everyday life. Students can organise their thoughts about learning outcomes and make connections between the knowledge they have learned. This is in line with the 5E learning strategy, the engagement phase.\n\nSome researchers think that the use of rhymes is an important technique to help students remember learning because the human brain easily connects with sounds for long-term memory.22–25 Animated interactive objects that serve as aids and guides for students to remember (Cognitivism Theory). In teaching, poems or rhymes can help change the learning environment to be more interesting. Figure 6 is one of the Let’s Read Module screens.\n\nThe Let’s Recognize Shapes module is a learning module for recognising 3D shapes. Figure 7 is the start screen of the Let’s Recognize Shapes module of the prototype E-visual application, MEL-VIS. The concept of scaffolding is applied in this section; guidance in the form of animation and audio is displayed for students as a guide to exploring this module. Figure 8 shows that the students can touch the 3D shape to hear the pronunciation of the shape, and the animation will also be displayed. In addition, the selected 3D shape changes the display with brighter and more attractive colours. This may pique the interest of elementary school students in observing the learned forms. The 5E method (engagement phase and exploration phase) has been applied in the design of the Let’s Recognize Shapes Module.\n\nThe Let’s Recognize Shapes module is built using the flash card concept. The use of flash cards is often recommended as an effective learning method for students.26–28 The use of this concept in the Let’s Recognize Shapes Module can effectively help students recognise 3D shapes in long-term memory. Students can relate the 3D shapes they have learned to real 3D objects they can see around them using flash cards, as shown in Figure 9, which helps them understand what they are learning. The movement of the human eye moves according to the location of the object on the screen. On the Let’s Recognize Shapes Module screen, all animated objects are placed symmetrically. Through that method, primary school students have the understanding to distinguish 3D shapes with different characteristics.\n\nThe Figure 10 and Figure 11 show the initial interfaces of the Let’s Learn Shapes Module. At the beginning of this module, there is an exploration guidance animation (Scaffolding Concepts). In addition, the concept of scaffolding is also applied to the help button (Figure 12) to guide students on how to use pyramid holography. This module is a mathematics learning module that explores the topic of 3D shapes in more depth with a holographic display that can be seen in Figure 13.\n\nThe students can choose the shape they want to learn for a more thorough and in-depth description of the shape. For example, students choose a pyramid shape. Aa description of the characteristics (vertices, surfaces, and sides) of the pyramid shape in animation and audio will be displayed. Animated learning functions as an element that activates sensory memory, namely short-term memory and long-term memory (Cognitivism Theory), which aims to interest and encourage students to ask questions (Constructivism Theory). The 5E learning strategy (engagement (engagement), exploration (exploration), explanation (explanation) and further explanation (elaboration) is applied in the design of the Let’s Learn Shapes module. The students get involved, explore 3D shapes and in addition, can add knowledge through explanation and further explanation of 3D shapes through holographic displays. This can help students with the processes of short-term memory and long-term memory (concept of constructivism).\n\nThere are three categories of questions out of a total of twelve questions in the Let’s Practice sub-module. In the first category (i), basic questions differentiate 3D shapes; in the second category (ii), questions consist of the characteristics of 3D shapes; and the third category (iii) is related to 3D shapes in daily life. The questions in the E-visual application prototype (MEL-VIS) are randomly generated every time. The questions provided in the module involved are according to the syllabus for the primary school mathematics subject and have been confirmed by three (3) experienced mathematics teachers. Also, the 5E learning strategy (Evaluation Phase) is applied in this sub-module. Figure 14 to Figure 16 are examples of questions in the Let’s Practice sub-module of the prototype E-visual application: MEL-VIS.\n\nIn the Let’s Play sub-module, primary school student complete tasks in stages through storytelling exploration. Based on this sub-module, students need to master each step to proceed to the next step. This is in line with active learning and mastery, or basic learning. The concept of serious games is also applied in the Let’s Play sub-module, where learning objectives are achieved after completing the sub-module tasks. Through the Let’s Play sub-module, two-dimensional (2D) and three-dimensional (3D) animation forms are used to narrate throughout the exploration of Iqa. Iqa is the main character in this story. Students are asked to help Iqa until she reaches home. The assignment given to students is related to the topic of basic 3D shapes in mathematics subjects. Figure 17 to Figure 20 are examples of the display screen of the Let’s Play sub-module prototype of the E-visual application, MEL-VIS.\n\nThis Let’s Play sub-module is also used to test the understanding and memory of primary school students about the 3D shapes that have been learned. The action that primary school students need to take for this sub-module is to drag the 3D shape label and place it on the correct 3D shape. The use of 3D shape labels instead of 3D shape images in the task is because six experienced teachers think matching labels with images is more effective in learning. This can help students achieve “higher mental function.” In addition, encouraging students to seek answers and think critically (Constructivism Theory).\n\nTo increase students’ level of understanding in learning sessions, scaffolding plays an important role. Scaffolding enables primary school students to master their learning level step by step and also provides assistance through animation. Through this sub-module, step-by-step help is presented through animation to give students ideas on how to complete the given task. Scaffolding is adapted into some of the Let’s Play sub-module activities, as shown in Figure 21.\n\nTable 1: Scaffolding Strategies in the Let’s Play Story Plot shows the scaffolding strategies found in the Let’s Play sub-module’s story plot, as well as where the concepts of learning while playing and serious games have been applied in the application. This strategy can arouse curiosity, attract the will to be involved, cultivate the will to think, and apply knowledge. The Let’s Play sub-module is built based on the MEL-VIS Human and Computer Interaction Model (HCI: MEL-VIS Model), as can be seen in Figure 22.\n\n\nMethods\n\nSummative testing through usability testing was carried out at a primary school in Putrajaya, involving a total of 80 students aged nine years during the COVID-19 pandemic lockdown. During this period physical distancing was enforced. Therefore, an oral information-giving and consent-seeking process had been conducted by school authorities. During the testing, a briefing was given to all students involved in usability testing. The post-test is administered to all students who participated in the pre-test. Students are given a ten-minute trial session using the E-visual, MEL-VIS application. After that, they were asked to complete the list of assignments given. Student performance in completing each task is recorded for analytical purposes. After finishing using the E-visual application, MEL-VIS, students were asked to complete a questionnaire about the application. Questionnaire: A set of questionnaires was constructed and administered to students after they used the prototype of the MEL-VIS application with the help of the teacher. The questionnaire has four questions and aims to test the constructs of ease of use and ease of learning. Task list: The task list is intended to put the construct of usability to the test. All the tasks that the students must do are stated in the list. Students are required to complete a list of assignments totalling 20 steps using MEL-VIS. A total of eight steps concentrates on the main menu, six on the use of the holographic display, three on the training sub-module, and three on the Let’s Play module. Testing for usability constructs is based on observation. Observations are recorded through performance indicators. When the students used the E-visual MEL-VIS application prototype for the first time, the researcher himself observed the procedures. All these tasks are the main interactions in the E-visual MEL-VIS application. The results of observation are recorded through student performance indicators, as shown in Table 2.\n\n\nResults and discussion\n\nThe following research findings are based on the research question: Is a visual electronic application, developed using a holographic display based on multi-touch technology, easy to use by primary school students for mathematics lessons? The ease-of-use construct process is based on the ease-of-use construct data analysis model, which can be seen in Figure 23. Table 3 shows the mean average success of students in implementing each type of instruction given according to the Steps. The study found that 89.00% of students successfully implemented the researcher’s instructions in the main menu, 91.33% of the students successfully implemented the researcher’s instructions in displaying the 3D holographic display, and 95.67% of the students successfully completed the instructions given by the researcher in the Let’s Practice sub-module. The highest success by students is in implementing the instructions in the Let’s Play sub-module, which is 96.67%. Table 4 shows the average mean student performance for each task step given. Based on Table 3, the increase in the mean average success rate of students successfully executing the given instructions increases from the main menu to the Let’s Play sub-module. This shows that the students can adapt easily when using the E-visual MEL-VIS application.\n\nBased on each test conducted, primary school students have given positive feedback to the prototype of the E-Visual MEL-VIS application. Thus, it can be concluded that the prototype of the E-visual MEL-VIS application is effective, easy to learn, and easy to use for student use in primary school mathematics subjects.\n\n\nConclusions\n\nThis study has produced research findings involving the development of an E-visual application prototype using a holographic display based on multi-touch technology and the evaluation of the MEL-VIS E-Visual application prototype for primary school students. An agile or agile methodology specially designed for the development of prototype E-visual MEL-VIS applications was built, which is the MEL-VIS Application Iteration-Evolution Development Model (PIEMEL-VIS), which involves five phases, namely: analysis, design, development, implications, and evaluation. The model is both a theoretical and practical contribution to the application development process for primary school mathematics learning. Based on this study, the application was designed and developed using the MEL-VIS E-Visual Application Prototype ID model that takes the needs of primary school students into account. The ID model is used in the application design and development process based on the content of the user requirement specification (URS) and system requirement specification (SRS). This study also produced a scaffolding model that was used as guidance for primary school students to use the E-visual application prototype more effectively.\n\nThis study on usability testing received a positive response. This shows that the development methodology and the built-in ID model successfully improve the usability of the E-Visual MEL-VIS application prototype. However, there is still room to refine the development of the application from a technical point of view and further diversify the content of the application. Overall, the research findings show that the prototype E-visual MEL-VIS application is effective in improving students’ understanding and achievement and is easy-to-use.",
"appendix": "Data availability\n\nOPEN DANS: PERCEIVED EASE OF USE ON VISUAL LEARNING APPLICATION FOR MATHEMATICS USING HOLOGRAPHY DISPLAY FOR THE TOPIC ON SHAPE AND SPACE, https://doi.org/10.17026/dans-zta-5svh.\n\nThis project contains the following underlying data:\n\n• Data file 1-4 (Task List Data in.dat and.sav format).\n\n• Data file 5 (MEL-VIS E-visual application task list: usability test in pdf format).\n\n• Data file 6 (Letter request permission to conduct testing in.pdf format).\n\n• Data file 7-8 (Confirmation of study approval in.pdf format).\n\n• Data file 9 (Questionnaire_MEL-VIS in.pdf format).\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nReferences\n\nKalarat K: The use of 3D holographic pyramid for the visualization of Sino-Portuguese architecture. J. 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Hong Kong: Dep. Inf. Syst. City Univ. Hong Kong; 1997; 319–338.\n\nZaman HB, Robinson P, Petrou M, et al.: Visual Informatics: Bridging Research and Practice: First International Visual Informatics Conference, IVIC 2009 Kuala Lumpur, Malaysia, November 11-13, 2009 Proceedings. Vol. 5857. Springer Science & Business Media; 2009.\n\nUrbano ICVP, Guerreiro JPV, Nicolau HMAA: From skeuomorphism to flat design: age-related differences in performance and aesthetic perceptions. Behav. Inf. Technol. 2022; 41(3): 452–467. Publisher Full Text\n\nAbdesselam B, Aziz MSA: Mobile Interface Design to suit the Algerian Culture: First initial design. Int. J. Perceptive Cogn. Comput. 2020; 6(2): 1–7. Publisher Full Text\n\nNovita Sari R, Sri Hayati R, Fujiati, et al.: Heuristic Evaluation in Mobile Augmented Reality Applications in Designing Houses.2020. Publisher Full Text\n\nVolkov S: Minimalism in Designing User Interface of the Online Platform ‘Higher School Mathematics Teacher’.2020.\n\nCheng KM, Koo AC, Nasir JSM, et al.: Playing edcraft at home: Gamified online learning for recycling intention during lockdown. F1000Res. 2021; 10: 890. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMohamad SNM, et al.: Promoting student engagement by integrating new technology into tertiary education: The role of the iPad. JOIV Int. J. Informatics Vis. 2020; 4(3): 14–26. Publisher Full Text\n\nBoyle EA, et al.: An update to the systematic literature review of empirical evidence of the impacts and outcomes of computer games and serious games. Comput. Educ. 2016; 94: 178–192. Publisher Full Text\n\nReed SK: Cognition: Theories and applications. CENGAGE learning; 2012.\n\nCook DA, Artino AR Jr: Motivation to learn: an overview of contemporary theories. Med. Educ. 2016; 50(10): 997–1014. Publisher Full Text\n\nBenbasat I, Todd P: An experimental investigation of interface design alternatives: icon vs. text and direct manipulation vs. menus. Int. J. Man. Mach. Stud. 1993; 38(3): 369–402. Publisher Full Text\n\nHuang H, Yang M, Yang C, et al.: User performance effects with graphical icons and training for elderly novice users: A case study on automatic teller machines. Appl. Ergon. 2019; 78: 62–69. Publisher Full Text\n\nWiedenbeck S: The use of icons and labels in an end user application program: an empirical study of learning and retention. Behav. Inf. Technol. 1999; 18(2): 68–82. Publisher Full Text\n\nArumugum L, Nadeson B, Thamburaj KP: Traditional teaching method-concept of moral education and pedagogy in Aathicuudi. Muall. J. Soc. Sci. Humanit. 2021; 176–182. Publisher Full Text\n\nAtchley RM, Hare ML: Memory for Poetry: More Than Meaning? Int. J. Cogn. Linguist. 2013; 4(1): 35.\n\nKohutics A: ENGLISH NURSERY RHYMES AS A SOURCE OF MOTIVATION TO YOUNG LEARNERS.2020.\n\nPowell N: The Poetry of Early Childhood.2021.\n\nDahniarti C, Siti M, Fajar A: Flashcard for Enriching and Developing the Child Vocabulary with Speech Delay to Improve Lingual Skill. Din. J. Ilm. Pendidik. Dasar. 2019; 11(2): 100–104. Publisher Full Text\n\nHung H-T: Intentional vocabulary learning using digital flashcards. Engl. Lang. Teach. 2015; 8(10): 107–112. Publisher Full Text\n\nWissman KT, Rawson KA, Pyc MA: How and when do students use flashcards? Memory. 2012; 20(6): 568–579. Publisher Full Text"
}
|
[
{
"id": "225663",
"date": "21 Dec 2023",
"name": "Rahmi Ramadhani",
"expertise": [
"Reviewer Expertise Mathematics Education",
"ICT in Teaching and Learning",
"Fliiped Classroom",
"Ethnomathematics",
"Rasch Measurement"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article does not provide clear information about the research procedures used. The author does not clearly explain what the novelty of the research is. This can be seen from the results of previous studies that are not well presented, so gap analysis and gap research are not found in this article. This article also does not explain the position of the research conducted. It appears in the article that this research is the result of a prototype test of the developed application. However, the author did not provide any preliminary information about the previous application development process. This is clearly due to the author not clearly describing the development research process. What developmental research was used? The author does not explain this in the research methods section, so this article does not provide clear information. This study used a questionnaire instrument to see students' responses after using the application. However, the author does not present the instrument analysis technique, what kind of instrument was used, whether it was self-developed or not, then whether it went through the validation process or not. Furthermore, no clear data collection and data analysis techniques are presented. The author only describes the table of indicators. The statistical analysis used is also not clearly described. I see that the author uses descriptive statistical analysis, but in the conclusion, the author states that student responses are positive and effective in improving student understanding. How does the author demonstrate this? The author uses only descriptive analysis with no qualified statistical test. I feel that this research has not found a clear direction due to the very brief interpretation of the research results, I feel that this article is more dominant in describing application development procedures rather than user testing of applications. It would be better if the author would reconsider where this research is actually reported.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "225641",
"date": "11 May 2024",
"name": "Niroj Dahal",
"expertise": [
"Reviewer Expertise --"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe title of the paper must be revisited and made more catchy for the readers.\nThe research contributions of the paper should be articulated more clearly. The abstract does not seem to properly convey the rigor of the research. The abstract could become much better if rewritten to state clearly the contribution of this study to the field as well as the gap this study intends to address in the field. The abstract could be much better if it properly introduced the study from a research standpoint. Also, the main findings could be stated more clearly in the abstract.\nIntroduction and literature review The introduction section would read better if the following were better stated and explained:\n(1) focus of research conceptual/theoretical framework, including relevant literature review studies that were used to conduct this research study\n(2) The introduction section must explain without any ambiguity why there was a need for this research, what research gap(s) it addresses, and how it contributes to the body of knowledge. In addition, it could explain the benefits of the study to the research and how and why the research advances knowledge in the field. In short, the importance and justification for the study need to be better articulated.\nLiterature Review\nSources are out of date. More recent studies should be included. Also, it should lead up to the research questions in a logical manner. Adding additional sources/references that could speak to the importance of the study will help to strengthen this section. The literature review is deficient in its addressal of the research gap and research model. It needs to be rewritten with a focus on the quality of the content. The theoretical background presentation could be improved by incorporating clarity and additional evidence regarding recent studies. The vague nature should be eliminated. It could be extended and expanded by including additional theoretical and empirical literature that supports the importance of the study. The literature review section could be improved by adding references to the theoretical framework underpinning the study and including a discussion of theories pertaining to learning and knowledge assimilation. There are not enough studies from around the world.\nPlease take the support of the theoretical framework for your study.\n\nMethodology\nThe methodology section needs more details, several clarifications, and, overall, a complete revision. Please consider rewriting using the feedback provided below.\nThe description of the methodology is not clearly presented and is scattered throughout the article. To make this section stronger, the methodology should be grounded in a theoretical or conceptual framework.\nThis section could be improved if the research questions are presented clearly and without ambiguity, and then the methods used for the collection and analysis of data are explained with respect to the research questions.\nThe methodology section should recognize and discuss aspects pertaining to the generalizability of the results in the phenomenum. Though the submission covers an interesting topic, the research questions and almost all the sections need to be revised to conform to the standards of rigorous research.\nThe methodology section could be improved by incorporating greater rigor into the results and discussion.\n\nResults and Discussion\nThis section needs to be rewritten, keeping in mind the research questions. The value of the research to the academician and the practitioner should be expressed in an unambiguous manner. Based on the concerns expressed on the manuscript, it is recommended that the authors conduct further data analysis. This will improve the paper and may result in more findings. Making the findings less contextualized and more informative for the readers is recommended.\nLikewise, improve the discussion to better ascertain what is unique / novel about your findings. This section could be improved by explaining in detail how the article contributes to new knowledge in the domain. Evidence from published research studies should be tied into the new contributions in the discussion section. This section could be improved by discussing the findings with reference to the theoretical framework used. To improve readability, it is recommended that the discussion section be separated into paragraphs with themes based on the paper research questions and preceding suggestions.\n\nConclusion\nThe conclusion section is currently a repeat or rehash of the preceding sections and needs to be rewritten to improve it, keeping in mind the following suggestions:.\nUpdate the conclusion to include the newly formulated theoretical contributions\nMention the limitations of the study in greater way and prospects for future research.\nSummarize the key results in compact form and re-emphasize their significance.\nSummarize how the article contributes to new knowledge in the domain.\nThis conclusion could be worded in such a manner as to emphatically motivate the academic community to get down to actionable, practical, engaged scholarship.\n\nReferences and Citation\nSupport your arguments with the most relevant literature.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-636
|
https://f1000research.com/articles/11-803/v1
|
19 Jul 22
|
{
"type": "Review",
"title": "Expert opinion on the habit forming properties of laxatives in patients with constipation",
"authors": [
"Avinash Balekuduru",
"Manoj Kumar Sahu",
"Manoj Kumar Sahu"
],
"abstract": "Constipation is a commonly reported disorder in many patients. Constipation treatment using laxatives on a regular and long term basis can lead to patient dependence, especially among the elderly. However, there is scanty data on the habit-forming potential of laxatives in Indian constipated patients. This review has explored literature evidence and expert opinion on patients’ experience regarding habit-forming attributes of stimulant and osmotic laxatives. Additionally, structured face-to-face discussions were conducted with 2 key opinion leaders to understand their clinical experience on the habit-forming aspects stimulant and osmotic laxatives in patients with constipation. Based on literature evidence, lactulose is not known to lead to any habit-forming behaviors in patients. Furthermore, experts pointed out that dependence on stimulant laxatives is common, but not on osmotic laxatives, and emphasized that milk of magnesia is not habit forming. In conclusion, no habit-forming characteristics or dependence was observed with the use of osmotic laxatives in India. Nevertheless, real-world, studies exploring patient and physician perspectives are warranted to establish the dependence and habit forming attributes of laxatives.",
"keywords": [
"Constipation",
"habit forming laxatives",
"treatment dependence",
"stimulant laxatives",
"osmotic laxatives"
],
"content": "Introduction\n\nConstipation is a common functional gastrointestinal disorder. In India, constipation has become a frequent health problem contradicting the popular belief that constipation may be infrequent due to high fiber vegetarian diet and higher frequency of bowel movement.1 According to a meta-analysis of 45 community studies, the global prevalence of constipation is 14%.2 Incidence of constipation is higher among women than men due to slow transit, pelvic floor dysfunction because of hard stool forms, obstetric trauma, and over-reporting.3–6 Among subjects aged >35 years, weekly stool frequency was lower in women than in men.7 It is also reported that with an advancing age, the incidence of constipation increases, specifically after the age of 65 years, with prevalence among the elderly ranging from 24% to 30%.8\n\nConstipation also impacts the quality of life of patients.9 Constipation can be physically and cognitively troublesome for many patients, as identified in several population-based studies, and can interfere with daily living and well-being, particularly in older patients. Moreover, constipation can have a substantial impact on healthcare utilization, resulting in greater economic burden.10 Testing for constipation can cost $6.9 billion, apart from treatment costs, assuming that 2.5 million people are annually evaluated for constipation.10 Furthermore, constipation has a negative impact on employment, work productivity, and physical ability. Findings from a recent National Health and Wellness Survey indicate that patients with constipation have a significantly greater percentage of missed work time and had impairment in daily activities.11\n\nVarious factors, such as delayed colonic transit, visceral hypersensitivity, altered central perception, and abnormalities in sensory/motor function, either independently or in combination, are thought to contribute to the pathophysiology of chronic constipation.12 Primary causes of constipation may be intrinsic impairment of anorectal or colonic function, whereas secondary causes may be related to systemic disease, organic disease, or medications.13\n\nDefecation disorders (DDs), which are a group of anatomical and functional abnormalities of the anorectum, can cause constipation symptoms because of patients’ inability to coordinate the rectoanal, pelvic and, abdominal floor muscles.14\n\nSlow transit can cause constipation as confirmed by colectomy specimens showing decrease in contractile G-proteins and increase in inhibitory G-proteins, corresponding to increase in progesterone receptors. Colectomy specimens also reveal a pan-colonic decrease in the volume of intestinal pace-making cells and interstitial cells of Cajal across the colon.15\n\nUse of certain drugs Certain antihypertensive drugs such as clonidine, ganglionic blockers, and calcium antagonists reduce smooth muscle contractility and can cause constipation.16 Tricyclic antidepressants, oral iron supplements, aluminum-containing drugs such as sucralfate and antacids, and analgesics, such as opiates and cannabinoids, can also cause constipation. Because of their anticholinergic and dopaminergic actions, anti-Parkinson, antiepileptic, and antipsychotic drugs are also known to cause constipation.13\n\nSeveral systemic diseases like parkinsonism, scleroderma, hypercalcemia, hypothyroidism, amyloidosis, multiple sclerosis, depression, diabetes, and eating disorders can be related to constipation.13\n\nManagement of constipation begins with patient education on changes needed in diet and lifestyle, training on toilet habits, and instruction on defecation dynamics. Figure 1 illustrates the algorithm for management of Rome IV functional disorders of chronic constipation.12 Clinical guidelines also suggest daily supplementation with 25-30 g of dietary fibers.17 Intake of dietary fibers was shown to improve stool frequency, but no improvement in stool consistency or painful defecation versus placebo.18 Bowel (habit) retraining is another form of lifestyle modification wherein patients are advised to defecate only when colonic motor activity is highest i.e. when there is an urge to defecate.19 The American Gastroenterological Association (AGA) Guidelines suggest gradual increase in fiber intake along with use of an osmotic agent such as milk of magnesia or polyethylene glycol (PEG) to manage constipation. Depending on the stool consistency, the next step in the treatment pathway may include supplementation with a stimulant laxative such as bisacodyl or glycerol suppositories.20 In a randomized, clinical trial involving patients with constipation, daily therapy with 17 g of PEG for 14 days significantly improved bowel movement frequency when compared with placebo treatment.21 Traditional therapies such as lactulose and psyllium have shown improvement in symptoms of constipation,22 but scare evidence is available on the use of other common agents, such as bisacodyl, milk of magnesia, senna, and stool softeners. Furthermore, long-term laxative use has been known to cause cathartic colon.23\n\nPEG, polyethylene glycol.\n\nFor patients with suspected contributing factors, a course of pharmacological treatment with laxatives before further evaluation may be reasonable. Laxatives aid defecation by decreasing stool consistency (softening) and/or artificially or indirectly promoting colon motility, via one or more number of mechanisms.24 A recent review on chronic constipation as per the Indian perspective recommended laxatives as the first line of pharmacotherapy.1 The mechanism of action, duration of treatment and benefits and side effects of the four major categories of laxatives, namely, bulk-forming, osmotic, lubricant, and stimulant are summarized in Table 1.1,21–28 Consensus provided by the Clinical Practice Guidelines of the Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology for the management of chronic constipation suggest that initial treatment should include osmotic laxatives with lifestyle modification.27\n\nIn children, the approach should focus on the nature of the disorder, and the initial therapeutic steps should include toilet training and treatment with laxatives.34 Very few randomized controlled trials (RCTs) have evaluated the efficacy of laxatives in children with constipation despite its high prevalence and chronicity among children.35–37 Among all laxatives, a good body of evidence has been found for PEG, a type of osmotic laxative which is used as first-line treatment in childhood constipation.38\n\nIn adults, management focuses on ruling out an underlying cause and distinguishing between different subtypes of constipation—normal transit, slow transit or evacuation disorder—all of which have significant therapeutic implications. Management of adult functional constipation involves lifestyle interventions, pelvic floor intervention if there is a rectal evacuation disorder, and pharmacological therapy.34 Osmotic laxatives are preferred as the first-line therapy for constipation in adult patients as well.9,39 Two placebo-controlled studies demonstrated that osmotic laxatives are efficacious in increasing stool frequency. If symptoms persist, stimulant laxatives are recommended in clinical guidelines.9,39\n\nIn elderly patients, treatment needs to be tailored according to patients’ medical history (comorbidities), mobility, level of independence, cost of therapy, and potential adverse effects.9 Bulk-forming agents such as soluble fiber supplements have shown improvement in constipation in elders and should be regarded as the first-line treatment among them.40 The inclusion of osmotic laxatives should be explored as a next step in patients who are not responding to bulk-forming laxatives alone. If patients have no bowel movements for two to three days, stimulant laxatives can be prescribed as rescue medications.41\n\nWhile laxatives can be very effective in the acute settings, their long-term use can lead to tolerance (i.e., need for higher doses to maintain the desired response) and eventually habituation (i.e., reduction or disappearance of laxative response). Both these responses are induced by damage to the colon or an adaptive mechanism that counteracts the laxative effect on motility or secretion.42 Furthermore, satisfaction with laxatives can be suboptimal because of limited efficacy, non-specific response not targeting the underlying pathophysiology, or association with undesirable side effects.43\n\nStimulant laxatives, have strong laxative activity and can produce adverse effects if used for longer periods of time. Stool softeners and bulk-forming laxatives are relatively mild and cause fewer adverse effects. Patients using laxatives should be cautioned about the risks associated with long-term use and about the need to consult a physician if laxative treatment effective after one week.44\n\nBulk-forming laxatives act by increasing the volume and softness of feces by absorbing water in the intestine, thereby promoting dilation of the intestinal wall and enhancing propulsive motor function. This group consists of natural or synthetic polysaccharides.45 These agents demonstrate no systemic effects, and the major concern is obstruction of the esophagus, stomach, small intestine, or colon when ingested without fluid. However, these agents are recommended for long-term use.46\n\nOsmotic laxatives act by drawing water into the intestinal lumen because of presence of poorly absorbable substances. The most commonly used osmotic laxatives are ‘milk of magnesia’ (magnesium hydroxide), lactulose, and PEG. Saline laxatives such as citrate salts and magnesium preparations have been shown to release cholecystokinin, which causes accumulation of fluid and electrolytes in the gut lumen and promotes small bowel and perhaps colonic transit.46 Kinnunen et al. compared the efficacy of magnesium hydroxide and bulk-laxatives in elderly, long-stay patients and found that bowel habits were more frequent and stool consistency was normal in patients receiving magnesium hydroxide versus bulk-forming laxative.47 Experts and clinicians support the use of magnesium salt for the management of mild to moderate chronic constipation, although there have been no RCTs demonstrating its efficacy.48 Because magnesium is renally excreted, it is not recommended in patients with renal insufficiency. Lactulose is a non-absorbable synthetic disaccharide that is classified as an osmotic laxative. It is the standard of care treatment for constipation against which newer agents are evaluated for efficacy and safety.22 Lactulose was found to significantly improve stool frequency in patients with functional and opiate-associated constipation.49–51 Another osmotic disaccharide laxative lacitol was found to significantly increase weekly stool frequency and consistency as compared to baseline.52 Furthermore, lactulose does not cause habituation or rebound constipation or withdrawal symptoms when discontinued.51 Despite the fact that no head to head trials have compared the two types of laxatives, most clinicians prefer osmotic laxatives as the first-line treatment.27\n\nLubricant laxatives also known as stool softeners, ease defecation due to their surfactant effect. Non-reabsorbable oils and oils that are very difficult to reabsorb such as paraffin, are included in this group.45 Prolonged use of paraffin may induce malabsorption of fat soluble vitamins, and it is recommended only in special circumstances, such as in some cystic fibrosis patients. Also, lipoid pneumonia may occur if the agent is aspirated, so it should not be used in debilitated patients or just before bedtime. Chronic use of paraffin decreases the absorption of fat-soluble vitamins (A, D, E, and K).53 Because of these side effects, lubricating laxatives are considered obsolete; however, they remain significant agents for the treatment of constipation in patients needing palliative care.45\n\nStimulant laxatives such as bisacodyl, cascara, senna, and sodium polystyrene sulfonate (SPS) improve intestinal secretions and motility by stimulating the myenteric and the Auerbach plexuses. They also decrease water absorption from the intestinal lumen. These laxatives are mostly used as rescue therapy in the absence of bowel movements for three days.54 The efficacy of bisacodyl and SPS for the treatment of chronic constipation have been studied in two clinical trials, and in both the studies, the mean number of complete spontaneous bowel movements increased per week as compared to placebo.55,56 Bisacodyl has gained popularity as preparation for diagnostic procedures and intermittent use for this purpose is acceptable. Stimulant laxatives do not appear to cause rebound constipation or tolerance on discontinuation or injury to the colon upon persistent use.57 Despite its availability for decades, the use of stimulant laxatives is hindered because of its safety, tolerability and lack of sufficient trials supporting its efficacy.\n\nProkinetic and prosecretory agents: This class of drugs includes prucalopride and lubiprostone.19 Prucalopride works on the serotonin receptors (5-hydroxytryptamine; 5-HT). It is a high-affinity, highly selective 5-HT4 agonist that promotes colonic motility and transit.58 Clinical trials have shown that prucalopride significantly reduced constipation-related symptoms, improved bowel function, and enhanced patient satisfaction and quality of life.59 The most common adverse effects associated with this drug are headache, abdominal pain or cramps, nausea, and diarrhea, all of which usually occur early after treatment initiation.60 Lubiprostone is a prosecretory agent that causes chloride secretion into intestine by opening the chloride channel protein two.61 Lubiprostone increases spontaneous bowel movements within 24 to 48 hours following the initial dose. The most frequent dose-dependent adverse effects of lubiprostone are headache nausea, and diarrhea.62\n\nThe ubiquitous availability of laxatives, combined with their relatively low cost, increases their potential for abuse and misuse. Due to the length of time of the abuse maintained, habit forming properties, and daily dose of laxatives, degenerative changes can occur and may lead to serious impairment of coordinated peristalsis of the gut. This impairment may lead to initial functional disorders of intestinal transport mechanism that may develop into acquired hypoganglionosis.\n\nAs prolonged treatment of constipation may be required, a laxative must be carefully chosen. It should have a gentle effect, with no systemic activity, no side effects like cramping or salt depletion, and no contraindications, and it must be neither be habit forming nor toxic.51 As a bowel regulator, a laxative should be non-habit forming, non-toxic, have a gentle action, and should not have side effects such as abdominal cramps or diarrhea.63\n\nBulk-forming laxatives increases the fecal mass by stimulating peristalsis. Bulk-forming laxatives are more appropriate for those patients with small hard stools, but are not suitable for patients that require an immediate relief from constipation as they take time to increase the fecal mass. These laxatives are mainly prescribed for patients with uncomplicated constipation, that have normal intestinal motility and where it is impractical to increase dietary intake of fiber any further.64 Bulk-forming laxatives are most importantly non-habit forming.65\n\nOsmotic laxatives such as PEG and milk of magnesia draw water into the stool resulting in more frequent and softer stools, which makes it easy to pass bowel movements.66 Osmotic laxatives like lactulose demonstrate their action by increasing osmotic pressure, volume, and peristalsis and decreasing colonic transit time.67 Moreover, osmotic laxative preparations like lactulose have demonstrated a persistent carry over effect. Return to normal bowel function is easier with lactulose, and habituation is less likely to occur with its use.63 Most studies have reported the common side effects that occur with use of osmotic laxatives; however, habit forming property has not been reported as one of the side effects. However, there is limited data reported in literature about the non-habit forming characteristics of osmotic laxatives.\n\nLubricant laxatives act by reducing the absorption of water and softening the stool, thus allowing easier passage of stools when given orally or rectally.68 Liquid paraffin is popular for treating constipation primarily because of its ease of titration and tolerability.69 Long-term use of lubricant laxatives reduces absorption of fat-soluble vitamins can potentially result in substantial deficiencies.70 Furthermore, the risk of developing colorectal cancer as a result of chronic use of laxatives should also be considered.71 The prevalence of constipation among the elderly is as high as 50%, which can increase to 74% in nursing home residents using daily laxatives.72–74 In these patients, laxatives treatments often precipitate loose stools and incontinence that can result in diarrhea of unknown etiology. There is no clinical evidence, however, that can confirm the habit forming attribute of lubricant laxatives.\n\nRegular use of stimulant laxatives can cause dependency and cathartic colon albeit there is no direct evidence to support this claim.75 Prolonged use of stimulant laxatives leaves users prone to drug dependence, malabsorption, and electrolyte imbalance, and can damage the enteric nervous system, weakening colonic strength and even giving rise to melanosis coli. Moreover, long-term use of stimulant laxatives can damage the myenteric plexus, reducing responsiveness of the colon to intestinal contents and weakening colonic motor function. It is even possible to lose the ability to defecate spontaneously, a condition known as “laxative colon.” Though powerful and fast-acting, stimulant laxatives are not currently recommended for long-term use by elderly patients due to the adverse reactions, and only short-term or intermittent use is advised slow transit constipation should be treated with bulk-forming or osmotic laxatives.76 Cathartic colon though observed in some chronic users of stimulant laxatives, it is unclear whether this effect is related to their prolonged use.33\n\nAlthough correction of faulty bowel habits and a change in dietary regimen is helpful in many cases of constipation, some patients cannot easily adapt to prescribed regimens or in some patients, no desired effect is obtained. In such patients, effective bowel regulation without the use of drastic laxatives is necessary. There is limited data reported in the literature about the habit forming characteristics of lubricant laxatives.\n\nAs limited literature exists on dependence and habituation associated with laxative use, we garnered real-world experience on the prevalence of constipation, its treatment, and habit-forming attributes of various classes of laxatives. We observed that acute constipation is common in Indian clinical practice with an average duration of <three months. The treatment approach includes exercise, patient education on scheduled toileting and bower retraining, and pharmacotherapy with osmotic laxatives, stool softeners or bulk-forming agents for a duration of 2-8 weeks depending on patient profile. Amongst the various laxative classes, dependence was observed to be rare in acute conditions, but it is observed with stimulant laxatives upon chronic use.\n\nConsistent with literature, we did not observe laxative abuse or habit-forming attributes with osmotic laxatives. Among the osmotic laxatives, we believe that milk of magnesia is not habit forming in acute conditions because it does not cause bowel contraction, given that it elicits it mechanism of action via osmosis i.e. increasing water content in the intestines thereby facilitating peristalsis. This increased water content liquefies the stools for easy defecation. Thus, degeneration of ganglia plexus, which is the primary pathophysiology associated with dependence and abuse, is not likely with milk of magnesia, thereby explaining the absence of habituation with this laxative. However, we recommend that caution should be exercised when recommending milk of magnesia in patients with renal failure and in cases where long-term treatment may be warranted, considering the potential for hypomagnesemia, hypophosphatemia, and secondary hypocalcemia.\n\nLiquid paraffin as a lubricant laxative and stool softener in acute constipation is not habit forming because it does not cause the bowel to contract or spasm and provides a smooth surface for easy passage of stools.69,77 Drugs that irritate the mucosa in the long-term cause degeneration of ganglia plexus and can cause abuse/dependence.78 Unlike certain other laxatives, neither milk of magnesia, nor liquid paraffin causes flatulence or bloating and can be beneficial in patients with fissures and hemorrhoids. In patients suffering from bloating or ascites, milk of magnesia can act as a stool lubricant on account of its osmotic effect. Moreover, liquid paraffin is not associated with abdominal cramps, diarrhea, or electrolyte disturbances. Considering the fast onset of action of milk of magnesia (0.5-six hours) and the relatively long duration of action of liquid paraffin (eight-ten hours), we believe that a combination of these laxatives can provide fast and sustained action, thereby making it a treatment of choice in clinical practice.\n\n\nConclusion\n\nIn summary, habit-forming properties are observed in patients with constipation upon use of stimulant laxatives, but not with osmotic laxatives such as milk of magnesia or lubricant laxatives such as liquid paraffin A combination of milk of magnesia and liquid paraffin may be beneficial in patients with constipation due to the fast and sustained action, absence of habit-forming attributes on account of their respective mechanisms of action, and absence of side effects such as bloating and flatulence. Nevertheless, real world, prospective studies evaluating patient and physician perspectives about dependence and habit-forming properties of various laxative agents are warranted.\n\n\nData availability\n\nNot applicable as this is a review article\n\n\nAuthor contributions\n\nBoth authors conceptualized the review and provided critical feedback on the manuscript draft and revisions to shape the manuscript. Both authors have also approved the final version for submission",
"appendix": "Acknowledgements\n\nThe authors thank PharmEdge for medical writing support.\n\n\nReferences\n\nGhoshal UC: Chronic constipation in Rome IV era: The Indian perspective. Indian J. Gastroenterol. 2017 May 1 [cited 2022 Mar 15]; 36(3): 163–173. PubMed Abstract | Publisher Full Text\n\nSuares NC, Ford AC: Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am. J. Gastroenterol. 2011 Sep [cited 2022 Mar 15]; 106(9): 1582–1591. PubMed Abstract | Publisher Full Text\n\nSong BK, Cho KO, Jo Y, et al.: Colon transit time according to physical activity level in adults. J. Neurogastroenterol. Motil. 2012 Jan [cited 2022 Mar 15]; 18(1): 64–69. PubMed Abstract | Publisher Full Text\n\nDegen LP, Phillips SF: How well does stool form reflect colonic transit? Gut. 1996 [cited 2022 Mar 15]; 39(1): 109–113. 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Publisher Full Text\n\nRichard L, Baker L: Constipation: Part 2-management and potential pitfalls. J. Mod. Pharm. 2000.\n\nGordon M, Macdonald JK, Parker CE, et al.Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane Database Syst. Rev. 2016 Aug 17 [cited 2022 Mar 31]; 2016(8). Free Full Text\n\nKarakan T, Tuohy KM, Janssen-van SG: Low-Dose Lactulose as a Prebiotic for Improved Gut Health and Enhanced Mineral Absorption. Front. Nutr. 2021 Jul 27; 8: 408.\n\nXing JH, Soffer EE: Adverse effects of laxatives. Dis. Colon Rectum. 2001 [cited 2022 Apr 5]; 44(8): 1201–1209. Publisher Full Text\n\nSharif F, Crushell E, O’Driscoll K, et al.: Liquid paraffin: A reappraisal of its role in the treatment of constipation. Arch. Dis. Child. 2001; 85(2): 121–124. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKumar V, Yoselevitz S, Gambert SR: Laxative use and abuse in the older adult: Part II. Clin. 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}
|
[
{
"id": "162774",
"date": "17 Feb 2023",
"name": "Eamonn M. M. Quigley",
"expertise": [
"Reviewer Expertise GI motility",
"FGIDs",
"microbiome."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an important topic - patients often voice concerns that they will become \"addicted\" to treatments for constipation. However, this review has number of problems:\n1. Far too much of the review is taken up with background information on constipation, in general. The focus should be on the issue of dependence.\n2. I would contend that there is no good evidence that laxative injure colonic nerve or muscle - the authors mention this but do not provide evidence to support it. Usually statements like this are based on the study by Barbara Smith from decades ago which has been widely debunked.\n3. Little or no evidence is provided to support the conclusions regarding whether some laxatives induce dependence or not. These statements must be rigorously supported.\n4. I really do not see the role of two expert opinions here. If they are a part of the writing process why not just include as authors and leave it as that. We are now in the era of evidence-based and not eminence-based medicine.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? No\n\nAre all factual statements correct and adequately supported by citations? No\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? No",
"responses": [
{
"c_id": "9691",
"date": "29 Nov 2023",
"name": "Avinash Balekuduru",
"role": "Author Response",
"response": "Comment #1: Far too much of the review is taken up with background information on constipation, in general. The focus should be on the issue of dependence. Response: We thank the reviewer for this suggestion. A lot of the background information has been removed and a discussion has been added on dependence just before the section on “Habit-forming properties of laxatives”. Comment #2: I would contend that there is no good evidence that laxative injure colonic nerve or muscle - the authors mention this but do not provide evidence to support it. Usually statements like this are based on the study by Barbara Smith from decades ago which has been widely debunked. Response: The following additional references have been included on the potential of laxatives to cause colonic nerve or muscle injury. Muller-Lissner SA, Kamm MA, Scarpignato C, Wald A. Myths and misconceptions about chronic constipation. Am J Gastroenterol. 2005;100(1):232-42. doi: 10.1111/j.1572-0241.2005.40885.x. Joo JS, Ehrenpreis ED, Gonzalez L, Kaye M, Breno S, Wexner SD, et al. Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited. J Clin Gastroenterol. 1998;26(4):283-6. doi: 10.1097/00004836-199806000-00014. Riemann JF, Schmidt H, Zimmermann W. The fine structure of colonic submucosal nerves in patients with chronic laxative abuse. Scand J Gastroenterol. 1980;15(6):761-8. doi: 10.3109/00365528009181527. Comment #3: Little or no evidence is provided to support the conclusions regarding whether some laxatives induce dependence or not. These statements must be rigorously supported. Response: The following text has been included with the support of above references on the potential of laxatives to cause dependence: Habituation or tolerance is a common concern with the long-term use of laxatives. Habituation implies a reduction or disappearance of laxative response, while tolerance refers to the need to increase laxative dose to achieve the required result [39]. The habit-forming property of laxatives is most commonly studied in chronic use of stimulant laxatives like anthraquinones, sennoside and bisacodyl [40, 41]. Due to the action on enteric nerves, it is often a matter of concern that there may be irreversible damage to the nerves on long-term use of these laxatives [42]. Joo et al investigated the impact of stimulant laxatives on damage and change in the enteric nerves and musculcature by observing changes following barium enema given to two groups of subjects, one ingesting stimulant laxatives (Group 1) and the other not (Group 2). Loss of haustral folds was observed in 27.6% of subjects in group 1 and no subjects in group 2 (p<0.005). This was particularly observed in patients who regularly used bisacodyl, phenolpthalein, senna, and casanthranol. The authors concluded that chronic use of stimulant laxative resulted in anatomic changes in the colon, which suggests neuronal injury or damage to colonic musculature [40]. Reimann et al have also studied the ultrastructural changes occurring as a consequent of long-term use of laxatives. Colonic biopsies from patients using stimulant laxatives like bisacodyl and anthraquinone derivates demonstrated submucosal nerve damage. There was a significant increase in the axonal area along with a reduction of neurotubules. Since a well-functioning enteric nervous plexus is required for having normal gut motility, it was concluded that such alterations in the nerves may be correlated to the alteration in gut motility in patients with long-term laxative abuse [41]. However, there is very limited evidence on whether laxatives cause any habituation or tolerance and specifically which classes of laxatives exhibit this effect. Moreover, the amount at which a stimulant laxative is damaging is not yet explored. In the next section of this review, we summarize the evidence available on the habit-forming properties of different laxative classes. We hope these statements are sufficient to support the conclusions of the review article. Comment #4: I really do not see the role of two expert opinions here. If they are a part of the writing process why not just include as authors and leave it as that. We are now in the era of evidence-based and not eminence-based medicine. Response: Both the experts are authors on the paper. The title of the article has been revised as follows: Habit-forming properties of laxatives for chronic constipation: A review"
}
]
}
] | 1
|
https://f1000research.com/articles/11-803
|
https://f1000research.com/articles/11-847/v1
|
28 Jul 22
|
{
"type": "Systematic Review",
"title": "Measurement of speech in individuals with selective mutism: A systematic review",
"authors": [
"Yuria Toma",
"Soichiro Matsuda",
"Soichiro Matsuda"
],
"abstract": "Background: The main characteristic of selective mutism (SM) is the failure to speak in specific social situations. Thus, assessing speech across social contexts is important for confirming a diagnosis of SM and for differentiating it from other disorders. The purpose of this review was to organize how the core symptom of SM, a lack of speech in specific social situations, has been assessed in previous studies. Methods: A systematic search of articles was conducted in three databases, Web of Science, PsycINFO, and PubMed and reviews of surveys or experimental studies that reported empirical data on individuals with SM were performed. We excluded review, qualitative, epidemiological, and intervention studies. The study summarized the diagnostic criteria, methods of confirming SM diagnosis, distinction of SM from other disorders, and methods of speech assessment. Results: A total of 447 articles were screened, where 60 articles were considered eligible. The results demonstrate that different interviews and questionnaires were used to establish the diagnosis of SM. However, the majority of interviews and questionnaires lacked validation. Only two (2/60) articles used validated methods of speech assessment to confirm SM diagnosis. Moreover, a consensus was lacking on the assessment method for differentiating SM from other disorders across studies. Specifically, 17 studies measured speech and are not intended for diagnosis. The majority of studies (16/17) used the questionnaire to assess the severity of the SM condition, and only one study conducted behavioral observation. Assessment methods based on the measurement of speech in real-life situations for individuals with SM were not established. Conclusion: We have the limitation that we did not review intervention studies. However, this systematic review revealed the problem that speech assessment methods for surveys or experimental studies of SM were not established. Future studies should establish methods of speech assessment across social situations to assess SM symptoms.\n背景：場面緘黙の主要な特徴は特定の社会的状況における発話の欠如である。したがって，場面緘黙の診断確定，場面緘黙と他の障害との鑑別のため，異なる社会的状況での発話評価が重要である。しかしながら，場面緘黙児・者の発話評価手法は未だ確立されておらず，直接行動を観察する評価手法は少ない。更に，異なる社会的状況における場面緘黙児・者の発話の評価方法について系統的なレビューを行った研究はこれまでにない。本システマティック・レビューの目的は，先行研究において，場面緘黙の主症状である特定の社会的状況における発話の欠如がどのように評価されてきたか，整理することだった。 方法：Web of Science，PsycINFO，PubMedの3つのデータベースを使用し，2020年1月28日に系統的検索を行った。場面緘黙児・者を対象とした実証データを報告した調査・実験研究をレビューの対象とした。展望論文，質的研究，疫学研究，介入研究は除外した。診断基準，場面緘黙診断確定手法，場面緘黙と他の障害との鑑別手法，発話評価手法について整理した。 結果：合計447編の研究についてスクリーニングを行い，採用基準に合致した研究は60編だった。場面緘黙診断を確定するため，様々な面接や質問紙が使用されていた。しかし，多くの面接や質問紙は妥当性が検証されていなかった。場面緘黙診断確定に関して妥当性検証済みの発話評価手法を用いた研究は2/60編のみだった。また，場面緘黙と他の障害を鑑別する評価手法は研究間で一致していなかった。17編の研究は，診断確定以外の目的で発話を測定していた。そのほとんどの研究（16/17編）で場面緘黙の重症度を評価するため，質問紙が使用されており，行動観察を行った研究は1編のみだった。実生活での発話測定に基づく場面緘黙児・者の評価手法は確立されていなかった。 結論：本研究は，介入研究をレビューしていないという限界がある。しかし，本研究によって，場面緘黙の調査・実験研究において発話評価手法が確立されていないという問題が明らかになった。今後の研究では，場面緘黙診断確定ため，また，場面緘黙と他の障害との鑑別のため，異なる社会的状況における発話評価手法を確立する必要がある。",
"keywords": [
"selective mutism",
"anxiety disorder",
"neurodevelopmental disorder",
"systematic review",
"assessment",
"speech"
],
"content": "I. 序論\n\n場面緘黙 (Selective Mutism) は，「他の状況で話しているにもかかわらず，話すことが期待されている特定の社会的状況（例 : 学校）において話すことが一貫してできない」 (American Psychiatric Association, 2013 髙橋・大野監訳，2014, p.193) ことによって特徴づけられる，不安症の一つであり，その有病率は 0.03-0.79% である (Driessen, Blom, Muris, Blashfield, & Molendijk, 2020)。ある特定の社会的状況において話す能力がある場合に限り，場面緘黙の診断が下されるため，特定の社会的状況に発話の障害が限定されないコミュニケーションの障害（e.g., 言語症，語音症，小児期発症流暢症，社会的コミュニケーション症などのコミュニケーション症，自閉スペクトラム症，知的能力障害などの神経発達症，統合失調症やその他の精神病性障害）とは区別される。Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) において，場面緘黙は不安症群に位置づけられているが，不安症群内の他の障害（特に社交不安症）との鑑別や，他の障害群である神経発達症群の自閉スペクトラム症等との鑑別方法が確立されていないことが指摘されている (Driessen et al., 2020; Steffenburg, Steffenburg, Gillberg, & Billstedt, 2018)。\n\n場面緘黙とその他の障害の併存についても，これまで数多く指摘されてきた。場面緘黙と社交不安症，自閉スペクトラム症の症状の併存について指摘した先行研究は複数存在しており (Driessen et al., 2020; Steffenburg et al., 2018)，場面緘黙児・者における社交不安症の併存率を調べた22編の研究を対象としたメタ分析では場面緘黙児・者の社交不安症の併存率が，0%-100%までのばらつきを示しており，平均 69% だったことを報告している (Driessen et al., 2020)。社交不安症の特徴である社交場面に対する恐怖は場面緘黙児・者も示すことがあるものの，場面緘黙は，特定状況下での発話の一貫した欠如が診断の基準に含まれている点が社交不安症と異なる。さらに，場面緘黙児・者の 62.9% が自閉スペクトラム症の特徴を有するという報告もある (Steffenburg et al., 2018)。自閉スペクトラム症児・者も社会的コミュニケーションの問題を示すが，場面緘黙児・者では社会的コミュニケーションの障害が特定状況下に限られる点で異なる。以上から，場面緘黙と他の障害との鑑別や，他の障害の併存を同定するためには，異なる社会的状況下での発話評価が重要である。\n\n数十年に及ぶ場面緘黙児・者を対象とした先行研究のほとんどは，様々な質問紙や面接を用いて，社交不安症や自閉スペクトラム症など他の障害との鑑別のため，発話を評価してきた。しかし，質問紙や面接による評価では，複数の社会的状況における発話の生起頻度やその形態に関するデータを直接収集していないため，信頼性に問題があることが考えられる。質問紙や面接の回答は事実そのものではなく回答者の認識であり，回答者の主観的な推論の影響を受けるという問題が指摘されている (Richardson, 2004)。場面緘黙児・者を対象とした研究においては，頑健な手法による，異なる社会的状況における発話の評価が重要である。それにもかかわらず，異なる社会的状況における発話の評価手法についての系統的な整理は，ほとんど行われていない。\n\nこれまで場面緘黙児・者を対象とした研究のシステマティック・レビューでは，介入方法や介入効果に関するものがほとんどだった (Cohan, Chavira, & Stein, 2006; Manassis, Oerbeck, & Overgaard, 2016; 水野・関口・臼倉，2018; Østergaard, 2018; Zakszeski & DuPaul, 2017)。場面緘黙の主症状の評価手法に関する系統的な整理を行った研究は近年出版された (Rodrigues Pereira, Ensink, Lindauer, De Jonge, & Utens, 2021)。Rodrigues Pereira et al. (2021) では場面緘黙のスクリーニング及び診断に用いられたツールに焦点を当て，各ツールの長所・短所について考察を行っている。しかし，先行研究で用いられた診断基準の整理や，他の診断との鑑別がどのように行われたかについての検討はされていなかった。本研究の目的は，場面緘黙児・者を対象とした調査・実験研究において，場面緘黙診断の確定方法や，場面緘黙と他の障害との鑑別手法も含め，発話がどのように評価されてきたかを整理することだった。また，レビュー結果に基づき，異なる社会的状況での発話について，信頼性の高い客観的な評価を行うための課題について考察することも目的とした。\n\n\nII. 方法\n\n優れたリサーチクエスチョンが満たすべき FINER (Feasibility; 実施可能性，Interesting; 科学的興味深さ, Novel; 新規性, Ethical; 倫理性, Relevant; 必要性)の基準 (Hulley, Cummings, Browner, Grady, & Newman, 2013 木原・木原訳，2014, p.19–21) を考慮し，実証的な研究において，場面緘黙児・者の発話はどのように評価されてきたか，をリサーチクエスチョンとした。\n\n英語で記述された場面緘黙児・者を対象とした実証データに基づく調査・実験研究をレビューの対象とした。英語以外の言語で記述された文献，展望論文，質的研究，疫学研究，介入研究は除外した。\n\nレビューの対象とする論文は，システマティック・レビューの方法の国際的規範となっている PRISMA の手順 (Liberati et al., 2009) に従い，選定した。Web of Science，PsycINFO，PubMed の 3 つのデータベースを使用し，論文の検索を行った。論文タイトルを検索対象とし， “selective mutism” OR “elective mutism” を検索キーワードとした。加えて，Web of Science ではドキュメントタイプを article に絞り込み，PsycINFO では Peer Reviewed Journal を条件として絞り込みをした。検索日は 2020 年 1 月 28 日であり，検索日までに出版された論文を対象とした。さらに過去に場面緘黙児・者を対象としたシステマティック・レビュー論文 (Kristensen, 1997; Muris & Ollendick, 2015; Sharp, Sheman, & Gross, 2007) においてレビューされている論文を加えた。レビューの対象とする論文を決定するため，2 名の著者が独立にスクリーニングを行った。1 段階目のスクリーニングとして題目と抄録に基づくスクリーニングを行った。著者間で判断に相違があった論文は2段階目のスクリーニングに含めることとした。2 段階目のスクリーニングとして本文全体に基づくスクリーニングを行った。著者間で判断に相違があった場合には，著者間で協議を行い，最終的にレビュー対象へ含めるかどうか決定した。\n\n情報の抽出と統合は，第一著者が行った上で，第二著者と協議の上，最終的に論文へ含める情報を決定した。本研究では，発話評価手法について概観することを目的としため，発話評価に関する内容として，(1) 診断基準，(2) 場面緘黙診断確定手法，(3) 場面緘黙と他の障害との鑑別方法，(4) その他の発話評価手法，に関する情報を抽出した。(1) 診断基準に関しては，用いられた基準が明記されていた研究数，各診断基準を用いた研究数について調べた。(2) 場面緘黙診断確定方法に関しては，診断を確定するために用いた方法が明記されていた研究数を示し，場面緘黙診断確定を目的として開発された手法について，測定法の種類ごとに用いられた研究数及び用いられた尺度について調べた。(3) 場面緘黙と他の障害との鑑別方法に関しては，場面緘黙群と他の障害群の群間比較研究を対象に，鑑別方法が明記されていた研究数，用いられた測定法の種類及び尺度，場面緘黙と他の障害の併存が認められた場合の群の割り当てについて調べた。(4) その他の発話評価手法に関しては，診断確定以外の目的で発話評価を行った研究を対象に，用いられた測定法の種類ごとに用いられた研究数，用いられた尺度について調べた。\n\n\nIII. 結果\n\nレビューの対象とする論文の選定結果を Figure 1 に示した。データベースによる検索の結果は，Web of Science が 255 編，PsycINFO が 308 編，PubMed が 246 編であった。二重検索を削除した結果，441 編になった。これ以外に過去のシステマティック・レビューの論文 (Kristensen, 1997; Muris & Ollendick, 2015; Sharp et al., 2007) においてレビューされている論文の中から 6 編を加え，合計 447 編となった。447 編の論文について，題目と抄録の内容によってスクリーニングを行った。英語以外の言語で記述された文献 96 編，書籍もしくはチャプター 32 編，レター 17 編，訂正記事1編，展望論文 56 編，質的研究 1 編，介入研究 164 編，疫学研究6編，合計 373 編を除外した。次に，残りの 74 編について本文全体の内容に基づき，スクリーニングを実施した。展望論文2編，質的研究3編，介入研究5編，場面緘黙児・者の実証データを取得していない研究 4 編，合計 14 編を除外した。最終的なレビュー対象の論文は 60 編だった。\n\n医学的診断基準を Table 1 に示した。レビュー対象のうち，使用した医学的診断基準が明記されていた論文は 44/60 編だった。単独で使用された診断基準の内訳は，DSM-5 (3 編)，DSM-IV-TR (7 編)，DSM-IV (25 編), DSM-III-R (2 編)，ICD-10 (3 編) だった。ただし，Cleator and Hand (2001) では，DSM-IV を用いていたものの，診断基準の A–D を満たすことを条件とし，診断基準Eは考慮されなかった。複数の診断基準を用いた研究では，DSM-IVとICD-10 (1 編)，DSM-III-R と DSM-IV (2 編)，ICD-9 と ICD-10 (1 編) の併用が認められた。\n\n診断基準，診断を確定するために用いられたと論文中で記載された測定法，測定法の種類について，出版年の新しい順に示した (Table 2)。場面緘黙の診断確定に用いられた測定法について，記載していた研究は 44/60 編あり，複数の方法の併用や医療記録によって総合的に判断した研究が最も多かった (24 編)。場面緘黙の診断を確定する目的で開発された測定法を使用した研究と，他の目的で開発された測定法を場面緘黙診断確定のために使用した研究があった。場面緘黙の診断を確定する目的で開発された測定法は Table 2 中に太字で示した。測定法の種類については，場面緘黙診断確定を目的として開発された測定法の種類を示した。診断を確定する測定法として面接 (22 編)，質問紙 (7 編)が用いられていた。\n\n場面緘黙の診断確定のために面接を用いた研究のほとんど (14/22 編) で，Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV; Silverman & Albano, 1996) が用いられていた。 ADIS-IVは，DSM-IVの診断基準に基づき，不安症と不安関連症の診断確定を行うための半構造化面接である。保護者をインフォーマントとする ADIS-IV-Parent version (ADIS-IV-P) と子ども本人をインフォーマントとする ADIS-IV-Children version (ADIS-IV-C) がある。ADIS-IV-P/C は Lyneham, Abbott, and Rapee (2007)，Silverman, Saavedra, and Pina (2001)，Wood, Piacentini, Bergman, McCracken, and Barrios (2002) で，一部の障害診断確定に関して妥当性検証は行われていたが，これらの研究では対象者の中に場面緘黙と診断された人々が含まれておらず，場面緘黙診断確定の妥当性は確認されていなかった。ADIS-IV-P は，Yes，No，Other で回答される診断確定のための質問（e.g., 彼または彼女は友人やその他の人々の質問に答えることを拒否しますか，彼または彼女は家庭で家族と一緒にいるときに話しますか）が 8 つ，9 段階で回答される重症度評価のための項目（この問題はあなたの子どもの生活をどの程度妨げていますか）が1つある。質問には，DSM-IVの診断基準 A, B, C に対応する項目が含まれている。診断基準 D （話していないことは，要求される話し言葉，快適な話し言葉の知識の不足によるものではない）に対応する項目は含まれていない。ADIS-IV-C では，場面緘黙の項目は，Screening Questions for Additional Childhood Disorders の中に含まれており，この面接の結果，場面緘黙の可能性が考えられる場合には更に詳細を確認する必要がある。レビュー対象に含まれた ADIS-IV-C を行った研究では，保護者版の ADIS-IV-P も併せて実施されていた。\n\nADIS-IVの他に用いられた診断確定のための面接には，Kinder-Version des Diagnostischen Interviews für Psychische Störungen (Kinder-DIPS; Adornetto, In-Albon, & Schneider, 2008) (3/22 編)，Diagnostic Interview for Children and Adolescents-IV (DICA-IV; Reich, Welner, Herjanic, & Multihealth Systems staff, 1997) (2/22 編)，Parent as Respondent Informant Schedule (PARIS; Klein & Mannuzza, 1992) (2/22 編)，Brief Child and Family Phone Interview (BCFPI; Cunningham, Boyle, Hong, Pettingill, Bohaychuck, 2009) (1/22 編)があった。Kinder-DIPS と DICA-IV は子ども本人と保護者，BCFPI 及び PARIS は保護者をインフォーマントとする。Kinder-DIPS は DSM-IV-TR 及び ICD-10 に，DICA-IV は DSM-IV 及び DSM-III-R，PARIS は DSM-III-R にそれぞれ対応している。Kinder-DIPS，DICA-IV, PARIS はそれぞれ小児精神疾患の診断確定を目的として開発された一方，BCFPI は，感情・行動上の問題を査定する目的で開発された。Kinder-DIPS は Adornetto et al. (2008) で，DICA-IV は Reich (2000) で，BCFPI は Cunningham et al. (2009) で，一部の障害診断確定に関して妥当性検証が行われていたものの，これらの研究では対象者の中に場面緘黙と診断された人々が含まれておらず，場面緘黙診断確定の妥当性は確認されていなかった。PARIS について妥当性を検証した研究は著者らの知る限り，執筆時点で存在しなかった。\n\n場面緘黙の診断確定に用いられた質問紙には，Speech Situations Questionnaire (Cunningham, McHolm, Boyle, & Patel 2004) (5/7 編)とFrankfurt Scale of Selective Mutism (FSSM; Gensthaler, et al., 2020) (2/7 編)の診断尺度があった。Speech Situations Questionnaire は保護者が回答する Speech Situations Questionnaire-P と教師が回答する Speech Situations Questionnaire-T がある (Nowakowski et al., 2011)。Speech Situations Questionnaire-P は，家庭，学校，地域社会での子どもの発話頻度を 3 件法で尋ねる 15 項目の質問紙である。Speech Situations Questionnaire-T は，教室，廊下，運動場など学校内の様々な場所での子どもの発話頻度を 3 件法で尋ねる 7 項目の質問紙である。Speech Situations Questionnaire-P/T について妥当性を検証した研究は著者らの知る限り，執筆時点で存在しない。\n\nFSSM は， 場面緘黙にあてはまるかを評価する診断尺度と場面緘黙の重症度を評価する重症度尺度から構成されている，保護者回答の質問紙である。診断尺度では，10 項目（e.g., 話すことが期待される特定の状況で話していない，家での話し方と外での話し方に明らかな違いがある）について「はい」か「いいえ」で回答を求める。FSSM 診断尺度は Gensthaler et al. (2020) で妥当性検証が行われている。\n\n定型発達群以外の対照群を設定し，群間比較を行った研究 (27 編) では，様々な障害群を対照群としていた。単一の障害で構成される対照群で最も多かったのは社交不安症群 (10/27 編) だった。場面緘黙以外の複数の不安症を対照群として設定した研究(10/27編)も多かった。また，不安障害に限らず，複数の疾患を一つの対照群として設定する研究 (6/27 編) もあった。その他には，全般不安症 (1/27 編)，場面緘黙と自閉スペクトラム症の併存 (1/27 編)，不安症と ADHD の併存 (1/27 編)も対照群として用いられていた。対照群の障害・疾患が不明な研究 (2/27 編) もあった。\n\n対照群を設定した研究では，診断の鑑別方法を記載していた研究が過半数 (18/27 編) だったが，記載していない研究もあった (9/27 編)。社交不安症群を対照群に含む研究 (10 編) では，診断を確定するために半構造化面接 (8/10 編)もしくは質問紙 (2/10 編) が用いられていた。半構造化面接を実施し場面緘黙群と社交不安症群を群分けした 8 編の研究では， Kinder-DIPS，ADIS-IV-C/P， DICA-IVが実施されていた。場面緘黙と社交不安症の併存が認められた場合には，場面緘黙の基準が優先され，場面緘黙群に含まれる手続きを用いた研究が多かった (5/8 編)。残り3編の研究では，両障害が併存した場合の手続きについて記述されていなかった。診断の確定に質問紙を使用した 2 編の研究では，場面緘黙の診断確定のために FSSM，社交不安症の診断確定のために Social Phobia and Anxiety Inventory for Children German Version (SPAI-C; Melfsen, Walitza, & Warnke, 2011) が使用されていた。質問紙を使用した2編の研究では，場面緘黙と社交不安症が併存していた場合，場面緘黙の診断が優先されていた。\n\n場面緘黙以外の不安症群を対照群に含む研究 (10 編) には，半構造化面接のみによって群分けを行った研究が 5/10 編，半構造化面接と質問紙の併用によって群分けを行った研究が 4/10 編，群分けの方法について記載のない研究が 1/10 編あった。半構造化面接のみを行った研究では ADIS-IVが実施されていた (1 編は Parent Version のみ，4 編は Child Version と Parent Version)。半構造化面接と質問紙を用いた研究には C-DISC-IV と Speech Situations Questionnaire を実施した研究が3編，C-DISC-IVと Speech Situations Questionnaire に加えて BCFPI を実施した研究が1編あった。不安症群を対照群とする研究においても，場面緘黙と他の不安症が併存する場合，場面緘黙の診断が優先し，場面緘黙群に含める研究が多かった (7 編)。障害が併存していた場合の手続きについて記載がない研究もあった (2 編)。\n\n場面緘黙と自閉スペクトラム症の併存群と場面緘黙群を比較した唯一の研究では，臨床面接，保護者対象の面接，質問紙 (DSM-IVチェックリスト，保護者または教師回答の質問紙，Autism Spectrum Screening Questionnaire) に基づいて医師が臨床心理士と相談した上で判断していた。対象児の示す症状が場面緘黙か自閉スペクトラム症のどちらかだけで説明できない場合に，2 つの障害を併存していると判断された。\n\n診断確定以外の目的で発話評価を行った研究は 17/60 編あった。診断確定以外の目的で用いられた発話評価の手法を出版年の新しい順に示した (Table 3)。発話評価の方法として質問紙 (16 編)，面接 (1 編)，観察 (1 編) が用いられていた。質問紙の回答者は，保護者 (14 編)，教師 (2 編)，場面緘黙児・者本人 (2 編) だった。保護者回答の質問紙を用いた研究 3/14 編，場面緘黙児・者回答の質問紙を用いた研究 2/2 編では，それぞれの研究オリジナルの質問紙を用いていた。\n\n保護者回答の質問紙 (14 編) には，Selective Mutism Questionnaire (SMQ) (10/14 編)，FSSM の重症度尺度(1/14 編)があった。SMQ は学校，家庭，その他の社会的状況の発話場面の項目 （e.g., たいていの同輩と学校で話す，他の人がいても家で家族と話す，医師や歯科医と話す）における発話頻度を，4 件法で評価する尺度で，Bergman, Keller, Piacentini, and Bergman (2008) により，17 項目について，妥当性検証，標準化が行われている。FSSM 重症度尺度は，学校，家庭，その他の社会的状況における場面緘黙の症状の項目（e.g., あなたの子どもは全般的に同級生と話しますか，見知らぬ人が来ていても家で親しい家族と話しますか，医師と話しますか）についてどの程度あてはまるか，5 件法で評価する尺度である(Gensthaler et al., 2020)。3–7 歳用 (41 項目)，6–11 歳用 (42 項目)，12–18 歳用 (41項目) の 3 種類がある。発話頻度を尋ねる項目の他，活動への参加頻度を尋ねる項目が含まれている。Gensthaler et al. (2020) で妥当性検証が行われている。\n\n教師回答の質問紙 (2 編) では，DortMus-Kita (Starke & Subellok, 2018) (1/2 編) か School Speech Questionnaire(Bergman Piacentini, & McCracken, 2002) (1/2 編) が使用されていた。DortMus-Kita は，園や学校での子どもの発話行動，集団への参加を評価する 17 項目（e.g., 遊び場面で他の子どもに話しかける，先生に声をかけられても黙っている）についてどの程度あてはまるかを，5 件法で評価する質問紙である (Starke, 2018)。Starke and Subellok (2018) により，妥当性検証が行われている。School Speech Questionnaire は，SMQ (Bergman, Keller, Wood, Piacentini, & McCracken, 2001) を基に作成されたものであり，学校での発話頻度を評価する 11 項目4件法の質問紙である (Bergman et al., 2002)。School Speech Questionnaire を使用したレビュー対象の研究 (Bergman et al., 2002) では，項目テスト相関の低かった 2 項目を除外した 9 項目が使用されていた。\n\n面接を行って発話評価をした研究 (Martinez et al., 2015) では，教師を対象とした面接である Teacher Telephone Interview: Selective Mutism and Anxiety in the School Setting (TTI-SM; Tannock, Fung, & Manassis, 2003) の場面緘黙下位尺度を用いていた。TTI-SM の場面緘黙下位尺度は，場面緘黙の症状に関する 15 項目（e.g., たいていの同輩と学校で話す，先生からの問いに答える）について 4 件法で回答を求める電話面接である。発話頻度を尋ねる項目の他，非言語コミュニケーションの頻度，話していないことによる学校成績への影響を尋ねる項目が含まれている。Martinez et al. (2015) により，妥当性検証が行われている。\n\n観察により発話評価した研究 (Edison et al., 2011) では，実験室での場面緘黙児とその保護者の会話場面を録画し，子どもの発話と保護者の発話について観察者が評価した。観察場面は，保護者への教示によって4つのセグメント（e.g., 自由遊び場面）に分けられていた。発話は，1 つの主節，あるいは 1 つの主節に従属節や埋め込まれた節が加わったものを1単位とする T 単位に分割された。子どもの発話は，自発的な発話と保護者への応答に分類され，それぞれ，T 単位の総数が算出された。\n\n\nIV. 考察\n\n研究によって使用された診断基準が異なっており，結果の解釈には注意が必要である。用いられた診断基準には，ICD-9，ICD-10 (World Health Organization, 1993; 中根・岡崎・藤原・中根・針間訳，2008)，DSM-III (American Psychiatric Association, 1980)，DSM-III-R (American Psychiatric Association, 1987)，DSM-IV (American Psychiatric Association, 1994)，DSM-IV-TR (American Psychiatric Association, 2000)，DSM-5 (American Psychiatric Association, 2013) があった。ICD-9 では，精神疾患に起因しない広範かつ持続的な発話の拒否という記述が認められたものの (National Center for Health Statistics, 1980, p.1091)，診断基準について詳細な情報は，著者らの調べる限りでは得られなかった。ICD-9 で “elective mutism: 選択的無言症” は確立された診断カテゴリーとして位置付けられておらず，“313: 児童期と青年期に特殊な感情障害” に含められていた。しかし，ICD-10 では “F94.0: elective mutism: 選択性緘黙”の診断が確立された上，“F94: 小児期および青年期に特異的に発症する社会機能の障害”の主要カテゴリーの下へ位置づけられたことは，ICD-9 と ICD-10 における場面緘黙の扱いが異なっていることを示している。DSM-IV，DSM-IV-TR，DSM-5 の診断基準は同一だが，これらの診断基準以外の診断基準では，社会的状況の種類や症状の持続期間など，それぞれ異なる点が存在している。DSM-III，DSM-III-R では，学校で話せないこと，多くの状況で話せないことが条件になっているが，他の診断基準では，話せない状況が学校である必要はなく，話せない状況が複数である必要もない。DSM-III，DSM-III-R では，症状の持続期間に関する明確な基準はないが，DSM-IV，DSM-IV-TR，DSM-5 では症状が1か月以上，ICD-10 では4週間以上持続することが診断基準に含まれている。言語表現及び言語理解について，ICD-10 では，標準化検査の得点が2標準偏差以内であることが基準として記載されているが，DSMはすべての版において明確な言語能力の基準はない。診断基準が異なる場合，研究で対象とする母集団が異なる可能性があるため，研究間で結果を単純に比較することはできない。個々の研究で用いた診断基準を考慮した上で，個々の研究の解釈や，研究間の比較をする必要がある。\n\n診断基準によって，社会的状況の種類や症状の持続期間などに違いはあるが，話すことができる社会的状況と話すことができない社会的状況の両方があるという点はすべての診断基準に共通していた。どの診断基準を使用する場合であっても，場面緘黙診断確定のためには複数の社会的状況下での発話行動を評価する必要がある。\n\n検査自体の妥当性を高めるためには，場面緘黙診断確定に使用する個々の面接や質問紙の標準化が必要である。診断確定に用いられた手法のうち，場面緘黙診断に関する妥当性が検証されていたのは FSSM のみだったが，FSSM を使用した研究は 60 編中 2 編だけだった。約 97% (58/60 編) の研究は，場面緘黙診断確定について，妥当性が検証されていない手法を用いていたか，診断確定方法についての十分な記載がなかった。標準化手続きを経た妥当性の高い評価手法でないと，妥当性の高い診断確定ができないため，標準化された手法を使用することが必要である。FSSM は原版のドイツ語版において，定型発達群，社交不安症群，内在化障害群（うつ病，限局性恐怖症，強迫症，全般不安症，分離不安症，パニック症特定不能の不安症，適応障害）との弁別能が支持されている (Gensthaler et al., 2020)。今後，他の多くの言語に翻訳され，妥当性検証が行われれば，幅広い地域で場面緘黙の診断確定が可能となるだろう。現在，日本語で使用可能な場面緘黙診断確定方法としては，Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) (Kaufman et al., 2016) が挙げられる。K-SADS-PL は DSM-IV に対応した版までは場面緘黙診断確定の項目は含まれていなかったが，DSM-5 に対応した版では場面緘黙の診断確定ができるようになっており，日本語版の妥当性が支持されている (Nishiyama et al., 2020)。Nishiyama et al. (2020) はサンプルサイズが小さかった(n=4)ため，さらなる検証が必要だが，K-SADS-PL は日本語で使用可能な場面緘黙診断確定面接として有望かもしれない。\n\n面接や質問紙の標準化に加えて，行動観察に基づく評価手法の開発も今後の課題である。質問紙や半構造化面接で扱われている内省的な報告は，実際の行動と乖離する可能性が，これまでの研究で問題点として指摘されている (Baumeister, Vohs, & Funder, 2007)。質問紙や面接だけでなく，行動観察による発話評価を併せて行うことが妥当性の高い診断確定には必要だろう。レビュー対象の論文でも観察を行った研究は少ないながらも存在したが (6/60 編)，それぞれの研究が独自の観察を行っており，場面緘黙診断確定のために確立された観察法はなかった。また，複数の評価指標や情報に基づき，総合的に場面緘黙の診断を下すことを提唱しているガイドライン (Dow, Sonies, Scheib, Moss, & Leonard, 1995) においても，複数の社会的状況下での発話行動の実測については言及されていない。今後の研究では，場面緘黙児・者の発話の観察を含めた評価手法の確立が望まれる。\n\n場面緘黙は他の不安症や神経発達症の併存が多く報告されており (Kristensen, 2000; Steffenburg et al., 2018)，妥当性の高い鑑別方法の確立が今後の課題である。先行研究においても，場面緘黙と他の障害との鑑別方法が確立されていないことが問題点として挙げられている (Driessen et al., 2020; Steffenburg et al., 2018)。本研究の結果，場面緘黙群と他の障害群を比較する研究において，鑑別方法が確立されていないことが明らかになった。場面緘黙診断確定の面接や質問紙の妥当性検証においては，コミュニケーションの問題を示す場面緘黙以外の障害（e.g., 言語症，自閉スペクトラム症）との弁別能の検証が必要である。FSSM は場面緘黙と社交不安症や内在化障害群（うつ病，限局性恐怖症，強迫症，全般不安症，分離不安症，パニック症特定不能の不安症，適応障害）との鑑別については有用性が示唆されている (Gensthaler et al., 2020)。コミュニケーションの障害を示す点で共通している場面緘黙と自閉スペクトラム症等の神経発達症との鑑別についても検証されることが望ましい。場面緘黙以外にも，コミュニケーションの問題が症状として表れる障害（e.g., 言語症，自閉スペクトラム症）は存在するが，場面緘黙は状況によって発話行動が異なる点が他の障害と異なる特徴である。したがって，複数状況下での発話行動の評価をアセスメントに含めることで，他の障害との鑑別が可能になるかもしれない。\n\n他の障害との鑑別が困難な理由として，場面緘黙の病因や行動特徴が場面緘黙児・者間で異なっている可能性や，介入効果が場面緘黙児・者間で共通していないことも影響しているかもしれない。よって，近年のレビュー論文 (Rozenek, Orlof, Nowicka, Wilczyńska, & Waszkiewicz, 2020) でも指摘されているように，場面緘黙は同質性のある (homogeneity) 障害としてではなく，異質性のある (heterogeneity) 障害として概念化していくことが重要かもしれない。場面緘黙児・者内で行動特徴や心理要因を比較・検討した研究が数多く存在することからも，場面緘黙の異質性については検討する価値があるだろう。Hayden (1980) では，病因や緘黙症状の意味によって場面緘黙児についてタイプ分けを行った結果，対象児は，保護者が支配的で保護者との結びつきが強い共生タイプ，自分の声を聞くことに恐怖を示すスピーチ恐怖タイプ，トラウマ体験をきっかけに発症した反応性タイプ，沈黙を武器として使用する受動的攻撃的タイプの4種に分類された。Cohan et al. (2008) では，発話の欠如以外の症状を基に場面緘黙児 についてタイプ分けを行い，対象児は，不安と軽度の反抗を示すタイプ，不安とコミュニケーションの遅れを示すタイプ，不安のみを示すタイプの3種に分類された。Diliberto and Kearney (2018) においても，発話の欠如以外の症状を基にタイプ分けが行われており，中程度の不安・攻撃性・不注意を示すタイプ，重度の不安と中程度の攻撃性・不注意を示すタイプ，軽度から中程度の不安と軽度の攻撃性・不注意を示すタイプの3種に分類された。このように，これまでにも複数のサブタイプに分類できる可能性が示されてきた。さらに，自閉スペクトラム症の症状を併存する場面緘黙児は，そうでない場面緘黙児と比べて，場面緘黙の発症が遅いことや(Steffenburg et al., 2018)，同じ介入プログラムの効果は場面緘黙児内で異なっており，顕著な介入効果があるケースと症状が持続するケースがある (Oerbeck, Stein, Pripp, & Kristensen, 2015; Oerbeck, Overgaard, Stein, Pripp, & Kristensen, 2018)。以上のことから，場面緘黙は異質性のある障害として再度概念化した上で，同質性 (homogeneity) と異質性 (heterogeneity) の両側面から，評価を進めていく必要があるのかもしれない。\n\n場面緘黙の発症に関する遺伝的要因についても，今後さらなる研究が求められる。これまでの研究では，一般人口と比べ，場面緘黙児・者の家族や親戚では，場面緘黙や社交不安症 (Black & Uhde, 1995)，精神疾患 (Brix Andersson & Thomsen, 1998; Steinhausen & Adamek, 1997) を有する割合の高いことが報告されている。また，自閉スペクトラム症との関連が示唆されている contactin-associated protein-like 2-gene (CNTNAP2) の遺伝的多型の 1 種 (rs2710102) が場面緘黙に関連していることも報告されている (Stein et al., 2011)。\n\n2008 年以降，SMQ，FSSM，DortMus-Kita，TTI-SM などの標準化された質問紙や面接が用いられるようになった。SMQ の日本語版である Selective Mutism Questionnaire-Revised (SMQ-R) (かんもくネット，2011) は，現在，妥当性検証が進められており（角田，2021），日本でも標準化質問紙によって場面緘黙児の発話評価が可能になると期待される。しかし，小児・青年を対象とした標準化尺度や面接が作成されてきた一方で，成人を対象に含む標準化質問紙や面接は存在しないことが，本研究によって示された。SMQ は 3-11 歳 (Bergman et al., 2008)，FSSM は 3-18 歳 (Gensthaler et al., 2020)，DortMus-Kita は 3 歳0か月から 6 歳 11 か月(Starke & Subellok, 2018) を対象として標準化されている。SMQ を基に作成された TTI-SM は 6-11 歳を対象として標準化された (Martinez et al., 2015)。小児期や青年期だけでなく，成人期に場面緘黙症状を示すケースもあるため (Ford, Sladeczek, Carlson, & Kratochwill, 1998; Walker & Tobbell, 2015)，成人場面緘黙者の発話を評価する標準化質問紙・面接の作成は今後の課題である。\n\n質問紙や面接による測定だけでなく，複数状況下での実際の発話を定量的に測定する研究が更に必要である。複数状況下での観察を行い，実際の発話を定量的に測定した研究は，レビュー対象の論文のうち，1 編のみだった (Edison et al., 2011)。日常場面の行動を理解するためには，行動を直接観察する方法が適しているという指摘があり (Baumeister et al., 2007)，場面緘黙児・者の発話行動の特徴を明らかにするためには，行動観察が重要である。Edison et al.(2011) では，実験室での複数種類の活動中の保護者との会話を観察し，場面緘黙児の自発的な発話と応答を定量的に評価した。質問紙調査によって場面緘黙児・者は場所，相手，活動によって発話頻度が異なると示されているが (Dummit et al., 1997)，場所，相手，活動による発話行動のを実験的検討は不足している。発話頻度以外の発話行動の特徴についても検討の余地がある。異なる場所での発話行動，異なる相手との発話行動，Edison et al. (2011) では検討されなかった異なる活動中の発話行動など，場面緘黙児・者の発話行動について，未検討の点が数多く残っている。今後は，発話行動に影響する複数の変数(場所，相手，活動など)について，場面緘黙児・者を対象とした実験的な研究を推進していくことが必要だろう。\n\n\nV. 結論\n\n本研究は，調査・実験研究のみを対象としており，介入研究をレビューしていないという限界がある。また，事前にレビュープロトコルが準備されなかったという方法論的課題もあった。しかし，本研究によって，場面緘黙の調査・実験研究において発話評価手法が確立されていないという問題が明らかになった。今後の研究では，場面緘黙診断確定のため，また，場面緘黙と他の障害との鑑別のため，異なる社会的状況における発話評価手法を確立する必要がある。\n\n本論文の研究結果の基礎となるデータはすべて本論文中に示されており，追加のソースデータは必要とされていない。\n\nOpen Science Framework: Measurement of speech in individuals with selective mutism: A systematic review. https://doi.org/10.17605/OSF.IO/ZS36Q (Toma & Matsuda, 2022).\n\n・PRISMA_2020_checklist.pdf (PRISMA2020チェックリスト)\n\n・PRISMA_2020_abstract_checklist.pdf (PRISMA2020抄録チェックリスト)\n\nデータは，Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication) の条件の下で利用可能です。",
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PubMed Abstract | Publisher Full Text\n\nCohan SL, Chavira DA, Stein MB: Practitioner review: Psychosocial interventions for children with selective mutism: A critical evaluation of the literature from 1990–2005. J. Child Psychol. Psychiatry. 2006; 47(11): 1085–1097. PubMed Abstract | Publisher Full Text\n\nCunningham CE, Boyle MH, Hong S, et al.: The Brief Child and Family Phone Interview (BCFPI): 1. Rationale, development, and description of a computerized children’s mental health intake and outcome assessment tool. J. Child Psychol. Psychiatry. 2009; 50(4): 416–423. PubMed Abstract | Publisher Full Text\n\nCunningham CE, McHolm AE, Boyle MH: Social phobia, anxiety, oppositional behavior, social skills, and self-concept in children with specific selective mutism, generalized selective mutism, and community controls. Eur. Child Adolesc. Psychiatry. 2006; 15(5): 245–255. PubMed Abstract | Publisher Full Text\n\nCunningham CE, McHolm A, Boyle MH, et al.: Behavioral and emotional adjustment, family functioning, academic performance, and social relationships in children with selective mutism. J. Child Psychol. Psychiatry. 2004; 45(8): 1363–1372. Publisher Full Text\n\nDiliberto RA, Kearney CA: Anxiety and oppositional behavior profiles among youth with selective mutism. J. Commun. Dis. 2016; 59: 16–23. Publisher Full Text\n\nDiliberto RA, Kearney CA: Latent Class Symptom Profiles of Selective Mutism: Identification and Linkage to Temperamental and Social Constructs. Child Psychiatry Hum. Dev. 2018; 49(4): 551–562. PubMed Abstract | Publisher Full Text\n\nDow SP, Sonies BC, Scheib D, et al.: Practical guidelines for the assessment and treatment of selective mutism. J. Am. Acad. Child Adolesc. Psychiatry. 1995; 34(7): 836–846. PubMed Abstract | Publisher Full Text\n\nDriessen J, Blom JD, Muris P, et al.: Anxiety in children with selective mutism: a meta-analysis. Child Psychiatry Hum. Dev. 2020; 51(2): 330–341. PubMed Abstract | Publisher Full Text\n\nDummit ES, Klein RG, Tancer NK, et al.: Systematic assessment of 50 children with selective mutism. J. Am. Acad. Child Adolesc. Psychiatry. 1997; 36(5): 653–660. PubMed Abstract | Publisher Full Text\n\nEdison SC, Evans MA, McHolm AE, et al.: An investigation of control among parents of selectively mute, anxious, and non-anxious children. Child Psychiatry Hum. Dev. 2011; 42(3): 270–290. PubMed Abstract | Publisher Full Text\n\nFord MA, Sladeczek IE, Carlson J, et al.: Selective mutism: Phenomenological characteristics. Sch. Psychol. Q. 1998; 13(3): 192–227. Publisher Full Text\n\nGensthaler A, Dieter J, Raisig S, et al.: Evaluation of a novel parent-rated scale for selective mutism. Assessment. 2020; 27(5): 1007–1015. PubMed Abstract | Publisher Full Text\n\nGensthaler A, Khalaf S, Ligges M, et al.: Selective mutism and temperament: the silence and behavioral inhibition to the unfamiliar. Eur. Child Adolesc. Psychiatry. 2016; 25(10): 1113–1120. PubMed Abstract | Publisher Full Text\n\nGensthaler A, Maichrowitz V, Kaess M, et al.: Selective mutism: The fraternal twin of childhood social phobia. Psychopathology. 2016; 49(2): 95–107. PubMed Abstract | Publisher Full Text\n\nHayden TL: Classification of elective mutism. J. Am. Acad. Child Psychiatry. 1980; 19(1): 118–133. Publisher Full Text\n\nHeilman KJ, Connolly SD, Padilla WO, et al.: Sluggish vagal brake reactivity to physical exercise challenge in children with selective mutism. Dev. Psychopathol. 2012; 24(1): 241–250. PubMed Abstract | Publisher Full Text\n\nHenkin Y, Feinholz M, Arie M, et al.: P50 suppression in children with selective mutism: a preliminary report. J. Abnorm. Child Psychol. 2010; 38(1): 43–48. 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Klein, NYU Child Study Center, 550 First Avenue, New York, NY 10016);1992.\n\nKlein ER, Ruiz CE, Morales K, et al.: Variations in Parent and Teacher Ratings of Internalizing, Externalizing, Adaptive Skills, and Behavioral Symptoms in Children with Selective Mutism. Int. J. Environ. Res. Public Health. 2019; 16(21): 4070. PubMed Abstract | Publisher Full Text\n\nKristensen H: Elective mutism—associated with developmental disorder/delay. Two case studies. Eur. Child Adolesc. Psychiatry. 1997; 6(4): 234–239. PubMed Abstract\n\nKristensen H: Selective mutism and comorbidity with developmental disorder/delay, anxiety disorder, and elimination disorder. J. Am. Acad. Child Adolesc. Psychiatry. 2000; 39(2): 249–256. PubMed Abstract | Publisher Full Text\n\nKristensen H: Multiple informants' report of emotional and behavioural problems in a nation-wide sample of selective mute children and controls. Eur. Child Adolesc. Psychiatry. 2001; 10(2): 135–142. PubMed Abstract | Publisher Full Text\n\nKristensen H: Non-specific markers of neurodevelopmental disorder/delay in selective mutism. Eur. Child Adolesc. Psychiatry. 2002; 11(2): 71–78. PubMed Abstract | Publisher Full Text\n\nKristensen H, Oerbeck B: Is selective mutism associated with deficits in memory span and visual memory?: An exploratory case–control study. Depress. Anxiety. 2006; 23(2): 71–76. PubMed Abstract | Publisher Full Text\n\nKristensen H, Torgersen S: MCMI-II personality traits and symptom traits in parents of children with selective mutism: A case-control study. J. Abnorm. Psychol. 2001; 110(4): 648–652. PubMed Abstract | Publisher Full Text\n\nLetamendi AM, Chavira DA, Hitchcock CA, et al.: Selective mutism questionnaire: Measurement structure and validity. J. Am. Acad. Child Adolesc. Psychiatry. 2008; 47(10): 1197–1204. PubMed Abstract | Publisher Full Text\n\nLevin‐Decanini T, Connolly SD, Simpson D, et al.: Comparison of behavioral profiles for anxiety‐related comorbidities including ADHD and selective mutism in children. Depress. Anxiety. 2013; 30(9): 857–864. PubMed Abstract | Publisher Full Text\n\nLiberati A, Altman DG, Tetzlaff J, et al.: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J. Clin. Epidemiol. 2009; 62(10): e1–e34. PubMed Abstract | Publisher Full Text\n\nLyneham HJ, Abbott MJ, Rapee RM: Interrater reliability of the Anxiety Disorders Interview Schedule for DSM-IV: child and parent version. J. Am. Acad. Child Adolesc. Psychiatry. 2007; 46(6): 731–736. PubMed Abstract | Publisher Full Text\n\nManassis K, Fung D, Tannock R, et al.: Characterizing selective mutism: Is it more than social anxiety? Depress. Anxiety. 2003; 18(3): 153–161. PubMed Abstract | Publisher Full Text\n\nManassis K, Tannock R, Garland EJ, et al.: The sounds of silence: Language, cognition, and anxiety in selective mutism. J. Am. Acad. Child Adolesc. Psychiatry. 2007; 46(9): 1187–1195. PubMed Abstract | Publisher Full Text\n\nManassis K, Oerbeck B, Overgaard KR: The use of medication in selective mutism: a systematic review. Eur. Child Adolesc. Psychiatry. 2016; 25(6): 571–578. PubMed Abstract | Publisher Full Text\n\nMartinez YJ, Tannock R, Manassis K, et al.: The teachers’ role in the assessment of selective mutism and anxiety disorders. Can. J. Sch. Psychol. 2015; 30(2): 83–101. Publisher Full Text\n\nMcInnes A, Fung D, Manassis K, et al.: Narrative Skills in Children with Selective Mutism. Am. J. Speech Lang. Pathol. 2004; 13: 304–315. PubMed Abstract | Publisher Full Text\n\nMelfsen S, Walitza S, Warnke A: Psychometrische Eigenschaften und Normierung des Sozialphobie und-angstinventars für Kinder (SPAIK) an einer klinischen Stichprobe. Z. Kinder Jugendpsychiatr. Psychother. 2011; 39: 399–407. PubMed Abstract | Publisher Full Text\n\n水野 雅, 関口 雄, 臼倉 瞳: 日本における場面緘黙児への支援に関する検討―2001~ 2015 年の論文を対象として― カウンセリング研究.2018; 51(2): 125–134.\n\nMuchnik C, Roth DAE, Hildesheimer M, et al.: Abnormalities in auditory efferent activities in children with selective mutism. Audiology and Neurotology. 2013; 18(6): 353–361. PubMed Abstract | Publisher Full Text\n\nMuris P, Ollendick TH: Children who are anxious in silence: A review on selective mutism, the new anxiety disorder in DSM-5. Clin. Child. Fam. Psychol. Rev. 2015; 18(2): 151–169. PubMed Abstract | Publisher Full Text\n\nNational Center for Health Statistics: The international classification of disease, 9th revision, clinical modification: ICD-9-CM. Washington, DC:Department of Health and Human Services Publication;1980; Vol. 3. : 1091.\n\nNishiyama T, Sumi S, Watanabe H, et al.: The Kiddie schedule for affective disorders and schizophrenia present and lifetime version (K-SADS-PL) for DSM-5: a validation for neurodevelopmental disorders in Japanese outpatients. Compr. Psychiatry. 2020; 96: 152148. PubMed Abstract | Publisher Full Text\n\nNowakowski ME, Cunningham CE, McHolm AE, et al.: Language and academic abilities in children with selective mutism. Infant and Child Development: An International Journal of Research and Practice. 2009; 18(3): 271–290. Publisher Full Text\n\nNowakowski ME, Tasker SL, Cunningham CE, et al.: Joint attention in parent–child dyads involving children with selective mutism: A comparison between anxious and typically developing children. Child Psychiatry Hum. Dev. 2011; 42(1): 78–92. PubMed Abstract | Publisher Full Text\n\nOerbeck B, Overgaard KR, Stein MB, et al.: Treatment of selective mutism: A 5-year follow-up study. Eur. Child Adolesc. Psychiatry. 2018; 27(8): 997–1009. PubMed Abstract | Publisher Full Text\n\nOerbeck B, Stein MB, Pripp AH, et al.: Selective mutism: follow-up study 1 year after end of treatment. Eur. Child Adolesc. Psychiatry. 2015; 24(7): 757–766. PubMed Abstract | Publisher Full Text\n\nØstergaard KR: Treatment of selective mutism based on cognitive behavioural therapy, psychopharmacology and combination therapy–a systematic review. Nord. J. Psychiatry. 2018; 72(4): 240–250. PubMed Abstract | Publisher Full Text\n\nReich W, Welner Z, Herjanic B, et al.: Diagnostic Interview for Children and Adolescents-IV. Toronto, Ontario, Canada:Multihealth Systems;1997.\n\nReich W: Diagnostic interview for children and adolescents (DICA). J. Am. Acad. Child Adolesc. Psychiatry. 2000; 39(1): 59–66. Publisher Full Text\n\nRichardson JT: Methodological issues in questionnaire-based research on student learning in higher education. Educ. Psychol. Rev. 2004; 16(4): 347–358. Publisher Full Text\n\nRodrigues Pereira C, Ensink J, Lindauer RJ, et al.: Diagnosing selective mutism: a critical review of measures for clinical practice and research. Eur. Child Adolesc. Psychiatry. 2021; 1–19.\n\nRozenek EB, Orlof W, Nowicka ZM, et al.: Selective mutism-an overview of the condition and etiology: is the absence of speech just the tip of the iceberg? Psychiatr. Pol. 2020; 54(2): 333–349. PubMed Abstract | Publisher Full Text\n\nSchwenck C, Gensthaler A, Vogel F: Anxiety levels in children with selective mutism and social anxiety disorder. Curr. Psychol. 2019; 1–8.\n\nSharp WG, Sherman C, Gross AM: Selective mutism and anxiety: A review of the current conceptualization of the disorder. J. Anxiety Disord. 2007; 21(4): 568–579. PubMed Abstract | Publisher Full Text\n\nSilverman WK, Saavedra LM, Pina AA: Test-retest reliability of anxiety symptoms and diagnoses with the Anxiety Disorders Interview Schedule for DSM-IV: child and parent versions. J. Am. Acad. Child Adolesc. Psychiatry. 2001; 40(8): 937–944. PubMed Abstract | Publisher Full Text\n\nSilverman WK, Albano AM: The Anxiety Disorders Interview Schedule for Children (ADIS-C/P) Psychological Corporation. San Antonio, TX:1996.\n\nStarke A: Effects of anxiety, language skills, and cultural adaptation on the development of selective mutism. J. Commun. Dis. 2018; 74: 45–60. Publisher Full Text\n\nStarke, Subellok: DortMuS-Kita: Dortmunder Mutismus-Screening für Kindertageseinrichtungen, 2018 年 2 月 22 日.2018. (2022 年 1 月 7 日閲覧).Reference Source\n\nSteffenburg H, Steffenburg S, Gillberg C, et al.: Children with autism spectrum disorders and selective mutism. Neuropsychiatr. Dis. Treat. 2018; 14: 1163–1169. 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Psychol. 2002; 31(3): 335–342. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic criteria for research. Geneva;Author;1993. 中根 允文・岡崎 祐士・藤原 妙子・中根 秀之・針間 博彦訳 (2008) ICD-10 精神および行動の障害― DCR 研究用診断基準―新訂版.医学書院，175.\n\nYeganeh R, Beidel DC, Turner SM: Selective mutism: more than social anxiety? Depress. Anxiety. 2006; 23(3): 117–123. Publisher Full Text\n\nYeganeh R, Beidel DC, Turner SM, et al.: Clinical distinctions between selective mutism and social phobia: an investigation of childhood psychopathology. J. Am. Acad. Child Adolesc. Psychiatry. 2003; 42(9): 1069–1075. PubMed Abstract | Publisher Full Text\n\nYoung BJ, Bunnell BE, Beidel DC: Evaluation of children with selective mutism and social phobia: A comparison of psychological and psychophysiological arousal. Behav. Modif. 2012; 36(4): 525–544. 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}
|
[
{
"id": "145713",
"date": "16 Aug 2022",
"name": "Shin-ichi Ishikawa",
"expertise": [
"Reviewer Expertise 臨床児童心理学"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n本論文は，場面緘黙児・者に対する評価方法を体系的に展望することを目的としています。著者らが本論文内で指摘しているように，場面緘黙について確立された評価方法が少ないという現状を踏まえると，本展望論文のもたらす情報は臨床的意義が高いと考えます。いくつかのコメントをさせていただきましたので，改稿の参考にしていただければ幸いです。\nメジャーなコメント １．診断基準の変遷について 場面緘黙がDSMやICDのバージョンによって異なる点は理解できました。しかし，それは全ての障害に当てはまるものかと思いますし，ある意味避けようのないことかと思います。もし特定の議論をする際に，許容できる範囲を超えて診断基準間の不統一が問題なのであれば，むしろ１つの基準で診断された研究のみを中心にレビューすべきかと思います。あるいは，たとえばASDや不安症などの変遷と比較しながら，場面緘黙特有の問題があれば論じていただければ意義深いかと思います。\n２．鑑別診断について おそらく場面緘黙は，他の障害と併存することもあるのだと思います。当該の議論には，もしクライエントが２つの障害を同時に持っているとして，①ある特定の障害がマスクしてしまっているケース，②適切に２つ以上の障害の併存を見極めているケース，があるかと思います。加えて，併存症はなく場面緘黙のみ純粋に有しているにもかかわらず，③誤って２つの障害を重複してつけてしまっているケースもあるかと思います（たとえば，場面緘黙と社交不安症）。このあたり，診断にかかる議論を整理して論じていただければと思います。その上で，７ページの結果の箇所は，診断基準自体の不統一性に焦点を当てているのか，それとも場面緘黙自体の特徴から，①や③の鑑別診断の難しさを述べているのか，明確にしていただければと思います。たとえば，本論文のTable 1に従いますと，ICD-10に基づいていればASDとの併存はないけれども，DSM-5であれば，その可能性を含むということは至極当然のように思います。上記の診断基準の変遷と合わせて議論すべき点を整理していただければ幸いです。また，下記３のコメントにも関連するのですが，どのような対象者に対して鑑別診断を試みているのかが，不統一のために議論が整理されづらくなっていると思います。対象者全員が場面緘黙であることが確定しているのであれば，その中から併存診断や鑑別診断をするのは分かりますが， 結果２をみると16研究は医学的診断基準がないとなっています。医学的診断のある研究と質問紙で判定した研究を同質としてシステマティックレビューに含める点は議論が残るかもしれません。そのため，対象となった研究を明確に定義していただくと，このあたりの解釈が分かりやすくなるかと思います。\n３．対象となる研究について 今回対象にしている研究は，場面緘黙を対象としてケースコントロールデザインを用いた観察研究という認識で良いのでしょうか（もしそうであれば，横断，縦断，回顧的などの情報もあると有益かもしれません）。いずれにせよ，選定基準に除外基準はあるのですが，結局どのような論文を含んでいるのかという包含基準が分かりませんでした。たとえば，全ての研究はどこかの段階で場面緘黙の診断プロセスを経ていて，そのことについて「3. 場面緘黙の診断確定に用いられた手法」で整理されており，その他の測定が「5. その他の発話評価手法」ということであれば，そのあたりを論文の選定基準に記載いただければと思います。ただ，そう考えると，コメント２にも関連して，７ページの「診断を確定する測定法として面接(22 編)，質問紙(7 編)が用いられていた。」という結果が少し不思議に思えます。質問紙を用いて“診断”した結果が，本研究の合致基準として適切かどうか，という疑問が残るからです（つまり，アナログ研究の可能性は否定できるのか，という疑問です）。単純に，「3. 場面緘黙の診断確定に用いられた手法」と「5. その他の発話評価手法」は，（本論文で新たに基準を設けているのではなく）各研究で独自に設定している独立変数と従属変数ということなのでしょうか。加えて，介入研究を加えなかった理由を教えてください。頑健なトライアルでは診断基準などを用いて，場面緘黙の対象者を選抜した上で，効果測定のための指標を複数用いていると思いましたので，本研究のレビューの目的に合致するのではないかと考えました。\n４．妥当性について さまざまな評価法について，妥当性がないことを問題として取り上げていますが，その際の妥当性が何を表しているのか具体的に記述いただければと思います。たとえば，質問紙であれば併存的妥当性などを指しているのではないかと推測しますが，診断面接などはどのような妥当性を想定しているのでしょうか。おそらく各評価手法によって，検証すべき妥当性の領域も異なってくるかと思います。また，必要に応じて，信頼性についても加筆いただければと思います。\n５．「5. その他の発話評価手法」について 上記コメント３とも関連しますが，このカテゴリが各論文によるものなのか，本研究での定義に基づいて抽出されたものであるのか，必要に応じて加筆修正をいただければと思います。FSSMのように「3. 場面緘黙の診断確定に用いられた手法」と一部重複があるので，それぞれについて，「4. 情報の抽出と統合」で示していただいている記述に基づいて，本研究での明瞭な定義を示していただければと思います。\nマイナーなコメント ４ページ：２段落で述べている併存率のばらつきがあまりに大きいので，分散等も併記いただいた方が良いかもしれません。 ８ページ：不安「障害」にここはなっています。 11ページ：T単位について追加の説明をしていただけますか。\n以上です。\n\nシステマティックレビューの根拠と目的は明確に示されていますか。 はい\n\n方法と分析について第三者による再現が可能となるよう十分な詳細が提示されていますか。 一部該当\n\n（該当する場合は要回答）統計分析および解釈は適切ですか。 対象外（統計を使っていない\n\n結論はレビューの結果により妥当な裏付けを得ていますか。 はい",
"responses": [
{
"c_id": "8982",
"date": "05 Dec 2022",
"name": "友里亜 藤間",
"role": "Author Response",
"response": "石川先生 査読コメントを下さり誠にありがとうございます。 以下のように加筆・修正を行いました。 １．診断基準の変遷について 診断基準の変遷に触れたのは，発話評価に着目する意義を示すという意図がありました。場面緘黙は診断基準によって一部基準が異なっており，対象としている集団が異なる可能性があります。しかし，状況によって発話行動が異なっており，特定の状況で発話が欠如していることを確認する必要があるという点は共通していました。そのため，どの診断基準に基づいても，場面緘黙症状の評価として，複数状況での発話評価が必要になります。したがって，発話評価手法についてのレビューに関しては，異なる診断基準を使用した研究を対象として問題ないと考えました。 本研究の主目的は，発話評価手法についてレビューすることだったため，診断基準の変遷に関しては，場面緘黙症状の評価に関わる補足的な内容として位置づけました。意図が明確になるように，序論の最終段落および考察１の記述を修正いたしました。 該当箇所 Ⅰ．序論 第4段落 …しかし，他の診断との鑑別がどのように行われたかについての検討はされていなかった。本研究の目的は，場面緘黙児・者を対象とした調査・実験研究において，場面緘黙診断の確定方法や，場面緘黙と他の障害との鑑別手法も含め，発話がどのように評価されてきたかを整理することだった。また，レビュー結果に基づき，異なる社会的状況での発話について，信頼性の高い客観的な評価を行うための課題について考察することも目的とした。以上の目的に関連して，場面緘黙の診断基準についても，その変遷を整理した。 Ⅳ．考察 1. 用いられた医学的診断基準 用いられた診断基準には，ICD-9，ICD-10（World Health Organization, 1993; 中根・岡崎・藤原・中根・針間訳，2008），DSM-Ⅲ（American Psychiatric Association, 1980），DSM-Ⅲ-R（American Psychiatric Association, 1987），DSM-Ⅳ（American Psychiatric Association, 1994），DSM-Ⅳ-TR（American Psychiatric Association, 2000），DSM-5（American Psychiatric Association, 2013）があった。ICD-9では，精神疾患に起因しない広範かつ持続的な発話の拒否という記述が認められたものの（National Center for Health Statistics, 1980, p.1091），診断基準について詳細な情報は，著者らの調べる限りでは得られなかった。DSM-Ⅳ，DSM-Ⅳ-TR，DSM-5の診断基準は同一だが，これらの診断基準以外の診断基準では，社会的状況の種類や症状の持続期間など，それぞれ異なる点が存在している。例えば，DSM-Ⅲ，DSM-Ⅲ-Rでは，学校で話せないこと，多くの状況で話せないことが条件になっているが，他の診断基準では，話せない状況が学校である必要はなく，話せない状況が複数である必要もない。DSM-Ⅲ，DSM-Ⅲ-Rでは，症状の持続期間に関する明確な基準はないが，DSM-Ⅳ，DSM-Ⅳ-TR，DSM-5では症状が1か月以上，ICD-10では4週間以上持続することが診断基準に含まれている。言語表現及び言語理解について，ICD-10では，標準化検査の得点が2標準偏差以内であることが基準として記載されているが，DSMはすべての版において明確な言語能力の基準はない。診断基準が異なる場合，個々の研究結果の解釈や比較をする際には，個々の研究で用いた診断基準を考慮する必要がある。一方で，診断基準ごとに社会的状況の種類や症状の持続期間などに違いはあるものの，話すことができる社会的状況と話すことができない社会的状況の両方があるという点はすべての診断基準に共通していた。したがって，どの診断基準を使用する場合であっても，場面緘黙診断確定および場面緘黙症状の測定のためには複数の社会的状況下での発話行動を評価する必要がある。 ２．鑑別診断について 場面緘黙と他の障害との鑑別に関して，おっしゃる通りの実態があり，場面緘黙のみを有している場合に場面緘黙のみの診断を下すこと，他の障害のみを有している場合に場面緘黙の診断を下さないこと，場面緘黙と他の障害が併存している場合に併存診断を下すことが適切にできることが求められると考えます。鑑別のために複数状況下での発話行動の評価が必要であると考えております。また，場面緘黙と他の障害が併存しているか否かを判断するためには，複数状況下での発話行動の評価による場面緘黙のアセスメントと，併存が疑われる障害のアセスメントの両方を実施し，症状が場面緘黙または他の障害だけでうまく説明されないことを確認することが必要であると考えられます。この旨を考察3に加筆しました。 場面緘黙と他の障害との鑑別診断に関して，「診断基準の不統一性」ではなく「場面緘黙の特徴による鑑別診断の難しさ」に焦点を当てました。そこで，結果4では，場面緘黙と他の障害との鑑別に用いられた手法は研究ごとに異なっており，その手法は確立されていないという旨を補足しました。 レビュー対象となった研究がどのような研究だったのか，方法2および結果1に加筆いたしました。レビュー対象となった研究は，場面緘黙児・者を対象とした調査・実験研究でした。他の障害群を対照群に含んでいた研究は27編であり，この27編について，場面緘黙と他の障害との鑑別手法をレビューしました。 該当箇所 Ⅱ．方法 2. 論文の選定基準 英語で記述された場面緘黙児・者を対象とした実証データに基づく調査・実験研究をレビューの対象とした。介入研究は多く実施されており，行動療法や認知行動療法，薬物療法が有効であるなど，介入に関する知見が蓄積されている（e.g., Cohan et al., 2006; Manassis et al., 2016）一方で，場面緘黙児・者がどのような特徴を有している集団なのかといった情報が不足しており，調査・実験研究が更に必要である。今後，調査・実験研究を進めるにあたり，これまでの調査・実験研究における評価手法に関するレビューが有用だと考え，本研究では，調査・実験研究を対象とした。英語以外の言語で記述された文献，展望論文，質的研究，疫学研究，介入研究は除外した。 Ⅲ．結果 1. レビュー対象論文の選定結果 第2段落 対象となった論文は，場面緘黙児・者のみを対象とした調査・実験研究が13編，対照群との比較を行った調査・実験研究は47編だった。群間比較研究には，定型発達群のみを対照群とした研究が20編，定型発達以外の群を対照群に含む研究が27編あった。 Ⅲ．結果 4. 場面緘黙と他の障害との鑑別に用いられた手法 第１段落 …鑑別方法が記載された研究間では，その方法が異なっており，場面緘黙と他の障害との鑑別方法が確立されていなかった。 Ⅳ．考察 3. 場面緘黙と他の障害との鑑別に用いられた手法 第1段落 …したがって，複数状況下での発話行動の評価をアセスメントに含めることで，他の障害との鑑別が可能になるかもしれない。場面緘黙と他の障害との鑑別に関して，場面緘黙のみを有している場合に場面緘黙のみの診断を下すこと，他の障害のみを有している場合に場面緘黙の診断を下さないことに加えて，場面緘黙と他の障害が併存している場合に併存診断を下すことが適切にできることが求められる。場面緘黙と他の障害が併存しているか否かを判断するためには，複数状況下での発話行動の評価による場面緘黙のアセスメントと，併存が疑われる障害のアセスメントの両方を実施し，症状が場面緘黙または他の障害だけでうまく説明されないことを確認することが必要であると考えられる。 ３．対象となる研究について 対象となった研究は，場面緘黙児・者のみを対象とした調査・実験研究が13編，対照群との比較を行った調査・実験研究は47編でした。群間比較研究には，定型発達群のみを対照群とした研究が20編，定型発達以外の群を対照群に含む研究が27編ありました。対象となった研究について結果1に加筆いたしました。 介入研究は多く実施されており，行動療法や認知行動療法，薬物療法が有効であるなど，介入に関する知見が蓄積されている一方で，場面緘黙児・者がどのような特徴を有している集団なのかといった情報が不足しており，調査・実験研究が更に必要であると考えています。今後，調査・実験研究を進めるにあたり，これまでの調査・実験研究における評価手法に関するレビューが有用だと考え，本研究では，調査・実験研究を対象としました。この点について方法2に加筆いたしました。 該当箇所 Ⅱ．方法 2. 論文の選定基準 …介入研究は多く実施されており，行動療法や認知行動療法，薬物療法が有効であるなど，介入に関する知見が蓄積されている（e.g., Cohan et al., 2006; Manassis et al., 2016）一方で，場面緘黙児・者がどのような特徴を有している集団なのかといった情報が不足しており，調査・実験研究が更に必要である。今後，調査・実験研究を進めるにあたり，これまでの調査・実験研究における評価手法に関するレビューが有用だと考え，本研究では，調査・実験研究を対象とした。 Ⅲ．結果 1. レビュー対象論文の選定結果 第２段落 対象となった論文は，場面緘黙児・者のみを対象とした調査・実験研究が13編，対照群との比較を行った調査・実験研究は47編だった。群間比較研究には，定型発達群のみを対照群とした研究が20編，定型発達以外の群を対照群に含む研究が27編あった。 ４．妥当性について 妥当性検証が行われている尺度については，どのような検証が行われていたのかを加筆いたしました。信頼性の指標の1つである再検査信頼性は妥当性を支持する1つの証拠として扱いました。内的一貫性は，妥当性の観点からの解釈が困難だと考え，本研究では取り上げませんでした。評価手法の種類にかかわらず，目的とする構成概念を測定できているかの検証は必要だと考えます。診断確定手法については，特に，場面緘黙児・者と非場面緘黙児・者の弁別能が検証されているかが重要だと考えます。 該当箇所 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第１段落 …場面緘黙診断を目的として開発された測定法には，面接と質問紙があり，面接が22編，質問紙が7編で用いられていた。場面緘黙診断確定を目的として開発された測定法について，妥当性検証の有無を確認した。再検査信頼性は信頼性の指標として，妥当性と区別して扱われる場合もあるが，村山（2012）を参考に，本研究では，妥当性を支持する証拠の1つとして扱った。また，信頼性の指標として，内的一貫性も挙げられる。しかし，内的一貫性が高すぎると，構成概念を網羅する幅広い項目が尺度に含まれていないことを示唆し，内的一貫性と妥当性の両立は困難であると指摘されている（村山，2012）。したがって，内的一貫性は妥当性の観点からの解釈が難しいと考え，本研究では妥当性の証拠として取り上げなかった。 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第2段落 …ADIS-Ⅳ-P/CはLyneham, Abbott, and Rapee (2007)，Silverman, Saavedra, and Pina (2001)，Wood, Piacentini, Bergman, McCracken, and Barrios (2002）で，一部の障害診断確定に関して妥当性検証は行われていた。具体的には，Lyneham et al. (2007) では，分離不安症，全般不安症，社交不安症，限局性恐怖症，強迫性障害について，評価者間一致率が確認された（κ = .80 - 1.0）。Silverman et al. (2001) では，分離不安症，社交不安症，限局性恐怖症，全般不安症について，再検査信頼性が確認された（κ = .63 - .80）。また，Wood et al.（2002）では，社交不安症，分離不安症，パニック症について，ADIS-Ⅳ-P/C による分類とMultidimensional Anxiety Scale for Children（MASC; March, 1997）の結果に収束性が示唆された。これらの研究では対象者の中に場面緘黙と診断された人々が含まれておらず，場面緘黙診断確定の妥当性は確認されていなかった。 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第3段落 …ただし，レビュー対象となったKinder-DIPSを使用した研究では保護者版のみが実施されていた。…Kinder-DIPS， BCFPI，DICA-Ⅳは一部の障害診断確定に関して妥当性について報告されていた。妥当性評価として，Kinder-DIPSの保護者版では，注意欠如・多動症，夜尿症，うつ病，分離不安症，限局性恐怖症，社交不安症について，評価者間一致率（κ = .74 - .96，Yules’Y = .98 - 1.00）が確認されたと報告されている（Adornetto et al., 2008）。BCFPIは確認的因子分析の結果，おおむね良好なモデル適合度（GFI = .880 - 904，CFI = .860 - 868，RMSEA = .038 - .056）が得られた（Cunningham et al., 2009）。DICA-Ⅳは，De la Osa et al.（1997）によって，医師の診断との一致率やCBCLの結果との収束性一致率が良好であることが確認され，また，再検査信頼性（6-12歳用：κ = .32 - .65，13-18歳用：κ = .59 - .92）の検証も行われたことが報告されている（Reich, 2000）。これらの研究では対象者の中に場面緘黙と診断された人々が含まれておらず，場面緘黙診断確定の妥当性は確認されていなかった。 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第5段落 …FSSM診断尺度はGensthaler et al. (2020) で妥当性検証が行われた。妥当性の検証として，ROC解析が行われ，場面緘黙群と定型発達群，社交不安症群，内在化障害群（うつ病，限局性恐怖症，強迫症，全般不安症，分離不安症，パニック症特定不能の不安症，適応障害）との弁別能が確認された（AUC = 0.97- 1.00）。 Ⅲ．結果 5. その他の発話評価手法 第2段落 …SMQは学校，家庭，その他の社会的状況の発話場面の項目（e.g., たいていの同輩と学校で話す，他の人がいても家で家族と話す，医師や歯科医と話す）における発話頻度を，４件法で評価する尺度であり，Bergman, Keller, Piacentini, and Bergman (2008) によって，標準化，妥当性検証が行われている。標準化の手続きとして，Bergman et al. (2008) 研究1において主成分分析が行われ，3つの下位尺度からなる合計17項目の尺度となった。Bergman et al. (2008) 研究2では，場面緘黙群と場面緘黙以外の不安症群との比較の結果，有意な群間差が示され，妥当性が支持された。…Gensthaler et al.（2020）で妥当性検証が行われ，臨床医による場面緘黙重症度評価とFSSM重症度得点に有意な相関が示された（r = .48 - .72）。 Ⅲ．結果 5. その他の発話評価手法 第3段落 …妥当性検証が行われており，場面緘黙群と非場面緘黙群の得点を比較し，有意な群間差が示されたと報告されている（Starke & Subellok, 2018）。 Ⅲ．結果 5. その他の発話評価手法 第4段落 …Martinez et al. (2015）により，妥当性を支持する証拠が得られた。妥当性検証として相関分析が行われ，ADIS-Pによる臨床診断，SMQとの間に有意な相関が示された。また，他の不安症の症状を評価する質問紙である，SASC-RおよびMASCの全体得点との相関が有意でないことが示された。さらに，場面緘黙群と場面緘黙以外の不安症群との比較の結果，有意な群間差が認められた。 Ⅳ．考察 2. 場面緘黙の診断確定に用いられた手法 …特に，場面緘黙児・者と非場面緘黙児・者の弁別能に関する妥当性の検証が重要であると考えられる。 ５．「５．その他の発話評価手法」について 対象者が場面緘黙に当てはまるか否かを判断するために使用された手法を「場面緘黙の診断確定に用いられた手法」，従属変数として研究中で使用された手法を「その他の発話評価手法」としました。この点について方法4に加筆いたしました。 FSSMは診断尺度と重症度尺度の２つの下位尺度で構成されており，診断確定には診断尺度，その他の評価には重症度尺度が使用されていました。Table2，3に下位尺度の別を加筆いたしました。また，SMQもTable2，3に重複しています。SMQは場面緘黙の重要度を評価する尺度であり，場面緘黙の診断確定を目的として作成された尺度ではありません。しかし，他の手法と組み合わせて，診断確定の手続きで使用したと記載されていた研究があり，Table2の診断確定の列に細字で記載しました。この点については結果3に加筆いたしました。 該当箇所 Ⅱ．方法 4. 情報の抽出と統合 …発話評価手法に関しては，対象者が場面緘黙に当てはまるか否かを判断するために使用されたと論文中に記載されている手法を（２）場面緘黙診断確定手法，従属変数として使用されたと論文中に記載されている手法を（４）その他の発話評価手法とした。 Table2 3，4行目 FSSM 診断尺度 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第１段落 …SMQは場面緘黙の重症度を評価する尺度だが，診断確定手続きに使用したと記載された研究があり，診断確定の列にも含まれている。診断確定を目的とした測定法ではないため，診断確定の列には細字で示した。 Table3 2行目 FSSM 重症度尺度 マイナーなコメント ご指摘いただいた箇所について，加筆・修正いたしました。 該当箇所 Ⅰ．序論 第2段落 …平均69％（95%CI = 0.52, 0.84）だった Ⅲ．結果 5. その他の発話評価手法 第5段落 …発話はT単位に分割された。T単位はHunt （1966）によって定義された，文として成立する最短の単位である。1つの主節，あるいは1つの主節に従属節や埋め込まれた節が加わったものを1単位とする。例えば，“They tried and tried but while they were trying they killed a whale and used the oil for the lamps they almost caught the white whale.”という文は，“They tried and tried.”，“But while they were trying they killed a whale and used the oil for the lamps.”，“They almost caught the white whale”の3つのT単位に分割される（Hunt, 1966）。"
}
]
},
{
"id": "145718",
"date": "18 Aug 2022",
"name": "Yoshihiro Kanai",
"expertise": [
"Reviewer Expertise 臨床心理学，不安症（特に社交不安症），認知行動療法"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n本研究は，場面緘黙児・者の発話評価に関するアセスメントについてPRISMAの手順に従って系統的レビューを行いました。場面緘黙の確定診断，および社交不安症や自閉スペクトラム症など，場面緘黙と併存しやすい疾患との鑑別のために，異なる社会的状況での発話評価が重要と考え，複数の状況における発話の評価がどの程度行われているか整理することが目的でした。その結果，診断のために使用されている面接や質問紙のほとんどは妥当性が検証されていないこと，発話評価に関する研究のほとんど（17編中16編）においては重症度測定のために質問紙が使用されており，行動観察を行った研究は１編のみであったことが明らかにされました。本研究によって，場面緘黙児・者の発話評価に関する現状が明らかになり，今後，必要な研究が明確になりました。また，場面緘黙診断について妥当性が検証された評価方法はFSSM（Frankfurt Scale of Selective Mutism）のみであるという情報や，日本語で使用可能な場面緘黙診断確定方法に関する情報もあり，読者にとっても有益です。 以下の点について検討されることで，より明確で有益な論文になると思われます。\n\n●Major comments コメント１ p.12 最終段落 場面緘黙の診断確定に用いられた手法のうち，行動観察に基づく評価手法が60編中６編であったこと，それぞれの研究が独自の観察を行っていたことが考察で述べられています。これらの行動観察に関する結果については，「結果」のセクションにも記載いただき，今後の研究のためにも，独自に行われていた観察がどのような観点でどのように評価していたのか（考察では，共通しているところと異なるところ；必要な観点があるかどうかなど）を加筆いただければと思います。\nコメント２ p.13 第２段落 場面緘黙の異質性に関する考察は大変興味深いと思います。これまでの発話評価手法ではいくつかの場面における発話頻度を主として測定していますが，ここにあげられているようにいくつかのタイプがあることを考えると，緘黙することがどのような結果をもたらしているのか，という機能に関するアセスメントも必要であるように思いました。本研究のテーマである発話評価という点と絡めて場面緘黙の異質性について考察していただく観点として機能的アセスメントなどがあげられると思いましたが，いかがでしょうか。著者らのお考えをご教示いただき，必要に応じて加筆いただければと思います。\nコメント３ p.13 本研究の主要な目的である「複数の状況における発話評価」という点について，p.13「４．その他の発話評価手法」において，実施されていたのかどうかを明記いただければと思います。その前の「３．鑑別に用いられた手法」のところでは「複数状況下での発話行動の評価をアセスメントに含めること」が必要と明記されています。「４．その他の発話評価手法」に関しては，既存の尺度で複数状況における発話評価はできているけれども，行動観察が十分ではない，という結果であったと理解してよろしいでしょうか。\nコメント４ Table 2など，尺度の略称については，noteなどで何の略かわかるように加筆いただけるとよいと思います。ただし，文量が多くなるため，編集の方針として本文中の記載にとどめるということであればご放念ください。\n\n●Minor comments 要旨 下から２行目 診断確定ため→診断確定のため\np.5 「情報の抽出と統合」２行目 目的としため→目的としたため\np.14 l.8 発話行動のを実験的検討は不足している→発話行動の実験的検討は不足している\n\nシステマティックレビューの根拠と目的は明確に示されていますか。 はい\n\n方法と分析について第三者による再現が可能となるよう十分な詳細が提示されていますか。 はい\n\n（該当する場合は要回答）統計分析および解釈は適切ですか。 はい\n\n結論はレビューの結果により妥当な裏付けを得ていますか。 はい",
"responses": [
{
"c_id": "8983",
"date": "05 Dec 2022",
"name": "友里亜 藤間",
"role": "Author Response",
"response": "金井先生 査読コメントを下さり誠にありがとうございます。 以下のように加筆・修正を行いました。 コメント１ p.12 最終段落 行動観察を実施していた6編の研究のうち5編で家庭場面の録画・録音によって，家庭で話していることが確認されていました。そのうち１編は，家庭場面の録画・録音に加えて，実験室場面の発話行動も確認されました。観察が行われた６編のうち1編は，どのような観察を実施したのか，詳細な記述はありませんでした。診断確定のために観察を実施した６編の研究について結果3に加筆いたしました。また，家庭以外の場面の観察が特に不足しており，今後，複数状況の観察が期待されるという旨を考察2に加筆いたしました。 該当箇所 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第1段落 …場面緘黙診断確定手法として確立された観察手続きはなかったが，発話行動の観察は診断確定のために重要であると考え，観察実施の有無と観察の内容についても確認した。 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第6段落 各研究独自の観察が診断確定に含まれていた研究が6/60編存在した（Arie et al., 2007; Bar-Haim et al., 2004; Henkin, Feinholz, Arie, & Bar-Haim, 2010; Kristensen, 2000; Kristensen & Oerbeck, 2006; Muchnik et al., 2013）。6編すべての研究において，観察と観察以外の手法を組み合わせて診断確定が行われていた。Bar-Haim et al.（2004），Henkin et al.（2010）， Muchnik et al.（2013）で実施された観察では，家庭場面の録画・録音によって，話す能力のあることが確認された。Kristensen（2000）では，家庭場面の録音によって，言語スキルが評価された。Arie et al.（2007）では，家庭場面の録画・録音による話す能力の確認に加え，実験室での保護者および見知らぬ実験者との相互作用中の発話行動も観察された。Kristensen and Oerbeck（2006）は，診断確定の手続きに直接観察が含まれていたと記載されていたが，どのような場面の観察を実施したのかについて詳細な記載はなかった。 Ⅳ．考察 2. 場面緘黙の診断確定に用いられた手法 第2段落 …面接や質問紙の標準化に加えて，行動観察に基づく評価手法の開発も今後の課題である。複数の評価指標や情報に基づき，総合的に場面緘黙の診断を下すことを提唱しているガイドライン（Dow, Sonies, Scheib, Moss, & Leonard, 1995）においても，複数の社会的状況下での発話行動の実測については言及されていない。しかし，質問紙や半構造化面接で扱われている内省的な報告は，実際の行動と乖離する可能性が，これまでの研究で問題点として指摘されている（Baumeister, Vohs, & Funder, 2007）。質問紙や面接だけでなく，行動観察による発話評価を併せて行うことが妥当性の高い診断確定には必要だろう。今後の研究では，場面緘黙児・者の発話の観察を含めた評価手法の確立が望まれる。レビュー対象の論文でも観察を行った研究は少ないながらも存在しており（6/60編），5/6編において家庭場面で問題なく話していることが確認されていた。1/6編の研究では，家庭場面の観察に加えて，家庭以外の場面の観察も実施された。ただし，それぞれの研究が独自の観察を行っており，場面緘黙診断確定のために確立された観察法はなかった。また，これまでの調査・実験研究では，一貫して話していない状況の観察が特に不足していた。場面緘黙児の多くは学校で話すことができないため（Rodrigues Pereira et al., 2021），学校場面の録画を提出するよう求めることが有用だと考えられるが，普段の授業時間や休み時間など，児童・生徒が多数いる状況を録画することについて同意を得るのは手続き上の困難があると推察される。場面緘黙当事者と，特定の話すことができない相手（例えば，担任教員）の同意を得て，同意が得られた人々だけの状況を設定してもらい，その状況を録画し提出するよう依頼するのが現実的かもしれない。このように設定された状況は，一貫して話していない普段の状況とは異なってしまうが，話していない状態は確認できる。…Arie et al.（2007）で実施されていたように複数状況での観察を行うことが望ましいと考えられる。複数状況での発話行動を定量的に評価し・比較し，状況によって発話行動が顕著に異なることを確認できるような観察手続きやチェック項目が確立されると，場面緘黙児・者を対象とした研究の参加者を選定する際に有用である。これまでの調査・実験研究では，観察を含む診断確定を行った研究は少なかった（6編）が，手法の確立によって，観察を実施する研究の増加が期待される。 コメント２ p.13 第2段落 ご指摘の通り，機能的アセスメントは場面緘黙を理解するうえで重要な視点だと感じました。発話の欠如という症状は共通していても，様々な機能があると考えられます。また，後続刺激だけでなく，先行刺激も緘黙症状の制御に関わっていると考えました。機能的アセスメントに関して，考察3に加筆いたしました。 該当箇所 Ⅳ．考察 3. 場面緘黙と他の障害との鑑別に用いられた手法 第2段落 …以上のことから，場面緘黙は異質性のある障害として再度概念化した上で，同質性（homogeneity）と異質性（heterogeneity）の両側面から，評価を進めていくことが必要だと考えられる。具体的には，場面緘黙は，特定状況下で一貫して話していないという症状は共通していてもその機能が異なる可能性が推察される。特定状況下での発話の欠如という共通した症状に対する介入も必要だが，個々の緘黙症状に応じた介入も考えていく必要がある。個に応じた介入を考える上で，機能的アセスメントが有効だと考えられる。例えば，他者からの注目を回避する，負の強化により沈黙する頻度が増加していることもあれば，他者からの援助行動を引き出す，正の強化により沈黙する頻度が増加していることもあるかもしれない。あるいは，特定の場所が先行刺激となり沈黙していることもあるかもしれない。どのような先行刺激によって発話が制御されており，どのような後続刺激によって発話が強化・弱化されているのかを、詳細に検討していくことが，今後必要だろう。 コメント３ p.13 その他の発話評価に関して，複数の状況における発話評価が実施された研究と学校場面だけの評価が実施された研究がありました。ご指摘の通り，質問紙や面接によって，複数状況における発話評価を行っている研究はありますが，行動観察が少ないという結果でした。結果5，考察4に加筆いたしました。 該当箇所 Ⅲ．結果 5. その他の発話評価手法 第2段落 保護者回答の質問紙（14編）には，Selective Mutism Questionnaire（SMQ）（10/14編），FSSMの重症度尺度（1/14編）があった。いずれも，複数状況下での発話行動を評価する質問紙だった。 Ⅲ．結果 5. その他の発話評価手法 第3段落 …DortMus-Kitaは，学校場面に限定された発話行動を尋ねる質問紙だが，DortMus-Kitaを使用したStarke（2018）は，保護者を対象としたオリジナルの質問紙を併用し，家庭や近所，公共の場での発話行動についても評価していた。…School Speech Questionnaire を使用したレビュー対象の研究（Bergman et al., 2002）では，学校以外の状況での発話行動については評価されていなかった。また，Bergman et al. (2002) では， School Speech Questionnaireのうち，項目テスト相関の低かった2項目を除外した9項目が使用されていた。 Ⅲ．結果 5. その他の発話評価手法 第4段落 …TTI-SMは，学校場面に限定された発話行動について尋ねる面接だが，TTI-SM を使用した研究（Martinez et al., 2015）は，家庭，学校，その他の社会的状況での発話行動を尋ねる保護者回答の質問紙であるSMQを併せて実施していた。 Ⅲ．結果 5. その他の発話評価手法 第5段落 観察により発話評価した研究（Edison et al., 2011）では，実験室での場面緘黙児とその保護者の会話場面を録画し，複数状況下での子どもの発話と保護者の発話について観察者が評価した。 Ⅳ．考察 4. その他の発話評価手法 第2段落 …質問紙や面接を用いて複数状況下での発話評価を行った研究はあったものの，複数状況下での観察を行い，実際の発話を定量的に測定した研究は，レビュー対象の論文のうち，1編のみだった（Edison et al., 2011）。 コメント４ Table2，3に注を加えました。 Minor comments ご指摘いただいた箇所を修正いたしました。"
}
]
},
{
"id": "145714",
"date": "29 Aug 2022",
"name": "Shoji Okamura",
"expertise": [
"Reviewer Expertise 特別支援教育 応用行動分析学"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n場面緘黙の鑑別の困難性を背景とした介入の困難性は以前から指摘されており、診断方法を含めた発話評価を整理した価値ある研究です。結果を踏まえて発話評価手法に関するさらなる考察を深めていただければと考えます。\n・P12L50 観察を行った研究は6編存在したとあるが、結果に示されていないため、「独自の観察の詳細」が不明です（Table2でもどの論文が対応するかが分かりません）。これらの内容を示しながら、どのような「発話の観察を含めた評価手法」が望まれるかについて考察してください。また、観察を行った研究がそもそも少ないことについてどう考察されますか（その他の発話評価方法も含め）。 ・P13 本研究の結果、場面緘黙群と他の障害群との鑑別方法が確立されていないことが明らかになった、とあります。しかしながら、P8の結果をみる限り、少なくとも不安症群との鑑別（FSSMの有用性を含め）についてはある一定の方法が示されているとも読み取れます。確立されていないものの、何がどこまで示されているかを丁寧に記述する必要があると考えます。 ・コミュニケーションの問題が症状として表れる障害との鑑別では、複数状況下での発話行動の評価により場面緘黙の診断は可能となると考えます。併存しているか否かを判断する場合には、どのようなアセスメントが求められるかを検討する必要があると考えます。 ・同質性と異質性についてタイプ分けの先行研究を示しながら論じ、両側面から評価を進める必要があるとしています。読者がタイプ分けに関する先行研究を挙げる意味を理解するためにも、同質性と異質性の内容をより具体的に論じる必要があると考えます。特異的気質、環境要因、発達障害といった素因と遺伝的要因の相互作用としての障害として捉え、それらと関連させながら、複数状況下での発話行動の評価を行う必要があると指摘したいのでしょうか。 ・P13「４ その他の発話評価手法」 複数の状況下での発話行動の定量的な測定、場所、相手、活動による発話行動、および頻度以外の発話行動の特徴に関する検討の必要性を指摘しています。診断確定以外の目的で発話評価を行った17編の研究をもとに考察しているため、介入にあたって必要な検討であると思われます。しかしながら、発話評価手法を検討するにあたって、診断確定を目的とする場合と介入のためのアセスメントや介入のための知見を示すことを目的とする場合で何がどう違うべきなのでしょうか。介入にあたっては、発話行動だけでなく、非言語行動を含めた行動全般の特徴を査定していくことが求められます。本レビューでは調査・実験研究を対象とはしていますが、目的に応じた評価手法について考察を展開していくことが望まれます。\n＜その他＞ ・「場面緘黙児・者の診断方法を含めた発話評価」など、題目（主題）を再考してください。 ・2段階目のスクリーニングで「著者間で判断易相違があった場合」には協議を行ったとあります。しかしながら、結果の選定結果では、主に調査・実験研究以外の研究が除外されており、相違が起こり得にくいと読み取れます。判断に相違があった場合の適格基準について明記してください。 ・医学的診断基準が明記されていた44編と診断確定に用いられた測定法について記載していた44編は一致していません。測定法が記載しているものの、使用した医学的診断基準が明記されていない論文があることは記述すべき事項かと考えます。 ・Table 1でICD-9の記述をしてください。 ・Table 2では44編中、36編が示されています。面接22編中、20編のみがチェックされています。理由を付記してください。 ・P7L39 FSSMの引用文献は以下でしょうか Gensthaler. A, Dieter. J, Raisig. S et al (2018) Evaluation of a novel parent-rated scale for selective mutism. Assessment. ・P7L52 群間比較を行った研究が27編あります。内訳として、社交不安症10編、複数の不安症10編、複数の疾患6編、障害・疾患が不明2編だけで28編になります。記述の仕方を再考してください。複数の疾患6編についてはその後の記述がありませんが、特記する必要はないのでしょうか。 ・Table 2のADIS-Ⅳは太字でしょうか。 ・診断確定以外の目的での発話評価手法で用いられた質問紙では妥当性検証が行われているものが多いですが、診断目的ではFSSMのみです。どう考察しますか。 ・P13L8 「発話行動のを実験的検討」→「を」削除\n\nシステマティックレビューの根拠と目的は明確に示されていますか。 はい\n\n方法と分析について第三者による再現が可能となるよう十分な詳細が提示されていますか。 はい\n\n（該当する場合は要回答）統計分析および解釈は適切ですか。 はい\n\n結論はレビューの結果により妥当な裏付けを得ていますか。 一部該当",
"responses": [
{
"c_id": "8984",
"date": "05 Dec 2022",
"name": "友里亜 藤間",
"role": "Author Response",
"response": "岡村先生 査読コメントを下さり誠にありがとうございます。 以下のように加筆・修正を行いました。 ・P12L50 観察を行った研究に関して Table2に観察実施の有無の列を追加し，どの研究が観察を実施したのか明らかにしました。行動観察を実施していた6編の研究のうち5編で家庭場面の録画・録音によって，家庭で話していることが確認されていました。そのうち１編は，家庭場面の録画・録音に加えて，実験室場面の発話行動も確認されました。観察が行われた６編のうち1編は，どのような観察を実施したのか，詳細な記述はありませんでした。診断確定のために観察を実施した６編の研究について結果3に加筆いたしました。 レビューの結果，家庭以外の場面の観察が特に不足していました。場面緘黙児の多くは学校で緘黙症状を示すため，学校場面の観察が有効だと考えられますが，手続き上の困難により，学校での観察が行われにくいのではないかと考え，考察2に加筆いたしました。 その他の発話評価方法として，複数状況の観察を行った研究は，Edison et al. (2011) 1編でした。Edison et al. (2011) は，複数の実験条件を設定し，場面緘黙児と保護者の会話を観察していました。異なる場所での発話行動，異なる相手との発話行動，Edison et al.（2011）では検討されなかった異なる活動中の発話行動など，場面緘黙児・者の発話行動について，さらに実験的検討が必要だと考えています。この点について，考察4に記載しました。 該当箇所 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第1段落 診断基準，診断を確定するために用いられたと論文中で記載された測定法，測定法の種類，観察実施の有無について，出版年の新しい順に示した（Table 2）。 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第1段落 …場面緘黙診断確定手法として確立された観察手続きはなかったが，発話行動の観察は診断確定のために重要であると考え，観察実施の有無と観察の内容についても確認した。 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第6段落 各研究独自の観察が診断確定に含まれていた研究が6/60編存在した（Arie et al., 2007; Bar-Haim et al., 2004; Henkin, Feinholz, Arie, & Bar-Haim, 2010; Kristensen, 2000; Kristensen & Oerbeck, 2006; Muchnik et al., 2013）。6編すべての研究において，観察と観察以外の手法を組み合わせて診断確定が行われていた。Bar-Haim et al.（2004），Henkin et al.（2010）， Muchnik et al.（2013）で実施された観察では，家庭場面の録画・録音によって，話す能力のあることが確認された。Kristensen（2000）では，家庭場面の録音によって，言語スキルが評価された。Arie et al.（2007）では，家庭場面の録画・録音による話す能力の確認に加え，実験室での保護者および見知らぬ実験者との相互作用中の発話行動も観察された。Kristensen and Oerbeck（2006）は，診断確定の手続きに直接観察が含まれていたと記載されていたが，どのような場面の観察を実施したのかについて詳細な記載はなかった。 Table 2 最右列 Ⅳ．考察 2. 場面緘黙の診断確定に用いられた手法 第2段落 …面接や質問紙の標準化に加えて，行動観察に基づく評価手法の開発も今後の課題である。複数の評価指標や情報に基づき，総合的に場面緘黙の診断を下すことを提唱しているガイドライン（Dow, Sonies, Scheib, Moss, & Leonard, 1995）においても，複数の社会的状況下での発話行動の実測については言及されていない。しかし，質問紙や半構造化面接で扱われている内省的な報告は，実際の行動と乖離する可能性が，これまでの研究で問題点として指摘されている（Baumeister, Vohs, & Funder, 2007）。質問紙や面接だけでなく，行動観察による発話評価を併せて行うことが妥当性の高い診断確定には必要だろう。今後の研究では，場面緘黙児・者の発話の観察を含めた評価手法の確立が望まれる。レビュー対象の論文でも観察を行った研究は少ないながらも存在しており（6/60編），5/6編において家庭場面で問題なく話していることが確認されていた。1/6編の研究では，家庭場面の観察に加えて，家庭以外の場面の観察も実施された。ただし，それぞれの研究が独自の観察を行っており，場面緘黙診断確定のために確立された観察法はなかった。また，これまでの調査・実験研究では，一貫して話していない状況の観察が特に不足していた。場面緘黙児の多くは学校で話すことができないため（Rodrigues Pereira et al., 2021），学校場面の録画を提出するよう求めることが有用だと考えられるが，普段の授業時間や休み時間など，児童・生徒が多数いる状況を録画することについて同意を得るのは手続き上の困難があると推察される。場面緘黙当事者と，特定の話すことができない相手（例えば，担任教員）の同意を得て，同意が得られた人々だけの状況を設定してもらい，その状況を録画し提出するよう依頼するのが現実的かもしれない。このように設定された状況は，一貫して話していない普段の状況とは異なってしまうが，話していない状態は確認できる。…Arie et al.（2007）で実施されていたように複数状況での観察を行うことが望ましいと考えられる。複数状況での発話行動を定量的に評価し・比較し，状況によって発話行動が顕著に異なることを確認できるような観察手続きやチェック項目が確立されると，場面緘黙児・者を対象とした研究の参加者を選定する際に有用である。これまでの調査・実験研究では，観察を含む診断確定を行った研究は少なかった（6編）が，手法の確立によって，観察を実施する研究の増加が期待される。 Ⅳ．考察 4. その他の発話評価手法 第2段落 質問紙や面接による測定だけでなく，複数状況下での実際の発話を定量的に測定する研究が更に必要である。質問紙や面接を用いて複数状況下での発話評価を行った研究はあったものの，複数状況下での観察を行い，実際の発話を定量的に測定した研究は，レビュー対象の論文のうち，1編のみだった（Edison et al., 2011）。日常場面の行動を理解するためには，行動を直接観察する方法が適しているという指摘があり（Baumeister et al., 2007），場面緘黙児・者の発話行動の特徴を明らかにするためには，行動観察が重要である。Edison et al.（2011）では，実験室での複数種類の活動中の保護者との会話を観察し，場面緘黙児の自発的な発話と応答を定量的に評価した。質問紙調査によって場面緘黙児・者は場所，相手，活動によって発話頻度が異なると示されているが（Dummit et al., 1997），場所，相手，活動による発話行動の実験的検討は不足している。また，発話頻度以外の発話行動の特徴についても検討の余地がある。異なる場所での発話行動，異なる相手との発話行動，Edison et al.（2011）では検討されなかった異なる活動中の発話行動など，場面緘黙児・者の発話行動について，未検討の点が数多く残っている。今後は，発話行動に影響する複数の変数（場所，相手，活動など）について，場面緘黙児・者を対象とした実験的な研究を推進していくことが必要だろう。 ・P13 場面緘黙と他の障害との鑑別方法に関して ご指摘の通り，FSSMは一部の障害との弁別能が支持されています。FSSMは，場面緘黙と社交不安症および内在化障害との鑑別の有用性が示唆されていました。しかし，場面緘黙と自閉スペクトラム症等の神経発達症との弁別能については未検討でした。この点について，考察3に記載いたしました。 該当箇所 Ⅳ．考察 3. 場面緘黙と他の障害との鑑別に用いられた手法 第1段落 …レビューの結果，場面緘黙と他の障害との弁別能が検証されている評価手法はFSSMのみだった。FSSMは場面緘黙と社交不安症や内在化障害群（うつ病，限局性恐怖症，強迫症，全般不安症，分離不安症，パニック症特定不能の不安症，適応障害）との鑑別については有用性が示唆されていた（Gensthaler et al., 2020）。しかし，コミュニケーションの障害を示す点で共通している場面緘黙と自閉スペクトラム症等の神経発達症との鑑別については未検証であり，今後検証されることが望ましい。 ・場面緘黙と他の障害が併存しているか否かを判断する場合 場面緘黙と他の障害が併存しているか否かを判断するためには，複数状況下での発話行動の評価による場面緘黙のアセスメントと，併存が疑われる障害のアセスメントの両方を実施し，症状が場面緘黙または他の障害のどちらかだけではうまく説明されないことを確認することが必要であると考えております。場面緘黙と他の障害の併存の判断について，考察3に加筆いたしました。 該当箇所 Ⅳ．考察 3. 場面緘黙と他の障害との鑑別に用いられた手法 第1段落 …場面緘黙と他の障害が併存しているか否かを判断するためには，複数状況下での発話行動の評価による場面緘黙のアセスメントと，併存が疑われる障害のアセスメントの両方を実施し，症状が場面緘黙または他の障害のどちらかだけではうまく説明されないことを確認することが必要であると考えられる。 ・同質性と異質性に関して タイプ分けを行った研究で示されてきたように，場面緘黙には異なるタイプが存在すると考えられます。先行研究で示された異なるタイプの場面緘黙では，緘黙の機能が異なっている可能性が考えられます。中核症状である特定状況下での発話の欠如が共通しているという同質性と，場面緘黙児・者の中でも緘黙の機能は異なっているという異質性，両側面を考慮し，発話評価を進める必要があると考えました。その旨，考察3に記載いたしました。 該当箇所 Ⅳ．考察 3. 場面緘黙と他の障害との鑑別に用いられた手法 第2，3段落 …以上のことから，場面緘黙は異質性のある障害として再度概念化した上で，同質性（homogeneity）と異質性（heterogeneity）の両側面から，評価を進めていくことが必要だと考えられる。具体的には，場面緘黙は，特定状況下で一貫して話していないという症状は共通していてもその機能が異なる可能性が推察される。特定状況下での発話の欠如という共通した症状に対する介入も必要だが，個々の緘黙症状に応じた介入も考えていく必要がある。個に応じた介入を考える上で，機能的アセスメントが有効だと考えられる。例えば，他者からの注目を回避する，負の強化により沈黙する頻度が増加していることもあれば，他者からの援助行動を引き出す，正の強化により沈黙する頻度が増加していることもあるかもしれない。あるいは，特定の場所が先行刺激となり沈黙していることもあるかもしれない。どのような先行刺激によって発話が制御されており，どのような後続刺激によって発話が強化・弱化されているのかを，詳細に検討していくことが，今後必要だろう。 場面緘黙の発症に関する遺伝的要因の解明も，場面緘黙と他の障害の鑑別に寄与すると考えられ，今後さらなる研究が求められる。 ・P13「４．その他の発話評価手法」 場面緘黙の中核症状が特定状況下での発話の欠如であることから，発話行動の評価が重要であると考え，本研究では発話評価に特に焦点を当てておりました。しかしながら，ご指摘の通り，場面緘黙の介入にあたっては，発話行動以外の行動の抑制についてもアセスメントおよび介入が必要であるため，発話行動以外の行動のアセスメントの必要性について考察4の末尾に加筆いたしました。 該当箇所 Ⅳ．考察 4. その他の発話評価手法 第1段落 場面緘黙の中核症状は，特定状況における発話の欠如であり，場面緘黙の調査・実験研究において発話行動の評価が重要である。 Ⅳ．考察 4. その他の発話評価手法 第2段落 …さらに，場面緘黙児・者では，発話以外の行動の抑制も症状として現れることがあり（河井・河井，1994），介入場面においては，発話以外の行動に関する評価・介入も必要である。FSSMに含まれるように，対象児・者が活動に参加しているかといった項目の評価も，発話行動の評価と併せて実施されることが望まれる。 その他 ・題目に関して 再考しました。診断や診断確定手法，鑑別手法に関する内容を多く含んでいるため，「場面緘黙児・者の診断確定手法を含めた発話評価」に改めることといたしました。 ・スクリーニングで，著者間で判断に相違があった場合に関して 判断に相違があったChavira et al. (2007) は最終的にレビューに含まれました。その理由に関して結果1に加筆いたしました。 該当箇所 Ⅲ．結果 1. レビュー対象論文の選定結果 …2段階目のスクリーニングにおいて，Chavira, Shipon-Blum, Hitchcock, Cohan, & Stein (2007) をレビューに含めるか否か，著者間で判断に相違があった。Chavira et al. (2007) は，主に場面緘黙児の保護者に関する調査だが，場面緘黙児に関するデータも取得していたことから，協議の末，レビューに含めることとした。 ・測定法が記載しているものの，診断基準が明記されていない論文があることに関して ご指摘いただき，記述する必要があると感じましたので，測定法が記載されており診断基準が記載されていない論文があることに関して結果3に加筆いたしました。 該当箇所 Ⅲ．結果 3. 場面緘黙の診断確定に用いられた手法 第1段落 …場面緘黙の診断確定に用いられた測定法について，記載していた研究は44/60編あった。測定法が記載された44編は，医学的診断基準が記載されていた44編とは一致しておらず，測定法が記載されているものの医学的診断基準が明確にされていない研究が11編存在した。診断確定の手法として，複数の方法の併用や医療記録によって総合的に判断した研究が最も多かった（24編）。 ・Table1でのICD-9の記述に関して 著者らの調べる限りでは，ICD-9の診断基準については情報が得られませんでした。その旨をTable1の注に記載しました。 ・Table2に関して ご指摘ありがとうございます。Table2に誤りがあり，下8行が欠けておりましたので修正いたしました。 ・P7L39 FSSMの引用文献に関して オンラインで出版されたのが2018年であり，雑誌に収録されたのが2020年でした。 ・P7L52 群間比較に関して 群間比較研究の数に関して，記述を改めました。また，場面緘黙以外の障害群との群分けの手法に関して，追記いたしました。 該当箇所 Ⅲ．結果 4. 場面緘黙と他の障害との鑑別に用いられた手法 第1段落 群間比較を行った研究は47編あり，そのうち，場面緘黙群と定型発達群を比較した研究は20編だった。それ以外の27編は，場面緘黙以外の障害群を対照群として含んでおり，その内訳は次の通りである。まず，社交不安症群を対照群に含む研究は合計で10/27編あり，この10編の中で，社交不安症群のみを対照群とした研究が3編，社交不安症群と定型発達群を対照群とした研究が4編，社交不安症群と内在化障害群（うつ病，限局性恐怖症，強迫症，全般不安症，分離不安症，パニック症特定不能の不安症，適応障害）と定型発達群を対照群とした研究が3編だった。次に，場面緘黙以外の複数の不安症を対照群として設定した研究は合計で10/27編あり，この10編の中で，不安症群のみを対照群とした研究が2編，不安症群と定型発達群を対照群とした研究が7編，不安症群と不安症とADHDの併存群を対照群とした研究が1編だった。その他には，場面緘黙と自閉スペクトラム症の併存群（1/27編），全般不安症群（1/27編），不安症や情緒障害を有する群（小児期の全般性不安障害（ICD-10 F93.80），小児期の情緒障害不特定のもの（ICD-10 F93.9），小児期の社会不安障害（ICD-10 F93.2））（1/27編），情緒障害群（不登校，恐怖反応，適応反応，不安，うつ，夜尿症，ヒステリー）（1/27編），場面緘黙以外の精神障害を有する群（小児期に特異的に発症する情緒障害（ICD-10 F93），特異的会話構音障害（ICD-10 F80.0），表出性言語障害（ICD-10 F80.1））（1/27編）を対照群とした研究が存在した。そして，対照群の障害・疾患が不明な研究が2/27編あった。 Ⅲ．結果 4. 場面緘黙と他の障害との鑑別に用いられた手法 第2段落 社交不安症群を対照群に含む研究（10編）では，場面緘黙群と社交不安症群の群分けのために半構造化面接（8/10編）もしくは質問紙（2/10編）が用いられていた。半構造化面接を実施し場面緘黙群と社交不安症群を群分けした8編の研究では， Kinder-DIPS，ADIS-Ⅳ-C/P， DICA-Ⅳが実施されていた。社交不安症群と内在化障害群（うつ病，限局性恐怖症，強迫症，全般不安症，分離不安症，パニック症特定不能の不安症，適応障害）と定型発達群を対照群とした研究（3編）では，内在化障害群および定型発達群の参加者に場面緘黙または社交不安症の症状が示された場合にはKinder-DIPSにより診断確定が行われたと記載されていた。 Ⅲ．結果 4. 場面緘黙と他の障害との鑑別に用いられた手法 第3段落 場面緘黙以外の不安症群を対照群に含む研究（10編）には，半構造化面接のみによって場面緘黙群と他の不安症群の群分けをした研究が5/10編，半構造化面接と質問紙の併用によって群分けした研究が4/10編，群分けの方法について記載のない研究が1/10編あった。半構造化面接のみを行った研究ではADIS-Ⅳが実施されていた（1編はParent Versionのみ，4編はChild VersionとParent Version）。不安症群と不安症とADHDの併存群を対照群とした研究（1編）では，ADIS-Ⅳ-C/Pによって場面緘黙と判断された対象者が場面緘黙群に分類された。群分けのために一般的な精神保健評価面接によって，現在の問題，発達歴，家族歴，治療歴も確認されたと記載されていた。 Ⅲ．結果 4. 場面緘黙と他の障害との鑑別に用いられた手法 第5，6，7段落 全般不安症群を対照群とした研究（1編）では，Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version （K-SADS-PL）によって群分けが行われていた。両障害が併存していた場合の手続きについては記載がなかった。 不安症や情緒障害を有する群（小児期の全般性不安障害（ICD-10 F93.80），小児期の情緒障害不特定のもの（ICD-10 F93.9），小児期の社会不安障害（ICD-10 F93.2））を対照群とした研究（1編），情緒障害群（不登校，恐怖反応，適応反応，不安，うつ，夜尿症，ヒステリー）を対象とした研究（1編）では，医療記録を基に群分けが行われていた。場面緘黙と他の障害が併存していた場合の手続きについては記載がなかった。 場面緘黙以外の精神障害を有する群（小児期に特異的に発症する情緒障害（ICD-10 F93），特異的会話構音障害（ICD-10 F80.0），表出性言語障害（ICD-10 F80.1））を対象群とした研究（1編）では，児童・青年精神科で受けた診断を基に群分けが行われていた。場面緘黙と他の障害が併存していた場合の手続きについては記載がなかった。 ・Table 2のADIS-Ⅳに関して ADIS-Ⅳは場面緘黙診断確定のために作成された質問が含まれており，太字にすべきでした。太字になっていない箇所があったため修正いたしました。 ・診断目的で用いられた手法では妥当性検証が行われた手法はFSSMのみだったことに関して 診断確定以外の目的で使用された発話評価手法は，場面緘黙の症状評価を目的として開発された手法でした。そのため，妥当性検証の際に，場面緘黙症状が妥当に評価できるかという点で検証が行われたのだと考えられます。一方で，診断確定のために使用された評価手法では，FSSM以外の手法は場面緘黙だけでなく，様々な障害の診断を確認することを目的として開発された手法でした。ADIS-Ⅳ，Kinder-DIPS，DICA-Ⅳ，BCFPIでは，評価者間一致率の確認や再検査信頼性の確認など，妥当性検証が実施されていましたが，対象者に場面緘黙児が含まれていなかったために，場面緘黙に関する妥当性検証はできていませんでした。場面緘黙の診断確定を主目的として開発された手法でないために，場面緘黙に関する妥当性検証が欠けてしまったのではないかと考えました。この点について，考察2に加筆いたしました。 該当箇所 Ⅳ．考察 2. 場面緘黙の診断確定に用いられた手法 第1段落 …いくつかの研究において診断確定に使用されたADIS-Ⅳ，Kinder-DIPS，DICA-Ⅳ，BCFPIは，一部の障害に関しては妥当性が検証されていたが，その検証において対象者に場面緘黙児が含まれておらず，場面緘黙に関しては妥当性検証がされていなかった。ADIS-Ⅳ，Kinder-DIPS，DICA-Ⅳ，BCFPIは，様々な障害の診断を目的として開発された手法であり，場面緘黙の診断を主目的としていたわけではないため，場面緘黙に関する妥当性検証が欠けたままになっているのではないかと考えられる。…FSSMは場面緘黙の評価を目的として開発された手法であり，原版のドイツ語版において，定型発達群，社交不安症群，内在化障害群（うつ病，限局性恐怖症，強迫症，全般不安症，分離不安症，パニック症特定不能の不安症，適応障害）との弁別能が支持されている（Gensthaler et al., 2020）。 ・P13L8 「発話行動のを実験的検討」→「を」削除 ご指摘の通り修正いたしました。"
}
]
}
] | 1
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https://f1000research.com/articles/11-847
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https://f1000research.com/articles/12-633/v1
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08 Jun 23
|
{
"type": "Research Article",
"title": "Modeling the spatio-temporal distribution of Karenia brevis blooms in the Gulf of Mexico",
"authors": [
"Gency L. Guirhem",
"Laurie Baker",
"Paula Moraga",
"Gency L. Guirhem",
"Laurie Baker"
],
"abstract": "Background: Harmful algal blooms (HABs) of the toxic dinoflagellate Karenia brevis impact the overall ecosystem health. Methods: K. brevis cell counts were extracted from Harmful Algal BloomS Observing System (HABSOS) in situ data and matched with 0.25º resolution environmental information from the Copernicus database to generate spatio-temporal maps of HABs in the Gulf of Mexico (GoM) between 2010 and 2020. The data was used to analyze the relationship between spatial and temporal variability in the presence/absence of K. brevis blooms (≥100,000 cells/L) and biotic and abiotic variables using Generalized Additive Models (GAM). Results: The variability of blooms was strongly linked to geographic location (latitude and salinity), and temporal variables (month and year). A higher probability of K. brevis blooms presence was predicted in areas with negative sea surface height (SSH) values, silicate concentration (0, 30-35 mmol. m-3), sea surface temperature of 22-28 oC, and water currents moving south-westward (225º). The smooth effect of each environmental variable shows a bimodal pattern common in semi-enclosed basins such as GoM. The spatial predictions from the model identified an important permanent area in (1) Southwest Florida (25.8-27.4o latitude), and four seasonally important areas, (2) North Central Florida (3) Central West Florida, (4) Alabama on Gulf Shores and (5) Mississippi with higher bloom probabilities during the fall to winter season (November-January). Results also suggest that HABs can extend until ≥ 300 km offshore; starting to form in March and reaching a peak in September, and were swept to the coastal area during fall and winter. This suggests the role of upwelling and water circulation in GoM for the accumulation of cells and HABs. Information on the spatio-temporal dynamics of K. brevis blooms and understanding the environmental drivers are crucial to support more holistic spatial management to decrease K. brevis blooms incidence in bodies of water.",
"keywords": [
"HABs",
"Karenia brevis",
"GAMs",
"Gulf of Mexico",
"water current",
"HABSOS",
"upwelling",
"spatio-temporal modeling"
],
"content": "Introduction\n\nHarmful algal blooms (HABs) are caused by microscopic algae that accumulate in bodies of water and produce toxic substances that endanger marine and terrestrial life.1 Shellfish poisoning, marine animals (mammals, fish, and waterfowl) mortality, tourism losses, and severe economic damage in coastal communities are caused by HABs.1–6 These events are estimated to cost millions of dollars. For example, the United States lost $100 million on an annual basis from 2002-2018 because of HABs.1,3 This cost does not include the monitoring and post-management of the effects of these events.1,3,7\n\nK. brevis blooms, also referred to as red tides, cause the death of fish, birds, and marine mammals due to the production of brevetoxin, which alters the sodium channels of vertebrate nervous systems.8 Moreover, brevetoxin can cause respiratory problems in humans and marine mammals when they become aerosolized.9 This toxin can cause behavioral changes in mammals such as bottlenose dolphins (Tursiops truncatus) by altering animal activity budget, heightening disease susceptibility, and increasing socialization and expanded ranging behavior due to changing resource availability and distribution.10\n\nIn the Gulf of Mexico (GoM), an estimated 75 species of freshwater, estuarine, coastal, and marine toxic microalgae proliferate and are routinely monitored by state agencies.8,11,12 Among them, K. brevis (syn. Gymnodinium breve and Ptychodiscus brevis) cause the most common bloom.8,12,13 Though HAB events have been caused by different species of toxic micro algae, for simplicity, in this study we use HAB to refer to algal blooms of K. brevis.\n\nHABs in GoM occur naturally at concentrations of 103 cells L-1 and can also generate large, dense blooms (≥105 cells L-1) in different Gulf states.14,15 HABs have been documented along the coastal waters of every state bordering the GoM. For example, recurrent intense blooms have been observed in Florida and Mississippi.9,14,16 In 1996, red tides occurred in all five Gulf states’ coastal waters which persisted for over a year along the coast of Florida, killing 150 endangered manatees.17 In the last 50 years, the Florida red tide blooms have become more common, frequent, and intense, especially along the West Florida Shelf (WFS) on the Southwest Florida coast during late summer and early spring.18–20 The Southwest coast of Florida, from Manatee to Collier County, has repeatedly experienced prolonged HABs since 2011 and 2017, which lasted for about 17 months and caused both hypoxic and anoxic events.18 In Alabama, algal cells of of K. brevis was found in Dauphin Island and within the state coastal zone, in areas with low salinity levels.21\n\nMonitoring HABs of K. brevis involves in situ quantification and microscopic examination of algae cells in water samples. However, this method is susceptible to spatial and temporal biases due to HABs being highly dependent on environmental conditions such as nutrient input and water circulation.22 Bio-optics advances have contributed to counteracting the biases during in situ data collection by providing a means of non-intrusive data collection at more frequent spatial and temporal scales in identifying potential incidence zones of HABs.23,24\n\nThere have been several agencies monitoring and forecasting K. brevis blooms for selected areas in the Gulf of Mexico, such as The National Center for Coastal Oceans (NCCOS) and Southwest Florida (NOAA Coastal Science), the Collaboration for Prediction of Red tides (CPR) Florida Fish and Wildlife Conservation Commission’s Fish and Wildlife Research Institute (FWC- FWRI) and the University of South Florida’s College of Marine Science (USF-CMS) in coastal waters of the southeastern United States.\n\nPresently, the critical areas for HAB research focus on identifying and quantifying the environmental conditions that contribute to the proliferation of HABs in both the coastal and oceanic environments.25,26 Factors linked to HAB abundance are depth, water column stability, temperature, and decreasing wind.27 There is a need for a more robust satellite-derived HAB index. Thus, a technique for detecting K. brevis blooms in the Gulf of Mexico that utilizes chlorophyll a (Chl-a) anomalies was introduced.28 The ability of satellite ocean color technology to provide near-daily, synoptic-scale imagery in near-real time is unmatched by any other detection technique despite limitations and challenges.29\n\nOne of the variables that were previously used to describe blooms is the wind pattern; however, in this study, we used water currents as it has a direct impact on ocean circulation. While wind plays a major role in shaping the water currents, it is not the main factor driving the overall water circulation.30 In the summer, there is an east and southeast water flow bringing water and nutrients from the Mississippi River plume onto the west Florida shelf at depths of 20–50 m. This water mass supplies utilizable inorganic and organic forms of nitrogen that promote the growth of K. brevis to pre-bloom concentrations in sub-surface waters in the mid-shelf region. In the fall, there is an onshore current transport leading to the physical accumulation of K. brevis blooms near the coast, resulting in fall blooms. Strong thermal fronts during the winter provide a mechanism for re-intensification of the blooms resulting in the winter blooms.31 Jackson et al. (2022) pointed out that there is a need to validate the possible westward migration of K. brevis blooms along the northcentral GOM into AL and MS, and the possible reduction in cell density as the blooms migrate.32\n\nThere have been several studies explaining the mechanisms of K. brevis blooms in Florida and Mississippi, but none for Alabama; however, most of these studies are patchy and are concentrated in small spatial scales.16,31,33 Thus, this study used all HABs reports comprising all three states (Florida, Alabama, and Mississippi) and compared bloom events in these three states. This study will contribute to the increasing knowledge of the factors that can describe HABs incidences for monitoring and detection systems. This will enable local and national agencies to work together to provide accurate forecasts on bloom presence, development, and transport. The monitoring and detection system is necessary to have realistic mitigation strategies that minimize the risks caused by HABs to human health and the economy.34 Forecasting is necessary to enable an alert before a bloom, to allow the development of management options and approaches, and to minimize the risk to living marine resources and humans to HAB or biotoxin exposure.35 Available information on HABs environmental covariates can enable the development of predictive models for the northern GoM.\n\nKnowledge of planktonic HABs over Florida has been increasing but is specific to an area and is patchy, for example, in Charlotte Harbor, West Florida Shelf, and Caloosahatchee River.12,36–39 The prediction in bigger spatial scales for complex coastal domains such as the GoM is still limited. Predicting the spatial and temporal presence of HABs requires knowledge of the spatial and temporal dynamics of a species and the associated environmental conditions. There is already an operational forecast system for K. brevis in the GoM which uses bloom extent and predicts the initiation and accumulation of cells along the coast; however, this model cannot be resolved at scales finer than 30 km.40 In addition, the University of South Florida has another forecast model based on physical transport, but mostly concentrated in Florida and freshwater lakes (USF).\n\nA Generalized Additive Model (GAM) was used to model HABSOS cell count data collected between 2010 and 2020 to analyze the environmental conditions influencing the relationship between the presence (≥100,000 cells/L) of HABs in the GoM in response to biotic and abiotic environmental variables and the spatial and temporal variability of locations of HABs presence. Since HABs are naturally and historically affected by water transport and in highly productive and nutrient-loaded regions, this study hypothesizes that the seasonal changes in the spatio-temporal distribution of HABs are linked to current circulation and upwelling areas in GoM. The resulting predictions of the probability of HABs presence were used to identify areas of potential high HAB proliferation, which may inform more holistic spatial management strategies to decrease the proliferation of HABs species and reduce their biological and economic impact in the GoM.\n\n\nMethods\n\nThis study covered three US states that border the northern GoM, namely the state of Florida, Alabama, and Mississippi (24° to 31°N and 80° to 89°W; see Supplementary Figure 1, Extended data). Supplementary Figure 1 shows study regions in the Gulf of Mexico of K. brevis blooms in the period between 2010-2020 plotted in Google Earth. The identified areas are (1) Southwest Florida, (2) North Central, (3) Central west Florida, (4) Alabama, and (5) Mississippi.\n\nIn GoM, the circulation and water inputs are dominated by the Straights of Yucatán, the Mississippi-Atchafalaya system, the Usumacinta River, and the Mobile River.33,41 The Loop Current, shaped by freshwater inflow from rivers and altered through water density differences and bathymetry, influences the general circulation transport near the Louisiana, Mississippi, and Alabama coastlines.41 Mesoscale and sub-mesoscale features associated with coastal topography and coastline irregularities can promote primary productivity. These features include upwelling filaments, fronts, shelf and oceanic cyclonic and anticyclonic eddies, and coastal countercurrents.42,43 West Florida in GoM is subjected to seasonal coastal upwelling, usually intensifying during the early spring to late summer. Along the meridional (southwest) coast, summer northerly winds force offshore transport of near-surface waters, promoting upwelling-favorable conditions.44,45 During fall, this regime is shifted to southerly winds, favoring downwelling conditions. Along the zonal (south) coast, upwelling conditions are associated with strong westerly winds, but the upwelling intensity is lower. During upwelling relaxation, there is connectivity between the east and west sectors in the Gulf.42 Precipitation exhibits a general decreasing trend from the east (Florida) to the west (Texas), while surface evaporation rates generally increase from east to west.46\n\nThe monthly mean tidal range is low in the winter and high in the late summer, with the highest range exhibited at stations in the central northern regions attributed to monthly changes in seawater density and atmospheric pressure changes.47 The salinity in the northern GoM estuaries is influenced by water exchange between the estuarine entrance and the coastal zone and local forcing (tidal advection, river discharge, precipitation) within the estuary.43 River discharge and storm conditions influence the salinity and temperature conditions of offshore waters, making the thermocline deeper and affecting circulation throughout the GoM.48\n\nHAB cell count was collected from the National Oceanographic and Atmospheric Administration (NOAA) National Centers for Environmental Information’s (NCEI) Harmful Algal BloomS Observing System.19,49 HABSOS is a system that gathers and distributes data that caters to and provides tracking and observing present and historical harmful algal bloom (HAB), mainly of K. brevis events in the GoM. Data are gathered from the US states such as Florida, Mississippi, Alabama, and other countries being served by NOAA. Florida’s cell counts are monitored and reported by monitoring entities networks; for example, the Florida Fish and Wildlife Research Institute (FWRI), Mote Marine Laboratory (MML), Sarasota County Health Department (SCHD), and Collier County Pollution Control and Prevention Department (CCPCPD). The Mississippi Department of Marine Resources (MDMR) collects monthly phytoplankton samples for routine and responsive (emergency) sampling in 15 stations in the Mississippi Sound. The samples undergo qualitative analysis followed by a quantitative analysis if a toxic bloom is present. Site-specific sampling is conducted by MDCR upon receipt of the bloom report, in addition to trained field technicians’ observations during sample collection upon completion of sample processing. The states submit the data to HABSOS at NCEI, where the data is archived and updated annually.32 In Alabama, HABs are collected and monitored by the Alabama Department of Public Health -Seafood Branch (ADPH) with the Alabama Department of Environmental Management (ADEM) under the regulation and guidance of the United States Food and Drug Administration (FDA) (HABSOS).\n\nIn this paper, K. brevis cell count expressed in cells per liter (cells/L) were modeled. Cell count information was collected in the states of Florida, Alabama, and Mississippi, which are the areas in the GoM with the highest presence of HABs in the HABSOS database.\n\nThe environmental variables considered to be potential predictor variables for the habitat modeling were nitrate (NO3), phosphate (PO4), silicate (Si), salinity (Salinity), sea surface height (SSH), mixed layer depth (MLD), sea surface temperature (SST), current velocity (Vel), eddy kinetic energy (Ke), and heading of the current (Heading) (Table 1). Table 1 shows a summary of the environmental variables used in the species distribution models for K. brevis blooms presence (≥100,000 cells/L). All variables were extracted with a 1/4° spatial and daily temporal resolution in the period 2010-2020 from the Copernicus Marine Environment Monitoring Service (CMEMS). Eddy kinetic energy (Ke), current velocity (Vel), and heading (Heading) of the current were derived using the eastward (Uo) and northward (Vo) current vectors. The resolution of the spatial and temporal variables is 0.25° and daily, respectively.\n\n* u is the eastward current velocity; v is the northward current velocity.\n\nDifferent environmental covariates were chosen as a proxy of biological, chemical, and physical accumulation in the GoM that can be linked with the presence of HABs. Nitrate, silicate, and phosphate are essential nutrients for the photosynthesis of phytoplankton.12,39,50,51 These are limiting nutrients, especially in oligotrophic water.12,39,50,51 Salinity reflects the biological preference of organisms and freshwater input from land; however, in this study, it was used as a proxy for longitude37,52–54 because of the high correlation between the two (Supplementary Figure 2, Extended data). SSH is associated with mesoscale processes and upwelling.13,38,51,54,55 Colder temperatures and MLD are signs of upwelling events that bring nutrients to the surface layer.56 Sea surface current flow (current velocity, eddy kinetic energy, and current heading) could also be linked to wind and physical accumulation and transport of HAB cells from the offshore environment to the coastal area.27,37,52\n\nEnvironmental variables were extracted from the marine ocean product of the EU Copernicus Marine Environment Monitoring Service (CMEMS). Globally, the Copernicus platform compiles information regarding the physical state, variability, and dynamics of the ocean and marine ecosystems.55,57 Environmental variables derived from models were selected over in situ observation and satellite products because they offered more spatial and temporal coverage and were less affected by cloud cover. This study used Near Real Time (NRT) and the past reanalysis (RAN) data. Since RAN only covers 2010–2018, NRT data was used for 2019–2020. All environmental variables matched the sampling data (latitude and longitude, observation date).\n\nA univariate GAM was used to explore the relationship between the presence/absence of HABs (≥100,000 cells/L) in the GoM and different abiotic and biotic variables. The presence/absence of HABS was modeled as follows:\n\nWhere g is the link function, which is logit for binomial family, μi is the probability of presence, α is the intercept, fn are the smooth functions, and xn are the covariates.58\n\nThe covariates modeled were the environmental variables (Table 1), spatial variables (Longitude and Latitude), and temporal variables (Month and Year). Month and Year variable were included to account for the seasonal and inter-annual variability in K. brevis blooms, respectively.\n\nA GAM was used in the modeling process to model the presence and absence of K. brevis blooms (≥100,000 cells/L) in GoM to provide a probability of the presence of HABs, irrespective of abundance.58 The binomial distribution was chosen because some areas have no presence of HABs, while others have more than 100,000 cells/L. Moreover, areas with abundance equal or higher than the threshold (100,000 cells/L) can have detrimental effects on the biological life in the region and significant socio-economic impacts on people.59–61\n\nThe smooth function degrees of freedom for each explanatory variable were restricted to avoid overfitting. The basis dimension of smoothers was set to k = 6 for the main effect and k = 20 for first-order interaction effects.62,63 GAMs were fitted using (i) a cyclic cubic regression spline for the variable month, and heading of the current to account for cyclical effects, (ii) a Duchon spline to account for spatial effects (latitude and salinity) considering Euclidean distance, and (iii) thin plate regression splines for all other covariates.64 GAMs were fitted using the R package mgcv v1.8.58,65 A univariate GAMs was done for each predictor variable to give information on the potential functional shape of each predictor variable and their contribution to the deviance explained (percentage of deviance).57,66\n\nTwo approaches to reduced correlation and collinearity between predictor variables were considered. First, Pearson’s rank correlation was used to examine all predictor covariates to identify highly correlated variables (Supplementary Figure 2A, Extended data). Only one of the correlated variables (Pearson correlation |r| > 0.6) was subjected to the variable selection process at a time and thus produced different model combinations.55 Second, the Variance Inflation Factor (VIF) (Supplementary Figure 2B, Extended data) was used to assess multicollinearity among the predictor variables with a threshold value of 367 using the function of from usdm package v 1.1-18.68\n\nA forward stepwise approach was used for variable selection to select the final model covariates.58 Variables were selected if they improved the model’s Akaike’s Information Criterion (AIC) by a value of 2.0 in the selection process.62 AIC (AIC = −2l + 2(p + 1)) prefers models that fit the data well and have few parameters.69 Moreover, as an additional measure to avoid overfitting in the selection process, only significant variables (p < 0.05) were kept, and non-significant variables were sequentially omitted.55 This approach was followed until all variables in the model were significant. The AICs of all best-fitting models were compared, and the lowest AICs were subjected to model validation (Supplementary Table 1, Extended data). Partial effect plots were used to assess the relative contribution of each predictor variable to the HABs presence for the final model with the lowest AICs.\n\nThe final models were validated using the k-fold cross-validation (k = 5) method to split the training (80%) and testing (20%) data using the k-fold function from the dismo package in R software.70 A five-fold cross-validation technique was used and was repeated five times over different random sets to determine the predictive performance of the model.71 A five-fold cross-validation technique was used to deal with the time-dependence structure of the data.\n\nThe model performance of the predicted and observed values were evaluated using a confusion matrix calculated from the PresenceAbsence package v1.1.9 in R.72 The area under the receiver-operating curve (AUC), the ‘specificity, the ‘sensitivity’ and the mean True Skill Statistic (TSS) indices were calculated from the confusion matrix.71 The AUC is threshold-independent and ranges from 0 to 1, an overall measure of accuracy. Values around 0.5 indicate that the prediction is as good as random, and values close to 1 indicate perfect prediction. This index measures the ability of the model to correctly predict where a species is present or absent.55,73 Specificity is an index depicting the proportion of observed absences predicted correctly, and sensitivity illustrates the proportion of observed presences correctly predicted. The TSS is an alternative measure of accuracy calculated as the sensitivity plus specificity minus 1. TSS values can range from −1 to +1. A TSS of 0 indicates no predictive skill, while a TSS value of +1 indicates perfect agreement and a value below zero (0) indicates no better than random performance.74 As opposed to AUC, a threshold-independent approach for model performance, approaches such as sensitivity, specificity, and TSS indices which are threshold-dependent approaches, were also used to determine model performance. To select the threshold, two methods were explored to transform the probabilities into binary predictions (presence/absence)75; (i) “sensitivity is equal to specificity” and (ii) “maximization of sensitivity plus specificity.” Ultimately, the “sensitivity is equal to specificity” threshold was used as it gives the most accurate predictions in cases where the dataset has a low prevalence and avoids omissions (false negative) errors.41,75 The performance scores from the four indices in combination were used to evaluate the predictive performance of the SDMs.\n\nThe probability of the presence of HABs in the final model was predicted with a spatial resolution of 0.25 latitude × 0.25 longitude grid cell and monthly temporal resolution between 2010-2020 using the prediction.gam function of the mgcv package v 1.8-36.58 The predictions were made using the environmental conditions (significant variables selected in the final model) present in each time step (month between 2010-2020) at a 0.25 × 0.25 spatial resolution. For the model prediction, the monthly predictions between 2010-2020 were averaged to calculate an overall mean prediction map and the standard deviation across the monthly prediction over the 11 years to capture uncertainty. Finally, yearly predictions between 2010-2020 were calculated by averaging the monthly predictions within each year for the probability of the presence of HABs. The ranges for the monthly environmental values for the prediction for the whole study period were checked to ensure that the values of environmental variables were within the environmental envelope used to calibrate the SDMs. About 1.50% of the environmental data used in the model prediction were outside the range of environmental values used to build the species distribution models for HABs.\n\nModel building, evaluation, and predictions were performed using R version 4.0.2.76\n\n\nResults\n\nThis paper studied the presence of HABs (≥100,000 cells/L) in Florida, Alabama, and Mississippi. Because the presence of HABs was mostly in parts of Florida, Florida was divided into three regions1 Southwest Florida,2 North Central Florida, and3 Central West Florida (Supplementary Figure 1, Extended data).\n\nFigure 1 shows the monthly spatial distribution of the presence (≥100,000 cells/L) and absence (<100,000 cells/L) of K. brevis blooms in the Gulf of Mexico from 2010−2020 (shaded 0.25 × 0.25 grids) from the Harmful Algal BloomS Observing System (HABSOS). The white cells mean no sample was collected in the grid cells. Time step 1–12 corresponds to a month in a year such as 1-January, 2-February, 3-March, 4-April, 5-May, 6-June, 7-July, 8-August, 9-September, 10-October, 11-November, 12-December.\n\nMost of the presence of HABs was concentrated in Southwest Florida from -81 to -82.5 longitude and 26 to 27.5 latitude. During January, February and December (winter), the highest HAB presence was observed in Southwest Florida (Figure 1). During March-May (spring), the recorded HABs presence was generally the same in all the sampling areas. Spring is the season with the lowest HAB presence with HABs more offshore in May. In June-August (summer), the highest number of HABs presence has been observed in Southwest and North Central Florida, with HAB presence in North Central Florida more offshore than the rest of the season. From September to November (fall), HABs presence recorded was highest in all areas compared to the other season with the highest recorded HAB presence in Southwest Florida. During this time, HABs started to move shoreward in November.\n\nFigure 2 shows yearly spatial distribution of the presence (≥100,000 cells/L) and absence (<100,000 cells/L) of K. brevis blooms in the Gulf of Mexico from 2010−2020 with 0.25 × 0.25 degree grids, from HABSOS. The white cells mean that no sample was collected in that grid cells. Figure 3 shows temporal patterns of the total number of observed presences (≥100,000 cells/L) of K. brevis blooms in the Gulf of Mexico from 2010-2020; Figure 3A shows the total number of presences (≥100,000 cells/L) of HABs sampling by month between 2010-2020 while Figure 3B shows the total number of observed sets with the presence of HABs by month between 2010–2020.\n\nIn terms of the year, HAB blooms were irregular and restricted to one state or could occur in two to three states (Figure 2). Blooms in a specific place can occur in consecutive years or every other year. In 2010, HABs occurred in all identified areas, with no area more prominent than others (Figures 2 and 3). In 2011, HABs presence was observed to increase in Southwest Florida offshore the Naples beach. In 2012 and 2013, HABs’ presence expanded from Naples’s beach up to Tampa. In 2014, HABs presence started to increase in North Central Florida in Apalachee Bay, which had the highest HAB presence in the said year. During these years (2010-2014) HABs were observed in Florida and Alabama while no HAB presence nor sampling was done Mississippi. In 2015, there was an increase in HAB presence in Southwest Florida, Central West Florida, Alabama, and Mississippi, with a noticeable decrease in North Central Florida with highest HABs in Tampa and Panama City beach in the Florida Panhandle. In 2016 and 2017, HABs covered only Florida and Alabama, while no presence was recorded in Mississippi. In 2018, HAB presence was highest in all areas. In 2019, only Southwest Florida had a noticeable HAB presence. In 2020, there was a noticeably low number of sampling and presence of HABs in the study area.\n\nThe lowest sampling of HABs was found to occur in 2020 (Figures 2A and 3A). The highest HAB monitoring was done from August to November, with increasing monitoring from 2016-2019. The highest level of monitoring regarding the number of samples collected was from September to November, which coincides with the fall season and the months of January and December, corresponding to the winter season. The presence of HABs was found to be highest in January, and October to December (Figures 2B and 3B) and from 2016-2019. Blooms majorly occurred in fall to winter regardless of year or state (Figure 1).\n\nAfter analyzing all possible combinations of covariates (10 candidate models), the final model was chosen based on the lowest AIC values (Supplementary Table 1, Extended data). Because of high correlation and collinearity among several variables, only one variable from the following five groups of covariates was included in the selection process and SDMs at a time (Supplementary Figure 2, Extended data): 1) latitude and longitude; 2) salinity and longitude; 3) nitrate and longitude; 4) nitrate and silicate; 5) nitrate and salinity; 6) nitrate and latitude; and 7) current velocity and eddy kinetic energy. Since latitude and longitude are correlated, we used salinity to replace longitude since salinity is correlated to longitude but not to latitude (Supplementary Figure 2A, Extended data). Therefore, the interaction of latitude and salinity was used to locate grids with a high probability of HABs and answer problems on spatial autocorrelation.\n\nFigure 4 shows the partial effect of the interaction of latitude and salinity in predicting the probability presence (≥100,000 cells/L) of K. brevis blooms in the Gulf of Mexico in the period 2010-2020 in 0.25 × 0.25 grids. White grids mean that there was no sample collected in that area. The interaction between latitude and salinity highlighted three potential areas (1) Southwest Florida, (2) North Central, and (3) Central West Florida, with a higher probability of HABs (Figure 4).\n\nThe results of the final model for K. brevis were summarized and presented (Table 2). The final model for HABs had 23.2% of the total deviance (adjusted r2= 0.123). This model included as predictor variables: the interaction between latitude and salinity, the environmental variables of SSH, silicate, SST, MLD, and heading of the current (Figure 5, Supplementary Animation 1, Extended data), and the temporal variability of month and year (Figure 6).\n\n*** p-value < 0.001.\n\n(A) Sea surface height [m]; (B) Silicate [mg/m3]; (C) Sea surface temperature [oC]; (D) Mix layer depth [m]; (E) Current heading [degrees].\n\nFigure 5 shows the partial effects of each individual covariate in the final model for predicting the probability of K. brevis HABs presence (≥100,000 cells/L) in the GoM from 2010−2020. The selected environmental variables were: A) SSH (m), B) Silicate (mmol m-3), C) SST, D) MLD (m), E) heading of the current (degree). The shaded regions correspond to t standard errors, above and below the estimate of the smooth terms. Short vertical lines located on the x-axis indicate the values at which observations were made. Figure 6 shows temporal variables selected in the final model of K. brevis HABs (≥100,000 cells/L) in the Gulf of Mexico from 2010−2020; The figure shows the partial effects of (A) month and B) year as categorical predictor variables in the final model for predicting the probability of occurrence of K. brevis blooms (≥100,000 cells/L). The dashed lines indicate the 95% confidence interval for the parametric terms, and the black boxes in the x-axis show the distribution of the data.\n\nThe Year variable was modeled as a categorical variable that also contributed to explaining the presence of K. brevis blooms. The Year variable was used to account for other variables that were not included in building the candidate models (Figure 6). Lower probabilities of HABs presence were predicted at the beginning of the study period (the year 2010), followed by an increase from 2011-2013 and a gradual decrease in 2014. There was an increase from 2015 to 2016. In 2017 there was an observed decrease in the probability of presence, followed by an increase in 2018. From 2019 there was an observed decrease until 2020. The piecewise construction of each variable for modeling HABs is provided in Supplementary Table 2 (Extended data), and the individual contribution to the percent deviance (Table 3). The time series of HAB probability of presence (Supplementary Animation 2, Extended data) and associated environmental variables used in building the candidate model is shown in Supplementary Figure 3 (Extended data).\n\nThe predictive performance of the final model for HABs (Table 4) was high, with AUC ≥ 0.8, despite the very low presence of HABs with (≥100,000 cells/L) (6.82%) than absence or HABs with <100,000 cells/L in the data set used.77 AUC values of ≥ 0.75 are considered to have good predictive power and can be used for conservation planning.66,78 The final model had a model sensitivity value of 0.76 which means that the model can identify areas where HABs are present 76% of the time. The model’s specificity was 0.75, which suggests that the model can identify areas where HABs are absent 75% of the time. The TSS score for the HAB species distribution model was 0.51.\n\nThe overall averaged predictions across 2010-2020 identified one important permanent area, (1) Southwest Florida, with higher probabilities of the presence of HABs (Figure 7A). However, the areas in (2) North Central Florida, (3) Central West Florida in the Gulf of Mexico, (4) Alabama, and (5) Mississippi had relatively lower probabilities of HAB presence and high variability based on the standard deviation (Figure 7B). For more detailed daily probabilities of HAB presence with cells ≥100,000 cells/L please see Supplementary Animation 2 (Extended data).\n\nThe monthly (Figure 8) and yearly (Figure 9) predictions also confirmed the five areas with higher probabilities of the presence of HABs, yet some areas persist over the year, and others are more seasonal. The probability of the presence of HABs is highest during the fall-winter period (November, December-February) in the five identified areas, suggesting a higher probability of presence during this period. In January all three states are prominent, giving Southwest Florida a higher probability of blooms relative to other states. There is also a formation of bands of blooms near the coast and approximately 120 km away from the shore which continue to be present until March. In February, algal growth is more prominent in Southwest Florida while in March, the probability of HABs decreases and there is no area that is more prominent than the other. In April the formation of more offshore blooms starts off the coast of Florida (-81.5 to -86 degrees longitude) and continues to develop and reach its peak in September. In October the offshore bloom was replaced by a more coastal bloom and Southwest Florida became prominent again. In November, the highest probability in all three states was observed. In December, the probability decreases slightly. The seasonal variability of the environmental variable used in building the candidate model is in Supplementary Figure 4 (Extended data).\n\nThe yearly prediction mainly shows only the permanent areas identified in Florida (Figure 9). Because the central West Florida, Mississippi, and Alabama HAB areas occur only in the fall-winter season, these areas were not reflected in the predicted yearly probabilities of the presence of HABs since it only occurs briefly, and yearly maps take the average of monthly predictions in a year. The interannual changes in the probability of the presence of HABs are driven by both the interannual variability and the changes in the final model environmental covariates (Figure 9). The higher probabilities of the presence of HABs were observed to peak in each area in different years and were more variable in Southwest Florida. Higher probabilities of the presence of HABs occurred in Southwest Florida in 2012, 2013, 2015, 2016, 2018, and 2019. The highest probability of HABs was observed in 2016 and 2018. The interannual variability of the environmental variable used in building the candidate model is in Supplementary Figure 5 (Extended data).\n\n\nDiscussion\n\nWe modeled the spatio-temporal distributions of K. brevis blooms in the GoM from HABSOS data collected by different US states between 2010 and 2020, using a GAM. The spatial, temporal, and environmental conditions associated with HABs presence showed some seasonal and interannual changes in response to the oceanographic dynamics in GoM. The model identified and highlighted the importance of five areas in the GoM: (1) Southwest Florida and (2) North Central Florida, (3) Central West Florida, (4) Alabama, and (5) Mississippi. The modeling of HABs in the GoM suggested that the higher probability of HABs presence can be associated with negative SSH, high silicate, sea surface temperature, low MLD and southwestward movement of the current, suggesting that HABs are affected by the upwelling and currents in GOM. This study also suggests a potential offshore source of HAB cells extending to more than 16-64 km (10 to 40 miles) which is more than what was previously reported.11\n\nK. brevis blooms or HABs were associated with low SSH associated with upwelling regions. SSH was chosen as one of the explanatory variables. Previous studies had related this variable to the position of the Loop Current, which is associated with changes in temperature and degree of upwelling.50 The area with the negative sea surface height mainly exhibited the cyclonic event and represented the upwelling event.79 For example, HABs in the fall of 2020 were preceded by anomalies of SSH and signs of cyclonic eddies where upwelling occurs.80 HABs generally occur after upwelling events.81 Thus, increasing upwelling events are likely to increase future incidences of HABs. Moreover, the oceanography of the GoM, such as the changes in Loop Current dynamics, can affect HABs proliferation in GoM. In the western Florida shelf, altimetry-derived offshore forcing was linked to the occurrence and severity of coastal blooms of Karenia brevis. Years without major blooms tend not to have prolonged offshore forcing, suggesting that the offshore areas can be a potential source of cells. Moreover, the initiation of a more uniform SSH that started in the summer and continued in the fall (Supplementary Figure 4.1B, Extended data) could have been a precursor of HABs, bringing cells offshore to the coastal areas of the GoM states. As such, this study suggests that offshore current forcing and uniform SSH can trigger blooms and demonstrates the importance of physical oceanography in shelf ecology.82\n\nHigh silicate values are often associated with blooms of diatoms. However, K. brevis don’t use silicate as an energy source; yet this study associated blooms with both low and high silicate concentration, due to the bimodal nature of the response of the variable to the presence of harmful levels of K. brevis blooms common in gulf studies. A previous study concluded an inverse correlation between dissolved inorganic nitrogen (DIN): Si (OH)4 and Karenia spp. blooms.83 Silicate is not a physiological requirement of Karenia, and was primarily an artifact of higher Si (OH)4 concentrations common in coastal areas in GoM.83 In addition, its association to high silicate can be explained by K. brevis’s competitive interactions with silicate-utilizing phytoplankton. High silicate areas suggest that there are no silicate-utilizing microalgae present in the area, which allows K. brevis to dominate pelagic communities.84 Thus, this study associates K. brevis blooms with higher levels of silicate due to its allelopathic mechanisms and due to its incapacity to utilize silicate as a food source.\n\nSST influences phytoplankton productivity, allowing them to thrive in specific temperature regimes and biochemical materials availability needed for their growth and development.85,86 Studies have shown a correlation between SST and algal bloom distributions globally.38,87–90 In this study, the blooms of K. brevis increased in the fall and winter primarily because of the ideal temperature conditions for HABs during these times of the year, which ranges from 22-28°C.38,91 However, in several cases, increased SST was found to be conducive to HAB development in the coastal waters of Oman92 and in the Gulf of Mexico.93 A study on Kamchatka HABs has found that temperature anomalies can trigger blooms as it is often followed by intense ocean level variability and formation of vortices and upwelling events in the photic layer of the water.80 Thus, in this study, we found that HABs were impacted by temperatures of 22-28°C and were found to decrease temperature >28 °C.\n\nHABs are associated with a relatively shallow MLD, which signifies that the water column is stable and highly stratified. There were two maxima for MLD (Figure 5E) that may reflect different conditions associated with high HABs presence in nearshore and offshore waters. The nearshore waters were generally characterized by shallower MLDs than the offshore waters (Supplementary Figures 4 and 5, Extended data). HABs are frequently located in the shallow mixed layer.94 A shallow mixed layer is a result of the decline in the wind speed and an increase in the air temperature and, thus, an increase in stratification.95 This increase in stratification is accompanied by a decrease in the amount of nutrients mixed into the surface layers. As such, this can make the bottom water depleted of oxygen, which can potentially develop into a dead zone because of the lack of mixing during HABs events.96,97 In addition, HABs are also associated with higher MLD associated with deeper offshore water (Supplementary Figure 4.1D, Extended data). A previous study showed that K. brevis undergoes vertical migration.37 This suggests that in a deeper MLD, in a more offshore environment, HABs start to proliferate but because of the oligotrophic characteristics of GoM, the cells are not able to form intense blooms. Thus, this study further illustrated the effects of shallow MLD on the proliferation of HABs in the Gulf of Mexico.\n\nThe heading of the current is also an important environmental variable for the HABs model. There is a high probability of HAB presence in currents moving southwestward. On the West Florida coast, the hydrographic features are influenced by the coastal current. The southwestward coastal current drives a subsequent offshore Ekman transport which might lead to coastal upwelling, transporting sub-surface water containing HABs cells closer to the coast.9 Moreover, inshore water is more favorable to HAB proliferation than offshore waters due to both anthropogenic input, such as sewage waste, and natural processes, such as coastal upwelling in the inshore environment as what was observed in coastal blooms in Florida (Figures 7-9). Thus, cyst (cell) concentration was higher inshore than offshore.9,98 Offshore water can be oligotrophic and change yearly depending on the interannual variability in the circulation in GoM.31,45,99 However, factors such as disturbances brought by cyclones can temporarily disrupt the circulation patterns, thus allowing more intense blooms of K. brevis to appear along the coasts.99 Thus, this study pointed out how currents can serve as a vector in transporting HABs from a non-bloom area to an area that is favorable for blooms, such as coastal waters.\n\nPredictions from the SDMs identified five important areas with a higher probability of HABs presence. Probabilities in (1) Southwest Florida, remained relatively stable and persistent throughout the year, suggesting these areas may be highly suitable for HABs year-round. In contrast, in some areas, blooms were irregularly distributed in time. In addition, blooms could be ephemeral and restricted to one state; the (2) North Central Florida, (3) Central West Florida, (4) Alabama, and (5) Mississippi area HAB blooms were more pronounced during the fall-winter season and, and lesser extent in summer seasons, thus, indicating a more seasonal presence. Blooms from the Florida Panhandle region are advected westward towards the Mississippi-Alabama coast that persisted until December. In contrast, the blooms in the West Florida Shelf can be advected by the Loop Current into the Florida Straits and Gulf Stream Current along the East Coast of the United States.100 Although circulation patterns favor westward transport during the fall season in the GoM, drifter data shows that there are no favorable westward currents from Florida to the Mississippi Sound during that time frame, except for a short time. This adds to several factors that explainwhy Mississippi blooms are more temporary.101 This study also provided evidence that the mid-shelf serves as a growth and accumulation region of the blooms and contributes to supplying the coastal blooms. Local eddy circulation in the northeast affects the retention and coastal distribution of blooms.100 This shows how the oceanography of GoM drives HABs and the connectivity of different regions in GoM.\n\nThe model identified strong seasonal patterns in HAB blooms in the GoM. Although Florida is the GoM state that most frequently experiences K. brevis blooms, all other coastal states of the GoM have been affected to a lesser extent. It is also worth noting that the important permanent areas for HABs presence are found in Florida, where water is more stagnant than in the rest of GoM. In contrast, the seasonal areas in Alabama and Mississippi, acted upon by tributary rivers that carry freshwater and high nutrient input, have blooms that are more seasonal.43 The authors hypothesized that in the seasonal areas identified, HABs could be triggered by more seasonal factors, such as an increase in nutrient load, and thus occur over a short time span. In contrast, for those identified permanent areas, HABs persist because of very slow flushing times and dead zones formed in those areas, as well as the currents acting upon it and its proximity to the potential offshore HABs source. The calculated along-isobath geostrophic flows are southeastward from December to March and northwestward in June, August, and September in the Big Bend.102 Such blooms are associated with the southwestward movement of the current (Figure 5) in fall/early winter (Figure 6) regardless of the year. In support of this, previous studies have shown that K. brevis blooms occurred irregularly over the years in the western GoM,103 and that K. brevis blooms occur in fall/winter in southwest Florida.9,99 Karenia brevis, the GoM’s ‘red tide’ organism, usually blooms on the southern/central West Florida Sound during late summer/early fall supported by the first minor peak in our Generalized Additive Model (GAM) model for months starting in August (Figure 6). It is likely that the northwestward along-isobath flow in June, August, and September is capable of transporting K. brevis blooms northward to the Big Bend shelf region during these months.102\n\nYearly variability in HABs was observed. There were also six years (Figure 9), 2012, 2013, 2015, 2016, 2018, and 2019, with high blooms. The blooms had a high probability of occurrence in Southwest Florida in those years. It is also worth noting that high bloom probability happens in consecutive years. Aside from Southwest Florida, the Mississippi area and Alabama experience less intense blooms and happen to be more seasonal. The Mississippi River delta has a presence of HABs but covers less area and is temporary.43 In 2015, blooms were first reported in Florida in September, and in Alabama and Mississippi in November and October, respectively. The 2018 HABs were intense because of the cells from the preceding 2017 bloom and the newly formed bloom in 2018, until 2019 when the offshore conditions were again favorable for bloom development.43,104 This is consistent with westward migration events of K. brevis blooms from areas in the northeast GOM that have been reported in the past, where blooms that originated in central or northern Florida were transported westward.16,102 Our results suggest that these migrating blooms may reach Alabama, such as the blooms in 2018, and Mississippi in 2015. Moreover, as the HABs are transported by water currents, the cell count can increase or decrease depending to how favorable the water is (Figure 5).\n\nWith the association of HABs with different environmental parameters, ocean warming, marine heatwaves, oxygen loss, eutrophication, pollution, and climate change are only a few of the different factors that contribute to the proliferation of HABs.105 In particular, climate change may magnify temperature effects on HABs cell metabolism, range of proliferation, and bloom duration. Hypoxia and anoxia, occurring as a result of elevated bloom biomass and/or the decomposition of HAB-related mortalities, are among the impacts of HABs that are of great concern.11 As global warming intensifies, HABs can occur earlier and attain higher biomass levels.106 As such, the coastal regions of the GoM, because of their relatively flat topography, land subsidence, and extensive coastal development, are particularly vulnerable to climate change and sea-level rise.107 Moreover, climate change, which impacts the water current forcing, and coastal eutrophication have likely increased the occurrence of HABs.11\n\nThis study provides insights into the spatio-temporal patterns and environmental preferences of K. brevis blooms. However, the modeling results should be interpreted with caution as they explain a small proportion of the total deviance (23.3%). The low deviance might be explained by the low percentage of data points which has a cell count of ≥100,000 cells/L (presence of HABs) in the HABSOS dataset. Areas below this cell count are considered a no-bloom area. Also, the use of relatively bigger spatial scales of environmental data contributed to the low percentage of deviance, however since this study aimed to observe spatio-temporal patterns in bigger scales and within a 11-year period, we used 0.25 × 0.25 degree resolution data. Despite the low deviance explained, it is typical for studies to model the spatio-temporal distribution to explain a small proportion of the total deviance (10–19 %).63,66,108 These variables are usually sufficient to explain the target species’ distribution and habitat suitability.109 This high percent deviance may be due to the quality and quantity of data covering the whole distribution of the data-richer species and the spatio-temporal scales used to conduct the analysis.\n\nThe authors acknowledge the biases associated with this data set. Sampling is concentrated if and when there is a bloom, although there are or have been years with more regular monitoring. Moreover, we acknowledge that a 0.25-degree grid is very coarse for identifying small-scale patterns; however, since the study comprised three states, we used a 0.25-degree resolution. Moreover, the said spatial resolution was proven enough to correlate the presence of K. brevis blooms (≥100,000cells/L) between physical/chemical influences on bloom dynamics, especially on the coast of the study areas.\n\nSeveral ways were suggested to improve and validate the species distribution models for HABs in the GoM. The information and types of data used for modeling species distributions are also growing and rapidly driven by technological improvements in data collection systems.110 For example, satellite applications are increasingly being used to inform and validate species distribution models. There are emerging statistical approaches (e.g., integrated species distribution models) capable of integrating and modeling different types of data sets and getting the most from the data revolution.110–112 Lastly, future modeling approaches could also explore the other environment and biological preferences of HABs.\n\nIn this study, the model residuals had both temporal and spatial autocorrelation due to the seasonal patterns observed in the sampling of HABs and the clustering of reported cell count in spaces. The authors thus suggest accounting for this autocorrelation in future studies.113\n\n\nConclusions\n\nKnowledge of the temporal, spatial, and environmental factors influencing HABs presence is essential to identifying areas with high HAB presence and developing measures to minimize their proliferation in bodies of water. Using HABSOS in situ data matched with 0.25°-resolution environmental information from the Copernicus database, this study was able to explore changes in the spatio-temporal distribution of HABs in the Gulf of Mexico. There are five important areas identified to have high HABs presence, including important permanent areas: (1) Southwest Florida, which were characterized by higher probabilities of HABs presence, predicted throughout the year; and four seasonally important areas, (2) North Central Florida (3) Central West Florida, (4) Alabama and (5) Mississippi with higher HABs probabilities during the late fall to winter season (November-January) and a minor peak identified during the late summer season. HABs are linked to SSH, silicate, SST, MLD and heading of the current. This study also provided a possible offshore source of cells that supplies HAB area transported by the currents and supported by the hydrodynamic characteristics of GoM. Identifying blooms in smaller areas needs information from in situ measurements of the environmental variables, in addition to the K. brevis cell density data sets, and thus would require collaboration from different institutions. Information on the spatio-temporal dynamics of HABs in the GoM and understanding the environmental drivers are crucial to support more holistic spatial management to decrease HABs incidence.\n\n\nAuthor contributions\n\nGLG and PM conceived the study and designed the methodology. GLG performed the analysis. GLG wrote the first draft of the manuscript. PM and LB provided feedback on the analysis and manuscript. All authors contributed to the manuscript revision and read and approved the submitted version.",
"appendix": "Data availability\n\nData used in this study were downloaded from the National Centers for Environmental Information (NCEI)- Harmful Algal BloomS Observation System (HABSOS) through this link: https://habsos.noaa.gov/. To download the dataset, you need to click the “data access and map” and then “access map”. Once on the interactive map, click “metadata”. You will be directed to the HABSOS layer information, click “cell count-metadata”. You can download the latest version of the data containing cell counts of K. brevis. Data Source: NOAA National Centers for Environmental Information (2014), https://www.ncei.noaa.gov/archive/accession/0120767 114\n\nZenodo: Modeling the spatio-temporal distribution of Karenia brevis blooms in the Gulf of Mexico, https://doi.org/10.5281/zenodo.7897979 115\n\nThis project contains the following extended data:\n\n- Supplementary Animation 1.mp4\n\n- Supplementary Animation 2.mp4\n\n- Supplementary Figure 1.docx\n\n- Supplementary Figure 2.docx\n\n- Supplementary Figure 3.docx\n\n- Supplementary Figure 4.docx\n\n- Supplementary Figure 5.docx\n\n- Supplementary Table 1.docx\n\n- Supplementary Table 2.docx\n\n- Supplementary_Figure2A.tiff\n\n- Supplementary_Figure2B.csv\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nGray DiLeone AM, Ainsworth CH: Effects of Karenia brevis harmful algal blooms on fish community structure on the West Florida Shelf. Ecol. Model. 2019 Jan; 392: 250–267. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nNOAA National Centers for Environmental Information: Physical and biological data were collected along the Texas, Louisiana, Mississippi, Alabama, and Florida Gulf coasts in the Gulf of Mexico as part of the Harmful Algal BloomS Observing System from 1953-08-19 to 2020-03-09 (NCEI Accession 0120767). [Cell Count Layer]. Dataset. NOAA National Centers for Environmental Information. 2014. [Accessed October 2019]. Reference Source\n\nGuirhem GL, Baker L, Moraga P: Modeling the spatio-temporal distribution of Karenia brevis blooms in the Gulf of Mexico.2023. Publisher Full Text"
}
|
[
{
"id": "177510",
"date": "13 Jul 2023",
"name": "Miles Medina",
"expertise": [
"Reviewer Expertise Water quality dynamics",
"K. brevis bloom dynamics",
"nonlinear dynamics and causality in complex systems",
"statistical modeling and time series modeling with GAMs"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study describes development of a statistical model for presence/absence of Karenia brevis blooms in the Gulf of Mexico (2010-2020). The model predicts K. brevis presence/absence over space and time using in situ K. brevis sample data from NOAA-HABSOS (response variable) and Copernicus ocean model products for physical and chemical parameters (as predictors). Overall, the model is potentially valuable as a monitoring/management tool. The authors set up processes for model selection and validation to avoid multicollinearity and overfitting.\nHowever, it is unclear whether the authors intended to develop a model primarily for prediction or for inference. This distinction is important and not made clear enough, in my opinion. The introduction touches on both prediction and inference. The results section emphasizes the predictive skill of the model (AUC, etc), and in the discussion section the authors emphasize inferences that can be drawn from their selected model without discussing the utility of the model as a predictive tool that could be useful in monitoring and management efforts.\nInference and prediction are two distinct scientific tasks that often require different approaches--the classic distinction between \"to explain or to predict\". I believe that the work that went into this paper is more in line with the task of prediction--given data on current (and perhaps recent) conditions, can we predict the presence/absence of red tide blooms over the Gulf of Mexico? In this respect, the authors' results seem promising and worthy of indexing. Prediction skill is relatively straightforward to quantify, and the model demonstrated good skill according to several metrics; it does not matter so much how the model arrives at predictions, as long as the predictions are acceptably accurate.\nRegarding inference, I believe the model's rigor and validity is insufficient for the nature of the claims made by the authors. The authors commit the \"Table 2 fallacy\" by presenting the model's coefficients and P-values as evidence of real-world mechanisms, without properly vetting the model specification and its implicit causal assumptions. The fundamental impossibility of validating models of thermodynamically open systems is well documented in the literature (e.g. see 10.1126/science.263.5147.641 and 10.1016/0304-3800(95)00152-2). The key point is that incorrect models can predict well, so models that predict well do not necessarily describe real-world causal mechanisms. To deal with this problem, others have proposed rigorous approaches for testing causal hypotheses using statistical models that are specified according to explicit causal assumptions represented using directed acyclic graphs (DAGs), based on work by Judea Pearl (see https://xcelab.net/rm/statistical-rethinking/ and associated YouTube videos by the author, R McElreath). Another non-statistical empirical approach for inferring causality in complex, nonlinear systems is convergent cross-mapping, developed by Sugihara et al. 2012 (see 10.1126/science.1227079).\nThe \"Table 2 fallacy\" is extremely common in many scientific domains, and I do not fault the authors personally for presenting the results of a statistical model as evidence of causal mechanisms. However, my advice is to re-frame the paper in terms of the development of the model as a predictive tool. In this regard I think the model has great potential utility in HABs monitoring, management, and perhaps forecasting. The authors' presentation of their literature review (evident in the discussion section) could be reframed in terms of justifying the inclusion of certain covariates in their pool of models, rather than using the literature as a baseline for comparison with inferences drawn from the author's selected model.\n\nIn addition, I would encourage the authors to share their data and code in an open-source repository and provide the URLs or DOIs.\nDetailed comments are organized below by section. For most comments, passages from the manuscript are quoted, followed by comments/questions.\nINTRODUCTION\n\"In the last 50 years, the Florida red tide blooms have become more common, frequent, and intense, especially along the West Florida Shelf (WFS) on the Southwest Florida coast during late summer and early spring.\"\nThis statement is not clearly supported by the cited sources, and unfortunately it is difficult to draw conclusions about long-term trends from the available data due to sampling bias associated with event-based sampling. The authors acknowledge such potential bias in the discussion/limitations section, but they should at least mention it earlier in the paper as well (perhaps the Methods section).\n\n\"However, this method [microscopy on in situ samples] is susceptible to spatial and temporal biases due to HABs being highly dependent on environmental conditions such as nutrient input and water circulation. Bio-optics advances have contributed to counteracting the biases during in situ data collection by providing a means of non-intrusive data collection at more frequent spatial and temporal scales in identifying potential incidence zones of HABs.\"\nThe first sentence is unclear, and the cited source simply proposes a lab technique for analyzing K. brevis samples. I think a more accurate and compelling statement in line with what I believe is the author's intent here would be that in situ sampling only gives a snapshot of conditions at a particular place and time. In the second sentence, is bio-optics referring to remote sensing approaches (i.e., satellite imagery)?\n\n\"Factors linked to HAB abundance are depth, water column stability, temperature, and decreasing wind.\"\nThis list of factors linked to HABs is not complete, and it need not be. The authors should either include other important factors identified in the literature, or indicate that the list is incompete (i.e., \"Factors linked to HAB abundance include but are not limited to...\"). One such unlisted factor linked to blooms on the Southwest Florida Coast is anthropogenic nutrient loading, per citation #12 (10.1016/j.scitotenv.2022.154149), although nutrient loading is mentioned elsewhere.\n\n\"Factors linked to HAB abundance are depth, water column stability, temperature, and decreasing wind. There is a need for a more robust satellite-derived HAB index.\"\nThere seems to be a lack of logical structure connecting the statements in this paragraph, particularly between the two sentences cited above. The intent here and in the two preceding paragraphs seems to be to justify the use of remote sensing for monitoring HABs in the GOM, but the logical thread connecting this idea across these paragraphs seems to get lost as the writing wanders from one topic to another.\n\nThere are two paragraphs beginning with the sentences below. The content in these may be a better fit in the methods or discussion section rather than the introduction, because they explain relevant conditions or link the study's conclusions to existing literature:\n\n\"One of the variables that were previously used to describe blooms is the wind pattern; however, in this study, we used water currents as it has a direct impact on ocean circulation...\"\n\n\"There have been several studies explaining the mechanisms of K. brevis blooms in Florida and Mississippi, but none for Alabama; however, most of these studies are patchy and are concentrated in small spatial scales...\"\n\n\"The prediction in bigger spatial scales for complex coastal domains such as the GoM is still limited. Predicting the spatial and temporal presence of HABs requires knowledge of the spatial and temporal dynamics of a species and the associated environmental conditions.\"\nYes, prediction can benefit from better knowledge of the system ('required' is too strong). However, prediction and inference are distinct scientific tasks that the authors seem to muddy throughout the paper, as I described at the top of this document.\nMETHODS\n\"In this paper, K. brevis cell count expressed in cells per liter (cells/L) were modeled. Cell count information was collected in the states of Florida, Alabama, and Mississippi, which are the areas in the GoM with the highest presence of HABs in the HABSOS database.\"\nHow did the authors account for sampling depth? Did they exclude samples below a certain depth? Are the results only relevant for K. brevis near the surface (e.g. within one meter of the surface)? As far as I can tell, the authors do not describe K. brevis cells' position in the water column and how this affects modeling or results.\n\n\"The environmental variables considered to be potential predictor variables for the habitat modeling were nitrate (NO3), phosphate (PO4), silicate (Si)...\"\nIt is worthwhile to consider nutrient concentrations estimated by the Copernicus model for building a model that can predict presence/absence of K. brevis in the GOM. However, like any numerical model, the biogeochemical component of Copernicus makes assumptions that may limit its reliability in certain applications. They authors should briefly describe the relevant limitations in the context of development of their model and what inferences can be drawn from it. Readers will have more confidence that the input data were used appropriately if the authors are transparent about limitations and indicate that these were carefully considered. For instance, how reliable are the nutrient concentrations estimated by Copernicus, considering that the data assimilation is not optimized in the NRT version? How much in situ data were actually available/used for data assimilation during the study period (2010-2020)?\n\n\"The covariates modeled were the environmental variables (Table 1), spatial variables (Longitude and Latitude), and temporal variables (Month and Year). Month and Year variable were included to account for the seasonal and inter-annual variability in K. brevis blooms, respectively.\"\nWas the K. brevis sampling depth used? Unless it is explained, it is easy to imagine cases where the sampling depth for K. brevis is different from the depth(s) associated with the Copernicus-estimated values.\n\n\"Moreover, as an additional measure to avoid overfitting in the selection process, only significant variables (p < 0.05) were kept, and non-significant variables were sequentially omitted.\"\nHere, it is very relevant whether the primary goal is prediction vs. inference. If the primary goal is prediction (as I believe it should be), then any number of 'variable selection' procedures can be considered useful/effective if in the end the model does a good job at predicting. However, to the extent the goal is inference, I take issue with the variable selection step described above (removing non-significant variables after fitting the GAM). Based on my training and experience, a lack of statistical significance does not justify kicking a covariate out of an inferential model. Inclusion of a covariate in the model must be determined by a justifiable theoretical/empirical foundation, not determined ad hoc based on the model's output. Otherwise, the variance that would be attributed to the non-significant covariate (which we believed was worth including for _some_ reason) may be incorrectly attributed to other covariates or unnecessarily put into the residuals.\nConsidering that the authors are concerned about multicollinearity, it may preferable to apply regularization. For instance, in mgcv::gam(), you can set select=TRUE to allow the model to effectively discard variables by estimating their coefficients at zero. At a minimum, the authors should justify their choices on this issue, or, they should consider exploring other approaches such as those described above, to see if the results are robust to these decisions.\nAgain, however, the goal of this study seems to be prediction, not inference, so multicollinearity, variable selection, coefficient estimates, and P-values need not be of great concern, if the model predicts well.\n\n\"The performance scores from the four indices in combination were used to evaluate the predictive performance of the SDMs.\"\nAs far as I can tell, the acronym SDM is not defined anywhere. Species distribution model?\n\n\"For the model prediction, the monthly predictions between 2010-2020 were averaged to calculate an overall mean prediction map and the standard deviation across the monthly prediction over the 11 years to capture uncertainty. Finally, yearly predictions between 2010-2020 were calculated by averaging the monthly predictions within each year for the probability of the presence of HABs.\"\nThis is unclear. Were the monthly predictions averaged to generate annual predictions (mean +/- sd)? If so, the language here seems redundant and confusing.\nRESULTS\n\"Figure 1 shows the monthly spatial distribution of the presence (≥100,000 cells/L) and absence (<100,000 cells/L) of K. brevis blooms in the Gulf of Mexico from 2010−2020 (shaded 0.25 × 0.25 grids) from the Harmful Algal BloomS Observing System (HABSOS). The white cells mean no sample was collected in the grid cells. Time step 1–12 corresponds to a month in a year such as 1-January, 2-February, 3-March, 4-April, 5-May, 6-June, 7-July, 8-August, 9-September, 10-October, 11-November, 12-December.\"\nThis information belongs in the caption of each figure, not in the main text.\n\n\"Figure 2 shows yearly spatial distribution of the presence (≥100,000 cells/L) and absence (<100,000 cells/L) of K. brevis blooms in the Gulf of Mexico from 2010−2020 with 0.25 × 0.25 degree grids, from HABSOS. The white cells mean that no sample was collected in that grid cells. Figure 3 shows temporal patterns of the total number of observed presences (≥100,000 cells/L) of K. brevis blooms in the Gulf of Mexico from 2010-2020; Figure 3A shows the total number of presences (≥100,000 cells/L) of HABs sampling by month between 2010-2020 while Figure 3B shows the total number of observed sets with the presence of HABs by month between 2010–2020.\"\nThis information belongs in the caption of each figure, not in the main text.\n\n\"The lowest sampling of HABs was found to occur in 2020 (Figures 2A and 3A). The highest HAB monitoring was done from August to November, with increasing monitoring from 2016-2019. The highest level of monitoring regarding the number of samples collected was from September to November, which coincides with the fall season and the months of January and December, corresponding to the winter season.\"\nDescriptions of the K. brevis dataset, such as when sampling was more or less frequent, should appear in Methods. Also, Figure 2 has only one panel, so I believe the reference to Figure 2A is incorrect.\n\nFigure 3.\nThe information in these plots is hard to interpret visually because of the large number of colors used, and it may be difficult for folks with colorblindness to distinguish these colors. A simpler color palette--for instance, the viridis palette (yellow to green to purple) or better yet, something monochromatic (e.g. a white to blue gradient)--may improve the visual communication (rather than the full ROYGBIV spectrum).\n\n\"Because of high correlation and collinearity among several variables, only one variable from the following five groups of covariates was included in the selection process and SDMs at a time (Supplementary Figure 2, Extended data): 1) latitude and longitude; 2) salinity and longitude; 3) nitrate and longitude; 4) nitrate and silicate; 5) nitrate and salinity; 6) nitrate and latitude; and 7) current velocity and eddy kinetic energy. Since latitude and longitude are correlated, we used salinity to replace longitude since salinity is correlated to longitude but not to latitude\"\nThis information about how the GAMs were specified may fit better in the methods section. More importantly, the choice to exclude longitude in favor of salinity is strange; likewise for other pairs listed above. I understand that longitude and salinity were correlated (more eastern longitudes closer to Florida's coast are more likely to have lower salinity due to freshwater inputs to estuaries). However, the geographic position (lat, long) seems at least intuitively relevant and likely useful for prediction. If multicollinearity is a concern, then regularization may be the solution, for example by setting select=TRUE in mgcv::gam(). The authors should at least comment on why they did not use regularization to deal with multicollinearity, or further, they could revisit the model specification to see if their results are robust when regularization is applied. But as stated before, I am not sure why the authors are so concerned about multicollinearity if the goal is prediction. That is, it should not matter how the model partitions variance among correlated predictors, as long as the model predicts well.\n\nTable 2.\nI take issue with presentation of this information in the main article because the primary goal of this paper should be to present a predictive model, not an inferential model. The coefficient estimates and P-values do not matter so much, and their inclusion here gives a false impression that valid inferences can be drawn. If the goal of this study were inference, then this information would be relevant but the authors should go about hypothesis testing differently. One must first state the hypotheses and then put forward a model specification for each hypothesis, with theoretical/empirical justification. Here, the authors commit the \"Table 2 fallacy\" by specifying a pool of regression models, each containing many covariates, and then presenting the coefficient estimates from the preferred model as evidence indicating which covariates are causally relevant to the response (K. brevis response/absence). There is much statistical scholarship criticizing this approach, askin to throwing everything at the wall to see what sticks. My advice is to remove Table 2 and remove any strong inferential claims from the paper, and instead focus on putting forward what is a potentially valuable predictive model for K. brevis blooms in the GOM.\n\n\"The overall averaged predictions across 2010-2020 identified one important permanent area, Southwest Florida, with higher probabilities of the presence of HABs.\"\nThis is only a semantic criticism, but the term \"permament area\" seems too strong here. I understand that blooms have occurred pretty much annually in this area during the study period, but we are talking about a single decade (2010-2020), and the blooms do not typically persist throughout the year. \"Permanent area\" too strongly suggests that K. brevis blooms have occured constantly throughout the year during this 10-year period, when in fact they typically occur seasonally (as stated elsewhere in the paper).\n\nIn the results section, the authors should clearly but briefly state relevant limitations with each set of results and point the reader to the discussion/limitations section for more detail. The HABSOS and Copernicus datasets each entail important limitations that affect interpretation of results.\nDISCUSSION\n\"The model identified and highlighted the importance of five areas in the GoM: (1) Southwest Florida and (2) North Central Florida, (3) Central West Florida, (4) Alabama, and (5) Mississippi.\"\nIs it possible that these areas are the focus of monitoring efforts, and the \"importance\" of these areas is to some extent an artifact of the spatial distribution of the monitoring effort? If they have not done so already, the authors should investigate whether these five areas coincide with monitoring hot spots, and then comment on any interesting findings, discrepancies, or doubts/uncertainties.\n\nThe discussion section quickly delves into mechanistic explanations that can be inferred from the preferred GAM model. As described above, this is problematic for a number of reasons. No mechanistic hypotheses were clearly stated in the introduction, and the model was not designed for hypothesis testing (see my comments about the Table 2 fallacy, above). This concern cannot be remedied by retroactively adding a mechanistic hypothesis to the introduction, because inference about real-world mechanisms is beyond the scope of the work that was done for this paper. Instead, in my opinion the authors should stick to describing the development of their predictive model, and the discussion section should focus on describing the utility of the model in the context of HAB monitoring and management, as well as limitations of the work and further work that can be pursued (both for the GOM and potentially more broadly). References to the literature that appear in this 'inference' section of the Discussion could perhaps fit in the Introduction or Methods, as justification for why certain covariates were considered for inclusion in the model.\n\n\"However, the modeling results should be interpreted with caution as they explain a small proportion of the total deviance (23.3%).\"\nThis % deviance explained is an important result that should be presented in the results section, not simply buried in the discussion/limitations section.\n\n\"The authors acknowledge the biases associated with this data set. Sampling is concentrated if and when there is a bloom, although there are or have been years with more regular monitoring.\"\nI am glad to see the authors acknowledge sampling bias in the K. brevis data. However, this information is currently buried in the discussion/limitations section. This bias issue should be introduced where the HABSOS dataset is first described (methods section) with an indication that more information about sampling bias is provided in the discussion/limitations section.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "177513",
"date": "11 Aug 2023",
"name": "Inia Mariel Soto Ramos",
"expertise": [
"Reviewer Expertise I am a biological oceanographer and my research focus on the use of satellite ocean color to study harmful algal blooms."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary: This manuscript combines Karenia brevis cell count data from 2010-2020 with biotic and abiotic (NO3, PO4, Si, Salinity, SSH, MLD, SST, current velocity, Ke) variables derived from the Generalized Additive Models (GAM) to predict the temporal and spatial distribution of Karenia brevis blooms in the Florida-Alabama-Mississippi region. While I think this is an interesting approach and of public interest, I will put in question the results as being driven by the limited cell count dataset and not necessarily by the output of the model. A temporal analysis of all the available cell count data (that goes back more than 20 years) would provide a more realistic view of the spatial/temporal distributions of HABs. The relationship between the GAM variables is informative, however, the way they were presented is concerning and possibly misleading. What concerned me the most is that Figures 1 and 2 do not match what we can publicly see in HABSOS. I am not sure if the issue is a misleading color scale, a wrong way to plot the data, or if the results are incorrect. For example, there were a handful of HABs (>100,000 cells/L) reported in South Florida, but nothing in northern FL, MS, or AL on the HABSOS database. At its current state, my overall recommendation for this manuscript is to be rejected or go under major revision, especially to address the mismatching of HAB data in their first two figures with what is available in HABSOS. This makes me highly question the results of the model, which don’t agree very well with what we see in the data. Below, I will provide a list of concerns and points to address.\n\nAbstract:\n\nWeak and broad introduction sentence.\n\nAdd a sentence that states the objective(s). The sentence “The data was used to analyze the relationship between …\" is confusing.\n\nVariability of HABs link to geographic location (latitude and salinity). I would not classify salinity as a location variable.\n\nsilica concentrations of 0 and 30-35? I don’t understand the “0” in the parenthesis.\n\nCurrent only moving at 225 deg? This should be a range...\n\nLast sentence: how is management going to decrease the incidence of K. brevis blooms with this work?\n\nIntroduction:\n\nClarify the first sentence of paragraph 4. Karenia brevis blooms can be toxic at levels of 10^3 ---these are not a naturally occurring concentrations. This is a bloom already.\n\nParagraph 7 about satellite HAB detection techniques: Please use current and relevant references. This paragraph is > 20 years outdated.\n\nLines between references #30 and #31, need a reference as well.\n\nReference 16 includes Alabama, therefore remove the “none for Alabama”? In the same sentence you say, “small spatial scales”. What do you mean by small? Satellite studies are in the order of 100 to 1000km, or even more?\n\nHow environmental covariates can enable the development of predictive models? This is important and the only sentence that better describes the objective of the manuscript. So, go ahead and provide more information.\n\nWhen you describe the current models, the references are outdated. Can you elaborate more on the current USF models?\n\nWhy did you select the timeframe from 2010-2020 and why the selection of your cell count threshold?\n\nWhat are the accuracy and uncertainty of your derived GAM variables?\n\nHow do you create the matchups between HABSOS and GAM variables, which are two different resolutions?\n\nResults:\n\nLatitude and Longitude labels are incorrectly placed on the wrong axis for all the figures.\n\nFigure 1-2: What does the color bar mean? Is that the real range: 0-~150? Mean of what, cell counts data points above 100,000 per grid pixel? Does the purple data mean you found data (at least one point) above >100,000? Figure 1 is showing data in purple that I cannot find in HABSOS. The plot looks as if all the samples with <100,000 cells/L (including the ones with no presence) were included in the plot. However, the caption says this is the presence of HAB’s (>100,000 cells/L) for those years. Labels need units and each map plot is very small to really see anything.\n\nText for Figures 1 and 2, should be corrected accordingly. For example, it says there were blooms in 2010 in all the regions. That is not true.\n\nFigure 4 doesn’t make any sense. What are the colors? How does this predict the probability of HABS? Is the x-axis salinity? It honestly looks like longitude ...\n\nFigure 7 highlights how the data is driving the model. Axis is labeled wrong.\n\nFigure 8. The results look unreal for months 7-9, and disagree with your yearly results or with the plots seen in Figures 1-2\n\nDiscussion:\n\nI will not go into detail, because the results are not making sense. Once the plots and data are clarified, then one can review the discussion. There are many examples of inconsistency between the results and the discussion. For example, “HABs in the fall of 2020 were preceded by anomalies in SSH …\", but there were no HABs plotted in 2020 in Figure 1 or 9. Although I thought the discussion has some very interesting and worth publishing information, the data presented in the figure's maps (1,2,8,9) are misleading and I will exert caution.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-633
|
https://f1000research.com/articles/12-632/v1
|
08 Jun 23
|
{
"type": "Systematic Review",
"title": "Infodemic in Public health a reemerging public health threat: a scoping review",
"authors": [
"Mithun Pai",
"Shweta Yellapurkar",
"Aishwarya Shodhan Shetty",
"Aishwarya Shodhan Shetty"
],
"abstract": "Background: Infodemic is a neologism of ‘information’ and ‘epidemic’ coined in the year 2003. Evidence mapping is a technique to appraise the literature which enables the extent of research activity in a specific area to be discovered. The main objective of this evidence synthesis presents the outcomes of an evidence map that was directed to know the extent of Infodemics and its effects on public health. Methods: The following methods were used to construct this evidence synthesis: Phase I. Construct a Broad Question Referring to the Field of Analysis. Phase II; Defining Key Variables to Be Mapped, identifying the characters of each variable and Outline Inclusion and Exclusion Criteria for the variables. Phase III: Literature search. Phase IV: Screening and Charting the Appropriate Evidence within the Synthesis. Results: Authors identified 55 records through database searching, after screening for duplicates, 53 records screened at title/abstract level of which, 16 records were removed because of lack of complete article or articles were not in English. 37 articles were eligible for full text screening, 37 full-text articles were than assessed for eligibility and only 22 articles were included as per inclusion criteria with an interrater Outcome Kappa value: 0.91. The strength of agreement was considered to be 'excellent'. Conclusions: This synthesis focused majorly on the gaps in the research focused on infodemic. The two main gaps identified were lack of systematically conducted research and poor digital health literacy. As infodemic is a new phenomenon with respect to the COVID-19 pandemic it was an eye opener at different levels of public health, furthermore this evidence map points out areas for further research on the impact of infodemic.",
"keywords": [
"COVID 19",
"evidence synthesis",
"infodemics",
"misinformation",
"management Public health",
"social media"
],
"content": "Introduction\n\nSocial media plays a pivotal role in dissemination of information. This information is always not credible, as it is believed to spread misinformation and disinformation. The spread of misinformation is not a new phenomenon but the magnitude of its spread was a concern during the COVID-19 pandemic.\n\nThe portmanteau word Infodemic is a neologism of ‘information’ and ‘epidemic’ coined in the year 2003.1 An infodemic means an excessive amount of information of which some are accurate and some inaccurate, usually occurring during a pandemic/epidemic. Similar to the pattern of spread of a pandemic, an infodemic spreads in the same mode, but through digital or/physical information systems, making it more complex for people to isolate a solid and reliable source of information.2,3\n\nInfodemics have been one of the most virulent phenomena known to humankind, capable of transiting the world instantly. In every possible aspect they mimic a disease, with an epidemiology of its own, symptoms similar to a disease. Sadly it is one of the most highly neglected and underestimated problems.4\n\nThe spread of COVID-19 correlated to the spread of misinformation, in terms of circulating conspiracy theories, often dispersed through social media platforms. This constituted a risk to the public and presented a major global health hazard. Delivering a vital source of evidence-based information to the general public during an outbreak of a pandemic aids in quick act of managing the disaster.5\n\nEvidence synthesis is a technique to appraise the literature which enables the extent of research activity in a specific area to be discovered. Systematic reviews usually detail a specific clinical question and seek to answer the question. Evidence mapping on the other hand provides a brief summary of the range, distribution and scope of evidence in a field of interest broadly.6 Evidence synthesis are formulated on an explicit research question concerning the field of interest, which are not in depth analysis of a question but rather a systematic accumulation of topics of interest.5,7 The evidence synthesis initiates search, and collation of, suitable evidence making use of clear and replicable methods at every step. The synthesis includes clear definition of components, evolution of a detailed and reproducible search strategy, development of clear exclusion and inclusion criteria, and clear conclusions about the level of evidence to be obtained from individual study.\n\nFor the present evidence synthesis an open access online tool CADIMA was used for management of evidence that was established by Julius Kühn-Institut (JKI) during a EU-funded project called GMO Risk Assessment and Communication of Evidence (GRACE). CADIMA is a free web tool guiding the conduct and furnishing the documentation of systematic reviews, systematic maps and further literature reviews.8 CADIMA is outlined to offer substantial evidence to users in the structure of prompts, that majorly differentiates between a meticulous systematic review and a quality literature review, this feature substantially reduces the difficulty in assimilation of evidence for new research.\n\nThe main objective of this evidence synthesis presents the outcomes of an evidence map that was directed to know the extent of infodemics and its effects on public health during the ongoing pandemic and attempts to explore the nature of evidence present in literature. The process assures a procedure of ‘stocktaking’ of the evidence as vital gateway in providing a sketch of the extensiveness of research activities in the field of infodemics. After consulting experts in Public Health (community medicine), Public Health Dentistry and also the nodal Covid officers of COVID 19, a relevant question was framed and the scope and frame of the was chalked out. The process disclosed two domains, mainly the causes of Infodemics and the effects of infodemics on public health, as the first question was the primary focus of the evidence synthesis two secondary questions were included to widen the scope of this evidence. The objectives of the present review were to screen for good-quality evidence on the effects of infodemics on public health during the Covid-19 pandemic and to know the impact of infodemics and various strategies to manage infodemics in public health during the Covid-19 pandemic.\n\n\nMethods\n\nThe authors established a baseline for defining variables for the literature search. The definition of infodemic was established from the World Health Organisation guidelines as ‘infodemic’- is too much information including false or misleading information in digital and physical environments during a disease outbreak’.9 The other key variables included COVID 19 defined as Coronavirus disease (COVID-19) which is an infectious disease caused by the SARS-CoV-2 virus and public health as the topic is novel we included all the available evidence present from Ramdomised control trail, non-randomised controlled trials, systematic reviews, overviews and meta-analyses, as the reviewers wanted to know the range of evidence that would be available for conducting a map for a template for future investigations to be carried out in the field of infodemics. Explanations of the type of review were not definable or are consistently explained as numerous differing terms are used, and many a times interchangeably, therefore only those reviews were included which used a simple methodical search strategy but were systematic in search strategies. There were no restrictions for year of publication but complete articles published in English or with an English translation were included.\n\nThe authors designed a search strategy using medical subject headings and specific keywords. There was no restriction on publication date but the language was restricted to English. A search was conducted in two databases namely MEDLINE and Scopus. The reference lists of the included studies were also searched for potential evidence.with the following key words Infodemic AND Public AND Health AND Covid-19 NOT Vaccine.\n\nThe search criteria for MEDLINE and Scopus were devised as they are the two most commonly used databases for medical literature searches. Multiple databases were not screened because this was an evidence synthesis.\n\nThe search included the keywords Infodemic AND Public AND Health AND Covid-19 NOT Vaccine. Filters were used for Abstract, Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Review, Systematic Review.\n\nTitles and abstracts of all articles deemed important and relevant were recognised by the searches of the two databases. Two reviewers separately selected all the evidence. The search outcomes were screened. Inclusion and exclusion criteria were applied with interrater Outcome Kappa value: 0.91. The strength of agreement was considered to be ‘excellent’.\n\nThe reviewers deliberated all studies, regardless of design, as eligible for inclusion. A population and outcome (PO) search strategy that was wide enough to cover all topics was developed for categorizing potentially significant studies in any topic area. We excluded review articles that did not have any systematic search strategies but scrutinized the bibliography for identifying other potentially appropriate evidence. There were no restrictions for year of publication but the articles published in English or with an English translation were included.\n\nThe selection of the retrieved articles involved the authors (MP and AS) independently and solved disagreements by consensus or consultation with a third reviewer (SY) Each time the title or abstract reported a keyword of relevance appearing to be eligible for the inclusion, the full article was obtained. All references were retained post the initial screening and later assessed for the inclusion and exclusion criteria the following information was extracted: (i) title, (ii) author, (iii) journal, (v) publication year, (vi) location of key words, (vii) type of article/study and (viii) comments based upon the full texts. all the articles were charted in a standard Excel format. The data extraction sheet can be found under Underlying data.25\n\nThe present review drives past the scope of only ‘evidence mapping’ if a systematic review was obtainable than that was inserted into the mapping process and can be considered as an umbrella review and evidence mapping and a brief qualitative explanation of the key results have been considered and each theme is described below (Figure 1).\n\n\nResults\n\nThe authors identified 55 records through database searching, after screening for duplicates, 53 records were screened at title/abstract level of which, 16 incomplete or non-English articles were removed and 37 were eligible for full text screening. 37 full-text articles were then assessed for eligibility and only 22 articles were included as per the inclusion criteria with an interrater Outcome Kappa value: 0.91. The strength of agreement was considered to be: ‘excellent’.\n\nThe majority of the studies focused on the first domain impact of infodemic followed by effect of infodemic and management in infodemic during the covid-19 pandemic. The studies explicitly mentioned the psychological impacts on infodemics, the health care burden, low digital health literacy, economic burden, financial losses, and desensitization of the public towards infodemics.\n\nThe studies failed to include some vital aspects such as ways to manage and overcome the infodemic during the covid 19 pandemic. A review article by Khan S et al.10 and Sharma DC4 elucidated some factors that contributed to the impact of infodemics on health care workers. They found that low immunity due to stress and drop in intellectual capacity due to inadequate resting time led to risk of acquiring infection and psychological traumas.11\n\nMisinformation is ‘false information shared by people who have no intention of misleading others. Disinformation is defined as false information deliberately created and disseminated with malicious intentions.’12 As this phenomenon spread at a faster rate, health professionals had to come up with a solution and very few health care workers came on social media to clarify this publicly (Tables 1 and 2).13,14\n\n\n\n• Psychological disturbances due to pandemic\n\n• Improvement in health journalism to improve health literacy\n\n• Flaws in conducting research\n\n• Faster publication process\n\n\n\n• Increased publications resulting in bias in peer reviewing process\n\n• Anxiety caused by infodemic\n\n• Psychological traumas\n\n\n\n• due to the uncontrolled circulation of mis information\n\n• Digital imbalance of the information\n\n• Repercussions of the infodemic on mental health of the elderly\n\n• Politicization of the virus\n\n\n\n• Research area focused on digital health literacy in indigenous populations\n\n• Shared decision making (SDM)\n\n• Artificial Intelligence (AI) to improve the digital health literacy and to fight infodemics\n\nA review by La Bella E15 points out a significant contribution of flaws observed in the systematic reviews that were being published, feeding flawed information to the internet. Bias occurring during peer review and the editorial process has led to the publishing of misinterpreted data to the public. In a cohort of low digital health literates which formed the major portion of the populous, believing deluded information was aphenomenon.16,17\n\nThe existing uncontrolled, unfiltered information provided by the top social media platforms need stricter vigilance, information screening and protection systems. Public awareness of health literacy has to be increased, poor health literacy is also an underestimated global public health problem, and the COVID-19 pandemic has amplified the need for health literacy across the world. Hong et al.18 evaluated the students majoring in healthcare on health literacy levels related to COVID-19 infection. Hong et al. specified that there was a need to educate and improve the health literacy among the students pursuing health sciences because they form the future of health profession whose responsibility is to educate the masses regarding infodemics if and when there is a future pandemic.\n\n\nDiscussion\n\nWe conducted a synthesis of 55 records from the databases, of which 22 articles were retrieved satisfying the inclusion criteria as predetermined. This amalgamation included 4 phases of systematic data synthesis - Phase 1 focused on the 3 domains, one - the impact of infodemic on public health, two - its effects on public health and, three – Management of infodemic. Our evidence synthesis revealed that the most effective way to overcome an infodemic phenomenon was to increase digital health literacy by educating the masses and the future research to be directed with an accurate methodological process that is supported by strong evidence.\n\nA review by Choukou et al.19 categorised the needs for digital health into five parts. They are 1) knowledge of the disease to be increased by digital health literacy, 2) to manage and cope with new practices and changes from the routine, 3) to overcome anxiety and fear regarding the disease (COVID 19), 4) to overcome the barriers to health literacy and 5) increase the acceptance to technology.19 A study by Li X20 revealed that during the COVID-19 pandemic the main barrier for cohorts with HIV/AIDS to understand their individual health, illness and treatment was considered to be poor health literacy.\n\nSocial media as a preventive approach could help in circulating the authentic news and information on diseases. This could help the public in adopting the necessary measures for control of the disease. Lack of digital equipment in vulnerable groups is the basis for poor digital health literacy in population, and resolving this situation through health care organisations reaching out to such groups and enabling access to an electronic source for information and health care of these groups should remain a priority.20\n\nA systematic review conducted to assess the media sources of information and knowledge levels about COVID-19 revealed that 40% of the population depended on social media as their primary source of information regarding the disease.21 The increased circulation of misinformation in social media platforms during the accelerated health emergency has led to a cataclysmal infodemic.\n\nResearchers have the advantage and the right medium to hold back this tide of infodemic and any paucity in conducting the research process could lead to either insufficient information or could be interpreted insufficiently. The rapid spread in false medical cures or false remedies was noticed during the pandemic in large populations. The examples for such false remedies include smelling spices and inhalation of steam with salt could kill COVID 19 before it reached the lower respiratory system.22 Implementing artificial intelligence to tackle this will help publish evidence based and systematically conducted research and filter out the biased publications during a pandemic.22 The quality of research published should be evaluated critically for any misinformation. Hence researchers have to comply with publishing and reporting strong scientific evidence.23\n\nThis review has exposed certain definite evidence gaps in the field of infodemics and the ways to manage infodemics during a pandemic. In this unprecedented world with many unexpected situations, infodemics will be a common phenomenon, hence studies on health literacy, and identification of cohorts at high risk of this phenomenon will be a way forward.\n\nOur evidence synthesis was conducted systematically, with inclusion of appropriate literature based on the study objective. The study highlighted the impact and effects of infodemics on public health and ways to manage this phenomenon. The study focused on research gaps in the field of infodemics and has paved way for further research by finding evidence gaps in literature for the same. The major limitation of the study was that we included data from only two databases as the focus was just on finding evidence gaps and exploring further avenues for new research.\n\n\nConclusion\n\nThis synthesis focused mostly on the gaps in the field of infodemics and public health. The two main gaps identified were lack of systematically conducted research and poor digital health literacy. As infodemics are a new phenomenon with respect to the COVID-19 pandemic, it was an eye opener at different levels of public health, furthermore this evidence map highlights the need for further research on the impact of infodemics and prevention of their spread. Hence further studies are required to strengthen public health infrastructure and prevent this digital virus.\n\nIt has been recommended that the application of Artificial intelligence (AI) in assisting to screen the data available for accurate translation, summarization, simplification and content filtering should be the immediate approach to address this catastrophe.",
"appendix": "Data availability\n\nFigshare: Infodemic in Public health a reemerging public health threat – evidence synthesis, https://doi.org/10.6084/m9.figshare.21929634. 24\n\nThis project contains the following underlying data:\n\n- critical_appraisal_outcome (1).xlsx (the outcomes of each article is critically appraised and described under Article ID, Study ID, Title, Publication year, Authors, Data location, Study name, comments)\n\n- data_extraction_sheet_2021 (1).xlsx (the study for data extraction described under article id, study id, author, publication year, title, data location and study name)\n\nFigshare: Infodemic in Public health a reemerging public health threat, https://doi.org/10.6084/m9.figshare.22132904. 25\n\n- Flow diagram\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nReferences\n\nAsif M, Zhiyong D, Iram A, et al.: Linguistic analysis of neologism related to coronavirus (COVID-19). Soc. Sci. Humanit. Open. 2021; 4(1): 100201. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMourad A, Srour A, Harmanani H, et al.: Critical Impact of Social Networks Infodemic on Defeating Coronavirus COVID-19 Pandemic: Twitter-Based Study and Research Directions. IEEE Trans. Netw. Serv. Manag. 2020; 17(4): 2145–2155. Publisher Full Text\n\nEysenbach G: How to fight an infodemic: The four pillars of infodemic management. J. Med. Internet Res. 2020; 22(6): e21820. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSharma DC, Pathak A, Chaurasia RN, et al.: Fighting infodemic: Need for robust health journalism in India. Diabetes Metab. Syndr. Clin. Res. Rev. 2020; 14(5): 1445–1447. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHetrick SE, Parker AG, Callahan P, et al.: Evidence mapping: Illustrating an emerging methodology to improve evidence-based practice in youth mental health. J. Eval. Clin. Pract. 2010; 16(6): 1025–1030. PubMed Abstract | Publisher Full Text\n\nBragge P, Clavisi O, Turner T, et al.: The global evidence mapping initiative: Scoping research in broad topic areas. BMC Med. Res. Methodol. 2011; 11: 11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhan G, Kagwanja N, Whyle E, et al.: Health system responsiveness: a systematic evidence mapping review of the global literature. Int. J. Equity Health. 2021; 20(1): 112–124. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKohl C, McIntosh EJ, Unger S, et al.: Online tools supporting the conduct and reporting of systematic reviews and systematic maps: A case study on CADIMA and review of existing tools. Environ. Evid. 2018; 7(1): 1–17. Publisher Full Text\n\nWorld Health Organization: WHO Competency Framework: Building a Response Workforce to Manage Infodemics. 2021. Reference Source\n\nKhan S, Siddique R, Xiaoyan W, et al.: Mental health consequences of infections by coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Brain Behav. 2021; 11(2): e01901. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOlff M: Stress, depression and immunity: The role of defense and coping styles. Psychiatry Res. 1999; 85(1): 7–15. PubMed Abstract | Publisher Full Text\n\nClemente-Suárez VJ, Navarro-Jiménez E, Simón-Sanjurjo JA, et al.: Mis–Dis Information in COVID-19 Health Crisis: A Narrative Review. Int. J. Environ. Res. Public Health. 2022; 19(9). PubMed Abstract | Publisher Full Text | Free Full Text\n\nTopf JM, Williams PN: COVID-19, Social Media, and the Role of the Public Physician. Blood Purif. 2021; 50(4-5): 595–601. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTangcharoensathien V, Calleja N, Nguyen T, et al.: Framework for managing the COVID-19 infodemic: Methods and results of an online, crowdsourced who technical consultation. J. Med. Internet Res. 2020; 22(6): e19659–e19658. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLa Bella E, Allen C, Lirussi F: Communication vs evidence: What hinders the outreach of science during an infodemic? A narrative review. Integr. Med. Res. 2021; 10(4): 100731. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen Q, Min C, Zhang W, et al.: Unpacking the black box: How to promote citizen engagement through government social media during the COVID-19 crisis. Comput. Hum. Behav. 2020; 110(March): 106380. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHernández-García I, Giménez-Júlvez T: Assessment of health information about COVID-19 prevention on the internet: Infodemiological study. JMIR Public Heal. Surveill. 2020; 6(2): 1–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHong KJ, Park NL, Heo SY, et al.: Effect of E-health literacy on COVID-19 infection-preventive behaviors of undergraduate students majoring in healthcare. Healthcare. 2021; 9(5). PubMed Abstract | Publisher Full Text | Free Full Text\n\nChoukou M-A, Sanchez-Ramirez DC, Pol M, et al.: COVID-19 infodemic and digital health literacy in vulnerable populations: A scoping review. Digit. Heal. 2022; 8: 205520762210769. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPasadino KDM, Lampert E: Virtual Perinatal Education During the Covid-19 Pandemic. MCN Am. J. Matern. Child Nurs. 2020; 45(6): 364–370. PubMed Abstract | Publisher Full Text\n\nAruhomukama D, Bulafu D: Demystifying media sources of information and levels of knowledge about COVID-19: a rapid mini-review of cross-sectional studies in Africa. F1000Res. 2021; 10: 345. Publisher Full Text\n\nFleming N: Coronavirus misinformation, and how scientists can help to fight it. Nature. 2020; 583(7814): 155–156. PubMed Abstract | Publisher Full Text\n\nBorges do Nascimento IJ, O’Mathúna DP, von Groote TC , et al.: Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews. BMC Infect. Dis. 2021; 21(1): 524–525. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPai M: Infodemic in Public health a reemerging public health threat – evidence synthesis. Dataset. figshare. 2023. Publisher Full Text\n\nPai M: Infodemic in Public health a reemerging public health threat. figshare. Figure. 2023. Publisher Full Text"
}
|
[
{
"id": "194131",
"date": "31 Aug 2023",
"name": "Shaina Raza",
"expertise": [
"Reviewer Expertise NLP",
"Informatics",
"public health",
"information retrieval"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper is very interesting and well written, the conciseness of the paper is impressive. A few suggestions:\nTalk more about annotators/reviewers biases, their demographics and how authors dealt with that.\n\nDifferentiate between misinformed vs biased information - may see Raza & Ding (2022)1 to support these definitions for citations.\n\nThe contents of table 2 should be mentioned in intro, for clarity (1-2 lines maybe).\n\nIs 53 and then 27 not a small number for such research (figure 1), also since no time limit is on search strategy, is anything missed? Or so what is the strict criteria?\n\nHow much time did the study take for all this?\n\nMention theoretical implication of this study a bit more.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": []
},
{
"id": "194128",
"date": "01 Sep 2023",
"name": "Vijaya Hegde",
"expertise": [
"Reviewer Expertise Dental Public Health",
"Bioethics"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a well-written manuscript that only needs to undergo a few minor changes. This review article focused mostly on the gaps in the field of infodemic and public health. It has recommended the improvement of digital health literacy and use of artificial intelligence as an immediate approach to address this catastrophe.\nThe COVID-19 pandemic had massive consequences not only on the societies and health systems across the world, but also has contributed to the development of ‘Infodemic’ to manage the crisis.\nAlthough one to one consultation between the doctor and the patient remains the gold standard in Medical Care, Infodemic has taken an upper hand during the pandemic. This has enabled simplified access to healthcare, reduction in distance between the patient and doctor, especially where health care is not accessible. However, it also has certain challenges like surplus information from various sources, which may be misinformation or disinformation. This misleads the users, affecting the decision making process thereby delaying health care. Hence an immediate, and collaborative effort is required to maintain the integrity and credibility of professional expertise and rebuild public trust.\nThis is an interesting and unique topic which is well structured and well written. However, I have provided few remarks based on my observation.\nTitle: Kindly specify if the focus is of the impact of COVID-19 related infodemic on Public Health or Infodemic on Public health.\nAbstract: The objective could be made more specific as in the manuscript the focus is on COVID -19 related infodemic and its impact on Public Health.\nIntroduction:\nPage 3, L 33-34: Kindly Rephrase the sentence.\n\nPage 3, L 36: Kindly mention the secondary questions.\n\nPage 3, L 38-39: Please be more specific.\nMethods:\nPage 3: Kindly indicate if a review protocol exists the web address where it can be accessed , registration information along with the registration number.\n\nPage 4: Kindly mention if any attempts were made to confirm the data from the investigators.\n\nPage 5: Kindly correct the number of studies included in the flow diagram.\n\nPage 6: Please provide the citations in Table 2.\nDiscussions:\nPage 7: Kindly suggest the other strategies to manage infodemics as mentioned in the introduction.\n\nPage 7: Please address the first domain, i.e the cause of infodemics.\n\nPage 7: Please consider providing information regarding the management of Psychological disturbance due to the impact of Infodemic.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-632
|
https://f1000research.com/articles/12-625/v1
|
07 Jun 23
|
{
"type": "Study Protocol",
"title": "Efficacy and safety of mizoribine in comparison with cyclophosphamide for treatment of lupus nephritis: Protocol for a multi-center, open-label, randomized controlled trial",
"authors": [
"Zheyi Dong",
"Jianhui Zhou",
"Yong Wang",
"Shiren Sun",
"Yani He",
"Zhaohui Ni",
"Hongli Lin",
"Xuefeng Sun",
"Li Zhang",
"Xiangmei Chen",
"Zheyi Dong",
"Jianhui Zhou",
"Yong Wang",
"Shiren Sun",
"Yani He",
"Zhaohui Ni",
"Hongli Lin",
"Xuefeng Sun"
],
"abstract": "Background: Monthly intravenous cyclophosphamide (IVCY) is a widely accepted induction therapy for lupus nephritis (LN) because this regimen balances the time needed for renal remission with the risk of adverse events. However, IVCY is associated with numerous severe toxicities. Mizoribine (MZR) was originally used as an antibiotic against Candida albicans, but researchers found it had strong immunosuppressive activity in various animal models. Previous clinical trials also examined the efficacy of MZR as an immunosuppressant, and it has been used for treatment of LN in Japan since 1990. We will conduct a phase 3 study in China to evaluate the efficacy and safety of oral MZR in comparison with standard IVCY in patients with LN. Methods: This study will be a multi-center, randomized, controlled, open-label clinical trial that consists of a screening period (seven days) followed by a treatment period (52 weeks). After screening, all eligible subjects will be randomized to an MZR or IVCY group in a 1:1 ratio. Then, subjects will initially receive methylprednisolone pulse therapy (0.5 g/day) for three days, followed by the study drug (MZR or CY) with oral corticosteroid therapy from visit two (day four). The efficacy and safety of oral MZR in comparison with standard IVCY will be determined. Discussion: This paper describes the protocol of a multi-center, open-label, randomized controlled trial that compares the efficacy and safety of MZR with IVCY for treatment of LN. The results may help determine whether LN should be considered an indication for this drug in China. Trial registration: ClinicalTrials.gov register, NCT02256150. Registered 2014-10-01. The protocol version number is 1.3 (2016-08-30).",
"keywords": [
"Mizoribine",
"Lupus Nephritis",
"randomized controlled trial",
"Cyclophosphamide"
],
"content": "Introduction\n\nSystemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of auto-antibodies and symptoms that result from the damage of multiple organs.1 Among the many organ complications, SLE with kidney involvement, known as lupus nephritis (LN), accounts for most of the morbidity and mortality in SLE patients.2–5 In particular, 10 to 30% of patients with LN develop end-stage renal disease (ESRD) within 15 years after diagnosis,6–10 and ESRD is a major cause of death in SLE patients.11,12\n\nIntravenous cyclophosphamide (IVCY) and glucocorticoids for induction of remission are accepted as a standard treatment for proliferative LN, and the standard monthly dose of 0.5 to 1 g/m2 provides an acceptable balance of the duration needed to achieve renal remission with the risk of gonadal and other toxicities.13 Nonetheless, cyclophosphamide (CY) can lead to severe adverse effects, such as infection, malignancies, and ovarian failure.4,14–16 Thus, another immunosuppressive drug, such as mycophenolate mofetil, tacrolimus, or mizoribine (MZR), may provide high efficacy and also have a better safety profile.\n\nMZR was originally used as an antibiotic against Candida albicans, but researchers found it had strong immunosuppressive activity in various experimental animal models.17 MZR is an imidazole nucleoside and its metabolite, MZ-5-P, inhibits inosine monophosphate (IMP) synthetase and guanosine monophosphate synthetase, thereby completely inhibiting guanine nucleotide synthesis and halting DNA synthesis. An immunosuppressant, MZR has selective inhibitory effects on inosine 5-monophosphate dehydrogenase (IMP-DH), a key enzyme in the de novo synthesis of purine nucleotides. This suppresses the proliferation of T lymphocytes and B lymphocyte, and manifests as inhibition of cell-mediated and humoral immune responses.18–21\n\nThe combination of glucocorticoids with IVCY is an effective treatment commonly used for patients with LN in China, but this treatment regimen has some disadvantages. For example, multi-target therapy using mycophenolate mofetil and tacrolimus is more effective than IVCY for inducing complete remission in patients with advanced LN (class V or IV22), for which glucocorticoid + IVCY is considered unsatisfactory. Kagawa et al. previously reported that MZR and tacrolimus with corticosteroids were well tolerated and provided an effective alternative multi-target therapy that can induce remission in patients with LN.23 The proposed study will compare the efficacy and safety of MZR treatment with standard IVCY treatment for patients with LN.\n\n\nProtocol\n\nA total of 250 participants from 44 hospitals in China were enrolled. A list of study sites is available as Extended data.24 We followed the SPIRIT checklist for reporting the protocol.24\n\nThe inclusion criteria are: diagnosis with SLE according to 1997 American College of Rheumatology criteria; kidney biopsy within 365 days prior to screening and confirmation of LN class III, III+V, IV, IV+V, or V according to the 2003 pathologic classification of the International Society of Nephrology/Renal Pathology Society; 24 h urinary protein level of 1.0 g or more; SLE disease activity index (DAI) of eight or more; male or female and between 18 and 70 years old (inclusive) at the time of providing informed consent; body weight between 40 and 80 kg (inclusive) at screening; and provision of written informed consent.\n\nThe exclusion criteria are: history of allergy to an investigational agent (MZR or CY) or glucocorticoids; accumulated CY dose of more than 3 g during the one year prior to screening; use of an immunosuppressant or a Chinese traditional medicine with an immunosuppressive effect within 30 days prior to screening; use of more than 1.0 mg/kg/day of prednisone or the equivalent dose of another oral glucocorticoid within 30 days prior to screening; use of other investigational drugs within 30 days prior to screening; use of plasma exchange therapy or immunoadsorption therapy within 30 days prior to screening; requirement for pentostatin or a live vaccine (not including the flu vaccine); undergoing renal replacement therapy; receipt of a kidney transplantation; a malignancy; severe hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure above > 100 mmHg) which is not effectively controlled; white blood cell count of 3×109/L or less; serum creatinine (SCr) level of 176.8 μmol/L or more; level of aspartate transaminase (AST) or alanine transaminase (ALT) more than 3-times of the upper limit of normal; positivity for hepatitis B, hepatitis C, or HIV; other suspected infection according to chest computed tomography (CT) or laboratory test results; unsuitability for participating in the study in the opinion of investigators (due to uncontrolled diabetes, central nervous system lupus, lupus encephalopathy, active psychosis, osteonecrosis of the femoral head, fulminant hepatitis, peptic ulcer, etc.); pregnancy, currently breast feeding, or willing to become pregnant; and any other disease that would affect the evaluation of drug efficacy or safety.\n\nIf patients need prohibited medication, they are to be withdrawn from the study. Subject premature withdrawal criteria are as follows: 1) Withdrawal by subject: a subject decides to withdraw from the study (including both screening period and treatment period. 2) Screen failure: A subject does not satisfy the inclusion criteria or satisfy exclusion criteria at Visit 0 or Visit 1. 3) Protocol violation: any serious violation against inclusion or exclusion criteria found after the first dose of the investigational drug; A subject takes prohibited medications or prohibited therapy before the last planned visit. Other major violation. 4) Pregnancy: A subject becomes pregnant. 5) Subject’s poor compliance with study drug: subject’s poor compliance with the protocol, including refusal of continued treatment or observation. 6) Investigator’s decision: any medical condition, including those listed under the exclusion criteria of the protocol, or personal circumstances, which in the opinion of the investigator, exposes the subject to substantial risk by continuing in the study or does not allow the subject to adhere to the requirements of the study protocol. 7) Adverse event: the occurrence of any clinically significant adverse event or serious adverse event, which in the opinion of the investigator warrants the subject’s premature withdrawal. If an adverse event is considered by the investigator as not clinically related to the study drug or if the benefits of continued study treatment are considered to outweigh the importance of the adverse event, the treatment may be continued at the discretion of the investigator. 8) Lost to follow-up: A subject does not come to a site for any reason before the planned last visit or the end of study visit. 9) Achieving endpoint event (progression to End-Stage Renal Disease” or “Doubling of serum creatinine (SCr)” through the study). 10) Others: it’s difficult for the subject to continue the study judged by the principal investigator or co-investigators.\n\nThe study is a multi-center, open-label, randomized controlled trial, which consists of a one-week screening phase followed by a 52-week treatment phase (Figure 1). For all eligible subjects, there will be a seven-day run-in screening period (day −7 to day −1, visit 0 [V0]) with no changes in the ongoing corticoid prescription. At day one (V1), subjects will be randomized into an MZR group or IVCY group in a 1:1 ratio stratified by renal biopsy pathology classification using permuted blocks by an Interactive Web Response System (IWRS).\n\nMedidata Balance is used as the IWRS system in this study. All required information was collected to complete the “Balance Design and Rave Integration Specification”, this file was sent to Medidata for Balance setup (Randomization Part). Once all settings pass Medidata internal quality control, the random number is generated. All settings will be copied to the production environment by Medidata and will be ready for go-live. The number of pathological types in the random stratification factors are three, and the pathological types are [III, III+V], [IV, IV+V], and [V only]. The site is not stratification factor. The random sequence for allocation (i.e. computer-generated random numbers) will be generated in the IWRS. When an investigator enrolls an eligible patient in the IWRS, a random sequence for allocation will be displayed on it, and the investigator will assign the participant to the intervention based on the information from the IWRS.\n\nDuring the 52-week treatment period, the subjects will be required to return to the study center every four weeks (V2 to V7), then every 12 weeks (V8, V9), and then after eight weeks (V10) for assessments of each parameter and for collection of blood and urine samples (Figure 2, Table 1).\n\nFor subjects randomized to the MZR group, methylprednisolone (MP) pulse therapy (0.5 g/day for three days) will begin on V1, and oral corticoid treatment will then be started following standard guidelines (see below). Starting from V2, 150 mg per day of oral MZR will be given (one 50 mg/tablet t.i.d.).\n\nThe standard oral corticoid therapy guidelines for V2 to V10 are oral corticoid therapy (0.8–1.0 mg/kg/day prednisone or equivalent dose of MP) for eight weeks (V2 to V4). The daily oral steroid dosage will not exceed 60 mg/day, and subjects weighing 80 kg will be given 60 mg/day. After eight weeks (V4), steroid-tapering will begin. The dose reduction will be 5 mg/day every two weeks until the dose is 20 mg/day. Dosing with 20 mg/day will continue for eight weeks. After that, dose reduction will be 2.5 mg/day every four weeks. The dose will be maintained between 5 and 15 mg/day up to week 52 (V10) (Table 2).\n\nFor subjects randomized to the IVCY group, the MP pulse therapy and oral steroid treatment will be the same as in the MZR group. Each IVCY dose will be given at V2 to V7 (every four weeks) and at V8 and V9 (every 12 weeks). The dosage will be calculated based on body surface area (BSA, m2) and will range from 0.5 g/m2 (minimum) to 1.0 g/m2 (maximum). BSA will be calculated using the Dubois & Dubois formula:\n\nWhen the subject’s condition faces deterioration eight weeks after randomization (V4), the original dosage of hormone therapies (at most) can be maintained for four weeks. After the end of adjusted hormone treatment, the investigator will assess the subject’s condition again. If the subject’s condition still meets the definition of deterioration, the subject should withdraw from the study.\n\nDeterioration is defined as 24 hours urine protein level greater than 150% of the baseline value or worsening Systemic Lupus Erythematosus Disease Activity Index (SLE-DAI) score in comparison with baseline.\n\nFor example, if the subject’s condition deteriorates at Visit 4, the dose of hormone therapies should be continued for two to four weeks (Table 2).\n\nThe primary efficacy variable will be total remission (TR, %) after the entire treatment period (V10), defined as the sum of complete remission (CR, %) and partial remission (PR, %) at that time. CR will be defined by the presence of all of the following criteria: 24 h urine protein below 0.3 g; serum albumin 35 g/L or more; and SCr level within the normal range, or not more than 25% above the baseline (V0) or decreased relative to baseline (V0). PR will be defined by the presence of all of the following criteria: 24 h urine protein decreased by 50% or more from the baseline (V0) and below 3.5 g; serum albumin 30 g/L or more; SCr level not more than 25% above the baseline (V0) or lower than the baseline; and lack of CR.\n\nThe secondary efficacy variables will be complete remission rate and partial remission rate; treatment failure (i.e., not achieving at least partial remission); 24 h urine protein and serum albumin; SCr, estimated glomerular filtration rate (eGFR) determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, and blood urea nitrogen (BUN); C3, anti-DNA antibodies, anti-nuclear antibodies, anti-Sm antibodies, and anti-phospholipid antibodies; SLEDAI score; and any endpoint event during the study, defined as progression to ESRD (need for long-term dialysis or renal transplantation) or doubling of SCr relative to baseline.\n\nSafety will be assessed by measuring the following variables: any reported adverse event, including severe adverse events, pregnancy, important treatment-related adverse events (granulocytopenia, infection, hemorrhagic cystitis, liver function impairment, hyperuricemia, malignancy, amenorrhoea, alopecia, nausea/vomiting), and adverse events leading to study discontinuation; laboratory test results, including routine blood cells tests, blood biochemistry, routine urine tests, and IgG; body weight; vital signs, including blood pressure, pulse, and body temperature; 12-lead electrocardiogram in the resting state; and chest CT.\n\nThe routine blood cell test will measure hemoglobin, hematocrit, white blood cells (WBCs), platelets, and red blood cells (RBCs). The blood biochemistry test will measure ALT, AST, total bilirubin, total protein, albumin, uric acid, total cholesterol, triglycerides, glucose, SCr, eGFR using the CKD-EPI formula,25 and BUN. The urine (dipstick) test will measure urine protein and glucose (at V0, V7, and V10), urine type, RBCs per high-power field (HPF), and WBCs/HPF.\n\nLaboratory tests will be performed by a central laboratory. The investigator will evaluate the clinical significance of each laboratory value outside the reference range. When the results from a local laboratory differ from those of the central laboratory, those of central laboratory will be used.\n\nThe time schedule of enrollment, interventions, assessments, and visits for participants are shown in Table 1 and summarized in Figure 1. The first study site was visited in November 2014, with the first participant enrolling in November 2014. The last participant was enrolled in March 2018 and the study was completed in March 2019.\n\nThe investigator recruited subjects from patients who attended the study center and placed ethically approved recruitment advertisements at the study center. If necessary, the investigator commissioned recruitment centers to recruit subjects in accordance with the principles of recruitment and retention in clinical trials.\n\nNon-inferiority testing will be used to assess the primary efficacy variable, as the relative risk ratio of TR (%) in the two groups after 12 months (52 weeks) of treatment for the per-protocol set (PPS) population. The sample size of 125 patients per group (total 250 patients) was determined based on a TR of 73% for both groups,26,27 a non-inferiority difference of 0.726, a power of 90%, a one-sided significance level of 2.5%, and a drop-out rate of 20%.\n\nAll data processing, summarization and analyses will be performed using Version 9.1.3 (or later) of the SAS® statistical software package (Windows OS). Relative risk ratio (MZR versus CTX) and its 95% confidence intervals (two-sided at α-level of 5%) will be calculated and non-inferiority testing will be applied. If the lower limit of the relative risk ratio for the PPS population is greater than 0.726, then the non-inferiority of MZR and CTX can be claimed.\n\nThe full analysis set (FAS) will include all subjects who were randomized and received at least one dose of a study drug and at least one post-treatment efficacy assessment. The PPS will include all FAS subjects without any other major protocol violation. The safety set (SS) will include all randomized subjects who received at least one dose of a study drug and had at least one subsequent safety assessment. Safety analysis will be based on the actually assigned treatments.\n\nThe primary efficacy variable is TR (%) after 12 months of treatment. A noninferiority test of TR (%) will be performed in the PPS population by comparing the two groups at V10. The relative risk ratios and two-sided 95% confidence intervals will be calculated.\n\nThe secondary analysis for the primary efficacy variable will be performed in the PPS at the end of the study and in the FAS at V10. The number of subjects who achieved TR will be calculated in each group at each visit in the PPS population. The secondary efficacy variables will be analyzed using descriptive statistics.\n\nSubgroup analysis will be performed as necessary. The following subgroup analyses are planned: pathologic classification, eGFR, C3, anti-DNA antibodies. Additional subgroup analyses will be pre-specified in the statistical analysis plan before locking the database. All safety data will be analyzed descriptively. High sensitivity C reactive protein (hs-CRP) is an exploratory variable that will be measured during the study visits V0 and V3 to V10, and values will be summarized at V4, V7, V8, V9, and V10.\n\nA data monitoring committee was not set up in this study because MZR has a high safety profile and was approved as an indication for LN in Japan as early as 1990. The primary endpoint of this study is to compare the overall response rate between the MZR and CTX groups after 52 weeks of treatment, therefore no interim analysis is planned. However, the criteria for suspension of investigational drug use and the subject’s premature withdrawal are clearly defined in the protocol.\n\nThe CRO’s QA department and authorized third-party auditors have undertaken monthly quality audits of the clinical trial. All medical records, the trial related files and correspondence, as well as the informed consent document, are accessible to the quality auditor.\n\nThis study was approved by the Medical Ethics Committee of the Chinese People’s Liberation Army General Hospital on 15 September 2014 (C2014-041-01). Written informed consent for publication was obtained from all participants. The trial was registered on ClinicalTrials.gov: NCT02256150 (Registered 2014-10-01).\n\nParticipant data is pseudonymised by assigning each participant an identifier number, which is used to identify the participant during the study and for any participant specific communication between the investigator and sponsor. These enrollment lists must be kept strictly confidential by the investigator and cannot be shared with the sponsor.\n\nThe investigator or authorized site staff will enter data into the eCRFs. Only medically qualified (sub)investigators are permitted to sign clinical assessment/safety data. Any changes made to the eCRF by the investigator or authorized site staff after the original entry will be automatically recorded in the system.\n\nAccording to the protocol, whether subjects complete the study visit or withdraw prematurely from the study visit, they must be assessed for all indicators at the last visit. Following the completion of the clinical trial, the investigator should monitor all adverse events and submit a follow-up report to the sponsor until they resolve, stabilize, the patient is lost to follow-up, or alternative explanations for the event can be provided (In the case of permanent damage, follow up until the adverse event is considered stable). Female subjects must notify the investigator and withdraw from the study if they become pregnant. The subject should be informed of the risks of continuing the pregnancy by the investigator and be monitored until the end of the pregnancy.\n\nFor this trial, the sponsor purchased “Human Clinical Trial” insurance from Chubb Insurance Company Limited and has included the following provision in the informed consent form for indemnification for risks resulting from involvement in the trial: From the enrollment in the trial to the end (duration 52 weeks), if any adverse event occurs, the investigator must determine whether it is related to the investigational drug and the diagnostic tests required by the protocol. If so, the participant can take treatment at the hospital where she/he participated in the trial, and the sponsor will be responsible for all medical expenses and financial compensation as required by law. However, the sponsor will not cover any costs that are unrelated to this trial. If the participant files a claim for compensation following any adverse event, the sponsor will contact the insurance company, then the insurance company will pay the compensation in accordance with the insurance contract.\n\nThe findings from this study will be submitted to peer reviewed journals to be considered for publication.\n\nThe study began in November 2014 and was completed in March 2019. A total of 250 participants from 44 hospitals in China were enrolled. Data analysis have been completed. The results are waiting for finalization by the Center for Drug Evaluation.\n\n\nDiscussion\n\nThe current study aims to evaluate the efficacy and safety of oral MZR in comparison with standard IVCY for treatment of LN. The efficacy endpoints are CR (%), PR (%), and treatment failure; 24 h urine protein and serum albumin; SCr, eGFR, and BUN; C3, anti-DNA antibody, ANA, anti-Sm antibody, and anti-phospholipid antibody; SLE-DAI; and attainment of any endpoint event during the study period. The exploratory objective of this study is to evaluate changes of hs-CRP in subjects who receive oral MZR compared with IVCY for treatment of lupus nephritis.\n\nThis study is the largest RCT to examine MZR, and also has the longest intervention and observation times among all large RCTs that examined MZR. Previous studies showed that despite aggressive treatment, the proportion of patients with renal responses was very low, and about 60% of patients did not achieve complete remission.28 Moreover, 27 to 66% of LN patients in remission experienced relapses,29 an important factor when considering exacerbations of renal damage and poor prognosis.30 Therefore, this study is designed to provide more therapeutic options and effective maintenance therapy for LN by studying the effects of MZR using a larger sample size and a longer observation period.\n\nThis study had an open label design rather than a double-blind design because of the different dosages and routes of administration of the study drugs. In particular, for a double-blind design all subjects would be required to receive oral MZR or oral placebo three times per day and eight intravenous injections of CYC or intravenous placebo, which would clearly be a significant treatment burden. In addition, LN can be dangerous in some cases, and use of double-blinding when serious adverse events occur may delay the timing of treatment. Therefore, an open study design will be used to ensure the safety of all subjects and reduce the burden of treatment.\n\nThe clinical efficacy of MZR as an immunosuppressant for renal transplantation was investigated in several Japanese institutions from 1978 to 1982 and MZR was first approved by the Japanese Ministry of Health, Labor and Welfare (MHLW) for the prevention of rejection following renal transplantation in 1984.31 The MHLW also approved MZR for the treatment of LN in 1990, rheumatoid arthritis in 1992, and primary nephrotic syndrome in 1995.31 In all these diseases, MZR is often used in combination with corticosteroids and/or anti-inflammatory drugs.\n\nPrevious clinical trials and post-marketing surveillance studies examined more than 4000 patients who received MZR for kidney transplantation, LN, rheumatoid arthritis, and nephrotic syndrome. The results of these studies showed that MZR was well-tolerated and had a good safety profile. MZR was approved in China for suppression of rejection following renal transplantation in 1999.\n\n\nConclusions\n\nThis paper describes the protocol of a multi-center, open-label, randomized controlled trial that compares the efficacy and safety of MZR with IVCY for treatment of LN. This study is the largest RCT to examine MZR, and also has the longest intervention and observation times among all large RCTs that examined MZR. The proposed study will examine the suitability of an additional indication for this drug in China.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nFigshare: data for ‘Efficacy and safety of mizoribine in comparison with cyclophosphamide for treatment of lupus nephritis: Protocol for a multi-center, open-label, randomized controlled trial’, https://doi.org/10.6084/m9.figshare.22358599.v5. 24\n\nThis project contains the following extended data:\n\n- Data management.pdf\n\n- List of study sites.pdf\n\nFigshare: SPIRIT checklist for ‘Efficacy and safety of mizoribine in comparison with cyclophosphamide for treatment of lupus nephritis: Protocol for a multi-center, open-label, randomized controlled trial’, https://doi.org/10.6084/m9.figshare.22358599.v5. 24\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nAcknowledgements\n\nWe are grateful to Kiyoshi Horie, Itaru Arimoto, and Hua Wang from Asahi Kasei Pharma Beijing for support with drug dispensing. Osamu Matsuki, Rika Oishi, and Seika Yamaguchi from Asahi Kasei Pharma Corporation provided literature support. The protocol was implemented by the study group, comprising 40 clinical centers across China. The network database was designed by the executive committee from the Department of Nephrology managed by Professor Guangyan Cai, First Medical Center of Chinese PLA General Hospital.\n\n\nReferences\n\nGuidelines for referral and management of systemic lupus erythematosus in adults: American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999; 42(9): 1785–1796. Publisher Full Text\n\nCameron JS: Lupus nephritis. J. Am. Soc. Nephrol. 1999; 10(2): 413–424. Publisher Full Text\n\nWard MM, Pyun E, Studenski S: Mortality risks associated with specific clinical manifestations of systemic lupus erythematosus. Arch. Intern. Med. 1996; 156(12): 1337–1344. Publisher Full Text\n\nAnders HJ, Saxena R, Zhao MH, et al.: Lupus nephritis. Nat. Rev. Dis. Primers. 2020; 6(1): 7. Publisher Full Text\n\nDavidson A, Aranow C, Mackay M: Lupus nephritis: challenges and progress. Curr. Opin. Rheumatol. 2019; 31(6): 682–688. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHoussiau FA, Vasconcelos C, D’Cruz D, et al.: The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann. Rheum. Dis. 2010; 69(1): 61–64. PubMed Abstract | Publisher Full Text\n\nCollado MV, Dorado E, Rausch S, et al.: Long-term Outcome of Lupus Nephritis Class II in Argentine Patients: An Open Retrospective Analysis. J. Clin. Rheumatol. 2016; 22(6): 299–306. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAustin HA 3rd, Boumpas DT, Vaughan EM, et al.: Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histologic data. Kidney Int. 1994; 45(2): 544–550. PubMed Abstract | Publisher Full Text\n\nAppel GB, Cohen DJ, Pirani CL, et al.: Long-term follow-up of patients with lupus nephritis. A study based on the classification of the World Health Organization. Am. J. Med. 1987; 83(5): 877–885. Publisher Full Text\n\nTektonidou MG, Dasgupta A, Ward MM: Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis. Arthritis Rheumatol. 2016; 68(6): 1432–1441. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaroz N, Segal MS: Lupus nephritis and end-stage kidney disease. Am. J. Med. Sci. 2013; 346(4): 319–323. Publisher Full Text\n\nBertsias GK, Boumpas DT: Connective tissue diseases: Lupus nephritis-winning a few battles but not the war. Nat. Rev. Rheumatol. 2011; 7(8): 441–442. PubMed Abstract | Publisher Full Text\n\nAlamilla-Sanchez ME, Alcala-Salgado MA, Alonso-Bello CD, et al.: Mechanism of Action and Efficacy of Immunosupressors in Lupus Nephritis. Int. J. Nephrol. Renov. Dis. 2021; 14: 441–458. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPetri M: Cyclophosphamide: new approaches for systemic lupus erythematosus. Lupus. 2004; 13(5): 366–371. Publisher Full Text\n\nOktem O, Guzel Y, Aksoy S, et al.: Ovarian function and reproductive outcomes of female patients with systemic lupus erythematosus and the strategies to preserve their fertility. Obstet. Gynecol. Surv. 2015; 70(3): 196–210. PubMed Abstract | Publisher Full Text\n\nLiu F, Zhang L, Feng X, et al.: Immunomodulatory Activity of Carboxymethyl Pachymaran on Immunosuppressed Mice Induced by Cyclophosphamide. Molecules. 2021; 26(19). PubMed Abstract | Publisher Full Text | Free Full Text\n\nKamata K, Okubo M, Ishigamori E, et al.: Immunosuppressive effect of bredinin on cell-mediated and humoral immune reactions in experimental animals. Transplantation. 1983; 35(2): 144–149. PubMed Abstract | Publisher Full Text\n\nKoyama H, Tsuji M: Genetic and biochemical studies on the activation and cytotoxic mechanism of bredinin, a potent inhibitor of purine biosynthesis in mammalian cells. Biochem. Pharmacol. 1983; 32(23): 3547–3553. PubMed Abstract | Publisher Full Text\n\nIchikawa Y, Ihara H, Takahara S, et al.: The immunosuppressive mode of action of mizoribine. Transplantation. 1984; 38(3): 262–266. Publisher Full Text\n\nKawasaki Y: Mizoribine: a new approach in the treatment of renal disease. Clin. Dev. Immunol. 2009; 2009: 681482. PubMed Abstract | Publisher Full Text | Free Full Text\n\nvon Groote TC , Williams G, Au EH, et al.: Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst. Rev. 2021; 2021(11): Cd004293. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBao H, Liu ZH, Xie HL, et al.: Successful treatment of class V+IV lupus nephritis with multitarget therapy. J. Am. Soc. Nephrol. 2008; 19(10): 2001–2010. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKagawa H, Hiromasa T, Hara T, et al.: Mizoribine, tacrolimus, and corticosteroid combination therapy successfully induces remission in patients with lupus nephritis. Clin. Exp. Nephrol. 2012; 16(5): 760–766. PubMed Abstract | Publisher Full Text\n\nDong Z: SPIRIT Checklist of Protocol of Efficacy and safety of mizoribine in comparison with cyclophosphamide for treatment of lupus nephritis: a multi-center, open-label, randomized controlled trial. [Dataset]. figshare. 2023. Publisher Full Text\n\nLevey AS, Stevens LA, Schmid CH, et al.: A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 2009; 150(9): 604–612. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang M, Xing CY, Liu J: Study of the efficacy of mizoribine in lupus nephritis in Chinese patients. Rheumatol. Int. 2013; 33(11): 2737–2742. PubMed Abstract | Publisher Full Text\n\nWang HY, Cui TG, Hou FF, et al.: Induction treatment of proliferative lupus nephritis with leflunomide combined with prednisone: a prospective multi-centre observational study. Lupus. 2008; 17(7): 638–644. PubMed Abstract | Publisher Full Text\n\nLiu Z, Zhang H, Liu Z, et al.: Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann. Intern. Med. 2015; 162(1): 18–26. Publisher Full Text\n\nSprangers B, Monahan M, Appel GB: Diagnosis and treatment of lupus nephritis flares--an update. Nat. Rev. Nephrol. 2012; 8(12): 709–717. PubMed Abstract | Publisher Full Text\n\nUgarte-Gil MF, Acevedo-Vásquez E, Alarcón GS, et al.: The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort. Ann. Rheum. Dis. 2015; 74(6): 1019–1023. PubMed Abstract | Publisher Full Text\n\nIshikawa H: Mizoribine and mycophenolate mofetil. Curr. Med. Chem. 1999; 6(7): 575–597. Publisher Full Text"
}
|
[
{
"id": "204599",
"date": "03 Nov 2023",
"name": "Liu Shuxin",
"expertise": [
"Reviewer Expertise Pathogenesis of glomerular diseases",
"hemodialysis",
"CKD-MBD"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the opportunity to review this paper.\nThe randomized controlled trials (RCT) described in the protocol were well designed and methodologically robust. Except the standard treatment of IVCY, more alternative treatment tragedy for LN is a key clinical question, and this study is expected to yield results that could achieve the above purpose.\nThe objective of the study is clear, the efficacy endpoint is appropriate and comprehensive, and the therapeutic effect can be evaluated from multiple angles. In addition, exploratory goals to assess changes in hs-CRP would provide a more in-depth look at the potential beneficial effects of MZR.\nThe open-label design of the study is reasonable given the different routes of administration and dosages of the investigational drugs. Safety precautions seem to be in place to protect the study participants, and it is quite thoughtful to reduce the treatment burden where possible for these patients.\nThe fact that this study is the largest and longest observed randomized controlled trial examining MZR adds significant weight to the potential value of its results.\nIn conclusion, this RCT study has the potential to make a significant contribution to treatment options for patients with LN in China and elsewhere. The results of this study could benefit the large number of patients living with this chronic disease.\nHere are some suggestions:\nINTRODUCTON: It would be useful, perhaps, to add a sentence or two about the expected impact or the current knowledge gap the study is seeking to fill, to give readers a better sense of why it’s crucial to conduct the RCT. Elaborate on the limitations of IVCY. If any resistance or insufficiency in treatment is documented, include this to strengthen the need for exploring alternatives like MZR.\n\nThe study's approach for data monitoring seems adequate considering the high safety profile of MZR. However, it seems like an independent data monitoring committee has not been established, which is typically recommended for RCTs to ensure unbiased data assessment and safety monitoring.\n\nDISCUSSION: Tie MZR’s mechanism of action to LN pathology. While you described well how MZR works, connecting this directly to the pathology of LN can make the argument for its potential effectiveness more convincing. The histopathological features of LN were mesangial cell and endothelial cell proliferation, podocyte lesion and inflammatory cell infiltration. MZR corrects defective nephrin biogenesis, inhibits mesangial cells proliferation as well as T cell and B cell proliferation1-3. All the above mechanisms may directly abbreviate LN pathology.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
},
{
"id": "308899",
"date": "04 Sep 2024",
"name": "Desmond Yat Hin Yap",
"expertise": [
"Reviewer Expertise lupus nephritis"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study proposed by the authors aims to investigate the efficacy and safety of mizoribine vs. IV CYC for the treatment of active lupus nephritis. The research question is important as there is no head-to-head comparison between these two treatments. My questions and concerns for the protocol are as follows: 1. The duration between treatment randomization and last biopsy is 365 days, which is too long. I would suggest to shorten to 3 or 6 months. 2. The study duration is only 1 years, which is now relatively short for international multi-centre clinical trials for lupus nephritis (usually up to 24 months follow up). 3. Inclusion did not mention on urinary sediments and importantly lupus serological status (ANA+; positive anti-dsDNA or any numerical values, C3/4 requirements etc). 4. There is no mention of the maintenance agent after IV CYC. Is it MMF or AZA? 5. I would suggest anti-microbial prophylaxis (e.g. anti-viral for HBV-positive patients, cotrimoxazole for PJP etc). 6. The definition of CR is a bit too loose (Not more than 25% increase in SCr from baseline); most studies used 15-20%.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Partly\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Partly",
"responses": [
{
"c_id": "12508",
"date": "24 Sep 2024",
"name": "Xiangmei Chen",
"role": "Author Response",
"response": "We would like to thank Mr. Desmond Yat Hin Yap for reviewing this paper and providing valuable comments and important suggestions. We take these questions very seriously, and here are our answers. We hope Mr. Desmond Yat Hin Yap will understand and approve the publication of this paper. 1. The duration between treatment randomization and last biopsy is 365 days, which is too long. I would suggest to shorten to 3 or 6 months. Thank you very much for your valuable advice. There are few national multicenter randomized controlled clinical trials (RCTs) on immunosuppressants for the treatment of lupus nephritis, especially in China. When designing the protocol, we referred to two trials: ALMS and LUNAR (References 1 and 2). ALMS required a renal biopsy within six months as you suggested, and LUNAR required a renal biopsy within 12 months. Currently, this trial has been completed. We have summarized the data of the subjects who completed the trial. The total number of subjects was 243, 225 of whom had a biopsy within 3 months before enrollment, 11 within 6 months, and 7 within 1 year. In fact, 97.12% of the subjects did undergo a biopsy within 6 months before enrollment. We fully understand your concerns about the validity period of the biopsy report, because lupus nephritis is more likely to undergo a change in pathological type than other kidney diseases, and the probability of repeating renal biopsy is also higher. Therefore, we will focus on the time of renal biopsy before the subjects were enrolled and the corresponding baseline conditions, and perform subgroup analysis. 2. The study duration is only 1 years, which is now relatively short for international multi-centre clinical trials for lupus nephritis (usually up to 24 months follow up). Your advice is very important. This trial mainly observed the therapeutic effect of the study drug in the induction phase. The induction treatment duration for lupus nephritis is generally 6 to 12 months, followed by maintenance treatment. This study is a registered Phase III clinical trial approved by CENTER FOR DRUG EVALUATION, NMPA. Taking into account regulatory requirements and funding considerations, we designed a one-year protocol covering mainly the treatment induction phase. After the end of this trial, the doctor will provide continued maintenance treatment and follow-up according to the patient's condition. 3. Inclusion did not mention on urinary sediments and importantly lupus serological status (ANA+; positive anti-dsDNA or any numerical values, C3/4 requirements etc). Thank you for your professional advice. The inclusion criteria of this protocol include SLE-DAI score>=8, and the SLE-DAI score items include tubular urine (the presence of granular casts or red blood cell casts), as well as lupus serological examination items (low complement (CH50, C3 or C4 decreased or below the lower limit of normal) and elevated DNA (>25% (Farr's method) or above the detection range). At the same time, immunological tests (including C3, anti-DNA antibodies, ANA, anti-small nuclear ribosomal nuclear protein antibodies, antiphospholipid antibodies) are one of the main laboratory tests of this study and is also used as a secondary efficacy indicator. In the future, when conducting clinical studies on SLE that are not limited to renal damage, we will also pay attention to these serological indicators. 4. There is no mention of the maintenance agent after IV CYC. Is it MMF or AZA? Thank you for your questions, which are also considered in the design of the project. Because this trial is a PCT comparing the efficacy and safety of MZR and CTX, MZR was administered orally continuously, and CTX was administered intravenously at regular intervals (V2-V7 were administered once each (every 4 weeks), and V8 and V9 were administered once each (every 12 weeks)) to achieve the target accumulation in vivo. At the same time, the dosage of steroids as combined drugs can be adjusted within a certain range. In order to exclude the influence of other immunosuppressants, this protocol does not allow the use of other immunosuppressants. When the condition worsens to the endpoint event causing the subject to withdraw early or when the trial is ended after the last visit (V10), the doctor may replace or add immunosuppressants according to the subject's condition. 5. I would suggest anti-microbial prophylaxis (e.g. anti-viral for HBV-positive patients, cotrimoxazole for PJP etc). As you have considered, the subjects in this study are a high-risk group of infection, so we attach great importance to the monitoring and treatment of infection during the program design and study process. Exclusion criteria for this protocol include infectious diseases: hepatitis B, hepatitis C, or HIV infection, as well as other suspected infections based on chest CT and/or laboratory test results, Therefore, subjects with existing or suspected infections will not be included in this trial. At the same time, the trial protocol stipulates that routine blood test、hs-CRP need to be monitored during V3 to V10, and a chest CT scan is required again during V3 to facilitate early detection and treatment of infection. The use of co-trimoxazole to prevent PJP in high-risk patients is a routine clinical treatment regimen, so it was not written into this protocol but was recorded in the investigator's manual. 6. The definition of CR is a bit too loose (Not more than 25% increase in SCr from baseline); most studies used 15-20%. Thank you for your comprehensive and thoughtful advice. The study protocol was designed with the criterion that an increase in SCr of no more than 25% from baseline in CR, as defined by the ALMS test (References1). Now that the test has been completed, we will conduct subgroup analysis considering SCr thresholds of no more than 20% or 15%, as per your suggestion. References1： Sinclair A, Appel G, Dooley MA, Ginzler E, Isenberg D, Jayne D, Wofsy D, Solomons N. Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS). Lupus. 2007;16(12):972-80. doi: 10.1177/0961203307084712. PMID: 18042591. References2： Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G; LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012 Apr;64(4):1215-26. doi: 10.1002/art.34359. Epub 2012 Jan 9. PMID: 22231479."
}
]
}
] | 1
|
https://f1000research.com/articles/12-625
|
https://f1000research.com/articles/12-516/v1
|
18 May 23
|
{
"type": "Research Article",
"title": "The journey of F1000Research since inception: through bibliometric analysis",
"authors": [
"Dilip Kumar",
"Abhinav Kumar Shandilya",
"Sandeep Srivastava",
"Dilip Kumar",
"Abhinav Kumar Shandilya"
],
"abstract": "Background: Bibliometric analysis is an approach adopted by researchers to understand the various analytics such as year-wise publications, their citations, most impactful authors and their contributions, identification of emerging keywords, multiple themes (niche, motor, basic, and emerging or declining) etc. F1000Research is one of the Q1 category journals that publishes articles in various domains, but a detailed journal analysis is yet to be done. Methods: This study is an effort to extract the F1000Research journey information through bibliometric analysis using VOS-viewer and Biblioshiny (R-studio) interface. The F1000Research journal started its journey in 2012; since then, 5767 articles have been published until the end of 2022. Most of the published articles are from medical science, covering Biochemistry, Genetics & Molecular Biology, Immunology & Pharmacology, Toxicology & Pharmaceutics. To understand the research journey, various analyses such as publication & citation trends, leading authors, institutions, countries, most frequent keywords, bibliographic coupling between authors, countries and documents, emerging research themes, and trending keywords were performed. Results: The United States is the biggest contributor, and COVID-19 is the most commonly occurred keyword. Conclusions: The present study may help future researchers to understand the emerging medical science domain. It will also help the editors and journal to focus more on developing or emerging areas and to understand their importance towards society. Future researchers can contribute their quality research studies, focusing on emerging themes. These authors’ research can guide future researchers to develop their research area around the most impacted articles. They can collaborate with them to bring that emerging theme forward.",
"keywords": [
"Bibliometric study",
"F1000Research",
"COVID-19",
"VOS-viewer",
"Biblioshiny",
"Bioinformatics",
"visualization."
],
"content": "Introduction\n\nF1000Research is a journal under Taylor and Francis Group which has published 4947000+ articles and published by F1000 Research Ltd. It publishes a wide range of themes like social sciences, science, humanities, medicine, engineering and technology, agricultural and veterinary sciences, and arts without any biases by an editorial board. It publishes papers in multi-disciplinary areas and provides wider opportunities for researchers through its open-access publishing platform, offering rapid and regular publication. Compared to other journals ranked in the Q1 category, it is relatively new. However, in 11 years, it has published a vast quantity of research papers, i.e., 5767, until 31st December 2022.\n\nF1000Research publishes peer-reviewed research articles in a periodical order and has an International Standard Serial Number (ISSN) of 2046-1402. F1000Research started its publishing journey in 2012, having an H-index - 72, an impact factor (2021) - 3.23, an overall ranking of 4485, SCImago Journal Rank (SJR) – 0.939 (Resurchify, 2023). SCImago Journal Ranking (SJI) has divided journals into four categories, namely Q1 (green) comprised of highest quality journals, Q2 is the second best quality journals, Q3 is the third best quality journal, and Q4 is the least quality journals (SCImago, 2023).\n\nF1000Research is a multi-disciplinary journal covering a vast publication domain; therefore, a bibliometric analysis was conducted to understand the journal’s past, present, and future research agenda to honour its stature. Bibliometric analysis help in measuring the journal’s progress journey through co-word, citation, and bibliographic coupling (Donthu et al., 2020). Journal performance, development and content insights can be helpful for researchers in studying a specific journal (Ratten et al., 2020). Recently, bibliometric analyses have been conducted in quality journals in the areas of nursing (Yanbing et al., 2020), money laundering (Saxena & Kumar, 2023), tourism (Leong et al., 2021), hospitality (Martorell Cunill et al., 2019), engineering (Modak et al., 2020), medicare (Lin et al., 2020), humanities (Nwagwu & Egbon, 2011) and management (Ratten et al., 2020). For every top-ranked journal, whether the “International Journal of Hospitality Management” or “International Marketing Review,” a bibliometric analysis study has been performed. However, a journal like F1000Research (a journal of great repute) has a bibliometric analysis not yet been conducted. This study aims to unveil the journey of F1000Research since its inception to understand its past, present, and future direction.\n\nVarious visualising software can be used for bibliometric analysis, such as VOS-viewer, Bibliometrix (R-studio), Gephi, CiteNet, Pajek, Sci2, and HiteCite (Van Eck & Waltman, 2013). In the present study, VOS-viewer and Biblioshiny (R-studio) are preferred over other visualising software due to their web-map pictorial representation, data-friendly features, and detailed analysis. This analysis helps in finding the research questions:\n\nRQ1: What are the publication trends of F1000Research since its inception (2012-2022)?\n\nRQ2: Who are the leading authors, organisations/institutions and countries publishing in the F1000Research journal?\n\nRQ3: What are the most frequent keywords used and cluster formation based on keywords appeared?\n\nRQ4: Which are the most cited publications and most impactful authors in the F1000Research journal?\n\nRQ5: What is the major bibliographic coupling regarding countries, authors, documents, and organisations?\n\nRQ6: What are the trending words and emerging research areas?\n\nRQ7: What are the future research directions in the present research publication domain?\n\nAs F1000Research is a multi-disciplinary journal; it therefore covers a broad area of research publications that can help present, and future researchers and editors identify emerging areas, contribute their efforts to society, and widen the research horizon. This paper is organised into various parts such as the reasons behind choosing F1000Research journal for bibliometric analysis, methodology, results discussion generated from the VOS-viewer and Biblioshiny (R-studio) regarding the research questions (authors, country, publications, citations, bibliographic coupling, co-citations, and co-occurrence of author keywords), future directions, and implications, and limitations of study.\n\n\nMethods\n\nIn 1969, Pritchard introduced Bibliometrics as “applying mathematical and statistical methods to books and other means of communication” (Pritchard, 1969). In the present scenario, it is widely seen in every field. It is a quantitative and qualitative research analysis used to understand and highlight the impact of authors, institutions, collaborations, emerging research areas and countries. The present study used a bibliometric technique through VOS-viewer and Biblioshiny (R-studio) to analyse the performance of the F1000Research since its inception (2012). It is a Q1 category journal indexed in Scopus, UGC CARE, DOAJ, and PubMed. Scopus is one of the best reliable databases, which has 1.8+ billion cited references, 84+ million records, 17.6+ million authors’ profiles, 94.8+ affiliation profiles, and 7+ thousand publishers, where 35% of publications are from the field of social sciences, 27% physical sciences, 23% health sciences and 15% life sciences (ELSEVIER, 2020). Hence, the Scopus database has been used to extract the metadata.\n\nMetadata extracted from the Scopus database has been analysed using VOS-viewer software developed by van Eck & Waltman (2010) and Biblioshiny (R-studio) interface developed by Aria & Cuccurullo (2017). Bibliometric metadata represents various relationships, such as publications and citations (Ding et al., 2017). The impact of the publications is measured through their citations, whereas the number of publications only quantifies their productivity (Svensson, 2010). H-index explains “the number of papers with citation number >h, as a useful index to characterise a researcher’s scientific output” (Hirsch, 2005), which has also been used in the present study.\n\nVarious studies have used keywords search index criteria (Chen et al., 2017; Maier et al., 2020; Kumar et al., 2022; Leong et al., 2021; Pesta et al., 2018; Singh et al., 2022) for extracting the Scopus metadata. It has prepared the base and design for data collection, which has also been used in the present study.\n\nStep 1: The Scopus database was searched with the keyword (ALL(F1000Research) AND PUBYEAR > 2011 AND PUBYEAR < 2023 AND (LIMIT-TO (EXACTSRCTITLE,“F1000research”)) AND (LIMIT-TO (LANGUAGE,“English”)) AND (LIMIT-TO (DOCTYPE,“ar”) OR LIMIT-TO (DOCTYPE,“re”))) in the ‘source title’ on 22nd March 2023 from the IP address of ‘Manipal Academy of Higher Education, Manipal, India.’ Metadata of 72396 documents appeared in the initial search.\n\nStep 2: Various journals appeared but were limited to an ‘F1000Research’ only., in which 5999 metadata appeared.\n\nStep 3: The result from 2012-2022 (31st December 2022), generated 5987 documents and then refined to the language ‘English,’ publication stage ‘Final’, limited to ‘article and review’ only generated 5767 documents.\n\nStep 4: Only 5727 metadata were downloaded, whereas the remaining 40 could not be downloaded due to a metadata error. Finally, a CSV file, including “Citations information, bibliographical information, abstracts and keywords, funding details and other information,” was downloaded.\n\nStep 5: Purification of data performed in CSV file using the conditional formatting features to remove the duplicate articles (202 articles) and removed seven articles due to retraction case. Finally, 5518 articles (metadata) were used for the final analysis using VOS-viewer software and Bibliometrix (R-studio) interface (Kumar, 2023).\n\nThe present study used VOS-viewer software version 1.6.19 and Biblioshiny (R-studio) 4.2.3 interface to analyse the F1000 research journey. A samples of 1000 papers considered as an good enough to generalise the result (Rogers et al., 2020). To analyse the publication trends of F1000Research, find out the leading authors, organisations, countries, frequent keywords, most cited publications, bibliographic coupling between authors, organisations and countries, and emerging research areas since its inception VOS-viewer and Biblioshiny were used. VOS-viewer uses a fractional counting method, whereas the Scopus database generates metadata under a full counting system; therefore, full and fractional both counting methods have been used. However, Biblioshiny (R-studio) interface generates a detailed analysis. However, data reading showed poor keywords details, a completely missing number of cited references, and a completely missing science categories, which specifies some missing data. Although extracted metadata provided enough information to be used in the final analysis.\n\n\nResults\n\nQuantifying publications and their citations play a significant role in assessing the journal’s global presence and recognition. In the present study, Figure 1 represents the number of publications that remained almost constant during 2016, 2017, 2020, and 2021 (ranging between 614-669), whereas, in 2018, publications increased drastically to 915 and again reduced in 2019 to 764. It shows that before COVID-19, upward growth in the publication was seen due to the journal’s recognition and popularity among the researchers. Citations which make the article journal more impactful, increased dramatically in 2016 to 16301 from 5162 (2015) and again started declining. Citations formed a bell-curve shape, which shows that they grew from 413 citations in 2012 to 16301 and reduced to 276 in 2022. New articles are still to create their impact in the researcher’s mind to cite them in their literature. F1000Research started its journey in 2012 and published only 43 articles, multiplied thrice in consecutive years.\n\nTable 2 represents the top 20 organisations that contributed to the F1000Research journal. A maximum number of articles published by “Faculty of Management, Multimedia University, Cyberjaya, Selangor, Malaysia,” i.e., 12 but got only seven citations as they have published their work recently (2021). Whereas the maximum number of citations received by “SIB Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland,” i.e., 1834, is exhibited in Figure 2. However, it has published only four articles. Following the “Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Aceh, Indonesia” published seven articles having a citation of 211. “Brawijaya Internal Medicine Research Center, Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, Indonesia”, ranked number three, has published eight documents but has g-citations of 202.\n\nEuropean, Asian (mainly Malaysia, Indonesia, and Saudi Arabia), and American (both south and north) organisations contributed to the top 20 organisations list. In contrast, African and Australian organisations are not in the top 20 organisations listed in Table 2. The organisation that published their articles in the F1000Research journal from 2016-2022 (22nd March) is represented in Figure 2. Organisations marked in yellow (“Faculty of Computing and Informatics,” “Faculty of Management,” “Faculty of Engineering,” “Molecular Diagnostic Laboratory,” and “Department of Community Medicine”) are relatively young in publishing their work in the F1000Research journal.\n\nTable 3 represents the country’s production over time, citations generated by the specific country and total link strength (TLS). Figure 3 illustrates the significant countries’ contributions/production over time (2012-2022). According to Worldometer (2023), there are 195 countries in the world, of which 164 countries have contributed their work to the F1000Research journal, ranging from 1 to 1893 publications. A major contribution was from the United States, United Kingdom, and Germany, respectively, i.e., 1893, 882 and 357. However, citations from the United States, United Kingdom, and Canada ranked in the top three (31765, 12866 and 5776, respectively) as shown in Table 3. India has also contributed 274 publications (7th in publication ranking), citations of 1589 (13th in citations ranking) and a TLS of 17025. A major chunk of Africa, Central Asia, and Greenland have contributed their work to the F1000Research journal, as shown in Figure 3. For global recognition and contribution, the journal should target the countries whose contribution is either less or not contributed. Quality publications can come from even the world’s smallest countries; therefore, more focus must be given to those countries.\n\nThe most frequent keyword visualisation shown in Figure 4 has been generated using the Biblioshiny (R-studio) interface. These keywords are based on the co-occurrence of author keywords, which helps understand the most impactful keywords and keyword popularity. Table 4 exhibits the top 20 most occurred, strongly linked, and high-impact keywords. Future researchers use highly cited keywords as they receive global attention very fast as compared to least cited keywords. Keywords such as “COVID-19,” “Bioinformatics,” and “SARS-Cov-2” should be used along with “Proteinaceous,” “Peru,” “Screening,” “Oxidative stress,” etc., to explore the new facts and relationships. Countries like India, Nepal, and Bangladesh (Asian countries) have linkages with the “COVID-19” keyword. Bibliometric analysis can be an essential tool to detect research trends for the present and future (Pesta et al., 2018).\n\nThe fine-grained tropical structure is better understood by combining the keywords and cited references in the research field which also helps develop the relationships between various topics and their sub-topics (Van den Besselaar & Heimeriks, 2006). VOS-viewer software helps identify the themes using the keywords co-occurrence analysis in the specific study area (van Eck & Waltman, 2020), resulting in bibliographic clusters and emerging and least explored themes (Donthu et al., 2020).\n\n1414 author keywords were found in the metadata extracted from the Scopus database. Only 78 keywords met the desired threshold when the minimum number of co-occurrences was restricted to 15 keywords. Figure 5 shows the visualisation of highly appeared keywords in various clusters marked in red (18 keywords), green (16 keywords), blue (13 keywords), yellow (12 keywords), purple (11 keywords), cyan (6 keywords), and orange (2 keywords) colours in the F1000Research journal since its inception. The red cluster is the most dominating and impactful cluster, whereas the orange is the least impactful cluster. Table 5 exhibits the 78 keywords that appeared in various clusters (depicted seven themes). These clusters emerged as different themes such as “bioinformatics” (69 occurrences), “treatment” (40 occurrences), “children” (33 occurrences), “COVID-19” (183 occurrences), “cancer” (66 occurrences), “inflammation” (35 occurrences) and “systematic review” (29 occurrences).\n\nIn Figure 5, keywords are depicted by a node whose size specifies occurrences (van Eck & Waltman, 2020). Bigger the node size, the greater the occurrences of the keyword. Total link strength (TLS) has been represented by the line thickness between the nodes, representing the keyword’s co-occurrence frequency within the links exhibited in Table 5.\n\nCluster 1 (Red) = Bioinformatics. This cluster comprises 18 keywords and is the most significant among the 7 clusters. “Bioinformatics” was found as the maximum occurred keyword having 69 appearances and the maximum TLS of 65 exhibited in Table 5. It is well connected with “genomic,” “machine learning,” “RNA-Seq,” “R,” “Reproducibility,” “open science”, and so on. It shows that the F1000Research journal mainly covers medical science articles where the “bioinformatics” keyword plays a significant role. “Bioinformatics” is over 50 years old and recently emerged to support next-gen data analysis. It has faced multiple challenges recently while managing big data and the reproducibility of results, which can help integrate the same into academics (Gauthier et al., 2019). To extract information from big data, various machine-learning algorithms are widely used and applied in bioinformatics (Min et al., 2017). Machine learning has revolutionised computational biology (part of bioinformatics) in transforming massive data through technology into knowledge which can help understand genomic, proteomics and system biology (Larrañaga et al., 2006). This cluster discusses the science involved in handling bioinformatics and their application in improving education through software and increasing visibility through open science.\n\nCluster 2 (Green) = Treatment. This cluster comprises 16 keywords represented in Table 5 has shown “treatment” as a maximum occurred keyword (40 appearances) and TLS (40). It is well connected with various keywords such as “pregnancy,” “diagnosis,” “surgery,” “microbiome,” “tuberculosis,” “vaccine”, and so on. This cluster discusses the treatment of various diseases, infections, vaccines, and clinical trials. Pregnant women will continue to be a priority group for treatment optimisation in the era of compulsory treatment as treatment duration and antiretroviral therapy (ART) alternatives increase, promoting both their health and the health of their kids exposed to ART (Bailey et al., 2018). Diagnosis and treatment go hand in hand; therefore, these two words are in the same cluster.\n\nCluster 3 (blue) = Children. This cluster comprises 13 keywords represented in Table 5. The maximum occurred keyword is “children”, having 33 occurrences and a TLS of 22. TLS denotes that “children” is linked up with 22 different keywords. Significant linkages are “obesity,” “depression,” “COPD,” “stroke,” “elderly,” “mental health”, and so on. This cluster discussed the disease and its impact on mental health and well-being. Obesity has become a global health problem, becoming common due to increased screen time (World Health Organization, 2005). The advertisement of junk and fast food impacts children’s minds towards that food and ultimately results in obesity (Strasburger et al., 2011). Therefore, this cluster needs special attention.\n\nCluster 4 = COVID-19. This cluster has 12 keywords, and these are highly correlated to COVID-19. COVID-19 has the maximum number of occurrences, i.e., 183 and TLS of 165 in the F1000Research journal. None of the keywords have even 100 occurrences, whereas COVID-19 has 183, which shows the impact of COVID-19-related publications in the journal. “COVID-19” has been linked with “SARS-CoV-2,” “epidemiology,” “HIV” “risk factors,” “coronavirus,” “Prevalence,” “public health” “pandemic,” “Bangladesh,” “Nepal,” and “India” exhibited in Table 5. SARS-CoV-2 spread globally and was declared a pandemic by World Health Organisation. It damaged health and wealth and increased poverty globally. A review proposed by Ciotti et al. (2020) provided information regarding epidemiology, its origin, infection to humans and safety issues. Various researchers (Pokhrel & Chhetri, 2021) have also contributed to digitally improving the teaching-learning process to fight against a COVID-19-like pandemic in future. This cluster mainly focuses on the COVID-19 pandemic and its impact on developing countries like India, Bangladesh, and Nepal.\n\nCluster 5 = Cancer. The fifth cluster consists of 11 keywords, clustered around the “Cancer” keyword, 66 occurrences and 36 TLS exhibited in Table 5. “Case report,” “genetics,” “breast cancer,” “development,” and “immunotherapy” are the significant keywords strongly linked with the “cancer” keyword. This cluster mainly focuses on a widely spreading disease, “Cancer”, which must be prevented early rather than curing the advanced stage (Nixon et al., 1973). Due to the increase of cancer worldwide, cancer immunotherapy's impact has gained popularity in cancer clinical care (Blank et al., 2016). To combat this deadly disease, Silverstein et al. (2006) insisted on understanding the relationship between cancer and the immune system to develop treatment options for patients. Similar genomic profiles of tumors can help apply therapies to cancer types (Hegde & Chen, 2020).\n\nCluster 6 = Inflammation. This cluster comprises six keywords. The most impactful keyword in this cluster is “inflammation”, have 35 occurrences and a TLS of 25 exhibited in Table 5. The remaining five keywords, “pain,” “metabolism,” “mitochondria,” “diabetes,” and “oxidative stress,” are highly linked with the most impactful keyword, “inflammation.” This cluster tried to explain the symptoms and the diseases. Many chronic inflammatory diseases are caused due to imbalance of mitochondria, metabolism and inflammation (Tschopp, 2011). Inflammation can be a possible mechanism and prevent diabetes in type 1 and type 2 (Tsalamandris et al., 2019). Inflammation and oxidative stress are affected by hypertension and increase blood pressure regardless of medicine use (Pouvreau et al., 2018).\n\nCluster 7 = Systematic review. This is the smallest cluster that has only two keywords. The “Systematic review” keyword has 29 occurrences and 25 TLS, whereas “meta-analysis” has 24 occurrences and 20 TLS exhibited in Table 5. These two keywords are used as powerful tools for overcoming the handling of large-scale data. They can help present results from different studies conducted on a similar topic. A thorough understanding of meta-analysis is required to understand and accept the conclusions of various studies (Ahn & Kang, 2018).\n\nOverlay visualisation of author keywords co-occurrences highlights the old and latest keywords through a bibliometric web map (van Eck & Waltman, 2010). Figure 6 exhibits the five clusters marked in five colours ranging from purple to yellow. Purple colours depicted the old keywords, such as “Genomics” “and Cytoscape,” whereas the latest keywords appeared yellow colour such as “COVID-19,” “Anxiety,” “Coronavirus,” “Obesity,” “Risk Factors,” and “Depression” are latest keywords. The latest and most popular keyword in 2020 was “COVID-19”; in the middle of 2019, the most popular keyword was “Machine learning.” It shows that COVID-19 fever is not yet over; researchers are still exploring this area as much as possible to fight against the deadly pandemic and to bring life back to normal.\n\nThe citation analysis explains the highly cited documents and authors (Waltman et al., 2020) in the specific journal, performed through VOS-viewer software. Analysis was performed by restricting a document's minimum number of citations to 100. Out of 5518 documents, only 71 met the desired threshold. Table 6 exhibited the top 20 authors and articles with maximum citations in F1000 research journals. 71 documents with more than 100 citations which the previous researchers have used and now can be used in theoretical concepts for future studies. “Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences”, authored by Soneson et al. (2015), has a maximum citation of 1570, which is almost thrice more than the second highest cited document (574 citations), i.e., “FastQ Screen: A tool for multi-genome mapping and quality control” authored by Wingett & Andrews (2018). “Leishmaniasis: A review”, authored by Torres-Guerrero et al. (2017), has 516 citations, “Bioconductor workflow for microbiome data analysis: from raw reads to community analyses” authored by Callahan et al. (2016) has 439 citations and “Current understanding of Alzheimer’s disease diagnosis and treatment” authored by Weller & Budson (2018) has 434 citations. These documents can prepare a base for future researchers to develop a robust theory.\n\nDuring the review of the F1000Research journal, 5290 authors were identified. While checking the citations analysis through VOS-viewer and limiting the maximum number of authors per document to 25 and the minimum number of documents of an author to two, only 225 authors met the desired threshold. Table 7 exhibits the top 20 authors, affiliations, country, total publications, total citations, and average cited documents since the journal’s evolution until 2022. Quantifying in publications is one of the criteria for increasing visibility on a global platform. However, it is challenging to gain popularity without citations of specific documents. Mainly European, Asian, and American continent authors’ visibility was found in the top-20 authors in terms of quantification of publication, whereas African and Australian authors did not appear in this list. The leading author’s impact is exhibited in Table 8 based on the h-index, g-index, and m-index. Various algorithms have been developed to calculate the most impactful author based on the publications, citations, author’s visibility, and continuity of publications. The g-indexed were designed to measure the global citation performance of articles or authors. It is also known as an improved version of the h-index (Egghe, 2006). The m-index is a metric used to measure the h-index divided by the start of the publication year until the latest year.\n\nTable 8 exhibits the top 20 most impactful authors based on the h-index given by Hirsch (2005). F1000Research journal is one of the premium journals where 5290 authors have published their articles. However, only a few authors have more than a five h-index. “Gary D. Bader” and “Sean Ekins” have the maximum h-index of nine amongst the authors, 12 g-index, 12 publications and 577 and 269 citations, although the first publication came in 2014. “Jürgen Bajorath,” ranked number three in the list, has eight h-index, 19 publications, and has been active in publishing since 2012. Identifying the most prolific authors and their research articles can help future researchers extend their research recommendations, understand their research area, and identify the research gaps, which can help conceptualise the future research problem.\n\nBibliographic coupling occurs when two papers cite a third common paper. The two papers address a common subject matter (Martyn, 1964). In the present study, the bibliographic links between authors, countries and organisations through overlay visualisation are shown in Figure 7, Figure 8, and Figure 9. While examining the bibliographic coupling of authors, the minimum number of documents of an author was restricted to 100. 5290 authors appeared, but only 225 met the desired threshold. However, the largest set of only 71 items connected items were found. Figure 7 depicts the bibliographic coupling between the authors at the various stages of a research journey. Author’s node marked in yellow highlights the youngest/recent (2021) coupling, whereas the authors in purple depicted the oldest (2016) coupling.\n\nFigure 8 shows the bibliographic coupling (overlay visualisation) of countries. During the VOS-viewer bibliometric analysis, countries that published at least five documents were considered for final analysis. Only 89 countries met the desired threshold values out of 164 countries. However, the largest set of connected items was only 88. The United States was found as the most significant contributor in terms of publications as well as citations. They have been involved in publishing papers marked in purple for a long time. In contrast, Asian countries like Indonesia, United Arab Emirates and Qatar are new in bibliographic coupling (marked in yellow).\n\nFigure 9 shows a bibliographic coupling (overlay visualisation) of the organisation. While performing the analysis using VOS-viewer, an organisation published at least four documents that were considered for the final analysis. Out of 14646 organisations, only 83 met the desired threshold criteria, but only 57 organisations had the largest set of connected items. Organisations marked in yellow are the youngest, and those marked in purple are the oldest in the F1000Research journal.\n\nKeywords that appeared during the analysis in VOS-viewer software or Biblioshiny (R-studio) were visualised through theme generation. In the present study, Biblioshiny (R-studio) software was used to understand the various themes (niche theme, motor theme, basic theme and emerging or declining theme), which have been divided into four quadrants (Q1, Q2, Q3, and Q4) (Cobo et al., 2011), identified based on centrality (X-axis) and density (Y-axis). The degree to which a topic is connected to other topics and, in turn, significant in a particular domain is measured by centrality, which assesses the level of inter-cluster relationships. The density, conversely, gauges the degree of intra-cluster cohesion, or more specifically, how closely related the keywords in a given cluster are to one another and how strongly a theme is established (Forliano et al., 2021). In Figure 10, the upper left (high density and low centrality) includes niche research themes containing the keywords “open science,” “treatment,” “inflammation,” and “diagnosis.” Niche themes suggest it is internally well developed but unable to influence others due to low centrality. Motor themes appeared in the upper right quadrant (high in density and centrality) and included the keywords “bioinformatics,” “genomics,” and “RNA-seq.” It suggests that themes are well-developed and highly influence the researcher. Basic themes appeared in the lower right quadrant (high in centrality and low in density), showing the themes are extending or lying across for discipline and can influence the other researcher/topics but are underdeveloped. Emerging or declining themes appeared in the bottom left quadrant (low centrality and density), which is neither well developed nor influenced by the researcher. Keywords that appeared here are “COVID-19,” “SARS-CoV-2,” and “Children” are a matter of great concern in the present scenario. Based on the thematic map analysis, it can be concluded that the keywords that appeared in niche themes are well-developed and highly influenced by the researchers. In contrast, future researchers need more focus on emerging or declining themes to develop a concrete plan to fight against these widespread (COVID-19, SARS-CoV-2, and children) keywords.\n\nThe present study visualises trending topics through Biblioshiny (R-studio), shown in Figure 11. Bubbles of the smallest size have shown a minimum of 50, middle 100, and biggest 150 appearances. Recently appeared topics (between 2021-22) are awareness, attitude and COVID-19, although their bubble size is small (minimum <50 and >100 appearances). COVID-19 again appeared between 2020-21 with the biggest bubble (<150 appearances) along with “SARS-Cov-2” (<100 appearances) and “systematic review” keywords. These topics emerged based on keywords in the author’s articles published in the F1000Research journal journey since its inception.\n\n\nDiscussion: Direction for future research\n\nBibliometric analysis suggests that future researchers/scholars for developing advanced theories and scholarly practices and utilising them for policy-making decisions (Mukherjee et al., 2022). Developing advanced approaches directly relates to the keywords' co-occurrences, which appeared during the bibliometric analysis. The present study generated seven clusters based on the keyword’s relevance and its TLS. In all seven clusters, majorly appeared keywords are “Bioinformatics,” “Treatment,” “Children,” “COVID-19,” “Cancer,” “Inflammation,” and “Systematic review”, on which researchers have worked recently. These areas can be further used to discuss the impact and applicability of improving health and immunity to fight against various life-threatening diseases.\n\nBioinformatics (Cluster 1 – Red colour): As per the Oxford English Dictionary, “Bioinformatics” is a conceptualisation of biology in molecular terms (physical chemistry), or it is a molecular information system of molecular biology. In medical science, it has various aims, such as – allowing researchers to access the current information and submission new information, developing tools which can be helpful in data analysis, and utilisation of the developed tools for data interpretation in a meaningful (biological) manner (Luscombe et al., 2001). The machine learning algorithm can be used to understand the term “Bioinformatics”, which can be helpful in education. Future studies can be done on software designing and data sharing areas through visualisation and “R” to explore the new facts of “Bioinformatics”.\n\nTreatment (Cluster 2 = Green colour): A healthy human being finds a physical change in the body, initially undetectable and later become detectable by laboratory testing through clinical trials by physicians during diagnosis (Scheuermann et al., 2009). There are various diseases caused due to infection, such as tuberculosis which can be deadly and epidemic if not diagnosed at the initial stage (Ahmad & Mokaddas, 2010). Vaccination is one of the milestone achievements to solve the problem permanently instead of going for treatment and remedy of diseases (Quilici et al., 2015). Future researchers should focus on proper diagnosis, vaccine, and pathogen identification for curing diseases and developing antibiotics through neuroimaging.\n\nChildren (cluster 3 = Blue colour): Worldwide, childhood obesity has increased significantly during the past few decades (Han et al., 2010). Paediatricians should be worried about childhood obesity and act fast to adopt therapies because it accounts for most adult obesity (Daniels et al., 2015). Children who are obese can develop type 2 diabetes, insulin resistance, and psychosocial problems. Additionally, it has been associated with greater adult morbidity and mortality. Obesity prevention is essential and can be effectively treated by food planning and increasing physical activity (Lifshitz, 2008). People in urban areas are more prone to asthma and obesity (Johnson et al., 2010). Asthma and hypertension are also prevalent diseases nowadays; both can be seen together. Prior research has suggested that asthmatic patients are more prone to hypertension than non-asthmatic patients (Lee et al., 2009). Further research is needed to understand the relationship between children, asthma, obesity, hypertension, stroke, and environmental risk.\n\nCOVID-19 (cluster 4 = Yellow colour): The COVID-19 pandemic brought the world to its knees because of its uniqueness and communicability. It has taken an important place in our daily routine. It became the most significant concern for the nations and society, and countries like India and China ranked no.1 and 2 in population, were assumed as the most affected countries by SARS-CoV-2. COVID-19 has highly impacted the heart surgeon clinical practice, suggesting the medical team's preparedness to tackle the challenges exposed by SARS-CoV-2 (Pericàs et al., 2020). Since the outbreak is not over, future researchers should evaluate and monitor everything carefully for a better understanding of the epidemiological properties of COVID-19, which can help develop mechanisms to safeguard public health.\n\nCancer (cluster 5 = Purple colour). Cancer is one of the fastest-growing diseases worldwide (Popat et al., 2013) in various types, such as breast, blood, liver, lung, ovarian, prostate, etc. Underarm deodorant, specific chemical’s regular and long-term use was found as one of the factors behind the development of breast cancer (under investigation) (Darbre, 2009). Gene mutation plays a crucial role in predisposition to breast cancer. However, understanding the genes pathways can play a vital role in developing a preventive target to fight against breast cancer (Sheikh et al., 2015). Few studies suggested immunotherapeutic strategies can help fight against the deadly breast cancer disease (Marra et al., 2019). Various clinical trials are developing strategies to counter this growing concern; therefore, future researchers can focus on gene mutation, immunotherapy, and reviewing cancer case reports to understand this deadly disease.\n\nInflammation (cluster 6 = Cyan colour). Inflammation studies can play a crucial role in understanding the origin and progression of the disease. A better understanding of the trigger mechanisms that cause inflammation is required to keep enough control over the inflammatory cascade (Schmid-Schönbein, 2006). Mitochondria are found as the master regulators and controllers of inflammation, but further research is needed to understand the mitochondrial functions as a controlling organelle in inflammatory reactions in patients (Marchi et al., 2023). Future researchers can focus on bioengineering analysis which can help open the door for inflammation treatment through new and improved interventions (Schmid-Schönbein, 2006).\n\nSystematic Review (cluster 7 = Orange colour). Most of the studies in the top-cited journals are either performed through systematic review or meta-analysis approach; therefore, it is recommended that future research should focus more on clinical trials or quantitative methods.\n\n\nConclusion\n\nThe present study attempts to present the publication journey of the F1000Research journal from its inception (2012) to 31st December 2022 through bibliometric analysis using VOS-viewer and Biblioshiny (R studio) interface. The publication trends and journal citation analysis were understood and exhibited in Figure 1. The journal gained popularity in 2015 and peaked in 2018 (published 915 articles).\n\nThe leading authors, leading organisations, highly cited documents, and leading countries’ contributions are also presented. Future researchers can collaborate with leading authors, organisations, and countries to escalate the work and extend their future recommendations in an unexplored area. Author keywords are presented through web map analysis which can be helpful for the future researcher to explore the unknown or least explored areas in their study and can be correlated with the theoretical concept. The prospective researcher can use the least explored keywords to understand the area minutely and its relationship with future keywords and their impact.\n\nThis study has also explored the significant clusters (seven) based on keywords co-occurrence analysis. It has been found that “COVID-19” has the maximum occurrences and highest TLS. “COVID-19” is a significant area of concern for the entire world. Therefore, researchers worldwide focus more on its impact on human beings, treatment, and vaccine development. Bioinformatics is one of the areas which is gaining popularity in the present context. Hence, future researchers can contribute their work to understanding medical science through machine learning and software.\n\nThe present study would help future researchers to understand the emerging medical science domain. It will also help the editors and journal to focus more on developing or emerging areas and to understand their importance towards society. Countries which have not contributed even a single article to the F1000Research journals are also a matter of concern; therefore, the editor and publisher must target those countries by providing some financial discount as the journal is on an open-access platform. Future research needs to be planned in virus immunology, virology, and bioinformatics through a clinical trial can be a milestone in medical science. Future researchers can contribute their quality research studies, focusing on emerging themes. It has been observed that there are very few articles having an h-index of more than 5. These authors’ research can guide future researchers to develop their research area around the most impacted articles. They can collaborate with them to bring that emerging theme a way forward.\n\nThe present study has also encountered some limitations during the data extraction and analysis stage. VOS-viewer software uses a fractional counting method, whereas the Scopus database generates metadata under a full counting system.\n\nBiblioshiny (R-studio) interface showed poor keywords details, a completely missing number of cited references, and a completely missing Science Categories. Co-occurrence analysis between all keywords and index keywords could not be performed due to poor keywords details.",
"appendix": "Data availability\n\nFigshare: Metadata extracted from the Scopus database, which is used to study the most impactful countries, authors, organisations, keywords in F1000Research. https://doi.org/10.6084/m9.figshare.22713604 (Kumar, 2023).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAhmad S, Mokaddas E: Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis. Respir. Med. CME. 2010; 3(2): 51–61. Publisher Full Text\n\nAhn E, Kang H: Introduction to systematic review and meta-analysis. Korean J. Anesthesiol. 2018; 71(2): 103–112. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAria M, Cuccurullo C: bibliometrix: An R-tool for comprehensive science mapping analysis. J. Informet. 2017; 11(4): 959–975. Publisher Full Text\n\nBailey H, Zash R, Rasi V, et al.: HIV treatment in pregnancy. Lancet HIV. 2018; 5(8): e457–e467. 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}
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[
{
"id": "174372",
"date": "01 Jun 2023",
"name": "Rahul Pratap Singh Kaurav",
"expertise": [
"Reviewer Expertise Destination marketing",
"bibliometric analysis",
"and qualitative research."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nOverall, the article \"The journey of F1000Research since inception: through bibliometric analysis\" provides a valuable analysis of F1000Research as a journal and its contributions to the field. Here is some feedback to further enhance the article:\nIntroduction: Consider providing a brief background on the significance of bibliometric analysis and its relevance in understanding the growth and impact of academic journals. This will help readers better understand the context and importance of the study.\n\nAbstract: The abstract effectively summarizes the objectives and methods of the study. However, it could be improved by briefly mentioning the key findings of the analysis. This will provide a glimpse of the main insights to attract readers' interest.\n\nMethods: Provide more details about the specific bibliometric analysis techniques and tools used, such as VOS-viewer and Biblioshiny. This will help readers understand the methodology employed and replicate the study if desired.\n\nResults: While the article mentions various analyses conducted, it would be helpful to provide a concise summary of the key findings under each analysis category. This will make it easier for readers to grasp the main trends and insights without delving into the detailed analysis.\n\nConclusion: The conclusion effectively highlights the potential implications of the study for future researchers, editors, and the journal itself. However, consider expanding on the practical implications and specific recommendations for researchers and editors based on the findings. This will provide actionable insights for readers.\n\nReferences: Ensure that the references are properly cited and formatted according to the appropriate style guide (e.g., APA). This will enhance the credibility and professionalism of the article.\nOverall, the article provides a comprehensive analysis of F1000 Research and its journey since its inception. By incorporating the suggested improvements, the article will become more engaging, informative, and actionable for readers interested in bibliometric analysis.\nI have suggested a few references to incorporate in the article. You may use them.\nThis one paper will help in explaining the multidisciplinary of the journal: Kaurav & Gupta (2022)1\n\nThese papers will help you verify and validate your paper's methodology section: Kaushal et al., (2021)2, Baber et al., (2023)3, Kanta et al., (2021)4\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "174375",
"date": "02 Jun 2023",
"name": "Ajit Singh",
"expertise": [
"Reviewer Expertise Sustainability",
"Augmented Reality",
"Tourism and Hospitality",
"Technology."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe research paper provides a comprehensive and well-structured analysis of the topic. The abstract successfully captures the study's goals and methodologies. However, the key findings may be added in the section. This addition would offer readers a glimpse into the primary insights, thereby piquing their interest.\nThe methodology employed in the study is rigorous and appropriate for the research objectives. However, the analysis could be enhanced by incorporating a thematic evaluation of the keywords. This could be done through Biblioshiny.\nThe findings of the research paper are supported by sound evidence and data, enhancing the credibility of the study.\nThe paper adheres to ethical considerations and provides appropriate acknowledgments and references.\nI have suggested a few papers that explain the thematic evolution of topics or keywords1-3. You can consider using them as references.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-516
|
https://f1000research.com/articles/12-617/v1
|
07 Jun 23
|
{
"type": "Research Article",
"title": "Discordant results among major histocompatibility complex binding affinity prediction tools",
"authors": [
"Austin Nguyen",
"Abhinav Nellore",
"Reid F. Thompson",
"Austin Nguyen"
],
"abstract": "Background: Human leukocyte antigen (HLA) alleles are critical components of the immune system’s ability to recognize and eliminate tumors and infections. A large number of machine learning-based major histocompatibility complex (MHC) binding affinity (BA) prediction tools have been developed and are widely used for both investigational and therapeutic applications, so it is important to explore differences in tool outputs. Methods: We examined predictions of four popular tools (netMHCpan, HLAthena, MHCflurry, and MHCnuggets) across a range of possible peptide sources (human, viral, and randomly generated) and MHC class I alleles. Results: We uncovered inconsistencies in predictions of BA, allele promiscuity and the relationship between physical properties of peptides by source and BA predictions, as well as quality of training data. We found amount of training data does not explain inconsistencies between tools and yet for all tools, predicted binding quantities are similar between human and viral proteomes. Lastly, we find peptide physical properties are associated with allele-specific binding predictions. Conclusions: Our work raises fundamental questions about the fidelity of peptide-MHC binding prediction tools and their real-world implications. The real-world use of these prediction tools for theoretical binding of peptides to alleles is worrying, as the range of allele promiscuity is substantial yet does not differentiate between potential foreign versus self-antigens. Evaluating more viruses – as well as bacteria, fungi, and other pathogens – and linking these analyses with metrics such as evolutionary distance may give greater insight into the relationship between HLA evolution and disease.",
"keywords": [
"Human leukocyte antigen",
"major histocompatibility complex",
"MHC",
"binding",
"allele",
"netMHCpan",
"immune system"
],
"content": "Introduction\n\nHuman leukocyte antigen (HLA) alleles are critical components of the immune system’s ability to recognize and eliminate tumors and infections.1 Infectious diseases in particular are thought to be a major source of selective pressure on the major histocompatibility complex (MHC) region which encodes HLA alleles and is one of the most diverse regions of the human genome.2–8 There is large diversity in the antigenic peptide sequences which individual HLA alleles can recognize and ultimately present to the adaptive immune system,9 with a positive correlation between increased sequence diversity recognition and fitness.10\n\nTools that can predict the extent to which a given HLA allele may have an affinity for a given peptide have critical implications for our ability to understand and translationally leverage antigen-specific immune response pathways. For instance, MHC binding affinity predictors have been – or otherwise have the potential to be – used to evaluate an individual or population’s susceptibility to viral infection,11 to develop an understanding of specific autoimmune conditions,12 to improve transplantation technologies,13 or even to assist in the development of personalized cancer vaccines.14–18 Numerous peptide-MHC binding prediction tools exist, and are key components in broader antigen prediction methodologies.19–22\n\nThe most widely adopted MHC binding prediction tools rely on neural network models trained on binding affinity (BA) and/or eluted ligand (EL) data. The most commonly cited tool, netMHCpan,23,24 uses both BA and EL data in a neural network architecture with a single hidden layer to predict allele-specific binding affinities. MHCflurry25 attempts to improve upon netMHCpan by increasing the number of hidden layers and augmenting BA and EL training data with unobserved decoys. MHCnuggets26 again trains on BA and EL data but uses a different architecture, with a long short-term memory layer and a fully connected layer to improve its predictions further across different peptide lengths. Lastly, HLAthena,27 while most similar in architecture to netMHCpan, relies on independently generated EL data from mono-allelic cell lines for training.\n\nWe sought to better characterize the outputs of these tools over a large and diverse set of peptides, across different tools and HLA alleles, as well as quantify the stability of these predictions. We also sought to measure allelic binding preferences and whether they may enrich for foreign v. self peptides. In this study, we performed a comprehensive in silico analysis of peptides from multiple viral proteomes, the human proteome, and randomly generated peptides across HLA class I alleles.\n\n\nMethods\n\nFASTA-formatted protein sequence data was retrieved from the National Center of Biotechnology Information (NCBI)28,29 using RefSeq as of 1-31-22 for BK, SARS-CoV-2, HHV-5, HHV-6, HSV-1, HSV-2, HSV-4, and Human. Protein sequence data was inputted into netchop v3.0 “C-term” model with a cleavage threshold of 0.1 to remove peptides that were not predicted to undergo canonical MHC class I antigen processing via proteasomal cleavage (of the peptide’s C-terminus). The results from netchop v3.0 were then kmerized sequentially into 8- to 12-mers. Code used for kmerization and netchop filtering can be found at: https://github.com/Boeinco/peptide-MHCassess. We additionally generated a set of 1 million random peptides of length 8-12 drawn uniformly at random. Peptide sets had negligible overlap (<1% shared between human vs viral vs random peptides).\n\nMHC class I binding affinity predictions were performed for the peptides generated from the kmerization process above using four tools: netMHCpan v4.1,23 HLAthena v1.0,27 MHCflurry v2.0,25 and MHCnuggets v2.3.30 netMHCpan was run with default options with the ‘-l’ option to specify peptides of lengths 8–12. MHCflurry was run with default options. MHCnuggets was run with default options. HLAthena was run using the dockerized version of HLAthena with default options, which predicts peptides of length 8–11. MHC class I binding affinity predictions were performed for each of 24, 26, and 2, HLA-A, -B, and -C alleles, respectively. Only alleles that were in common between all four tools were used (52 total alleles in common between 2489 possible alleles). Binding affinity values were converted to binding probability values for MHCflurry and MHCnuggets using 1- log (binding affinity) /log(50000) in order to match HLAthena and netMHCpan binding probability predictions. Alleles were grouped into supertypes when applicable using the HLA class I revised classification.31\n\nPeptides were converted into physical property matrices using amino acid sequence mapping into a 4*kmer length matrix containing each amino acid’s properties in sequence. The following physical properties of the amino acids were encoded: side chain polarity was recorded as its isoelectric point (pI),32 the molecular volume of each side chain was recorded as its partial molar volume at 37°C,33 the hydrophobicity of each side chain was characterized by its simulated contact angle with nanodroplets of water34 and conformational entropy was derived from peptide bond angular observations among protein sequences without observed secondary structure.35\n\nEach dimensional reduction was performed on the pooled set of k-mers. UMAP dimensionality was performed using uwot UMAP R implementation v0.1.11. PCA was performed using default prcomp() functions in base R v4.1.3.\n\nFor each peptide source, binned matrices were computed using the bin2() function with 40×40 (1600) bins from the Ash v1.0.15 package36 in R v4.1.3. Bin values were then divided by the total number of peptides to create bins with the % of total peptides. In order to compare between two peptide sources, a matrix, called the difference matrix, is created by subtracting one matrix of a peptide source from another. Taking the absolute value of each bin in the difference matrix, then summing the values together, results in a single metric ranging from 0–2 measuring the difference in binned density between two peptide sources, the value 2 indicating that no peptides were shared between bins and the value 0 indicating the same percentage of peptides in every bin (Figure 1).\n\nBin values were then divided by the total number of peptides to create bins with the % of total peptides. In order to compare between two peptide sources, a matrix, called the difference matrix, is created by subtracting one matrix of a peptide source from another. Taking the absolute value of each bin in the difference matrix, then summing the values together, results in a single metric ranging from 0–2.\n\nFor each allele-peptide source combination, the percentage of peptides predicted to bind with a binding probability score of 0.5 or greater was calculated for all processed peptides.37 A binding score of 0.5 is estimated to be equivalent to 250–300 nM depending on the tool used. For each peptide source, alleles were ranked from best to worst binders (most to least peptides ≥ 0.5 score) t. In order to compute allele ordering similarity between two peptide sources for a single tool, Spearman’s Rank Correlation Coefficient was calculated between the two sets of allele ranks.\n\nFor the random group 1 vs random group 2 analysis, we conducted 100 replicates of dividing the randomly generated peptides into two random groups and performed a Spearman rank test of allele ordering between these groups for each of the tools.\n\nIntraclass correlation coefficients (ICCs) were calculated using the ICC () function from the IRR v0.84.1 R package.38 Binding prediction scores for all one million randomly generated peptides were separated by tool and HLA allele, and an ICC was calculated as the interrater reliability metric between the four tools for each allele. ICC was also between the four tools on a per peptide basis, each peptide receiving a score across four tools using predictions separated by tool and peptide.\n\nAn earlier version of this article can be found on bioRxiv (https://doi.org/10.1101/2022.12.04.518984). Source code can be found on Github.39\n\n\nResults\n\nWe first assessed the consistency of peptide-specific MHC I binding affinity predictions across four tools (MHCnuggets, MHCflurry, HLAthena, netMHCpan) and 52 different HLA alleles. We found substantial disagreement in peptide-specific predictions between each tool, independent of allele (Figure 2A), with median intraclass correlation coefficient (ICC) of 0.207 and only 0.48% of peptides having ICC >0.75. On a per-allele basis, we found a wide range in consistency of predictions across tools, with a mean intraclass correlation as low as 0.12 for A02:07 and as high as 0.64 for A23:01 (Figure 2B). Among all of the peptides predicted by at least one tool to bind to at least one allele, only 7.9% were consistently predicted across all tools to bind to the same allele (Figure 2C).\n\nA) Histogram of intraclass correlation coefficients (ICC) calculated for a set of 1 million random peptides across four tools (MHCnuggets, MHCflurry, HLAthena, netMHCpan), with ICC calculated as the overall correlation among tools across 52 HLA alleles. The dotted vertical line indicates the median ICC value (0.207) across all peptides. B) Histogram of ICCs for 52 HLA alleles between four tools (MHCnuggets, MHCflurry, HLAthena, netMHCpan). The number of alleles is shown on the y-axis and the ICC is shown on the x-axis. The dotted lines show the mean ICC for alleles belonging to each HLA class. Red, green, and blue colors represent data from -A, -B, and -C alleles, respectively. C) Detailed comparison of the complete set of random peptides predicted to bind (binding score ≥ 0.5) to HLA alleles according to each of four tools. Patterns of agreement or disagreement among groups of peptides predicted by different combinations of tools across 1 million random peptides are shown along each column (e.g. the first column corresponds to peptides predicted by HLAthena while the final column corresponds to peptides predicted by all tools). Each row indicates the predictions associated with the indicated tool. The number of peptides in each column (vertical bars) corresponds to the size of the subset predicted by the indicated combination of tools.\n\nWe next investigated aggregate peptide binding predictions across different HLA alleles according to each tool. As others have noted differential HLA allelic promiscuity in peptide presentation,31,40–42 we too found a wide range in the proportion of peptides a given allele was predicted to bind (Underlying data: Supplementary Figure 137). We uncovered significant inconsistencies in these predictions between tools (Figure 3). Note that this phenomenon is independent of binding affinity threshold (Underlying data: Supplementary Figure 237).\n\nThe lower left grouping of plots displays scatter plots of peptides predicted to bind (≥ 0.5 binding probability score) between 2 tools with each point representing the number of predicted binders for each HLA allele. The upper right grouping represents the Spearman correlation of the number of peptides predicted to bind to all alleles between tools. Note that MHCnuggets has a number of alleles with 0 random peptides predicted to bind. The diagonal panels show distribution of HLA allelic presentation from the random proteome for each tool. The number of peptides that putatively bind to each of the HLA alleles is shown along the x-axis as a series of horizontal bars with green, orange, and purple colors representing HLA-A, -B, and -C alleles, respectively, sorted in order of decreasing quantity of binders.\n\nAs each allele has a different amount of training data, we were next interested in exploring to what extent the quantity and quality of training data available to each tool might influence its allele-specific predictions. Indeed, some netMHCpan predictive models for some alleles are based on as few as 101 peptides, while others from MHCflurry are based on as many as 31,775 peptides (Underlying data: Supplementary Table 137). Note that we excluded from consideration the ~95% of alleles (4108) that were available for prediction but had no underlying allele-specific training data available (Underlying data: Supplementary Table 237). Ultimately, we found that the amount of training data available was not significantly related to the consistency of binding predictions between tools (Figure 4A), nor was it clearly related to the quantity of binding peptides predicted by tools (Figure 4B).\n\nA) Scatterplot of ICC vs mean training data across 4 tools with each point representing data for a single HLA allele. The mean number of training peptides is shown on the x-axis while the ICC score is shown on the y-axis. B) Scatterplot of the relationship between training data and predicted peptide binding. The number of peptides used as training data for an allele is shown on the x-axis whereas the number of peptides predicted to bind for the same allele is shown on the y-axis. Each dot is a single allele with each color representing a different tool: red circles (HLAthena), green triangles (MHCflurry), blue squares (MHCnuggets), purple plus signs (netMHCpan). We note that netMHCpan does not make all of their training data available, thus the depicted quantity of training data represents an estimate.\n\nAccording to the pathogen driven selection theory of MHC evolution, different HLA alleles are anticipated to be particularly attuned to foreign as opposed to self-antigens.3,8,43–46 We therefore sought to compare the predicted capacity of different HLA alleles to present different viral vs. self-antigens. Further, we wished to establish which specific alleles had the propensity to bind a larger fraction of peptides in general (allele promiscuity) by observing the relationship between an allele’s ability to bind random peptides versus peptides from a viral or human proteome.\n\nWe examined distribution of predicted allelic promiscuity across alleles for nine sets of peptides of viral, human, and random origin (See Methods). Confining attention to human and viral proteomes, we again found a wide range in the proportion of peptides a given allele was predicted to bind and also significant inconsistencies between tools (Underlying data: Supplementary Figure 337).\n\nWe found that the alleles with highest mean binding percentage for human and viral peptides were B15:03 (2.68%) and B15:02 (2.36%) and the allele lowest mean binding percentage were B18:01 (0.24%) and A01:01 (0.33%) (Underlying data: Supplementary Table 337). No alleles were predicted by any tool to preferentially present either viral or human peptides. Further, the distribution of predicted allelic promiscuity across alleles was highly consistent between human and viral proteomes, but not when applied to a set of random peptides (Figure 5). We noted that this phenomenon holds for closely related viruses across all tools and to a lesser extent for more distantly related viruses (Underlying data: Supplementary Figure 437).\n\nA) Heatmap of spearman correlation between peptide sources for HLAthena-based predictions for human peptides, viral peptides, and randomly generated peptides. Numbers show Spearman correlation coefficients between each pair respectively, while color reflects the Spearman correlation with red approaching a Spearman correlation of 1. Analogous data is shown for netMHCpan, MHCflurry, and MHCnuggets in panels B, C, and D, respectively.\n\nConfining attention to the nine alleles whose predictive models were likely most robust (based on a minimum of 2000 training peptides for every tool), we again found that the distribution of predicted allelic promiscuity across alleles was consistent between closely related viruses and to a lesser extent between more distantly related viruses (Underlying data: Supplementary Figure 537).\n\nReasoning that differences in peptide characteristics were the likeliest explanation for predicted differences in binding affinity between different alleles and peptide sources, we next studied the distribution of physical properties among different peptide sets. Human, viral, and random peptide sets all exhibited the same range of physical properties but were differentially enriched among different physical properties (Underlying data: Supplementary Figure 637). Between individual peptide sets, the differential enrichment ranged from 10% (CMV v. human) to 63% (BK v. random) of peptides (Underlying data: Supplementary Figure 737).\n\nWe next sought to discover the relationship between the peptide similarity in physical property space and distribution of predicted allelic promiscuity across alleles. Across all tools, there was a positive relationship between similarity in physical property space and distribution of predicted allelic promiscuity across alleles as evidenced by the negative correlation between peptide set difference and Spearman correlation coefficient (Figure 6).\n\nA) Scatterplot for HLAthena-based predictions, where each point represents predictions for a species vs species pair. Peptide dissimilarity is shown on the x-axis, whereas Spearman correlation coefficients of predicted allelic promiscuity across alleles. Color represents the length of peptide, with 8-, 9-, 10-, and 11-mers shown in red, green, blue and purple, respectively. Analogous data is shown for netMHCpan, MHCflurr, and MHCnuggets in panels B, C, and D, respectively.\n\nNext, we found that each allele has distinct preferences for different peptide physical properties, independent of peptide length (Figure 7A, Supplementary Figure 837). Some alleles (e.g. A01:01 and B08:01) have stronger preference for certain physical properties (Figure 7B, C), while others (B45:01) do not have as clear of a preference (Figure 7D).\n\nA) The plotting coordinates represent the first two dimensions of a UMAP transform of peptide physical properties, which is divided into 1600 (40×40) equivalently-sized square bins (see Methods). For each bin where there is at least one HLA allele with >0.2% difference in proportion of all peptides predicted to bind v. non-binders, the identity of the most enriched allele is shaded in the color corresponding to that allele’s supertype as corresponding to the legend. B-D) Example plots of three different alleles (A01:01, B08:01, and B45:01) with different distributions of binders. Each box represents enrichment as the percent peptide difference between predicted binders and non-binders for the given allele. The color scale shows the percent of peptides difference in the given box, with red meaning a larger number of predicted binders and blue meaning a larger number of predicted non-binders.\n\n\nDiscussion\n\nTo the best of our knowledge, this is the first study to examine the consistency of predictions of peptide-MHC binding across different tools, and to explore the quality and quantity of training data in this context. We note several limitations to this work. Firstly, we confined attention to MHC class I peptides and did not include predictions for MHC class II,47 of which there are numerous alleles. We also excluded from consideration any potential contributions of proteasomal cleavage or other antigen processing machinery to MHC binding.48–50 We did not seek to comprehensively assess all available tools for peptide-MHC binding affinity prediction, but rather confined our attention to four of the most widely used tools. The majority of our randomly generated peptides are not known to be found in nature and may not represent the optimal background distribution for measuring allele promiscuity or interrater reliability between tools primarily used for human and pathogenic peptides. While our analysis of peptides leveraged four essential and well-described amino acid physical properties, there may exist unassessed latent features that could capture additional variance and improve dimensionally-reduced comparisons. We did not assess the extent to which mass spectrometry biases in the training datasets might affect peptide-MHC predictions.51–54 Lastly, we did not evaluate individual tool performance based on known epitopes as this has been previously reported.23–27,55–59\n\n\nConclusions\n\nOur work raises fundamental questions about the fidelity of peptide-MHC binding prediction tools. Why, for instance, can predictions be so discordant among tools for which training datasets are otherwise so similar? We especially worry about the real-world use of these prediction tools for alleles without any direct basis in training data. Why is the predicted range of allele promiscuity so substantial, and yet not demonstrative of any meaningful differences in enrichment between potential foreign versus self-antigens? Moreover, is this differential promiscuity a universal biological phenomenon, with certain alleles being generally poor functional presenters of antigen? If this is the case, what selective advantage might have evolutionarily maintained these alleles in the population? Evaluating more viruses – as well as bacteria, fungi, and other pathogens – and linking these analyses with metrics such as evolutionary distance may give greater insight into the relationship between HLA evolution and disease.",
"appendix": "Data availability\n\nZenodo: Underlying data for ‘Discordant results among MHC binding affinity prediction tools’, https://doi.org/10.5281/zenodo.7850939. 37\n\nThis project contains the following underlying data:\n\n• Supplementary figures.docx\n\n• Supplementary tables 1–3.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nDendrou CA, Petersen J, Rossjohn J, et al.: HLA variation and disease. Nat. Rev. Immunol. 2018 May; 18(5): 325–339. Publisher Full Text\n\nBlackwell JM, Jamieson SE, Burgner D: HLA and Infectious Diseases. Clin. Microbiol. Rev. 2009 Apr; 22(2): 370–385. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMeyer D, Aguiar VRC, Bitarello BD, et al.: A genomic perspective on HLA evolution. Immunogenetics. 2018; 70(1): 5–27. 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Res. 2014 Dec; 2(12): 1154–1162. PubMed Abstract | Publisher Full Text\n\nBjerregaard AM, Nielsen M, Hadrup SR, et al.: MuPeXI: prediction of neo-epitopes from tumor sequencing data. Cancer Immunol. Immunother. CII. 2017 Sep; 66(9): 1123–1130. PubMed Abstract | Publisher Full Text\n\nWood MA, Nguyen A, Struck AJ, et al.: neoepiscope improves neoepitope prediction with multivariant phasing. Bioinformatics. 2020 Feb 1; 36(3): 713–720. PubMed Abstract | Publisher Full Text\n\nHundal J, Carreno BM, Petti AA, et al.: pVAC-Seq: A genome-guided in silico approach to identifying tumor neoantigens. Genome Med. 2016 Jan 29; 8(1): 11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBais P, Namburi S, Gatti DM, et al.: CloudNeo: a cloud pipeline for identifying patient-specific tumor neoantigens. Bioinforma. Oxf. Engl. 2017 Oct 1; 33(19): 3110–3112. PubMed Abstract | Publisher Full Text | Free Full Text\n\nReynisson B, Alvarez B, Paul S, et al.: NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res. 2020 Jul 2; 48(W1): W449–W454. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJurtz V, Paul S, Andreatta M, et al.: NetMHCpan-4.0: Improved Peptide–MHC Class I Interaction Predictions Integrating Eluted Ligand and Peptide Binding Affinity Data. J. Immunol. 2017 Nov 1; 199(9): 3360–3368. PubMed Abstract | Publisher Full Text | Free Full Text\n\nO’Donnell TJ, Rubinsteyn A, Laserson U: MHCflurry 2.0: Improved Pan-Allele Prediction of MHC Class I-Presented Peptides by Incorporating Antigen Processing. Cell Syst. 2020 Jul; 11(1): 42–48.e7. PubMed Abstract | Publisher Full Text\n\nShao XM, Bhattacharya R, Huang J, et al.: High-Throughput Prediction of MHC Class I and II Neoantigens with MHCnuggets. Cancer Immunol. Res. 2020; 8: 396–408. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSarkizova S, Klaeger S, Le PM, et al.: A large peptidome dataset improves HLA class I epitope prediction across most of the human population. Nat. Biotechnol. 2020 Feb; 38(2): 199–209. PubMed Abstract | Publisher Full Text | Free Full Text\n\nO’Leary NA, Wright MW, Brister JR, et al.: Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation. Nucleic Acids Res. 2016 Jan 4; 44(D1): D733–D745. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBrister JR, Ako-Adjei D, Bao Y, et al.: NCBI viral genomes resource. Nucleic Acids Res. 2015 Jan; 43(Database issue): D571–D577. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShao XM, Bhattacharya R, Huang J, et al.: High-throughput prediction of MHC class I and class II neoantigens with MHCnuggets. Cancer. Immunol. Res. 2019 Dec 23; canimm.0464.2019.\n\nSidney J, Peters B, Frahm N, et al.: HLA class I supertypes: a revised and updated classification. BMC Immunol. 2008 Jan 22; 9(1): 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLide D: CRC handbook of chemistry and physics, 1992-1993: a ready-reference book of chemical and physical data.1992 [cited 2022 Sep 4]. Reference Source\n\nHackel M, Hinz HJ, Hedwig GR: A new set of peptide-based group heat capacities for use in protein stability calculations - ScienceDirect. [cited 2022 Sep 4]. Reference Source\n\nZhu C, Gao Y, Li H, et al.: Characterizing hydrophobicity of amino acid side chains in a protein environment via measuring contact angle of a water nanodroplet on planar peptide network. Proc. Natl. Acad. Sci. U. S. A. 2016 Nov 15; 113(46): 12946–12951. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFogolari F, Corazza A, Fortuna S, et al.: Distance-Based Configurational Entropy of Proteins from Molecular Dynamics Simulations. PLoS One. 2015; 10(7): e0132356. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaluzny S original by DWSR port by AG adopted to recent SP by S. ash: David Scott’s ASH Routines.2015 [cited 2022 Jul 11]. Reference Source\n\nNguyen A: Underlying data for ‘Discordant results among MHC binding affinity prediction tools’. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nShrout PE, Fleiss JL: Intraclass correlations: uses in assessing rater reliability. Psychol. Bull. 1979 Mar; 86(2): 420–428. Publisher Full Text\n\nNguyen A: Boeinco/peptide-MHCassess: F1000ReleaseV1 (Version F1000). [Code]. Zenodo. 2023; Publisher Full Text\n\nPaul S, Weiskopf D, Angelo MA, et al.: HLA class I alleles are associated with peptide-binding repertoires of different size, affinity, and immunogenicity. J. Immunol. Baltim. Md. 1950. 2013 Dec 15; 191(12): 5831–5839. Publisher Full Text\n\nPavlos R, McKinnon EJ, Ostrov DA, et al.: Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles. Sci. Rep. 2017 Aug 17; 7(1): 8653. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbelin JG, Keskin DB, Sarkizova S, et al.: Mass Spectrometry Profiling of HLA-Associated Peptidomes in Mono-allelic Cells Enables More Accurate Epitope Prediction. Immunity. 2017 Feb; 46(2): 315–326. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSpurgin LG, Richardson DS: How pathogens drive genetic diversity: MHC, mechanisms and misunderstandings. Proc. R. Soc. B Biol. Sci. 2010 Apr 7; 277(1684): 979–988. PubMed Abstract | Publisher Full Text | Free Full Text\n\nManczinger M, Boross G, Kemény L, et al.: Pathogen diversity drives the evolution of generalist MHC-II alleles in human populations. PLoS Biol. 2019 Jan 31; 17(1): e3000131. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWhite CF, Pellis L, Keeling MJ, et al.: Detecting HLA-infectious disease associations for multi-strain pathogens. Infect. Genet. Evol. 2020 Sep 1; 83: 104344. PubMed Abstract | Publisher Full Text\n\nPrugnolle F, Manica A, Charpentier M, et al.: Pathogen-Driven Selection and Worldwide HLA Class I Diversity. Curr. Biol. 2005 Jun 7; 15(11): 1022–1027. PubMed Abstract | Publisher Full Text\n\nRoche PA, Furuta K: The ins and outs of MHC class II-mediated antigen processing and presentation. Nat. Rev. Immunol. 2015 Apr; 15(4): 203–216. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWeeder B, Wood MA, Li E, et al.: pepsickle rapidly and accurately predicts proteasomal cleavage sites for improved neoantigen identification. Bioinformatics|Oxford Academic. [cited 2022 Oct 2]; 37: 3723–3733. PubMed Abstract | Publisher Full Text Reference Source\n\nRitz U, Seliger B: The Transporter Associated With Antigen Processing (TAP): Structural Integrity, Expression, Function, and Its Clinical Relevance. Mol. Med. 2001 Mar; 7(3): 149–158. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLópez de Castro JA: How ERAP1 and ERAP2 Shape the Peptidomes of Disease-Associated MHC-I Proteins. Front. Immunol. 2018 [cited 2022 Oct 2]; 9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDincer AB, Lu Y, Schweppe DK, et al.: Reducing Peptide Sequence Bias in Quantitative Mass Spectrometry Data with Machine Learning. J. Proteome Res. 2022 Jul 1; 21(7): 1771–1782. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEdwards NJ: Novel peptide identification from tandem mass spectra using ESTs and sequence database compression. Mol. Syst. Biol. 2007 Jan; 3(1): 102. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPrakash A, Piening B, Whiteaker J, et al.: Assessing Bias in Experiment Design for Large Scale Mass Spectrometry-based Quantitative Proteomics. Mol. Cell. Proteomics. 2007 Oct 1; 6(10): 1741–1748. PubMed Abstract | Publisher Full Text\n\nTimp W, Timp G: Beyond mass spectrometry, the next step in proteomics. Sci. Adv. 2020 Jan 10; 6(2): eaax8978. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPaul S, Croft NP, Purcell AW, et al.: Benchmarking predictions of MHC class I restricted T cell epitopes in a comprehensively studied model system. PLoS Comput. Biol. 2020 May 26; 16(5): e1007757. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTrolle T, Metushi IG, Greenbaum JA, et al.: Automated benchmarking of peptide-MHC class I binding predictions. Bioinformatics. 2015 Jul 1; 31(13): 2174–2181. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhao W, Sher X: Systematically benchmarking peptide-MHC binding predictors: From synthetic to naturally processed epitopes. PLoS Comput. Biol. 2018 Nov 8; 14(11): e1006457. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVenkatesh G, Grover A, Srinivasaraghavan G, et al.: MHCAttnNet: predicting MHC-peptide bindings for MHC alleles classes I and II using an attention-based deep neural model. Bioinformatics. 2020 Jul; 36(Suppl 1): i399–i406. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBhattacharya R, Sivakumar A, Tokheim C, et al.: Evaluation of machine learning methods to predict peptide binding to MHC Class I proteins. bioRxiv. 2017 Jul 27; 154757."
}
|
[
{
"id": "177522",
"date": "13 Jul 2023",
"name": "André Leier",
"expertise": [
"Reviewer Expertise Bioinformatics",
"Computational Biology",
"Machine learning",
"Gene-targeted Therapies",
"RNA Biochemistry"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe work by Nguyen et al. compares outputs of four ML-based predictors of MHC binding affinity, namely NetMHCpan (2015), HLAthena, MHCflurry (2018), and MHCnuggets (2017), which, according to the authors, are widely used in investigational and therapeutic applications. Their comparison is based on predictions involving human, viral, and randomly generated peptide sources and 52 MHC class I alleles.\nTo assess the consistency of these prediction tools the authors present results from various analyses, such as:\n(a) an intraclass correlation coefficient analysis,\n(b) tool-vs-tool comparison of predicted binder numbers per allele, Spearman correlations between tools based on peptide numbers predicted to bind to all alleles, and each tool’s HLA allelic presentation obtained per allele (for 1 million random peptides),\n(c) scatterplot analysis of the relationship between size of training data and consistency of predictions,\n(d) distributions of predicted allelic promiscuity across alleles and correlation between peptide sources (human, viral, random),\n(e) correlations between peptide physical property similarity and peptide binding similarity for each tool, and\n(f) differential distributions of UMAP-transformed physical properties of peptides predicted to bind to specific HLA alleles or, combined, for all alleles.\nIn summary, the data shows convincingly the inconsistencies in prediction outcomes between the tools for the given MHC class I alleles. However, the manuscript has also some weaknesses.\nCriticisms:\nThe authors compare four popular tools. However, there are many other and also newer tools available: NetMHCcons (2012) is a tool based on a consensus approach including 4(?) individual predictors. Its already older but has still been very competitive for 10- and 11-mer MHC class I binders (Prediction of Major Histocompatibility Complex Binding with Bilateral and Variable Long Short Term Memory Networks, Jiang et al., 2022). NetMHCpan 4.0 (2017) learns from mass spec data, which has improved the prediction accuracy compared to earlier versions. Recently, several deep learning methods have been developed, which perform better than previous neural networks: AI-MHC (2018), a deep learning architecture for human Class I and Class II MHC binding prediction, BVLSTM-MHC (2021) and BVMHC (2022) (Prediction of Major Histocompatibility Complex Binding with Bilateral and Variable Long Short Term Memory Networks, Jiang et al., 2022). I am sure the reader would be interested in having these included in the comparison. The manuscript should cite these and other (especially newer) predictors. That said, comparing even more tools could further reduce the number of alleles that the tools have in common. Lastly, to be fair, the authors acknowledge this point in their discussion stating that they deliberately chose four of the most widely used tools.\n\nTo compare the four tools, the authors must convert binding affinities used by MHCflurry and MHCnuggets into binding probabilities used by NetMHCpan and HLAthena. It is not clear how the formula 1- log (binding affinity) /log(50000) was derived. What does it mean that binding affinities were converted “in order to match [..] binding probability predictions”?\n\nThe main text refers to a subfigure 2C. The caption to figure 2 describes 2C - but there is no subfigure C in the figure!\n\nIt is not clear which prediction tool/data was used for obtaining allele-specific differential distributions of physical properties (Fig. 7). The authors show that different alleles have different preferences for peptide physical properties but is this distribution similar across the four tools? What is the conclusion of this observation (e.g., what does this mean for the consistency of predictions)?\n\nThe discussion only summarizes the limitations of the work. The conclusions lists questions that this work raises. In both sections I would have liked to see more content. What are the implications of your study? This brings me to my last point:\n\nWhile I find this analysis interesting, I am a bit at loss what the take home message is. Should we not use any of the tools, or use all as part of a new consensus approach? Which tool is better/more accurate? This raises the question if there is not a better benchmark test for MHC binding affinity predictors? Why not use experimentally verified MHC binding peptides? The four tools are already at least 6 years old. Would it not make sense to compare the tools based on allele-peptide pairs (or just peptides) that the ML/DL algorithm has not been trained on? By the same token, would it not make sense to base the promiscuity analysis on verified bindings rather than predictions of tools that are obviously inconsistent? These and other questions could be discussed also in the discussion/conclusion section.\n\nMinor issues:\nThe authors write “as well as quantify the stability of these predictions”. It is not entirely clear what the stability of a prediction is. Do the authors mean accuracy or consistency?\n\nCould the authors provide the list of the 52 alleles that all four tools have in common?\n\nSentence: “For each peptide source, alleles were ranked from best to worst binders (most to least peptides ≥ 0.5 score) t.” -> Remove t.\n\n“and the allele lowest mean binding”-> “and the alleles with the lowest mean binding”.\n\nDoes the entire analysis presented here, in particular the investigation of allelic promiscuity and the correlation between peptide sources, is based only on the 52 alleles that all four tools have in common?\n\nFig. 6, …”is shown on the x-axis, whereas Spearman correlation coefficients of predicted allelic promiscuity across alleles.” -> “is shown on the y-axis” is missing.\n\nNote: I have not tested the source code.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "210784",
"date": "01 Nov 2023",
"name": "Michael E Birnbaum",
"expertise": [
"Reviewer Expertise I am an immunologist studying pMHC-TCR interactions"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn the manuscript “Discordant results among major histocompatibility complex binding affinity prediction tools”, Nguyen and colleagues discuss the discordances when four MHC binding tools, netMHCpan, HLAthena, MHCflurry, and MHCnuggets, are compared against one another. Surprisingly, despite being similarly designed and trained, the authors report large discordances in the results of the tools. This raises important questions about where these discrepancies come from, as such predictions are regularly used for the study of immunology and the design of immunogens.\nWhile this work is of interest, I think there are areas that would help better contextualize these results:\nFrom Figures 3-4, it seems like a large source of the discordances are from MHCnuggets. This is a relatively newer tool. It would be interesting to understand exactly why this difference is occurring here. It is especially curious that random peptides are not predicted to bind at all for some alleles.\n\nMore generally, I am somewhat curious/concerned about setting a binding probability of 0.5 as a cut-off for assessing tools, especially when some of the tools need their output transformed to match this metric. It is possible this is an issue regarding scaling of predictions rather than totally missing predictions. What happens if the threshold is changed from 0.5?\n\nIt would be interesting to understand more about the sequence properties of peptides that are more universally well predicted, vs. those that were only predicted as binders for certain tools. Seeing these as (for example) sequence logos would be helpful. A comparison to orthogonal experimental data would be even better, but understood that may be hard to come by.\n\nI think the authors somewhat overstate the importance of sequence differences between self and pathogen peptide sequences (such as the conclusion) – since the motifs that demarcate peptide binding to MHC molecules tend to be relatively minimal (certain residue preferences as P2 and P9/10, with contributions possible at positions such as P3), there are not likely to be strong signals for those that bind to self peptides vs those that bind to pathogen peptides, especially when taking into account the common constraints set by protein secondary structure (alpha helices, beta sheets) are common for all phyla of life.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "210811",
"date": "20 Nov 2023",
"name": "Nikolaos G Sgourakis",
"expertise": [
"Reviewer Expertise Molecular Immunology",
"Bioinformatics"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis body of work presents a comparison of four peptide/HLA binding prediction tools. The authors evaluate the consistency in binding predictions for netMHCPan, HLAthena, MHCflurry, and MHCnuggets initially across a set of one million random peptides of varying lengths to 52 alleles. After discovering that these methods do not converge in their predictions, they attempt to rationalize differences based on the amount of training data used for each allele. Next, Nguyen et al. investigated the allelic promiscuity by comparing binding to human, viral, and random peptides for all four tools. They again found inconsistencies between the methods. The authors found that the difference in physical properties of the peptides roughly correlated with predicted allelic promiscuity. Finally, they showed that alleles have different preferences for the peptides they are predicted to bind. Overall, this manuscript supports that popular, well-established tools to predict binding between peptides and HLAs are inconsistent, suggesting their inaccuracy.\n\nMajor issues:\nWhat is “kmerization”? This concept is not explained clearly in the manuscript.\n\nHow many human and viral peptides were evaluated and what is the breakdown per virus?\n\nFigure 2C is referenced in the article and described in the figure legend, but the plot is not in Figure 2 itself. Thus, the conclusions made in the main text cannot be evaluated.\n\nAs different alleles have a variable binding affinity that can be considered “strong”, is there a particular reason why predicted binding affinity is converted to the binding score rather than converting a percentile-based value as given in NetMHCPan? Also, the rationale for converting MHCflurry and MHCnuggets values using the “1- log (binding affinity) /log(50000)” equation is not clear.\n\nHow was the training data estimated for netMHCPan? The legend of Figure 4 does not provide any details on how this prediction was conducted.\n\nThe correlation coefficients of the best-fit lines shown in Figure 6 should be provided so readers can understand how strong the “negative correlation” indicated in the text is.\n\nIt is not clear which method is being used to predict binders in Figure 7 and Supplementary Figure 8. Additionally, throughout the manuscript, the authors maintain that the four tools they tested are inconsistent, yet likely rely on these same tools to draw conclusions on allelic binding preferences.\n\nTo advance the field, the authors should consider proposing potential solutions to improving these tools or at least provide a brief summary of newer, less popular tools and potential improvements, if any, have been made/different approaches that have been pursued. An example is Motmaen et al., PNAS 2023 who use a structure-based prediction method and see remarkable accuracy beyond pHLAs.\n\nOther comments:\nAbbreviations should be clarified explicitly on first use. For instance, in the ‘Sequence retrieval, peptide filtering, and kmerization’ of Methods, it is unclear what ‘BK’ stands for.\n\nThe exact value pertaining to each dotted line in Figure 2B should be stated as was done in Figure 2A.\n\nIn Supplementary Figure 1, the boxplots need to be defined in the legends in terms of minima, maxima, center, bounds of box and whiskers, and percentile.\n\nWhat do the red point, black circle, and red line refer to in the plots in Figure 3 and in Supplementary Figures 2 and 3?\n\nThe number of alleles should be delineated in Figure 4 for clarity.\n\nThe number of peptides tested should be made clear in Supplementary Figure 3.\n\nPanel letters are missing in Supplementary Figure 4. The number of peptides in each column should be indicated in the legend.\n\nThe number of peptides evaluated should be listed in the legend of Figure 5.\n\nThe alleles analyzed in Supplementary Figure 5 should be provided in a Supplementary Table.\n\nThe number of peptides analyzed in each subplot of Supplementary Figure 6 should be delineated. Also, it is not clear what these plots are showing – are they the result of dimension reductionality? What are the x and y-axes?\n\nThe number of peptides analyzed in each plot should be delineated in Supplementary Figure 7.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-617
|
https://f1000research.com/articles/12-611/v1
|
06 Jun 23
|
{
"type": "Research Article",
"title": "Predicting diabetic ketoacidosis in pediatric patients using machine learning",
"authors": [
"Waad Mohammed Eid",
"Hana Alharthi",
"Nida Aslam",
"Irfan Ullah Abdur rab",
"Alaa Madani",
"Nida Aslam",
"Irfan Ullah Abdur rab",
"Alaa Madani"
],
"abstract": "Background Machine learning is a powerful tool to define relationships between large data variables through computing algorithms. In medicine, machine learning can find the association between a given disease and disease-related complications such as the relationship between Diabetes and development of diabetic ketoacidosis (DKA). The aim of this study is to develop and evaluate a predicting model for diabetic ketoacidosis among pediatric cases to define the leading factors that can predict diabetic ketoacidosis.\n\nMethods We evaluated the medical records of 3737 pediatric patients between the ages of 0 and 18 years who attended diabetic clinics and were diagnosed with diabetes. After the initial data preprocessing, we used Orange, an open source software, for data visualization, and machine learning for data analysis. The study used six prediction models: Decision Tree, Random Forest, kNN, Gradient Boosting, CN2 rule inducer and AdaBoost. Data imbalance was managed using oversampling technique. Variables analyzed included age, sex, hemoglobin A1C level, visits to the diabetic education clinic, and number of appointments to diabetic clinic. Models were evaluated based on the Area under the Curve (AUC), accuracy, precision, recall and F1-score using the stratified 5-fold cross validation technique.\n\nResults The results show that the Random Forest is the highest performance classifier (AUC=0.98; F1 score=0.92; and recall=0.93). Furthermore, HbA1c was the most contributing factor to the prediction model.\nConclusion This study shows the importance and effectiveness of machine learning modeling to predict the association between diabetes and the development of DKA. Flagging those patients who are at a higher risk of developing DKA provides a better point of care for these patients.",
"keywords": [
"Predictive analytics",
"classifiers",
"Diabetes",
"DKA"
],
"content": "Introduction\n\nType 1 diabetes, an autoimmune disease of insulin resistance, is predicted to affect one person per 10 individuals in the world by the year 2040.1 It was formerly known as juvenile diabetes because it is typically diagnosed during childhood. Complications with diabetes can adversely affect multiple organs such as the heart, the brain, the kidneys, eyes, and even the limbs, such as diabetic foot ulcers that can lead to foot amputations. Uncontrolled diabetes increases the risk of Alzheimer’s disease.2 One of the most serious complications of type 1 diabetes is ketoacidosis (DKA). DKA occurs when the body has high levels of sugar for a long period of time and the body then produces blood acids called ketones. Ketoacidosis can disrupt the normal body workflow which causes serious complications such as pulmonary and cerebral edema, hypokalemia and organ damages.3 DKA can cause neurocognitive impairment in children, such as memory loss, poor concentration, and/or deficits in learning and emotional connection.4 High occurrence of DKA can also increase patients’ admission to the hospital which results in higher management cost which creates an economic burden on the healthcare system.5 Machine learning is the scientific branch of artificial intelligence that focuses on how computers learn from data to define relationships between data variables through computing algorithms.6 In medicine, machine learning can be used to study diagnosis and disease patterns in large patient datasets. For example, machine learning can predict how fast a disease can develop. Also, it can predict which patients are at a higher risk of developing a condition or disease progression. These predictions can support physicians in their point of care decisions, whether it is preventive care or disease management, to provide a high level of care to these patients to improve healthcare outcomes.7 As such, machine learning can be used to flag patients with health risks and enable the healthcare team to provide the best course of treatment for their patients. In a study which used machine learning to predict the likelihood of diabetes occurrence in patients. Specifically, three classification algorithms, decision tree (DT), the support vector machine (SVM), and the naive Bayes (NB), were employed. The data used is a diabetes dataset named PIDD which is taken from the UCI machine learning repository. The data included 768 female patients with two values: 1 as positive for diabetes and 0 as negative. In addition, multiple attributes or risk factors, were included such as number of times pregnant, plasma glucose concentration, diastolic blood pressure, skinfold thickness, 2 hours serum insulin level, BMI ratio, diabetes pedigree function and age. Moreover, researchers tested the three algorithms performance evaluating precision, accuracy, F-measures and recall. The result shows NB has the highest accuracy level with 76.30% in comparison with other algorithms.8 However, the attributes included in the test did not include the known diagnostic tests such as hemoglobin (A1C) form of hemoglobin that is chemically linked to a sugar, random blood glucose, and fasting blood glucose; this requires further research using the same algorithms and models. Another study used the National Health and Nutrition Examination Survey data (NHANES) to predict patients at risk of diabetes and cardiovascular diseases.9 NHANES is a comprehensive national program in the United States to assess the status of health and nutrition among its population. Data from NHANES were used to predict diabetes and cardiovascular diseases. In the study, scientists used different models such as SVM,RF,GBT,WEM to classify patients at risk of diabetes and cardiovascular diseases, they provided the program with the training data which contained the observations and labels for the category of the observations. This can give the algorithm the ability to predict the output label associated with a new observation if presented to the program. Results showed that machine learning models based on the survey used can provide an automated identification method for patients at risk for diabetes and cardiovascular diseases and they were also able to identify major contributors to the prediction results.9 Given that this study was based on extraction of variables from a national survey rather than electronic health records data, the findings underscore the challenges of data set for machine learning as data from surveys can point to findings that are different from data extracted from electronic health records data. Additional studies aimed to create a prediction program which can detect high risk group who are more likely to develop type 2 diabetes. One in particular used the Synthetic Minority Over-sampling Technique to balance the dataset and included six features (body mass index (BMI), diet, smoking, blood pressure, sex and geographic region. The study evaluated the algorithms using the balanced data, they used nine classifiers which are, Logistic Regression (LR), Average Perceptron (AP), Naïve Bayes (NB), Neural Network (NN), Support Vector Machine (SVM), LD, Decision Jungle (DJ), Decision Forest (DF), and Boosted Decision tree (BDT). The Decision Forest (DF) model had better performance than other classifiers with an accuracy rate of 83%. The results of this study can help to establish a web-based service to assess a disease risk in preventative medical care.10 Another study, aimed to detect diabetic retinopathy where various classifiers were used such as, RF, kNN, SVM, LDA and RRF. The RF model showed the best performance among other classifiers, with an accuracy of 86%.11 Collectively, these studies underscore the potential of machine learning to be used in preventative medicine as well as in assistive decision making to improve healthcare. Table 1 summarizes the literature gap of machine learning in diabetic field.\n\nIn a project conducted in Texas children’s hospital in the United States to provide the best care for high risk patients with type 1 diabetes. The hospital developed a model using machine learning classifiers, which can predict the occurrence of DKA. The project aimed to reduce the number of hospitalizations related to diabetes or DKA from 9.5% to 5% by the year 2018 and to reduce the admissions of DKA by at least 1% every year to reach a goal of maximum 5% DKA admissions per year. A predicting risk model for DKA was developed. The model used data such as risk index for poor glycemic control (RIPGC), socioeconomic status, clinical data such as fasting blood glucose level, hemoglobin A1C, and number of clinical visits per year. The team then proceeded with developing a risk stratification tool and divided patients into four tiers; high risk, moderate risk, mild risk, and lowest risk. They then provided care according to their risk prediction model. This targeted approach resulted in decreasing the recurrent DKA cases admission by 30.9% per year and it showed higher documentation rate of RIPGC in the electronic system. In addition to a risk index for DKA for all the patients.12\n\nIn this study we used machine learning as a tool to predict DKA occurrence among a pediatric population and identify the most important factors in predicting DKA.\n\n\nMethods\n\nThis research was ethically reviewed and approved by the institutional review board at Imam Abdulrahman bin Faisal University (IRB-PGS-2020-03-431). It was also approved by the institutional review board at King Fahad Medical city. (IRB Log Number: 21-186E) This study is an experimental study aimed to create a predicting model for diabetic ketoacidosis among pediatrics cases and find the most important factors predicting diabetic ketoacidosis. The target variable is the DKA and the attributes are sex, age, HbA1c levels, number of patient appointments in the diabetic clinic, number of patient appointments in the health education clinic, and the number of patients those who do not attend appointments at the health education clinic. The dataset included the medical records of pediatric patients aged 18 and younger who attended the Diabetic clinic in King Fahad medical city from starting January 2018 to until December 2020. We excluded any patients who were above 18 at the time of data collection and patients who did not have any laboratory results registered in the system. The total sample size was 1537 patients.\n\nThe dataset was received in excel format from King Fahad Medical City health information system in Riyadh, Saudi Arabia. It was divided into four sections. The first section was the list of appointments in the pediatric Diabetes clinic, which also included whether the patient attended the appointment or was registered as a no-show, and the demographics (e.g., nationality, sex). The first section data size was 3737. The second section was the laboratory results of the patients, which contained their Hemoglobin A1c levels. The third section was the list of patients who were diagnosed with DKA. The fourth section is the list of patients’ ages. All patient identifications have been removed to ensure patients privacy and confidentiality. We created a new spreadsheet to consolidate this information. It included the lab results where duplicated Medical record number (MRN) numbers were removed using the remove duplicates function in excel. We used the VLOOKUP function which looks up a value in the columns of a table and returns the value in the same row from a column which the user specifies. Using the patient’s MRN, we matched the patients’ age, sex and DKA diagnosis to their laboratory results and the data size was reduced to 1543 data records. we used the COUNTIFS function in excel, which counts the number of cells specified by a given set of conditions or criteria, to count the number of appointment visits versus no shows. The variables assessed included sex, age, HbA1c level, number of appointments, number of health education clinic appointment and number of no shows to health education clinic appointment The target variable was DKA status with two values of yes and no.\n\nTo analyze the data we used Orange Data Mining (RRID:SCR_019811) V3.30. Orange is an open source software which is used for data visualization, machine learning and data mining purposes. There are different classifiers available in Orange, which include: Random Forest, which creates a set of decision trees. Every tree is created from a small sample from the training data. When the classifier develops an individual tree, a random subset of attributes is drawn then the best attribute is selected. The final model is based on the majority selected individual developed trees in the forest. KNN, which uses algorithms to search for the closest training examples in a feature and uses the average to form the prediction. AdaBoost, is an algorithm that merges weak learners and adapts to each training sample. CN2 rule inducer uses an algorithm as a classification technique through making of simple, comprehensible rules.13 Tree simply uses an algorithm to separate the data into nodes. It is similar to Random Forest. Gradient Boosting is a technique that produces a prediction model in the form of an joined of weak prediction models, typically decision trees.\n\nTo analyze descriptive statistics for the variables, we used a feature statistics tool in Orange, also ranked the attributes to demonstrate the most contributing factor to DKA among pediatric patients.\n\ndataset showed an imbalance among DKA cases (17.5%) and none DKA (82.5%). To balance the data set, a data sampler tool in Orange V3.30 was used. This tool is used to develop different types of complementary samples from the input data. The fixed sample size method develops a certain number of data instances with replacements, which means always sampling from the entire dataset and does not delete instances from the subset data. We also maintained the sampling pattern by checking replicable sampling settings in the data sampler. This technique to oversample the DKA instances. The positive DKA instances were replicated by 1308 to equalize it with the negative 1308 DKA instances and overcome the data imbalance. Furthermore, Python was used to oversample the data as a comparison method with the data sampler in Orange. The oversampling technique has been used in research which aimed to evaluate the performance of supervised learning algorithms on imbalanced class datasets.14\n\nWe used stratified 5-folds to cross validate our data which is the default parameters in Orange. This technique splits the dataset into folds such as N. One-fold will be used for testing while the remaining N-1 will be used for training in each N iterations. In the current study the dataset is divided into 5 stratified folds and in each fold there are approximately equal number of samples for each class.\n\nThis matrix shows the number and proportion of instances in the predicted and actual class. This allows the reporting of cases that were misclassified or were accurately classified.\n\nIt scores variables that can be calculated using the information from the confusion matrix.\n\nIs model performance evaluation technique that indicate the ability of the classifier to distinguish between classes. The higher the AUC score, the better performance for the classifier to distinguish between true positives and true negatives.\n\nIs a measure to evaluate the performance of a classifier by calculating the number of correct predictions divided by the total number of predictions.\n\nIs the number of true positives among instances classified as positive.\n\nIs the number of correctly predicted positive class sample, among all the positive class in the dataset.\n\nIt represents the harmonic mean among the precision and the recall.\n\n\nResults\n\nSeveral Orange classifiers were used to predict the incidences of DKA among a pediatric cohort. Figure 1 illustrates the workflow performed in Orange. The workflow begins with imported data followed by outlier’s extraction. After the extraction, we balanced the data using the data sampler widget. The data is inserted into the six classifiers and evaluated by Area under the curve (AUC) level (test and score widget). A total of 1536 patient data points were imported into the program. Data showed an 82% imbalance. To overcome this imbalance, a data sampler tool in the Orange program was used. Moreover, Python was additionally used as another oversampling technique which showed similar performance results to the Orange data sampler tool with the Random Forest being the best predicting model with an AUC higher than 0.9. Female and male distribution are approximately equal as shown in Table 2 and Figure 2. Incidences of DKA distribution were normalized after applying the over sampling technique as shown in Figure 3. For age, the youngest patient was 2 years old and the oldest was 18 years old with a mean of 12 years old. For the HbA1c the maximum level was 16.3 and the minimum was 4 with a mean of 9.99 as shown in Table 2. To test the prediction performance on our data, we used six classifiers which are Random Forest, AdaBoost, CN2 rule inducer, kNN, Gradient Boosting and Decision Tree. Through the test and score feature we evaluated the classifiers prediction performance through cross validation technique and the AUC score as it is a highly reliable method to evaluate the performance. The result showed that Random Forest had the highest performance result with an AUC score of 0.98 followed by AdaBoost and CN2 rule inducer with a score of 0.97 and 0.93, respectively As shown in Table 3. The confusion matrix for the performance of the Random Forest classifiers is shown in Table 4. The Random Forest classifier made 86.5 % (n=885) correct predictions, 27.16 % (n=33) false prediction for the no incidence of DKA and 88.6% (n=1077) correct prediction and 11.35 (n=138) false prediction for the incidence of DKA. Additionally, the HbA1c level was the most contributing attribute to the occurrence of DKA followed by the health education appointments as shown in Table 5. Furthermore, sex was the least contributing attribute (Table 5).\n\n\nDiscussion\n\nRecurrent admission of patients due to DKA can be prevented with proper education and targeted strategic programs.15,16 In this research, we focused on developing a prediction model which can detect high risk groups for DKA to decrease admission cost to the healthcare organization and prevent the readmission of patients. These predictions can inform better patient quality of life and help to develop better education programs for these patients. Our data showed an 82% imbalance. To overcome this imbalance, a data sampler tool in the Orange program was used. This program is used as a tool to oversample the DKA incidence and replicate the positive DKA instances to equalize it with the non DKA incidence. Moreover, Python was additionally used as another oversampling technique which showed similar performance results to the Orange data sampler tool with the Random Forest being the best predicting model with an AUC higher than 0.9. The ability of different machine learning prediction models to predict DKA incidence using data imported from the electronic medical records. We found that the HbA1c level was the most contributing attribute to the occurrence of DKA followed by the health education appointments. Although six attributes were used in this research, other similar studies have used other clinical attributes such as the fasting blood glucose, HbA1c, vital signs, injection therapy vs pump therapy. It also included sex, race and ethnicity, BMI, healthy diet, smoking status.10,17 However, not all of these attributes can be found in the electronic medical records such as race and ethnicity, smoking status, healthy diet in our study. Our data is consistent with others.8–11 Similar research has been conducted previously which explored similar models and their performances on predicting DKA. All demonstrated an AUC level of 0.7 and higher.10,17,18 On the other hand, the highest AUC level scored in the current was by the Random Forest model with a score of 0.97 followed by AdaBoost and CN2 rule inducer with a score of 0.95 and 0.92 respectively. Lastly, although this research showed promising results in the prediction performance, it had some limitations which could be improved in future studies. To refine the prediction model additional clinical attributes should be included such as the fasting blood glucose, BMI, and medication adherence and type of treatment.\n\n\nConclusions\n\nDKA is considered to be a serious complication of diabetes which can be prevented with proper education and targeted strategic health care delivery. We aimed to create a predicting model for diabetic ketoacidosis among pediatric cases. Therefore, a real dataset was collected from Fahad Medical City health information system in Riyadh, Saudi Arabia. Several machine learning models have been used such as Random Forest (RF), Decision Tree (DT), kNN, Gradient Boosting (GB), CN2 rule inducer and AdaBoost. Furthermore, several preprocessing and data sampling techniques were applied. We found Random Forest model achieved the highest performance with the AUC of 0.98. Furthermore, HbA1c was the most contributing factor to the prediction model. Further research is required to refine the prediction model with additional clinical attributes such as the fasting blood glucose, BMI, medication adherence and type of treatment. Moreover, it is required to test the model’s performance with the multi-center balanced patient’s sample.\n\n\nAuthor contributions\n\nWaad Eid: conception and design of the paper and data analysis\n\nHana Alharthi: conception and design of the paper, data analysis, critical and final revision of the article\n\nNida Aslam: Data analysis and model framework.\n\nIrfan Ullah Abdur rab: Data analysis and model framework.\n\nAlaa Madani: acquisition of data.\n\n\nConsent\n\nThe authors report that all patient data used in this research is anonymous, thus no consent for publication was required, and no alterations was done that would distort scientific meaning",
"appendix": "Data availability statement\n\nThe data that support the findings of this study are available from King Fahad Medical City but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors (Waad Eid, Email: wmeid@iau.edu.sa & waadeid@gmail.com) upon reasonable request and with permission of King Fahad Medical City.\n\n\nReferences\n\nZou Q, Kaiyang Q, Luo Y, et al.: Predicting diabetes mellitus with machine learning techniques. Front. Genet. 2018; 9: 11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nstaff Mayo clinic: Diabetic ketoacidosis.2019.\n\nstaff Mayo clinic: Type 1 diabetes in children.2020.\n\nGhetti SPD, Lee JKBA, Sims CEBA, et al.: Diabetic ketoacidosis and memory dysfunction in children with type 1 diabetes. J. Pediatr. 2010; 156(1): 109–114. PubMed Abstract | Publisher Full Text Reference Source\n\nMaldonado MR, Chong ER, Oehl MA, et al.: Economic impact of diabetic ketoacidosis in a multiethnic indigent population. Diabetes Care. 2003; 26(4): 1265–1269. PubMed Abstract | Publisher Full Text Reference Source\n\nDeo Rahul C: Machine learning in medicine. Circulation. 2015; 132(20): 1920–1930. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRajkomar A, Dean J, Kohane I: Machine learning in medicine. N. Engl. J. Med. 2019; 380(14): 1347–1358. Copyright - Copyright © 2019 Massachusetts Medical Society. All rights reserved. PubMed Abstract | Publisher Full Text Reference Source\n\nSisodia D, Sisodia DS: Prediction of diabetes using classification algorithms. Procedia Comput. Sci. 2018; 132: 1578–1585. Publisher Full Text Reference Source\n\nDinh A, Miertschin S, Young A, et al.: A data-driven approach to predicting diabetes and cardiovascular disease with machine learning. BMC Med. Inform. Decis. Mak. 2019; 19(1): 211. 1472-6947. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSyed AH, Khan T: Machine learning-based application for predicting risk of type 2 diabetes mellitus (t2dm) in saudi arabia: A retrospective cross-sectional study. IEEE Access. 2020; 8: 199539–199561. 2169-3536. Publisher Full Text\n\nAlabdulwahhab KM, Sami W, Mehmood T, et al.: Automated detection of diabetic retinopathy using machine learning classifiers. Eur. Rev. Med. Pharmacol. Sci. 2021; 25(2): 583–590. Publisher Full Text Reference Source\n\nHealth Catalyst: Texas children’s take the reins in preventing dka in high risk pediatrics patients.2016.\n\norange: widget-catalog.2021. Reference Source\n\nKaur H, Kumari V: Predictive modelling and analytics for diabetes using a machine learning approach. Appl. Comput. Inform. 2018; 18: 90–100. Publisher Full Text\n\nVellanki P, Umpierrez GE: Increasing hospitalizations for dka: A need for prevention programs. Diabetes Care. 2018; 41(9): 1839–1841. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nDhatariya KK, Nunney I, Higgins K, et al.: National survey of the management of diabetic ketoacidosis (dka) in the uk in 2014. Diabet. Med. 2016; 33(2): 252–260. PubMed Abstract | Publisher Full Text\n\nWilliams DD, Dass S, Bass J, et al.: 1303-p: Comparative performance of a recurrent neural network (rnn) and logistic regression (lr) model to predict diabetic ketoacidosis (dka) among youth postdiagnosis with type 1 diabetes (t1d). Diabetes. 2020; 69(Supplement 1): 1303-P. Publisher Full Text Reference Source\n\nLi L, Lee C-C, Zhou FL, et al.: Performance assessment of different machine learning approaches in predicting diabetic ketoacidosis in adults with type 1 diabetes using electronic health records data. Pharmacoepidemiol. Drug Saf. 2021; 30(5): 610–618. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "249422",
"date": "30 Aug 2024",
"name": "Simon Cichosz",
"expertise": [
"Reviewer Expertise Diabetes",
"technology",
"machine learning"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript explores the potential for risk stratification of pediatric patients based on their likelihood of developing Diabetic Ketoacidosis (DKA), a model with significant clinical implications. However, several important concerns warrant attention:\nThe authors employ oversampling techniques on both the training and test datasets, resulting in an unrealistic performance assessment for real-world applications. Oversampling to address imbalanced datasets should be limited to the training data exclusively.\nAuthors are strongly encouraged to adhere to & submit the TRIPOD checklist or a similar guideline to ensure essential information is included in the manuscript.\nThe discussion section requires expansion, including a dedicated segment on the limitations of the study.\nThe manuscript could benefit from a discussion of its findings in the context of related studies concerning the prediction of adverse events in diabetes, such as DKA. For instance:(Cichosz SL, et al, 2024) (Ref-1)\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-611
|
https://f1000research.com/articles/12-401/v1
|
14 Apr 23
|
{
"type": "Systematic Review",
"title": "The role of salivary orosomucoid 1 as an early diagnostic and prognostic biomarker of hepatocellular carcinoma related to Hepatitis B: A systematic review",
"authors": [
"Edward Kurnia Setiawan Limijadi",
"Ardiyana Ar",
"Nurul Azizah Dian Rahmawati",
"I Nyoman Sebastian Sudiasa",
"Kevin Christian Tjandra",
"Edward Kurnia Setiawan Limijadi",
"Ardiyana Ar",
"Nurul Azizah Dian Rahmawati",
"I Nyoman Sebastian Sudiasa"
],
"abstract": "Background: Salivary orosomucoid 1 (ORM1) is highly increased in hepatocellular carcinoma related to hepatitis B. Thus, this study aims to investigate the role of salivary ORM1 as an early diagnostic and prognostic biomarker of HCC related to hepatitis B. Methods: The sources included were original articles published from 2013 until 2023 (last date searched, January 2023) from ProQuest, Google Scholar, Springer, and ScienceDirect. The inclusion criteria were original research articles (observational cohort or diagnostic studies). Other article reviews, meta-analyses, non-comparative research, and in silico, in vitro and in vivo studies, technical reports, editor responses, conference abstracts, non-English, non-full-text, and irrelevant articles that were not related to either salivary ORM1, or hepatocellular carcinoma, hepatitis B, or kidney failure were excluded. Then, the ROBINS-I took was used to assess bias . The result was constructed with PICOS criteria within the table created in the google spreadsheet. This systematic review followed the PRISMA guidelines. Results: We included five diagnostic studies with 533 samples conducted in China and Japan. Even though limited original studies with homogenous PICO was a limitation, the evidence output of this study can still be well presented. Salivary ORM1 may be useful to detect early cancer diagnosis as rapidly increased levels of ORM1 can be observed in the early stages of HCC (four times higher than usual) and the biomarker has a sensitivity of 81.67% and a specificity of 77.5%. This biomarker is also able to detect the prognosis of individuals with the disease with or without chemotherapy because the higher the level of ORM1, the more liver damage occurs that leads to a poorer prognosis. Conclusions: Salivary ORM1 is a potential early diagnostic biomarker of HCC related to hepatitis B and a biomarker of the disease prognosis. Registration: Open Science Framework (OSF) (March 16, 2023).",
"keywords": [
"Salivary Orosomucoid 1",
"Hepatocellular Carcinoma",
"Early Diagnostic",
"Prognostic",
"Biomarker"
],
"content": "Introduction\n\nSalivary orosomucoid 1 (ORM1) or alpha-1-acid glycoprotein (AGP) is an acute phase protein of about 1-3% of all plasma proteins. ORM1 is normally produced by hepatocyte cells but can also be produced and found in extrahepatic tissues such as endothelial cells and some tumor cells.1 ORM1 is expressed in inflammatory injuries, infections, and stress conditions.2 ORM1 is predominantly synthesized in the liver so liver disease, especially hepatocellular carcinoma (HCC) induced by hepatitis B can affect changes in its concentration or expression more in saliva as well as serum. The expression pattern of ORM1 shows a rapid increase in saliva and serum at the beginning of HCC induced by hepatitis B because a characteristic of this disease is that liver cell destruction happens from very early stages.2,3 Even though ORM1 is not only used to detect HCC related to hepatitis B, HCC related to hepatitis B is the only disease that has a specific behavior as mentioned above.2,4\n\nOrosomucoid is produced by hepatocyte cells and it increases when there is inflammation in the body, especially the liver as the place of production. When inflammation occurs, hepatocyte cells will secrete ORM1 as an inflammatory expression agent that can be detected through saliva, urine, and serum.1 HCC related to hepatitis B is associated with a massive inflammatory response that leads to the production of a huge amount of ORM1. It indicates that ORM1 is suitable for early diagnosis of HCC related to hepatitis B.2 Malignant cells in hepatocytes can affect the function of the liver in the body. The liver is the place of albumin synthesis in the human body, and if HCC is detected, it will be followed by hypoalbuminemia in laboratory tests.5 So hypoalbuminemia is one of the early diagnostic parameters that can be assessed besides ORM1.\n\nModalities of early detection of HCC are usually looking at biomarkers. Alpha-fetoprotein (AFP) is one of the biomarkers that is often used in detecting the presence of hepatic cancer. However, AFP has the disadvantage of having low specificity and cannot detect early-stage hepatic cancer compared to ORM1.6\n\nSaliva is a molecule rich in protein, DNA, RNA, and microorganisms, and can be considered a library of biomarkers. Cancer biomarkers present in the blood can also be found in saliva, and changes in their concentration can be used as biomarkers to detect cancer early and monitor response to treatment management. Saliva is a biomarker that is non-invasive, simple and does not require professional medical personnel, and has the ability to last longer than blood and urine. Screening methods using saliva can be used to detect the incidence of cancer.2\n\nGani et al. (2015) found ORM1 to have significantly higher expression in the saliva of patients with HCC compared to the non-HCC group (p < 0.001) and ORM1 expression in saliva liver cancer was significantly higher than adjacent normal tissue (p < 0.001).7 ORM1 expression differs in each response to a disease condition, be it infection, drug sensitivity or cancer. However, its role in HCC remains largely unknown. Therefore, ORM1 may become an enhanced diagnostic tool for HCC. In addition, in a study by Higuchi et al. (2020) it was found that ORM1 was expressed differently in HCC tumors and non-tumor tissues using a combination of in vitro, in silico, and clinical sample immunohistochemistry methods. Thus, ORM1 can be considered as a potential target for the development of future therapies against HCC.8\n\nThis article aims to fulfil two objectives. First, we try to investigate the role of salivary ORM1 as an early diagnostic biomarker of HCC related to hepatitis B, including sensitivity and specificity. Second, we try to identify the general prognosis of the patient with HCC induced by hepatitis B, i.e., whether the outcome will be favorable or unfavorable, using levels of salivary ORM1 as a biomarker.\n\n\nMethods\n\nThis systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).9 This review was registered with Open Science Framework (OSF) (March 16, 2023).\n\nWe included original articles published in 2013 until 2023 (last date searched January 2023). The study comprised original research articles or research reports that used observational cohort or diagnostic studies as the inclusion criteria. Scientific posters, study protocols, narrative reviews, systematic reviews, meta-analyses, non-comparative research, in silico studies, in vitro studies, in vivo studies, technical reports, editor responses, and conference abstracts were all disqualified. Additionally, non-English, non-full-text, and irrelevant articles that were not related to either salivary ORM1, or HCC, or hepatitis B, or kidney failure were also excluded. The eligibility criteria for articles were as follows: i) Population, adults with cancer or hepatitis B or kidney failure; ii) Intervention, measuring salivary ORM1; iii) Comparison, healthy patient (control); and iv) Outcomes, level of ORM1.\n\nOutcome measure\n\nORM1 is the parameter assessed as the outcome measure in this systematic review. This parameter is synthesized by hepatocytes and has a normal plasma concentration between 0.6–1.2 mg/mL (1–3% plasma protein). ORM1 can be found in several types of fluid, including saliva, urine, and plasma. Since it’s produced by hepatocytes, the level of this parameter can increase in conditions that affect hepatocytes’ activity and damage its product (albumin), such as hepatitis, cancer, and kidney failure.\n\nIndex test\n\nStudies that provided the data of evaluations of ORM1 are included in this systematic review.\n\nReference standard\n\nReference standards are professional research using observational cohorts or diagnostic studies to assess the transition of ORM1 serum levels.\n\nResearch for this study were gathered through ProQuest (RRID:SCR_006093), Google Scholar (RRID:SCR_008878), Springer, and Science Direct database searches. Boolean operators were utilized among the keywords. In Table 1, the keywords used in each database are displayed.\n\nThe filters used for each database included year (from 2013 until January 2023), type of documents from ProQuest was filtered by scholarly journal, any type of article was used in Google Scholar, content type article was used as the Springer database filter, and research article type was used for Science Direct database filter. The last date the databases were searched was 10 January 2023. The database search gave a total result of 2,482 studies (324 ProQuest, 1,683 Google Scholar, 221 Springer, and 254 Science Direct). Once the aforementioned filters were added, 712 studies were then imported to the Mendeley Group Reference Manager in the authors’ library before the selection process.\n\nAfter using the search terms listed in Table 1, four independent reviewers (KCT, AA, NADR, and INSS) and one validator (EKSL) merged the results from four databases. They then screened the abstracts and full text to eliminate the irrelevant articles and keep the relevant articles and expelled non-cohort and non-diagnostic articles. From this process, 655 studies were excluded, then the 57 studies left were checked for whether the full text could be retrieved. As a result, only 17 full text articles could be retrieved. Following this, 12 articles were excluded due to duplication, as found using the title, year of publication, and DOIs. A total of five included studied were assessed for eligibility using the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool. From this procedure, all the five included studies passed the assessment bias check. The research selection processes were recorded in the PRISMA flow chart.\n\nAfter the final screening, the pertinent information from the studies was retrieved and entered into a Google Spreadsheet. Data were recorded and validated by all five authors into columns as follows: i) First, author and year; ii) second, country; iii) third, study design; iv) fourth, sample size; v) fifth, gender; vi) sixth, mean age; vii) seventh, intervention name; viii) eighth, intervention length; ix) ninth, comparison; and x) tenth, outcome consisting of ORM1 expression levels.\n\nThe main outcome of interest was the concentration of ORM1, sensitivity, and specificity in detecting HCC related to hepatitis B. Expression of ORM1 related genes, correlation between ORM1 and prognosis or other medical conditions were decided as secondary outcomes.\n\nThe ROBINS-I tool was used by five independent reviewers (KCT, AA, NADR, INSS, and EKSL) to evaluate each study that was included in this analysis. Later, the disagreements were discussed and settled between the reviewers, and we decided to exclude article with critical overall bias from ROBINS-I assessment.\n\nAccording to the ROBINS-I assessment bias conducted by KCT, AA, NADR, INSS, and EKSL, All the five included articles did not show any critical overall bias as mentioned in Figure 1 so we did not remove any articles.\n\n\nResults\n\nOverall, 2,482 studies were produced by doing a literature search using four databases: ProQuest, Google Scholar, Springer, and ScienceDirect. In order to exclude non-cohort studies, automation techniques from each database were employed, which led to the exclusion of 1,770 publications. A total of 655 irrelevant topic articles were removed after authors evaluated every last article from the title and abstract for relevance. Then, 40 non-retrieved articles were excluded due to the inability to access the full text document. In total, 12 duplicate study papers were then removed. The complete texts of five articles were then obtained. Last but not least, the author determined the eligibility of each study and all five articles passed the eligibility criteria. Five papers were included in this systematic review. Our study selection process is presented in the PRISMA diagram flow chart in Figure 2.\n\nIn total, 533 people participated in the five studies included in this systematic review. Three studies were conducted in China such as Dalian city, while two studies were conducted in Japan, including Maebasi City, and Sapporo City. The complete study characteristics, including the PICO of each study, are stated in Table 2.\n\nWith the use of the ROBINS-I risk-of-bias tool for observational studies, the quality of each study was rigorously evaluated. No bias was indicated in five of the studies. Figure 1 provides a summary of the bias risk assessment.\n\nThe journal selection method that has been carried out produced five studies that were used in the systematic review process. The five studies were conducted by Yazawa et al. (2016),10 Gu et al. (2022),11 Higuchi et al. (2020),8 He et al. (2022)2 and Li et al. (2016).1 Brief profiles of the five studies are shown in Table 2.\n\n\nDiscussion\n\nThis systematic review confirms the evidence of salivary ORM1 as a possible early diagnostic and prognostic biomarker for HCC related to hepatitis B. From the studies included, we can generally find how ORM1 has a role in the early stage of HCC induced by hepatitis B and could be a potential early stage biomarker and determine the correlation of ORM1 level related to patient prognosis.\n\nThe methodical approach to the identification, selection, and extraction of data using a causality framework that offers a framework for the assessment of varied sources of evidence and a substantial number of review questions are the study’s strengths. To our knowledge, this is the first systematic review that assesses the levels of ORM1 in patients with cancer along with the diagnostic and prognostic evidence. The main limitation of the traditional systematic review was high workload and time necessary to maintain it. Another disadvantage was the time required to settle inter-reviewer variations in the interpretation of qualifying requirements. This might have led to subjectivity in judgments about inclusion in the review. Although a second reviewer examined all extractions, changes in the review team might cause inconsistency. We utilized case definitions as given by authors in individual articles, as we did in the baseline review.\n\nEven though this systematic review can qualitatively analyze the evidence of the included studies, the limited number of original studies with homogenous PICO is our limitation. In the future with more original related studies, it will be possible to conduct quantitative analyses.\n\nOrosomucoid is a component of plasma protein that has numerous roles in body physiology, including capillary barrier regulation, metabolism, and the immune system.12 ORM1 or alpha-1-acid glycoprotein (AGP) is a class of proteins with carbohydrate content up to 45% and protein pI 2.8-3.8, which often appears during the acute phase of the disease.6 ORM is formed by the liver and finally secreted throughout the body with a normal value of 0.4–1.2 mg/ml plasma in the human body. If the amount increases, it can be a sign of an unusual condition in the body, such as pregnancy, drug use, or certain diseases. The alpha (1)-acid glycoprotein glycan structure is shown in Figure 3.10\n\nThis figure is reproduced from Yazawa et al., 2016.10\n\nThe human ORM is located on the long arm of chromosome 9 in the AGP-A, AGP-B, and AGP-B′ clusters.11,13 α-1 acid glycoprotein (AGP) or ORM is a class of plasma glycoproteins consisting of many N-linked glycan branches and a total molecular weight of 41–43 kD.10 The ORM structure consists of 201 polypeptide chain residues, of which 22 residues distinguish ORM1 and ORM2. Structural analysis of ORM1 shows a combination of N-linked glycan chains associated with neutral hexagons, fructose, sialic acid, hexosamine (N-acetylglucosamine), mannose, and galactose.4 Theoretically, each of the five N-linked glycans can join branches with different degrees, express other glycan chains, and form more than 105 other glycoforms of ORMs.\n\nAs aforementioned, if ORM1 is produced in hepatocyte cells in the liver, it will then be distributed to the peripheral circulation, even in saliva, and it will increase its value if the tissue is inflamed or malignant.4 Serum is the gold standard in the detection of ORM levels, but the potential of saliva and urine for a similar role is currently being developed. It has been investigated whether there are differences between those three media, and which results showed that the correlation between the reference method and assay of ORM1 serum was 0.97 (p < 0.001). Meanwhile, the saliva also gave a similar result as serum, that is 0.97 (p < 0.001) higher than in media that showed 0.93 (p < 0.001).12\n\nORM1 is synthesized by hepatocytes and parenchymal cells of the liver. Orosomucoid synthesis is upregulated by inflammatory cytokines and then released into the blood where it is distributed in body fluids, such as saliva, urine, plasma, and mucus.14–16 ORM1 expression is regulated by TGF-β and mediated by the TGF-β/Smad signaling pathway.2 ORM1 concentration can elevate 1–10 times during pathological conditions depending on the severity of the disease. Inflammation level and degree of injury are also factors that can increase the concentration of ORM1. ORM gene expression in liver cells is related to inflammatory mediators, such as glucocorticoids, cytokines, interleukins, and TNF-alpha. Hepatocytes and the liver are the primary sources of ORM synthesis.17–20\n\nORM1 has various biological functions, including being a biomarker for disease, immunomodulatory effects, and roles in important drug-binding processes, transporting proteins in the serum with albumin and lipoproteins, maintaining capillary barrier function, and various metabolisms. ORM1 serum and saliva concentration can change due to stressful stimuli, such as physical trauma, bacterial infection, and unspecific inflammatory stimuli.4 Due to its immunomodulatory effects, Higuchi et al., stated that ORM1 can be used as a possible therapeutic molecular target. ORM1 concentration was found to be significantly higher after kidney transplant due to cytokine mediated NFxB and STAT3 activation in primary kidney tubular cells.8 ORM1 could also be used as a potential biomarker for cancers in the pancreas, bladder, and liver cancer by determining the level of ORM1 in the serum of body fluids, saliva, urine, and blood.10 Damage in the hepatocytes due to liver cancer may cause a change of ORM1 serum levels. He et al., showed that salivary ORM1 is significantly increased in HCC related to hepatitis B virus.2 Gu et al., also stated that the expression levels of ORM1 were strongly correlated with the tumor stage and grade of HCC.11 From these studies, we can conclude that even if salivary ORM1 is significant in several other cases, the highest increased level compared to normal controls happened in HCC related to hepatitis B, which is 4.02 times higher than the normal level.2,8,10\n\nORM1 functions as a transport protein in the bloodstream. ORM1 plays an important role in modulating immune system activity during acute phase inflammation.20 A previous study showed that serum ORM levels are increased in inflammatory and lymphoproliferative disorders and cancers such as liver, lung, breast, and ovarian cancer.1 ORM1 has a down-regulating effect on the inflammatory cascade, thereby protecting against tissue damage due to excessive inflammation and malignancy.\n\nORM1 increases in types of cancer such as invasive breast carcinoma and colon adenocarcinoma. ORM1 is also differentially expressed between tumoral and non-tumor tissues. ORM1 expression was found to be higher in embolic cancer than in surrounding tumor cells, indicating that ORM1 expression is associated with vascular invasion thereby reducing the overall prognosis of patients with HCC.11\n\nORM1 is predominantly synthesized in the liver, therefore liver disease has more influence on its expression, ORM1 can be induced by injury in the liver and can activate the liver cell cycle to achieve liver regeneration. He et al., reported that ORM1 expression was highly correlated with tumor growth according to tumor grade and stage.2 This is consistent with the finding that salivary ORM1 increased significantly in patients with advanced liver cancer compared to patients with early-stage liver cancer, that is advanced HCC ORM level is 9.39 times higher than the normal level, while early-stage HCC is only 4.02 times higher than the normal level.2 Elevated salivary ORM1 may be a risk factor for poor prognosis in patients with HCC.\n\nAs shown in the study conducted by He et al. (2022) salivary ORM1 and AFP are significantly higher in other liver diseases. In the same study, it was found that ORM1 had significantly higher expression in the saliva of patients with HCC compared to the non-HCC group (p < 0.001) and ORM1 expression in liver cancer tissue was significantly higher than in adjacent normal tissues.2 There are different levels of salivary AFP expression and salivary ORM1 expression in total HCC, liver cirrhosis (LC), chronic hepatitis B (CHB), and normal control (NC) groups. On the same finding, salivary ORM1 showed good specificity and sensitivity for detecting HCC, especially in HCC associated with hepatitis B.7 The sensitivity and specificity of salivary ORM1 reached 81.67% and 77.5%.\n\nAs an acute-phase protein, AGP has been studied for its potential physiological significance, and both quantitative and qualitative changes to the molecule’s glycan structure have been examined in relation to inflammation and malignancy of the liver.2,21–23 The comparison value of liver disease related to hepatitis B shows in a sequence of normal liver, LC, CHB, early HCC, HCC, and advanced HCC is 429, 657, 1,073, 1,723, 2,143 and 4,029 ng/ml, respectively.2\n\nThe first rapidly increased level of ORM1 shown in early HCC (four times higher than normal) indicates that ORM1 can detect HCC in the early stage with high sensitivity and specificity. This early diagnostic biomarker has a sensitivity of 77.5% and a specificity of 81.67%.2\n\nAccording to the study conducted by Yazawa et al. (2016) the reason ORM1 can be used as an early diagnostic biomarker is that it is exclusively synthesized in the liver by the encoded FUT6 gene, then this enzyme acts as a catalyzer for many reactions related to L-fucose addition to the receptor in order to protect liver cells from damage caused by HCC related to hepatitis B.10 Moreover, this biomarker is also able to detect the prognosis of the disease with or without chemotherapy, this is because the higher the level of ORM1, the more liver damage occurs that leads to a poor prognosis.12\n\nA combination of salivary ORM1 and AFP is specific and sensitive in detecting HCC as written in a study conducted by He et al. (2022). Thus, salivary ORM1, α 1,3 fucosyltransferase, and AFP are going to be a sensitive and specific combination in detecting HCC related hepatitis B as well as prognosis, microvascular invasion (MVI), and sorafenib drug sensitivity. This method of using salivary ORM1, α 1,3 fucosyltransferase, and AFP is also a promising and less invasive method, so it has a high potential to be commercialized.2\n\nSalivary ORM1 is a potential early diagnostic biomarker of HCC related to hepatitis B, as well as a biomarker of disease prognosis. This biomarker has a sensitivity of 81.67% and a specificity of 77.5%.\n\nIn order to increase the sensitivity and specificity of ORM1 as an early diagnostic biomarker, a combination of other biomarkers may be a good topic for further research and application. The sensitivity and specificity of combined salivary AFP and salivary ORM1 tend to be 95% and 74.17%, respectively. In order to overcome the lack of specificity of the aforementioned biomarker combination, hypoalbuminemia detection from albumin assessment as an additional sign of poor liver function is suggested. Therefore, the combination of salivary ORM1, salivary AFP and albumin assessment may be able to provide high sensitivity and specificity in detecting HCC related to hepatitis B.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nMendeley Data: PRISMA checklist for ‘The role of salivary orosomucoid 1 as an early diagnostic and prognostic biomarker of hepatocellular carcinoma related to Hepatitis B: A systematic review’. https://doi.org/10.17632/ykr5jtj6sx.1. 9\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nLi F, Yu Z, Chen P, et al.: The increased excretion of urinary orosomucoid 1 as a useful biomarker for bladder cancer. Am. J. Cancer Res. 2016 Jan 15; 6(2): 331–340. PubMed Abstract | Free Full Text\n\nHe J, Zheng Z, Liu T, et al.: Salivary orosomucoid 1 as a biomarker of hepatitis B associated hepatocellular carcinoma, 18 May 2022, PREPRINT (Version 1) available at Research Square.Publisher Full Text\n\nQin XY, Hara M, Arner E, et al.: Transcriptome Analysis Uncovers a Growth-Promoting Activity of Orosomucoid-1 on Hepatocytes. EBioMedicine. 2017; 24: 257–66. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLuo Z, Lei H, Sun Y, et al.: Orosomucoid, an acute response protein with multiple modulating activities. J. Physiol. Biochem. 2015; 71(2): 329–340. PubMed Abstract | Publisher Full Text\n\nLotfollahzadeh S, Recio-Boiles A, Babiker HM: Liver Cancer. StatPearls. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Reference Source\n\nSingh G, Yoshida EM, Rathi S, et al.: Biomarkers for hepatocellular cancer. World J. Hepatol. 2020; 12(9): 558–573. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGani RA, Suryamin M, Hasan I, et al.: Performance of Alpha Fetoprotein in Combination with Alpha-1-acid Glycoprotein for Diagnosis of Hepatocellular Carcinoma Among Liver Cirrhosis Patients. Acta Med. Indones. 2015; 47(3): 216–222. PubMed Abstract\n\nHiguchi H, Kamimura D, Jiang J-J, et al.: Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation. Int. Immunol. 2020; 32(5): 335–346. Publisher Full Text\n\nLimijadi EKS, Tjandra KC, Ar A, et al.: PRISMA checklist for ‘The role of salivary orosomucoid 1 as an early diagnostic and prognostic biomarker of hepatocellular carcinoma related to Hepatitis B: A systematic review’. [Dataset]. Mendeley Data. 2023; V1. Publisher Full Text\n\nYazawa S, Takahashi R, Yokobori T, et al.: Fucosylated Glycans in α1-Acid Glycoprotein for Monitoring Treatment Outcomes and Prognosis of Cancer Patients. PLoS One. 2016; 11(6): e0156277. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGu J, Xu S, Chen X, et al.: ORM 1 as a biomarker of increased vascular invasion and decreased sorafenib sensitivity in hepatocellular carcinoma. Bosn. J. Basic Med. Sci. 2022; 22(6): 949–958. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGannon B, Glesby M, Finkelstein J, et al.: A point-of-care assay for alpha-1-acid glycoprotein as a diagnostic tool for rapid, mobile-based determination of inflammation. Elsevier. Curr. Res. Biotechnol. 2019; 1: 41–48. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElpek GO: Orosomucoid in liver diseases. World J. Gastroenterol. 2021; 27(45): 7739–7747. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBerger EG, Alpert E, Schmid K, et al.: Immunohistochemical localization of alpha1-acid-glycoprotein in human liver parenchymal cells. Histochemistry. 1977; 51: 293–296. Publisher Full Text\n\nCayol M, Tauveron I, Rambourdin F, et al.: Whole-body protein turnover and hepatic protein synthesis are increased by vaccination in man. Clin. Sci. 1995; 89(4): 389–396. PubMed Abstract | Publisher Full Text\n\nDaveau M, Liautard J, Gaillard JP, et al.: IL-6-induced changes in synthesis of alpha 1-acid glycoprotein in human hepatoma Hep3B cells are distinctively regulated by monoclonal antibodies directed against different epitopes of IL-6 receptor (gp80). Eur. Cytokine Netw. 1994; 5(6): 601–608. PubMed Abstract\n\nKomori T, Kai H, Shimoishi K, et al.: Up-regulation by clarithromycin of α1-acid glycoprotein expression in liver and primary cultured hepatocytes. Biochem. Pharmacol. 2001; 62(10): 1391–1397. Publisher Full Text\n\nLin TH, Sugiyama Y, Sawada Y, et al.: Effect of surgery on serum alpha 1-acid glycoprotein concentration and serum protein binding of DL-propranolol in phenobarbital-treated and untreated rats. Drug Metab. Dispos. 1987; 15(1): 138–140. PubMed Abstract\n\nMouthiers A, Mejdoubi N, Baillet A, et al.: Retinoids increase alpha-1 acid glycoprotein expression at the transcriptional level through two distinct DR1 retinoic acid responsive elements. Biochim. Biophys. Acta Gene Struct. Expr. 2004; 1678(2–3): 135–144. PubMed Abstract | Publisher Full Text\n\nHou L, Li F, Zeng Q, et al.: Excretion of urinary orosomucoid 1 protein is elevated in patients with chronic heart failure. PLoS One. 2014; 9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStelma F, van der Ree MH , Sinnige MJ, et al.: Immune phenotype and function of natural killer and T cells in chronic hepatitis C patients who received a single dose of anti-MicroRNA-122, RG-101. Hepatology. 2017; 66(1): 57–68. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPracoyo W, Raflizar S: Hubungan antara Pengetahuan Responden yang Pernah Menderita Hepatitis tentang Perilaku Penularan Hepatitis C dengan Antibodi Anti Hepatitis C (Titer Anti-HCV) di Indonesia. mpk. 2018; 28: 289–294. Publisher Full Text\n\nSupardi S, Sari D: Titer Anti-HCV di Indonesia. Media Litbangkes. 2018; 28: 4."
}
|
[
{
"id": "169865",
"date": "28 Apr 2023",
"name": "Maria Komariah",
"expertise": [
"Reviewer Expertise Nursing",
"cancer",
"general medicine",
"systematic review",
"and meta-analysis"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis systematic review provides a comprehensive overview of the current literature regarding the use of salivary ORM1 as a biomarker for HCC related to hepatitis B. The authors provide a clear summary of the results of the studies included in the review and make well-supported recommendations for further research. The strengths of the article lie in the clarity of the writing, the thoroughness of the literature search, and the validity and reliability of the data analysis.\nTitle and abstract Overall, I think the title and abstract provide a clear and concise overview of the systematic review. However, there are a few areas that could be improved:\nThe abstract could benefit from a sentence that highlights the main objective or question of the systematic review. For example, \"This systematic review aimed to investigate the diagnostic and prognostic value of salivary orosomucoid 1 (ORM1) in patients with hepatocellular carcinoma related to hepatitis B.\"\n\nIt would be helpful to include the number of databases searched in the methods section, as this is an important aspect of a systematic review.\n\nThe sentence \"This biomarker is also able to detect the prognosis of individuals with the disease with or without chemotherapy because the higher the level of ORM1, the more liver damage occurs that leads to a poorer prognosis\" could use further clarification. It is not clear how ORM1 levels relate to prognosis, and the sentence could benefit from further explanation or references to support the claims made.\n\nIntroduction Your introduction section provides a clear and informative overview of salivary orosomucoid 1 (ORM1) and its potential role in the diagnosis and prognosis of hepatocellular carcinoma (HCC) related to hepatitis B. However, here are a few areas that could be improved:\nThe introduction could benefit from a concise and clear statement of the research question or objective. For example, \"The objective of this systematic review is to investigate the diagnostic and prognostic value of salivary orosomucoid 1 (ORM1) in patients with hepatocellular carcinoma related to hepatitis B, including its sensitivity and specificity as an early diagnostic biomarker, and its potential prognostic value.\"\n\nSome of the sentences could be simplified, such as \"ORM1 is expressed in inflammatory injuries, infections, and stress conditions,\" which could be shortened to \"ORM1 is produced in response to inflammation, infections, and stress.\"\n\nTry to avoid repeating information. For example, the discussion of the advantages of saliva as a biomarker could be consolidated into a single paragraph or sentence.\n\nThe introduction could benefit from a more concise and focused overview of the current state of knowledge regarding ORM1 and HCC related to hepatitis B. You could consider trimming some of the less essential or tangential details to keep the focus on the main topic of the review.\n\nMethods Your methods section appears to be quite comprehensive, but here are a few areas that could use some clarification or improvement:\nIn the Eligibility criteria section, you mention that non-comparative research was disqualified, but it's not clear what this means. Can you provide more information about what you mean by \"non-comparative research\"?\n\nIn the Selection process section, it would be helpful to provide more information about why the 655 excluded studies were removed, and whether any specific criteria were used for exclusion (beyond the abstract screening and full-text retrieval).\n\nIn the Data collection process section, it would be helpful to provide more details about how disagreements between reviewers were resolved, and whether any inter-rater reliability statistics were calculated.\n\nRegarding the risk of bias assessment, it would be helpful to include a brief overview of the domains assessed by the ROBINS-I tool, and how each domain was scored for each study.\n\nIn the Reporting bias assessment section, it would be helpful to clarify whether any reporting bias was identified in the included studies, or whether this section simply reflects the results of the risk of bias assessment.\n\nResults and discussion Overall, the results and discussion section is well-written and provides a clear summary of the main findings in the systematic review. The section is well-organized and provides adequate information about the salivary ORM1 biomarker, its function, and production. The discussion of the limitations of the study is also thorough and provides insight into the potential sources of bias. In terms of strengths, the discussion highlights the methodical approach of the review process and the assessment of varied sources of evidence. The discussion also emphasizes the novel contribution of the study as the first systematic review to assess the levels of ORM1 in patients with cancer along with diagnostic and prognostic evidence.\nThe section provides a comprehensive overview of ORM1 as a biomarker, specifically its function and production. The discussion of the mechanism of action in cancer provides clear explanations of how salivary ORM1 could be a potential biomarker for cancers in the pancreas, bladder, and liver cancer.\nRegarding the role of salivary ORM1 as an early diagnostic biomarker in hepatitis B associated with hepatocellular carcinoma, the discussion provides a clear summary of the study's findings, including the sensitivity and specificity of the biomarker. Additionally, the section highlights the potential of using a combination of salivary ORM1, α 1,3 fucosyltransferase, and AFP for detecting HCC related to hepatitis B and for assessing prognosis, microvascular invasion, and sorafenib drug sensitivity.\nConclusion Clear\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": [
{
"c_id": "9722",
"date": "06 Jun 2023",
"name": "Kevin Christian Tjandra",
"role": "Author Response",
"response": "This systematic review provides a comprehensive overview of the current literature regarding the use of salivary ORM1 as a biomarker for HCC related to hepatitis B. The authors provide a clear summary of the results of the studies included in the review and make well-supported recommendations for further research. The strengths of the article lie in the clarity of the writing, the thoroughness of the literature search, and the validity and reliability of the data analysis. Title and abstract Overall, I think the title and abstract provide a clear and concise overview of the systematic review. However, there are a few areas that could be improved: Query 1 The abstract could benefit from a sentence that highlights the main objective or question of the systematic review. For example, \"This systematic review aimed to investigate the diagnostic and prognostic value of salivary orosomucoid 1 (ORM1) in patients with hepatocellular carcinoma related to hepatitis B.\" Response 1 The suggestion has been added in the background of the abstract “Salivary orosomucoid 1 (ORM1) is highly increased in hepatocellular carcinoma related to hepatitis B. Thus, this systematic review aimed to investigate the diagnostic and prognostic value of salivary orosomucoid 1 (ORM1) in patients with hepatocellular carcinoma related to hepatitis B” Query 2 It would be helpful to include the number of databases searched in the methods section, as this is an important aspect of a systematic review. Response 2 This suggestion has been added to the method of the abstract Query 3 The sentence \"This biomarker is also able to detect the prognosis of individuals with the disease with or without chemotherapy because the higher the level of ORM1, the more liver damage occurs that leads to a poorer prognosis\" could use further clarification. It is not clear how ORM1 levels relate to prognosis, and the sentence could benefit from further explanation or references to support the claims made. Response 3 The corresponding sentence has been clarified to show the correlation between salivary ORM1 and prognosis of the prognosis. The reference from He et al is available in the discussion to support the claim of the sentence “We included five diagnostic studies with 533 samples conducted in China and Japan. Even though limited original studies with homogenous PICO was a limitation, the evidence output of this study can still be well presented. Salivary ORM1 may be useful to detect early cancer diagnosis as rapidly increased levels of ORM1 can be observed in the early stages of HCC (four times higher than usual) and the biomarker has a sensitivity of 81.67% and a specificity of 77.5%. This biomarker is also able to detect the prognosis of individuals with the disease with or without chemotherapy. It is because level of salivary ORM1 related to liver damage, the higher the level of ORM1, the more liver damage occurs that leads to a poorer prognosis.” Introduction Your introduction section provides a clear and informative overview of salivary orosomucoid 1 (ORM1) and its potential role in the diagnosis and prognosis of hepatocellular carcinoma (HCC) related to hepatitis B. However, here are a few areas that could be improved: Query 4 The introduction could benefit from a concise and clear statement of the research question or objective. For example, \"The objective of this systematic review is to investigate the diagnostic and prognostic value of salivary orosomucoid 1 (ORM1) in patients with hepatocellular carcinoma related to hepatitis B, including its sensitivity and specificity as an early diagnostic biomarker, and its potential prognostic value.\" Response 4 The suggestion has been added to the last paragraph of the Introduction part Query 5 Some of the sentences could be simplified, such as \"ORM1 is expressed in inflammatory injuries, infections, and stress conditions,\" which could be shortened to \"ORM1 is produced in response to inflammation, infections, and stress.\" Response 5 The Suggestion has been resolved to simplified several sentence in the introduction Query 6 Try to avoid repeating information. For example, the discussion of the advantages of saliva as a biomarker could be consolidated into a single paragraph or sentence. Response 6 The repeating information has been revised Query 7 The introduction could benefit from a more concise and focused overview of the current state of knowledge regarding ORM1 and HCC related to hepatitis B. You could consider trimming some of the less essential or tangential details to keep the focus on the main topic of the review. Response 7 The introduction has been revised to be more focus on research question and remove less essential information. Methods Your methods section appears to be quite comprehensive, but here are a few areas that could use some clarification or improvement: Query 8 In the Eligibility criteria section, you mention that non-comparative research was disqualified, but it's not clear what this means. Can you provide more information about what you mean by \"non-comparative research\"? Response 8 Non-comparative research means that the research with no treatment or control group. This information has been added to the eligibility criteria subsection Query 9 In the Selection process section, it would be helpful to provide more information about why the 655 excluded studies were removed, and whether any specific criteria were used for exclusion (beyond the abstract screening and full-text retrieval). Response 9 The more information why the 655 articles were removed has been updated “lack of relevant information related to the research question (diagnostic and prognostic value of salivary orosomucoid 1 (ORM1) in patients with hepatocellular carcinoma related to hepatitis B) and the study design do not meet the inclusion criteria (cohort and diagnostic study)” We also want to confirm that we did not use any specific criteria for the exclusion, we only screened the article based on abstract and full text screening, and full text retrieval to assess whether the articles meet the inclusion or exclusion criteria. Query 10 In the Data collection process section, it would be helpful to provide more details about how disagreements between reviewers were resolved, and whether any inter-rater reliability statistics were calculated. Response 10 The disagreements were resolved by comprehensive discussions. Inter-rater reliability statics were not calculated in this study Query 11 Regarding the risk of bias assessment, it would be helpful to include a brief overview of the domains assessed by the ROBINS-I tool, and how each domain was scored for each study. Response 11 The brief overview and assessment criteria has been updated to the relevant subsection Query 12 In the Reporting bias assessment section, it would be helpful to clarify whether any reporting bias was identified in the included studies, or whether this section simply reflects the results of the risk of bias assessment. Response 12 We clarify that this section simply reflects the results of the risk of bias assessment. Results and discussion Overall, the results and discussion section is well-written and provides a clear summary of the main findings in the systematic review. The section is well-organized and provides adequate information about the salivary ORM1 biomarker, its function, and production. The discussion of the limitations of the study is also thorough and provides insight into the potential sources of bias. In terms of strengths, the discussion highlights the methodical approach of the review process and the assessment of varied sources of evidence. The discussion also emphasizes the novel contribution of the study as the first systematic review to assess the levels of ORM1 in patients with cancer along with diagnostic and prognostic evidence. The section provides a comprehensive overview of ORM1 as a biomarker, specifically its function and production. The discussion of the mechanism of action in cancer provides clear explanations of how salivary ORM1 could be a potential biomarker for cancers in the pancreas, bladder, and liver cancer. Regarding the role of salivary ORM1 as an early diagnostic biomarker in hepatitis B associated with hepatocellular carcinoma, the discussion provides a clear summary of the study's findings, including the sensitivity and specificity of the biomarker. Additionally, the section highlights the potential of using a combination of salivary ORM1, α 1,3 fucosyltransferase, and AFP for detecting HCC related to hepatitis B and for assessing prognosis, microvascular invasion, and sorafenib drug sensitivity."
}
]
}
] | 1
|
https://f1000research.com/articles/12-401
|
https://f1000research.com/articles/12-605/v1
|
06 Jun 23
|
{
"type": "Opinion Article",
"title": "Tackling “half” of the non-communicable disease burden in Bangladesh: a diagonal service delivery model with a life-course approach",
"authors": [
"Sifat Parveen Sheikh",
"Abu Sayeed MD Abdullah",
"Abu Sayeed MD Abdullah"
],
"abstract": "In the context of increasing morbidity and mortality due to non-communicable diseases (NCDs) globally and particularly in low-resource countries, it has become important to explore newer health systems delivery models. In low-and middle-income countries (LMICs) women traditionally challenged with multiple barriers in accessing health services, are at even greater disadvantage compared to men. In Bangladesh, women constitute almost half of the country’s population and are disproportionately affected by NCDs like other LMICs. The country’s reproductive, maternal, newborn, child and adolescent health (RMNCAH) services are well established and designed to reach women in their households through community health workers (CHWs). This paper discusses how NCDs screening and control measures could be integrated into the existing RMNCAH pathway and proposes a conceptual model for such diagonal service delivery integration. The paper also describes multiple RMNCAH service delivery touchpoints that could be utilized for screening and treating women for NCD risk factors, across their life-course.",
"keywords": [
"Non-communicable diseases (NCDs)",
"maternal and child health",
"diagonal integration",
"women’s health",
"life-course",
"LMICs",
"Bangladesh"
],
"content": "Background\n\nAnnually, non-communicable diseases (NCDs) contribute to a total of 41 million deaths, which is 74% of all deaths worldwide.1,2 NCDs now constitute the leading cause of death and disability among women with approximately two out of every three women dying from an NCD, which translates to 19 million deaths annually.3 Eighty percent of all NCDs-related deaths occur in low-and middle-income countries (LMICs) which have undergone rapid epidemiologic transition.4 As an LMIC, Bangladesh experiences similar phenomena with 68% of the country’s total mortality occurring due to NCDs.5 Households with NCDs were reported to have borne 6.7% higher catastrophic medical expenditure compared to those households without NCDs; households with NCDs have an 85% higher likelihood of selling assets or borrowing money for covering the treatment expenses for NCDs.6 The rising NCDs burden disproportionately affects women as they are already faced with several barriers to accessing healthcare in low-resource settings.7 Despite availability of reproductive health services for women, the overall health status of women in Bangladesh remains below par.8 Since existing policies and programs largely focus on reproductive, maternal, child, and adolescent health (RMNCAH),9 the magnitude of NCDs-related disability and deaths do not receive adequate focus. Moreover, risk factors overlapping between NCDs and sexual and reproductive disorders are not taken into account.9 For instance, mothers who suffer from gestational diabetes have a greater risk of developing Type 2 Diabetes Mellitus later in life.10 The antenatal period provides a window of opportunity for early intervention for prevention of diabetes mellitus among these women.11 Also, certain exposures (multiple sexual partners, infection with human papilloma virus) during reproductive years are risk factors for female cancers, classified as NCDs at an older age.12 Women in their postmenopausal years face higher risks of developing the five major NCDs (hypertension, diabetes mellitus, chronic respiratory diseases, cancer and mental disorders) plus other NCDs such as osteoporosis.13 However, as women age beyond their reproductive years, they are likely to lose contact with the health system.14 Women in Bangladesh have limited decision-making power and financial capacity that restrict their ability to seek health services on their own.15 Although current RMNCAH services attempt to reach all rural women at their doorstep, women who are not in their childbearing age are not included within the scope of such services.16\n\nThe Sustainable Development Goals (SDGs) sets the target “to reduce premature mortality from NCDs by a third relative to 2015 levels, and to promote mental health and wellbeing.”17 As women constitute about 50% of the population of Bangladesh,18 it is essential to support the NCDs-related healthcare needs of women to achieve the aforementioned SDG. Women in Bangladesh face several challenges in accessing health care: distance to health facility/lack of transportation, lack of knowledge/cultural stigma and misperceptions, lack of opportunity and time to travel to a health facility due to excessive involvement in household chores, absence of financial ability and decision-making power.19 Even if they manage to make a preliminary visit to the health facility, at some point they are lost to follow-up. Introducing a seperate NCDs screening and referral system targeted towards women require considerable resources.20 To immediately address the rising burden of NCDs among women, a care continuum with a life-course approach can be established by expanding “diagonally” on existing RMNCAH services.21 The community health workers (CHWs) who are currently involved in delivering RMNCAH services, can play an important role in the prevention and screening of NCDs risk factors.22 Similar approaches have been tested and implemented in other LMICs.23–25 In Sub-Saharan Africa, CHWs who primarily deal with sexually transmitted diseases in the community are tasked with screening for relevant NCDs.26 In Pakistan, a lifestyle intervention was delivered by trained CHWs that significantly controlled the increase in blood pressure among children and young adults.27,28 In Kerala, India, CHWs successfully conducted a large NCDs prevalence study among 113,462 individuals in five village councils.29 A health system model that takes on an integrated and synergistic approach to RMNCAH and NCDs services can ensure cost-effective delivery of services that span across the life course of women. This paper introduces the concept of a women-centred, life-course approach for NCDs control based on existing RMNCAH service delivery pathway in Bangladesh, which may be applicable to other low-resource settings.\n\n\nOpportunities within existing RMNCAH services\n\nRMNCAH services in Bangladesh provide multiple opportunities for women to interact with the health system: at least four ante-natal checkups (ANC) during pregnancy, post-natal visits, post-partum family planning (PPFP) visits, immunization visits, family planning visits and more recently, the government has focused on adolescent counseling and services30,31 (Table 1). The national program for screening and control of breast and cervical cancers utilize the existing RMNCAH care pathway.32 Incorporating other NCDs could potentially prove to be an effective measure. Educating women about the importance of a balanced diet, physical activity and optimal breastfeeding practices can lead to healthier pregnancies and at the same time, reduce the risk of NCDs.33 Breastfeeding promotion and support can reduce the risks of obesity and type 2 diabetes among children later in life, and the mother’s risks of type 2 diabetes, breast and ovarian cancers34 (Table 1). Monitoring of blood pressure during pregnancy not only allows to screen for preeclampsia/eclampsia but also identifies risk factors for cardiovascular diseases35 (Table 1). Multiple service delivery touchpoints within the RMNCAH pathway present an important opportunity to reach the most vulnerable and underserved women, who otherwise would not seek NCDs services.36 Moreover, such repeated interactions can address loss-to -follow-up, one of the important challenges in NCDs management.37 Women with identified NCDs risk factors can then be referred and linked to the mainstream NCDs control program. Adolescent girls and older women in the family could also be screened by CHWs during household visits.\n\n\n\n• Pregnant women\n\n• Adolescent girls and elderly female family members (during household visits/those accompanying mother and newborn to health facilities)\n\n\n\n• Health education on balanced and nutritious diet, physical activity for prevention of obesity and associated NCDs risk\n\n• Promotion of optimal breastfeeding practices\n\n• Screening and referral for pregnant mother with gestational diabetes and hypertension\n\n• Screening and referral of elderly women in the family for diabetes, hypertension, chronic respiratory illnesses\n\n• Providing calcium supplements to all women in the household for bone health (prevention of osteoporosis)\n\n\n\n• Mother\n\n• Newborn\n\n\n\n• Management of gestational diabetes, preeclampsia/eclampsia during childbirth\n\n• Promotion of optimal breastfeeding practices to prevent future obesity in newborn child and breast and ovarian cancers in mother\n\n• Screening for signs of post-partum depression\n\n\n\n• Recently delivered mother\n\n• Newborn\n\n\n\n• Reassessing NCDs risk factors of mothers with diabetes and hypertension during pregnancy\n\n• Advice on adequate and nutritious diet for the lactating mother\n\n• Educating the mother on optimal sunlight exposure for healthy bone development in newborn\n\n• Screening for signs of post-partum depression\n\n\n\n• Mother\n\n• Child\n\n• Elderly female family members (during household visits/those accompanying mother and newborn to health facilities)\n\n\n\n• Educating the mother on optimal sunlight exposure for healthy bone development for all family members\n\n• Screening the mother for signs of post-partum depression\n\n• Providing calcium supplements to women in the family for bone health (prevention of osteoporosis)\n\n• Counseling and referring eligible women for breast and cervical cancer screening\n\n\n\n• Women of reproductive age\n\n• Elderly female family members (during household visits/those accompanying mother and newborn to health facilities)\n\n\n\n• Counseling and referring eligible women for breast and cervical cancer screening\n\n• Screening for hypertension and diabetes among elderly women in the household (blood pressure and blood glucose measurement)\n\n\n\n• Adolescent girls\n\n\n\n• Counseling on menstrual health and hygiene, safe sex practices for prevention of cervical cancer\n\n• Health education on balanced and nutritious diet, physical activity for prevention of obesity and associated NCDs risk\n\n• Screening for signs of depression during puberty\n\n• Counseling on the dangers of early marriage and childbearing and how they contribute to early onset of NCDs\n\n\nA diagonal service-delivery model\n\nA diagonal approach to health system strengthening for NCDs focuses on integrating specific components of NCDs prevention and management within an existing framework of healthcare delivery.38 In Bangladesh, the Non-Communicable Disease Control (NCDC) Program of the Directorate General of Health Services (DGHS) has operationalized the World Health Organization’s (WHO) Package of Essential Noncommunicable (PEN) diseases initiative to integrate NCDs management at primary health care (PHC) settings across Bangladesh.39 However, the recent COVID-19 pandemic has stalled the progress of most health-related programs and interventions due to greater health systems focus on the pandemic.40 While the national NCDs control program is still at the implementation phase, morbidity and mortality associated with NCDs continue to rise. Moreover, the mainstream NCDs control program does not provide particular emphasis on improving access to NCDs-related health services for women, particularly in underserved areas.\n\nIn Bangladesh, RMNCAH services are provided through a network of government health facilities and CHWs41,42 (Figure 1).\n\nHousehold level: When the CHW visits a household for delivering routine reproductive health services and counseling (antenatal care, postnatal care, family planning), she will also screen for specific NCDs risk factors such as high blood pressure, blood glucose level and BMI. Besides women of reproductive age, she (CHW) will also screen adolescent girls and older women in the household and counsel on how to maintain a balanced diet and physical activity depending on the life-stage of the woman. If any risk factor is identified, she will refer the woman to the nearest healthcare facility for further evaluation (Figure 1).\n\nPrimary health facilities: The primary health facilities include community clinics (CC), union health and family welfare centre (UHFWC), union subcentre, upazila health complex (UHC).42 When a woman first visits the nearest primary health facility, she will be screened for NCDs risk factors. Women with risk factors such as high blood pressure and/or blood glucose will be referred to the secondary health facilities for further evaluation and management and will be counseled about her NCDs risk factors and how it can affect her now and in the future. Pregnant women with high blood pressure and/or high blood glucose levels require frequent follow-up and close monitoring and require facility delivery. In many cases, caesarean section maybe necessary. The woman’s family will also be counseled on such issues (Figure 1).\n\nSecondary health facilities: Secondary public health facilities include district hospitals (DH), maternal and child welfare centers (MCWCs).42 In several DHs, there are NCDs corners dedicated to evaluate patients with NCDs risk factors. After being referred from the primary facilities, the patient will be further evaluated at the secondary health facility and if available, treatment will be provided. Patients with moderate to severe risk factors who are not manageable at the secondary level, will be referred to the tertiary level government facilities (Figure 1).\n\nTertiary level health facilities: Tertiary health facilities include medical college hospitals and specialized institutes for NCDs management.42 National level specialized institutes for NCDs management are National Institute of Cardiovascular Diseases (NICVD), National Institute of Kidney Diseases & Urology (NIKDU), National Institute of Neuro Sciences & Hospital (NINH), National Institute Of Mental Health And Hospital (NIMH) among others.43 Patients with diagnosed NCDs, who require better management will be referred to the tertiary level. Laboratory tests will be conducted as necessary along with more advanced treatment advice and counseling from specialist physicians. Patients with severe and/or complicated conditions will be referred to specialized institutes for higher level management. Once the patient returns to the community after treatment, the CHW will follow-up on the patient at regular intervals (Figure 1).\n\n\nImplications for policy and practice\n\nRMNCAH programs designed across the reproductive life-cycle of women are strongly positioned to play a crucial role in NCDs prevention.44,45 Several existing reproductive health services and counseling contribute to NCDs prevention, such as promotion of balanced diet during pregnancy, promotion of optimal breastfeeding practices.46 Existing activities can be slightly expanded to incorporate an NCDs prevention focus, which will reduce costs and pluralism.46,47 CHWs can screen adolescents and older women for NCDs risk factors during household visits thus broadening their scope of work.47 This would be a critical step to focus on women who are not in their reproductive age and are currently overlooked. However, a criticism of the model proposed in this paper is the existing workload and capacity of CHWs. In Bangladesh, CHWs are tasked with multiple responsibilities, largely RMNCAH services and activities.48,49 Adding more tasks to their existing workload would require additional capacity building and resources. A possible solution would be to employ additional CHWs, particularly in hard-to-reach areas and/or to increase the wages for existing workers.\n\nIn Bangladesh, a multisectoral approach is necessary to support a sustainable initiative for NCDs control across the life-course for both women and men.50 For example, the education sector could emphasize on promoting healthy food and physical education at schools. The food industry and the media can come together to commercialize healthier food options for children and adolescents. The ministries of health and family planning can work together to integrate NCDs screening measures within the existing RMNCAH activities. Community-based organizations can work in collaboration with farmers in utilizing local agricultural resources to make nutritious food available to poor women at a reasonable cost. Thus, engaging all relevant stakeholders can help provide accessible, timely and cost-effective NCDs control services for women in Bangladesh.51\n\n\nConclusions\n\nThe rising burden of NCDs in Bangladesh and the fact that it disproportionately affects women calls for shifting health systems priorities. NCDs among mothers means an intergenerational cycle of NCDs risk factors leading to increased morbidity and mortality among future generations. Bangladesh has achieved exemplary success in providing RMNCAH services for women residing in rural and remote communities. To achieve success in NCDs control, the government could consider the service delivery model proposed in this paper and similar models implemented in other LMICs. This can have multiple benefits such as cost containment, reducing redundancy and pluralism in health services, preventing loss-to follow-up and reaching the most vulnerable and underserved populations. A multi-sectoral life-course approach to NCDs management can potentially reduce half of the morbidity and mortality due to NCDs. The intergenerational impacts are anticipated to be even greater. Further research should focus on piloting of diagonal NCDs-RMNCAH service delivery model for women in rural Bangladesh and if found feasible, such interventions should be recommended for scale-up.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nForouzanfar MH, Afshin A, Alexander LT, et al.: Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8; 388(10053): 1659–1724. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Health Organization: Key Facts: Non-communicable Diseases 2021. Accessed on April 18, 2023. Reference Source\n\nWomen and NCDs: NCD Alliance. Accessed on April 18, 2023. Reference Source\n\nNdubuisi NE: Noncommunicable diseases prevention in low-and middle-income countries: an overview of Health in All Policies (HiAP). INQUIRY: The Journal of Health Care Organization, Provision, and Financing. 2021 Aug; 58: 004695802092788. 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Publisher Full Text\n\nKim C, Newton KM, Knopp RH: Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care. 2002 Oct 1; 25(10): 1862–1868. Publisher Full Text\n\nKalra S, Malik S, John M: Gestational diabetes mellitus: A window of opportunity. Indian J. Endocrinol. Metab. 2011 Jul; 15(3): 149–151. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKashyap N, Krishnan N, Kaur S, et al.: Risk factors of cervical cancer: a case-control study. Asia Pac. J. Oncol. Nurs. 2019 Jul 1; 6(3): 308–314. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGupta S, Gupta N, Khandekar J, et al.: Risk Factor Profile for Non Communicable Diseases among Postmenopausal Women in Delhi. Indian J. Public Health Res. Dev. 2013; 4(1): 158.\n\nEnsor T, Cooper S: Overcoming barriers to health service access: influencing the demand side. Health Policy Plan. 2004 Mar 1; 19(2): 69–79. PubMed Abstract | Publisher Full Text\n\nSenarath U, Gunawardena NS: Women’s autonomy in decision making for health care in South Asia. Asia Pac. J. Public Health. 2009 Apr; 21(2): 137–143. Publisher Full Text\n\nHossen A, Westhues A: Improving access to government health care in rural Bangladesh: the voice of older adult women. Health Care Women Int. 2011 Dec 1; 32(12): 1088–1110. PubMed Abstract | Publisher Full Text\n\nBennett JE, Kontis V, Mathers CD, et al.: NCD Countdown 2030: pathways to achieving Sustainable Development Goal target 3.4. Lancet. 2020 Sep 26; 396(10255): 918–934. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBangladesh Bureau of Statistics (BBS): Report of the Bangladesh Population & Housing Census 2011. Dhaka, Bangladesh: Bangladesh Bureau of Statistics; 2012.\n\nHamiduzzaman M, De Bellis A, Abigail W, et al.: Elderly women in rural Bangladesh: Healthcare access and ageing trends. South Asia Res. 2018 Jul; 38(2): 113–129. Publisher Full Text\n\nStrong K, Wald N, Miller A, et al.: Current concepts in screening for noncommunicable disease: World Health Organization Consultation Group Report on methodology of noncommunicable disease screening. J. Med. Screen. 2005 Mar 1; 12(1): 12–19. PubMed Abstract | Publisher Full Text\n\nMishra GD, Anderson D, Schoenaker DA, et al.: InterLACE: a new international collaboration for a life course approach to women’s reproductive health and chronic disease events. Maturitas. 2013 Mar 1; 74(3): 235–240. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: Managing programmes on reproductive, maternal, newborn, child and adolescent health.2021. Accessed on April 2, 2023. Reference Source\n\nPfaff C, Singano V, Akello H, et al.: Early experiences integrating hypertension and diabetes screening and treatment in a human immunodeficiency virus clinic in Malawi. Int. Health. 2018; 10(6): 495–501. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nJafar TH, Islam M, Hatcher J, et al.: Community based lifestyle intervention for blood pressure reduction in children and young adults in developing country: cluster randomised controlled trial. BMJ. 2010; 340: c2641. Publisher Full Text\n\nMishra SR, Neupane D, Preen D, et al.: Mitigation of non-communicable diseases in developing countries with community health workers. Glob. Health. 2015 Dec; 11(1): 1–5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMenon J, Joseph J, Thachil A, et al.: Surveillance of noncommunicable diseases by community health workers in Kerala: the epidemiology of noncommunicable diseases in rural areas (ENDIRA) study. Glob. Heart. 2014 Dec 1; 9(4): 409–417. PubMed Abstract | Publisher Full Text\n\nJahan R: Securing maternal health through comprehensive reproductive health services: lessons from Bangladesh. Am. J. Public Health. 2007 Jul; 97(7): 1186–1190. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAinul S, Bajracharya A, Reichenbach L, et al.: Adolescents in Bangladesh: a situation analysis of programmatic approaches to sexual and reproductive health education and services.\n\nBhatla N, Nessa A, Oswal K, et al.: Program organization rather than choice of test determines success of cervical cancer screening: case studies from Bangladesh and India. Int. J. Gynecol. Obstet. 2021 Jan; 152(1): 40–47. PubMed Abstract | Publisher Full Text\n\nJacob CM, Killeen SL, McAuliffe FM, et al.: Prevention of noncommunicable diseases by interventions in the preconception period: A FIGO position paper for action by healthcare practitioners. Int. J. Gynecol. Obstet. 2020 Sep; 151: 6–15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBranca F, Piwoz E, Schultink W, et al.: Nutrition and health in women, children, and adolescent girls. BMJ. 2015 Sep 14; 351.\n\nGarovic VD, Hayman SR: Hypertension in pregnancy: an emerging risk factor for cardiovascular disease. Nat. Clin. Pract. Nephrol. 2007 Nov; 3(11): 613–622. Publisher Full Text\n\nNewson RS, Lion R, Crawford RJ, et al.: Behaviour change for better health: nutrition, hygiene and sustainability.\n\nMaher D, Harries AD, Zachariah R, et al.: A global framework for action to improve the primary care response to chronic non-communicable diseases: a solution to a neglected problem. BMC Public Health. 2009 Dec; 9: 1–7.\n\nFrenk J, Gómez-Dantés O, Knaul FM: The health systems agenda: prospects for the diagonal approach. The handbook of global health policy. 2014 Apr 24; pp. 425–439. Publisher Full Text\n\nThe 4th Health, Population and Nutrition Sector Program (4th HPNSP), NCD Control Operation Plan (OP), January 2017-June 2022, Ministry of health and Family Welfare (MoH&FW), Government of the People’s Republic of Bangladesh.2017.\n\nIslam K, Huque R, Saif-Ur-Rahman KM, et al.: Implementation status of non-communicable disease control program at primary health care level in Bangladesh: Findings from a qualitative research. Public Health Pract. 2022 Jun 1; 3: 100271. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAhmed S, Alam B, Anwar I, et al.: Bangladesh Health System Review. World Health Organization; 2015. Accessed January 20, 2021. Google Scholar. Reference Source\n\nMridha MK, Anwar I, Koblinsky M: Public-sector maternal health programmes and services for rural Bangladesh. J. Health Popul. Nutr. 2009 Apr; 27(2): 124–138. PubMed Abstract | Publisher Full Text\n\nGovernment of Bangladesh: Multi-sectoral action plan for prevention and control of non-communicable diseases 2018–2025. Accessed on April 5, 2023. Reference Source\n\nAlam N, Mamun M, Dema P: Reproductive, maternal, newborn, child, and adolescent health (RMNCAH): Key global public health agenda in SDG era. Good Health and Well-Being. 2020; pp. 583–593. Publisher Full Text\n\nBrumana L, Arroyo A, Schwalbe NR, et al.: Maternal and child health services and an integrated, life-cycle approach to the prevention of non-communicable diseases. BMJ Glob. Health. 2017 Aug 1; 2(3): e000295. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKikuchi K, Ayer R, Okawa S, et al.: Interventions integrating non-communicable disease prevention and reproductive, maternal, newborn, and child health: A systematic review. Biosci. Trends. 2018 Apr 30; 12(2): 116–125. PubMed Abstract | Publisher Full Text\n\nMaina WK: Integrating noncommunicable disease prevention into maternal and child health programs: Can it be done and what will it take? Int. J. Gynecol. Obstet. 2011 Nov; 115: S34–S36. PubMed Abstract | Publisher Full Text\n\nPuett C, Coates J, Alderman H, et al.: Does greater workload lead to reduced quality of preventive and curative care among community health workers in Bangladesh? Food Nutr. Bull. 2012 Dec; 33(4): 273–287. Publisher Full Text\n\nRahman SM, Ali NA, Jennings L, et al.: Factors affecting recruitment and retention of community health workers in a newborn care intervention in Bangladesh. Hum. Resour. Health. 2010 Dec; 8: 1–4.\n\nCerf ME: Healthy lifestyles and noncommunicable diseases: nutrition, the life-course, and health promotion. Lifestyle Medicine. 2021 Apr; 2(2): e31. Publisher Full Text\n\nMisra A, Tandon N, Ebrahim S, et al.: Diabetes, cardiovascular disease, and chronic kidney disease in South Asia: current status and future directions. BMJ. 2017 Apr 11; j1420. Publisher Full Text"
}
|
[
{
"id": "197690",
"date": "18 Aug 2023",
"name": "Felix P. Chilunga",
"expertise": [
"Reviewer Expertise Global health (cardiometabolic diseases)"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article presents a thoughtful and relevant exploration of the challenges posed by non-communicable diseases (NCDs) among women in Bangladesh. The authors propose an innovative approach of integrating NCDs prevention and management into the existing Reproductive, Maternal, Newborn, Child, and Adolescent Health (RMNCAH) services. This \"diagonal\" service-delivery model aims to address the disproportionate impact of NCDs on women's health, particularly in low-resource settings. Suggestions for Improvement:\nWhile the article acknowledges the potential challenges in implementing the proposed model, it would be beneficial to delve deeper into these challenges and provide more concrete strategies for overcoming them. Specifically, addressing the additional workload and capacity-building requirements for community health workers (CHWs) would enhance the feasibility of the approach.\n\nWhile the authors provide examples of similar approaches in other low- and middle-income countries, it would strengthen the argument to include more detailed case studies or data demonstrating the effectiveness of integrating NCDs prevention within existing healthcare services.\n\nThe authors discuss the importance of engaging various sectors and stakeholders, but more guidance could be provided on how to initiate and sustain such collaborations. Concrete examples or recommendations for fostering partnerships would enhance the practicality of the proposed approach.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-605
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https://f1000research.com/articles/12-463/v1
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03 May 23
|
{
"type": "Research Article",
"title": "An empirical investigation on the impact of attitudes towards organ donation in India",
"authors": [
"Vinod C. Nayak",
"Smitha Nayak",
"Vinod C. Nayak"
],
"abstract": "Background: Organ shortage is a global issue and it is imperative to take steps to bridge this gap. In the Indian context, despite its demographic dividend, the rate of organ donation has been abysmally low. This emphasizes a need to demystify the antecedents of organ donation intention among the Indian population. Methods: Using a cross-sectional research design and adopting a post-positivism research philosophy, this study identified 259 respondents by adopting a purposive sampling approach and data on knowledge of organ donation was collected using a structured, pretested questionnaire. Results: Awareness of organ donation law in India is low on specific issues and respondents from the health science & medicine discipline scored better on knowledge about organ donation. The findings show that most participants had heard about organ donation and had a favourable attitude toward it. The primary sources of information on organ donation were television and newspapers, and healthcare service providers. A complementary partial median is established (β = .217, t = 5.889, p < .001) which implies that willingness to discuss with family significantly mediates the association between attitude towards organ & tissue donation and willingness to sign the donor card. Conclusion: This study revealed that there is a general awareness of organ and tissue donation among the Indian population, but they lack clarity on certain specific issues. Mass media has to be effectively used to build awareness campaigns revolving around enhancing knowledge on a specific issue and building acceptance of the concept of organ and tissue donation.",
"keywords": [
"organ donation",
"attitude",
"awareness",
"knowledge",
"donor card"
],
"content": "Introduction\n\nOrgan donation is a significant milestone in the process of evolution of modern medicine. The act of donating an organ or a portion of an organ for transplantation to another person is known as organ donation. The Transplantation of Human Organs Act (Section 2), 1994, defines “transplantation as the grafting of any human organ from any living person or deceased person to some other living person for therapeutic purposes”. This is the only way to prolong life and enhance the quality of life for people with terminal organ failures (Bedi et al., 2015). When Joseph E Murray and his colleagues performed the very first successful kidney transplant in Boston in 1954, the concept of organ donation gained traction (Watts, 2011). In the seven decades since organ transplantation has emerged to be a successful practice worldwide with kidneys, liver, and heart being the most transplanted solid organs (WHO, 2020) and musculoskeletal grafts & cornea being the most transplanted tissues. The International report on Organ Donation and Transplantation Activities (WHO, 2022) reported 129681 solid organ transplants globally in 2020. Despite this number of reported donations, there is still a supply-demand imbalance in the organ and tissue donation (OTD) space. The report further cites 17 deaths occurring every day due to the non-availability of organ donors and the existing donations are only catering to less than 10 percent of the global need. There is a significant difference between nations in the availability of appropriate transplantation procedures as well as in the level of safety, effectiveness, and quality of human cells and, OTD & transplantation. These systemic factors contribute to broadening the need-availability gap.\n\n\nLiterature review\n\nIn the Indian context, despite its demographic dividend, the rate of organ donation has been abysmally low. There is a significant mismatch between the demand and supply status in India. Despite the fact that approximately 180,000 people are estimated to suffer from renal failure each year, with only 6,000 kidney transplants are performed (Chang et al., 2020). A timely liver transplant could save approximately 15% of the two lakh individuals who succumb in India every year from liver cancer or liver failure. As a result, India requires between 25,000 to 30,000 liver transplants per year, but only about 1,500 are carried out. Similarly, over 50,000 people die from heart failure each year in India, but only 10% to 15% of heart transplants are performed (Tamuli et al., 2019). Despite a 100,000 need, only approximately 25,000 Cornea transplants are performed each year (Mohan et al., 2020). These figures are not encouraging, regardless of the efforts of the government and voluntary organizations. The government has attempted to bring in a systemic change to ensure a transparent system of OTD and to stop human organ trafficking. The Government legalized organ donation under the “Transplantation of Human Organs Act” (THOA, 1994), and the Act has undergone various amendments since then The National Organ Transplant Program was initiated in the 12th five-year plan of the Government of India to promote organ transplantation (THOA, 1994). The National Organ and Tissue Transplantation Organization (NOTTO) has been established as a nodal agency for this program, and it serves as a national-level registry for organ donation and transplantation.\n\nOrgan shortage is a global issue, and it is imperative to take steps to bridge this gap. The Government and Non-Governmental organizations have in tandem taken various steps to encourage people to register for organ donation. Several initiatives that spread fundamental knowledge, and enhance familiarity with and develop positive attitudes toward organ donation have been adopted. For instance, legalising organ donation and organ donation awareness campaigns on various media platforms are examples of initiatives that have been implemented by private and public organizations (Meena et al., 2023).\n\nIntention to donate organs is shaped by an individual's knowledge of organ donation, attitude, and behaviour, and is further influenced by cultural and religious orientations (Chung et al., 2008; Rithalia et al., 2009; Mekahli et al., 2009; Ramadurg & Gupta, 2014; Manish et al., 2015; Vijayalakshmi et al., 2016, Vincent et al., 2022). Age, gender and socio-economic status, and education have been reported to have a significant influence on attitudes toward organ donation (Bilgel et al., 2004; Spigner et al., 2002; Saleem et al., 2009; Balwani et al., 2015). A study undertaken by Gorczyca and Hartman (2017) emphasized the importance of including millennials in a larger conversation about organ donation and transplantation as they could contribute to future campaign tactics at local and national governmental levels. As India has a 34.8 percent representation of millennials in the population, or people aged 17 to 34 (according to the data furnished by the Social Statistics Division of the Central Statistics Office, Ministry of Statistics and Programme Implementation, Government of India, as of 2011), they could contribute to accelerating reach of the campaigns. In a similar study, to this evidence, undertaken by the United States Department of Health and Human Services (2013), it was identified that people above the age of 65 were less likely to sign up for organ donation compared to those of the age group 18-34 years. Loughery et al. (2018) have also cited the age and education status of the donor as significant barriers to organ donation. Additionally, a study undertaken by Alex et al. (2017) provided evidence of an inadequate level of knowledge on organ donation among medical students served as a barrier to OTD. Hence it is imperative to assess the current knowledge level, attitude, and willingness to register for organ donation among various age groups and whether it varies across the population with the discipline of education.\n\nThere exists sufficient research evidence to conclude a positive significant association between willingness to discuss OTD with family and attitudes toward OTD (Knox et al., 2017; Kopfman, 2002; Thompson et al., 2004; Wu & Tang, 2009). Although this association has been established, the details of the discussion are still an enigma. Most of the research evidence indicates a similar influence on the intention of organ donation, although there is a lack of empirical evidence proving this hypothesis. Knowledge of organ donation also has a positive association with discussion intention (Guadagnoli et al., 1999). Among gender, women were more likely to discuss organ donation intention than men (Thompson et al., 2004). Even though there is a direct effect of willingness to discuss with family on intention to enrol as an organ donor, the mediating role of this construct has not been explored. This study will also explore the mediating role of willingness to discuss organ donation between the attitude toward OTD and the intention to enrol as an organ donor. The conceptual framework that has been proposed is shown below (Figure 1).\n\n\nMethods\n\nThis study was reviewed and approved by the Scientific Committee Manipal Academy of Higher Education, Manipal, India on 16th March 2022. While administering the questionnaire, written informed consent was taken from the participants. Participants were ensured that the collected data would be used for research purposes and that the data would be sufficiently de-identified.\n\nThis proposed research endeavour is cross-sectional by research design and is quantitative by nature. The “post-positivism” research philosophy that is being considered in this study concerns the development of empirical methods for comprehending and investigating human behaviour. The conceptual framework for this study proposes a relationship between the independent, dependent, and mediating factors. Demographic factor like education is considered moderating variables.\n\nAs per the report submitted by the Health and Family Welfare, Ministry of Karnataka, Karnataka state has been one of the forerunners in terms of organ donation in India (Kute et al., 2020). As per the current statistics, 143 organ donations have been recorded in 2022 which has given a fresh lease of life to 397 people. Hence, this study was undertaken in Karnataka state. In Karnataka, Dakshina Kannada” and Udupi Districts were chosen by a simple random sampling technique. The target population for this study was the general population residing in the above districts who were free of organ failure and who knew English. No other inclusion criteria were adopted. A purposive sampling technique was adopted to identify participants at four shopping malls; two located in each district. Participants were approached at the malls and after applying the inclusion criteria, were briefed on the objective of the research. On obtaining consent, the participants were requested to fill the questionnaire. Data collection was undertaken from November 2022 to January 2023.\n\nThis investigation used a purposive sampling approach (non-probability by nature), which was adopted due to the absence of a sampling frame. Data was collected from 259 respondents. The study comprises of respondents from three age groups (18-26, 27-42, and 42 and above). Respondents who know English were requested to fill the questionnaire.\n\nThe sample size was determined by multiplying the number of rating scale elements by ten [15] i.e. 15*10 = 150. Considering 10% of the unanswered sample (i.e.15) gives rise to 165 (150 + 15 = 165). Finally, 259 participant data were collected.\n\nData was collected using a structured questionnaire. A copy of the questionnaire is also placed the Extended data (Nayak & Nayak, 2023). The questionnaire was divided into five parts. Part 1 captured the demographic details of the participants, like age, income, education, and gender. In addition, two questions on participants' awareness of OTD and sources of information on OTD were also incorporated. Part 2 assessed the knowledge of participants on OTD Jacob et al. (2008). This section included eight items with true or false response options, which were further subdivided into four sub-scales: general donation-related statistics (two items), understanding of what signing a donor card entails (three items), medical fitness for donation (two items), and knowledge of religious institutions' approach to donation (one item). The maximum score in this component was 8, with one mark for each correct response. The third part of the questionnaire consisted of seven items to measure attitudes toward OTD (Morgan & Miller, 2001). The next section of the questionnaire inquired about the participant's willingness to talk about OTD with family and friends (Morgan & Miller, 2002). The final part of the questionnaire captured the participant's willingness to sign the organ donor card adopted from Horton and Horton (1991). All responses were coded using a 5-point Likert scale, with 1 representing strong disagreement and 5 representing strong agreement.\n\nPrior to the final data collection, the research instrument was subject to a pilot test to assess construct validity. Data were collected from 25 respondents through a purposive sampling technique. Cronbach Alpha was estimated to establish construct validity using IBM SPSS Statistics 27 (RRID: SCR_016479; Armonk, NY: IBM Corp). Cronbach alpha of the endogenous construct (willingness to sign the organ donor card = 0.875) and exogenous constructs (attitudes towards OTD=0.724& willingness to discuss OTD=0.867) were well above 0.7, indicating acceptable levels of internal consistency. Loadings of all factors and communalities were significantly greater than 0.5, and the \"Kaiser-Meyer-Olkin and Bartletts Test\" was significant (>0.8).\n\nThe negatively worded items were reverse coded and considered for final data analysis. IBM SPSS Statistics 27 (RRID: SCR_016479; Armonk, NY: IBM Corp) RRID: SCR_016479; Armonk, NY: IBM Corp) was used to undertake a descriptive analysis of the demographic variables and is presented in the results section. To test the hypotheses and perform the mediation analysis, the statistical package SmartPLS4 (RRID: SCR 022040) was used. PLS-SEM is becoming more popular as a statistical package due to its versatility and dependability in analyzing composite and empirical studies. Structural Equation Modelling performed in this study can also be undertaken by using jamovi (RRID:SCR_016142), which is a free source software.\n\n\nResults\n\nThe demographic characteristics of the participants were analysed using IBM SPSS Statistics 27 software (Table 1). For the complete dataset, see Underlying data (Nayak & Nayak, 2023). Of the 259 respondents, 173 (67%) were female and 171 were between 18 to 26 years of age. 113 respondents had enrolled or completed their Bachelor's education in the healthcare domain like medicine, life science, nursing, health science, and allied health (Table 1). All the participants reported that they are aware of organ and tissue donation but only 125 (41%) stated that they were aware of OTD (Table 2). A “chi-square test of independence” displayed that there was a significant association between education and awareness of the OTD act in India Χ2 (1, N = 259) = 6.980, p = 0.06).\n\nParticipants' knowledge of OTD was assessed by posing eight questions (Table 3). A majority (96.5%) of the participants were aware of the demand for transplants exceeding availability. They were also aware of the fact that many people were losing their lives due to the non-availability of organs to be transplanted (91.15%). Three questions were posed to the respondents to assess their knowledge of the implications of signing a donor card. The majority (95.8%) were aware they could specify the organs and tissues they want to donate on the donor card but only 33% of them knew that they could change their mind after signing the donor card. Two-thirds of the participants thought that the next of kin (family) must permit donation to occur even if the donor had signed the donor card. Participants were also assessed on their knowledge of how medical viability for donation is determined. More than half of the participants (51.7%) were not aware that the age or medical condition of the donor is important antecedent of becoming an organ donor. Whereas 82% of the participants knew that signing up for organ donation would not change the line of treatment they would receive in the future. Around 68% of the respondents believed that religious people would not oppose OTD. However, standard deviation and mean of the knowledge score was estimated to be 1.116 and 5.25.\n\nThe measurement model was evaluated to determine the constructs' reliability and validity. (Table 4) and the Structural Model evaluation is presented in Figure 2. First, the factor loadings of all items in the model were checked to ensure that they were greater than the minimum acceptable value of 0.5 (Hair et al., 2017). Vinzi et al. (2010) opine a minimum acceptable factor loading of 0.7 but in social science studies, researchers frequently obtain lower outer loadings. Instead of automatically eliminating the indicators, it would be better to assess the impact of their elimination on the improvement in the reliability and validity of the constructs. Hair et al. (2017) recommend the elimination of the indicators with factor loading in the range of 0.4 to 0.7 only if it increases the value of composite reliability (Average Variance Extracted) beyond the threshold value. In our research endeavour, the removal of item (A1, loading = 0.504 & A6, loading =0.431) had a significant influence on composite reliability and hence was eliminated.\n\n*** p < 0.01.\n\n** p < 0.1.\n\nCronbach's alpha, rho a, and composite reliability were used to assess reliability; statistical values were higher than the recommended threshold value of 0.7 (Wasko & Faraj, 2005). The value of rho_a was found to be in between composite reliability (Sarstedt et al., 2017) and Cronbach’s alpha, and was also above 0.7 indicating excellent reliability (Henseler et al., 2016). “Average Variance Extracted” (AVE) was higher than 0.5 hence establishing convergent validity. Fornell & Larcker method was employed to establish discriminant validity (Table 5).\n\nThe structural model reflects the hypothesised path of the research framework. R2, Q (Ahlawat et al., 2013), and the significance of the paths are used to evaluate the structural model. The R2 value, which indicates the strength of each structural path in the model, can be used to assess a model's goodness. Falk and Miller claim (1992), the R2 value should be equal to or above 0.1. This establishes the predictive capacity of the model. Q2 value is used to establish the predictive relevance of the endogenous construct. Q2 value above 0 indicates the predictive relevance of the construct. In the current study, both R2 and Q2 values are above this threshold value (Table 6) hence indicating the goodness of the model. Furthermore, the “model fit” was evaluated using the Standard Root Mean Square Residual (SRMR). The value of the SRMR residual was 0.084 which was well within an acceptable range (Hair et al., 2017).\n\nAbbreviation: BI, bias-corrected.\n\n*** p < 0.01.\n\n** p < 0.1.\n\nIn addition, the hypothesis was tested to explore the significance of the relationship. H1 evaluates if the attitude towards OTD has a significant impact on the intention to sign the donor card. Results revealed that attitude towards OTD has a significant impact on intention to sign the donor card (β = .258, t = 5.220, p < .001). Hence H1 was supported. H2 proposed an association between attitude towards OTD and willingness to discuss with family and was also supported (β = .407, t = 6.535, p < .001). Results also revealed that willingness to discuss with family had a significant positive association with intention to sign the donor card (β = .534, t = 9.851, p < .001). Table 6 shows the 95% confidence interval generated by the study of 5000 resamples. A confidence interval that is not zero indicates that there is a significant relationship.\n\nMediation analysis was performed to check if the willingness to discuss with family mediates the association between attitude towards OTD and willingness to sign the donor card. A complementary partial median is established (H4: (β = .217, t = 5.889, p < .001) which implies that willingness to discuss with family significantly mediates the association between attitude towards OTD and willingness to sign the donor card.\n\nTo explore if the attitude towards OTD varied across participants from the health science domain and engineering, management, and humanities, the Mann-Whitney U Test was utilized. The test revealed a significant difference in OTD among participants from the health science domain (Media = 30, n = 113) and engineering, management, and humanities (Media = 29, n = 146), U = 6838, z = 2.367, p = 0.018, r = 0.14). Hence, we can conclude that the discipline of education has a significant influence on attitude towards OTD. Even though education is determined to increase knowledge on OTD, it is suggested by Meier et al. (2000) that most donors do not explore organ donation before pledging to donate the organ.\n\nThe Important-Performance Matrix Analysis (IPMA) elucidates the relative importance and performance of exogenous (attitude towards OTD & willingness to discuss with family) and endogenous constructs (intention to sign the OTD card) in relation to one another. Total effects and index values represent their significance and performance. Importance reveals the overall effect on the endogenous variable. The performance demonstrates the potential of latent variable scores. The X and Y axes are used to quantify importance and performance. The total effect is represented by the X-axis, while performance is represented by the Y-axis. A construct performs better when it has a higher mean value. (Hair et al., 2016; Hock et al., 2010; Rigdon et al., 2011; Schloderer et al., 2014; Volckner et al., 2010) (Figure 3 and Table 7). The results of IPMA analysis reveal that willingness to discuss with family displays a high performance of 69.581 and a high total effect of 0.534 in comparison with the other exogenous (attitude towards OTD) displaying a performance of 83.028 and a total effect of 0.475. Hence a unit of increase in performance of attitude towards OTD enhances intention to sign donor card from 66.087 to 66.562. Similarly, an increase in one unit of construct, willingness to discuss with family would increase the performance of construct intention to sign OTD card by 0.534 points to 66.621 points. Figure 4 represents the IPMA map.\n\n\nDiscussion\n\nThis study intended to explore the knowledge of OTD across age groups in the Indian population. The goal was to assess the general public's knowledge and attitude toward organ donation. The findings show that most participants had heard about organ donation and had a favourable attitude toward it. These research findings are similar to results obtained by previous studies by Vijayalakshmi et al. (2016), Mithra et al. (2013), Sarveswaran et al. (2018). Results show that people are aware of OTD but only 41% were aware of the organ donation law in India. Awareness of THOA in 1994 was astonishingly low. The knowledge score was moderate across the population of the study.\n\nIn line with previous studies, we observed that the primary sources of information on organ donation were television and newspapers, healthcare service providers, and followed by social media and the internet. In line with the previous studies, healthcare service providers played an integral role in creating awareness of OTD (Vijayalakshmi et al., 2016; Narendran et al., 2022). They could be the primary motivators in raising awareness among their family, friends, relatives, and neighbours. A recent 5-year retrospective case record analysis revealed that only 10 (5%) of 205 patients diagnosed as brain dead had their organs donated (Sawhney et al., 2013). This study again highlights the lack of awareness of the concept of organ donation and the need for the relevant stakeholders to collectively work together to strengthen awareness of OTD. As a result, both governmental and non-governmental organizations should play an active role in raising public awareness about brain death. THOA was enacted in 1995, but only 42% of participants were aware of organ donation legislation. These findings were comparable to previous studies that found 5.7% (Vijayalakshmi et al., 2016) & 13.9% (Pouraghaei et al., 2015). The stakeholders could adopt television and digital campaigns to enhance awareness of OTD, the process involved, and THOA. According to the Global Overview report 2022, 35% of the Indian population resides in the urban landscapes of the country and most of this population has access to television, the internet, and social media (Digital 2022 Global Overview Report, 2022). Hence, emphasis on television and digital campaigns could contribute strongly to creating awareness and registering for OTD as most of the participants (96%) are aware that people are dying due to lack of availability of organs. In general, the donor will be given the organ donation card after signing it, and if the donor changes their mind about donating organs could tear up the organ donation card (Gungormüs & Dayapoglu, 2014). The majority of our study's participants (66%) believed that once they signed the organ donation card, they couldn't change their minds. As a result, these issues must be addressed when creating public awareness programs. Issues concerning the signing of organ donation cards should be clarified by the government and non-governmental organizations. 68% of all those surveyed believed that various religions oppose OTD. These findings were consistent with the documented literature, which indicated that religious beliefs were the most significant barrier to organ donation (Patthi et al., 2015; Vijayalakshmi et al., 2016). In India, the family traditionally looks after its members, even when they are sick. As a result, the consent of the next of kin is required for organ donation from a deceased donor (Ahlawat et al., 2013). Moreover, 61% of respondents agreed that knowing their family's wishes after their death was important. As a result, family members must have a positive attitude toward organ donation. Around one-third of the respondents thought that various religions opposed OTD. These findings echo the findings of the research endeavours of Vijayalakshmi et al. (2016) and El-Menyar et al. (2020). Religious prohibitions were reported as a cause of not donating an organ by Hameed et al. (2016).\n\nIn line with the previous research evidence (Vijayalakshmi et al., 2016; Pouraghaei et al., 2015; Narendran et al., 2022) it is proved that attitude toward organ donation is significantly associated to becoming an organ donor (Melissa et al., 2013; Teoh et al., 2020). In research studies undertaken in India, all have reported positive attitudes toward OTD and a considerable amount of awareness of OTD. The challenge encountered in developing regions like India is that despite the population being considerably aware of OTD, very few registered for organ donation. Having a positive attitude toward OTD is a significant antecedent to registering for OTD. The research undertaken by Topic et al. (2006) and Sengul and Sahin (2022) present evidence for the fact that the nature of education was significantly associated with attitude towards OTD. It was observed that health science professionals had a more positive attitude towards OTD in comparison to their colleagues from other professional disciplines. Our study echoes this evidence as it is observed that respondents from a medical and health science domain had a more positive attitude towards OTD. Hence there is a need to create awareness and build a positive attitude toward OTD among the non-health/medical science population as attitude defines the intention to be an organ donor.\n\nWillingness to discuss with family is reported to have a positive mediation between attitude towards OTD and intention to be an organ donor. Hence there is a need for government and non-governmental stakeholders to normalize the discussion on OTD in society. There appears to be a lack of consideration for the topic which creates a communication barrier (Feeley & Servoss, 2005). An OTD-friendly environment and family can increase the willingness to donate organs. Seeing family approval and willingness may help individuals make positive decisions about the subject (Sengul & Sahin, 2022) As a consequence, it is essential to explain the issue to all family members through community educational activities using plans and brochures for all family members. It may be beneficial to plan mass communication campaigns to strengthen acceptance of the topic among the population at large.\n\n\nConclusion\n\nThis study provides several insights into the OTD scenario in India. This study revealed that there is a general awareness of OTD among the Indian population but they lack clarity on certain specific issues. The majority of participants were unaware of the legislation or the donation process & clarity on the role of family when the donor had signed the donor card was ambiguous. It was established that the willingness of the donor to discuss with family played an instrumental role in strengthening the intention to donate an organ. Attitudes toward organ donation was significantly different among people with health science or medical backgrounds and from engineering, management, and humanities domains. This situation highlights the need for governmental and non-governmental institutions to take up the mandate of creating awareness that could lead to bridging the demand-supply gap of organs in India.\n\nThe cross-sectional research design serves as a limitation of this research endeavour. Further studies could adopt qualitative or experimental approaches to explore the rationale of OTD. Future studies could investigate if the knowledge, attitude towards OTD, and organ donation intention varied across Generation Z (born between 1996-2000) and Millennials (born between 1981 to 1995) (Thangavel et al., 2021). This will enable stakeholders to design appropriate campaigns and adopt the most appropriate media to create awareness of OTD thereby bridging the demand-supply gap.",
"appendix": "Data availability\n\nFigshare: Dataset, https://doi.org/10.6084/m9.figshare.22099580 (Nayak & Nayak, 2023).\n\nThis project contains the following underlying data:\n\n• Organ Donation Raw Data.xls\n\nFigshare: Dataset, https://doi.org/10.6084/m9.figshare.22099580 (Nayak & Nayak, 2023).\n\nThis project contains the following extended data:\n\n• Questionnaire with codes.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAhlawat R, Kumar V, Gupta AK, et al.: Attitude and knowledge of healthcare workers in critical areas towards deceased organ donation in a public sector hospital in India. The National Med. J. India. 2013; 26(6): 322–326.\n\nAlex P, Kiran KG, Baisil S, et al.: Knowledge and attitude regarding organ donation and transplantation among medical students of a medical college in South India. Int. J. Community Med. Public Health. 2017; 4(9): 3449–3454. 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Publisher Full Text\n\nMorgan S, Miller J: Communicating about gifts of life: The effect of knowledge, attitudes, and altruism on behavior and behavioral intentions regarding organ donation. J. Appl. Commun. Res. 2002; 30(2): 163–178. Publisher Full Text\n\nMeier DE, Schulz K, Kuhlencordt R, et al.: Effects of an educational segment concerning organ donation and transplantation. Transplant. Proc. 2000; 32: 62–63. PubMed Abstract | Publisher Full Text\n\nMorgan SE, Miller J: Beyond the organ donor card: The effect of knowledge, attitudes, and values on willingness to communicate about organ donation to family members. Health Commun. 2001; 14: 121–134.\n\nNational Organ and Tissue Transplant Organisation: Act and rules of transplant of human organs act (THOA).Reference Source\n\nNarendran V, Padmavathi S, Sangeetha S, et al.: Knowledge, awareness and attitude of eye donation among non-clinical staff of a tertiary eye hospital in South India. Indian J. Ophthalmol. 2022; 70(10): 3490–3495. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPatthi B, Jain S, Singla A, et al.: Beliefs and barriers for organ donation and influence of educational intervention on dental students: A questionnaire study. J. Indian Assoc. Public Health Dent. 2015; 13(1): 58. Publisher Full Text\n\nPouraghaei M, Tagizadieh M, Tagizadieh A, et al.: Knowledge and attitude regarding organ donation among relatives of patients referred to the emergency department. Emergency. 2015; 3(1): 33–39. PubMed Abstract\n\nRamadurg UY, Gupta A: Impact of an educational intervention on increasing the knowledge and changing the attitude and beliefs towards organ donation among medical students. J. Clin. Diagn. Res. 2014; 8(5): JC05–JC07. PubMed Abstract | Publisher Full Text\n\nRithalia A, McDaid C, Suekarran S, et al.: Impact of presumed consent for organ donation on donation rates: a systematic review. BMJ. 2009; 338: a3162. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSarveswaran G, Sakthivel MN, Krishnamoorthy Y, et al.: Knowledge, attitude, and practice regarding organ donation among adult population of urban Puducherry, South India. J. Educ. Health Promot. 2018; 7.\n\nSaleem T, Ishaque S, Habib N, et al.: Knowledge, attitudes and practices survey on organ donation among a selected adult population of Pakistan. BMC Med. Ethics. 2009; 10: 1–12. Publisher Full Text\n\nSengul S, Sahin MK: The willingness and attitudes of medical students regarding organ donation and transplantation: a cross-sectional study from Turkey. Rev. Assoc. Med. Bras. 2022; 68: 1631–1637. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSawhney C, Kaur M, Lalwani S, et al.: Organ retrieval and banking in brain dead trauma patients: Our experience at level-1 trauma centre and current views. Indian J. Anaesth. 2013; 57(3): 241–247. PubMed Abstract | Publisher Full Text\n\nSpigner C, Weaver M, Cardenas V, et al.: Organ donation and transplantation: ethnic differences in knowledge and opinions among urban high school students. Ethn. Health. 2002; 7(2): 87–101. PubMed Abstract | Publisher Full Text\n\nTeoh JYC, Lau BSY, Far NY, et al.: Attitudes, acceptance, and registration in relation to organ donation in Hong Kong: a cross-sectional study. Hong Kong medical journal = Xianggang yi xue za zhi. 2020; 26(3): 192–200. PubMed Abstract | Publisher Full Text\n\nThe Transplantation of the Human Organs Act: 1994. ([Last accessed on March 16, 2023). Reference Source\n\nThompson TL, Robinson JD, Kenny RW: Family conversations about organ donation. Prog. Transplant. 2004; 14(1): 49–55. Publisher Full Text\n\nTopic I, Brkljacic T, Grahovac G: Survey of medical students about attitudes toward organ donation. Dialysis & transplantation. 2006; 35(9): 571–574. Publisher Full Text\n\nTamuli RP, Sarmah S, Saikia B: Organ donation–“attitude and awareness among undergraduates and postgraduates of North-East India”. J. Family Med. Prim Care. 2019; 8(1): 130. Publisher Full Text\n\nThangavel P, Pathak P, Chandra B: Millennials and Generation Z: A generational cohort analysis of Indian consumers. BIJ. 2021; 28: 2157–2177. Publisher Full Text\n\nU.S. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau: National Survey of Organ Donation Attitudes and Behaviors. Rockville, MD: U.S. Department of Health and Human Services; 2013. Reference Source\n\nVijayalakshmi P, Sunitha TS, Gandhi S, et al.: Knowledge, attitude and behaviour of the general population towards organ donation: An Indian perspective. Natl. Med. J. India. 2016; 29(5): 257–261. PubMed Abstract\n\nVincent BP, Randhawa G, Cook E: Barriers towards deceased organ donation among Indians living globally: an integrative systematic review using narrative synthesis. BMJ Open. 2022; 12(5): e056094. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWasko MM, Faraj S: Why should I share? Examining social capital and knowledge contribution in electronic networks of practice. MIS Q. 2005; 29: 35–57. Publisher Full Text\n\nWatts G: Joseph Murray: innovative surgeon and pioneer of transplantation. Lancet. 2011; 377(9770): 987. Publisher Full Text\n\nWu AMS, Tang CS: Solving the dilemma: family communica-tion about organ donation among Chinese, Japanese, and Cau-casian American College students. J. Appl. Soc. Psychol. 2009; 39(7): 1639–1659. (1) (PDF) A Systematic Literature Review and Research Agenda for Organ Donation Decision Communication. [accessed Dec 22 2022]. Publisher Full Text Reference Source\n\nWorld Health Organization: Human organ and tissue transplantation.2020. Reference Source\n\nWorld Health Organization: The International report on Organ Donation and Transplantation Activities.2022. Reference Source"
}
|
[
{
"id": "171952",
"date": "12 May 2023",
"name": "Alok Atreya",
"expertise": [
"Reviewer Expertise My area of research is Forensic Medicine & Toxicology. Other broad areas of interest are injury",
"violence",
"trauma",
"abuse",
"medical ethics",
"medical education",
"forensic pathology",
"forensic anthropology",
"criminal law",
"etc."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAbstract: The abstract is well-structured, presenting the background, methods, and results. It provides a clear overview of the study's objectives and findings.\nIntroduction: The manuscript provides a clear and detailed introduction to the topic of organ donation and transplantation, including the current state of affairs, challenges faced, and existing initiatives undertaken by governments and NGOs to promote organ donation.\nMethodology: The methodology section is also comprehensive, describing the study design, data gathering, and data analysis techniques used. However, there are some areas where the manuscript could benefit from improvement or clarification.\nThe manuscript would benefit from a clear and concise research question, which is missing from the introduction section. While the overall goal of the study is clear, a specific research question would help to focus and guide the study and make the authors' aims and objectives more explicit.\n\nThe sampling technique used could be improved. The authors state that a purposive sampling approach was adopted due to the absence of a sampling frame, but it is unclear how the four shopping malls were selected. It would have been better to state clearly the criteria for selecting these malls and why they were chosen. Additionally, the sample size calculation could be explained more clearly and justified in the methods section.\n\nThe authors could provide more detail on the questionnaire used for data collection. While the items included in the questionnaire are briefly described in the methods section, a clearer explanation of how the questionnaire was developed and validated would help to establish its reliability and validity.\n\nThe authors should provide more detail on the data analysis methods used. While it is stated that SmartPLS4 and jamovi were used for data analysis, the statistical tests used, and their justification should be described in more detail.\nResults: This section is well-written and provides a comprehensive analysis of the research study findings. The authors use appropriate statistical methods to analyze the data and report their results in a clear and concise manner. However, it is essential to note that the manuscript section does not provide information on the sampling strategy used to select the participants, which can impact the generalizability of the results. Additionally, the authors do not mention any potential biases that may have affected the results, such as response bias or social desirability bias.\nDiscussion: There are also some limitations to the study that need to be considered. The cross-sectional research design can limit the ability to establish causal relationships or determine changes over time. Moreover, the study participants were only from urban areas, so the findings may not be generalizable to the entire population. Lastly, the manuscript did not provide detailed information on the sample size or the sampling procedure, which makes it difficult to evaluate the representativeness of the sample or the potential for bias.\nIn General: The manuscript has several strengths, including a clear and concise writing style, a comprehensive literature review, and a well-organized presentation of the study results. The authors also make some important recommendations for future research, including exploring the knowledge, attitudes, and intentions of organ donation across different generations and investigating the reasons for the low donation rates in India.\nOverall, the manuscript is well-written and provides valuable insights into the knowledge, attitudes, and intentions of organ donation in India. However, the limitations of the study should be considered, and future research should address these limitations to build on the findings presented in this manuscript.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9764",
"date": "14 Jun 2023",
"name": "smitha nayak",
"role": "Author Response",
"response": "Thank you for the feedback provided for our manuscript; each has significantly added value to it. We have responded to each one of them and presented our responses below: 1. Introduction: no changes suggested 2. Methodology: a. The research objective derived from the research questions has been incorporated in Pg 4 of the manuscript. The need for the study has been included as follows: \"Hence it is imperative to assess the current knowledge level, attitude, and willingness to register for organ donation among various age groups and whether it varies across the population with the discipline of education\" b. Sampling: Clarity on each point and the appropriate changes incorporated in the manuscript Mall identified: \"Footfalls are a metric that indicates the popularity of the mall and also reflects homogeneity in tenant mix and visitors to the mall (Mohan and Tandon, 2015). Hence 4 malls in each of the districts having the highest footfalls were identified to undertake the survey. Further, a simple random technique was employed to identify the malls in Dakshina Kannada and Udupi districts for data collection c: Sample size calculation: \"The sample size was calculated based on the number of items on the rating scale multiplied by 10 as proposed by Hair, Sarstedt, Ringle, & Gudergan(2017). Hence, The sample size was determined by multiplying the number of rating scale elements by ten [15] i.e. 15*10 = 150. Considering 10% of the unanswered sample (i.e.15) gives rise to 165 (150 + 15 = 165). Finally, 259 participant data were collected.\" 3: Questionnaire: Construct wise details have been presented in the Data Gathering section of the manuscript. The items of each construct ( detailed questionnaire) is uploaded in Figshare, hence publicly available. The DOI of the same has been mentioned in the manuscript. The reliability and validity of the scales was done through the pilot study, the results of which are presented in the \"Data Collection\" section of the manuscript. 4 PLS: as we have opted for a blend of probability and nonprobability sampling techniques, and the presence of a mediator in the conceptual framework, PLS-SEM was the tool chosen against Jamovi or AMOS. \"To test the hypotheses and perform the mediation analysis, the statistical package SmartPLS4 (RRID: SCR 022040) was used. PLS-SEM is becoming more popular as a statistical package due to its versatility and dependability in analyzing composite and empirical studies. Structural Equation Modelling performed in this study can also be undertaken by using jamovi (RRID:SCR_016142), which is a free source software.\" 5. Results: The biases are presented as limitations of the research work undertaken. 6. Discussion: Cross section research design: has been employed in the study. Experimental and Qualitative research has been suggested as a direction for future research. The results are generalizable as the scope and research setting are justified in the manuscript. Future research is suggested from a geographical perspective of the study."
}
]
},
{
"id": "171950",
"date": "16 May 2023",
"name": "Soumya Swaroop Sahoo",
"expertise": [
"Reviewer Expertise My areas of research are Non-Communicable Diseases (Cancer",
"Diabetes)",
"HIV",
"Tuberculosis",
"One Heath",
"and Health systems."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTitle:\nThe study was conducted in two districts of India, so writing it as attitude towards Organ Donation in India is misleading. The authors can write as \" South India\"\nAbstract:\nThe abstract is structured and well articulated. However, they need to mention the actual numbers and percentages in the results section rather than \"Awareness of organ donation law in India is low on specific issues and respondents from the health science & medicine discipline scored better on knowledge about organ donation. The findings show that most participants had heard about organ donation and had a favourable attitude toward it.\"\nIntroduction:\n\nThe introduction is extensive and aptly describes the background and rationale of the study.\nMethods:\nThe sample size calculation with formula needs justification.\n\nThe post positivism approach needs to be explained more to justify its use here.\n\nHow were the malls selected in the two cities? Justify.\n\nSince apparently malls have visitors from urban population, it should be mentioned in the limitations.\nResults:\nThe results are well described with the appropriate use of statistical tests.\n\n\"A “chi-square test of independence” displayed that there was a significant association between education and awareness of the OTD act in India Χ2 (1, N = 259) = 6.980, p = 0.06).\" - How was this significant as a p-value less than 0.05 is considered significant?\nDiscussion:\nThe discussion might include more studies conducted on the Indian population in recent times.\n\nBiases affecting the study results should be mentioned in the limitations.\nOverall:\nThe manuscript is well written with a comprehensive literature review, good statistical analysis, and clear interpretation of the results. However, the gaps and suggestions outlined above might be given consideration.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9690",
"date": "05 Jun 2023",
"name": "smitha nayak",
"role": "Author Response",
"response": "We thank you for your valuable feedback. We have discussed the feedback and incorporated changes, wherever necessary, in the manuscript. We present our response to your comments below: 1. Abstract: The quantified output is presented in the abstract and changes are incorporated in the manuscript. This has added value and brought clarity to the manuscript. Methods : 2. Sample size calculation. The sample size was calculated based on the number of items on the rating scale multiplied by 10 as proposed by Hair, Sarstedt,Ringle, & Gudergan(2017). The same has been incorporated in the manuscript and added to the reference list.(Hair JF Jr, Sarstedt M, Ringle CM, et al.: Advanced issues in partial least squares structural equation modeling. Sage Publications; 2017) 3. Post positivism approach: The philosophical assumption in the backdrop of Post positivism approach is that consent from the participants has been taken to uphold the nature of research ethics and it is primarily quantitative nature of inquiry. Hence, we have undertaken this research in Post positivism approach. The same has been incorporated in the manuscript. 4. Malls selection: Footfalls is a metric that indicates the popularity of the mall and also reflects homogeneity in tenant mix and visitors to the mall (Mohan and Tandon, 2015). Hence 4 malls in each district with the highest footfalls were identified to undertake the survey. Further, a simple random technique was employed to identify the malls for data collection. Mohan, M., & Tandon, K. (2015). Mall Management: An analysis of customer footfall patterns in Shopping Malls in India. International Journal of Scientific and Research Publications, 5(3), 1-15. 5. Limitations: Since apparently malls have visitors from the urban population, it should be mentioned in the limitations. This has been addressed and mentioned in the limitations section of the manuscript. 6. Results: The results are well described with the appropriate use of statistical tests. \"A “chi-square test of independence” displayed that there was a significant association between education and awareness of the OTD act in India Χ2 (1, N = 259) = 6.980, p = 0.06).\" - How was this significant as a p-value less than 0.05 is considered significant? Due apologies for the typo error. We have incorporated the changes. 7. Overall Structure : The purpose of the research is strengthened in the manuscript. We hope we have incorporated/justified the revisions made in the manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/12-463
|
https://f1000research.com/articles/10-946/v1
|
21 Sep 21
|
{
"type": "Research Article",
"title": "General public awareness, knowledge and attitude toward COVID-19 infection and prevention: a cross-sectional study from Pakistan",
"authors": [
"Beenish Fatima Alam",
"Abdullah A. Almojaibel",
"Khalid Aziz Ansari",
"Mohammad Haroon",
"Sara Noreen",
"Saman Tauqir",
"Khalid Almas",
"Faraz A. Farooqi",
"Saqib Ali",
"Beenish Fatima Alam",
"Abdullah A. Almojaibel",
"Khalid Aziz Ansari",
"Mohammad Haroon",
"Sara Noreen",
"Saman Tauqir",
"Khalid Almas",
"Saqib Ali"
],
"abstract": "Background: The aim of this study is to evaluate the knowledge, perceptions, and attitude of the public in Pakistan (using social media) towards COVID-19. Methods: A cross-sectional study was conducted amongst 1120 individuals nationwide. A self-developed, pre-tested questionnaire was used that comprised of sections covering demographic characteristics, medical history, hygiene awareness, COVID-19-related knowledge, and learning attitude. Descriptive statistics were used for frequencies, percentages, averages and standard deviations. Inferential statistics were done using the Student’s t-test and ANOVA. Results: The average age of participants was 31 years (range 18-60 years). In total 56 individuals (5%) had completed primary or secondary school education; 448 (40%) were employed (working from home) and 60% were jobless due to the COVID-19 crisis. Almost all the study subjects (1030 (92%)) were washing their hands multiple times a day. A total of 83% had awareness regarding quarantine time, 82% used face masks whenever they left their homes, 98% were aware of the origin of the disease, and 70% had knowledge regarding the most common symptoms of COVID-19. Conclusion: It can be concluded from the current study that female participants had higher level of education, and more awareness regarding the coronavirus. The majority of the participants followed proper hand washing regimes and washed their faces. Further knowledge and awareness should be promoted.",
"keywords": [
"COVID-19",
"Awareness",
"Knowledge",
"Perception",
"Pakistan",
"Pandemic"
],
"content": "Introduction\n\nThe first case of COVID-19 was identified within the Wuhan city of China in December 2019.1 By February, a tremendous increase in the number of cases and number of deaths due to Covid-19 started being reported. Due to the rapid spread of infection from China to different countries, and with the number of cases exceeding the cases reported by the Chinese government, COVID-19 was declared a global pandemic by the World Health Organisation in March 2020.2,3 This epidemic has now affected more than 200 different countries across the globe.4\n\nCOVID-19 is a highly contagious infection that spreads through human to human contact causing serious health problems within communities.5 Currently very little scientific information is available regarding this novel virus. However, it has been identified as an enveloped RNA virus that is further categorised into alpha, beta, gamma and delta.6 Depending upon the immune system of an individual it can cause symptoms ranging from mild to severe. Symptoms identified comprise of fever, cough, difficulty in breathing, loss of smell, while in extreme cases can lead to pneumonia, multi-organ failure and death.7 The rapid spread of this infection is principally through respiratory droplets of 5-10 μm in diameter, spread through the mouth or nose, when an infected person coughs or sneezes.8 A study conducted in Singapore has identified that these droplets can be transmitted across a distance of 4.5 metres.9,10 Moreover symptoms can be identified within a day or two after acquiring infection, extending up to 14 days.11\n\nThe first positive case of COVID-19 in Pakistan was identified on 26th February 2020. In order to control the spread of the disease, on 23rd March 2020 a complete lockdown was imposed throughout the country. This included closure of all the educational organizations that comprised of schools, colleges, and universities along with religious schools.12 All ceremonies and religious gatherings in any form were adjourned to prevent the spread of infection to the general public.13 It was highlighted that elderly people and individuals having systemic disease, such as heart disease, diabetes, cancer and respiratory disease, are at high risk of acquiring this infection, while children appear to be less susceptible towards this disease. Proper protocol must be followed to prevent the spread of this disease.14\n\nCurrently there is a secondary wave or surge reported from many parts of the world; therefore it is of great importance for the general public to have appropriate awareness regarding the signs and symptoms and the causative factors of this disease and preventive protocols that need to be followed, including social distancing, following proper hand hygiene protocol and use of face masks. As Pakistan is a developing country with limited resources, the country has introduced different strategies to increase the awareness of the general public. Therefore, this study was undertaken to analyse the level of awareness, knowledge and practices of the public of Pakistan using an online survey regarding COVID-19 and various measures to be undertaken to prevent the spread of this disease.\n\n\nMethods\n\nThis cross-sectional study was undertaken among the public of Pakistan using and online questionnaire. The questionnaire was sent to the general public through various social platforms (Whatsapp, Twitter, Emails, Facebook messengers).\n\nIndividuals of both genders, within the age group of 18 to 60 years of age, of all education levels were included in this survey. Informed consent was taken from all the participants before asking them to complete the survey. Responses were kept anonymous to maintain the confidentiality of the participants. Five to seven minutes were required to complete the survey.\n\nDue to complete closure of public places, an online survey was conducted using Google forms. Data was collected from May through to June 2020.\n\nThe questionnaire used for this study was developed by the authors and adapted from Ali et al.29 Before collecting the data, pilot testing of the questionnaire was carried out among 20 individuals (selected from social media groups within the community) to test the reliability and validity of the questionnaire. Following their responses, necessary corrections (simplification of terms) were carried out.\n\nThe questionnaire utilised for this study was divided into multiple sections as follows: demographic characteristics (gender, education level, income earned, job status); section related to health (presence of any systemic disease and smoking habits); hygiene awareness (frequency of washing hands and face, type of soap used, duration of hand washing, frequency of touching face); COVID-19 related knowledge (origin, symptoms and transmission route for COVID-19); measures taken for prevention against COVID-19 (knowledge regarding usage, indications and different types of face masks); and lastly learning attitudes regarding COVID-19. There were 7 main questions covering COVID-19 knowledge. Three of which had multiple correct answers, each correct answer was given 1 point and wrong answer counted as 0. Total maximum knowledge score was 16.\n\nSPSS version 22 was used for data analysis. Descriptive statistics including frequencies, percentages, means and standard deviations were used to determine demographical information, health history and knowledge related questions. Student’s t-test and ANOVA were used for comparing knowledge score with demographical information and awareness related responses. Multiple comparisons were done between demographics of participants in case of significant relation found. P-value <0.05 was considered as statistically significant. Univariate and multivariate regression analysis was used to investigate the factor associated with knowledge score. P-value 0.10 was considered as cut off for significant value for factors in univariate analysis.\n\nEthical permission was obtained from the Bahria Medical and Dental College Ethics Review committee to conduct the study (reference number ERC 55/2020). A participation consent statement was added before the survey as follows: “Your participation in this study is completely voluntary. There are no foreseeable risks associated with this project. However, if you feel uncomfortable answering any questions, you can withdraw from the survey at any point”. Participation in the survey was therefore taken as consent to participate.\n\n\nResults\n\nA total of 1,120 participants completed the questionnaire. Table 1 shows the demographic characteristics and health history of participants. Average age of participants was 31 years (ranged from 18 to 60 years). Of the sample, 52% were in age range of 30 to 45 years. Most of the participants were male (604; 54%); there were 516 (46%) women. Almost half of the participants had postgraduate degrees (526; 47%), 470 (42%) were college graduates and 6% had doctorates. Only 56 (5%) individuals had completed primary or secondary education and could read or write. A total of 448 (40%) individuals were employed (working from home), while more than half (60%) were jobless due to the COVID-19 crises. Most belonged to the lower income group ranging from 10,000 to 30,000 PKR. A total of 862 (77%) of the participants were free from any allergy or respiratory diseases, with only 10% suffering from seasonal allergies. Similarly, 840 (75%) participants expressed themselves as fit and medically healthy.\n\nMost of the participants (70%) claimed that they have good knowledge of novel COVID-19 disease. Mean knowledge score was 9.48±2.88 out of 16, which can be considered as good knowledge about the disease. Figure 1 shows the correct answer percentages of knowledge questions asked: 83% had awareness regarding the quarantine time; 82% used face masks whenever they left their homes; 98% were aware of the origin of the disease; fever and difficulty of breathing were correctly described as most common symptoms by 70%; 69% correctly stated that the disease can be transferred by touching each other or infected surfaces; and 21% stated that transmission of disease could be through running nose and aerosol.\n\nComparisons of mean knowledge score with demographic characteristics are shown in Table 2. There was no significant difference between male and female participant’s knowledge score (9.45 ± 2.8 and 9.51 ± 2.95, respectively; p = 0.86). Age showed significant variation with a higher mean score of knowledge obtained in the 30-45 age group (10.01 ± 2.46) and lower mean score obtained from younger individuals (9.04 ± 2.8) (p = 0.040). Postgraduate participants showed highest mean score (10.5 ± 2.88), although comparison with non-postgraduate groups was not significant (p-value 0.137). Those working from home have significantly higher mean score (9.78 ± 2.8) as compared to those who were not employed (8.02 ± 1.8) (p = 0.029). Participants with seasonal or medicinal allergies showed higher knowledge score (10.44 ± 2.8) than disease free participants, but the difference was not statistically significant (p = 0.32). Similarly, arthritis patients have higher knowledge of COVID-19 as compared to others but not significant (12 ± 3.66). The most stated source of getting information regarding COVID-19 was social media (89%), the television and radio (56%), followed by family friends (34%) and print media (newspapers; 30%) (Figure 2).\n\nTable 3 reveals the hand hygiene awareness of the participants. Almost all of the participants (1030; 92%) were washing their hands multiple times a day). Face washing as a part of Wadu (ablution before prayers) was observed by 504 (45%) individuals and 39% washed their face multiple times. Plain soap and antiseptic solution was found as most popular type of soap used for washing hands (426; 38% and 414; 37%, respectively). More than half (660; 59%) were aware regarding the hand washing technique.\n\nThose who wash their hands twice a day showed significantly higher knowledge scores (11.0 ± 3.6; p = 0.0001; Table 4). Those who washed their face multiple times also have significantly higher knowledge of COVID-19 (11.14 ± 2.7; p = 0.005). Duration of hand washing and awareness of the technique did not show any significant relation with knowledge score (p = 0.369 and p = 0.286, respectively).\n\nIn total 45% of the participants were afraid of COVID-19 and 47% would like to have more information about the virus and its development. The majority of participants (65%) agreed that the virus is deadly and is life threatening. Only 196 (18%) of the participants had a friend or relative infected with the disease (Table 5).\n\nMultiple liner regression showed that male gender (vs female, β – 0.319) and respondents earning between 30K to 50K (vs 10K-30K, β – 0.184) presented low knowledge score, whereas 30-45 year olds (vs 15-30 year, β – 1.148, P = 0.003) presented significantly highest knowledge scores. Age increases and knowledge score decreases β – 1.076 (Table 6).\n\n*Significant at 0.05, F = 2.575, p = 0.019, R2 = 0.054, R2 adjusted showed that regression had 3% predictive accuracy.\n\n\nDiscussion\n\nTo the best of author’s knowledge this is among the first studies evaluating the awareness, knowledge and preventive practice of the public in Pakistan during the pandemic. Overall, 70% of the public studied gave the correct answers related to knowledge of COVID-19. These results are in agreement with a study conducted in India where a knowledge rate of 74% has been reported,15 while it is comparatively less when compared with study conducted in China (90%).16 However these findings are higher when compared to the response received by a study conducted in Jordan 40%.17 The reason for such a high response rate within China may be due to difference in time and circumstance in which the study was conducted. On the contrary, in the current study the high response can be attributed to the campaigns related to COVID-19 awareness initiated by the Pakistani government just after the first cases started being reported within neighbouring countries and also possibly due to the fact that many participants had higher education levels that included 42% graduates and 47% postgraduates.\n\nThe commonest source of acquiring information related to COVID-19 was through social media (89%), followed by television/radio. Similar results had been revealed by a study conducted in China.16 The majority of participants (83%) knew that the incubation period for coronavirus is 14 days, whereas another study from China reported it as 2.5 days.18 However, the CDC also suggested it can be range from 2 to 14 days.19 Common symptoms of COVID-19 are fever, cough, fatigue and shortness of breath.20 However, elderly people with underlying medical condition, such as hypertension, heart disease, chronic obstructive pulmonary disease coronary patients and those with chronic respiratory disease and frontline health providers are at a greater risk of acquiring the infection.21\n\nIn total, 75% of participants from the current study had awareness regarding COVID-19 symptoms, while 82% knew the importance of wearing face masks as preventive measures, and 69% had sufficient knowledge regarding coronavirus being transmitted through different surfaces. Our findings are in line with another study conducted among Pakistani university students, their knowledge about incubation was lower at 53%, whereas the awareness with common symptoms was higher (93.7%).22 The transmission of COVID-19 can occur through direct or indirect close contact with the infected person or through discharge of saliva, and respiratory emissions or droplets which can be emitted from infected persons during coughing, sneezing or spiting.23,24 Respiratory droplets normally are greater than 5-10 μm and aerosol droplets are less than 5 μm in diameter; they can be transferred to any individual when a normal person comes in close contact with the infected person.25 Aerosol transmission awareness was noted to be significantly lower in this study (21%), which is in agreement with a study conducted in India.15 Hence, there is a need to increase the awareness level of people regarding the modes of transmission of COVID-19 and to acknowledge its significance.\n\nAnother study from China showed that 93% of study participants agreed that COVID-19 transmission can be prevented by thoroughly washing hands with soap.26 These facts agree with the findings of the study; 92% of the participants washed their hands multiple times a day. As a preventive practice using antibacterial soap was significantly associated with knowledge score (10.5 ± 3.41; p < 0.001) which is similar to a study conducted in Jordan where 87% adopted hand washing as a preventive measure.17 Almost 60% of participants in the present study were aware of hand washing technique. A former study concluded that washing hands with soap and water is enough to reduce the risk of viral infections and when it is practiced with the recommended protocol of hand washing technique it reduces the rate of transmission of COVID-19.27\n\nThe findings of the current study suggested that the majority of participants had good learning attitude towards COVID-19; however lower knowledge level and negative attitudes were also recorded. A total of 63% individuals were tired of listening and did not want further information about the virus. One reason may be that majority (78%) had no relative or friend who had been infected with the virus. Additional educational campaigns are needed for the general public for further guiding them regarding the mode of transmission, isolation period and the different adoptive preventive strategies (like social distancing, avoiding handshakes, wearing masks and gloves), along with the risk of personal and family infection with COVID-19. The strength of the current study was that it was a nationwide survey with a large sample, and that the research was conducted during the surging stage of the COVID-19 pandemic.\n\nThe study is not a true representative sample of Pakistan’s general population. It’s a convenience sample through social media, which has its own limitations. Social media statistics are dynamic and can change according to its popularity and due to specific group of users being educated and having access to that information. This is the reason most of the participants were graduates and above.\n\n\nConclusion\n\nIt can be concluded from the current study that female participants had a higher level of education, and more awareness regarding the coronavirus. The majority of the participants followed a proper hand washing regime and washed their face. It also highlighted the power of social media as the source of information. Further knowledge and awareness should be promoted. Future work should focus on a larger, national representative sample population.\n\n\nData availability\n\nHarvard Dataverse: General Public Awareness, Knowledge and Attitude toward COVID-19 infection and prevention: A cross sectional study from Pakistan, https://doi.org/10.7910/DVN/1K5LDD.28\n\nHarvard Dataverse: General Public Awareness, Knowledge and Attitude toward COVID-19 infection and prevention: A cross sectional study from Pakistan, https://doi.org/10.7910/DVN/1K5LDD.28\n\nThis project contains the following extended data:\n\n- Questionnaire\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "Acknowledgments\n\nThe authors are thankful to all the participants who participated contributed in this study. We are also grateful to all friends and family who provided support in the distribution of this online questionnaire.\n\n\nReferences\n\nAli S, Noreen S, Farooq I: COVID-19 and health care workers in Pakistan. Are we losing the fight? J Med Sci . 2020; 28(2): 186–188.\n\nCucinotta D, Vanelli M: WHO declares COVID-19 a pandemic. Acta Biomed. 2020; 91: 157–160. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAli S, Farooq I, Abdelsalam M, et al.: Current clinical dental practice guidelines and the financial impact of COVID-19 on dental care providers. European Journal of Dentistry . 2020. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTripathi R, Alqahtani SS, Albarraq AA, et al.: Awareness and Preparedness of COVID-19 Outbreak Among Healthcare Workers and Other Residents of South-West Saudi Arabia: A Cross-Sectional Survey. Front Public Health. 2020 Aug 18; 8: 482. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAhmed F, Ahmed N, Pissarides C, et al.: Why inequality could spread COVID-19. Lancet Pub Health. 2020; 5: e240. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Wilde AH, Snijder EJ, Kikkert M, et al.: Host factors in coronavirus replication. Curr Top Microbiol Immunol. 2018; 419: 1–42. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAhmed EF, Shehata MA, Elheeny AA: COVID-19 awareness among a group of Egyptians and their perception toward the role of dentists in its prevention: a pilot cross-sectional survey.\n\nHl W, Huangc J, Casper JPZ, et al.: Facemask shortage and the novel coronavirus disease (COVID-19) outbreak: reflections on public health measures. EClinicalMedicine. 2020; 100329: 21. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBourouiba L: Turbulent gas clouds and respiratory pathogen emissions: Potential implications for reducing transmission of Covid-19. JAMA . 2020. PubMed Abstract | Publisher Full Text\n\nLoh NW, Tan Y, Taculod J, et al.: The impact of high-flow nasal cannula (hfnc) on coughing distance: Implications on its use during the novel coronavirus disease outbreak. Can J Anaesth . 2020. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLabban L, Thallaj N, Labban A: Assessing the level of awareness and knowledge of COVID 19 pandemic among syrians. Arch. Med. 2020; 12(8). Publisher Full Text\n\nFarooq I, Ali S, Moheet IA, et al.: COVID-19 outbreak, disruption of dental education, and the role of teledentistry. Pak J Med Sci . 2020; 36(7): 1726–1731. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSalman M, Mustafa ZU, Asif N, et al.: Knowledge, attitude and preventive practices related to COVID-19: a cross-sectional study in two Pakistani university populations. Drugs Ther Perspect. 2020 May; 9: 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLabban L, Thallaj N, Labban A: Assessing the level of awareness and knowledge of COVID 19 pandemic among syrians. Arch Med. 2020; 12(2): 8. Publisher Full Text\n\nNarayana G, Pradeepkumar B, Ramaiah JD, et al.: Knowledge, perception, and practices towards COVID-19 pandemic among general public of India: A cross-sectional online survey. Curr Med Res Pract. 2020; 10(4): 153–159. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhong BL, Luo W, Li HM, et al.: Knowledge, attitudes, and practices towards COVID-19 among Chinese residents during the rapid rise period of the COVID-19 outbreak: a quick online cross-sectional survey. Int J Biol Sci. 2020; 16(10): 1745. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhader Y, Al Nsour M, Al-Batayneh OB, et al.: Dentists’ awareness, perception, and attitude regarding COVID-19 and infection control: cross-sectional study among Jordanian dentists. JMIR Public Health Surveill. 2020; 6(2): e18798. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi Q, Guan X, Wu P, et al.: Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia. N Engl J Med. 2020, Jan 29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCenters for Disease Control and Prevention. Symptoms of coronavirus. Accessed April 21, 2020. View in Article. 2020. Reference Source\n\nAli S, Noreen S, Farooq I, et al.: Risk assessment of health care workers at the frontline against COVID-19. Pak J Med Sci . 2020; 36(COVID19-S4): S99–S103. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPan A, Liu L, Wang C, et al.: Association of public health interventions with the epidemiology of the COVID-19 outbreak in Wuhan. China. Jama. 2020 May 19; 323(19): 1915–1923. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSalman M, Mustafa ZU, Asif N, et al.: Knowledge, attitude and preventive practices related to COVID-19: a cross-sectional study in two Pakistani university populations. Drugs Ther Perspect. 2020 May; 9: 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu J, Liao X, Qian S, et al.: Community transmission of severe acute respiratory syndrome coronavirus 2, Shenzhen, China, 2020.PubMed Abstract | Publisher Full Text | Free Full Text\n\nLuo L, Liu D, Liao X, et al.: Modes of contact and risk of transmission in COVID-19 among close contacts (pre-print). MedRxiv. 2020. Publisher Full Text\n\nInfection Prevention and Control of Epidemic-and Pandemic-prone Acute Respiratory Infections in Health Care.Geneva: World Health Organization; 2014. Reference Source\n\nGiao H, Han NTN, Van Khanh T, et al.: Knowledge and attitude toward COVID-19 among healthcare workers at District 2 Hospital, Ho Chi Minh City. Asian Pacific J Tropical Med. 2020; 13: 260. Publisher Full Text\n\nChaudhary NK, Chaudhary N, Dahal M, et al.: Fighting the SARS CoV-2 (COVID-19) pandemic with soap.2020. Publisher Full Text\n\nFarooqi F: General Public Awareness, Knowledge and Attitude toward COVID-19 infection and prevention: A cross sectional study from Pakistan. Harvard Dataverse, V1, UNF:6:eaVw+BRDoDM36rxmbuGufg== [fileUNF]. 2021. Publisher Full Text\n\nAli S, Alam BF, Farooqi F, et al.: Dental and Medical Students’ Knowledge and Attitude toward COVID-19: A Cross-Sectional Study from Pakistan. Eur J Dent. 2020 Dec 7; 14(S1): S105-12. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "96322",
"date": "14 Oct 2021",
"name": "Mohmed Isaqali Karobari",
"expertise": [
"Reviewer Expertise Dentistry",
"Endodontics",
"Restorative",
"Dental education",
"COVID"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript under review attempts to evaluate the general public awareness, knowledge, and attitude towards COVID-19 infection and prevention amongst the Pakistani population. In general, the manuscript captures the details of the study design and implementation of the project. All the sections of the manuscript are well written and concluded, although several limitations exist, and it has been presented in the manuscript. The study is of sound design and clear practical and clinical interest, and I suggest accepting this article with minor revisions.\n\nFollowing are the minor comments:\nAbstract:\nBackground: The authors have mentioned aims; either change the subheading to aims and add another subheading as background or write an introduction of the study.\n\nResults: Kindly mention the statistical significance.\nMethods:\nIs the study conducted in a Pakistani subpopulation or a Pakistani population?\n\nResults:\nThe description in the results section is a duplication of tables and figures. Kindly avoid the repetition of data that is already presented in the tables and figures.\nDiscussion:\nKindly avoid writing results in the discussion; the authors can mention the significant difference.\n\nWrite future recommendations.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9518",
"date": "05 Jun 2023",
"name": "Faraz Farooqi",
"role": "Author Response",
"response": "Abstract: Background: The authors have mentioned aims; either change the subheading to aims and add another subheading as background or write an introduction of the study. Response: separate section of background and aims has been added in the abstract section. Results: Kindly mention the statistical significance. Response: has been added. Methods: Is the study conducted in a Pakistani subpopulation or a Pakistani population? Response: the study was conducted on the Pakistani population, not a subpopulation. Results: The description in the results section is a duplication of tables and figures. Kindly avoid the repetition of data that is already presented in the tables and figures. Response: has been corrected. Discussion: Kindly avoid writing results in the discussion; the authors can mention the significant difference. Response: has been corrected. Write future recommendations. Response: Has been added."
}
]
},
{
"id": "94965",
"date": "15 Oct 2021",
"name": "Anand Marya",
"expertise": [
"Reviewer Expertise Orthodontics",
"oral health",
"dental public health"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI would like to thank the editor for inviting me to review this manuscript. I would also like to compliment the authors on a well-conducted study that is very relevant during the current pandemic.\nThe authors have made an effort to conduct a KAP study on the public in Pakistan to evaluate their response towards COVID-19. They conducted a survey using 1120 people for data collection and also ran the Student's t-test and ANOVA after the data collection. They concluded that female participants in the study had a higher awareness regarding the SARS-CoV2 pandemic and also found out that people generally had good awareness about hand hygiene methods.\nI only have a few suggestions to help improve the quality of the paper:\nPlease include a power of the sample part/discussion. Although the investigators have taken a sample of 1120, it would be a good idea to run a power of the sample test to demonstrate the population this sample would represent.\n\nPlease include a few points of collecting information online in the limitations section. Each study has its own limitations and online surveys generally have their own limitations and bias. Kindly elaborate on this in a separate section.\nAlso, you may find the following studies helpful to add to your discussion. The reason for using these studies is they are relevant to your paper and also would help you add to the discussion and limitations sections as both are online surveys on very closely related topics that have been published in high-impact journals.\n\nMarya et al., 20211: This study focuses on what measures are being taken to curtail the spread of COVID-19 by dentists to ensure no contact spread or cross-contamination occurs.\n\nAlbargi et al., 20212: This is a very important paper that highlights the attitude of the patients in many situations where they do not divulge proper information regarding their COVID-19 status. Again, this paper is very important in demonstrating the attitude of the general public towards COVID-19.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9519",
"date": "05 Jun 2023",
"name": "Faraz Farooqi",
"role": "Author Response",
"response": "I only have a few suggestions to help improve the quality of the paper: Please include a power of the sample part/discussion. Although the investigators have taken a sample of 1120, it would be a good idea to run a power of the sample test to demonstrate the population this sample would represent. Response: Power calculation has been included. Please include a few points of collecting information online in the limitations section. Each study has its limitations and online surveys generally have their own limitations and bias. Kindly elaborate on this in a separate section. Response: has been elaborated. Also, you may find the following studies helpful to add to your discussion. The reason for using these studies is they are relevant to your paper and also would help you add to the discussion and limitations sections as both are online surveys on very closely related topics that have been published in high-impact journals. Marya et al., 20211: This study focuses on what measures are being taken to curtail the spread of COVID-19 by dentists to ensure no contact spread or cross-contamination occurs. Albargi et al., 20212: This is a very important paper that highlights the attitude of the patients in many situations where they do not divulge proper information regarding their COVID-19 status. Again, this paper is very important in demonstrating the attitude of the general public toward COVID-19. Response: the suggested articles have been added."
}
]
}
] | 1
|
https://f1000research.com/articles/10-946
|
https://f1000research.com/articles/11-1582/v1
|
23 Dec 22
|
{
"type": "Research Article",
"title": "The performance of lipid profiles and ratios as a predictor of arterial stiffness measured by brachial-ankle pulse wave velocity in type 2 diabetic patients",
"authors": [
"Soebagijo Adi Soelistijo",
"Robert Dwitama Adiwinoto",
"Agung Pranoto",
"Deasy Ardiany",
"Agung Pranoto",
"Deasy Ardiany"
],
"abstract": "Background: Early identification of arterial stiffness in Type 2 diabetes mellitus (T2DM) patients before the manifestation of atherosclerosis would be clinically beneficial. Our study aimed to explore the correlation of lipid profiles and ratios with arterial stiffness, and construct a predictive model for arterial stiffness in T2DM patients using those parameters. Methods: One hundred and eighty-four adult T2DM patients in the diabetes outpatient clinic at the Dr. Soetomo general academic hospital were enrolled in this cross-sectional study in 2015 and 2019. Sociodemographic, glycosylated hemoglobin (HbA1c), lipid profiles, and brachial-ankle pulse wave velocity (ba-PWV) data were collected from all subjects. The subjects were divided into a group with arterial stiffness (ba-PWV > 18 m/sec) and without arterial stiffness (ba-PWV ≤ 18 m/sec). A correlation test was used to evaluate the association, and receiver operator characteristics (ROC) curves analysis were used to determine the cut-off value, sensitivity, and specificity. The risk analysis model was calculated using bivariate logistic regression analysis. Results: The group with arterial stiffness had higher lipid profiles: total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipid ratios. A significant positive correlation was found between TC, TG, LDL-C, and all lipid ratios with ba-PWV. A negative correlation was found between HDL-C and ba-PWV. All lipid ratio parameters can be used as predictors of arterial stiffness, especially non-HDL-C with cut-off value: 150 mg/dL (sensitivity 96.8% and specificity 52.9%) and TG/HDL-C ratio with cut-off value: 4.51 (sensitivity 81.0% and specificity 74.2%). Elevated TG/HDL-C ratio and non-HDL-C displayed higher risk (OR: 12.293 and 16.312; p < 0.05) of having arterial stiffness compared to other lipid ratios. Conclusions: Lipid profiles and lipid ratios, especially TG/HDL-C ratio and non-HDL-C, are potential biochemical markers for arterial stiffness in T2DM patients.",
"keywords": [
"dyslipidemia",
"arterial stiffness",
"cardiovascular disease",
"risk",
"type 2 diabetes mellitus"
],
"content": "Introduction\n\nType 2 diabetes mellitus (T2DM) is a major health concern and prevalence is increasing worldwide. More than 460 million people are already affected, or 9.3% of the global population, and there are projected to be around 578 million cases by 2030. Indonesia is among the top ten countries with the most prevalent occurrence of diabetes, estimated to be around 10.7 million cases in 2019 and projected to increase to 13.7 million in 2030 and to 16.6 million in 2045.1,2 The consequence of the growing rates of T2DM is the increase in diabetes-related complications, especially macrovascular and microvascular. The prevalence of macrovascular and microvascular complications was estimated to be 27.2% and 53.5%, respectively.3 However, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in T2DM patients.4 The economic impact of T2DM regarding the medical care costs and the indirect costs due to decreased productivity associated with diabetes-related morbidity is also significant.5\n\nCoronary artery disease, peripheral artery disease (PAD), heart failure, and cerebral infarction are the typical manifestations of atherosclerotic CVD (ASCVD) in T2DM. Abnormal lipid metabolism (dyslipidemia) is the main pathogenesis for the development of ASCVD; meanwhile dyslipidemia is common in T2DM patients, affecting 60–70% of T2DM.6 The association between cholesterol and the cardiovascular outcome is well established. Recently, many risk factors for CVD have been published in international studies, implying more complex lipoprotein disorders in atherosclerosis development. Lipid ratios (TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C) application, in terms of cardiovascular risk stratification and lipid-lowering therapy efficacy assessment, are promising options. Besides the advantage of being practical in clinical settings, changes in these ratios have indicated better measures of the reduction in cardiovascular risk compared with the conventional lipid parameters.7\n\nArterial stiffening depicts degenerative changes of the extracellular matrix (ECM) in the arterial media layer, marked with collagen deposition, cross-linking, and elastin fatigue fracture. From a pathological perspective, arterial stiffening is different from atherosclerosis. However, both processes commonly occur in the same vascular area, are part of the vascular aging process, and share the same risk factors. Moreover, several clinical studies have reported a significant association between arterial stiffness and the degree of atherosclerosis and also with the risk of cardiovascular event incidents.8 Early recognition of arterial stiffness in the high-risk population, such as T2DM, before the manifestation of clinical ASCVD, is substantially beneficial.9 Carotid-femoral pulse wave velocity (cf-PWV) represents primarily the aortic stiffness and is considered the gold standard for arterial stiffness measurement.10 Nowadays, ba-PWV has been widely used in clinical settings and it has strong positive association with cf-PWV. Because ba-PWV is easier to obtain and more convenient for patients, it could serve as an alternative to cf-PWV measurement.11,12\n\nSerum HDL-C, in the middle-aged and elderly population, has been associated with protection against arterial stiffness. Previous studies have also investigated the degree of association between a single atherogenic lipid parameter or ratio (the LDL-C, TG/HDL-C, and non HDL-C) with arterial stiffness. However, each of those studies claimed some lipid parameters or ratios superior to one another.9 Furthermore, the data regarding the use of those lipid ratios as a predictive biochemical marker for arterial stiffness in T2DM are lacking, especially in the Indonesian population.\n\n\nObjectives\n\nTherefore, this study aimed to explore the correlation of lipid profiles and ratios with arterial stiffness, construct a predictive model for arterial stiffness in T2DM patients, and ultimately analyze the performance (sensitivity and specificity) of the lipid ratios to detect arterial stiffness in T2DM patients.\n\n\nMethods\n\nThis study was approved by the ethical committee of Dr. Soetomo General Academic Hospital, Surabaya, Indonesia: 316/Panke.KKE/V/2015 (May 29th, 2015) and 1311/KEPK/V/2019 (July 20th, 2019). After receiving an explanation from the researchers about the research procedure, all eligible subjects gave written informed consent.\n\nThis was a cross-sectional design study conducted in the Endocrinology and Diabetes outpatient clinic at the Dr. Soetomo General Academic Hospital in Surabaya, Indonesia, during February–May 2016 and September–November 2019.\n\nThe sample size of this study was calculated using the following formula to determine the minimum sample needed.\n\nSignificance = 95%; power = 80%; correlation coefficient = 0.217 from previous study.9 Therefore, the minimum number of subjects for this study was 165. The subjects were recruited consecutively according to the inclusion and exclusion criteria. The inclusion criteria were adult patients (over 18 years of age) who had been diagnosed with T2DM. The exclusion criteria were current smoker, end-stage, or chronic kidney disease (CKD), subjects with active infection, known PAD, and subjects with a recent history of cerebral infarction (within 30 days).\n\nThe dependent variable was arterial stiffness measured by ba-PWV. The independent variables were lipid profiles (total cholesterol, triglyceride, HDL-C, LDL-C, and non-HDL-C) and lipid ratios (TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C).\n\nAll participants were subjected to complete history, physical examination, and ba-PWV measurement. Lipid profiles and HbA1c data were obtained from the recent blood biochemistry examination in the last three months from the medical record, should the data be available. Otherwise, a venous blood sample was collected and sent to the laboratory of Dr. Soetomo General Academic Hospital in Surabaya, Indonesia for biochemical analysis. The TC/HDL-C is the ratio of the value of TC levels divided with HDL-C levels. The TG/HDL-C ratio is the result of the value of TG levels divided with HDL-C levels. The LDL-C/HDL-C ratio is the result of the value of LDL-C levels divided with HDL-C levels. The Non-HDL cholesterol value was calculated from HDL-C subtracted with TC levels.13\n\nPulse wave velocity is calculated from the ratio of the distance between two measurement points divided by the time required for the pressure wave to travel the distance. The travel distance was defined as the measurement from the center of the brachial cuff to the center of the ankle cuff. The pulse transit time (PTT) was obtained from two peak points of the diastolic pulse wave.8,12 Brachial-ankle pulse wave velocity measurement was carried out using Va-Sera VS-1000 (Fukuda Denshi, Tokyo, Japan). The cut-off value of ba-PWV to define arterial stiffness is 18 m/sec.14\n\nData were analyzed using SPSS version 22.0 for Windows (IBM Corporation, New York, USA). Descriptive statistics for data that were normally distributed were expressed using mean and standard deviation, otherwise median and minimum maximum were used. An independent t-test or Mann–Whitney U-test was used to detect differences in lipid profile and lipid ratio values between groups with and without arterial stiffness. The correlation between HbA1c levels, lipid profiles, and lipid ratios with arterial stiffness was evaluated using Pearson or Spearman correlation test. Analysis of receiver operating characteristic curves (ROC) were used to determine the cut-off value, sensitivity, and specificity for each lipid ratio for arterial stiffness. Finally, bivariate logistic regression analysis was used to estimate risk prediction of lipid ratios against arterial stiffness in T2DM. Statistical significance was considered at p value < 0.05 and 95% confidence interval (CI).\n\n\nResults\n\nA total of 184 T2DM patients matched the inclusion criteria.15 There were no significant differences in the sociodemographic (age and sex) and clinical (hypertension and obesity) characteristics between groups with and without arterial stiffness (p > 0.05). The HbA1c levels in the group with arterial stiffness appeared to be higher than the group without arterial stiffness and the difference was significant (p = 0.038). The lipid profile result was significantly higher in the group with arterial stiffness (p < 0.05) except for the LDL-C levels (p = 0.261). The HDL-C levels were significantly lower in the group with arterial stiffness compared to the group without arterial stiffness (p < 0.05). Lipid ratio findings were also significantly higher in the group with arterial stiffness. The comparison is presented in Table 1.\n\n* Significant (p < 0.05).\n\nThe Spearman correlation test was used to evaluate the correlation between HbA1c, lipid profiles and lipid ratios with ba-PWV values since the ba-PWV values were not normally distributed. We did not find a significant correlation between HbA1c and ba-PWV (p > 0.05). The lipid profiles and lipid ratios were significantly correlated with ba-PWV (p < 0.05) with various degrees of correlation. A negative correlation was found between HDL-C levels and ba-PWV values (ρ = -0.221) implying an inverse correlation. Lipid profiles (TC, TG, HDL-C, and LDL-C) had a weak correlation with ba-PWV when used alone. However, an increase in the correlation coefficient was observed when used as lipid ratios (TC/HDL-C, TG/HDL-C, LDL-C/HDL-C, and non HDL-C). The TC/HDL-C ratio demonstrated a moderate correlation (ρ = 0.419) among other lipid ratios. The correlation is described in Table 2.\n\n* Significant (p < 0.05).\n\nAn ROC analysis was applied for lipid ratios to arterial stiffness as the outcome of this study (Figure 1). Overall lipid ratios TC/HDL-C, TG/HDL-C, and non-HDL-C had a good performance to be used as predictive models (AUC > 0.7), except for LDL-C/HDL-C. Non-HDL-C had a sensitivity of 96.8% for arterial stiffness; however, the specificity was 52.9% with cut-off value 150 mg/dL. TG/HDL-C ratio had a specificity of 81.0% and sensitivity of 74.2% with cut-off value 4.51. The characteristics of the lipid ratios are presented in Table 3.\n\n* Significant (p < 0.05).\n\nThe cut-off value of each lipid ratio derived from the ROC curve was used to determine the presence of arterial stiffness. Values above the cut-off point were classified as elevated, while values below or equal to the cut-off point were classified as normal. All lipid ratios demonstrated significant association as a risk factor for arterial stiffness in T2DM patients through bivariate logistic regression analysis (OR > 1; p < 0.05). Elevated TG/HDL-C ratio and non-HDL-C displayed higher risk (OR 12.293 and 16.312) of having arterial stiffness compared to elevated TC/HDL-C or LDL-C/HDL-C ratio (OR 5.347 and 4.502). The risk analysis model of the lipid ratios is presented in Table 4.\n\n* Significant (p < 0.05).\n\n\nDiscussion\n\nTo our knowledge, our present study is the first to evaluate not only the correlation of lipid ratios with arterial stiffness in T2DM patients but also define the cut-off value of lipid ratios which might contribute new insight in managing dyslipidemia and CVD risk in T2DM. The main findings of our study were: 1) the lipid ratios were correlated with arterial stiffness; 2) the lipid ratios, especially TG/HDL-C ratio and non-HDL-C, had good sensitivity to detect arterial stiffness; 3) elevated TG/HDL-C ratio and non HDL-C levels increased the risk of having arterial stiffness in T2DM. These findings indicate that lipid ratios are independently associated with the risk of arterial stiffness in the T2DM population.\n\nAtherosclerosis is the main pathogenesis of CVD; however, early atherosclerosis is asymptomatic, therefore the majority goes undetected in the early stages. Arterial stiffness is involved in these early stages of atherosclerosis. Even though the relationship between arterial stiffness and atherosclerosis is still unclear, the interaction between the two may involve several complex hemodynamic, mechanical, metabolic, and enzymatic pathways. The increase in arterial stiffness results in increased blood pressure which promotes arterial remodeling leading to atherosclerosis.16 The increase in intra-luminal pressure also promotes atheroma formation and deposition of excessive collagen in arterial walls.8 These mechanisms are even more pronounced in T2DM in which endothelial dysfunction, a pivotal event in the initiation of atherosclerosis, is accelerated by the presence of hyperglycemia and advanced glycation end products (AGEs).17 Moreover, T2DM is characterized by abnormal metabolism of lipoprotein which contributes to the pathomechanism of atherosclerosis. Therefore, the detection of arterial stiffness in T2DM before the development of clinical ASCVD is crucial.\n\nDyslipidemia and DM commonly occur together, affecting 60–70% of people with T2DM. The pathophysiology of dyslipidemia in T2DM is complex, involving a different number of abnormalities. The key abnormality is the increased production of very low-density lipoprotein (VLDL) by the liver, which is commonly found as elevated TG levels. Elevated TG-rich lipoproteins will affect other lipoproteins and result in lower Apo A-I and HDL-C levels. Increased LDL-C association with CVD is well established in T2DM patients, as in the non-diabetic population. However, a significantly reduced LDL-C still carries residual CVD risk in T2DM.18 Therefore, a new CVD risk predictor is needed, and lipoprotein ratios can provide a better picture of the complex metabolic and clinical interactions between conventional lipid profile parameters. This is consistent with our findings in which lipid ratios showed a higher correlation with ba-PWV compared to conventional lipid profile parameters alone.\n\nIn our study, a significant correlation between TG/HDL-C ratio and arterial stiffness were observed (ρ = 0.326). Moreover, the TG/HDL-C ratio of > 4.51 predicts arterial stiffness with a sensitivity of 74.2% and specificity of 81.0%. An elevated TG/HDL-C ratio also increased the risk for arterial stiffness (OR: 12.293; 95% CI: 4.996–30.247). These findings are consistent with the study conducted by Chen & Dai19 and Zhao et al.9 which found that TG/HDL-C ratio is positively correlated with ba-PWV, but the participants of those studies were not limited to T2DM patients. The TG/HDL-C ratio has long been associated with insulin resistance and cardiometabolic risk. Insulin resistance states and chronic hyperinsulinemia induce the local activity of the renin-angiotensin-aldosterone system, followed by the expression of angiotensin II receptors in vascular tissue, resulting in vessel wall hypertrophy, fibrosis, and reduced arterial elasticity. Furthermore, insulin resistance is strongly associated with endothelial dysfunction, marked with an imbalance between nitric oxide (NO) and endothelin-1, two important determinants of arterial stiffness.8,20\n\nOur present study found that non-HDL-C positively correlated with arterial stiffness, and non-HDL-C levels of >150 mg/dL predict arterial stiffness with a sensitivity of 96.8% and specificity of 52.9%. An elevated non-HDL-C level also increased the risk for arterial stiffness (OR: 16.312; 95% CI: 3.760–70.780). These findings are similar to previous studies by Bando et al.21 and de Oliveira et al.22 which reported that elevated non-HDL-C levels are associated with an increased risk of arterial stiffness. Unlike LDL-C, the non-HDL-C represents the cholesterol content in all the atherogenic lipoproteins, namely: VLDL-C, intermediate-density lipoprotein cholesterol (IDL-C), and lipoprotein (a) cholesterol.23 In T2DM patients, non-HDL-C levels emphasize the role of the TG-rich lipoproteins in the development of arterial stiffness. The TG-rich lipoproteins through the TG hydrolysis process by lipoprotein lipase (LPL) contribute to low-grade inflammation of the arterial wall.24 Inflammation has a pivotal role in both arterial stiffening and atherosclerosis.25 In an in vitro study, C-reactive protein (CRP) decreased endothelial NO synthase (NOS) secretion and activity, resulting in “functional” arterial stiffening. Furthermore, inflammation may result in dysregulation between elastin breakdown and production. Some elastolytic enzyme expressions i.e. matrix metalloproteinase-9, are induced by pro-inflammatory cytokines.8\n\nOur present study was limited by its cross-sectional design in nature. Other factors which might affect the association between lipid profiles or ratios and arterial stiffness, such as race-ethnicity, duration of diabetes, and medications (statins, antihypertensive, and antidiabetics), were not controlled for in this study; therefore, a bias is likely to be present.\n\n\nConclusions\n\nLipid profiles and lipid ratios, especially TG/HDL-C ratio and non-HDL-C, are potential biochemical markers for arterial stiffness in T2DM patients. Type 2 DM patients with arterial stiffness were likely to have elevated lipid profiles and lipid ratios. We recommend further research with a better design (cohort) and larger scale before applying these parameters in clinical practice.",
"appendix": "Data availability\n\nFigshare: Underlying data for ‘The performance of lipid profiles and ratios as a predictor of arterial stiffness measured by brachial-ankle pulse wave velocity in type 2 diabetic patients’. https://doi.org/10.6084/m9.figshare.21572874. 15\n\nFigshare: STROBE checklist for ‘The performance of lipid profiles and ratios as a predictor of arterial stiffness measured by brachial-ankle pulse wave velocity in type 2 diabetic patients’. https://doi.org/10.6084/m9.figshare.21572874. 15\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nKhan MAB, Hashim MJ, King JK, et al.: Epidemiology of type 2 diabetes–global burden of disease and forecasted trends. J. Epidemiol. Glob. Health. 2020 [cited 2022 Nov 8]; 10(1): 107–111. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaeedi P, Petersohn I, Salpea P, et al.: Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes Res. Clin. Pract. 2019 [cited 2022 Nov 8]; 157: 107843. PubMed Abstract | Publisher Full Text\n\nLitwak L, Goh SY, Hussein Z, et al.: Prevalence of diabetes complications in people with type 2 diabetes mellitus and its association with baseline characteristics in the multinational A1chieve study. Diabetol. Metab. Syndr. 2013 [cited 2022 Nov 8]; 5(1): 1–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEinarson TR, Acs A, Ludwig C, et al.: Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc. Diabetol. 2018; 17(1): 83. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLeon BM, Maddox TM: Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research. World J. Diabetes. 2015 [cited 2022 Nov 8]; 6(13): 1246–1258. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLow Wang CC, Hess CN, Hiatt WR, et al.: Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus–mechanisms, management, and clinical considerations. Circulation. 2016 [cited 2022 Nov 8]; 133(24): 2459–2502. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPereira T: Dyslipidemia and cardiovascular risk: lipid ratios as risk factors for cardiovascular disease. Dyslipidemia-From Prevention to Treatment. 2012; 14: 279–302. Publisher Full Text\n\nPalombo C, Kozakova M: Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vasc. Pharmacol. 2016 [cited 2022 Nov 8]; 77: 1–7. PubMed Abstract | Publisher Full Text\n\nZhao W, Gong W, Wu N, et al.: Association of lipid profiles and the ratios with arterial stiffness in middle-aged and elderly Chinese. Lipids Health Dis. 2014 [cited 2022 Nov 8]; 13(1): 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMancia G, Fagard R, Narkiewicz K, et al.: 2013 ESH/ESC practice guidelines for the management of arterial hypertension: ESH-ESC the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press. 2014 [cited 2022 Nov 8]; 23(1): 3–16. Publisher Full Text\n\nTanaka H, Munakata M, Kawano Y, et al.: Comparison between carotid-femoral and brachial-ankle pulse wave velocity as measures of arterial stiffness. J. Hypertens. 2009 [cited 2022 Nov 8]; 27(10): 2022–2027. PubMed Abstract | Publisher Full Text\n\nBaier D, Teren A, Wirkner K, et al.: Parameters of pulse wave velocity: determinants and reference values assessed in the population-based study LIFE-Adult. Clin. Res. Cardiol. 2018 [cited 2022 Nov 8]; 107(11): 1050–1061. PubMed Abstract | Publisher Full Text | Free Full Text\n\nArtha IMJR, Bhargah A, Dharmawan NK, et al.: High level of individual lipid profile and lipid ratio as a predictive marker of poor glycemic control in type-2 diabetes mellitus. Vasc. Health Risk Manag. 2019; 15: 149–157. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTomiyama H, Matsumoto C, Shiina K, et al.: Brachial-ankle PWV: current status and future directions as a useful marker in the management of cardiovascular disease and/or cardiovascular risk factors. J. Atheroscler. Thromb. 2016 [cited 2022 Nov 9]; 23(2): 128–146. Publisher Full Text\n\nSoelistijo SA, Adiwinoto RD, Pranoto A, et al.:Soelistijo2022_Lipid ratios & ba-PWV data.xlsx. [Dataset]. figshare. 2022. Publisher Full Text\n\nHansen L, Taylor WR: Is increased arterial stiffness a cause or consequence of atherosclerosis? Atherosclerosis. 2016 [cited 2022 Nov 12]; 249: 226–227. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKolluru GK, Bir SC, Kevil CG: Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing. Calvert JW, editor. Int. J. Vasc. Med. 2012; 2012: 918267. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWarraich HJ, Rana JS: Dyslipidemia in diabetes mellitus and cardiovascular disease. Cardiovasc. Endocrinol. 2017 [cited 2022 Nov 12]; 6(1): 27–32. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen C, Dai JL: Triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio and arterial stiffness in Japanese population: a secondary analysis based on a cross-sectional study. Lipids Health Dis. 2018 [cited 2022 Nov 13]; 17(1): 130–139. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMulè G, Nardi E, Geraci G, et al.: The relationships between lipid ratios and arterial stiffness. J. Clin. Hypertens. 2017 [cited 2022 Nov 13]; 19(8): 777–779. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBando Y, Wakaguri H, Aoki K, et al.: Non-high-density cholesterol level as a predictor of maximum carotid intima-media thickness in Japanese subjects with type 2 diabetes: a comparison with low-density lipoprotein level. Diabetol. Int. 2016; 7(1): 34–41. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Oliveira AR , Mourao-Junior CA, Magalhães GL, et al.: Non-HDL cholesterol is a good predictor of the risk of increased arterial stiffness in postmenopausal women in an urban Brazilian population. Clinics. 2017 [cited 2022 Nov 13]; 72: 106–110. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVirani SS: Non-HDL cholesterol as a metric of good quality of care: opportunities and challenges. Tex. Heart Inst. J. 2011; 38(2): 160–162. PubMed Abstract\n\nNordestgaard BG: Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology. Circ. Res. 2016 [cited 2022 Nov 13]; 118(4): 547–563. Publisher Full Text\n\nArdiany D, Pranoto A, Soelistijo SA, et al.: Association between neutrophil–lymphocyte ratio on arterial stiffness in type-2 diabetes mellitus patients: a part of DiORS Study. Int. J. Diabetes Dev. Ctries. 2022; 42(2): 305–312. Publisher Full Text"
}
|
[
{
"id": "169341",
"date": "16 May 2023",
"name": "Martin Haluzík",
"expertise": [
"Reviewer Expertise diabetes",
"obesity",
"insulin resistance"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nEarly identification of arterial stiffness in Type 2 diabetes mellitus (T2DM) patients before the signs of overt atherosclerosis would be clinically beneficial. Current study aimed to explore the correlation of lipid profiles and ratios with arterial stiffness, and construct a predictive model for arterial stiffness in T2DM patients using those parameters. The study included one hundred and eighty-four adult T2DM patients in the diabetes outpatient clinic at the Dr. Soetomo general academic hospital in 2015 and 2019. Sociodemographic, glycosylated hemoglobin (HbA1c), lipid profiles, and brachial-ankle pulse wave velocity (ba-PWV) data were collected from all subjects. The subjects were divided into a group with arterial stiffness (ba-PWV > 18 m/sec) and without arterial stiffness (ba-PWV ≤ 18 m/sec). A correlation test was used to evaluate the association, and receiver operator characteristics (ROC) curves analysis were used to determine the cut-off value, sensitivity, and specificity. The risk analysis model was calculated using bivariate logistic regression analysis.\nThe group with arterial stiffness had higher lipid profiles: total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipid ratios. A significant positive correlation was found between TC, TG, LDL-C, and all lipid ratios with ba-PWV. A negative correlation was found between HDL-C and ba-PWV. All lipid ratio parameters can be used as predictors of arterial stiffness, especially non-HDL-C with cutoff value: 150 mg/dL (sensitivity 96.8% and specificity 52.9%) and TG/HDL-C ratio with cut-off value: 4.51 (sensitivity 81.0% and specificity 74.2%). Elevated TG/HDL-C ratio and non-HDL-C displayed higher risk (OR: 12.293 and 16.312; p < 0.05) of having arterial stiffness compared to other lipid ratios. Lipid profiles and lipid ratios, especially TG/HDL-C ratio and non-HDL-C, are potential biochemical markers for arterial stiffness in T2DM patients\nThis is an interesting study on a reasonable number of patients. The paper is well written and the results are appropriate.\nI have only one minor comment: is there any reason why the authors included only lipids to their estimation. Why not include e.g. HbA1c and body weight as another important and easily obtainable parameters?\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "174157",
"date": "30 May 2023",
"name": "Agata Stanek",
"expertise": [
"Reviewer Expertise vascular medicine",
"PAD",
"thromboembolism"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study aimed to explore the correlation of lipid profiles and ratios with arterial stiffness, construct a predictive model for arterial stiffness in T2DM patients, and ultimately analyze the performance (sensitivity and specificity) of the lipid ratios to detect arterial stiffness in T2DM patients. This was a cross-sectional design study conducted in the Endocrinology and Diabetes outpatient clinic at the Dr. Soetomo General Academic Hospital in Surabaya, Indonesia, during February–May 2016 and September–November 2019.\nIt is quite an interesting paper. The Authors have presented sufficient data. The appropriate tables and figures have been provided. The article is easy to read and logically structured. The authors used appropriate statistical methods. The conclusions are consistent with the presented evidence and arguments.\nThe Authors should address the following issues:\nHow many patients have metabolic syndrome? We know that metabolic syndrome (MS) is not a single disease but a cluster of metabolic disorders associated with increased risk for the development of diabetes mellitus and its complications. Please discuss this issue and cite the newest papers in this field.\n\nPlease describe more precisely the measurement of arterial stiffness (according to which recommendations f.e.\n\nthe measurement was carried out in appropriate conditions, such as, among others: a quiet, dry room, ensuring thermal comfort; moreover, the measurement should be carried out after a ten-minute rest in a lying position. The BP value and heart rate (HR) should also be taken into account during the interpretation of the PWV value, as these parameters can influence the PWV measurement result\n\n{doi: 10.1161/HYP.0000000000000033]\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9728",
"date": "29 Nov 2023",
"name": "Robert Dwitama Adiwinoto",
"role": "Author Response",
"response": "1. We appreciate the reviewer's feedback regarding the prevalence of metabolic syndrome in our research subjects. We aware that metabolic syndrome is a cluster of metabolic disorders independently associated with the development of diabetes-related complication. As a matter of fact, we have considered the components of metabolic syndrome (obesity, hypertension, and dyslipidemia) in our present study. However, we did not consider it as a condition per se; therefore, we described it in the table 1, using the latest criteria of metabolic syndrome as a reference in our revised paper. We also reevaluate how the presence of metabolic syndrome might affect the main findings of our study using multivariate analysis. 2. We appreciate the reviewer's feedback regarding the measurement of arterial stiffness using the ba-PWV method. As a matter of fact, we have the ba-PWV measured under appropriate conditions, as mentioned by the reviewer. However, we did not state those conditions in the methods section; therefore, we added the procedure of ba-PWV measurement accordingly in the revised paper."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1582
|
https://f1000research.com/articles/12-595/v1
|
02 Jun 23
|
{
"type": "Research Article",
"title": "Association of elevated IL-6 with poor glycemic control in periodontitis patients",
"authors": [
"V. Kalaivani",
"Y. Pradeep Kumar",
"K. Rajapandian",
"Harinath Parthasarthy",
"Raghavendra Vamsi Anegundi",
"Abedalrahman shqaidef",
"Harshit Atul Kumar",
"Alberto Ibanez Fernandez",
"Divya VC",
"B Shivprasad Rai",
"V. Kalaivani",
"Y. Pradeep Kumar",
"K. Rajapandian",
"Harinath Parthasarthy",
"Raghavendra Vamsi Anegundi",
"Abedalrahman shqaidef",
"Alberto Ibanez Fernandez",
"Divya VC",
"B Shivprasad Rai"
],
"abstract": "Background: Interleukin-6 (IL-6) is a proinflammatory cytokine expressed in numerous chronic inflammatory diseases whose ability to alter the pathophysiology and progression of periodontitis is well documented. Further its role in diabetes mellitus by creating an insulin resistance responsible for poor glycemic control is also being evaluated. The aim was to compare the levels of IL-6 in gingival crevicular fluid in periodontitis patients with and without diabetes and to analyze these levels in patients with poor glycemic control (HBA1c), in order to assess its role in the progression of periodontal destruction. Methods: 60 chronic periodontitis patients confirmed with CPITN index of age group 30-70 years were enrolled for the study. GCF samples from 30 patients with diabetes confirmed using HBA1c reports and 30 without diabetes using Cimasoni method were collected and stored at -70degreescelsiusand subjected to ELISA for IL-6 using krishgen human IL-6 ELISA kit as per manufacturer's instruction. Descriptive and inferential statistics were used using SPSS software. Results: While the diabetic group readings ranged from 4.4 Pg/µl to 7.0 Pg/µl with a mean of 5.8pg/µl, the non- diabetic group ranged from 1.5 Pg/µl to 4.8 Pg/µl with a mean value of3.24 pg/µl. There was a prominent increase in the IL-6 levels in diabetic when compared to non- diabetic which was statistically significant with p value < 0.001. Further, among the diabetic groups, patients with poor HBA1c with reading more than 7.7% showed a significant increase in IL-6 levels when compared to below 6.8%. Conclusions: The IL-6 levels in GCF were increased in chronic periodontitis patients with diabetes and more so in patients with poor glycemic control when compared to non-diabetic group. Therefore, periodontitis along with diabetes can play a major role in the inflammatory response within the periodontium.",
"keywords": [
"Periodontitis",
"Diabetes",
"ELISA",
"gingival crevicular fluid",
"Interleukin-6"
],
"content": "Introduction\n\nPeriodontitis is a common inflammatory condition of the periodontium that affects 20–50% of the world’s population.1 Its etiology is linked to a specific or group of specific periodontal microorganisms, and it causes bone loss and loss of tooth attachment. Porphyromonas gingivalis, Tannerella forsynthesis, Prevotella intermedia are few periodontal pathogens which are known to invade the cells of periodontium, possess the ability to activate the immune cells such as monocyte and macrophage and hence ensue an increased production of inflammatory mediators like Interleukin-6 (IL-6), Tumor necrosis factor alpha (TNF α) and IL-1 in both systemic and local environment.2,3\n\nThese inflammatory mediators are encountered in high levels in gingival crevicular fluid (GCF), saliva, serum and inflamed gingival tissues in patients with periodontitis.4,5 Increased IL-6 levels can affect the activities of cells such as leukocytes, osteoclasts and osteoblasts, therefore, affecting the remodeling of tissues, there by responsible for alveolar bone resorption in periodontitis patients.6–9 Further, they are also accountable for mediating MMPs and other collagenolytic enzymes,10,11 and hence contributing to additional loss of tooth supporting collagenous structures.12,13\n\nIL-6 and C-reactive protein are demonstrated as major inflammatory indicators of systemic inflammation. Amidst the diverse inflammatory mediators, IL-6 is of particular importance. Being a multifunctional cytokine, it performs a salient role in proliferation and differentiation of hematopoietic stem cells, T and B cells, stimulate hepatic CRP in liver, also has it influences on nerve cells, hepatocytes, keratinocytes, renal mesangial cells, megakaryocytes and myeloma/plasmacytoma cells to name a few. As a result, IL-6 plays a significant part in how the body reacts to infection, inflammation, and tissue damage.14\n\nMeanwhile, studies have documented the involvement of deregulation of IL-6 gene expression in the pathogenesis of polyclonal and monoclonal B cells abnormalities, namely rheumatoid arthritis and multiple myeloma. Additionally, researchers have also observed higher circulating levels of IL-6 in obesity, diabetes and cardiovascular diseases amongst others.15 Furthermore, records do suggest its role in glucose and lipid metabolism, thereby16 increase in circulating IL-6 levels have shown to aggravate the glycemic status by enhancing the insulin resistance.17\n\nLiterature suggests that, on the establishment of periodontal disease, complications in diabetes control have been recorded. Moreover, disturbance in the homeostasis with increase in severity of micro vascular and macrovascular components have also been described.18\n\nType 2 Diabetes, a chronic public health menace, associated with economic burden is a global concern. Studies estimate that more than 80% of world diabetic population may be concentrated in developing countries and 60% and more so in Asian countries.19 Diabetes might be a potential epidemic in India with an upsurge in cases recorded across the states and the different challenges being reported within its large population.20 According to an epidemiological survey, Nanditha et al. observed that over a period of 10 years (2006-2016) in Tamil Nadu, South India, there was an increase in the prevalence of diabetes and prediabetes within the population studied.21 Blas et al. states that 95% of Indian population are affected by periodontitis.22 While the prevalence of 26.2% of mild to moderate and 19% of severe periodontitis, was observed in a systematic review conducted among the Indian adults with highest among urban population. The authors do suggest that nearly half of the Indian population may have some form of periodontal condition.23 Balaji et al. reported a 42.3% prevalence of periodontal diseases in a population of 1000 adults screened for periodontitis in Tamil Nadu, India, and concluded the existence of a definitive inflammatory burden within the population.24\n\nThe alarming escalation in the demographics on diabetes and periodontitis and the speculative molecular relationship necessitates unraveling the association and the possible influencing factors shared between them. Therefore, the present study aims to quantify and compare the GCF levels of IL-6 in periodontitis patients between diabetic and non-diabetic group from South Indian population to determine the association between periodontitis and diabetes. Further, the study also aims to analyze IL-6 levels in patients with poor glycemic control (HBA1c) thereby evaluating its role in the progression periodontal destruction.\n\n\nMethods\n\nThe Institutional Review Board (IRB) and ethical committee of the SRM Dental College, Ramapuram, Chennai (SRMU/M&HS/SRMDC/2011/M. D. S. PG Student/201) approved the procedures for conducting the current study. A sample size of 60 was chosen (for a 95% confidence interval, P = 0.01) based on the statistician’s recommendations. The study recruited periodontology outpatients from SRM Dental College and SRM General Hospital in Ramapuram, Chennai. Participants were informed of the study’s purpose and gave written consent.\n\nSixty participants within the age group between 30-70 years old with chronic periodontitis (patient has probing depth ≥ 4 mm) with minimum dentition of 24 teeth with or without diabetes mellitus were included. Patients with systemic condition other than diabetes mellitus, pregnant and lactating women, patients with other chronic inflammatory diseases, cancer patients, rheumatoid arthritis, smokers and alcoholics, acute oral conditions, sepsis, excessive obesity and patients who underwent periodontal and antibiotic therapy six months prior to the study were excluded.\n\nClinical examination was carried out using a mouth mirror, graduated Williams periodontal probe, sickle shaped explorer and CPITN probe. Oral hygiene status was assessed by Plaque Index (PI) and Oral Hygiene Index (OHI). Periodontitis was confirmed with Community Periodontal Index and Treatment Needs (CPITN) index. The chronic periodontitis participants were then grouped into Group 1 comprising of 30 diabetic subjects with positive confirmation of HBA1c reports who were under oral diabetes agents and Group 2 of 30 non-diabetic subjects who served as controls.\n\nParticipants selected for the study were seated comfortably in an upright position on the dental chair with proper illumination. The site with the maximum probing depth was selected for sampling. The supragingival plaque was gently removed after being gently dried and carefully isolated with cotton rolls. Crevicular fluid was obtained by placing 1-5 microliter calibrated volumetric micro-capillary pipette (Sigma-Aldrich chemical company, Bangalore, India) at the gingival margin as per Cimsoni method. Samples of GCF if contaminated by blood or saliva were discarded. The samples later were drained into Eppendorf tubes and stored at -70 degree celsius until further analysis.\n\nLater, the samples were assayed for IL-6 concentration using krishgen human IL-6 ELISA kit (Krishgen Corporation, Mumbai, India- Catalog No. – KB1068) as per manufacturer’s instructions in the central research laboratory of Sri Ramachandra Medical College and Research Institute, Chennai, India. Intensity of measurable signal produced by antibody-target complex and substrate solution were read using ELISA Reader.\n\nThe data was recorded, tabulated and interpreted for statistical analysis using SPSS, Microsoft Word and Excel programme. Descriptive and inferential statistics such as mean, standard deviation, central tendency, ANOVA, Pearson’s chi-square (χ2) test, student T-TEST were used.\n\n\nResults\n\nOn the demographics front, 27 females and 33 males with a mean age of 49.2 ± 12.7 years comprised the total 60 study participants. While diabetic group included 18 males & 12 females, non-diabetic group consisted of 15 males and 15 females.\n\nPatient with CPITN score of 3 (21 Patients in both the groups) and 4(9 patients in both the groups) with fair (28 diabetic patients with Fair OHI, 29 non-diabetic patients with Fair OHI) to poor (2 diabetic patients with poor OHI, 1 non-diabetic patients with poor OHI) Oral Hygiene Index (OHI), Plaque index (PI) (patient with fair PI were 29 patients in both the groups, patient with poor PI were 1 patients in both the groups) status were employed to confirm chronic periodontitis among the participants and also were considered to evaluate the difference between the diabetic and non-diabetic groups.\n\nIn diabetic group with HBA1c values below 6.8% were 17participantsand HBA1c 6.8-7.7% were 6participants and above 7.7% of HBA1c where 7 participants were included in the study.\n\nOn evaluating the immunoassay reading, group 1 samples expressed a range of 4.4 Pg/μl to 7.0 Pg/μl of IL-6 levels with a mean value of 5.8 Pg/μl. The IL-6 expression in group 2 comprised of the non-diabetic group ranged from 1.5 Pg/μl to 4.8 Pg/μl with the mean value of 3.2 Pg/μl (Table 1).\n\nOn comparing the mean IL-6 values using Student-T test, an increased expression of IL-6 was evident in the diabetic group than the non-diabetic group. Further, the elevated values were statistically significant in diabetic group with p value <0.001 (Table 2).\n\nIn diabetic group, the patients mean IL-6 levels were 6.7 Pg/μl for patients with poor plaque and OHI values while 5.7 Pg/μl for fair plaque and OHI values. No statistical significance was observed on comparison of IL-6 values between patients with poor PI and fair PI values and poor OHI and fair OHI using student T test. Mean IL-6 levels were 5.7 Pg/μl in patients with CPITN score 3 and 5.8 Pg/μl with CPITN score 4 with no statistical significance on comparison.\n\nIn non-diabetic group, the patients mean IL-6 levels were 3.9 Pg/μl for patients with poor plaque and OHI values while 3.2 Pg/μl for fair plaque and OHI values. No statistical significance was observed on comparison of IL-6 values between patients with poor PI and fair PI values and poor OHI and fair OHI using student T test. Mean IL-6 levels was 3.1 Pg/μl in patients with CPITN score 3 and 3.2 Pg/μl with CPITN score 4 with no statistical significance on comparison (Table 3).\n\nThe analysis was further extended on the HBA1c values and the expression of IL-6 in the diabetic group. The mean IL-6 values in participants with HBA1c below 6.8% was 5.1 Pg/μl, HBA1c 6.8-7.7% was 6.3 Pg/μl and above 7.7% of HBA1c was 6.8 Pg/μl. On intra-group comparison of IL-6 values among the diabetic group with HBA1c reading above 7.7% and below 6.8% showed a statistically significant increase of IL-6 with the p value < 0.001 (Table 4).\n\nTherefore, the above data is suggestive of an increased expression of IL-6 levels in the GCF of diabetic group when compared to non-diabetic group. Further, a significant raise in the expression of IL-6 values were elicited in participants with poor glycemic control as represented by correlating HBA1c values with the IL-6 expression.\n\n\nDiscussion\n\nPeriodontal disease and diabetes mellitus are both chronic, very common diseases that have a lot in common pathobiologically. Obesity and insulin resistance are two related antecedent states that may be quite important in these dynamics. Recent discoveries and studies have revealed the role of inflammation as a key component in this connection. Diabetes clearly raises the risk of periodontal diseases, and numerous examples of biologically plausible reasons have been found. The effects of periodontal disorders on the glycemic management of diabetes and the processes by which this occurs are less apparent. In a manner comparable to obesity, periodontal disorders may initiate or spread insulin resistance, making glycemic control more difficult.\n\nIn diabetes, the high affinity cell surface receptor RAGE on monocytes and macrophages interacts with the synthesis of AGES to cause the release of numerous inflammatory mediators. Diabetes alters how immune cells, such as neutrophils, monocytes, and macrophages, function.25 As poor neutrophil adherence, chemotaxis, and phagocytosis frequently prevent bacteria from being killed in the periodontal pocket, this dramatically increases the risk of periodontal damage.26 Despite the fact that diabetes frequently impairs neutrophil function, the monocyte/macrophage cell line may show up-regulation in response to bacterial antigens. The production of proinflammatory cytokines and mediators such TNF-, IL-6, and IL-1 is dramatically elevated as a result of monocytes’ and macrophages’ hyper reactivity.27\n\nTreatment for periodontitis will therefore lessen not only local inflammation but also the systemic and local availability of these mediators, preventing the periodontium’s cells and their functions from being adversely affected.28,29 According to Miller,30 between pre-treatment baseline values and 2- to 3-month post-treatment values, periodontal therapy was linked to a 10% drop in HbA1c levels. Consequently, the objective of the current investigation was to compare diabetic patients with chronic periodontitis to non-diabetic patients in terms of the activity of the proinflammatory cytokine IL-6 in GCF. Moreover, in the diabetic group, there was a correlation between IL-6 expression and HBA1C levels.\n\nIn the current investigation, patients in group 1 (diabetic periodontitis patients) had statistically higher levels of IL-6 (5.8 pg/l) than patients in group 2 (non-diabetic periodontitis patients; p0.001). These findings are in line with earlier research by Duarte PM et al.31 who found that GCF IL-6 levels were significantly higher in diabetic periodontitis patients as a result of long-term poor glycemic control, which increases the formation of AGES, which then couples with RAGE present on monocytes, macrophages, endothelial cells, and other cells, increasing the secretion of various inflammatory cytokines including IL-6.\n\nThere was a statistically significant link between the level of IL-6 and the HBA1C value in the current study’s diabetic patients (good control = 5.18, fair control = 6.38, poor control = 6.89). Those with poorly managed diabetes who had an increased IL-6 level had a p value of less than 0.001. The findings support Débora C. Rodrigues et al. investigation’s which found that persistent AGES build up led to monocyte/macrophage activation and enhanced IL-6 secretion32 and thus elevated IL-6 levels.\n\nAccording to a study by Mark C. Genovese et al., IL-6 Receptor blockage with sarilumab was linked to a decrease in HbA1c in people with rheumatoid arthritis and diabetes. Hence, these findings imply that IL-6 significantly contributes to the deterioration of glycemic control.33 Clinical and metabolic outcomes following conventional periodontal therapy were examined between patients with and without type 2 diabetes mellitus by Faria-Almeida R et al. After receiving basic non-surgical periodontal treatment, both patient groups displayed a clinical improvement. After periodontal therapy, the diabetic patients had better metabolic control (lower HBA1c) at 3 and 6 months.34 So, in the future, inhibiting the IL-6 receptor combined with periodontal therapy can lower IL-6 activity and thereby minimise the inflammatory reactions in both illnesses, as well as the complications associated with treating patients with diabetes and periodontitis. According to a study by B Kurtis et al., the expression of IL-6 in healthy subjects was 0.62 Pg/μl and 1.31 Pg/μl in adult periodontitis. However, when compared to the results of the current study, it was found that the non-diabetic group with periodontitis had an increased expression of IL-6 (3.24 Pg/μl).17\n\nReverse transcription polymerase chain reaction (RT-PCR) and ELISA tests, as well as several investigations by many other authors, revealed that individuals with periodontitis had higher levels of IL-6 mRNA and protein expression.35,36 Hence, the results of the current study’s IL-6 levels in 30 patients with periodontitis who did not have diabetes, as measured by ELISA, were consistent with findings from earlier research that suggested periodontitis might spread insulin resistance by upregulating IL-6 expression. As a result of their reciprocal interaction, diabetes and periodontitis both have an impact on interlukin-6 levels.37–39 IL-6 levels in GCF of teeth with periodontitis may be impacted by periodontal treatment, such as periodontal scaling and root planing, according to a study by Hua Xi Kou et al. from 2001.40 Also, in a study conducted in 2003 by Nishimura F ET AL, serum levels were evaluated both before and after scaling and root planning. According to the findings, there was a shift in blood IL-6 levels between pre- and post-treatment.41 As a result, periodontal therapy may lower inflammatory mediators like IL-6 in both the blood and the GCF, according to the findings of the Nishimura F ET AL study and the Hua Xi Kou et al study. In order to reduce the additional systemic inflammatory burden and potentially avert diabetes, cardiovascular disease, and other systemic morbidities, Mattson JS et al. 2001 advises that efforts to battle diabetes sequelae, particularly periodontitis and gingivitis.28\n\nIn terms of sex-related differences in the prevalence of periodontitis and diabetes, the current study’s data show that men had higher rates of both conditions than women did, which is consistent with findings from studies by Anna Nordström et al. on the prevalence of diabetes and Ashish Jain et al. on sex-related differences in the prevalence of periodontitis.42,43\n\nThis study’s findings on PI, CPITN, and OHI scores were in agreement with a study by Roberto Del Giudice et al.44 on their favourable correlation with IL-6 levels. By comparing the levels of IL-6 in GCF between diabetic subjects and non-diabetic (healthy subjects) without periodontitis as well as between the levels of IL-6 in GCF before and after periodontal management, more research is needed to understand the function and potential mechanism of IL-6 in the pathogenesis of diabetes and periodontitis. The study’s limitation is the relatively small sample size, which reduces the statistical analysis’s power.\n\n\nConclusion\n\nThe results of the present study concluded that the IL-6 activity was enhanced more in diabetic subjects than non-diabetic subjects with periodontitis. Among the diabetic group the subjects with good diabetic control have shown less activity of IL-6 in GCF than poor controlled diabetic subjects. So, diabetes may play a major role in the activity of proinflammatory cytokine IL-6 in the progression of periodontitis.",
"appendix": "Data availability\n\nFigshare: ASSOCIATION OF ELEVATED IL-6 WITH POOR GLYCEMIC CONTROL IN PERIODONTITIS PATIENTS, https://doi.org/10.6084/m9.figshare.22269604. 45\n\nThis project contains the following underlying data:\n\n- Ethical clearance certificate and Data in excel.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nNazir MA: Prevalence of periodontal disease, its association with systemic diseases and prevention. Int. J. Health Sci. 2017 Apr; 11(2): 72–80. PubMed Abstract\n\nPapanicolaou DA: Interleukin-6: the endocrine cytokine. J. Clin. Endocrinol. Metabol. 2000 Mar 1; 85(3): 1331–1333. Publisher Full Text\n\nBarnes TC, Anderson ME, Moots RJ: The many faces of interleukin-6: the role of IL-6 in inflammation, vasculopathy, and fibrosis in systemic sclerosis. Int. J. Rheumatol. 2011 Oct; 2011: 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVieira Ribeiro F, de Mendonça AC , Santos VR, et al.: Cytokines and bone-related factors in systemically healthy patients with chronic periodontitis and patients with type 2 diabetes and chronic periodontitis. J. Periodontol. 2011 Aug; 82(8): 1187–1196. PubMed Abstract | Publisher Full Text\n\nJaved F, Al-Askar M, Al-Hezaimi K: Cytokine profile in the gingival crevicular fluid of periodontitis patients with and without type 2 diabetes: a literature review. J. Periodontol. 2012 Feb; 83(2): 156–161. PubMed Abstract | Publisher Full Text\n\nCazalis J, Tanabe SI, Gagnon G, et al.: Tetracyclines and chemically modified tetracycline-3 (CMT-3) modulate cytokine secretion by lipopolysaccharide-stimulated whole blood. Inflammation. 2009 Apr; 32: 130–137. Publisher Full Text\n\nSorsa T, Tjäderhane L, Konttinen YT, et al.: Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann. Med. 2006 Jan 1; 38(5): 306–321. PubMed Abstract | Publisher Full Text\n\nBirkedal-Hansen H: Role of cytokines and inflammatory mediators in tissue destruction. J. Periodontal Res. 1993 Nov; 28(7): 500–510. Publisher Full Text\n\nLalla E, Lamster IB, Feit M, et al.: Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice. J. Clin. Invest. 2000 Apr 15; 105(8): 1117–1124. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUitto VJ, Overall CM, McCulloch C: Proteolytic host cell enzymes in gingival crevice fluid. Periodontol. 2003 Feb; 31(1): 77–104. PubMed Abstract | Publisher Full Text\n\nOkada H, Murakami S: Cytokine expression in periodontal health and disease. Crit. Rev. Oral Biol. Med. 1998 Jul; 9(3): 248–266. Publisher Full Text\n\nPozo P, Valenzuela MA, Melej C, et al.: Longitudinal analysis of metalloproteinases, tissue inhibitors of metalloproteinases and clinical parameters in gingival crevicular fluid from periodontitis-affected patients. J. Periodontal Res. 2005 Jun; 40(3): 199–207. Publisher Full Text\n\nDeCarlo AA Jr, Windsor LJ, Bodden MK, et al.: Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis. J. Dent. Res. 1997 Jun; 76(6): 1260–1270. PubMed Abstract | Publisher Full Text\n\nPradhan AD, Manson JE, Rifai N, et al.: C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001 Jul 18; 286(3): 327–334. Publisher Full Text\n\nTuttolomondo A, La Placa S, Di Raimondo D, et al.: Adiponectin, resistin and IL-6 plasma levels in subjects with diabetic foot and possible correlations with clinical variables and cardiovascular co-morbidity. Cardiovasc. Diabetol. 2010 Dec; 9: 1–7\n\nNoack B, Genco RJ, Trevisan M, et al.: Periodontal infections contribute to elevated systemic C-reactive protein level. J. Periodontol. 2001 Sep; 72(9): 1221–1227. PubMed Abstract | Publisher Full Text\n\nKurtis B, Develioglu H, Taner IL, et al.: IL-6 levels in gingival crevicular fluid (GCF) from patients with non-insulin dependent diabetes mellitus (NIDDM), adult periodontitis and healthy subjects. J. Oral Sci. 1999; 41(4): 163–167. PubMed Abstract | Publisher Full Text\n\nCairo F, Rotundo R, Frazzingaro G, et al.: Diabetes mellitus as a risk factor for periodontitis. Minerva Stomatol. 2001 Sep 1; 50(9-10): 321–330. PubMed Abstract\n\nRamachandran A, Snehalatha C, Shetty AS, et al.: Trends in prevalence of diabetes in Asian countries. World J. Diabetes. 2012 Jun 6; 3(6): 110. Publisher Full Text\n\nKaveeshwar SA, Cornwall J: The current state of diabetes mellitus in India. Australas Med. J. 2014; 7(1): 45–48. Publisher Full Text\n\nNanditha A, Snehalatha C, Satheesh K, et al.: Secular TRends in DiabEtes in India (STRiDE–I): change in prevalence in 10 years among urban and rural populations in Tamil Nadu. Diabetes Care. 2019 Mar 1; 42(3): 476–485. PubMed Abstract | Publisher Full Text\n\nBlas E, Kurup AS: Equity, social determinants and public health programmes. World Health Organization; 2010.\n\nJanakiram C, Mehta A, Venkitachalam R: Prevalence of periodontal disease among adults in India: A systematic review and meta-analysis. J. Oral. Biol. Craniofac. Res. 2020 Oct 1; 10(4): 800–806. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBalaji SK, Lavu V, Rao S: Chronic periodontitis prevalence and the inflammatory burden in a sample population from South India. Indian J. Dent. Res. 2018 Mar 1; 29(2): 254–259. PubMed Abstract | Publisher Full Text\n\nResearch, Science and Therapy Committee of The American Academy of Periodontology: Position paper; Diabetes and periodontal diseases. J. Periodontol. 1999 Aug; 70(8): 935–949. Publisher Full Text\n\nManouchehr-Pour M, Spagnuolo PJ, Rodman HM, et al.: Comparison of neutrophil chemotactic response in diabetic patients with mild and severe periodontal disease. J. Periodontol. 1981 Aug; 52(8): 410–415. Publisher Full Text\n\nSalvi GE, Collins JG, Yalda B, et al.: Monocytic TNFα secretion patterns in IDDM patients with periodontal diseases. J. Clin. Periodontol. 1997 Jan; 24(1): 8–16. PubMed Abstract | Publisher Full Text\n\nMattson JS, Cerutis DR: Diabetes mellitus: a review of the literature and dental implications. Compend. Contin. Educ. Dent. 2001 Sep 1; 22(9): 757–760. PubMed Abstract\n\nD’aiuto F, Parkar M, Brett PM, et al.: Gene polymorphisms in pro-inflammatory cytokines are associated with systemic inflammation in patients with severe periodontal infections. Cytokine. 2004 Oct 7; 28(1): 29–34. PubMed Abstract | Publisher Full Text\n\nMiller LS, Manwell MA, Newbold D, et al.: The relationship between reduction in periodontal inflammation and diabetes control: a report of 9 cases. J. Periodontol. 1992 Oct; 63(10): 843–848. PubMed Abstract | Publisher Full Text\n\nDuarte PM, De Oliveira MC, Tambeli CH, et al.: Overexpression of interleukin-1β and interleukin-6 may play an important role in periodontal breakdown in type 2 diabetic patients. J. Periodontal Res. 2007 Aug; 42(4): 377–381. PubMed Abstract | Publisher Full Text\n\nRodrigues DC, Taba M Jr, Novaes AB Jr, et al.: Effect of non-surgical periodontal therapy on glycemic control in patients with type 2 diabetes mellitus. J. Periodontol. 2003 Sep; 74(9): 1361–1367. PubMed Abstract | Publisher Full Text\n\nGenovese MC, Burmester GR, Hagino O, et al.: Interleukin-6 receptor blockade or TNFα inhibition for reducing glycaemia in patients with RA and diabetes: post hoc analyses of three randomised, controlled trials. Arthritis Res. Ther. 2020 Dec; 22: 1–2. Publisher Full Text\n\nFaria-Almeida R, Navarro A, Bascones A: Clinical and metabolic changes after conventional treatment of type 2 diabetic patients with chronic periodontitis. J. Periodontol. 2006 Apr; 77(4): 591–598. PubMed Abstract | Publisher Full Text\n\nBotero JE, Contreras A, Parra B: Profiling of inflammatory cytokines produced by gingival fibroblasts after human cytomegalovirus infection. Oral Microbiol. Immunol. 2008 Aug; 23(4): 291–298. PubMed Abstract | Publisher Full Text\n\nChung RM, Grbic JT, Lamster IB: Interleukin-8 and β-glucuronidase in gingival crevicular fluid. J. Clin. Periodontol. 1997 Mar; 24(3): 146–152. PubMed Abstract | Publisher Full Text\n\nLalla E, Lamster IB, Feit M, et al.: Blockade of RAGE suppresses periodontitis-associated bone loss in diabetic mice. J. Clin. Invest. 2000 Apr 15; 105(8): 1117–1124. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGrossi SG: Treatment of periodontal disease and control of diabetes: an assessment of the evidence and need for future research. Ann. Periodontol. 2001 Dec; 6(1): 138–145. PubMed Abstract | Publisher Full Text\n\nDíaz-Romero RM, Ovadía R: Diabetes and periodontal disease: A bidirectional relationship. Med. Biol. 2007; 14(1): 6–9\n\nWu Y, Zhao C, Zhang J: Interleukin-6 levels in the gingival crevicular fluid before and after periodontal treatment. Hua xi kou Qiang yi xue za zhi= Huaxi Kouqiang Yixue Zazhi= West China Journal of Stomatology. 2001 Apr 1; 19(2): 99–101. PubMed Abstract\n\nNishimura F, Iwamoto Y, Mineshiba J, et al.: Periodontal disease and diabetes mellitus: the role of tumor necrosis factor-α in a 2-way relationship. J. Periodontol. 2003 Jan; 74(1): 97–102. PubMed Abstract | Publisher Full Text\n\nNordström A, Hadrévi J, Olsson T, et al.: Higher prevalence of type 2 diabetes in men than in women is associated with differences in visceral fat mass. J. Clin. Endocrinol. Metabol. 2016 Oct 1; 101(10): 3740–3746. Publisher Full Text\n\nJain A, Bhavsar NV, Baweja A, et al.: Gender-Associated Oral and Periodontal Health Based on Retrospective Panoramic Radiographic Analysis of Alveolar Bone Loss. Clinical Concepts and Practical Management Techniques in Dentistry. IntechOpen; 2020 Sep 30.\n\nLo Giudice R, Militi A, Nicita F, et al.: Correlation between Oral Hygiene and IL-6 in Children. Dent. J. 2020 Aug 11; 8(3): 91. Publisher Full Text\n\nAtul Kumar H: ASSOCIATION OF ELEVATED IL-6 WITH POOR GLYCEMIC CONTROL IN PERIODONTITIS PATIENTS. [Dataset]. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "194122",
"date": "23 Jan 2024",
"name": "Lalitha Tanjore Arunachalam",
"expertise": [
"Reviewer Expertise Immunology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study is well thought and conceived but some minor corrections to be addressed.\n\n1. It is well established that uncontrolled type 2 DM modulates the cytokine levels in periodontitis patients towards a proinflammatory profile including IL 6.\n2. Methodology:\nPatient selection and group selection can be written clearly. Periodontitis was diagnosed based only on CPITN? Please add a reference for that.\n\nCimsoni – check spelling.\n\n-70C for GCF storage – Please check.\n3. Results:\nPlease add statistics separately. Only T test is reflected in tables, ANOVA , Pearsons chi square test are not seen.\n\nDemographics table not present.\n\nMention the p value in table 3 and 4.\n\nAdd footnotes for every table.\n\nOverall, results can be written with better clarity, especially the second paragraph of the results.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "292181",
"date": "21 Jun 2024",
"name": "Tarcília Aparecida Silva",
"expertise": [
"Reviewer Expertise Oral Pathology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAbstract 1-I suggest rephrasing the aim. “…without diabetes and to analyze these levels in patients with poor glycemic control (HBA1c)”. When authors mention poor glycemic control, the authors expect to see another comparison group “diabetic patients with good glycemic control”. Indeed, the comparisons between these two diabetic groups were done, so disclose it. 2-I suggest avoiding acronyms without a proper description e.g. “CPITN index” 3-Detailed methodological information may be suppressed e.g. “using Cimasoni method were collected and stored at -70 degrees Celsius and subjected to ELISA for IL-6 using Krashen human IL-6 ELISA kit”. 4-Replace “readings” to “concentrations” 5-The conclusion is not focused on the aims and results. Authors aimed to “… compare the levels of IL-6 … in order to assess its role in the progression of periodontal”. The conclusion went in another direction. Mostly important, when you mention progression the idea of longitudinal evaluation came to the surface. I suggest revision to keep the consistency. 6-Mention the type of diabetes. Introduction 7-While the introduction is well-written, it lacks details about the relationship of periodontal diseases and diabetes and also the direction of this relationship, as recently reviewed by Stöhr J et al. Sci Rep. 2021 and others. Moreover, IL-6 should be included in this context. 8-The authors mention that the aim of study is to determine the association between periodontitis and diabetes. This objective cannot be reached from the study´s experimental design. I suggest to re-organize the last paragraph of introduction section to clarify the aims and perspectives of study. Methods 9-The authors report that performed a sample size calculation, what is very nice, but at this time I would like to see the power of sample. 10-“excessive obesity” is not a specific exclusion criteria, please revise it 11-It would be important to inform who did the periodontal examinations and examiner training and calibration procedures. 12-Provide references for Plaque Index (PI), Oral Hygiene Index (OHI) and Community Periodontal Index and Treatment Needs (CPITN) index. Also, for Cimsoni method and GCF collection. 13-In how many locations per tooth were periodontal measurements performed? 14-Why was periodontitis not graded in stages according to current criteria. I strongly advise to use the current classification (Tonetti MS et al. (2018) Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol 89:S159-S172. https://doi.org/10.1002/JPER.18-0006). 15-Were the ELISA values corrected by volume or protein concentration? 16-To make the groups comparable I consider that authors match patients and also the sites analyzed. It is expected that sites with higher PD have more IL-6 despite the systemic status of patient. So, it would be important that authors assess it in the statistical analysis. 17-Confirm that the authors tested the normality of the sample and report what was the distribution found. Results 18-A Table with all demographic and clinical data should be provided as well as the comparisons between the groups with respective p values. It is important to assess the impact of possible confounding factors in the results. The multivariate analysis would be important to understand the effect of other variables besides diabetes in the concentration of IL-6. It is particularly relevant because it seems that the periodontal status of non-diabetic group is better that diabetics and results might be impacted by that and not necessarily by the diabetic state. 19-Please provide the p values for all the tables. Discussion 20-It is not necessary to repeat the numeric results. 21-It is important to mention the cells sources of IL-6 in GCF 22- A description of strengths of the study and how the results contribute to improve knowledge in relation to the previous literature should be done. Also the authors should expand the limitations of study, e.g. cross-sectional design. Minor There are minor text formatting and grammar errors.\nCompeting Interests: No competing interests were disclosed.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-595
|
https://f1000research.com/articles/12-497/v1
|
15 May 23
|
{
"type": "Research Article",
"title": "Prevention and Mitigation of Rural Higher Education Dropout in Colombia: A Dynamic Performance Management Approach.",
"authors": [
"Alfredo Guzman Rincón",
"Sandra Barragán",
"Federico Cosenz",
"Favio Cala Vitery",
"Sandra Barragán",
"Federico Cosenz",
"Favio Cala Vitery"
],
"abstract": "Dropout is a socio-educational phenomenon that has the scope to limit the benefits of higher education, as well as widen social disparities. For this reason, governments have implemented various public policies for its prevention and mitigation. However, in rural populations, such policies have proven to be inefficient. This paper aims to simulate public policy scenarios for the treatment of dropout in rural higher education from a Dynamic Performance Management perspective. This method supports policymakers in better understanding the core dynamics underlying the rise of this phenomenon, thus providing additional insights on how to tackle its further overflow. Due to the complexity of educational systems, the present study was developed in the Colombian context, however the model is operationalizable in any other country. As a result, the adoption of such a simulation-based approach suggests that the policies of expanding the coverage of educational loans and financial support, as well as adding a subsidy to the family income, allow for reducing the number of dropouts.",
"keywords": [
"Simulation models",
"higher education",
"rural areas",
"Dynamic Performance Management",
"dropping out"
],
"content": "Introduction\n\nApart from a few success stories of personalities such as Steve Jobs, Mark Zuckerberg, Larry Ellison, and Bill Gates, who did not complete higher education,1 student dropout has been a consistent challenge for policy decision makers globally.2,3 Dropping out of higher education can limit the benefits that come with educational level for society and exacerbate social disparities in certain areas.2,4,5 The negative effects of dropout in higher education are related to learning factors, which can make it impossible to obtain better jobs in the long run due to a lack of educational capital.6,7 This makes it difficult to improve the average income level of the population,8 decreases the skilled workforce,9 and destroys social capital,10 among other things. Dropout in higher education also hinders efforts to reinforce civic and democratic values.10 Moreover, dropout from higher education leads to an increase in poverty rates as students and their families have to bear the sunk costs related to education.5\n\nBased on the literature, certain student populations experience dropout in higher education more frequently, due to the interaction of individual, socioeconomic, academic, and institutional variables that induce them to abandon their education prematurely, as in the case of rural populations.5,11–13 In response, both developed and developing countries have sought to mitigate and prevent dropout in rural student populations.5 Western states have focused on designing, developing, and implementing public policies that fund tuition and other educational expenses, as well as creating quality standards that evaluate the role of Higher Education Institutions (HEIs) in mitigating and preventing dropout.2,14\n\nDespite the existence of public policies aimed at reducing the dropout rate in rural higher education, the rate remains high, averaging over 50% in countries such as Colombia, India, and South Africa.5,11,15,16 The root causes of this phenomenon are often linked to the ineffective implementation of existing policies, or the absence of comprehensive policies that address critical individual, socioeconomic, academic, and institutional variables (or combinations of them) that lead to students dropping out.\n\nIn order to address this issue, it is necessary to evaluate the treatment of other explanatory variables that can help to combat dropout in higher education within the context of public policy. However, literature linking dropout to rural populations and public policies is scarce, so the academic community has provided feedback to decision-makers aimed at identifying variables that explain the possible causes of rural higher education student dropout.2,13,17–20 An example of this was the study carried out by Guzmán et al.,2,5 in which a model based on systems thinking was used to indicate to public policy decision-makers, the need to improve student performance at previous academic levels, improve connectivity and access to information and communication technologies, and generate financial support, among others. Nonetheless, it is still unclear how incorporating these variables into public policies could positively impact the prevention and mitigation of dropout in the rural student population. This is due to the fact that most related studies of dropout in rural higher education make use of cross-sectional methods (e.g., Refs. 2, 12, 13, 21), and those that are longitudinal tend to be ex post facto non-predictive in nature, as in the study by Faizullina et al.,22 where data was taken from 2,388 students analysing their retention and dropout status, in order to find out the causes of dropout. Thus, there is a need for models that provide information over time to public policy makers on the long-term impact of their decisions in addressing dropout in rural higher education.\n\nAgainst this backdrop, the objective of this article is to simulate public policy scenarios for the treatment of school dropout in rural higher education in Colombia from a Dynamic Performance Management approach. Given the complexity of the global educational system, the study is limited to Colombia due to the high dropout rate in its rural areas, which can be as high as 50% per year and in some departments (states or provinces) can be even higher than 80%.23 This study aims to provide new insights into this educational issue, which is heavily influenced by social disparities resulting from armed conflicts, drug trafficking, and State abandonment, among other factors.2,5 The study seeks to provide possible solutions for preventing and mitigating dropout in the rural student population by designing a model that evaluates the impact of public policy decisions prior to their implementation. Furthermore, it aims to contribute to the field of study by using Dynamic Performance Management modelling to understand how the treatment of explanatory variables for dropout affects students over time.\n\nAs the study focuses specifically on rural higher education in Colombia, the model is limited to the explanatory variables of dropout that the Ministry of National Education evaluates over time. Therefore, subsequent sections will not consider all variables studied within the framework of this educational phenomenon. This article is organized into four sections. The first section presents the theoretical framework and Colombian public policies for the treatment and mitigation of dropout. The second section describes the methodology used and the scenarios to be simulated. The third section outlines the results, including the Dynamic Performance Management Chart, Causal Loop Diagram, Forrester Diagram, Mathematical Model, and the results of the simulations. Finally, the fourth section provides a discussion and conclusions.\n\n\nTheoretical framework\n\nDropout is a complex and multi-causal phenomenon that involves various actors within the educational system, including State entities, HEIs, students, their families, and financial institutions. There are numerous variables that explain this phenomenon, such as academic performance, socioeconomic status, age, gender, attendance at wellness programs, etc., which can influence students’ decision to terminate their training process prematurely in higher education.2 Due to the interdisciplinary nature of the study of dropout, there are multiple conceptualizations of this phenomenon, depending on the actor analysing it.\n\nAcademic conceptualizations provide an overall epistemic value. Among these definitions, the Alfa Guía Project stands out, which sought to contribute to the reduction of dropout rates in Higher Education through the cooperative work of a Network of Educational Institutions formed by 138 different institutions from 30 different countries. Thus, dropout was conceptualised from this project where dropout is defined as\n\n“the cessation of the relationship between the student and the training program that leads to a degree of higher education before it is achieved. A complex, multidimensional, and systemic event can be understood as cause or effect, failure or reorientation of a training process, mandatory choice or response, or as an indicator of the quality of the educational system”.24\n\nIn contrast, various countries such as Colombia, Spain, United Kingdom and United States, use technical definitions to facilitate the counting of dropout students and identify variables that explain the phenomenon and its causes. In Colombia, for example, dropout is defined based on the number of academic periods that a student was not linked to an HEI. A student is considered to have dropped out if they did not enrol in the program in two consecutive periods and did not graduate or withdrew for disciplinary reasons.25\n\nBoth the academic community and the Colombian definition are not exclusive but complement each other to analyse dropout in higher education from different perspectives. To analyse dropout, public policy development and academic research have used four determinants to conglomerate the explanatory variables of this phenomenon: individual, socioeconomic, academic, and institutional.2,5,26–29 These determinants are defined as follows by Guzman et al.2:\n\n(1) Individual: It corresponds to the characteristics of the students and their personal environment, which directly and indirectly affect dropout.\n\n(2) Socioeconomic: It refers to the influence of the social and economic context in which the students develop and that can lead them to not complete their training.\n\n(3) Academic: It conglomerates the variables related to learning outcomes, competencies, abilities, performance, and other aspects of the teaching and learning process at all levels of education completed or in progress, both formal and informal.\n\n(4) Institutional: It concerns the aspects and institutional policies of HEIs that can lead the students to finish their training early.\n\nIn the context of global dropout rates, research on students in rural higher education has shown that women are typically responsible for domestic and childcare duties, leading to less time for studying, while men’s study time is reduced due to work obligations.2,19,30 Additionally, entering higher education at a later age in rural areas often means increased family and work responsibilities, which can result in dropping out of school.30,31 A study by Guzmán et al.,2 found that in Colombia the lack of support structures due to low social capital in rural families was associated with students’ intentions to drop out, a finding also reported by De Hart and Venter in South Africa.30 Low social capital is connected to parents’ educational levels and, subsequently, to the delayed entry into higher education, which is attributed to lower perceived value of higher education in rural societies.30 Due to social disparities, rural students who drop out, as well as their families, generally have lower incomes than the national average, for the case of the United States,12 and sometimes even below the minimum wage.5 Such factors make it challenging to afford tuition fees, educational expenses, and overall training development in a fair and equitable manner compared to students’ urban counterparts.32\n\nInequality is not limited solely to socioeconomic factors but also affects academic processes themselves. Rural students often have lower academic performance at earlier levels, inadequate teacher training, and limited access to education-related services and technology.21 To address this issue, studies suggest that implementing Permanence and Timely Graduation Plans (P&GO according to its Spanish acronym) in HEIs can help prevent and reduce dropout rates among rural students.33 Other factors related to rural student dropout include dissatisfaction with the chosen academic program,31 inadequate information about the program prior to enrolment,19 limited access to resources and technology at HEIs,34 and the type of school from which they graduated.35\n\nIt is recognised that only some of the variables studied are linked to the development of public and institutional policies because statistical information is needed for their treatment or simply because of the level of complexity that makes direct state intervention difficult. Examples of this type of variable are the level of self-regulation, student motivation, satisfaction with their studies, etc. Consequently, the model proposed in the following sections focuses on those variables for which statistical information from state information systems is available and which can be intervened through public policies.\n\nWhen discussing public policies aimed at preventing and mitigating student dropout in higher education, it is important to revisit the initial efforts made by the Colombian Ministry of National Education in 2003 to understand and contextualize them. That year, the State set out to:\n\n(1) Facilitate student migration between programs.\n\n(2) Improve regulatory mechanisms for admitting students who are simultaneously studying at other HEIs.\n\n(3) Increase and enhance the information provided to applicants about the programs offered.\n\n(4) Create financial aid programs for low-income students from other cities.\n\n(5) Promote prior vocational or professional guidance.36\n\nTo this end, the Ministry of National Education developed the Higher Education Dropout Prevention System (SPADIES, according to its Spanish acronym) in the first phase to determine the actual dropout rate and the possible variables that influenced this phenomenon. The State then designed a public policy in which it sought to finance higher education through credits,5 in order to mitigate socioeconomic variables related to dropout. In addition, as the State regulates the educational system, it established a series of policies for HEIs related to educational quality regarding dropout rates, access, permanence, and timely graduation. HEIs created Early Warning Systems (SAT, according to its Spanish acronym) and P&GO to accurately identify students with the intention of dropping out and intervene timely.\n\nAs a result of the implementation of these policies, the dropout rate in Colombia ranged from 7.56% to 12.8% for the period spanning 2017 to 2021,37 which is relatively low compared to the situation in other Latin American countries or in the Organization for Economic Cooperation and Development (OECD), where dropout rates of 54% and 64.5%, respectively, were registered.38,39 However, when the analysis is focused on rural areas, the reality is different. It has been estimated that the dropout rate for training programs aimed at rural students reaches 50% at the national level.23 Nevertheless, the dropout rate varies between departments, with the poorest ones experiencing the most significant challenges. Examples are the departments of Putumayo, La Guajira and Arauca, where the dropout rate in higher education was 80.2% and 55.6%, respectively.23\n\nAt present, there are no differentiated state public policies for the rural population. Hence, it is necessary to analyse through modelling which variables should be addressed to allow for students’ persistence and timely graduation in rural areas.\n\n\nMethods\n\nTo achieve the objective of this article, we utilized the Dynamic Performance Management approach, which combines planning and control systems with System Dynamics modelling.40,41 This method involves identifying auxiliary variables, flows, and levels within a system or subsystems, as well as the relationships between these elements, to recreate their structures. Equations are then developed to simulate possible system behaviours over time.41 In this case, we used this approach to model the social and higher education structures and measure their performance based on the number of enrolled, graduated, and dropout rural students. To conceptualize and simulate these structures, we followed the Dynamic Performance Management approach.42,43\n\nThis approach centres decision-making processes on strategic resources, which are modelled as tangible and intangible factors that can be modified through input and output flows.44,45 These flows are influenced by public policy variables, and the dynamics of the system are characterized by feedback loops with time lags, resulting in delays between decision-making, implementation, and behaviour modification.\n\nBuilding on previous works such as Bivona and Cosenz,46 Herrera et al.,47,48 Bivona,49 Cosenz et al.,50 Bianchi et al.,51 Feng et al.,52 and Yin et al.,53 we developed a model in five phases.54 The first phase involved identifying the strategic resources, performance drivers, and results and documenting the Dynamic Performance Management (DPM) Chart. The second phase focused on developing the Causal Loop Diagram to establish the behaviour of the system and interactions between variables based on the DPM Chart. In the third phase, we created the Forrester or Stocks and Flows Diagram to synthesize the differential equations and establish the system’s structure, achieving dynamic behaviour as a function of time. The fourth phase involved defining equations that replicate the system’s behaviour, with software-generated equations chosen for consistency and replicability (for all equations, see Extended data63). The fifth and final phase tested the consistency of the model by comparing results with the suggested behaviour in the Causal Loop Diagram.\n\nTo parameterize the model, we used official sources of historical data from the Colombian State. The aggregate data of the level of higher education for the rural populations of the SPADIES, of the dropouts, as well as those of the Rural Higher Education Plan (PESR, according to its acronym in Spanish for Plan de Educación Superior Rural),23 were taken. In the case of SPADIES,37 the information can be freely consulted by registering on the application’s web portal; for the information extracted from the PESR, this was done through the link provided in Ref. 23. The data and sources are presented in Table 1.\n\nAdditionally, we used the database from the study by Guzmán et al.,55 to develop some graphic functions (data and sources are in Table 1). A graphical function in system dynamics is a visual representation of how a variable changes over time in a dynamic model. The variable is represented on the vertical axis, while time is represented on the horizontal axis. These graphical functions can show how a variable varies as a function of initial conditions, system inputs and interactions between different variables in the model. From the above, graphical functions were developed by crossing two variables. An example of this was the average age of admission and the time people spend on their work duties, where from the scatter diagram generated, the points for the generation of the graphical function were taken.\n\nWith the model and the initial parameters (see Table 1), we proceeded to its execution and to evaluate public policies that could be implemented to mitigate and prevent the dropout in rural higher education in Colombia. For this, the following simulations were carried out (see Table 2). Additionally, Table 3 proposes the modification of the parameters in each of the simulations. In the case of SIM-2 to SIM-4, only one parameter was modified, so the other variables followed the Ceteris Paribus condition.\n\nAfter conducting the simulations using the model and initial parameters from Table 1, the system’s behaviour was compared to SIM-1 using descriptive and inferential statistics. The goal was to determine the difference in means between the system’s behaviour with the initial parameters and the parameters modified by the simulations. Specifically, the Wilcoxon Sign Rank Test was used with a significance level of p-value < 0.05.56 This analysis was limited to the levels of enrolled, graduated, and dropout rural students.\n\nFinally, the computational work regarding the model and the simulations were implemented in the Stella Architect Software in version 1.9.5.,57 the model which is available in Ref. 58 can be replicated using Vensim.59 The following model adjustments were taken into account: ti= 0, tf= 50, where tirepresented the year 2016 first semester and tf the year 2041 semester two, likewise it was taken as Δt = 20, where t represents the time in academic periods; additionally, Euler was used as the integration method. In the case of statistical analysis, the SPSS Software version 28 was used.60\n\n\nResults\n\nIn accordance with the methodological section, the results are presented in the three sections below. The first one shows the development of the DPM Chart; the second one, the Forrester and Causal Loop Diagram; and the third one presents the results of the simulations.\n\nTo develop the DPM Chart, we have identified 11 strategic resources, nine performance drivers, and six end results (five outcomes and one output) as shown in Figure 1. The first strategic resource pertains to the average admission age to higher education, which means that the higher the age of admission, the more time students will spend on family obligations (second resource) and work (third resource), competing with the time devoted to study (fourth resource).2,30\n\nThe average income levels of rural families (fifth resource) limit access to higher education, prompting the State to create and encourage programs to facilitate access to educational level. Low average income levels of families may lead to students being unable to enrol, resulting in them abandoning their educational process.5 Western countries have provided loans and educational support (sixth resource) to rural students. HEIs have also created the P&GO (seventh resource) to intervene in variables of the individual determinant, especially those related to psychological aspects of the student, in addition to some of the academic and institutional determinants. In summary, the first and seventh resources impact the outcome of change in defectors.\n\nThe other four resources are: the number of dropouts (eighth), which will increase over time if the State and HEIs do not treat dropouts adequately; high school graduates (ninth), who are the potential population to enter higher education; enrolled students (tenth) corresponding to the population linked to a training program; and graduates (eleventh) who represent the population of students who obtained their degree. If students drop out, they will once again be part of the population of high school graduates.\n\nIn terms of the end results, we considered five outcomes, namely: the change in time spent on family obligations, the change in time spent on work obligations, the change in dropout students, the change in enrolled students, and the change in median family income. According to the logic of Dynamic Performance Management, the outcomes are not entirely explained by the modelled structures, but other systems intervene for their full explanation. Regarding the outputs, we only identified one, which corresponds to the P&GO intervention.\n\nBased on the DPM Chart, and the interaction between strategic resources, performance drivers, and end results, a Causal Loop Diagram (CLD) was proposed with five reinforcement loops and two balancing ones. Figure 2 presents the CLD. The R1 loop shows that the higher the average age of admission to higher education, the more time students spend on family obligations, which decreases the time spent on studying, leading to more dropouts. The greater the number of dropouts, the lower the number of enrolees and graduates, making it impossible to increase the average family income, and thus, impact the average age of entry to higher education.\n\nNote: R represents reinforcing loops and B balance loops. The sign “+” means proportional relationships, and “-” stands for inversely proportional relationships.\n\nIn the R2 reinforcement loop, if the average family income increases, students spend less time on family obligations since they have the financial support to delegate care responsibilities to third parties. This affects the time spent studying, decreases the number of dropouts, and increases the number of enrolees and graduates. As a result, more people with professional degrees in the family lead to a higher average family income.\n\nIn the R3 loop scenario, the higher the number of dropouts, the lower the number of students enrolled, which decreases the number of P&GO interventions, thus increasing the number of dropouts. Finally, the number of educational credits and supports for R4 depends on the number of high school graduates and enrolees. Thus, the greater the number of credits and aids, the lower the number of dropouts, more students enrolled, and more credits and educational aids granted.\n\nRegarding the first balancing loop B1, the greater the number of dropouts, the fewer enrolees and graduates, decreasing the average family income. In the event of a low average family income, the number of credits and educational aid granted by the state will increase to prevent dropouts. For the B2 balancing loop, the greater the number of high school graduates, the higher the number of students enrolled in higher education, and the number of graduates, decreasing the number of people with only high school degrees.\n\nBased on the CLD, a Forrester Diagram was developed for operationalizing the dynamic hypotheses. The diagram consisted of 11 stocks, 16 flows, and 22 auxiliary variables, which were used to define 32 equations, nine graphic functions, and six constants for the simulation model. These equations allowed for the development of the model and are presented in Extended data.63 The simulation model is available in Ref. 58.\n\nUnder SIM-1, it was projected that the average age of admission to higher education for rural students in the year 2041 (t = 50) would be 37 years, an increase of 12 years from the year 2016 (t = 0). The simulation model predicted that rural students would spend 14 hours on family care, 35.5 hours on their jobs, and 34.5 hours on their studies for t = 50. The analysis of Figure 3b indicated that rural students would allocate only 13 hours to their training between t = 30 and t = 40, representing the shortest time for the simulated semesters.\n\nThe average family income would grow by 89.6% by 2041, reaching $2,380,000 COP (USD 506.95) due to the increase in the number of graduates in higher education, which was estimated to be 89,900 for t = 50. Educational loans and aid would impact 337,000 rural students if current policies are maintained. The number of P&GO interventions would be similar to the number of students enrolled, which was estimated to be 2.650 interventions for t = 50.\n\nThe simulation model predicted a decreasing trend in the number of students graduating from high school, which suggests that maintaining current policies will result in a greater link of students to higher education. For t = 50, it was estimated that 65,200 students will have a bachelor’s degree. The maximum number of students enrolled in higher education would be reached for t = 20, with 41,100 students, and the system’s behaviour would show a gradual decrease in enrolled students, ending at t = 50 with 33,800 students. The simulation model also predicted that the number of graduate students in the year 2041 would be 89,900, and the number of dropouts would be 808,000. The flow of enrolling would decrease, ending at t = 50 with 14,300 students starting their training, while the flows called graduating and dropping out would behave in a decreasing way in coherence with the decrease in enrolled students. Figure 4 displays the results of SIM-1.\n\nUnder SIM-2, if the State were to allocate more educational credits and support to rural students, there would be no changes in the strategic resources compared to SIM-1. However, there would be a change in policy for t = 20, with the number of educational credits and supports increasing to 857,000. The maximum number of P&GO interventions would occur between t = 7 and t = 13, with 3,570 interventions. The system’s behaviour in terms of high school graduates, enrolled students, graduates, and dropouts would be similar to that of SIM-1. For t = 50, there would be 64,000 high school graduates, 33,100 enrolled, 90,600 graduates, and 786,000 dropouts. Figure 4 illustrates the behaviour of the system in the SIM-2 scenario.\n\nIn the case of SIM-3, where there is an increase of $500,000 COP in the average family income, the average age of admission changes compared to SIM-1. Between t = 10 and t = 20, the average age increases by 12 years compared to the initial age of 25 years. However, after t = 20, the average age would decrease and reach 21 years for t = 50. As a result, there would be a readjustment in the distribution of the average time devoted to family, work, and study obligations, with 11.4, 24.7, and 48 hours allocated to each, respectively, for t = 50. In the year 2041, if the family income increase policy remains fixed due to the effect of State subsidies, the average family income is estimated to be $8,470,000 COP (USD 1,804.16). The number of educational credits and grants delivered would be $341,000 COP for t = 50. The maximum number of P&GO interventions would occur between t = 14 and t = 20, with 3,570 intervention sessions, and subsequently decrease. The behaviour of high school graduates would continue to decrease, with 61,000 for t = 50. However, the level variables of enrolled students, graduates, and dropouts would stabilize at 33,600, 92,600, and 773,000, respectively, for the year 2041. Figure 5 displays the results of SIM-3.\n\nThe results of the fourth simulation (SIM-4) indicate that the average age for entering higher education, as well as the average time spent on family, work, and study obligations, and the average family income, remain the same as those in SIM-1. In this scenario, it is expected that the State would have granted 337,000 educational loans and support. The maximum number of P&GO interventions would reach 14,900 students, and for t = 50, the interventions would be 11,600. The number of high school graduate students, enrolled students, graduates, and dropouts for t = 50 would be the same as those in SIM-1, which are 65,200, 33,800, 89,900, and 808,000, respectively. Figure 6 illustrates the system’s behaviour in SIM-4.\n\nIn SIM-5, a proposal for the simultaneous implementation of public policies, it is evident that this scenario would lead to a decrease in the average age of admission to higher education for rural populations, reaching 21.1 years by t = 50. As a result, there would be an increase in the average time dedicated to studying, which would be 48 hours by t = 50. In contrast, by 2041, the average time spent on work and family obligations would decrease by 24.7 and 11.4 hours, respectively. The average family income would increase due to State support and the income generated by the increase in the number of graduates. Thus, the family’s average income would be $8,470,000 COP (USD 1,804.16) by t = 50.\n\nIn this scenario of multiple policies, the number of subsidies delivered would reach 866,000 by t = 50. Similarly, between t = 6 and t = 18, it is estimated that the P&GO interventions would reach their maximum point at 15,600. After this period, the interventions would decrease, being equal to 11,600 by t = 50. As for the number of high school graduates by t = 50, there would be 59,900, with a decreasing curve from t = 1. The number of enrolees, graduates, and dropouts would be 32,900, 93,100, and 751,000, respectively, by t = 50. Figure 7 displays the behaviour of this simulation scenario.\n\nFrom the results of the simulations, they were identified for the case of the number of students enrolled in higher education for SIM-2 (Z = -0.45, p-value = 0.65) and SIM-4 (Z = 0.60, p-value = 0.54). There would be no significant statistical differences with respect to SIM-1. Otherwise, in the scenario proposed in SIM-3, there would be significant differences with Z equal to -5.13 and a p-value less than 0.01, as well as in SIM 5 with Z equal to -5.47 and a p-value less than 0.01. With this in mind, for SIM-1, the average enrolment during the simulated periods was 37,182 students. For SIM-3, it was 38,231, and for SIM-5, it was 38,567. Regarding the number of dropouts, significant statistical differences were observed for SIM-2, SIM-3, and SIM-5 concerning SIM-1 (Z = -6.09, p-value < 0.01; Z = -6.17, p-value < 0.01; Z = -6.09, p-value < 0.01), only for SIM-4 it was not possible to determine the existence of said difference (Z = 0-90, p-value = 0.36). Thus, the mean number of student dropouts was 432,037 for SIM-1, 418,670 for SIM-2, and 404,870 for SIM-5. Finally, for the number of graduates, there were statistically significant differences in SIM-2, SIM-3, and SIM5 (Z = -6.09, p-value < 0.01; Z = -5.51, Z -value < 0.01; Z = -6.09, p-value < 0.01). The mean number of graduates was 48,689 for SIM-1, 49,681 for SIM-2, 49,910 for SIM-3, and 50,897 for SIM-5.\n\n\nDiscussion and conclusions\n\nThe aim of this study was to simulate public policy scenarios for the treatment of school dropout in rural higher education in Colombia from a Dynamic Performance Management approach. The model presented the strengthens of the literature on educational dropout in rural populations, by linking individual, socioeconomic, academic, and institutional determinants to the extent that it relates to dropout in higher education and rural populations over time. This includes variables such as age of entry to higher education, hours dedicated to studying, family and work obligations, educational credits, and financial support.\n\nThe simulation results demonstrate that expanding the coverage of educational loans and financial support for rural populations, which is the central axis of public policies in Western countries,61 does not decrease the average age of admission to higher education. On the contrary, it increases it. This results in an increase in the time dedicated to family obligations30 and work obligations,2 which subsequently decreases the average time spent studying and increases the risk of dropout. However, this cannot be generalized for all simulated periods, as for t = 38, the time dedicated to studying increases while that dedicated to work obligations decreases. This is explained by the increase in average family income due to a greater number of people with professional degrees.\n\nThe implementation of policies that offer credits and educational aid for higher education in rural populations can indirectly decrease the probability of dropout due to payment and increase the number of graduates. The implementation of such a policy reduced the number of dropouts by 2.7% for t = 50. However, it should be considered whether indebtedness of the vulnerable rural population with limited economic income is the best strategy to prevent and mitigate dropout, as it can increase economic disparities that are already experienced in rural areas in developing countries.5,61\n\nAn alternative public policy approach involves improving the average income of rural families, which can lower the age of admission to higher education for students from these areas. This eliminates the competition between the average times of labour obligations and relatives with those dedicated to studying. The implementation of this policy had an effect on the number of dropouts of 4.33%. This is possible since the average income of the family increases, benefiting all its members. This approach contrasts with Lewine et al.,21 who indicated that subsidizing only the student would not reduce the number of dropouts because it generated pressure from the family to share their limited wealth, leading to partial or complete work and eventually dropout.\n\nRegarding the increase in P&GO interventions resulting from changes in public policies regarding HEI quality criteria, there were no statistically significant differences for rural populations. This is due to the fact that the variables addressed in P&GO focus on academic, institutional, and individual (psychological) aspects that are difficult to modify through public policies, as stated by Guzmán et al.,62 Castleman & Meyer,12 Ramírez et al.,32 and Lewine.21\n\nHowever, a simulation combining the three public policy options showed that their simultaneous application decreased dropout rates by up to 7.05%. This highlights the importance of coupling public policies beyond education to effectively and efficiently address the dynamic complexities of student dropout in higher education for rural populations, particularly in developing countries where social inequalities are pronounced.\n\nWhile the developed model considered some of the most significant variables in studying dropout rates in rural populations, there are still opportunities for future research in various disciplines, such as the consideration of sex, prior academic competencies, academic and social capital at the start of higher education, and the type of IES, among others. It is also recognized that the incorporation of new variables may alter the effect of the evaluated public policies.\n\nAlthough the data collected was already affected by COVID-19, it was not included as a study variable. However, it should be included in future model replications if the data does not already include this specific situation. Additionally, as there is a lack of related data in Colombia regarding the dropout rate from the educational system, the model assumes a continuity of the flow of students. However, once data on this variable is available, it must be incorporated, thus affecting the absolute amount of each level variable but not the system’s behaviour.",
"appendix": "Data availability\n\nDANS-EASY: Simulation Results, https://doi.org/10.17026/dans-zjb-5rsd. 63\n\nThis project contains the following underlying data:\n\n• Dataset of simulations.csv\n\nFigshare: Extended data, https://doi.org/10.6084/m9.figshare.22658989.v2. 64\n\nThis project contains the following extended data:\n\n• Equations used by the model.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nZając TZ, Komendant-Brodowska A: Premeditated, dismissed and disenchanted: higher education dropouts in Poland. Tert. Educ. Manag. 2019; 25: 1–16. Publisher Full Text\n\nGuzmán A, Barragán S, Cala-Vitery F: Rurality and Dropout in Virtual Higher Education Programmes in Colombia. Sustainability. 2021; 13: 4953. Publisher Full Text Reference Source\n\nArias Ortiz E, Dehon C: Roads to Success in the Belgian French Community’s Higher Education System: Predictors of Dropout and Degree Completion at the Université Libre de Bruxelles. Res. High. Educ. 2013; 54: 693–723. Publisher Full Text\n\nHällsten M: Is Education a Risky Investment? The Scarring Effect of University Dropout in Sweden. Eur. Sociol. Rev. 2017; jcw053. Publisher Full Text\n\nGuzmán A, Barragán S, Cala-Vitery F: Rural Population and COVID-19: A Model for Assessing the Economic Effects of Drop-Out in Higher Education. Front. Educ. 2021; 6: 812114. Publisher Full Text\n\nAina C, Baici E, Casalone G, et al.: The determinants of university dropout: A review of the socio-economic literature. Socio Econ. Plan. Sci. 2022; 79: 101102. Publisher Full Text Reference Source\n\nSosu EM, Pheunpha P: Trajectory of University Dropout: Investigating the Cumulative Effect of Academic Vulnerability and Proximity to Family Support. Front. Educ. 2019 [cited 2022 Nov 22]; 4: 6. Publisher Full Text\n\nGhignoni E: Family background and university dropouts during the crisis: the case of Italy. High. Educ. 2017; 73: 127–151. Publisher Full Text\n\nÖzdoğan E: Dynamic effects of higher education expenditures on human capital and economic growth: an evaluation of OECD countries. Policy Rev. Higher Educ. 2021; 5: 174–196. Publisher Full Text\n\nLance L: Nonproduction Benefits of Education. Handbook of the Economics of Education. Elsevier; 2011 [cited 2023 Jan 27]; pp. 183–282. Reference Source\n\nGuzmán A, Barragán S, Cala VF: Dropout in Rural Higher Education: A Systematic Review. Front. Educ. 2021; 6: 727833. Publisher Full Text\n\nCastleman BL, Meyer KE: Can Text Message Nudges Improve Academic Outcomes in College? Evidence from a West Virginia Initiative. Rev. High. Educ. 2020; 43: 1125–1165. Publisher Full Text Reference Source\n\nByun S, Meece JL, Irvin MJ: Rural-Nonrural Disparities in Postsecondary Educational Attainment Revisited. Am. Educ. Res. J. 2012; 49: 412–437. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHerbaut E: Overcoming failure in higher education: Social inequalities and compensatory advantage in dropout patterns. Acta Sociologica. 2021; 64: 383–402. Publisher Full Text\n\nGupta A: Focus on Quality in Higher Education in India. Indian J. Public Adm. 2021; 67: 54–70. Publisher Full Text\n\nAdonis CK, Silinda F: Institutional culture and transformation in higher education in post-1994 South Africa: a critical race theory analysis. Crit. Afr. Stud. 2021; 13: 73–94. Publisher Full Text\n\nTroester-Trate KE: Food Insecurity, Inadequate Childcare, & Transportation Disadvantage: Student Retention and Persistence of Community College Students. Community Coll. J. Res. Pract 2020; 44: 608–622. Publisher Full Text\n\nBania EV, Kvernmo SE: Tertiary education and its association with mental health indicators and educational factors among Arctic young adults: the NAAHS cohort study. Int. J. Circumpolar Health. 2016; 75: 32086. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPillay AL, Ngcobo HSB: Sources of Stress and Support among Rural-Based First-Year University Students: An Exploratory Study. S. Afr. J. Psychol. 2010; 40: 234–240. Publisher Full Text\n\nRapley P, Davidson L, Nathan P, et al.: Enrolled nurse to registered nurse: Is there a link between initial educational preparation and course completion? Nurse Educ. Today. 2008; 28: 115–119. PubMed Abstract | Publisher Full Text Reference Source\n\nLewine R, Manley K, Bailey G, et al.: College Success Among Students From Disadvantaged Backgrounds: “Poor” and “Rural” Do Not Spell Failure. J. Coll. Stud. Retent.: Res. Theory Pract. 2021; 23: 686–698. Publisher Full Text\n\nFaizullina K, Kausova G, Kalmataeva Z, et al.: Career Intentions and Dropout Causes Among Medical Students in Kazakhstan. Medicina. 2013; 49: 45. Publisher Full Text Reference Source\n\nMinistry of National Education: Plan rural de educación superior: Estrategias de fortalecimiento de capacidades para el desarrollo territorial. 1st ed.Bogotá: Colombia: Ministry of National Education; 2009.\n\nProyecto ALFAGUIA: Estudio sobre Políticas Nacionales sobre el abandono en la Educación Superior en los países que participan en el Proyecto ALFA-GUIA. 1st ed.Madrid: Gestión Universitaria Integral del Abandono; 2013.\n\nMinistry of National Education: Deserción estudiantil en la educación superior colombiana: Metodología de seguimiento, diagnóstico y elementos para su prevención. 1st ed.Bogotá: Colombia: Ministry of National Education; 2009.\n\nSegovia-García N, Said-Hung E, García Aguilera FJ: Educación superior virtual en Colombia: factores asociados al abandono. EducXX1. 2022; 25: 197–218. Publisher Full Text Reference Source\n\nBarragán S, Gonzalez O: Explanatory Variables of Dropout in Colombian Public Education: Evolution Limited to Coronavirus Disease. European J. Ed. Res. 2022; 11: 287–304. Publisher Full Text Reference Source\n\nBarragán SP, González L: Acercamiento a la deserción estudiantil desde la integración social y académica. Rev. Educ. Super. 2017; 46: 63–86. Publisher Full Text Reference Source\n\nFonseca G, García F: Permanencia y abandono de estudios en estudiantes universitarios: un análisis desde la teoría organizacional. Rev. Educ. Super. 2016; 45: 25–39. Publisher Full Text Reference Source\n\nDe Hart K, Venter JMP: Comparison of urban and rural dropout rates of distance students. Perspect. Educ. 2013 [cited 2021 May 28]; 31: 66–76. Reference Source\n\nNishat N, Islam YM, Biplob KBMB, et al.: Empowering tertiary level students to solve their own study-related problems to improve study performance. JARHE. 2020; 12: 1117–1133. Publisher Full Text\n\nRamírez SMR, Velásquez DU, Zapata EP, et al.: Perfiles de riesgo de deserción en estudiantes de las sedes de una universidad colombiana. Rev. Psicol. 2020; 38: 275–297. Publisher Full Text Reference Source\n\nWarner L: WIST — A science and technology access programme for rural women: The determinants of success. Distance Educ. 1993; 14: 85–96. Publisher Full Text\n\nPérez CN, Cerón EA, Suárez RP, et al.: Deserción y repitencia en estudiantes de la carrera de Enfermería matriculados en el período 2010-2015. Universidad Técnica de Manabí. Ecuador. 2017. Educ. Medica. 2019; 20: 84–90. Publisher Full Text Reference Source\n\nWheat JR, Brandon JE, Carter LR, et al.: Premedical Education: The Contribution of Small Local Colleges. J. Rural. Health. 2003; 19: 181–189. PubMed Abstract | Publisher Full Text\n\nMinistry of National Education: Guía para la implementación del modelo de gestión de permanencia y graduación estudiantil en instituciones de educación superior. 1st ed.Bogotá: Colombia: Ministry of National Education; 2015.\n\nMinistry of National Education: Sistema para la Prevención de la Deserción de la Educación Superior.2022. Reference Source\n\nOECD: Tertiary graduation rate. Paris: OECD; Reference Source\n\nBecerra M, Alonso JD, Frias M, et al.: Latin America and the Caribbean: Tertiary Education. The World Bank. 2020. Reference Source\n\nBianchi C, Bereciartua P, Vignieri V, et al.: Enhancing Urban Brownfield Regeneration to Pursue Sustainable Community Outcomes through Dynamic Performance Governance. Int. J. Public Adm. 2021; 44: 100–114. Publisher Full Text\n\nForrester JW: Industrial Dynamics. Eastford: Martino Publishing; 2013.\n\nBianchi C, Nasi G, Rivenbark WC: Implementing collaborative governance: models, experiences, and challenges. Public Manag. Rev. 2021; 23: 1581–1589. Publisher Full Text\n\nMorecroft JDW: Strategic modelling and business dynamics: a feedback systems approach. Chichester, England; Hoboken, NJ: John Wiley & Sons; 2007.\n\nBianchi C: Dynamic Performance Management. Cham: Springer International Publishing; 2016. Publisher Full Text\n\nBala BK, Arshad FM, Noh KM: System Dynamics. Singapore: Springer Singapore; 2017. Publisher Full Text\n\nBivona E, Cosenz F: Designing a Multi-Sided Platform business model assessment framework: a Dynamic Performance Management perspective. Syst. Res. Behav. Sci. 2021; 38: 93–107. Publisher Full Text\n\nHerrera MM, Dyner I, Cosenz F: Alternative Energy Policy for Mitigating the Asynchrony of the Wind-Power Industry’s Supply Chain in Brazil.Qudrat-Ullah H, editor. Innovative Solutions for Sustainable Supply Chains. Cham: Springer International Publishing; 2018; pp. 199–221. Publisher Full Text\n\nHerrera MM, Dyner I, Cosenz F: Assessing the effect of transmission constraints on wind power expansion in northeast Brazil. Util. Policy. 2019; 59: 100924. Publisher Full Text Reference Source\n\nBivona E: Determinants of performance drivers in online food delivery platforms: a dynamic performance management perspective. IJPPM. 2022. Publisher Full Text\n\nCosenz F, Rodrigues VP, Rosati F: Dynamic business modeling for sustainability: Exploring a system dynamics perspective to develop sustainable business models. Bus. Strateg. Environ. 2020; 29: 651–664. Publisher Full Text\n\nBianchi C, Bereciartua P, Vignieri V, et al.: Enhancing Urban Brownfield Regeneration to Pursue Sustainable Community Outcomes through Dynamic Performance Governance. Int. J. Public Adm. 2021; 44: 100–114. Publisher Full Text\n\nFeng J, Wu C-L, Zhu J: Airport route development strategy planning and performance measurement with a dynamic performance management framework. Wang T (David), editor. PLoS One. 2022; 17: e0271452. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYin Y, Zhang Y, Jin K: System Dynamics Modeling of the Supply Chain Performance of Prefabricated Construction Based on the Stakeholder Analysis. J. Phys. Conf. Ser. 2021; 1827: 012109. Publisher Full Text\n\nSterman J: Business dynamics: systems thinking and modeling for a complex world. Massachusetts: Massachusetts Institute of Technology; 2012.\n\nGuzmán A, Barragán S, Cala-Vitery F: Comparative Analysis of Dropout and Student Permanence in Rural Higher Education. Sustainability. 2022; 14: 8871. Publisher Full Text Reference Source\n\nScheff SW: Nonparametric Statistics. Fundamental Statistical Principles for the Neurobiologist. Elsevier; 2016 [cited 2023 Apr 25]; pp. 157–182. Reference Source\n\nIsee systems: [cited 2023 Apr 25]. Reference Source\n\nGuzmán A, Barragán M, Cosenz F, et al.: Model of simulation. Isee Exchange.2023. Reference Source\n\nVensim: [cited 2023 Apr 25]. Reference Source\n\nSPSS Statistics - Visión general: [cited 2023 Apr 25]. Reference Source\n\nMoreno W, Segovia N, Grillo C, et al.: Naturaleza del endeudamiento como base de la propuesta de política pública para la educación superior en Colombia desde 2013. Innovación Docente e Investigación en Ciencias Sociales, Económicas y Jurídicas. Madrid: Dykinson; 2019; pp. 25–36.\n\nGuzmán A, Barragán S, Cala-Vitery F, et al.: Deserción en la Educación Superior Rural: Análisis de Causas desde el Pensamiento Sistémico. Qualitative Research in Education. 2022; 11: 118–150. Publisher Full Text Reference Source\n\nGuzmán A, Barragán M, Cosenz F, et al.: Simulation Results. DANS. 2023. Publisher Full Text\n\nGuzmán A, Barragán S, Cosenz F, et al.: Extended data.2023 [cited 2023 Apr 25]. 16361 Bytes. Publisher Full Text Reference Source"
}
|
[
{
"id": "173754",
"date": "18 May 2023",
"name": "Robinson Salazar Rua",
"expertise": [
"Reviewer Expertise System Dynamics",
"Performance Management",
"Performance Measurement",
"Dynamic Performance Management",
"Systems Science",
"Computational modeling",
"Education policies",
"Health policies"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper is highly readable, informative, and transparent. It furthers research on the treatment of dropout in rural higher education by using a Dynamic Performance Management (DPM) Approach. This is an important topic in Colombia, and I have approved the manuscript with reservations. At this point, improvements are needed but they could be addressed by taking into account the following suggestions.\n1) In the design section, I suggest expanding the discussions of the DPM approach since it is the main method to reach the objective of the article. In particular, I recommend deepening on the concepts of strategic resources, performance drivers, and end/results. In addition, it is pertinent to clarify what the added value of the DPM is in respect to the Causal Loop Diagram (CLD) and Forrester Diagram.\n2) In the last lines of the design section, it was mentioned that the consistency of the model was tested by comparing simulation results with the suggested behavior from the causal loop diagram (i.e., reference mode). I will encourage the authors to use other tests to increase the reliability and robustness of the model. Below you will find two references to support such endeavor.\n\nBarlas Y (1996) Formal aspects of model validity and validation in system dynamics. Syst Dyn Rev 12(3):183–210\n\nSchwaninger, M., Groesser, S. (2020). System Dynamics Modeling: Validation for Quality Assurance. In: Dangerfield, B. (eds) System Dynamics. Encyclopedia of Complexity and Systems Science Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-8790-0_540\nMoreover, the authors might consider conducting sensitivity analyses to determine the robustness of the model and its associated policies under parameter uncertainty. In addition, they might analyze loop dominance by using the new feature in Stella Architect that was incorporated for such purpose. This supports the identification of important leverage points in the system by means of an analytical approach.\n\n3) In the first lines of the simulation section, it says “With the model and the initial parameters, we proceeded to its execution and to evaluate public policies that could be implemented to mitigate and prevent the dropout in rural higher education in Colombia”. After reading this line, one question came to my mind. Was the model set in dynamic equilibrium before testing the policies? It is considered as a best practice to do it. However, it is not always the case. I think it would be beneficial to the reader, who has a background in system dynamics, to clarify this question.\n\n4) In the analysis of the simulation data, perhaps the time step is 2 instead of 20. However, I would like the authors to confirm it. I would assume the time step to be 2 since the model is running in a period of 25 years (from 2016 to 2041), the initial time is zero and the final time is 50 semesters.\n\nIn case the authors confirm the time step to be 20, I would like to know why the Euler, instead of Runge Kutta 4th order, method was selected. The higher the time step, the higher the integration error. When the time step is high, it’s better to use more efficient integration methods to reduce the calculation errors by the software.\n\n5) In the results section, I would suggest putting the Table 1 (Data and sources of model parameterization) in an appendix. In addition, I would suggest making bigger Figure 1. After printing the article, I noticed the names of the strategic resources, performance drivers, and end-results are too small and it’s difficult to read. In addition, I would recommend renaming Figure 1 by using a more illustrative name for the case study than just naming it as DPM chart.\n\n6) In the section Causal loop and Forrester Diagrams, the authors immediately start discussing the reinforcing and balancing loops from the CLD. However, I think it would be beneficial to spend some lines on explaining what a balancing and reinforcing loop is for those readers who are not familiarized with such concepts. In addition, I was doubting whether it would be beneficial to rename the section since the Forrester Diagram was cited in the last paragraph but, unlike the CLD, it was not explicitly displayed in the article by means of a figure.\n\n7) It would be beneficial to sort the references in alphabetical order.\n\n8) I also suggest the following book and article to complement the relevant ideas - related to the education sector in the Colombian context- t hat were discussed throughout this article.\n\nSalazar Rua R. 2023. Improving consistency in performance measurement system design: The case of the Colombian public schools. Switzerland: Springer Cham.\n\nBianchi C, Salazar Rua R. 2020. A feedback view of behavioral distortions from perceived public service gaps at ‘street-level’ policy implementation: The case of unintended outcomes in public schools. System Research and Behavioral Science. pp: 1–22.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9686",
"date": "01 Jun 2023",
"name": "Alfredo Guzmán Rincón",
"role": "Author Response",
"response": "Dear PhD. Robinson Salazar Rua, We sincerely appreciate the time you dedicated to reviewing our work. Likewise, we believe that each of your comments has helped strengthen our article, especially regarding the simulation model. With that said, we will proceed to address each of the points and how they were addressed in the revised version of the article. Comment 1: In the design section, I suggest expanding the discussions of the DPM approach since it is the main method to reach the objective of the article. In particular, I recommend deepening on the concepts of strategic resources, performance drivers, and end/results. In addition, it is pertinent to clarify what the added value of the DPM is in respect to the Causal Loop Diagram (CLD) and Forrester Diagram. Response 1: In the initial version of the article, we hadn't considered clarifying aspects related to the DPM approach. Therefore, in the methods section, under the design subsection, we added a description of the DPM approach and its differentiation from the Causal Loop Diagram (CLD) and Forrester Diagram. Additionally, we provided definitions for the concepts of strategic resources, performance drivers, and end/results. Comment 2: In the last lines of the design section, it was mentioned that the consistency of the model was tested by comparing simulation results with the suggested behavior from the causal loop diagram (i.e., reference mode). I will encourage the authors to use other tests to increase the reliability and robustness of the model. Below you will find two references to support such endeavor. • Barlas Y (1996) Formal aspects of model validity and validation in system dynamics. Syst Dyn Rev 12(3):183–210 • Schwaninger, M., Groesser, S. (2020). System Dynamics Modeling: Validation for Quality Assurance. In: Dangerfield, B. (eds) System Dynamics. Encyclopedia of Complexity and Systems Science Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-8790-0_540 Moreover, the authors might consider conducting sensitivity analyses to determine the robustness of the model and its associated policies under parameter uncertainty. In addition, they might analyze loop dominance by using the new feature in Stella Architect that was incorporated for such purpose. This supports the identification of important leverage points in the system by means of an analytical approach. Response 2: Considering the suggestion regarding model validation, we reviewed the recommended references and made adjustments to the validation process. In this regard, the selected method was sensitivity analysis based on the consistency of the model's behavior. This change led to an expansion of the results section. Additionally, in the simulation results section for SIM-1, we added the dominance of causal loops generated by the system. Comment 3: In the first lines of the simulation section, it says “With the model and the initial parameters, we proceeded to its execution and to evaluate public policies that could be implemented to mitigate and prevent the dropout in rural higher education in Colombia”. After reading this line, one question came to my mind. Was the model set in dynamic equilibrium before testing the policies? It is considered as a best practice to do it. However, it is not always the case. I think it would be beneficial to the reader, who has a background in system dynamics, to clarify this question. Response 3: In response to this comment, the simulation section was amended to include the following text: \"For the present model, simulations were not conducted from a dynamic equilibrium due to three reasons. First, it is related to the DPM approach, which focuses on the adaptation and active improvement of the system's performance in response to changes in the environment. This implies that the model can be analyzed and evaluated even if it is not in a state of dynamic equilibrium. Second, considering the objective of the article, it involves testing and evaluating how the system would react to different interventions and policies in a dynamic environment. In this case, there is no strict requirement for a prior dynamic equilibrium since the focus is on exploring the dynamics and effects of policies in the system. Lastly, the limitation of data availability plays a role since establishing dynamic equilibrium requires historical data for all variables in the system, and the data obtained in the study by Guzmán et al. [55] were cross-sectional rather than longitudinal.\" Comment 4: In the analysis of the simulation data, perhaps the time step is 2 instead of 20. However, I would like the authors to confirm it. I would assume the time step to be 2 since the model is running in a period of 25 years (from 2016 to 2041), the initial time is zero and the final time is 50 semesters. In case the authors confirm the time step to be 20, I would like to know why the Euler, instead of Runge Kutta 4th order, method was selected. The higher the time step, the higher the integration error. When the time step is high, it’s better to use more efficient integration methods to reduce the calculation errors by the software. Response 4: Regarding the comment, indeed, the method used was Euler with a Δt = 20. The decision to use Euler as the integration method was based on computational considerations and acceptability in the approximation of the public policy simulation. In this regard, the following considerations were taken into account: Euler's method is computationally more efficient than the 4th order Runge-Kutta method, especially when using a larger time step. Since the simulation data analysis is conducted over a period of 25 years with a time step of 20, using Euler's method allows for faster and more efficient execution of the model. Although Euler's method may introduce a higher integration error compared to the 4th order Runge-Kutta method, in certain cases, it can provide an acceptable approximation of the results. Given the overall objective of the article, which is to understand the effect of implementing public policies rather than focusing solely on precision, Euler's method was deemed suitable. These reasons were explained to the readers of the article in the section on data analysis methods. Comment 5: In the results section, I would suggest putting the Table 1 (Data and sources of model parameterization) in an appendix. In addition, I would suggest making bigger Figure 1. After printing the article, I noticed the names of the strategic resources, performance drivers, and end-results are too small and it’s difficult to read. In addition, I would recommend renaming Figure 1 by using a more illustrative name for the case study than just naming it as DPM chart. Response 5: The journal does not handle supplementary materials or appendices, which is why the table is included in the main text. Regarding Figure 1, a request has been made to the Editor to allocate a full page for it in the new version. Additionally, the name of the Figure has been adjusted. Comment 6: In the section Causal loop and Forrester Diagrams, the authors immediately start discussing the reinforcing and balancing loops from the CLD. However, I think it would be beneficial to spend some lines on explaining what a balancing and reinforcing loop is for those readers who are not familiarized with such concepts. In addition, I was doubting whether it would be beneficial to rename the section since the Forrester Diagram was cited in the last paragraph but, unlike the CLD, it was not explicitly displayed in the article by means of a figure. Response 6: A conceptual introduction was provided in the section where the Causal Loop Diagram (CLD) is presented. Additionally, the section name has been adjusted to accurately reflect its content. Considering the valuable contribution, the same adjustments have been made to the DPM section. Comment 7: It would be beneficial to sort the references in alphabetical order. Response 7: According to the journal's guidelines, references must be numbered and cannot be organized alphabetically. Comment 8: I also suggest the following book and article to complement the relevant ideas - related to the education sector in the Colombian context that were discussed throughout this article. Salazar Rua R. 2023. Improving consistency in performance measurement system design: The case of the Colombian public schools. Switzerland: Springer Cham. Bianchi C, Salazar Rua R. 2020. A feedback view of behavioral distortions from perceived public service gaps at ‘street-level’ policy implementation: The case of unintended outcomes in public schools. System Research and Behavioral Science. pp: 1–22. Response 8: The suggested documents were reviewed, and some of the ideas in the article were complemented with them. Additionally, other documents were also consulted and incorporated to enhance the content."
}
]
}
] | 1
|
https://f1000research.com/articles/12-497
|
https://f1000research.com/articles/12-6/v1
|
03 Jan 23
|
{
"type": "Case Report",
"title": "Case Report: Right atrial organized thrombus three years after tricuspid annuloplasty",
"authors": [
"Mohannad Abbass",
"Silvia Mariani",
"Sami Musa",
"Nicoletta Erba",
"Franco Masini",
"Salvatore Lentini",
"Mohannad Abbass",
"Sami Musa",
"Nicoletta Erba",
"Franco Masini",
"Salvatore Lentini"
],
"abstract": "Background: Occurrence of right atrial masses, especially in patients with history of cardiac surgery, is rare. Differential diagnosis between malignant and non-malignant aetiologies might be cumbersome, and surgery is often required to prevent complications or disease evolution. Case: We report the case of a 16-year-old girl from a rural area of Sudan, who underwent surgery for a modified De Vega’s tricuspid annuloplasty, and mitral and aortic valve replacement with mechanical prostheses. The patient was on regular follow-up but demonstrated a poor compliance to anticoagulation therapy with a time in therapeutic range between 52% and 20%. She remained asymptomatic, but a right atrial mass was diagnosed by transthoracic echocardiography during a follow-up visit 41 months after the first operation. Surgical removal of the mass revealed an organized thrombus arising from the point where the Prolene stitches for the tricuspid annuloplasty were previously passed. The patient recovered from surgery, was discharged home on post-operative day 10 and the first follow-up visit at 30 days after discharge confirmed a good clinical status and a normal transthoracic echocardiography (TTE). Conclusions: This case report describes the diagnostic and therapeutic work-out of a thrombus formation on the suture lines of a tricuspid annuloplasty. Moreover, it highlights the importance of a strict and long follow-up after valvular surgery and of the adherence to anticoagulation therapy, especially for patients living in rural areas of developing countries.",
"keywords": [
"tricuspid valve repair",
"right atrial thrombus",
"intracardiac mass",
"follow-up"
],
"content": "Introduction\n\nIntracardiac masses are not frequent and they may arise in all of the four chambers of the heart.1 Their aetiologies include thrombi, vegetations, and neoplasms.1 Despite the pivotal role of echocardiography and other imaging techniques, differential diagnosis might be challenging, and surgery might be indicated to avoid complications and rule out malignancies. Intracardiac masses may arise also in patients that underwent previous cardiac surgery with implantation of valve prosthesis or valve repair.2,3 Herein, we report a case of a girl that underwent triple valve surgery and was diagnosed with a right atrial mass more than three years after the indexed operation. This case report follows the CARE guidelines.12\n\n\nCase presentation\n\nWe present the case of a 16-year-old Black African girl from a rural area of Sudan, with a history of recurrent tonsillitis, chest infections and untreated rheumatic fever. She was first referred to our hospital due to severe mitral, aortic and tricuspid regurgitation when she was 13 years old. Indication for urgent surgery was confirmed. The patient underwent mitral valve replacement with a 27 mm SJM Master mechanical prosthesis (Abbott, Burlington, MA USA), aortic valve replacement with a 19 mm SJM Regent mechanical prothesis (Abbott, Burlington, MA USA), and tricuspid annuloplasty with two separate Prolene 4/0 sutures with pledgets. The postoperative period was uneventful, and the patient was discharged home in good general condition on post-operative day 10. The pre-discharge transthoracic echocardiography (TTE) showed a mildly depressed left ventricular systolic function (46%), good result of the tricuspid repair with mild residual regurgitation and good function of the mechanical prostheses. The patient remained in regular follow-up at our outpatient clinic, restarted a normal life and went back to school. Two years after surgery she experienced menorrhagia with severe anaemia (haemoglobin: 5.6 g/dl) and oral aspirin (100 mg/day) was discontinued. She demonstrated a low compliance with the anticoagulation therapy (warfarin with a target international normalized ratio of 2.5–3.5), and a time in therapeutic range (TTR) of 52% during the first year after surgery, 34% during the second year, 34% during the third year and 20% during the first six months of the fourth year. No history of hypercoagulopathy and contraceptive use was reported. The patient remained in sinus rhythm during the whole follow-up.\n\nAt the follow-up visit 41 months after surgery, the TTE showed a mobile mass measuring 10 x 15 mm and arising from the atrial wall just above the tricuspid annulus (Figure 1). The right atrium was normal in size and structure (diameter: 31 mm; area: 15 cm2). The mass appeared mobile with the cardiac cycle, but no interference with the tricuspid valve function was noticed. Surgical indication was given based on the significant dimension of the mass, its position close to the tricuspid valve, the risk for embolization and the possible neoplastic nature.\n\nPreoperative echocardiography demonstrating a mass measuring 11×12 mm attached at the junction of the right atrium and tricuspid annulus as shown in the right ventricle inflow view (A) and parasternal short axis view (B).\n\nThe patient underwent re-sternotomy, cardiopulmonary by-pass was established with bicaval and aortic cannulation, the heart was arrested, and the right atrium was opened. The mass appeared to be attached to the atrial wall between the pectinate muscles and the anterior tricuspid annulus (Figure 2). In detail, the mass was arising from the point where the Prolene stitches for the tricuspid annuloplasty were previously passed but did not involve the valve leaflets. The mass had a curved shape and hard texture with a smooth surface. It was removed from the atrial wall using a knife, the atrium was closed, and the surgery completed. The macroscopic analysis showed a 15 × 15 × 8 mm homogenous light brown soft-tissue mass. The microscopic section showed several layers of hyalinized tissue containing red blood cells, scattered mixed inflammatory cells and fibrosis. The histological features were consistent with an organized thrombus.\n\nIntraoperative surgical view demonstrating the presence of a pedicled mass attached to the atrial wall between the pectinate muscles and the anterior tricuspid annulus.\n\nThe post-operative course was uneventful, and the patient was discharged home 12 days after surgery. The first follow-up visit at 30 days after discharge confirmed a good recovery and a normal TTE.\n\n\nDiscussion\n\nOccurrence of right atrial masses, especially in patients with history of cardiac surgery, is rare. This case report describes the diagnostic and therapeutic work-out of a thrombus formation on the tricuspid valve annulus after a modified De Vega’s annuloplasty. Moreover, it highlights the importance of a strict follow-up after valvular surgery and of the adherence to anticoagulation therapy, especially for patients living in rural areas of developing countries. To the best of our knowledge, this is the first report of a long-standing thrombus developed on the suture lines of a tricuspid annuloplasty and diagnosed more than three years after surgery.\n\nMany types of masses can be found in the right atrium, from benign thrombus to malignant sarcoma.1 For example, angiosarcoma may infiltrate the right atrioventricular junction, the atrial wall and also the tricuspid valve.4,5 Lymphoma, hamartoma and pericardial mesothelioma can also affect the right atrium.6,7 Vegetations on the tricuspid valve can be seen in case of infective endocarditis while non-infective masses have been reported in patients with antiphospholipid antibody syndrome.8 Calcified masses such as the calcified amorphous tumour have been reported in patients with end stage renal failure,9 and cardiac hydatid cysts on the tricuspid valve has also been described.10 In case of previous cardiac surgery, the presence of prosthetic material can orient the aetiological diagnosis toward the presence of a thrombus.2,3 Nevertheless, all other causes cannot be excluded, especially when the mass presents years after the operation.\n\nDiagnosis is usually made initially by imaging through TTE as first-line modality, and cardiac computed tomography or magnetic resonance to better characterize the tissues. Finally, 18-Flurodeoxyglucose positron emission tomography may identify an increased metabolic activity of tumours. In the case described above, echocardiography was the only diagnostic tool available and precise differentiation among all aetiologies was not possible. However, yearly follow-up visits and TTE were pivotal to diagnose the mass and give surgical indication before the occurrence of any complication.\n\nFinally, direct excision of the mass and subsequent histological analysis revealed the thrombotic origin of the mass. Although right-sided prosthetic materials have demonstrated a higher thrombotic potential than their left-sided ones, there are no specific postoperative antithrombotic management recommendations after tricuspid valve repair, especially in the case of all types of De Vega’s annuloplasty techniques.3 Moreover, the association between tricuspid procedures and other indications for postoperative anticoagulation (e.g., concomitant left-sided mechanical valves like in the case presented) may contribute to the low incidence of this diagnosis, especially in case of infrequent TTE and follow-up contacts with the patient. This may become a problem in rural areas or developing countries where the follow-up programs might be difficult.11 Moreover, difficult access to the tertiary cardiac surgery centre can reduce the patient’s compliance to the anticoagulation therapy as it happened in the presented case. Indeed, she demonstrated a low TTR with a decreasing trend as time passed since the first surgery. We can, thus, speculate that such a low compliance could have favoured the development of a thrombus over the annuloplasty stitches. Further screenings for any hypercoagulopathy could have helped in the characterization of the case but they could not be performed for economical and logistic reasons.\n\nIn conclusion, this case report highlights the importance of adequate follow-up programs for young patients undergoing valve surgery for rheumatic heart disease in developing countries. Moreover, it shows how tricuspid annuloplasty can carry a certain degree of thrombotic risk, even years after surgery. Further studies are required to investigate the fate of patients receiving tricuspid annuloplasty associated to left-sided valve surgery for rheumatic heart disease.\n\n\nConsent\n\nWritten informed consent for data collection and publication was obtained from the patient and the patient’s mother, as legal guardian. We confirm that we have obtained permission to use images included in this presentation from the patient and the mother, as legal guardian.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nFigshare: CARE checklist for ‘Case Report: Right atrial organized thrombus three years after tricuspid annuloplasty’. https://doi.org/10.6084/m9.figshare.21640205. 12\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nReferences\n\nL’Angiocola PD, Donati R: Cardiac Masses in Echocardiography: A Pragmatic Review. J. Cardiovasc. Echogr. 2020; 30(1): 5–14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEfe SÇ, Unkun T, İzci S, et al.: Thrombus Formation on the Tricuspid Valve After De Vega’s Annuloplasty and Repair of Endocardial Cushion Defect. J. Cardiovasc. Thorac. Res. 2014; 6(3): 203–204. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCastano M, Gualis J, Martin CE, et al.: Early thrombosis of a tricuspid annuloplasty ring and mild hyperhomocysteinemia. Ann. Thorac. Surg. 2011; 92(6): e125–e126. PubMed Abstract | Publisher Full Text\n\nLi J, Zhu H, Hu SY, et al.: Case report: Cardiac metastatic leiomyoma in an Asian female. Front. Surg. 2022; 9: 991558. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDi Bella G, Gaeta M, Patanè L, et al.: Tissue characterization of a primary cardiac angiosarcoma using magnetic resonance imaging. Rev. Esp. Cardiol. 2010; 63(11): 1382–1383. PubMed Abstract | Publisher Full Text\n\nDi Bella G, Mileto A, Gaeta M, et al.: Atrial lipomatous hypertrophy causing reduction in systemic venous return. Herz. 2011; 36(2): 147–148. PubMed Abstract | Publisher Full Text\n\nZhou X, Zhou Y, Zhaoshun Y, et al.: Hamartoma of mature cardiomyocytes in right atrium: A case report and literature review. Medicine (Baltimore). 2019; 98(31): e16640. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMigliorini S, Santoro C, Scatteia A, et al.: A Rare Case of Tricuspid Valve Libman-Sacks Endocarditis in a Pregnant Woman with Primary Antiphospholipid Syndrome. J. Clin. Med. 2022; 11(19). PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu H, Tu X, Zhang H, et al.: Case report: A primary calcified cardiac mass in right atrium partially obstructs the tricuspid valve in a patient on hemodialysis. Front. Cardiovasc. Med. 2022; 9: 950628. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBajdechi M, Manolache D, Tudor A, et al.: Cardiac hydatid cysts in a young man: A case report and a literature review. Exp. Ther. Med. 2022; 24(3): 550. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMiccio R, Quattrociocchi M, Valgoi L, et al.: Treating Children With Advanced Rheumatic Heart Disease in Sub-Saharan Africa: The NGO EMERGENCY’s Project at the Salam Centre for Cardiac Surgery in Sudan. Front. Pediatr. 2021; 9: 704729. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMariani S, Lentini S: Case Report: Right Atrial Organized Thrombus 3 Years after Tricuspid Annuloplasty. [Dataset]. figshare. 2022. Publisher Full Text"
}
|
[
{
"id": "158878",
"date": "08 Mar 2023",
"name": "Tong Li",
"expertise": [
"Reviewer Expertise mechanical circulatory support and heart transplantation"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe authors contributed a very rare and meaningful case to us. The etiological background, preoperaitve exams and surgery details have been clearly presented in this case report. There are only several known cases of right atrial thrombus after tricuspid annuloplasty published in the history. The known cases are all old patients from east Asia, which the patients also maybe experienced the country developing processes. From this young African girl's stroy, the doctors in the developing countries maybe reinforce their postoperaive and follow-up guidances to the patients, especially those who live in rural areas. Meanwhile, the surgeon can be more focused on and cautious to the intraoperative procedures to facilitate the long term results, for example the De Vega annuloplasty, considering their patients may not have statifying compliance. I would like to suggest the authors adding the patients' BMI at 13 years old and 16 years old to let the whole story more vivid.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "9726",
"date": "01 Jun 2023",
"name": "Salvatore Lentini",
"role": "Author Response",
"response": "We are grateful for the opportunity to submit a revised version of our manuscript “Case Report: Right atrial organized thrombus three years after tricuspid annuloplasty” to F1000 Research and are thankful for the very constructive and helpful comments of the Reviewers. In addition to responding to the comments, we revised the manuscript, and hope that the changes and responses satisfy the Editors and Reviewers` requests. Reviewer 1 The authors contributed a very rare and meaningful case to us. The etiological background, preoperaitve exams and surgery details have been clearly presented in this case report. There are only several known cases of right atrial thrombus after tricuspid annuloplasty published in the history. The known cases are all old patients from east Asia, which the patients also maybe experienced the country developing processes. From this young African girl's story, the doctors in the developing countries maybe reinforce their postoperaive and follow-up guidances to the patients, especially those who live in rural areas. Meanwhile, the surgeon can be more focused on and cautious to the intraoperative procedures to facilitate the long term results, for example the De Vega annuloplasty, considering their patients may not have statifying compliance. I would like to suggest the authors adding the patients' BMI at 13 years old and 16 years old to let the whole story more vivid. We thank the reviewer for his positive evaluation on our manuscript. As suggested, we added the patient’s BMI to the case report description. Changes: case presentation She was first referred to our hospital due to severe mitral, aortic and tricuspid regurgitation when she was 13 years old (body mass index 12.65). […] At the follow-up visit 41 months after surgery (16 years old, body mass index 18.49)"
}
]
},
{
"id": "158882",
"date": "03 May 2023",
"name": "Sossio Perrotta",
"expertise": [
"Reviewer Expertise Endocarditis"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI would like to gratulate the author for reporting this interesting and rare case of a patient with a thrombus formation on the tricuspid valve annulus after a modified De Vega’s annuloplasty. The patient underwent surgery with removal of the thrombus and discharged home 12 days after surgery.\nThe article is well written, but few points should be clarified. I would like the authors to comment on the following points\nThe author should provide some information about the preoperative symptoms and the preoperative echocardiographic finds at the time of the first operation.\nWhich was the anticoagulation therapy at discharge?\nThe author states that aspirin was discontinued two years after the surgery. Why was aspirin needed two years after the surgery? Probably due to the low compliance to anticoagulation therapy. But since the compliance to anticoagulation was low at the third and fourth year was the aspirin reintroduced?\nI notice that the author uses two specific mechanic valves in aortic and mitral position. On the market is available a different mechanical valve prosthesis, that can be used in both mitral and aortic position. For this specific mechanical valve the anticoagulation therapy can be carried out with a lower INR in combination with aspirin. Has the author thought to change the used mechanical valves in consideration to the special social contest in which he practices and the difficulties for the patients to adhere to the needed anticoagulation therapy?\nThe author states that the patient had a low compliance with regard to the anticoagulation therapy, but no information is given if the patient had trombi on the mitral and aortic valves or if she had peripheral embolism.\nTo remove the mass in the right atrium, the patient underwent a second surgery and the heart was arrested. Why the author used this surgical approach? This kind of surgery can be performed as well with a beating heart. Since the patient had a mildly depressed left ventricular systolic function (46%), why to expose this heart to ischaemic time when it was possible to avoid it?\n\nI think the the article can be deemed suitable for indexing with minor corrections\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "9725",
"date": "01 Jun 2023",
"name": "Salvatore Lentini",
"role": "Author Response",
"response": "We are grateful for the opportunity to submit a revised version of our manuscript “Case Report: Right atrial organized thrombus three years after tricuspid annuloplasty” to F1000 Research and are thankful for the very constructive and helpful comments of the Reviewers. In addition to responding to the comments, we revised the manuscript, and hope that the changes and responses satisfy the Editors and Reviewers` requests. Reviewer 2 I would like to gratulate the author for reporting this interesting and rare case of a patient with a thrombus formation on the tricuspid valve annulus after a modified De Vega’s annuloplasty. The patient underwent surgery with removal of the thrombus and discharged home 12 days after surgery. The article is well written, but few points should be clarified. I would like the authors to comment on the following points. We are grateful to the Reviewer for the very constructive and helpful comments. In addition to responding to the comments, we revised the manuscript, and hope that the changes and responses satisfy the Reviewers` requests. The author should provide some information about the preoperative symptoms and the preoperative echocardiographic finds at the time of the first operation. We thank the Reviewer for this suggestion. We added a brief description of the pre-operative symptoms and echocardiographic findings. Changes: case presentation Her symptoms started with shortness of breath on exertion, dry cough, palpitations and lower limb oedema. She was first referred to our hospital due to signs of acute decompensation (raised jugular venous pressure, limb oedema and dyspnoea) when she was 13 years old (body mass index 12.65). Transthoracic echocardiography showed retracted rheumatic mitral and aortic leaflets associated with severe mitral and aortic regurgitation. The left atrium and ventricle were dilated, and a secondary severe tricuspid regurgitation was diagnosed. Which was the anticoagulation therapy at discharge? The Reviewer pointed out an interesting clinical detail. We modified the manuscript adding details about the anticoagulation therapy at discharge: Changes: case presentation The anticoagulation therapy included warfarin with a target international normalized ratio of 2.5–3.5 and was associated with oral aspirin (100 mg/day). The author states that aspirin was discontinued two years after the surgery. Why was aspirin needed two years after the surgery? Probably due to the low compliance to anticoagulation therapy. But since the compliance to anticoagulation was low at the third and fourth year was the aspirin reintroduced? We thank the reviewer for this interesting question. Aspirin was associated with warfarin as the patient was a woman in fertile age living in a rural area. Thus, the patient was at higher risk of low compliance for the anticoagulation therapy and a possible pregnancy would have required association with anti-platelet therapy as previously reported in a study from our group on pregnancy outcomes in women with mechanical valve prostheses using vitamin K antagonist therapy (PMID: 35899137), and following guidelines (PMID: 33342587). After the menorrhagia experienced by the patient, aspirin was not re-introduced despite the low compliance due to the previous bleeding event. Changes: case presentation The anticoagulation therapy included warfarin with a target international normalized ratio of 2.5–3.5 and was associated with oral aspirin (100 mg/day) as the patient was a woman in fertile age living in a rural area. I notice that the author uses two specific mechanic valves in aortic and mitral position. On the market is available a different mechanical valve prosthesis, that can be used in both mitral and aortic position. For this specific mechanical valve the anticoagulation therapy can be carried out with a lower INR in combination with aspirin. Has the author thought to change the used mechanical valves in consideration to the special social contest in which he practices and the difficulties for the patients to adhere to the needed anticoagulation therapy? The Reviewer is correct and, indeed, the On-X valve was evaluated for possible use in our patients. Despite the possible better outcomes in our patients, the costs of this valve are higher compared to the valve which are currently used at the Salam Center. The Salam Center is financially supported by the local government and by an NGO called “Emergency”. Based on the limited financial resources available, unfortunately the routine use of the On-X valve was not possible and, thus, was limited to very few selected patients (i.e. redo patients). The author states that the patient had a low compliance with regard to the anticoagulation therapy, but no information is given if the patient had trombi on the mitral and aortic valves or if she had peripheral embolism. We thank the Reviewer for this remark. We specified in the case presentation that the patient did not have any clot formations nor embolism events. Changes: case presentation No other masses or possible thrombi were noticed on the left heart prosthetic valves, nor episodes of systemic or pulmonary embolism were reported. To remove the mass in the right atrium, the patient underwent a second surgery and the heart was arrested. Why the author used this surgical approach? This kind of surgery can be performed as well with a beating heart. Since the patient had a mildly depressed left ventricular systolic function (46%), why to expose this heart to ischaemic time when it was possible to avoid it? We agree with the Reviewer on the fact that operations on the right heart could be completed with a beating heart approach. Indeed, this is the approach used at Salam Centre for most surgeries on tricuspid valves. However, in this case, a possible diagnosis of malignant tumour could not be ruled out before surgery. Therefore, the heart was stopped to reduce the risk of tumour embolization resulting from mass manipulation and allow for a radical removal of the mass in case of malignant diagnosis. Changes: case presentation The surgery was completed at arrested heart to reduce the risk of neoplastic embolization in case of malignant diagnosis and allow for a radical removal of the mass. I think the the article can be deemed suitable for indexing with minor corrections. We thank the Reviewer for the attention and efforts in reviewing our manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/12-6
|
https://f1000research.com/articles/12-591/v1
|
01 Jun 23
|
{
"type": "Research Article",
"title": "Diabetes Mellitus and quality of life: lower socio-economic status patients in Indian tertiary healthcare – a cross sectional study",
"authors": [
"Oishee Bhattacharya",
"Rhea Alva",
"Prajwal K.P",
"G V Abhinay Reddy",
"Himani Kotian",
"Oishee Bhattacharya",
"Prajwal K.P",
"G V Abhinay Reddy",
"Himani Kotian"
],
"abstract": "Background: Diabetes mellitus has emerged as one of the most severe diseases in regards to impact on lifestyle. It behaves as a syndrome rather than a single illness owing to its long term complications. Improving the quality of life (QoL) is the main goal to be achieved, thereby making it an essential factor to prognosticate the long term health consequences. Decreased QoL has been observed in patients with long standing diabetes mellitus and worsens when comorbidities add up to it. Routine activities in patients with diabetes is associated with massive physical and psychosocial implications that can lead to lack of self-care, thereby affecting glycaemic control, leading to early development of complications, and finally affecting quality of life. The goal of this study is to understand the relation between the domains of QoL among patients with diabetes mellitus belonging to lower socio-economic status of coastal India.\nMethods: A cross sectional study focused on individuals seeking services of our tertiary health facility. The study analyzed 100 samples over various domains of QoL. The BG Prasad scale for socio-economic status and the MDQoL-17 questionnaire was used. SPSS version 25.0 was utilized for data analysis. Descriptive statistics namely standard deviation, mean and proportions were used for expressing the outcomes.\nResults: Data from 100 participants was evaluated of which 63% were males. The mean ages were between 57.2±1.2 years with 31% belonged to ages between 51-60 years. Socio-economic category 4 was highest (52%). Majority of the participants had diabetes since 1-5 years (44%) and >6.5 HbA1c was seen among 95%. A p-value of <0.001 was observed with physical functioning, physical health, emotional wellbeing, emotional health, social functioning and general health that was suggestive of statistical significance.\nConclusions: The study was able to correlate various determinants of overall QoL affected, necessitating a targeted approach.",
"keywords": [
"Quality of life",
"Diabetes Mellitus",
"lower socio-economic status",
"India"
],
"content": "Introduction\n\nThe World Health Organization (WHO) defines QoL as “an individual’s perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns.”1 Improved QoL is the main goal to be achieved in management of long lasting ailments, thereby making QoL an essential health consequence.2 QoL consists of four categories; environmental, physical, social and psychological. Decreased QoL is observed in patients having diabetes and worsens when comorbidities or complications occur. Metabolic diseases comprising of hyperglycaemia without treatment constitute diabetes. Etiopathology of diabetes is mixed and it consists of defective action and/or secretion of insulin along with derangements in metabolism of proteins, fats and carbohydrates. Individuals having “fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dl)”, “2-h post-load plasma glucose ≥ 11.1 mmol/L (200 mg/dl)”, “HbA1c ≥ 6.5% (48 mmol/mol)”; or “random blood glucose ≥ 11.1 mmol/L (200 mg/dl)” along with appropriate clinical features are regarded as diabetic patients. “Type I diabetes (T1DM)” and “Type II diabetes (T2DM)” are the “2” essential types. The difference between these two types is according factors like need for insulin treatment, insulin resistance, age at onset, involvement of diabetes-associated antibodies and β cell function loss. Neuropathy, nephropathy and retinopathy are the explicit side effects seen in diabetes in the long run. There is also presence of association with ailments involving tuberculosis, cerebrovascular disease, heart, erectile dysfunction, obesity, non-alcoholic fatty liver disease and cataract. Confirmation of diabetes comes with various consequences for patients, in respect of their health, plus the existence of several social stigmas. A diabetes diagnosis can in turn affect various aspects of their life such as their social opportunities, employment, driving status, life and health insurance and carrying out ethical and cultural customs.4 Patients often feel burdened by their ailment and its daily management necessities and these challenges are considerable; making innumerable decisions on a daily basis.4 Management of diabetes, for instance, insulin administration, can reduce symptoms of hyperglycaemia or can increase symptoms of hypoglycaemia; which therefore has a beneficial or negative affect on quality of life. A life with diabetes can be a psychosocial burden. This can in turn lead to repercussions in terms of lack of self-care and thus, can affect glycaemic control in turn leading to development of long-term complications, and finally affecting QoL.5 The benefits of self-care in lifestyle management of diabetes is influenced by psychosocial factors and its variables are strong determinants of end results, such as hospitalization and death as compared to physiologic and metabolic adjustments.6 Diabetes is one of the topmost hazards to public health worldwide and in the case of countries with low to middle-income, such as India, the situation becomes more frightful, where the disease burden has steadily increased and will continue to rise further in the future.7 India is experiencing a rise in incidence and a transition in prevalence of diabetes from older to younger individuals, the wealthy to the poor and from urban to rural areas.8 The ultimate goal of healthcare interventions is evaluation of QoL in clinical practice and research settings. From various QoL research studies, several findings of clinical use have been reported.5 Routine assessments of QoL in clinical practice has the ability to improve doctor-patient relationships, identify issues that are often ignored, prioritise obstacles, and assess the outcome of restorative attempts at the individual level.5 This study aims to understand the relation between various domains of quality of life affected among patients belonging to lower socio-economic status with Diabetes Mellitus in our setting.\n\n\nMethods\n\nIt was approved by the Institutional Ethics Committee (IEC) Kasturba Medical college, Mangalore (IEC KMC MLR 08/2022/342). Permission was obtained from the Medical Superintendent of the tertiary healthcare affiliated to the institution, to collect data from patients seeking out-patient and in-patient services from the hospital for a duration of one month. Written informed consent was obtained from all participants.\n\nThe study was conducted in the tertiary level health care set-up affiliated to investigators’ medical college during September 2022. A cross sectional study design was adopted for this study. The sample size calculated was approximately 100, using the formula N = Z2σ2/d2, where Z = 1.96 is a standard abnormal value at 5% level of significance, σ is the Standard Deviation = 15.07 and d is the clinically significant difference = 3.9\n\nAll participants were selected on the basis of non-probability sampling method, therefore no particular sex was given any preference for selection of eligible participants. According to the inclusion criteria, chosen participants were above 18 years old, who are known cases of Type II diabetes mellitus and belonging to socio-economic status Category 4 (monthly per capita income ₹1,166-2,253), or Category 5 (monthly per capita income < ₹1,166) according to B. G Prasad classification, 2021.8 Individuals below 18 years old or those who are not a known to have Type II diabetes mellitus or fall under Category 1 (monthly per capita income > ₹7,770), Category 2 (monthly per capita income ₹3,808-7,769), or Category 3 (monthly per capita income ₹2,253-3,808) of B. G Prasad Classification, 2021, were excluded.8\n\nNecessary information was noted in the proforma, which consisted of socio-demographic data, such as sex, age, B. G Prasad socio-economic status category, details about diabetes mellitus such as duration of disease, type of treatment used, HbA1c value, presence of other comorbidities and presence of complications.15 The QoL was calculated using the MDQoL-17 questionnaire.15 Microsoft Excel was used for entry of data.14 For statistical analysis, IBM SPSS for Macintosh version 25.0, Armonk, New York. 25.0 was employed.16 Descriptive statistics such as proportion, standard deviation and mean were used for procuring the results. The Chi-square test was applied for analysis of the relation between different factors and overall QoL and a p value <0.05 was considered to be statistically significant.\n\n\nResults\n\nData obtained from 100 participants was evaluated. Table 1 stands for the baseline characteristics namely sex, age and B. G Prasad category.10 The majority of the participants were males (63%) as compared to females (37%). The mean age of the patients was 57.2 ± 1.2 years. The highest number of participants belonged to 51-60 years old age bracket (31%), followed by 41-50 years (25%) and 61-70 years (18%). In the case of socio-economic status, there was almost equal distribution of participants with a higher number in Category 4 (52%) as compared to Category 5 (48%). Table 2 represents details about diabetes mellitus such as duration, HBA1c, medications, comorbidities and complications. In terms of the duration of the disease, the majority of the participants belonged to 1-5 years (44%), followed by 6-10 years (28%) and >20 years (9%). >6.5 HbA1c was seen among 95% participants and <6.5 among 5%. Most of the patients were on only OHA (87%), followed by Insulin (8%), followed by combination of both OHA and Insulin (5%). There was an almost equal distribution of participants among presence (51%) and absence (49%) of comorbidities. The majority of the participants had microvascular complications (43%), followed by macrovascular (29%), followed by absence of any complications (24%), followed by both macrovascular and microvascular complications (4%). Table 3 represents the distribution of the QoL scores and its various determinants. As per the cut-off set by the MDQoL-17 questionnaire, a QoL score above 70 suggests a better QoL as compared to a score of 50-70 which indicates moderate QoL and score less than 50 suggests a poor QoL.9 Table 4 depicts the association between various factors and the overall QoL. A p-value of <0.001 was observed when physical functioning, physical health, emotional wellbeing, emotional health, social functioning and general health were compared with overall QoL, suggestive of extreme significance. Remaining determinants showed a p-value of >0.05 when compared with overall QoL.\n\n\nDiscussion\n\nIn our study we assessed the quality of life and its various domains among 100 diabetic patients belonging to lower socioeconomic groups as classified by the B.G. Prasad category 4 and 5. The average age of the participants was around 57 years old, with most being male. A similar distribution with regard to age and gender was noted in a study of global prevalence of diabetes by Wild et al., as well as regional studies with the average age of diabetic patients around 45-65 years.9,11,12 Quality of life significantly worsened with age and duration of diabetes as supported by similar studies on quality of life of diabetic patients.9,13\n\nIn this study we note lower quality of life scores among females as compared to the male patients. A similar observation was also made in studies conducted among the general population in different parts of the world.3,13,17 Diabetes seems to have a more severe impact on quality of life of women, irrespective of their socioeconomic status or race.\n\nThough more than 95% participants had an HbA1C of more than 6.5% and 76% had diabetic complications, only 13% were receiving insulin therapy. Many factors may have contributed to the poor compliance of these patients to initiate or continue insulin therapy such as accessibility, cost, storage and difficulty in administering insulin.\n\nMost patients demonstrated an overall moderate to poor quality of life with determinants such as physical health, emotional wellbeing, social functioning and general health significantly affected. Increased energy fatigue, decreased energy levels, sleep disturbances and problems in social or work life were noted in the participants further impairing quality of life.\n\nA lack of self-care and awareness of the course of the disease may have affected the general health of the patients.\n\nWe need to conduct follow up visits of diabetic patients, especially those belonging to lower socioeconomic status and ensure compliance to treatment. Regular follow up visits with the doctor will improve the doctor patient relationship, glycaemic control and also enable early identification of factors affecting quality of life. Patients should be encouraged to maintain a healthy diet and regular exercise and self-care. Complications can be detected early and managed accordingly without causing significant morbidity. The visits may also provide an opportunity to address any problems they may be facing concerning their physical or emotional health. Screening for depression should be done routinely. These measures may improve their quality of life which is the main goal while managing chronic ailments.\n\n\nConclusion\n\nThe study demonstrates a significantly affected QoL in diabetic patients belonging to lower socioeconomic strata in terms of physical health, emotional wellbeing and social functioning. We need to address common problems faced by patients in lower socioeconomic groups; lack of patient education and the financial burden of the disease can negatively affect their compliance with treatment.\n\nWith a better interpretation of the various domains of QoL affected in diabetic patients belonging to lower socioeconomic status we can use targeted approach to improve QoL. This study highlights the need for routine evaluation of these patients to assess compliance to treatment, identify complications and timely intervention thus improve their QoL.",
"appendix": "Data availability\n\nFigshare: ‘Quality of life in patients with Diabetes Mellitus belonging to lower socio-economic status in a tertiary healthcare setup in coastal India’, https://doi.org/10.6084/m9.figshare.21904497.v2. 14\n\nThis project contains the following underlying data:\n\n• data collection-2.xlsx\n\nFigshare: ‘Diabetes Mellitus and quality of life: lower socio-economic status patients in Indian tertiary healthcare – a cross sectional study’, https://doi.org/10.6084/m9.figshare.21971933.v1. 15\n\nThis project contains the following extended data:\n\n• Questionnaire.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nThe authors thank the support provided by Manipal Academy of Higher Education.\n\n\nReferences\n\nWHOQOL group: Development of the WHOQOL: Rationale and current status. Int. J. Ment. Health. 1994; 23: 24–56. Publisher Full Text\n\nSkevington S, Lotfy M, O’Connell KA, et al.: The World Health Organization’s WHOQOL-BREF quality of life assessment: Psychometric properties and results of the international field trial. A report from the WHOQOL group. Qual. Life Res. 2004; 13: 299–310. PubMed Abstract | Publisher Full Text\n\nTrikkalinou A, Papazafiropoulou AK, Melidonis A: Type 2 diabetes and quality of life. World J. Diabetes. 2017; 8(4): 120–129. PubMed Abstract | Publisher Full Text\n\nClassification of diabetes mellitus. Geneva: World Health Organization; 2019.\n\nRubin RR, Peyrot M: Quality of life and diabetes. Diabetes Metab. Res. Rev. 1999; 15(03): 205–218. PubMed Abstract | Publisher Full Text\n\nRosenthal MJ, Fajardo M, Gilmore S, et al.: Hospitalization and mortality of diabetes in older adults: a three-year prospective study. Diabetes Care. 1998; 21: 231–235. Publisher Full Text\n\nPradeepa R, Mohan V: Epidemiology of type 2 diabetes in India. Indian J. Ophthalmol. 2021; 69(11): 2932–2938. PubMed Abstract | Publisher Full Text\n\nPradeepa R, Mohan V: Prevalence of type 2 diabetes and its complications in India and economic costs to the nation. Eur. J. Clin. Nutr. 2017; 71(7): 816–824. PubMed Abstract | Publisher Full Text\n\nPrajapati VB, Blake R, Acharya LD, et al.: Assessment of quality of life in type II diabetic patients using the modified diabetes quality of life (MDQOL)-17 questionnaire. Brazilian J. Pharm. Sci. 2017 Jan 1; 53(4): e17144.\n\nKhairnar MR, Kumar PG, Kusumakar A: Updated BG prasad socioeconomic status classification for the year 2021. J. Indian Assoc. Public Health Dent. 2021; 19: 154–155. Publisher Full Text\n\nWild S, Roglic G, Green A, et al.: Global prevalence of dibetes: estimate for the year 2000 and projections for 2030. Diabetes Care. 2004; 27(5): 1047–1053. Publisher Full Text\n\nGholami A, Azini M, Borji A, et al.: Quality of Life in Patients with Type 2 Diabetes: Application of WHOQoL-BREF Scale. Shiraz E-Med. J. 2013; 14(3): 162–171.\n\nGlasgow RE, Ruggiero L, Eakin EG, et al.: Quality of life and associated characteristics in a large national sample of adults with diabetes. Diabetes Care. 1997; 20(4): 562–567. PubMed Abstract | Publisher Full Text\n\nBhattacharya O, Alva R, Prajwal KP, et al.: Quality of life in patients with Diabetes Mellitus belonging to lower socio-economic status in a tertiary healthcare setup in coastal India. Dataset. figshare. 2023. Publisher Full Text\n\nBhattacharya O, Alva R, Prajwal KP, et al.: Diabetes Mellitus and quality of life: lower socio-economic status patients in Indian tertiary healthcare – a cross sectional study. Dataset. figshare. 2023. Publisher Full Text\n\nIBM Corp: Released 2017. IBM SPSS Statistics for Macintosh, Version 25.0. Armonk, NY: IBM Corp.\n\nRedekop WK, Koopmanschap MA, Stolk RP, et al.: Health-related quality of life and treatment satisfaction in Dutch patients with type 2 diabetes. Diabetes Care. 2002; 25: 458–463. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "176372",
"date": "19 Jun 2023",
"name": "Pasquale J. Palumbo",
"expertise": [
"Reviewer Expertise Mathematical Modeling in Biology and Medicine"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe Authors propose a study on the Quality of Life (QoL) for 100 individuals in Bangalore. According to my understanding the Authors proposed a simple interview and then partitioned the acquired data according to gender, socioeconomic groups, etc.\nAccording to this reviewer opinion, there seem to be too little material for a scientific publication: there is no statistical analysis, and, moreover, the 100 individuals do seem too little to obtain statistical significance.\nBelow follow further comments.\n1) page 3, lines 9-11: I guess these data are taken from references [1,2]. If this is the case, the Authors should be more explicit\n2) page 3, formula N=Z^2\\sigma^2/d^2: Where does this formula come from? The Authors have to explain it in details, since it seems it has been exploited to assess the number of patients under investigation\n3) page 3, dealing with monthly per capita income: I guess the character refers to currency in Mangalore, but it should be explained and, also, referred to euros/dollars\n4) more details on the MDQoL questionnaire\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "205110",
"date": "17 Oct 2023",
"name": "Mohd Ashraf Ganie",
"expertise": [
"Reviewer Expertise Endocrine disorders"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nStudy title: Diabetes Mellitus and quality of life: lower socio-economic status patients in Indian tertiary healthcare – a cross sectional study\nWith a sample size of 100, The study demonstrates a significantly affected QoL in diabetic patients belonging to lower socioeconomic strata in terms of physical health, emotional well being and social functioning.\nMentioned below are the corrections I could suggest to the current manuscript.\nMethods:\nSeeing the burden of type 2 DM, sample size is too small for scientific publication\n\nNo details about MDQoL-17 questionnaire provided\n\nNo proper statistical analysis and 100 individuals do seem too little to obtain statistical significance\n\nResults:\nMajority were having short duration of diabetes, 1-5 years (44%), but in general QoL worsens with longer duration of diabetes, so difficult to apply interpretions of this study on general population\n\nType of Comorbidities are not defined\n\nIn general associated comorbidities with type 2 DM can lead to more poorer QoL, in this study, among 49 subjects without comorbidities, 24 had poor QoL and only 5 had better QoL, on the other hand, among 51 subjects with comorbidities, 20 had poor QoL, but 12 had better QoL , any explanation for this discripency\nDiscussion:\n> 95% were having HbA1c more than 6.5%, which means poor control in majority of patients which can lead to bias in apply results of this study in general diabetic population, as majority in this study were having poorly controlled diabetes\n\nLine 20, paragraph 5, change spelling of glycaemic to glycemic\nFinal comment: seem too little material for a scientific publication\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-591
|
https://f1000research.com/articles/12-582/v1
|
31 May 23
|
{
"type": "Research Article",
"title": "Health professionals KAP study on rabies exposure assessment and NTV administration in Ethiopia",
"authors": [
"Abebe M. Aga",
"Demise Mulugeta",
"Yeweynshet Tesera",
"Birhanu Hurisa",
"Hailu Lemma",
"Ayele Bizuneh",
"Jemal Mohammed",
"Mekoro Beyene",
"Yimer Mulugeta",
"Bayeh Ashenafi",
"Samuel Woldekidan",
"Dereje Nigussie",
"Abebe M. Aga",
"Samuel Woldekidan"
],
"abstract": "Background: Globally, it’s estimated 60,000 human deaths occur due to rabies with 95% of cases occurring in Africa and Asia. Annually, thousands of people are infected with rabies in Ethiopia and more than 2700 people die. In Ethiopia, the neural-based vaccine has been used since the 1950’s. Due to the old method of production, low immunogenicity and vaccine associated adverse events, WHO discourage the use of this vaccine and recommend replacing it with a safe and effective modern cell culture vaccine. There was no specific guidelines and training for this vaccine and health professional mismanage the nerve tissue vaccine (NTV) with cell culture vaccine resulting in vaccination failure. This study identifies professional knowledge, attitude and practice (KAP), vaccine related adverse events and the burden of rabies cases in humans. Methods: Data were collected from health professionals in selected health facilities using structured questionnaire to identify the level of KAP. Results: The study identified overall gaps in the professionals KAP as below standard which is not more than 25%. The majority of the respondents (97%) reported vaccine associated local adverse events followed by 20% systemic complications during vaccination. Only 2.4% of the respondents reported post-vaccine complications. Rabies cases in humans at those covered health facilities were reported to be 32 during the one-year study period with an average of two cases at each facility. Conclusions: Gaps identified in the professional KAP result indicate the need to provide specific training based on standard guidelines. Generally, the study indicates the need to strengthen rabies prevention and control efforts through inter-sectoral collaboration, and facilitating the establishment of facility-based rabies palliative care centers. In addition, it is recommended to work on technology transfer to replace old method of NTV production with safe and effective modern cell culture based anti-rabies vaccine production for effective rabies PEP.",
"keywords": [
"Human rabies case",
"Knowledge attitude practice",
"Nerve tissue vaccine",
"Rabies palliative care",
"Vaccine adverse events"
],
"content": "Introduction\n\nRabies is a viral zoonotic disease with the highest case fatality rate. The disease is 100% fatal once clinical signs appear. Domestic dogs are responsible for up to 99% of rabies virus transmission to humans. The incubation period can range from days to years, with an average length of 3-8 weeks (WHO, 2018).\n\nThe classic signs of rabies include abnormal behavior, altered vocalization, pica, hyper sexuality, drooling saliva, aimless wandering, aggression, incoordination, paralysis and convulsions. Rabies is a highly fatal viral disease of all warm-blooded animals, including humans (Baer et al., 1990). It is widely distributed throughout the world and endemic in most African and Asian countries and estimated to cause at least 60,000 deaths per year worldwide, about 56% of which occur in Asia and 44% in Africa (Knobel et al., 2005; WHO, 2013). Globally, only a few countries, mainly islands and peninsulas, are free of the disease.\n\nRabies is endemic in developing countries in Africa and Asia, and most human deaths due to the disease occur in these endemic countries. Ethiopia is highly endemic for rabies with approximately 2,700 people estimated to die of rabies annually, which makes it one of the worst affected countries in the world (Deressa et al., 2015; Rohit et al., 2015). The first rabies epidemic in Ethiopia occurred in Addis Ababa in August 1903 as reported by Lincon, a physician at the Italian Legacion. The Ethiopian national rabies baseline survey 2012 showed that the incidence rates of rabies 12 exposure per 100,000 population and 1.6 death/100,000 population with a proportion of exposure is high among those less than 15 years of age (WHO, 2010; Ali et al., 2012). Dogs are the principal source of infection for humans and livestock (CDC, 2017; Reta et al., 2014).\n\nAs rabies is one of the worst diseases with no proven effective antiviral or other treatment, palliative care is an imperative to minimize patient suffering. Suspicion of rabies encephalomyelitis depends on recognizing the classic symptomatology and eliciting a history of exposure to a possibly rabid mammal. This type of care center is an important part of health care to minimize suffering of the patient with signs and symptoms of rabies disease (WHO, 2018).\n\nRabies is a vaccine-preventable disease, and it is still a significant public health problem in Ethiopia as a result of domestic animals, mostly dogs and wildlife, mostly foxes. Mass vaccination of the dog population is the only way to reduce or eliminate rabies. Nerve tissue origin, an old type of anti-rabies vaccine (nerve tissue vaccine) used in Ethiopia since the 1950’s. Currently, the consumption of this vaccine is more than 33,000 full doses annually. The vaccine prepared from small animal brains which contain protein called myelin sheath neural elements responsible for nerve complication as an autoimmune disorder at a rate estimated as 0.3-0.8 per thousand treated patients. Thus, this vaccine is no longer recommended by WHO due to its serious side effects and low immunogenicity (Tullu et al., 2003; WHO, 2007). Even though this vaccine has drawbacks, it is still distributed throughout the country to save the lives of a thousand people each year (Aga et al., 2021).\n\nEven though the nerve tissue vaccine (NTV) has been used for a long period of time in this country, there was no standard guideline for rabies exposure assessment and proper vaccine administration. The other issue is that the patient with sign and symptom of rabies needs an organized palliative care center to minimize suffering due to the disease. Therefore, the main objective of this study was to assess the knowledge, attitude and practice of health professionals in delivering facility-based service for rabies exposure assessment and vaccine administration. The study also identifies NTV vaccine associated complication during the course of vaccination. In addition to that, the study was aimed to assess the availability of a palliative care center for the care required for patients with specific rabies signs and symptoms.\n\n\nMethods\n\nHealth facilities delivering rabies post exposure vaccination (PEP) were selected based on the list available at VDPD, EPHI. Across the country, 28 health facilities delivering this service were included in the study except some western and northern parts which were excluded due to security concerns. Regions and selected health facilities receiving NTV vaccine from EPHI were included for this professional knowledge, attitude and practice (KAP) assessment and vaccine associated adverse event study. Some regions were intentionally excluded as a result of low vaccine demand compared to others.\n\nHealth professionals delivering rabies related services; rabies exposure risk assessment, vaccine cold chain management and vaccine administration were asked for their KAP about the service they have been providing. Five to eight health professionals were selected from each health facility based on the service they provide and asked to respond to structured questions provided for this purpose. Nerve tissue vaccine associated adverse events observed were included in the questionnaire. The number of human deaths due to rabies at those facilities, and availability and status of rabies case palliative care centers were included in the questionnaire to identify death due to rabies and case-based palliative care service delivery.\n\nThe study protocol was reviewed and approved by Institutional Review Borad at Ethiopian Public Health Institute (EPHI-IRB). Following protocol approval, the study was conducted according to national and international research ethics guidelines. Health professionals were asked for their consent to participate in this study before filling questionnaires, and signed consent forms were documented for individual participants. Therefore, this is to declare that there was no ethical concern raised during the study.\n\nData was converted to SPSS version 20 and analyzed for professional knowledge related to rabies related service delivery.\n\n\nResults and discussion\n\nIn this study, health professionals with different education backgrounds and work experience were included to reflect their practice on rabies related service. The majority of the respondents (64.8%) were bachelor’s degree holders, followed by a diploma, which accounted for 19.2% of the study participants (Table 1).\n\nCollective health professional’s KAP about the service they provide were analyzed to identify gaps and recommend appropriate solutions. Majority of respondents obtained general knowledge for this study to be 25%, which is considered as a low level. From comparison of KAP results between professions, medical doctors obtained about 48% of general knowledges which was high compared to diploma and BSc holders. As a general, this study result indicates that it requires appropriate intervention to upgrade the knowledge of health professionals for quality service delivery (Table 1).\n\nIn addition to the professionals KAP study, NTV associated vaccine adverse events (VAE) were assessed to estimate professional report within the period of the study time. According to a summary from professionals’ response, majority of respondents (77.6%) report local adverse events (local pain, redness, swelling and pus at injection site) followed by reports of systemic complications as indicated by 20% of respondents. Post-vaccine adverse events were reported by 2.4% of the respondents (Table 2).\n\nThis data contradicts with the previous retrospective data collected from health facility documentation and feedback report at EPHI which indicate no NTV associated complication (Aga et al., 2021). On the other hand, recent report by health professionals about NTV related adverse reactions were more closely related to previous WHO report (WHO, 2007).\n\nRabies related human case and death data reported by health professionals were also analyzed to identify human rabies cases occurring during the study period at the targeted health facilities during this study. Human rabies cases were reported by health professions with the total number of human deaths to be 32 at 28 health facilities included in this study with an average of two deaths reported in each health facility (Table 3).\n\n\nConclusion and recommendations\n\nRabies post exposure prophylaxis is one of the major interventions to prevent rabies cases in humans following exposure to suspected animals. The main vaccine used to prevent rabies in humans in Ethiopia is a nerve tissue anti-rabies vaccine which is produced at EPHI. Currently, more than 32,000 doses of this vaccine are utilized annually for PEP. Even though this vaccine has been used in Ethiopia since 1950’s, no specific guideline to be utilized by health professional regards to exposure case screening, vaccine administration, vaccine handling and transportation. This study identifies gaps in health professionals about KAP in delivering this vaccine for further recommended solutions. Accordingly, the study identifies that there is a gap in professionals’ KAP which requires organized work-related guidelines and a training program for capacity building. Similarly, the study identifies that NTV vaccine associated adverse event is reported by health professionals with 77.6% of reports indicating local adverse event, 20% of respondents reported systemic reaction and 2.4% indicating post-vaccine complications. This data support WHO’s recommendation to replace the NTV vaccine with a safe and effective modern cell culture vaccine for rabies prevention in humans. Based on respondent data, the study has identified rabies cases in humans with 32 cases annually reported at those health facilities with an average of two cases per facility. Availability of a facility-based palliative care center for rabies case handling was also assessed. According to this study, there is no human rabies case isolation center identified. Thus, based on available opportunity and feasibility for rabies palliative care centers, health facilities were identified for further establishment. Generally, training for health professionals is mandatory to fulfill gaps in KAP using specific standard guidelines available for this purpose. In the meantime, it is recommended to facilitate technology transfer to replace the old method of rabies NTV production with a safe and effective cell culture anti-rabies vaccine.",
"appendix": "Data availability\n\nZenodo: Health professionals KAP on rabies, https://doi.org/10.5281/zenodo.7488297 (Aga, 2022).\n\nThis project contains the following underlying data:\n\n- KAP analysis.spv\n\n- KAP rabies.sav\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAga AM:Health professionals KAP on rabies (Version 1). [Data set]. Zenodo. 2022. Publisher Full Text\n\nAga AM, Mekoro B, Anberber A, et al.: The Status of Rabies Post Exposure Prophylaxis using Nerve Tissue Anti-Rabies Vaccine in Ethiopia. J. Vaccines Vaccination. 2021; 195.\n\nAli, et al.: Proceedings of The National Workshop on Rabies Prevention and Control in Ethiopia.2012.\n\nBaer GM, Bellini WJ, Fishbein DB:Rhabdoviruses. Virology. Fields BN, Knipe DM, editors.2nd edition.New York:Raven Press;1990. pp. 867–930.\n\nCDC: Rabies in Ethiopia. World rabies day report.2017.\n\nDeressa A, et al.: Longitudinal Study of Animal and Human Rabies Incidence in Addis Ababa during 2010-2012. J. Vet. Adv. 2015; 5(11): 1153–1162.\n\nKnobel D, Sarah C, Paul GC, et al.: Re-evaluating the burden of rabies in Africa and Asia. Bull. World Health Organ. 2005; 83: 360–368. PubMed Abstract | Free Full Text\n\nReta T, Teshale S, Deresa A, et al.: Rabies in animals and humans in and around Addis Ababa, the capital city of Ethiopia: A retrospective and questionnaire-based study. J. Vet. Med. Anim. Health. 2014; 6(6): 178–186. Publisher Full Text\n\nRohit G, Ravi CV, Lam Sau K, et al.: The science of rabies in tropical regions: From epidemiological pandemonium to prevention. Front. Life Sci. 2015; 8: 3.\n\nTullu M, Rodrigues S, Muranjan M, et al.: Neurological complications of rabies vaccines. Indian Pediatr. 2003; 40(2): 150–154. PubMed Abstract\n\nWHO: Recommendations for inactivated rabies vaccine for human use produced in cell substrates and embryonated eggs, TRS 941.2007.\n\nWHO: Rabies: A neglected zoonotic disease. WHO Programs and projects.2010; 85: 309–320.\n\nWHO: WHO Expert Consultation on Rabies, second report.2013.Reference Source\n\nWHO: Rabies vaccines: WHO position paper.2018."
}
|
[
{
"id": "196332",
"date": "04 Sep 2023",
"name": "Scott Brunt",
"expertise": [
"Reviewer Expertise Rabies",
"infectious disease",
"zoonoses",
"molecular diagnostics",
"statistics",
"bioinformatics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n\"As rabies is one of the worst diseases...\" should be re-written, \"Rabies is a severe disease...\"\nThis sentence is a little unclear and should be re-written:\n\"The vaccine prepared from small animal brains which contain protein called myelin sheath neural elements responsible for nerve complication as an autoimmune disorder at a rate estimated as 0.3-0.8 per thousand treated patients.\" I'd suggest \"The nerve tissue vaccine prepared in small animal brains contains myelin basic protein, which can cause the development of an antibody against the protein at a rate estimated as 0.3-0.8 per thousand treated patients\"\nPlease define VDPD and EPHI in your first sentence of the methods section.\nPlease mention which regions weren't included in the study.\nWhen you say \"Collective health professional’s KAP about the service they provide were analyzed to identify gaps and recommend appropriate solutions. Majority of respondents obtained general knowledge for this study to be 25%, which is considered as a low level.\"---- where is the KAP data? You describe the education data but do not quantify the general knowledge.\nThe first column of Table 2 is unclear.\nI would appreciate seeing the questionnaire as a supplemental document or figure.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "11077",
"date": "13 Apr 2024",
"name": "Abebe Mengesha Aga",
"role": "Author Response",
"response": "I have addressed all comments that require clarification. However, it is worth noting that many of the reviewer responses have already highlighted the strengths of the article, eliminating the need for further explanation."
}
]
},
{
"id": "216972",
"date": "03 Nov 2023",
"name": "Claude Sabeta",
"expertise": [
"Reviewer Expertise Epidemiology",
"veterinary diagnostics",
"rabies"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript on \"Health Professionals KAP study on rabies exposure assessment and NTV administration in Ethiopia\" by Aga et al bears reference. The WHO has recommended for the replacement of the rabies nerve tissue vaccine (NTV) with a cell-culture vaccine. Although the authors undertook the KAP study among health professionals, I am wondering why this study was also not undertaken with the producers of the vaccine?\nWhat do the producers of the NTV say? It would have been interesting to also interview them.\n\nSecond para in the introduction - Are the clinical signs mentioned here displayed in animals or humans - if so, please specify.\n\nPara 6 - 'symptom' should read 'symptoms'.\n\nOn page 4, include a reference for the SPSS software.\n\nOn page 4, 7th para - case and death should read \"cases and deaths\".\n\nWhat is the drawback in moving away from the NTV and replacing it with a cell culture based vaccine?\n\nHow will the findings from this study be taken up by other stakeholders? The arguments for me are not that strong.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "10522",
"date": "29 Nov 2023",
"name": "Abebe Mengesha Aga",
"role": "Author Response",
"response": "The manuscript on \"Health Professionals KAP study on rabies exposure assessment and NTV administration in Ethiopia\" by Aga et al bears reference. The WHO has recommended for the replacement of the rabies nerve tissue vaccine (NTV) with a cell-culture vaccine. Although the authors undertook the KAP study among health professionals, I am wondering why this study was also not undertaken with the producers of the vaccine? 1. What do the producers of the NTV say? It would have been interesting to also interview them. Yes, WHO has already discourage the production and use of NTV vaccine and recommend its replacement with cell culture vaccine. Ethiopia is currently in the process of transitioning from the outdated production method to cell culture vaccine production. In the meantime, the country is procuring anti-rabies vaccine through NTV production and cell culture procurement from external sources. The producer of NTV has desire to conduct an assessment in order to understand the incorrect administration of PEP due to a lack of knowledge regarding the vaccination procedure. The objective of this study is to identify any gaps and organize a training program for healthcare professionals working in this health care activities. 2. Second para in the introduction - Are the clinical signs mentioned here displayed in animals or humans - if so, please specify. Yes, it is sign in human. 3. Para 6 - 'symptom' should read 'symptoms'. Comment accepted as symptoms. 4. On page 4, include a reference for the SPSS software. I have already included and used reference for the source of SPSS software. 5. On page 4, 7th para - case and death should read \"cases and deaths\". Comment accepted as cases and deaths! 6. What is the drawback in moving away from the NTV and replacing it with a cell culture based vaccine? The transfer from NTV to cell culture poses a significant challenge due to its high cost and stringent technology transfer process, which involves extensive GMP work and regulatory requirements. As a result, the transition can be time-consuming and costly for the community, making it a challenging situation to make happen. 7. How will the findings from this study be taken up by other stakeholders? The arguments for me are not that strong. The results of the study suggest that there are significant deficiencies in the ability of healthcare providers to administer PEP using NTV anti-rabies vaccine. Therefore, urgent action is needed to enhance the capacity of healthcare professionals through the provision of short-term training programs. Furthermore, given the prevalence of NTV-related complications in healthcare facilities, it is imperative that the government prioritize the immediate action required in transfer of NTV to cell culture vaccine production technology."
},
{
"c_id": "11077",
"date": "13 Apr 2024",
"name": "Abebe Mengesha Aga",
"role": "Author Response",
"response": "I have addressed all comments that require clarification. However, it is worth noting that many of the reviewer responses have already highlighted the strengths of the article, eliminating the need for further explanation."
}
]
}
] | 1
|
https://f1000research.com/articles/12-582
|
https://f1000research.com/articles/12-577/v1
|
31 May 23
|
{
"type": "Systematic Review",
"title": "Effect of addition of titanium dioxide nanoparticles on the antimicrobial properties, surface roughness and surface hardness of polymethyl methacrylate: A Systematic Review.",
"authors": [
"Pragati Kaurani",
"Amit D Hindocha",
"Rasika Manori Jayasinghe",
"Umesh Y Pai",
"Kavita Batra",
"Carrie Price",
"Pragati Kaurani",
"Amit D Hindocha",
"Rasika Manori Jayasinghe",
"Kavita Batra",
"Carrie Price"
],
"abstract": "Background: Polymethyl Methacrylate (PMMA) denture-base resins have poor surface properties that facilitates microbial adhesion causing denture stomatitis. This systematic review aims to evaluate the effect of different sizes and percentages of titanium dioxide nanoparticles (TiO2NP) on the antimicrobial property, surface roughness and surface hardness of PMMA denture base resin. Methods: A systematic search of English peer-reviewed articles, clinical trial registries, grey literature databases and other online sources was performed using the PRISMA-S Guidelines for In-Vivo and In-Vitro studies. Qualitative data synthesis was performed to analyse sample dimensions, acrylic used, treatments of nanoparticles, methods used for testing and effect of size and percentage of nanoparticle. Risk of bias assessment was done using modified Cochrane risk of bias tool. Results: Out of 1376 articles, 15 were included. TiO2NP of size less than 30 nm was most frequently used. Both antimicrobial property and surface hardness improved irrespective of the size of the added TiO2NP. Three studies reported increase in the surface roughness with less than 50 nm TiO2NP. 3% TiO2NP was most frequently used. On increasing the percentage, three studies reported an increase in antimicrobial property, while two studies found no change. With TiO2NP greater than or equal to 3%, six studies reported an increase in surface hardness, while two reported increase in surface roughness. Large methodological variations were observed across studies. All studies except one were of moderate quality. Conclusions:\n\nOn addition of TiO2NP to heat polymerized PMMA, the antimicrobial property and surface hardness improved irrespective of the size of the TiO2NP, however, addition of nanoparticles less than 50 nm increased the surface roughness. Increasing the percentage of TiO2NP increased the surface hardness but did not always increase the antimicrobial property. Addition of 3% TiO2NP provided optimum results with regards to antimicrobial effect and surface hardness, but increase in the surface roughness.",
"keywords": [
"Nanoparticles",
"titanium dioxide nanoparticles",
"mechanical properties",
"antimicrobial properties",
"denture base resins"
],
"content": "Introduction\n\nPolymethyl methacrylate (PMMA) is a widely used denture base material and its extensive usage can be attributed to certain advantages, such as ease in manipulation, achieving good finish and polish, not requiring expensive processing equipment, stability in the dynamic oral environment and biocompatibility with the oral tissues.1,2 Despite these advantages, it has surface properties like roughness, surface porosities, free surface energy and contact angle that facilitate adhesion of microorganisms, such as Candida Albicans.3–5 These microbial adhesions lead to the formation of denture biofilm, which eventually leads to denture stomatitis, an oral condition with reportedly high incidence that affects nearly 65% of denture wearers.6,7 Therefore, numerous efforts are being made to improve the mechanical and biological properties in PMMA by making modifications in the structure or by nanoscale reinforcing additives.\n\nThe recently introduced advances in nanotechnology aim at improving antimicrobial and mechanical properties of dental materials by the addition of nanoparticles (NPs).8–10 The mixture of polymer matrix and fillers at the nanoscale makes a new polymeric nanocomposite.11 Studies have shown that addition of such nanoscale reinforcing additives lead to the formation of a nanocomposite, which shows improved mechanical and biological properties.12 The properties of the resulting new nanocomposite depend on several factors, such as size, morphology and quantity of NPs being added.13\n\nAmong the various NPs that have been used, metal oxides particularly have gained more attention owing to their proven antimicrobial effects.14,15 Among others, the effect of addition of titanium dioxide nanoparticles (TiO2NP) on the mechanical and biological properties of PMMA has also been extensively studied.1,2,8 Given the advantages and properties of TiO2NP (e.g. non-toxicity, chemical stability, white in color, biocompatibility, availability and cost-effectiveness), makes it a highly desirable additive.16–18 Moreover, TiO2NP has the intrinsic antimicrobial properties due to the production of cytotoxic oxygen radicals, thereby providing antimicrobial effect to PMMA denture base.19 With the addition of NPs, certain properties of PMMA are observed to improve, however, when added into the polymer matrix, NPs can alter the surface roughness and surface hardness.18 Such alterations on the surface properties may occur due to the distribution and concentration of the NPs within the acrylic matrix.20\n\nGiven the observed effects of TiO2NP on the antimicrobial, surface roughness (SR) and surface hardness (SH) properties of PMMA denture base resin, numerous studies have been undertaken to analyse these effects at varying concentrations of the NPs. Further, studies are being undertaken to analyse effects of nanohybrid composites, in which two or more NPs are mixed, such as TiO2NP mixed with another metal oxide NP (hybrid form), with the aim of obtaining improved properties or having a synergistic effect.21\n\nFor a better understanding of the effect TiO2NP (in pure or hybrid form) on the antimicrobial, surface roughness and surface hardness of PMMA and their possible clinical usage, there is a need to produce collective evidence utilizing a systematic and robust method. Therefore, the objective of the current systematic review was to analyse the effect of addition of different sizes and percentages of TiO2NP on the antimicrobial, surface roughness and surface hardness of TiO2NP impregnated heat polymerized PMMA denture base resin fabricated using conventional methods or Computer-Aided Design/Computer-Aided Manufacturing (CAD/CAM) when compared to heat polymerized PMMA.\n\n\nMethods\n\nThe study is reported in accordance with the PRISMA 2020 guidelines.22 The study protocol was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/#aboutpage), with registration number CRD42021252315 and was revised once as agreed upon by all authors.23\n\nThe eligibility criteria for inclusion of studies were defined using the PICOS criteria, Population (P) = PMMA heat polymerized or manufactured by CAD/CAM. Intervention (I) = Addition of TiO2NP in pure or hybrid form in PMMA. Studies based on TiO2 nanotubes, fillers, fibres and coating on PMMA were excluded. Control (C) = Heat polymerized PMMA without any addition of NPs or fibres. Outcome measure (O) = Antimicrobial properties, SR and SH of PMMA. Study designs (S) = In-Vivo and In-Vitro studies were included. Studies based on TiO2 nanotubes, fillers, fibres and coating on PMMA were excluded. Case-reports, systematic and narrative reviews, letters to the editor, short commentaries, pilot studies or studies with preliminary results and studies that were not related to the field of dentistry were excluded.\n\nA comprehensive search strategy was developed for each database by an experienced librarian [C.P] and sent for peer reviewing using PRESS-Guidelines.24 Electronic searches in various databases were performed and reported using the PRISMA-S search extension wherein searches were done in databases, study registries, grey literature and other online sources.25 Based on the PRISMA-S guidelines, a rerun of the search was done with a gap of six months to search studies between January 2000 to April 2022, and carried out in three databases PubMed (NCBI), WHO Virtual Health Library and Cochrane Library.25 Two clinical trial registries (Clinicaltrials.gov and Clinical Trials Registry of India), six other online sources (Ingenta Connect, Google Scholar, Research Gate, Dimension, Crossref and The Lens) and three sources for grey literature (BASE, OpenGrey and Grey Literature Report) were also searched. The PubMed search included both controlled vocabulary (Medical Subject Headings, or MeSH) and keyword terms for the concepts of “nanoparticles”, “titanium dioxide”, “PMMA”, “dentures”, “CAD/CAM”, “surface roughness”, “surface hardness”, “antibacterial” and “antifungal” and were used as the basis for all searches in other sources, with no usage of published search filters. Citation chasing and manual citation searching was performed of the reference lists of all the included articles by one researcher and E-mail alerts were set. The details of all the sources and their respective searches can be found in the (Supplementary Table 1, available online (Pragati, 2022)). De-duplication was performed using EndNote software.\n\nInitially, two researchers (P.K. and A.H.) independently screened the titles and abstracts of the exported articles in Rayyan Software (https://www.rayyan.ai/). Full-text articles were retrieved for potentially relevant articles and screened using the eligibility criteria by the same researchers. Wherever the full articles could not be retrieved, the corresponding authors were contacted, and the articles were obtained.\n\nAntimicrobial Property was referred to as a collective term when there was an inhibition of the growth of bacteria and fungi, prevention of the formation of microbial colonies or destruction of microorganisms. Studies showing results of TiO2NP potential for the treatment of denture stomatitis were also included. Studies without a suitable control group, where the studies evaluated the antimicrobial capacity of the nanoparticle material by themselves, independently of their incorporation into PMMA were excluded. In case of disagreements, conflicts were resolved, however, articles in which the conflicts could not be resolved, the two reviewers (U.P. and M.J.) were consulted for the final decision. Two researchers (P.K. and A.H.) independently studied each of the included articles and extracted the data. (Supplementary Tables 1 and 2, available online (Pragati, 2022)) For data that was found to be missing, NS (not stated) was used and when not clear, ‘unclear’ was written.\n\nThe assessment of the quality of the included articles was performed using the modified Consolidated Standards of Reporting Trials (CONSORT) guidelines.26 The selected parameters were reported as “yes” or “no” on the screening of articles (Table 1). The risk of bias was assessed individually by two researchers P.K. and A.H. and any disagreements were resolved by the third reviewer U.P. based on the modified Cochrane Risk of Bias tool and scored as described in previous study27 (Table 2).\n\nDue to the large methodological heterogeneity observed, narrative synthesis of the data was performed and quantitative analysis of the data was not performed.\n\n\nResults\n\nThe systematic search identified 386 articles through the three databases searched, 62 articles were found from trial registries and 1565 from other sources (online sources, citation searching and email alerts). After de-duplication, 637 articles were removed and subsequently, 37 potentially relevant articles were accessed for analysis of the full text. Out of these, 17 studies were excluded due to the following reasons: articles in which TiO2 was added as a nanotube or coating,28 studies carried out on auto-polymerized acrylic resin,29–31 clinical trial reports in which full reports could not be retrieved or were not complete,32–35 control group was not heat polymerized PMMA,36–38 articles not in English,39–41 article published as a preliminary study,42 particle size was not nano.21,43 The details of the articles excluded can be found in the (Supplementary Table 2, online (Pragati, 2022)). Finally, 15 articles that fulfilled the inclusion criteria were included and is depicted as modified PRISMA-2020 flow diagram made most optimal for the current review.44–58,59 (Figure 1).\n\nOut of 15 studies included 14 were in-vitro studies and one was a randomized control trial, 7 studies evaluated antimicrobial properties of TiO2NP,45,47,51,53,54,57,58 5 studies evaluated SR,46,50,51,52,58 8 studies evaluated SH44–46,48–50,54,56 and 2 studies evaluated both.46,50 The methodological quality assessments revealed that only one study scored above 90%55 (Table 1). The risk of bias assessment revealed moderate risk of bias for all except one study that showed a low risk of bias55 (Table 2). None of the studies used random allocation sequence, five studies provided information on sample size,47,49,50,52,55 and only one study provided information on blinding.55\n\nAll the studies used conventional heat polymerized PMMA with only one study that evaluated the effect of addition of TiO2NP on high impact heat polymerized PMMA and only one study used hybrid NPs.48,57 Considerable variations in the size of TiO2NP used was observed, the particle sizes varied from being less than 15 nm to 100 nm. TiO2NP of the size less than 30 nm, was found to be used most frequently across studies. Similarly, the percentage of TiO2NP added varied considerably ranging from 0.1% to 7.5% with 3% by weight being the most frequently used percentage (Supplementary Tables 1 and 2, available online (Pragati, 2022)).\n\nAll studies reported an increased anti-microbial effect, irrespective of the size of addition of TiO2NP, but different effects was observed on increasing the percentage of the addition of TiO2NP. Three studies found an increase in the antimicrobial properties, while two studies did not report improved antimicrobial properties on increasing the percentage of addition of TiO2NP. Cascione et al. found a reduction in the Candida colonization area by 19% on addition of 3% TiO2NP compared to the 16% reduction observed with 1% TiO2NP.51 On similar lines one study found that on increasing the percentage of TiO2NP the antimicrobial effect increased from 1% to 3%, while another study found that on increasing the percentage of TiO2NP from 1% to 3%, the bacterial adhesion of E. faecalis and P. aeruginosa reduced to 50% and 92% respectively.45,55 Contrary to this, despite showing antimicrobial effect, Giti and others found no significant increase in the antimicrobial properties with increase in the percentage from 2.5% to 7.5%.53 Similarly, Song and others found better results on using 0.3% of TiO2NP compared to 0.4% and 0.5%.57\n\nWith regards to the SR, Cascione and others found a decrease in SR with large sized TiO2NP (greater or equal to 50 nm),51 but three studies reported an increase in SR with the addition of less than 50 nm TiO2NP,46,50,52 and one study found in-significant improvement in SR.58 Three studies found an increase in the SR on addition of 3% and 2% TiO2NP,46,50,52 while one study found 54% and 72% roughness reduction with 1% and 3% TiO2NP,51 and one study found an insignificant increase in SR with 5% TiO2NP.58\n\nContrary to the effect on SR but similar to antimicrobial effect, SH was found to increase irrespective of the size of the added TiO2NP. Studies that used TiO2NP less than 50 nm particle size41,46,48,54,56,50 as well as greater than 50 nm reported improved SH.45 Further, the results indicate that on addition of TiO2NP greater than or equal to 3%, there is an observed increase in the SH.44–46,48,49,54On the other hand, when used less than 3%, TiO2NP either caused no change or reduction in SH.44,48,50Alhotan et al. found no improvement in the hardness by adding 1.5% TiO2NP,44 Ashur Ahmed and others found no significant difference on adding 1% TiO2NP and Bangera and others found values close to the control groups on addition of 1% TiO2NP.45,50 The only exception to this were Alrahlah and others, who found an 18% and 24% increase in the SH on addition of 1% and 2 % TiO2NP respectively.45\n\n\nDiscussion\n\nThe effects of addition of different sizes (less than and greater than 50 nm) and percentages of TiO2NP on the antimicrobial, SH and SR of heat cured denture base resins was narratively synthesized. It was found that size of the TiO2NP had less influence on these properties, but with increase in the percentage of TiO2NP these properties were affected.\n\nDifferences in the sample dimensions between the studies were observed, indicating methodological inconsistencies. Four studies mentioned the sample fabrications as per the recommended standardizations.47,50,52,55 Even though the intent of the study was to include the effects of the addition of TiO2NP into CAD/CAM dentures, evidence on the comparison of these effects with conventional heat cured resins was found to be lacking.37,42 Only one study used high impact acrylic resin and found that the hardness further increased by addition of 5 % TiO2NP, the difference being statistically significant.48 Despite the fact that polishing of the acrylic affects the surface properties and subsequent microbial adhesion, only seven studies were found to have mentioned the procedures adopted for finishing and polishing44,45,49,51,53,58 and six studies mentioned details of sample storage.45,46,48,52,54\n\nThe methods of dispersion and surface treatments of NPs play a significant role in affecting the mechanical properties. NPs when treated with low molecular weight organosilicon surface treatment agents or silane coupling agents facilitate formation of a molecular bridge between the interface of the organic and inorganic substance. This results in increasing the NPs dispersion and enhanced the properties.60–62 Even though the treatment can affect the resultant properties, only four studies mentioned the process of treating the NPs using silanization or any other form of surface treatment.44,46,47,51 As surface treatment of the NPs has shown to improve properties, future studies must mention methods used for surface treatments.\n\nThorough mixing of NPs is essential as TiO2NP have high surface energies and agglomerate formation can act as stress concentrating centres thereby adversely affecting the properties.52,57 Different methods of mixing and dispersion of the particles were used in the selected studies such as speed mixer, vacuum mixer, twin screw extruder, ultrasonication, planetary ball mill and ultrasonic homogeniser.\n\nConsiderable heterogeneity in methods of testing was observed in which researchers used methods such as antibacterial adhesion test, minimum inhibitory concentrations (MIC) of the NPs using microbroth dilution method and biofilm formation, MIC by broth culture, the plate count method were used.45,47,51,53,55,57,58 Similarly, variation in the methods for testing SH was observed such as in Shore D hardness,46,50 Vicker’s Hardness,48,49,54 and Rockwell Hardness.56 While, SR was evaluated using a profilometer,46,50,52 perthometer,58 and digital microscope.51\n\nThe results of the current study indicate that the size of the added TiO2NP did not affect the observed antimicrobial effect and SH as studies that used smaller TiO2NP (less than 50 nm)52,53,55,57,58 as well as those that used relatively larger sized NPs (greater than 50 nm),45,51 reported improved antimicrobial properties. Previous studies have found that smaller sized NPs improve properties as they can penetrate between linear chains and form homogenous mixture, and additionally can easily attach and penetrate cell membranes.63–65 Although studies reported conflicting results regarding the effect on SR, SH was found to increase irrespective of the size of TiO2NP added to PMMA. In-order to provide stronger evidence on the optimum size of NPs to achieve improved properties, future studies must justify selection of a size as well as analyse the effect of increasing or decreasing the size of NPs on the given properties.\n\nPrevious studies have found that a smaller percentage of the added NPs ensures that the NPs are well embedded into the resin.66,67 From the analysis of the obtained results it was found that increasing the percentage of addition of TiO2NP did not always improve the antimicrobial effect. The most promising results were obtained with 3% of addition of TiO2NP, as four studies demonstrated improved antimicrobial effect with 3% TiO2NP.45,47,51,55 The observed antimicrobial effects can be attributed to the different mechanisms of action such as the ability of TiO2NP to produce cytotoxic oxygen radicals, reduction in the bacterial attachment and biofilm formation onto polymer surfaces and deactivation of cellular enzymes causing to cell death.47,68–72\n\nRegarding the effect on SH, the current analysis found that although with an increase in the percentage of TiO2NP, the SH of the nanocomposite increases, little or no improvement occurred with percentages below 3%. The variations in the SH are said to be due to the dispersion of the NPs other factors such as use of silane coupling agent, mixing methods used for dispersion for minimum agglomerates formation and the greater presence of cross-linking in the surface layers than the internal layers of the material.45,73–75\n\nWith regards to the SR, the conclusive effect of increasing the percentage could not be obtained, however, at 3% the SR was found to increase. Factors such as the dispersion of the NP to close the gap in the resin matrix, presence of the amount of nanoparticle on the surface and hydrophobicity of the nano-resin composite play important roles to determine the SR.76–78 The clinical significance of this property cannot be underestimated as with the increase in the SR larger number of sites are available for microbial adhesion, however only two studies evaluated the microbial adhesion on addition of different concentrations of TiO2NP.18,51,58,79\n\nThe current review differs from previous reviews as the effect of nanohybrid combination using TiO2NP was also evaluated, wherein it was observed that the nanohybrid combination of TiO2 and SiO2 showed antimicrobial action against Streptococcus M.57 Studies have found that TiO2NP on doping with other metals or metal oxides, showed improved photocatalytic activity thereby showing improved antimicrobial properties.80,81 Keeping in view with the limited available evidence but with promising results, future research on analysing combination of metal oxide NPs with TiO2NP can be undertaken.\n\nBased on the results of the current systematic review, the use of TiO2NP size up to 100 nm and at 3% concentration can be recommended to achieve optimum antimicrobial effect, SH and SR, however, additional efforts must be undertaken to improve the SR so as to minimize the microbial adhesion. Future studies can be undertaken to assess the impact to different methods to improve the SR with their impact on the microbial adhesion.\n\nThe current study has certain limitations. Firstly, due to the significant diversity within the primary studies, meta-analysis of the results could not be performed and the conclusions are drawn based on narrative synthesis. Secondly, the results of the current review must be interpreted with careful understanding as included studies showed moderate results in methodological and risk assessments due to the in-vitro nature of the majority of the studies, where uniform guidelines are currently missing.82,83 The strength of the current study is the use robust methodology and use of a comprehensive methodology of a literature search based on the recently introduced PRISMA-S guidelines, minimizing the publication bias and following a robust methodology in the conduction of the systematic review and provides updated information on the use of the pure form and hybrid TiO2NP.\n\n\nConclusions\n\nBased on the evidence synthesized, it can be concluded that on addition of TiO2NP to heat polymerized PMMA denture base resin, the antimicrobial property and SH improved irrespective of the size of the TiO2NP, however, addition of TiO2NP less than 50 nm increased the SR. Increasing the percentage of TiO2NP showed an increase in the SH, but did not always increase the antimicrobial property. Addition of 3% TiO2NP provided optimum results with regards to antimicrobial effect and SH, however, with 3% TiO2NP, SR was found to increase. Due to insufficient data currently available, the effect of addition of TiO2NP on CAD/CAM PMMA denture base resins could not be established.",
"appendix": "Data availability\n\nNo underlying data are associated with this article.\n\nOSF: Effect of addition of titanium dioxide nanoparticles on the antimicrobial properties, surface roughness and surface hardness of polymethyl methacrylate: A systematic Review. DOI: 10.17605/OSF.IO/AV56D (Pragati, 2022).\n\nThis project contains the following underlying data:\n\n• PRISMA Flowchart 2020 (Flowchart of all the sources searched and the results obtained)\n\n• PRISMA 2020 Checklist (Checklist of reporting guidelines)\n\n• Table 1 and 2 (Data Extraction Sheet of the effect of titanium dioxide nanoparticles on the antimicrobial properties, surface hardness and surface roughness)\n\n• Supplementary Material (Details of search strategies used, peer review of the search strategy, list of included and studies)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nThe authors would like to acknowledge the efforts of librarian, Kate Lobner MLIS, Welch Medical Library, John Hopkins University for reviewing the search strategy and providing valuable inputs for the same.\n\n\nReferences\n\nAhmed MA, Ebrahim MI: Effect of Zirconium Oxide Nano-Fillers Addition on the Flexural Strength, Fracture Toughness, and Hardness of Heat-Polymerized Acrylic Resin. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nHiggins JP, Altman DG, Gøtzsche PC, et al.: Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011 Oct 18; 343: d5928. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbdulrazzaq NS, Behroozibakhsh M, Jafarzadeh KTS, et al.: Effects of incorporation of 2.5 and 5 wt% TiO2 nanotubes on fracture toughness, flexural strength, and microhardness of denture base poly methyl methacrylate (PMMA). J. Adv. Prosthodont. 2018 Apr; 10: 113–121. Epub 2018 Apr 18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnwander M, Rosentritt M, Schneider-Feyrer S, et al.: Biofilm formation on denture base resin including ZnO, CaO, and TiO2 nanoparticles. J. Adv. Prosthodont. 2017 Dec; 9: 482–485. Epub 2017 Dec 14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHashem M, Al Rez MF, Fouad H, et al.: Influence of Titanium Oxide Nanoparticles on thePhysical and Thermomechanical Behavior of PolyMethyl Methacrylate (PMMA): A Denture Base Resin. Sci. Adv. Mater. 2017; 9: 938–944. Publisher Full Text\n\nSodagar A, Khalil S, Kassaee MZ, et al.: Antimicrobial properties of poly (methyl methacrylate) acrylic resins incorporated with silicon dioxide and titanium dioxide nanoparticles on cariogenic bacteria. J. Orthod. Sci. 2016 Jan-Mar; 5: 7–13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nClinicalTrials.gov: Bethesda (MD): National Library of Medicine (US). 2000 Feb 29- Identifier: NCT03666195. Badran MMI. The Antimicrobial Effect of Titanium Dioxide Nano Particles in Complete Dentures Made for Edentulous Patients.Sep 2018. Reference Source\n\nClinicalTrials.gov: Bethesda (MD): National Library of Medicine (US). 2000 Feb 29- Identifier: NCT02950584. Ismail EG. Surface Roughness of Heat Cured Acrylic Resin Versus Acrylic Resin With Titanium Dioxide.October 2016. Reference Source\n\nClinicalTrials.gov: Bethesda (MD): National Library of Medicine (US) 2000 Feb 29- Identifier: NCT02950623. Mahmoud MMAE. Microbiological Study on Maxillary Complete Dentures of Two Different Materials.October 2016. Reference Source\n\nClinicalTrials.gov: Bethesda (MD): National Library of Medicine (US) 2000 Feb 29- Identifier:NCT03700489. Shamardal AM. Mycological Comparative Study on Maxillary Dentures of Two Different Materials. October 2018. Reference SourceReference Source\n\nChen R, Han Z, Huang Z, et al.: Antibacterial activity, cytotoxicity and mechanical behavior of nano-enhanced denture base resin with different kinds of inorganic antibacterial agents. Dent. Mater. J. 2017 Nov 29; 36: 693–699. PubMed Abstract | Publisher Full Text\n\nChen SG, Yang J, Jia YG, et al.: TiO2 and PEEK Reinforced 3D Printing PMMA Composite Resin for Dental Denture Base Applications. Nanomaterials (Basel). 2019 Jul 22; 9: 1049. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTotu EE, Nechifor AC, Nechifor G, et al.: Poly (methyl methacrylate) with TiO2 nanoparticles inclusion for stereolithographic complete denture manufacturing - the future in dental care for elderly edentulous patients? J. Dent. 2017 Apr; 59: 68–77. Epub 2017 Feb 20. Erratum in: J Dent. 2021 Sep;112:103739. PubMed Abstract | Publisher Full Text\n\nLiu J, Ge Y, Xu L: Study of antibacterial effect of polymethyl methacrylate resin base containing Ag-TiO2 against Streptococcus mutans and Saccharomyces albicans in vitro. Hua Xi Kou Qiang Yi Xue Za Zhi. 2012 Apr; 30: 201–5. Chinese. PubMed Abstract\n\nPutranti DT, Fadilla A: Titanium Dioxide Addition to Heat Polymerized Acrylic Resin Denture Base Effect on Staphylococcus aureus and Candida albicans. J. Indones. Dent. Association. 2018; 1: 21–27. Publisher Full Text\n\nTao JX, Song XL, Yao YY, et al.: Self-cleaning and antimicrobial properties of methacrylic acid coupled TiO(2)/PMMA denture base resin. Shanghai Kou Qiang Yi Xue. 2012 Apr; 21: 130–3. (Chinese). PubMed Abstract\n\nTotu EE, Cristache CM, Isildak I, et al.: Preliminary Studies on Cytotoxicity and Genotoxicity Assessment of the PMMA-TiO 2 Nanocomposites for Stereolithographic Complete Dentures Manufacturing. REV.CHIM.(Bucharest). 2018; 69: 1160–1165. Publisher Full Text\n\nNejatia T, Johnson A, Van Noort R: Reinforcement of Denture Base Resin. Adv. Sci. Tech. 2006; 49: 124–129.\n\nAlhotan A, Yates J, Zidan S, et al.: Flexural Strength and Hardness of Filler-Reinforced PMMA Targeted for Denture Base Application. Materials (Basel). 2021 May 19; 14: 2659. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlrahlah A, Fouad H, Hashem M, et al.: Titanium Oxide (TiO2)/Polymethylmethacrylate (PMMA) Denture Base Nanocomposites: Mechanical, Viscoelastic and Antibacterial Behavior. Materials (Basel). 2018 Jun 27; 11: 1096. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlwan SA, Alameer SS: The effect of the addition of silanized Nano titania fillers on some physical and mechanical properties of heat cured acrylic denture base materials. J. Bagh. Coll. Dent. 2015 Mar 14; 27: 86–91. Publisher Full Text\n\nAnehosur GV, Kulkarni RD, Naik MG, et al.: Synthesis and Determination of Antimicrobial Activity of Visible Light Activated TiO2 Nanoparticles with Polymethyl Methacrylate Denture Base Resin Against Staphylococcus Aureus. J. Gerontol. Geriatr. 2012; 01: 1. Publisher Full Text\n\nAshour Ahmed M, El-Shennawy MM, Althomali Y, et al.: Effect of Titanium Dioxide Nano Particles Incorporation on Mechanical and Physical Properties on Two Different Types of Acrylic Resin Denture Base. World Journal of Nano Science and Engineering. 2016; 06: 111–119. Publisher Full Text\n\nAzmy E, Al-Kholy MRZ, Al-Thobity AM, et al.: Comparative Effect of Incorporation of ZrO2, TiO2, and SiO2 Nanoparticles on the Strength and Surface Properties of PMMA Denture Base Material: An In vitro Study. Int. J. Biomater. 2022 Apr 28; 2022: 5856545. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBangera MK, Kotian R, Natarajan S, et al.: Behavior of nanosilver and nanotitanium reinforced polymethyl methacrylate for dental applications. Polym. Compos. 2022 Feb; 43: 741–752. Publisher Full Text\n\nCascione M, De Matteis V, Pellegrino P, et al.: Improvement of PMMA Dental Matrix Performance by Addition of Titanium Dioxide Nanoparticles and Clay Nanotubes. Nanomaterials (Basel). 2021 Aug 9; 11: 2027. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChowdhury AR, Kaurani P, Padiyar UN, et al.: Effect of Addition of Titanium Oxide and Zirconium Oxide Nanoparticles on the Surface Roughness of Heat Cured Denture Base Resins: An In-Vitro study. SVOA Mater. Sci. Technol. 2021; 36–43.\n\nGiti R, Zomorodian K, Firouzmandi M, et al.: Antimicrobial Activity of Thermocycled Polymethyl Methacrylate Resin Reinforced with Titanium Dioxide and Copper Oxide Nanoparticles. Int. J. Dent. 2021 Jan 30; 2021: 6690806–6690808. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMansour MM, Al-Nassr MS, Shon AA, et al.: Effect of titanium dioxide nanoparticles on mechanical properties of denture base resin: an in vitro study. Al-Azhar J. Dent. Sci. July 2017; 20: 261–265. Publisher Full Text\n\nRagheb N, Borg H: Antimicrobial Effect of Titanium Oxide (Tio2) Nano Particles in Completely Edentulous Patients. A Randomized Clinical Trial. Adv. Dent. J. 2021; 3: 173–184. Publisher Full Text\n\nRashahmadi S, Hasanzadeh R, Mosalman S: Improving the Mechanical Properties of Poly Methyl Methacrylate Nanocomposites for Dentistry Applications Reinforced with Different Nanoparticles. Polym.-Plast. Technol. Eng. 2017; 56: 1730–1740. Publisher Full Text\n\nSong R, Jiao X, Lin L: Improvement of mechanical and antimicrobial properties of denture base resin by nano-titanium dioxide and nano-silicon dioxide particles. Pigm. Resin Technol. 2011; 40: 393–398. 0369-9420. Publisher Full Text\n\nThabet Y, Moustafa D, El Shafei S: The Effect Of Silver Versus Titanium Dioxide Nanoparticles On Poly methylmethacrylate Denture Base Material. Egypt. Dent. J. 2022 Jan 1; 68(1): 915–921. Publisher Full Text\n\nRethlefsen ML, Page MJ: PRISMA 2020 and PRISMA-S: common questions on tracking records and the flow diagram. J. Med. Libr. Assoc. 2022 Apr 1; 110: 253–257. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAydınoglu A, Yoruç ABH: Effects of silane-modified fillers on properties of dental composite resin. Mater. Sci. Eng. C. 2017; 79: 382–389. PubMed Abstract | Publisher Full Text\n\nKarmaker A, Prasad A, Sarkar NK: Characterization of adsorbed silane on fillers used in dental composite restoratives and its effect on composite properties. J. Mater. Sci. Mater. Electron. 2007; 18: 1157–1162.\n\nChen SG, Yang J, Jia YG, et al.: TiO2 and PEEK Reinforced 3D Printing PMMA Composite Resin for Dental Denture Base Applications. Nanomaterials (Basel). 2019 Jul 22; 9: 1049. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGad MM, Rahoma A, Al-Thobity AM: Effect of Polymerization Technique and Glass Fiber Addition on the Surface Roughness and Hardness of PMMA Denture Base Material. Dent. Mater. J. 2018; 37: 746–753. Publisher Full Text\n\nAbushowmi TH, AlZaher ZA, Almaskin DF, et al.: Comparative Effect of Glass Fiber and Nano-Filler Addition on Denture Repair Strength. J. Prosthodont. 2020; 29: 261–268. PubMed Abstract | Publisher Full Text\n\nAgnihotri S, Mukherji S, Mukherji S: Size-controlled silver nanoparticles synthesized over the range 5–100 Nm using the same protocol and their antibacterial efficacy. RSC. 2014; 4: 3974–3983. Publisher Full Text\n\nKarci M, Demir N, Yazman S: Evaluation of Flexural Strength of Different Denture Base Materials Reinforced with Different Nanoparticles. J. Prosthodont. 2019; 28: 572–579. Publisher Full Text\n\nZidan S, Silikas N, Alhotan A, et al.: Investigating the Mechanical Properties of ZrO2-Impregnated PMMA Nanocomposite for Denture-Based Applications. Materials. 2019; 12: 1344. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEsra K, Lütfü IA, Ruhi Y: Evaluation of thermal conductivity and flexural strength properties of polymethyl methacrylate denture base material reinforced with different fillers. J. Prosthet. Dent. 2016; 116: 803–810.\n\nHøiby N, Ciofu O, Johansen HK, et al.: The clinical impact of bacterial biofilms. Int. J. Oral Sci. 2011; 3: 55–65. Publisher Full Text\n\nHengzhuang W, Wu H, Ciofu O, et al.: Pharmacokinetics/pharmacodynamics of colistin and imipenem on mucoid and nonmucoid Pseudomonas aeruginosa biofilms. Antimicrob. Agents Chemother. 2011; 55: 4469–4474. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHengzhuang W, Wu H, Ciofu O, et al.: In vivo pharmacokinetics/pharmacodynamics of colistin and imipenem in Pseudomonas aeruginosa biofilm infection. Antimicrob. Agents Chemother. 2012; 56: 2683–2690. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHøiby N, Bjarnsholt T, Givskov M, et al.: Antibiotic resistance of bacterial biofilms. Int. J. Antimicrob. Agents. 2010; 35: 322–332. Publisher Full Text\n\nBangera MK, Kotian R, Madhyastha P: Effects of silver nanoparticle-based antimicrobial formulations on the properties of denture polymer: A systematic review and meta-analysis of in vitro studies. J. Prosthet. Dent. 2021 Jun 25; 129: 310–321. PubMed Abstract | Publisher Full Text\n\nZhang XY, Zhang XJ, Huang ZL, et al.: Hybrid Effects of Zirconia Nanoparticles with Aluminum Borate Whiskers on Mechanical Properties of Denture Base Resin PMMA. Dent. Mater. J. 2014; 33: 141–146. PubMed Abstract | Publisher Full Text\n\nZhang X, Zhang X, Zhu B, et al.: Mechanical and Thermal Properties of Denture PMMA Reinforced with Silanized Aluminum Borate Whiskers. Dent. Mater. J. 2012; 31: 903–908. PubMed Abstract | Publisher Full Text\n\nTurki MM, Abdul-Ameer FM: Influence of Silver Nanoparticles on the Specific Properties of Acrylic Resin for Ocular Prosthesis. Biomed. Pharmacol. J. 2018; 11: 1573–1581. Publisher Full Text\n\nAndreotti AM, Goiato MC, Moreno A, et al.: Influence of nano particles on color stability, micro hardness and flexural strength of acrylic resins specific for ocular prosthesis. Int. J. Nanomedicine. 2014; 9: 5779. Publisher Full Text\n\nBürgers R, Eidt A, Frankenberger R, et al.: The anti-adherence activity and bactericidal effect of microparticulate silver additives in composite resin materials. Arch. Oral Biol. 2009; 54: 595–601. PubMed Abstract | Publisher Full Text\n\nTeughels W, Van Assche N, Sliepen I, et al.: Effect of material characteristics and/or surface topography on biofilm development. Clin. Oral Implants Res. 2006; 17: 68–81. Publisher Full Text\n\nSikong L, Kongreong B, Kantachote D, et al.: Photocatalytic activity and antibacterial behavior of Fe3+-doped TiO2/SnO2 nanoparticles. Energy Res. J. 2010; 1: 120–125. Publisher Full Text\n\nTrapalis C, Keivanidis PE, Kordas PG, et al.: TiO2(Fe3+) nanostructured thin films with antibacterial properties. Thin Solid Films. 2003; 433: 186–190. Publisher Full Text\n\nTallarico M, Fiorellini J, Nakajima Y, et al.: Mechanical Outcomes, Microleakage, and Marginal Accuracy at the Implant-Abutment Interface of Original versus Nonoriginal Implant Abutments: A Systematic Review of In vitro Studies. Biomed. Res. Int. 2018 Dec 30; 2018: 2958982. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChander NG: Standardization of in vitro studies. J. Indian Prosthodont. Soc. 2016 Jul-Sep; 16: 227–228. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "179884",
"date": "30 Jun 2023",
"name": "Veena B. Benakatti",
"expertise": [
"Reviewer Expertise Artificial intelligence in Dentistry"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt is a well-conducted research with a robust methodology. The findings of the study would benefit the field of dental science.\nThe methodology and findings/values of the antimicrobial property, surface hardness, and surface roughness of the individual studies can be summarized in a table that will give a general view of the selected studies.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "179872",
"date": "05 Jul 2023",
"name": "Rekha Gupta",
"expertise": [
"Reviewer Expertise Clinical research related to oral health problems",
"maxillofacial Prosthodontics",
"Dental Implants",
"Dental materials used in Prosthodontics"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe systematic review has been presented in a detailed and precise manner and deals with an important aspect of denture fabrication and its subsequent use. The inclusion and exclusion criteria along with the search strategy have been sufficiently described and are reproducible. The prescribed guidelines have also been followed.\nMinor modifications are suggested as under:\nResults:\n\"With regards to the SR, Cascione and others found a decrease in SR with large sized TiO2NP (greater or equal to 50 nm), but three studies reported an increase in SR with the addition of less than 50 nm TiO2NPand one study found in-significant improvement in SR.”\nThe statement, though seemingly states that a decrease in particle size has been found to be associated with an increase in surface roughness (SR), has been written in a contradictory and confusing way. The authors may modify the language for better understanding.\nIn, Recommendations for future clinical practice and research:\n“Based on the results of the current systematic review, the use of TiO2NP size up to 100 nm and at 3% concentration can be recommended to achieve optimum antimicrobial effect, SH and SR, however, additional efforts must be undertaken to improve the SR so as to minimize the microbial adhesion.”\nHowever, in Conclusion the authors state that:\n“Based on the evidence synthesized, it can be concluded that on addition of TiO2NP to heat polymerized PMMA denture base resin, the antimicrobial property and SH improved irrespective of the size of the TiO2NP, however, addition of TiO2NP less than 50 nm increased the SR.”\nThe authors need to clarify the proposed size of the nanoparticles based on the findings of Surface roughness as the results vary at <50nm and >50nm particle size, with the antimicrobial property and SH remaining unaffected.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "189294",
"date": "08 Aug 2023",
"name": "Carlos Enrique Cuevas-Suárez",
"expertise": [
"Reviewer Expertise Adhesive dentistry"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nPlease consider to resolve the following issues:\nPlease consider to state a null hypothesis for the study.\n\nAuthors stay \"Studies based on TiO2 nanotubes, fillers, fibres and coating on PMMA were excluded.\". However, for control, it's stated that heat polymerized PMMA without any addition of NPs or fibre, were included. So, it's difficult to understand if the works using TiO2 fibres were included.\n\nAuthors stay as control the use of heat polymerized PMMA. Does the cold-cure PMMA was excluded?\n\nIn the PICO strategy, the intervention should be: Addition of TiO2NP in pure or hybrid form in heat-polymerized PMMA.\n\nThe risk of bias analysis should be performed again using specific tools. My suggestion is to use the RoNDEMAT tool for the analysis of the in-vitro studies, while the clinical trial should be assessed using the RoB 2 tool.\n\nPlease include a Table summarizing the main characteristics of the studies.\n\nSome parts of the discussion should be moved to the results section; i.e. Sample dimensions, acrylic used and treatment of NPs; Methods for testing properties.\n\nThe conclusion section should be re-written again. Without a proper statistical analysis, the authors are not able to determine which concentration of NP's are optimal for improving the properties of the material.\n\nI suggest that the entire manuscript be proof-read. Some parts of the manuscript are difficult to read.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-577
|
https://f1000research.com/articles/12-569/v1
|
30 May 23
|
{
"type": "Research Article",
"title": "Cryopreservation of human embryos in an in-vitro fertilisation procedure: the need for a legal framework in Nigeria",
"authors": [
"Joy Victoria Ayeni",
"Taiye Joshua Omidoyin",
"Ifeoluwayimika Bamidele"
],
"abstract": "Background: The opportunity to completely ‘stop biological time’ using cryopreservation, as it is used in embryo cryopreservation, provides for the selection and long-term storage of high-quality preimplantation embryos for future usage. While this is a beneficial medical procedure, it has however posed some legal issues such as the legal status of an embryo, ownership of the embryo, reproductive autonomy, posthumous reproduction, surrogacy, and the required storage period for embryos. The ethical debate has been around what to do with surplus frozen human embryos, such as donation, adoption, and destruction of embryos. The aim of this research is to assess the need for a legal framework regarding cryopreservation of human embryos. Methods: The objectives are to examine and analyze the legal and ethical implications of the cryopreservation process of human embryos in an in-vitro fertilization procedure to identify the shortcomings of the 2016 Assisted Reproductive Technology Bill. This is legal research and adopts the doctrinal method of research, using both the primary and secondary sources of information. The primary sources include legislation, international instruments and case laws; the secondary sources include textbooks and journal articles. The doctrinal approach was employed to describe and analyse the legal and ethical issues relating to cryopreservation in Nigeria, focused on the analysis of legal principles available in Nigeria in relation to cryopreservation of human embryos. Results: This study finds that there are no laws on assisted reproductive technology regulating the cryopreservation of human embryos in an in-vitro fertilisation procedure in Nigeria. The study concludes that the lack of a legal framework on assisted reproductive technology in Nigeria is the major issue that has left the legal and ethical issues without direction. Conclusions: This work recommends the need for a legal framework for ART in Nigeria and a review of the Assisted Reproductive Technology Bill 2016.",
"keywords": [
"Infertility",
"cryopreservation",
"human embryos",
"assisted reproductive technology",
"in-vitro fertilisation."
],
"content": "Introduction\n\nThe expectation of pregnancy or parenthood after marriage or after a specific period of relationship has been met with infertility challenges as some couples have not been able to conceive nor even carry a pregnancy to term. Couples have challenges conceiving as a result of medical challenges or other associated factors and this causes sadness, depression, or even divorce. Infertility affects millions of people around the world who are of reproductive age and affects their families and communities, it is estimated that between 48 million couples and 186 million people worldwide suffer from infertility.1\n\nIn response to these infertility challenges, the recent development in medicine and technology help provide an alternative to natural conception. This innovation is referred to as assisted reproductive technology in which in-vitro fertilisation (IVF) was developed to help infertile couples conceive with the help of medical advancement. Couples dealing with infertility are faced with family pressure, societal pressures, and religious pressures as a result of their inability to conceive. This has however increased the desire and growth of assisted reproductive technology amongst these individuals. The opportunity to completely ‘stop biological time’ using cryopreservation, as it is used in embryo cryopreservation, provides for the selection and long-term storage of high-quality preimplantation embryos that are surplus is required for fresh transfer in an IVF procedure.2 The benefit of freezing embryos if IVF doesn’t work is that the couple can try transferring at least once, if not more, without having to undergo additional infertility treatments. On the other side, if the first attempt is successful, the couple can keep the frozen embryos and use them if they decide to have more children in the future.3\n\nAs beneficial as cryopreservation of human embryos are in an IVF process. In Nigeria, it appears that the law is silent on assisted reproductive technology and the procedures employed under in-vitro fertilisation, there is an absence of legal framework or regulations to determine if the practice of cryopreservation is lawful or illegal in Nigeria. In Nigeria, the National Health Act4 forbids the import, export, and alteration of any genetic material, as well as the use of human zygotes or embryos. Additionally, the legislation forbids any action, such as nuclear transfer or embryo division for human cloning. Anyone found guilty of violating one of these rules faces a mandatory minimum sentence of five years in jail without the possibility of a reduced sentence.5 However, there are currently two bills before the National Assembly, the National Health Act (Amendment) Bill 2016 and the Assisted Reproductive Technology Bill 2016 (ART). These bills both passed the second reading in 2017, but they now seem to have been abandoned. The Assisted Reproductive Technology Bill 2016 would have provided a proper legal and supervisory framework for cryopreservation, duration of storage, and the pre-implantation genetic diagnosis which would have included the process by which an IVF embryo is checked for certain illnesses before being transferred, which would have averted the birth of children with various genetic abnormalities such as sickle cell anaemia, Down syndrome, Huntington’s disease, Alzheimer’s, and muscular dystrophy. Based on the issues identified, this study will be looking into why infertile couples in Nigeria would attempt to preserve or freeze their embryos in an in-vitro fertilisation process. This study would as well look into the possible reasons for the absence of laws and rules in Nigeria.\n\n\nCryopreservation of embryos\n\nOne of the areas of medicine that have advanced the fastest over the past few decades is assisted reproductive technologies (ART). Numerous studies have been conducted in this field because they are the primary way of fertility treatment.6 Cryopreservation of embryos is a crucial component of assisted reproduction. The storage of gametes (sperm and oocytes), embryos, and reproductive tissues (ovarian and testicular tissues) for use in assisted reproductive techniques is included in the field of fertility cryopreservation, which is vital to reproductive science.7 We are now able to retain cells and tissues by freezing them to incredibly low temperatures, such as 195.79°C, as cryopreservation techniques progress (the boiling point of liquid nitrogen).8 There are two procedures used in cryopreservation and they include vitrification and slow freezing, When exposed to liquid nitrogen, vitrification converts biological material and the liquid solution surrounding it into an amorphous glass-like solid that is devoid of any crystalline structures.9 Cryoprotectants are necessary for vitrification at much higher quantities. However, they could have toxic and osmotic effects.10 Traditional cryopreservation methods like slow freezing rely on cryoprotective agents (CPA) that aren’t very concentrated and a slow chilling pace to reduce cell/tissue toxicity while leaving room for ice formation.11 These cryopreserved embryos are stored for future usage either for procreation, donation for research or for implantation at a different time.\n\n\nThe purpose of cryopreservation of the human embryo process in an in-vitro fertilisation procedure\n\nCryopreservation of human embryos has made it possible for couples to explore IVF options while still having their embryos saved in case, they want to have more children or if the implanted embryo doesn’t survive in the womb. This procedure has made it possible for individuals or couples to become pregnant at a later time due to infertility issues. Other women who lack the ability to make eggs or who have a hereditary condition have the option to receive donated embryos thanks to cryopreservation.12 Age-related changes in gender, infertility treatment damages, gender transitioning, preimplantation genetic testing, and ovarian hyperstimulation syndrome are among the reasons why some people choose to have this surgery.\n\n\nThe legal and ethical implications of cryopreserved human embryos in an in-vitro fertilisation procedure\n\nThis study will discuss the legal and ethical issues surrounding the cryopreservation of human embryos during an IVF procedure, including the embryo’s ownership status and legal standing, reproductive autonomy, posthumous reproduction, surrogacy, and the required storage period for embryos.\n\nThe human embryo is not regarded as a person and is not required to be treated as such by any legal standard; persons only join the legal system after birth.13 Nonetheless, this does not imply that a human embryo is completely unprotected by the law.14 Legal academics and jurists have currently believe that there are only three classifications that frozen embryos can fit into: (1) property, (2) early human life, or (3) an entity possessing an interim state.15 The embryo needs to be preserved even though it has no rights and is not a person because it could one day develop into a person or another unique thing.16 Concerning human embryos, we will behave differently depending on the perspective we adopt, either treating them as things or as people.17\n\nA human embryo is a fully developed, living individual of the human species, unlike other sorts of animal organisms like a dog or cat, parts of a cell in an organism like the heart, kidneys, or skin or an unorganized accumulation of cells waiting to undergo some sort of miraculous metamorphosis.18 There are three important characteristics of the human embryo: To begin with, the embryo is fundamentally distinct from any cell of the mother or father from the moment it is formed; the embryo is human because it possesses genetic traits unique to humans, which is the second reason; and perhaps most significantly, the embryo is a whole, mature, and full-grown organism.19 The argument that a cryopreserved embryo also qualifies as an unborn child under this definition is that it is the product of conception and is in a stage of development prior to live birth.20\n\nIf the frozen embryo is seen as nothing more than property, the owners of this undeveloped property would have the same rights that they would have if they had purchased a couch, automobile, or beach chair, as the frozen embryo is to be viewed as chattel, a transportable object of personal property. several options for what to do with the embryos, including trading, selling, and discarding, in the event that the embryos are converted, a third party may be held accountable for the embryos’ fair market value.21\n\nThe majority of critics and courts favour a conceptual compromise between treating the frozen embryo as a human person and treating it as simply property, if only in theory.22 The frozen embryo, according to the majority, is a being “entitled to special respect” since it represents potential life.23 Defining respect in this situation, though, is challenging. The distinction between a human embryo and the ethical dilemmas are not any clearer since it is a potential person, a project of a person, or a human being in development. unclear whether embryos should be viewed as things or as potential individuals.24\n\nThe Nigerian judiciary has not been able to test the waters regarding human embryo cryopreservation in relation to the use of assisted reproduction Because of this, the Nigerian judiciary has been unable to define what a human embryo is when its life first begins. Nevertheless, this work would assume that the Nigerian court could define a human embryo as a person or potential being by taking into account public policy and the citizens’ value for life and family.\n\n\nOwnership of the embryo\n\nWhen a human embryo is viewed as a piece of property, ownership of the said embryo becomes a legal matter, and the owner has the ultimate right to decide what will happen to the cryopreserved human embryo, to become an embryo, an egg needs to be fertilized outside of a woman’s body. Embryo using procedures like IVF, Zygote Intra-Fallopian Transfer (ZIFT), and Intra-Cytoplasmic Sperm Injection. In the case that there are surplus embryos, which frequently occur with IVF, excess embryos are frequently cryopreserved in accordance with.25,26\n\nBinding agreements between parties\n\nIn the event of divorce, illness, death, or other altering circumstances, enforceable agreements shall be made to specify the intended use and disposition of the embryos should be signed before the development of the embryos.27 Even though these contracts help set expectations and settle conflicts over ownership of embryos, they might create legal confusion because they are still governed by state laws and judicial precedents.\n\nState statutes\n\nPublic policy also forbids the purposeful destruction of the embryo due to the state’s limits on abortion, as a result, if a couple gives up their claim to the embryo, it must be made available for donation.28 Many conflicts are likely to be settled through litigation because there aren’t many state laws that expressly cover frozen embryos and because there aren’t any comprehensive laws in place. Currently, there is no legal regime regulating freezing of embryos in Nigeria, which is a gap this current study intends to fill by suggesting the need towards a legal framework for the cryopreservation of human embryos.\n\nAdjudication\n\nIVF contracts that address the disposition of frozen embryos often take one of two forms: they can either be drafted by an attorney or incorporated into the consent document provided by the IVF clinic.29 What happens to the embryos in the case that a divorce is commonly covered by both IVF contracting techniques.30 No matter how a couple decides to an agreement before beginning IVF,31 Most couples have formal, mutually endorsed agreements that state what will happen to the embryos in the event of divorce.32 When parties are trying to enforce a contract but cannot agree on how to handle the frozen embryos, a frozen embryo dispute may occur in court. Courts have used one of three theories to rule on disputes involving the distribution of frozen embryos:33 the three approaches are hybrid approach implementation, contemporaneous consent, balancing test, and pure contractual.34\n\nPure contractual approach\n\nThe approach most usually used to interpret and uphold IVF contracts is known as the pure contractual approach.35 IVF contracts are handled using the Pure Contractual Approach similar to any other contract kind where courts settle disputes based on the terms of the contract signed by the parties, which must be in conformity with the existing laws of the land as the law cannot be used to enforce an illegal or immoral contract.36 General contract law norms, such as the requirement of consent at the time of the agreement, are followed in the interpretation and execution of IVF contracts and do not rely on any particular procedures in the event of a dispute.37 This method is supported by the notion that competent people are free to enter into contracts and that those contracts should be interpreted in accordance with the parties’ intentions, just as they would be in other types of agreements.38 This technique of IVF contract’s interpretation, safeguards, limitations, and defences available in any other contract dispute applies to enforcement.39\n\nBalancing test approach\n\nA subjective test used by courts to balance conflicting interests is known as the balancing test approach.40 A judge is most likely to use a balancing test in a complicated situation where an equitable outcome can only be reached by taking into account a number of different factors that are relevant to the parties in the current case; this approach gives the judge a great deal of discretion in deciding how the dispute will be resolved.41 Despite introducing a weakness that effectively rendered disposition agreements useless by providing legal weight to either party’s change of heart, the court’s assertion that it would be ready to maintain such agreements posed a problem.42 If there is a later disagreement, the interests of the parties are determined using a balancing test similar to the Davis v. Davis method, with a lot of weight placed on the interests of the party trying to avoid procreation.43 The balancing test ensures that parties are treated fairly to the greatest extent possible, but it frequently causes parties to be uncertain about the case’s conclusion because the judge has complete discretion over the cryopreserved embryo in question’s ultimate fate. The court’s discretion was purely guided by the parties’ interests. The Assisted Reproductive Technology Bill 2016 failed to mention the balancing test approach as one of the adjudications mechanisms in resolving disputes on the ownership of an embryo which is the insufficiency of the ART bill in Nigeria even if the Bill has been abandoned since 2016, as it is the Bill is insufficient in regulating cryopreservation of human embryo in Nigeria.\n\nContemporaneous consent approach\n\nThe contemporaneous consent approach should be used to interpret and enforce IVF contracts since it preserves the fundamental rules of contract law while still defending couples’ competing interests in the event of a dispute.44 The fundamentals of contract law are upheld by the contemporaneous consent approach, which also includes an extra measure of protection. Courts frequently interpret and enforce IVF contracts in accordance with this technique without requiring a change of heart on the part of any party at the time of enforcement.45 Iowa Courts will not make any challenged agreements enforceable, regardless of the outcome of enforcement.46\n\nHybrid approach implementation\n\nThe hybrid approach sees embryos as having the ability to develop into human beings, better balancing the needs of parents and future children. this is due to the fact that embryos differ from other types of personal property or marital assets in that they can be used to conceive a biological child by either party, allowing for the balancing of the interests of both the parties who created the embryos as well as those of any future children who might be born as a result of one party’s use of the embryos,47 when attempting to determine the right allocation of frozen embryos, the hybrid approach eventually gives judges more discretion.48 In contrast to simply upholding the original intent of the contracting parties to a dispositional agreement, the hybrid approach places emphasis on the necessity of striking a balance between the interests of both partners as well as those of any potential children. However, in the event that a dispositional agreement was properly entered into by both parties, the Hybrid Approach still considers the parties’ express original intent when calculating how much of the asset should go to which party.49 In a recent case involving a frozen embryo, Jocelyn P. v. Joshua P., Jocelyn, who used IVF to become pregnant after receiving a primary infertility diagnosis with her former spouse, Joshua. The conflict was settled by the Maryland Court of Special Appeals using a hybrid contractual balancing method.50 At their fertility clinic, a consent document for in vitro fertilization, intracytoplasmic sperm injection, assisted hatching, and embryo creation was signed by Jocelyn and Joshua before they started the IVF procedure.51 When a contract does not reflect the progenitors’ intent, the balancing test must be utilized to evaluate their reproductive rights as well as a variety of other non-exhaustive factors, including:52 (1) the intended use of the party seeking to preserve the frozen embryos; (2) the physical ability or incapacity of a party seeking to implant the frozen embryos in order to have biological children through other methods; (3) the parties’ initial reasons for pursuing IVF; (4) hardship for the party seeking to avoid becoming a genetic parent; (5) either party’s bad faith or attempt to use the frozen embryos as leverage in the divorce; and (6) other pertinent case-by-case factors.53\n\n\nReproductive autonomy\n\nThere is a growing belief that choosing to have children is a very private and personal matter that should be decided by the parties themselves.54 The idea of procreative liberty encompasses the idea that individuals should have the last say in their reproduction.55 The concept of procreative liberty is directly at odds with the idea of forced parenting since it removes the parties’ decision-making authority and places it in the court’s hands. Even if a party succeeds in obtaining both legal and monetary free themselves from all obligations to the possible child, avoiding formal paternity,56 a court nevertheless imposes biological parentage on a party even if it grants despite the opposing party’s protests, one party was given access to the frozen embryos.57 These include permission, the ability to reproduce, and the right to refrain from doing so.\n\n\nPosthumous reproduction (PHR)\n\nPHR happens when a party donates gametes before passing away and the receiver wants to use them later.58 This typically occurs when a spouse whose gametes were preserved for eventual use dies and the remaining spouse wants to use them, or when a child who has passed away has donated their gametes to their parents, who subsequently wish to use them.59 Any of these circumstances involves people who are exercising their freedom to procreate, although noncoital.60 The strictest standards for the industry on this topic were published in 2006 by the European Society for Human Reproduction and Embryology.61 This state that in order for posthumous reproduction to be legal, the following requirements must be satisfied: the decision must be made by the surviving partner in the relationship; the deceased must have given written consent regarding the use of gametes at the time of storage; and the surviving partner must wait at least a year to allow themselves time to grieve before using the gametes. If these conditions are met, children born through posthumous reproduction should not be treated differently from children born before a parent passes away.62 After years of attempting to conceive and undergoing fertility therapy, Ted Jennings lost his wife Fern-Marie Choya unexpectedly in 2019 while she was expecting twin girls.63 Choya had not provided written authorization for posthumous surrogacy, thus the fertility authority, the Human Fertilisation and Embryology Authority (HFEA), denied Jennings’s request to be able to use their final frozen embryo to have a family.64 The high court’s family division determined that Jennings may use the final remaining embryo for posthumous reproduction in order to carry out his late wife’s desires.\n\n\nSurrogacy\n\nSurrogacy, often referred to as ’“womb renting”,65 is a situation in which one person, the ‘Surrogate Mother’, bears a child for another, the ‘Commissioner’, and the former completely cedes all rights to the latter regarding the kid, including custody, upbringing, care, and parenting.66 Ruth and Daniel Nahmani chose to undergo IVF after experiencing infertility for a while.67 Ruth Nahmani was unable to conceive, so the couple decided to use a surrogate from California to carry their child.68 After IVF but before the surrogacy plan could be put into action, Daniel Nahmani moved in with another lady, had a child, and then left his wife.69 Ruth Nahmani desired to carry out the insertion of the frozen embryos despite her refusal to divorce her husband. Ruth and Daniel no longer desired to become parents, and Daniel preferred that the embryos be destroyed. Ruth launched a lawsuit after being denied her request to have the embryos released from the hospital. The surrogate’s due to the fact that Ruth was no longer able to create eggs at the time of the hearing, the implantation of the embryos represented her last chance to pass down her genetic material.70\n\nA written contract is required for every patient using third-party reproduction. There should be independent legal advice for each party engaged. The names of both partners may not be allowed to appear on the birth certificate, Dependent on the nation or state the males are from and the location of the surrogate’s delivery. The patient must be aware of the legislation of their home state, the surrogate’s home state, and the state where the surrogate gives birth, as paid surrogacy arrangements may occasionally be prohibited in some jurisdictions.71 This gives a transgender person who has had gender reassignment surgery the chance to become pregnant later on using a surrogate; however, this practice is prohibited in Nigeria.72\n\n\nStatutory storage period for embryos\n\nCryopreserved embryos should be permitted to expire under the law as it stands if they are not used when the maximum storage time has passed for any reason for which permission has been granted. At the thought of letting several embryos die when they could be utilized for treatment, both licensed clinics and patients are becoming increasingly concerned.73 The possibility of expanding the maximum storage term is thus brought up. The regulation governing IVF practice in each nation determines the longest period of time that cryopreserved embryos may be kept in various ART facilities worldwide. The maximum storage term is therefore set at five years in England,74 France,75 and Canada,76 While in Australia, this time frame is increased to ten years.77 The Human Fertilization and Embryology Authority (HFEA) in the United Kingdom recently came to the conclusion that there would be many more benefits to extending the maximum storage duration than disadvantages. The HFEA proposes maintaining a five-year guideline for embryo storage, while there should be a provision at the end of that time for medical or social reasons to allow the couple to specifically reaffirm their agreement to increase the storage time to 10 years.78 A provision to permit an extension beyond 10 years in exceptional circumstances would put women who might want to store embryos in the same position as men, who are allowed to store gametes until they are 55 years old for exceptional medical reasons. Cryopreserved embryos may be kept for a maximum of five years in Israel, with a second five-year extension possible after the first five years have passed.79 While in Australia, if a couple cannot agree on what to do with their cryopreserved embryos after the 10-year window has passed, the Institutional Ethics Committee will make the decision.80 In Nigeria, due to the lack of legal framework or regulation, it would appear that embryos can be stored in perpetuity. Society will eventually have to decide who, if anyone, should be given these abandoned embryos, and that time is rapidly approaching. Medically and morally, using or donating cryopreserved embryos is acceptable. Rather than destroying these embryos, research projects should be supported.\n\nDestruction of embryos\n\nFor the couples that develop the embryos as well as for society at large, the disposition of unneeded embryos presents moral and ethical questions.81 Initially, it is not a contentious matter to retain embryos for potential usage in the future. It only turns into one when the viability or suitability of the embryos for transfer is questioned after they have been stored frozen for a number of years. The unknown is the maximum amount of time an embryo can be frozen before it becomes unsafe to utilize in IVF.82 Because the Catholic Church views ART and all of its effects as being unacceptable, it avoids discussing the topic of abandoning embryos explicitly. Jewish law allows for the passive killing of excess embryos by allowing them to defrost and perish naturally. The disposition of the embryos is a private matter for the couple involved in most Protestant religions.83 The pro-life viewpoint contends that because a new, genetically distinct live human being exists, upon conception or fertilization, a new person is created. The fertilized egg and early embryo are so entitled to the rights and respect due to people, and they cannot be killed or aborted. The opposing viewpoint acknowledges that the prenatal, living human entity is genetically distinct, alive, and human with the capacity to become a person, but it disputes that these qualities render the embryonic, live person is a subject of rights or obligations.84 According to John Harris, there is no moral justification for killing or permitting the death of embryos when they could instead be used for our common good. He also believes that there is little justification for letting human remains rot when they could be used to save many lives through, for instance, transplantation orders or other similar measures.85\n\nAdoption of embryos\n\nIn embryo adoption, a woman agrees to adopt the kid who is born as her child in order to preserve the only possible means of living a human being’s life.86 For individuals who desire children but are unable to have them, Pascual also believes that embryo adoption may be a legal option, but only if the adoption procedure is handled in the same manner as when adopting children without parents.87 Tonti-Filippini88 contends that creating and approving a pregnancy using an already created embryo diminishes the marital partnership’s sacredness since it contradicts the union-promoting goals of marriage. Tad Pacholzyk,89 opposes embryo adoption because, in his view, it would go against the intrinsic rights of spouses to marital union, particularly the right of the husband to his wife’s body. He is a member of the National Catholic Bioethics Center. Additionally, he says that practices that violate marriage’s core values specifically, their exclusive usage within the union are unacceptable. Collard,90 claims that, more than any other kind of reproduction due to problems with ontology and kinship, embryo adoption poses moral dilemmas and further difficulties about illation. A lot of couples decide to place their unborn children up for adoption, to help other infertile couples, several organizations around the country organize the donation of frozen embryos, and the defrosted adopted embryos are then implanted into the adoptive mother’s uterus. Such an approach is less expensive than IVF and does away with the need for the adoptive mother’s ovarian hyper-stimulation.91 Couples can have children as long as they’re married, hence Islamic law does not permit embryo adoption. Adoption of embryos is prohibited because the father of the embryo is not married to the mother of the child. Jewish law has a problem with embryo adoption since it could lead to incest because the adopted child might unintentionally marry their genetic sibling.92\n\nEmbryo donation\n\nCouples who undergo IVF frequently choose to transfer many embryos and freeze the remaining ones, presumably for a future pregnancy. However, the genetic parents typically never use these excess embryos, thus they are stored in storage forever.93 Surprisingly many of these embryos are kept in storage on other continents. It is estimated that 400,000 embryos are being cryopreserved in the United States alone, many of which won’t be used by their genetic parents.94 The prohibition of financial gain on all elements of the human body as a whole is a fundamental principle articulated in Article 21 of the Convention on Human Rights and Biomedicine. Article 2 of the Convention on Human Rights and Biomedicine makes it clear that human interests and wellbeing come before those of society or science as a whole. Article 15 of the Convention, which stated that scientific study in the domains of biology and medicine shall be conducted freely in accordance with the principles of this convention and other legislation ensuring the protection of human beings, applied this concept to research.95 However, this freedom is not absolute because it is constrained by the fundamental human rights that safeguard the individual. Embryo donation may be an option for some couples if the woman has an early ovarian failure or does not respond well to standard ovarian stimulation and the man has severe abnormalities in gamete production is a viable alternative for starting a family.96 Donating embryos may also be recommended for couples who are carriers of a hereditary illness that could result in the kid developing seriously ill.97 More than 40% of clinics appear to be focused on younger women, who often produce eggs of greater quality but may not have considered the long-term ramifications of donation, despite the American Society for Reproductive Medicine (ASRM)’s recommendation that donors be at least 21 years old.98 The donors of the embryos are required to sign an informed consent form granting authorization to utilize their embryos for donation and waiving any claims to the embryo(s) and any children who could be born as a result of the transfer of these embryos.99 In order to stop the transfer of these illnesses to the receiver or the offspring, they should be examined for genetic and infectious conditions.100\n\nDonation towards research\n\nInternationally, there has also been fierce debate regarding the use of embryos for research, notably in connection with human stem cells. As a result, many national laws governing this topic have been passed.101 As a result, the decision to support research was deemed to be “the least harmful” one.102 The Catholic Church holds that any exploitation or experimentation on human embryos violates respect for human dignity.103 The experimentation on living human embryos cannot be justified in any manner, regardless of how noble the goal may be, such as benefits to other people or society as a whole.104 An embryo, is a potential human being who requires special respect, according to the ASRM. The ASRM is in favour of embryonic research if it is carried out humanely and is anticipated to produce fresh insights that will benefit human health. As a result, the ASRM only supports the use of embryonic stem cell research if the couple grants their consent, as informed consent is the cornerstone of all human subject research.105\n\nThe sustainability of many marriages depends on the desire to become parents, this is however subject to the couple’s desires to be a parent. The number of assisted reproductive technology procedures has increased recently as more couples and people have turned to alternative therapies and conception techniques to conceive or treat infertility in Nigeria. The National Assembly attempted to pass the Assisted Reproductive Technology Bill in 2016, which was supported by Senator Lanre Tejuoso.106 This attempt came about as a result of the increased demand for a legislative framework to control the use of assisted reproductive technology. Professors Oladapo Ashiru, an embryologist, and Osato Giwa-Osagie, an endocrinologist, delivered Nigeria’s first IVF child on March 17, 1989, at the Lagos University Teaching Hospital/College of Medicine, University of Lagos. It was the first test-tube fetus to be born in Nigeria, however, the parents have thus far declined to give their approval for the child to be made public out of fear of stigmatization.107 The Assistive Reproductive Technology (Regulation) Bill 2016 is the closest Nigeria has come to regulating the cryopreservation of human embryos after an IVF process. Unfortunately, that Bill has not yet become a legal document. Despite this, Nigeria has not made the cryopreservation of human embryos during an IVF process a crime as it is not specified as an offence by any written legislation and has no associated penalties. As a result, it cannot be stated that someone who participates in the cryopreservation of human embryos during an IVF treatment in Nigeria has broken the law. Section 50 of the National Health Act108 forbids the importation and exportation of human zygotes or embryos as well as the manipulation of any genetic material. Additionally, any action like nuclear transfer or embryo division for human cloning is prohibited by the law. Anyone found guilty of violating one of these rules faces a mandatory minimum sentence of five years in jail without the possibility of a reduced sentence. As the entire process does not involve embryo manipulation or embryo splitting, this section cannot be understood as a legal framework governing the cryopreservation of human embryos. However, because it prohibits the importation or exporting of a cryopreserved embryo, subsection (c) does apply.\n\nThis law was intended to establish a national framework for the control and oversight of concerns relating to assisted reproductive technologies. This Bill’s goals are to ensure a legal framework for clarity and a broad outline of the general control to vest updates on the operation of the regulations at the national and state levels; provide minimum staffing and facility requirements for the various types of assisted reproductive clinics; to ensure that assisted reproduction technology operations are legal; and to control how patients are chosen for such procedures; promote the creation and maintenance of a national infertility database; enact regulations and give patients all the information and guidance they require on the many facets of assisted reproduction technology operations; enact laws governing the study of human embryos; Specify the parameters for collecting data from sperm and gamete donors; Encourage the creation and advancement of education and research in the area of assisted reproduction.109\n\nThe National Framework for Assisted Reproductive Technology (ART) Regulation and Supervision Bill for an Act is divided into nine (IX) chapters:110 Chapter I: Introductory; Chapter III: Clinic Procedures for Assisted Reproductive Technology; The establishment of authorities to oversee assisted reproductive technology is covered in Chapter II. Chapter V covers the sourcing, handling, and record-keeping of gametes, embryos, and surrogates. Chapter VI covers the regulation of embryonic research. Chapter VII covers the rights and obligations of patients, donors, surrogates, and children. Chapter VIII covers offenses and penalties. Chapter IX covers other topics. Assisted Reproductive Technology Clinic Tasks, Chapter IV. Chapters 1, Chapter iii, Chapter iiv, Chapter v, Chapter vi, Chapter vii, Chapter viii, and Chapter ix will be looked at in this study.\n\nSection 2(h) of the Bill defines an embryo as a fertilized ovum that has started cellular division and has continued development up to the blastssocyst stage until the end of five days. Section 2(f) gives a precise description of cryopreservation as the freezing and storing of gametes, zygotes, and embryos. The problem with this definition is that the definition of embryo according to the Bill ends five days after the end of blastocyst development.111 The use and production of embryos outside the human body for the purpose of treating infertility are stated in Section 13(3)(b) of the Bill; this section of the Bill acknowledges that during an IVF procedure, an embryo can exist outside the human embryo; subsection (c) of the Bill acknowledges the process and storage of gametes; and subsection (d) of the Bill acknowledges research on embryos for the purpose of treating infertility and genetic disorders or diseases.112\n\nSection 23 of the Bill prescribes the duties of the assisted reproductive technology clinic using gametes and embryos, and subsection (6) allows for posthumous reproduction through ART.113 The impressive implication of this act states that where posthumous reproduction has not been expressly included in the cryopreservation contract between party (ies) and the clinic, the consent can be implied from the desires of the deceased person’s or spouse to engage in cryopreservation. Pre-implantation genetic diagnosis (PGD) is acknowledged in Section 24 of the Bill, which also specifies that PGD shall only be used for the purpose of screening embryos for known, antecedent, diseases that run-in families or are genetic, or as the Registration Authority may specify. According to subsection (2), it is only permitted to destroy or donate an embryo with the consent of the patient if the embryo has a pre-existing, hereditary, life-threatening, or genetic condition. Section 25 criminalises the practice of sex selection on cryopreserved embryos before implantation.114 This disadvantage is that in Nigeria, where there is a need for a male child, patients who desire ART for the purpose of having a male child may not be legally permitted. The implication of this is that there is a possibility for illegal sex selection to be the norm and may even result in an unlicensed fertility clinic taking advantage of patients’ desperation to choose the sex of their embryos before implantation.\n\nThe Bill’s Section 27 specifies that embryos must be kept for no longer than five years.115 The fertility clinic has the legal right to destroy or donate the embryo to a recognized research organization, but there is an exception if the storage fees are not paid. This research disagrees with the maximum storage period because advances in medicine may call for a longer period of time for patients undergoing chemotherapy or other treatments that impair their ability to conceive. Section 29 of the Bill restricts the sale of embryos.116 The restriction in this Bill provision is supported by this research. In accordance with Section 30’s regulations on embryonic research, subsection (1) forbids and even makes illegal the export of embryos for research purposes. This research disagrees, nevertheless, with the state of the medical field in Nigeria, and the Bill must take this into account and increase funding for such technological innovation. Research may have been done on genetic illnesses, which Nigeria may not have access to. The provisions in Section 31 of the Bill on the regulation of research are supported by this research.117 This study supports the chapter vii provision Since it strives to protect both the participants to a surrogacy agreement and the child or children born as a result of that arrangement under ART, it focuses on the rights and obligations of patients, donors, surrogates, and children. This study concurs with the ART Bill’s chapters viii, ‘Offenses and Penalties’, and ix, ‘Miscellaneous’, since they both seem feasible and likely to be adopted in Nigeria.\n\nThe work recommends a systematic recognition of assisted reproductive technology in Nigeria by the legislators; the need for a legal framework in Nigeria regulating the in-vitro fertilisation process in Nigeria by withdrawing and redrafting the assisted reproductive technology bill 2016; this study recommends that a public hearing be held when the art bill is being redrafted and that medical practitioners, medical doctors with expertise in art, and legal professionals should be included and public sensitization of cryopreservation procedure, its purpose, the possible abuse and the need for a legal framework in Nigeria.\n\n\nConclusion\n\nIn conclusion, it is clear from the development of ART throughout the years and the technological innovations addressing infertility and offering treatments and cures for couples. ART provides alternatives to help them achieve their goals. Despite its benefits in treating infertility and giving a different method of conception than the normal ways of creation. The introduction of the cryopreservation process into IVF is meant to end biological infertility and make sure that embryos are kept in pristine condition to avoid cell damage, couples or individuals may elect to undergo this procedure as part of fertility treatment or preimplantation genetic testing in an effort to avoid or significantly reduce the number of children born with genetic diseases in the near future, as well as individuals undergoing gender reassignment surgery. This work concludes that there is a lack of legal framework in Nigeria as regards cryopreservation of human embryos in an in-vitro fertilisation. The cryopreservation of human embryos during an IVF procedure is not regulated by Section 50 of the National Health Act because this procedure does not manipulate or clone embryos; rather, it preserves the embryo for use in the future. As a result, those who participate in or engage in the cryopreservation procedure are not subject to the punishments outlined in this section. The National Health Act’s interpretation section does not describe an embryo in terms of ART or IVF; rather, it defines an embryo as a human progeny within the first eight weeks of conception. Any studies that increase our understanding of the origins of disease, the evolution of medicine, or the development of novel uses for medical technology are considered to be part of the field of health research. To conclude, because ART use has expanded in Nigeria, the ART Bill 2016’s abandonment has been damaging to the practice of human embryo cryopreservation there.\n\nThe Assisted Reproductive Technology Bill 2016 was intended to provide a legal framework for assisted reproductive technology in treating infertility in Nigeria and this Bill would have provided directions and regulations for the cryopreservation of human embryos in an in-vitro fertilization. It gives the method a legal basis for regulation, ensuring that it is practiced safely and morally. The Bill is a crucial step toward regulating the practice of cryopreservation during an in-vitro fertilization cycle. Despite this positive step toward creating a legal framework to control, protect patients, and practice cryopreservation, this work concludes that the Bill is a workable progress despite the issues raised in this chapter. The Bill can be passed and establish a legal foundation for the practice of cryopreservation of human embryos during an in-vitro fertilization treatment with a few revisions and redrafts.\n\n\nData availability\n\nNo data are associated with this article.",
"appendix": "Footnotes\n\n1 World Health Organization, ‘Infertility’ (14 September 2020) <https://www.who.int/news-room/fact-sheets/detail/infertility#:~:text=Estimates%20suggest%20that%20between%2048%20million%20couples%20and,shape%20%28morphology%29%20and%20movement%20%28motility%29%20of%20the%20sperm> accessed 4 October 2022\n\n2 Helen Hunter, Natalie Getreu, Maureen Wood, and Barry Fuller, ‘Cryopreservation of Human Embryos: Basic Principles and Current Considerations’ in G. N. Allahbadia et al. (eds.), Textbook of Assisted Reproduction (Springer Nature Singapore Pte Ltd. 2020) 505\n\n3 H.W. Michelmann, and P. Nayudu, ‘Cryopreservation of human embryos’ (2006) 7 Cell and Tissue Banking 136\n\n4 National Health Act, 2014 Cap A2 (Act No 8), s 50(1)\n\n5 ibid s50 (2)\n\n6 Iavor Vladimirov, Desislava Tacheva and Vladislav Dobrinov, ‘The Present and Future of Embryo Cryopreservation’ in Bin Wu and Huai L. Feng eds, Embryology -Theory and Practice (Intechopen, 2018) 1,2\n\n7 Francesca Ciani, Natascia Cocchia, Luigi Esposito and Luigi Avallone, ‘Fertility Cryopreservation’ in Bin Wu (ed) Advances in Embryo Transfer (InTech, Croatia 2012) 225\n\n8 D. Whittingham, S. Leibo, and P. Mazur, ‘Survival of Mouse Embryos Frozen to −196 and −269 C’ (1972) 178 (4059) Science 412\n\n9 W.F Rall, and G.M Fahy, ‘Ice-free cryopreservation of mouse embryos at -196°C by vitrification’ (1985) 313 Nature 573\n\n10 Eliezer Girsh and Irina Ayzikovich, A Textbook of Clinical Embryology (1st edn. Cambridge University Press 2021) 145,147\n\n11 ibid\n\n12 E.C Wood, ‘The future of in vitro fertilization’ (1988) 541 Ann. NY Acad. Sci. 715\n\n13 Yao-Jin Peng, Xiaoru Huang, and Qi Zhou, ‘Ethical and Policy Considerations for Human Embryo and Stem Cell Research in China’ (2020) (27) (4) Cell Stem Cell 512\n\n14 ibid\n\n15 Diane K. Yang, ‘What’s Mine is Mine, but What’s Yours Should Also be Mine: An Analysis of State Statutes That Mandate the Implantation of Frozen Preembryos’ (2002) 10 J.L. & Pol’y 587, 592\n\n16 Maria Aluaş, Claudia Diana Gherman, and Cristiana Iulia Dumitrescu, ‘Is the human embryo legally defined and protected? Causes and consequences’ (2017) (58) (2) Rom J Morphol Embryol 695\n\n17 ibid\n\n18 Robert P George and Christopher Tollefsen, A Defense of Human Life (2nd edn, Witherspoon Institute 2011) 13\n\n19 Ibid 50\n\n20 BS van Loggerenberg, The legal nature of a cryopreserved human embryo: A legal comparative analysis (PhD Thesis Faculty of Law, North-West University, 2021) 183\n\n21 Shirley Darby Howell, ‘The Frozen Embryo: Scholarly Theories, Case Law: Scholarly Theories, Case Law, and Proposed State Regulation’ (2013) (14) (3) Depaul Journal of Health Care Law\n\n22 Davis v. Davis, (1992) 842 S.W.2d. 588, 597\n\n23 ibid\n\n24 Aluaş supra (n49) pg 698\n\n25 Jenna Casolo, Campbell Curry-Ledbetter, Meagan Edmonds, Gabrielle Field, Kathleen O’neill, And Marisa Poncia, ‘Assisted Reproductive Technologies’ (2019) (31) (3) The Georgetown Journal Of Gender And The Law 319\n\n26 Melinda Traeger, ‘Comment, The Legal Status of Frozen Pre-Embryos When a Dispute Arises During Divorce’ (2003) 18 J. Am. Acad. Matrim. L. 563\n\n27 CP Kindregan and M McBrien, Assisted Reproductive Technology: A Lawyer’s Guide to Emerging Law and Science (2ndAmerican Bar Association Chicago 2011) 212, 215.\n\n28 Shelly R. Petralia, ‘Note, Resolving Disputes Over Excess Frozen Embryos Through the Confines of Property and Contract Law’ (2002) (17) (1) J. L. & Health 104\n\n29 Deborah L. Foreman, ‘Embryo Disposition and Divorce: Why Clinic Consent Forms Are Not the Answer’ (2011) 24 J. Am. Acad. Matrim. Law 57\n\n30 Sarah B. Kirschbaum, ‘Who Gets the F Who Gets the Frozen Embryos During a During a Divorce? A Case for the Contemporaneous Consent Approach’ (2019) (21) (2) N.C. J.L. & Tech. 122\n\n31 ibid\n\n32 Anna El-Zein, ‘Embry-Uh-Oh: An Alternative Approach to Frozen Embryo Disputes’, Mo. L. Rev. (2017) (82) 881\n\n33 M.T Flannery ‘Rethinking’ Embryo Disposition Upon Divorce’ (2013) (29) (2) Journal of Contemporary Health Law & Policy 233-234\n\n34 Melissa Boatman, ‘Comments: Bringing Up Baby: Maryland Must Adopt an Equitable Framework for Resolving Frozen Embryo Disputes after Divorce’ (2008) (37) U. Balt. L. Rev. 285\n\n35 ibid\n\n36 El-Zein supra (n65)\n\n37 ibid\n\n38 ibid\n\n39 Tracy J. Frazier, ‘Comment of Property and Procreation: Oregon’s Place in the National Debate Over Frozen Embryo Disputes’ (2009) 88 Oregon Law Review 932\n\n40 Cornell Law School, ‘Legal Information Institute’ (July, 2022) <https://www.law.cornell.edu/wex/balancing_test#:~:text=A%20%E2%80%9Cbalancing%20test%E2%80%9D%20is%20defined,to%20decide%20which%20interest%20prevails.> accessed 5 May 2023\n\n41 ibid\n\n42 Frazier, supra pg 719\n\n43 ibid pg 716\n\n44 Kirschbaum (n63)\n\n45 Carl H. Coleman, ‘Procreative Liberty and Contemporaneous Choice: An Inalienable Rights Approach to Frozen Embryo Disputes’ (1999) (84) (55) Minn. L. Rev. 88\n\n46 In re Marriage of Witten (2003) 672 N.W.2d 768, 783\n\n47 Andrea Howell, ‘Resolving Disputes Of Resolving Disputes Over Embryo Allocation Upon Divorce: A Need For a Hybrid Approach by Illinois Courts’ (2022) (71) (3) Depaul Law Review 868\n\n48 ibid\n\n49 ibid\n\n50 Jocelyn P. v. Joshua P., 250 A.3d 373, 379 (Md. App. 2021).\n\n51 ibid\n\n52 ibid pg 405\n\n53 ibid pg 403\n\n54 Christina C. Lawrence, ‘Procreative Liberty and the Preembryo Problem: Developing a Medical and Legal Framework to Settle the Disposition of Frozen Preembryos’ (2002) 52 Case W. Res. L. Rev. 721\n\n55 ibid\n\n56 Lee M. Silver, and Susan Remis Silver, ‘Confused Heritage and the Absurdity of Genetic Ownership’ (1998) (11) Harv. J.L. & Tech. 593\n\n57 Coleman supra (n77)\n\n58 PHR occurs where a child is conceived “after the death of one or both genetic parents, CP Kindregan and M McBrien, Assisted Reproductive Technology: A Lawyer’s Guide to Emerging Law and Science (2nd American Bar Association Chicago 2011) Where consent has been obtained from the deceased, the ethical concerns regarding the violation of patient autonomy do not arise”. Robey Posthumous Semen Retrieval and Reproduction 4-9 observes that this is, however, only one such concern. Others include the welfare of the child, the interests of the requesting party, as well as the interests of the physician. Orr and Siegler 2002 J Med Ethics 299 identify only consent, respectful treatment of the dead body, and the potential welfare of the child as possible ethical concerns. RD Orr and M Siegler ‘Is Posthumous Semen Retrieval Ethically Permissible?’ (2002) 28 J Med Ethics 299-303\n\n59 ibid 580\n\n60 C van Niekerk, ‘Assisted Reproductive Technologies and the Right to Reproduce under South African Law’ (2017) (20) per/pelj 8\n\n61 ibid\n\n62 ibid\n\n63 ibid\n\n64 Ted Jennings Applicant v Human Fertilisation and Embryology Authority [2022] EWHC 1619 (Fam)\n\n65 The Centre for Bio-Ethics and Culture Networks, Surrogacy: A 21st Century Human Rights Challenge, <https://cbc-network.org/issues/making-life/surrogacy/> accessed 15 January 2023\n\n66 O. Umah, Why Surrogacy is Unlawful in Parts of Nigeria? The Nigerian Lawyer. (thenigerialawyer, 5 May 2021) Available at <https://thenigerialawyer.com/why-surrogacy-is-unlawful-in-parts-of-nigeria/> accessed 15 January 2023\n\n67 Nahmani v. Nahmani [1996] 4 IsrLR 50 CA 2401/95\n\n68 ibid\n\n69 ibid\n\n70 ibid\n\n71 Ilana B. Ressler, Same-Sex Couples and Single Women Undergoing Medically Assisted Reproduction in Gautam Nand Allahbadia, Baris Ata Steven, R. Lindheim, Bryan J. Woodward, Bala Bhagavath Textbook of Assisted Reproduction (Springer Nature Singapore Pte Ltd. 2020)348\n\n72 Same Sex Marriage (Prohibition) Act, 2013 CapA2, LFN, 2004\n\n73 Richard J. Paulson, ‘Cryopreservation of Embryos: Medical, Ethical, and Legal Issues’ (1996) 13 (10) Journal of Assisted Reproduction and Genetics 759\n\n74 United Kingdom Human Fertilization and Embryology Act, July 1990\n\n75 J Cohen, ‘The French Bioethic Law’ (1995) 12 (29) J Assist Reprod Genet 663--664\n\n76 M J Ashwood-Smith, ‘Frozen Canadian zygotes’ (1995) 10 Hum Reprod 308\n\n77 D.M Saunders, M.C Bowman, A Grierson, F Garner, ‘Frozen embryos: Too cold to touch? The dilemma ten years on’ (1995) 10 Hum Reprod 3081\n\n78 ibid\n\n79 J G Schenker, ‘In vitro fertilization (IVF), embryo transfer (ET) and assisted reproduction in the State of Israel’ (1987) 2 Hum Reprod 759\n\n80 D M Saunders, M C Bowman, A Grierson, F Garner, ‘Frozen embryos: Too cold to touch? The dilemma ten years on’ (1995) 10 Hum Reprod 3083\n\n81 Sufiya Ahmed, Embryo Freezing and Donation: Ethical-Legal Issues, ILI Law Review (Summer Issue 2018) 124\n\n82 ibid 124\n\n83 Linda Bickerstaff, Technology and Infertility: Assisted Reproduction and Modern Society (The Rosen Publishing Group, New York, 2009) 47\n\n84 Ahmed supra (n115) 126\n\n85 Peter Saunders, The Moral Status of the Embryo (nucleus summer 2006) 24 <https://humanjourney.org.uk/articles/the-moral-status-of-the-embryo/> accessed 15 January 2023\n\n86 Justo Aznar, Miriam Martínez-Peris, and Pedro Navarro-Illana, ‘Moral Assessment of Frozen Human Embryo Adoption in The Light of The Magisterium of The Catholic Church’ (2017) (23) (1) Acta Bioethica 141\n\n87 F Pascual, La mayoría de embriones de fecundaciones in vitro terminan destruidos. Ideas Claras in Justo Aznar, Miriam Martínez-Peris, and Pedro Navarro-Illana, ‘Moral Assessment of Frozen Human Embryo Adoption In The Light Of The Magisterium Of The Catholic Church’ (2017) (23) (1) Acta Bioethica 141\n\n88 E.C Brugger, Rescuing Frozen Embryos. Is Adoption a Valid Moral Option? in Justo Aznar, Miriam Martínez-Peris, and Pedro Navarro-Illana, ‘Moral Assessment of Frozen Human Embryo Adoption In The Light Of The Magisterium Of The Catholic Church’ (2017) (23) (1) Acta Bioethica 141\n\n89 United States Conference of Catholic Bishops, Natural family planning USCCB Forum 2009, in Justo Aznar, Miriam Martínez-Peris, and Pedro Navarro-Illana, ‘Moral Assessment of Frozen Human Embryo Adoption In The Light Of The Magisterium Of The Catholic Church’ (2017) (23) (1) Acta Bioethica 141\n\n90 C Collard, S Kashmeri, ‘De embriones congelados a siempre familias: Ética del parentesco y ética de la vida en la circulación de embriones entre las parejas donantes y las adoptantes en el programa Snowlakes’, Rev Antropol Soc (2009) (18) 45\n\n91 Ahmed supra(n115)\n\n92 Linda Bickerstaff, Technology and Infertility: Assisted Reproduction and Modern Society (The Rosen Publishing Group, New York, 2009) 48\n\n93 M. S. Paul, R. Berger, E. Blyth, and L. Frith, ‘Relinquishing frozen embryos for conception by infertile couples’ (2010) (28) (3) Families, Systems and Health 259\n\n94 ibid\n\n95 ibid\n\n96 Ahmed supra (n115)\n\n97 Viveca Söderström-Anttila, Tuija Foudila Ulla-Riitta, and Ripatti Rita Siegberg, ‘Embryo donation: outcome and attitudes among embryo donors and recipients’ (2001) (16) (6) Human Reproduction 1121\n\n98 Jason Keehn, Eve Holwell, Ruqayyah Abdul-Karim, Lisa Judy Chin, ‘Recruiting egg donors online: an analysis of in vitro fertilization clinic and agency websites’ adherence to American Society for Reproductive Medicine guidelines’ (2012) (98) (4) Fertil. Steril. 995\n\n99 Söderström-Anttila supra (n131)\n\n100 Claudia Borrero, Gamete and Embryo Donation in Effy Vayena, Patrick J. Rowe, P. David Griffin (ed) Current Practices and Controversies in Assisted Reproduction” Report of a meeting on Medical, Ethical and Social Aspects of Assisted Reproduction held at WHO Headquarters in Geneva, Switzerland (World Health Organization Geneva, 2002)\n\n101 T. Kalista, H. A. Freeman, B. Behr, R. R. Pera, and C. T. Scott, ‘Donation of embryos for human development and stem cell research’ (2011) (8) (4) Cell Stem Cell 360\n\n102 Aviad Raz, Jonia Amer-Alshiek, Mor Goren-Margalit, Gal Jacob, Alyssa Hochberg, Ami Amit, Foad Azem, and Hadar Amir, ‘Donation of surplus frozen pre-embryos to research in Israel: underlying motivations’ (2016) (5) (25) Israel Journal of Health Policy Research 5\n\n103 Charter of The Rights of The Family, art. 4(b) 1983\n\n104 ibid\n\n105 Ethics Committee, ‘American Society for Reproductive Medicine, Disposition of Abandoned Embryos’ (1997) (67) (1) Fertility & Sterility 253\n\n106 Assisted Reproductive Technology (ART) Bill (2016-2017) SB.325 (Placbillstrack, 2017) <https://placbillstrack.org/8th/upload/SB325.pdf> accessed 30 January 2023\n\n107 Chinelo A Ekechi-Agwu and Anthony O Nwafor, ‘Regulating assisted reproductive technologies (ART) in Nigeria: lessons from Australia and the United Kingdom’ (2020) (24) (4) African Journal of Reproductive Health 90\n\n108 (2014) CapA172 no 8\n\n109 Senator Lanre Tejuoso supra (n140)\n\n110 ibid\n\n111 ibid pg c2606\n\n112 ibid pg c2614\n\n113 ibid pg c2621\n\n114 ibid pg c2622\n\n115 ibid pg c2624\n\n116 ibid pg c2625\n\n117 ibid"
}
|
[
{
"id": "247999",
"date": "12 Apr 2024",
"name": "Swati Gola",
"expertise": [
"Reviewer Expertise Surrogacy laws",
"ART regulation"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThere is definitely an argument for the need of regulating cryptopreservation. However, authors have failed to make the argument adequately. To begin with, there is no central argument and a theoretical underpinning, i.e., why cryptopreservation of embryo is to be regulated and if the authors think that the ART Bill adequately addressed the issues arising from the cryptopreservation of embryo. Secondly, there is no logical structure. It is not clear why authors decided to start discussion with legal and ethical implications. Is it to show the necessity of regulation? That link is missing, and it affects the rest of the writing because relevance of many sections especially the IVF contracts is not clear. On top of that concepts are often not made clear, like consent approach to dispute resolution, what is that? What is the relevance of discussing foreign cases? Are foreign judgments applicable in Nigeria? At times, arguments are presented as given, eg, public policy forbids purposeful destruction of embryo in sub-section State statutes. Is it the public policy in Nigeria? Argument/point are not fully developed, eg, Jocelyn v Joshua case. In the absence of a clear research question or central argument, it is often not clear what is the relevance of any section, eg, reproductive autonomy. It is not clear what was the argument here, how is forced parenting relevant to the discussion? Similarly, relevance of section on surrogacy along with the example is incomprehensible. The paper is descriptive and there is no attempt at analysis. In fact, it failed to show legal and ethical issues as such. It only describes the implications but doesn't address the issues they raise. There is some attempt at critiquing the ART Bill but poorly done. Writing suffers from unclear sentences and will benefit from comprehensive proofreading. It is recommended that the authors take time and begin with the basics, i.e., a theoretical framework and a central research question and then organise the structure accordingly. They must then connect each point back to that central point, eg, how legal and ethical issues emerging from cryptopreservation of embryo necessitate a strong, clear regulatory framework. If the ART Bill in its present form sufficiently addressed those issues or not. And if not, then how can the opportunity of its lapse can be used by amending/inserting certain provisions to fortify regulation in light of the issues raised.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-569
|
https://f1000research.com/articles/11-159/v1
|
08 Feb 22
|
{
"type": "Research Article",
"title": "Effectiveness of antepartum breathing exercises on the outcome of labour: A randomized controlled trial",
"authors": [
"Sushmitha R Karkada",
"Judith A Noronha",
"Shashikala K Bhat",
"Parvati Bhat",
"Baby S Nayak",
"Sushmitha R Karkada",
"Shashikala K Bhat",
"Parvati Bhat",
"Baby S Nayak"
],
"abstract": "Abstract Background\nChildbirth is a life-transforming intense event to a woman and her family. Even though a variety of non-pharmacological techniques are readily available to alleviate the distress of women in labour, the majority of women are unaware of its benefits. The objective of the study was to explore the impact of a simple non-pharmacological technique i.e., antepartum breathing exercises on maternal outcomes of labour among primigravid women. Methods A single centre prospective, single-blinded, randomized controlled trial was conducted at the antenatal outpatient clinic of a secondary healthcare institution. Eligible primigravid women were randomized into intervention and standard care groups. Both groups received standard obstetrical care. In addition, the intervention group were taught antepartum breathing exercises and were advised to practise daily and also during the active stage of labour. The primary outcome of the trial was the maternal outcome of labour measured in terms of onset of labour, nature of delivery, duration of labour, and need for augmentation of labour. Data was collected using World Health Organization (WHO) partograph, structured observational record on the outcome of labour. Results A total of 98 (70%) primigravid women who practised antepartum breathing exercises had spontaneous onset of labour. The odds of spontaneous onset of labour after randomization in the intervention group was 2.192 times more when compared to standard care at a (95% confidence interval 1.31–3.36, p<.001). Also, the requirement for augmentation of labour was minimal and there was a reduction in the rate of caesarean deliveries (p <.05) based on the χ2 test. The overall mean duration of labour was less compared to standard care group F(1)= 133.800, p <.001. Conclusion Antepartum breathing exercises during labour can facilitate spontaneous vaginal birth, shorten the duration of labour, and reduce the need for operative interference.",
"keywords": [
"Breathing exercises",
"antenatal",
"pregnancy childbirth",
"labour",
"complementary alternative therapies",
"Lamaze breathing",
"natural birth",
"spontaneous labour"
],
"content": "Introduction\n\nThe health and well-being of mother and child during pregnancy and childbirth are public health concerns because both of them have special needs, which cannot be catered to by general health services.1 Prompt continuum of antenatal care is a significant maternal service that a woman needs to receive during pregnancy to have an optimal health outcome, facilitate timely treatment and prepare for childbirth.\n\nChildbirth is a life-transforming intense event to a woman and her family.2 It is the time to maintain balance between fulfilling expeience and reality of expectations. Although childbirth is higly considered as one of the medical concern, yet lot of emphasis is given to natural birth with minimal intervention. Therefore, this becomes an ideal time to advise women on the normal physiological processes of pregnancy and childbirth that would help them to be prepared. The birthing environment greatly influences the experience during labour.3 Most of the birthing centres in the country are restrictive with routine use of medications, intravenous fluids, continuous electronic fetus monitoring, and numerous procedures that are carried out as part of typical labour. All these may disrupt the normal process and craft difficulties that, in turn, must be managed with greater labour interventions.\n\nA systematic review on childbirth education reports that childbirth preparation helps in building self-esteem, self-confidence and control, but weakly validates impact on reducing interventions during labour.4 Non-pharmacological interventions/techniques or complementary therapies integrated into the routine antenatal childbirth education framework offers remarkable benefits to women during pregnancy and labour to have a satisfying labour experience with minimum labour interventions.5\n\nA variety of non-pharmacological techniques such as relaxation, breathing techniques, positioning/movement, massage, hydrotherapy, hot/cold therapy, music, guided imagery, acupressure, and aromatherapy are available to women in labour. Women are encouraged to employ any of these techniques, as they are non-invasive and appear to be safe for mother and baby.\n\nBreathing is one of the simple, cost-effective non-pharmacological techniques, which connects the mind and the body, combination of controlled breathing and conscious relaxation are power-packed tools for labour.6 Breathing distracts the focus away from pain and enables the mother-to-be to give birth awake and aware.7 It also enables the woman to control her response to labour8 and adjust her breathing levels as labour progresses.9\n\nA clinical trial conducted on pregnant women to assess the efficacy of supervised antenatal yoga program, which included breathing patterns on perceived maternal labour pain and birth outcomes reported that women experienced lower pain intensity, required decreased need for labour induction, showed lower rates of caesarean deliveries and experienced a shorter duration of second as well as the third stage of labour.10\n\nThe Cochrane Systematic Review on the effectiveness of the non-pharmacological intervention on pain management for labour, reports relaxation, massage acupuncture, and hydrotherapy helped in the management of labour with few side effects; however, more exploration is needed to establish the efficacy of these techniques.11\n\nIn response to the need to establish a strong evidence base for non-pharmacological intervention, we undertook a randomized controlled trial to test the hypothesis that women who participated in an antepartum breathing exercise program, in addition to usual antenatal care, would experience the spontaneous onset of true labour, spontaneous vaginal birth, shorter duration of labour, and lesser demand for augmentation of labour than antenatal women who receive standard antenatal care alone.\n\n\nMethods\n\nThe antepartum breathing exercise program was based on the Lamaze method, with the Lamaze breathing component for use during pregnancy and childbirth. Antenatal women were recruited to a two-arm study consisting of an intervention group, who received training of the antepartum breathing exercise program in addition to usual care, and a standard care group, who received standard care alone. The study was a single-blinded and prospective randomized controlled trial (RCT). This trial was developed based on the extension of the CONSORT statement for reporting RCT.12\n\nEthical clearance was obtained from the Institutional Ethics Committee of Kasturba Hospital, Manipal (IEC 212/2012) and the trial was registered under The Clinical Trials Registry - India (CTRI). The registration number for this trial was CTRI/2016/02/006621, registered on 05.02.2016 (Available at URL http://www.ctri.nic.in).\n\nWomen attending the antenatal clinic were eligible to participate in the study from 36 weeks of gestation. They were provided with a subject information sheet. Those women who were willing, interested, and eligible to participate, signed individual consent forms. Women were eligible to enter the trial if they had a singleton pregnancy with a cephalic presentation, had low risk (no pre-existing medical complications or existing obstetric complications), and were first-time childbearing women (primigravida). Women were excluded from entering the trial if they had pre-identified risk factors like eclampsia, preterm labour, placenta previa, multiple gestation, malpresentation and malposition or had been previously randomized to the trial. Recruitment was undertaken at one tertiary health care hospital in Udupi, Karnataka. All eligible antenatal women were approached in the antenatal clinic individually and were randomized to the study.\n\nWe used block randomization to randomize participants into the groups. Randomization was done in a 1:1 allocation ratio to ensure equal numbers in each group. Further allocation of participants to the intervention and standard care groups was done by an outpatient nurse with the help of a sequentially numbered opaque sealed envelope (SNOSE). The randomization of the study is illustrated in the reporting guidelines [ref https://doi.org/10.6084/m9.figshare.19076597.v1].\n\nFive breathing patterns were introduced namely- cleansing breathing for relaxation, slow-paced breathing, modified-paced breathing and patterned-paced breathing. These patterns were used during and following contractions. Gentle pushing, and breath-hold during pushing were instructed during the second stage of labour which encouraged descent of the baby (Figure 1). The pattern of intervention was as follows:\n\nAt 36 weeks of gestation\n\nAn educational video explaining five patterns of breathing exercises was shown and their benefits were taught to women enrolled in the intervention group during the first appointment. These breathing patterns were demonstrated by the investigator to the women on a one-to-one basis. Women were asked to repeat these breathing patterns immediately after teaching and were advised to practice them twice daily for 15 minutes. Instructions were given to continue during the active phase of the first stage of labour under the supervision of labour room nurses.\n\nAt 37– 40 weeks\n\nWomen in the intervention group continued practising breathing exercises and compliance was monitored with help of a daily log along with the daily fetal movement count (Sadovsky method, as advised by obstetrician). This daily log was followed-up by the investigator during weekly antenatal visits. Occasionally the investigator checked for compliance through phone calls and enquired if they had any difficulties.\n\nDuring labour\n\nMonitoring during labour was done at the active phase of labour by the observers (nurses in the labour room), who were oriented on breathing exercises.\n\nStandard care\n\nLikewise, the women randomized to the standard care group received health talk on antepartum care and services according to local health care provision. They were also monitored during the active phase of labour by the observers in the labour room.\n\nMaternal and neonatal outcomes were measured using structured observational records on outcomes of labour. The tool consisted of 25 items that observed outcomes, which were the outcome of labour, nature of delivery, duration of labour, rate of episiotomy, augmentation of labour, gestational age at birth, birth injuries, and APGAR score at birth. The tool shows an accepted validity with an inter-rater reliability of one. Observational checklist on the performance of antepartum breathing patterns during the active phase of labour had 24 items; was reliable with an inter-rater reliability of .92, and .89 for test-retest reliability.\n\nThe sample size calculation was based on two independent means derived from the pilot study. The trial was designed to demonstrate minimum detectable differences in the duration of labour between two groups as one hour and anticipate an attrition rate of 10% since outcomes were measured until 40 weeks of gestation. This required a total sample size of 140 primigravid women in each arm of the trial for 80% power at a significance level of p<.05. Recruitment continued until at least 140 women had been enrolled, and from those randomized to the intervention group, 138 completed the study and two were excluded due to elective Lower Segment Caesarean Section (LSCS) or non-reactive Non Stress Test (NST). A low dropout rate (<7%) was observed for the overall study population.\n\nThe demographic data included the background information of the women’s age, period of gestation, last menstrual period (LMP), expected date of delivery (EDD), parity, years of marriage, religion, type of family, education, occupation, family income, height, current weight, and total weight gained during pregnancy. Maternal and neonatal outcomes were measured using structured observational records on the outcome of labour. This tool consisted of 12 items; maternal outcome included the onset of labour, duration of labour, the rate of episiotomy, and mode of delivery. Gestational age at birth, birth weight, birth injuries, APGAR score, and presence/absence of birth injuries were the parameters for neonatal outcomes. The performance of antepartum breathing exercises by the women during the active phase of labour was observed by the labour room nurses using an observation checklist. This tool included a stepwise performance of breathing patterns with ‘yes’ or ‘no’ options. If the women followed the steps, a score of ‘1’was given and if they failed to demonstrate, a score of ‘0’ was given.\n\nCategorical data were expressed as frequency and percentages and analyzed with the χ2 test and Fisher's exact test. All continuous variables were expressed as the mean with standard deviation and analyzed using a two-way ANOVA test to compare the interaction between the independent variable on the dependent variable. Logistic regression analysis was performed to determine the independent predictive factors for spontaneous onset of labour. The data collected was analyzed using Statistical Package for Social Sciences (SPSS) version 17.0 SPSS (RRID:SCR_002865), URL: http://www-01.ibm.com/software/uk/analytics/spss/, significance was set at an α of 0.05, reporting on relative risk with a 95% CI.\n\n\nResults\n\nOut of 292 participants recruited, 280 participants were randomized into intervention or standard care groups. Nineteen women (2 from intervention group and 17 from the standard care group) were excluded from the study because they had elective caesarean deliveries and non-reassuring NST. Ultimately, 261 participants were enrolled with 138 in intervention group and 123 in standard care groups as shown in CONSORT flow diagram (Figure 1). The mean age was 26.51 (SD 2.88) years. The majority (92%) were married for 1-3 years. Most (66%) belonged to a joint family. Two-thirds (64%) were homemakers. The mean period of gestation at the time of recruitment for the study was 36.76 (SD 0.83) weeks. Since no significant differences were found, the groups were homogenous concerning demographic characteristics at the time of recruitment to the study (Table 1).\n\nOnset of labour\n\nA statistically and clinically significant difference was found in the onset of true labour in our study. Among 138 primigravid women in the intervention group, 98 (70%) had spontaneous onset of labour (women came with term gestation, vertex presentation and spontaneous uterine contractions with or without rupture of membranes) as compared to those women in the standard care group. The logistic regression analysis (Table 2) showed that odds of spontaneous onset of labour in the intervention group was 2.192 times more when compared to the standard care group with a 95% confidence interval (1.31–3.36) p <.001.\n\nNature of delivery\n\nWomen in the intervention group 67 (48%) were more likely to experience a spontaneous vaginal birth, 33% of women had induced vaginal deliveries and 19% had caesarean deliveries (Table 3). The rate of spontaneous vaginal delivery was significantly lower and caesarean delivery was higher in the standard care group.\n\nDuration of labour\n\nA statistically and clinically significant difference was found in the mean duration of labour (in hours) between intervention 5.5127 (SD 1.998) hours and standard care group 7.238 ± 3.678 hours, resulting in a mean of 132 minutes, p<.001 (Figure 2).\n\nAmong 98 women in the intervention group who had spontaneous onset of labour, 68% had a spontaneous vaginal delivery with episiotomy, 18% had assisted vaginal delivery with outlet forceps due to failure of maternal power, decreased bearing down efforts and prolonged second stage of labour and 13% had vacuum delivery. Whereas in the standard care group, 26% had a spontaneous vaginal delivery, 34% had forceps and 40% had vacuum vaginal delivery (Data not shown).\n\n\nDiscussion\n\nFindings from our study suggested that breathing patterns when done regularly during the antenatal period as well as the active phase of labour had a positive impact on outcomes of labour. Excessive interventions at the time of labour were minimized preserving autonomy and ultimately enabling women to attain self-control. The biological characteristics in the study such as age and period of gestation were consistent with the findings of the earlier reports.13\n\nThe benefits of control over maternal weight gain during pregnancy seen in our study supports the findings of study by Narendran S, et al., suggesting that practicing yoga could prevent excessive weight gain and obesity during pregnancy.13 Supervised exercise of light to moderate intensity can be used to prevent excessive gestational weight gain, especially in normal-weight women.14\n\nThe most convincing reason to let labour begin on its own is the activation and stimulation of hormones like oxytocin, endorphins, catecholamines, and prolactin which regulate labour and birth.15 The present study adds to the evidence that the odds of a natural onset of labour in the intervention group was 2.192 times more when compared to the standard care group with a 95% confidence interval [1.31-3.36], p<.001. Various other studies have shown that beta-endorphin levels were high after exercise (p <.001), which is necessary for the spontaneous onset of labour,16 and exercise during labour excited uterine contraction.17\n\nBreathing exercises during pregnancy revealed various beneficial effects like reduction in preterm birth, longer gestational age, increase in birth weight, reduction in the rate of caesarean birth and assisted vaginal birth.18 The current study revealed that most women - almost 48% had a spontaneous vaginal birth and only 33% required the augmentation of labour with oxytocin in the intervention group. Supporting the findings of our study, a RCT carried out by Bergstro et al., reports that among the women who were taught psychoprophylaxis method (including breathing exercises) 321 (66%) had spontaneous vaginal birth, 67 (14%) had instrumental birth and 96 (20%) had caesarean birth.19 A similar result was reported in a systematic review by Curtis et al. (2012).20 A study by Karkada et al. (2017) reported that women who had spontaneous onset of labour had 1.93 odds (95% CI, 1.30-2.86, p<.001) of having a spontaneous vaginal birth.21\n\nLabour is a multidimensional physiological event that involves the balance of hormonal factors.22 If these hormones are systematically promoted, supported, and protected throughout pregnancy to birth, it would help to enhance wellbeing and empower childbirth transition. The present study indicated that the mean duration of labour in the intervention group was 5.5127 (SD 1.998) hours and the standard care group was 7.238 (SD 3.678) hours, consistent with previous studies.23,24\n\nFirst, the participants were low-risk pregnant women above 36 weeks of gestation without any major complications and thus the study did not focus on the high-risk pregnancy population. Second, as it was a single-blinded study, the researcher was aware of the group assignment. Hence, a reporting bias may have occurred. Third, generalizability was limited as participants were recruited from a single centre and recruitment from many centres is needed to replicate the findings.\n\nThe study provides policymakers with the evidence of incorporating comprehensive childbirth education that introduces women to a variety of options, which is not commonly practiced in India, especially in a setting where research was carried out. Instituting midwifery-led collaborative care services in community health centres and rural centres will aid in the utilization of these strategies and thus be sustainable. Secondly, a combination of evidence-based practice framework with an active-learning approach supports the development of an educational intervention that is intended to bring about a change in practice and meet the learning needs of labour and delivery.\n\n\nConclusion\n\nConsidering the special needs of childbearing women, a personalized and focused protocol is best indicated, that adapts to a variety of practices, and which provides and promotes a holistic approach to health. It must also fosters participants with a framework with which they can integrate this practice during pregnancy and childbirth. Evidence from various studies and the present study support that antepartum breathing exercises are suitable for pregnancy and have an optimistic outcome. To add strength to the study, more standardized programs along with obstetricians should be conducted, which would bring improvements to evidence-based evaluations in a research environment.\n\n\nData availability\n\nOSFHOME: Underlying data for “Effectiveness of antepartum breathing exercises on the outcome of labour: A randomized controlled trial”, https://doi.org/10.17605/OSF.IO/NSMB3. CC0 license.25\n\nThis project contains the following underlying data:\n\n- Deidentified demographic information\n\n- Deidentified comparison scores of primary outcomes between standard care and intervention group.\n\nFigshare: CONSORT checklist for‘[Effectiveness of antepartum breathing exercises on the outcome of labour: A randomized controlled trial]’. https://doi.org/10.6084/m9.figshare.19074524.v1\n\n[CONSORT flowchart] https://doi.org/10.6084/m9.figshare.19076597.v1\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAuthor contribution\n\n",
"appendix": "Acknowledgements\n\nThe researcher is very grateful to all participants for their valuable contribution to the study.\n\n\nReferences\n\nVora KS, Mavalankar DV, Ramani KV, et al.: Maternal Health Situation in India: A Case Study. J. Health Popul. Nutr. 2009; 27(2): 184–201.\n\nLassi ZS, Musavi NB, Maliqi B, et al.: Systematic review on human resources for health interventions to improve maternal health outcomes: Evidence from low- and middle-income countries. Hum. Resour. Health. 2016; 14(1): 10. PubMed Abstract | Publisher Full Text\n\nStenglin M, Foureur M: Designing out the Fear Cascade to increase the likelihood of normal birth. Midwifery. 2013; 29(8): 819–825. PubMed Abstract | Publisher Full Text\n\nSvennson J, Barclay L, Cooke M: Effective antenatal education: Strategies recommended by expectant and new parents. J. Perinat. Educ. 2008; 17: 33–42. PubMed Abstract | Publisher Full Text\n\nLevett KM, Smith CA, Bensoussan A, et al.: Complementary therapies for labour and birth study: A randomised controlled trial of antenatal integrative medicine for pain management in labour. BMJ Open. 2016; 6: e010691. PubMed Abstract | Publisher Full Text\n\nSmith CA, Levett KM, Collins CT, et al.: Relaxation techniques for pain management in labour. Cochrane Database Syst. Rev. 2011; (12): CD009514. Publisher Full Text\n\nLothian JA: Lamaze breathing: What every pregnant woman needs to know. J. Perinat. Educ. 2011; 20(2): 118–120. PubMed Abstract | Publisher Full Text\n\nEkerholt K, Bergland A: Breathing: A sign of life and a unique area for reflection and action. Phys. Ther. 2008; 88(7): 832–840. PubMed Abstract | Publisher Full Text\n\nRuhl C, Adams ED, Besuner P, et al.: Labor support. Exploring its role in modern and high tech birthing practices. AWHONN Lifelines. 2006; 10(1): 58–65. PubMed Abstract | Publisher Full Text\n\nFereshteh J, Fatemeh S, Hamid H, et al.: Yoga during pregnancy: The effects on labor pain and delivery outcomes (A randomized controlled trial). Complement. Ther. Clin. Pract. 2017; 27: 1–4. PubMed Abstract | Publisher Full Text\n\nJones L, Othman M, Dowswell T, et al.: Pain management for women in labour: An overview of systematic reviews. Cochrane Database Syst. Rev. 2012; 3: CD009234. Publisher Full Text\n\nSchulz KF, Altman DG, Moher D: CONSORT 2010 Statement CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. Development. 2010; 375(2): 1136–1136. Publisher Full Text\n\nNarendran S, Nagarathna R, Narendran V, et al.: Efficacy of Yoga on Pregnancy Outcome. J. Altern. Complement. Med. 2015; 11(2): 237–244. PubMed Abstract | Publisher Full Text\n\nBarakat R, Lucia A, Ruiz JR: Resistance exercise training during pregnancy and newborn’s birth size: A randomised controlled trial. Int. J. Obes. 2009; 33(9): 1048–1057. PubMed Abstract | Publisher Full Text\n\nAmis D: Healthy Birth Practice # 1: Let Labor Begin on Its Own. J. Perinat. Educ. 2014; 23(4): 178–187. PubMed Abstract | Publisher Full Text\n\nDe Punzio E, Neri P, Metelli MS, et al.: The relationship between maternal relaxation and plasma beta endorphin levels during parturition. J. Psychosom. Obstet. Gynaecol. 2009; 15(4): 205–210. PubMed Abstract | Publisher Full Text\n\nHartmann S, Bung P, Schlebusch H: The analgesic effect of exercise during labor. Z. Geburtshilfe Neonatol. 2005; 209(4): 144–150. PubMed Abstract | Publisher Full Text\n\nBeddoe AE, Lee KA: Mind-Body interventions during pregnancy. J. Obstet. Gynecol. Neonatal. Nurs. 2008; 37(2): 165–175. Publisher Full Text\n\nBergstrom M, Kieler H, Waldenstro U: Effects of natural childbirth preparation versus standard antenatal education on epidural rates, experience of childbirth and parental stress in mothers and fathers: A randomised controlled multicentre trial. An Internal Journal of Obstetrics and Gynecology. 2009; 116(9): 1167–1176. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCurtis K, Weinrib A, Katz J: Systematic Review of Yoga for Pregnant Women: Current Status and Future Directions. Evid. Based Complement. Alternat. Med. 2012: 715942. Publisher Full Text\n\nKarkada SR, Bhat PV, Bhat S, et al.: Antepartum breathing Exercises and Predictors for Spontaneous Vaginal Delivery Among primigravid and Multigravid Women: A Randomized Controlled Trial. Indian J. Public. Health. Res. Dev. 2017; 8(4): 271–275. Publisher Full Text\n\nSnegovskikh V, Park JS, Norwitz ER: Endocrinology of parturition. Endocrinol. Metab. Clin. N. Am. 2006; 35(1): 173–191. Publisher Full Text\n\nChuntharapat S, Petpichetchian W, Hatthakit U: Yoga during pregnancy: Effects on maternal comfort, labor pain and birth outcomes. Complement. Ther. Clin. Pract. 2008; 14(2): 105–115. PubMed Abstract | Publisher Full Text\n\nEun Sun J, Kyoul JC: Effects of Yoga during Pregnancy on Weight Gain, Delivery Experience and Infant’s Birth Weight. Korean J. Women Health Nurs. 2009; 15(2): 121. Publisher Full Text\n\nSushmitha: Effectiveness of antepartum breathing exercises on the outcome of labour: A randomized controlled trial 2021.Publisher Full Text"
}
|
[
{
"id": "149155",
"date": "09 Sep 2022",
"name": "Lily Podder",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe writing style of the manuscript is very captivating. The guidelines of writing manuscripts are appropriately followed. The grant information is delineated adequately. The abstract of the manuscript is written in a crisp and clear manner. Introduction incorporates scientific evidences depicting the current scenario and need of the study.\nResearch methodology is written adequately with relevant explanations and covered all the important elements of planning and conducting research. However, participants’ information is not matched with the CONSORT flowchart (290) with the information available at Pg no: 5 (292) of the manuscript under participants characteristics heading. Clarification is also required about randomizing the samples of 280 from recruited samples of 292. Explanation is also required for reason/s for excluding 09 participants while assessing for eligibility.\nThe researcher crafted intervention is very extensively planned and implemented. The researcher is competent in providing the crafted interventions with added credentials.\nAnalysis and interpretation of the data are well organized as per the research objectives. Extensive and Exhaustive analysis of the data done and presented with robust statistical operations.\nSummary, discussion, implications, conclusion of the research is presented and discussed in accordance with the findings of the present study.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "8754",
"date": "02 Nov 2022",
"name": "SUSHMITHA KARKADA",
"role": "Author Response",
"response": "Dear Dr Lily Podder, I appreciate the time and effort that you have dedicated to provide your valuable feedback on my manuscript. Here are my clarifications for the comments: Will correct the error in Table 1, as the total samples enrolled based on eligibility criteria was 290. Based on the sample size calculation, 140 samples to be recruited in each arm (140x2), thus 280 samples were selected through block randomization. Nine samples were excluded as they opted government hospital for delivery. Look forward to hearing from you regarding the submission and to respond to any further questions and comments you may have."
}
]
}
] | 1
|
https://f1000research.com/articles/11-159
|
https://f1000research.com/articles/12-568/v1
|
30 May 23
|
{
"type": "Research Article",
"title": "Dietary patterns, body mass index, physical activity level and energy intake among the female elderly population in Mauritius",
"authors": [
"Yashwinee Bye Ishnoo",
"Abdulwahed Fahad Alrefaei",
"Rishi Ram Doobaree",
"Nadeem Nazurally",
"Rajesh Jeewon",
"Yashwinee Bye Ishnoo",
"Abdulwahed Fahad Alrefaei",
"Rishi Ram Doobaree",
"Nadeem Nazurally"
],
"abstract": "Background: The aging population is becoming a global issue and Mauritius has experienced a 20.4 % growth in the last four years. There is a lack of information regarding nutrition among the Mauritian elderly. This study aimed to investigate dietary patterns and energy intake and their associated factors, to determine the relationship between body mass index (BMI), physical activity level (PAL), nutrition knowledge (NK) and energy intake among the female older adults. Methods: The study was carried out among 167 female participants aged 60 and above from both urban and rural areas in Mauritius. A questionnaire was used to determine their eating habits and food frequency, PAL, NK, anthropometric measurements and demographic data. Three 24-hour dietary recalls over three weeks were used to calculate the energy intake using the Tanzania food composition table and Nutritionist Pro software. SPSS was used to analyse the data. The main statistical tests used were ANOVA, Independent-samples t-test (ISTT), Pearson correlation and Chi-squared. Results: A significant relationship was found between age group and energy intake (p = 0.027), with individuals aged 70–89 having higher energy intake. Both BMI and PAL were significantly associated with energy intake (p ˂0.001). There was a moderate significant negative relationship between NK scores and energy intake (r = -0.474, p ˂0.001). Vegetarianism, eating difficulties and residence area did not have a statistically significant relationship with energy intake. There was a negative and significant correlation between consumption frequency of whole-grain carbohydrates and BMI and a significant positive relationship between BMI and consumption frequency of refined carbohydrates. Conclusions: The mean energy intake of the participants was much higher than the recommended daily allowance of caloric intake in India and other countries. Furthermore, the dietary pattern of the subjects was diversified including both healthy and unhealthy eating habits.",
"keywords": [
"body mass index",
"dietary patterns",
"energy intake",
"female elders",
"nutrition knowledge",
"physical activity level"
],
"content": "Introduction\n\nAging refers to a series of unstoppable changes that occur from birth to death.1 As population economics, healthcare facilities, and social well-being are rising, aging is gradually conquering the world. This, however, poses challenges as well as opportunities.2 Mauritius, an island nation, located in the southwest Indian Ocean, has a mixed economic system and is a multi-cultural and multi-ethnic country.3 According to the Worldometers' elaboration of the most recent UN data, Mauritius' population is 1,275,555, as at 20th April 2022 (https://www.worldometers.info/)4 including 95,635 (https://countrymeters.info/) people above 64 years old.5 According to a national assessment of non-communicable diseases (NCDs) conducted in Mauritius in 2015, 19.1% of people were obese.3 Healthy aging is defined by the World Health Organization as “the process of developing and maintaining functional ability that enables wellbeing in old age”.6 Healthy aging focuses on health-span rather than lifespan, while some definitions refer to aging in the absence of illness. In some regions of the world, individuals aged 85 and above are the fastest growing demographic. However, only a small percentage of people reach this age without getting chronic health conditions. Therefore, it is essential to comprehend the impact of modifiable lifestyle factors like diet in achieving remarkable longevity, as well as the role of these factors in health-span, if any.7\n\nFood and energy intake decrease as people get older. Malabsorption, immobility, a loss in the sensations of taste and smell, having trouble chewing, and financial and social challenges are some of the causes behind this.8 Furthermore, factors such as gender, household composition, marital status, physical activity, nutrition knowledge (NK), body mass index (BMI), smoking and health issues influence the eating patterns of the elderly. Retirement also degrades general health and raises the risk of disease development.9 A study reported that diet-related health remains an issue for the senior citizen including those at malnutrition risk.10 In general, elderly individuals are less energetic, so the need to reduce energy intake is important due to a drop-in basal metabolic rate. Some people, nevertheless, assume that they do not need to modify their amount of food consumption and eating patterns because they are already eating adequately. Obesity may arise as a result which may further contribute to the emergence of non-communicable diseases.11 According to the WHO, approximately 2.3 billion elder people worldwide are overweight, with over 700 million obese. Obesity is prevalent among the elder people in the United States, with 42.5% of women and 38.1% of men in the 60–79-year age group being obese. Obesity was found in 20% of women and 18% of men aged above 60, according to research from the Netherlands. The prevalence of overweight and obesity among older African Americans are even higher, especially among women.12\n\nThe relationship between energy intake and expenditure largely determines body fat mass. So, obesity develops when energy intake exceeds calorie expenditure.13 It appears that energy intake has increased, as has the consumption of meat, dairy products, fats, and oils. This is justified by a 2004 survey of people aged 60 and above.2 Socioeconomic status, availability of food, physical activity level, housing arrangements and nutrition knowledge are all factors that influence energy intake. Social and economic issues have commonly been cited as the cause of unbalanced nutrient consumption. Higher socioeconomic groups tend to consume more nutritious foods, for example, low-fat and whole-grain products than those with a lower socioeconomic status. Research has shown that individuals with higher socioeconomic status have lifestyles that can help with energy balance. However, this alone is insufficient to account for the socioeconomic inequalities in obesity.14 There is an interrelationship between physical exercise and energy intake because physical activity has the capacity to alter energy expenditure, and when done repeatedly, leads to either weight loss or the requirement to increase energy intake.11 A study showed that there is insufficient data to support the recommendation that physical activity may help to mitigate the decline in appetite and energy intake that happens as people age15. Nutrition knowledge is a less well-studied factor that can have an equal impact on the dietary habits of elderly people. A study found that participants who consumed less fish and more unhealthy fats, potatoes, fried foods, pasta and beer had a lower education level.14\n\nTherefore, understanding an older person’s dietary patterns and energy intake may aid in the development of programmes to enhance nutrition and weight management.12 Nutrition is crucial in preventing NCDs, thus, must be closely monitored.2 It is important to calculate energy intake since it determines nutrient requirements and diet nutrient composition. Twenty-four-hour dietary recalls and a food composition table have been utilised by numerous energy intake studies to determine the mean energy intake of individuals of various demographics. In Mauritius, there is a scarcity of data on the daily energy intake of elderly people.14 Thus, the aim of this study is to conduct a survey to assess the factors influencing the energy intake of the Mauritian female elderly population aged 60 and above.\n\nThe main objectives of this study are as follows:\n\n• To investigate the dietary patterns and energy intake of the female elderly population.\n\n• To determine the correlation between BMI, physical activity level (PAL) and energy intake among the female elderly population.\n\n• To determine whether nutrition knowledge affects the amount of energy consumed.\n\n• To investigate the factors affecting the energy dietary patterns of older females.\n\n\nMethods\n\nThe study included a total of 167 older females recruited by simple random sampling from different regions of Mauritius. Four age groups were used to categorize the participants: 60 to 69, 70 to 79, 80 to 89 and 90 to 100. Samples from various ethnic groups present in Mauritius were taken into consideration, including Indo-Mauritians and African Mauritians. Prior to the start of the project, ethical approval was granted by the Departmental Research Ethics Committee (Ref number: DHSDREC/01/2022) dated 28th January 2022 at the University of Mauritius. All participants were fully informed of the project and a written consent was obtained from participants for the use and publication of collected data. Participants were assured that all of their responses would be handled with absolute confidentiality and that the survey was completely anonymous, with no mention of participant names or addresses.\n\nThe data needed to achieve the stated objectives was collected using a self-designed questionnaire. The survey was conducted in-person since it was expected that respondents could clearly articulate themselves and that many elderly people may have low levels of knowledge. Moreover, simple Creole, the most common language in Mauritius, was used to interview the participants to make sure that the questions were properly understood. Enough time was allowed for each participant to accurately answer each question. The questionnaire, which was composed primarily of closed-ended questions, consisted of five sections: I, II, III, IV and V. The questionnaire has been deposited in Figshare, a public repository.16\n\nSection I: Eating habits and food frequency\n\nThe food frequency section was designed by using questions from the Short Form Food Frequency Questionnaire17 that was created by the Leeds University Nutritional Epidemiology department. It included approximately 59 items divided into the following categories: carbohydrates (grains and tubers), beans/pulses, meat and eggs, seafoods, soybeans and products, dairy products, vegetables, high-fat and high-sugar snacks, and beverages.18 Participants could choose from seven frequency categories for each food item and scores as shown in Table 1.\n\nSection II: Physical activity\n\nQuestions from a short version of International Physical Activity Questionnaire (IPAQ) were used to assess physical activity.19 PAL was calculated in metabolic equivalents (MET), minute per week, and classified as low, moderate, or high intensity. The scores were as follows: low (<600 MET), moderate (600–1500 MET), and high (>1500) PAL. Table 2 shows the criteria for classification of PAL.19\n\nSection III: Nutrition knowledge assessment\n\nTen nutrition-related questions from a general nutrition knowledge questionnaire for adults were utilised and modified.20 The original questionnaire's food items were modified to reflect the Mauritian environment. The questions selected were mostly about calorie, sugar, fat and protein content. An overall score of 25 was achievable with higher scores implying participants were highly knowledgeable. A score of 1 was assigned for a right answer and a score of 0 for a wrong answer and \"don't know\".14\n\nSection IV: Anthropometric measurements\n\nPhysical measurements, including weight and height were obtained using the same tools to reduce the possibility of errors. A measuring tape and ruler was used to measure the height and the participant stood bare foot with the head horizontal against the wall. A portable bathroom scale was used to measure weight. The BMI of the participants was then determined using the formula, weight (in kilograms) divided by height (squared in meters); and were categorised as normal, underweight, overweight or obese according to WHO classification.21\n\nSection V: Personal and sociodemographic data\n\nAge, residential area, education level, marital status, ethnic group and type of pension were all included in the sociodemographic data. Vegetarianism and eating difficulties were also assessed.\n\nSection VI: A three-day 24-hour dietary recall\n\nNutritional guidelines from EPIC-Norfolk were used to create a 24-hour dietary recall form.14 Food consumption was recorded for two weekdays and one weekend over three weeks. Typically, the 24-hour recall was carried out in the sequence of consumption starting from morning to night. This form requires a list of all meals and drinks consumed the day prior, including snacks. The recall was not conducted if a person was following a special fasting regimen or had previously attended any event where people have a tendency to overeat. On the first day of the recall, the participants were shown a variety of readily accessible household utensils in order to help them accurately report the portion sizes of their meals. The utensils used were teaspoons, tablespoons, cups and glasses. Moreover, the participants were asked to recall eating and drinking incidents by time period in order to avoid concerns with inaccurate or incomplete reporting. Three dietary recalls were used to calculate the subjects' energy intake using a food composition table mostly based on the Tanzania food composition table22 and also with the help of the Nutritionist Pro Version 6.1, a licensed software which is accessible at the University of Mauritius laboratory (An open-access equivalent that performs a similar function is https://www.wikihow.com/). The mean energy intake was then calculated for each participant to be used for statistical analyses.\n\nThe data of this study was analysed using the software SPSS (Statistical Package for the Social Sciences, version 16.0). Percentages were used to express descriptive tests. ANOVA test, independent sample t-test, Pearson correlation and the Chi-squared test were used to show the relationship between the variables. Statistical significance was defined as P ˂0.05.\n\n\nResults\n\nTable 3 displays the socio-demographic details of the 167 respondents by age group, area of residence, education level, marital status and ethnic group. Of the 167 respondents, 47.3% were between the ages 60 and 69, 39.5% were between the ages 70 and 79, 12.6% were between the ages 80 and 89 and only 0.6% were between the ages 90 and 100. The majority of the participants were from rural areas, which accounted for 52.7%.\n\nThe mean energy intake of the 167 respondents was 2362.87 kcal. The mean BMI was 25.86 kg/m2. According to the results obtained, BMI had a significant impact on energy intake demonstrating that the mean energy intake for overweight and obese participants is higher than that of normal and underweight participants (p ˂0.001). The energy intake of participants aged 70–79 and 80–89 was found to be higher, and this finding was statistically significant (p = 0.027). The mean energy intake was found to be lower in vegetarians, according to an independent sample t-test; however, this relationship was not statistically significant (p = 0.407). Moreover, eating difficulties had no significant impact on energy intake (p = 0.377). The study also indicated that participants who engage in low physical activity had a higher energy intake than those who engage in moderate or high physical activity. And, there was a statistically significant relationship between PAL and energy intake (p ˂0.001). Furthermore, results showed a moderate negative and significant relationship between NK scores and energy intake (p ˂0.001). It was found that the mean energy intake of participants residing in rural areas was higher; however, this relationship was not statistically significant (p = 0.074).\n\nIn general, vegetables were consumed most (M = 6.87 ± 0.50) followed by tea/coffee (M = 6.53 ± 077), butter/margarine (M = 5.50 ± 1.28), fruits (M = 5.37 ± 1.07), white rice (M = 5.25 ± 1.62), beans/pulses (M = 5.08 ± 0.71), oatmeal (M = 4.87 ± 1.65) and semi-skimmed milk (M = 1.48 ± 1.48), low fat cheese (M = 1.48 ± 1.23), brown bread (M = 1.55 ± 1.22) being the food items less frequently consumed.\n\nRelationship between BMI and frequency of different food items consumed\n\nThe results in Table 4 show a moderate significant negative correlation, a small significant positive correlation and a moderate positive correlation between BMI and the food items listed in the table.\n\n** : Correlation is significant at the 0.01 level (2-tailed).\n\n* : Correlation is significant at the 0.05 level (2-tailed).\n\nRelationship between NK and consumption frequency of different food items\n\nThere is a statistically significant relationship (p ˂0.001) between nutrition knowledge and education level. The results of the Pearson correlation showed that there was a small significant negative correlation at 0.01 level between NK and consumption frequency of sweet pastries/cakes, deep fried snacks and full cream yoghurt (p ˂0.001). At the 0.05 level of significance, there was a small significant negative correlation between NK and frequency of sweet biscuits/sweets (p = 0.016), chocolates (p = 0.033), butter (p = 0.048), soft drinks (p = 0.011), pasta (p = 0.040) and chicken (p = 0.035) consumption. Furthermore, a moderate significant positive correlation at the 0.01 level was obtained between NK and frequency of brown bread, brown farata, skimmed milk and fruit consumption (p ˂0.001). Another significant relationship at the 0.01 level was found between BMI and frequency of brown rice (p ˂0.001) and low-fat yoghurt (p = 0.007) consumption. This correlation was small and positive.\n\nEffect of PAL on frequency of different food items consumed\n\nThere was a statistically significant difference between PAL and brown bread [F (2, 164) = 4.61, p = 0.011], brown rice [F (2, 164) = 3.86, p = 0.023], white rice [F (2, 164) = 3.87, p = 0.023], white bread [F (2, 164) = 4.83, p = 0.009], fish [F (2, 164) = 3.21, p = 0.043], full cream yoghurt [F (2, 164) = 5.30, p = 0.006] and soft drinks [F (2, 164) = 4.75, p = 0.010] consumption. Table 5 also demonstrates that participants who had low PAL ate a higher amount of white rice and white bread. On the other hand, those with high PAL consumed fish and white rice in greater quantities.\n\nRelationship between residence area and consumption frequency of food items\n\nThe results of the ISTT revealed a statistically significant difference between participants living in urban and rural areas and consumption frequency of brown bread, brown rice, white rice, oatmeal, Weetabix, pasta, fish, low fat yoghurt and fruit. Table 6 also demonstrates that brown bread, oatmeal, beans/pulses, vegetables and fruit were highly consumed food items by elderly female participants living in urban areas.\n\nRelationship between energy intake and consumption frequency of different food items\n\nThe results obtained show a moderate positive and statistically significant correlation between energy intake and white rice, chicken, full cream milk, sweet pastries, chocolates and soft drinks (p ˂0.001, significant at the 0.01 level).\n\nA small significant positive correlation was found between energy intake and\n\n• White bread (p ˂0.001, significant at 0.01 level)\n\n• Pasta (p = 0.002, significant at 0.01 level)\n\n• Full cream yoghurt (p = 0.001, significant at 0.01 level)\n\n• Sweet biscuits/sweets (p = 0.008, significant at 0.01 level)\n\n• Butter/margarine (p = 0.018, significant at 0.05 level)\n\nMoreover, a moderate significant negative correlation was obtained between energy intake and brown bread, skimmed milk and fruit (p ˂0.001, significant at 0.01 level). And a small negative and significant relationship was found between energy intake and brown rice (p = 0.001, significant at 0.01 level), soybeans and products (p = 0.011, significant at 0.05 level) and low-fat yoghurt (p = 0.023, significant at 0.05 level).\n\nA negative relationship was found between oatmeal, Weetabix, fish and energy intake (EI) while a positive relationship was observed between potato, beans/pulses, tea/coffee and EI. But these relationships were not statistically significant.\n\n\nDiscussion\n\nThe mean EI of the 167 female elderly participants in this study was 2363 kcal/day; and this was not consistent with any recommended dietary allowances of other countries as it was much higher than that of other countries like Indonesia, Malaysia, Philippines and Thailand, which recommend 1850, 1780, 1620–1410 and 1550 kcal respectively for its female senior citizens.23 In the southwestern United States, elderly females reported a mean EI of 1555 ± 63.2 kcal/day, which did not support the results here.24 The increase in EI of the female senior citizens of this study may be due to significant changes in diet composition such as an increased use of cooking oils, increased consumption of carbohydrates and high-energy processed foods including cakes, instant noodles and cookies.25 However, the results of this study do coincide to a little extent with one study conducted in Mauritius in 2007 whereby the energy intake was higher (1978 kcal) when compared to dietary reference intakes for older adults. This increase in EI would offer a reasonable explanation for why being overweight was more common in the elderly female participants.26\n\nA statistically significant relationship was obtained between age and EI in this study. The participants aged between 70 to79 and 80 to 89 had the highest mean EI (2492.83 ± 703.54, 2561.24 ± 740.26 kcal respectively) while those aged 60–69 had a mean EI of 2210.56 ± 631.68 kcal. In contrast to the results found here, which showed that the age group 60–89 had higher EI, a study in the southern United States revealed that females in the 51–70 age range had a lower mean EI value of 1571 ± 29.3 kcal.24\n\nThe mean BMI of the 167 participants was 25.86 kg/m2, which suggests that they were mostly overweight. Additionally, results indicate that as EI increases, BMI increases; the underweight individuals had the lowest EI (1299.57 ± 62.06 kcal) and obese participants had the highest EI (3326.55 ± 281.39 kcal). Therefore, this study shows that EI had a significant impact on BMI. This result supports a Chinese women's study, which found that overweight and obese women consumed a significantly higher proportion of their dietary energy from carbohydrates than lean women, indicating a link between EI and BMI.27 Similar results were observed in Perth, Western Australia, where EI in elderly women was linked to a higher BMI; but they were under-reporting their EI.28 The results of the present study has been further supported by Trichopoulou et al., (2000)29 who revealed that energy intake and BMI have a positive relationship and the BMI of females was found to be much higher than males.\n\nThis study demonstrates that the PAL of elderly females in Mauritius was low for the majority of the participants (52.10%) and there was a statistically significant relationship between PAL and energy intake. The study also showed that participants who engaged in low physical activity had a higher energy intake than those who engaged in moderate or high physical activity (Table 5). Another study, on the other hand, reported conflicting results, arguing that there is no sufficient evidence to corroborate that physical activity has an effect on EI.30 Moreover, a systematic review showed that there was no consistent evidence to support the recommendation that physical activity may reduce the decrease in appetite and energy intake that occurs with age.15\n\nThe results showed that there was a statistically significant relationship between NK and education level. This study demonstrates that the female elderly participants having a lower education level had least nutrition knowledge. This finding was supported by a study which found that the majority of Taiwanese female elderly participants who had no formal education and attended only primary school had poor NK.31 Furthermore, a study in England discovered that those with degrees had a much higher NK than participants without formal education.32\n\nThe results show a moderate negative and significant correlation between NK and energy intake, indicating that EI decreases with increasing NK. A study showed that older women having a higher education level had the biggest relationship with a higher label reading score33 and this led to a decline in EI among them.14 Another study demonstrated that women with a higher level of knowledge were more likely to be concerned about calories and consumed less sweets, soft drinks and salty snacks,34 implying that cutting back on these unhealthy meals will not result in an increase in energy intake.\n\nIn the current study, some food items were found to be consumed more often among female older people aged between 60 to 100. For instance, the results indicated that vegetables, tea/coffee, butter/margarine, fruit, white rice, beans/pulses, oatmeal, white bread, potato and chicken were more frequently consumed. On the other hand, food items like semi-skimmed milk, low-fat cheese, brown rice, chocolates, soft drinks, skimmed milk and oily fish were less frequently consumed. According to a previous study done in Mauritius, it was found that the older individuals consumed a lot of rice, vegetables, and little pasta because rice is one of the country's staple foods.26 The result can be further supported by a study who reported that elderly people consumed a lot of carbohydrates.35\n\nRelationship between BMI and frequency of different food items consumed\n\nThe findings of the current study revealed that the majority of participants were classified as normal or overweight. There were also a considerable number of obese respondents (12%). This could be explained by the correlation between aging and a redistribution of both body fat and fat-free mass. With aging, loss of skeletal muscle occurs and this could be a reason why there is a bigger relative rise in intra-abdominal fat than subcutaneous or total body fat, and a relatively greater decline in peripheral fat than central fat-free mass.36A study revealed that BMI may be influenced by the type of carbohydrates consumed.37 In the present study, there was a negative and significant correlation between consumption frequency of whole-grain carbohydrates such as brown bread, brown rice, and brown farata/chapatti and BMI. This indicates that as consumption of wholegrain carbohydrates increases, BMI decreases. Results from meta-regression on cross-sectional data support these findings, which show a negative relationship between wholegrain consumption and BMI.38 In this study, there was also a negative correlation between BMI and oatmeal and Weetabix intake but it was not statistically significant. Moreover, a positive and significant relationship was found between BMI and consumption frequency of refined carbohydrates such as white bread, white rice and white farata/chapatti in this study. This indicates that as consumption of refined carbohydrates increases, BMI increases. These results corroborate those of a Mediterranean cohort which found that white bread consumption (≥ two servings per day) had a strong relationship with the risk of becoming overweight or obese.39 A positive relationship was observed between chicken, full cream yoghurt, full cream milk, sweet pastries/cakes, sweet biscuit/sweets and chocolates intake and BMI, indicating that high consumption of these food items leads to an increase in BMI; between BMI and consumption frequency of fish, low fat yoghurt, skimmed milk and fruit, a significant negative relationship was noted. To support these findings, one study reported that low-fat dairy products were inversely connected to changes in body weight, whereas whole fat dairy products were linked to a little but substantial rise in body weight; the highest category of dairy consumption was also linked to a lower chance of being overweight and having abdominal obesity.40 Regarding beverage consumption (soft drinks and tea/coffee), the positive correlation between BMI reported in this study corresponds with a study on Mauritian women whereby higher intake of soft drinks resulted in high BMI.3 Another study demonstrated that soft drink consumption was linked to an increased risk of abdominal obesity over a 10-year period.41 However, in one study, consuming one or more portions of tea per day was linked to obesity, but the link was not statistically significant.42\n\nRelationship between nutrition knowledge and consumption frequency of different food items\n\nIn the current study, a significant negative relationship was found between NK and consumption frequency of sweet pastries/cakes, deep fried snacks, full cream yoghurt, sweet biscuits/sweets, chocolates, butter, soft drinks, pasta and chicken. This shows that some subjects with low NK consumed high amount of these food items and vice-versa. Moreover, it was also observed that NK and frequency of brown bread, brown farata, skimmed milk, fruit, brown rice and low-fat yoghurt consumption had a positive and significant correlation. This indicates that subjects with high NK consumed more of these food items, which were healthier. A study reported that an older population with less education consistently had a higher likelihood of eating a diet high in sweets and low in protein-rich vegetables.43 However, no significant relationship was discovered between the other foods and NK. Although older persons have high nutrition knowledge, their eating habits may not be consistent with NK due to their inability to put their technical nutrition knowledge to use.44\n\nRelationship between residence area and consumption frequency of food items\n\nThe results of this study revealed a statistically significant difference between participants living in urban and rural areas and consumption frequency of brown bread, brown rice, white rice, oatmeal, Weetabix, pasta, fish, low fat yoghurt and fruit. Table 6 demonstrates that brown bread, oatmeal, beans/pulses, vegetables and fruits were the highly consumed food items by the elderly female participants living in urban areas while in rural areas white rice, oatmeal, beans/pulses, vegetables and fruit were highly consumed. It can be seen that in both urban and rural areas consumption of oatmeal, beans/pulses, vegetables and fruit were high. However, the other food items showed no significant difference. Few studies have been conducted to study the relationship between residence area and frequency of food items consumed.\n\nRelationship between energy intake and consumption frequency of different food items\n\nIntake of energy was positively correlated with consumption of white bread, white rice, pasta, chicken, full cream yoghurt, full cream milk, sweet pastries, sweet biscuits, chocolates and soft drinks, as shown in Table 4. This indicates that consumption of these food items increases energy intake. The main function of carbohydrates is to supply the body's cells with energy and dietary fibre.45 However, data from the USDA's food consumption surveys from 1989 to 1991 and 1994 to 1996 showed that a higher intake of carbohydrates was the main factor contributing to increased energy intake.46 This corroborates the result of the current study showing that high intake of white bread, white rice and pasta increased energy intake. Chicken was found to increase energy intake among the participants. Certain parts of the chicken, such as the breasts, are frequently sold with or without the skin. Typically, thighs, wings, and drumsticks are sold with the skin still attached. Skin increases the amount of fat and calories in the chicken piece. The cooking methods for chicken including deep frying, cooking with extra fat, sugar, or salt in marinades and pan frying in oils or butter can all contribute to an increase in calories and fat.47 Therefore, this explains why consumption of chicken led to an increase in energy intake. This study also discovered that frequent consumption of sweet pastries, sweet biscuits and chocolates increased energy intake and this was consistent with a study conducted among Norwegian adults which classified these food items as snacks and they were among the top five in an energy-contributing food group.48 A study concluded that energy-dense snacks may increase energy intake and weight when consumed in higher amounts.49 Soft drinks frequently include sweeteners like high-fructose corn syrup, that can greatly increase EI and cause obesity50 and this is consistent with the current study. Moreover, a meta-analysis discovered definite correlations between soft drink use and higher energy intake and body weight. There was persistent evidence that consumers did not reduce their intake of other foods to compensate for the extra energy they get from soft drinks, leading to higher total energy intake.51\n\n\nConclusions\n\nThe present study discovered that the mean energy intake of the female elderly participants was much higher than the recommended daily allowance of caloric intake in India and other countries. It was also found that age was significantly associated with energy intake whereby respondents aged 80–89 and 70–79 had a higher energy intake. Moreover, BMI had a significant impact on energy intake and the overweight and obese subjects had a higher energy intake. The majority of the female older adults were overweight. There were a few factors that had influenced the energy intake of the respondents, namely PAL and NK. For instance, the majority of the participants having low PAL were found to have a higher energy intake. Furthermore, a negative correlation was found between NK and energy intake, indicating that participants with good NK had lower energy intake. It should be noted that having a good NK was connected with having a high degree of education. However, some factors including vegetarianism, eating difficulties and residence area did not significantly affect energy intake. In general, the dietary pattern of the subjects was diversified. Consumption frequency of carbohydrates, dairy products, vegetables, fruit, beans/pulses, oatmeal and Weetabix were high. It was observed that refined carbohydrates (white bread, white rice, white farata/chapatti) were consumed more frequently than the whole-grain carbohydrates (brown bread, brown rice, brown farata/chapatti). In addition, low-fat dairy products were not consumed regularly. The study also reported that the participants consumed snacks high in fat and sugars such as sweet biscuits, sweet pastries, deep fried snacks, chocolates and soft drinks to some extent. Various factors were found to have an impact on the dietary pattern of the participants. Firstly, a positive correlation was obtained between BMI and consumption frequency of refined carbohydrates. In other words, a high consumption of refined carbohydrates was linked to a higher BMI. Also, consumption of sweet biscuits, sweet pastries, deep fried snacks, chocolates and soft drinks may have led to an increase in the BMI. Additionally, the dietary pattern was influenced by NK. It was also observed that participants living in urban areas had a healthier dietary pattern, which included more whole-grain carbohydrates and low-fat dairy products. The present study’s findings are both positive and disappointing in terms of how NK affects food choices because higher NK levels were linked to higher consumption of both nutritious and unhealthy meals, while no links were observed between NK and the other food items.",
"appendix": "Data availability\n\nFigshare: Underlying data for ‘Dietary patterns, BMI, PAL and energy intake among the female elderly population in Mauritius’, https://doi.org/10.6084/m9.figshare.22201381. 16\n\nThis project contains the following underlying data:\n\n• Data file: Raw data.xlsx\n\n• Data file: Codebook for SPSS docx\n\nFigshare: Extended data for ‘Dietary patterns, BMI, PAL and energy intake among the female elderly population in Mauritius’, https://doi.org/10.6084/m9.figshare.22201381. 16\n\nThis project contains the following extended data:\n\n• Data file: Final Questionnaire Survey.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nAcknowledgements\n\nWe would like to express our gratitude to the University of Mauritius for their support with this research project. 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[
{
"id": "194249",
"date": "06 Oct 2023",
"name": "Ogechi Chinyere Nzeagwu",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nComments on the different sections\n1) Title – Remove ‘s’ in patterns and ‘the’ before female\n2) Abstract – Still remove ‘the’ before female. In methods, questionnaire cannot be used to determine anthropometric measurements, rather state that ‘the values for anthropometric measurements were recorded in the questionnaire’. Also indicate at which level you judged the relationships as significant.\n3) Introduction – In the second paragraph, line 9 into 10 where you have ‘According to WHO ……. ending with 700 million obese’ should have a reference as well as the next sentence starting with ‘Obesity is prevalent …… down to research from the Netherlands should also have reference.\nIn the third paragraph line seven ‘Research has shown ……..help with energy balance should also have a reference\nLast paragraph, In Mauritus, there is scarcity of data instead of a scarcity of data\nObjectives – On the main objectives, there should have been one like ‘to assess the nutrition knowledge of the study population’ before the third one ‘to determine whether nutrition knowledge affects the amount of energy consumed’\n4) Methods – Section IV – Anthropometric measurements – It might be necessary for the authors to indicate if there were exclusion criteria here because of older persons that have kyphosis or are bent and will have difficulty standing erect for height measurement or did they use proxy for height for such people.\n5) Results – The authors should have presented result on energy intake before bringing up factors influencing energy intake\nUnder factors affecting dietary patterns – Relationship between BMI and frequency of different food items consumed, it might be necessary for the authors to explain what they meant by small, moderate significant positive correlation etc\nAgain in the relationship between NK and consumption frequency of different food items – the result presented did not represent what the caption is saying.\n5) Discussion was well handled\n6) References – Some of the references were more than 10 years back. The Authors should try to replace some of the old references with more current and recent references\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-568
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https://f1000research.com/articles/12-315/v1
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22 Mar 23
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{
"type": "Research Article",
"title": "Formulation and in vitro evaluation of meloxicam as a self-microemulsifying drug delivery system",
"authors": [
"Saja Abdulkareem Muhammed",
"Khalid Kadhem Al-Kinani",
"Khalid Kadhem Al-Kinani"
],
"abstract": "Background: The nonsteroidal anti-inflammatory medication meloxicam (MLX) belongs to the oxicam family and is used to reduce inflammation and pain. The aim of this study was to improve MLX's dispersibility and stability by producing it as a liquid self-microemulsifying drug delivery system since it is practically insoluble in water. Methods: Five different formulations were made by adjusting the amounts of propylene glycol, Transcutol P, Tween 80, and oleic acid oil and establishing a pseudo-ternary diagram in ratios of 1:1, 1:2, 1:3, 1:4, and 3:4, respectively. All of the prepared formulations were tested for a variety of properties, including thermodynamic stability, polydispersity index, particle size distributions, dilution resistance, drug contents, dispersibility, in vitro solubility of the drug, and emulsification time. Results: F5 was chosen as the optimal MLX liquid self-microemulsion due to its higher drug content (99.8%), greater in vitro release (100% at 40 min), smaller droplet size (63 nm), lower polydispersity index (PDI) value (0.3), and higher stability (a zeta potential of -81 mV). Conclusions: According to the data provided here, the self-microemulsifying drug delivery system is the most practical method for improving the dispersibility and stability of MLX.",
"keywords": [
"Pseudo-ternary phase diagram",
"Dissolution rate",
"SMEDDS",
"Meloxicam"
],
"content": "Introduction\n\nAbout half of all novel medication compounds are poorly soluble in water, and when given orally, they show little bioavailability. Solutions to these problems are presently being achieved via the use of a wide variety of formulation techniques, such as solid dispersion, cyclodextrin inclusion complexes, particle size reduction, oils, surfactants, penetration boosters, salt formulations, microparticles, and many more. Lipid solutions, emulsions, and emulsion pre-concentrates are physically stable formulations often employed for encapsulating poorly soluble medicines.1\n\nSelf-micro emulsifying drug delivery systems (SMEDDS) are non-ionized, translucent, and thermodynamically stable systems. When injected into the aqueous phase with mild agitation, these systems spontaneously produce an oil/water microemulsion with globule diameters generally less than 200 nm, consisting of the co-surfactant, surfactant, oil, and medication. The agitation needed to generate microemulsions may be found in the digestive motility of the gastrointestinal system.2 To increase the oral bioavailability of medications with limited water solubility, SMEDDS works to increase colloidal dispersibility and retain small oil globules containing the medication as it travels through the digestive tract.3\n\nNonsteroidal anti-inflammatory medication (NSAID) meloxicam (MLX) works by blocking prostaglandin production, mainly the cyclooxygenase-2 (COX-2) isoform of cyclooxygenase, making it an effective treatment for pain and inflammation, fluid retention, and fever. When compared to other NSAIDs, it is shown to provide therapeutic advantages associated with osteoarthritis, rheumatoid arthritis, and other joint conditions. It is also showing great promise as a medication for treating diseases like Alzheimer's disease and cancer. However, MLX is only moderately soluble in aqueous solvents, leading to varying oral bioavailability and making it challenging to produce effective pharmaceutical formulations. Several techniques, including the creation of salts, have been tried to improve medication solubility. On the other hand, there is no guarantee that using a salt will be preferable to using the substance in its free form. Free MLX and its salt forms are both weakly soluble in aqueous systems at pH 4. MLX may produce sodium, potassium, and ammonium salts.\n\nTo overcome the low solubility of MLX, a self-emulsifying drug delivery system (SEDDS) might be used. This study aimed to prepare and characterize MLX as a liquid (SMEDDS) to improve its stability, solubility, and colloidal dispersibility for appropriate MLX delivery through the oral cavity, since according to biopharmaceutical classification system (BCS) parameters, MLX belongs to class II, which is of low solubility and high permeability.4\n\n\nMethods\n\nThis research was done at the Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq.\n\nMLX was obtained from Hyperchem (China), Transcutol p from Gattefosse Sas (France), Tween 80 and propylene glycol from Chemical Point (Germany), oleic acid oil from Central Drug House(P) LTD (India), methanol from Sigma-Aldrich (Bljika), and hydrochloric acid from ReAgent Chemicals (UK).\n\nA 2 mL glass tube of the selected vehicle was spiked with a large quantity of MLX powder. After the mixture was sealed, it was sonicated for five minutes, and then subjected to shaking for 48 hours in a shaker water bath at (25°C). The mixture was then centrifuged at 3,000 rpm for 20 minutes, filtered through a 0.45 μm membrane filter, and dilution of oils, surfactant, co-solvent, and co-surfactant with methanol as a solvent. Then, the drug concentrations were determined using spectrophotometry at their respective max. Solubility data were expressed as mean±SD.5\n\nTranscutol P, propylene glycol, Tween 80, and oleic acid oil were used as the co-surfactant, co-solvent, surfactant, and oil phase, respectively, to conduct hydrophilic-lipophilic balancing value and solubility investigations. As a means of establishing the relative amounts of SMEDDS components, a pseudo-ternary phase diagram was drawn using a water titration method. The ratio of surfactant to co-surfactant has been adjusted, and the resulting mixture is called Smix (1:1, 1:2, 1:3 1:4 and 3:4). The Smix:oil combination was titrated with distilled water under mild magnetic stirring until a stable, clear, and transparent system was produced, the point of shift from clear to unclear was recorded. Origin 2018 64Bit software6 (free alternative, GnuPlot) was used to generate a ternary plot using the gathered data.7\n\nA series of liquid SMEDDS formulas were created (Table 1) by combining oleic acid as the oil, Tween 80 as the surfactant, Transcutol P as the co-surfactant and propylene glycol as the cosolvent in the ratios (1:1, 1:2, 1:3, 1:4, and 3:4), while keeping the oil: Smix ratio constant (1:9). The SEDDS components, such surfactants and oils, poorly dissolve MLX. A concentrated basic solution of salts, such as tris (hydroxymethyl) aminomethane (Trizma), can be added to the SEDDS in order to establish a suitably basic environment to solubilize MLX. The ratio of base to water in a solution is 1:2 by weight. The pH measurements showed that the solution has a pH of 11.1. The SMEDDS of oleic acid was created by adding the following substances to the Trizma buffer (20%) in the specified order: oleic acid, Tween 80, propylene glycol, and Transcutol p. All calculations were done based on actual weight. Ingredients were combined in a beaker using a magnetic stirrer and heated at 60°C for 30 minutes in a water bath to obtain a clear solution. Next, 7.5 mg MLX was added to the mixture, and it was blended for an additional hour, resulting in a clear, yellow liquid. The formulations were then kept for 48 hours while being visually inspected for turbidity and phase separation before droplet size distribution tests were performed.8\n\nSMEDDS, Self-micro emulsifying drug delivery system.\n\nThermodynamic stability studies\n\nNumerous thermodynamic stability tests (centrifugation, heating-cooling cycle, and freeze-thaw cycle) were done on all the prepared liquid SMEDDS formulations to determine the effect of centrifugation and temperature on the stability of self-microemulsions and to avoid selecting metastable formulations for further development and characterization.9\n\nCentrifugation test\n\nAll SMEDDS formulations were centrifuged in Eppendorf Centrifuge at 3,500 rpm for 30 minutes and tested for phase separation, creaming, precipitation, and cracking. For the heating-cooling cycle, stable formulations were chosen.10\n\nHeating-cooling cycle (H/C cycle)\n\nThe H/C cycle was used to investigate the temperature-dependent stability of self-microemulsions. Six cycles were performed. The cycles were performed between refrigerator temperatures (5°C) and 45°C, with each temperature being held for at least 48 hours. Formulations that remained stable at these temperatures were exposed to a freeze-thaw cycle.11\n\nFreeze-thaw cycle\n\nFor all manufactured SMEDDS formulations, three freeze-thaw cycles between -21 and +25°C were performed, with storage at each temperature for at least 48 hours. Formulations that passed these thermodynamic stress tests were chosen for additional tests.12\n\nDroplet size measurement and polydispersity index (PDI)\n\nIn order to determine the mean droplet size and PDI, 0.5 mL SMEDDS was dissolved in 250 mL distilled water, and the mixture was gently stirred with a magnetic stirrer at 25°C. The droplet size and PDI were measured using a Malvern Zetasizer, which analyses the variation in light scattering due to Brownian motion of the particles. The angle of incidence was 173°, and the temperature was 25°C, to measure light scattering.13\n\nRobustness to dilution\n\nIn two separate glass vials, the obtained SMEDDS formulations were diluted to 50-, 100-, 1,000-, and 3,000-fold with distilled water (D.W) and 0.1 N HCl. After 24 hours, the diluted microemulsion formulations were shaken and visually evaluated for any phase separation, droplet coalescence, or drug precipitation.14\n\nDispersibility tests and self-microemulsifying time\n\nThe efficiency and self-microemulsifying time were to be determined using the USP dissolving equipment II (paddle type). A half milliliter of SMEDDS formulation was added to 500 mL D. W and gently agitated at 37°C with a stirring speed of 50 rpm. When a transparent homogeneous system was created, the in vitro effectiveness of the formulations was visually examined.15 Utilizing a grading system, the time (in minutes) for full microemulsifying was determined,16 as shown in Table 2.\n\nSMEDDS, Self-micro emulsifying drug delivery system.\n\nDetermination of drug content\n\nThe drug content in SMEDDS formulation was determined by UV/visible Spectrophotometer. A quantity of 0.4 g (equivalent to 7.5 mg MLX) of each formulation was accurately measured and diluted to 100 mL with methanol. The resultant solutions were then analyzed spectrophotometrically at its λ max in methanol using UV-Visible Spectrophotometer Shimadzu 1650 pc-Japan.17\n\nIn vitro dissolution study\n\nAll prepared SMEDDS formulations (those with a size less than 200 nm) were tested for drug release in vitro using the USP dissolution apparatus-II (paddle method) and 0.1N HCl as the dissolution media (900 mL) at 37±0.5°C and 50 rpm.18 Dialysis bag technique (8,000-14,000 Da) was used. The dialysis bags were washed with deionized water and soaked in 0.1N HCl overnight to equilibrate.19 A dialysis bag was filled with 0.4 g SMEDDS containing MLX equivalent to one dose (7.5 mg) and 5 mL of the dissolution medium was withdrawn every 10 minutes for 60 minutes (10, 20, 30, 40, 50 and 60 min). To maintain sink conditions, the withdrawn samples were replaced with an equal volume of fresh medium (0.1 N HCl). UV/visible spectrophotometer analysis determined the amount of drug dissolved in the withdrawn samples.20\n\nAccording to the in vitro evaluation studies (droplet size measurement, PDI, in vitro dissolution study and drug content) the best MLX liquid SMEDDS formula was chosen.\n\nZeta potential measurements\n\nOnly the chosen liquid SMEDDS formulation was subjected to zeta potential measurements. A magnetic stirrer was used to gently mix 1 mL SMEDDS and 10 mL DW at 25°C in order to perform the measurement. Zeta potential was determined using a Malvern Zetasizer instrument.21\n\nAtomic force microscopy (AFM)\n\nThe mode used in this characterization was the contact mode, which was done when the AFM tip makes direct contact with the sample surface, and the surface profiles are created by either fixed altitude or static load operation.22 The device used was NaioAFM Nanosurf Switzerland.\n\nField emission scanning electron microscope (FESEM)\n\nThe chosen liquid SMEDDS formula's morphology was evaluated using FESEM. A section of the microemulsion sample was analyzed using FESEM TESCAN MIRA3 FRENCH. The samples were inspected at a variety of magnifications, and the resulting photographs were uploaded to computers for further analysis.23\n\nTransmission Electron Microscope (TEM)\n\nThe geometry and morphology of the final liquid SMEDDS formulation were analyzed by TEM. The powder is mixed with ethyl alcohol, then ultrasonically dispersed for 10 minutes before a single drop of the solution is poured onto a copper mesh with an amorphous carbon coating. After the specimen dried, it was examined using TEM equipped with a titanium filament as the electron beam projector and an image sensor.24 These photos were taken by TEM Philips EM208S-100 Kv.\n\nThe experimental data were summarized as the mean standard deviation of three samples (in triplicate), and one-way analysis of variance (ANOVA) followed by post hoc Tukey’s test was performed at a significance level of P<0.05 to assess whether or not the changes in the applied parameters were statistically significant.\n\n\nResults and discussion\n\nTo identify the most suitable solvents for MLX dissolution, a saturation solubility test was carried out. Researchers have looked at whether or not MLX is soluble in a wide range of co-surfactants, co-solvent, oils, and surfactants. The solubility of MLX in oleic acid oil exhibited the highest solubility (Table 3).42\n\n* SD standard deviation from mean, n=3.\n\nAs shown in Table 4,40,44 the surfactant Tween 80, the co-surfactant Transcutol P, and the cosolvent propylene glycol exhibited the highest solubility for MLX and were therefore selected for the study.\n\n* SD standard deviation from mean, n=3.\n\nPseudo-ternary phase diagrams were constructed to identify the self-emulsifying regions. The pseudo-ternary phase diagram were plotted for different Smix ratios (Tween 80: Transcutol P, Propylene glycol (1:1, 1:2,1:3,1:4 and 3:4)), as shown in Figure 1.45 In the pseudo-ternary phase plot, the pink shaded area represents the area of microemulsions. The plot with a larger shaded area indicates the presence of good micro-emulsifying activity of formulated microemulsions and beneficial interaction among the Smix, oil and aqueous phase. Bancroft's rule states that the phase in which the surfactant is more soluble represents the continuous phase and determines the type of microemulsion produced (either o/w or w/o).25 According to this rule, Tween 80 used as a surfactant, which is a hydrophilic molecule with HLB value of 15, is more soluble in aqueous phase and this favors the formation of o/w microemulsion. The pseudoternary phase diagrams demonstrate that the zone of microemulsion was largest in SMEDDS prepared with Tween 80:(Transcutol P, Propylene glycol Smix). Formulas selected with oil: Smix 1:9 ratios for all Smix ratios remained as microemulsions even upon infinite water titration or dilution. This is possible as Tween 80 with Transcutol P and propylene glycol mixture is strongly localized on the surface of the microemulsion droplets, minimizes the interfacial free energy and provides a mechanical barrier to coalescence resulting in a spontaneous dispersion.26\n\nPseudo ternary phase diagrams for self-microemulsion composed of oil phase (Oleic acid), surfactant (Tween 80), cosurfactant (Transcutol P), cosolvent (propylene glycol) and water. (A) Smix 1:1, (B) Smix 1:2, (C) Smix 1:3, (D) Smix 1:4 and (E) Smix 3:4.\n\nBased these findings, the optimal micro-emulsification qualities are achieved with an increasing Tween 80 ratio. In order to avoid disagreeable side effects, it is crucial to accurately measure the surfactant concentration and use the optimal surfactant and co-surfactant concentrations in the formulation.27\n\nThis current study involved the use of pre-concentrates consisting of oil and Smix, and the pseudoternary diagram was used to select the appropriate oil that solubilized the drug, surfactant and co-surfactant mixtures.\n\nThere is no visible phase separation or drug precipitation in any of the observed liquid MLX SMEDDS formulations, and all of the mixtures are a uniform, clear and yellow to brown color.\n\nAssessment of the prepared liquid SMEDDS\n\nThermodynamic stability studies\n\nThe thermodynamic stability test was passed by all of the prepared MLX SMEDDS formulations because there was no evidence of phase separation or drug precipitation at the end of all cycles. The purpose of this stability study is to identify metastable formulations and to suggest that the formulations were stable against storage in extreme conditions.28\n\nDroplet size measurement and PDI\n\nThe rate, extent, and absorption of drug release are all influenced by the droplet size of the microemulsion, making it the most important factor in self-emulsification performance. The relationship between droplet size and surface area explains the effect of microemulsion droplet size on drug release and bioavailability. It is well known that the smaller the droplet size, the greater the surface area available for drug release and absorption.29\n\nTable 545 displays the droplet sizes and PDIs for the several SMEDDS formulations that were created. The droplet sizes ranged from 63.22 nm to 347.8 nm, and the PDIs ranged from 0.3 to 0.5069. The low polydispersity index indicates good droplet size distribution uniformity after dilution with water.30 The results showed that the size of the droplets gets smaller as the Smix ratio and the ratio of surfactant to co-surfactant increase. This is because there are more surfactants at the oil/water interface.31\n\nPDI, poly dispersity index; SMEDDS, Self-micro emulsifying drug delivery system.\n\nRobustness to dilution\n\nDilution is caused by gastrointestinal fluids, and it is impossible to precisely identify the amount of water present to form the microemulsion with the formulation. Dilution resistance was tested using an excess of water and 0.1 N HCl, and formulations were stored for 24 hours. This test was passed by all MLX SMEDDS formulations, which were visually examined as clear with no precipitation or phase separation. The ability of the SMEDDS formulation to withstand aqueous dilution was found to be excellent. This is due to the excipients' high solubilizing properties, as well as their ability to form a relatively stable microemulsion with small droplet sizes. This meant that the formulations were resistant to extreme dilution and could be diluted indefinitely with water.32\n\nDispersibility tests and self-nano emulsification time\n\nEmulsification studies are critical for determining the self-emulsifying properties of designed formulations. SMEDDS should completely and rapidly disperse in aqueous dilution with mild agitation.33 When determining how effective emulsification is, one crucial index to consider is the rate at which it occurs. With grade A, all of the prepared MLX SMEDDS formulations formed the microemulsion in less than 1 minute. The difference in self-emulsification times between the different formulas in the bulk liquid SMEDDS was very small, and because the observation times were short (in seconds), it was difficult to distinguish between the formulas. Smix in SMEDDS reduces interfacial tension between the oil and aqueous phases, facilitating dispersion and the formation of o/w microemulsions.34\n\nDrug content within the prepared SMEDDS\n\nDrug content of the prepared MLX SMEDDS at the nanoscale was more than 97%, which meets USP requirements and is within an acceptable range (90–110%), indicating that there was no precipitation of drug in any of the prepared formulations.35 The drug content percentage of the MLX SMEDDS is shown in Table 6.41\n\nData are presented as mean±SD, n=3. SMEDDS, Self-micro emulsifying drug delivery system.\n\nIn vitro dissolution study\n\nThe in vitro drug release profiles regarding F2 to F5 and pure MLX have been assessed in 0.1 N HCl, 50 rpm and 37°C are shown in Figure 2.43 The F1 was disregarded due to the size of the droplet (347.8 nm). Dialysis membranes were used in this test because they are less prone to blockage and have very small pores.5 The prepared MLX SMEDDS formulations showed drug release percentage of more than 94% at the end of 60 min. However the F5 showed higher release percentage of 99.87% at 40 min. The drug is released more quickly because it is dissolved in the SMEDDS. The faster release is due to the fine particle size and high concentration of surfactant mixture, which can easily emulsify the oil for finer globules.36\n\nMLX, meloxicam; SMEDDS, Self-micro emulsifying drug delivery system.\n\nPure MLX has a slower release profile than prepared SMEDDS formulations, reaching 11.6% after 60 minutes in the absence of a dialysis membrane. The release profile of the ordinary MLX powder is significantly different from the prepared SMEDDS formulations. Finally, the SMEDDS formulations resulted in the spontaneous creation of microemulsion with tiny droplet size, which enabled rapid rate of the drug release to the aqueous phase, much quicker than that of the pure drug powder. F5 has significant differences from other formulations (similarity factor<50).\n\nF5 was chosen as the optimal MLX liquid self-microemulsion due to its higher drug content, greater in vitro release, smaller droplet size, and lower PDI value.\n\nZeta potential measurement\n\nThe zeta potential of an emulsion reveals how much force is exerted by the droplets against one another. No matter their charge, a normal zeta potential value is above 30 mV,37 for just accepted absolute electrostatic stabilization. Zeta potential value of the produced microemulsion was found to be -81.29 mV, as shown in Figure 3.46 Anionic groups of fatty acids and glycols in oils, surfactants, and co-surfactants may contribute to the occurrence of negative zeta potential. This test was performed only for the selected formula F5.\n\nSMEDDS, Self-micro emulsifying drug delivery system.\n\nThe droplets' negative charge would prevent them from clumping together. Emulsifiers prevent oil droplets from coalescing in part by acting as a mechanical barrier and in part by forming surface charges (zeta potential) that can produce repulsive electrical forces between approaching oil droplets.\n\nDue to the enhanced zeta potential (negative charge) and steric stabilization effect, the optimized SMEDDS (F5) does not display threshold agglomeration.38\n\nAtomic force microscopy (AFM)\n\nIn addition to proving the nanoscaled potential of microemulsions by conventional means, AFM topographic pictures give a broad size summary and defining the form and surface structure of the studied sample.39 The mean size of the droplet was 91 nm with smooth surface of the formula. The AFM results are shown in Figure 4.\n\n(A) Report of AFM. (B) 3D-surface morphology. AFM, Atomic force microscopy; SMEDDS, Self-micro emulsifying drug delivery system.\n\nField emission scanning electron microscopy (FESEM)\n\nThe result shows a droplet size of 89 nm that is around AFM result, which means that the formula is monodispersed and the shape of the droplet is spherical. The result of FESEM is shown in Figure 5.\n\nFESEM, Field emission scanning electron microscope; MLX, meloxicam.\n\nTransmission electron microscopy (TEM)\n\nTEM defines the morphology of microemulsion, as seen in Figure 6, spherical shape and uniform nanometric size of the droplets with smooth surface of the formula.\n\nTEM, Transmission Electron Microscope; SMEDDS, Self-micro emulsifying drug delivery system.\n\n\nConclusions\n\nThe results of this research indicate that SMEDDS is a promising route for developing an oral dosage regimen for MLX that is poorly soluble in water. The SMEDDS method, which included the use of oleic acid oil, Tween 80, Transcutol P, and propylene glycol, was crucial in enhancing the stability, hydrophilicity, dissolution, and dissolution rates of MLX. Effective MLX SMEDDS have been created and evaluated in vitro. Drug solubility is enhanced by nanosized formulations because of the greater surface area provided for drug release and absorption.",
"appendix": "Data availability\n\nZenodo: Cosurfactants saturation solubility. https://doi.org/10.5281/zenodo.7600515 40\n\nZenodo: drug cotents. https://doi.org/10.5281/zenodo.7600527 41\n\nZenodo: Oils saturation solubility. https://doi.org/10.5281/zenodo.7600535 42\n\nZenodo: RELEASE OF FORMULATIONS. https://doi.org/10.5281/zenodo.7600539 43\n\nZenodo: Surfactants saturation solubility. https://doi.org/10.5281/zenodo.7600545 44\n\nZenodo: Formulation size and ternary plot. https://doi.org/10.5281/zenodo.7600547 45\n\nZenodo: Image for (Formulation and in vitro evaluation of meloxicam as a self-microemulsifying drug delivery system). https://doi.org/10.5281/zenodo.7660921 46\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nJassim ZE, Al-Kinani KK, Alwan ZS: Preparation and Evaluation of Pharmaceutical Cocrystals for Solubility Enhancement of Dextromethorphan HBr. Int. J. Drug Deliv. 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Pharm. 2006; 312(1–2): 187–195. Publisher Full Text\n\nNasr A, Gardouh A, Ghorab M: Novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of olmesartan medoxomil: Design, formulation, pharmacokinetic and bioavailability evaluation. Pharmaceutics. 2016; 8(3). Publisher Full Text\n\nMadan JR, Patil K, Awasthi R, et al.: Formulation and evaluation of solid self-microemulsifying drug delivery system for azilsartan medoxomil. Int. J. Polym. Mater. Polym. Biomater. 2021; 70(2): 100–116. Publisher Full Text\n\nWang L, Yan W, Tian Y, et al.: Self-microemulsifying drug delivery system of phillygenin: Formulation development, characterization and pharmacokinetic evaluation. Pharmaceutics. 2020; 12(2): 1–17. Publisher Full Text\n\nYadav PS, Yadav E, Verma A, et al.: Evaluation of Hydrochlorothiazide Loaded Self-Nanoemulsifying Drug Delivery Systems. Sci. World J. 2014; 2014: 1–10. Publisher Full Text\n\nMedina-Lopez JR, Orozco-Juarez JA, Hurtado M: Dissolution performance of meloxicam formulations under hydrodynamics of usp paddle apparatus and flow-through cell method. Int. J. Appl. Pharm. 2019; 11(4): 182–188. Publisher Full Text\n\nD’Souza S: A Review of in vitro Drug Release Test Methods for Nano-Sized Dosage Forms. Adv. Pharm. 2014; 1–12.\n\nDrais HK, Hussein AA: Formulation Characterization and Evaluation of Meloxicam Nanoemulgel to be Used Topically. Iraqi J. Pharm. Sci. 2017; 26(1): 9–16. Publisher Full Text\n\nLu GW, Gao P: Emulsions and Microemulsions for Topical and Transdermal Drug Delivery. Handbook of Non-Invasive Drug Delivery Systems. 2010; 59–94. Publisher Full Text\n\nHo TM, Abik F, Mikkonen KS: An overview of nanoemulsion characterization via atomic force microscopy. Crit. Rev. Food Sci. Nutr. 2022; 62(18): 4908–4928. Publisher Full Text\n\nAlwadei M, Kazi M, Alanazi FK: Novel oral dosage regimen based on self-nanoemulsifying drug delivery systems for codelivery of phytochemicals – Curcumin and thymoquinone. Saudi Pharm J. 2019; 27(6): 866–876. Publisher Full Text\n\nAssi RA, Abdulbaqi IM, Ming TS, et al.: Liquid and solid self-emulsifying drug delivery systems (Sedds) as carriers for the oral delivery of azithromycin: Optimization, in vitro characterization and stability assessment. Pharmaceutics. 2020; 12(11): 1–29.\n\nBasit ELMAW: Modified-release oral drug delivery. Pharmaceutics The Design and Manufacture of Medicines. 2018; pp. 564–579.\n\nSalim FF, Rajab NA: Formulation and characterization of piroxicam as self-nano emulsifying drug delivery system. Iraqi J. Pharm. Sci. 2020; 29(1): 174–183.\n\nAggarwal G, Harikumar S, Jaiswal P, et al.: Development of self-microemulsifying drug delivery system and solid-self-microemulsifying drug delivery system of telmisartan. Int. J. Pharm. Investig. 2014; 4(4): 195. Publisher Full Text\n\nRehman FU, Farid A, Shah SU, et al.: Self-Emulsifying Drug Delivery Systems (SEDDS): Measuring Energy Dynamics to Determine Thermodynamic and Kinetic Stability.2022; 15(9): 1064.\n\nAnuar N, Sabri AH, Bustami Effendi TJ, et al.: Development and characterisation of ibuprofen-loaded nanoemulsion with enhanced oral bioavailability. Heliyon. 2020; 6(7): e04570. Publisher Full Text\n\nDanaei M, Dehghankhold M, Ataei S, et al.: Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018; 10(2): 1–17. Publisher Full Text\n\nTadros TF: 9. Surfactants in microemulsions. An Introduction to Surfactants. 2014; pp. 153–168. Publisher Full Text\n\nNastasa V, Samaras K, Andrei IR, et al.: Study of the formation of micro and nano-droplets containing immiscible solutions. Colloids Surfaces A Physicochem. Eng. Asp. 2011; 382(1–3): 246–250. Publisher Full Text\n\nOverview AN, Dyslexia ON: Treatment ITS. J. Glob. Pharma. Technol. 2016; (May).\n\nArticle R: Biomedical application of microemulsion delivery systems: A review.2022; 26(5): 1052–1064.\n\nFormulary THEN: Usp 41|the united states pharmacopeia.2018; 3.\n\nDeshmukh A, Kulakrni S: Novel Self Micro-emulsifying drug delivery systems (SMEDDS) of Efavirenz. J. Chem. Pharm. Res. 2012; 4(8): 3914–3919.\n\nLimited MI: Zeta potential: An Introduction in 30 minutes. Zetasizer Nano Serles Tech Note MRK654-01. 2011; (2): 1–6.\n\nSamimi S, Dorkoosh F, Nanoma- B: Lipid-Based Nanoparticles for Drug Delivery Systems Multifunctional nanocrystals for cancer therapy: a potential nanocarrier Emulsions and Microemulsions for Topical and Transdermal Drug Delivery. Lipid-Based Nanoparticles Drug Deliv Syst. 2019; 47–76. Publisher Full Text\n\nVerma S, Singh SK, Verma PRP, et al.: Formulation by design of felodipine loaded liquid and solid self nanoemulsifying drug delivery systems using Box-Behnken design. Drug Dev. Ind. Pharm. 2014; 40(10): 13570–13580.\n\nMuhammed SA, Al-Kinani KK: Cosurfactants saturation solubility. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nMuhammed SA, Al-Kinani KK: drug cotents. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nMuhammed SA, Al-Kinani KK: Oils saturation solubility. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nMuhammed SA, Al-Kinani KK: RELEASE OF FORMULATIONS. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nMuhammed SA, Al-Kinani KK: Surfactants saturation solubility. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nMuhammed SA, Al-Kinani KK: Formulation size and ternary plot. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nMuhammed SA, Al-Kinani KK: Image for (Formulation and in vitro evaluation of meloxicam as a self-microemulsifying drug delivery system). [Dataset]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "167515",
"date": "11 Apr 2023",
"name": "Mohd Yasir",
"expertise": [
"Reviewer Expertise Pharmaceutics (Formulation design",
"Nano drug delivery",
"Nose to brain drug delivery",
"Transdermal drug delivery",
"Oral drug delivery",
"Lipid Naoparticles",
"etc"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Author\nThank you for providing a study associated with “Meloxicam as a selfmicroemulsifying drug delivery system for oral delivery”. The author requires to respond to the following major comments before the final decision on the manuscript\n\nComments\n\nAuthor is required to mention physiochemical characters that make Meloxicam as a suitable drug for designing SMEDDS.\n\nPlease mention the specifications (model number, company, etc) of all machines like centrifuge, used for the research.\n\nDuring the mixing for preparation of SMEDDS/Smix, what was the end point of mixing of oil with Trizma buffer (water), etc. how they identify the final end point.\n\nFor the measurement of droplet size and polydispersity index, dilution was made with distilled water but in my opinion it should made with deionized water.\n\nDruing measurement of drug content, what was the value of absorption maxima (ʎmax) used for UV/visible Spectrophotometer measurement. Moreover Please mentioned the model number and company of UV/visible Spectrophotometer in bracket.\n\nBetter if author describe the zeta potential after particle size. So move it from here and describe just after particle & PDI heading in both cases viz method and result & discussion.\n\nPage 8: Author mentioned the reference in Table 545 . Have they taken this table from this reference. Please check it\n\nWhy the author gave the reference in this sentence “The drug content percentage of the MLX SMEDDS is shown in Table 6.41”. Please check it and correct.\n\nAgain same issue associated reference “The in vitro drug release profiles regarding F2 to F5 and pureMLXhave been assessed in 0.1NHCl, 50 rpm and 37°C are shown in Figure 2.43”. please check it and remove the reference.\n\nPlease add the error bars in figure 2\n\nPlease elaborate the conclusion\n\nCheck the manuscript for the grammar and punctuation issue.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "9672",
"date": "30 May 2023",
"name": "Saja Muhammed",
"role": "Author Response",
"response": "Thanks for your response, your time, your rich information, and your helpful review. I will reply to all comments below. Comments Author is required to mention physiochemical characters that make Meloxicam as a suitable drug for designing SMEDDS Meloxicam is suitable for this system due to its poor water solubility, which causes low absorption, low dosage, no substantial first-pass metabolism, is highly soluble in the system ingredients, and has a high log p of 3.43This is added to the article Please mention the specifications (model number, company, etc) of all machines like centrifuge, used for the research Centrifuge, Eppendorf, Germany, Hettich EBA20 During the mixing for preparation of SMEDDS/Smix, what was the end point of mixing of oil with Trizma buffer (water), etc. how they identify the final end point In the preparation of the SMEDDS the mixing of ingredients according to specific weight of them and mixing until obtain a clear liquid. For the measurement of droplet size and polydispersity index, dilution was made with distilled water but in my opinion it should made with deionized water. I respect your opinion but the instrument operator usually use a double distilled water in our measurements. During measurement of drug content, what was the value of absorption maxima (ʎmax) used for UV/visible Spectrophotometer measurement. Moreover Please mentioned the model number and company of UV/visible Spectrophotometer in bracket The value of absorption maxima (ʎmax) used for UV/visible Spectrophotometer measurement is 355 nm UV-Visible Spectrophotometer Shimadzu 1650 pc-Japan UV mini 1240 This is added to the article. Better if author describe the zeta potential after particle size. So move it from here and describe just after particle & PDI heading in both cases viz method and result & discussion. I agree with your opinion but since the zeta potential is done on the optimum formula so we put it according to the sequence of the steps in the study Page 8: Author mentioned the reference in Table 545 . Have they taken this table from this reference. Please check it Why the author gave the reference in this sentence “The drug content percentage of the MLX SMEDDS is shown in Table 6.41”. Please check it and correct Again same issue associated reference “The in vitro drug release profiles regarding F2 to F5 and pureMLXhave been assessed in 0.1NHCl, 50 rpm and 37°C are shown in Figure 2.43”. please check it and remove the reference Those tables are the result of the study but due to the guidelines of the journal this reference is only to get the table in more details with the underlying data. Please add the error bars in figure 2 See amended figure here. This also added in the article's figure Please elaborate the conclusion The results of this research indicate that SMEDDS is a promising route for developing an oral dosage regimen for MLX that is poorly soluble in water. The SMEDDS method was crucial in enhancing the stability, hydrophilicity, dissolution, and dissolution rates of MLX. The F-5 (10% oleic acid oil, 38.57% Tween 80, 25.72% propylene glycol, and 25.72% Transcutol P) showed a higher release percentage of 99.87% at 40 minutes. The drug is released more quickly because it is dissolved in SMEDDS. The faster release is due to the large surface area due to the fine droplet size and high concentration of the surfactant mixture, which can easily emulsify the oil into finer globules. The best formula has a zeta potential of -81 mV, which means it is stable. The AFM, FESEM, and TEM showed uniform particle size at the nanoscale and a spherical particle shape with a smooth surface. Drug solubility is enhanced by nanosized formulations because of the greater surface area provided for drug release and absorption. This is added in the article."
}
]
},
{
"id": "169588",
"date": "18 Apr 2023",
"name": "Michael Adu-Frimpong",
"expertise": [
"Reviewer Expertise Preparation of delivery systems for active compounds of plants"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReviewer’s comment Muhammad et al incorporated meloxicam (MLX) into self-microemulsifying drug delivery system, which improved solubility and oral bioavailability of the drug. This work is relevant for development of drug delivery system. The authors need to address the following concerns before possible indexing.\nGeneral comment\nThe particle size of the formulation is in nanoscale. Why the authors did use ‘microemulsifying’ instead of ‘nanoemulsifying’\n\nIntroduction\nIn order to justify the need for this delivery system for MLX, the authors should indicate other existing delivery systems of the drug and their shortcomings\nMethods and materials\nIn determining the drug content, did authors estimate of the entrapment efficiency and loading capacity of MLX liquid SMEDDS?\n\nWhy did the authors determine in vitro drug release in only pH 1.2 but not in pH 7.4?\nResults and Discussion\nBased on these findings, the optimal micro-emulsification qualities... seems better\n\nIn confirming the transparency of the formulation, did the authors determine the percentage transmittance of the MLX liquid SMEDDS?\n\nThe authors should explain why the SMEDDS formulations resulted in the spontaneous creation of microemulsion with tiny droplet size\n\nThe authors should comment on the stability of the formulation. Did the authors study the long-term storage stability of MLX liquid SMEDDS?\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9671",
"date": "30 May 2023",
"name": "Saja Muhammed",
"role": "Author Response",
"response": "Thanks for your response, your time, your rich information, and your helpful review. I will reply to all comments below. General comment The particle size of the formulation is in nanoscale. Why the authors did use ‘microemulsifying’ instead of ‘nanoemulsifying’ Knowing that microemulsion droplet size is in the nanoscale and not in the microscale which is misleading most of the times but it is a known fact. Introduction In order to justify the need for this delivery system for MLX, the authors should indicate other existing delivery systems of the drug and their shortcomings There are many delivery systems that can be used to formulate MLX, like nanoemulsion, microemulsion, soild dispersion, etc. The microemulsion delivery system has the disadvantage of having a large amount of surfactants; stability is influenced by temperature and pH; and substances with high melting points have limited solubility capacity. The nanoemulsion delivery system has the disadvantage of a large concentration of the surfactant and expensive techniques for preparation. The disadvantages of solid dispersion are that they form crystalline solid dispersion as they are prepared using crystalline carriers like urea and sugars. Crystalline solid dispersions were more thermodynamically stable, which lowered their dissolution rate as compared to amorphous ones. While the SMEDDS deliver the drug with the easiest technique and faster drug release. Methods and materials In determining the drug content, did authors estimate of the entrapment efficiency and loading capacity of MLX liquid SMEDDS? I respect your opinion but since the system is not vascular most of the reference not include this test and only carried out the drug contents which is give a good result of drug loading. Why did the authors determine in vitro drug release in only pH 1.2 but not in pH 7.4 SMEEDS delivery system is not conventional dosage form,and we know that meloxicam is a weakly acidic drug and release is fater in the acidic media,and this article is a part of thesis in which we actually use 7.4 PH buffer which give slower release than 1.2 PH media. Based on these findings, the optimal micro-emulsification qualities... seems better In confirming the transparency of the formulation, did the authors determine the percentage transmittance of the MLX liquid SMEDDS The most of references in our study don’t determine the percentage transmittance of the liquid SMEDDS, they did this test mostly in micro and nano emulsion and also this system is not vascular system and the formula is a clear liquid as you noticed in the results. The authors should explain why the SMEDDS formulations resulted in the spontaneous creation of microemulsion with tiny droplet size Due to interfacial tension caused by the s.mix which resulted in tiny droplets with different nanoscales. The authors should comment on the stability of the formulation. Did the authors study the long-term storage stability of MLX liquid SMEDDS? Due to highly thermodynamic stability of the formulations and this article is a part of thesis that study the long term stability of the formulations for three months and give a good result of release and drug content."
}
]
}
] | 1
|
https://f1000research.com/articles/12-315
|
https://f1000research.com/articles/12-425/v1
|
20 Apr 23
|
{
"type": "Study Protocol",
"title": "Suicide prevention program (SPP) in South Asian Countries: A protocol for systematic review",
"authors": [
"Kallabi Borah",
"Tessy Treesa Jose",
"Anil Kumar Mysore Nagaraj",
"Lorna Moxham",
"Kallabi Borah",
"Anil Kumar Mysore Nagaraj",
"Lorna Moxham"
],
"abstract": "Introduction: Every year, over 703,000 individuals lose their life by suicide and many individuals attempt suicide. Suicide occurs in all age groups and is the fourth major cause of death among 15–29-year-olds globally in 2019. A suicide prevention program (SPP) is a capacity-building program that helps gatekeepers to identify the risk of suicide. The objective of the review is to determine the effectiveness of SPP on the improvement of knowledge, attitude, and gatekeeper behaviour among gatekeepers in South Asian countries. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PICO (Population, Intervention, Comparison, Outcome) format will be followed in this review. This review will include all interventional studies that provided a suicide prevention program to the gatekeepers as an intervention. The full-text articles will be included from the following databases, Scopus, PubMed (MEDLINE), Cochrane, PsycINFO, Web of Science, and CINAHL, published in peer-reviewed, indexed, and English language journals from the date of inception to 2022. A grey literature search and hand-search of reference lists of the included studies will also be done. A search strategy will be developed using keywords and MeSH terms for each database. Cochrane ROB-2 tool, JBI Critical Appraisal Checklist, Critical Appraisal Skills Program (CASP), and Mixed Methods Appraisal Tool (MMAT) will be used to evaluate the quality of individual studies. Analysis of the data will be done using narrative synthesis. Conclusions: This review will provide information on knowledge, attitude, and gatekeeper behaviour toward suicide prevention in college students and will be helpful for the prevention of suicide. Therefore, the authors plan to publish the review outcome through a peer-reviewed journal. Registration: The review is registered in PROSPERO (CRD42023387020).",
"keywords": [
"systematic review",
"South Asian countries",
"college students",
"suicide prevention",
"suicide prevention program."
],
"content": "Introduction\n\nSuicide is an emergency problem in psychiatry. It is one of the major causes of death among today’s youth.1 Several factors such as biological, psychological, and environmental factors are associated with youth suicide, varying from family issues to rapid urbanization and a weak psychological system.2 Childhood abuse (physical, emotional, and sexual) also plays a role in future suicidal ideation among youth.3,4\n\nThe suicide rate is increasing every year. The World Health Organization (WHO) reported that one individual dies by suicide every 40 seconds. Worldwide, every year more than 700,000 individuals take their life by suicide, and many individuals attempt suicide.5 The UN’s Sustainable Development Goal (SDG) 3 is “Ensure healthy lives and promote well-being for all at all ages” and the target SDG 3.4 explains “By 2030, reduce by one-third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being” under which one indicator (SDG3.4.2) is the suicide mortality rate.6 A total of 79% of the world’s suicide occurred in low and middle-income countries.7 Worldwide, a total of 1.4% of all deaths are associated with suicide among those aged 15-24 years (Web-based Injury Statistics Query and Report System [WISQARS], 2017) and it is the fourth major cause of death among those aged 15 to 29.8 The calculated age-standardized suicide rate among those aged 15 years or more was 22.0 per 100,000.9\n\nIndia has the highest suicide rate in the Southeast Asia region.10 According to a WHO report (Sep 9, 2019), the rate of suicide in India is 16.5 per 100,000 people.11 In India (2021) out of 13,089 students who died by suicide, 7,396 were male and 5,693 were female.12 A review reported that compared to other high-income countries, Asia has higher average suicide rates.13 Very few reviews are available on suicide in South Asia, and only India and Sri Lanka have been included in most of the reviews.14\n\nThe National Crime Records Bureau (2017) reported that one student commits suicide every hour, and one of the major causes of suicide is a failure in examinations.15,16 The other causes that lead to suicide among students are depression, relationship issues, psychiatric problems requiring medical attention, a history of psychiatric hospitalization, and academic obstacles.17\n\nA gatekeeper can be anyone (e.g., teachers, parents, hostel wardens, community leaders, police, layperson, counsellors, among others) who is ready to give time and effort to prevent suicide at the community level.18 A gatekeeper training program is a capacity-building suicide prevention program recommended by WHO that aims to assist individuals with the skills and knowledge required to be first responders to someone who is in psychological distress and potentially suicidal and helps them to get better services as needed. As suicide is a growing problem among adolescents, suicide prevention program will help the gatekeepers identify the risk of suicide at the grass root level. Therefore, this review is intended to determine the effect of suicide prevention programs among gatekeepers on the prevention of suicide among college students in South Asia (Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka)19 and to improve their knowledge, attitude, and gatekeeper behaviour through suicide prevention program.\n\nThe objective of the review is to determine the effectiveness of suicide prevention programs (SPP) on the improvement of knowledge, attitude, and gatekeeper behaviour among gatekeepers so that the number of suicide cases will be reduced among college students in South Asia countries.\n\n\nReview question\n\n\n\n• Are suicide prevention programs effective among gatekeepers in the prevention of suicide among college students?\n\n• What types of suicide prevention programs are effective in the prevention of suicide among college students?\n\n• What are the components that make suicide prevention programs effective?\n\n• Does the suicide prevention program help in the improvement of knowledge, attitude, and gatekeeper behaviour among gatekeepers?\n\n\nMethods\n\nThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)20 will be used to report systematic reviews. The PICO (Population, Intervention, Comparison, Outcome) format will be adopted to define the methods of the review. The protocol was registered on PROSPERO (CRD42023387020).\n\nTypes of studies\n\nAll interventional studies that provide suicide prevention programs to the gatekeepers as an intervention to prevent suicide in college students, and published in indexed and peer-reviewed, English language journals from the date of inception to 2022 in South Asia will be included. A grey literature search and hand-search of reference lists of included studies will be done. The conference proceedings, reports, review papers, letters to the editor, or responses to articles, as well as studies published in other than English will not be included.\n\nParticipants\n\nGatekeepers who have undergone any suicide prevention program as an intervention will be the participants in the present review.\n\nIntervention\n\nWe will include studies that provide suicide prevention programs as an intervention in the form of a workshop, different methods of teaching, and a module/booklet.\n\nComparison\n\nWe will include studies that compare the intervention group (receiving any intervention in suicide prevention) and the control group (not receiving any intervention in suicide prevention).\n\nOutcome measures\n\nThe outcome measures will be suicide prevention, knowledge, attitude, and gatekeeper behaviour.\n\nPrimary studies will be searched by two independent authors through electronic databases: Scopus, PubMed (MEDLINE), PsycINFO, Cochrane, Web of Science, and CINAHL using MeSH terms, Emtree and synonyms of keywords of a suicide prevention program, South Asia, gatekeepers, and college students. Boolean operators (AND, OR) will be used to create specific search strategies for each database.\n\nAdditional searches\n\na) Hand searching: To find out additional studies, authors will hand-search reference lists of all primary studies and review articles.\n\nb) Grey literature: Authors will conduct a grey literature search to find out the studies not indexed in the above-listed databases.\n\nSearch strategy\n\nWe include the search strategy in Figshare (Extended data).21\n\nData management\n\nRevMan 5 software22 will be used for the screening and data extraction of the review. The collected search results from the databases will be kept in one folder and will be imported into EndNote and will be arranged by databases, inclusion criteria, and exclusion criteria.\n\nSelection process\n\nA stepwise approach will be followed by the authors to identify the eligibility of the studies for inclusion in this review. To identify eligibility and remove duplicates, titles and abstracts of the studies will be screened by two authors independently. The full-text article screening will be done for the potentially eligible studies. The full-text studies will be retrieved and assessed for inclusion in the review by two reviewers. A third reviewer or an independent opinion may be requested if the first two reviewers are unsure about the study’s eligibility in the analysis. The results from independent reviewers will be sent to a third reviewer, who will compare the results and compile a list of included studies. Discrepancies between the results from both reviewers will be discussed with the third reviewer until an agreement is reached. If the full-text study is not accessible through institutional membership, then the study authors will be contacted to retrieve the manuscript. The study will be included based on inclusion criteria. After eliminating the duplicate studies, a final list of included studies will be made. The reason for the excluded study and the study selection procedure will be recorded in the PRISMA flow diagram.\n\nData collection process\n\nFollowing the study selection process, the extraction of the data will be completed independently by two authors. To ensure consistency in the data extraction, the authors will first pilot the data extraction tool and the extraction process on the first ten articles. Outcome data and characteristics of the study will be included if reported within the individual studies (study authors will be contacted to collect missing information relevant to this review). A data extraction form will be used to extract the data by two independent authors.\n\nBibliometric information such as authors’ names, titles, journal names, publication year, and settings will be collected along with included study characteristics such as type of study, research question, objective, observation, duration, intervention, outcome variables, and key findings.\n\nThe evidence generated through this review will be presented in the form of tables and figures and based on the study objectives narrative synthesis will be done.\n\nThe Cochrane ROB-2 tool will be used to assess the risk of bias in individual studies.23 Quality assessment will be performed by two authors to conclude inconsistency by consulting with a third author.\n\nQuantitative studies\n\nThe Joanna Briggs Institute (JBI) Critical Appraisal Checklist will be used to assess the risk of bias and selection bias.\n\nQualitative studies\n\nThe Critical Appraisal Skills Program (CASP) checklist will be used to assess the quality of the studies.24\n\nMixed methods studies\n\nThe risk of bias for mixed-method studies will be assessed by the Mixed Methods Appraisal Tool (MMAT).25 The assessment will be done based on the following domains of bias: (i) randomization process, (ii) deviation from intervention (allocation concealment sequence), (iii) outcome assessment, (iv) incomplete outcome data, (v) selective reporting, and (vi) absolute bias. Based on the risk of bias assessment, the studies will be classified as high, or low risk of bias.\n\nCollected data will be described and synthesized according to the type of sources, context, and key themes. The authors will perform a meta-analysis where feasible. As part of the preliminary analysis, the sensitivity and specificity of the included studies will be shown by forest plots and receiver operating characteristics curve. A summary table will be used to depict the most important aspects of the selected studies, such as the research area, and how the suicide prevention program is effective in suicide prevention. Factors gleaned from quantitative investigations will be presented in a narrative study. Thematic analysis will be done to study the qualitative data to track down the variables. The data will be coded, and subthemes will be developed after that.\n\nSensitivity analysis\n\nTo determine the low impact of quality studies on the review findings sensitivity analyses will be performed. A high or unclear risk of bias studies as identified by the ROB-2 tool will be excluded.\n\nReporting bias assessment\n\nReporting bias will not be assessed due to a lack of sensitive statistical methods.\n\nThe Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidance26 will be used by two reviewers independently to assess the quality of evidence and it will be classified as high, moderate, low, or very low.\n\n\nDiscussion\n\nThe gatekeeper training helps the gatekeepers to improve their knowledge and lower their judgmental attitude towards suicide prevention.27 Previous studies also revealed that gatekeeper training (GKT) improves the teachers’ competency and confidence in managing suicide-risk students.28,29 The study also reported that GKT brushed up the self-perceptions of college staff in working with suicidal students and improve their skill for providing intervention.30\n\nEthical clearance is not applicable as the present review will include only published articles from different databases and no human will participate in this review. A manuscript will be prepared for publication in a Scopus-indexed, peer-reviewed journal and the results will be presented at a national and international conference after the completion of the analysis.\n\nThe present systematic review will include interventional studies which provide suicide prevention program to the gatekeepers as an intervention. This review will focus on suicide prevention among college students. Only studies published in the English language in South Asian countries will be included.\n\nFormal search has not been started.\n\n\nAuthor contributions\n\nKallabi Borah: Conceptualization, analysis, methodology, supervision, validation, writing- original draft preparation, writing- review & editing.\n\nTessy Treesa Jose: Conceptualization, analysis, methodology, supervision, validation, visualization, writing- review & editing.\n\nAnil Kumar Mysore Nagaraj: Conceptualization, analysis, methodology, supervision, validation, visualization, writing- review & editing.\n\nLorna Moxham: Conceptualization, methodology, supervision validation, visualization, writing- review & editing.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nFigshare: Supplementary material 1, https://doi.org/10.6084/m9.figshare.22249906. 31\n\nThis project contains the following extended data:\n\n- PRISMA flow diagram of study selection for, “Suicide prevention program (SPP) in South Asian Countries: A protocol for systematic review”\n\nFigshare: Supplementary material 3, https://doi.org/10.6084/m9.figshare.22253254. 21\n\nThis project contains the following extended data:\n\n- Search strategy for “Suicide prevention program (SPP) in South Asian Countries: A protocol for the systematic review”\n\nFigshare: PRISMA-P checklist for, “Suicide prevention program (SPP) in South Asian Countries: A protocol for systematic review, https://doi.org/10.6084/m9.figshare.22252309. 32\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nNesari V: Evaluate the effectiveness of a planned teaching programme on suicidal prevention among undergraduate students. Int. J. Adv. Nur. Management. 2014; 2(3): 125–131.\n\nSreevani R: A Guide to mental health and psychiatric nursing. 4th ed.New Delhi: JAYPEE; 2016; 253–254.\n\nArun P, Garg R, Chavan BS: Stress and suicidal ideation among adolescents having academic difficulty. Ind. Psychiatry J. 2017; 26: 64–70. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGlenn JJ, Werntz AJ, Slama SJ, et al.: Suicide and self-injury-related implicit cognition: A large-scale examination and replication. J. Abnorm. Psychol. 2017 Feb; 126(2): 199–211. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Health Organization: Suicide. Geneva: World Health Organization; 2021 June 17. Reference Source\n\nUnited Nations: The sustainable development goals report.2022. Reference Source\n\nCentre for the evaluation of value and risk in mental health: Suicide prevention: A global priority for investment.2020 Jan 23. Reference Source\n\nWorld Health Organization: Preventing global suicide: a global imperative. Geneva: World Health Organisation; 2019.\n\nSnowdon J: Indian suicide data: What do they mean? Indian J. Med. Res. 2021; 150(4): 315–320. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Health Organization: Suicide in the world: global health estimates. Geneva: World Health Organization.Reference Source\n\nMannekote TS, Shankarapura NM, Bada MS: Suicide in India: A preventable epidemic. Indian J. Med. Res. 2019 October; 150(4): 324–327. Publisher Full Text Reference Source\n\nCareers 360: Over 13,000 students died by suicide last year: NCRB report 2021.Reference Source\n\nChen Y-Y, Wu KC-C, Yousuf S, et al.: Suicide in Asia: opportunities and challenges. Epidemiol. Rev. 2012; 34 (1): 129–144. Reddy KJ, Menon KR, Thattil A. Academic stress and its sources among university students. Biomed J. 2018; 11(1). PubMed Abstract | Publisher Full Text Reference Source\n\nJordans MJD, Kaufman A, Brenman NF, et al.: Suicide in South Asia: A scoping review. BMC Psychiatry. 2014; 14(1): 1–9. Publisher Full Text\n\nReddy KJ, Menon KR, Thattil A: Academic stress and its sources among university students. Biom. J. 2018; 11(1): 531–537. Publisher Full Text Reference Source\n\nSharma K: The soaring rates of teen suicides: what can we learn? The times of India.2020. Reference Source\n\nCimini MD, Rivero EM, Bernier JE, et al.: Implementing an audience-specific small-group gatekeeper training program to respond to suicide risk among college students: A case study. J. Am. Coll. Heal. 2014; 62(2): 92–100. PubMed Abstract | Publisher Full Text\n\nSuicide is Preventable: NIMHANS Centre for well being.Reference Source\n\nWikipedia: South Asia.Reference Source\n\nPage MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71. Publisher Full Text\n\nKallabi B, Jose T, Nagaraj AKM, et al.: Supplementary material 3. Dataset. figshare. 2023. Publisher Full Text\n\nCochrane training: RevMan 5 download.Reference Source\n\nHiggins JP, Savović J; on behalf of the RoB2 Development Group et al.: Revised Cochrane risk-of-bias tool for randomized trials (rob2).2019.\n\nLong HA, French DP, Brooks JM: Optimising the value of the critical appraisal skills programme (CASP) tool for quality appraisal in qualitative evidence synthesis. Res. Methods Med. Health Sci. 2020 Sep; 1(1): 31–42. Publisher Full Text\n\nPluye P: Mixed kinds of evidence: synthesis designs and critical appraisal for systematic mixed studies reviews including qualitative, quantitative and mixed methods studies. Evid. Based Med. 2015 Apr; 20(2): 79. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBMJ best practice: What is grade?Reference Source\n\nPersaud S, Rosenthal L, Arora PG: Culturally informed gatekeeper training for youth suicide prevention in Guyana: A pilot examination. Sch. Psychol. Int. 2019; 40(6): 624–640. Publisher Full Text\n\nHashimoto N, Takeda H, Fujii Y, et al.: Effectiveness of suicide prevention gatekeeper training for university teachers in Japan. Asian J. Psychiatr. 2021; 60(March): 102661. PubMed Abstract | Publisher Full Text\n\nReis C, Cornell D: An Evaluation of Suicide Gatekeeper Training for School Counselors and Teachers. Prof. Sch. Couns. 2008; 11(6): 386–394. Publisher Full Text\n\nShannonhouse L, Lin YWD, Shaw K, et al.: Suicide intervention training for college staff: Program evaluation and intervention skill measurement. J. Am. Coll. Heal. 2017; 65(7): 450–456. PubMed Abstract | Publisher Full Text\n\nKallabi B, Jose T, Nagaraj AKM, et al.: Supplementary material 1. figshare. Figure. 2023. Publisher Full Text\n\nKallabi B, Jose T, Nagaraj AKM, et al.: Supplementary material 2. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "170502",
"date": "05 May 2023",
"name": "Sheela Pavithran",
"expertise": [
"Reviewer Expertise Chemotherapy and Breast Cancer"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTitle How effective is Suicide Prevention Programme (SPP) in preventing suicide among college students?\nThe review The authors have chosen an area of great concern to the present day - suicide among the adolescent/college students.\n\nObjectives are clearly articulated in the review.\n\nThe study population, intervention and the outcomes are presented clearly\nAuthors have used an exhaustive search strategy and included all the major sources of evidence, a grey literature search and hand search ensured inclusion of all the relevant interventional studies that used SPP among gatekeepers to prevent suicide among the college students. This offers room for replication of the study too.\nConceptual homogeneity could be established by the statistical methods mentioned.\n\nAs the study is need of the hour - the escalating incidence of suicide among the youth, a focused intervention by the key gatekeepers as appropriate is necessary.\n\nBased on the proposal presented here, the systematic review can b e approved.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "9706",
"date": "29 Nov 2023",
"name": "Tessy Treesa Jose",
"role": "Author Response",
"response": "Thank you for peer-reviewing our article. Titled “ Suicide prevention program (SPP) in South Asian Countries” is registered in PROSPERO."
}
]
},
{
"id": "170503",
"date": "10 May 2023",
"name": "Stuart Leske",
"expertise": [
"Reviewer Expertise Suicide prevention research and systematic reviews."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThank you for the opportunity to review this systematic review protocol. The review plans to examine the effectiveness of gatekeeper training for suicide prevention in college students in South Asian countries.\nAbstract, introduction: If the 703,000 figure is taken from WHO’s suicide estimates worldwide in 2019, it’s just 703,000 (not more), or you could say ‘over 700,000’.\nAbstract, introduction: What would be the reason for calling the intervention a suicide prevention program (SPP), rather than using the term ‘gatekeeper training’? Note that all of the previous reviews in this field use the latter term:\nYonemoto, N., Kawashima, Y., Endo, K., & Yamada, M. (2019). Implementation of gatekeeper training programs for suicide prevention in Japan: a systematic review. International journal of mental health systems, 13, 1-6.\n\nMorton, M., Wang, S., Tse, K., Chung, C., Bergmans, Y., Ceniti, A., ... & Rizvi, S. (2021). Gatekeeper training for friends and family of individuals at risk of suicide: a systematic review. Journal of community psychology, 49(6), 1838-1871.\n\nTorok, M., Calear, A. L., Smart, A., Nicolopoulos, A., & Wong, Q. (2019). Preventing adolescent suicide: A systematic review of the effectiveness and change mechanisms of suicide prevention gatekeeping training programs for teachers and parents. Journal of adolescence, 73, 100-112.\n\nNasir, B. F., Hides, L., Kisely, S., Ranmuthugala, G., Nicholson, G. C., Black, E., ... & Toombs, M. (2016). The need for a culturally-tailored gatekeeper training intervention program in preventing suicide among Indigenous peoples: a systematic review. BMC psychiatry, 16, 1-7.\n\nMo, P. K., Ko, T. T., & Xin, M. Q. (2018). School-based gatekeeper training programmes in enhancing gatekeepers’ cognitions and behaviours for adolescent suicide prevention: a systematic review. Child and adolescent psychiatry and mental health, 12, 1-24.\n\nBurnette, C., Ramchand, R., & Ayer, L. (2015). Gatekeeper training for suicide prevention: A theoretical model and review of the empirical literature. Rand health quarterly, 5(1).\n\nIsaac, M., Elias, B., Katz, L. Y., Belik, S. L., Deane, F. P., Enns, M. W., ... & Swampy Cree Suicide Prevention Team (12 members) 8. (2009). Gatekeeper training as a preventative intervention for suicide: a systematic review. The Canadian Journal of Psychiatry, 54(4), 260-268.\n\nHolmes, G., Clacy, A., Hermens, D. F., & Lagopoulos, J. (2021). The long-term efficacy of suicide prevention gatekeeper training: a systematic review. Archives of suicide research, 25(2), 177-207.\n\nYonemoto, N., Kawashima, Y., Endo, K., & Yamada, M. (2019). Gatekeeper training for suicidal behaviors: A systematic review. Journal of affective disorders, 246, 506-514.\n\nPerhaps you could say ‘gatekeeper training for suicide prevention’?\nAbstract, methods: I think you don’t need to mention PICO here, as it is within PRISMA-P.\nAbstract, methods: When mentioning ‘interventional studies’, you may need to specify study designs. Would these be any intervention study design, controlled or uncontrolled?\nAbstract, methods: If looking purely at effectiveness, the authors may not need all these study quality assessment tools. For example, the MMAT may not be needed if the authors don’t plan to synthesise qualitative data.\nIntroduction, first paragraph: You could probably say that suicide is a global public health issue, as it’s typically considered to be, rather than just a problem for psychiatry.\nIntroduction, first paragraph: Who does ‘today’s youth’ refer to? Is this in India or globally? Perhaps state where it ranks in the leading causes of death among these youth. The two sentences on youth may also need to be about all ages if this review does not look at gatekeeper interventions for youth specifically.\nIntroduction, first paragraph: I’m not sure what is meant by a ‘weak psychological system’, but you need to revise the language here to make this term more technical.\nIntroduction, second paragraph: The statement ‘The suicide rate is increasing every year’ is incorrect. WHO’s Global Health Estimates reported that ‘In the 20 years between 2000 and 2019, the global age-standardized suicide rate decreased by 36%’ -https://www.who.int/publications/i/item/9789240026643\nIntroduction, second paragraph: ‘The statement that 79% of the world’s suicide occurred in low and middle-income countries.’ Is a secondary citation in the document you cite. The primary citation is WHO data from 2016, and is actually 77% rather than 79%. I recommend instead citing https://www.who.int/publications/i/item/9789240026643. The updated figure for 2019 is 77%, the same as the 2016 figure but with a better citation.\nIntroduction, second paragraph: WISQARS would need to be referenced in the reference list. I understand that WISQARS is US only. You could instead cite the WHO global health estimates again, and paraphrase a statement like: ‘Suicide was the fourth leading cause of death in young people aged 15–29 years for both sexes’ https://www.who.int/publications/i/item/9789240026643. Reference 8 is a 2014 document, but is superseded now by these estimates.\nIntroduction, third paragraph: I think the first sentence of this just needs updating with the WHO report again. https://www.who.int/publications/i/item/9789240026643 It now looks like Sri Lanka has a higher rate for both sexes.\nIntroduction, third paragraph: I think reference 13 is outdated now, and the WHO global estimates for 2019 should be used instead. With regards to reference 14, I think you should look at the most recent review of gatekeeper training to see if studies from South Asia were included, as that is most relevant to your review and justifies why this new review is necessary.\nIntroduction, fourth paragraph: Best to avoid the word ‘commits’, and say ‘dies by suicide’ instead.\nIntroduction, fifth paragraph: It isn’t clear in the abstract that the review will be about college students only. Could you check that it is consistent? You also just need to cite citation 6 in the Wikipedia page, which is the Encyclopedia of Modern Asia.\nMethods, types of studies: Is it possible that the authors can include studies in languages they speak, which might include some languages other than English? This would be a major strength of the review if you could do this and found studies in your languages.\nMethods, outcome measures: I think you need to describe the outcome measures more specifically. How would you measure suicide prevention and gatekeeper behaviour? And you may just need to specify what ‘knowledge’ and ‘attitude’ refer to…\nMethods, hand searching – do you mean included studies, when you say primary studies? It might be better to say ‘included’ studies, as primary studies mean every bit of original research you find.\nStudy records, data management: You just need to cite EndNote: https://support.clarivate.com/Endnote/s/article/Citing-the-EndNote-program-as-a-reference?language=en_US\nData synthesis - What do you mean by the sensitivity and specificity of the included studies? Their ability to rule in and rule out what condition? What do you mean by ‘to track down the variables?’\nDiscussion – I’m not sure the first paragraph is necessary as it’d be good to talk about your review here.\nExtended data – you don’t need to include the PRISMA flow diagram at this stage.\nExtended data – with the search terms, you just need to clarify if this is for PubMed?\nI think you might need to make the case for why this review is necessary, as I’m not sure it will find a lot of studies. You could say that previous reviews last searched the literature in February 2017 (Yonemato et al., 2019) and May 2018 (Torok et al., 2019), and you know that studies have been published since. Or maybe these reviews were limited to developed settings, although I don’t think this would be the case.\nJust related to PRISMA-P, I couldn’t see:\nWho the guarantor is for the review\n\nA statement on funding\n\nThe section on outcomes and prioritization needs to discuss if any outcomes are primary and if any are secondary, and just describe the outcomes in more detail. I would see the PRISMA-P explanation and elaboration statement for an understanding of what you need to say here: http://www.bmj.com/content/349/bmj.g7647\n\nYou would need to talk about whether you wanted to assess meta-biases with for example, a funnel plot for publication bias. I’d encourage seeing the E and E statement on this item again: http://www.bmj.com/content/349/bmj.g7647\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": [
{
"c_id": "9707",
"date": "29 Nov 2023",
"name": "Tessy Treesa Jose",
"role": "Author Response",
"response": "Thank you for peer-reviewing our article. Abstract, introduction: If the 703,000 figure is taken from WHO’s suicide estimates worldwide in 2019, it’s just 703,000 (not more), or you could say ‘over 700,000’. The authors are thankful for your kind suggestion. As per the suggestions, modifications are carried out in the revised manuscript. Abstract, introduction: What would be the reason for calling the intervention a suicide prevention program (SPP), rather than using the term ‘gatekeeper training’? In the present systematic review, suicide prevention program (SPP) refers to any teaching intervention/program in the form of a workshop/ different methods of teaching/ module/booklet to gatekeepers on suicide prevention in college students. Therefore, the authors used the term “suicide prevention program”. Abstract, methods: I think you don’t need to mention PICO here, as it is within PRISMA-P. The authors completely agree with the reviewer on this point. Abstract, methods: When mentioning ‘interventional studies’, you may need to specify study designs. Would these be any intervention study design, controlled or uncontrolled? We thank the reviewer for this comment. In this review, the authors will include any interventional study designs (controlled and uncontrolled). Abstract, methods: If looking purely at effectiveness, the authors may not need all these study quality assessment tools. For example, the MMAT may not be needed if the authors don’t plan to synthesise qualitative data. Modification is done accordingly. Introduction, first paragraph: You could probably say that suicide is a global public health issue, as it’s typically considered to be, rather than just a problem for psychiatry. We would like to thank the reviewer for your kind suggestion. Modifications are made in the revised manuscript. Introduction, first paragraph: Who does ‘today’s youth’ refer to? Is this in India or globally? Perhaps state where it ranks in the leading causes of death among these youth. The two sentences on youth may also need to be about all ages if this review does not look at gatekeeper interventions for youth specifically. We thank the reviewer for this comment. This sentence is restructured. Introduction, first paragraph: I’m not sure what is meant by a ‘weak psychological system’, but you need to revise the language here to make this term more technical. We thank the reviewer for this comment. Modifications are made accordingly. Introduction, second paragraph: The statement ‘The suicide rate is increasing every year’ is incorrect. WHO’s Global Health Estimates reported that ‘In the 20 years between 2000 and 2019, the global age-standardized suicide rate decreased by 36%’ -https://www.who.int/publications/i/item/9789240026643 We thank the reviewer for this comment. This sentence is removed from the revised manuscript. Introduction, second paragraph: ‘The statement that 79% of the world’s suicide occurred in low and middle-income countries.’ Is a secondary citation in the document you cite. The primary citation is WHO data from 2016, and is actually 77% rather than 79%. I recommend instead citing https://www.who.int/publications/i/item/9789240026643. The updated figure for 2019 is 77%, the same as the 2016 figure but with a better citation. We would like to thank the reviewer for your kind suggestion. Modifications are made accordingly. Introduction, second paragraph: WISQARS would need to be referenced in the reference list. I understand that WISQARS is US only. You could instead cite the WHO global health estimates again, and paraphrase a statement like: ‘Suicide was the fourth leading cause of death in young people aged 15–29 years for both sexes’ https://www.who.int/publications/i/item/9789240026643. Reference 8 is a 2014 document, but is superseded now by these estimates. We thank the reviewer for the valuable suggestion. Modifications are made accordingly. Introduction, third paragraph: I think the first sentence of this just needs updating with the WHO report again. https://www.who.int/publications/i/item/9789240026643 It now looks like Sri Lanka has a higher rate for both sexes. We thank the reviewer for the suggestion. India and Sri Lanka (12.9%) have the highest suicide rate in the Southeast Asia region. Introduction, third paragraph: I think reference 13 is outdated now, and the WHO global estimates for 2019 should be used instead. With regards to reference 14, I think you should look at the most recent review of gatekeeper training to see if studies from South Asia were included, as that is most relevant to your review and justifies why this new review is necessary. We thank the reviewer for the suggestion. Unfortunately, the authors could not find out the most recent reviews of gatekeeper training in South Asian Countries. Reference 13 deals with the comparison of suicide rates between high-income countries and Asia whereas “Suicide Worldwide in 2019: Global Health Estimates” specifies a comparison between Africa, Europe, and Southeast Asia. Introduction, fourth paragraph: Best to avoid the word ‘commits’ and say ‘dies by suicide’ instead. Thank you for notifying me of this point. The text is modified as per the reviewer’s suggestion in the revised manuscript. Introduction, fifth paragraph: It isn’t clear in the abstract that the review will be about college students only. Could you check that it is consistent? You also just need to cite citation 6 in the Wikipedia page, which is the Encyclopedia of Modern Asia. We thank the reviewer for the constructive suggestion. Modifications are made accordingly. We have not taken citation 6 from the Wikipedia page. Methods, types of studies: Is it possible that the authors can include studies in languages they speak, which might include some languages other than English? This would be a major strength of the review if you could do this and found studies in your languages. The authors completely agree with the reviewer on this point. Methods, outcome measures: I think you need to describe the outcome measures more specifically. How would you measure suicide prevention and gatekeeper behaviour? And you may just need to specify what ‘knowledge’ and ‘attitude’ refer to… Modifications are made accordingly. Methods, hand searching – do you mean included studies, when you say primary studies? It might be better to say ‘included’ studies, as primary studies mean every bit of original research you find. Modifications are made accordingly. Study records, data management: You just need to cite EndNote: https://support.clarivate.com/Endnote/s/article/Citing-the-EndNote-program-as-a-reference?language=en_US Modifications are made accordingly. Data synthesis - What do you mean by the sensitivity and specificity of the included studies? Their ability to rule in and rule out what condition? What do you mean by ‘to track down the variables?’ Thank you for notifying me of this point. This paragraph is restructured. Discussion – I’m not sure the first paragraph is necessary as it’d be good to talk about your review here. We thank the reviewer for the kind suggestion. Modifications are made accordingly. Extended data – you don’t need to include the PRISMA flow diagram at this stage. The authors completely agree with the reviewer on this point. Extended data – with the search terms, you just need to clarify if this is for PubMed? Search terms are for all databases. I think you might need to make the case for why this review is necessary, as I’m not sure it will find a lot of studies. You could say that previous reviews last searched the literature in February 2017 (Yonemato et al., 2019) and May 2018 (Torok et al., 2019), and you know that studies have been published since. Or maybe these reviews were limited to developed settings, although I don’t think this would be the case. As per the authors’ knowledge, few reviews have been done to estimate the prevalence of suicide, and factors associated with suicide among students in South Asia. But this review will be done to determine the effectiveness of suicide prevention program (SPP) on the improvement of knowledge, attitude, and gatekeeper behaviour among gatekeepers in South Asian countries so that the number of suicide cases will be reduced among college students in South Asia countries. Just related to PRISMA-P, I couldn’t see: Who the guarantor is for the review : Corresponding author. A statement on funding : Modification is made accordingly. The section on outcomes and prioritization needs to discuss if any outcomes are primary and if any are secondary, and just describe the outcomes in more detail. I would see the PRISMA-P explanation and elaboration statement for an understanding of what you need to say here: http://www.bmj.com/content/349/bmj.g7647 : Modification is made accordingly. You would need to talk about whether you wanted to assess meta-biases with, for example, a funnel plot for publication bias. I’d encourage seeing the E and E-statement on this item again: http://www.bmj.com/content/349/bmj.g7647 : Modification is made accordingly."
}
]
}
] | 1
|
https://f1000research.com/articles/12-425
|
https://f1000research.com/articles/12-565/v1
|
30 May 23
|
{
"type": "Opinion Article",
"title": "Endocranial volumes and human evolution",
"authors": [
"Ian Tattersall"
],
"abstract": "Enlarging brains have been held up as the classic (if not the only) example of a consistent long-term trend in human evolution. And hominin endocranial volumes certainly expanded four-fold over the subfamily’s seven-million-year history, while on a very coarse scale later hominids showed a strong tendency to have larger brains than earlier ones. However, closer scrutiny of this apparent trend reveals that it was extremely episodic and irregular, a fact that argues against the notion that it was driven by social interactions internal to the hominin clade. In addition, an overall tendency to brain volume increase was expressed independently and concurrently within at least three separate lineages of the genus Homo – suggesting that, whatever the exact influences were that promoted this global trend, they need to be sought among stimuli that acted comprehensively over the entire vast range of periods, geographies and environments that members of our subfamily occupied. Significantly, though, the dramatic recent shrinkage of the brain within the species Homo sapiens implies that the emergence of modern human cognition (via the adoption of the symbolic information processing mode, likely driven by the spontaneous invention of language in an exaptively enabled brain) was not the culmination of the overall hominin trend towards brain enlargement, but rather a departure from it.",
"keywords": [
"human",
"hominin",
"evolution",
"brain expansion",
"endocranial volumes",
"cognition"
],
"content": "Introduction\n\nHominin endocranial volumes, particularly as corrected for body size, have long held an iconic position in narratives of human evolution. Partly this is because the large brain of Homo sapiens is not only one of our species’ most conspicuous morphological characteristics, but is also one that is somehow associated with our most prized behavioral attribute, namely the unique way in which we think. And partly it is because endocranial volume, its close proxy, is both easily measurable and fairly readily available from fossils that represent nearly all chronological periods of human evolution. But perhaps above all, endocranial volume is iconic in paleoanthropology because it is one of the few hard-tissue hominin characteristics that seems to provide support for the existence among hominins of a long-term evolutionary trend of the kind Charles Darwin (1859) told us we should expect to find in the fossil record generally. This is important because, ever since the ornithologist Ernst Mayr sternly lectured us in 1950 that the human ecological niche was too broad to permit more than one hominin species to exist in the world at any one time, and that human evolution must perforce have consisted of the steady modification over time of a single lineage (Mayr, 1950), paleoanthropologists have been mesmerized by a strictly gradualist notion of human evolution ultimately harking back to a time when a useful hominin fossil record barely existed (see Tattersall, 2009). This obsession is, conspicuously, not shared with other areas of vertebrate paleontology, in which the focus is nowadays typically upon how the rich taxic diversity of the living world was generated; and the unfortunate result of the insular paleoanthropological preoccupation with slow transformation has been a staunchly minimalist approach to hominin systematics.\n\nThis minimalist bias, which favors stuffing the maximum number of fossils into the minimum number of analytical units (species), has been steadfastly maintained even as evidence has increasingly accumulated of a remarkably wide range of morphologies in the hominin fossil record (Tattersall, 2022): a range that cannot plausibly be contained within any linear model of hominin evolution. Nonetheless, the linear perspective tenaciously persists; and no hominin feature has seemed to justify it more strongly than the apparently inexorable enlargement of the hominin brain (Figure 1) that has taken place over the past few million years (if, indeed, there is such a thing as the hominin brain, in contradistinction to the brains of multiple species belonging to the hominin subfamily). On the face of it, the implication of steady brain size increase would appear to be that, as the millennia passed, “smarter” individuals simply out-reproduced “dumber” ones: a conclusion that might well seem self-evident to members of a species that prides itself above all on its “intelligence” (however one might care to measure that elusive quality). Yet it appears increasingly likely that the evolutionary message actually encoded in this averaged-out brain size expansion is entirely different.\n\nThe trend is superficially accurate, but it suffers from an inadequate taxonomy and disguises a more irregular underlying pattern. From Tattersall (2008).\n\n\nEvolutionary process and the fossil record\n\nBefore we ask whether or not the notion that our “intelligence” was gradually perfected over the eons has led us up a blind alley, we need first to inquire whether the reigning linear/minimalist expectation is itself realistic or not. And that means looking briefly at the nature of the evolutionary process that ultimately transformed a relatively unremarkable Miocene ape ancestor into the “know thyself” hominin of today. Incidentally, Linnaeus (1758) may have thought he was simply sidestepping an awkward issue by replacing an expected diagnosis of Homo sapiens with that rather cryptic exhortation, but his advice actually reflects directly on the uniquely explicit nature of modern human knowing.\n\nBy the middle of the twentieth century, anglophone evolutionary thought was pretty thoroughly dominated by a “hardened” (Gould, 1983) version of the New Evolutionary Synthesis. This held that virtually all evolutionary phenomena could be ascribed to the gradual effects of natural selection within lineages, as environmental forces gradually honed the adaptations of each one. The lineage splitting that was self-evidently necessary to give rise to the biodiversity so glaringly characteristic of the living world was generally viewed as a special case of the same gradual process; and the general effect of this bias was the emphasis of gradual transformative change at the expense of splitting, as in the case of Mayr’s (1950) diatribe on the paleoanthropological record.\n\nIt took several decades for most paleontologists to realize that this description of the evolutionary process (or more accurately, processes) was actually a rather breathtaking oversimplification. Not only did it transpire that in the past environments had typically changed erratically, and on short timescales that would have rendered any adaptations rapidly obsolete, but it was also soon recognized that it was the fates of species as wholes, rather than of individuals within them, that most importantly determined macroevolutionary patterns. It is after all of little advantage in the long run to be the best-adapted member of your species in some respect, if that entire species is going extinct as a result of environmental change or because of new competition.\n\nWhat is more, the individuals on whom classical natural selection is expected to act are complex bundles of overwhelmingly polygenic characteristics that are typically influenced by massively pleiotropic genes, so that the favoring by natural selection of one particular attribute will probably come at the cost of destabilizing others that may be equally or even more important to individual success. And whatever the molecular mechanism of change, it is clearly the entire organism that succeeds or fails in the ecological struggle, not its individual parts: a reality that makes it fruitless to try to follow the “evolution of the brain,” or the “evolution of the foot,” independently of the taxa in which those structures are embedded. Given all this, it is hardly surprising that, rather than acting as a powerful agent of gradual directional change, classical natural selection has emerged as more typically a force for homeostasis, trimming off the less fortunate extremes from populations that are thereby kept fit to participate in the unceasing struggle for ecological space (see Tattersall, 2022). In practical terms, this means that in seeking the sources of phylogenetic novelties and the agents of their natural triage, it makes most sense to look at whole species or populations, and at the competition that takes place among those larger-scale actors on the ever-shifting ecological stage.\n\nSadly, adopting this perspective only increases our operational difficulties. This is because we paleoanthropologists are the victims not only of a history that has largely eschewed the vital matter of systematic diversity in favor of linear schemes, but also of a particularly acute expression of the complications that always lurk when systematists attempt to recognize species in the fossil record. Those difficulties arise because none of the three key attributes of fossils (time, place, and morphology) is closely associated with speciation (Tattersall, 1986); and the resulting uncertainties will inevitably be especially severe in the case of a very recently evolved and closely-knit group such as Homininae, in which both time scales and degrees of morphological differentiation will often be minimal. The unfortunate combination of history with operational impediments has led to the woeful absence of the reliable and readily testable phylogeny of our subfamily that we need to underpin our further inquiries. And while most paleoanthropologists still tend to dismiss concerns about the alpha taxonomy of the hominins as merely “quibbling about names,” it remains true that if you don’t know who the actors are, you will never understand the play. And almost certainly, the known human fossil record actually contains more species – more independent evolutionary actors – than we are currently able to recognize.\n\nFortunately, the underestimation of species diversity will not distort the overall form of a phylogeny as gravely as the spurious impression of branching that is imparted by excessive splitting (Tattersall, 1992). Nonetheless, if we cannot accurately know how individual fossils should be properly classified, we will remain unable to determine either the morphological or temporal limits of the species to which they belong; and if our bias is towards underestimation, we will end up with a smaller number of recognized taxa that, at the extreme, might approximate uncomfortably to a linear pattern, particularly if we are unduly influenced by how ancient we believe the fossils concerned to be. In paleoanthropology, the received linear perspective has encouraged us to see fossils essentially as chains running through time, which in turn has deeply influenced their nomenclature and classification – despite the fact that morphology alone has a necessary connection to phylogenetic relationship (Eldredge and Tattersall, 1975). The unpalatable fact that we are working with an inadequate phylogeny thus severely limits what we can say about the history of any single and inherently variable morphological attribute – in this case, endocranial volume – in human phylogeny. Nonetheless, it is clear that our inherited attitudes toward human evolution have been a source of important source of distortion in our perceptions of the process by which we Homo sapiens became the entirely unprecedented cognitive entity we are today.\n\n\nEndocasts and archaeology\n\nWhere not credited otherwise, the brain volumes (and species averages) cited below are taken from Holloway et al. (2004). These values were obtained from the water displacement of physical endocasts (which often required reconstruction prior to measurement). More recently, neurocranial volumes have more commonly been obtained by digital extraction from CT scans (see Weber, 2014), a procedure that also commonly requires varying degrees of reconstruction. Occasionally the two methods produce significantly different results; for example, the Ngawi calvaria from Java was estimated to be 870 ml by water displacement (Holloway et al., 2004), and 959 ml by digital extraction (Kaifu et al., 2015). In general, however, it is probable that errors in volume estimation are likely to be more heavily influenced by the condition of the individual specimen than by the measurement method used.\n\nRaw brain sizes are sometimes converted into Encephalization Quotients (EQs) by calculating the ratio of the measured brain volume to expected body volume. However, this fairly simple expedient actually introduces a variety of complications, not least among them the choice of the appropriate regression for deriving the expected value. Additionally, in the case of measured fossil crania, a) body size is usually unknown, and b) it is not possible to closely determine the relative volumes of different brain regions, let alone such physiological features as neuron densities. And while there are numerous potentially informative convolutions and fissures on the surface of the brain, paleoneurologists actually remain the most disputative members of the already highly fractious profession of paleoanthropology.\n\nThese numerous sources of uncertainty mean that neurocranial endocasts have yet to come anywhere close to providing us with even the most basic information on brain function and “intelligence” that we would ideally wish to have when addressing the evolution of human cognition. However, when we are seeking the origins of the unique modern cognitive style the biological record gives us nowhere else to turn; and few would contest that brain volume must mean something, especially when it can be related in some way to body size. It is an element that can never be forgotten, even when its exact cognitive implications are impossible to know. The resulting uncertainty makes it fortunate that we also have the archaeological record, the material testament to ancient human behaviors subsequent to the invention of stone tool making. Because, as frustratingly selective and incomplete as it is, this record does enable us to glimpse some ancient human cognitive styles at work.\n\n\nBrain volumes in early human evolution\n\nThe earliest putatively hominin species yet documented in the fossil record are represented by a rather motley and generally fragmentary assortment of African remains that are attributed to four species and dated to between about seven and four Ma (million years ago). Only two of those very early species furnish any information on endocranial volume, and one alone is well enough known to support even a guess about encephalization. The earlier of them, Sahelanthropus tchadensis from Toros-Menalla in the central-western African Republic of Chad, dates from around 7 Ma (Brunet et al., 2002; Lebatard et al., 2008) and is the most ancient hominoid yet proclaimed to be hominin (Figure 2). Virtual reconstruction of the single cranium available yielded an endocranial volume estimate of 360–370 ml (Zollikofer et al. 2005), well below the modern chimpanzee average of 405 ml. Unfortunately, the affinities of a supposedly associated partial postcranial skeleton remain robustly debated (Macchiarelli et al., 2020; Daver et al., 2022), although on skull size it seems reasonable to suppose that the individual’s body weight may have been toward the lower end of the very broad (30–60 kg) chimpanzee range. The other relevant “early hominin” species is Ardipithecus ramidus (White, Suwa and Asfaw 1994, 1995), a much later form known from a handful of eastern African sites and dated to between about 4.5 and 4.3 Ma. The cranial volume of the one reasonably complete individual of this species is reported to be in the region of 300–350 ml (White et al., 2009), implying a rather modest degree of encephalization (plausibly comparable to that of Sahelanthropus), since at about 50 kg her body weight was plausibly within the chimpanzee range (Lovejoy et al., 2009). All in all, then, the little we currently know about the brains of the most ancient hominins supports the idea that in this early period hominin encephalization, and by extension “intelligence,” compared a little unfavorably with that of today’s great apes, which recent studies have shown to be remarkably sophisticated creatures (e.g., Krupenye et al., 2016).\n\nFrom Tattersall (2022).\n\nNot a great deal had apparently changed in respect of brain size by the time the “australopiths” (genera Australopithecus and Paranthropus) appeared on the scene after about 4.2 Ma (see Table 1). That is, at least, the implication of the one cranium we know of the earliest australopith species, Australopithecus anamensis. This has an estimated endocranial volume of around 370 ml (Haile-Selassie et al., 2019), closely akin to that of Sahelanthropus. If the australopiths as currently conceived are a genuinely monophyletic group (not a sure bet), brain enlargement, or even a tendency towards it, was evidently not one of its founding apomorphies.\n\n1 Includes A. prometheus.\n\n2 Turkana only, see text.\n\n3 Java and China only, includes Ngandong.\n\n4 Europe and Africa only, including China yields a mean of 1,248 ml.\n\n5 Provisional nomenclature.\n\n6 Misclassified as Homo.\n\n7 Misclassified as Homo, arbitrarily includes all Dmanisi hominins.\n\nIt is only with the reported mean endocranial volume of the much better-known (and briefly coeval: approximately 3.9 to 3.0 Ma) Australopithecus afarensis (446 ml) that we find a noticeable inflection in the fossil record. That mean value, which is fairly close to those of the other non-anamensis australopith species in the 3.9 to 1.5 Ma time range (Table 1), represents a volumetric increase of around 20 percent relative to Sahelanthropus and Ardipithecus, and an excess of about nine percent relative to the chimpanzee average of 405 ml. What was happening within the australopith radiation to promote and metabolically sustain this upward tick in brain size (and encephalization, given that body weights were likely within the general chimpanzee range) is hard to say, and there is certainly no very clear correlation with time. For example, whereas the earlier “robust” species Paranthropus aethiopicus has a lower mean endocranial volume (432 ml) than the later P. boisei (515 ml) and P. robustus (493 ml), the single value of 420 ml reported for the relatively recent (2 Ma) “gracile” species A. sediba is below the adult range reported for its earlier close relative A. africanus (although the endocast itself apparently shows more “humanlike” orbitofrontal proportions: Carlson et al., 2011).\n\nWhat might be even more puzzling, especially to anyone given to linear thinking, is that it is hard to associate brain size with what was arguably the most consequential of all cognitive innovations in human evolution. This was, of course, the invention and manufacture of Mode 1 stone tools, a practice that by the standards of the day made extreme cognitive demands, and that was introduced by one, or perhaps more, australopith species in the period before about 2.8 Ma (Plummer et al., 2023). Besides being demonstrably beyond the behavioral range of today’s great apes, this new behavior would clearly have done a lot to promote the leap in dietary quality that brain enlargement metabolically required. However, especially if the slightly larger brain volumes of the later robust species were themselves related to greater body weights, this fateful innovation is conspicuously unassociated with any concomitant or subsequent brain size increases among the australopiths. And the single measurable individual of the 2.5 Ma species A. garhi, while presumptively associated with early cut-marked bones (De Heinzelin et al., 1999), has an endocranial volume of 450 ml, basically identical to the 446 ml mean (Table 1) of its earlier close relative A. afarensis.\n\nIn Leakey et al. (2001), Meave Leakey and colleagues created the new genus and species Kenyanthropus platyops for a crushed but distinctively flat-faced 3.5 Ma hominin cranium found to the west of Lake Turkana in northern Kenya. Its endocranial volume could not be precisely measured but was estimated to lie in the australopith range. The specimen’s describers also called attention to resemblances with the much later (1.9 Ma) and larger-brained (752 ml) KNM-ER 1470 specimen from the other side of the lake, which many researchers were by then allocating to Homo rudolfensis. If, as seems likely, the two fossils do indeed belong to the same clade distinct from the australopiths, in this case we can justify perceiving a modest trend toward neurocranial enlargement over time.\n\n\nBrain volumes in the genus Homo\n\nOur lingering fealty to Ernst Mayr’s (1950) linearity has assured the persistence of a conventional wisdom whereby all hominin fossils other than those classified as Kenyanthropus, Paranthropus or “earliest hominins,” must belong either to Australopithecus or Homo. This makes the allocation of a fossil to either genus essentially a matter of exclusion (“it’s not Australopithecus, so it must be Homo,” and vice versa). And it is certainly the only plausible explanation for the inclusion in the genus Homo (see for example Lordkipanidze et al., 2013) of the 1.9 Ma individuals from the Caucasian site of Dmanisi, the earliest hominin fossils we have from outside Africa. These have no clear morphological claim to membership in any genus that is defined by H. sapiens (Schwartz et al., 2014); and indeed, they constitute a rather heterogeneous assemblage that is united principally by small brain volumes averaging 640 ml (range 546–775 ml, n = 5). This is admittedly an unremarkable set of values for any hominin of their period, and it is only marginally greater than the australopith range. Diagnosis by exclusion is even more evident in the cases of the remarkably recent, small-bodied, and small-brained hominin species dubbed H. floresiensis (Brown et al., 2004) and H. naledi (Berger et al., 2015). The former is dated to around 100 thousand years ago (Ka) and has a single endocranial value of 426 ml (Kubo et al., 2013); the latter dates from around 300 Ka (Dirks et al., 2017) and has brain sizes ranging from 465 to 560 ml (Garvin et al., 2017, n = 2). Most probably, the distinctive hominin lineages represented by these two species primitively maintained relatively low brain to body size ratios. But whatever the exact reality may be, we have absolutely nothing to gain (in terms of understanding brain size trends, or anything else) by shoveling any of the hominins just discussed into the genus Homo just because they are patently not Australopithecus. Until the alpha taxonomy here has been properly sorted out, these fossils are better omitted from any discussion of brain size trends within the genus Homo.\n\nUntil Louis Leakey, Phillip Tobias and John Napier described Homo habilis from Tanzania’s Olduvai Gorge some 60 years ago (Leakey et al., 1964), the concept of “early Homo” was exemplified by Homo erectus from Trinil (endocranial volume 940 ml), Sangiran (mean: 917 ml, range 813–1,059 ml, n = 5) and Ngandong (mean: 1,148 ml, range 1013–1231 ml, n = 6) in Java, and Zhoukoudian in China (mean: 1,046 ml, range 915–1,225 ml, n = 4). All were thought at the time to date from the early Middle Pleistocene, and all comfortably exceeded Arthur Keith’s (1948) 750 ml “cerebral Rubicon” for the achievement of “humanity,” by which he broadly meant membership in the genus Homo. And although Leakey and colleagues’ new hominin was the presumptive manufacturer of the Mode 1 stone tools found at Olduvai (hence the name), its allocation to the genus Homo was and remains entirely problematic. Just for a start, it was dated to a then-staggering 1.8 Ma (Leakey et al., 1961), right at the beginning of the Pleistocene; and among its type materials were two partial braincases that had estimated volumes of 687 and 650 ml., only very modestly out of the australopith range.\n\nUnsurprisingly, then, general acceptance of Homo habilis came only a decade later, as a result of discoveries in northern Kenya’s Turkana Basin by researchers who shared Leakey’s agenda (see discussion in Tattersall, 2009). This acceptance required entirely disassociating membership in our genus from any rational appraisal of morphology, and the floodgates were opened. A motley assortment of fossils dating from over 2 Ma to around 1.5 Ma have now been assigned to Homo habilis, with the six available cranial volumes estimated at between 582 and 687 ml. Those who still regard the Kenyanthropus rudolfensis specimens as belonging to Homo habilis would augment this range with two additional endocranial volumes: 752 and 825 ml. However, the two endocranial volumes recorded for the coeval K. rudolfensis are both well above anything attributed to H. habilis. This not only strongly supports the notion of multiple taxa in this assemblage, but also suggests a stronger tendency to brain expansion in the Kenyanthropus lineage than we see in the rump attributed to Homo habilis.\n\nThe species Homo erectus is defined by the 940 ml Trinil skullcap, which is of very distinctive morphology and is now plausibly dated to around 800 Ka (Hilgen et al., 2023). With this specimen we can very generally associate the slightly older or approximately coeval Sangiran (1.3–1.0 Ma, 917 ml) and Zhoukoudian (770 Ka, 1,046 ml) fossils, and the much younger and larger (ca. 110 Ka, 1148 ml) Ngandong materials (possibly of a different but closely related species: Schwartz and Tattersall, 2000), plus the crania from nearby Sambungmacan (probably 500 Ka or slightly younger; mean: 986 ml, range 917–1,035 ml, n = 3). Among the Javan specimens, at least, there appears to be a time-transgressive trend: crania from the Sangiran Dome and Trinil, the earliest sites, show the lowest volumes overall; the temporally intermediate Sambungmacan fossils exhibit an intermediate mean value; and the much younger Ngandong specimens are substantially larger yet. It should be noted that there is overlap in the ranges up the Javan succession, and that the Zhoukoudian specimens appear on average more voluminous than those of comparable age from Java; but within the clade as a whole, the temporal trend toward enlargement is nonetheless striking.\n\nDuring the 1970s a succession of startling eastern African discoveries was made of hominin fossils that dated between <2.0 and 1.5 Ma and that showed larger brains than almost anything previously known from the time. After a period of limbo as Homo sp., these fossils were attributed to “early African Homo erectus” (e.g. Leakey and Walker, 1976). More reasonably, many would now assign them to the species Homo ergaster (Groves and Mazak, 1975); but even so, they make up a very unwieldy assemblage, and it would almost certainly be highly misleading to cite a single endocranial mean for everything that has been called Homo ergaster or “early African Homo erectus.” Early in this period (1.78–1.6 Ma) the Mode 2 stone tool making tradition appeared; but beyond some degree of refinement of handaxe manufacture over time there is subsequently very little evidence of other conceptual advances.\n\nThe first two crania East African crania to be referred to Homo erectus or H. ergaster were the East Turkana KNM-ER 3733 and 3883 calvariae (Leakey and Walker, 1976, both ca. 1.6 Ma: 848 and 804 ml., respectively). The endocranial volume of the KNM WT-15000 “Nariokotome Boy” cranium from West Turkana (1.5–1.6 Ma), described a decade later, is a broadly comparable 900 ml. But while the three crania are close in age, size, and geography, the morphological differences among them are striking. Even more remarkably, to one degree or another the same observation holds true for other eastern African crania generally assigned to this group. Those heterogeneous fossils include the KNM-ER 42700 calvaria from Ileret in East Turkana (~1.55 Ma, 721–744 ml: Spoor et al., 2007; its tiny volume may be at least partially attributable to slightly subadult status: Baab, 2008); the Olduvai OH 9 fossil (1.2–1.4 Ma, 1067 ml), the earliest known hominin with a cranial volume in excess of 1000 ml; the Daka calvaria NME BOU-VP 2/66 from Ethiopia (~1 Ma, 995 ml), the Buia cranium UA 31 from Eritrea (~1 Ma, 995 ml: Bruner et al., 2016); and the Olorgesailie partial calvaria KNM OG 45500 from southern Kenya (~900 Ka, 700–800 ml: Potts et al., 2004). In this rather motley assortment of fossil hominins it is hard to detect any consistent trend in endocranial volume over time. Indeed, if anything there is a tendency for later clearly adult individuals to have smaller brains. On current evidence it is impossible to say to what extent that effect might be due to non-randomly sampled smaller body sizes. But while this morphologically heterogenous eastern African assemblage of specimens almost certainly harbors representatives of multiple lineages (the temporal and morphological limits of which cannot be guessed), if as some believe just the single species Homo ergaster was involved, it was evidently a species that essentially showed stasis in brain volumes rather than any tendency toward expansion over its long (800 kyr) time span.\n\nWhere we do get a signal of brain enlargement is with the arrival of the species Homo heidelbergensis. This hominid had already appeared in both Africa and Europe by around 600 Ka, and it seems to have been gone by about 200 Ka (maybe rather less in eastern China: see below). However, dating for many important specimens remains very approximate. Exactly how the distinctive new lineage emerged from within the medley of earlier hominins is unclear; but with a mean endocranial volume of 1,227 ml and a range of 1,165–1,325 ml for the European Arago, Ceprano, and Petralona fossils plus the African Bodo, Kabwe, and Saldanha crania (a greatly reduced sample compared to that used by Holloway et al., 2004), there is no doubt that members of the new species boasted significantly larger brains than ever before. This brain expansion, and the cognitive advance it implies, does correlate broadly with a significant inflection in the archaeological record: it is during the tenure of Homo heidelbergensis, for example, that for the first time we encounter evidence of throwing spears, hafted tools, constructed shelters, Mode 3 tools, and so forth.\n\nHomo heidelbergensis, which is also known from fossils found in eastern Asia (Dali, possibly ~550 Ka, 1,120 ml: Wu, 1981; Jinniushan, ~260 Ka, 1,330 ml: Rosenberg et al., 2006; and possibly Harbin [aka H. longi], 146 Ka, 1,420 ml: Ni et al., 2021), was the first cosmopolitan human species. And very generally, despite generally poor age controls, it appears that its later representatives tended to have larger brains than the earlier ones, a tendency particularly apparent in China, especially if the Harbin cranium is properly attributed to H. heidelbergensis. What is more, as apomorphic as its known representatives may be, many believe (in the absence of any better fossil alternatives) that in some general sense H. heidelbergensis was the ultimate source of later humans. If (a big “if”) this is correct, in Europe and western Asia some early and very plesiomorphic version of H. heidelbergensis gave rise, without any detectable change in average brain size, (Table 1) to the lineage represented by the 448 Ka (Demuro et al., 2019) hominins from the Sima de los Huesos in Spain’s Atapuerca Massif (mean 1,233 ml, range 1,057–1,436 ml, n=14: Poza-Rey et al., 2019). In good linear fashion, the Sima hominins were initially assigned to the (morphologically very distinct) H. heidelbergensis; but their describers have since relented, admitting them to a separate lineage (Arsuaga et al., 2014) that foreshadowed Homo neanderthalensis. The Sima hominins have not yet been formally given their own species name; but pending closer scrutiny of the matter one might provisionally call them H. steinheimensis, applying the name borne by the rather later (<350 Ka) Steinheim cranium from Germany with which they share some Neanderthal-like aspects of facial morphology. The endocranial volume of the German fossil was, however, estimated by Prossinger et al. (2003) to be around 1,140 ml which, although just within the lower limit of the Sima sample, is considerably below its mean.\n\nHomo neanderthalensis itself was well established in Europe by about 175 Ka (Biache St Vaast: Guipert et al., 2011, ca 1200 ml), or even considerably earlier (Stringer and Hublin, 1999) if the English Swanscombe braincase (1,325 ml) is properly attributed to this species. Before its extinction after about 40 Ka, this hominin left behind extensive archaeological and fossil records. Over the years, Neanderthal fossils have been rearranged into various morphs; but the species itself was highly distinctive, and the mean endocranial value of 25 adult Neanderthal individuals from all parts of its temporal and geographical distributions is 1,415 ml (Table 1; the values used are taken from Holloway et al., 2004, but do not include all individuals identified as Neanderthal therein), with a range of 1,172 to 1,740 ml. Earlier Neanderthal individuals tended to have lower endocranial volumes than later ones; but the temporal trend within the species is not clear-cut. Within the larger Neanderthal clade, the major events we can infer evidently involved substantial morphological innovation; quite likely, very rapid increases in mean endocranial size heralded the appearances of both H. steinheimensis and H. neanderthalensis.\n\nIt is clear that Homo sapiens originated in Africa. And, purely for want of a better alternative, we can again surmise that its lineage originated in some plesiomorphic early population of H. heidelbergensis. The thankfully now largely defunct category of “Archaic Homo sapiens” (which embraced forms as various as the Ndutu partial cranium, ~350 Ka and ~1,100 ml: Rightmire, 1983; the Ngaloba LH 18 cranium, 120 Ka and 1,200 ml: Magori and Day, 1983; the Florisbad face and frontal (aka H. helmei), ~260 Ka: Grün et al., 1996, and somewhere between 1,280 and 1,450 ml: Bruner and Lombard, 2020; and the Jebel Irhoud 1 and 2 crania, ~300 Ka: Richter et al. 2017, and 1,375 and 1,467 ml respectively: Neubauer et al. 2018) helped divert attention from a remarkable morphological diversity among African members of the genus Homo in the latter part of the Pleistocene; but what is perhaps even more noteworthy is that at present there is nothing in the fossil record that seems to anticipate the highly apomorphic structure of the modern human skull and postcranial skeleton (see Tattersall and Schwartz, 2008). Unlike the Neanderthals, then, modern humans as yet have no known immediate fossil precursors. Nonetheless, we can very safely surmise that the notably large-brained earliest fossil Homo sapiens from Africa, including the Ethiopian Omo 1 (230 Ka: Vidal et al., 2022, but unfortunately too fragmentary for exact assessment of brain size), and Herto 1 crania (~160 Ka and ~1,450 ml: White et al., 2003), were ultimately descended from much smaller-brained forerunners. In other words, something like the trend toward increasing brain volume we have noted happening independently in eastern Asian Homo erectus and in the European Neanderthal lineage, must also have occurred autonomously in Africa as well.\n\nExactly what it was that propelled the metabolically expensive but common trend among discrete hominin lineages spanning a great range of time, geographies, and environments, is currently anybody’s guess – although it is hugely tempting to associate the brain size expansion involved with a generalized increase in “intelligence” that we see also reflected in the complexifying archaeological record. It would not, however, explain the appearance of the qualitatively different symbolic cognitive mode that we see in Homo sapiens today. Or the remarkable decline in human endocranial volumes that seems to have occurred since the late Pleistocene.\n\n\nBrain volumes and cognition in Homo sapiens\n\nModern Homo sapiens processes information in what is almost certainly an entirely unique fashion that is qualitatively distinct from even its most direct precursors. We modern humans deconstruct our surroundings and experiences into a vocabulary of discrete mental symbols that we can shuffle around, according to rules, to make statements about the world not only as it is, but as it might be (see Tattersall, 2012). Unlike other organisms, which live more or less directly in the worlds with which nature presents them, we live for most of the time in the worlds that we reconstruct in our heads. This cognitive innovation is the basis of the formidable planning ability that has enabled us so rapidly and unprecedentedly to eliminate all of our hominin competition, and that also accounts both for the explicit nature of human knowledge and the unprecedented impact (intended or otherwise) that our species has had on the planet that (so far) supports it (see discussion in Tattersall, 2012). Counterintuitively, though, the adoption of the symbolic algorithm was followed by a significant reduction in human endocranial volume (Table 1). The mean volume of 29 Upper Paleolithic Homo sapiens braincases listed by Holloway et al. (2004) is 1,499 ml (range: 1,285–1,775 ml). This value is somewhat greater than the overall Neanderthal mean of 1,415 ml, although it is below the mean of 1,567 ml (range: 1,305–1,740 ml) for ten “Classic” and late eastern Neanderthals taken from the same list. Effectively, then, we can reasonably conclude that Neanderthals and Pleistocene Homo sapiens had brains of effectively the same size, probably even relative to body size. But the same source gives a mean value of 1,330 ml (range: 1,250–1,730 ml) for a sample of over 500 modern Homo sapiens, a value that represents an apparent reduction in average brain size of some 12.7 percent since the early days of our species.\n\nThis is an abrupt reversal of what had been a long-term tendency within the genus Homo, so to what might we attribute this striking reduction? I have reviewed the various available explanations (Tattersall, 2018), and have concluded that the observed overall brain size reduction is most plausibly ascribed to the adoption of the symbolic cognitive algorithm. If so, symbolic information processing must have turned out to be more metabolically frugal than its “brute force” intuitive predecessor with the result that, whereas the quality of intuitive processing scaled generally with overall brain size, symbolic processing required a lesser overall volume of brain tissue to produce a superior cognitive result. This processing change would have required substantial prior innovation in the internal reorganization of the human brain, innovation that is most reasonably associated with the radical developmental alteration implicit in the structural changes that produced the highly autapomorphic Homo sapiens (Tattersall, 1998, 2017). The anatomical modifications that announce the arrival of our own species are visible today only in the preserved hard tissues; but they are widely distributed throughout the skeleton, and the ontogenetic reorganization they reflect must surely have had ramifications in the soft tissues as well, including the nervous system. What exactly those changes might have been is beyond my remit here; but they evidently had to do largely with the refinement and multiplication of internal signaling pathways, as well as with the differential expansions of the brain structures associated with globularization and discussed by Neubauer et al. (2018).\n\nEvidence from the Omo Basin in Ethiopia indicates that the new species Homo sapiens, and by extension its new biology, was already in existence by around 230 Ka (Vidal et al., 2022). But current archaeological evidence suggests that the switch to symbolic information processing, along with its behavioral consequences, were not expressed until rather later, at some time around (Tattersall, 2012), or somewhat before (Marean, 2015), about 100 Ka. If so, whereas the enabling biology was acquired exaptively at the origin of Homo sapiens, modern cognition itself is a slightly later acquisition: an emergent potential based on anatomical innovation that had to be “discovered” behaviorally, much as ancestral birds only very belatedly discovered they could use their feathers to fly. The behavioral stimulus involved was almost certainly the spontaneous invention of language – which is, after all, the ultimate symbolic behavior, and one that could easily have been acquired in the short-term event (Senghas et al., 2004; Berwick and Chomsky, 2016) that is all the record gives time for. The new way of communicating, and the cognitive capacity of which it was both cause and effect, would have spread fast among members of a species who already shared a “language-ready” brain. This would in turn have opened the way for the rapid spread of Homo sapiens within and beyond Africa, along with a whole panoply of unprecedented behaviors that made the new species competitively insuperable (see discussion in Tattersall, 2012). The earliest Homo sapiens were, then, still working on the old intuitive cognitive algorithm that made brain enlargement beneficial. But once symbolic information processing had been established, larger-than-necessary brains evidently became a metabolic liability. And average cranial volumes decreased, even as Homo sapiens was becoming the dominant component of terrestrial ecosystems worldwide.\n\n\nConclusion\n\nIts recent shrinkage notwithstanding, the major overall signal in the long history of the hominin brain was undoubtedly one of remarkably rapid enlargement over time. The earliest hominins had brains of around 350 ml in volume, whereas at its high point in the late Paleolithic our species Homo sapiens boasted a mean of 1,499 ml: a striking four-fold increase over a period of some seven million years. What is more, on a very coarse scale there is a strong and undeniable tendency for later hominins to have had larger brains than earlier ones. But it is nonetheless clear that the precise pattern of endocranial expansion (even as obscured by an inexact taxonomy) was not the smooth and gradual one we might expect to find if the trend toward greater brain size had been governed by social or other within-species processes. Remarkably often, within the overall picture of expansion we find patterns of stasis on both regional and Old World-wide scales, and instances in which current taxonomy is a disappointing predictor of brain volume.\n\nThe very early hominins had brains (and by implication brain:body size ratios) that were somewhat smaller than those of today’s great apes, although they were presumably comparable to those of their hominoid contemporaries. What small brain sizes may have meant in cognitive terms (theory of mind, for example) is impossible to specify; but given the phylogenetic position of these hominins they are hardly surprising. Odder, perhaps, is that the earliest species of Australopithecus, A. anamensis, boasted a brain comparable in size to that of the very much older Sahelanthropus tchadensis, and very much smaller than those of the later Australopithecus species which were indeed enlarged relative to the modern ape benchmark. To what influences we can attribute the substantial brain size difference between A. anamensis and the later but slightly overlapping A. afarensis, is as obscure as the cause of the relative stasis that we see subsequently among the other australopiths despite the introduction of the first stone tools at some time over 2.6 Ma. Most authorities reckon that, for energetic reasons, this hugely consequential cultural innovation was prerequisite to the later expansion that occurred among species of the genus Homo (which is itself generally supposed to have emerged from within the australopith group); but the availability of cutting tools apparently had no effect on australopith brain sizes. The fact that substantial brain enlargement did occur within the Kenyanthropus lineage between 3.5 and 1.9 Ma (if indeed this is a true lineage) makes one wonder if we might be looking for the antecedents of Homo in the wrong place.\n\nAmong the most striking morphological features of the fossils generally allocated to “early Homo” (apart from the anomalous H. floresiensis and H. naledi which, although misallocated to Homo, are at least on the face of it good examples of stasis) is a significant increase in brain size at the base of the lineage. In insular eastern Asia the record starts with Homo erectus, in which modestly-sized braincases consistently yield to increasing endocranial volumes over the period between >1 ma and 0.1 Ma. This contrasts with what we see approximately concurrently in Africa, where analysis is complicated by the lack of an adequate systematic structure, but where the endocranial volumes available demonstrate absolutely no consistent tendency towards enlargement in the period between about 2 Ma and 900 Ka. It is only with the arrival of Homo heidelbergensis at around 600 Ka that we find another apparent leap in African endocranial volumes. This is followed by another period of taxonomic uncertainty, at the end of which there had been further net brain size increases in the African lineages that resulted in Homo sapiens on the one hand, and the Jebel Irhoud hominin on the other. In Europe, the large Sima de los Huesos sample possessed a mean endocranial volume virtually identical to that of European and African Homo heidelbergensis; but within a very few hundred thousand years their presumed descendant Homo neanderthalensis was boasting a brain that was on average around 15 percent larger.\n\nThe major implication in all of this is that most, if not all, increments in hominin endocranial volume tended to coincide with the arrival of new species. There is relatively little suggestion, except possibly in insular eastern Asia, of any clear-cut intraspecies trends (and these fade if the Ngandong fossils are indeed their own species). So we have strong support for two different notions: first, that we will never properly understand the biological history involved without an adequate taxonomy; and second, that the driver of hominin brain size increase is more plausibly to be sought in inter-species than in intra-species interactions. And, while over the long haul the signal of brain size increase within the genus Homo is a very powerful one, that tendency seems to have been expressed independently in Africa, Europe and Asia, suggesting that its driver was something common to Homo populations in all periods, areas and environments. What exactly that driver might have been remains unknown, although it must have been related in some way to the apparently equally episodic cognitive and behavioral complexification we see reflected in the archaeological record.\n\nWhat none of this will ever explain, however, is the emergence of the modern human symbolic style. This represents a radical departure from anything that preceded it, and it was clearly not just a refinement of an existing cognitive architecture. The archaeological record tells us emphatically that our recently extinct fossil relatives were extremely complex beings, capable of a wide array of behaviors that we once thought were unique to us; but up to now it has furnished no unequivocal evidence that any hominin other than Homo sapiens ever routinely exhibited symbolic behaviors. Evidently, it is possible to be extremely refined and accomplished, both cognitively and behaviorally, without being symbolic. There is clearly more than one way to be a really smart hominin. What is more, in Homo sapiens the adoption of symbolic cognition (which was necessarily enabled by a pre-existing – and exaptive – neural capacity) was followed by a significant decrease in overall brain size. That final step in human brain evolution was clearly based on both a history and governing circumstances that were unique to the Homo sapiens lineage; and, although built on earlier brain enlargement, it occurred entirely independently of the factors responsible for the striking but very irregular increase in cranial capacity that had previously dominated hominin evolution.",
"appendix": "Data availability\n\nNo new data are associated with this article.\n\n\nReferences\n\nArsuaga JL, Martinez I, Arnold NJ: Neandertal roots: Cranial and chronological evidence from Sima de los Huesos. Science. 2014; 344(6190): 1358–1363. PubMed Abstract | Publisher Full Text\n\nBaab KL: A re-evaluation of the taxonomic affinities of the early Homo cranium KNM-ER 42700. Jour. Hum. Evol. 2008; 55(4): 741–746. Publisher Full Text\n\nBerger LR, Hawks J, de Ruiter DJ , et al.: Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa. elife. 2015; 4: e09560. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBerwick RC, Chomsky N: Why Only Us: Language and Evolution. Cambridge, MA: MIT Press; 2016.\n\nBrown P, Sutikna T, Morwood MJ, et al.: A new small-bodied hominin from the Late Pleistocene of Flores, Indonesia. Nature. 2004; 431: 1055–1061. 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}
|
[
{
"id": "175885",
"date": "29 Jun 2023",
"name": "Dominique Grimaud-Herve",
"expertise": [
"Reviewer Expertise Paleoanthropology",
"paleoneurology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article is a synthesis of the data and results concerning the morphological evolution of the brain in relation to the cultural evolution of hominins, well referenced and argued. All species of the genus Homo, such as Australopithecus, Kenyanthropus and Paranthropus are reviewed. Individual value or average (when it comes to several specimens in the same deposit) of their endocranial volume of the species is considering, related to their chronological age, which allows the author to evoke and argue the possible origin of human groups coming from Africa as the migration routes to Asia and Europe. The latest discoveries of fossils, news species or results are discussed, argued and taken into account or not.\nThe question of the relationship between the increase in cranial capacity and more efficient cognitive capacities is raised to be confronted with the contradiction of the decrease in endocranial volume since the end of the Pleistocene. The author presents few hypotheses to explain this reduction of cranial volume without really concluding, what we cannot blame him for, this subject of the relationship between the aspects: - functional and therefore the performance of the required task and - metabolic, i.e. the amount of energy required without becoming a handicap, is always still the subject of discussion in the scientific community.\nOne of the results which highlights the independence of the evolutionary trend according to the continents is interesting and joins that observed on the skulls of which it has been shown that the species adapted to the environmental conditions of their geographical area, without being able to go further, in biological, cognitive or behavioral explanation or interpretation. The acquisition of symbolic thought, followed by a decrease in the overall size of the brain therefore remains unexplained, just because no study or analysis has yet come to fruition.\nIn conclusion, this article is a good synthesis of the state of the question, which summarizes and analyzes the results of the bibliography, including that of the author who proposes several hypotheses to explain the arrival of symbolic behavior in Homo sapiens, and then the decrease in cranial capacity just after this cultural acquisition. The reviewer suggests evoking the case of the SH whose skeletons at the bottom of the pit were discovered with a magnificent biface in rose quartz never used and which could be interpreted as an offering and therefore a symbolic behavior?\nFew comments :\nChronological age of Dmanisi hominins is 1.8 et not 1.9 (Lorkipanidze et al.,20131)\n\nIn the very often cited publication of Holloway (2004), which is a general synthesis of the work of many researchers, it would be preferable to quote the author of the research and the results obtained for each of the specimens to enhance their work.\n\nIn figure 1, rather than putting a brain of HS of different sizes depending on the species, replace it with a drawing of the endocranium of each species? In effect, the cerebral form is not the same according to the species of hominins. This seems to reinforce the misconception that human evolution is linear. Appropriate drawings showing the different position of the cerebral lobes relative to each other according to the species, and therefore their cerebral reorganization, would better support the idea of an arboreal evolution?\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
},
{
"id": "205817",
"date": "22 Sep 2023",
"name": "Pasquale Raia",
"expertise": [
"Reviewer Expertise Anthropology",
"evolutionary biology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTattersal assembled a beautifully written, well-balanced, and informative review about what we know, and almost equally importantly what we don’t know, about the evolution of brain size (actually endocranial volume) in Homo. The author makes a fantastic job in debunking the simplistic idea – which is very common among non-experts- that endocranial volumes increased almost linearly during human evolution. More to the point, he clearly shows that there is a noticeable gap between what most people understand as early Homo (that is up to erectus included) and heildebergensis. He also very clearly points out that our understanding of the tempo and mode of endocranial evolution in Homo is made difficult by the absence of a clear, well-understood alpha taxonomy and phylogeny. Over the last chapter, the author replicates his older tenet that symbolic thought and language (the earnest evidence of ‘mentalese’) sets apart morphologically early Homo sapiens as found in Omo valley to the behaviorally modern humans appeared around 100ka.\nThe paper is timely, easy to read and very informative review of the current knowledge on endocranial volume evolution, whether or not the author is correct in assigning to language the emergence of modern brain functioning, and to globularity its external manifestation.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nAre arguments sufficiently supported by evidence from the published literature? Yes\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-565
|
https://f1000research.com/articles/11-783/v1
|
12 Jul 22
|
{
"type": "Research Article",
"title": "Automated detection of over- and under-dispersion in baseline tables in randomised controlled trials",
"authors": [
"Adrian Barnett"
],
"abstract": "Background: Papers describing the results of a randomised trial should include a baseline table that compares the characteristics of randomised groups. Researchers who fraudulently generate trials often unwittingly create baseline tables that are implausibly similar (under-dispersed) or have large differences between groups (over-dispersed). I aimed to create an automated algorithm to screen for under- and over-dispersion in the baseline tables of randomised trials. Methods: Using a cross-sectional study I examined 2,245 randomised controlled trials published in health and medical journals on PubMed Central. I estimated the probability that a trial's baseline summary statistics were under- or over-dispersed using a Bayesian model that examined the distribution of t-statistics for the between-group differences, and compared this with an expected distribution without dispersion. I used a simulation study to test the ability of the model to find under- or over-dispersion and compared its performance with an existing test of dispersion based on a uniform test of p-values. My model combined categorical and continuous summary statistics, whereas the uniform uniform test used only continuous statistics. Results: The algorithm had a relatively good accuracy for extracting the data from baseline tables, matching well on the size of the tables and sample size. Using t-statistics in the Bayesian model out-performed the uniform test of p-values, which had many false positives for skewed, categorical and rounded data that were not under- or over-dispersed. For trials published on PubMed Central, some tables appeared under- or over-dispersed because they had an atypical presentation or had reporting errors. Some trials flagged as under-dispersed had groups with strikingly similar summary statistics. Conclusions: Automated screening for fraud of all submitted trials is challenging due to the widely varying presentation of baseline tables. The Bayesian model could be useful in targeted checks of suspected trials or authors.",
"keywords": [
"automation",
"randomisation",
"trials",
"fraud",
"reporting errors",
"Bayesian analysis"
],
"content": "Introduction\n\nPapers describing the results of a randomised trial often include a table that compares the randomised groups at baseline (hereafter called a “baseline table”). This baseline table presents summary statistics that describe the groups, such as average age and the percentage of males. The table’s purpose is to demonstrate that the randomisation produced similar groups, which strengthens the case that any differences between groups are due to the randomised treatment.1 A baseline table is recommended by the CONSORT guidelines, which were designed to improve the reporting of randomised trials.2\n\nResearchers who fabricated randomised trials have been discovered because their baseline tables were not realistic.3–5 When fabricating the baseline table they created highly comparable groups that would pass peer review. In trying to avoid raising alarms during peer review, they unwittingly raised an alarm at post peer review. Fraudulent researchers might also create baseline data with unusually large differences between groups, likely because they do not understand how to create realistic summary statistics when data are truly random.6 Fraudulent researchers may not be uncovered by one baseline table alone, but an odd table might prompt a wider investigation.7\n\nFraudulent researchers have so far been found in ad hoc ways, including concerns being raised by whistleblowers and researchers noticing strange patterns whilst reading papers in their field or conducting systematic reviews.8,9 Other problems have been found by dedicated researchers trawling through papers. Manually extracting data from papers is time consuming and automatic data extraction would be a useful advance.10 Automated detection algorithms would save time and increase scrutiny.11,12\n\nPrevious statistical methods for finding problems in baseline tables have used the p-values from tests comparing groups at baseline, and then tested if the distribution of p-values is uniform.13,14 However, it is possible to get a non-uniform distribution of p-values when the two groups were randomised, for example, for skewed data.15 Another limitation with this approach is that it can only use summary statistics of the mean and standard deviation for continuous variables, so summary statistics using percentages are not included.16,17 This is a large loss as percentages are commonly used in baseline tables. I aimed to create a method that could use summary statistics from both continuous and categorical variables.\n\nThe aim of this paper is not to provide undeniable evidence for fraud. Baseline tables that appear to have a problem could occur for a range of non-fraudulent reasons. These include planned or unplanned factors to do with randomisation, such as dynamic randomisation to create highly comparable groups, or subversion of the random allocation.18 Problems can also be due to mislabelled summary statistics or reporting errors.11,14 My aim was to create an automated algorithm that could be used to flag potential problems at the submission stage, which would help researchers improve their paper prior to publication.19\n\n\nMethods\n\nI report PubMed Central ID numbers to highlight examples without citing papers. The example baseline tables can easily be examined by interested readers using the PubMed Central site (see extended data).\n\nThere are two parts to the methods and results: 1) The new Bayesian test for under- or over-dispersion, 2) The automated extraction of baseline tables.\n\nAn example of a baseline table from a randomised trial is shown in Table 1. The table compares the continuous variable of age using the mean and standard deviation, and the categorical variable of gender using numbers and percents.\n\nThis is illustrative data and not from a real trial.\n\nThe key idea of this work is to use the summary statistics to examine if there is under-dispersion (the statistics are too similar) or over-dispersion (the statistics are too different) given that the data are from a randomised trial. I combined continuous and categorical or binary summary statistics from the baseline table by summarising the difference between randomised groups using the independent samples t-statistic. It may be surprising to use the t-statistic to compare categorical data like gender, but the t-test is robust in situations where the chi-squared test would be a common choice, even for small sample sizes.20\n\nI excluded rows from the baseline table that were the inverse of the previous row, for example the percentage male followed by the percentage female. In this case the t-statistics for males and females would be perfectly negatively correlated and including these results twice would artificially increase the sample size. I excluded rows where the t-statistic was the inverse of the previous, but not where the t-statistic was zero. This approach only excludes rows that are a perfect inverse and would miss other grouped results, such as rows for three age groups. The effect of including these correlated table rows are examined in the simulation study.\n\nI did not use summary statistics that were the median and quartiles or minimum to maximum, as I could not compare these statistics using the parametric t-test.\n\nI created t-statistics for all pairs of comparisons. For example, for the three-group trial in Table 1 there would be three comparisons: A vs B, A vs C, B vs C.\n\nThe observed differences (d) in the summary statistics of randomised groups were modelled using a t-distribution.\n\nThe pooled inverse-variance is the precision and was modelled as\n\nEach trial had a “switch” Pi ∈ (0, 1), that determined whether it is part of the spike or slab. The spike at zero, with Pi = 0, was for trials where the differences between randomised groups were as expected (σi,j−2=si,j−2). The slab, with Pi = 1, was for trials with under- or over-dispersion. This difference was modelled using a normal distribution where over-dispersed results have a negative ϵi (and multiplier under 1, γi < 1) and under-dispersed results have a positive ϵi (γi > 1). The variance for this normal prior of 10 is small compared with typical vague priors in Bayesian models, but in preliminary modelling I found this covered the full range of possibilities, including where the summary statistics were identical between randomised groups, and variances larger than 10 caused convergence issues. The binary switch for each trial (Pi) was modelled using a Bernoulli distribution.\n\nFor continuous data I used the difference in group means and pooled variance as follows (dropping the i and j subscripts for simplicity):\n\nThe degrees of freedom (df) for trial i is the total sample size minus one (n1 + n2 − 1), which allows for greater variance in differences for smaller trials.\n\nTwo statistics can be used to judge whether a baseline table has under- or over-dispersion:\n\n• The estimated trial-specific probability of under- or over-dispersion P¯i=∑j=1MPij/M, for which I examined a threshold of P¯i>0.95 to flag a potential problem by averaging over the M Markov chain Monte Carlo estimates.\n\n• The estimated precision ϵ¯i which indicates larger under- or over-dispersion for values further from zero. This is also averaged over the Markov chain Monte Carlo estimates.\n\nTo examine how the method performed for trials that are very likely fraudulent, I used the trials published by Yuhji Saitoh which were identified as problematic by Carlisle and colleagues.22 I extracted the baseline tables for the first ten trials in date order and examined how the evidence of under- or over-dispersion accumulated over time. For comparison, I calculated the existing uniform test of p-values.13 I calculated the statistics using continuous summary statistics only, and for combining continuous and categorical summary statistics.\n\nI used a simulation study to examine differences between the new Bayesian method using the t-distribution and the existing method using p-values and the uniform distribution. I simulated data using two scenarios described by Bland15 with no concern about randomisation but where the p-value distribution would be non-uniform, meaning the uniform test could return a high percentage of false positives:\n\n• Small trials with a sample size of 10 and summary statistics using binary data (e.g., percent of males)\n\n• Large trials with a sample size of 1,000 and summary statistics using skewed continuous data (e.g., length of hospital stay)\n\nAs a comparison with the small binary scenario, I added a large binary scenario which would be expected to have more uniform p-values due to the larger sample size:\n\n• Large trials with a sample size of 1,000 and summary statistics using binary data\n\nTo examine the power of my Bayesian method to detect problematic tables, I used three additional scenarios that used a 50:50 mix of binary and continuous summary statistics and where the underlying data were:\n\n• Under-dispersed: randomised groups were too similar. Achieved by copying half of the means and percentages from one group to the other.\n\n• Over-dispersed: randomised groups were too different. Achieved by adding a large number to the group means or percentages.\n\n• As expected for a randomised trial.\n\nTo create realistic tables, simulation parameters were based on a large sample of baseline table data from my automated extraction applied to PubMed Central (see extended data). These parameters were: the ratio of continuous:binary summary statistics and the distributions of group sample sizes and table rows. The group sample sizes were randomly generated using an exponentiated gamma distribution with shape of 11.2 and rate of 3.0, which gives a median sample size of 37 and first to third quartile of 19 to 83. The number of rows per baseline table were randomly generated using a gamma distribution with shape 2.2 and rate 0.15, which gives a median number of rows of 12 and first to third quartile of 7 to 19.\n\nSummary statistics in baseline tables are often rounded, and hence I rounded the mean to one decimal place and the standard deviation to 2 decimal places. To examine stronger rounding I rounded the mean to zero decimal places and a standard deviation to 1 decimal place. Rounded statistics could create under-dispersion by concealing the differences between groups.\n\nTo examine a scenario where the uniform test should perform well, I used a simulation with no dispersion, all continuous summary statistics, and means rounded to 3 decimal places.\n\nTo examine the effect of including multi-group categorical data (e.g., low, middle, high income), I simulated categorical data with three groups.\n\nFor all scenarios I created 500 simulated trials and each trial had two randomised groups with equal sample size. I compared the statistics graphically using distributions of the p-values and t-statistics. For the existing uniform test, I tested if the p-values for each study followed a uniform distribution using the Kolmogorov–Smirnov test, and counted the number of simulations where the null hypothesis was rejected using the 0.05 threshold. Using my Bayesian model, I examined the number of trials where the estimated probability of under- or over-dispersion (P¯) was higher than 0.95.\n\nTo create a large and generalisable sample of baseline tables, I extracted tables from the National Library of Medicine’s PubMed Central open access subset which has 3.7 million papers. The steps are outlined below and the complete code is available on GitHub.23\n\nI downloaded a list of published randomised trials from the trialstreamer web page24 using the PubMed Central ID (PMCID). The trialstreamer data was downloaded on 9 August 2021 and had 57,109 trials with a PMCID. For logistical reasons I reduced the full list to a random sample of 10,000.\n\nI next accessed the available papers from the open access subset using the PMCID. All available papers were download in XML format and read into R.\n\nI excluded papers that were not randomised trials, including: i) trial protocols, and ii) papers that re-used trial data for other study designs (e.g., diagnostic accuracy). This exclusion was made based on the title and abstract, but some protocols were not identified in the title or abstract and hence were wrongly included.\n\nThe algorithm searched the full text for the baseline table using key words and phrases in all table captions. These words included “baseline”, “characteristic” and “demographic”. I also searched for words and phrases in the caption that ruled out baseline tables, such as “drug information” and “change from baseline”. The key words and phrases were found using trial and error.\n\nIf a baseline table was found, then I extracted: all the summary statistics, the type of summary statistics (e.g., median or percentage), and the group sample sizes. A challenging step was estimating what summary statistics were used in each row of the baseline table. This was estimated based on the text in the rows and columns (e.g., “Mean”, “%”, etc) and the variable label, as some variables such as age and BMI were often continuous, whereas other variables such as gender were categorical.\n\nA key step was estimating the groups’ sample sizes. These were first estimated by searching the column and row headers for key indicators such as “N=”. If no samples sizes could be found, then they were estimated from all available percentages in the baseline table. These estimated sample sizes were only used if there was a strong agreement, defined as an inter-quartile range of less than 1. For example, estimated sample sizes from four percentages of 65, 65, 65 and 64, would be acceptable and would use the mode of 65. A paper was excluded if the sample sizes could not be extracted.\n\nI applied my Bayesian model to all the baseline tables extracted from PubMed Central to give the probability of under- or over-dispersion for each trial. I then examined whether there were study design characteristics associated with the probability of under- or over-dispersion. I used a multiple linear regression model with a dependent variable of the study-level probability of a non-zero dispersion (0≤P¯i≤1), and independent variables that described the paper, study design and features of the table. I included independent variables of the journal and country of first author, using a combined “other” if a journal had fewer than 10 trials and a country fewer than 20 trials. For the study design, I included if the study was a pilot (based on the title), a cluster-randomised trial (based on the title and abstract), or used the standard error of the mean instead of the standard deviation (based on the baseline table). Features of the baseline table included as predictors were the number of rows, number of columns, sample size, largest difference in sample size between groups, proportion of continuous summary statistics and average number of decimal places for summary statistics. I selected a smaller subset of key predictors from the larger set using the elastic net as a variable selection tool.25\n\nAll the R code to extract the tables and run the Bayesian model is openly available https://github.com/agbarnett/baseline_tables.23 An interactive version of my Bayesian model is available via shiny: https://aushsi.shinyapps.io/baseline/. The Bayesian models were fitted using WinBUGS Version 1.4.326 for the paper and nimble version 0.12.127 for the shiny application. The Bayesian models used two chains with a burn-in of 2,000 followed by 2,000 samples thinned by 2. The data management and plotting were made using R version 4.1.1.28\n\nI used publicly available data that were published to be read and scrutinised by researchers and hence ethical approval was not required.\n\n\nResults\n\nExample results applied to known problematic trials are shown in Figure 1, and show the new Bayesian method and existing test based on the uniform distribution. The results are cumulative to show the effect of accumulating evidence, which was 3 table rows in trial 1 up to 38 table rows for trials 1 to 10. Ten (26%) of these rows were categorical summary statistics.\n\nThe results are cumulative to highlight the effect of accumulating evidence over time.\n\nThe Bayesian probability of under- or over-dispersion (P¯i) using continuous and categorical data is 1 from the first trial and remains at 1 for all ten trials, strongly signaling an issue with the tables. The Bayesian probability just using continuous data is relatively high, but dips when trials 3 and 9 are added. The p-value from the uniform test is zero across all ten trials, strongly signaling an issue with the tables. However, the p-value gradually increases with accumulating trials when using only continuous summary statistics, and was 0.09 when using all 10 trials.\n\nThe Bayesian precision shows that the summary statistics are under-dispersed and the 95% credible intervals narrow with accumulating evidence. However, when using only continuous summary statistics, the intervals widen greatly when including trials 3 and 9 and the intervals include potential over-dispersion.\n\nThe results for the nine simulated scenarios are in Table 2. The uniform test performed well for the simulations that used continuous data with minimal rounding or large binary data, with rejection rates close to the expected 5%. However, it had high false positive percentages for the other five scenarios where there was no under- or over-dispersion, doing particularly badly for small binary data and skewed data. The uniform test did have good power to detect under- and over-dispersed data. Examples for single simulations are shown in the extended data and show the non-uniform distribution when the data are skewed, small binary or rounded.\n\nThe Bayesian model rarely flagged trials where there was no under- or over-dispersion, hence there were few false positives. The Bayesian model was successful at detecting trials that were over-dispersed, with 84.4% of the simulations flagged at the 0.95 threshold. The model was less successful at detecting trials that were under-dispersed, with 16.0% of the simulations flagged as under-dispersed at the 0.95 threshold.\n\nI validated my algorithm to extract baseline tables using manually-entered baseline data from randomised trials. To find eligible trials I searched PubMed for randomised trials between 2017 and 2020 that were available open access on PubMed Central and were not protocols, which gave 25,760 trials. A random selection of 200 trials was made, with the results compared between the algorithm and manually entered data. 118 papers were excluded by the algorithm, with the three most common reasons because the paper was not openly available (n = 48), there was no baseline table (n = 36), or there was no comparison between groups in the table (n = 16). A further 9 papers could not be compared because the manually entered data were judged not to be randomised trials. This left 73 baseline tables to compare.\n\nDetailed comparisons of the algorithm and manual results are in the extended data. In summary, my algorithm correctly determined the summary statistic 87% of the time (795 out of 909; 95% CI: 85% to 90%). The biggest differences were when the algorithm wrongly chose continuous for a median (2%) or could not chose any statistic when the row was a percentage (5%). The algorithm was able to extract the sample size, with a mean difference of 0 (5% to 95% percentile: 0 to 0). The algorithm accurately estimated the size of the baseline table, with a median difference of 0 (5% to 95% percentile: –1 to 4) for the number of rows, and 0 (5% to 95% percentile: 0 to 0) for the number of randomised groups.\n\nThe accuracy of the algorithm is reasonable given the large variety in the presentation of baseline tables, an issue that has been flagged by others.29 Failures of the algorithm sometimes meant the table data were excluded as the algorithm could not extract the numbers, this means that I was not able to completely screen the literature. Failures when the wrong data were extracted, for example wrongly extracting a total column as a randomised group, sometimes led to the trial being flagged by my model and I examine this issue in the next section.\n\nThe majority of the 10,000 potential trials were excluded (Table 3). The three most common reasons were:\n\n• there was no baseline table or one could not be detected by my algorithm,\n\n• the XML file was not available despite being on the open access PubMed Central database,\n\n• it was not a randomised trial.\n\nThere were 2264 included trials with a total of 72,090 table rows. The median number of rows per baseline table was 15 and the median number of columns was 2. The central 50% of publication dates were between 15 June 2016 and 15 June 2020. The summary statistics extracted from the baseline tables of the included trials are in Table 4.\n\nThe first column indicates if the statistics were included in the tests of under- or over-dispersion.\n\nAfter excluding summary statistics that were medians and ranges, which cannot be compared using t-statistics, and excluding perfectly correlated table rows, there were 2245 trials with 52,615 table rows available for the Bayesian model. There were a relatively large number of trials that had baseline tables that were over-dispersed: 18.3% for the 0.95 threshold. There were fewer trials that were flagged as under-dispersed: 3.6% for the 0.95 threshold.\n\nThe t-distributions for three trials that were flagged as over-dispersed (P¯i=1,ϵ¯i<1) are plotted in Figure 2. For comparison, three randomly selected trials with no dispersion (P¯i=0) are also plotted. The three flagged trials were selected using the smallest multiplier of the precision (ϵ¯i) and hence show the most extreme over-dispersed trials. For each trial there are a small number of extremely large t-statistics.\n\nFor comparison there are three randomly selected trials that were not flagged. The scales on the count axes differ by trial. The panel headings show the PubMed Central ID number.\n\nTwo trials that are flagged as over-dispersed are due to errors in the data extraction algorithm (PMC7553102 and PMC7301747). For PMC7553102 the bottom five rows of the table were wrongly assigned by the algorithm as continuous instead of percentages which creates t-statistics over 200. The result for PMC7301747 is an example of where an error in my data extraction creates a false impression of variability. The error occurs due to large numbers such as “15,170 (7,213)” which my algorithm extracts as three statistics: 15170, 7 and 213, instead of the correct two statistics: 15179 and 7213. This is because a comma is used both for large numbers and as a separator of two statistics such as a range. The t-statistic for this row is over 1,000 and hence the trial is flagged as over-dispersed.\n\nThe baseline table in trial PMC7302483 had a complex layout with four summary statistics per group in four separate columns, which the algorithm interpreted as separate groups rather than summary statistics for the same group.\n\nThe t-distributions for three trials that were flagged as under-dispersed (P¯i=1,ϵ¯i>1) are plotted in Figure 3. One study flagged as under-dispersed had an error where a mean was outside the confidence interval (PMC7259582), which meant the summary statistics were not recognised as a confidence interval and were instead wrongly guessed as a mean and standard deviation.\n\nFor comparison there are three randomly selected trials that were not flagged. The scales on the count axes differ by trial. The panel headings show the PubMed Central ID number.\n\nOne flagged study was not a randomised trial but was a case–control study with an age and gender matched control group (PMC2176143), hence it was not surprising that the summary statistics in the baseline table were very similar.\n\nOne trial labelled proportions as percentages and hence it appeared as if there were lots of zero percentages which meant the two randomised groups appeared highly similar (PMC7578344).\n\nThe most extreme results in terms of under- and over-dispersion were often failures in the algorithm’s data extraction, sometimes due to poor reporting. Hence, I next examine less extreme results by excluding flagged trials that are in the tails of the precision distribution (ϵ¯), which were the extremely under- or over-dispersed results (see extended data for the distribution). All flagged trials have a probability of under- or over-disperion of 1 (P¯i=1).\n\nThree further examples of over-dispersion are in Figure 4. One trial stratified the randomised groups by severity which created large between group differences and hence the over-dispersion (PMC4074719).\n\nFor comparison there are three randomly selected trials that were not flagged. The scales on the count axes differ by trial. The panel headings show the PubMed Central ID number.\n\nA trial that was flagged as over-dispersed had standard deviations for height that were zero (PMC6230406). This is likely a reporting error as zero standard deviations would require all participants to have exactly the same height.\n\nOne study was not a trial but was an observational study with some very large differences between groups at baseline, with 4 absolute t-statistics larger than 10, including a table row that was labelled as not significantly different based on a Mann–Whitney test but had a t-statistic of 19 (PMC6820644).\n\nThree examples for under-dispersion using the lower threshold of a multiplier are in Figure 5. All three trials have strikingly similar summary statistics, with all six t-statistics within –0.4 to 0.4 (PMC5863571), all twelve t-statistics within –0.7 to 0.5 (PMC7245605), and all five t-statistics within –0.2 to 0.6 (PMC7443541). One trial (PMC7443541) appeared to exclude two participants, potentially based on their baseline values, which may partly explain the under-dispersion.\n\nFor comparison there are three randomly selected trials that were not flagged. The scales on the count axes differ by trial. The panel headings show the PubMed Central ID number.\n\nI examined which study design features were associated with the trial-specific probability of under- or over-dispersion (P¯i). The five predictors selected by the elastic net approach are in Table 5. The variables not selected were: number of table rows, pilot trial, block randomisation, average number of decimal places, journal, and first author’s country.\n\nThe probability of under- or over-dispersion was much higher in baseline tables that wrongly used the standard error of the mean instead of the standard deviation. This is as expected given that the standard error will be far smaller than the standard deviation and hence small differences could look like over-dispersion.\n\nThe probability of under- or over-dispersion increased when there were large differences in group sample sizes. An examination of examples of these trials found that some were not a simple comparison of, for example, treatment versus control (two columns), but included subgroups, such as gender or disease severity. These strata will likely create over-dispersion as the comparisons are no longer between randomised groups.\n\nThe probability of under- or over-dispersion increased when the baseline table had a greater proportion of continuous variables. This is likely because of the greater statistical power for continuous variables compared with categorical. Similarly the probability increased with greater sample size and more columns, which both increase the statistical power. The number of rows in the table was not selected, but in a separate simulation I confirmed that—as expected—the power to detect under-dispersion increased for larger tables (see extended data).\n\nNo journals or countries were selected by the elastic net variable selection, meaning none were associated with dispersion. However, the total number of trials were small for most journals and some countries, which reduces the statistical power. The largest number of trials for a single journal was 85.\n\n\nDiscussion\n\nIn the simulation study, my Bayesian model based on the distribution of t-statistics outperformed the test using the distribution of p-values. My model dealt well with data that was skewed and categorical, or where the summary statistics were rounded, whereas the uniform test often wrongly flagged these trials as under- or over-dispersed.\n\nThe uniform test had a high false positive percentage because it is overly sensitive to small departures from the uniform distribution. Skewed or categorical data can cause spikes in the p-value distribution, causing the uniform test to be rejected even for randomised data. The Bayesian model using t-statistics is less sensitive to small departures as it examines the variance of the distribution, which is a summary statistic of the distribution rather than the entire distribution.\n\nA previous simulation study similarly found that p-values in a baseline table for categorical data can be non-uniform even for trials that were randomised, and hence recommended against including categorical data.17 My model using t-statistics can use continuous and categorical summary statistics, and as 56% of summary statistics in the PubMed Central data were numbers or percentages (Table 4) this greatly increases the available data. The advantage of using both categorical and continuous summary statistics was shown in the example using known problematic trials, where the continuous-only results had lower probabilities and much greater uncertainty (Figure 1).\n\nMy automated algorithm was able to flag baseline tables that would be worth querying with the authors during journal peer review. However, this was not always due to under- or over-dispersion, but was sometimes because of an error in the table, because the authors had mislabelled their study as a trial, or because of the exclusion of valid data (PMC7443541). Flagging these issues with authors at the submission stage could reduce errors and improve reporting. Arithmetic and calculation errors were considered an important and common mistake by medical journal editors.30\n\nAt times my algorithm flagged papers where the baseline table was not a baseline table for a randomised trial, but was a study that re-used the data from a trial. For example, a study which examined responders and non-responders to a randomised treatment, and the table compared non-randomised groups meaning over-dispersion is likely (PMC7660513). It is challenging to exclude these studies using automation as the abstract and title naturally talk about the randomised trial. Any automated flags raised for papers like this would need to be filtered by a person, or the authors whose study was flagged could simply explain that it was not a randomised trial. An automated algorithm to detect fake papers containing “tortured phrases” used a two-stage (or semi-automated) approach, where results that are flagged by an algorithm need to be checked by a person.31\n\nPublishers have trialled automated algorithms to check statistics and reporting completeness.32–34 If applied by a publisher, my algorithm could be adapted to suit the publisher’s style; the current algorithm tried to cover all journals. The statistics that control which papers are flagged (P¯i and ϵ¯i) could be tuned with experience to reduce false positives.\n\nMy algorithm flagged some trials that were under-dispersed with a striking similarity in the baseline characteristics of randomised groups. Flagging trials where the baseline table is under-dispersed might protect journals from publishing fraudulent papers, as this has been a clue in previous fraud investigations.35 It is better to prevent the publication of fraudulent papers, as post-publication retractions can be long and costly.5 A study of randomised trials submitted to the journal Anaesthesia, estimated that around one quarter of trials had false data that was problematic enough to invalidate the trial.5 Research fraud may be increasing due to fierce competition for funding and promotion that often depend on publication counts.36\n\nThere were many potential trials that were excluded because they were not randomised trials (Table 3). Two key reasons for this were poor reporting in the title and abstract,37 and studies that re-used data from a trial in other study designs (e.g., PMC6761647). Some baseline tables were excluded or flagged as under- or over-dispersed because of atypical descriptions in the caption or because of complex formatting in the table. There is a great variance across journals in how baseline tables are reported, including varied uses of symbols, labels and punctuation. Ideally commas would not be used to separate two numbers as they are also used to indicate thousands and millions.\n\nI found many mistakes in baseline tables, some of which meant the trial was flagged as under- or over-dispersed. Mistakes included misreported statistics (e.g., continuous summary statistics labelled as percentages), missing labels, typographical errors, means reported without standard deviations, zero standard deviations, incorrect confidence intervals, incorrect p-values, and percentages that did not match the numerator divided by the denominator. Researchers should take more care and accurately report their results.38\n\nGreater use of standardised reporting—such as recommended by CONSORT—would increase the amount and accuracy of data that can be captured using automation. Even supposedly simple statistics such as age and gender were inconsistently presented in baseline tables, and a previous study similarly found highly varied reporting in age and gender in the clinicaltrials.gov database.29 Publishers who wanted to use my algorithm to screen trials may need to provide more guidance to authors, although journal editors have raised concerns that authors rarely read instructions,39 and there is no systematic study of whether journal instructions are read.40\n\nCarlisle plotted the distribution of standardised mean differences for continuous summary statistics from randomised trials and graphically compared the distribution to a standard normal to visually check for under- or over-dispersion.41\n\nA number of automated algorithms have been created to detect numerical problems in papers, including statcheck for p-values42 and SPRITE for summary statistics.43 An automated check of p-values and confidence intervals found up to 5% had large errors, suggesting there are likely tens of thousands of published papers containing undetected errors.44 These automated checks had a similar motivation: to automate the laborious process of checking numerical results and improve the quality of published papers and/or correct errors in published papers.\n\nA previous study found that 92% of trials included a baseline table,1 whereas my algorithm only extracted a baseline table for 25% of trials, hence I very likely excluded eligible trials where the algorithm did not detect a baseline table. Often this was because the baseline table was in graphical format meaning the table could not be extracted. There were other exclusions where the study was not a randomised trial, and hence no baseline table was included. There were also trials that did not include a baseline table (e.g., PMC3574512).\n\nI assumed one sample size per group, but there were tables where the sample size varied by row (e.g., PMC7086156) and hence my calculated t-statistics will be inaccurate. Some trials had multiple baseline tables (e.g., PMC7908111), however I just used the first table. Some baseline tables were in an appendix and I only extracted tables from the main text in XML format.\n\nIn the simulation study, I assumed a that 50% of statistics were copied when the data were under-dispersed, but fraudsters may copy fewer statistics on average or use an entirely different process for falsifying data.\n\nI report whether a baseline table has a potential problem, but make no attempt to differentiate between fraud and honest errors.35,45 Checking for fraud needs to be done by examining other details, such as ethics clearances, plausible recruitment rates, and other work by the same authors. However, my automated check could still be a useful flag when papers are submitted.46\n\nI used t-statistics to test for issues in baseline tables, but other methods could be applied such as Benford’s law.35,47\n\nStatistical approaches have been used to detect fraud in trials using individual patient data.3,6,48 Problems can be more accurately detected in individual data than summary statistics and this also avoids any rounding errors.5,6 My approach could be extended to examine the dispersion in individual data at baseline, which would greatly increase its ability to detect under- or over-dispersion.5 Journals could request that authors provide the underlying trial data at submission to perform detailed checks.49,50 Authors may raise concerns about participant confidentiality and data security,51 but many data sets in health collect anonymised data and authors need not commit to openly sharing their data or sharing any variables that include personal information.\n\nI have created a shiny app where researchers can upload the summary statistics for a trial to examine the distribution of t-statistics and get the results from my Bayesian model https://aushsi.shinyapps.io/baseline/. This app should be useful for researchers who are concerned about particular papers.\n\n\nConclusions\n\nMy automated algorithm is potentially useful as an initial screening of randomised trials, but needs human validation of the trials that are flagged as under- or over-dispersed as the automated data extraction is imperfect. Similar automated tools are likely to become more widely used as journals struggle to find reviewers due to increasing submission numbers and over-burdened reviewers.52\n\n\nData availability statement\n\nZenodo: baseline tables. https://doi.org/10.5281/zenodo.6647853.53\n\nThis project contains the following underlying data:\n\n• simulated_data_bland.RData. The simulated trial data.\n\n• trialstreamer.RData. The trials identified by trialstreamer and downloaded from PubMed Central.\n\n• hand_entered_data.RData. The manually entered data used in the algorithm’s validation.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license.\n\n\n\n• Github: “Supplement: Automated detection of over- and under-dispersion in baseline tables in randomised controlled trials” (baseline_tables_supplement.docx)\n\n• Github: “Algorithm validation: Comparison of the statistics extracted from baseline tables by the algorithm and manually” (3_compare_algorithm_hand.docx)\n\nThis project contains the following extended data: https://doi.org/10.5281/zenodo.6647853.\n\n\nReporting guidelines\n\nRepository: STROBE checklist for “Automated detection of over- and under-dispersion in baseline tables in randomised controlled trials”. https://github.com/agbarnett/baseline_tables/tree/main/checklist.\n\n\nAuthor contributions\n\nAdrian Barnett: Conceptualization, Investigation, Methodology, Software, Visualization, Writing - Original Draft.",
"appendix": "Acknowledgements\n\nThanks to John Carlisle for useful comments on the study design and first draft.\n\nThanks to the National Library of Medicine for making the PubMed Central data available for research.\n\n\nReferences\n\nPocock SJ, Assmann SE, Enos LE, et al.: Subgroup analysis, covariate adjustment and baseline comparisons in clinical trial reporting: current practiceand problems. Stat. Med. 2002; 21(19): 2917–2930. PubMed Abstract | Publisher Full Text\n\nSchulz KF, Altman DG, Moher D: CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010; 340(mar23 1): c332–c332. PubMed Abstract | Publisher Full Text\n\nSimonsohn U: Just post it. Psychol. Sci. 2013; 24(10): 1875–1888. Publisher Full Text\n\nAdam D: How a data detective exposed suspicious medical trials. Nature. 2019; 571(7766): 462–464. PubMed Abstract | Publisher Full Text\n\nCarlisle JB: False individual patient data and zombie randomised controlled trials submitted to Anaesthesia. Anaesthesia. 2020; 76(4): 472–479. PubMed Abstract | Publisher Full Text\n\nBuyse M, George SL, Evans S, et al.: The role of biostatistics in the prevention, detection and treatment of fraud in clinical trials. Stat. Med. 1999; 18(24): 3435–3451. PubMed Abstract | Publisher Full Text\n\nLi W, van Wely M , Gurrin L, et al.: Integrity of randomized controlled trials: challenges and solutions. Fertil. Steril. 2020; 113(6): 1113–1119. PubMed Abstract | Publisher Full Text\n\nRoberts I, Smith R, Evans S: Doubts over head injury studies. BMJ. 2007; 334(7590): 392–394. PubMed Abstract | Publisher Full Text\n\nBolland MJ, Avenell A, Gamble GD, et al.: Systematic review and statistical analysis of the integrity of 33 randomized controlled trials. Neurology. 2016; 87(23): 2391–2402. Publisher Full Text\n\nVorland CJ, Allison DB, Brown AW: Semi-automated screening for improbable randomization in pdfs. Computational Research Integrity Conference. 2021.\n\nBordewijk EM, Li W, van Eekelen R , et al.: Methods to assess research misconduct in health-related research: A scoping review. J. Clin. Epidemiol. 2021; 136: 189–202. PubMed Abstract | Publisher Full Text\n\nSchulz R, Barnett A, Bernard R, et al.: Is the future of peer review automated? BMC. Res. Notes. 2022; 15(1): 203. PubMed Abstract | Publisher Full Text\n\nCarlisle JB, Dexter F, Pandit JJ, et al.: Calculating the probability of random sampling for continuous variables in submitted or published randomised controlled trials. Anaesthesia. 2015; 70(7): 848–858. Publisher Full Text\n\nCarlisle JB: Data fabrication and other reasons for non-random sampling in 5087 randomised, controlled trials in anaesthetic and general medical journals. Anaesthesia. 2017; 72(8): 944–952. PubMed Abstract | Publisher Full Text\n\nBland M: Do baseline p-values follow a uniform distribution in randomised trials? PLoS One. 10 2013; 8: 1–5. Publisher Full Text\n\nBolland MJ, Gamble GD, Avenell A, et al.: Rounding, but not randomization method, non-normality, or correlation, affected baseline p-value distributions in randomized trials. J. Clin. Epidemiol. 2019; 110: 50–62. Publisher Full Text\n\nBolland MJ, Gamble GD, Avenell A, et al.: Baseline p value distributions in randomized trials were uniform for continuous but not categorical variables. J. Clin. Epidemiol. Aug. 2019; 112: 67–76. Publisher Full Text\n\nKennedy ADM, Torgerson DJ, Campbell MK, et al.: Subversion of allocation concealment in a randomised controlled trial: a historical case study. Trials. 2017; 18(1): 204. PubMed Abstract | Publisher Full Text\n\nWeissgerber T, Riedel N, Kilicoglu H, et al.: Automated screening of COVID-19 preprints: can we help authors to improve transparency and reproducibility? Nat. Med. 2021; 27(1): 6–7. Publisher Full Text\n\nD’agostino RB, Chase W, Belanger A: The appropriateness of some common procedures for testing the equality of two independent binomial populations. Am. Stat. 1988; 42(3): 198–202. Publisher Full Text\n\nIshwaran H, Rao JS: Spike and slab variable selection: Frequentist and Bayesian strategies. Ann. Stat. Apr. 2005; 33. Publisher Full Text\n\nCarlisle JB, Loadsman JA: Evidence for non-random sampling in randomised, controlled trials by yuhji saitoh. Anaesthesia. Dec. 2016; 72: 17–27. Publisher Full Text\n\nBarnett A: agbarnett/baseline_tables: Testing for under- and over-dispersion in baseline tables.June 2022.\n\nMarshall IJ, Nye B, Kuiper J, et al.: Trialstreamer: A living, automatically updated database of clinical trial reports. J. Am. Med. Inform. Assoc. 2020; 27(12): 1903–1912. PubMed Abstract | Publisher Full Text\n\nHastie T, Tibshirani R, Wainwright M: Statistical Learning with Sparsity: The Lasso and Generalizations. Chapman & Hall/CRC Monographs on Statistics & Applied Probability, CRC Press;2015.\n\nLunn DJ, Thomas A, Best N, et al.: WinBUGS - a Bayesian modelling framework: Concepts, structure, and extensibility. Stat. Comput. 2000; 10(4): 325–337. Publisher Full Text\n\nde Valpine P , Paciorek C, Turek D, et al.: NIMBLE: MCMC, Particle Filtering, and Programmable Hierarchical Modeling. 2021. R package version 0.12.1.\n\nR Core Team: R: A Language and Environment for Statistical Computing. Vienna, Austria:R Foundation for Statistical Computing;2022.\n\nCahan A, Anand V: Second thoughts on the final rule: An analysis of baseline participant characteristics reports on ClinicalTrials.gov. PLoS One. Nov. 2017; 12: e0185886. PubMed Abstract | Publisher Full Text\n\nFernandes-Taylor S, Hyun JK, Reeder RN, et al.: Common statistical and research design problems in manuscripts submitted to high-impact medical journals. BMC. Res. Notes. 2011; 4(1). PubMed Abstract | Publisher Full Text\n\nCabanac G, Labbé C, Magazinov A: Tortured phrases: A dubious writing style emerging in science. evidence of critical issues affecting established journals. CoRR. 2021; abs/2107.06751.\n\nBMJ Open: BMJ Open trials Penelope.2017.\n\nFrontiers: AI-enhanced peer review: Frontiers launches next generation of efficient, high-quality peer review.2018.\n\nHeaven D: AI peer reviewers unleashed to ease publishing grind. Nature. 2018; 563(7733): 609–610. PubMed Abstract | Publisher Full Text\n\nGeorge SL, Buyse M: Data fraud in clinical trials. Clin. Investig. Feb. 2015; 5: 161–173. PubMed Abstract | Publisher Full Text\n\nGopalakrishna G, ter Riet G , Vink G, et al.: Prevalence of questionable research practices, research misconduct and their potential explanatory factors: A survey among academic researchers in The Netherlands. PLoS One. 02 2022; 17: 1–16. Publisher Full Text\n\nGlasziou P, Altman DG, Bossuyt P, et al.: Reducing waste from incomplete or unusable reports of biomedical research. Lancet. 2014; 383(9913): 267–276. Publisher Full Text\n\nPrager EM, Chambers KE, Plotkin JL, et al.: Improving transparency and scientific rigor in academic publishing. J. Neurosci. Res. Dec. 2018; 97: 377–390. Publisher Full Text\n\nTobin MJ: Authors, authors, authors—follow instructions or expect delay. Am. J. Respir. Crit. Care Med. 2000; 162(4): 1193–1194. Publisher Full Text\n\nMalički M, Jerončić A, Aalbersberg IJ, et al.: Systematic review and meta-analyses of studies analysing instructions to authors from 1987 to 2017. Nat. Commun. 12(1): 2021. Publisher Full Text\n\nCarlisle JB: The analysis of 168 randomised controlled trials to test data integrity. Anaesthesia. 2012; 67(5): 521–537. PubMed Abstract | Publisher Full Text\n\nNuijten MB, Polanin JR: “statcheck”: Automatically detect statistical reporting inconsistencies to increase reproducibility of meta-analyses. Res. Synth. Methods. 2020; 11: 574–579. PubMed Abstract | Publisher Full Text\n\nHeathers JA, Anaya J, van der Zee T , et al.: Recovering data from summary statistics: Sample parameter reconstruction via iterative TEchniques (SPRITE). PeerJ PrePrints. May 2018.\n\nWren JD: Algorithmically outsourcing the detection of statistical errors and other problems. EMBO J. 2018; 37(12). PubMed Abstract | Publisher Full Text\n\nMascha EJ, Vetter TR, Pittet J-F: An appraisal of the carlisle-stouffer-fisher method for assessing study data integrity and fraud. Anesth. Analg. 2017; 125(4): 1381–1385. PubMed Abstract | Publisher Full Text\n\nBero L: Stamp out fake clinical data by working together. Nature. Jan. 2022; 601: 167–167. PubMed Abstract | Publisher Full Text\n\nBradshaw MS, Payne SH: Detecting fabrication in large-scale molecular omics data. PLoS One. 11 2021; 16: 1–15. Publisher Full Text\n\nWu X, Carlsson M: Detecting data fabrication in clinical trials from cluster analysis perspective. Pharm. Stat. 2010; 10(3): 257–264. PubMed Abstract | Publisher Full Text\n\nRoberts I, Ker K, Edwards P, et al.: The knowledge system underpinning healthcare is not fit for purpose and must change. BMJ. 2015; 350(jun02 17): h2463–h2463. Publisher Full Text\n\nShamseer L, Roberts J: Disclosure of data and statistical commands should accompany completely reported studies. J. Clin. Epidemiol. Feb. 2016; 70: 272–274. PubMed Abstract | Publisher Full Text\n\nHardwicke TE, Ioannidis JPA: Populating the data ark: An attempt to retrieve, preserve, and liberate data from the most highly-cited psychology and psychiatry articles. PLoS One. 2018; 13(8): e0201856. PubMed Abstract | Publisher Full Text\n\nSeverin A, Chataway J: Overburdening of peer reviewers: A multi-stakeholder perspective on causes and effects. Learned Publishing. May 2021; 34: 537–546. Publisher Full Text\n\nBarnett A: Underlying data for “Automated detection of over- and under-dispersion in baseline tables in randomised controlled trials”, [Dataset].2022. Publisher Full Text"
}
|
[
{
"id": "150544",
"date": "16 Sep 2022",
"name": "Erik van Zwet",
"expertise": [
"Reviewer Expertise I am a statistician at a university hospital."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper addresses the important problem of the detection of fraudulent RCTs. The basic idea is to analyze the baseline table or “table 1” and test if the group differences are either too large or too small. The author cites previous work on this approach.\nThe novelty of the paper is to propose a Bayesian model that can switch between the distribution of the differences between the groups that would be expected from chance alone, versus and over- or underdispersed distribution that would result from manipulation. For numerical outcomes the central t-distribution is appropriate when there is no fraud, and over- or underdispersion can be modelled by multiplying the dispersion with some trial-specific factor (gamma). Somewhat surprisingly, the t-distribution is also used for categorical outcomes with the author mentioning that the t-test is robust even for small sample sizes.\nA minor comment is that the prior probability of fraud is taken to be 50%, which seems rather pessimistic.\nI do have one serious reservation which led me to report that the statistical analysis and interpretation are \"partly\" appropriate. Although it is not mentioned explicitly, it seems that the Bayesian model assumes that the variables in the baseline table are independent, or at least uncorrelated. This does not seem realistic. Suppose the baseline table has, among other variables, age and blood pressure. If, by chance, a large number of old people are selected in group A, then it is likely that group A will also have a large number of people with high blood pressure.\nIndependence certainly does not hold among the pairwise group differences when there are more than 2 groups. Now, I’m worried that the dispersion parameter will pick up on this dependence, which could result in the false detection of fraud.\nFrom the description of the simulation experiment, it seems that the variables were independently generated. It would be important to also examine scenarios with varying degrees of dependence.\nThe result from the simulation study (p.7) that underdispersion was detected in only 16% of the cases is a little disappointing. Especially since underdispersion seems more likely than overdispersion as fraudsters presumably want their Table 1 to look beautifully balanced.\nFinally, I always recommend the paper of Morris et al., when I review a simulation study that does not cite it already1.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "8821",
"date": "30 May 2023",
"name": "Adrian Barnett",
"role": "Author Response",
"response": "A minor comment is that the prior probability of fraud is taken to be 50%, which seems rather pessimistic. Response: Yes, this could be viewed as pessimistic. When considering a single trial, it has the least amount of prior information, because it gives equal probability to both scenarios: dispersion and no dispersion. However, there may be prior knowledge about the expected probability of dispersion which could be lower, say 0.10. I have updated the shiny app to allow users to give their own prior probability. I do have one serious reservation which led me to report that the statistical analysis and interpretation are \"partly\" appropriate. Although it is not mentioned explicitly, it seems that the Bayesian model assumes that the variables in the baseline table are independent, or at least uncorrelated. This does not seem realistic. Suppose the baseline table has, among other variables, age and blood pressure. If, by chance, a large number of old people are selected in group A, then it is likely that group A will also have a large number of people with high blood pressure. Independence certainly does not hold among the pairwise group differences when there are more than 2 groups. Now, I’m worried that the dispersion parameter will pick up on this dependence, which could result in the false detection of fraud. From the description of the simulation experiment, it seems that the variables were independently generated. It would be important to also examine scenarios with varying degrees of dependence. Response: I have added three new simulations that examine correlated data. I simulated correlated continuous data, such as age and blood pressure, with separate simulations for correlation strengths of low (0.2) and high (0.6). I also added a simulation with 3 treatment arms. None of these simulations had over- or under-dispersion, so they were used to check for false positives. The Bayesian model did have an inflated false positive percentage for the high correlated data of 11%. However, it performed well for the 3-arm simulation, whereas the uniform test again had a high false positive probability of 23%. As per the recommended paper of Morris, it is: “useful to have unrealistically extreme data-generating mechanisms to understand when and how each method fails”. Trials with only multiple continuous variables with a correlation of 0.6 are not “unrealistically extreme”, but are likely rare. However, knowing that the approach can return false-positives in this scenario is useful to know, and I have added a comment on this to the discussion. Overall, I believe the new simulations show that the Bayesian method is relatively robust to correlated data. The result from the simulation study (p.7) that underdispersion was detected in only 16% of the cases is a little disappointing. Especially since underdispersion seems more likely than overdispersion as fraudsters presumably want their Table 1 to look beautifully balanced. Response: I agree this is a disappointing result. This lack of power can be somewhat overcome by combining tables from the same author or research group, as per the example in Figure 1. I have also mentioned this disappointing result in the discussion. Over-dispersion is generally easier to detect, because it is unbounded, and even one row of the table with a large difference could mean a high probability of over-dispersion. Whereas under-dispersion is bounded at zero, and hence generally needs multiple table rows with small differences to increase the probability of under-dispersion. Finally, I always recommend the paper of Morris et al., when I review a simulation study that does not cite it already. Response: Thanks for recommending this paper. I have heeded the advice of Morris et al. and included the standard error of the uncertainty in a supplemental plot and added some information justifying the sample size."
}
]
},
{
"id": "170574",
"date": "12 May 2023",
"name": "J Wilkinson",
"expertise": [
"Reviewer Expertise Stats",
"trials",
"detection of inauthentic trials"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper describes an automated approach to extracting baseline tables from RCTs and testing for under or over-dispersion. The work is timely, as there is currently lots of interest in and awareness around the issue of fabricated RCT data. Efficient methods to flag trials with apparent problems are needed – as the author notes, manual checking of published papers (as well as of the underlying individual participant data, if an investigation proceeds to that stage) is very time-consuming. My view of the work is positive – below I make some comments on applicability of the comparison between the new approach versus the approach based on uniformity of p-values.\nThe uniform test has been applied to binary variables in the simulation study – as the author notes, this is incorrect – and we probably don’t need another simulation study to tell us this. A more useful comparison might have been to compare the t-statistic method (on all variables) to the uniform p-value method applied to continuous variables only. Do we miss any studies using the uniform method because we have to omit binary variables? As it stands, we appear to have a comparison between the new approach and the uniform p-value approach applied to variables which are not suitable. Since one of the possible strengths of the new method is that it allows binary variables to be inspected, it would have been useful to know whether including them (vs dropping them with the uniform p-value method) actually led to different results.\n\nAside from the test of dispersion, the ability to reliably extract baseline table results would itself be very useful. This could be used to apply other checks (e.g. GRIM, checking accuracy of reported p-values, checks of digit preference) and if it could be done on a large scale, could facilitate identifying duplication between tables. So the ability of the tool to reliably extract this information is of interest. This appears to be challenging – tables were extracted from 25% of papers, when they will probably be reported by nearly all of them. Still, as someone who investigates a lot of papers for integrity issues, the ability to automatically extract for 1 in 4 papers would be welcome.\n\nThe paper mentions ‘dynamic randomisation’ as a challenge to investigating dispersion – not sure what specifically was meant by this term, but any method for creating balance in baseline characteristics will cause issues here (stratified randomisation, minimisation). However, when looking at study features associated with dispersion, this sort of covariate-adaptive randomisation doesn’t appear to have been considered – blocked randomisation has been considered, but this balances group sizes, rather than covariates.\n\nAs presented, results in Table 5 may be misleading (due to ‘Table 2 fallacy’ - Table 2 Fallacy: Presenting and Interpreting Confounder and Modifier Coefficients | American Journal of Epidemiology | Oxford Academic (oup.com)).\n\nVarious limitations of the approach are helpfully documented by the author.\n\nThe suggestion to focus on t-statistics is interesting, and is a useful contribution to the ongoing methodological work on this topic. There remains considerable scope to evaluate the approach, and to consider how it might sit alongside other approaches for integrity checking.`\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "9703",
"date": "29 Nov 2023",
"name": "Adrian Barnett",
"role": "Author Response",
"response": "The uniform test has been applied to binary variables in the simulation study – as the author notes, this is incorrect – and we probably don’t need another simulation study to tell us this. A more useful comparison might have been to compare the t-statistic method (on all variables) to the uniform p-value method applied to continuous variables only. Do we miss any studies using the uniform method because we have to omit binary variables? As it stands, we appear to have a comparison between the new approach and the uniform p-value approach applied to variables which are not suitable. Since one of the possible strengths of the new method is that it allows binary variables to be inspected, it would have been useful to know whether including them (vs dropping them with the uniform p-value method) actually led to different results. Response: This is a useful comparison and I have added this simulation to the results (Table 2). There were times when there was too little data for the uniform test to run, so there would likely be a loss of scrutiny in practice. Aside from the test of dispersion, the ability to reliably extract baseline table results would itself be very useful. This could be used to apply other checks (e.g. GRIM, checking accuracy of reported p-values, checks of digit preference) and if it could be done on a large scale, could facilitate identifying duplication between tables. So the ability of the tool to reliably extract this information is of interest. This appears to be challenging – tables were extracted from 25% of papers, when they will probably be reported by nearly all of them. Still, as someone who investigates a lot of papers for integrity issues, the ability to automatically extract for 1 in 4 papers would be welcome. Response: Yes, the wide variety of table presentations makes this challenging. To somewhat help, I have added the ability to download automatically extracted baseline tables to the shiny app: https://aushsi.shinyapps.io/baseline/. Although this is only for trials with the full text available on PubMed Central. The paper mentions ‘dynamic randomisation’ as a challenge to investigating dispersion – not sure what specifically was meant by this term, but any method for creating balance in baseline characteristics will cause issues here (stratified randomisation, minimisation). However, when looking at study features associated with dispersion, this sort of covariate-adaptive randomisation doesn’t appear to have been considered – blocked randomisation has been considered, but this balances group sizes, rather than covariates. Response: I’ve added a note to the limitations stating that under-dispersion could be due to covariate-adaptive randomization techniques. As presented, results in Table 5 may be misleading (due to ‘Table 2 fallacy’ - Table 2 Fallacy: Presenting and Interpreting Confounder and Modifier Coefficients | American Journal of Epidemiology | Oxford Academic (oup.com)). Response: This is worth considering, although all five variables might have independent effects on dispersion. The “standard error” is a presentation error, “Difference in group sample sizes of 10+” is a potential detector of non-randomised trials, “Proportion continuous” is the mix of binary and continuous statistics presented, “Number of table columns” indicates trials with multiple arms, and “sample size” gives the trial’s size. The causal pathways for these effects could be independent. Looking at the empirical associations between the variables did not indicate any great concern. I have added a descriptive plot to the GitHub page. Various limitations of the approach are helpfully documented by the author. Response: Thank you. One more has been added, with the potential for false positives for highly correlated data. The suggestion to focus on t-statistics is interesting, and is a useful contribution to the ongoing methodological work on this topic. There remains considerable scope to evaluate the approach, and to consider how it might sit alongside other approaches for integrity checking. Response: I agree. There is related ongoing work comparing my table-extraction approach to an alternative system that extracts tables from PDFs."
}
]
}
] | 1
|
https://f1000research.com/articles/11-783
|
https://f1000research.com/articles/12-552/v1
|
26 May 23
|
{
"type": "Research Article",
"title": "Serum angiopoietin 1 level in patients with severe COVID-19: An observational study",
"authors": [
"Muhammed Turki",
"Ali A. Kasim",
"Ali A. Kasim"
],
"abstract": "Background: Exocytosis of the endothelial storage granules, Weibel-Palade bodies, upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion with the consequent release of P-selectin and Von Willebrand factor, as well as several chemokines, results in hypercoagulability. Angiopoietin-2 is a chemokine stored in Weibel-Palade bodies; it is a context-dependent competitive antagonist of angiopoietin-1. Disruption of the angiopoietin/Tie2 pathway contributes to vascular dyshomeostasis in sepsis. This study aimed to investigate serum levels of angiopoietin-1 in patients with severe coronavirus disease 2019 (COVID-19). Methods: A total of 85 participants were enrolled in the study and divided into two groups: the first group included 45 patients with severe COVID-19, and the second group included 40 healthy individuals of comparable age and sex to serve as the control group. ELISA was used to measure serum angiopoietin-1 levels. Results: Serum angiopoietin-1 levels were significantly lower in patients with severe COVID-19 than in control subjects (14.52 (5.56) ng/ml and 30.56 (17.56) ng/ml, respectively; p < 0.001). Moreover, at a cut-off value ≤21.05 ng/ml, serum angiopoietin-1 level had 97.8% sensitivity and 100% specificity in differentiating between severe COVID-19 patients and non-infected individuals (p-value <0.001). Conclusions: Serum angiopoietin-1 levels were lower in patients with severe COVID-19 than in control subjects, and it has potential to be used as a diagnostic marker for patients with severe COVID-19.",
"keywords": [
"Angiopoietin-1",
"COVID-19",
"Hypercoagulation",
"Angiogenesis",
"Tie2"
],
"content": "Introduction\n\nIn 2019, a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused a contagious disease known as coronavirus disease 2019 (COVID-19). The condition was declared to be a pandemic in March 2020 by the World Health Organization.1,2 COVID-19 ranges from being asymptomatic in some cases3 to causing mild symptoms in the majority of cases, including fever and upper respiratory and gastrointestinal tract symptoms.4,5 However, it can progress to severe cases of pneumonia, multi-organ failure, and, ultimately, death.6–8\n\nAkin to other coronaviruses, SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), which is a membrane-bound peptidase, as a gateway to enter the host cells9,10; ACE2 expression was reported to be correlated with increased viral load in human cell lines11,12 as well as rodents.13\n\nCOVID-19 patients display a state of increased coagulability and thrombotic tendency.14,15 Antithrombotic prophylaxis represents an essential part of the treatment plan to prevent the development of pulmonary embolism and deep vein thrombosis that develop in severe cases or cases with increased d-dimer.16–18 However, despite antithrombotic prophylaxis, approximately 30% of patients with severe COVID-19 admitted to the intensive care unit have developed arterial and venous thrombotic events, increasing the mortality risk in these patients by 5.4 times.19 Several mechanisms mediate the hypercoagulability of COVID-19 patients.20\n\nAmong these mechanisms is the exocytosis of Weibel-Palade bodies from the vascular endothelium upon SARS-CoV-2 invasion.21–23 Weibel-Palade bodies are endothelial storage granules of mediators involved in inflammation and coagulation, primarily P-selectin and von Willebrand factor.24,25 Weibel-Palade bodies contain several chemokines.26\n\nAngiopoietins are members of a family of vascular growth factors that play crucial roles in angiogenesis by binding to their physiologic receptors, tyrosine kinase with immunoglobulin-like and epidermal growth factor (EGF)-like domains 1 (Tie-1) and Tie-2, where Tie-2 is the primary receptor. Angiopoietin-1 is primarily produced in pericytes and smooth muscle cells; however, large quantities are produced and released from platelets upon activation.27 It is critical for endothelial cell integrity, survival, migration, and the suppression of inflammatory gene expression.28,29 Angiopoietin-2, on the other hand, is a context-dependent competitive antagonist of angiopoietin-1, promoting endothelial apoptosis and disrupting vascularization.30 Angiopoietin-2 is a chemokine stored in Weibel-Palade bodies, and its serum level is elevated in patients with severe COVID-19.31 Parikh, suggests that disruption of the angiopoietin/Tie2 pathway contributes to vascular dyshomeostasis in sepsis.32\n\nThis study aimed to investigate serum levels of angiopoietin-1 in patients with severe COVID-19.\n\n\nMethods\n\nThe ethics committee of the College of Pharmacy, University of Baghdad, approved the research protocol (approval code:112021A) on 5th November 2021. Verbal consent was obtained from all participants after they were informed of the purpose of the study. Verbal consent was obtained because several participants indicated that they were more comfortable in providing verbal consent rather than written consent. The reason given was that the latter might have some element of risk in breaching the anonymity of the participants. When the proposal was submitted to the ethics committee, it included comprehensive information on the study’s purpose and methodology. One of these details was the method of acquiring consent from participants, which was verbal consent recorded on a digital recorder.\n\nThis observational, case-control study compared hospitalized adult patients with severe COVID-19 and healthy control individuals.\n\nThis multicenter study was conducted in Baghdad/Iraq, in the Dar Al Salam, Al Ata’a, and Al Khadymia hospitals, from 10th November 2021 to June 2022. As both these affiliations (teaching healthcare institutes) and the University of Baghdad are Government Institutions, they have direct official contact to conduct research under continuous supervision.\n\nThe main objective of this study was to compare the serum angiopoietin-1 levels between hospitalized patients with severe COVID-19 and control subjects.\n\nG*Power (RRID: SCR_013726) version 3.1.9.7 software estimated the required number of participants. A two-tailed alpha of 0.05, with a confidence interval of 95%, power of 90%, and effect size of 0.80, was used. Therefore, the required sample size was 80 (f). In this research, 85 participants were enrolled, 45 in the COVID-19 group and 40 in the healthy control group.\n\nThe COVID-19 participants were adults (20-60 years old) who had severe infection confirmed by positive RT-PCR for SARS-CoV-2 aided by radiological evidence, mainly chest X-ray or computed tomography (CT) scan. The severity was assessed clinically following the National Institute of Health Categorization for severe COVID-19 infection displaying oxygen saturation lower than 94% at room air and sea level with shortness of breath, alongside fever, cough, chest tightness, and pain.33 While the control group participants were healthy with comparable sex and age to the COVID-19 patients’ group.\n\nPatients with the following conditions were excluded from the study: diabetes mellitus; cardiovascular, hepatic, or renal diseases; those who smoke tobacco; and those on any medication that may interfere with serum angiopoietin-1 levels or measurements.\n\nBias was minimized by randomly selecting participants without prior knowledge of the outcome; participants’ enrolment was done in a way that did not favor individuals with high or low exposure to COVID-19. As for the control participants, in addition to their history being taken during sampling, they were asked if they had experienced COVID-19 symptoms previously.\n\nData regarding diagnosis, tests, case history, and comorbidities were obtained from the patient’s case files and directly from the participants. Blood samples (3 mL) were collected in gel tubes, left to sit for 10–20 min to allow coagulation, and then centrifuged at 3,000 rpm to collect the serum. Eppendorf tubes were used to store the collected serum at -20°C until sample collection was completed. Serum angiopoietin-1 levels were measured using sandwich enzyme-linked immunosorbent assay kits.34\n\nSpecifications of the human angiopoietin-1 ELISA kit are presented in Table 1.\n\nSPSS (RRID:SCR_013726) version 25 was used for statistical analysis in this study, and the Shapiro-Wilk test was used to check the distribution uniformity of the data. Continuous variable data were presented as the median and interquartile range (IQR), and the significance of the difference between the groups was analyzed using the Mann-Whitney U test. Percentages and frequencies were used to present categorical variables, and the chi-squared test was used to analyze the significance of differences between the groups. Statistical significance was considered when the p-value was <0.05. Receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC), optimal cut-off, sensitivity, and specificity values of serum angiopoietin-1 levels to check their diagnostic potential to differentiate between severe COVID-19 and non-infected individuals.\n\n\nResults\n\nNo significant difference was detected between patients with severe COVID-19 and the control subjects regarding age and sex. Therefore, demographic data are summarized in Table 2.45\n\nSerum angiopoietin-1 level was significantly lower [14.52 (5.56) ng/ml] in the patients with severe COVID-19 than in the control subjects [30.56 (17.56) ng/ml], (p-value <0.001) (Table 3).\n\n* p<0.05, statistically significant.\n\nSerum angiopoietin-1 levels displayed diagnostic potential in differentiating between patients with severe COVID-19 and non-infected individuals according to the ROC curve (Table 4 and Figure 1).\n\n* p<0.05, statistically significant.\n\nROC, receiver operating characteristic.\n\n\nDiscussion\n\nCOVID-19 was hypothesized to be a vascular disease with endothelial damage or dysfunction, angiogenesis, and hypercoagulation.35 Endothelial cell integrity is crucial for protecting the thrombotic environment and developing inflammation in COVID-19 patients. Disruption of the endothelial thromboprotective role might lead to hypercoagulation, as primarily described in these patients.14,15 In a prospective study, Smadja et al., showed that SARS-CoV-2 infection is accompanied by elevated levels of the soluble endothelial activation markers, namely, soluble E-selectin and angiopoietin-2, in critically ill hospitalized COVID-19 patients.31\n\nAngiopoietin-2, a context-dependent competitive antagonist of angiopoietin-1, is an essential regulator of endothelial homeostasis, angiogenesis, and proliferation through the angiopoietin/Tie-2 pathway.30 Elevated serum angiopoietin-2 levels have been reported in patients with sepsis or acute respiratory distress syndrome (ARDS).36 On the other hand, circulating angiopoietin-1 levels have been found to be lower in patients with sepsis-induced multiple organ dysfunction syndrome and to be correlated with the clinical course of the condition.37 Whitney et al., showed that the angiopoietin-2/angiopoietin-1 ratio is higher in septic patients with ARDS than in septic patients without ARDS, which in turn is higher than in the control subjects, suggesting that endothelial dysfunction mediated by alterations in angiopoietins levels is involved in the pathogenesis of ARDS in the course of extrapulmonary sepsis.38\n\nIn COVID-19, infected endothelial cells are stimulated to release angiopoietin-2 from the Weibel-Palade bodies. Once in circulation, angiopoietin-2 competitively inhibits angiopoietin-1, disrupting its thromboprotective role.39 Higgins et al., showed that diminished Tie2 signaling develops before overt disseminated intravascular coagulation and that exogenous angiopoietin-1 administration normalizes hypercoagulability in endotoxemic mice. This implies that the angiopoietin-1/Tie2 pathway is central in protecting against microvascular thrombus formation during sepsis, even without inflammation.40\n\nIn the present study, serum angiopoietin-1 levels were significantly lower in patients with severe COVID-19 than in the control group.\n\nAbou-Arab et al., showed that the serum angiopoietin-2/angiopoietin-1 ratio is significantly higher in critically ill patients than in patients with severe COVID-19. However, serum angiopoietin-1 level was not significantly different between the two groups.41 Compared to the present study, Abou-Arab et al., did not exclude patients with other comorbidities and did not compare serum angiopoietin-1 levels with healthy controls.41 Similarly, Vassiliou et al., reported that serum angiopoietin-1 levels were not significantly different between survivors and non-survivors of critically ill COVID-19 patients admitted to the intensive care unit.42\n\nAs mentioned earlier, platelets produce and release a significant amount of angiopoietin-1.27 Thrombocytopenia is a common finding in severe COVID-19 infections, and it is associated with poor clinical outcomes.43 Thrombocytopenia in severe COVID-19 conditions was attributed to platelet apoptosis and platelet consumption by incorporation into microthrombi.44 Thus, lower serum angiopoietin-1 levels in patients with severe COVID-19 may be a consequence of thrombocytopenia.\n\nIn the present study, serum angiopoietin-1 showed good potential as a diagnostic marker to differentiate severe COVID-19 from non-infected individuals, with an AUC of 0.98, 100% specificity, and 97.8% sensitivity at a cut-off value of ≤21.05 ng/ml with a confidence interval of 0.94–1.00. On the other hand, Vassiliou et al., found that the serum angiopoietin-2, an angiopoietin-1 antagonist, is an excellent diagnostic marker to differentiate between severe and critically ill COVID-19 patients with an AUC of 0.86, with 77.3% specificity and 88.9% sensitivity at a cut-off value of ≥4 ng/ml with a confidence interval of 0.72–0.99.42 This emphasizes the role of disturbed serum angiopoietin levels during COVID-19.\n\nThe number of participants in this study was modest; thus, we recommend a future larger-scale prospective study including COVID-19 patients with different severity levels of infection.\n\n\nConclusions\n\nPatients with severe COVID-19 have lower serum angiopoietin-1 levels, and serum angiopoietin-1 levels have diagnostic potential for differentiating between patients with severe COVID-19 and non-infected individuals.",
"appendix": "Data availability\n\nZenodo: Measurement of Serum Angiopoietin 1 level in Severe COVID-19 patients: An observational study, https://doi.org/10.5281/zenodo.7747903. 45\n\nThis project contains the following underlying data:\n\n‐ Article data.xlsx (Measurement of Serum Angiopoietin 1 level in Severe COVID-19 patients: An observational study).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nWe express our gratitude to the COVID-19 care units for their support and help with sample collection and to the participants in this study.\n\n\nReferences\n\nAdil MT, Rahman R, Whitelaw D, et al.: SARS-CoV-2 and the pandemic of COVID-19. Postgrad. Med. J. 2021; 97(1144): 110–116. Publisher Full Text\n\nJoshi M, Deshpande JD: Polymerase chain reaction: methods, principles and application. Int. J. Biomed. 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PubMed Abstract | Publisher Full Text\n\nAbd HA, Kasim AA, Shareef LG: Serum levels of α1-antitrypsin, interleukin-1β and interleukin-6 in Iraqi COVID-19 patients: A cross-sectional study [version 1; peer review: awaiting peer review]. F1000Res. 2022; 11: 921. Publisher Full Text\n\nConnors JM, Levy JH: COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020; 135(23): 2033–2040. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRen B, Yan F, Deng Z, et al.: Extremely high incidence of lower extremity deep venous thrombosis in 48 patients with severe COVID-19 in Wuhan. Circulation. 2020; 142(2): 181–183. PubMed Abstract | Publisher Full Text\n\nThachil J, Tang N, Gando S, et al.: ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J. Thromb. Haemost. 2020; 18(5): 1023–1026. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlok F, Kruip M, Van der Meer N, et al.: Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis. Thromb. Res. 2020; 191: 148–150. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPoveda-Jaramillo R: Coronavirus disease 2019-induced hypercoagulability and its clinical implications. Asian Cardiovasc. Thorac. Ann. 2022; 30(5): 515–523. PubMed Abstract | Publisher Full Text\n\nEscher R, Breakey N, Lämmle B: ADAMTS13 activity, von Willebrand factor, factor VIII and D-dimers in COVID-19 inpatients. Thromb. Res. 2020; 192: 174–175. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHelms J, Tacquard C, Severac F, et al.: High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020; 46(6): 1089–1098. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStreetley J, Fonseca A-V, Turner J, et al.: Stimulated release of intraluminal vesicles from Weibel-Palade bodies. Blood. 2019; 133(25): 2707–2717. Publisher Full Text\n\nBonfanti R, Furie BC, Furie B, et al.: PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood. 1989; 73(5): 1109–1112. PubMed Abstract | Publisher Full Text\n\nWagner DD, Olmsted JB, Marder VJ: Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J. Cell Biol. 1982; 95(1): 355–360. PubMed Abstract | Publisher Full Text | Free Full Text\n\nØynebråten I, Bakke O, Brandtzaeg P, et al.: Rapid chemokine secretion from endothelial cells originates from 2 distinct compartments. Blood. 2004; 104(2): 314–320. PubMed Abstract | Publisher Full Text\n\nLi JJ, Huang YQ, Basch R, et al.: Thrombin induces the release of angiopoietin-1 from platelets. Thromb. Haemost. 2001; 85(2): 204–206. PubMed Abstract | Publisher Full Text\n\nPeters KG, Kontos CD, Lin PC, et al.: Functional significance of Tie2 signaling in the adult vasculature. Recent Prog. Horm. Res. 2004; 59: 51–71. PubMed Abstract | Publisher Full Text\n\nBrindle NP, Saharinen P, Alitalo K: Signaling and functions of angiopoietin-1 in vascular protection. Circ. Res. 2006; 98(8): 1014–1023. Publisher Full Text\n\nMaisonpierre PC, Suri C, Jones PF, et al.: Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997; 277(5322): 55–60. PubMed Abstract | Publisher Full Text\n\nSmadja DM, Guerin CL, Chocron R, et al.: Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients. Angiogenesis. 2020; 23(4): 611–620. PubMed Abstract | Publisher Full Text | Free Full Text\n\nParikh SM: Dysregulation of the angiopoietin-Tie-2 axis in sepsis and ARDS. Virulence. 2013; 4(6): 517–524. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHealth NIo: Clinical Spectrum of SARS-CoV-2 Infection. NIH; 2022. Reference Source\n\nAydin S: A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides. 2015; 72: 4–15. PubMed Abstract | Publisher Full Text\n\nMahjoub Y, Rodenstein DO, Jounieaux V: Severe Covid-19 disease: rather AVDS than ARDS? Crit. Care. 2020; 24(1): 327. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi F, Yin R, Guo Q: Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies.2020; 14: 1753466620905274.\n\nLin SM, Chung FT, Kuo CH, et al.: Circulating angiopopietin-1 correlates with the clinical course of multiple organ dysfunction syndrome and mortality in patients with severe sepsis. Medicine. 2015; 94(20): e878. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWhitney JE, Zhang B, Koterba N, et al.: Systemic Endothelial Activation Is Associated With Early Acute Respiratory Distress Syndrome in Children With Extrapulmonary Sepsis. Crit. Care Med. 2020; 48(3): 344–352. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIba T, Connors JM, Levy JH: The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm. Res. 2020; 69(12): 1181–1189. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHiggins SJ, De Ceunynck K, Kellum JA, et al.: Tie2 protects the vasculature against thrombus formation in systemic inflammation. J. Clin. Invest. 2018; 128(4): 1471–1484. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbou-Arab O, Bennis Y, Gauthier P, et al.: Association between inflammation, angiopoietins, and disease severity in critically ill COVID-19 patients: a prospective study. Br. J. Anaesth. 2021; 126(3): e127–e130. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVassiliou AG, Keskinidou C, Jahaj E, et al.: ICU admission levels of endothelial biomarkers as predictors of mortality in critically ill COVID-19 patients. Cells. 2021; 10(1): 186. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLippi G, Plebani M, Henry BM: Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin. Chim. Acta. 2020; 506: 145–148. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRohlfing AK, Rath D, Geisler T, et al.: Platelets and COVID-19. Hamostaseologie. 2021; 41(5): 379–385. PubMed Abstract | Publisher Full Text\n\nTurki M: Serum Angiopoietin 1 level in Severe COVID-19 patients: An observational study. [Dataset]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "175833",
"date": "20 Jun 2023",
"name": "Esra Laloglu",
"expertise": [
"Reviewer Expertise Medical Biochemistry"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn the abstract: \"Serum angiopoietin-1 levels were lower in patients with severe COVID-19 than in control subjects,” You used the same sentence in the result part, this sentence is suitable for the result part.\n\nSpecify the reference you used to calculate the sample size.\n\nHas pcr been done for healthy people, can they be asymptomatic Covid 19?\n\nPlease, write important laboratory parameters of patients. I would like to see the correlation between the laboratory results of the patients and ANG 1, especially, is the relationship between D dimer, PT, PTT, INR, Fibrinogen, thrombocyte level and ANG 1 significant?\n\nDo patients have comorbidities that will affect ANG 1 level?\n\nHave you ever had a COVID 19 patient who developed arterial or venous thromboembolism, and if so, wıll you compare the ANG1 level of those with and without thromboembolism?\n\nIn Conclusion: “Patients with severe COVID-19 have lower serum angiopoietin-1 levels, and serum angiopoietin-1 levels have diagnostic potential for differentiating between patients with severe COVID-19 and non-infected individuals”.\nIn order to say ANG 1 is a diagnostic marker, necessary laboratory studies must be done, this is a very definite statement, a sentence containing probability must be written (for example ”may be”).\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-552
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https://f1000research.com/articles/12-74/v1
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19 Jan 23
|
{
"type": "Research Article",
"title": "Towards a dialogical and progressive educational policy framework: Manoeuvring a middle way among the polarised constructs",
"authors": [
"Solomon Arulraj David"
],
"abstract": "Policy science and practice around the world, including educational policies, are dominated by popular, extreme approaches such as market-orientated approaches at one end and critical argumentative approaches at the other end. This study therefore aims to manoeuvre a middle way to propose a dialogical and progressive educational policy framework and explores the research question: ‘how could a middle way (a dialogical and progressive framework) be manoeuvred among the polarised policy constructs?’ The study embraces Lynham’s five phases of theory building as the basis for this research, which includes conceptual development, operationalisation, confirmation/disconfirmation, application, and continuous refinement. The study explores some of the known existing policy frameworks for conceptual mapping, investigates the underlying dynamics and discourses to operationalise, uses diverse arguments in the literature to confirm/disconfirm and proposes to mark the emerging patterns, trends, and gaps in policy research to apply and refine. The study contends that if it is possible to have a polarised market-oriented and critical argumentative policy frameworks, it is then possible to have a dialogical, progressive middle-way policy framework. The study had to limit to the most important and related theories, and models to focus. Future works could explore a wide range of other relevant theories and models to further investigate this framework. Furthermore, application of the proposed dialogical, progressive educational policy framework in specific context/case may help to refine it. The study contends that the proposed middle way is not a perfect space but a potential space in which a dialogical and progressive educational policy may thrive.",
"keywords": [
"Public and Social Policy",
"Educational Policy",
"Policy Polars and Centre",
"Dialogical Approach",
"Progressive Policy Framework"
],
"content": "Introduction\n\nThere are a number of approaches to policy design, dissemination, and evaluation. However, public policies including educational policies across the world increasingly embrace the emergence of neo-managerialism that favours neo-liberal, market driven policy frameworks (David, 2014). Such trends are often countered by radical critical approaches, such as argumentative policy frameworks. It is argued that the growing libertarianism favours laissez-faire capitalism where the market strongly influences public and social policy making and analysis processes. This seemingly leads to the antagonism between agency/ structure, individual/institution, public/ state, and market/state (Berkhout & Wielemans, 1999).\n\nEducation and educational policy have strongly embraced the dominant trends in the world outside education sector making it conducive, while often missing exploring potential alternatives. It is argued that all policy frameworks may have some strengths and some limitations. This study believes that the discontentment of the neo-managerial policy orientation and the polarised critical alternatives create a space for the search of a progressive policy framework. And it considers a dialogical progressive policy framework to stimulate dialogue among polarised frameworks as a middle way. The study therefore aims to manoeuvre a middle way to propose a dialogical and progressive educational policy framework. The polar (north/south or east/west) in this study is ideological rather than geographical. The study streams away from the classical empirical approach and embraces rationalist and hermeneutic approaches by critically reviewing and interpreting relevant literature and making essential meaning by careful reflection and rationalisation.\n\nThis research follows Lynham’s five phases of theory building as elaborated in the methodology. The study particularly takes the courage to look for a progressive alternative among existing policy polars. It further explores some of the theoretical blind spots, particularly looking at spaces where conventional theorists seldom visit. The study also explores some of the alternative cognitive models such as the epistemic third space (Seremani & Clegg, 2015), cognitive justice (Visvanathan, 2019) and others as potential middle way among the polarised constructs. The study contents that if it is possible to have polarised market oriented and critical argumentative policy frameworks, it is then possible to have a dialogical, progressive middle way policy framework.\n\n\nMethodology\n\nThe study aimed to manoeuvre a middle way to propose a dialogical and progressive educational policy framework amidst the polarised constructs. Exploration of the relevant theories, models and literature supported the formulation of the general research question relevant to the focus of the study: ‘how could a middle way (a dialogical and progressive framework) be manoeuvred among the polarised (new-liberal/managerial vs argumentative/critical frameworks) policy constructs? The general method of theory building in applied disciplines approach by Lynham (2002) is used as the methodological basis in this study in search of answers and evidence for the above research question. This study follows the first three of the five phases of Lynham’s theory building such as conceptual development, operationalisation, confirmation/disconfirmation, application, and continuous refinement. The last two phases; application and refinement could be extended when this framework is applied in a specific case or context. This research began by mapping out some of the dominant existing policy frameworks for conceptual development. The study then explored the underlying dynamics, cross-cutting discourses using discourse analysis to operationalise the framework. It accounted for diverse arguments in the scholarly world and used a constant comparison approach to confirm and disconfirm. Further, it highlighted the emerging patterns and trends for application and continuous refinement through critical reflection, interpretation, and rationalisation.\n\nStandard protocols of literature review, meta-analysis, and meta-synthesis were followed in the study (Xiao & Watson, 2017). Relevant literature was searched using relevant search tools and words. Suitable academic databases such as ERIC, EDSCO and journals on public and educational policies such as Public Administration Review, Journal of Comparative Policy Analysis, Review of Policy Research, Educational Policy, Educational Evaluation and Policy Analysis and others were supportive as information sources in search of comprehensive and relevant literature well situated in the field of the study. The study used inclusion/eligible criteria suitable to the nature of the study, particularly sorting theories, models, and literature on three policy polars such as the ‘extreme right’, ‘extreme left’ and ‘the centre’ to select relevant literature for review. The selected literature became the resources and data for further analysis. The use of skimming and scanning helped to sort out recent related literature for further in-depth review. For Aguinis et al. (2011), meta-analysis is a central method for knowledge accumulation in many scientific fields. Qualitative meta-analysis focusing on the conceptual focus of the study helped to achieve a comprehensive understanding (Hansen, Steinmetz & Block, 2022). Meta-synthesis was supportive in summarising, analysing, interpreting the findings. Erwin et al. (2011) consider meta-synthesis as a coherent approach to analyse and report qualitative data. This study particularly embraced integrative approach (Synder, 2019) in summarising and synthesising the review to reach a comprehensive meaning making. The study also relied on constant comparison and thick descriptions among related and polarised policy frameworks to analyse, interpret, and synthesise (Creswell, 2007) to develop the proposed middle way ‘dialogical and progressive educational policy framework’.\n\n\nReview and analysis\n\nConceptual development is the first phase of theory building for Lynham, which “requires that the theorist formulate initial ideas in a way that depicts current, best, most informed understanding and explanation of the phenomenon, issue, or problem in the relevant world context (2002, p.231)”. Glaser & Strauss (1967) suggest that conceptual thinking and theory building is interrelated with the qualitative research method approach ‘grounded theory’. Some of the pressing questions while conceptualising public and educational policies are: Why do we need policy? What should a policy address? Who designs policy? For whose interest? Who should be involved in policy processes? Who and what should be consulted in policy making, implementing and evaluation? What are the general trends, patterns, procedures, gaps in policy making and analysing? These and other related questions on policy making, implementation and evaluation may help in making a good conceptual development on educational policy making, implementation and evaluation.\n\nDefining public policy would be the foundation for establishing a good conceptual understanding. Public policy is a set of government decisions with a certain common purpose for the public. Birkland (2005) highlights the following as common traits of public policy. For him, public policy is made in the name of the public; and it is generally made or initiated by government, it is interpreted and implemented by public and private actors, it is what the government intends to do, and it is what the government chooses not to do. The term policy has range of definitions. It is often used in synonym with other terms such as principles, rules, and guidelines. According to Compliance Dictionary (2022), policies are formulated or adopted by an organisation to reach its long-term goals and it is usually published in a booklet or in another form that is widely accessible by all. Public policy is the laws and regulations that are made by legislative statesmen and implemented by public administration personnel (Wu & He, 2009). Most often, the terms ‘policy and law’ are used interchangeably. It is necessary to clarify the differences between the two terms. According to Education and Training Unit (2018), a policy lists what a government ministry wants to achieve and the methods and principles it will instrument to attain them, while laws set out standards, procedures, and principles that must be followed. A policy document is not a law, but it will often identify new laws needed to achieve its goals. And laws must be guided by current government policies. It is important to observe the gap between the intention and the outcome of a policy. Qian & Walker (2011) indicate the gap between the policy intent and policy effect of the curriculum. Often, the end users’ experience of a policy is far from the intentions embedded during the design (David & Hill, 2020). In furthering the conceptual development on policy making and evaluation, Haddad’s (1995) conceptual framework for policy making and analysis is worth mentioning, as that includes “analysis of the existing situation, the process of generating policy options, evaluation of policy options, making the policy decision, planning policy implementation, policy impact assessment, subsequent policy cycle (p.18)”. The following table offers the scope of policymaking, implementation, and evaluation, adapted from Haddad (1995, p.19).\n\nThe above table offers necessary foundation for the conceptual development. The framework indicates that if the issue is high in a global context, complex and diverse programmes would be favourable with broad and universal strategies. For Haddad (1995), the scope of policymaking, implementation and evaluation must consider the issue, programme, and strategies. The issues could be low, precise, and narrow. The programme can be complex, with several alternatives and criteria along with the decision environment, while the strategies could be high, imprecise, and broad. If the issue is medium and the context is regional, dynamic and several programmes are suitable with narrow and priority strategies. And if the issue is low and the context is local, specific and few programmes are relevant with precise and focused strategies. The choices of the programmes and strategies may change if the issues and contexts are different as indicated in Table 1. Policy is a broad notion including any kind of management activity. The term ‘policy’ as such defines the art of the state management. Policy means authority and decision-making. Thus, policy is referred to as the management of an activity or influence on such management. Many things in the world today have largely been shifted by globalisation phenomenon, which impacts the policy processes (David, 2014). However, the changes induced by globalisation may not happen the same way across the world. Countries and activities in different countries differ in responding to the process of globalisation according to their capacities and preferences. Yet, they are increasingly governed by similar pressures, procedures, and organisational patterns (Schugurensky, 1990). This reality is experienced at all levels of governance and at all levels of social sectors. The way, in which the economy, politics, culture were organised at supranational, national, and sub-national level has changed during the globalisation regime (Wielemans, 2002) and these changes have implications for policy processes.\n\nMany scholars including Burbules & Torres (2000) elaborate on the way globalisation is impacting education policies of nation-states. They indicate the supranational institutions’ influence on national policies (with a set of global rules), the impact of neo-liberalism as a hegemonic policy discourse, reflected in policy making at different levels (David, 2014). For some public policy is firmly held in the grip of the free market principles (profit as the ultimate goal) (Cerny & Evans, 2004). Moreover, economic forces, labour market requirements exercise considerable impacts on public decision making. This paves the way for public and educational policies to be measured in terms of its capacity to be useful and to serve the labour market (Wielemans, 2000, David & Wildemeersch, 2014). It is important to note that the free market economy only works adequately if certain conditions are met (with due economic return). Thus, the strong dependency of public policy making, with free market economic principles might damage public and social interest (David, 2017a). In this conceptualisation, it is important to notice the polarised constructs in the existing policy arena. The polarised constructs are essential for the proposed progressive framework (middle way) to thrive. An important question at this stage is: ‘Is balancing possible?’ assuming that the two polarised tendencies in policy-making are social and economic responsiveness. For which, accounting for different stakeholders’ views are essential to understand the policy arena (David, 2017b). The Figure 1 is conceptualising the polarised policy arena with the two polars such as the social responsive end and the economic responsive end.\n\nThe above conceptualisation of the polarised policy arena hints the two extreme ends of the policy space that are led by social responsive end on one side and economic responsive end on the other side. The social responsive end is driven by social activism and governed by welfare states, while the economic responsive end is driven by corporate activism and governed by neo-liberal states (David, 2016). The social responsive policy is measured by its focus on public interest and social justice agenda, influenced by civil societies, while the economic responsive policy is measured by corporate interest and development agenda, influenced by the global and local market (Rensburg, Motala & David, 2016). As this polarised conceptualisation compels the question, is balancing possible? The potential answer would be that it is possible, if a middle and progressive way is explored. Therefore, the fundamental assumption of this study is that if it is possible for us to have the polarised neo-managerial, market oriented and critical, argumentative policy frameworks, it should be then possible to have a dialogical, progressive middle way policy framework. In such conceptualisation a dialogical progressive middle way policy framework is explored.\n\nOperationalisation is the second phase of theory building for Lynham (2002). For her, the purpose of operationalisation phase of theory building research is essentially an explicit connection between the conceptualisation phase and practice. Understanding public policy in light Durkheim’s (1968) construct of collective or common consciousness is important in looking for a progressive policy environment. For him, a good society is based on a moral order and the moral order is achieved through collective consciousness, as society commands us because it is exterior and superior to us. He sees social and public policy as a social/group decision making, which is a cult of a collective consciousness process. However, it is important to distinguish group decision making from groupthink. Lunenburg (2010) differentiates group decision making from groupthink, that group decision making is the tendency of cohesive groups to reach a consensus on issues without offering, seeking, or considering alternative viewpoints, while groupthink (Janis, 1991) is a result of group pressures to reach a consensus which might lead to a deterioration of mental efficiency, poor tasting of reality and lack of moral judgement for individuals. As policy making involves decision making, Etzioni (1967) recommends mixed scanning approach for social decision making. The rationalist approach is utopian and as incremental approach lacks empirical facts. Therefore the mixed scanning approach that makes detailed search for higher order fundamental decisions. In order to operationalise the dialogical progressive policy framework, it is necessary to further theorise this framework. Exploring some of the established theories to argue the need and relevance for a public policy becomes fundamental. The Hobbesian problem of social order (Ellis, 1971) and social norms (Hampton, 1987), Kant’s social contract (Stanford, 2016) insist on the need for a social and public policy that would stabilise social order. They viewed that the social order could be established by the formation of the state where individuals’ compliance to social norms would create social order. Marx & Engels’ view on ‘state as a necessary institution for social order’ further poses the need for social and public policy to be facilitated by a social institution such as the state (Sanderson, 1963). For them the state as a social institution could manage class conflict and with class compliance with social norms would create social order. Social institutionalism legitimises that the social and cultural norms are essential for public management and social and public policy making. Sceptics such as Proudhon were not convinced that the state could be an absolute end for social order. Proudhon’s list of the ‘domestic inconveniences of the state’ indicates the states’ limitations in establishing social order, who further recommends ‘self-government and the citizen state’ (Panarchy, 2019), Foucault’s notions, such as bio power and social control (Lacombe, 1996), recommend controlling and disciplining society by exercising power to normalise society. On the contrary, Noam Chomsky argued that social change and norms must be founded on some concepts of human nature and freedom (Wilkin, 1999). Buchanan & Tullock’s public choice theory (Holcombe, 1989) highlights that the political behaviour of citizens in the public choices they make influence on the political processes and outcomes that are essentially important in understanding and operationalising the progressive policy framework. Baumer & Van Horn’s (2014) policy making spectrum includes three types of policy decisions such as narrow/private, moderate/representative democracy and broad/public. The narrow decision is made by corporate governance and capitalism, the moderate decision is made by elected candidates and conventional law making, the broad decision is made by elections and aroused public opinion. In such understanding of public policy making and decision-making processes, a conducive environment for progressive policy is speculated. The following framework presents a conducive environment for progressive policy (Figure 2).\n\nThe above framework on conducive environment for progressive policy envisions a space in which a progressive policy making could thrive. Progression is viewed as a broad policy making type, which considers wider public engagement, while retrogression is viewed as a narrow policy making type that relies on mere conventional law and midtrogression is a moderate policy making type, which is representative. Each of these three types could apply their approaches in low, medium, and high levels. The high progressive end is the ideal conducive environment for progressive policy, with public common good and with wider public engagement. Following the development of the conducive environment for progressive policy making the framework for dialogical and progressive framework is designed. The proposed ‘dialogical and progressive public and educational policy framework’ is partly drawn from Mitchell’s (2018) progressivism and the evolution of education policy. His classification of progressivism includes emphasis on structural reforms, policy shift toward access and participation, shifting away from centralised control and accounting for change. The proposed framework investigates the frameworks of Lejano (2006) that provides the evolution of policy analysis framework from positivist foundations, post-positivist’s perspectives, and post-constructivist’s sentiments. As Peters (2005) indicates that it is important to understand the policy problem well before further conceptualising the design, tool and strategies, the design makes necessary attention to ranges of approaches to policy making theories while designing the proposed dialogical, progressive policy framework.\n\nThe proposed ‘dialogical and progressive policy framework’ is partly drawn from John’s (2011) idea of making policy work, in which he considers information, persuasion and deliberation as key to make a policy work better. He considers the following as crucial to achieve this; public information campaigns, persuading the citizens directly, smart information provision, using social pressure, social support, thinking, not just nudging, and educating. Fowler (2004) offers evaluation tool to determine if the policy works. He insists that evaluation is an integral part of policy process, evaluation must be professional, there should be good purposes for evaluation, there must be good criteria for judging evaluation (such as usefulness, feasibility, propriety (legal/ethical), accuracy), needs to classify evaluation (summative, formative and pseudo), and evaluation process must include goals, indicators, data collection instruments, report, response to evaluator’s recommendations. The Figure 3 presents the dialogical, progressive policy framework.\n\nThe above framework on dialogical and progressive policy is drawn as a middle way between the two polarised ends of neo-managerial/technocratic policy at one end and argumentative and critical policy on the other end. These two polarised ends are supported and opposed by different theories, models, and practical implications, throughout the policy processes such as the planning, implementation, evaluation, and adoption (David & Motala, 2017). It is necessary to also acknowledge that the centralised policies do as well have discrepancies (Mavrogordato & White, 2017). In establishing such dialogical and progressive policy framework, it is necessary to consider a range of theories and models in public policy studies. Chakrabarty & Chand (2016) recommend a range of theories and models for consideration, such as; institutional approach (traditional tool of studying political activities of the government), group theory (group interest and attitude are influential factors in public polices), elite theory (public policy as the interests, preferences and values of the government elite), rational policy-making model (policy-making is a choice among policy alternatives on rational grounds), Simon’s bounded rationality (human rationality is limited and bounded to preferences), incremental model (continuum of the previous government activities), normative-optimal model (which tries to avoid both extremes), game theory (helps understand collective human activity as the outcome of interactive decisions), system approach (public policy as an outcome of political process) and public choice theory (the application of economic analysis on the choices public make). Howlett & Ramesh (2009) offers the levels of analysis in relevant policy related theories. If the unit of analysis is individual, public choice theory fits as a good approach, if the unit of analysis is collective, class analysis, group analysis is favourable, and if the unit of analysis is structure and system, institutionalism fits well.\n\nPeters & Pierre (2006) propose argumentative policy processes (APA) as a constructive tool for public policy analysis. APA includes pathos (a quality that evokes pity and sadness), ethos (the set of beliefs, ideas about the social behaviours), and logos (a principle of order and knowledge). They draw the framework from Toulmin method of argumentation, which includes fact, warrant, backing, conclusion, and rebuttal (Moxley, 1993). The cost-benefit analysis has been very influential in policymaking and analysis process, largely in the neo-managerial policy processes (Rensburg, Motala & David, 2015a). Weimer & Vining (2017) indicate that the cost benefit analysis includes the following steps: specify current and alternative policies, costs and benefits count, catalogue relevant impacts, predict impacts, monetize all impacts, discount benefits and costs, compute the present value of net benefits, perform sensitivity analysis. Kraft & Furlong’s (2018) orientations to policy analysis, such as scientific and political is worth exploring. Obviously, each of these orientations have its own strengths and limitations. The Vicker’s Model (1965) of decisional analysis as promoted by Sapru (2017) recommend the consideration of reality judgements (What is out there? What is the problem? What predictions can be made?), value judgements (What values/norms are set? What ought to be?), and action judgements (what to do? How to do it? What actions to take? What solutions are good enough?) to operationalise decision. This theoretical exploration needs to be verified and confirmed with arguments for and against in scholarly world that may further take the proposed model to be tested and validated.\n\nConfirmation/disconfirmation is the third phase of theory building for Lynham (2002). This phase falls within the practice component of applied theory building for her. Comparing policy processes would benefit the establishment of rigorous theories and models of policy framework, as constant comparison supports the development of rich descriptions in theory building (Fram, 2013). As Young & Lewis (2015) hint that consulting similar research on educational policies complements, challenges and sometimes complicates further research, confirming and disconfirming process is not easy. For Creswell (2007) grounded theory research attempts to derive a general, abstract theory of a process, action, or interaction grounded in the views of participants in a study. Creswell considers that the two popular approaches to grounded theory according to him are the systematic procedures of Strauss and Corbin and the constructivist approach of Charmaz. This study particularly applies the constructivist approach of Charmaz. The constructionist approach deals best with what people construct and how this social construction process unfolds (Charmaz, 2008). Constant comparison and grounded theory approaches are widely used in policy research. Heikkila & Cairney (2017) suggest three criteria for the theoretical approaches to compare the policy process. The first criterion is the extent to which the basic elements of a theory are covered, which includes: a defined scope of analysis, a shared vocabulary/concepts, explicit assumptions, identified relationship among key concepts, and a model of the individual grounding of the theory. The second criterion is the development of research, that covers: how the approach has been employed actively by researchers and published as journal articles and books, how it has been tested, inclusive of diverse policy issues, different political systems and with multiple methods, how the scholars involved in using theory and research, and how the theory has been adapted or modified over time, particularly for the minimum common good for all (David, 2019).\n\nThe third criterion is the development of indicators on whether the theory explains a large part of the policy process. It is important to realise that the policy process is complex and there is no general theory. Therefore, they suggest simplifying a complex world to understand it better by asking a fundamental question; which elements do policy scholars treat as crucial to explanation? And they consider the following crucial elements and the interaction between them to provide an overall explanation of the policy making process and systems. These elements include actors, making choices, institutions, networks or subsystems, ideas or beliefs, policy context and events. The complexity of social policy processes depends on the political and managerial processes attached to it. Berkhout & Wielemans’ (1999) integrative approach to education policy indicate that the conceptualisation and understanding of education policy in complex socio-political systems is more problematic than merely as the set of executive, administrative, deliberative, official texts that direct education at the various levels of government. Their integrated approach to educational policy analysis spans from the classroom practices to the broader social systems. The following is a combined approach to public and social policy processes, called the blended progressive dialogical policy framework, which is drawn from several frameworks, particularly from Berkhout & Wielemans’ (1999) integrative approach to education policy and Haddad’s (1995) conceptual framework of policy (Figure 4).\n\nThe above blended framework for policy processes elaborates on the interrelation of policy with complex and dynamic political, social, and managerial processes. The blended policy framework considers the interrelation with global realities, national priorities, ministry or organisational strategies and the local actualities with end users. The framework in interrelating with global realities understands the emergence of dominant culture, the role and advocacy of global institutions, the impacts of trade agreements and the implications of the dominant and powerful political ideologies. In consideration to the national priorities, the framework looks into the political systems in the country, social pressure from different interest groups, the quest for economic growth and development, and the national values. With reference to the ministry or organisational strategies, the framework reviews the level of planning, administration, consultation, delegation, and quality of the policy processes (David & Abukari, 2019). In the consideration of the local actualities, the framework pays attention to the involvement of teachers, parents, students, educational administrators, and other stakeholders in institutional and classroom management practices. These interrelations at the blended policy framework occurs throughout with policy processes such as policy formulation, implementation, evaluation, and adoption. The blended policy framework makes careful policy alternatives considering the feasibility, affordability, and desirability (David & Hill 2021). And the blended policy framework takes into consideration of the policy consequences by value judging the policy processes. Robertson (1998) states that policies may fail either by not achieving their goals or may fail to retain political support.\n\nThere are several theories of policy processes. Schlager & Blomquist’s (1996) three dominant political theories of the policy processes, such as Sabatier’s advocacy coalitions framework (ACF), institutional rational choice (IRC), and Moe’s political theory of bureaucracy have gained wide attention. There is a different classification of policy processes. The six criteria of policy processes, according to Schlager & Blomquist (1996), include the boundaries of inquiry, the model of the individual, the roles of information and beliefs in decision making and strategy, the nature and roles of groups, the concept of levels of action, and the ability to explain action at various stages of the policy process. Howlett & Ramesh (2009) classify the stages of policy cycle, which includes agenda setting, policy formulation, decision-making, policy implementation and policy evaluation, and the key actors involved are policy universe, policy sub-system, government decision makers, policy sub-system, policy universe. Evidence based policy that was possibly introduced by Adrian Smith, made remarkable impact on policy studies. In his 1996, presidential address to the Royal Statistical Society urged for a more evidence-based approach commenting that it has valuable lessons to offer (Wikepedia, 2018). Evidence based policy (EBP) is a set of methods which informs the policy process, rather directly affect the eventual goals of the policy. A rational, rigorous, and systematic approach is recommended by EBP. The pursuit of EBP is based on the premise that policy decisions should be better informed by available evidence with rational analysis (Sutcliffe & Court, 2005). The following are the steps in evidence-based policymaking: programme assessment, budget development, implementation oversight, outcome monitoring, targeted evaluation (The Pew Charitable Trust & MacArthur Foundation, 2014).\n\nExplicit policymaking is more a new approach many policy researchers advocate. It is linked to the “explicit rationing or explicit decision-making process referring to decisions made by an administrative authority as to the amounts and types of resources to be made available, eligible populations, and specific rules for allocation. Significant amounts of explicit rationing occur in public and private plans regarding levels of available technology, location of facilities and programmes and expenditure levels. In contrast, the implicit rationing refers to discretionary decisions made by managers, professionals functioning within a fixed budgetary allowance (Taylor, 2012, Para.4)”. The quality of policy objectives impacts on the policy processes and outcomes. ISO 9001 quality objectives of policy include having measurable objectives, doing gap analysis, having project plans, taking necessary training, documentation, using and improving quality management system, doing internal audits, and ISO registration (International Organization for Standardisation, 2008). Critical policy analysis is one of the prominent policy analysis tools, several researchers use. Dryzek (2008) considers policy analysis process as a critique. He suggests the following approaches: critique and its opposites – technocracy (identify cause and effect), critique and its politics (technocratic analysis is centre-left, accommodative analysis adjusts to conservative fashion, critical is political ideological free), policy as a science of democracy, policy as progressive democratization of mankind. He considers critical communication, argumentative turn, linguistic turn, the claim to truth, sincerity, comprehensibility, and appropriateness attached to inter-subjective communication as critical standards, which he draws from the critical theory of Habermas. Grover & Rihani (2010) call for humane public policy. They believe that using a complexity framework may help social and public policy actors to avoid major challenges and problems. These arguments as discussed about the polarised views and practices on policy processes, compels to explore the possibilities manoeuvre the middle way as presented below (Figure 5).\n\nThe proposed middle way as presented in the Figure 5 circles around the dialogical progressive centre. This dialogical progressive centre relates to all the constructs around the polarised ends. The middle way process relates to the argumentative and critical end through the instruments of realistic reasoning and consultative, engaging approaches. The argumentative and critical end is stimulated by ideological constructs, such as left and south, while the neo-managerial and administrative end is stimulated by ideological constructs, such as right and north. The argumentative and critical end is complemented by participatory and consensus approaches that emerge through social responsiveness and extreme rationalism. The middle way process relates to the neo-managerial and administrative end through the instruments of pragmatic strategies and result orientation. The neo-managerial and administrative end is complemented by technocratic and cost-benefit analysis, which results through economic responsiveness and extreme empiricism. Thus, the middle way of the dialogical and progressive educational policy framework aims to engage a wide range of ideas, ideologies, actors, processes, and systems. The middle way is not a perfect space but a potential space in which a dialogical and progressive policy making may thrive.\n\n\nConclusion\n\nThe study aimed to manoeuvre a middle way to propose a dialogical and progressive educational policy framework amidst the polarised constructs. The first three phases of Lynham’s (2002) theory building such as conceptual development, operationalisation and confirmation/disconfirmation helped to explore answers to the research question of the study: ‘how could a middle way (a dialogical and progressive framework) be manoeuvred among the polarised (new-liberal/managerial vs argumentative/critical frameworks) policy constructs? The first three phases and the exploration of relevant theories, models and related literature helped the study to content that if it is possible to have a polarised neo-managerial, market oriented and critical, argumentative policy frameworks, it should be then possible to have a dialogical, progressive middle way policy framework. The fourth phases ‘application’ and the fifth phase ‘continuous refinement’ could be explored by future research on the proposed dialogical progressive educational policy framework. As a theory is never complete, it is important that the theory be continually refined and developed (Rensburg, Motala & David, 2015b). The outcome of the application of the framework will help to refine and further develop this dialogical progressive policy framework. Every research and every research method have their own limitations. Lynham (2002) acknowledges that this five-phase theory building method in applied disciplines is much less programmatic and the method could be further refined by theorists, however, that is not the aim of this research. As this research aims to develop a dialogical progressive policy framework, it mainly focused on developing, operationalising, confirming, and disconfirming, of this dialogical progressive policy framework. The study had to make careful choices of the theories, models and approaches that spans the public and educational policy spectrum, however, the research had to limit to the most important theories, models which possibly impacted the exclusion of other relevant theories and models. Future refinement of this framework could address such limitations. As Peters (2005) points out that the instruments used to address policy problems have much less developed conceptions of those problems themselves and as Dryzek (2008) indicates that policy processes as an ongoing dialogue and critique, the proposed ‘dialogical and progressive policy framework’ would evolve further depending on the constructive critiques and dialogues. The research is open for any such constructive critiques to further this framework and strongly believes that the policy science and practice might continue to evolve with much openness. The dialogical and progressive (middle way) educational policy framework aims to engage a wide range of ideas, ideologies, actors, processes, and systems. The study believes that the proposed middle way is not a perfect space but a potential space in which a dialogical and progressive educational policy may thrive.",
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Dev. 2015b; 6(3): 262–278. Publisher Full Text\n\nRensburg I, Motala S, David SA:Research Collaboration among Emerging Economies: Policy and Economic Implications for BRICS Nations. Int. J. Econ. Policy Emerg. Econ. 2016; 9(4): 344–360. Publisher Full Text\n\nRobertson DB:Planned Incapacity to Succeed? Policy-Making Structure and Policy Failure. Rev. Policy Res. 1998; 8(2): 241–263. Publisher Full Text\n\nSanderson J:Marx and Engels on the State. The Western Political Quarterly. 1963; 16(3): 946–955. Publisher Full Text\n\nSapru R: Public Policy a Contemporary Perspective. New Delhi:Sage Publications Ltd.;2017.\n\nSchlager E, Blomquist W:A Comparison of Three Emerging Theories of the Policy Process. Polit. Res. Q. 1996; 49(3): 651–672. Publisher Full Text\n\nSchugurensky D:Higher Education Restructuring in the Era of Globalization, Towards a Heteronomous Model?Arnove FR, Torres CA, editors. Comparative Education: The Dialectic of the global and the Local. New York:Rowman & Littlefield;1990; 284–304.\n\nSeremani TW, Clegg S:Post colonialism, Organization, and Management Theory: The Role of “Epistemological Third Space”. J. Manag. Inq. 2015; 25(2): 171–183. Publisher Full Text\n\nStanford:Kant’s Social and Political Philosophy.2016.Reference Source\n\nSutcliffe S, Court J: Evidence-Based Policymaking: What is it? How does it work? What relevance for developing countries? London:Overseas Development Institute;2005.\n\nSynder H:Literature review as a research methodology: An overview and guidelines. J. Bus. Res. 2019; 104: 333–339. Publisher Full Text\n\nTaylor D:Explicit v. implicit rationing. The Incidental Economist: The health services research blog.2012.Reference Source\n\nThe Pew Charitable Trust & MacArthur Foundation: Evidence-Based Policymaking: A guide for effective government. Washington D.C:2014.\n\nVisvanathan S:The search for cognitive justice.2019.Reference Source\n\nXiao Y, Watson M:Guidance on conducting a systematic literature review. J. Plan. Educ. Res. 2017; 39(1): 93–112. Publisher Full Text\n\nWeimer DL, Vining AR: Policy Analysis: Concepts and Practice. New Yok:Routledge;2017.\n\nWielemans W: The underlying principles of free market economy and their consequences for education. Leuven:KULeuven;2000.\n\nWielemans W: Globalisation and Educational Change: A comparative Approach. In an International Academic Workshop on Educational Systems in East Asia and West Europe: A Comparative Approach. Leuven:KULeuven;2002.\n\nWilkin P:Chomsky and Foucault on Human Nature and Politics: An Essential Difference? Soc. Theory Pract. 1999; 25(2): 177–210. Publisher Full Text\n\nWu, He:Paradigm Shift in Public Administration: Implications for Teaching in Professional Training Programs. Public Adm. Rev. 2009; 69: S21–S28. 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}
|
[
{
"id": "166893",
"date": "30 Mar 2023",
"name": "Hugo Horta",
"expertise": [
"Reviewer Expertise Science and public policy",
"Higher Education"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper offers a relevant contribution to the advancement of knowledge to the field, and I believe it only needs some minor revisions before it can be indexed. I offer below, my suggestions for the improvement of the paper:\n\nAlthough I understand the standpoint of the author, it may be a bit too bold to say that this is the first study trying to complement different views into one that assumes a more middle ground stance. A more moderate stance would be welcome. One also has the impression from the text that education policies tend to be essentially polarized, when in fact most of the times what happens is a constant balancing act and dialogue between polarizing policy and related ideological views, and often views that we believe to be dominant are not as dominant as we consider them to be. The paper by Capano and Pritoni1 proves this point for example and should be taken into account.\n\nMore information about the literature review would also be helpful. For example, the author may want to be detailed in his search for relevant literature. I would be expecting to see some keyword searching in databases such as Scopus and the Web of Science, and an analysis of policy and policy topics in specialized education levels. For example, in higher education, there is a journal that is essentially focused on policy (Higher Education Policy) and the broad journals such as Higher Education and Studies in Higher Education often analyze policy, values, ideology and the public/private dialectic in the field. It may be worthwhile to have a look at some of these journals.\n\nThere are two spheres that I have not seen so present in the paper and that I would have liked to. One of them is the policy process (including the design stage) in its relevance with uncertainty (what some authors call illities) and understand the parallels between those policies that cover safer and certain topics (thus more conservative and usually supported by international organizations) and those policies that assume a bolder perspective because they are dealing with new topics, that attempt to meet policy goals that are uncertain and in a set dominated by overall uncertainty. The other sphere that I would have liked to see more evident in the paper, is the issue of culture, which is key in mediating/moderating the design (and implementation) of policies in different countries and settings. The very idea of public and corporate interest – as an example – can be strongly shaped by the cultural dimensions of a government, country, ethnic group, region, etc. In a way, culture works as a balancing/moderating factor between different perspectives that seem polarizing. Essentially, more debate, conceptualization and reflection on these issues should be included in the current version of the paper to add further value to it.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "169854",
"date": "02 May 2023",
"name": "Terry Wotherspoon",
"expertise": [
"Reviewer Expertise sociology of education",
"social policy analysis",
"social inequality"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper provides a potentially useful contribution to a theoretical approach to social policy, oriented to guide what the author poses as “a dialogical and progressive educational policy framework.” In addressing the central question of how a middle way for policy construction and formulation be navigated within the current (educational) policy environment, the discussion covers an extensive range of relevant policy literature and themes.\nWhile the aims of the paper are worthwhile exploring, the discussion could benefit from considerable tightening of its scope and focus in order to offer a more compelling case. In particular, it would be useful to provide readers with a stronger sense of why or how this question matters, or what the main focus is in advancing such a question. This clarify of focus would offer a clearer understanding of the relationship between policy analysis (theoretical approaches oriented to the understanding or explanation of policy-related matters) and policy processes (stages in the framing and implementation of policy, which the paper seeks to inform or influence); the paper in its current form blurs this distinction as it moves repeatedly back and forth from one to the other. The discussion is positioned as a form of theory-building and ideological investigation, and therefore focuses on the more abstract dimensions associated with the former, but in trying to make the case that a middle way position should be implemented, it also highlights more substantive processes associated with the latter. In the process, the paper loses some of its potential impact by trying to cover too many disparate themes and bodies of literature while leaving aside important points of clarification and elaboration most pertinent to the intended focus. Four main sets of revisions are suggested:\nAlthough the paper makes clear that its focus is not empirical, it addresses matters that require at least some attention to actual factors that drive or influence policy directions and policy-related decision-making. While drawing from literature that highlights the managerial and neo-liberal influences on current policy frameworks, current educational policy frameworks are in fact highly complex in nature; it should not be assumed that educational policies are fully coherent, nor that they are influenced by any single policy orientation. The literature on path dependence (e.g., P. Pierson) demonstrates the barriers governments have encountered even if strongly committed to neoliberal policy directions, while critical analysis of education (e.g., M. Apple, M. Carnoy and H.M. Levin) highlights ongoing tensions and contradictions in the formation of educational policies. The paper aims “to stimulate dialogue among polarised frameworks” but, of course it is not approaches but actors who engage in policy dialogue, employing particular discourses derived not only from various ideological or political stances, but also on practical considerations including resources and governance structures. How, in other words, or at what level, would the anticipated dialogue be conducted? Surprisingly, the paper makes no reference to literature in which such a dialogue has actually been initiated – the ‘third way’ approach advanced initially in the work of Anthony Giddens, as well as broader ‘social investment’ policy orientations in which education features centrally.\n\nThe discussion would be strengthened by the inclusion of a bit more detail or specificity in the discussion of the methodology employed in the analysis. While described, variously, as a rationalist and hermeneutic approach, applied through discourse analysis, these terms and how they are understood by the author are not defined explicitly in the paper. A brief statement in this regard, along with further information as to how they were actually employed in the analysis, would be useful. This would provide the reader with further information about how decisions were made to classify certain statements, thereby helping to justify more fully some of the main points or conclusions presented in the paper.\n\nIn many places discussion that is somewhat superfluous to the main focus could be removed. Some of the sections (in particular the section on Operationalization, but in other places as well) include discussions presented as distinct literature reviews, making reference to disparate themes, concepts, and authors which are not fully integrated with one another and which appear to be somewhat secondary to the main analysis. It would be possible to remove some of this material, thereby enhancing or concentrating attention to the main points within the analysis while making space to address the revisions proposed in the previous two points.\n\nCareful proofreading is recommended in order to address minor editorial points and clarify some a few ambiguous statements.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-74
|
https://f1000research.com/articles/12-10/v1
|
04 Jan 23
|
{
"type": "Brief Report",
"title": "Chinese culture became more individualistic: Evidence from family structure, 1953-2017",
"authors": [
"Yuji Ogihara"
],
"abstract": "Previous research has indicated that some aspects of Chinese culture became more individualistic. However, prior studies have suggested a decrease in individualism in other aspects of China. Thus, it was unclear whether China became more individualistic. Therefore, the current research investigated whether Chinese culture became more individualistic by examining historical changes in family structure. Specifically, I analyzed temporal shifts in the divorce rate and household size, which have been confirmed as valid representative indicators of individualism. Results showed that the divorce rate increased between 1978 and 2017 and household size decreased between 1953 and 2017, indicating a rise in individualism. Moreover, analyses suggested that the one-child policy was unlikely the sole and major factor in the decrease in household size. Additionally, the aggregated score of divorce rate and household size demonstrated a clear increase in individualism. Therefore, the present research provided further evidence of the rise in individualism in China.",
"keywords": [
"individualism",
"family",
"cultural change",
"China",
"temporal change",
"divorce",
"household",
"family structure"
],
"content": "Introduction\n\nPrevious research has indicated that Chinese culture has become more individualistic over time. Taras, Steel, and Kirkman (2012) conducted a meta-analysis of studies that used Hofstede (1980)’s cultural framework (four dimensions; individualism, power distance, masculinity, uncertainty avoidance). In this research, they found that individuals in China came to hold more individualistic values from the 1980s to the 2000s, which shows that Chinese culture became more individualistic at the individual level.\n\nNot only at the individual level, but also at the cultural (group) level, Chinese culture has changed toward greater individualism. A previous study examined historical changes in individualism-collectivism in China between 1950 and 2008 (Hamamura and Xu, 2015). It analyzed changes in the frequency of first-person singular/plural pronouns used in Chinese published books over the period by utilizing a database of millions of books published in various languages (Google Books Ngram). It found that the rate of first-person singular pronouns increased and the rate of first-person plural pronouns decreased. These results suggest an increase in individualism in China (also see, Yu et al., 2016). Moreover, Zeng and Greenfield (2015) have indicated that the prevalence of words that were considered to reflect individualistic values/behaviors (e.g., “autonomy”, “choose”) increased in Chinese books published between 1970 and 2008, reflecting a shift toward greater individualism in Chinese culture.\n\nNot only values but also behaviors may have become more individualistic. It has been claimed that unique names increased in China between 1950 and 2009, suggesting a rise in the need for uniqueness and individualism (Cai, Zou, Feng, Liu, & Jing, 2018; Bao, Cai, Jing, & Wang, 2021; but also see, Ogihara, 2020b).\n\nIn contrast, regarding values, some studies have indicated that Chinese culture has become less individualistic. It has been reported that individuals in China came to hold less individualistic values between 1990 and 2007 (Santos, Varnum, & Grossmann, 2017). This study demonstrates that at the individual level, China has shifted toward a less individualistic culture.\n\nFurther, Zeng and Greenfield (2015) found that, contrary to their hypothesis, the prevalence of the two words (“obliged” and “give”; out of eight words examined) that were considered to reflect collectivistic values/behaviors increased in usage in Chinese books published between 1970 and 2008. This result may show that China became less individualistic at the cultural level.\n\nThus, it is unclear whether Chinese culture has become more individualistic. Particularly, there has been only one study examining changes in the behavioral aspect in China (naming; Cai et al., 2018). Thus, it is important to examine cultural changes in China by using other behavioral measurements. Therefore, the current research investigated cultural changes in China using two other behavioral indicators of individualism that have already been validated but have not been used to examine cultural changes in China: divorce rates and household size.\n\nDivorce rates and household size are behavioral measurements reflecting individualistic tendencies. In individualistic cultures, family structure tends to be freer and looser compared to that in collectivistic cultures (e.g., Georgas et al., 2001; Triandis, 1995). This leads people to live separately and independently of other family members, contributing to higher divorce rates and smaller households.\n\nIndeed, divorce rates and household size are correlated with the indices of individualism developed by Hofstede (1980) and Triandis in the predicted direction at the national level (e.g., Diener, Diener, & Diener, 1995; Hamamura, 2012; Lester, 1995; Toth & Kemmelmeier, 2009). Moreover, prior research has shown that both indicators are associated with variables whose relations to individualism have been conceptually and empirically confirmed, such as pronoun drop (Kashima & Kashima, 1998) and pathogen prevalence (Murray & Schaller, 2010) at the national level (e.g., Hamamura, 2012).1 Thus, divorce rates and household size have been frequently used as indices of individualism (e.g., Diener et al., 1995; Grossman & Varnum, 2015; Hamamura, 2012; Ogihara, 2018b, 2020a; Vandello & Cohen, 1999).2\n\n\nMethods\n\nAs the measure of divorce rates, the divorce-to-marriage ratio was used. Data covered the period between 1978 and 2017 and came from the National Bureau of Statistics of China (2018). Data on household sizes covered the period between 1953 and 2017 and were drawn from the National Bureau of Statistics of China (2018).\n\nAlthough divorce rates and household size have been confirmed as valid indicators of individualism, each indicator may be simultaneously influenced by factors other than individualism. For instance, celebrity divorces may impact divorce rates. By aggregating the two indicators, the random errors of each indicator cancel each other out, successfully reducing the influence of these random errors. Thus, an aggregated score was calculated by averaging the divorce rate (z-transformed) and household size (z-transformed and reversed). This strategy of analysis has been frequently used in prior research (e.g., Diener et al., 1995; Grossmann & Varnum, 2015; Hamamura & Xu, 2015; Ogihara, 2018b, 2020a; Santos et al., 2017; Yu et al., 2016; Vandello & Cohen, 1999).\n\n\nResults\n\nSimple Pearson’s and Kendall’s correlation coefficients among each indicator are shown in Table 1.\n\nFigure 1 shows historical shifts in the divorce rate between 1978 and 2017 in China. The divorce rate significantly rose over the last 40 years. In 1978, 4.8 out of 100 couples divorced, but in 2017, 41.1 out of 100 couples experienced a divorce. The correlation between the year and the divorce rate was strongly positive (Table 1), suggesting an increase in individualism.\n\nFigure 2 indicates temporal shifts in household size between 1953 and 2017 in China. Household size declined over the past 60 years. In 1953, the average household consisted of 4.3 people, but in 2017 the average was 3.1 people. The correlation between year and household size was highly negative (Table 1), which indicates a rise in individualism.\n\nThe one-child policy and household size. One might expect that the decrease in the average household size was caused solely by the one-child policy and may thus not reflect an increase in individualism. China’s one-child policy, which was introduced in 1980 and ended in 2015, penalized parents for having more than one child. This policy may have decreased the birth rate, in turn decreasing the average household size.\n\nHowever, it is difficult to assert that the decrease in the average household size was caused solely by the one-child policy for three reasons. First, it is not necessarily correct that the one-child policy continued to decrease the birth rate (Whyte, Feng, & Cai, 2015). Indeed, after the one-child policy was introduced in 1980, the fertility rate did not continue to decrease (Figure 3A). Contrary to a common myth, even after the implementation of the one-child policy, the fertility rate increased between 1983 and 1986, and between 2000 and 2017. For more than half period of time (22 years; 1983-1986, 2000-2017) when the one-child policy was introduced (36 years; 1980-2015), the fertility rate did not decrease.\n\nNote. Data were drawn from the World Bank (2019).\n\n(A) 1980-2017 (B) 1960-2017.\n\nSecond, it is not always correct that decreases in birth rate lead to decreases in household size. Indeed, for these periods when the fertility rate increased (1983-1986, 2000-2017), the household size continued to decrease. Moreover, the fertility rate remarkably decreased before, rather than after, the one-child policy was adopted in 1980 (Figure 3B). In 1960, approximately six babies were born to one woman, whereas in 1979 approximately three babies were born to one woman. Even during this period when the fertility rate remarkably decreased, the average household size did not seem to decrease.\n\nThird, even after the one-child policy ended in 2015, the average household size continued to decrease. If the one-child policy had a strong influence on household size, after the policy ended, household size should have increased (but it decreased).\n\nThus, although the one-child policy may have contributed to the decrease in household size to some extent, its effect was not large. Therefore, the one-child policy was unlikely to be the sole and major factor in this decrease in the average household size.\n\nThe aggregated score of divorce rate and household size showed a clearer and more consistent pattern of increased individualism than each indicator (Figure 4). The correlation between the year and the aggregated score was strongly positive (Table 1), suggesting an increase in individualism.\n\nNote. The aggregated score was calculated by averaging the divorce rate (z-transformed) and household size (z-transformed and reversed).\n\nWhen the crude divorce rate (rate per 1,000 persons) was used instead of divorce-to-marriage ratio, the results were unchanged (Table 2; Figure 5; Figure 6). The Pearson’s and Kendall’s correlation coefficients between crude divorce rate and divorce-to-marriage ratio were .95 and .92, respectively.\n\nNote. The aggregated score was calculated by averaging the crude divorce rate (z-transformed) and household size (z-transformed and reversed).\n\n\nDiscussion\n\nThe current research showed that Chinese culture became more individualistic over the past 60 years by using behavioral indicators that had not been sufficiently examined. Past research showed the rise in individualism in China (Cai et al., 2018; Hamamura & Xu, 2015; Taras et al., 2012; Yu et al., 2016; Zeng & Greenfield, 2015). However, some studies indicated the fall of individualism in China (Santos et al., 2017; Zeng & Greenfield, 2015). Thus, it remained unclear whether Chinese culture became more individualistic. Particularly, it was unclear whether China shifted toward greater individualism in the behavioral aspect. The present research investigated temporal changes in the two behavioral indicators (divorce rate and household size), which have been used to examine cultural changes in other countries (e.g., Hamamura, 2012; Grossmann & Varnum, 2015; Ogihara, 2018b, 2020a).\n\nResults showed that the divorce rate increased dramatically between 1978 and 2017, and that household size steadily shrank between 1953 and 2017, suggesting an increase in individualism in China. Further, analyses indicated that the one-child policy was not the major factor of the decrease in household size. Moreover, the aggregated score of divorce rate and household size demonstrated a clearer pattern of the increase in individualism than each indicator. Therefore, this research contributes to the accumulation of the literature demonstrating the rise in individualism in China by using different behavioral indicators of individualism.\n\nIt is more likely that these mixed changes are found in historically collectivistic cultures that are becoming more individualistic. Indeed, such changes were also found in Japan, another country in East Asia (for a review, see Ogihara, 2017, 2018a).\n\nOn the one hand, people in Japan came to live more independently from other family members (Hamamura, 2012; Ogihara, 2018b), increasingly gave more unique names to their babies (Ogihara, 2015, 2021a, 2021b; Ogihara et al., 2015), and came to hold more individualistic values (Hamamura, 2012; Taras et al., 2012), indicating an increase in individualism. On the other hand, a decrease in and non-change of individualistic values have been reported (Hamamura, 2012).\n\nIt is suggested that these mixed changes may be related to difficulties in adapting to a new environment (e.g., Ogihara, 2016; Ogihara & Uchida, 2014; Ogihara et al., 2014, 2016). Still, it is difficult to say that there is a sufficient amount of research on how cultures change and how people adapt to such cultural changes in East Asia. Therefore, it is important to investigate historical changes in these cultures in more detail.\n\nThe current research used family structure (divorce rate and household size) as representative indicators of individualism. Nevertheless, it is still unclear whether other aspects of individualism show the same trend. To examine cultural changes in China, it is necessary to investigate various aspects of cultural changes by analyzing different indicators from a broad set of perspectives.\n\nAlthough the present research demonstrated that Chinese culture became more individualistic, it is not clear why this change arose. There are many possible factors to cause this change (e.g., economic wealth, social mobility, subsistence styles, ecological/societal threats, and urbanization). Future studies should answer this question.",
"appendix": "Data availability\n\nData used in this study are available from the National Bureau of Statistics of China (2018) website (http://www.stats.gov.cn/english/).\n\n\nAcknowledgement\n\nI thank Muwei Chen and Yuyan Chen for their assistance in data collection. I appreciate Pamela Taylor for her helpful comments on earlier versions of the manuscript.\n\n\nReferences\n\nBao HW, Cai H, Jing Y, et al.: Novel evidence for the increasing prevalence of unique names in China: A reply to Ogihara. Front. Psychol. 2021; 12: 731244. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCai H, Zou X, Feng Y, et al.: Increasing need for uniqueness in contemporary China: Empirical evidence. Front. Psychol. 2018; 9: 554. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDiener E, Diener M, Diener C: Factors predicting the subjective well-being of nations. J. Pers. Soc. Psychol. 1995; 69: 851–864. 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Beverly Hills, CA:Sage;1980.\n\nKashima ES, Kashima Y: Culture and language the case of cultural dimensions and personal pronoun use. J. Cross-Cult. Psychol. 1998; 29: 461–486. Publisher Full Text\n\nLester D: Individualism and divorce. Psychol. Rep. 1995; 76: 258. Publisher Full Text\n\nMurray DR, Schaller M: Historical prevalence of infectious diseases within 230 geopolitical regions: A tool for investigating origins of culture. J. Cross-Cult. Psychol. 2010; 41: 99–108. Publisher Full Text\n\nNational Bureau of Statistics of China:2018. Chinese Statistical Yearbook.Reference Source\n\nOgihara Y: Characteristics and patterns of uncommon names in present-day Japan. J. Hum. Environ. Stud. 2015; 13: 177–183. Publisher Full Text\n\nOgihara Y: The change in self-esteem among middle school students in Japan, 1989-2002. Psychology. 2016; 7: 1343–1351. Publisher Full Text\n\nOgihara Y: Temporal changes in individualism and their ramification in Japan: Rising individualism and conflicts with persisting collectivism. Front. Psychol. 2017; 8: 695. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOgihara Y:Economic shifts and cultural changes in individualism: A cross-temporal perspective.Uskul A, Oishi S, editors. Socioeconomic environment and human psychology: Social, ecological, and cultural perspectives. Oxford:Oxford University Press;2018a; (pp. 247–270).Publisher Full Text\n\nOgihara Y: The rise in individualism in Japan: Temporal changes in family structure, 1947-2015. J. Cross-Cult. Psychol. 2018b; 49: 1219–1226. Publisher Full Text\n\nOgihara Y: Regional differences in individualism in Japan: Scoring based on family structure. Front. Psychol. 2020a; 11: 1677. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOgihara Y: Unique names in China: Insights from research in Japan—Commentary: Increasing need for uniqueness in contemporary China: Empirical evidence. Front. Psychol. 2020b; 11: 2136. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOgihara Y: Direct evidence of the increase in unique names in Japan: The rise of individualism. Curr. Res. Behav. Sci. 2021a; 2: 100056. Publisher Full Text\n\nOgihara Y: How to read uncommon names in present-day Japan: A guide for non-native Japanese speakers. Front. Commun. 2021b; 6: 631907. Publisher Full Text\n\nOgihara Y, Fujita H, Tominaga H, et al.: Are common names becoming less common? The rise in uniqueness and individualism in Japan. Front. Psychol. 2015; 6: 1490. Publisher Full Text\n\nOgihara Y, Uchida Y: Does individualism bring happiness? Negative effects of individualism on interpersonal relationships and happiness. Front. Psychol. 2014; 5: 135.PubMed Abstract | Publisher Full Text | Free Full Text\n\nOgihara Y, Uchida Y, Kusumi T: How do Japanese perceive individualism? Examination of the meaning of individualism in Japan. Psychologia. 2014; 57(3): 213–223. Publisher Full Text\n\nOgihara Y, Uchida Y, Kusumi T: Losing confidence over time: Temporal changes in self-esteem among older children and early adolescents in Japan, 1999-2006. SAGE Open. 2016; 6: 215824401666660–215824401666668. Publisher Full Text\n\nSantos HC, Varnum ME, Grossmann I: Global increases in individualism. Psychol. Sci. 2017; 28: 1228–1239. Publisher Full Text\n\nTaras V, Steel P, Kirkman BL: Improving national cultural indices using a longitudinal meta-analysis of Hofstede's dimensions. J. World Bus. 2012; 47: 329–341. Publisher Full Text\n\nToth K, Kemmelmeier M: Divorce attitudes around the world: Distinguishing the impact of culture on evaluations and attitude structure. Cross-Cult. Res. 2009; 43: 280–297. Publisher Full Text\n\nTriandis HC: Individualism and Collectivism. Boulder, CO:Westview Press;1995.\n\nVandello JA, Cohen D: Patterns of individualism and collectivism in the United States. J. Pers. Soc. Psychol. 1999; 77: 279–292. Publisher Full Text\n\nWhyte MK, Feng W, Cai Y: Challenging myths about China’s one-child policy. China J. 2015; 74: 144–159. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThe World Bank: Fertility rate, total (births per woman).2019.Reference Source\n\nYu F, Peng T, Peng K, et al.: Cultural value shifting in pronoun use. J. Cross-Cult. Psychol. 2016; 47: 310–316. Publisher Full Text\n\nZeng R, Greenfield PM: Cultural evolution over the last 40 years in China: Using the Google Ngram Viewer to study implications of social and political change for cultural values. Int. J. Psychol. 2015; 50: 47–55. PubMed Abstract | Publisher Full Text\n\n\nFootnotes\n\n1 Although the validities of the two indicators have been confirmed at the national level, it is desirable to check the validities at the area (e.g., provincial) level in China.\n\n2 In some studies, other socio-demographic variables were used as indicators representing individualism such as percentage of self-employed people (e.g., Vandello & Cohen, 1999) and the ratio of single-child families relative to multi-child families (e.g., Grossmann & Varnum, 2015). Although their conceptual associations with individualism are understandable, their empirical relations with individualism are not sufficiently clear so far. Thus, in this research, divorce rates and household sizes, which have already been empirically confirmed to be valid indicators of individualism (e.g., Hamamura, 2012; Grossmann & Varnum, 2015), were used."
}
|
[
{
"id": "158975",
"date": "13 Jan 2023",
"name": "Han-Wu-Shuang Bao",
"expertise": [
"Reviewer Expertise Cultural psychology",
"Cultural change",
"Individualism",
"Name",
"China"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this article, the author summarized previous contradictory findings on the changes in individualism in China over the past decades, and provided further evidence from two social indicators (i.e., divorce rate and household size) for the increasing individualism in China. While data on such indicators are publicly available and quite easy to be collected from the National Bureau of Statistics of China (data.stats.gov.cn), it was indeed surprising that to date no studies have reported these indicators as evidence for cultural changes in China. Thus, the author’s current brief report would be necessary for a more complete understanding of Chinese cultural changes.\nNonetheless, I have some suggestions for the author to further improve this article, and also expect a revised version of the manuscript from the author.\nThe author collected the data in 2018, which covered the period only until 2017. This made the results somewhat out of date. Based on my own search (data.stats.gov.cn), it is certain that now the National Bureau of Statistics of China has updated the data until 2021. Therefore, I strongly suggest the author collecting more data points (i.e., 2018, 2019, 2020, and 2021) to provide the latest evidence. This would strengthen the potential impact of this article, and also help address the concern about the one-child policy because more data points (than merely 2016 and 2017) could be tested after the policy’s end in 2015 (i.e., to check whether household size continued to decrease even when Chinese parents are encouraged to give birth to more than one child since 2015).\n\nIt would be better to disclose the limitations of previous findings, which would help readers better evaluate different pieces of evidence. For example, in Santos et al.’s (2017) study, they only had 4 data points for China (1990, 1995, 2001, 2007) on three self-report items of cultural values1. This could be main limitations of this specific finding and would make the idea that “individualism is decreasing in China” less convincing. The author may provide further critical comments when summarizing the literature.\n\nSince Bao et al. (2021) has provided more valid evidence for the increasing name uniqueness in China2 and has addressed Ogihara’s (2020)3 concerns on Cai et al. (2018)4, it is necessary to also cite Bao et al. (2021)2 when citing Cai et al. (2018)4 in this article:\nP. 2 (of the pdf version of the article) “Particularly, there has been only one study examining changes in the behavioral aspect in China (naming; Cai et al., 2018).” should be “Particularly, there has been two studies examining changes in the behavioral aspect in China (naming; Bao et al., 2021; Cai et al., 2018).”\n\nP. 8 “Past research showed the rise in individualism in China (Bao et al., 2021; Cai et al., 2018; …)”.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Yes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9572",
"date": "19 Jul 2023",
"name": "Yuji Ogihara",
"role": "Author Response",
"response": "Dear Dr. Han-Wu-Shuang Bao, Thank you very much for reviewing my manuscript and providing valuable comments. I have modified the manuscript according to your comments. I offer my responses to each comment below. I have copied and pasted all of your comments without making changes. In this article, the author summarized previous contradictory findings on the changes in individualism in China over the past decades, and provided further evidence from two social indicators (i.e., divorce rate and household size) for the increasing individualism in China. While data on such indicators are publicly available and quite easy to be collected from the National Bureau of Statistics of China (data.stats.gov.cn), it was indeed surprising that to date no studies have reported these indicators as evidence for cultural changes in China. Thus, the author’s current brief report would be necessary for a more complete understanding of Chinese cultural changes. Nonetheless, I have some suggestions for the author to further improve this article, and also expect a revised version of the manuscript from the author. 1. The author collected the data in 2018, which covered the period only until 2017. This made the results somewhat out of date. Based on my own search (data.stats.gov.cn), it is certain that now the National Bureau of Statistics of China has updated the data until 2021. Therefore, I strongly suggest the author collecting more data points (i.e., 2018, 2019, 2020, and 2021) to provide the latest evidence. This would strengthen the potential impact of this article, and also help address the concern about the one-child policy because more data points (than merely 2016 and 2017) could be tested after the policy’s end in 2015 (i.e., to check whether household size continued to decrease even when Chinese parents are encouraged to give birth to more than one child since 2015). I appreciate your constructive comment. I agree with you that including more data points is important in providing the latest evidence. Nevertheless, the four data points (2018, 2019, 2020, 2021) have not been newly added for three reasons. First, it is necessary to consider the complex effects of COVID-19 from 2019. This pandemic should have enormously affected Chinese culture and people. For example, the pandemic might have made Chinese people less individualistic. This hypothesis should be investigated in an independent study in detail, considering a series of previous studies regarding pandemics (e.g., Na et al., 2021; Schaller et al., 2022). Second, the main purpose of this article is to examine temporal changes in individualism in China. This purpose is already fulfilled in the current version of the article, which investigated changes over the past 65 years between 1953 and 2017. Again, I agree that adding the four data points would describe the latest situation, but describing the latest situation is not the main purpose of this article. Third, it is not always necessary to analyze the latest data when researchers publish academic articles. As you know, it takes time to publish academic articles. When I conducted this study, the data after 2017 were unavailable. However, if you think adding the four data points is a must, I will reconsider this point. Na, J., Kim, N., Suk, H. W., Choi, E., Choi, J. A., Kim, J. H., ... & Choi, I. (2021). Individualism-collectivism during the COVID-19 pandemic: A field study testing the pathogen stress hypothesis of individualism-collectivism in Korea. Personality and Individual Differences, 183, 111127. https://doi.org/10.1016/j.paid.2021.111127 Schaller, M., Murray, D. R., & Hofer, M. K. (2022). The behavioural immune system and pandemic psychology: the evolved psychology of disease-avoidance and its implications for attitudes, behaviour, and public health during epidemic outbreaks. European Review of Social Psychology, 33, 360-396. https://doi.org/10.1080/10463283.2021.1988404 2. It would be better to disclose the limitations of previous findings, which would help readers better evaluate different pieces of evidence. For example, in Santos et al.’s (2017) study, they only had 4 data points for China (1990, 1995, 2001, 2007) on three self-report items of cultural values1. This could be main limitations of this specific finding and would make the idea that “individualism is decreasing in China” less convincing. The author may provide further critical comments when summarizing the literature. Thank you for your helpful comment. Following your suggestion, I have added some explanations of the limitations of previous findings (Santos et al., 2017; Zeng & Greenfield, 2015) in Footnotes 1 and 2 as below. “Although this study described global trends of temporal changes in individualism, it has some limitations. For example, the authors aggregated three items from the World Values Survey to examine temporal shifts in individualistic values, but the inter-item correlations were not high (.11 < τ s < .24; ordinal-level Kendall’s τ ), possibly implying that the validity of these items may be low. Moreover, as the authors already noted in their article, the data points for China were only four (1990, 1995, 2001, and 2007), and they covered a relatively short period of time (17 years). This limited number of data points might have led to a failure to detect actual historical changes in individualistic values in China. These limitations may be related to the inconsistency of the findings. Indeed, their study showed that most (39 out of 53) of the countries they examined indicated a substantial increase in individualistic values, whereas only five countries (China, Armenia, Croatia, Ukraine, and Uruguay) exhibited a nonnegligible decrease in individualistic values.” (Footnote 1) “However, these words increased in frequency only slightly. As the authors emphasized in their article, the contrasting individualistic words (“choose” and “get”) that were analyzed increased more remarkably (for the details of their interpretation, see Zeng and Greenfield, 2015).” (Footnote 2) 3. Since Bao et al. (2021) has provided more valid evidence for the increasing name uniqueness in China2 and has addressed Ogihara’s (2020)3 concerns on Cai et al. (2018)4, it is necessary to also cite Bao et al. (2021)2 when citing Cai et al. (2018)4 in this article: 1. P. 2 (of the pdf version of the article) “Particularly, there has been only one study examining changes in the behavioral aspect in China (naming; Cai et al., 2018).” should be “Particularly, there has been two studies examining changes in the behavioral aspect in China (naming; Bao et al., 2021; Cai et al., 2018).” 2. P. 8 “Past research showed the rise in individualism in China (Bao et al., 2021; Cai et al., 2018; …)”. I appreciate your suggestion. Actually, I already cited Bao et al. (2021) in the text (p. 3 in the PDF file) and the reference list in the previous version of the article, but I failed to cite the study in some points. Thus, following your comment, I have added the reference (Bao et al., 2021) in the two points in the new version of the article as you suggested. Thank you for your further consideration of this manuscript. I look forward to hearing from you at your earliest convenience. Sincerely, Yuji Ogihara, Ph.D. Department of Psychology, College of Education, Psychology and Human Studies, Aoyama Gakuin University Address: 4-4-25 Shibuya, Shibuya-ku, Tokyo, 150-8366, Japan E-mail: yogihara@ephs.aoyama.ac.jp Web: https://sites.google.com/site/yujiogiharaweb/english"
}
]
}
] | 1
|
https://f1000research.com/articles/12-10
|
https://f1000research.com/articles/12-550/v1
|
25 May 23
|
{
"type": "Research Article",
"title": "Obesogenic Environment in the medical field: First year findings from a five-year cohort study",
"authors": [
"Jo Ann Andoy-Galvan",
"Shyamkumar Sriram",
"Tey Jin Kiat",
"Lim Zig Xin",
"Wong Jun Shin",
"Karuthan Chinna",
"Shyamkumar Sriram",
"Tey Jin Kiat",
"Lim Zig Xin",
"Wong Jun Shin",
"Karuthan Chinna"
],
"abstract": "Background: Doctors with a normal BMI and healthy living habits have shown to be more confident and effective in providing realistic guidance and obesity management to their patient. This study investigated obesogenic tendencies of medical students as they progress in their medical studies. Methods: A cohort of forty-nine medical students enrolled in a five-year cohort study and was followed up after one year. At the initiation of the cohort, socio-demography and information on anthropometry, accommodation, eating behavior, stress and sleeping habits of the students had been recorded. Follow-up data were collected using a standardized self-administered questionnaire. Results: Thirty-seven percent of the students in the cohort are either obese or overweight in the one-year period. A year of follow-up suggests that there is an increase in BMI among the male students (P=0.008) and the changes are associated with changes in accommodation (P=0.016) , stress levels (P=0.021), and sleeping habits (P=0.011). Conclusion: Medical education system should seriously consider evaluating this aspect in the curriculum development to help our future medical practitioners practice a healthy lifestyle and be the initiator of change in the worsening prevalence of obesity worldwide.",
"keywords": [
"Cohort",
"obesity",
"overweight",
"medical students"
],
"content": "Introduction\n\nIt is widely recognized that obesity is influenced by behavioral and genetic factors. However, recently, environmental factors are being investigated as it can be an independent risk factor in the causation of obesity which the medical community calls the “obesogenic environment”.1 The term ‘obesogenic environment’ has been defined as ‘an environment that promotes weight gain and not conducive to weight loss,’ which is believed to be the driving force of the escalating obesity epidemic.2\n\nAccording to the World Health Organization (2020), obesity is defined as excessive or abnormal fat accumulation in the body and it is measured by Body Mass Index (BMI). Obesity increases the risk to health through developing various non-communicable diseases such as diabetes, stroke, and cardiovascular diseases.3 The worldwide prevalence of obesity has tripled from 1975 to 2016, resulting in a global obesity epidemic by reckoning over 650 million adults with obesity in 2016, and an estimated one billion adults with obesity by 2025.3,4 Recent investigations have evolved from imbalance of energy intake and consumption to establishing “obesogenic environment”. These environmental factors include the availability of high-calorie, low-nutrient foods, larger portion sizes, and an increase in sedentary activities due to technological advancements.5 The obesity prevalence presented by WHO will be higher if the Asian BMI cut-off value (≥27.5 kg/m2) is used instead of WHO international classification (≥30 kg/m).6 In Malaysia, according to the National Health and Morbidity Surveys (NHMS), the prevalence of obesity in adults aged 18 years and above was 29.1% in 2006 and 33.7% in 2019, an increase of 15.8% in a decade now. Malaysia is the most obese Southeast Asian country.7–9\n\nNobody is immune to obesogenic tendencies, including doctors and medical students.10 Studies show that medical students are actually more prone to obesity and weight gain due to the nature of their curriculum which leads to lack of leisure time, sedentary lifestyle, and increased stress as they progress towards clinical year.11,12 Doctors with a normal BMI and healthy living habits have shown to be more confident and effective in providing realistic guidance and obesity management to their patients.13,14 A study conducted at a Malaysian medical university found that the prevalence of obesity and overweight among the medical students was high at 30%.15\n\nA study conducted in 2019 in the same university revealed low prevalence of obesity of medical students in comparison with the national prevalence of the same age group though male students were found out to be 4.3× more likely to be obese compared to females. This study recommends further exploration of obesity development among medical students as they progress in their studies as there is no existing available data on this.16 Therefore, this prospective study is conducted to determine the obesogenic tendencies of male and female medical students as they progress in their medical training and identify the risk factors involved. This paper presents the first year findings of the said prospective study.\n\n\nMethods\n\nA prospective cohort study with yearly follow-up was initiated in 2019 among first-year medical students. In the cohort, socio-demography, measurement of height and weight, details about their accommodation, eating behavior, stress, and sleeping habits had been recorded by data collectors as Semester 1. Subsequent follow-up data were collected using a standardized self-administered questionnaire six months after as Semester 2 and one year after as Semester 3.\n\nOur study targeted all first-year medical students presently enrolled during the study period.\n\nThe questionnaire used in this research was designed with reference to several studies conducted by different universities.11,12,15,17 The questionnaire consisted of four sections and twenty-five questions: In Section 1, background information, personal information (socio-demographic info), self-reported anthropometric measurements (height and weight), and stress level information (DASS-21 based questions); In Section 2 consisted of physical activity level (weekly exercise duration) while in Section 3 consisted information of eating behaviors; In Section 4, lifestyle behavior (smoking habits, alcohol intake, and sleeping habit) was asked. A copy of the questionnaire can be found in the Extended data. The participants’ answers to the “Accommodation” represent two living conditions of students which are staying at hostel with irregular cooks and living with family with regular cook. While the answers to stress were categorized as either “High Stress” or “Low stress”. As per the DASS-21 stress questionnaires and category, those under severe and extremely severe were reclassified as “High Stress” and those under mild, normal and moderate as “Low Stress”. “Poor Sleep” and “Good Sleep” were determined using the sleeping hours recommendation by National Sleep Foundation for adults aged 18 to 25 years old which is about 7-9 hours. Good sleep is considered for those participants who answered 7 to 9 hours of sleeping.18 Any duration less than 7 hours or more than 9 hours were considered as “poor sleep”. The answers for alcohol drinking were classified into 2 groups, non-drinker which is no alcohol taken for past 30 days and drinker if they have taken alcohol regardless of number of drinks for past 30 days. This is the same for smoking, non-smoker for no cigar or vape for the past 30 days and smoker, if they have taken nicotine regardless of number for past 30 days. Physical Activity in this study less than 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity physical activity is classified as inadequate physical activity, while more than 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity physical activity is classified as adequate physical activity.19 Eating behaviour is assessed by determining the eating habits of the students namely, number of meals per day (<3 meals, 3 meals, >3 meals), servings of fruit and vegetable in a day (1-5, >5 servings), type of diet practiced (vegetarian, non-vegetarian, mixed diet), number of fast foods per week , number of days of breakfast taken in a month Responses are further classified under yes or no for skipping breakfast for the past 30 days; Inadequate or Adequate for daily servings of fruits and vegetables; Regular or Irregular for number of daily meals; rarely or often for consumption of snacks, carbonated soft drinks and fast food; and unvaried or varied diet for type of diet practiced.\n\nA pilot test was conducted on students from a class to determine the questionnaire acceptability and ease of use by the participants and the data collected for analysis. All the suggestions and feedback were collected and integrated accordingly into the questionnaires.\n\nBaseline height and weight were measured by the researchers. Baseline height was used to calculate BMI of the three follow up periods while the weight for Semesters 2 and 3 were measured by the participants at home. Sections 1-4 of the questionnaire were answered online by the participants through Google form in all the study periods.\n\nThe questionnaire used in this research was fully typed in English and was approved by Taylor’s University Human Ethics Committee with reference number HEC 2019/119. The active participation in and completion of the online form were taken as consent, and the ethical committee approved the consent protocols and procedures.\n\nIBM Statistical Package for Social Sciences (SPSS) version 25 was used to describe and analyze the data collected. For descriptive data, frequency, mean and standard deviation (SD) were used to summarize the data. Generalized Estimating Equations (GEE) were employed to test the association between BMI overtime and sex assigned at birth throughout the cohort study. The independence t-test was also used to test the difference between mean BMI and sex assigned at birth over time. The predicted variables associated with BMI were tested using ANOVA one-way analysis. Any variables with p < 0.250 in the ANOVA test were tested again with GLM multivariate analysis for regression analysis. A 95% of confidence interval was fixed throughout the cohort study, with any obtained p-value lesser than 0.05 is considered significant.\n\n\nResults\n\nA total of 50 (17 males and 32 females) first-year medical students from Taylor’s University School of Medicine were included in this study. The response rate was 82% (50/61). One student withdrew from the study during Semester 2. Characteristics of year one medical students who participated in the study are presented in Table 1.\n\na WHO Expert Consultation.6\n\nPrevalence of obesity among Taylor’s University year one medical students as they progress towards clinical year\n\nCompared with the national reported prevalence value of obesity in adults (33.7%),8 the prevalence of obesity among the medical students in this study based on the Asian cut-off value was high at 36.7% (Table 3).\n\na WHO Expert Consultation.6\n\nComparison of mean BMI changes of Taylor’s University year one medical student over a year\n\nBased on the BMI result obtained (Table 4), the difference between mean BMI overtime in three studies was found not significant (p > 0.05). On the contrary, the difference between gender and BMI over time in this study was notable (p < 0.05) (Table 5). As shown in Table 5, there is no difference (p > 0.05) in mean BMI between the gender during Semester 1. However, during Semesters 2 and 3, the BMI among the males was significantly higher (p < 0.05) compared with females (refer to Figure 1).\n\nEvaluation of risk factors associated with BMI among Taylor’s University year one medical student\n\nWhen the predicted variables were tested with ANOVA one-way analysis, significant associations (p < 0.05) were found between BMI with accommodation and stress level. Other predicted variables were not significantly associated with BMI, but variables (Sleeping habit and Carbonated soft drinks intake) with p < 0.250 were then subjected to GLM Multivariate Analysis.\n\nThere were significantly lower average BMI levels of those who can cook/live with people who can cook, 21.53 kg/m2, compared to 24.63 kg/m2 of those who cannot cook/living with people who cannot cook. This is also seen in the p-value of 0.018, indicating great significance between this factor and BMI/weight gain. Based on Table 6, we can assume stress levels are among the leading players in determining the change in a medical student’s BMI. This can be seen in the participants’ mean BMI levels, which are the highest recorded average at 26.57 kg/m2 (p-value = 0.018).\n\nAfter GLM Multivariate analysis, it revealed that accommodation (p-value = 0.016), stress level (p-value = 0.021) and sleeping habit (p-value = 0.011) were the independent predictor of BMI changes in year one medical students (Table 7).\n\n\nDiscussion\n\nThe predominant proportion of participants who had both higher BMI and also an increased BMI overtime is the male sex (assigned at birth) (refer to Table 5 and Figure 1). This is consistent with study findings conducted on medical students in Malaysia,15 India,11 and in Pakistan.20 On the contrary, the findings of our study contradicted the findings of two studies conducted by Anupama21 and Fernandez,22 which showed that the predominant proportion of their medical students who have higher BMI overtime is female. All the above mentioned studies were conducted through cross-sectional study design where there is generally no evidence of the temporal relationship between the variables and BMI, thus could not establish causality. Our cohort study shows the temporal relationship between the predicted variables where BMI changes can be identified over time. However, the presence of predominant proportion of male medical students with higher BMI might be due to their higher muscle mass than female (sex assigned at birth) students.\n\nIn our study, accommodation turned out to be the most significant factor in determining risk factors for weight gain. This finding is in line with other studies, which also mentioned that people who had more home-cooked meals in their weekly diet are less obese than those who do not.23–25 Similar studies from a Pakistan medical school also reported that medical students who had more meals at home reported lower obesity rates than those having food outside their home.20 A possible reason could be that foods consumed outside are usually higher in fat-content and also contain unhealthy additions than home-cooked food. Our research shows that medical students who lived alone/or cannot cook themselves had higher BMI values than medical students who could cook/live with people who could cook.\n\nOur study revealed that the number of medical students who experienced high levels of stress has decreased over the year, which might be possibly because most of the participants were living with their parents during this period. This might help lessen the medical students’ burden as they receive the best support-system at their homes. However, a higher BMI value is noticed in medical students with high stress, which might be due to the sudden shift in learning methods where students were forced to adapt to online learning. Similar findings were found from studies done in America which also found that medical students are experiencing severe stress and thought that online learning is a burden.26\n\nOur findings on sleep are similar with Eveline.27 We found that majority (59.2%) of medical students having a poor sleep compared to their 60%. From this, we found medical students who experienced poor sleep had a higher average BMI than those who experienced good sleep, which correlates with research findings from Zailinawati et al.28 This might be due to the intense workload and vast topic to learn in the medical field that often leads to a sacrifice in sleeping time for revisions. However, the findings of this study are not supported by the recent study done by Hameed.29\n\nThere were some limitations of this study. This study was done during the COVID-19 pandemic, though the baseline data was collected few months before the pandemic. BMI was calculated using measured weight and height during Semester 1, while BMI for the subsequent periods were calculated using the baseline height and their self-reported weight. The movement restrictions during follow ups which required all education sectors to shift to online classes might have contributed to the outcome of the study.\n\n\nConclusion\n\nThe prevalence of obesity and overweight in Taylor’s University year one medical students was considered high in all three semesters (40%, 30.6% and 36.7%). A year of follow-up suggests that there is an increase in the BMI of male students and the changes are associated with changes in accommodation, stress levels, and sleeping habits.\n\nThere must be a radical change in medical education. Medical students should be given a balanced lifestyle, with time for adequate sleep, and exercise, and access to a proper diet. Online studies which are becoming more popular even before the pandemic should be combined with some hybrid form of learning to increase the physical activity of students.",
"appendix": "Data availability\n\nHarvard Dataverse: OBESOGENIC ENVIRONMENT IN THE MEDICAL FIELD: FIRST YEAR FINDINGS FROM A 5-YEAR COHORT STUDY, https://doi.org/10.7910/DVN/7G1VD8. 30\n\nThis project contains the following underlying data:\n\n• SPSS Merged File (Repeated Measures)\n\nHarvard Dataverse: OBESOGENIC ENVIRONMENT IN THE MEDICAL FIELD: FIRST YEAR FINDINGS FROM A 5-YEAR COHORT STUDY, https://doi.org/10.7910/DVN/7G1VD8. 30\n\nThis project contains the following extended data:\n\n• A copy of the questionnaire\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgments\n\nThe authors would like to express their deepest gratitude to Dr. Low Bin Seng for his active and invaluable guidance throughout this research paper and to Taylor’s University medical students who took part in this study.\n\n\nReferences\n\nPowell P, Spears K, Rebori M: What is obesogenic environment? University of Nevada; 2010 [cited 20 July 2021]. Reference Source\n\nSwinburn B, Egger G, Raza F: Dissecting obesogenic environments: the development and application of a framework for identifying and prioritizing environmental interventions for obesity. Vol. 29. . ELSEVIER; 1999; pp. 563–570. Publisher Full Text\n\nObesity and overweight: World Health Organization, Int.c2020 [20 July 2021]. Reference Source\n\nPrevalence of obesity: World Obesity Federation.c2019 [20 July 2021]. Reference Source\n\nhttp\n\nWHO Expert Consultation (WHO): Appropriate body-mass index for Asian population and its implications for policy and intervention strategies. Lancet. 2004; 10: 157–163.\n\nInstitute for Public Health (IPH) 2008: The third national health and morbidity survey (NHMS III). Kuala Lumpur: Ministry of Health Malaysia; 2006.\n\nInstitute for Public Health (IPD): National health and morbidity survey 2019 (NHMS 2019). Vol. I: NCDs – Non-communicable Diseases: Risk Factors and other Health Problems. Kuala Lumpur: Ministry of Health Malaysia; 2019.\n\nMalaysia ‘most obese Asian country’. BBC News, Int.; c2020 [20 July 2021]. Reference Source\n\nBarnett K: Physician obesity: the tipping point. Glob. Adv. Health Med. 2014; 3(6): 8–10. Publisher Full Text\n\nThomas E, Geethadevi M: Prevalence and determinants of overweight and obesity among medical students. Natl. J. Physiol. Pharm. Pharmacol. 2019; 01: 1–7. Publisher Full Text\n\nBertsias G, Mammas I, Linardakis M, et al.: Overweight and obesity in relation to cardiovascular disease risk factors among medical students in Crete, Greece. BMC Public Health. 2003; 3: 3. Publisher Full Text\n\nBleich S, Bennett W, Gudzune K, et al.: Impact of physician BMI on obesity care and beliefs. Obesity. 2012; 20(5): 999–1005. Publisher Full Text\n\nAbramson S, Stein J, Schaufele M, et al.: Personal exercise habits and counseling practice of primary care physicians: a national survey. Lippincott Williams & Wilkins Inc.; 2000 [20 July 2021]; vol. 10. : 40–48. Reference Source\n\nBoo NY, Chia GJ, Wong LC, et al.: The prevalence of obesity among clinical students in a Malaysian medical school. Singap. Med. J. 2010; 51(2): 126–132.\n\nGalvan JAA, Sriram S, Chinna K, et al.: Low prevalence of Overweight and obesity among medical students at a University in Malaysia. Southeast Asian J. Trop. Med. Public Health. 2019; 50(6): 1179–1187.\n\nAlcohol and public health: Centers for Disease Control and Prevention.c2020 [20 July 2021]. Reference Source\n\nParuthi S, Brooks LJ, D’Ambrosio C, et al.: Recommended Amount of Sleep for Pediatric Populations: A ConsensusStatement of the American Academy of Sleep Medicine. J. Clin. Sleep Med. 2016 Jun15; 12(6): 785–786.\n\nMinistry of Health Malaysia: Clinical practice guidelines on primary & secondary prevention of cardiovascular disease. Kuala Lumpur: Ministry of Health Malaysia; 2017.\n\nMahmood S, Perveen T, Najjad M, et al.: Overweight and obesity among medical students of public sector’s institutes in karachi, Pakistan.2013 [cited 20 July 2021]. Reference Source\n\nAnupama M, Iyengar K, Rajesh S, et al.: A study on prevalence of obesity and life-style behavior among medical students. Research Gate. 2017; 4: 3314–3317. Publisher Full Text\n\nFernandez K, Singru S, Kshirsagar M, et al.: Study regarding overweight/obesity among medical students of a teaching hospital in pune, India. Med. J. DY. Patil. Univ. 2014; 7: 279–283. Publisher Full Text\n\nTani Y, Fujiwara T, Doi S, et al.: Home Cooking and Child Obesity in Japan: Results from the A-CHILD Study.2019 [cited 20 July 2021]. Reference SourceReference Source\n\nSusanna M, Heather B, Wendy W, et al.: Frequency of eating home cooked meals and potential benefits for diet and health: cross-sectional analysis of a population-based cohort study. BMC. 2017 [cited 20 July 2021]; 14: 109. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDavid C, Kylie B, Gita M, et al.: Which food-related behaviours are associated with healthier intakes of fruits and vegetables among women? Cambridge University Press; 2007 [cited 20 July 2021]. Reference Source\n\nEric W: American Medical Student Perceptions of the Online Learning Environment, their Quality of Life, and the School of Medicine’s Response During COVID-19 Pandemic.[cited 20 July 2021]. Reference SourceReference Source\n\nEvelina P, Darius L, Virginija A: Associations of quality of sleep with lifestyle factors and profile of studies among Lithuanian students MDPI.2010 [cited 20 July 2021]. Reference Source\n\nZailinawati AH, Teng CL, Chung YC, et al.: Daytime sleepiness and sleep quality among Malaysian medical students.2009 [cited 20 July 2021]. Reference SourceReference Source\n\nHameed R, Bhat A, Nowreen N: Prevalence of overweight and obesity among medical students and its correlation with sleep pattern and duration. ResearchGate. 2019; 6. Publisher Full Text\n\nGalvan JA: OBESOGENIC ENVIRONMENT IN THE MEDICAL FIELD: FIRST YEAR FINDINGS FROM A 5-YEAR COHORT STUDY [Dataset]. Harvard Dataverse. 2021. Publisher Full Text"
}
|
[
{
"id": "204772",
"date": "25 Sep 2023",
"name": "Gajanan D Velhal",
"expertise": [
"Reviewer Expertise Epidemiology",
"Research Methodology",
"Health Planning & Management",
"MH care",
"communicable and non communicable diseases"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nPresent cohort study, in progress, undertaken by Jo Ann Andoy-Gavlan et al, at Malaysia need special appreciation for having touched the important aspects in the life of Medical students during their study period in the medical college. It is well known that getting into the environment of Medical College after completing conventional education in schools/junior college, invites lot of adjustments/modifications in the behaviour patterns of the students, that too at their tender stage in life i.e. late adolescent’s. Contrary to the expectations - in relation to burden of medical studies, stress of getting adjusted to surrounding environment, and being away from parental home, here it is found that there is tendency on the part of the student’s to gain weight and increase BMI, that too more significantly among males as compared to females, in the first year of study . This needs more elaboration by interviewing the participants directly as well as organizing focus group discussions on the topic among students, teachers, care takers in the hostel etc. over and above, collecting the information on questionnaires. Of course the cohort is going to be followed for next four years, which will provide still more meaningful conclusions to the policy makers and administrator’s to look into this important aspects of medical students with due attention to promote health of students in long run.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "209970",
"date": "20 Oct 2023",
"name": "Selvamani Yesuvadian",
"expertise": [
"Reviewer Expertise Demography",
"Social epidemiology and Food and nutrition security"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is an interesting article about obesogenic environment in the medical field. The rates of obesity are increasing in the general population. Medical students, as future physicians, have an important role and responsibility to play in advising our society about obesity and also treating obesity and the related wide spectrum of metabolic illnesses that accompany obesity. This article is particularly very interesting and useful because the study highlights the contribution and effects of the living environment of medical students to the changing patterns of BMI. This is particularly important in the scenario with epidemiological burden and transition with increasing incidence of non-communicable diseases even affecting the younger generations. The results suggest regular monitoring of the physical health of the students is important. The implications of this study could be used for wider policy implications and bringing about changing and lifestyle modification interventions in the medical field among both the medical and allied health science students. I accept the paper without any reservations considering the importance of the issue addressed in the paper and the robust methodology used here. Given the cohort nature of this study, further research that is done in this area will help to establish causality which will serve very vital for policy development in the area. It is necessary to be sure that medical students are in good health and without obesity before they can take up the advisory and treating role as a physician in the community.\nI believe that the paper is good in its current format and I accept it. I would like to advise that making the following changes would be good. Table 7 adjusted for other covariates such as socio-demographic variables. It would be better if Table 1 had all other covariates also.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-550
|
https://f1000research.com/articles/12-549/v1
|
25 May 23
|
{
"type": "Opinion Article",
"title": "Understanding influences on mental health among over 70-year-olds in Kenya using a life course theory",
"authors": [
"Adelaide M Lusambili",
"Robert Nyakundi",
"Christine Ngaruiya",
"Kizito L Muchanga",
"Ahaya L Ochieng",
"Laurie M Vusolo",
"Newton Joseph Guni",
"Robert Nyakundi",
"Christine Ngaruiya",
"Kizito L Muchanga",
"Ahaya L Ochieng",
"Laurie M Vusolo",
"Newton Joseph Guni"
],
"abstract": "World Health Organization (WHO) estimates that by 2050 “older adults” (OAs)—denoting those over 70 years old in this article—will constitute 21% of the global population, with over half living in low or middle-income countries (LMICs). Old age is associated with increased multiple chronic conditions (MCCs) such as cancer, hypertension, arthritis, diabetes and mental health. According to WHO, 20% of older adults in Africa are affected by mental health – and dementia and Alzheimer’s diseases are likely to increase, adding expenditure on public services. Knowledge and understanding of OAs experiences and histories and how they contribute to mental health are critical to informing measures and strategies to safeguard older adults. Like many sub-Saharan African (SSA), these experiences have not been documented in Kenya. In this article, we use a life course theory (LCT) to reflect on the intersection between historical and current environmental and socioeconomic factors and their effects on the mental health of OAs. We hope to enrich future researchers by providing core yet overlooked historicities to guide research and policies in an understudied population in sub-Saharan Africa. We conclude with policy and research recommendations on ageing and health.",
"keywords": [
"Older people",
"elderly",
"ageing",
"mental health",
"life course theory",
"Kenya and Africa."
],
"content": "Introduction\n\nWhile half of the “older adults” (OAs) population is projected to live in low or middle-income countries such as Kenya by 2050,1 there is limited research to inform mental health interventions and policies. According to WHO (2013),2 mental health is an essential part of health and well-being, and it encompasses not only individual characteristics but also social, cultural, economic, political and environmental factors.2 An increase in life expectancy is linked to chronic conditions ingrained in ageing, such as dementia and psychological and behavioural disorders. Factors predisposing OAs to mental health are contextual, - and understanding the ageing process and mental health by examining individual historicities within their environment is critical to prevention, early diagnosis, treatment and interventions. This paper uses a life course theory (LCT) to map out historical and environmental intersectionalities and their contributions to OAs mental health in Kenya.\n\nThe LCT is an interdisciplinary perspective or framework that seeks to understand the multiple factors that shape people’s lives from birth to death. It emerged in the 1960s and encompasses ideas and observations from an array of disciplines.3,4 The basic concept of LCT includes cohorts, trajectories, transitions, turning points and life events within which the study of family life and social change can ensue.\n\nThe life course theory views each person as a product of their environment as well as their genetics, which consequently act as a determinant for their health and healthcare. Emphasis is not placed on single steps in a life’s path but an integrated continuum of exposures, experiences and interactions.5–7 In studying gerontology, with a central focus on ageing, LCT has the potential to help practitioners understand complex interacting factors affecting the overall health of a population both at the individual level and as it affects generations.\n\nIn understanding and mapping the life course of older adults (OAs) in Figure 1 below, we highlight individual episodes of stress, or isolated life experiences, and their impact on an individual’s trajectory. Moreover, according to LCT, the cumulative effect of multiple negative experiences over time may have an inimical impact on health and development.8 By way of example, in Figure 1, we demonstrate a LCT schematic with various effects that contribute to the trajectory of mental health among OAs in the context of Kenya. We present this model for consideration of contexts similar to Kenya, including other countries in SSA. Across the lifespan, populations are connected to social structures which may link to historical events such as urbanization and globalization. This, in turn, shapes opportunities such as those involving access to care; these factors act as determinants for the availability of care and ultimately affect health outcomes.9 By incorporating historical influences and recognizing the cumulative effects of multiple factors, this framework is valuable for understanding mental health among OAs and guiding effective policies and programs.10\n\n\nIntersection between urbanization, globalization and disintegration of traditional social fabrics\n\nIn Kenya, most OAs live in rural areas.11 Historically, rural areas were held together by tight-knit socio-cultural mores, which provided pathways for social protection and care in advanced age. However, rapid urbanisation after Kenya’s attainment of independence in the 1960s ushered in rural-urban migration and a move towards a primary focus on the nuclear family. This process weakened the traditional social fabrics of integration and interdependence that had typically supported care for OAs (extended family members).\n\nGlobalisation and urbanisation specifically began intensifying in SSA after the second world war (1939–1945).12,13 After the war, many returning African soldiers had attained a mindset that associated nationalism with urbanization. Hence, the rural-urban dichotomy disintegrated the traditional ties. The process of globalisation further contributed to the severing of traditional ties. While providing complex interconnectedness, linkages and cultural interactions that had not existed previously left OAs feeling isolated in terms of their ethnic identities.14\n\nFurthermore, age related social inequalities—with regards to access to the available resources—worsened as technological advances increased.15,16 Many OAs in Sub-Saharan Africa have no access to modern technological platforms such as smart phones, social media and games; hence having little to no contact with family members who are domiciled in urban areas. Children raised in urban cities that have been most rapidly influenced by globalization have become less grounded in traditional mores that conventionally provided pathways for the care of older adults.17–20 Such inaccessibility exacerbates loneliness that contributes towards worsening mental health.21,22\n\n\nStructural adjustment program (SAPS)\n\nThe majority of living OAs in Kenya were subject to the destructive effects of the World Bank Structural Adjustment Programs (WB-SAPs) - implemented in the 1980s and developed through the 1990s. The SAPs had far reaching consequences for people in these communities, and particularly the current OAs population. The WB-SAPs policies lowered the living standards as many Kenyan government employees were retrenched through a government approach that encouraged them to take a ‘handshake’ and leave their jobs; the majority being men.23\n\nA ‘handshake’ was a lump sum of money that was given to all those opting to retire early as a way for governments to contain wages. These individuals were primarily in their forties and early fifties at the time, constituting the demographic cohort coined “baby boomers” and the majority of current living OAs. The SAPs retrenchment program although lauded for decreasing wages and salaries on the government payroll in the initial stages, however, it increased poverty characterized with inequalities in education and accessing healthcare particularly for vulnerable populations.24 The implications were that many people who took the handshake plunged into poverty after a few years as it was inadequately funded.25,26 Moreover, there have been concerns that among the OAs who received the handshake and retired early were not given enough practical, long term business skills by the government.\n\nAt the same time, the feminisation of poverty increased, as many women who were traditionally domesticated in rural areas while their husbands worked in cities migrated to urban areas in search of informal jobs.27 The migration of women, many of whom were wives and mothers, to urban areas in search of employment fragmented the traditional family structure. Consequent to challenges with migration, many women settled in the slums and took on jobs in which they were poorly remunerated.28 The shift to the feminisation of poverty not only contributed to the vulnerability among women, but also to the imbalance and disorientation in the family set up.\n\nMoreover, the SAPs were associated with budget cuts and privatization, both weakening the health system, and limiting access to its services.29 Consequently, urban and rural inequalities increased as the number of public hospitals decreased, and care provided by private hospitals was rendered too expensive for the majority of the population.30–32\n\nFinally, spending cuts in the education ministries—as guided by the SAP driven policies—saw the reduction of student enrollment into schools and the consequent drop out of trainees.33,34 The addition of school dropouts put further stress on OAs who also took on the burden of these uneducated children; this resulted in increased financial demands for already strained OAs. In sum, the SAPs are widely blamed for a short-changing of the country’s capacity for local investment, autonomous prioritization of government spending by sovereign nations, and a downward quality in social services and other priorities available to its citizens.35\n\n\nHuman immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS)\n\nDuring the era of SAPs, HIV/AIDS ravaged communities in Sub-Saharan Africa and other low or middle income countries (LMICs). In fact, evidence supports the link between SAPs and the increase in the HIV/AIDS burden.36 Due to the abject poverty brought on by SAPS, women were forced to engage in risky behaviours, such as prostitution, in order to make a living leading to HIV infections.37–40 At the same time, HIV/AIDS related mortality and morbidity rates among young men increased, leaving behind a generation of orphaned children.41 Consequently, the generation that constitutes OAs in Kenya today took on the responsibility of raising children whose parents had died by providing social and material support.42 A survey within one of Kenya’s largest tribes, found the mean age of caretakers was 63.5 and in around a quarter of the studied households (23.2%, n=108/465), at least one orphan was sheltered.43 Inadequate access to funds for food and schooling are cited as prominent issues and this economic burden on OAs, alongside the shift in care-giving responsibility, fell concomitant with the already ongoing, negative economic toll in the country caused by SAPs.43 The intersection between SAPs and the HIV/AIDS pandemic imply that OAs in Africa have a distinct history and experience compared to other generations who are not in this age bracket. However, the effects these experiences have had on their mental health have been poorly described. Furthermore, interventions to recuperate or remunerate their loss have gone unaddressed.\n\n\nTechnological advancement and marginalization\n\nMore recently, the advent of computers and information technology has widened the gap between generations and further isolated OAs. Fleming et al. (2018),43 highlights the predominant lack of consideration for OAs in the development and implementation of technological interventions despite its promise to conversely advance equity of access in many sectors. However, by excluding the behaviours of OAs, potential patterns of use, and daily practices in the inherent design of digital technology, it has instead marginalized this population from its use.44\n\nFirstly, the majority of OAs live in rural areas where access to computers and smart phones are less likely. Secondly, the vast majority of OAs in Kenya are illiterate, which further alienates them from computer or even smart phone literacy despite potentially having access.45 The latter (smart phones) of note, are unfortunately required for the delivery of most digital mental health tools or interventions that have been developed.46 Meanwhile, urbanization and globalization have led to the reliance of younger populations on these and other technologies. While technology has enormous benefits, it has disconnected OAs from younger generations as communication is limited, particularly for those who are illiterate. The social fabrics that held communities together have now been disrupted by technology leaving OA especially in those in remote or rural communities, subject to increased marginalization, isolation and loneliness.47\n\nThe advent of ‘mobile-money’ has created new avenues for interaction and the provision of basic sustenance that did not exist previously for city-dwelling family members and their elderly relatives in rural settings. By way of background, a mobile money system called ‘Mpesa’ was designed and implemented in 2007 in Kenya. ‘Mpesa’ is used by the vast majority of Kenyans to transfer funds, including the sending of remittances from bread-winning family members to other family members, such as OAs in remote locations.48–50 However, the effects of successful money transactions with family members, albeit beneficial at face value, is not solvent in addressing the significant changes in social interactions that have well-established negative consequences for mental health.51–53 Moreover, these changes have taken place at such an expedient rate leaving OAs little time to adapt, and for their family and friends to accommodate. Additionally, government investments in their benefits, health care, mental health and well-being have not kept up.\n\nAnother pronounced impact of technology on OAs is their access to cash transfer programs (CTPs) through mobile phones. Kenya has implemented CTPs as part of the social protection program to identify and promote immediate relief from poverty among poor and vulnerable OAs. However, not all vulnerable OAs can access the CTPs, especially those living in remote areas. The program has been fraught with delays and unfavourable payment modes. For example, paying through banks and post offices that may not be accessible to illiterate OAs and those without access to phones or transportation. Thus, this approach has increased inequalities and poverty among older people who lack consistent income.\n\n\nClimate change and its impact on older peoples’ mental health\n\nAfrica today, like the rest of the world, suffers from unpredictable weather and climate changes that have resulted in whole regions becoming drier, wetter, hotter, or colder than before—vicissitudes that have had drastic negative effects on human health and wellbeing.54 Similarly, in Kenya, there has been abnormally heavy rainfall, strong winds, cyclones, ice storms, extended periods of drought, and fatal heat waves in recent years.55–57 During periods of extreme cold in Kenya, snow has fallen in places where this has never occurred before. The new weather extremes adversely affect food production and limit access to basic needs, including water, and services, such as health care. All of this disproportionately affects populations already vulnerable to these afflictions, such as individuals living in drought-ridden areas, having consequently been exposed to further harsh climates and increased drought. Evidence suggests that climate is likely to have especially strong negative effects on OAs, many of whom have reduced mobility and cognitive abilities.58–61\n\nThe impact of extreme weather such as flooding, disruption of infrastructure, lack of water, displacements due to flooding and a lack of proper pathway to care for older people can cause anxiety, stress and trauma.62–65 As discussed, effects of climate change are altering social, communal and familial structures. Climate change can enable environmental degradation and loss of profitable social-cultural networks that can improve mental health, particularly for the older adults who remain isolated in rural areas in Kenya and similar contexts. The stressors emanating from both extreme heat and heavy rainfall are further augmented by the already eroding traditional family support and social-cultural networks (as discussed earlier in the paper), necessitated by urbanization and technological changes. Increased emotional and physical insecurity, due to heavy rainfall associated with flooding and destruction of rural infrastructure, has led to increased poverty, homelessness and a loss of profitable social networks.\n\n\nCOVID-19\n\nThe older populations in Kenya have been particularly vulnerable in the era of Coronavirus disease 2019 (COVID-19). As the population that suffered the highest morbidity and mortality rates among other sub-groups globally, older populations were disproportionately affected by the direct effects of the disease.66 However, negative indirect effects also prevailed. Kenya has undergone extended periods of lockdowns where older people, many of whom reside in previously discussed rural and remote villages, went without seeing their families or attending community functions such as church services, funerals and weddings. These gatherings constitute routine sociocultural practices, and often are the only form of social contact they may have. Extended periods of lockdown have then, unsurprisingly, increased the prevalence of loneliness.67,68 The majority who are frail, and who suffer from underlying conditions, have experienced difficulties in accessing medical care in addition to having lost loved ones. Further, economic deprivation has increased, as family remittance has dwindled due to exacerbated unemployment caused by retrenchment and reduced commercial activities due to lockdowns. In the context of COVID-19, there is also the fear of living alone, increasing anxiety due to poverty have increased as OAs are made redundant and remittance from relatives reduced.69 COVID-19 found an already fragile population of OAs plagued by effects of climate change, technology, poverty, globalisation and historical experiences of HIV/AIDS and SAPS and augmented their difficulties.\n\n\nFuture research recommendations and approaches\n\nIn order to tackle the rising burden of mental health issues in OAs in Kenya, we propose intentional, versatile and inter-sectional research that particularly focuses on this population. There are several approaches we would recommend based on our thesis and additional existing literature outside of the scope of our article.\n\nFirstly, we propose that literature reviews, content analyses, and needs assessments are conducted in order to identify existing data on mental health in the older Kenyan community. We recommend that these analyses address the historical and sociocultural effects on resultant mental health decline. We anticipate that such reviews would be exploring the work of non-conventional social research methods, as well as reviews of policy documents that may provide important historical context on these changes – such as in the case of the effects of SAPs that are as yet to be fully explored.\n\nSecondly, while strategies targeting mental health on the continent has continued to progress in Africa over the past decade, we have found that the majority of this work is exclusive of older adults.70 This is specifically with regards to effective treatment approaches, currently available modalities and their access, as well as coping strategies that have otherwise been effective in this population. Community-based and rural studies (CBRS) may need to be pursued in this case, because this population may not routinely access healthcare in hospital-based settings, as we have presented. Ethnographies provide an appropriate strategy to assess traditional and cultural biases or practices that may otherwise be missed by more conventional research methods.\n\nFinally, when considering sampling strategies for mental health studies on the continent, older adults should be sampled for equitably, such as through the use of stratified sampling, or targeted follow-ups that are anticipated in the design given a high likelihood of non-response or loss to follow up of this group. Additionally, community sensitization and consent approaches need to be carefully considered during study design in order to help optimize inclusion and voluntary participation while also securing this important data.71,72 Intersectionality approaches to assess the direct and indirect health impact vulnerabilities brought by climate change, technology and COVID-19 on the ageing population in sub-Saharan Africa should be considered.\n\n\nConclusion\n\nWe conclude that the LCT theory offers an invaluable framework to better understand both the ageing process and the mental health issues associated with it. While great strides have been made to understand mental health among the OAs in Kenya, much work is yet to be done to understand the different age groups in the ageing cycle, as well as the intersectionalities and linkages of different life dynamics as contributing factors to mental health. As we have shown in our discussions, mental health problems among OAs do not occur in isolation; rather a plethora of outcomes and factors throughout the lives of people significantly contribute to the same. This also has to be viewed as the gradual and incremental accrual of coping scenarios to different socio-economic and physical challenges that occur throughout the lifetime.\n\n\nAuthors’ contributions\n\nAdelaide M Lusambili: Conceptualization, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing\n\nRobert Nyakundi: Data Curation, Methodology, Project Administration, Writing – Review & Editing\n\nChristine Ngaruiya: Validation, Visualization, Writing – Review & Editing\n\nKizito L Muchanga: Validation, Visualization, Writing – Review & Editing\n\nAhaya L Ochieng: Validation, Visualization, Writing – Review & Editing\n\nLaurie M Vusolo: Validation, Visualization, Writing – Review & Editing\n\nNewton Joseph Guni: Supervision, Validation, Visualization, Writing – Review & Editing",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nWHO: Ageing and health.2022. Reference Source\n\nWHO: Mental health action plan 2013—2020. 2013. Reference Source\n\nElder GH Jr: Life course dynamics. Ithaca, NY: Cornell University Press; 1985.\n\nHareven TK: Aging and generational relations: life course and cross-cultural perspectives. New York: Aldine de Gruyter; 1996.\n\nElder GH Jr.: The life course.Borgatta EF, Montgomery RJV, editors. Encyclopedia of sociology. Vol. 3. . 2nd ed.New York: Macmillan; 2000; pp. 1614–1622.\n\nKomp K, Johansson S: Population ageing from a lifecourse perspective: Critical and international approaches. Bristol: Policy Press; 2015.\n\nKomp K, Johansson S: Population ageing in a lifecourse perspective: Developing a conceptual framework. Ageing Soc. 2016; 36(9): 1937–1960. Publisher Full Text\n\nJuster RP, McEwen BS, Lupien SJ: Allostatic load biomarkers of chronic stress and impact on health and cognition. Neurosci. Biobehav. Rev. 2010; 35(1): 2–16. PubMed Abstract | Publisher Full Text\n\nAlwin DF, Wray LA: A life-span developmental perspective on social status and health. J. Gerontol. Soc. Sci. 2005; 60(Special Issue II): S7–S14. Publisher Full Text\n\nO’rand AM: the precious and the precocious: understanding cumulative disadvantage and cumulative advantage over the life course. Gerontologist. 1996; 36: 230–238. PubMed Abstract | Publisher Full Text\n\nNjenga FG, Kigamwa PA: Mental health policy and programmes in Kenya. Int. Psychiatry. 2005; 2(8): 12–14. Publisher Full Text\n\nMyrice E: The Impact of the Second World War on the Decolonization of Africa.2015.\n\nKeiser J, Utzinger J, De Castro MC, et al.: Urbanization in Sub-Saharan Africa and Implication for Malaria Control.Breman JG, Alilio MS, Mills A, editors. The Intolerable Burden of Malaria II: What’s New, What’s Needed: Supplement to Volume 71(2) of the American Journal of Tropical Medicine and Hygiene. Northbrook (IL): American Society of Tropical Medicine and Hygiene; 2004 Aug. Reference Source\n\nKhan H, Powell J: Ageing and globalization: A global analysis. J. Glob. Stud. 2013; 4: 137–146.\n\nNeves BB, Meod G: Digital Technology and Older People: Towards a Sociological Approach to Technology Adoption in Later Life—Barbara Barbosa Neves, Geoffrey Mead, 2021. 2020, December 22. Publisher Full Text\n\nMarshall BL, Dalmer NK, Katz S, et al.: Digitization of Aging-in-Place: An International Comparison of the Value-Framing of New Technologies. Societies. 2022; 12(2): 35. Publisher Full Text\n\nWilson G: (PDF) Globalisation and support in old age. 2001. Reference Source\n\nPhillipson C: Population Aging and Globalization: The Impact of Cultural and Social Change. Oxford Research Encyclopedia of Psychology. 2019, February 25. Publisher Full Text\n\nHarper S: Addressing the implications of global ageing. J. Popul. Res. 2006; 23(2): 205–223. Publisher Full Text\n\nGakahu N: The Social Implications of a Global Culture to Africa: Kenya’s Case. 2011; 9.\n\nKimamo C, Kariuki P: Taking care of the aged in Kenya: the changing trends. MOJ Gerontol. Ger. 2018; 3(1): 13–14. Publisher Full Text\n\nNzabona A, Ntozi J, Rutaremwa G: Loneliness among older persons in Uganda: Examining social, economic and demographic risk factors. Ageing Soc. 2016; 36(4): 860–888. Publisher Full Text\n\nKiggundu M: Retrenchment programs in Sub-Saharan Africa: Lessons for demobilization. 1997. Reference Source\n\nRono JK: The impact of the structural adjustment programmes on Kenyan society. J. Soc. Dev. Afr. 2002; 17: 18.\n\nWilliamson RC, Rinehart AD, Williamson RC: Early Retirement: Promises and Pitfalls. Springer; Softcover reprint of the original 1st ed.1992.\n\nKemal AR, Naseem SM: Structural Adjustment, Employment, Income Distribution and Poverty [with Comments]. Pak. Dev. Rev. 1994; 33(4): 901–914. Publisher Full Text\n\nOtieno GO: The impact of structural adjustment programs on rural households in K’ombura location Kisumu district. 1997; 166.\n\nMwangi C: An Assessment of Impact of Poverty on Female Headed Households in Kangemi, Kenya. 2017; 61.\n\nForster T, Kentikelenis AE, Stubbs TH, et al.: Globalization and health equity: The impact of structural adjustment programs on developing countries. Soc. Sci. Med. 2020; 267: 112496. PubMed Abstract | Publisher Full Text\n\nAhmed I, Lipton M: Impact of structural adjustment on sustainable rural livelihoods: A review of the literature. 1997. Reference Source\n\nThomson M, Kentikelenis A, Stubbs T: Structural adjustment programmes adversely affect vulnerable populations: A systematic-narrative review of their effect on child and maternal health. Public Health Rev. 2017; 38(1): 13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nForster T, Kentikelenis AE, Stubbs TH, et al.: Globalization and health equity: The impact of structural adjustment programs on developing countries. Soc. Sci. Med. 2020; 267: 112496. PubMed Abstract | Publisher Full Text\n\nMuasya IW: The impact os structural adjustment programmes (SAPs) on education in Kenya.Reference Source\n\nKamau Gachunga K: The effect of structural adjustment programmes on the university education sector in Kenya.\n\nBarnett T, Blackwell M: Structural adjustment and the spread of HIV/AIDS. 2004.\n\nRichardson J: Structural adjustment and environmental linkages: A case study of Kenya. Overseas Development Institute; 1996.\n\nThiboutot M: The Combined Effects of HIV/AIDS and Structural Adjustment Programs on Ugandan Underdevelopment. HIM. 2004; 1990–2015. Reference Source\n\nBarnett T, Blackwell M: Structural adjustment and the spread of HIV/AIDS [Monograph]. Christian Aid. 2004. Reference Source\n\nLingam L: Structural Adjustment, Gender and Household Survival Strategies: Review of Evidences and Concerns.2005; 22.\n\nSylla NS: In Africa, structural adjustment did not trigger fast growth, but had a contractive impact. D+C. 2018. Reference Source\n\nAkuma JM: Social Protection for Orphaned and Vulnerable Children in Kenya: Initiatives, Opportunities and Challenges. European Journal of Social Sciences Education and Research. 2014; 2(1): 235. Publisher Full Text\n\nNyambedtha EO, Wandibba S, Aagarard-Hansen J: “Retirement Lost”-the new role of elderly as caretakers for Orphans in Western Kenya. J. Cross Cult. Gerontol. 2003; 18(1): 33–52. Publisher Full Text\n\nFleming A, Mason C, Paxton G: Discourses of technology, ageing and participation. Palgrave Commun. 2018; 4(1): 1–9. Publisher Full Text\n\nLeburu K, Grobler H, Bohman D: Older people’s competence to use mobile phones: An exploratory study in a South African context. Gerontechnology. 2018; 17(3): 174–180. Publisher Full Text\n\nKomen LJ: Engaging the disengaged: Examining the domestication of mobile telephony among older adults in Trans-Nzoia and Bungoma Counties in Western Kenya. J. Dev. Commun. Stud. 2020; 7(1–2): 23. Publisher Full Text\n\nGathongo T: Older adults and technology adoption: Investigating the use of online banking among the seniors in Nairobi County. 2019.\n\nMilusheva S, Bkorkegren D, Viotti L: Can we trust smartphone mobility estimates in low-income countries? 2021. Reference Source\n\nM-Pesa and PayPal are partnering to boost e-commerce in Kenya. Quartz Africa.2018.\n\nWhy does Kenya lead the world in mobile money? De Economist. 2015.\n\nSuri T, Jack W: The long-run poverty and gender impacts of mobile money. Science. 2016; 354(6317): 1288–1292. PubMed Abstract | Publisher Full Text\n\nKrendl AC, Perry BL: The Impact of Sheltering in Place During the COVID-19 Pandemic on Older Adults’ Social and Mental Well-Being. J. Gerontol. B Psychol. Sci. Soc. Sci. 2021; 76(2): e53–e58. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNoguchi T, Nojima I, Inoue-Hirakawa T, et al.: Role of non–face-to-face social contacts in moderating the association between living alone and mental health among community-dwelling older adults: A cross-sectional study. Public Health. 2021; 194: 25–28. PubMed Abstract | Publisher Full Text\n\nSchmidt LL, Johnson S, Genoe MR, et al.: Social Interaction and Physical Activity Among Rural Older Adults: A Scoping Review. J. Aging Phys. Act. 2021; 30(3): 495–509. PubMed Abstract | Publisher Full Text\n\nUNFCCC: Climate Change Is an Increasing Threat to Africa. UNFCCC; 2020. Reference Source\n\nSaulo M: Drop by drop, Kenyans struggle with climate change. Africa Renewal. 2011, April 15. Reference Source\n\nPietromarchi V: ‘We will all die’: In Kenya, prolonged drought takes heavy toll. 2021. Retrieved July 6, 2022. Reference Source\n\nFitchett J: Kenya is experiencing strange weather. What’s behind it. The Conversation. 2020. Reference Source\n\nCianconi P, Betrò S, Janiri L: The Impact of Climate Change on Mental Health: A Systematic Descriptive Review. Front. Psych. 2020; 11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nClayton S, Manning C, Krygsman K, et al.: Mental health and our changing climate: Impacts, Implications and guidance. 2017. Reference Source\n\nDodgen D, Donato D, Kelly N, et al.: The impacts of climate change on human health in the United States; A scientific Assessment. 2016. Reference Source\n\nMartin-Latry K, Goumy M-P, Latry P, et al.: Psychotropic drugs use and risk of heat-related hospitalisation. Eur. Psychiatry. 2007; 22(6): 335–338. PubMed Abstract | Publisher Full Text\n\nOstapchuk J, Harper S, Willox AC, et al.: Exploring Elders’ and Seniors’ Perceptions of How Climate Change is Impacting Health and Well-being in Rigolet, Nunatsiavut. Int. J. Indig. Health. 2015; 9(2): 6–24. Publisher Full Text\n\nTaylor S: Anxiety disorders, climate change, and the challenges ahead: Introduction to the special issue. J. Anxiety Disord. 2020; 76: 102313. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchwartz SEO, Benoit L, Clayton S, et al.: Climate change anxiety and mental health: Environmental activism as buffer. Curr. Psychol. 2022; 1–14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGifford E, Gifford R: The largely unacknowledged impact of climate change on mental health. Bull. At. Sci. 2016; 72: 292–297. Publisher Full Text\n\nDocherty S, Haskell-Ramsay CF, McInnes L, et al.: The Effects of COVID-19 Lockdown on Health and Psychosocial Functioning in Older Adults Aged 70 and Over. Gerontol. Geriatr. Med. 2021; 7: 233372142110399. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWu B: Social isolation and loneliness among older adults in the context of COVID-19: A global challenge. Glob. Health Res. Policy. 2020; 5: 27. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSolanki T: Atypical Covid-19 presentations in older people – the need for continued vigilance. British Geriatrics Society; 2020. Reference Source\n\nReliefWeb: Kenyan government must urgently release emergency funds promised for older people—Kenya|ReliefWeb. 2020, April 21. Reference Source\n\nJanssens W, Pradhan M, de Groot R , et al.: The short-term economic effects of COVID-19 on low-income households in rural Kenya: An analysis using weekly financial household data. World Dev. 2021; 138: 105280. Publisher Full Text\n\nKalaria RN, Maestre GE, Arizaga R, et al.: Alzheimer’s disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol. 2008 Sep; 7(9): 812–826. Epub 2008 Jul 28. Erratum in: Lancet Neurol. 2008 Oct;7(10):867. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBoga M, Davies A, Kamuya D, et al.: Strengthening the informed consent process in international health research through community engagement: The KEMRI-Wellcome Trust Research Programme Experience. PLoS Med. 2011; 8(9): e1001089. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "299237",
"date": "02 Aug 2024",
"name": "Maria Cattell",
"expertise": [
"Reviewer Expertise Maria G. Cattell is a social anthropologist who has done longterm research on aging and older people in Kenya and also a short project in South Africa. Based on two years of research in Samia and Bunyala Locations in Kenya's Busia County in the mid-1980s",
"her PhD dissertation concerns \"Old Age in Rural Kenya: Gender",
"the Life Course and Social Change\" (Bryn Mawr College",
"1989). She has made many return visits to Kenya to follow up on various aspects of her original research including family relations and other topics. She has a chapter about the modern life course in Jay Sokolovsky's The Cultural Context of Aging (Praeger",
"2009) and reported on the situation of \"Older Kenyans in the Twenty-First Century\" in Aging Across Cultures: Growing Old in the Non-Western World (ed. Helaine Selin",
"Springer",
"2021)."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article presents information on older Kenyans (defined as age 70+) and the impacts of various historical trends (urbanization, globalization, technological advancement, climate change) and specific historical events (the HIV/AIDS epidemic, Kenya's Structural Adjustment Program and the Covid-19 epidemic) which have increased poverty and affected family relations, which in turn have contributed to mental health issues experienced by older Kenyans. The authors advocate for the use of life course theory as useful in understanding these \"historicities\" and their impacts on older Kenyans.\nDefining older Kenyans. In my research on older Samia people in Busia County, based upon what Samia people told me, I decided that 50+ was a reasonable (but not perfect) choice for considering people to be old. Later, the WHO came to the same conclusion regarding sub-saharan Africa (Sagner, Kowal & Dowd, 2002)(Ref 1). More generally, the WHO uses age 60+ or 65+ as its definition. Why did you decide on age 70+?\nLife course theory. You advocate for the use of life course theory but your own use of it is falls short. First of all, for the benefit of your readers you need to explain the theory in detail, not with the one sentence you give to it: \"The basic concept of LCT includes cohorts, trajectories, transitions, turning points and life events within which the study of family life and social change can ensue.\" What do these terms (concepts) mean? And how does the theory tie them together?\nFigure 1 shows the impacts on older Kenyans of the historicities without relating them to the specifics of a life course framework. Indeed, though you say this is an \"inter-sectional framework,\" I don't see any representation of a life course framework. I also wonder if the idea of an \"inter-sectional framework\" clarifies or complicates. What exactly do you mean by intersectional? And in the HIV/AIDS box, what are \"general gaps\"? Gaps in what?\nKenyan families. Here and there you express the idea that Kenyan (and other African) families and traditional social networks today have eroded, fragmented, disintegrated. These are strong words. (Some earlier researchers even spoke of \"the disappearance of the African family\" but they were just plain wrong.) I would argue that families in Kenya are very much in evidence. They have changed, adapting to their world as it has changed, but families are still there. As probably all of you know from your own experiences, and as one of you expressed in an African Warrior Magazine article.\nIn this article, Dr. Ngaruiya (who was born in the US but relocated to Kenya at a young age, though she returned to the US as an adult) is quoted as saying: \"It is like being raised by a village‒one giant community....I distinctly remember growing up with my cousins. Here in America, families can be distant, but not in Kenya. Cousins call each other 'brother.' I’m still very close to them today.\" Perhaps experiences with your own families could suggest the benefit of developing a deeper understanding of the situation of Kenyan families today\nFor the most part, I have not bothered with less important matters, as my comments above need to be addressed first and will entail some rewriting. But here are some other things I noticed as I read your paper.\nAuthors. You need to identify yourselves by your affiliations or whatever is appropriate (and the \"4 others\" is actually \"5 others,\" though this phrase is unnecessary).\nAbstract. You say: \"...20% of older adults in Africa are affected by mental health.\" Do you mean they are affected by mental health problems? Might you say something along the lines of \"the mental health of 20% of older adults in Africa is affected by processes such as urbanization...\"?\nAcronyms. Some publications regularly use acronyms but I find that their use can be annoying if I have to look back to check the meaning time and again. You introduce two acronyms (CBRS, MCC) that do not appear again. LMIC appears only once, and SSA only twice. Why not just write them out wherever they occur? OA/OAs occurs many times, but as an OA myself, I find being referred to as an OA dehumanizing, even disrespectful. I would prefer to be called an \"older adult.\" Finally, for me, seeing LCT on a page seems less impactful than reading \"life course theory.\" (Of course WHO is a commonly used acronym in many different types of publications and is completely acceptable.)\nIntroduction. You say, \"An increase in life expectancy is linked to chronic conditions ingrained in ageing...\" Ingrained? For me, \"ingrained\" suggests something inescapable, perhaps genetic. But many older persons do not experience dementia, hearing loss, etc., and psychological and behavioral disorders occur among people of all ages. Perhaps you mean something like \"chronic conditions experienced by many (or some) older adults\"?\nRural-urban migration. You say \"rapid urbanization after Kenya's attainment of independence in the 1960s ushered in rural-urban migration...\" This is factually incorrect. Rural-urban migration in Kenya began in the first two decades of the 20th century, with British efforts to develop an African labor force through the introduction of money, taxes and cash crops among people who had been subsistence farmers, the commodification of labor and the colonialists' push to get men to go where the British needed labor (in towns, on tea plantations, building the railroad, etc.), and other factors (see, e.g., Kitching, Class and Economic Change in Kenya) (Ref 2)\nIn the paragraph beginning \"Furthermore, age related...\" -- \"urban cities\" is redundant.\nKenya's SAP. You describe the \"handshake\" retirements of government employees associated with this program and state that \"these individuals [those getting or at least eligible for handshakes] constituted \"the majority of current living OAs.\" That seems unlikely. The government may have many employees but how many of them were old enough to be asked to retire? And about 2/3 of Kenya's people live in rural areas and probably not many rural dwellers are government employees. It would seem likely that only a relatively small proportion of older Kenyans would have been eligible for the handshakes (regardless whether they ever got the money).\nWomen and the SAP. You say \"many women who were traditionally domesticated in rural areas while their husbands worked in cities....\" What do you mean by women being \"domesticated\"? Women in most rural areas are usually hard-working farmers, whatever else they may do with their time and labor, which usually includes cooking, fetching water, caring for children, etc. Saying they were \"domesticated\" demeans and devalues these women.\nIn the same paragraph you use \"many\" several times. Many is vague. Do the research projects (references 27 and 28) provide specific (numerical) data?\nIn the next paragraph you say \"the SAPs were associated with budget cuts and privatization...\" Privatization of what?\nCaregiving by grandparents. The HIV/AIDS epidemic did increase caregiving by older Kenyans. But caregiving (especially of grandchildren) is nothing new for elders, e.g., the \"grandmother house,\" called esibinje among Luyias and siwindhe by Luos. Makoni (2008)(Ref 3) found that African elders view caregiving as a responsibility, not a burden. Also, the longitudinal research of Dr. Gillian Ice and her Kenyan team (Ice et al., 2010)(Ref 4) , which compared the physical and mental health of Luo grandparent caregivers and non-caregivers, did not support the idea that caregiving in itself was a psychosocial or economic stressor.\nNote that the sentence beginning \"A survey within one of Kenya's largest tribes...\" is attributed to reference 43. These data actually come from the Nyambedha et al. article (#42).\nThe rural-urban divide. Contacts between rural and urban family members may be infrequent, but for many people, they are not non-existent. A fair amount of research has been done on Nairobi's older inhabitants by the Nairobi Urban Demographic Surveillance System, including one project (Mberu et al., 2013) (Ref 5) which indicated that most (80%) of age 60+ persons in two Nairobi informal settlements had contact with their rural kin in the past year. Also, people who return to their rural homes when they retire from urban employment are likely to have kept up their family ties over the years so they will not be viewed as strangers when they return.\nReferences. References need cleaning up. Some items are incomplete, some contain extraneous words such as Publishers Full Text and Reference Source. In the text, the numbers for references are not superscripts, which is a bit confusing. Small error: In the second sentence of the introduction, the reference number (2) occurs twice, following (2013) and again, after the last word of the sentence.\n\nIs the topic of the opinion article discussed accurately in the context of the current literature? Partly\n\nAre all factual statements correct and adequately supported by citations? No\n\nAre arguments sufficiently supported by evidence from the published literature? Partly\n\nAre the conclusions drawn balanced and justified on the basis of the presented arguments? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-549
|
https://f1000research.com/articles/12-548/v1
|
25 May 23
|
{
"type": "Study Protocol",
"title": "Comparative evaluation of Chlorhexidine and Triphala with Rajat Bhasma jelly as against Chlorhexidine mouth rinse in prevention of bacterial accumulation in fixed orthodontic assembly: A randomized interventional study",
"authors": [
"NISHU AGARWAL",
"Pallavi Daigavane",
"Ranjit Kamble",
"Pallavi Daigavane",
"Ranjit Kamble"
],
"abstract": "Background: By offering numerous mechanical retention sites, fixed orthodontic treatment increases the build-up of bacterial plaque, rendering teeth more susceptible to gingivitis and periodontitis. Chlorhexidine is a frequently utilised adjuvant to mechanical oral hygiene techniques and is regarded as the gold standard. As compared to chemicals and allopathy, nowadays patients are showing great inclination for the herbal products. Commercially available herbal mouhrinses are emerging in the market. Due to their lack of purity, these is a need for more herbal alternative mouthrinses like Triphala. As known, silver coated wire has antimicrobial and antiadherent properties, still not commercially available. Some reasons could be cost, toxicity levels, etc. Thereby, to evaluate the effects herbal mouthwashes in adjunct with herbal form of silver i.e. Rajat bhasma, present study has been taken up to check the antimicrobial and anti-adherent properties with various combinations Objectives: 1. To evaluate the efficacy of chlorhexidine mouthrinse and Rajat bhasma jelly as an antimicrobial agent 2. To evaluate the efficacy of Triphala mouthrinse and Rajat bhasma jelly as an antimicrobial agent 3. To compare the antimicrobial potency of chlorhexidine, triphala with rajat bhasma jelly combinations as against chlorhexidine on bacterial accumulation (streptococcus mutans and lactobacillus). Methods: Plaque will be collected from the left molar to right molar of the upper arch with a disinfected curette at 3 time periods: T 0 = just prior bonding, following full prophylaxis. T 1 = one month following bonding. T 3 = two months following bonding Streptococcus mutans and lactobacilli will be quantified by colony count procedure. Expected results: Patients receiving orthodontic treatment experience a greater reduction in plaque buildup attributable to the synergistic effects of rajat bhasma and different mouthrinses. Conclusion: It is expected that, Rajat bhasma and triphala being ayurvedic products cause no harm and show plaque reduction. Trial number: CTRI/2022/07/044130",
"keywords": [
"Rajat Bhasm",
"Triphala",
"Chlorhexidine",
"Streptoccocus mutans",
"plaque"
],
"content": "Introduction\n\nBy providing numerous mechanical retention sites like brackets and wires, fixed orthodontic treatment increases the accumulation of bacterial plaque. Additionally, physiological factors like thick saliva, poor oral hygiene, and difficulty performing oral hygiene procedures due to multiple attachments among orthodontic patients may make them more susceptible for plaque accumulation that causes gingivitis and periodontitis.\n\nThe retention of dental plaque is more likely with multibracket orthodontic assembly, making oral hygiene a difficult work for patients.1 Due to the inaccessibility of cleaning the minute areas of these appliances, patients having orthodontic brackets have enamel demineralization risk.2 Oral ecological changes such as plaque may build as a result of increased salivary lactobacilli and streptococcus mutans brought on by orthodontic treatment.3 One of the key colonisers in the multispecies dental biofilm is Streptococcus mutans and lactobacilli.4 During the use of fixed orthodontic appliances, it has been discovered that the number of germs might grow up to five times.4 This imply the need for prophylactic measures against colonization of streptococcus mutans and lactobacilli.4 Orthodontic attachments and bonding materials that plaque and encourage the establishment of “white spot lesions”, increased friction during retraction, decreased desired tooth movement and dental caries as well.5 Streptococcus mutans and Lactobacilli are the most frequent bacteria that cause plaque to form.6\n\nCaries-preventive operations, optimum dental hygiene maintenance, noncariogenic diet, and systematic fluoride supplementation are generally inadequate in preventing demineralization and initiation of new carious lesions in fixed orthodontic appliance therapy in subjects with increased caries susceptibility.3 Direct chemotherapeutic drug suppression of the cariogenic oral microbiome, as well as improved oral hygiene, have been employed as preventive interventions in these vulnerable populations. Using exogenous anti-caries compounds has been shown to be effective for preventing caries, reducing plaque buildup, and demineralization during orthodontic treatment.2\n\nTo prevent plaque accumulation and for daily interventions, mouth rinses are used since a long ago (in both herbal, chemical form). However, the reasoning and cautious justification for the use of chemical components have only recently been the focus of scientific study and clinical testing.7\n\nA cationic bisbiguanide with a very wide range of antibacterial action is chlorhexidine, which is frequently used both on its own and as addition to mechanical methods of oral hygiene.8 The main benefit of chlorhexidine is its substantivity, which allows it to bind to both soft and hard tissues in the oral cavity and act for an extended period of time following application of a formulation.8 In our department’s orthodontic clinic, chlorhexidine mouthwash is frequently administered to patients. However, extended use of chlorhexidine is prohibited due to a number of documented negative effects, including tooth discolouration, changed taste perception, increased calculus formation, oral mucosa desquamation.\n\nDentists work in a time when patients are more concerned with both their oral and overall health and medical well-being with a long-term effect rather than a short term. As compared to chemicals and allopathy, now a days patients are showing great inclination for the herbal products as they have no allergy, no side effects and safe to use with no chemical Ingredients.\n\nCommercially available herbal mouhrinses are emerging these days in the market. But these are not 100% pure. Because of their lack of purity, these is a need for more herbal alternative mouthrinses like Triphala. Herbal medicine offers a preventive and promotional approach to oral health. Scientific research has shown that natural remedies such as Triphala Amalaki, bibitaki, haritaki, Tulsi Patra (Ocimum sanctum), Jyestiamadh (Glycyrrhiza glabra), (Neem Azadirachta Indica), Clove oil (Caryophyllus aromaticus), Pudina (Menthaspicata), Ajwain (Trachyspermum ammi), and Sushruta Samhita’s 20th shloka states that triphala can be used as a mouthwash for dental problems.9\n\nSeldon studies have specifically targeted Streptococcus mutans and lactobacilli for reducing plaque accumulation. In traditional Ayurvedic medicine, “Triphala” is one of the most often employed formulations.\n\nComposed of the fruits of three trees, Indian gooseberry Amalaki (Embilica offi cinalis), Bibhitaki (Terminalia beleria), and Haritaki (Terminalia chebula),\n\nTriphala is a tonic that is prized for its capacity to regulate the digestive and elimination processes. It is made up of the fruits of three different trees: the Indian gooseberry Amalaki (Embilica officinalis), the Bibhitaki (Terminalia beleria), and the Haritaki (Terminalia chebula). Triphala may be used to treat periodontal disorders, according to research by Maurya et al. The effectiveness of triphala mouthwash in reducing the number of Streptococcus counts was examined by Jagtap and Karkera.10\n\nIn the theory of friction mechanics, tooth movement is accomplished by guiding or walking a tooth along a continuous arch wire while wearing a bracket. Friction created at the bracket-wire interface limits tooth movement. Silver-coated wire has been shown to have antibacterial and antiadhesive qualities.11 The frictional property of ss wires may be affected by this silver coating. Despite it being an effective antiplaque agent, it is not yet commercially available. Cost, toxicity levels, etc., are only a few of the possible explanations. Therefore, the current study has been undertaken to assess the antibacterial and anti-adherent qualities using various combinations in order to evaluate the effects of herbal mouthwashes in adjunct with herbal form of silver, i.e. Rajat bhasma.12\n\nIt was believed that mouthwash, in addition to its other benefits including ease of accessibility and affordability, could be a useful substitute for orthodontic patients. The goal of this study is to compare the anticariogenic efficacy of triphala mouthwash, developed at the Mahatma Gandhi Ayurveda College, Hospital and Research Centre, Datta Meghe Institute of Medical Sciences (DMIMS), with the already well-established chemotherapeutic chlorhexidine.\n\nThe goal of the study is to compare the antimicrobial effectiveness of herbal triphala mouthwash, traditional chlorhexidine mouthwash, and commercially available herbal mouthwash in conjunction with Rajat bhasma jelly in patients receiving fixed orthodontic treatment.\n\n\nObjectives\n\n\n\n1. To evaluate the efficacy of chlorhexidine mouthrinse and Rajat bhasma jelly as an antimicrobial agent\n\n2. To evaluate the efficacy of Triphala mouthrinse and Rajat bhasma jelly as an antimicrobial agent\n\n3. To compare the antimicrobial potency of chlorhexidine, triphala with rajat bhasma jelly combinations as against chlorhexidine on bacterial accumulation (streptococcus mutans and lactobacillus).\n\n\nMethods\n\nThis study will be conducted at the Department of Orthodontics and Dentofacial Orthopaedics, SPDC Wardha in collaboration with Department of Microbiology, JNMC, Wardha and Department of Rasashastra and Bhaishajya Kalpana, MGAC, Salod, Maharashtra.\n\nTrial registration number: CTRI/2022/07/044130.\n\nTotal 45 patients will be selected. Patients will be selected from OPD and consent will be taken for the participation in the study.\n\nThe total cases will be divided into 3 groups:\n\n1. Group I: Chlorhexidine mouthrinse with rajat bhasma jelly\n\n2. Group II: Triphala mouthrinse with rajat bhasma jelly\n\n3. Group III: Distilled water with rajat bhasma jelly\n\nThe procedure will be explained at length to the patients. Before the treatment, and during every follow up visits, oral hygiene instructions to be explained to the patients. Verbal directions and physical demonstration will be provided on how to perform the procedure to the patients.\n\nPlaque will be collected from the left molar to right molar of the upper arch with a sterile curette at 3 intervals:\n\nT 0 = just prior bonding, following full prophylaxis.\n\nT 1 = one month following bonding.\n\nT 3 = two months following bonding Streptococcus mutans and lactobacilli will be quantified by colony count procedure.\n\nA. Initial drug preparation of Triphala mouth rinse\n\n• Raw materials of plant origin will be obtained from Dattatraya Ayurveda Rasashala Sawangi, Wardha.\n\n• These raw materials will be then identified and authenticated by a taxonomist.\n\n• Pharmaceutical preparation of Triphala mouth rinse will be conducted at Dattatraya Ayurved Rasashala, Mahatma Gandhi Ayurveda College, Hospital and Research centre, Salod (H) Wardha, Maharashtra.\n\n• The preparation will be tested for organoleptic characters, physicochemical analysis, and microbial contamination in analytical lab as per API standards.\n\n• Ingredients of Triphala mouth rinse are depicted as follows:\n\n• “Haritaki” (“Terminalia Chebula Retz”): Fruit pulp-1 part (astringent and laxative)\n\n• “Bibhitaki” (“Terminalia Belerica Roxb”): Fruit pulp1 part (laxative)\n\n• “Amalaki” (“Emblica officinalis Gaertn”): Fruit pulp1 part (anti-inflammatory)\n\n• Water for decoction: 16 parts\n\n• Alcohol (Ethanol): 5%(disinfectant)\n\n• Menthol (Peppermint): 0.042%(flavoring agent)\n\n• Thymol (Thymus vulgaris): 0.064%(fungicide)\n\n\n\n• The procedure of Kwatha kalpana will be followed for the preparation of Triphala mouth rinse.\n\n• All the above-mentioned raw ingredients will be coarsely powdered, weighed individually, and then amalgamated together meticulously.\n\n• This amalgamation will be diluted 16 times by addition of distilled water, and boiled in a steel vessel at 90-100° C temperature till the solution gets reduced to 1/4th of its original volume.\n\n• Throughout the procedure, the solution will be continuously stirred.\n\n• The decoction will be then sieved through a piece of cloth.\n\n• 5% alcohol, 0.042% Menthol and 0.064% Thymol will be added and mixed with a stirrer to get a homogenous liquid.\n\n• Finally, it will be filled in 200 ml amber-coloured plastic bottles and packed with air tight lid.\n\nB. Preparation of Rajat bhasma jelly\n\n• 125 mg of Rajat bhasma powder to be mixed with 1 table spoon of ghee.\n\n• 1 table spoon is approximately 7.6 ml\n\n• Jelly consistency to be formed and stored in plastic containers in refrigerators.\n\n\nMethods\n\n\n\n• Plaque will be gathered from the buccal surface of maxillary teeth (molar to molar) between the bracket and the gingival surface with the use of disinfected curette, before bonding after complete prophylaxis, to govern the patient’s cart of Streptococcus Mutans and Lactobacilli, which will be referred to as T0. A chosen region of the anterior dentition will be isolated with cotton rolls for swab collection.\n\n• The appliance bonding procedures will be then carried out.\n\n• Patients will be given instructions about how to use the mouth rinse and the application of Rajat bhasma jelly and a checklist, in the form of an instruction chart, for the purpose of making them adhere to the guidelines of the study and to maintain a level of stringency while following oral hygiene protocol.\n\n• Following the collection of samples for T0, patients will be instructed to maintain oral hygiene by using mouthwash and rajat bhasma jelly, and they will be divided into three groups at random (simple random sampling in the ratio of 1:1:1).\n\n• The three groups will be based on the different mouth rinse with rajat bhasma jelly being used by the patient.\n\n• Group I: Chlorhexidine mouthrinse with rajat bhasma jelly\n\n• Group II: Triphala mouthrinse with rajat bhasma jelly\n\n• Group III: Distilled water with rajat bhasma jelly\n\n• 2nd reading termed T1 will be taken 1month after bonding procedure.\n\n• These results will be compared to T0 to see if there is a difference in streptococcus mutans and lactobacilli colonisation installation of permanent appliances both before and after.\n\n• Next reading will be taken 2 months after bonding procedure. Samples will be collected again, and the readings will be termed as T2.\n\nT0, T1 and T2 readings will be compared to one another using the proper statistical techniques, and the variation in S. Mutans and lactobacilli colonisation at each interval will be noted in order to reach a conclusion evaluating the synergistic effect of each of the aforementioned mouthwashes with rajat bhasma jelly.\n\n\n\n• The amount of S. Mutans will be quantified by colony count procedures in Microbiology lab in JNMC.\n\n• Plaque samples will be collected in a dry area using a sterile curette, then placed in a test tube with 2 ml of transport fluid (brainheart infusion broth), and transferred within 2 hours to the microbiology lab for processing.\n\n• After that, S. Mutans and Lactobacilli will be identified by plating samples on blood agar.\n\n• Streaking will be carried out using sterile, 4mm-diameter nichrome loops.\n\nRandomized, Parallel, Multiple arm, allocated in the ratio of 1:1:1 in superiority framework\n\n\n\n1. Patients with aligned arches irrespective of the type of molar relation requiring fixed orthodontic treatment in the departmental OPD.\n\n2. Using edgewise brackets that have already been modified for patients.\n\n3. Patients in which lig-o-rings will be used to secure the wire in the brackets.\n\n4. Patient who donot show any history of hypersensitivity with the materials that are used for the study like metal allergy based on the clinical history.\n\n5. Age group of 15-25 years will be included in the study.\n\n\n\n1. Patients with gingivitis and periodontitis.\n\n2. Patients who have undergone orthodontic treatment more than 1 month.\n\n3. Patients undergoing orthodontic treatment with lingual, self-ligating brackets or myofunctional appliances.\n\n4. Patients with cleft lip and palate and other dentofacial anomalies.\n\n5. Syndrome patients that are unable to practise good dental hygiene.\n\n6. Patients with dental crowding as crowding will require more time to reach to 16×22” wire and also crowded arch will have more plaque than aligned arches.\n\n7. Patients with very short clinical crown or patient started when the teeth are in erupting Phase.\n\nFor terminating or changing the prescribed therapies for a specific research participant, two requirements must be met: the presence of dangers or participant request.\n\nOutcomes:\n\nPrimary: reduction in plaque accumulation.\n\nThis is an in-vivo, randomized, parallel, multiple arm type of study.\n\nWe are using Rajat Bhasma jelly for our study and so no such type of study has been done before using the same.\n\nSo by using the convenient non-random sampling method, we will be collecting the sample from our Departmental OPD during the period of 1.5 years.\n\nTotal number of groups to be studied = 3.\n\nTherefore, total sample size = 3×15 = 45.\n\nSo, three samples are to be collected from each patient = 3×15 = 45.\n\nThe procedure will be explained to and educated upon by the patients. All 45 patients will be asked for written consent that has been fully informed.\n\nAccording to the study’s goals, participants from the departmental OPD who were recommended for treatment with a fixed stainless steel preadjusted edgewise appliance would be divided into 3 groups with 15 participants in each group at a ratio of 1:1:1.\n\n• Group I: Chlorhexidine mouthrinse with rajat bhasma jelly\n\n• Group II: Triphala mouthrinse with rajat bhasma jelly\n\n• Group III: Chlorhexidine mouthrinse\n\nAll patients will be first sent for oral prophylaxis after which the 1st reading will be collected.\n\nRecruitment: Techniques for increasing participant enrollment to the desired sample size.\n\nVia publication.\n\nPlaque accumulation causes friction in orthodontic brackets which interfere with the treatment, so by the use of these ayurvedic products, which will cause no harm to the overall health of the patient (unlike other products available in the market) plaque accumulation can be reduced. Also, these products are more economic.\n\nNot started.\n\nResearch ethics approval: Institutional ethics committee Approved.\n\nConsent or assent: Informed and written both type of consent will be taken from the patients.\n\nConfidentiality: To guarantee confidentiality before, during, and after the trial, personal information regarding enrolled and prospective participants will be gathered, exchanged, and maintained.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZenodo: Comparative evaluation of Chlorhexidine and Triphala with Rajat Bhasma jelly as against Chlorhexidine mouth rinse in prevention of bacterial accumulation in fixed orthodontic assembly- A randomized interventional study, https://doi.org/10.5281/zenodo.7818109. 13\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nJurišić S, Verzak Ž, Jurišić G, et al.: Assessment of efficacy of two chlorhexidine mouthrinses on oral hygiene and gingival health in adolescents wearing two types of orthodontic brackets. Int. J. Dent. Hyg. 2018 May; 16(2): e52–e57. PubMed Abstract | Publisher Full Text\n\nHo CSF, Ming Y, Foong KWC, et al.: Streptococcus mutans forms xylitolresistant biofilm on excess adhesive flash in novel exvivo orthodontic bracket model. Am. J. Orthod. Dentofac. Orthop. 2017 Apr; 151(4): 669–677. PubMed Abstract | Publisher Full Text\n\nFard BK, Ghasemi M, Rastgariyan H, et al.: Effectiveness of Mouth Washes on Streptococci in Plaque around Orthodontic Appliances. ISRN Dent. 2011; 2011: 1–4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaffari F, Ardakani MD, Zandi H, et al.: The Effects of Chlorhexidine and Persica Mouthwashes on Colonization of Streptococcus mutans on Fixed Orthodontics O-rings.\n\nArtun J, Brobakken BO: Prevalence of carious white spots after orthodontic treatment with multibonded appliances. Eur. J. Orthod. 1986 Nov 1; 8(4): 229–234. PubMed Abstract | Publisher Full Text\n\nNimbulkar G, Garacha V, Shetty V, et al.: Microbiological and Clinical Evaluation of Neem Gel and Chlorhexidine Gel on Dental Plaque and Gingivitis in 20-30 Years Old Adults: A Randomized Parallel-Armed, Double-Blinded Controlled Trial. J. Pharm. Bioallied Sci. August 2020; 12(1): 345–351. Publisher Full Text\n\nParwani SR, Parwani RN, Chitnis PJ, et al.: Comparative evaluation of anti-plaque efficacy of herbal and 0.2% chlorhexidine gluconate mouthwash in a 4-day plaque re-growth study. J. Indian Soc. Periodontol. 2013 Jan; 17(1): 72–77. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNiranjane P, Gilani R, Rathi B, et al.: Triphala mouthwash in chronic generalized gingivitis in patients undergoing orthodontic treatment.2016; 4: 6.\n\nBhor K, Shetty V, Garcha V, et al.: Effect of 0.4% Triphala and 0.12% Chlorhexidine Mouthwash on Dental Plaque, Gingival Inflammation, and Microbial Growth in 14-15-Year-Old Schoolchildren: A Randomized Controlled Clinical Trial. J. Indian Soc. Periodontol. 2021; 25(6): 518–524. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNaiktari RS, Gaonkar P, Gurav AN, et al.: A randomized clinical trial to evaluate and compare the efficacy of triphala mouthwash with 0.2% chlorhexidine in hospitalized patients with periodontal diseases. J. Periodontal. Implant Sci. 2014 Jun 1; 44(3): 134–140. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGhasemi T, Arash V, Rabiee SM, et al.: Antimicrobial effect, frictional resistance, and surface roughness of stainless steel orthodontic brackets coated with nanofilms of silver and titanium oxide: a preliminary study. Microsc. Res. Tech. 2017 Jun; 80(6): 599–607. PubMed Abstract | Publisher Full Text\n\nMhaske AR, Shetty PC, Bhat NS, et al.: Antiadherent and antibacterial properties of stainless steel and NiTi orthodontic wires coated with silver against Lactobacillus acidophilus—an in vitro study. Prog. Orthod. 2015 Dec; 16(1): 1–6.\n\nDr. Agarwal N , Dr. Daigavane P , Dr. Kamble R : Comparative evaluation of Chlorhexidine and Triphala with Rajat Bhasma jelly as against Chlorhexidine mouth rinse in prevention of bacterial accumulation in fixed orthodontic assembly - A randomized interventional study. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "197710",
"date": "14 Nov 2023",
"name": "Sangeeta Nayak",
"expertise": [
"Reviewer Expertise -"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nStudy aim and objectives need to be specified.\n\nMethodology needs clarification - whether CHX and Tripala was used separately or or as a single product with rajat bhasma. patient usage instructions are clearly mentioned.\n\nDiscussion part is missing\n\nOverall manuscript needs improvement ,\n\nplease specify - study status- not started\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? No\n\nAre the datasets clearly presented in a useable and accessible format? Partly",
"responses": []
},
{
"id": "217740",
"date": "24 Nov 2023",
"name": "Péter Vályi",
"expertise": [
"Reviewer Expertise Non-surgical periodontal treatment",
"adjuvant chemotherapy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study protocol meet with requirement of publishing, but some correction is needed:\n„By providing numerous mechanical retention sites like brackets and wires, fixed orthodontic treatment increases the accumulation of bacterial plaque. Additionally, physiological factors like thick saliva, poor oral hygiene, and difficulty performing oral hygiene procedures due to multiple attachments among orthodontic patients may make them more susceptible for plaque accumulation that causes gingivitis and periodontitis”. - This section could be removed from the manuscript\n„One of the key colonisers in the multispecies dental biofilm is Streptococcus mutans and lactobacilli „– one of the key first colonizers\n„Caries-preventive operations, optimum dental hygiene maintenance, noncariogenic diet, and systematic fluoride supplementation are generally inadequate in preventing demineralization and initiation of new carious lesions in fixed orthodontic appliance therapy in subjects with increased caries susceptibility” – original references – original references Oegaard et al 1994, 1997\n„The main benefit of chlorhexidine…” – CHX is a gold standard\n„However, extended use of chlorhexidine is prohibited due to a number of documented negative effects, including tooth discolouration, changed taste perception, increased calculus formation, oral mucosa desquamation” – has not supported by references\n„Composed of the fruits of three trees, Indian gooseberry Amalaki (Embilica offi cinalis), Bibhitaki (Terminalia beleria), and Haritaki (Terminalia chebula), - It could be removed, because „– It has mentioned two times in the text\nMy suggestion is to establish a control group without adjuvant treatment.\nThe Helsinki declaration is missing.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-548
|
https://f1000research.com/articles/12-368/v1
|
05 Apr 23
|
{
"type": "Systematic Review",
"title": "A comprehensive systematic scoping review for physiotherapy interventions for people living with long COVID",
"authors": [
"Md. Feroz Kabir",
"Khin Nyein Yin",
"Mohammad Saffree Jeffree",
"Fatimah Ahmedy",
"Muhamad Faizal Zainudin",
"K M Amran Hossain",
"Sharmila Jahan",
"Md. Waliul Islam",
"Md. Abu Khayer Hasnat",
"Abdullah Ibn Abul Fazal",
"Md. Feroz Kabir",
"Mohammad Saffree Jeffree",
"Fatimah Ahmedy",
"Muhamad Faizal Zainudin",
"K M Amran Hossain",
"Sharmila Jahan",
"Md. Waliul Islam",
"Md. Abu Khayer Hasnat",
"Abdullah Ibn Abul Fazal"
],
"abstract": "Background: A diverse spectrum of long COVID symptoms (LCS) have the scope of physical rehabilitation. Due to limited resources, very little is known about the physiotherapy and rehabilitation interventions for LCS and their clinical application. This study aims to explore the role of physiotherapy and rehabilitation interventions in the management of musculoskeletal, neurological, cognitive, cardiorespiratory, mental health, and functional impairments of LCS. Methods: The study was a systematic scoping review of the literature published between April 2020 and July 2022. Results: 87 articles were extracted followed by a standard process of The Preferred Reporting Items for Systematic reviews and meta-analysis (PRISMA) extension for Scoping reviews (PRISMA-ScR). The included studies had a 3223 LCS population. All types of primary and secondary articles were retrieved except for qualitative studies. The evidence was evaluated by an appraisal scoring tool followed by the guidelines of the “Enhancing the Quality and Transparency of health Research (EQUATOR) network”. The included papers had a mean appraisal score of 0.7807 on a 0 to 1 scale (SD 0.08), the minimum score was for study protocols (0.5870), and the maximum score was for Cohort studies (.8977). Sixty seven (67) evidence-based interventions were documented from 17 clinical categories. Conclusion: LCS can be treated by physiotherapy, exercise, and physical rehabilitation for musculoskeletal, neurological, cognitive, cardio-respiratory, mental health, and functional impairments at home or in clinical setups such as primary care settings by in-person care or telerehabilitation.",
"keywords": [
"Long COVID",
"Physiotherapy",
"Rehabilitation",
"Scoping review"
],
"content": "Introduction\n\nWHO working group defines Long COVID (LC) as symptoms experienced for more than 12 weeks after the provable or confirmed diagnosis of COVID-19 that can’t be explained with any other diagnosis. With the progression of time, the global prevalence of long COVID symptoms (LCS) is increasing from 10 to 36 percent.1 Between 16.2% and 25.2% of Bangladeshi people are experiencing LCS.2,3 The respondents reported a broad spectrum of LCS, those were reported as fatigue, musculoskeletal pain, headache, loss of concentration, anxiety, depression, and post-exertion dyspnea. The presentation of LCS was noted as a relapsing remittent nature, which might not be described as related to a single biological system or organ involvement in the human body. With each relapsing episode, LCS had new symptoms, and symptoms were reported to be lasting more than a year.4 The management of LCS is multidisciplinary, as it has impacts on multiple organs in humans.5 WHO living guideline reports, rehabilitation is the key to managing the persistent illness that interferes with body function, daily activities, and overall quality of life. This guideline also states rehabilitation is an integral part of universal health and well-being and the global scope of rehabilitation stands for 2.4 billion people; 50% of the people living in lower-middle-income countries are out of reach of the scope. In the household LCS survey, Bangladeshi people had significant impairments in the musculoskeletal, neurological, and cognitive domains,4 and there is an emerging scope of physiotherapy and rehabilitation. Moreover, managing this significant scope will be another challenge because the COVID-19 pandemic changed the paradigm of rehabilitation service by adding a set of new impairments within the spectrum of rehabilitation.6\n\nIn a lower middle-income country like Bangladesh, it is important to study symptom responses and impairments to determine the scope of rehabilitation and generate clinical trials and shreds of evidence. From recent studies in Bangladesh,2,3 we understand the symptom responses, disease spectrum, and scope of rehabilitation but there are inconclusive answers on the rehabilitation interventions for LCS. From the fact sheets of WHO, we know rehabilitation interventions play an important for the clinical management of LCS. To elicit the outcome of rehabilitation, clinical trials are necessary. And to design the trial interventions and achieve the greater clinical benefit, a review of the literature and consensus is important. There is a research gap in studies focusing on physiotherapy and rehabilitation interventions for LCS, and this comprehensive systematic scoping can address the research gap.\n\nThis study aims to determine the physiotherapy and rehabilitation interventions in the management of (1) musculoskeletal symptoms, (2) neurological and cognitive symptoms, (3) cardiorespiratory symptoms, (4) mental health issues, and (5) Functional limitations for Long COVID.\n\n\nMethods\n\nWe conducted a systematic scoping review of the literature published between April 2020 and July 2022. To maintain the rigor of the paper we followed Preferred Reporting Items for Systematic reviews and meta-analysis (PRISMA) extension for Scoping reviews (PRISMA-ScR) (Extended data 1100).\n\nTo generate the review question, we have used the “PICO” format (Table 1). The short review question was “What is the physiotherapy and rehabilitation management for Long COVID?”. The detailed question was “What is known from literature about physiotherapy, exercise, or rehabilitation for the management of musculoskeletal symptoms, neurological and cognitive symptoms, cardiorespiratory symptoms, mental health issues, and functional limitations for Long COVID?\n\n\n\n• Articles fall within the LCS population and Physiotherapy and Rehabilitation criteria.\n\n• All types of primary and secondary literature (cohort, RCT, case-control, case report, case series), reviews and editorials, viewpoints, guidelines, letters to editors, and commentaries.\n\n• Articles published or accepted for publication between April 2020 and July 2022.\n\n• Grey literature that was published between April 2020 and July 2022.\n\n\n\n• Qualitative study design because it falls into different steps of evaluation, data curation, and extraction.\n\n• Literature in another language except for English\n\n• Unavailable full texts\n\n• Journals or publishers included in Beall’s List – of Potential Predatory Journals and Publishers\n\nWe have adopted a search strategy following the Boolean method and conducted the study in four phases. We have searched in Cochrane Library, PsycINFO, PubMed, Embase, Scopus, PEDro, Hinari Summon 2.0, CINHAL, and the Web of Sciences. Searching keywords are stated in Table 2. The result was reviewed and categorized using Endnote 20 and Microsoft Excel 2016. We removed the duplicate publications and downloaded all the papers. Two authors conducted a comprehensive study of the paper and matched it with the eligibility criteria. Another two authors followed the reference list of the primarily selected studies and included other relevant studies. In phase II, after finalizing the papers, two authors categorized the papers according to major keywords and checked for the comprehensiveness of the scope of physiotherapy & Rehabilitation. In phase III, we looked at google scholar for articles’ citing and current publications, maximizing our efforts to collect all relevant studies. In phase IV, 87 papers were finalized and distributed to four authors. The authors checked the quality of evidence with an “author-generated appraisal system” and documented the appraisal score. Also, they made a synopsis of every article and filled up the quantitative questionnaire form for review. Finally, we analyzed the information from the quantitative questionnaire form and the appraisal scores in the Statistical Package of Social Sciences (SPSS) V.20 for data analysis and formulating results.\n\nWe prepared a scoring system to determine the quality of the evidence. We have followed the appropriate guidelines of the “Enhancing the Quality and Transparency of health Research (EQUATOR) network” as indicators of the scoring system. For systematic reviews, we have made a 27-score checklist (Extended data 2100) followed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For randomized control trials, we made a 25-score checklist (Extended data 3100) followed by the Consolidated Standards of Reporting Trials (CONSORT) guideline. The observational studies were reported with a 22-score checklist (Extended data 4100) followed by The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement, case reports by a 13-score checklist (Extended data 5100) Consensus-based Clinical Case Reporting (CARE) Guideline, Clinical practice guidelines by 23-score checklist (Extended data 6100) The Appraisal of Guidelines for Research and Evaluation (AGREE) guideline, and the study protocols by 33-score checklist (Extended data 7100) Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guideline (Extended data 7100). The scoring was prepared and converted to a uniform range between 0 and 1 to analyze and visualize the data. Viewpoints, Editorials, Communication, and Letter to the editor were not evaluated as there is no guideline to evaluate this evidence.\n\nThe scoring checklist has been prepared from the guidelines of EQUATOR NETWORK, and the copyright states, “No material may be modified, edited or taken out of context such that its use creates a false or misleading statement or impression as to the positions, statements or actions of the EQUATOR Network.” We didn’t make any modifications to the original guidelines, we made a score out of the guideline checklist.\n\nData were extracted by a quantitative questionnaire consisting of information on the first author, date of publication, type of study, keywords, the population of the study, score in applicable checklist designed according to EQUATOR guidelines, category of papers according to the scope of physiotherapy and rehabilitation, and key interventions explained. Four authors extracted the data in Microsoft Excel for analyzing the scores. From the raw scores, the scores were further converted between 0 and 1 and calculated the mean, median, and 95% Confidence interval (CI). The presentation of all studies with their relative strength with 95% CI was presented in Figure 5. Figure 6 represents the strength of the papers by mean and median of the converted score. In the discussion, the interventions were presented in chronological order of scope of practice according to study objectives.\n\n\nResults\n\nThe study followed the guideline of PRISMA extension for scoping reviews (PRISMA-ScR).6 From the Boolean searching strategy (Table 2) we found 142 publications. After that, we removed the duplicates (14), and then 128 publications were screened for the relevance of the title and abstract and categorized according to the main keywords. 96 publications were checked for the accessibility of full text, among those 24 articles were not within the objectives of the paper, and 8 publications couldn’t be accessed, hence 32 articles were excluded. Then, we had gone through the reference list of the included papers and found 23 relevant additional papers, and finally, 87 papers7–93 were selected for this review study. Figure 1 shows the process of literature searching, data extraction, and finalization of review papers according to the PRISMA extension for scoping reviews (PRISMA-ScR).\n\nEighty seven papers were included in the study. Reviews and case study or series was the majority at 23% and 21.8% respectively (Table 3). About 6.9% papers were practice guidelines, 5.7% were Randomized control trials (RCT), 2.3% were quasi-experimental studies, 4.6% were cohort studies, 2.3% were Case-control study designs, 11.5% were cross-sectional studies, 2.3% Delphi consensus study, 3.4% study protocols and 16.1% were viewpoints, editorials, communication, or letter to editors.\n\nFigure 2 shows, the publications were published between 2020 and 2022. Most of the publications retrieved were published in 2021. From the studies of 2021, case studies and reviews were retrieved most. The 2020 studies were editorials and guidelines. In the studies of 2022, every area of primary and secondary sources of evidence was available.\n\n*Viewpoints, editorials, communication, or letter to editors; **Systematic reviews, Narrative reviews, Scoping reviews, Reviews.\n\nThe papers were from different categories according to their main keywords, titles and abstracts, and subject context. Figure 3 shows the categories of included papers according to subspecialty. Forty two papers (48.3%) were primary literature, and 45 papers were secondary literature (48.3%). Twenty three percent (23%) of the literature was about pulmonary rehabilitation, 18.4% on overall rehabilitation, 11.5% on exercise therapy, 9.2% on physiotherapy alone, 4.6% on telerehabilitation, 4.6% on neuro-rehabilitation, 6.9% on functional rehabilitation, 4.6% on long COVID symptom responses, and 6.9% on post-acute rehabilitation. Other papers were on early mobilization, pain rehabilitation, cardiovascular rehabilitation, geriatric rehabilitation, pediatric rehabilitation, community-based rehabilitation, and psychological rehabilitation.\n\nThe study included a reviewed paper with a total of 3223 COVID-19 cases. The minimum study had 1 sample and the maximum was 782 samples. The median sample number was 26, and the interquartile range was 99. The studies in 2020 had 309 samples, and studies in 2021 had 2344 samples, and the studies in 2022 had 570 samples. Figure 4 shows, Cohort had the highest median of population 260, followed by case-control 101, Randomized control trial 99, cross-sectional 68, and quasi-experimental 42 samples.\n\nError bar, 95% Confidence interval (95% CI).\n\nFigure 5 and 6 shows the strength of included evidence. The evidence scores were calculated according to the reporting guideline checklist of the EQUATOR network. For the study protocols, SPIRIT converted score (0-1) was between .363 and .742, with a mean of .601 ± .206 (95% CI .08, 1). The Delphi-based consensus CREDES converted score was between .776 and .778, mean of .777 ± .001 (95% CI .77765, .7779). For case studies and case, series CARE converted score ranged from .57 to .92, mean of .79 ± .094 (95% CI .74, .83). For the Cross-sectional study STROBE checklist converted score was a minimum of .52 and a maximum of 1, a mean was .75 ± .156 (95% CI .64, .86). Case-control study converted score of STROBE ranges from .72 to .90, mean .81 ± .206 (95% CI .03, 1). The cohort study converted score mean was .88 ± .13 (95% CI .06, 1), with a minimum of.72 and a maximum of 1. The Quasi-experimental study was evaluated by TREND and the converted score mean was .81 ± .206 (95% CI .009, 1). Randomized control trial converted CONSORT score ranges between .70 and .98, mean .86 ± .12 (95% CI .6, 1). Reviews were evaluated by PRISMA and the converted score mean was .73 ± .23 (95% CI .6, .8), the score varied from .2 to 1. However, the practice guidelines were evaluated by the converted score of AGREE checklist, the mean was .63 ± .23 (95% CI.38, .88) and the minimum to the maximum range was between .3 and .9. Figure 5 shows the median of the converted score (0-1) of the studies with 95% error bar. The studies marked as non-evaluative scored 0 for the studies with no reporting checklist. Figure 6, the radar plot indicates almost all the studies had 60% to 80% adherence to the EQUATOR network guideline checklist.\n\nSPIRIT, Standard Protocol Items; Recommendations for Interventional Trials; CREDES, Conducting and Reporting Delphi Studies; CARE, Case Reports; STROBE CS, Strengthening the Reporting of Observational Studies in Epidemiology for Cross-sectional study; STROBE CC, Strengthening the Reporting of Observational Studies in Epidemiology for Case-Control study; STROBE Co, Strengthening the Reporting of Observational Studies in Epidemiology for Cohort study; TREND, Transparent Reporting of Evaluations with Nonrandomized Designs; CONSORT, Consolidated Standards of Reporting Trials; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; AGREE, Appraisal of Guidelines for Research and Evaluation; Non-evaluative, scored as 0 for the studies with no reporting checklist from the EQUATOR network as Viewpoint, Editorials, Communication, and Letter to the editor; Scores ranged as continuous variables, scoring sheets supplied to Extended dataset. Scores are calculated by the converted unit in the 0-1 range, and then displayed with the median of the converted scores with an Error bar representing a 95% Confidence interval (95% CI).\n\nThe converted Score range between 0 to 1, 0 indicates the absence of the standard of the criteria in the EQUATOR network and 1 indicates absolute strength as complete fulfillment of standard criteria.\n\n\nDiscussion\n\nThe discussion section is narrated into 5 categories where we present perspectives around (1) the management of musculoskeletal symptoms, (2) the management of neurological and cognitive symptoms, (3) the management of cardiorespiratory symptoms, (4) the management of mental health issues, and (5) Functional rehabilitation. Detailed interventions are provided in the extended data 8.\n\nManagement of Musculoskeletal impairments is focused on pain, fatigue, muscle loss, muscle weakness, and fatigue. Self-directed exercise and lifestyle advice prescribed through telemedicine or in-person consultation was recommended for managing chronic pain in LCS.22 To battle chronic pain along with physical limitations and low exercise tolerance, strengthening exercises, multi-component training, and guided walking practice were recommended.28,50 Pain associated with myalgia and arthralgia was advised to be treated by neuromuscular exercises, however, functional electrical stimulation (FES) can be promising to restore function and muscle performance.36 For musculoskeletal pain, studies suggest42,46 aerobic exercise and respiratory re-education, and pacing exercises as an initial bout, progressing to strengthening, pelvic bridging, and core stability exercises. These interventions are also effective in managing generalized pain associated with lower back pain and sudden weight gain.42,46 Fatigue, muscle pain, and muscle weakness were the commonly reported symptoms, and a wide range of manual therapy, manipulative therapy, exercise therapy, and electrotherapy was suggested.24,25,41,50,58,62 Manual and manipulative therapy approaches included soft tissue techniques, relaxation techniques, release techniques, and trigger point therapy. Exercise therapy included aerobic training, range of motion exercise, and dynamic muscle training. Respiratory exercises were suggested as pacing, deep breathing exercise, thoracic expansion exercise, and aerobic exercise. Swimming and hydrotherapy were also suggested for LCS cases with myalgia and fatigue. Neuromuscular electrical stimulation (NEMS) was found to be effective in managing fatigue-related weakness, fatigue associated with neuromuscular weakness. Fall is a consequence of neuromuscular weakness and fall prevention strategies included passive range of motion exercises progressing to active range of motion exercises and strengthening exercises.36 To prevent muscle loss rated to long-term physical inactivity and frailty27 early mobilization and positioning in ICU were found to be effective. To manage sarcopenia,48 aerobic exercise, resistance training, a multidisciplinary approach of physiotherapy, nutrition, and cognitive behavioral therapy were recommended.\n\nMajor neurological symptoms and consequences were anosmia, ageusia, headache, cerebrovascular accidents, Guillain-Barré syndrome, seizures, and encephalopathy,14,15,21,23 and recommended exercises were neuro-physiotherapy interventions, motor training exercises, balance, and coordination practice, walking training, music therapy and robotic rehabilitation through the in-person or telerehabilitation approach. For these conditions, cognitive behavioral therapy was also recommended. Headache was another prominent symptom,28,35 the study recommended relaxation through breathing exercises, diaphragmatic breathing, and exercise therapy as aerobic exercise, and strengthening or vigorous physical exercise was effective. However, mindfulness training and resistance training improves memory loss.35,64\n\nA variety of interventions were recommended for cardio-respiratory impairments. To manage primary dyspnea16,18,20,24,29,30,63 breathing exercises such as pursed lip breathing, yoga, and pranayama (ancient Indian technique), and a low-intensity pulmonary rehabilitation program were recommended. Managing dyspnea as LCS needs to cover a comprehensive approach35,39,40,41,42,47,57,60,70 on aerobic training, strengthening exercises, diaphragmatic breathing techniques, and mindfulness training. Moreover, stretching exercises, warm-up, breathing exercises, resistance training, respiratory rehabilitation, respiratory muscle training exercises, coughing exercises, slow, deep, and sustained inhalations, patient Education, functional activity training, and behavioral changes were found to be significant. In case of chest pain associated with fatigue or breathlessness23,24,26,31,38,46 intervention starts with primary healthcare management with medical screening, meditation, and gradual pacing of stretching exercises, strengthening exercises, stretching exercises, resistant training, coping and ADL strategies (including management of energy and drive functions), ES, FES cycling was recommended. If there are productive cough with dyspnea25,31,38,53 recommended treatments were bronchial hygiene techniques such as assisted cough, postural drainage, and percussion, breathing exercises and mobilization, active-assisted or active ROM exercises, achieving mobilization, whole body muscle strengthening exercises, incentive spirometry for patients having sputum and productive cough. The utilization of devices for individual use such as Tri-flow, flutter breathing device, acapella, cornet, positive expiratory pressure (PEP), aerobic exercises, strength exercises, and resistance training were effective. In case of shortness of breath,26,62 goal-directed therapy should be applied. Dyspnea associated with fatigue and tachycardia can be managed by oxygen therapy, noninvasive ventilation, spontaneous prone positioning, and early mobilization. Oxygen therapy and pacing are recommended for low saturation levels and hypoxia.56\n\nAnxiety and depression17,18,26,41,42,54 were the most prominent issues in LCS cases. The issues can be managed by respiratory rehabilitation, aerobic training, hydrotherapy, and thermotherapy coping and ADL strategies (including management of energy and drive functions), strength exercises, resistance training, postural gymnastics, and respiratory re-education. Mood disturbances and sleep disturbances24,36,41,50 can be managed by cycle ergometer exercises and muscular strengthening, aerobic exercises, strength exercises, resistance training, and vibration exercises. Impairments in the functional status due to sleep issues,24 and functional capacity issues27 can be managed through proper primary care management, along with aerobic training, hydrotherapy and thermotherapy, coping, and ADL strategies (including management of energy and drive functions).\n\nThe review found a multi-directional and multi-professional role in LCS. But we focused on the treatment regimen of physiotherapy, related therapy, and rehabilitation perspectives. Our study met the research gap on the large-scale rehabilitation intervention-focused review that was insufficient and with a small scale in the previous reviews.94–96 To our best knowledge, this is the larger scale review of LCS focused on rehabilitation interventions concerning the number of included papers and study population. We did not measure the sources of bias in the included study separately, instead, we evaluated the papers with a comprehensive appraisal by our appraisal tools for each type of included study following EQUATOR guidelines (Extended data 2-7). Scoping reviews do not require a complete appraisal and evaluation of the strength of included articles,97 we have included additional analysis to present the reader with a comprehensive scenario of the intervention recommendations and the strength of information sources. The appraisal tool was an innovative concept. There are a few appraisal tools, mostly for randomized control trials or reviews,98,99 our appraisal scoring was for cross-sectional, case-control, cohort, randomized control trials, study protocols, and Delphi-consensus. The scoring tools had no psychometric validation yet, but the system has a significant rigor as they are designed and adhered to the established EQUATOR guideline. A different type of study was evaluated with different scoring parameters, to present a uniform approach, the score was converted between 0 to 1. In that appraisal scoring evaluation, the minimum score of included studies was 0.6 out of 1. That means the lowest quality articles included in this study had 60% adherence to the EQUATOR standard for reporting research.\n\nThe primary limitation of the study was the insufficiency of randomized control trials, and level I studies. Long COVID is a relatively new term and clinical evidence is yet to be explored, hence we had a few pieces of evidence due to our focus on physiotherapy and rehabilitation. The future study recommendations will be systematic reviews and meta-analyses on RCTs or cohorts of LCS. Moreover, the paradigm of long covid rehabilitation needs more clinic-based and community-based trials.\n\n\nConclusion\n\nLong COVID is managed by multidisciplinary approach. There is significant scope for physiotherapy, exercise, and physical rehabilitation in musculoskeletal, neurological, cognitive, cardio-respiratory, mental health, and functional impairments. Physiotherapy and rehabilitation interventions can be provided at home or in clinical setups such as primary care settings, specialized rehabilitation services, community care, and telerehabilitation. Current understanding is limited to the appropriate doses of rehabilitation interventions and the long-term outcome of rehabilitation.",
"appendix": "Data availability\n\nMendeley Data: LCS ScR, www.doi.org/10.17632/w7m3bhnvcr.1. 100\n\nThis project contains the following underlying data:\n\n- Scoping final dataset.xlsx\n\n- Scoping SPSS.sav\n\nMendeley Data: LCS ScR, www.doi.org/10.17632/w7m3bhnvcr.1. 100\n\nThis project contains the following extended data:\n\n- Extended data 2: 27-score PRISMA checklist\n\n- Extended data 3: 25-score CONSORT Checklist\n\n- Extended data 4: 22-score STROBE checklist\n\n- Extended data 5: 13-score CARE checklist\n\n- Extended data 6: 23-score AGREE checklist\n\n- Extended data 7: 33-score SPIRIT checklist\n\n- Extended data 8: Recommended Physiotherapy and rehabilitation strategies summary\n\nMendeley Data: PRISMA-ScR checklist for “A comprehensive systematic scoping review for physiotherapy interventions for people living with long COVID”, www.doi.org/10.17632/w7m3bhnvcr.1. 100\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nCastanares-Zapatero D, Chalon P, Kohn L, et al.: Pathophysiology and mechanism of Long Covid: A comprehensive review. 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PubMed Abstract | Publisher Full Text\n\nBoutou AK, Asimakos A, Kortianou E, et al.: Long COVID-19 pulmonary sequelae and management considerations. J. Pers. Med. 2021 Sep; 11(9): 838. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNurek M, Rayner C, Freyer A, et al.: Recommendations for the recognition, diagnosis, and management of long COVID: a Delphi study. Br. J. Gen. Pract. 2021 Nov 1; 71(712): e815–e825. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBarbara C, Clavario P, De Marzo V, et al.: Effects of exercise rehabilitation in patients with long COVID-19. Eur. J. Prev. Cardiol. 2022 Jan 25; zwac019.\n\nMorrow AK, Ng R, Gray Vargas DTJ, et al.: Postacute/Long COVID in Pediatrics: Development of a Multidisciplinary Rehabilitation Clinic and Preliminary Case Series. Am. J. Phys. Med. Rehabil. 2021; 100(12): 1140–1147. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGarcía-Molina A, Espiña-Bou M, Rodríguez-Rajo P, et al.: Neuropsychological rehabilitation program for patients with post-COVID-19 syndrome: A clinical experience. Neurologia (Barcelona, Spain). 2021 Sep 1.\n\nBesnier F, Bérubé B, Malo J, et al.: Cardiopulmonary Rehabilitation in Long-COVID-19 Patients with Persistent Breathlessness and Fatigue: The COVID-Rehab Study. Int. J. Environ. Res. Public Health. 2022; 19(7): 4133.\n\nGhram A, Ayadi H, Knechtle B, et al.: What should a family physician know about nutrition and physical exercise rehabilitation ‘advices to communicate to “long-term COVID-19” patients? Postgrad. Med. 2022; 134: 143–147. (just-accepted). PubMed Abstract | Publisher Full Text\n\nDuncan E, Cooper K, Cowie J, et al.: A national survey of community rehabilitation service provision for people with long Covid in Scotland. F1000Res. 2020; 9.\n\nCattadori G, Di Marco S, Baravelli M, et al.: Exercise Training in Post-COVID-19 Patients: The Need for a Multifactorial Protocol for a Multifactorial Pathophysiology. J. Clin. Med. 2022 Apr 15; 11(8): 2228. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcNarry MA, Berg RM, Shelley J, et al.: Inspiratory Muscle Training Enhances Recovery Post COVID-19: A Randomised Controlled Trial. Eur. Respir. J. 2022 Jan 1; 60: 2103101. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWagner B, Steiner M, Markovic L, et al.: Successful application of pulsed electromagnetic fields in a patient with post-COVID-19 fatigue: a case report. Wien. Med. Wochenschr. 2022 Jan 10; 1–6.\n\nAvancini A, Belluomini L, Benato G, et al.: Exercise for counteracting post-acute COVID-19 syndrome in patients with cancer: an old but gold strategy? Acta Oncol. 2022; 61(3): 388–392. PubMed Abstract | Publisher Full Text\n\nSantos S, Flores JA: Musculoskeletal physiotherapy in physical sequelae of SARS-CoV-2 infection: A case report. Physiother. Res. Int. 2022; e1938.\n\nJayasinghe S, Misra A, Hills AP: Post-COVID-19 syndrome and type 2 diabetes: Primacy of exercise in prevention and management. Diabetes Metab. Syndr. 2022; 16(1): 102379. PubMed Abstract | Publisher Full Text | Free Full Text\n\nParkin A, Davison J, Tarrant R, et al.: A multidisciplinary NHS COVID-19 service to manage post-COVID-19 syndrome in the community. J. Prim. Care Community Health. 2021; 12: 21501327211010994.\n\nRathod KS, Deviprasad L, Hajare BR, et al.: COVID and Post COVID Physical Therapy of a 63 year old male with affection of Balance: A Case Report. Int. J. Physiother. Res. 2021; 9(6): 4079–4086. Publisher Full Text\n\nSrinivasan V, Kandakurti PK, JagatheesanAlagesan PS, et al.: Efficacy of pursed lip breathing with bhastrika pranayama vs incentive spirometry in rehabilitating post Covid 19 follow up-a randomized control study. Turk. J. Physiother. Rehabil. 2021; 32: 3.\n\nRahman MS: Rehabilitation of COVID 19 Patients, Bangladesh Perspective. J. Bangladesh Coll. Phys. Surg. 2022 Jan 3; 40(1): 52–56. Publisher Full Text\n\nFowler-Davis S, Platts K, Thelwell M, et al.: A mixed-methods systematic review of post-viral fatigue interventions: Are there lessons for long Covid? PLoS One. 2021 Nov 9; 16(11): e0259533. Publisher Full Text\n\nCrook H, Raza S, Nowell J, et al.: Long covid—mechanisms, risk factors, and management. BMJ. 2021 Jul 26; 374. Publisher Full Text\n\nVink M, Vink-Niese A: Could cognitive behavioural therapy be an effective treatment for long COVID and post COVID-19 fatigue syndrome? lessons from the Qure study for Q-fever fatigue syndrome. Healthcare. Multidisciplinary Digital Publishing Institute; 2020 Dec; (Vol. 8(No. 4): p. 552).\n\nSivan M, Taylor S: NICE guideline on long covid. BMJ. 2020 Dec 23; 371. Publisher Full Text\n\nMunteanu C, Păun DL, Șuță AM, et al.: Diabetes mellitus and COVID-19 in the post-acute phase patients-possible links with physical and rehabilitation medicine and balneotherapy. Balneo Res. J. 2020; 11: 350–367. Publisher Full Text\n\nBickton FM, Chisati E, Rylance J, et al.: An Improvised Pulmonary Telerehabilitation Program for Postacute COVID-19 Patients Would Be Feasible and Acceptable in a Low-Resource Setting. Am. J. Phys. Med. Rehabil. 2021 Mar; 100(3): 209–212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRaveendran AV, Misra A: Post COVID-19 syndrome (“Long COVID”) and diabetes: challenges in diagnosis and management. Diabetes Metab. Syndr. Clin. Res. Rev. 2021 Sep 1; 15(5): 102235. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSaigal A, Naidu SB, Shah AJ, et al.: S54 ‘Long-COVID’: the need for multi-disciplinary working.\n\nPinto M, Gimigliano F, De Simone S, et al.: Post-acute COVID-19 rehabilitation network proposal: from intensive to extensive and home-based IT supported services. Int. J. Environ. Res. Public Health. 2020 Jan; 17(24): 9335. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVitacca M, Migliori GB, Spanevello A, et al.: Management and outcomes of post-acute COVID-19 patients in Northern Italy. Eur. J. Intern. Med. 2020 Aug 1; 78: 159–160. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRafii QF, Hidayat MF, Aryudha T: Rehabilitation in acute post COVID-19 symptoms with intracranial space occupying lesion: a case report. International Journal of Research in Medical Sciences. 2022 Jan; 10(1): 264.\n\nCastro JP, Kierkegaard M, Zeitelhofer M: A call to use the multicomponent exercise Tai Chi to improve recovery from COVID-19 and long COVID. Front. Public Health. 2022; 175.\n\nSpielmanns M, Pekacka-Egli AM, Schoendorf S, et al.: Effects of a comprehensive pulmonary rehabilitation in severe post-COVID-19 patients. Int. J. Environ. Res. Public Health. 2021 Jan; 18(5): 2695. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBenzarti W, Toulgui E, Prefaut C, et al.: General practitioners should provide the cardiorespiratory rehabilitation “minimum advice” for long COVID-19 patients. Libyan J. Med. 2022 Jan 1; 17(1): 2009101. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDemeco A, Marotta N, Barletta M, et al.: Rehabilitation of patients post-COVID-19 infection: a literature review. J. Int. Med. Res. 2020 Aug; 48(8): 030006052094838. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCeravolo M, Arienti C, De Sire A, et al.: Rehabilitation and COVID-19: the Cochrane Rehabilitation 2020 rapid living systematic review.Publisher Full Text\n\nPrabawa IM, Silakarma D, Prabawa IP, et al.: Physical rehabilitation therapy for long covid-19 patient with respiratory sequelae: A systematic review. Open Access Macedonian. J. Med. Sci. 2022 Jun 6; 10(F): 468–474. Publisher Full Text\n\nPham MT, Rajić A, Greig JD, et al.: A scoping review of scoping reviews: advancing the approach and enhancing the consistency. Res. Synth. Methods. 2014 Dec; 5(4): 371–385. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoseley AM, Rahman P, Wells GA, et al.: Agreement between the Cochrane risk of bias tool and Physiotherapy Evidence Database (PEDro) scale: a meta-epidemiological study of randomized controlled trials of physical therapy interventions. PLoS One. 2019 Sep 19; 14(9): e0222770. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFenton L, Lauckner H, Gilbert R: The QATSDD critical appraisal tool: comments and critiques. J. Eval. Clin. Pract. 2015 Dec; 21(6): 1125–1128. PubMed Abstract | Publisher Full Text\n\nHossain KMA, Kabir MF: LCS ScR. [Dataset]. Mendeley Data. 2022; V1. Publisher Full Text"
}
|
[
{
"id": "169253",
"date": "04 May 2023",
"name": "Romy Parker",
"expertise": [],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a timely and well conducted scoping review which clearly identifies the need for a better understanding of Long COVID Symptoms (LCS) and their response to the range of rehabilitation strategies used by physiotherapists. The introduction provides an insightful overview into the multisystem nature of LCS with a comprehensive list useful for the clinical context.\nThe methods are well described, and the authors are to be commended for their rigorous approach to screening and selecting data. A novel method has been used to normalise analysis of the quality of evidence from studies using different methods e.g. case reports vs observation studies. The study provides a broad overview of the different rehabilitation interventions currently used in the field of physiotherapy for LCS. Helpfully, some discussion such as combining CBT and strength training are of clinical interest.\nThe main limitation of this work is the lack of weighting of the evidence itself in the results. The quality of the data are summarised by methodology, however there is no analysis or weighting of the evidence for each rehabilitation modality. We strongly recommend that the authors consider generating a table for each of the rehabilitation strategies e.g. guided walking; FES with the relevant scoring of the quality of the studies; and appropriate effect sizes, NNT or other measure for interpretation of the clinical effectiveness of the modality.\nThis limitation results in the discussion being no more than a listing of what rehabilitation modalities are described in the literature with no discussion of the proposed mechanism of action of these modalities nor discussion which would enable the reader to consider one rehabilitation modality as preferential to another. For the researcher, the discussion is also limited as it does not highlight the strength of the evidence for each modality, thus providing no clarity about which of these modalities is worth exploring further.\nThe limited engagement with the strength of the evidence for each of the rehabilitation strategies, means that the conclusion lacks direction giving a generic recommendation for more research into physiotherapy for LCS. An engagement with the strength of the evidence and proposed mechanism of action for the specific rehabilitation strategies would provide more specific direction for future research and guidance for clinical application.\nEditing of the grammar would be helpful to facilitate understanding.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? No",
"responses": [
{
"c_id": "9676",
"date": "20 Jul 2023",
"name": "Khin Nyein Yin",
"role": "Author Response",
"response": "Response to reviewer 1 APPROVED WITH RESERVATIONS This is a timely and well conducted scoping review which clearly identifies the need for a better understanding of Long COVID Symptoms (LCS) and their response to the range of rehabilitation strategies used by physiotherapists. The introduction provides an insightful overview into the multisystem nature of LCS with a comprehensive list useful for the clinical context. The methods are well described, and the authors are to be commended for their rigorous approach to screening and selecting data. A novel method has been used to normalise analysis of the quality of evidence from studies using different methods e.g. case reports vs observation studies. Author’s response: Thank you for your scholarly review. We hope your recommendations improved the clarity and strength of the paper. The study provides a broad overview of the different rehabilitation interventions currently used in the field of physiotherapy for LCS. Helpfully, some discussion such as combining CBT and strength training are of clinical interest. Author’s response: An RCT (cited as Reference 82) found CBT as an effective intervention, but no study found CBT combined with strengthening exercises. We recommended CBT as the strongest evidence among RCTs, hence due to arranging evidence according to the evidence pyramid, RCTs were aligned after the review or systematic reviews. In the discussion, we discussed the most weighted interventions. The main limitation of this work is the lack of weighting of the evidence itself in the results. The quality of the data are summarised by methodology, however there is no analysis or weighting of the evidence for each rehabilitation modality. We strongly recommend that the authors consider generating a table for each of the rehabilitation strategies e.g. guided walking; FES with the relevant scoring of the quality of the studies; and appropriate effect sizes, NNT or other measure for interpretation of the clinical effectiveness of the modality. This limitation results in the discussion being no more than a listing of what rehabilitation modalities are described in the literature with no discussion of the proposed mechanism of action of these modalities nor discussion which would enable the reader to consider one rehabilitation modality as preferential to another. For the researcher, the discussion is also limited as it does not highlight the strength of the evidence for each modality, thus providing no clarity about which of these modalities is worth exploring further. The limited engagement with the strength of the evidence for each of the rehabilitation strategies, means that the conclusion lacks direction giving a generic recommendation for more research into physiotherapy for LCS. An engagement with the strength of the evidence and proposed mechanism of action for the specific rehabilitation strategies would provide more specific direction for future research and guidance for clinical application. Author’s response: We have added Table 4 as the weighting of the evidence. We have revised the result section adding a table and key results from the weighting of evidence. In the discussion, we have added the recommended intervention according to the strength of evidence and their adherence to NICE guidelines on Long COVID rehabilitation. In conclusion, we concluded with recommended interventions. We had an extensive revision of the abstract also. Editing of the grammar would be helpful to facilitate understanding. Author’s response: Our author's experienced with English proofreading revised the manuscript for grammar editing. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? No Author’s response: We have revised the conclusion as per the reviewer’s recommendations. Competing Interests No competing interests were disclosed."
}
]
}
] | 1
|
https://f1000research.com/articles/12-368
|
https://f1000research.com/articles/12-545/v1
|
24 May 23
|
{
"type": "Research Article",
"title": "The impact of right bundle branch block and SIQIII-type patterns in determining risk levels in acute pulmonary embolism",
"authors": [
"Majed Hassine",
"Mohamed Yassine Kallala",
"Ahmed Jamel",
"Ines Bouanene",
"Nidhal Bouchahda",
"Marouen Mahjoub",
"Kais Memmi",
"Najeh Ben Halima",
"Habib Gamra",
"Mohamed Yassine Kallala",
"Ahmed Jamel",
"Ines Bouanene",
"Nidhal Bouchahda",
"Marouen Mahjoub",
"Kais Memmi",
"Najeh Ben Halima",
"Habib Gamra"
],
"abstract": "Background: Electrocardiography (ECG) findings in acute pulmonary embolism (PE) are known to be related to various right ventricular (RV) alterations. These abnormalities are not included in risk stratification algorithms despite emerging evidence of their association with patient outcomes. We aimed to analyze the impact of right bundle branch block (RBBB) and/or SIQIII patterns as indicators for determining the level of risk in patients with PE. Methods: We performed a retrospective cohort study including all patients with confirmed acute PE hospitalized from January 2008 to December 2019 in two tertiary care cardiology departments. The first ECG taken at admission was selected and the analysis focused on the presence of a complete or an incomplete RBBB and SIQIII-type patterns. Results: A total of 255 patients were divided into two groups: Group I (47.8%, n=122) included patients with PE without RBBB nor SIQIII patterns, and Group II (52.2%, n=133) included patients with RBBB and/or SIQIII patterns. Patients in group II presented significantly more frequently with acute right heart symptoms (45.1% vs. 18%, p<0.001) and cardiogenic shock at admission (31.6 vs. 4.1%, p<0.001). Echocardiographic parameters indicating right heart injury also occurred more significantly in group II patients (p<0.001). By univariate analysis, patients in group II were found to be significantly associated with in-hospital mortality (22.6 vs. 6.1%, p=0.002) and major cardiovascular events (MACEs) during hospitalization (43.3 vs. 13.7%, p<0.001). Multivariate logistic regression analysis identified five independent factors predictive of MACEs: SIQIII and/or RBBB, renal failure, positive troponin levels, RV dysfunction and right heart failure symptoms during initial presentation. Kaplan-Meier survival analysis identified the inclusion in Group II and the presence of SIQIII pattern as predictors of overall mortality (p<0.001). Conclusions: Our study suggests an important and independent prognostic value of RBBB and SIQIII patterns and their usefulness in determining the outcome of PE patients.",
"keywords": [
"Electrocardiogram",
"Pulmonary embolism",
"Prognosis",
"Mortality"
],
"content": "Introduction\n\nPulmonary embolism (PE) is a common and potentially life-threatening medical condition. It is estimated that thrombo-embolism affects over 1,000,000 people in the United States each year and results in over 25,000 deaths annually.1\n\nRisk stratification is important in determining the likelihood of poor outcomes for patients with acute PE. It dictates the attitude towards patients with PE from early discharge to urgent care in intensive care units. Thus, recent risk stratification algorithms rely on various clinical, laboratory, and imaging factors to estimate the risk of complications and guide treatment decisions.2 A major area of uncertainty in the risk stratification of acute PE is the potential role of electrocardiography (ECG) abnormalities in predicting the risk of complications as several ECG abnormalities have been identified in patients with acute PE, including right ventricular strain and S1Q3T3 type pattern.3–5 These changes are primarily related to right ventricular (RV) overload and reflect right ventricular dysfunction (RVD), injury and enlargement in patients with acute PE.6–9 Furthermore, ECG abnormalities associated with acute PE are more likely to be present in patients with a confirmed diagnosis of PE.2,10 Despite their potential prognostic value, none of these ECG changes are included in the current guidelines for PE risk stratification due to the lack of specificity.2,11 Encouraging evidence has emerged showing the relationship between the right bundle branch block (RBBB) and SIQIII patterns in acute PE events with poor outcomes.10,12,13 In addition, more research is needed to clarify the potential role of ECG abnormalities in the risk stratification of acute PE. By addressing these gaps in the literature, we can improve our ability to manage patients with this common and potentially life-threatening condition.12,14\n\nOur study aimed to examine the impact of RBBB and/or SIQIII-type patterns as indicators for determining the level of risk in patients with acute PE.\n\n\nMethods\n\nThis study was a retrospective observational cohort study that did not involve human testing and did not challenge human rights. The ethical approval was obtained retrospectively as we did not initially believe that this study needed ethical approval. This issue has been a subject of debate inside our team and that belief has since been revised and updated. Data collection for our study began in January 2011 in two Tunisian tertiary care cardiology departments: Cardiology A Department, Fattouma Bourguiba University Hospital affiliated to the University of Monastir and the Cardiology Department of Kairouan affiliated to the University of Sousse. Our study was retrospectively approved by the Research Ethics Committee of the Faculty of Medicine of Monastir (an independent organization under the aegis of the Tunisian Ministry of Public Health) under the number IORG 0009738 N°114/OMB 0990-0279. We obtained this approval on the 16th of March 2023.\n\nThe initial approval to start the study was obtained by consensus from both research teams under the supervision of both heads of the aforementioned departments at the University of Monastir and University of Sousse. The study was performed in compliance with the Declaration of Helsinki. We ensured that participants’ privacy and confidentiality were maintained, and the study results were reported in a way that protected the participants’ identities.\n\nOral informed consent was obtained from patients, whenever possible. This verbal consent was obtained during initial hospitalization. Each patient was informed that their anonymized data could serve for future research purposes. We did not conceptualize the content of this article at the time of information gathering and we could not obtain this consent in patients initially presenting with critical conditions and fatal outcomes. Verbal consent was approved retrospectively when we received ethical approval and deemed adequate by the ethics committee.\n\nWe conducted a retrospective cohort study. We included all patients with confirmed acute PE hospitalized from January 10th, 2008, to December 31st, 2019, in two Tunisian tertiary care cardiology departments: Cardiology A Department, Fattouma Bourguiba University Hospital affiliated to the University of Monastir and the Cardiology Department of Kairouan affiliated to the University of Sousse. The data were gathered by reviewing patients’ hospital records from each hospitalization, supplemented with comprehensive in-hospital assessments and follow-up interviews conducted either in person or via telephone.\n\nPE was diagnosed primarily by either computed tomography (CT) or scintigraphic ventilation-perfusion (V/Q) scans. The CT pulmonary angiogram (CTPA) demonstrated the existence and the extension of a filling defect in the pulmonary artery system. In the cases where V/Q scintigraphic scanning was employed, the results were interpreted by a nuclear medicine specialist. A high-probability V/Q scan was considered sufficient for the diagnosis of acute PE. This examination showed the presence of at least two segmental perfusion defects without ventilatory or radiological abnormalities in the same territories.2,15 PE diagnosis was also assessed by a positive venous doppler ultrasound consistent with deep venous thrombosis (DVT) in patients with high clinical suspicion of PE and positive D-dimer values.2 All CT, scintigraphy and venous doppler ultrasound scans were analyzed and interpreted by experienced specialists.\n\nComplete RBBB was identified according to the Minnesota Code criteria (7-2-1) as a QRS duration must be ≥120 ms in addition to R′ wave>R wave in lead V1 and/or V2 in most beats of leads I, II, III, aVL, aVF; or a QRS complex being predominantly upright with an R-peak duration ≥60 ms in lead V1 and/or V2 or; an S wave duration > to R wave duration in all beats in lead I and/or II.16,17\n\nIncomplete RBBB was identified according to the Minnesota Code criteria (7-1) by a QRS duration in each of leads I, II, III, aVL, and aVF being <120 ms in addition to an R′>R wave in lead V1 and/or V2.16,17\n\nSIQIII-type ECG patterns were defined as a qualitative presence of S wave in lead I and Q wave in lead III.\n\nRight ventricular dysfunction (RVD) was defined as a decreased systolic function of the RV (TAPSE <17 mm) and/or the presence of a paradoxical interventricular septal movement and/or a systolic pulmonary artery pressure ≥40 mmHg.\n\nMajor Adverse Cardiovascular Events (MACE) were defined as the presence of at least one of the following: death during hospitalization, cardiogenic shock in initial presentation or the presence of a thrombus in the right heart.\n\nRenal failure was defined as an eGFR < 60 ml/min per 1.73 m2.18\n\nPositive troponin levels were defined as any value above the 99th percentile of the upper reference limit.19\n\nPatients with PE with a systolic blood pressure (SBP) <90 mmHg at admission were classified as high-risk of mortality patients.2\n\nThe sex of each participant was defined based on self-report and assigned following external examination of body.\n\nPatients were eligible if: i) The diagnosis of PE was confirmed using one of the three diagnostic tools described above; ii) they were managed in Cardiology A Department, Fattouma Bourguiba University Hospital affiliated to the University of Monastir and the Cardiology Department of Kairouan affiliated to the University of Sousse; and iii) aged 18 years or above.\n\nExclusion criteria included: i) patients aged under 18 years and ii) if the diagnosis of acute PE was unclear.\n\nA standard 12-lead ECG was assessed in the Emergency Department immediately upon initial contact. This first ECG taken at admission was selected for analysis. Both the ECG and echocardiography exams were performed and interpreted by experienced examiners. The retrospective analysis of ECG parameters focused on the existence of RBBB, either complete or incomplete, and SIQIII-type patterns.\n\nData analysis was performed using IBM SPSS Statistics (RRID:SCR_016479) version 26.0. The mean ± standard deviation (SD) was used to describe the normally distributed data. The median and interquartile range (IQR) was used to describe the skewed distribution data.\n\nFrequencies and percentages were used to present categorical variables. The comparison between frequencies was performed using the Chi-squared test (χ2 test) or Fisher’s exact test. Means were compared using the Student’s t test for independent samples. A Kaplan–Meier survival analysis was performed to assess the association between the RBBB and/or SIQIII and overall mortality using the log-rank test. In order to identify the independent factors associated with the occurrence of MACEs, univariate and multivariate analyses were performed. First, covariates with a p-value less than or equal to 0.20 were retained in the multivariable model. Then, a binary logistic regression was performed for assessing the independent risk factors for MACEs.\n\nAssociations were reported as adjusted Odds Ratios (aOR) with 95% Confidence Interval (95% CI). A p-value≤0.05 was considered as statistically significant.\n\n\nResults\n\nA total of 255 patients were included in the analysis. All of the medical reports for these patients included a usable ECG from the time of their acute PE episode. Patients were divided into two groups: i) Group I (n=122, 47.8%) included patients with PE without RBBB nor SIQIII patterns; and ii) group II (n=133, 52.2%) included patients with RBBB and/or SIQIII type patterns. Patients in both groups did not differ by age nor sex. The proportion of diabetes mellitus (DM), hypertension (HTN) and dyslipidemia were homogeneous between the two groups (Table 1).25\n\nHTN, hypertension; VTE, venous thromboembolism; SBP, systolic blood pressure; DBP, diastolic blood pressure; TTE, transthoracic echocardiogram; IVS, intact ventricular septum; SPAP, systolic pulmonary artery pressure; RVD, right ventricular dysfunction; TAPSE, tricuspid annular plane systolic excursion; ECG, electrocardiography; RBBB, right bundle branch block; MACE, major cardiovascular event.\n\nGroup II patients had an active cancer (17.3% vs. 12.3%) more frequently but this difference did not reach statistical significance (p=0.29). Patients presenting with SIQIII pattern and/or RBBB were also significantly more likely to have history of systolic or diastolic heart failure (13.5% vs. 4.9%, p=0.03).\n\nWe analyzed the association between the presence of RBBB and/or SIQIII type pattern with PE severity and patient outcome.\n\nPatients in group II presented more frequently with acute right heart symptoms (45.1 vs. 18%, p<0.001), more often showed cardiogenic shock (31.6 vs. 4.1%, p<0.001) and had lower systolic blood pressure (SBP) (110.3 vs. 122.8 mmHg, p<0.001) and diastolic blood pressure (DBP) (67.5 vs. 73.9 mmHg, p<0.001) at admission. The difference was statistically significant for all these parameters. Syncope occurred more frequently in Group II patients but the difference did not reach statistical significance (14.3 vs. 9%, p=0.24) (Table 1).\n\nPatients in group I had a significantly lower likelihood of positive Cardiac troponin I (cTnI) or high-sensitivity cardiac troponin (hs-cTn) levels (26.9 vs. 51.1%, p<0.001).\n\nEchocardiographic parameters indicating a right heart injury also occurred more frequently in group II patients: SPAP >40 mmHg (63.2 vs. 28.3%, p<0.001), paradoxical interventricular septum (51.6 vs. 26.5%, p<0.001), tricuspid annular plane systolic excursion (TAPSE) <17 mm (55.6 vs. 4.2%, p<0.001), the presence of a thrombus in the right heart (25 vs. 4.2%, p<0.001). Thus, RVD was significantly more frequent in Group II patients by univariate analysis (p<0.001).\n\nA total of 101 patients (39.6%) had RBBB, 66 (26%) had SIQIII type patterns, and 34 patients (13.4%) had both SIQIII pattern and RBBB.\n\nNegative T waves in leads V1-V3 were significantly more frequently associated with Group II patients in univariate analysis (p=0.01) (Table 1).\n\nThere were slightly more patients with atrial fibrillation (AF) in Group I patients, but this was not statistically significance (10.6 vs. 7.6%, p=0.4).\n\nGroupe II patients were significantly associated with in-hospital mortality (22.6 vs. 6.1%, p=0.002) and MACEs during hospitalization by univariate analysis (43.3 vs. 13.7%, p<0.001) (Table 1).\n\nMultivariate logistic regression analysis demonstrated five independent predictors of MACE: SIQIII and/or RBBB (OR=2.4; 95% CI: 1.04, 5.9; p=0.039), renal failure (OR=2.5; 95% CI: 1.08, 5.8; p=0.031), positive troponin levels (OR=5.4; 95% CI: 2.34, 12.6; p<0.001), RVD (OR=7.9; 95% CI: 2.16, 28.8; p=0.002) and right heart failure symptoms during initial presentation (OR=2.5; 95% CI: 1.1, 5.8; p=0.025) (Table 2). Using these models, SIQIII pattern (OR=4.8; 95% CI: 1.9, 12.2; p=0.001), RVD (OR=15.2; 95% CI: 1.9, 12.4; p=0.01) and cardiogenic shock at admission (OR=2.7; 95% CI: 1, 6.9; p=0.034) were independently associated with in-hospital mortality, on the other hand, no association was found between in-hospital mortality and group II patients (Table 3).\n\nMACE, major cardiovascular event; RBBB, right bundle branch block; RVD, right ventricular dysfunction; OR, odds ratio; CI, confidence interval.\n\nRVD, right ventricular dysfunction; OR, odds ratio; CI, confidence interval.\n\nA medium or long term follow-up was done for 83% of the cohort. The Kaplan–Meier survival analysis also demonstrated SIQIII patterns as a predictor of overall mortality (p<0.001) (Figure 1). The Kaplan–Meier analysis also identified the presence of SIQIII and/or RBBB patterns as a predictive factor for overall mortality (p<0.001) (Figure 2).\n\n\nDiscussion\n\nEarly and risk-oriented diagnosis and management of patients with acute PE are key for a better prognosis.2 In our study, RBBB and SIQIII-type patterns at admission were found to be associated with worsening clinical, echographic and biological profiles and with a poor clinical outcome.\n\nMeta-analyses by Shopp et al., reported different ECG patterns, such as inverted T wave in leads V1-V4, a QR pattern in lead V1, SIQIII, complete or incomplete RBBB and ST elevation in lead aVR as being associated with increasing severity and poor outcomes.4\n\nECG scoring by Daniel et al., was notable for providing an applicable and reliable prognostic tool.5 However, recent studies indicate that there are several ECG abnormalities that can provide valuable prognostic information, but are not currently included in these scores.9 These ECG findings were also associated with early clinical deterioration.20 Despite these findings, ECG abnormalities were not included nor recommended in the latest guidelines for risk stratification of acute PE.2 This is probably due to the lack of specificity as these changes can be encountered in acute and chronic cor pulmonale.21\n\nThe SIQIII pattern was found to be a strong independent predictor of in-hospital mortality, contrary to RBBB. Acute onset of SIQIII patterns mirror a longitudinal dextrorotation of the RV and appears to be more associated with poor hemodynamic outcomes than RBBB. RBBB alone was not found to be independently associated with in-hospital mortality The findings concerning RBBB were interpreted as follows: this characteristic can be observed in both acute pulmonary embolism (PE) and different conditions affecting the right ventricle (RV). Consequently, distinguishing between a new onset RBBB and a preexisting chronic RBBB is challenging. Furthermore, this challenge may be attributed to the limited sample size in various studies exploring the correlation between ECG abnormalities and risk assessment in acute PE.\n\nNew onset SIQIII and/or RBBB is likely to increase right heart failure, cardiogenic shock and intra-hospital mortality. These ECG changes seem to profoundly impact the overall survival as patients with SIQIII and/or RBBB patterns, and especially those with SIQIII, have significantly lower survival rates with curves diverging in less than a year. Parallel to the Pulmonary Embolism Severity Index (PESI) and to the simplified Pulmonary Embolism Severity Index (SPESI) scores, these findings suggest the importance of the RBBB and SIQIII patterns as important criteria in risk stratification of PE.12 The recent onset of these patterns may improve its specificity especially if other causes of acute cor pulmonale are ruled out.\n\nGiven the predictive value of these parameters, it would be beneficial to integrate them into new and more accurate risk stratification scores for future guidelines. This would probably outperform guideline-backed risk scores.22\n\nFurthermore, our study suggests that ECG alone is a useful tool in determining the outcome of PE, particularly in limited resources environments where advanced diagnostic tools are not available.23,24\n\n\nConclusions\n\nRisk stratification is key for the management of patients with acute PE. New-onset RBBB and/or SIQIII and especially SIQIII patterns are likely to worsen patient outcomes. Our study suggests important and independent prognostic values of RBBB and SIQIII patterns and their usefulness in determining the outcome of acute PE patients.",
"appendix": "Data availability\n\nFigshare: EP registre 2023 MONASTIR _ KAIROUAN final - SAFE HARBOR.sav. https://doi.org/10.6084/m9.figshare.22153379. 25\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nVirani SS, Alonso A, Aparicio HJ, et al.: Heart Disease and Stroke Statistics—2021 Update. Circulation. 23 févr 2021; 143(8): e254–e743. PubMed Abstract | Publisher Full Text\n\nKonstantinides SV, Meyer G, Becattini C, et al.: 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur. Heart J. 21 janv 2020; 41(4): 543–603. PubMed Abstract | Publisher Full Text\n\nStein PD, Dalen JE, Mclntyre KM, et al.: The Electrocardiogram in Acute Pulmonary Embolism.\n\nShopp JD, Stewart LK, Emmett TW, et al.: Findings From 12-lead Electrocardiography That Predict Circulatory Shock From Pulmonary Embolism: Systematic Review and Meta-analysis. Jones AE, éditeur. Acad. Emerg. Med. oct 2015; 22(10): 1127–1137. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDaniel KR, Courtney DM, Kline JA: Assessment of Cardiac Stress From Massive Pulmonary Embolism With 12-Lead ECG. Chest. août 2001; 120(2): 474–481. PubMed Abstract | Publisher Full Text\n\nPunukollu G, Gowda RM, Vasavada BC, et al.: Role of Electrocardiography in Identifying Right Ventricular Dysfunction in Acute Pulmonary Embolism. Am. J. Cardiol. août 2005; 96(3): 450–452. PubMed Abstract | Publisher Full Text\n\nStein PD, Matta F, Sabra MJ, et al.: Relation of Electrocardiographic Changes in Pulmonary Embolism to Right Ventricular Enlargement. Am. J. Cardiol. déc 2013; 112(12): 1958–1961. PubMed Abstract | Publisher Full Text\n\nCouto Pereira S, Valente Silva B, Silverio Antonio P, et al.: Electrocardiography: an usefull tool for prediction of the diagnosis and severity of pulmonary embolism. EP Eur. 19 mai 2022; 24(Supplement_1): euac053.002. Publisher Full Text\n\nDigby GC, Kukla P, Zhan ZQ, et al.: The Value of Electrocardiographic Abnormalities in the Prognosis of Pulmonary Embolism: A Consensus Paper: Pulmonary Embolism & ECG. Ann. Noninvasive Electrocardiol. mai 2015; 20(3): 207–223. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCasazza F, Pacchetti I, Rulli E, et al.: Prognostic significance of electrocardiogram at presentation in patients with pulmonary embolism of different severity. Thromb. Res. mars 2018; 163: 123–127. PubMed Abstract | Publisher Full Text\n\nIslamoglu MS, Dokur M, Ozdemir E, et al.: Massive pulmonary embolism presenting with hemoptysis and S1Q3T3 ECG findings. BMC Cardiovasc. Disord. déc 2021; 21(1): 224. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKeller K, Beule J, Balzer JO, et al.: Right bundle branch block and SIQIII-type patterns for risk stratification in acute pulmonary embolism. J. Electrocardiol. juill 2016; 49(4): 512–518. PubMed Abstract | Publisher Full Text\n\nBolt L, Lauber S, Limacher A, et al.: Prognostic Value of Electrocardiography in Elderly Patients with Acute Pulmonary Embolism. Am. J. Med. déc 2019; 132(12): e835–e843. PubMed Abstract | Publisher Full Text\n\nCo I, Eilbert W, Chiganos T: New Electrocardiographic Changes in Patients Diagnosed with Pulmonary Embolism. J. Emerg. Med. mars 2017; 52(3): 280–285. PubMed Abstract | Publisher Full Text\n\nReid JH, Coche EE, Inoue T, et al.: Is the lung scan alive and well? Facts and controversies in defining the role of lung scintigraphy for the diagnosis of pulmonary embolism in the era of MDCT. Eur. J. Nucl. Med. Mol. Imaging. mars 2009; 36(3): 505–521. PubMed Abstract | Publisher Full Text\n\nBussink BE, Holst AG, Jespersen L, et al.: Right bundle branch block: prevalence, risk factors, and outcome in the general population: results from the Copenhagen City Heart Study. Eur. Heart J. 7 janv 2013; 34(2): 138–146. PubMed Abstract | Publisher Full Text\n\nMacfarlane PW: Minnesota coding and the prevalence of ECG abnormalities. Heart. 1 déc 2000; 84(6): 582–584. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRossing P, Caramori ML, Chan JCN, et al.: KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. nov 2022; 102(5): S1–S127. PubMed Abstract | Publisher Full Text\n\nThygesen K, Alpert JS, Jaffe AS, et al.: Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 13 nov 2018; 138(20). Publisher Full Text\n\nWeekes AJ, Raper JD, Thomas AM, et al.: Electrocardiographic findings associated with early clinical deterioration in acute pulmonary embolism. Acad. Emerg. Med. oct 2022; 29(10): 1185–1196. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSreeram N, Cheriex EC, Smeets JLRM, et al.: Value of the 12 lead Electrocardiogram at Hospital Admission in the Diagnosis of Pulmonary Embolism. J. Cardiol. 1994; 73: 296–303.\n\nChoi SH, Cha SI, Park JE, et al.: Electrocardiographic changes as a prognostic tool for hospitalized patients with pulmonary embolism. Thromb. Res. août 2020; 192: 61–63. PubMed Abstract | Publisher Full Text\n\nQaddoura A, Digby GC, Kabali C, et al.: The value of electrocardiography in prognosticating clinical deterioration and mortality in acute pulmonary embolism: A systematic review and meta-analysis. Clin. Cardiol. oct 2017; 40(10): 814–824. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGeibel A: Prognostic value of the ECG on admission in patients with acute major pulmonary embolism. Eur. Respir. J. 1 mai 2005; 25(5): 843–848. PubMed Abstract | Publisher Full Text\n\nKallala MY, Hassine M, Jamel A: EP registre 2023 MONASTIR _ KAIROUAN final - SAFE HARBOR.sav. [Dataset]. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "210932",
"date": "16 Oct 2023",
"name": "Talel Trimech",
"expertise": [
"Reviewer Expertise Cardiovascular diseases",
"heart failure",
"pulmonary embolism"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI found the article to be interesting. The exploration of ECG modifications and their correlation with acute pulmonary embolism risk stratification has been a matter of several debates. Using such simple methods, if proven accurate, might sharpen the sensibility of such predictive models.\n\nThe bicentric study design with a substantial number of patients adds considerable weight to the findings, enhancing the credibility of the study and positioning it as one of the most credible papers addressing the relationship between ECG modifications and risk stratification. The statistical analysis carried out in the study has solid standards, and the inclusion of survival curves added a valuable dimension to the interpretation of the data.\nI therefore, have two minor remarks:\nThe definition of MACE included the presence of a thrombus in the right heart. This can be asymptomatic and not leading to a major cardiovascular event. Although the definition of MACE has not been standardized, I think that the inclusion of such TTE findings might be a matter of discussion.\n\nHow were the SPAP calculated when the TAPSE was <17 mm. Using the tricuspid regurgitation flow might underestimate the PAP values in such cases.\nOverall, I commend the authors for their work in conducting this study and presenting the results in a clear and impactful manner. This research has the potential to influence clinical practice positively.\nThank you for considering my feedback.\nBest regards\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "279907",
"date": "28 May 2024",
"name": "Boris Dzudovic",
"expertise": [
"Reviewer Expertise acute cardiac conditions includin acute PE and CTEPH."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary: The study investigates the prognostic significance of right bundle branch block (RBBB) and SIQIII patterns on the risk stratification and outcomes of patients with acute pulmonary embolism (PE). Conducted as a retrospective cohort study involving 255 patients over a period of 11 years, the research provides valuable insights into the association between these ECG patterns and clinical outcomes, emphasizing their potential utility in risk stratification. Review: 1. Is the work clearly and accurately presented and does it cite the current literature? Yes. The manuscript is well-written and clearly presents its findings. It adequately references current and relevant literature, contextualizing its contributions within the existing body of knowledge. 2. Is the study design appropriate and is the work technically sound? Yes. The study design is appropriate for the research question. The use of a bicentric study design with a substantial patient cohort enhances the robustness of the findings. The methods, including statistical analyses, are solid and align with the study objectives. 3. Are sufficient details of methods and analysis provided to allow replication by others?Yes. The methods section is detailed, allowing for reproducibility. The descriptions of ECG criteria, inclusion/exclusion criteria, and statistical methods are thorough and clear. 4. If applicable, is the statistical analysis and its interpretation appropriate? Yes. The statistical analyses are appropriate, with a comprehensive use of univariate and multivariate logistic regression analyses to identify independent predictors of major adverse cardiovascular events (MACEs) and in-hospital mortality. Kaplan-Meier survival analyses further enrich the interpretation of the data. 5. Are all the source data underlying the results available to ensure full reproducibility? Yes. The underlying data is available as cited, ensuring transparency and reproducibility. 6. Are the conclusions drawn adequately supported by the results? Yes. The conclusions are well-supported by the data presented. The study effectively demonstrates the prognostic value of RBBB and SIQIII patterns in patients with acute PE. Specific Comments: Definition of MACE: - The inclusion of right heart thrombus as part of the MACE definition is debatable as it may not always lead to major cardiovascular events and can sometimes be asymptomatic. A clearer rationale for this inclusion or a standardized definition would enhance the robustness of the findings. SPAP Calculation: - The calculation of systolic pulmonary artery pressure (SPAP) when tricuspid annular plane systolic excursion (TAPSE) is <17 mm requires clarification. The potential underestimation of PAP using tricuspid regurgitation flow in these cases should be addressed, as it impacts the interpretation of right ventricular dysfunction. Ethical Considerations: - While the study is retrospective and received ethical approval, the initial lack of ethical approval and subsequent retrospective approval should be more transparently discussed, especially regarding the collection of verbal consent from critically ill patients. Minor remarks: 1. The study provides valuable contributions to the field and has the potential to influence clinical practice by incorporating ECG findings into risk stratification models for PE. 2. The presentation of survival curves adds a significant dimension to understanding the prognostic implications of the ECG patterns studied. Conclusion: The article is a significant contribution to the literature on PE and its risk stratification. The findings support the integration of RBBB and SIQIII patterns into risk stratification algorithms, potentially improving patient management. Addressing the minor issues noted would further strengthen the study. Recommendation: Accept with minor revisions.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-545
|
https://f1000research.com/articles/12-544/v1
|
24 May 23
|
{
"type": "Research Article",
"title": "Anti-angiogenic activity of Ficus deltoidea L. Jack silver nanoparticles using chorioallantoic membrane assay",
"authors": [
"Retno Aryani",
"Rudy Agung Nugroho",
"Hetty Manurung",
"Muhammad Hafidz Rulimada",
"Erin Maytari",
"Angeline Siahaan",
"Rudianto Rudianto",
"Wibowo Nugroho Jati",
"Retno Aryani",
"Hetty Manurung",
"Muhammad Hafidz Rulimada",
"Erin Maytari",
"Angeline Siahaan",
"Rudianto Rudianto",
"Wibowo Nugroho Jati"
],
"abstract": "Background: Ficus deltoidea L. Jack is a folk medicinal plant known for its pharmacological properties, including anti-inflammatory, anticancer and anti-angiogenic. This study aimed to evaluate the anti-angiogenic properties of silver nanoparticles biosynthesized using F. deltoidea leaf extract (AgNPs-Fd). Methods: The AgNPs-Fd were synthesized by mixing 100 mL 1 mM aqueous silver nitrate (AgNO3) and 100 mL 0.1% F. deltoidea ethanolic leaf extract. The resulting AgNPs-Fd were observed for color change and Tyndall effects. Reaction mixture color change from pale brown to reddish brown was observed at 48 h at 37°C. The characterization of AgNPs-Fd was completed with UV–Vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. For quantitative analysis of the vascular network in the chorioallantoic membrane (CAM) assay, AngioTool open-source software was used. Results: The plasmon resonance peak for AgNPs-Fd at 430 nm was visible in the UV-Visible spectrum, indicating the formation of AgNPs-Fd. The F. deltoidea extract and nanoparticles interacted well according to FTIR analysis. The AgNPs-Fd morphology of 20 nm particle sizes was observed using TEM. The chromatographic analysis of AgNPs-Fd identified potential anti-angiogenic compounds, such as phytol, stigmasterol, lupeol and sitosterol. The angiogenic inhibition properties of AgNPs-Fd were tested using the CAM assay. The 90 mg dose AgNPs-Fd treatment in CAMs demonstrated significant anti-angiogenesis, indicating effectiveness in controlling vessel formation. Conclusions: The present study suggests that eco-friendly work and the “green” process of AgNPs-Fd is potentially applicable for nanobiotechnology in anti-angiogenic fields.",
"keywords": [
"anti-angiogenic",
"Ficus deltoidea",
"green synthesize",
"nanomaterials"
],
"content": "Introduction\n\nFicus deltoidea is a well-known medicinal plant that has been historically used by various ethnic groups in Indonesia. This plant, from the Moraceae family, is an epiphyte with a shrub habit that is found in secondary forests. The F. deltoidea leaf is used to treat diabetes mellitus,1 for anti-inflammation,2 as an antibacterial3 and for cancer inhibition.4 Additionally, F. deltoidea is reported to be antinociceptive, anti-inflammatory, antidiabetic, anti-obesity, anti-melanogenic, antioxidative and a free radical scavenger.5\n\nFurthermore, F. deltoidea leaf extract may suppress cancer development through three mechanisms: apoptosis via the intrinsic route, migration and invasion inhibition, and angiogenesis inhibition.6,7 The aqueous and ethanol extracts of F. deltoidea are known to have anticancer activities on human ovarian carcinoma cells. The F. deltoidea aqueous extract has an IC50 of 224.39±6.24 g/mL, while the F. deltoidea ethanolic extract has an IC50 of 143.03±20.21 g/mL. However, cell growth is affected differently by exposure to the different extracts. Cell release is triggered with the aqueous extract, while cell growth is reduced with the ethanol extract.8\n\nRecently, technology surrounding nanoparticles, which can be biologically synthesized, has grown, since the nano-size items exhibit different characteristics of its bulk components due to variations in their surface–volume ratio.9 Most nanomaterials have demonstrated outstanding quantum confinement with unique catalytic features in many biological reactions and a variety of applications in various sectors that enhance the approach for electrical, environmental and medicinal objectives.10 Nanomaterials are employed in biological imaging, diagnostics, biosensing, gene therapy, and antibacterial and anticancer drugs.11\n\n“Greener” nanoparticle synthesis is advantageous over previous approaches as it is simple, inexpensive, and relatively repeatable, typically resulting in more stable compounds. Nanoparticles can also be created using microorganisms. However, the rate of synthesis is slower, and the process is limited regarding accessible sizes and forms when compared with approaches employing plant-based components. The green synthesis process does not require high pressure, energy, temperature, or harmful ingredients; as a result, many scientists have abandoned synthetic approaches. Moreover, plants generate more stable nanoparticles than other technologies and are easily scaled up.11\n\nPrevious studies revealed that silver nanoparticles synthesized using Ficus deltoidea extract (AgNPs) have been biosynthesized using various plant extracts, including Salvia spinosa,12 Origanum vulgare L.,13 Araucaria angustifolia,14 Myrmecodia sp bulb,15 Eleutherine americana,16 and Citrus medica.17 The biosynthesis of AgNPs using various plant extracts is a simple and rapid method, with its success easily determined by color changes and UV-Vis spectrophotometry. Furthermore, to characterize the resulting AgNPs, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) are employed.18\n\nSeveral studies using plant derived AgNPs involving cancer and angiogenesis have been performed. Previous research reported that the green synthesis of AgNPs using rapeseed flower pollen potentially reduced angiogenesis.19 Similar findings were also described by Vimalraj and Ashokkumar,20 who stated that green synthesis of gold nanoparticles mediated by Mangifera indica seed water extracts demonstrated anti-angiogenic properties. Baharara and Namvar21 revealed that AgNPs generated from Achillea biebersteinii flower extracts were well-dispersed and stable using green techniques and exhibited potential therapeutic advantages against angiogenesis. In addition, the biosynthesized-AgNPs successfully reduced angiogenesis in an embryonated chicken model, and this anti-angiogenic property of AgNPs can be investigated as a potential therapeutic against pathological angiogenesis and solid tumors by targeting the vasculature.22\n\nVarious in vivo angiogenesis assays have been conducted to study the angiogenic processes and to discover new therapeutic agents that inhibit or trigger angiogenesis. One of the most common laboratory methods used to study angiogenesis and anti-angiogenesis is the chorioallantoic membrane (CAM) assay of chicken embryos. The CAM methodology has several advantages, such as a high embryo survival rate, simple procedure, not requiring high sterility, low cost and a high level of reproducibility and reliability. The CAM assay was first performed by Judah Folkman and colleagues for testing angiogenic activity in tumor tissue.23–25\n\nThough several studies of AgNPs and anti-angiogenic properties of plant extracts have been conducted, the anti-angiogenic properties of AgNPs biosynthesized using F. deltoidea (AgNPs-Fd) has yet to be defined. Thus, the present research aimed to evaluate the anti-angiogenic properties of AgNPs-Fd using the CAM method. The biosynthesis of AgNPs-Fd was characterized by observing the color change, Tyndall effect, UV-Vis spectrophotometry, TEM, XRD and FTIR. Phytochemical analysis of AgNPs-Fd was also conducted using gas chromatography-mass spectrometry (GC-MS). For quantitative analysis of the vascular network in the CAM assay, AngioTool open-source software was used.26\n\n\nMethods\n\nPresent methods has been deposited step-by-step on protocols.io with DOI: dx.doi.org/10.17504/protocols.io.14egn2nj6g5d/v1.\n\nThe Ethics Research and Community Service Mulawarman Universitas approved the use of chicken embryos to be used in the chorioallantoic membrane assay (Contract Number: 464/UN17.L1/HK/2022; 10 May 2022). This study is reported in line with ARRIVE guidelines.53\n\nLeaves of the F. deltoidea were collected from a local farmer at East Kalimantan, Indonesia. The collected leaves were identified using a floras identification manual. The dry leaves were cut into small pieces and ground using a mechanical blender. The leaf powder was extracted using ethanol, concentrated using a rotary evaporator and stored at 4°C until further use.\n\nAqueous silver nitrate (AgNO3) (100 mL, 1 mM) was combined with 100 mL 0.1% F. deltoidea leaf extract. The pH of the solution was adjusted to 7.0, and it was subsequently incubated on a rotary shaker at 150 rpm for 48 h at 28°C. The fabrication of AgNPs-Fd was observed macroscopically by color change and the Tyndall effect.\n\nThe resulting AgNPs-Fd were confirmed using UV-Vis spectrophotometry (Shimadzu, UV-1280, Japan) in the range of 350–750 nm. The TEM (MIRA3 model, Czech Republic) was operated to display the surface morphology of the AgNPs-Fd. XRD was applied to evaluate the chemical characterization of AgNPs-Fd. To determine phytochemicals surrounding the AgNPs-Fd, FTIR spectroscopy (Agilent, Cary 630 model, US) was performed.27\n\nPhytochemical analysis of the AgNPs-Fd was performed using GC-MS (HP-5MS UI, Agilent, USA) to evaluate the chemical compounds that potentially serve as anti-angiogenic. For this, samples of AgNPs-Fd were dissolved in ethanol in a microtube, vortexed and centrifuged for three minutes at 9,500 rpm. The resulting supernatant was used for identification and injected into the GC-MS apparatus. The condition of the GC-MS is as follows: column: HP-5MS UI, gas carrier: helium UHP (He), injector temperature: 290°C, split flow: 10 ml/min, split ratio: 10; front inlet flow: 1.00 ml/min, MS transfer line temp: 230°C, ion source temp: 200°C, mass list range (amu): 40–500, purge flow: 3 ml/min, gas saver flow: 5 ml/min, and gas saver time: five minutes.\n\nTo analyze AgNPs-Fd for anti-angiogenic properties, a CAM assay was performed following previous methods by Ribatti,24 Camposano and Torre,28 and Gamallo and Espere.29 In total, 24 chicken eggs were collected in preparation for the CAM analysis and were dosed with F. deltoidea extract (Fd) or AgNPs-Fd. The doses used in the paper disk for the CAM assay were as follows: negative control (30 ng basic fibroblast growth factor (bFGF); positive control (30 μg cortisone acetate with 30 ng bFGF); treatment groups (30 ng bFGF with AgNPs-Fd at 45, 60, 75 and 90 μg, respectively). A basic fibroblast growth factor (bFGF-Thermo Fisher Scientific, USA) is a group of proteins secreted by tissues to regulate cell metabolism, proliferation, differentiation, and survival. The bFGF was used to induce neovascularization.30\n\nBefore incubation, eggshells were cleansed with 70% alcohol. The eggs were incubated in for six days at 37−39°C with 50−60% humidity. The boundaries of the air space, which indicated the location of the embryo, were marked on all eggshells with a pencil (1 × 1 cm). Candling, with egg binoculars, was used to determine the location of the embryo. By using a povidone-iodine solution, the eggshell was cleaned at the pole containing the air space and the part above the embryo. Using a needle, a small hole was made in the air chamber and vacuumed until the air moved from the pole to the top of the egg.\n\nNext, a window measuring 1×1 cm was made on the marked area using a mini drill. Paper discs for each treatment were then embedded onto the CAM through this window. The holes in the polar regions and 1×1 cm windows were sealed with paraffin film after they had been planted according to the treatment. The eggs were then incubated for 48 h at 37−39°C with 50−60% humidity. After, the eggs were removed and subsequently killed by freezing for 24 h. The eggs were then opened by cutting the eggshell into two parts, beginning with the part closest to the air cavity. The egg contents were slowly and carefully removed, keeping the CAM attached to the shell. Each CAM was photographed and analyzed using AngioTool 0.6 software (RRID:SCR_016393).\n\nAngioTool is a small, easy-to-use application that allows for the quick, hands-free and reproducible measurement of vascular networks in micrographs. AngioTool calculates a variety of morphological and geographical data, such as the area covered by a vascular network, the number of vessels, vessel length, vascular density and lacunarity. AngioTool also computes the “branching index” (branch points/unit area), which quantifies specimen sprouting activity.26\n\nData from the AgNPs-Fd characterization were evaluated as graphs and images. Notations and arrow marks were added to the images, and they were cropped and the resolution was increased to 300 dpi, all of which were performed using Adobe photoshop (RRID:SCR_014199) (Adobe Photoshop, adobe, Inc., USA). Meanwhile, data from the CAM assays, such as vessel area, total number of junctions, junction density, total vessel length, average vessel length and total number of end points, were presented as the mean±standard errors. Significant differences among the treatment groups were assessed using analysis of variance (ANOVA) with IBM SPSS Statistics (RRID:SCR_016479) ver. 22 (IBM Corp., USA). A Duncan’s multiple range test (DMRT) was performed if significant differences were detected from ANOVA analysis. Significance was defined as p<0.05.\n\n\nResults\n\nThe solution began to change color once the plant extract was added to the AgNO3 solution. When the reaction began, the solution was light brown. After 30 minutes of constant stirring, the solution gradually darkened (Figure 1).52 Further, Tyndall scattering was performed to confirm the biosynthesis of AgNPs-Fd. As depicted in Figure 2, the solution of colloidal AgNPs-Fd (Figure 2b) demonstrated the Tyndall effect (beam of light visible from the side) due to the presence of lyophobic sol particles large enough for light dispersion, while genuine solutions (Figure 2a and c) did not exhibit light dispersion. Thus, the presence of AgNPs-Fd in aqueous solution as colloids was deduced.\n\n(A) Plant extract; (B) colloidal AgNPs-Fd; (C) AgNO3 solution. AgNPs-Fd, silver nanoparticles synthesized using Ficus deltoidea extract; AgNO3, aqueous silver nitrate.\n\n(A) Plant extract; (B) colloidal AgNPs-Fd; (C) AgNO3 solution. AgNPs-Fd, silver nanoparticles synthesized using Ficus deltoidea extract; AgNO3, aqueous silver nitrate.\n\nA peak in the UV-Vis absorption spectra of AgNPs-Fd at 430 nm with respect to 2.25 absorbance was observed, whereas the ethanol extract of the F. deltoidea leaf absorbed at 490 nm (Figure 3). This finding is similar to previous studies reporting that the UV-Vis maximum absorbance of AgNPs was 430 nm when mediated by the Pedalium murex leaf extract,31 Alternanthera dentata leaf extract32 and Tecomella undulata leaf extract.33\n\nThe highest absorbance of AgNPs-Fd was observed at 430 nm with an absorbance of 2.25. AgNPs-Fd, silver nanoparticles synthesized using Ficus deltoidea extract.\n\nThe morphology and size of the AgNPs-Fd were analyzed using TEM images. Figure 4 shows a TEM image of AgNPs biosynthesized from ethanolic extract of F. deltoidea leaves. The AgNPs-Fd shape was spherical in nature. The AgNPs-Fd were surrounded by a faint, thin layer of other substances, which were assumed to be organic material from the F. deltoidea extract. Few particles were agglomerated among the 20 nm nanoparticles that were produced. A recent study performed by Ref. 34 mentioned that the TEM results of the AgNPs mediated using Terminalia arjuna leaf extract have spherically-shaped nanoparticles approximately 10–50 nm in size.\n\nYellow markings and notations in the TEM image have been made by using Adobe Photoshop. TEM, transmission electron microscope; AgNPs-Fd, silver nanoparticles synthesized using Ficus deltoidea extract.\n\nThe crystalline nature of the biosynthesized AgNPs-Fd was evaluated using XRD. The XRD pattern obtained revealed that AgNPs-Fd had a face-centered spherical structure in nature (Figure 5), and there were several characteristic diffraction peaks indexed from 21.386 to 76.655.\n\nXRD, X-ray diffraction; AgNPs-Fd, silver nanoparticles synthesized using Ficus deltoidea extract.\n\nBiomolecules for the capping and effective stability of the metal nanoparticles produced using the ethanolic extract of F. deltoidea leaves were identified through FTIR analysis. Figure 6 presents the FTIR spectrum of AgNPs-Fd. The bands at 3,356, 3,200, and 3,243 cm-1 correspond to H-bonded alcohols and phenols with O-H stretching. The signals at 2,917 and 2,849 cm-1 correspond to carboxylic acids with an O-H stretch. The assignments in 1,711, 1,610, 1,516, and 1,449 cm-1 correspond to primary amines with a bent N-H. The peak at 1,376 cm-1 relates to C-N stretching of an aromatic amine group, and the band at 1,242 cm-1 pertains to a C-N bond, which is either an amine or an amide molecule.\n\nFTIR, Fourier transform infrared spectroscopy; AgNPs-Fd, silver nanoparticles synthesized using Ficus deltoidea extract.\n\nPhytosterols appear to suppress carcinogen generation, cancer cell development, angiogenesis, invasion, and metastasis, as well as promote apoptosis in malignant cells through a variety of methods. Phytosterol consumption potentially increases the activity of antioxidant enzymes, lowering oxidative stress.35 The present study found several phytosterols in the AgNPs-Fd biosynthesized using ethanolic extract of Ficus deltoidea leaves (Figure 7 and Table 1).\n\nAgNPs-Fd, silver nanoparticles synthesized using Ficus deltoidea extract.\n\nAgNPs-Fd, silver nanoparticles synthesized using Ficus deltoidea extract.\n\nThe CAM assay is commonly used as an in vivo testing system for anti-angiogenesis research. It has the advantage of being cost-efficient and lends itself to large-scale screening by testing the efficacy of an inhibitor using various stimulators alone or in combination with an anti-angiogenic medication. The present study used AgNPs-Fd as an anti-angiogenic compound and found that AgNPs-Fd at 90 μg in the CAM analysis resulted in higher anti-angiogenic activities than other treatment groups. The anti-angiogenic activities were demonstrated through the reduction of vessel area, total number of junctions, junction density, total vessel length, average vessel length and the total number of endpoints (Table 2).\n\n\nDiscussion\n\nThe green synthesis of nanoparticles using biological systems, particularly plant extracts, is an emerging subject in nanotechnology. Various plant extracts and several methodologies have been investigated to explore the benefits of these nanomaterials. In the field of medicine, specifically angiogenesis, which is an essential physiological process and important in several pathological diseases, including tumor development and metastasis, the utilization of plant extracts is a low-cost and environmentally friendly method for producing nanoparticles. The present work aimed to investigate the anti-angiogenic properties of AgNPs biosynthesized using the ethanolic extract of F. deltoidea leaves on chick CAMs.\n\nIn the biosynthesis of the nanoparticles, the color change in is an indicator of AgNPs-Fd formation. Similar findings were revealed by Anju and Parvathy,36 who mentioned that the visual confirmation of AgNPs generation via green synthesis is possible by evaluating the color shift. The color shift is caused by the reduction of silver ions (Ag+) to AgNPs37 and is facilitated by bioactive phytochemicals in the F. deltoidea leaf extract, such as flavonoids.38 Flavonoids may be responsible for the rapid reduction and capping of Ag+ into AgNPs-Fd observed in this research. The flavonoids in F. deltoidea leaf extracts are potent reducing agents, suggesting that AgNPs-Fd may be synthesized by AgNO3 reduction. The flavonoid components of F. deltoidea ethanolic extract may actively be involved in and liable for Ag+ to silver (II) oxide (Ag0) reduction.39 Another investigation also found that water-soluble flavonoids were involved in the reduction of metal ions utilizing plant extracts.40\n\nMeanwhile, the Tyndall effect was especially relevant to colloidal suspensions at room temperature, with the production of AgNPs-Fd exhibiting an immediate pale brown color. It also demonstrated that the AgNPs-Fd were strongly formed and stable in the aqueous phase, with no precipitation.41 Furthermore, previous reports on AgNPs revealed that absorbance at approximately 430 nm UV-Vis spectrophotometer is a hallmark of the noble metal particles.42 It was noticed that the surface plasmon resonance at 430 nm indicated the retention of AgNPs-Fd in the colloidal solutions due to the emergence of the pale brown color for particle stabilization.\n\nCharacterization of resulting AgNPs-Fd using TEM found few particles had a size of about 20 nm. A past study performed previously34 mentioned that the TEM results of the AgNPs mediated using Terminalia arjuna leaf extract have spherically shaped nanoparticles approximately 10–50 nm in size. In addition, the crystalline nature of the biosynthesized AgNPs-Fd detected using XRD revealed that AgNPs-Fd have a face-centered spherical structure in nature, and there were several characteristic diffraction peaks indexed from 21.386 to 76.655, which contained some functional groups.\n\nAmines/proteins and metabolites comprising functional groups of alcohols, ketones, aldehydes and carboxylic acids surrounded the generated AgNPs-Fd. The carbonyl group of amino acid residues and proteins has the highest capacity to bind metal, suggesting that proteins may be able to encapsulate metal nanoparticles, including AgNPs, to avoid agglomeration and stabilize the medium.43 The present study identified an assortment of chemicals compounds of AgNPs-Fd that were detected through GC-MS analysis. From Figure 7 and Table 1, the GC-MS of AgNPs-Fd contains several bioactive compounds that have anti-angiogenic and anticancer activities, such as phytol (PHY), stigmasterol, lupeol and sitosterol.\n\nPrevious studies revealed that PHY, or 3,7,11,15-tetramethylhexadec-2-en-1-ol, has anticancer properties and a variety of pharmacological features, including toxicity and cytotoxicity. Furthermore, PHY modulates pro-carcinogens as well as produced genotoxicity and death in breast cancer cells. It has also demonstrated DNA damage repair capabilities in mouse lymphocytes.44 Additionally, PHY increases the activity of natural killer cells, which identify and eliminate cancer cells, and stimulates macrophage roles in immunity.45 Phytol exhibits anti-angiogenic properties by inducing apoptosis in cancer cells, such as lung adenocarcinoma cells.46\n\nMeanwhile, stigmasterol and lupeol are potent compounds that exhibit anti-angiogenic properties. Stigmasterol and lupeol are two major phytosterols found in many herbal plants, with anti-inflammatory properties and have been proposed as anticancer agents. Though their mechanisms in inhibiting cancer are unclear, past studies report that cell survival, migration, and morphogenesis of human umbilical vein endothelial cells, but not cholangiocarcinoma cells, were inhibited by stigmasterol and lupeol. Both compounds lowered the transcript level of tumor necrosis factor-α considerably in expression studies.47\n\nFurthermore, a growing body of research suggests that β-sitosterol (BSS) may have anti-angiogenic properties. BSS impedes synovial angiogenesis by inhibiting the proliferation and migration of endothelial cells.48 Current findings align with previous research performed by Nurhidayati et al.49 who used the ethanol extract of Ficus septica Burm. f. leaves, revealing that the number of new blood vessels had been decreased as the dose of the extract increased. The anti-angiogenic effects of AgNPs-Fd also involved the phytochemical contents in the nanomaterial, which was produced during the biosynthesis of the AgNPs.\n\nFurther, the application of 90 μg AgNPs-Fd in the CAM assay had similar effects of anti-angiogenic activities to the positive control (cortisone acetate 30 μg and 30 ng bFGF), which confirms its anti-angiogenic properties. Cortisone acetate acts as an inhibitor of angiogenesis in CAM chicken embryos. Cortisone acetate is a corticosteroid compound in the glucocorticoid class, which is typically used in the treatment of angiogenesis-related diseases such as diabetic retinopathy and solid tumors. Meanwhile, glucocorticoids also regulate angiogenesis through several mechanisms, namely suppressing the proliferation, migration and growth of endothelial cells and reducing the secretion or expression of cytokines.50,51\n\n\nConclusions\n\nF. deltoidea leaves can be used as a reductor agent for the biosynthesis of AgNPs. Color change and Tyndall effects were an indicator of green synthesis of AgNPs-Fd. The surface plasmon resonance, which was identified at 430 nm, is the optimum peak of AgNPs-Fd. Several phytochemically active groups were identified in AgNPs-Fd using FTIR analysis, and it was observed that the morphology of the AgNPs-Fd had particle sizes of 20 nm, based on TEM characterization. The GC-MS analysis of the Fd leaf extract and AgNPs-Fd highlighted potential anti-angiogenic compounds, such as phytol, stigmasterol, lupeol and sitosterol. Fd or AgNPs-Fd treatments at 90 μg doses demonstrated significant anti-angiogenesis in CAM chicken embryo analysis, indicating greater effectiveness in controlling vessel formation. The AgNPs-Fd displayed anti-angiogenesis properties as indicated by the reduction of vessels in the CAM model. The anti-angiogenic properties of AgNPs-Fd in the CAM model were exhibited through the parameters of vessel area, total number of junctions, junction density, average vessel length and total number of end points. The 90 μg of AgNPs-Fd provided optimal anti-angiogenic effects. From a technical standpoint, the resulting AgNPs-Fd offer a simple technique to synthesize AgNPs. This method contains various benefits, such as cost-effectiveness, suitability for medical and pharmaceutical applications, and large-scale commercial manufacturing potential. The present research also suggested that AgNPs mediated by F. deltoidea leaf ethanolic extract have potential as anti-angiogenic agents.",
"appendix": "Data availability\n\nFigshare: Raw data antiangiogenic 2022, https://doi.org/10.6084/m9.figshare.22256071. 52\n\nThis project contains the following underlying data:\n\n- Raw data GCMS (Table 1 and Figure 7).zip\n\n- Raw data FTIR (Figure 6).zip\n\n- Spectrophotometer data (Figure 3).xlsx\n\n- Raw image TEM Tbat barito.tif\n\n- Raw data for XRD (Figure 5).zip\n\nFigshare: ARRIVE checklist for ‘Anti-angiogenic activity of Ficus deltoidea L. Jack silver nanoparticles using chorioallantoic membrane assay’, https://doi.org/10.6084/m9.figshare.22090673. 53\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nAll authors thank Ministry of Education, Culture, Research and Technology, Indonesia for grant funding financial year: 2022. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nQian K, Zheng XX, Wang C, et al.: β-Sitosterol Inhibits Rheumatoid Synovial Angiogenesis Through Suppressing VEGF Signaling Pathway. Front. Pharmacol. 2021; 12: 816477. Publisher Full Text\n\nNurhidayati LG, Nugroho AE, Retnoaji B, et al.: Antiangiogenesis Activity of Awar-Awar Leaf Extract (Ficus Septica Burm. F.) In Chorioallantoic Membrane Assay. Indonesian J. Pharm. 2021; 32(1). Publisher Full Text\n\nLiu B, Goodwin JE: The effect of glucocorticoids on angiogenesis in the treatment of solid tumors. J. Cell. Signal. 2020; 1(3): 42–49. PubMed Abstract | Publisher Full Text\n\nPietras RJ, Weinberg OK: Antiangiogenic steroids in human cancer therapy. Evid. Based Complement. Alternat. Med. 2005; 2(1): 49–57. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNugroho R: Raw data antiangiogenic 2022. [Dataset]. figshare. 2023. Publisher Full Text\n\nNugroho R: ARRIVE. [Dataset]. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "295259",
"date": "06 Jul 2024",
"name": "Ramón Marcos Soto-Hernández",
"expertise": [
"Reviewer Expertise Phytochemistry",
"natural products isolation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript describes the anti-angiogenic activity of F. deltoidea L. Jack silver nano particles using chorioallalntoic membrane assay, and apparently seems quite interesting, but the authors should consider some details to increase its quality. Some of them are: 1. In the extraction process, there is a lack of some details as the duration of the extraction: what method was used to conduct the process (maceration, Soxhlet, ultrasound, etc). In the analysis by GC-EM also there are missing some details as retention times, Kovax index, relative abundance. These data are important because they could be related to the biological activity detected. The conclusions should be re written considering these details.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-544
|
https://f1000research.com/articles/12-542/v1
|
24 May 23
|
{
"type": "Data Note",
"title": "Time-resolved small RNA transcriptomics of the ichthyosporean Sphaeroforma arctica",
"authors": [
"Andrej Ondracka",
"Omaya Dudin",
"Jon Bråte",
"Andrej Ondracka",
"Omaya Dudin"
],
"abstract": "Ichthyosporea, a clade of holozoans, represent a clade closely related to animals, and thus hold a key phylogenetic position for understanding the origin of animals. We have previously discovered that an ichthyosporean, Sphaeroforma arctica, contains microRNAs (miRNAs) as well as the miRNA processing machinery. This was the first discovery of miRNAs among the closest single-celled relatives of animals and raised intriguing questions about the roles of regulatory small RNAs in cell development and differentiation in unicellular eukaryotes. Like many ichthyosporeans, S. arctica also undergoes a transient multicellular developmental life cycle. As miRNAs are, among other roles, key regulators of gene expression during development in animals, we wanted to investigate the dynamics of miRNAs during the developmental cycle in S. arctica. Here we have therefore collected a comprehensive time-resolved small RNA transcriptome linked to specific life stages with a substantially higher sequencing depth than before, which can enable further discovery of functionally relevant small RNAs. The data consists of Illumina-sequenced small RNA libraries from two independent biological replicates of the entire life cycle of S. arctica with high temporal resolution. The dataset is directly linked and comes from the same samples as a previously published mRNA-seq dataset, thus enabling direct cross-functional analyses.",
"keywords": [
"Ichthyosporea",
"Sphaeroforma arctica",
"small RNA",
"microRNA",
"miRNA",
"gene regulation",
"cell differentiation",
"origin of animals"
],
"content": "Introduction\n\nIchthyosporeans hold a key position in the evolutionary tree for understanding the origin of animals and animal multicellularity. Ichthyosporea is a clade of holozoans, of which many characterized representatives undergo multinucleate (coenocytic) life cycles and exhibit a transient multicellular stage during cellularization of the coenocytes.1,2 Among ichthyosporeans, the life cycle of Sphaeroforma arctica has been best characterized. Multiple nuclear division cycles in a single cell occur with highly regular timing, forming multinuclear coenocytes,3 which is followed by actomyosin-dependent cellularization.4 The whole life cycle has been characterized through mRNA transcriptomics, showing dynamic transcriptional regulation during the life cycle, including transcriptional regulation of the putative key regulators of cellularization.4\n\nmicroRNAs (miRNAs) are short RNA molecules that, among many roles, regulate the activity of genes important for multicellular development in both animals and plants (e.g., Refs. 5, 6). Although miRNAs have been reported from other eukaryote groups spanning the tree of life, such as brown and green algae (e.g., Refs. 7, 8) Amoebozoa (e.g., Ref. 9) excavates (e.g., Ref. 10) and unicellular Holozoa,11 their presence and function in many cases remain controversial.12 Nevertheless, these discoveries raise the intriguing question of whether small regulatory RNAs also play a role during development in unicellular and facultatively multicellular organisms. To understand whether miRNAs play a role in its development, we collected a high-quality small RNA dataset in S. arctica at both high depth and high temporal resolution throughout its entire developmental cycle.\n\n\nMethods\n\nThe purpose of this study was to generate a dataset in order to (1) investigate the temporal dynamics of miRNA expression in S. arctica and to provide potential functional insights into the miRNAs, (2) discover novel miRNA genes in S. arctica, and (3) discover other potentially functionally relevant small RNAs, such as piRNAs (e.g., Refs. 13, 14).\n\nWe have acquired high throughput sequencing datasets of the fraction of RNA molecules smaller than approximately 200 nucleotides (small RNAs). We have isolated and sequenced the small RNA content from synchronized cultures every six hours over a period of 72 hours, spanning the entire cell cycle. The sequencing was done in two biological replicates. The experiment was performed in parallel with the previously published mRNA transcriptome dataset4 and the small RNA libraries were prepared from the same total RNA samples; thus, the present dataset can be analyzed simultaneously with the mRNA data.\n\nThe cultures were prepared according to the protocol originally described in Ref. 4. In detail, S. arctica cells were cultured in Marine Broth media (Marine Broth, Difco BD, NJ, USA; 37.4 g/L) in sterile culture flasks at 12°C in dark conditions. The cultures were grown to a stationary phase, which has been shown to synchronize the coenocytic cycles (see Ref. 3). At the start of the experiment, the saturated cultures were diluted 1:300 into fresh marine broth media. Aliquots were collected every six hours for 72 hours, spanning an entire coenocytic life cycle. RNA was extracted using the miRNeasy Mini Kit (QIAGEN, Venlo, Netherlands) from approximately 50 mL of culture for each culture aliquot, and RNA integrity was evaluated using a Bioanalyzer 2100 (Agilent, CA, US).\n\nThe small RNA libraries were prepared using the NEBNext Small RNA Library Prep Set for Illumina (New England Biolabs, MA, US). A total of 50 bp single-end reads were obtained by sequencing the libraries on the Illumina HiSeq 2500 platform with the v4 chemistry and high output mode. Library preparation and sequencing was carried out by the CRG Genomics core unit, Barcelona, Spain. The data presented here is not processed in any way. The sequencing libraries contained on average 22.7 million reads (SD = 5.3 mill reads). Together, this data represents a more than 40-fold higher sequencing depth than the previous study,11 where small RNA reads were obtained from only two samples.\n\nThe small RNA extractions were sequenced as is, without any external, or spiked-in, controls.",
"appendix": "Data availability\n\nEuropean Nucleotide Archive: Sphaeroforma arctica small RNAs. Accession number PRJEB55646; https://identifiers.org/ena.embl:PRJEB55646\n\nTable 1 details the individual files under accession number PRJEB55646.\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nWe thank Arthur A. B. Haraldsen for discussions and valuable contributions to the project, and the CRG Genomics core unit for library preparation and sequencing.\n\n\nReferences\n\nMendoza L, Taylor JW, Ajello L: The class mesomycetozoea: a heterogeneous group of microorganisms at the animal-fungal boundary. Annu. Rev. Microbiol. 2002; 56: 315–344. Publisher Full Text\n\nJøstensen J-P, Sperstad S, Johansen S, et al.: Molecular-phylogenetic, structural and biochemical features of a cold-adapted, marine ichthyosporean near the animal-fungal divergence, described from in vitro cultures. Eur. J. Protistol. 2002; 38: 93–104. Publisher Full Text\n\nOndracka A, Dudin O, Ruiz-Trillo I: Decoupling of Nuclear Division Cycles and Cell Size during the Coenocytic Growth of the Ichthyosporean Sphaeroforma arctica. Curr. Biol. 2018; 28: 1964–1969.e2. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDudin O, Ondracka A, Grau-Bové X, et al.: A unicellular relative of animals generates a layer of polarized cells by actomyosin-dependent cellularization. elife. 2019; 8: e49801. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBartel DP: Metazoan MicroRNAs. Cell. 2018; 173: 20–51. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoran Y, Agron M, Praher D, et al.: The evolutionary origin of plant and animal microRNAs. Nat. Ecol. Evol. 2017; 1: 0027. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCock JM, Liu F, Duan D, et al.: Rapid Evolution of microRNA Loci in the Brown Algae. Genome Biol. Evol. 2017; 9: 740–749. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMolnár A, Schwach F, Studholme D, et al.: miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii. Nature. 2007; 447: 1126–1129. PubMed Abstract | Publisher Full Text\n\nAvesson L, Reimegård J, Wagner EG, et al.: MicroRNAs in Amoebozoa: deep sequencing of the small RNA population in the social amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs. RNA. 2012; 18: 1771–1782. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuang PJ, Lin WC, Chen SC, et al.: Identification of putative miRNAs from the deep-branching unicellular flagellates. Genomics. 2012; 99: 101–107. PubMed Abstract | Publisher Full Text\n\nBråte J, Neumann RS, Fromm B, et al.: Unicellular Origin of the Animal MicroRNA Machinery. Curr. Biol. 2018; 28: 3288–3295.e5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTarver JE, Donoghue PCJ, Peterson KJ: Do miRNAs have a deep evolutionary history? BioEssays. 2012; 34: 857–866. PubMed Abstract | Publisher Full Text\n\nOzata DM, Gainetdinov I, Zoch A, et al.: PIWI-interacting RNAs: small RNAs with big functions. Nat. Rev. Genet. 2019; 20: 89–108. PubMed Abstract | Publisher Full Text\n\nGrimson A, Srivastava M, Fahey B, et al.: Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature. 2008; 455: 1193–1197. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "252697",
"date": "01 Apr 2024",
"name": "Rafał Milanowski",
"expertise": [
"Reviewer Expertise Phylogeny",
"evolution and genomics of protists"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIchthyosporea is a group of Opisthokonta that plays a crucial role in discussions about the origins of animals and animal multicellularity. The Data Note article by Ondracka et al. describes the previously unpublished small RNA transcriptome associated with specific life stages of the ichthyosporean species Sphaeroforma arctica. This dataset holds the potential to facilitate further discovery of functionally relevant small RNAs in this species.\nThe methodological section of the manuscript provides detailed procedures for culturing, RNA extraction, library preparation, and sequencing, thereby enabling the replication of all experiments. Data files are well-organized, summarized in a table, and deposited in the RNA database under a unique accession number. The references are thoughtfully selected, offering opportunities for deeper exploration of the topic.\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
},
{
"id": "248045",
"date": "11 May 2024",
"name": "Arkadiy Garber",
"expertise": [
"Reviewer Expertise My area of expertise is in microbiology",
"bioinformatics",
"and evolutionary biology. I also have a background in molecular biology (including DNA and RNA)."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this data report, Ondracka and Dudin present a number of small RNA libraries corresponding to different life stages of ichthyosporean Sphaeroforma arctica. I believe that this data will be very useful to the research community. My only recommendation to the methods would be to more explicitly state how S. arctica cells were processed for RNA extraction. For example, how were the cells lysed? Was there any centrifugation to pellet the cells or cell debris? Was there any rRNA depletion done during library prep?\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-542
|
https://f1000research.com/articles/12-538/v1
|
23 May 23
|
{
"type": "Clinical Practice Article",
"title": "Coexisting nephrotic syndromes influences in st elevation myocardial infarction patient and chronic limb-threatening ischemia patient: is there any correlation?",
"authors": [
"Iwan Dakota",
"Taofan Taofan",
"Suci Indriani",
"Jonathan Edbert Afandy",
"Mikhael Asaf",
"Swastya Dwi Putra",
"Suko Adiarto",
"Renan Sukmawan",
"Iwan Dakota",
"Suci Indriani",
"Jonathan Edbert Afandy",
"Mikhael Asaf",
"Swastya Dwi Putra",
"Suko Adiarto",
"Renan Sukmawan"
],
"abstract": "Background: ST elevation myocardial infarction (STEMI) and chronic limb-threatening ischemia (CLTI) were cardiovascular emergencies and require urgent reperfusion treatment. Both diseases shared same traditional cardiovascular risk factors. Nephrotic syndrome (NS) patients were known for risk of thromboembolic complications that may present as STEMI or CLTI, result of hypercoagulable state stemming leading to thrombus formation. Case illustration: Three cases were described in a case series. The first case presented with anterior extensive STEMI, coroangiography revealed total occlusion at proximal left anterior descending artery with high burden thrombus, treated with defered stenting and medical therapy. The second case presented with CLTI, imaging modality showed occlusion with thrombus in infra-renal abdominal aorta until bilateral superficial femoral artery (SFA), the patient refused any interventional treatment, so he was treated with medical therapy only. The third case presented with CLTI on left leg and chronic limb ischemia on right leg, imaging modality showed occlusion at left external iliac artery and 1/3 distal of right SFA with prominent plaque calcification, treated with percutaneous transluminal angioplasty, and medical therapy. All patients achieved significant improvement in the disease. Conclusion: NS is a risk factor for STEMI and CLTI. Even corticosteroids for NS treatment also a risk factor for thromboembolic complications. Controlling the disease severity with precaution of the therapy side effect should be achieved. If thromboembolic complications related to NS happen, the management mainly follows the available guidelines.",
"keywords": [
"nephrotic syndrome",
"acute coronary syndrome",
"STEMI",
"peripheral artery disease",
"chronic limb-threatening ischemia",
"thromboembolism",
"young adult"
],
"content": "Introduction\n\nAcute coronary syndromes (ACS) are clinical entity characterized by a sudden reduction in blood supply to the heart and often reflects a degree of damage to the coronary arteries by atherosclerosis; plaque rupture, thrombosis, and inflammation.1,2 The current classification of ACS depends on Electrocardiogram (ECG) findings at admission: non-ST Elevation Myocardial Infarction and ST Elevation Myocardial Infarction (STEMI) representing the most dangerous form of the pathology and therefore requiring urgent reperfusion treatment.3 Chronic limb-threatening ischemia (CLTI) is a manifestation of peripheral arterial disease that is characterized by chronic, inadequate tissue perfusion at rest.4 CLTI is defined by the presence of peripheral artery disease (PAD) in combination with rest pain or tissue loss (gangrene, ulceration) for more than two weeks duration.5 Both ACS and PAD shared the same traditional cardiovascular risks factors such as advanced age, male sex, smoking, hypertension, diabetes, and dyslipidemia.1,6\n\nNephrotic syndrome (NS) is a condition characterized by the presence of peripheral edema, heavy proteinuria, and hypoalbuminemia, often with hyperlipidemia. The syndrome can be due to intrinsic renal disease or secondary to an underlying medical condition.7 Patients with NS have long been assumed to be at increased risk for atherosclerosis and cardiovascular disease because of NS-associated hyperlipidemia and hypertension.8 NS patients were also at risk of thromboembolism that may form in either arteries or veins result of the hypercoagulable state stemming from imbalances in the coagulation cascade leading to thrombus formation that obstructs blood flow.8,9\n\nAlthough NS-caused venous thromboembolism is well recognized, arterial thrombosis has rarely been reported.10 This case series aims to describe a case of STEMI and two cases of CLTI in young adults with nephrotic syndrome and how to overcome the disease in National Cardiovascular Center, Harapan Kita, Jakarta, Indonesia.\n\n\nCase illustration\n\nA 29-year-old Javanese male presented with chest pain radiating to his left arm followed by sweating, nausea, and vomiting for the last 18 hours. He has been diagnosed with nephrotic syndrome in the past 12 years without any other risk factors such as hypertension, dyslipidemia, diabetes mellitus, smoking, or family history. He consumed steroids for NS but stopped this medicine for the last 2 months.\n\nPhysical examination revealed high blood pressure with normal heart rate and fever with temperature of 38°C. Chest auscultation showed crackles in both lungs without any rales or wheezing. ECG on 18 hours of chest pain onset showed ST elevation and pathological Q waves in V1-V6, I, and aVL (Figure 1A). Laboratory examination showed leukocytosis, high level of high-sensitive troponin T, hypoalbuminemia, proteinuria, and hyperlipidemia. Chest X-ray revealed infiltrate in both lungs. Echocardiography showed reduced left ventricular ejection fraction (LVEF) of 43%, hypokinetic at anterior and lateral segments, and left ventricle thrombus.\n\nA. After 18 hours onset of chest pain, ST elevation and pathological Q waves were seen in V1-V6, I, and aVL. B. After percutaneous coronary intervention and medical therapy, no dynamic ST-T changes was seen in the ECG.\n\nThe patient was diagnosed with STEMI anterior extensive, Killip I, TIMI 3/14, nephrotic syndrome, and community-acquired pneumonia. Coroangiography (CAG) revealed total occlusion at proximal left anterior descending (LAD) artery, thrombus grade 5, and TIMI flow 1 (Figure 2A). The patient was then planned to receive plain old balloon angioplasty (POBA) in LAD. After multiple attempts of extensive POBA, CAG showed TIMI flow 1 with residual thrombus in LAD and shifting thrombus to distal left circumflex artery (LCx) (Figure 2B). It was decided to defer further maneuvers and proceeded to medical treatment with intravenous antiplatelet infusion and anticoagulan.\n\nA. Before percutaneous coronary intervention, total occlusion at proximal left anterior descending artery, thrombus grade 5, and TIMI flow 1. B. After percutaneous coronary intervention, TIMI flow 1 with residual thrombus in LAD and shifting thrombus to distal left circumflex artery. C. After 4 months follow-up, normal coronary arteries without any apparent atherosclerotic lesion.\n\nThe patient received eptifibatide infusion, heparinization, oral dual antiplatelet with aspirin and ticagrelor, ACE inhibitor, statin, nitrate, and antibiotic. On the following day, there was no chest pain and ECG did not show any dynamic ST-T changes (Figure 1B). The patient was then received steroid therapy and discharged with stable condition. Four months later, without any signs and symptoms, he underwent CAG that showed normal coronary arteries without any apparent atherosclerotic lesions (Figure 2C).\n\nA 30-year-old Sundanese male presented with a chief complaint of wound in his leg since 6 months ago accompanied by resting pain. At first, he complained of pain in both legs when walking for distance in the past 6 years. The patient had history of NS since 12 years ago, but he didn’t take any medication routinely. He was also a smoker, smoking 1 pack of cigarettes per day. He denied history of hypertension and diabetes mellitus.\n\nHis vital signs were within normal limits. Physical examination showed cold extremities, non-palpable bilateral dorsalis pedis artery pulsation, and gangrene on left toe (Figure 3A). Significant laboratory examination results were erythrocyte sedimentation rate of 99 mm/hour, D-dimer of 3250 ng/mL, fibrinogen of 734 mg/dL, albumin of 0.8 g/dL, total cholesterol of 347 g/dL, LDL of 257 g/dL, HDL of 54 g/dL, triglyceride of 278 g/dL, +3 urinary protein with 24-hour urinary protein of 19840 mg/24 hour. Left ankle brachial index (ABI) of the patient was 0.25 and right was 0.33. Lower extremity duplex ultrasound (DUS) was consistent with lower extremity CT-Scan Angiography (CTA) revealed occlusion with thrombus in abdominal aorta starting from 2 cm below renal artery until bilateral superficial femoral artery (SFA), distal flow filled from collateral from branch of coeliac trunk and branch of superior mesenteric artery (Figure 4).\n\nA. Gangrene was seen on the left toe at presentation. B. Resolution of gangrene after 3 weeks follow-up.\n\nOcclusion with thrombus in abdominal aorta starting from 2 cm below renal artery until bilateral superficial femoral artery, distal flow filled from collateral from branch of coeliac trunk and branch of superior mesenteric artery.\n\nThe patient was diagnosed with CLTI (Rutherford III-5, WIFi Score 2-3-0) in aortio-iliaca occlusive disease, TASC II type D lession, and nephrotic syndrome. The patient unfortunately refused any intervention therapy. Then, he was planned for albumin transfusion, methylprednisolone therapy with titration method, heparinization, clopidogrel, lumbrokinase, simvastatin, diltiazem, candesartan, and some supportive symptomatic medication. After 5 days, the patient was discharged with lesser degree of leg pain. His albumin increased to 2.9 g/dL and better 24-hour urinary protein of 5685 mg/24 hour. His take-home medications were 3 × 16 mg methylprednisolone, 1 × 75 mg clopidogrel 1 × 75mg, 1 × 40 mg simvastatin, 1 × 16 mg candesartan, and 1 × 100 mg diltiazem. Follow-up after 3 weeks showed significant leg pain improvement and resolution of gangrene (Figure 3B).\n\nA 32-year-old Javanese male presented with chief complaints of leg pain. The pain has been experienced for one year, at first, felt only when walking for distances, but it got worse, and he started to feel resting pain in the past one month. The patient had nine years history of NS confirmed by kidney biopsy with result of focal segmental glomerulosclerosis. He denied history of hypertension, diabetes, or smoking. At presentation, he took 2 × 360 mg mycophenolic acid and 1 × 8 mg methylprednisolone daily.\n\nVital signs were within normal limits. Physical examination revealed ulcer, hair loss, and atrophy on the left leg (Figure 5). Significant laboratory examination results were D-Dimer of 2990 ng/mL, total cholesterol of 233 g/dL, LDL of 187 g/dL, triglycerides of 164 g/dL, and urine albumin of 413 mg/L. His serum albumin was normal (184 g/dL). His right ABI was 0.5 on left was 0.33. Lower extremity DUS and CTA showed occlusion at level of left external iliac artery and 1/3 distal of right SFA with prominent plaque calcification (Figure 6A).\n\nUlcer (covered by bandage), hair loss, and atrophy were seen on the left leg.\n\nA. Pre-intervention, occlusion at level of left external iliac artery and 1/3 distal of right superficial femoral artery with prominent plaque calcification. B. Before 2nd intervention, positive flow until distal of the left leg with patent stent.\n\nThe patient’s diagnosis at the time was CLTI with ulcer on the left leg (Rutherford III-5, WIFi Score 1-3-0), chronic limb ischemia on the right leg (Rutherford I-3, WIFi Score 0-2-0), TASC II type D lession, and nephrotic syndrome. He was treated with heparinization and two episodes of percutaneous transluminal angioplasty (PTA). First, with POBA done at left Iliac Artery and SFA with addition of 6.0 × 120 mm drug-eluting stent (DES) overlapped with 6.0 × 80 mm (Boston Scientific, Marlborough, MA, USA) at SFA (Figure 7A). Second, POBA at mid–distal right SFA 5 months later (Figure 7B). CTA after the first procedure (Figure 6B) and angiography after second procedure with lower extremity DUS confirmed positive flow until distal vessel of both lower limbs. The patient was discharged without any complaint and received rivaroxaban, clopidogrel, aspirin, simvastatin, mycophenolic acid, and methylprednisolone as his routine medication. he was also educated to do exercise therapy.\n\nA. First intervention, contrast flow until distal of left leg artery after percutaneous transluminal angioplasty. B. Second intervention, contrast flow until distal of right leg artery after percutaneous transluminal angioplasty.\n\n\nDiscussion\n\nAccording to a publication by Mahmoodi, et al.,11 the annual incidence of arterial thromboembolism rate in NS patients was 1.48%. The most common first ATE presentation in NS patients was myocardial infarction (44%), followed by unstable angina pectoris (14%), peripheral artery disease (14%), ischemic stroke (11.5%), cerebral transient ischemic attack (11.5%), amaurosis fugax (2%), and aorta thrombosis (2%).\n\nThe pathophysiology of ATE in NS patients hasn’t known clearly. It was postulated that protein plasma alteration involves coagulation and fibrinolysis disturbance, increased aggregation of platelet, low albumin plasma, hyperviscosity, and dyslipidemia.11,12 Chronic excessive proteinuria with long-term abnormal hemostasis and lipid profiles such as in NS patients.13 There are three proposed mechanisms related to the hypercoagulable state in NS patients. First, enhanced coagulation related to low molecular weight protein loss such as factors IX, XI, and XII from urine, thereby the liver increased synthesis of factors II, VII, VIII, X, XIII, and fibrinogen to compensate the hypoalbuminemia state. Second, decreased anticoagulation such as Antithrombin III that has been observed in low serum albumin condition. Third, fibrinolytic system imbalance related to decreased levels of plasminogen and raised levels of plasminogen activator that correlate with the degree of hypoalbuminaemia.\n\nOur 1st and 2nd patient were in acute phase of nephrotic syndrome which may increase the predisposition to develop thromboembolic events with known low levels of serum albumin. Thromboses are frequent at plasma albumin levels <2 g/dl.14 However, our 3rd patient had good control of the disease, known from relatively normal serum albumin. We suspected that long-term corticosteroid use by our patient promotes a hypercoagulable state since it increased factors II, V, VII, IX, X, and XII and fibrinogen, thereby increasing risk for thrombosis.15 Hyperlipidemia in all of our patients is also known to be a risk factor for thrombosis since it induced platelet hyperaggregability.16\n\nCurrently, there is no consensus according to the management of thromboembolic complications related to NS.17 The management mainly follows the available guidelines and depends on the location and hypercoagulable state. We found that the 1st, patient possible pathogenesis of myocardial infarction is due to coronary thrombosis which is shown by high burden thrombus (HTB) in CAG. Publication by Xie, et al.13 supported our findings by showing that most NS patients CAG identified acute coronary thrombosis rather than atheromatous plaque. A thrombus in coronary artery with a score of ≥4 is defined as high thrombus burden (HTB), which deferred stent placement has been associated with a better outcome.18 Pharmacological therapies that are used for HTB treatment include antiplatelet, anticoagulant, thrombolytic, statins, and vasodilators.\n\nIn CLTI, existing evidence argues strongly for selective revascularization based on specific clinical and anatomical criteria for optimal treatment.5 Endovascular intervention in CLTI relies upon the ability to cross the Femoro-Popliteal lesion, including techniques for vessel preparation and definitive therapy.19 Unfortunately, there is only a small number of publications for guidance to choose specific endovascular techniques for CLTI patients. CLTI patients are recommended to receive pharmacological therapy with antiplatelet and moderate-to-high-intensity statin therapy to reduce the risk of major adverse cardiovascular events. For patients that are not suitable for revascularization, there are few options for non revascularization interventions, pharmacotherapy, and conservative management. We would like to choose endovascular approach for our 2nd and 3rd patient, however, the 2nd patient refused any intervention, so we optimized the pharmacological therapy. Both of our patients achieved significant improvement in the disease.\n\nTreatment of NS patients with immunosuppressive therapy combined with steroids can reduce disease activity, which reduced approximately 40% risk of progression to end-stage renal disease compared to no treatment or supportive treatment alone.20 Prophylaxis for thromboembolism also can be given to NS patients depending on histological subtype, bleeding risk, and serum albumin level, which are received by our patients.21\n\n\nConclusion\n\nWe’ve reported three cases of NS-caused arterial thromboembolism complication in young patient. NS is a risk factor for STEMI and CLTI due to thrombosis and/or atherosclerotic processes. Even corticosteroids for NS treatment also induce a hypercoagulable state and become risk factor for thromboembolic complications. Controlling the disease severity with precaution of the therapy side effect should be achieved. If thromboembolic complications related to NS happen, the management mainly follows the available guidelines.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and clinical images was obtained from the patients.",
"appendix": "Acknowledgements\n\nWe would like to thank the patients for allowing us to have their case published.\n\n\nReferences\n\nRalapanawa U, Kumarasiri PVR, Jayawickreme KP, et al.: Epidemiology and risk factors of patients with types of acute coronary syndrome presenting to a tertiary care hospital in Sri Lanka. BMC Cardiovasc. Disord. 2019 Oct 21; 19(1): 229. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBhatt DL, Lopes RD, Harrington RA: Diagnosis and Treatment of Acute Coronary Syndromes: A Review. JAMA. 2022 Feb 15; 327(7): 662–675. Publisher Full Text\n\nDiop KR, Mingou JS, Beye SM, et al.: Epidemiological Aspect of ST-Segment Elevation Myocardial Infarction (STEMI) in Saint-Louis of Senegal. World J. Cardiovasc. Dis. 2022 Dec 20; 12(12): 544–555. Publisher Full Text\n\nFarber A: Chronic Limb-Threatening Ischemia. N. Engl. J. Med. 2018 Jul 12; 379(2): 171–180. Publisher Full Text\n\nConte MS, Bradbury AW, Kolh P, et al.: Global vascular guidelines on the management of chronic limb-threatening ischemia. J. Vasc. Surg. 2019 Jun; 69(6 Suppl): 3S–125S.e40. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAday AW, Matsushita K: Epidemiology of Peripheral Artery Disease and Polyvascular Disease. Circ. Res. 2021 Jun 11; 128(12): 1818–1832. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTapia C, Bashir K: Nephrotic Syndrome. StatPearls. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2023 Mar 13]. Reference Source\n\nCharfeddine S, Yousfi C, Maalej B, et al.: Acute myocardial infarction in a child with nephrotic syndrome. Rev. Port. Cardiol. Engl. Ed. 2021 Jun 1; 40(6): 457.e1–457.e4. PubMed Abstract | Publisher Full Text\n\nKerlin BA, Ayoob R, Smoyer WE: Epidemiology and Pathophysiology of Nephrotic Syndrome–Associated Thromboembolic Disease. Clin. J. Am. Soc. Nephrol. CJASN. 2012 Mar; 7(3): 513–520. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKimura A, Nishimura K, Miyasaka S, et al.: A Case of Acute Arterial Thrombosis Caused by Nephrotic Syndrome. Ann. Vasc. Dis. 2010; 3(1): 68–70. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMahmoodi BK, ten Kate MK , Waanders F, et al.: High Absolute Risks and Predictors of Venous and Arterial Thromboembolic Events in Patients With Nephrotic Syndrome. Circulation. 2008 Jan 15; 117(2): 224–230. Publisher Full Text\n\nBoussetta A, Jaber C, Jellouli M, et al.: Thromboembolic complications in children with primary nephrotic syndrome: A Tunisian series. Tunis Médicale. 2022 Jan; 100(1): 33–36.\n\nXie L, Tang Y, Liu J, et al.: Acute myocardial infarction in patients of nephrotic syndrome: a case series. J. Geriatr. Cardiol. JGC. 2017 Jul; 14(7): 481–484. PubMed Abstract | Publisher Full Text\n\nAndrassy K, Ritz E, Bommer J: Hypercoagulability in the nephrotic syndrome. Klin. Wochenschr. 1980 Oct 1; 58(19): 1029–1036. Publisher Full Text\n\nRastoder E, Sivapalan P, Eklöf J, et al.: Systemic Corticosteroids and the Risk of Venous Thromboembolism in Patients with Severe COPD: A Nationwide Study of 30,473 Outpatients. Biomedicines. 2021 Aug; 9(8): 874. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBarale C, Frascaroli C, Senkeev R, et al.: Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia. Biomed. Res. Int. 2018 Oct 1; 2018: 1–11. Publisher Full Text\n\nArrab R, Bourrahouate A, Sbihi M, et al.: Thrombose artérielle du membre inférieur sur un syndrome néphrotique. Nephrol. Ther. 2017 Jun 1; 13(4): 248–250. PubMed Abstract | Publisher Full Text\n\nIbanez B, James S, Agewall S, et al.: 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur. Heart J. 2018 Jan 7; 39(2): 119–177. PubMed Abstract | Publisher Full Text\n\nBeckman JA, Schneider PA, Conte MS: Advances in Revascularization for Peripheral Artery Disease: Revascularization in PAD. Circ. Res. 2021 Jun 11; 128(12): 1885–1912. Publisher Full Text\n\nvon Groote TC , Williams G, Au EH, et al.: Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst. Rev. 2021 [cited 2023 Mar 11]; 2021. Publisher Full Text\n\nLin R, McDonald G, Jolly T, et al.: A Systematic Review of Prophylactic Anticoagulation in Nephrotic Syndrome. Kidney Int. Rep. 2020 Apr 1; 5(4): 435–447. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "225876",
"date": "18 Dec 2023",
"name": "Yopie Afriandi Habibie",
"expertise": [
"Reviewer Expertise Cardiovascular Medicine",
"Vascular Surgery",
"Surgery",
"Endovascular Theraphy",
"Thoracic Surgery",
"Cardiac Surgery"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nCongratulations to all the authors for writing a well-written article. In the article, the author shares their experience with three Nephrotic Syndrome patients. However, it would be helpful to add some suggestions about alternative therapies for CLTI patients in the Discussion Chapter, including surgical measures that can be performed for cases unsuitable for endovascular treatment.\n\nIs the background of the cases’ history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the conclusion balanced and justified on the basis of the findings? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-538
|
https://f1000research.com/articles/11-1443/v1
|
06 Dec 22
|
{
"type": "Research Article",
"title": "Oral manifestations associated with Novel Coronavirus Disease - 2019 (COVID-19): A questionnaire based hypothetical study",
"authors": [
"FARAZ MOHAMMED",
"ARISHIYA THAPASUM FAIROZEKHAN",
"SHAMAZ MOHAMED",
"SAUD ABDULLAH ALMOUMEN",
"AMR S. BUGSHAN",
"ZAINAB I. ALMOMEN",
"AMINAH MOHAMMAD ALMOMEN",
"SHASHI KIRAN M",
"KHALID S. ALMULHIM",
"FARAZ MOHAMMED",
"SHAMAZ MOHAMED",
"SAUD ABDULLAH ALMOUMEN",
"AMR S. BUGSHAN",
"ZAINAB I. ALMOMEN",
"AMINAH MOHAMMAD ALMOMEN",
"SHASHI KIRAN M",
"KHALID S. ALMULHIM"
],
"abstract": "Background: Since the Coronavirus disease 2019 (COVID-19) outbreak in 2019, the virus has evolved drastically, presenting with sets of mutations that influence its properties, including transmissibility and antigenicity. The oral mucosa is postulated as probable portal entry and several oral manifestations have been identified, which places dental professionals in a position to recognize probable COVID-19 patients depending on oral signs and symptoms in the initial phases of the disease itself. As co-existing with COVID-19 seems to be a new reality, greater understanding is required regarding early oral signs and symptoms which can be predictors for timely intervention and prevention of complications in COVID-19 patients. The objective of the study is to identify the distinguishing oral signs and symptoms among COVID-19 patients and to establish possible correlation between severity of COVID-19 infection and oral symptoms. Methods: This study recruited 179 ambulatory, non-hospitalized COVID-19 patients from the Kingdom of Saudi Arabia’s Eastern Province's designated hotels for COVID-19 and home isolated patients from the same region using a convenience sample method. Data was collected by qualified and experienced investigators, including two physicians and three dentists, using a validated comprehensive questionnaire through telephonic interviews with the participants. The X2 was used to assess the categorical variables, and odd's ratio was calculated to determine the strength of the association between general symptoms and oral manifestations. Results: Oral and nasopharyngeal lesions or conditions like loss of smell and taste, xerostomia, sore throat, and burning sensation were predictors of COVID-19-related systemic symptoms such as cough, fatigue, fever, and nasal congestion were identified to be statistically significant (p<0.05). Conclusions: The study reveals the occurrence of olfactory or taste dysfunction, dry mouth, sore throat, and burning sensation along with COVID-19 generic symptoms, should be considered as suggestive yet not conclusive indicators of COVID-19.",
"keywords": [
"COVID-19",
"oral symptoms",
"prevalence",
"anosmia",
"ageusia",
"xerostomia."
],
"content": "Introduction\n\nThe outbreak of COVID-19 was followed by a span of evolutionary dormancy. The hallmark of this disease is that it goes undetected for particular period of time, either because it lies dormant or because it is present in just trace amounts. COVID-19 was not detected in nasopharyngeal/sputum samples in many of the instances examined.1 Ever since, COVID-19 has evolved drastically presenting with sets of mutations that influence viral properties, including transmissibility and antigenicity.2 The COVID-19 pandemic has spawned a state of stasis across the world for almost two years. The World Health Organization (WHO), reported 229,373,963 diagnosed cases of COVID-19 with 4,705,111 deaths on September 22, 2021.3\n\nAmple clinical and epidemiological evidence suggests that the COVID-19 virus is extraordinarily virulent, contagious and extensively transmissible among populations by respiratory secretions and via contact and fomites.4 The oral mucosa is thought to be a probable portal of entry for the COVID-19 virus as its cellular entry receptor ACE2 is present in different tissues of oral mucosa, notably in tongue and floor of the mouth.5 With the likelihood of deleterious mutations of COVID-19 virus amidst the new confirmation of effective destruction of some SARS-CoV-2 variants by the newly developed immunizers; it is crucial to have greater understanding of the oral link so that dental professionals can identify potential COVID patients or carriers and provide timely interventions to prevent transmission.\n\nClinical records have proven that self-reported ageusia and anosmia are strong pointers for the detection of COVID-19 even at a preliminary stage of the disease.6 Various COVID-19-related oral symptoms include xerostomia, mucosal ulcerations, sialadenitis, and periodontal disease apart from gustatory dysfunction.7 The initial COVID-19 symptom of loss of taste, that often precedes fever and or other symptoms, corroborates the hypothesis that perhaps oral cavity, in particularly mucosal membrane of tongue, might be an early niche of viral infection.5\n\nSeveral underlying mechanisms have been proposed for COVID-19-related oral manifestations. It is possible that dysregulation of the immune system releases inflammatory cytokines that trigger the onset of oral mucosal ulcers.7 Several studies have mentioned different strategies by which SARS-CoV-2 may induce dysgeusia in COVID-19 patients.8 The proposed mechanisms include neural invasion of the virus into gustatory nerves, direct damage of the taste buds by the virus, angiotensin II hormone imbalance, improper sialic acid function, hyposalivation and hypozincemia.8–13 Direct damage of the salivary glands by the virus, zinc deficiency and inflammatory damage of the glands may cause dry mouth in COVID-19 patients.8,13 SARS-CoV-2 is evident in saliva of patients with COVID-19 and proven to be detected by salivary reverse transcriptase-polymerase chain reaction (RT-PCR) as it is a more sensitive and reliable testing tool than nasopharyngeal swab test.14\n\nDental professionals by virtue of the nature of dental practice procedures are at an increased risk of being exposed to body fluids. Close positioning of dental staff to the patients implies that COVID-19 patients or asymptomatic carriers could easily disseminate the disease to dental professionals, and vice versa if appropriate and adequate protective measures are not taken.15\n\nThis study was designed to identify the distinguishing oral signs and symptoms in COVID-19 patients and to establish a possible correlation between oral symptoms and gravity of COVID-19 infection.\n\n\nMethods\n\nA survey was carried out to determine the prevalence of oral diagnostic features among patients who were diagnosed with COVID-19. The Institutional Review Board of Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia approved the study (IRB# 2020-02-220).\n\nInclusion criteria were based on the diagnostic recommendations for new coronavirus pneumonia (NCIP) of the seventh edition to make sure that the patients included in the research, had positively tested for COVID-19 nucleic acid through the use of RT-PCR or/and next-generation sequencing (NGS) methods before collection of data.16 The study population consisted of ambulatory, non-hospitalized patients who were quarantined in the Kingdom of Saudi Arabia’s Eastern Province’s designated hotels for COVID-19 and those who were home quarantined in the same region. The contact details of the patients were ethically obtained in an anonymous format, without violating the personal privacy of the patients from the authorized COVID-19 testing laboratories’ s Health Electronic Surveillance Network (HESN) database located in the Eastern Province.\n\nA convenience sampling method was adopted for recruiting participants in this study. As it was considerably difficult to get study participants because of the infectious nature of the disease and the social stigma associated with strict COVID-19 protocols, all participants who fulfilled the inclusion requirements and consented were recruited in the study; hence sample size was not taken into consideration. For obtaining consent for participation in the study, a Short Message Service text message (SMS) was sent to all those targeted patients asking them to reply to the same SMS if they were agreeing to involve themselves in the study. Those patients who responded with SMS consent were recruited in the study. Later, one-to-one telephonic interviews were conducted with the respective patients, based on the survey questionnaire, by qualified and experienced investigators including two physicians and three dentists. The study conducted from 21/08/2020 to 07/12/2020.\n\nData collection was done by means of a comprehensive survey questionnaire which was converted into an online format by using the QuestionPro® software, to enquire about the systemic and oral manifestation related symptoms of COVID-19 patients. The questionnaire was in accordance with the current literature available about the novel SARS-CoV-2 and COVID-19, including its unique properties, signs and symptoms, recovery after infection, and methods of prevention. The initial component of the survey form included basic demographic details of the participating patients such as age group, gender and type of profession. The latter part of the questionnaire evaluated the COVID-19-related oral and general signs and symptoms. Patients were also asked to report any history of underlying comorbid conditions like diabetes mellitus, hypertension etc. and psychosocial habits including tobacco and substance abuse. The last part of the questionnaire included the questions related to recovery from COVID-19 infection.\n\nThe questionnaire was checked for face validity by two independent reviewers. Further, to guarantee the clarity and validity of the questions, the survey form was pilot tested on 15 patients. Based on the responses obtained from the pilot study, certain modifications were made; for the same reason these results were eliminated from the final data which was considered for final analysis. Data collection was based only on telephonic interviews and no clinical examination was performed on any of the study subjects.\n\nThe Statistical Package for Social Sciences Software (SPSS V-22, Armonk, NY: IBM Corp) was used to analyse the data. Results were summarised and displayed as frequency distribution tables. The X2 was used to assess the categorical variables, and odd's ratio was calculated to determine the strength of the association between general symptoms and oral manifestations. Statistical significance was inferred when the p value was ≤ 0.05.\n\n\nResults\n\nThe current study was designed to obtain insights about the various oral and nasopharyngeal lesions or conditions among patients with history of COVID-19. Participation in the research study was agreed to by 230 patients by SMS. Data analysis was done based on responses obtained for individual questions telephonically and fed into QuestionPro by 179 COVID-19 patients. Only 179 COVID-19 patients were included for the analysis as few of them did not respond to most questions telephonically. According to sociodemographic data (Figure 1), the study population comprised more females (57.0%) than males (43.0%). The subjects were divided into six age groups; maximum number of subjects (29%) belonged to 21-30 years’ while the pediatric group of subjects aged below 10 years constituted the least number (5.0%). The majority of subjects were non-health professionals (82.7%) and remaining few were engaged in health care related professions (17.3%)\n\nConsidering COVID-19 related symptoms (Table 1), the order of prevalence in decreasing order were Fatigue (75.0%), Body pain (74.1%), Headache (64.1%), Cough (58.7%), Fever (55.2%), Dizziness (51.5%), Subjective fever (48.77%), Diarrhea (42.9%), Runny nose (37.3%), Nasal congestion (32.3%) and Shortness of Breath (26.1%). Most of the subjects reported that these symptoms had begun before initiation of COVID-19 related treatment. Fever without chills (61.1%) and dry cough (63%) were relatively more common among the study subjects than fever with chills or productive cough.\n\nAccording to frequency distribution of Oral and Nasopharyngeal lesions or conditions (Figure 2), Loss of smell (61.9%), Loss of taste (51.9%), Xerostomia (22.1%), Sore throat (19.2%), Burning sensation (11.3%), Xerostomia with Burning sensation (8.9%), Ulcers (8.2%), Vesicles (7.0%), Altered taste (5.0%), Tingling sensation (3.8%) and Papules (3.2%) were reported in decreasing order of frequency by study subjects when they were down with COVID-19.\n\nRegarding the prevalence of oral lesions and conditions based on location (Figure 3), Gingiva was found to be the most common site for the occurrence of Burning sensation (5.0%) and ulcers (4.4%). The tingling sensation was most frequently felt on posterior tongue, lips, and floor of the mouth (1.3%). The lips were the most common location for vesicles (2.5%) while the most frequent sites for occurrence of papules were uvula and tonsils (1.9%).\n\nThe frequency distribution of oral and nasopharyngeal lesions and conditions associated with COVID-19 in different age groups (Table 2) revealed statistically significant differences (p0.05) with regard to sore throat, loss of taste and smell. The ‘21 to 30’ and ‘31 to 40’ age groups reported the greatest frequency of loss of taste and smell, followed by the ‘41 to 50’ age group. Loss of smell was least common among children below 10 years of age and none of these children experienced loss of taste. The incidence of sore throat was highest among 41 to 50 years old and lowest among those aged 10 to 20 years age groups.\n\nGender based comparison for occurrence of Oral and Nasopharyngeal lesions or conditions (Table 3) showed that Anosmia, Ageusia, Xerostomia, Sore throat, Burning sensation and Vesicles were more commonly reported by females while males had a higher prevalence of ulcers; however these differences were statistically insignificant (p>0.05).\n\nOdds’ ratios showing strength of association (Table 4) showed that Oral/Nasopharyngeal lesions or conditions like Anosmia, Ageusia, Xerostomia, Sore throat and Burning Sensation can be predictors of COVID-19 related systemic symptoms like cough, fatigue, subjective fever and nasal congestion were found to be statistically significant (p≤0.05). Anosmia, Ageusia, Sore throat and Burning Sensation showed statistically significant (p≤0.05) association with symptoms of Body pain and Shortness of Breath. The strongest predictor was observed for occurrence of burning sensation and body pain (OR=16.18) which indicates that there was 16 times more chances of burning sensation to be reported among those with COVID-19 related body pain than without. Statistically significant association(p≤0.05) of symptoms like fever, runny nose and diarrhoea were limited only to oral findings like xerostomia, burning sensation and sore throat respectively.\n\n\nDiscussion\n\nThe disastrous impacts of the widespread COVID-19 pandemic on all sectors has detrimentally afflicted the quality of life globally. Though two years have elapsed, coexisting with Covid-19 seems to have become the ‘New normal’ as the world has recognized and accepted the reality that Covid-19 and its mutant variants are here to stay for quite a long time.17\n\nWith the development and easy availability of COVID-19 vaccines, most countries are now relaxing the restrictions for wearing masks and socializing as an attempt to resolve the economic, social and medical burden which are resultant aftermath of the pandemic. So, it is quite normal for undiagnosed COVID-19 patients or carriers to spend time with healthy individuals during social or official gatherings, which can initiate waves of fresh infection. For the same reason the dental fraternity should be cautious about infectious carriers of COVID-19 who might present themselves for routine dental treatment procedures. It is said that oral health mirrors general health; surprisingly till date there is only scanty data related to the prevalence of oral lesions and its association with other COVID-19 related symptoms. Much of the available literature in this field is in the form of case reports, case series and systematic reviews making completely valid and meaningful comparisons with other similar observational studies a difficult challenge.\n\nIn the present study oral symptoms were significantly associated with many of the COVID-19 related general symptoms showing that these could be suitable predictors for confirmation of COVID-19 without waiting for diagnostic test reports.\n\nAnosmia, sore throat, ageusia, burning sensation and xerostomia were among the most prevalent Oral and Nasopharyngeal lesions or conditions reported by the respondents of the present study. Orilisi et al. in their systematic review mentioned the occurrence of functional disorders like xerostomia, ageusia, dysgeusia and burning mouth as early manifestations of hospitalized patients affected by COVID-19 infection.18 This is in accordance with the findings of current study where these commonly reported symptoms had begun before initiation of COVID-19 related treatment. This indicates that these findings can be attributed as distinguishing features of COVID -19 and not as any side effects of drugs used for COVID-19 treatment.\n\nAccording to the present study, Anosmia and Ageusia, were reported by 61.9% and 51.9% of the study subjects respectively. This is similar to the conclusions made by Mullol et al., in their review article stating that Smell impairment is frequent and presents as an early and abruptly occurring distinguishing symptom in COVID-19 in at least 1 out of 5 patients.19 Anosmia and Ageusia, were the most reported differentiating symptoms among COVID-19 patients in studies by Kumar et al.20 Ageusia was a dominant symptom noted in other observational studies by Ganesan et al., (51.2%)21, Elkady et al., (34.5%)22 and Natto et al., (43.4%)23 The incidence of smell and/or taste disorders ranged from 5% to 98%, based upon on region of the study and study design.19 There is substantial evidence that loss of Anosmia or Ageusia is strongly linked with COVID-19 and can be used as questions to screen the patients in medicine and dentistry clinics to limit the risk of disease transmission.24\n\nXerostomia was yet another prominently reported symptom in this study, with a prevalence of 22.1% which was consistent with the findings of Ganesan et al.,21 and Elkady et al.,22. However, in a case series by Fathi et al., 60% of cases gave history of dry mouth, 3–4 days prior as a prodromal symptom which was not in agreement to our results.25 Soares et al., detected COVID-19 virus in the vacuolated cells of the superficial epithelium and also in the salivary glands of COVID-19 patients, indicating that salivary glands can be considered as a viral pool and saliva may possibly be the main source of the contagion.26\n\nSore throat was prevalent among 19.2% of current respondents which did not tally with studies by Savtale et al., (47.2%)27, or Alsofayan et al., (81.6%)28 but was in close alignment with reports by Al-Omari et al., (21.9%)29 and Biadsee et al., (26.6%)30. The difference could have been due to difference in age groups, gender or presence of other comorbidities among the study subjects.\n\nIn the current study, ulcers, vesicles, and papules were also more or less frequently found findings. Such lesions might result from different conditions like infections, poor oral hygiene, immunosuppression states, trauma or neoplasms.18,31 An elevated level of tumor necrosis factor (TNF)- α in individuals with COVID-19 can lead to chemotaxis of neutrophils to the oral mucosa and thus growth of aphthous-like lesions. Other plausible reasons for the formation of such lesions in these patients include concomitant stress and immunosuppression brought on by the COVID-19 infection.14 These oral lesions thereby cannot be considered as COVID-19 specific manifestations.\n\nGeneral systemic symptoms like Fatigue, Body pain, Headache, Cough, Fever, Dizziness, Subjective fever, Diarrhea, Runny nose, Nasal congestion, and Shortness of Breath were commonly prevalent among our study subjects which were similar to observations by Al-Omari et al.,29 and Rothan et al.32\n\nBased on calculated odds ratios for the present study which showed statistically significant association, Anosmia was twice more likely to be present among those with cough and dizziness, thrice more common among those with headache, body pain and shortness of breath, four times commonly associated with subjective fever and five times with nasal congestion; whereas loss of taste was thrice more likely to occur in subjects with headache, four times with fatigue, subjective fever and shortness of breath and five times more likely to be found among those with cough and body pain. According to Kumar et al.,20 the association between olfactory or gustatory impairment and fever was substantial and favourable (Odds ratio = 10.60) which was higher than OR≈4 in our study; positive association was also reported with diarrhoea (Odds ratio = 4.86); however, no significant association was detected for loss of taste or smell with occurrence of diarrhoea in the present study. The difference in the age groups considered for both studies could be a possible explanation for the differences in odds ratios observed. The current study also showed OR≈3, associating xerostomia with fatigue, fever and cough and OR≈2 for association with nasal congestion but no possible comparative studies were available associating xerostomia, sore throat or burning sensation with COVID-19 general symptoms.\n\nThe results of this study indicate that the presence of olfactory (smell) or gustatory (taste) dysfunction, dry mouth, sore throat, and a burning sensation, along with COVID-19 generic symptoms, should be regarded as suggestive but not definite markers of COVID-19. In spite of the fact that the research was only conducted in Eastern Province, it was able to identify and include the very first cases of COVID-19 in the Eastern Province of the Kingdom of Saudi Arabia. In addition to this, the social factors of the patients were accounted for, and the sample size was adequate, covering a broad spectrum of clinical data. It was unable to fully analyse the clinical data for some patients because there was insufficient information available regarding the frequency and duration of these patients' self-reported symptoms. Further research is definitely required and should include parameters like viral load, quantitative assessment of symptoms and evaluation of histopathological parameters to confirm the extent of cause effect relation between oral and systemic findings of COVID-19. With detailed oral screening, dental professionals are in an optimal position to take adequate precautions for prevention and timely intervention for early diagnosis and prompt treatment to avoid potential complications and community spread.",
"appendix": "Data availability\n\nFigshare: Data set - Oral manifestations associated with Novel Coronavirus Disease - 2019 (COVID-19): A questionnaire based hypothetical study, https://doi.org/10.6084/m9.figshare.21546324.v1. 33\n\nFigshare: Questionnaire - Oral manifestations associated with Novel Coronavirus Disease - 2019 (COVID -19): A questionnaire based hypothetical study, https://doi.org/10.6084/m9.figshare.21528999.v1. 34\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nSharma A, Ahmad Farouk I, Lal SK: COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention. Viruses. 2021 Jan 29; 13(2): 202. PubMed Abstract | Publisher Full Text\n\nHarvey WT, Carabelli AM, Jackson B: SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 2021; 19: 409–424. PubMed Abstract | Publisher Full Text\n\nWHO Coronavirus disease 2019 (COVID-19) Situation Report-September 21, 2021. Edition 58\n\nPeng X, Xu X, Li Y, et al.: Transmission routes of 2019-nCoV and controls in dental practice. Int. J. Oral Sci. 2020 Mar. 3; 12(1): 1–6. Publisher Full Text\n\nRen YF, Rasubala L, Malmstrom H, et al.: Dental Care and Oral Health under the Clouds of COVID-19. JDR Clin Trans Res. 2020 Jul; 5(3): 202–210. PubMed Abstract | Publisher Full Text\n\nLondon KC; Loss of smell and taste a key symptom for COVID-19 case.\n\nHuang C, Wang Y, Li X: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223): 497–506. PubMed Abstract | Publisher Full Text\n\nTsuchiya H: Oral Symptoms Associated with COVID-19 and Their Pathogenic Mechanisms: A Literature Review. Dent J (Basel). 2021; 9(3). Publisher Full Text\n\nMahmoud MM, Abuohashish HM, Khairy DA, et al.: Pathogenesis of dysgeusia in COVID-19 patients: a scoping review. Eur. Rev. Med. Pharmacol. Sci. 2021; 25(2): 1114–1134. PubMed Abstract | Publisher Full Text\n\nJarrahi A, Ahluwalia M, Khodadadi H: Neurological consequences of COVID-19: what have we learned and where do we go from here?. J. Neuroinflammation. 2020; 17(1): 296. Publisher Full Text\n\nEshraghi AA, Mirsaeidi M, Davies C, et al.: Potential Mechanisms for COVID-19 Induced Anosmia and Dysgeusia. Front. Physiol. 2020; 11(1039). PubMed Abstract | Publisher Full Text\n\nAlexandre J, Cracowski JL, Richard V, et al.: Renin-angiotensin-aldosterone system and COVID-19 infection. Ann. Endocrinol. 2020; 81(2–3): 63–67. PubMed Abstract | Publisher Full Text\n\nHarikrishnan P: Etiogenic Mechanisms for Dysgeusia in SARS-CoV-2 Infection. J. Craniofac. Surg. 2021; 32(1): e111–e112. PubMed Abstract | Publisher Full Text\n\nIranmanesh B, Khalili M, Amiri R, et al.: Oral manifestations of COVID-19 disease: A review article. Dermatol. Ther. 2021; Jan; 34(1): e14578. PubMed Abstract | Publisher Full Text\n\nBanakar M, Bagheri Lankarani K, Jafarpour D: COVID-19 transmission risk and protective protocols in dentistry: a systematic review. BMC Oral Health. 2020; 20: 275. PubMed Abstract | Publisher Full Text\n\nNational Health Commission of the People’s Republic of China: Diagnosis guidelines for the new coronavirus pneumonia (NCIP) of the seventh edition.\n\nWorld Health Organization: From the “new normal” to a “new future”: A sustainable response to COVID-19.\n\nOrilisi G, Mascitti M, Togni L, et al.: Oral Manifestations of COVID-19 in Hospitalized Patients: A Systematic Review. Int. J. Environ. Res. Public Health. 2021; 18(23): 12511. PubMed Abstract | Publisher Full Text\n\nMullol J, Alobid I, Mariño-Sánchez F, et al.: The Loss of Smell and Taste in the COVID-19 Outbreak: a Tale of Many Countries. Curr Allergy Asthma Rep. 2020; 20(10): 61. PubMed Abstract | Publisher Full Text\n\nKumar L, Kahlon N, Jain A, et al.: Loss of smell and taste in COVID-19 infection in adolescents. Int. J. Pediatr. Otorhinolaryngol. 2021; 142(110626): 110626. PubMed Abstract | Publisher Full Text\n\nGanesan A, Kumar S, Kaur A: Oral Manifestations of COVID-19 Infection: An Analytical Cross-Sectional Study. J Maxillofac Oral Surg. 2022; 1–10. PubMed Abstract | Publisher Full Text\n\nEl Kady DM, Gomaa EA, Abdella WS, et al.: Oral manifestations of COVID-19 patients: An online survey of the Egyptian population. Clin Exp Dent Res. 2021 Oct; 7(5): 852–860. PubMed Abstract | Publisher Full Text\n\nNatto ZS, Afeef M, Khalil D, et al.: Characteristics of Oral Manifestations in Symptomatic Non-Hospitalized COVID-19 Patients: A Cross-Sectional Study on a Sample of the Saudi Population. Int J Gen Med. 2021 Dec; 14: 9547–9553. PubMed Abstract | Publisher Full Text\n\nHopkins C, Kelly C: Prevalence and persistence of smell and taste dysfunction in COVID-19; how should dental practices apply diagnostic criteria?. BDJ In Pract. 2021; 34: 22–23. Publisher Full Text\n\nFathi Y, Hoseini EG, Atoof F, et al.: Xerostomia (dry mouth) in patients with COVID-19: a case series. Futur. Virol. 2021; 16: 315–319. Publisher Full Text\n\nSoares CD, Souza LL, Carvalho MGF, et al.: Oral Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Clinicopathologic and Immunohistochemical Study. Am. J. Surg. Pathol. 2022; 46(4): 528–536. PubMed Abstract | Publisher Full Text\n\nSavtale S, Hippargekar P, Bhise S, et al.: Prevalence of Otorhinolaryngological Symptoms in Covid 19 Patients. Indian J Otolaryngol Head Neck Surg. 2021 Feb 8; 1–7.\n\nAlsofayan YM, Althunayyan SM, Khan AA, et al.: Clinical characteristics of COVID-19 in Saudi Arabia: a national retrospective study. J. Infect. Public Health. 2020; 13(7): 920–925. PubMed Abstract | Publisher Full Text\n\nAl-Omari A, Alhuqbani WN, Zaidi ARZ, et al.: Clinical characteristics of non-intensive care unit COVID-19 patients in Saudi Arabia: A descriptive cross-sectional study. J. Infect. Public Health. 2020 Nov; 13(11): 1639–1644. PubMed Abstract | Publisher Full Text\n\nBiadsee A, Biadsee A, Kassem F, et al.: Olfactory and Oral Manifestations of COVID-19: Sex-Related Symptoms-A Potential Pathway to Early Diagnosis. Otolaryngol. Head Neck Surg. 2020 Oct; 163(4): 722–728. PubMed Abstract | Publisher Full Text\n\nCuevas-Gonzalez MV, Espinosa-Cristóbal LF, Donohue-Cornejo A, et al.: COVID-19 and its manifestations in the oral cavity: A systematic review. Medicine (Baltimore). 2021 Dec;23; 100(51): e28327. PubMed Abstract | Publisher Full Text\n\nRothan HA, Byrareddy SN: The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J. Autoimmun. 2020; 109: 102433. PubMed Abstract | Publisher Full Text\n\nMohammed F, Fairozekhan AT, Mohamed S, et al.:Data set - Oral manifestations associated with Novel Coronavirus Disease - 2019 (COVID -19): A questionnaire based hypothetical study. figshare. Dataset.2022. Publisher Full Text\n\nMohammed F, Fairozekhan AT, Mohamed S, et al.:Questionnaire - Oral manifestations associated with Novel Coronavirus Disease - 2019 (COVID -19): A questionnaire based hypothetical study. figshare. Dataset.2022. Publisher Full Text"
}
|
[
{
"id": "157555",
"date": "16 Jan 2023",
"name": "Muhammad Amber Fareed",
"expertise": [
"Reviewer Expertise Dental biomaterials and restorative dentistry research"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI’ve reviewed the manuscript titled “Oral manifestations associated with Novel Coronavirus Disease - 2019 (COVID-19): A questionnaire-based hypothetical study” with interest. The authors of this study presented data on the correlation between the severity of COVID-19 infection and oral symptoms while distinguishing oral signs and symptoms among ambulatory and non-hospitalized COVID-19 patients presented in Saudi Arabia during the COVID-19 pandemic outbreak in 2020. This is useful and relevant research in relation to the most recent pandemic condition of the COVID-19 pandemic. The finding of this study certainly provides some recommendations and supports health workers to better understand COVID-19 manifestation of oral conditions.\nPlease, find my following comments and questions about this manuscript:\nThe title and abstract look ok as they cover the main idea and condense the key findings.\n\nIntroduction: The authors have provided a brief over and introduction to the topic and have highlighted several underlying mechanisms for COVID-19-related oral manifestations. It would be interesting if the authors may clarify and include a similar study using the patient interview and may comment on whether earlier research had some limitations and use these gaps to explain the novelty of this research. Please also provide any relevant recent references on the same topic from Saudi Arabia to explain whether similar studies that reported the oral manifestations associated with coronavirus disease.\n\nMethod: Please provide more details on how the sample size was calculated.\n\nDiscussion: Authors have provided a reasonable argument to support the finding of this study however, I would encourage authors to discuss the finding of this work in relation to the case reports published including the parameters on viral load, quantitative assessment of symptoms and evaluation of histopathological parameters.\n\nThe conclusions are missing.\n\nIt would a good idea to provide the “comprehensive survey questionnaire” as additional resource.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "9663",
"date": "23 May 2023",
"name": "FARAZ MOHAMMED",
"role": "Author Response",
"response": "ABSTRACT Reviewer comment: The title and abstract look ok as they cover the main idea and condense the key findings. Authors Reply: Thank you so much for your constructive comment. Introduction: Reviewer comment: The authors have provided a brief over and introduction to the topic and have highlighted several underlying mechanisms for COVID-19-related oral manifestations. It would be interesting if the authors may clarify and include a similar study using the patient interview and may comment on whether earlier research had some limitations and use these gaps to explain the novelty of this research. Please also provide any relevant recent references on the same topic from Saudi Arabia to explain whether similar studies that reported the oral manifestations associated with coronavirus disease. Authors Reply: The authors have now included a similar study using the patient interview and also have commented on the limitations and gaps from the previous studies. As far as the other concern of the esteemed reviewer to include a similar study from Saudi Arabia, we the authors like to inform our reviewer that, our study was the very first study to be carried out in the Kingdom of Saudi Arabia during the period 21/08/2020 to 07/12/2020, further that no similar studies were published from the Kingdom of Saudi Arabia when we first submitted our manuscript for publication. Method: Reviewer comment: Please provide more details on how the sample size was calculated. - Given in the result section. Authors Reply: A convenience sampling method was adopted for recruiting participants in this study. As it was considerably difficult to get study participants because of the infectious nature of the disease and the social stigma associated with strict COVID-19 protocols, all participants who fulfilled the inclusion requirements and consented were recruited in the study; hence sample size was not taken into consideration. This statement is been included in the manuscript. Discussion: Reviewer comment: Authors have provided a reasonable argument to support the finding of this study however, I would encourage authors to discuss the finding of this work in relation to the case reports published including the parameters on viral load, quantitative assessment of symptoms and evaluation of histopathological parameters. Authors Reply: Thank you so much for your constructive comment on the written discussion. We have already included the case reports and correlated and discussed the findings elaborately in the manuscript. But for the comment to include and discuss the evaluation of histopathological parameters, we the authors have not taken any biopsy from the studied samples due to the fact considerably difficult to get study participants because of the infectious nature of the disease and the social stigma associated with strict COVID-19 protocols. So we could not discuss this aspect in our manuscript. Conclusion: Reviewer comment: The conclusions are missing. Authors Reply: Earlier the conclusion was merged in the discussion paragraph itself. Now the conclusion and limitations part are separated from the discussion part and added separately in the manuscript. Reviewer comment: It would a good idea to provide the “comprehensive survey questionnaire” as additional resource. Authors Reply: Yes, the authors have already provided and also deposited the “comprehensive survey questionnaire” as well as the complete “data set” in Repository with the following hyperlinks: Data availability Underlying data Figshare: Data set - Oral manifestations associated with Novel Coronavirus Disease - 2019 (COVID-19): A questionnaire based hypothetical study, https://doi.org/10.6084/m9.figshare.21546324.v1 Extended data Figshare: Questionnaire - Oral manifestations associated with Novel Coronavirus Disease - 2019 (COVID -19): A questionnaire based hypothetical study, https://doi.org/10.6084/m9.figshare.21528999.v1 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)."
}
]
},
{
"id": "160633",
"date": "01 Feb 2023",
"name": "Shruthi Acharya",
"expertise": [
"Reviewer Expertise Oral Cancer Diagnosis",
"Potentially malignant oral disorders",
"CBCT",
"Oral mucosal lesions",
"Management of oral complications of cancer therapy"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI congratulate the authors for performing the study to understand the oral manifestations of COVID-19 infection. The study was done under challenging circumstances. I appreciate the efforts put in by the authors to conduct the study.\n\nI have a few queries:\nKindly justify why the term “hypothetical” is used in the title to describe the study\n\nIntroduction - well written\n\nPatients and Methods - IEC approval was obtained, Inclusion criteria is defined and the questionnaire was vetted.\n\nResults\n\nKindly rephrase and reorder sentences in the first paragraph of the results section.\n\nChildren less than 10 years were included in the study - were they able to comprehend and explain their symptoms like papule/ vesicle, etc. over the telephone?\n\nKindly use uniform spelling for “Diarrhea” in the text and table.\n\nTable 1 - kindly restructure the table. Symptoms with Yes/No response to be put together, Symptoms with Before the treatment/During the treatment/ after treatment responses together.\n\nFigure 3- The text and legends are not visible clearly. Kindly improve the resolution of the figure.\n\nKindly do not unnecessarily capitalize words between a sentence.\n\nTable 4 - kindly provide reference categories and 95% confidence intervals for all the variables. Also, provide legends to the tables.\n\nDiscussion\nKindly do not unnecessarily capitalize words between a sentence.\n\nDrawbacks of study\nIt can be described as a separate heading.\n\nIs there a possibility of recall bias?\n\nConclusion can be clearly stated.\n\nReferences\nSome references are not complete.\n\nReferences should have both start and end page numbers.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9664",
"date": "23 May 2023",
"name": "FARAZ MOHAMMED",
"role": "Author Response",
"response": "Reviewer comment: Kindly justify why the term “hypothetical” is used in the title to describe the study. Authors Reply: The term hypothetical was used in the title because, this study was conducted in the very early phase of COVID-19 era. At that particular time no data was published on the oral manifestations associated with COVID-19 except for loss of taste. Since we knew few oral signs & symptoms of few other viral infections, we took this study as a hypothetical study. Reviewer comment: Introduction - well written Authors Reply: Thank you so much Reviewer comment: Kindly rephrase and reorder sentences in the first paragraph of the results section. Authors Reply: Thank you so much for the constructive comment. We have now rephrased and reordered sentences in the first paragraph of the results section. Reviewer comment: Children less than 10 years were included in the study - were they able to comprehend and explain their symptoms like papule/ vesicle, etc. over the telephone? Authors Reply: Since the questionnaire was drafted both in English and Arabic languages. Moreover, the doctors who interviewed these patients were well versed in the native language and they could clearly explain to the patient. At times we took the help of the parents. Reviewer comment: Kindly use uniform spelling for “Diarrhea” in the text and table. Authors Reply: Sorry, we have now used the uniform spelling. Reviewer comment: Kindly do not unnecessarily capitalize words between a sentence. Authors Reply: Sorry, we have now removed the unnecessarily capitalize words from between a sentence. Reviewer comment: Table 4 - kindly provide reference categories and 95% confidence intervals for all the variables. Also, provide legends to the tables. Authors Reply: We have now provided 95% confidence intervals for all the variables. The legends to the table are also provided. Discussion Reviewer comment: Kindly do not unnecessarily capitalize words between a sentence. Authors Reply: Sorry, we have now removed the unnecessarily capitalize words from between a sentence. Drawbacks of study Reviewer comment: It can be described as a separate heading. Authors Reply: Yes, we have now included a separate paragraph as “Conclusion & Limitations”. Reviewer comment: Is there a possibility of recall bias? Authors Reply: This study was conducted in the very early phase of COVID-19 where the patients had just recovered from COVID-19 infection, thereby there was very less chances of patients forgetting a past events of their infection. Moreover, 230 patients participated in this study. But, only 179 COVID-19 patients were included for the statistical analysis as few of them did not respond to most questions. So completely elimination the recall bias. Conclusion Reviewer comment: Conclusion can be clearly stated. Authors Reply: Yes, we have now included a separate paragraph as “Conclusion”. References Reviewer comment: Some references are not complete. Authors Reply: Now we have updated the references according to the journal norms. Most of the articles from the MDPI journals have a single page number. And the references are automatically generated according to journal norms. Reviewer comment: References should have both start and end page numbers. Authors Reply: Now we have updated the references according to the journal norms."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1443
|
https://f1000research.com/articles/12-536/v1
|
23 May 23
|
{
"type": "Research Article",
"title": "Anion gap(AG) or serum lactate-in search of a better prognostic marker in sepsis a cross-sectional study in a rural tertiary care hospital",
"authors": [
"Apurva Dubey",
"Sourya Acharya",
"Sunil Kumar",
"Samarth Shukla",
"Satish Mahajan",
"Shilpa Bawankule",
"Anamika Giri",
"Sourya Acharya",
"Sunil Kumar",
"Samarth Shukla",
"Satish Mahajan",
"Shilpa Bawankule",
"Anamika Giri"
],
"abstract": "Background: In intensive care units, sepsis is a common diagnosis. Serum lactate rise has been established as an essential measure for predicting the outcome of sepsis. Higher anion gap(AG) has been associated with an increased risk of death in critically ill individuals. We measured blood lactate levels and AG and looked at how these predicted in-hospital outcomes (death or discharge).This study aimed to estimate anion gap values in sepsis syndrome, to measure the serum lactate levels in sepsis syndrome, to correlate the anion gap and serum lactate values with the outcome (mortality and discharge) in patients with sepsis syndrome.\nMethods: The Department of Medicine at Jawaharlal Nehru Medical College conducted this single-center, prospective, observational cross-sectional study with a cohort design. A total of 160 patients with sepsis were screened in the ICU. Sepsis was diagnosed using SEPSIS-3 criteria.\nResults: In this study, we included 160 patients with sepsis with sequential organ failure assessment (SOFA) score >2.Mean serum lactate was 5.1±1.2 mmol/L and it was ≥4 mmol/L in 90% of patients. Mean AG was 14.0±3.9 and it was ≥12 in 75.6% of patients. Similarly, the proportion of patients who had lactate levels ≥4 mmol/L was higher in those with AG ≥12 than AG <12 (95.9% vs. 71.8%, p<0.0001). The AUC of ROC in predicting mortality was significant for both serum lactate (AUC 0.797, p<0.0001) and AG (AUC 0.835, p<0.0001).\nConclusions: Along with other parameters predicting mortality, serum lactate and AG also act as important predictors of mortality in sepsis patients. We conclude that on admission serum lactate ≥4 mmol/L and AG ≥12 can be used in predicting short-term mortality in patients with sepsis.",
"keywords": [
"acid base balance",
"SOFA score",
"sepis-3 criteria",
"critically ill patients",
"unmeasured anions",
"serum lactate",
"prognostic marker",
"cross sectional study."
],
"content": "Introduction\n\nSevere sepsis and septic shock are chief health care complications, affecting millions of individuals around the globe per year, killing one in four (and frequently more), and increasing in occurrence.1 Sepsis, is a physiologic and pathologic condition, including biochemical abnormalities brought on by the infection, is a serious community health issue that cost the US healthcare system more than $20 billion (5.2%).2 According to the Global Burden of Diseases 2017, the percentage of sepsis associated deaths in each country was shown using mixed-effects for different ages, genders, locations, disease causes, using data from 8 million unique hospital records. A total of eleven million sepsis-associated deceases were documented, accounting for a projected 48.9 million cases of sepsis and 19.7 percent of all death cases globally. Between the years 1990 till 2017, age-standardized sepsis incidences declined by 37 percent, while death dropped by 52.8 percent. The occurrence and mortality of sepsis varied greatly by area, with Oceania, South Asia, East-Asia sub-Saharan Africa, Oceania, South Asia, and South-East Asia weighing the heaviest burdens.3 Sepsis remains to be a main source of health loss wide-reaching, with a particularly high health-associated burden in Sub-Saharan Africa, despite dropping age-standardized prevalence and mortality cases.3 A thorough evaluation of the literature by the World Health Organization estimated the hospital death rate from sepsis to be 27%,4 in patients receiving treatment for sepsis in critical care, mortality is expected to be 42%.\n\nSepsis incidence and mortality statistics are largely based on information from Western nations. In India, tropical illnesses like leptospirosis, malaria, dengue, tuberculosis, and enteric infections are also important reasons of severe sepsis or septic shock, in dissimilarity to the Western nations where septic infections by the Gram-negative organisms is the main origin of sepsis. Severe sepsis has a documented death rate >50% in the Indian setting.5\n\nNovel definitions for sepsis and septic shock cases were released in the month of February (2016) by a Task Force accumulated by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine.2 Earlier, the systemic inflammatory response syndrome (SIRS) criteria were not used in the new sepsis definitions, which associated Sepsis-3 sepsis to Sepsis-2 severe sepsis. Additionally, Sequential organ failure assessment (SOFA) score was used to operationalize organ dysfunction, and clear criteria were planned to diagnose septic shock, congruent with a number of clinical parameters in order to guide the clinical care, future studies, and healthcare planning. The task-force sepsis conditions, the necessity for a vasopressor to continue a Mean Arterial Pressure (MAP) of ≥65 mmHg and a Serum Lactate level of ≥2 mmol/L in the absence of hypovolemia.2\n\nSepsis patients may exhibit clinical presentations with the signs/symptoms hours before the situation gets worse. To screen these high-risk patients, early warning scores like the Modified Early Warning Score (MEWS), the National Early Warning Score (NEWS), or the Early Warning Scoring System (EWSS), were created. These results indicated a tendency toward better results, when emergency department (ED) teams enable prompt use of the most effective medicines when septic patients are identified.6 The formative evaluation and therapy of sepsis patients frequently take place in the ED. However, a few factors make it difficult to quickly determine which patients are utmost possible to develop severe illness, especially with septic infections due to the deficiency of the specificity of the systemic inflammatory response syndrome (SIRS) criteria for the infection; the heterogeneity of the clinical manifestations, including the clinical signs/symptoms, sites of infection, related complications, the etiologic pathogens; and the task of identifying patients most likely to develop to severe illness or death, especially among patients not severely ill during the initial evaluations.7 Early detection of high-risk individuals is necessary, either through a clinical decision rule that can be quickly evaluated or an easily accessible laboratory parameter.8 In the patients admitted to intensive care units (ICUs) who met severe sepsis criteria at twenty-four hours, the annual occurrences of severe sepsis was 51 per 10,000 patients, and the fatality rate was 47%. Sepsis patients made up 33% of hospital-bed days and 45 percent of ICU bed days.9\n\nThe initial and accurate identification of patients who benefit from the dynamic optimal medical interventions is critical if improved outcomes in terms of survival is needed to be attained. A substantial improvement in the survival can be achieved with an early goal-directed therapy (EGDT) in the emergency department prior to the ICU admissions. Detecting the time when pathophysiological processes can be stopped by the proper therapies is of immense importance for the final outcome.10 The diagnosis of sepsis is often confirmed by microbiological culture, which requires a 24 to 48-hour delay before antibiotics are administered. Early presentations may include an infectious source and aberrant biology and analytical data. Chest X-rays and computed tomography scans cannot reliably distinguish between different sepsis etiologies and permit the abuse of antibiotics. This is especially true for elderly individuals, for whom non-specific symptoms or organ malfunction may take the place of the typical sepsis presentation. This necessitates the use of sensitive sepsis biomarkers in these unusual presentations.11\n\nRecent years have seen an increase in interest in research on lactate in severe sepsis. According to current theories, increased lactate in sepsis settings is linked to anaerobic cell metabolism because of disproportion between the body's mandate and supply for ATP and oxygen under circumstances like hypoperfusion or organ malfunction in sepsis patients. Several studies in literature have shown a greater mortality rate in people with hyperlactatemia who have severe sepsis and/or septic shock presentation. Because the lactate is generated from the tissues in the hypoperfusion condition before actual hypotension, it is a critical component in the diagnosis of the sepsis. Compared to revival without lactate monitoring or central venous oxygen saturation treatment, the lactate-guided recovery reduced mortality in the patients with septic shock. Lactate, a biomarker of shock, suggests the need for rapid fluid resuscitation, in addition to the diagnosis.12 Patients with blood lactate levels below 4 mmol/L are classified as in need of fluid resuscitation as per Surviving Sepsis Campaigns, 2012 and 2016.13 Normalizing lactate is often a resuscitation endpoint. However, due to the deficiency of access to readily available investigational equipment, particularly in poorer nations, point-of-care (POC) lactate measurement is not commonly employed.14,15\n\nAnother trending concept is of the serum anion gap (AG). It has been detected and it has also been used to spot paraproteins, assess patients with suspected acid-base diseases, such as sepsis, and find errors in electrolyte measurement.16 A larger AG is often recognized when it reaches the upper limit of normal (ULN). An increase in the anion concentration can exist without increase in AG, though, due to the wide range of typical values (commonly 8–10 mEq/L). Additionally, lactic acidosis is more severe than ketoacidosis in terms of the degree of increase in AG relative to the variation in the serum bicarbonate depending on the kind of retained anion.16\n\nCurrent evidence is supportive to the fact that serum lactate is the predictor of mortality in sepsis.17,18 Serum lactate and AG can have a substantial link with one another in individuals with septic shock, but lactate and base excess demonstrated a modest correlation. Therefore, both indicators can be utilized interchangeably to assist in identifying septic shock in patients early.12 However, other reports identified that AG was not a sensitive indicator of an elevated lactate level within the initial hour of the onset of lactic acidosis. The AG increased more than the serum lactate, and only about 30% of the change in the AG could be attributed to rising serum lactate levels, indicating that other anions may be involved in the anion gap in lactic acidosis.19 Serum bicarbonate and AG are ineffective predictors of death and changes in lactate. Lactate is still the recommended biomarker, although AG levels of 20 mEq/L may be employed in situations with limited resources if lactate is not available to additional risk-stratify patients for the continued sepsis treatment.20 Between AG and the corrected AG (cAG) in terms of identifying hyperlactatemia, the cAG is not superior to the AG.21 Few studies reported high AG being a fairly sensitive and specific way to find individuals with sepsis who have elevated lactate levels.12,20–22 Despite these pieces of evidence, there’s still an excessive deal of interest in the biomarkers representing different pathogenic pathways. Given the general lack of studies in Indian settings with comparative evaluations of lactate and AG in sepsis, we performed this current study to determine the AG and serum lactate levels in the sepsis patients and their role in predicting the in-hospital mortality.\n\n\nAim\n\nTo study serum lactate vis-a-vis anion gap as prognostic markers in sepsis in rural tertiary care hospital.\n\n\nObjectives\n\n\n\ni. To estimate anion gap values in sepsis syndrome\n\nii. To measure the serum lactate levels in sepsis syndrome.\n\niii. To correlate the anion gap and serum lactate values with the outcome (mortality and discharge) in patients with sepsis syndrome.\n\n\nMethods\n\nThis single-center, prospective, observational cross-sectional study with a cohort design was conducted in the Department of Medicine, Jawaharlal Nehru Medical College and its attached hospital Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi (Meghe), Wardha. The suspicious sepsis patients were admitted to theICU, a 40-bed unit of the hospital under the Medicine Department of Acharya Vinoba Bhave Hospital, Sawangi (Meghe) associated to Datta Meghe Institute of Medical Sciences, Wardha.\n\nThe entire study was conducted as per the principles of the Declaration of Helsinki and local regulations. Relevant regulations and Good Clinical Practices and were followed throughout the study duration by each study team member. The present study was conducted after the clearance of the Institutional Ethical Committee (IEC number, DMIMS (DU)/IEC/2020-21/9300) of Acharya Vinoba Bhave Rural Hospital (AVBRH). Patients who showed their active interest to follow the projected research study design after a detailed written informed consent process were enrolled in the study by signing the informed consent.\n\nThis mid-term study was conducted during November 2020 to April 2022 as we found that peaks of infectious diseases leading to sepsis were at peak level during this time.\n\nPatient enrollment was conducted at the Department of Medicine, Jawaharlal Nehru Medical College and its attached hospital Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi (Meghe), Wardha. Subjects were screened in the ICU between Nov 2020 to Apr 2022 were eligible with a diagnosis of sepsis. Sepsis was diagnosed on SEPSIS-3 criteria.\n\n\n\n1) Age of the patients ≥18 years admitted to the ICU of the hospital.\n\n2) Patients’ suspicion of infection based on ICU presentation as noted in the ICU chart's section in relation to medical decision-making.\n\n3) SOFA score >2.\n\n4) Patients willing to consent and participate.\n\n\n\n1) Patients with either hepatic dysfunction, chronic kidney disease.\n\n2) Patients with burns.\n\n3) Patients with carbon monoxide intoxication, cyanide intoxication, and methanol intoxication.\n\n4) Patients with collagen vascular diseases.\n\nSee Figure 1 for a plan of the study.\n\nMedical residents under the direction of surgeons and clinicians from several medical disciplines made up the ICU's medical staff. Fellows with specialized training in detecting potential sepsis patients as per SOFA criteria went four times a day to the ICU to look for people who met the inclusionary criteria. Without being aware of the patients' subsequent hospital courses, we prospectively identified the patients and studied the ICU documents. In order to locate patients, we looked through the daily ICU log for admissions with an infection-related diagnosis (such as pneumonia, shortness of breath, etc). To confirm a suspect of infection based on ICU presentation as recorded in the medical decision-making section of the chart, all records of patients with infection or a probable infection underwent a confirmatory review.\n\nAccording to institutional protocol, individuals with suspected of sepsis with SOFA score >2 had their venous lactate levels checked. The Glasgow Coma Score was assessed and recorded in the patient's record. Several other parameters like significant vitals, blood cultures, antibiotics, fluid therapy, resuscitation, length of hospital stay, complication, if any were also taken into account. The hospital ICU team's choices were unaffected by the researcher. We followed the study participants from initial admission to the hospital ICU until discharge or death.\n\nThe first venous serum lactate levels (mmol/L) obtained in the ICU were collected, together with the basic chemistry panel, estimated AG ([Na mEq/L] [Cl mEq/L] [HCO3 mEq/L]). The lactate levels were tested using a chemical analyzer from serum taken in a heparinized tube. According to normal reference range established by our institutional laboratory, we defined clinically relevant lactate to be >4 mmol/L and an anion gap of >12 was regarded as the highest limit of normal. Survival to hospital was referred to as a secondary outcome of in-hospital mortality.\n\nThe medical record number, baseline vital signs (BP, HR, RR), AG, and serum lactate, collected by venous sample, were obtained and documented by the ICU doctors in collaboration with the study team members upon ICU presentation and fulfilment of inclusion criteria. The following formula is used by to determine the anion gap:\n\nSerum Lactate levels were measured by Lactate was measured by an enzymatic lactate oxidase assay using the Cobas 6000® analyzer, (Roche Diagnostics, IN, USA).\n\nSample size calculation:\n\nMinimum sample size required\n\nEstimated specificity of anion gap=0.84\n\nPrevalence of positive character (Prev)=0.283\n\nEstimation Error 5%=7%\n\nn=148\n\nMinimum sample size required is 148, considering the drop out 10% sample size required was 163.3 samples drop out from the study, as per protocol analysis total 160 samples taken for observations.\n\nThe sampling method was consecutive sampling with a sample size of 160 subjects.\n\nThe data from ICU admitted sepsis patient inclusionary of SOFA Score was entered into the Microsoft Excel sheet version 2016. Data were analyzed using SPSS software version 15 (SPSS IBM statistics, Chicago, USA), we can recommend R-studio software as a proprietary free alternative. We presented categorical variables as frequency and percentage. The continuous variables were presented as mean and standard deviation. In order to accurately characterize the results, demographic data were expressed as means with standard deviation, medians (interquartile range), or percentages. The student’s t-test was used to compare the means of two independent sets of quantitative variables. The Friedman and the Mann-Whitney test were used to gauge the non-symmetrical distributions of the variables. The Chi-square test was used to make proportional comparisons. Receiver operating curves were obtained to determine the area under curve with serum lactate and AG in prediction of mortality, P value was considered significant if p<0.05.\n\n\nResults\n\nIn this study, we included 160 patients with sepsis with SOFA score >2. Table 1 enlists the baseline characteristics in study population. Mean age of the population was 53.1±17.0 and 61.9% were males. Hypertension (41.3%) and diabetes (30%) were major comorbidities. Respiratory etiology (78.1%) was most common cause of sepsis. On admission, mean HR was 123.1±20.8 bpm, mean RR was 29.8±9.2 per min, mean SBP was 82.3±28.7 mmHg, and O2 saturation level was 84±12%. The mean SOFA score was 9.5±5.3. 53.8%, patients had alerted mental status. 58.8% required ventilator whereas 63.1% needed inotrope support.\n\nTable 2 provides the details of various laboratory parameters assessed at baseline in study population. In hematological parameters, the mean Hb was 10.5±2.8 gm/dl, and leukocyte count was 23920±19050 cells/cmm. In liver function tests, the mean total bilirubin was 1.8±2.5 mg/dl, and the mean serum albumin was 3.0±0.8 mg/dl. The mean serum creatinine was 2.6±2.6 mg/dl. The mean serum lactate was 5.1±1.2 mmol/L and it was ≥4 mmol/L in 90% of patients. The mean AG was 14.0±3.9 and it was ≥12 in 75.6% of patients.\n\nThe mean hospital stay of 10.6±8.8 days and nearly 50% of patients had hospital stay duration of more than 10 days as shown in Table 3.\n\nTable 4 shows the outcome of patients during hospital stay. Mortality occurred in 45.6% of patients whereas 54.4% were discharged from the hospital.\n\nThe mean lactate level was significantly higher in patients with high AG (5.6±1.1 vs. 4.1±0.8 mmol/L, p<0.0001). Similarly, the proportion of patients who had lactate levels ≥4 mmol/L was higher in those with AG ≥12 than AG <12 (95.9% vs. 71.8%, p<0.0001) as shown in Table 5. The sensitivity of AG ≥12 in detecting sepsis as defined by serum lactate ≥4 was 80.6% whereas specificity was 57.9%.\n\nAmong non-survivors, serum lactate level was significantly higher than survivors (5.8±1.1 vs. 4.5±0.9 mmol/L, odds ratio 4.55 (95% CI 2.68-7.70), p<0.0001). All non-survivors had lactate levels ≥4 mmol/L (Table 6). Among non-survivors, mean AG was significantly higher than survivors (15.8±3.7 vs. 11.9±3.4, odds ratio 1.39 (95% CI 1.23-1.56) p<0.0001). AG ≥12 was seen in significantly higher proportion non-survivors than survivors (89% vs. 64.4%, p<0.0001) (Table 7).\n\nFigure 2 shows the ROC curves for AG and serum lactate.\n\nAs shown in Table 8 the AUC of ROC in predicting mortality was significant for both serum lactate (AUC 0.797, p<0.0001) and AG (AUC 0.835, p<0.0001).\n\nAmong various other parameters, significant predictors of mortality were elevated HR, RR, SOFA score and lower levels of SBP, O2 saturation, PiO2/FiO2 ratio. Also, need of ventilator and inotropes predicted mortality. Hospital stay was shorter in non-survivors than survivors.\n\n\nDiscussion\n\nIn this study, we included 160 patients with sepsis with SOFA score >2.\n\nMean age of the population was 53.1±17.0 and 61.9% were males. Hypertension (41.3%) and diabetes (30%) were major comorbidities. On admission, mean HR was 123.1±20.8 bpm, mean RR was 29.8±9.2 per min, mean SBP was 82.3±28.7 mmHg, and O2 saturation level was 84±12%. The mean SOFA score was 9.5±5.3. 53.8%, patients had alerted mental status. 58.8% required ventilator whereas 63.1% needed inotrope support. Among laboratory parameters, mean Hb was 10.5±2.8 gm/dl, mean serum albumin was 3.0±0.8 mg/dl and mean serum creatinine was 2.6±2.6 mg/dl.\n\nMean serum lactate was 5.1±1.2 mmol/L and it was ≥4 mmol/L in 90% of patients.\n\nMean AG was 14.0±3.9 and it was ≥12 in 75.6% of patients. During a mean hospital stay of 10.6±8.8 days, mortality occurred in 45.6% of patients. Mean lactate level was significantly higher in patients with high AG (5.6±1.1 vs. 4.1±0.8 mmol/L, p<0.0001). Similarly, the proportion of patients who had lactate levels ≥4 mmol/L was higher in those with AG ≥12 than AG <12 (95.9% vs. 71.8%, p<0.0001). Among non-survivors, serum lactate level was significantly higher than survivors (5.8±1.1 vs. 4.5±0.9 mmol/L, odds ratio 4.55 (95% CI 2.68-7.70), p<0.0001). All non-survivors had lactate levels ≥4 mmol/L. Among non-survivors, mean AG was significantly higher than survivors (15.8±3.7 vs. 11.9±3.4, odds ratio 1.39 (95% CI 1.23-1.56) p<0.0001). AG ≥12 was seen in significantly higher proportion non-survivors than survivors (89% vs. 64.4%, p<0.0001). The area under curve of receiver operating characteristic (AUC of ROC) in predicting mortality was significant for both serum lactate (AUC 0.797, p<0.0001) and AG (AUC 0.835, p<0.0001).\n\nAmong various other parameters, significant predictors of mortality were elevated HR, RR, SOFA score and lower levels of SBP, O2 saturation, PiO2/FiO2 ratio. Also, need of ventilator and inotropes predicted mortality. Hospital stay was shorter in non-survivors than survivors.\n\nSepsis is one the commonly encountered diagnoses in ICU setting. In an Indian setting, beside the Gram-negative bacterial infections, tropical illnesses like dengue, malaria, leptospirosis, enteric fever, and tuberculosis are also significant causes of severe sepsis/septic shock.5 In the sepsis diagnosis and predicting the outcome of sepsis, multiple scores and biomarkers are used across the world. CRP, procalcitonin, proinflammatory cytokines, complement system biomarkers, and organ dysfunction biomarkers are employed.23 Elevation of serum lactate levels has been identified as important marker for predicting the outcome of sepsis.24 An elevated corrected AG usually reflects the presence of metabolic acidosis caused by the overproduction or decreased excretion of organic acids. In addition, elevated AG has been reported as a predictor of mortality in critically ill patients.25 We estimated the serum lactate levels and AG in sepsis patients and evaluated their role in predicting the in-hospital outcome (death or discharge). Below we discuss the findings from our study.\n\nAge and gender\n\nIn our study, mean age was 53.1±17.0 years and 38.1% were in age group pf 41 to 60 years and 36.9% were above 60 years.\n\nA recent Sepsis in India Prevalence Study (SIPS) from Hammond et al. reported median age of 60 years among patients admitted in ICU.26\n\nChatterjee et al. reported a mean age of 59.4±17.9 years in their study.27\n\nA study from Mohamed et al. observed 44% of patients of sepsis being over the age of 60 years. Thus, sepsis is more common in middle-age to elderly population than younger population.28\n\nMales were affected with slightly greater frequency. In our study, the proportion of males was 61.9%. Chatterjee et al. reported proportion of males affected to be 56.8%.27\n\nMohamed et al. also reported 71.25% of males in their study diagnosed with sepsis. These data indicate males are a slightly higher risk of sepsis than female.28\n\nComorbidities\n\nHypertension (41.3%) and diabetes (30%) were major comorbidities in our study.\n\nHammond et al. in their SIPS study reported diabetes (44.0%) and chronic renal failure (11.6%) as common comorbidities.26\n\nMohamed et al. reported type 2 diabetes mellitus and systemic hypertension 46.25% of patients each. This is similar to our observations.28\n\nSepsis etiology\n\nWe observed respiratory etiologies as most common cause of sepsis in our study followed by gastrointestinal and urinary etiologies.\n\nSimilar to our findings, Mohamed et al. reported respiratory tract as the suspected source of sepsis in 66.25% cases.28\n\nAnother study from Chatterjee et al reported similar results with respiratory tract (53.3%) as the most frequent site of infection followed by abdomen (14.9%), blood stream (14.3%) and urinary tract (12.9%).27\n\nA study from Abu-Humaidan et al. from Jordan identified gastrointestinal cause (37.8%) as most frequent one leading to sepsis followed by respiratory causes (24.4%), genitourinary etiology (24.4%), skin and soft tissue infections (13.3%) and others (17.8%). These results indicate that respiratory, GI and urinary infections are the most frequent causes of sepsis.29\n\nIn-hospital outcome\n\nIn our study, during a median hospital stay of 9 days, mortality occurred in 45.6% of cases. A study from West Bengal by Chatterjee et al. reported in-hospital mortality rate of 63.6% whereas the ICU and 28-day mortality rates were 56% and 62.8% respectively.27 A study in Brazilian cohort of patients with sepsis by Sogayar et al. reported mortality rate of 49.1% and 36.7% in public and private hospitals.30 Another study from North India by Nasa et al. reported ICU mortality ranging 45.6% to 60.7% and 78.9% among younger (<60 years), old (60 to 80 years) and very old (>80 years) patients who were diagnosed with sepsis.31\n\nThese data support our observation and indicate that sepsis is associated with significantly higher risk of mortality.\n\nSerum lactate levels and anion gap estimates\n\nMean serum lactate levels in our study were 5.1±1.2 mg/dL and 90% had lactate levels of 4 mmol/L. A study from Mikkelsen et al. reported median serum lactate levels of 2.9 mmol/L (interquartile range: 2.0 – 4.4). The proportion of patients who had serum lactate levels >4 mmol/L was 24.7% and 50% among patients who presented without and with septic shock respectively.32 Another study from Shapiro et al. reported serum lactate levels of >4 mmol/L in 10.5% of cases.33 A study from Singh et al reported mean serum lactate level at admission to be 2.87 ± 1.25 mmol/L.34 The relatively higher on admission lactate levels in our study population can be due to majority of patient presenting in septic shock as was observed by Mikkelsen et al.32\n\nIn our study, mean AG was 14.0±3.9. High AG (AG ≥12) was seen in 75.6% of patients. A study from Berkman et al. involving 1419 adult patients with sepsis, the mean AG was 11.8±3.6 whereas the mean lactate level was 2.1±1.3 mmol/L.22 A study from Mitra et al. involved 441 patients with sepsis. The initial median AG was 15.2 (13.8–17.4) and the median lactate level was 2.1 (1.5–2.9) mml/L.35 L-lactic acidosis and ketoacidosis are the 2 most prevalent endogenous causes of high-AG metabolic acidosis (HAGMA). Type A and Type B L-lactic acidosis are the two subtypes into which L-lactic acidosis is typically subdivided. Type A L-lactic acidosis, which can be brought on by hypovolemia, heart failure, sepsis, acute severe anemia, convulsions, or cardiopulmonary arrest, is the outcome of marked tissue hypoperfusion. In patients with shock brought on by sepsis, the initial serum lactate level and the rate at which lactate levels recover are indicators of survival. If tissue perfusion cannot be quickly restored, the prognosis is typically quite poor.36 The high anion gap in our study indicates significant acidosis induced by hyperlactatemia.\n\nSerum lactate levels and anion gap association with mortality\n\nWe first studied the association of lactate levels with AG. The mean serum lactate level was significantly higher in patients with high AG (p<0.0001). Also, 95.9% of patients with high AG (≥12) had serum lactate levels ≥4 mmol/L. Berkman et al. reported 80% sensitivity and 69% specificity of elevated AG (>12) that predicted lactate levels >4 mmol/L. They also observed a 7.3-fold increased risk of having a lactate >4 mmol/L for patients who had high AG in the emergency department. It indicates that sepsis patients may have anion gap abnormalities that is related to increased lactic acid levels. It is therefore advisable that high anion gap should be considered in the assessment of sepsis.22\n\nThe lactate level was significantly elevated in non-survivors compared to survivors (p<0.0001) and all non-survivors had elevated lactic acid levels. Similarly, the AG was significantly higher in non-survivors than survivors (p<0.0001). High AG (≥12) was seen in 89% of non-survivors than 64.4% of survivors (p<0.0001). Serum lactate levels had odds ratio of 4.55 and AG had odds ratio of 1.39 suggesting higher risk of mortality with both markers. Multiple studies have reported similar outcomes. Shapiro et al. reported higher mortality with serum lactate levels of >4 mmol/L (4.9%) compared to 2.5 mmol/L (9.0%) and 2.5 to 3.9 mmol/L (28.4%).33 In a retrospective cohort study of severe sepsis patients, Mikkelsen et al. found that in hemodynamically stable individuals with intermediate lactate levels (2.0-4.0 mmol/L) were also at substantial risk, as opposed to patients with levels <2.0 mmol/L. They used lactate cut-off of 4.0 mmol/L as a screening tool for sepsis.32 Another retrospective cohort study from Wacharasint et al. has confirmed this finding, by observing a significantly higher mortality in those with lactate levels >4 mmol/L than among patients with high normal lactate levels (1.5–2.3 mmol/L) and intermediate lactate levels (2.3–4.0 mmol/L).37 A study from Khosravani et al. reported 1.94–10.89-fold higher fatality rate with on admission serum lactate levels >2 mmol/L when compared to values below 2 mmol/L.38 Claridge et al. reported that not only the admission lactate levels but also the persistent hyperlactatemia predicts in-hospital mortality.39 Mitra et al. reported mortality rates with elevated lactate and AG levels. They reported in-hospital mortality rate of 11.7% among 231 patients with lactate >2 mmol/L and 14.9% among 221 patients with elevated AG (>16).35 Berkman et al. reported significantly higher mortality with elevated AG (>12) than lower AG (<12) (9.5% vs. 3.8%, relative risk 2.50). They also stated that compared to AG threshold of >16 and >20, AG>12 performed the best in predicting mortality.22 Adams et al. in a retrospective cohort analysis identified lactic acidosis with a sensitivity of 58.2%, specificity of 81.0%, and negative predictive value of 89.7% by using AG cutoff 12. Thus, it can be concluded that AG > 12 might be considered as one of the important predictors of in-hospital mortality in sepsis. This is further substantiated by our observations of AUC of ROC being 0.797 (95% confidence interval 0.728-0.865, p<0.0001) for AG and 0.835 (95% confidence interval 0.773 – 0.896, p<0.0001) for lactate in predicting mortality.40 Shapiro et al. reported that ROC AUC for lactate level as a predictor of death was 0.670. This finding is nearly similar to our results.33 Also, Mitra et al. reported AUC of 0.630 and 0.6800 for serum lactate and AG for predicting in-hospital mortality. Thus, both parameters have good sensitivity in predicting the mortality in sepsis.35\n\nOther predictors of mortality\n\nWe observed that higher heart rate, higher respiratory rate, lower systolic BP, lower O2 saturation, need of invasive ventilation, inotrope requirements, higher SOFA scores, lower PaO2/FiO2 and lower hospital stay were associated with in-hospital mortality in sepsis patients. A study from Kerala by Mohamed et al. reported elevated CRP (>100), APACHE II score >25, and need of invasive ventilation as predictors of mortality in adult patients with severe sepsis. A higher heart rate and lower mean arterial pressure at the time of admission to the ICU were also predictors of mortality.28 Vincent et al. reported significantly higher mortality in patients undergoing mechanical ventilation. This imply that need of invasive mechanical ventilation could be a predictor of mortality in severe sepsis.41 A systematic review by Minne et al. identified SOFA score in patients at presentation and at 48 hours are significant predictors of mortality.42 Similarly, various other studies have identified predictors of mortality. Bale et al. reported SOFA score, Shrestha et al. reported anemia, SOFA score, SAPS II and III scores and Mohan et al. reported SAPS III, anemia, and SOFA scores as predictors of mortality.43–45 Beside these, thrombocytopenia, and acute renal failure are also identified as predictors of mortality in other studies.46,47\n\nThis was one of the few studies that evaluated AG as parameter for predicting mortality in sepsis. Higher AG can be associated with increased mortality. However, our study has certain limitations. We did not assess other commonly used biomarkers such as CRP, procalcitonin. Comparison of lactate and AG with these parameters might provide greater insights as to which parameters can be best predictor of mortality. We did not assess APACHE II score to determine the severity of illness as APACHE II score has been identified as predictor of mortality. Also, we assessed in-hospital mortality only. Assessing 28-day or 90-day mortality can provide different picture in associating AG with such short-term mortality figures.\n\n\nConclusions\n\nIn this, of adult patients with sepsis, the in-hospital mortality rate was 45.6% during a mean hospital stay of 10.6±8.8 days. We observed that serum lactate was associated with significantly higher mortality with increased odds by 4.5 times for mortality in hospital. Similarly, anion gap was associated with 1.3 times higher risk of mortality. High AG (>12) was significantly associated with mortality. The association between serum lactate and AG was significant with 95.9% of patients with high AG having serum lactate levels ≥4 mmol/L. Both parameters had good predictive ability with AUC in ROC being higher than 0.7 for both parameters. Along with other parameters predicting mortality, serum lactate and AG also act as important predictors of mortality in sepsis patients. We conclude that on admission serum lactate ≥4 mmol/L and AG ≥12 can be used in predicting short-term mortality in patients with sepsis. Comparison of lactate and AG with these parameters might provide greater insights as to which parameters can be best predictor of mortality. We did not assess APACHE II score to determine the severity of illness as APACHE II score has been identified as predictor of mortality. Also, we assessed in-hospital mortality only. Assessing 28-day or 90-day mortality can provide different picture in associating AG with such short-term mortality figures.\n\nThe present study was conducted after the clearance of the Institutional Ethical Committee (IEC number, DMIMS (DU)/IEC/2020-21/9300) of Datta meghe institute of medical sciences.",
"appendix": "Data availability\n\nZenodo, ANION GAP OR SERUM LACTATE-IN SEARCH OF A BETTER PROGNOSTIC MARKER IN SEPSIS A CROSS-SECTIONAL STUDY IN A RURAL TERTIARY CARE HOSPITAL, https://doi.org/10.5281/zenodo.7824864.\n\nZenodo, strobe cross sectional checklist, https://doi.org/10.5281/zenodo.7824918.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nI would like to acknowledge to all the nurses and other staff members, patients and their relatives, laboratory technicians of the hospital during this study duration.\n\n\nReferences\n\nDellinger RP, Levy MM, Carlet JM, et al.: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit. Care Med. 2008; 36(1): 296–327. PubMed Abstract | Publisher Full Text\n\nSinger M, Deutschman CS, Seymour C, et al.: The third international consensus definitions for sepsis and septic shock (sepsis-3). 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PubMed Abstract | Publisher Full Text\n\nKhosravani H, Shahpori R, Thomas HT, et al.: Occurrence and adverse effect on outcome of hyperlactatemia in the critically ill. Crit. Care. 2009; 13(3): 1–5.\n\nKaplan LJ, Kellum JA: Initial pH, base deficit, lactate, anion gap, strong ion difference, and strong ion gap predict outcome from major vascular injury. Crit. Care Med. 2004; 32(5): 1120–1124. Publisher Full Text\n\nHammond NE, Kumar A, Kaur P, et al.: Estimates of Sepsis Prevalence and Outcomes in Adult Patients in the ICU in India: A Cross-sectional Study. Chest. 2022; 161(6): 1543–1554. PubMed Abstract | Publisher Full Text\n\nChatterjee S, Bhattacharya M, Todi SK: Epidemiology of adult-population sepsis in India: a single center 5 year experience. Indian J. Crit. Care Med. 2017; 21(9): 573–577. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMohamed AKS, Mehta AA, James P: Predictors of mortality of severe sepsis among adult patients in the medical Intensive Care Unit. Lung India. 2017; 34(4): 330–335. PubMed Abstract | Publisher Full Text\n\nAbu-Humaidan AHA, Ahmad FM, Al-Binni MA, et al.: Characteristics of Adult Sepsis Patients in the Intensive Care Units in a Tertiary Hospital in Jordan: An Observational Study. Crit. Care Res. Prac. 2021; 2021: 1–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSogayar AMC, Machado FR, Rea-Neto A, et al.: A multicentre, prospective study to evaluate costs of septic patients in Brazilian intensive care units. PharmacoEconomics. 2008; 26(5): 425–434. PubMed Abstract | Publisher Full Text\n\nNasa P, Juneja D, Singh O, et al.: Severe sepsis and its impact on outcome in elderly and very elderly patients admitted in intensive care unit. J. Intensive Care Med. 2012; 27(3): 179–183. Publisher Full Text\n\nMikkelsen ME, Miltiades AN, Gaieski DF, et al.: Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit. Care Med. 2009; 37(5): 1670–1677. Publisher Full Text\n\nShapiro NI, Howell MD, Talmor D, et al.: Serum lactate as a predictor of mortality in emergency department patients with infection. Ann. Emerg. Med. 2005; 45(5): 524–528. Publisher Full Text\n\nSingh S, Bhardawaj A, Shukla R, et al.: The handheld blood lactate analyser versus the blood gas based analyser for measurement of serum lactate and its prognostic significance in severe sepsis. Med. J. Armed Forces India. 2016; 72(4): 325–331. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMitra B, Roman C, Charters KE, et al.: Lactate, bicarbonate and anion gap for evaluation of patients presenting with sepsis to the emergency department: A prospective cohort study. EMA - Emerg. Med. Australas. 2020; 32(1): 20–24. PubMed Abstract | Publisher Full Text\n\nEmmett M: Review of Clinical Disorders Causing Metabolic Acidosis. Adv. Chronic Kidney Dis. 2022; 29(4): 355–363. Publisher Full Text\n\nWacharasint P, Nakada TA, Boyd JH, et al.: Normal-range blood lactate concentration in septic shock is prognostic and predictive. Shock. 2012; 38(1): 4–10. PubMed Abstract | Publisher Full Text\n\nKhosravani H, Shahpori R, Thomas HT, et al.: Occurrence and adverse effect on outcome of hyperlactatemia in the critically ill. Crit. Care. 2009; 13(3): 1–5.\n\nClaridge JA, Crabtree TD, Pelletier SJ, et al.: Persistent occult hypoperfusion is associated with a significant increase in infection rate and mortality in major trauma patients. J. Trauma. 2000; 48(1): 8–15. PubMed Abstract | Publisher Full Text\n\nAdams BD, Bonzani TA, Hunter CJ: The anion gap does not accurately screen for lactic acidosis in emergency department patients. Emerg. Med. J. 2006; 23(3): 179–182. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVincent JL, Sakr Y, Sprung CL, et al.: Sepsis in European intensive care units: results of the SOAP study. Crit. Care Med. 2006; 34(2): 344–353. PubMed Abstract | Publisher Full Text\n\nMinne L, Abu-Hanna A, de Jonge E : Evaluation of SOFA-based models for predicting mortality in the ICU: A systematic review. Crit. Care. 2008; 12(6): 1–3.\n\nBale C, Kakrani AL, Dabadghao VS, et al.: Sequential organ failure assessment score as prognostic marker in critically ill patients in a tertiary care intensive care unit. Int. J. Med. Public Health. 2013; 3(3): 155. Publisher Full Text\n\nShrestha P, Mohan A, Sharma S, et al.: To determine the predictors of mortality and morbidity of sepsis in medical ICU of all India Institute of Medical Sciences (AIIMS), New Delhi, India. Chest. 2012; 142(4): 407A. Publisher Full Text\n\nMohan A, Shrestha P, Guleria R, et al.: Development of a mortality prediction formula due to sepsis/severe sepsis in a medical intensive care unit. Lung India. 2015; 32(4): 313–319. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Oliveira T , Boechat M, da Silveira FBB , et al.: Thrombocitopenia in sepsis: an important prognosis factor. SciELO Bras. 2012; 24(1): 35–42.\n\nOppert M, Engel C, Brunkhorst FM, et al.: Acute renal failure in patients with severe sepsis and septic shock–a significant independent risk factor for mortality: results from the German Prevalence Study. Nephrol. Dial. Transplant. 2008; 23(3): 904–909."
}
|
[
{
"id": "174836",
"date": "16 Aug 2023",
"name": "Zhongheng Zhang",
"expertise": [
"Reviewer Expertise Sepsis",
"septic shock"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt seems not a good practice to link a biomarker with outcome in sepsis; lactate and AG have long been noticed to link to sepsis mortality; the current finding is not surprising.\n\nThe novelty and clinical utility of the study is not well defined.\n\nAn improvement can be that to add lactate and AG to existing scores to see whether these biomarkers can further improve the diagnostic performance of these scores.\n\nThe age and gender distribution is not the task of the current study, these are epidemiological features and needs large sample size to address this issue.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-536
|
https://f1000research.com/articles/12-535/v1
|
23 May 23
|
{
"type": "Study Protocol",
"title": "Comparative evaluation of the effectiveness of Titanium platelet rich fibrin (T-PRF) membrane and collagen membrane combined with xenograft in the treatment of mandibular class II furcation defects – A study protocol of randomized controlled trial",
"authors": [
"Ruchita Patil",
"Prasad V Dhadse",
"Prasad V Dhadse"
],
"abstract": "BACKGROUND Class II furcation is a significant clinical problem in dentistry. Its presence indicates advanced periodontitis. Different xenografts are available for the treatment of furcation involvement. Platelet concentrates that have been assimilated have a high concentration of growth factors, which has the added benefit of improving and accelerating healing. This study aims to compare the evaluation of effectiveness of T-PRF with xenograft and collagen membrane with xenograft in class II furcation defects. METHODS A one-year timeframe is going to be utilized to carry out the planned protocol, which is a randomised clinical trial. According to the inclusion criteria, 26 systemically healthy patients with class II furcation defects in mandibular molars will be included in the study. In Group I, xenograft and T-PRF (test group) will be condensed and in Group II, xenograft and collagen membrane (control group) will be condensed after the complete debridement of the furcation defect. Plaque index (PI), papillary bleeding index (PBI), Periodontal pocket depth (PPD), relative attachment level (R-CAL) and relative gingival marginal level (R-GML) will be evaluated as the clinical parameters. Cone-beam computed tomography (CBCT) will be performed to measure furcation height (FH), furcation width (FW), and furcation depth (FD) defects of mandibular molars. Data from each group will be evaluated at the time of surgery (baseline), and three and six months after the surgery. EXPECTED OUTCOMES Using xenograft (FIX OSS) combined with T-PRF, the authors anticipate better outcomes for class II mandibular furcation defects (test group). Improved clinical and radiographic outcomes in terms of PPD, R-CAL, R-GML and FH, FW, FD, are anticipated. CONCLUSIONS Using xenograft in combination with the T-PRF procedure is anticipated to have a better combined effect on periodontal parameters, including hard tissues and soft tissue outcomes. Registration: CTRI REF/2023/03/064367.",
"keywords": [
"Periodontitis",
"bovine derived-xenograft",
"regenerative treatment",
"GTR",
"collagene membrane",
"clinical trial."
],
"content": "Introduction\n\nPeriodontitis is “an infectious condition that affects the teeth's supporting tissues and is brought on by a particular bacterium or collection of bacterias, causing the alveolar bone and periodontal ligament to eventually degenerate and the production of greater probing depths”.1 Periodontitis leads to tooth loss and due to its widespread occurrence, it has grown to be a major problem for public health.1 Periodontitis is a condition that affects multi-rooted teeth more frequently and, if left untreated, damages the periodontal attachment and tooth-supporting tissues, eventually leading to intraosseous defects or furcation defects.2,3 Class II furcation is of significant clinical concern because it leads to the loss of connective tissues as well as continuous resorption of alveolar bone.4\n\nFurcation involvement is a complex anatomical structure that makes it challenging to complete debridement using traditional periodontal instruments.5,6 For many years, mechanical debridement has been used in periodontal treatment to remove bacterial infections.7 Non-surgical mechanical debridement alone frequently causes disease progression in extensive furcation involvements.8 In the interest of preventing the progression of the disease, surgery enables access for periodontal regeneration, root debridement, osseous recontouring, odontoplasty, and detoxification while preserving periodontal attachment.9\n\nA lost or damaged component is recreated or repaired by periodontal regeneration such that the structure and functionality of the tissue are fully restored. For the regeneration of the furcation, influencing factors include the use of bone grafts or bone replacement implants, as well as organic and synthetic barrier membranes, biological mediators, and growth factors.10\n\nOne of the most popular treatments is the use of varieties of bone grafts to fill the furcation defects and to restore the lost periodontal apparatus.11 Among various bone grafts are autogenous bone, alloplasts, allografts and xenografts. In an autogenous graft, the patient's own bone is actually removed and used to induce osteogenesis, osteoinduction, and osteoconduction in order to make new bone. Allografts obtained from cadavers contain the osteoinductive and osteoconductive properties but not osteogenic ones. Xenografts and alloplasts often only have osteoconductive properties.12\n\nHigh osteoconductive activity of deproteinized bovine bone material leads to extracellular bone matrix deposition and they are the most commonly utilised amongst natural bone fillers.13 The xenograft, which is made of bovine bone that has undergone acidic decalcification to remove its mineral content while maintaining its organic portion, contains some osteoinductive growth factors.14 FIX OSS is a new bovine derived xenograft which is a highly purified bone substitute material. The porous interconnecting architecture of FIX OSS mimics the natural bone structure and promotes faster bone regeneration and remodelling of the new bone.\n\nGuided tissue regeneration (GTR) is a regeneration method that mainly entails repopulating the previously damaged root surface with selected progenitor cells while eliminating direct contact with the gingival epithelium and connective tissue.15 Fix Gide GTR is a bovine derived resorbable collagen membrane which has a unique bilayer structure that offers superior tissue compatibility and prevents the ingrowth of soft tissue into the augmented site.\n\nIn 2013, Tunali created titanium-prepared platelet rich fibrin (T-PRF) using biocompatible titanium tubes.16 It is a fibrin that resembles PRF but differs from PRF in that it has a denser fibrin network. Leukocytes and platelets are abundant. In order to extend intra-tissue fibrin resorption and progressively release growth factors, this denser fibrin structure is required.17 There is little recognition of the effectiveness T-PRF's profile.18\n\nIn order to address class II mandibular furcation defects, this study procedure was developed using T-PRF as a regeneration material along with xenograft. The aim of this randomized clinical trial protocol is the evaluation of the efficacy of xenograft and T-PRF in the management of class II mandibular furcation defects.\n\n\n\n\nThis clinical trial has been registered with Clinical Trial Registry of India on 04/03/2023, ref REF/2023/03/064367.\n\nThe study proposal is approved by the institutional ethics committee on 02/02/2023 with Ref No. DMIHER (DU)/IEC/2023/574. Patients’ informed consent will be taken prior to the procedure, including both written and verbal consent.\n\nThe present study is a randomised clinical trial and will be performed over a period of one years. Trial design will be an interventional type of trial. Allocation ratio will be 1:1.\n\nThe study participants’ allocation will be done by a dentist, according to the inclusion and exclusion criteria in the Outpatient Department (OPD) of Periodontics and Implantology, Sharad Pawar Dental College, Sawangi (Meghe), Wardha, Maharashtra, India after taking written informed consent.\n\nSample size calculation\n\nSample size was calculated using OpenEpi, version 3, open-source calculator, sum of square mean.\n\nFormula using mean difference\n\nPrimary variable (periodontal attachment level-vertical)\n\n(Mandibular class II furcation, difference after 6 months) Mean ± SD. = 1.7 ± 1.5\n\nAs per reference articles - Andrej Djurkin et al., 2019.\n\nTotal samples required = 13 per group.\n\n• Inclusion criteria\n\n1) Buccal/lingual involvement with class II mandibular furcation defects.\n\n2) Horizontal defect depth (HDD) not more than 6mm.\n\n3) Vertical defect depth (VDD) of 3 mm.\n\n4) The height of the proximal bone of the tooth involved in the study should be coronal to the level of the interradicular bones.\n\n5) An adequate amount of keratinized tissue should be present (at least 2mm should be present from mucogingival junction to gingival margin).\n\n6) The level of the affected tooth's gingival margin should be coronal to the fornix of the furcation.\n\n7) Molars with radiographic indications of furcation defects (buccal, mesiobuccal or distobuccal and lingual).\n\n• Exclusion criteria\n\n1) Patients not adhering to continuance of periodontal maintenance programme.\n\n2) A habit of smoking or consuming tobacco.\n\n3) Presence of mobility in the selected tooth.\n\n4) Allergic reactions to any materials involved.\n\n5) Any earlier or previous periodontal regeneration procedures performed into chosen location or site.\n\n6) Females who are pregnant or nursing.\n\n7) Infectious disease in patients like hepatitis, HIV, or tuberculosis.\n\n8) Patients having a history of systemic illness.\n\n• Clinical parameters\n\nPapillary bleeding index (PBI), plaque index (PI), periodontal pocket depth (PPD), relative attachment level (R-CAL), and relative gingival marginal level (R-GML) are the clinical parameters that will be reported. Furcation height (FH), furcation width (FW), and furcation depth (FD) will be measured radiographically. Prior to surgery (at baseline), three- and six-months following surgery, all clinical parameters will be collected. The study's radiographic bone fill will serve as the primary result, while gains in CAL and PPD will serve as the secondary results.\n\nThe full-mouth plaque index will be measured before the anaesthesia at the baseline as well as six months later.19 The papillary bleeding index will be used to assess gingival inflammation (PBI).20\n\nA UNC-15 calibrated periodontal probe (University of North Carolina, Hu-Friedy) will be used to measure all clinical parameters while utilising surgical stents. At three locations on every furcation defect—line angle of distal and mesial as well as surface of midbuccal or midlingual— R-CAL and R-GML with the vertical probing pocket depth (V-PPD) will be recorded and the highest measurement will be considered.\n\nThe gingival margin will be measured from the inferior border of the acrylic stent's slots using the UNC-15 probe, and this measurement will be reported as the relative gingival marginal level (R-GML). The space between the pocket's base and the pocket and the inferior border of the stent will be measured using the UNC-15 probe to determine the relative clinical attachment level (R-CAL). From the pocket's base to its gingival margin, the vertical probing pocket depth will be determined (PPD). Using a curved, color-coded furcation probe with marks for 0-3, 3-6, and 6-9 mm, the furcation's horizontal probing depth (HPD) will be identified. Using the UNC-15 Probe, the keratinized gingiva’s (WKG) width will be estimated from the mucogingival junction's apical most point to the crest of the gingival edge. All clinical parameters will be documented at baseline, one and six months thereafter.\n\nMeasurements of the following radiographic parameters will be made using cone-beam computed tomography (CBCT):\n\n1) Furcation height (FH): this is the height between the base of the alveolar bone and the furcation fornix, which is the roof of the furcation.\n\n2) Furcation width (FW): this term refers to the distance between the two roots that are the furthest distance from one another above the crest of the alveolar bone.\n\n3) Furcation depth (FD): the distance between the inter-radicular bone and the crest of the alveolar bone.\n\n• T-PRF membranes preparation\n\n10 millilitres of blood will be drawn from the participants' antecubital veins by venepuncture in order to prepare T-PRF. The samples will be placed in the centrifuge and titanium test tubes in 30 seconds. For 10 minutes, it will be centrifuged at 2700 rpm. It will be possible to acquire the T-PRF clot after centrifugation. The fibrin clot that has formed in the centre of the tube and the remaining red blood cells will be eliminated. To obtain T-PRF membranes, the clot will be placed over PRF box and pushed.21\n\n• Surgical procedure\n\nThe subjects will be instructed to gargle for one minute with a solution of 0.2% chlorhexidine gluconate before the treatment starts. The procedure will be conducted under asepsis. The area will be anaesthetized by nerve block and infiltration using 2% Xylocaine with a concentration of 1:80,000 epinephrine (Ligno-Ad local anaesthetic, Proxim Remedies, India). Among all local anaesthetic substances, lignocaine is regarded as the gold standard.19\n\n• Flap design (incisions)\n\nA crevicular incision will be made using a number 15 blade, on the buccal or lingual surfaces of the affected tooth. The incisions will be made interproximally to close the primary wound and fix the interdental papillae. The flap will cover the region proximal and distal to the affected tooth.\n\n• Flap reflection\n\nWith the use of a periosteal elevator (24 G Hu-Friedy, USA), a full thickness mucoperiosteal flap shall be raised on the affected site to reveal the underlying defect margin. Extra caution will be required when removing granulation tissue to prevent flap perforation or papilla loss.\n\n• Debridement and root surface management\n\nCurettes (Osung), ultrasonic devices (Woodpecker HW-3H), and hand tools (GDC) will be used to debride the furcation dome on the root surface which is denuded. The root surfaces and furcation defects will be planed until a smooth, firm consistency is obtained.\n\nAt the site of the furcation, intraoperative measurements of the horizontal and vertical defect depth will be taken after physiologic saline solution irrigation and achieving hemostasis.\n\n1) Horizontal defect depth (HDD): using UNC 15, the furcation area will be recorded horizontally at its deepest area, and a second probe will be positioned at the root surface's prominence to use as a reference the initial probe.\n\n2) Vertical defect depth (VDD): using the furcation fornix as a constant point of reference, the depth of the furcation defect will be determined vertically. The sites will then assign by computer a random number to either the test or control group following the intraoperative measurements.\n\nProcedure for test group\n\nThe full thickness flap will be raised and the area to be treated will achieve total isolation and hemostasis. Xenograft and T-PRF will be compressed in the furcation defect. After the membrane has been stabilised, suture and periodontal pack (COE Pack) will be given to the treated site.\n\n• Procedure for control group\n\nThe site will achieve total isolation and hemostasis. Following the thorough debridement of the furcation defect, the xenograft and collagen membrane will be condensed. After stabilising the membrane, the flap will be stitched. On the site of treatment, a periodontal pack (COE Pack) will be placed.\n\n• Post-operative care\n\nPatients will be prescribed amoxicillin 500 mg, three times a day, along with ibuprofen 400 mg and paracetamol 325 mg after surgery for five days. The use of 0.2% chlorhexidine gluconate as a gargle is prescribed for patients for 4-6 weeks, two times a day. Patients will be instructed not to brush over the surgical area for 7 days after surgery. 7 days after the surgery, the periodontal pack and sutures will be removed and healing will be evaluated. With the use of rubber cups, polishing paste, and saline irrigation, the affected location should be protected. Subjects will be instructed to use a gentle toothbrush and cotton pellets to clean the operated site in an apico-coronal direction. Re-evaluation will be done one, three and six months post-operatively.\n\n• Maintenance care\n\nThe participants will undergo another evaluation one, three, and six months after surgery. At each subsequent session, dental hygiene advice and a complete mouth oral prophylaxis using ultrasonic tools will be provided. During the first three months following the surgery, no clinical measurements will be taken.\n\n• Statistical analysis (in OpenEpi, version 3)\n\nAll clinical measurements, including plaque index (PI), papillary bleeding index (PBI), pocket probing depth (PPD), relative clinical attachment level (R-CAL), and relative gingival marginal level (R-GML), will be calculated using the mean and standard deviation measurements. Data on the day of surgery, i.e., at baseline, to six months will be analysed using the Student’s paired t-test. To compare the two groups at baseline and six months later, we will use Student’s unpaired t-test. The Student's paired t-test will be used to compare the baseline and six-month PBI and PI. If the probability value (p) is less than 0.05, the difference will be deemed significant; if it is greater than 0.05, it will be deemed non-significant. To determine differences among each group, the Wilcoxon test or paired Student's t-test will be used. Student's t-test or Mann-Whitney will be used independently used to assess all hard and soft tissue factors.\n\n\nDiscussion\n\nThe effectiveness of a bovine-derived xenograft that with or without a collagen membrane for the treatment of Class II mandibular furcations on 32 furcation defects was examined by Andrej Djurkin et al. in a randomised clinical trial published in 2019. All clinical parameters were assessed at the six-month follow-up using a straight probe and a modified \"Nabers probe\". After six months, there was a favourable evolution in both the vertical and horizontal attachment levels. The measures taken did not differ significantly (*p >.05, unpaired t-test). Authors stated that a statistically significant difference was not found between the two treatments and that both were clinically effective.\n\nIn order to compare the effectiveness of xenograft alone or in conjunction with platelet rich fibrin (PRF) in the treatment of grade II furcation deformities, Ahmed Abdallah Khalil (2019) conducted a study in which they clinically and radiographically investigated a total of 40 grade II furcation defects in 20 split mouth patients. For open flap surgery, the chosen sites were split into two groups and treated with either xenograft (cerabone®) alone in Group I or xenograft (cerabone®) + PRF membrane in Group II. Clinical and radiographic evaluations were carried out at baseline (before to surgery) and six months following surgery. Plaque index (PI), gingival index (GI), horizontal clinical attachment level (HCAL), and vertical clinical attachment level (VCAL) were among the clinical criteria examined. The furcation depth (FD), furcation height (FH), and furcation width (FW) were measured at baseline and six months after surgery, using cone-beam computed tomography (CBCT). Both groups had a statistically significant decline in each clinical and radiographic assessment from the beginning to six months following surgery. After six months following surgery, Group II had significantly higher FD, FH, FW, and HCAL values than Group I. The authors claim that xenograft (cerabone®) plus PRF significantly improved on xenograft (cerabone®) alone in treating furcation grade II defects.\n\nIn this protocol, we propose using the novel approach using T-PRF in grade II furcation defects. The combined effects of using T-PRF along with xenograft (FIX-OSS) will expect positive outcomes for better healing. This study plan is to accelerate the improvement of hard tissue outcomes and other periodontal parameters.\n\nAfter the completion of the study the data will be publicly available. The raw data will be shared through a suitable repository (figshare).\n\nThe recruitment will begin September 2023.",
"appendix": "Data availability\n\nNo data are associated with this protocol.\n\nSPIRIT checklist for ‘Comparative evaluation of the effectiveness of titanium platelet rich fibrin (T-PRF) membrane and collagen membrane combined with xenograft in the treatment of mandibular class II furcation defects – a randomized controlled trial’. https://doi.org/10.5281/zenodo.7779917. 22\n\n\nReferences\n\nClinical and Cone-beam Computed Tomography Evaluation of Xenograft alone or in combination with Platelet Rich Fibrin in the Treatment of Grade II Mandibular Furcation Involvement. Oral Medicine, X-Ray, Oral Biology & Oral Pathology. April 2019; Volume 65(2): Page 1377–1387. Article 23. Publisher Full Text\n\nBevilacqua L, Fonzer A, et al.: outcome of different surgical approaches in the treatment of class II furcation defects in mandibular molars: A randomized clinical trial. the international journal of periodontics and restorative dentistry. 2020; 40(5): 693–701. PubMed Abstract | Publisher Full Text\n\nRani N, Kaushal S, Singh S: Evaluation of the relative efficacy of autologous platelet-rich fibrin membrane in combination with β-tricalcium phosphate (Septodont-resorbable tissue replacement)™ alloplast versus β-TCP alloplast alone in the treatment of grade II furcation defects. National journal of maxillofacial surgery. 2018; 9(2): 196.\n\nBjorn A, Hjort P: Bone loss of furcated mandibular molars. A longitudinal study. J. Clin. Periodontol. 1982; 9: 402–408. PubMed Abstract | Publisher Full Text\n\nChowdhary Z, Mohan R: Furcation involvement: Still a dilemma. Indian Journal of Multidisciplinary Dentistry. 2017 Jan 1; 7(1): 34. Publisher Full Text\n\nPisulkar SK, Agrawal R, Belkhode V, et al.: Perception of buccal corridor space on smile aesthetics among specialty dentist and layperson. J. Int. Soc. Prev. Community Dent . 2019 Sep; 9(5): 499–504. PubMed Abstract | Publisher Full Text\n\nBjorn A, Hjort P: Bone loss of furcated mandibular molars. A longitudinal study. J. Clin. Periodontol. 1982; 9: 402–408. PubMed Abstract | Publisher Full Text\n\nGhangurde AA, Ganji KK, Bhongade ML, et al.: Role of Chemically Modified Tetracyclines in the Management of Periodontal Diseases: A Review. Drug research. 2017 May; 67(05): 258–265. Publisher Full Text\n\nCarnevale G, Pontoriero R, di Febo G : Long-term effects of root-resective therapy in furcation-involved molars. A 10-year longitudinal study. J. Clin. Periodontol. 1998; 25: 209–214. PubMed Abstract | Publisher Full Text\n\nRaja S, Nath G, Emmadi P: Treatment of an isolated furcation involved endodontically treated tooth-a case report. J. Conserv. Dent. 2007 Oct 1; 10(4): 129. Publisher Full Text\n\nCarnevale G, Cairo F, Tonetti MS: Long-term effects of supportive therapy in periodontal patients treated with fibre retention osseous resective surgery. I:recurrence of pockets, bleeding on probing and tooth loss. J. Clin. Periodontol. 2007; 34: 334–341. PubMed Abstract | Publisher Full Text\n\nDohan DM, et al.: Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2006; 101(3): e37–e44. Publisher Full Text\n\nNart J, Barallat L, Jimenez D, et al.: Radiographic and histological evaluation of deproteinized bovine bone mineral vs. deproteinized bovine bone mineral with 10% collagen in ridge preservation. A randomized controlled clinical trial. Clin. Oral Implants Res. 2017 Jul; 28(7): 840–848. View at: Publisher Site|Google Scholar. PubMed Abstract | Publisher Full Text\n\nKamadjaja DB, Sumarta NPM, Rizqiawan A: Stability of tissue augmented with deproteinized bovine bone mineral particles associated with implant placement in anterior maxilla. Case Reports in Dentistry. 2019; vol. 2019: 1. Article ID 5431752. View at: Publisher Site|Google Scholar. Publisher Full Text\n\nKannan AL, Bose BB, Muthu J, et al.: Efficacy of combination therapy using anorganic bovine bone graft with resorbable GTR membrane vs. open flap debridement alone in the management of grade II furcation defects in mandibular molars–A comparative study. Journal of International Society of Preventive & Community Dentistry. 2014 Nov; 4(Suppl 1): S38–S43. PubMed Abstract | Publisher Full Text\n\nOza R, Dhadse P: Evaluation of the effectiveness of Titanium-prepared Platelet rich Fibrin (T-PRF) and Demineralized Freeze-dried Bone Allograft (DFDBA) in socket preservation followed by implant placement using two stage approach. JPRI. 2021; 33(60B): 3763–3770. Publisher Full Text\n\nMitra DK, Potdar PN, Prithyani SS, et al.: Comparative study using autologous platelet-rich fibrin and titanium prepared platelet-rich fibrin in the treatment of infrabony defects: An in-vitro and In-vivo study. J. Indian. Soc. Periodontal. 2019; 23: 554–561. Publisher Full Text\n\nUzun BC, Ercan E, Tunah M: Effectiveness and predictability of titanium-prepared platelet-rich fibrin for the management of multiple gingival recession. Clin. Oral Investig. 2018; 22(3): 1345–1354. PubMed Abstract | Publisher Full Text\n\nTuresky S: Gilmore, Glickman: Reduced plaque formation by the chloromethyl analogue of vit C. J. Periodontol. 1970; 41: 41–43. PubMed Abstract | Publisher Full Text\n\nMuhlemann HR: Psychological and chemical mediators of gingival health. J. Prev. Dent. 1977; 4: 6–17. PubMed Abstract\n\nGarg S, Arora SA, Chhina S, et al.: Multiple gingival recession coverage treated with vestibular incision subperiosteal tunnel access approach with or without platelet-rich fibrin-A case series. Contemp Clin. Dent. 2017; 8(3): 464–468. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDr Patil RT , Dr Dhadse PV : Comparative evaluation of the effectiveness of titanium platelet rich fibrin (T-PRF) membrane and collagen membrane combined with xenograft in the treatment of mandibular class II furcation defects –A Randomized Controlled Trial.2023. Publisher Full Text"
}
|
[
{
"id": "203490",
"date": "15 Sep 2023",
"name": "Lorenzo Bevilacqua",
"expertise": [
"Reviewer Expertise Periodontology and Implantology"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI was invited to review this manuscript. Title: Comparative evaluation of the effectiveness of Titanium platelet rich fibrin (T-PRF) membrane and collagen membrane combined with xenograft in the treatment of mandibular class II furcation defects - A study protocol of randomized controlled trial. Even though I applauded the work by the authors, however, I have concerns of this study protocol trial. This paper have high level of biases.\nIntroduction\nDo not give a literature review here. There is a lack of studies on the influences of morphologic characteristics of the furcation defects. Also missing the results of previous clinical trials on the subject.\n\nReferences are wrong (no matches and missing references). Whole text should be revised.\n\nPlease clearly outline your research question. Both aims and objectives must be convincingly elaborated.\n\nA clear and indisputable null hypothesis would seem missing.\nMethods\nPlease add the section. So it is not clear.\n\nWith all materials and methodologies, please use general names with your text, followed by (brand name; manufacturer, city, country) in parentheses. Check for uniform writing/formatting. Please provide complete information, and remember to ensure future readers to repeat your study.\n\nWhat is the primary variable? In the section “Sample size calculation” is written Periodontal attachment level vertical along the text radiographic bone fill…However, there is not detail how evaluated these parameters.\n\nTo me, the control group is another test group should be without regenerative fill (e.g OFD).\n\nThere is not enough detail for Surgical procedure in order to replicate your study (coronal advancement? Type Sutures? Suspended sutures? Hand tools? Reconturing?…)\n\nPeriodontal pack is not used for regenerative therapy.\n\nIt is missing when the defect is radiographically revalued. One year? At 3 months or 6 is too short…overtreatment?\n\nNo test of normality of the distribution is provided. Why will the authors be used parametric data? For recall time points, which statistic analysis do you want use?\nDiscussion and Conclusions\nNote to discuss the the limitations of the study more thoroughly. Are there any fatal shortcomings or drawbacks? Does your study provide opportunities to inform future research?\n\nAll in all, this section would not seem well elaborated, and is considered too short when reflecting on the topic bearing much wealth.\nReferences\nThis section is in need of a thorough revision.\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? No\n\nAre sufficient details of the methods provided to allow replication by others? No\n\nAre the datasets clearly presented in a useable and accessible format? No",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-535
|
https://f1000research.com/articles/12-530/v1
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22 May 23
|
{
"type": "Study Protocol",
"title": "Comparative evaluation and correlation of CVMI stages in Class II (vertical) and Class II (horizontal) cases with Class I malocclusion, as evaluated using 3D-DVT and lateral cephalogram",
"authors": [
"Lovely Bharti",
"Sunita Shrivastav",
"Abhishek Sanchla",
"Ranjit Kamble",
"Sunita Shrivastav",
"Abhishek Sanchla",
"Ranjit Kamble"
],
"abstract": "Background: The cervical vertebrae have attracted the interest of orthodontists, as the cervical portion of the spine serves as a reference structure to guide the normal head position. Skeletal age is determined by examining changes occurring in the morphology of the cervical vertebrae. There is relatively little data available from all the examinations that compare cervical vertebral phases between the various malocclusions. The purpose of this study was to compare the cervical vertebral maturation index (CVMI) stages of skeletal Class I and Class II malocclusions in the horizontal as well as vertical growth patterns. With distinct malocclusions, however, there are differences in cervical vertebral phases.\nAim: To evaluate, compare and correlate the skeletal maturation using CVMI stages in cases with Class II (horizontal and vertical) using 3D-DVT and lateral cephalogram.\nMethodology: In the present observational study, a total of 45 adult patients reporting at the Orthodontics department at a dental college and hospital set up in Wardha district and diagnosed with Class II Horizontal and/or Class II vertical will be recruited. The patients will be divided into three sub-groups and biosafety measures will be taken.\nConclusions: This study would give us a scope to compare the efficiency of lateral cephalogram versus 3D-DVT in estimating the skeletal maturity of patients who need to undergo growth modification in the orofacial region and orthodontic treatment.",
"keywords": [
"Cervical vertebrae",
"lateral cehalogram",
"3D-DVT"
],
"content": "Introduction\n\nThe degree of ossification development in bone is referred to as skeletal maturation. Every bone undergoes a series of changes during growth, and the order of these changes is largely constant for a particular bone in each individual. Because everyone has their own biological clock, the timing of skeletal development differs, and treatment can be scheduled accordingly.1\n\nKnowing the rate of face growth and the proportion of facial growth left is critical for appropriate growth modification intervention in orthodontic treatment planning.\n\nFurthermore, knowing how much growth is left after orthodontic treatment can help with retention planning and preventing post-treatment rebound. Physiologic criteria such as peak growth velocity in standing height, pubertal markers such as voice changes in males, menarche in females, radiographic assessment of bone maturation, chronological age, and dental development staging have all been used to measure human skeletal development.2\n\nDetermining the skeletal maturity in individuals is very important to assess the outcomes of dental operations such as orthodontic treatment and orthognathic surgery. Some treatments may be hampered by residual bone growth, whereas others are better performed on patients who are still growing.3 As a result, accurate and precise determination of skeletal maturity is critical for timely dental interventions. Many authors have recommended a variety of growth evaluation methods, but the key difficulty is their dependability.4 The cervical vertebrae are regarded as a reliable measure of biological maturity and skeletal growth prediction. The size and shape of cervical vertebrae in growing subjects are becoming more popular as a biological sign of skeletal maturity.5 The lateral radiograph of the patient’s skull (cranium) is used to evaluate the cervical vertebrae maturation (CVM). This radiographic image is routinely used by orthodontic clinicians to investigate craniofacial morphologies and growth patterns. This is the primary reason for the method’s increasing popularity. Because properly used cervical vertebrae give a valid assessment of pubertal development spurt, using these films will be a useful process as the number of exposures is reduced.2\n\nComputed tomography (CT) scans, cone beam computed tomography (CBCT), magnetic resonance imaging (MRI), and digital volume tomography (3D-DVT) are some of the 3-D procedures employed nowadays. When compared to two-dimensional approaches, they enable exact visualization and measurements.6 Since 1997, 3D-DVT, in particular, has been employed as a diagnostic tool. It operates on the same principles as CT scans but with the added benefit of lower radiation exposure. CT and MRI require a significantly larger dose of radiation as well as a significant investment in equipment. DVT allows us to see any and all relevant structures in all three planes of space; it is utilized in orthodontics to image any impacted teeth, bone height, and space availability, among other things.7\n\nIt features a user-friendly interface, allows for easy manipulation of the needed structures, and is widely available at the institute. It is the radiography technique of choice for bone mapping due to other advantages such as short scan duration, display options, and high contrast characteristics. There is just a small body of research that uses this novel imaging technology to measure and compare craniofacial traits.8 The orthodontist can assess the structures in all three dimensions and get a sense of the craniofacial structures’ natural boundaries with the 3-D image. Clinicians should be familiar with normal anatomy as shown on radiographs, as well as any differences in the morphology of the structures, in order to detect any anomalies that could indicate pathological states before they manifest clinically.9\n\nThe aim of the present study is to examine and compare the morphology of Class II vertical and Class II horizontal growth patterns, as well as to distinguish them from a Class I orthognathic control group. Orthodontists will be able to better comprehend the variations between malocclusions by comparing craniofacial morphology. Understanding these differences is crucial because it will provide us with much-needed information regarding the orthodontic treatment restrictions that exist between the different growth patterns. This will assist physicians in ensuring that the correct treatment strategy is delivered based on the type of malocclusion, ensuring that the patient receives the best possible treatment results.7\n\nTo evaluate, compare and correlate the skeletal maturation using cervical vertebral maturation index (CVMI) stages in cases with Class II (horizontal) and Class II (vertical) using 3D-DVT and lateral cephalogram.\n\n\n\n‐ To evaluate the CVMI stage in Class I, Class II (horizontal), and Class II (vertical) cases using lateral cephalogram (2D Evaluation).\n\n‐ To evaluate the CVMI stage in Class I, Class II (horizontal), and Class II (vertical) using 3D-DVT.\n\n‐ To correlate the CVMI stage in Class I, Class II (horizontal), and Class II (vertical) cases using 3D-DVT and lateral cephalogram.\n\n‐ To compare the CVMI stage in Class II (horizontal) and Class I cases using 3D-DVT and lateral cephalogram.\n\n‐ To compare CVMI in Class II (vertical) and Class I cases using 3D- DVT and lateral cephalogram.\n\n‐ To compare CVMI in Class II (horizontal) and Class II (vertical) cases using 3D-DVT and lateral cephalogram.\n\n\nMethods\n\n\n\n• The observational study will take place at the Sharad Pawar Dental College, Datta Meghe Institute of Higher Education and Research at Sawangi (M), Wardha, in the Department of orthodontics and dentofacial orthopedics.\n\n• A total of 45 adult patients (Class II horizontal, class II vertical) will be chosen from Sharad Pawar Dental College’s outpatient department (OPD) of Orthodontics and Dentofacial Orthopaedics at Sawangi, Wardha (Figure 1).\n\nThe study design will be an observational study.\n\nThe following exclusion criteria will be applied:\n\n1. Patient with a history of any systemic diseases.\n\n2. Full visibility of the cervical vertebrae is impaired in 3D-DVT pictures.\n\n3. The presence of pathological alterations in pictures of the cervical vertebrae.\n\n4. The presence of foreign bodies in the cervical vertebrae pictures.\n\n\n\n• Based on the cephalometric value skeletal growth pattern of the patient they will be divided into three groups: Class I, Class II vertical, and Class II horizontal (Table 1).\n\n• Lateral cephalogram and 3D-DVT of each group will be taken.\n\n• Correlation of CVMI stages will be done on both lateral cephalograms and 3D-DVT will be done for each group separately.\n\n• Comparison of CVMI stages will be done for each group based on the above observations.\n\nOutcomes\n\nFor radiologists and orthodontists, it will be easier to predict the growth of children at a very earlier stage by looking at the cervical vertebrae stages through lateral cephalogram as well as 3-D DVT and based on this both two-dimensional (2-D) and three-dimensional (3-D) views can be considered. For those cases which are borderline and difficult to predict from a 2-D view, 3-D DVT can help in such cases. It can be used to predict the remaining growth of an individual so that growth modifications can be done at a very earlier stage and further deterioration of malocclusion can be prevented at the very initial stage only.\n\nBias\n\nMinimum bias will be there as patients will be randomly selected based on inclusion and exclusion criteria.\n\nStudy sample\n\nThe calculation of sample size was done as follows:\n\nA total of 15 patients will be allotted for three groups each (Figure 1).\n\nHence:\n\nTotal sample size = 45\n\nGroup A - 15 Class I malocclusion\n\nGroup B -15 Class II malocclusion (vertical growth)\n\nGroup C -15 class II malocclusion (horizontal growth)\n\nThe outcome of this study will probably provide positive correlation of CVMI stages with various growth pattern malocclusions. Using this modality, clinicians will be able to predict the accurate timing of growth modulation therapy in various malocclusions. Based on the outcome of this study we will be able to draw a protocol for early, effective and timely management of patients with skeletal malocclusions.\n\nThe study has been initiated; patient selection has been done along with lateral cephalogram. 3D-DVT examination is yet to be initiated.\n\n\nDiscussion\n\nThe study of growth is part of orthodontics. The term “growth assessment” refers to determining a person’s maturity level. Skeletal maturity indicators aid in the presentation of data on distinct patterns of growth and the degree to which each pattern has been achieved for each patient.\n\nThe examination and identification of skeletal maturity in individuals is a key factor to determine the outcomes of various dental operations, including orthodontic treatment and orthognathic surgery.\n\n• Lampraski (1972) found that using cervical vertebrae to determine skeletal age was more reliable and valid than using a hand-wrist radiograph. Using five vertebrae, he devised a standard for determining skeletal age in both male and females (second to sixth vertebrae). Because the vertebrae are already recorded on the lateral cephalogram, this approach provides the benefit of calculating the need for an additional radiographic exposure.\n\n• Julian Singer (1980)10 described a few characteristics of hand-wrist film which could be of significance to the clinician in determining the timing of orthodontic treatment. Six stages were described (i.e.) early, prepubertal, pubertal onset, pubertal, pubertal deceleration, and growth completion, each with specific characteristics. The study concluded that, hand-wrist film can be used as an indicator of the maturational status of the orthodontic patient.\n\n• Keith Grave, Grant Townsend (2003)11 investigated the application of a modified cervical vertebral maturation (CVM) method in indigenous Australian population and subsequently correlated the events of ossification with the timing of peak growth in mandible as well as statures. The CVM stages were restricted to some specific periods of growth. The authors observed that a majority of the population experienced stage 1 during the pre-peak period while stages 2, 3 and stages 4, 5 were observed during the peak and post-peak period of growth respectively. The study reported that the findings were in accordance with authors who reported in other ethnic groups. This reveals that the procedure can be used in daily orthodontic practices to evaluate and monitor the growth activity of children.\n\n• Marco A E Bonfim et al.,1 evaluated the performance of CBCT three-dimensional (3D) reconstructions and sagittal sections to estimate CVMI and suggested that CBCT may be useful for estimation of skeletal maturation.\n\nThis study will assist in identifying and diagnosing CVMI stages at the very early phase of treatment so that possible modification can be done for the growth of an individual. Further, precise recognition of cervical vertebrae can also be done through 3D-DVT, and two-dimensional radiographic errors can also be minimized.\n\nEthical approval received by Datta Meghe Institute of Higher Education and Research, Sawangi, Wardha (Approval Number DMIMS (DU)/IEC/2022/944).",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZenodo: STROBE checklist for “Comparative evaluation and correlation of CVMI stages in Class II (vertical) and Class II (horizontal) cases with Class I malocclusion, as evaluated using 3D-DVT and lateral cephalogram”, https://doi.org/10.5281/zenodo.7846411. 12\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nBonfim MA, Costa AL, Fuziy A, et al.: Cervical vertebrae maturation index estimates on cone beam CT: 3D reconstructions vs sagittal sections. Dentomaxillofac. Radiol. 2016 Jan; 45(1): 20150162. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPichai S, Rajesh M, Reddy N, et al.: A comparison of hand wrist bone analysis with two different cervical vertebral analysis in measuring skeletal maturation. J. Int. Oral Health. 2014 Sep; 6(5): 36.\n\nChatzigianni A, Halazonetis DJ: Geometric morphometric evaluation of cervical vertebrae shape and its relationship to skeletal maturation. Am. J. Orthod. Dentofac. Orthop. 2009 Oct 1; 136(4): 481–483. Publisher Full Text\n\nGrave K, Townsend G: Cervical vertebral maturation as a predictor of the adolescent growth spurt. Aust. J. Orthod. 2003; 19: 25–31.\n\nJeon JY, Kim CS, Kim JS, et al.: Correlation and Correspondence between Skeletal Maturation Indicators in Hand-Wrist and Cervical Vertebra Analyses and Skeletal Maturity Score in Korean Adolescents. Children. 2021 Oct; 8(10): 910. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJoshi V, Yamaguchi T, Matsuda Y, et al.: Skeletal maturity assessment with the use of cone-beam computerized tomography. Oral Surg. Oral Med Oral Pathol. Oral Radiol. 2012 Jun 1; 113(6): 841–849. Publisher Full Text\n\nDargahwala HS, Daigavane P, Vausdevan SD, et al.: Comparison of Cervical Vertebral Body Volume in Class II Vertical and Class II Horizontal Cases With Class I Cases Using 3D-DVT. J. Indian Orthod. Soc. 2020 Oct; 54(4): 332–337. Publisher Full Text\n\nTorres FC, Yamazaki MS, Jóias RP, et al.: Evaluation of the cervical vertebrae maturation index in lateral cephalograms taken in different head positions. Braz. Dent. J. 2013 Sep; 24: 462–466. Publisher Full Text\n\nKiran S, Sharma VP, Tandon P: Correlative and comparative study of Fishman′ s skeletal maturity indicators with CVMI and chronological age in Lucknow population. Eur. J. Gen. Dent. 2012 Sep; 1(03): 161–165. Publisher Full Text\n\nLampraski DG: Skeletal age assessment utilizing cervical vertebrae. Master of Science Thesis University of Pittsburgh. 1972.\n\nGrave K, Townsend G: Cervical vertebral maturation as a predictor of the adolescent growth spurt. Aust. Orthod. J. 2003 Apr; 19(1): 25–32. PubMed Abstract\n\nBharti L, Shrivastav S, Sanchla A, et al.: Comparative Evaluation and Correlation Of CVMI Stages In Class II (Vertical) And Class II (Horizontal) Cases with Class I Malocclusion Cases, as Evaluated using 3D-DVT and Lateral Cephalogram. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "208708",
"date": "17 Oct 2023",
"name": "Dhruv Jain",
"expertise": [
"Reviewer Expertise Dental science ( Orthodontics & Dentofacial Orthopedics)"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSkeletal maturation age is highly important in formulating an appropriate diagnosis and planning orthodontic treatment accordingly. Cervical vertebral maturation stage is one such method which is popularly used for this rationale. 3D-DVT technology can be utilized to determine the appropriate stage of cervical vertebrae.\nThe rationale, objectives and methodology for the study have been appropriately described by the authors.\nHowever, it is suggested to please provide details of any documented literature pertaining to the reliability 3D-DVT in the assessment of cervical vertebral morphology.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
},
{
"id": "240498",
"date": "15 Feb 2024",
"name": "Yu Li",
"expertise": [
"Reviewer Expertise orthodontic",
"orthopedic",
"biomechanics orthodontics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI would like to thank the authors for giving me the opportunity to review their present submission, \"Comparative evaluation and correlation of CVMI stages in Class II (vertical) and Class II (horizontal) cases with Class I malocclusion, as evaluated using 3D-DVT and lateral cephalogram \" The aim of this research Paper was to evaluate, compare and correlate the skeletal maturation using CVMI stages in cases with Class II (horizontal and vertical) using3D-DVT and lateral cephalogram. I can see the authors have worked hard to prepare this paper for submission as a study protocol (a comparative study design). The topic has its appeal, but the manuscript exhibits some drawbacks. Please find my comments below：\n1- The work does not discuss appropriately in the context of the current literature. It is better to add past literature findings of previous studies to the manuscript. 2-The method used in this protocol was not clear enough to decide if the method used was accurate or not. The method of work should be written in detail to make it easier for the reader to understand the content of the manuscript. 3- In the method section the authors stated that (A total of 45 adult patients (Class II horizontal, class II vertical). using cervical vertebrae maturation (CVM) mainly for observation of growth and development period. but the authors used it with adult patients, which means that they had already reached to sixth stage of maturation (pubertal deceleration, and growth completion). How do you explain that? 4- In the method section in Table 1; what were the authors mean by Class II horizontal and Class II vertical. could you explain, please? 5- There was no sufficient information about the comparison and how they did it.\nMy decision: Approved with Reservations:The reviewer believes the paper has academic merit, but has asked for a number of small changes to the article, or specific, sometimes more significant revisions.\n\nMany thanks!\nYu li\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-530
|
https://f1000research.com/articles/12-527/v1
|
22 May 23
|
{
"type": "Study Protocol",
"title": "Effect of proprioceptive neuromuscular facilitation technique and TENS on improving lower limb sensorimotor function, balance and quality of life in chemotherapy induced peripheral neuropathy in gynecological cancer: A randomized controlled trial protocol",
"authors": [
"Nikita H. Seth",
"Irshad Quershi",
"Irshad Quershi"
],
"abstract": "Gynecological cancers are the most prevalent cancers in women, making it a significant public health concern. Chemotherapy drugs are an extremely effective approach for reducing cancer progression since they have various targets and mechanism of action focused at killing quickly multiplying cancer cells. Unfortunately, these drugs also affect normal cells and structures of the body, resulting in a variety of deleterious effects. Most common among them is chemotherapy induced peripheral neuropathy (CIPN). Taxanes, platinum medicines, vinca alkaloids and thalidomide are examples of popular pharmaceuticals that are prone to cause CIPN. When CIPN develops during active chemotherapy phase, it may result in the discontinuation or reduction of chemotherapy dose, which may render the dosage ineffective in cancer management. As a result, it is essential that physiotherapists investigate novel approaches to successfully manage the side effects that survivors must deal with. Here’s the idea we suggest by conducting a study which aim to assess the effectiveness of Proprioceptive Neuromuscular Facilitation Technique (PNF) with Transcutaneous Electrical Nerve Stimulation (TENS) and closed kinetic chain exercises with TENS on subjects with CIPN in Gynecological Cancer in two arm parallel superiority randomized control trial (RCT) on improving lower limb sensorimotor function, balance & quality of life. The total participants in the study will be divided into two equal groups and then the\n\nintervention will be given for 8 weeks to both the groups with 5 days in a week with 50 minute session each day. The results will be evaluated after 8 weeks of treatment and 3 weeks after completion of intervention for follow up. If the hypothesis of our study proves to be effective, this physiotherapy intervention could be included in management of CIPN. Along with it, it will help in reducing the rate of discontinuation of chemotherapy dose due to neuropathy.",
"keywords": [
"Gynecological cancer",
"Chemotherapy Induced Peripheral Neuropathy",
"Physiotherapy Intervention",
"Balance",
"Quality of Life."
],
"content": "Introduction\n\nThe fact that gynecological cancers are among the most prevalent cancers in women makes them a serious public health concern. Due to heterogeneous pathology, a lack of effective screening facilities in developing nations like India, and the fact that most women report at advanced stages, prognosis and clinical outcomes are affected. With rates of occurrence rising over time, ovarian cancer has emerged as one of the most prevalent malignancies affecting women in India. Even though it has decreased, cervical cancer is still the second most common cancer in women, only after breast cancer.1\n\nEvery year, 122,844 women in India are diagnosed with cervical cancer, with 67,477 dying from the illness. Chemotherapy for ovarian cancer is typically a combination of two distinct types of medications. Using a combination of medications rather than just one drug as a first-line treatment for ovarian cancer appears to be more successful. Typically, the combination includes a platinum component (typically Cisplastin or Carboplatin) and another type of chemotherapy medication known as a taxanes, such as paclitaxel or docetaxel; these are the drugs most likely to induce peripheral neuropathy. Taxanes, platinum medicines, vinca alkaloids, thalidomide, and bortezomib are examples of popular pharmaceuticals with a high risk of causing CIPN. Clinically, CIPN manifests as varying degrees of sensory, muscular, and/or autonomic dysfunction.2\n\nWhen CIPN happens during active chemotherapy, the chemotherapy dose may be terminated or reduced, rendering the dosage ineffective in cancer management. As a result, it is essential that physiotherapists research novel methods to treating cancer survivors and managing the side effects that survivors must deal with. The most common side effects of chemotherapy is CIPN, and there has been little study into non-pharmacological treatments to manage its symptoms. There is a paucity of research on the use of PNF in the therapy of CIPN symptoms. There is paucity of research into improving equilibrium in chemotherapy-induced peripheral neuropathy caused by gynecological cancer. There is a scarcity of data concerning physical therapy intervention and outcomes in CIPN.3\n\nTranscutaneous Electrical Nerve Stimulation (TENS) and closed kinetic chain exercises are the usual methods for improving sensorimotor function and balance. TENS is the application of a low-level electrical current to neurons via electrodes. TENS has been shown to alleviate pain and is safe to use in chemotherapy patients. The TENS device modulates the frequency, width, length, and intensity of the pulse. TENS is defined as having a high frequency > 50 Hz and a low intensity, implying that it causes paraesthesia without causing discomfort or motor contraction. Exercise has been shown to help several aspects of CIPN following treatment. However, the potential for prevention has gotten less attention, and the results are sometimes contradictory.4\n\nSince it has been discovered that exercise regimens aimed at improving balance in the elderly should include coordination and Proprioception activities as well as strength exercises, the Proprioceptive neuromuscular facilitation (PNF) method is presented as an intriguing option. During PNF movement execution, muscles are temporarily stretched before contracting, stimulating neuromuscular terminals that generate higher levels of force.5 PNF motions are also performed in a diagonal pattern parallel to muscular topography, replicating physiological movements such as gait. It has also been suggested that PNF training results in a better balance of agonistic and antagonistic muscle activation, with less co activation. There is no written evidence that Proprioceptive Neuromuscular Facilitation can be used to treat CIPN symptoms.6\n\nThe aim of this study is to test the effectiveness of Proprioceptive Neuromuscular Facilitation Technique with Transcutaneous Electrical Nerve Stimulation (TENS) and closed kinetic chain exercises with TENS on subjects with chemotherapy Induced Peripheral Neuropathy in Gynecological Cancer in two arm parallel superiority/equivalence randomized control trial (RCT) on improving lower limb sensorimotor function, balance & quality of life in end point results on marginal difference.\n\n\n\n1. To study the subjects with lower limb peripheral Neuropathy (Modified Total Peripheral Neuropathy Scoring Criteria), balance (Berg Balance Scale) & Quality of life (Fact/GOG Ntx) due to Chemotherapy Induced Peripheral Neuropathy in Gynaecological cancers treated with Proprioceptive Neuromuscular Facilitation Technique (PNF) and Transcutaneous Electrical Nerve Stimulation (TENS) on its effect on improving the sensorimotor Function, balance and Quality of life in the overall population.\n\n2. To study the subjects with chemotherapy Induced Peripheral Neuropathy in Gynaecological Cancer for the change in pain (measured on VAS), Sensory function (Semmes Weinstein Monofilament Test) treated with Proprioceptive Neuromuscular Facilitation Technique (PNF) and TENS, if it can reduce pain and improve sensory function in overall population.\n\n3. To study the efficacy over the treatment of Proprioceptive Neuromuscular Facilitation Technique along with Transcutaneous Electrical Nerve Stimulation (TENS) and Closed kinetic chain exercises along with TENS on mTNS for change in lower limb sensorimotor Function,balance & quality of life for the population with chemotherapy Induced Peripheral Neuropathy in Gynaecological Cancer.\n\nTrial Design - Single Centric, two arm parallel open label equivalence randomized controlled trial.\n\nThis is hospital-based study where participants consent will be received in written format and will be recruited from Siddharth Gupta Memorial Cancer Hospital constituent branch of Acharya Vinobha Bhave Hospital Sawangi, Meghe, Wardha, Maharashtra, after receiving approval from the institutional ethics committee of Datta Meghe institute of higher education & research the population over the region with inclusion exclusion criteria for the study. Study participant will be distributed in to two arms. Arm-A (PNF and TENS) & Arm-B (Closed kinetic chain Exercises and TENS) by randomization for 1:1 allocation with intent to treat purpose. Subjects will be invited & screened for inclusion process of this study. Randomization process will be run for subject allocation using randomization process with computer generated list. Study will be carried out as open label with cut-off values at baseline parameters will be used for the inviting the participants considering inclusion & exclusion criteria for selection. For more participants in the study if required second source of recruitment will be done throughout the period of recruitment of six months. Active group will receive Proprioceptive Neuromuscular Facilitation Technique (PNF) plus TENS therapy control group will receive Closed Kinetic Chain Exercises (CCK) plus TENS therapy to assess improvement of lower limb sensorimotor Function, balance & quality of life at end point results on marginal difference. Participants will be included and will be assessed over different time scheduled mentioned as -visit 1 for subject enrolment, visit 2 for participants screening, at baseline, 8 weeks and 3 weeks post treatment for follow up at which primary & secondary parameters will be measured. The study design is visualized in Figure 1.\n\nTENS - Transcutaneous Electrical Nerve Stimulation.\n\n\n\n1) A newly diagnosed patient with stage I to III gynaecologic cancers, including ovarian, uterine, and cervical cancer, who intends to undergo a fixed amount of platinum-based compounds chemotherapy.\n\n2) Patients who are administered Taxanes and Platinum-based compounds - Cisplastin, Carboplatin, and Oxaliplatin.\n\n3) Patients with Grade I or II peripheral neuropathy according to the National Cancer Institute’s standard toxicity criteria.\n\n4) Planned to undergo a minimum of four cycles of chemotherapy treatment utilizing one of the chemotherapy agents (Platinum based compound).\n\n5) Women aged 50 to 70 years.\n\n\n\n1) The Male Patient.\n\n2) Patients with a history of peripheral nerve damage.\n\n3) Type 2 Diabetes Mellitus Patient with Autoimmune and Inflammatory Disorders.\n\n4) Patients with Grade III, IV, or V peripheral neuropathy, as defined by the National Cancer Institute’s common toxicity guidelines, are excluded from the study.\n\n5) Previous exposure to any of the involved chemotherapy agents within the previous 5 years, which may have caused peripheral neuropathy.\n\n6) Cancer in the fourth stage.\n\n7) Patients with metal devices.\n\n8) Patients who have an artificial pacemaker.\n\n9) Any traumatic injury to the lower leg of the patient.\n\nExperimental group\n\nAfter identifying the area with pain the TENS will be applied along the distribution of the nerve for the duration of 15 minutes, High Frequency (50 to 100 Hz) with intensity such that it causes paraesthesia without pain or motor contraction followed by Proprioceptive Neuromuscular Facilitation Techniques which include hold – relax, contract- relax, slow reversal and rhythmic stabilization along with diagonal patterns of the lower limb. Each technique was repeated for 10 minutes with adequate pacing between each repetition. Total duration of treatment is approximately 50 min.7\n\nControl group\n\nAfter identifying the area with pain the TENS will be applied along the distribution of the nerve for the duration of 15 minutes, High Frequency (50 to 100 Hz) will be used with intensity such that it causes paraesthesia without pain or motor contraction.8 Along with the closed kinetic chain exercises will be given which will be as follows (Table 1).\n\nCriteria for discontinuing or modifying allocated interventions for a given trial participant is drug dose change in response to harms, participant request, or worsening of disease.\n\nRelevant concomitant care include considering the fatigue there will be adequate pacing between the exercises, care of skin at the site of TENS application.\n\nPrimary outcome\n\n1. Change in modified total peripheral Neuropathy Score\n\nThe modified Total Neuropathy Score incorporates data from scoring signs, symptoms, and quantified sensory tests to provide one indicator of neuropathy. The TNS has high inter- and intrarater dependability. (0.966 & 0.986 respectively). The mTNS is scored from 0 to 24, with every neuropathy item graded 0-4. A higher overall prevalence indicates that the neuropathy is more severe. When the first iteration of the TNS (a 0-21 scoring system) was developed in 1994, the results scores were divided into three levels: 0-7, 8-14, and 15-21 for mild, intermediate, and severe neuropathy, respectively.9\n\n2. Change in Berg Balance Score\n\nThe measure was designed specifically to assess balance in the elderly. It has a dependability grade of 0.97. It earned a total of 56 points. It comprises of 14 items, each with a maximum score ranging from 4.0 to 20: A individual with this score will almost certainly need the assistance of a wheelchair to move around safely. A person with a score of 21 to 40 will need some type of walking assistance, such as a cane or walker. 41-56: A individual with a score in this range is considered independent and ought to be able to move around safely without a cane or walker.10\n\n3. Change in FACT - GOG (Quality of life) Scoring\n\nIt is a reliable and valid instrument to evaluate the impact of neuropathy on health-related aspects of life. The Ntx the subscale demonstrated sensitivity to therapeutic distinction and alterations over time. The FACT/GOG-NTX measures peripheral neuropathy symptoms such as sensory, motor, and auditory difficulties, as well as cold sensitivity. This instrument has been shown to be reliable, with internal consistency, content validity, and concurrent validity, as well as sensitivity to change over time, in various samples of cancer patients getting chemotherapy.11\n\n\n\n\nSecondary outcome\n\n1. Reduction in VAS Score\n\nThe visual analogue scale (VAS) is a subjective, verified measure of acute and chronic pain. Scores are recorded by drawing a handwritten mark on a 10-cm line representing a pain scale ranging from “no pain” to “worst pain”.12\n\n2. Change in Semmes Weinstein Monofilament Grading\n\nThe greater the labelled number, the thicker the filament becomes and the more force is required to stretch the filament. The strands are graded from 1 to 5 based on their thickness: 1.65-2.83 equal’s grade 5, 3.22-3.61 equals grade 4, 3.84-4.31 equals grade 3, 4.56-6.45 equals grade 2, and 6.65 equals grade. It is a clinical test that uses a numerical quantity to assess the reaction of the monofilament to a touching sensation. It has a sensitivity of 98% and a specificity of roughly 99%.13\n\nWe perform the sample size calculation through Power analysis at 80% power and 5% Type 1 error calculated for the primary variable – modified total peripheral neuropathy score in comparison with the difference between PNF and TENS & Closed kinetic chain exercises and TENS treatment groups from baseline to end visits in frequency (%) We used prior estimated effect size difference in % from the RCT for study in, [Citation],.We expected 30% of margin improvement in comparison to control group considerable for clinically relevant margin for superiority at 30% through expertise opinion.\n\n\n\nZ alpha = 1. = 1.965 Type I error at 5%\n\nZ beta = 0.84 = Type II error at 20%\n\nPrimary Variable: - Modified Total Neuropathy score (mTNS)\n\nP1 - Effect of Closed Kinetic chain exercises on sensorimotor function - 52% change (Reference)\n\nP1 - Effect of Proprioceptive Neuromuscular facilitation Technique on sensorimotor function = 82% (Expected as discussed with expertise opinion)\n\nClinically relevant Difference (P2-P1) = 30%\n\nMinimum sample size N = 2 * (1.965 + 0.84)2 ((0.52) (1-0.52) + (0.82) (1-0.82)/(0.30))2 = 36 each in 2 groups.\n\nConsidering 10% drop out = 40 samples each group.\n\nReference Article – Effect of lower limb closed kinetic chain exercises on balance in patients with chemotherapy induced peripheral neuropathy-pilot study, International Journal of Rehabilitation Research, Jorida Fernandes et al (Pg -368).8\n\nAnalysis - Results over the outcome variables will be tabulated & described using descriptive statistics; data over the outcome variables will be tested for normal distribution for the mean and standard deviation (SD) median statistics will positioned for finding skewed distributions and interquartile range (IQR). Frequency and percentages for binary and categorical variables will be tabulated for descriptive statistics. R-software free version will be used for all statistical analysis. The inferential statistics will be analyzed as per the description given below.\n\nPrimary outcome: - Inferential statistics will be used for comparing the two groups for measurement score resulted (active treatment versus control treatment) for their mean change in primary variable (mTNS, BBS, FACT - GOG) between baseline and 8 weeks applying the linear mixed model. Participants will be tested for the results considering difference in primary variable from baseline to timeline measured during the study (visit1 and after the end of 8 weeks and follow up after 3 weeks of completion of intervention). Random effects will be generalized for study subjects, fixed effects will be analyzed by considering treatment group and visit number. Effect size over mean change difference on primary variable from baseline to end line visit at 8 week and 3 weeks follow up will be measured with corresponding 95 % confidence interval (CI) will be presented.\n\nPrimary End Point (Description): Secondary outcomes (Simmens monofilament test, VAS) will be analyzed as per the above linear mixed model effect for predicting effect size difference between active and control group. T test (Unpaired) will be used to measure the significant difference between the means in comparison between the two groups if the data follows the normal distribution. For non normal distribution Mathematical algorithms will be used for conversion of the data to normal distribution.If Data over primary variable still follows the non normal distribution then we will use alternate non parametric test (Chi square, Mann Whitney, Wilcoxon test.\n\nPlanning to publish in indexed journal and present the study in National Conference Proceedings.\n\nThe Recruitment of participants is yet to be started.\n\nInstitutional Ethical Clearance has been obtained on 4/2/2023\n\nIEC No – DMIHER (DU)/IEC/2023/48\n\nCTRI Registration was obtained 13/3/2023",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nI would like to acknowledge Mr Laxmikant Umate who has helped me in sample size calculation and data analysis planning.\n\n\nReferences\n\nMaheshwari A, Kumar N, Mahantshetty U: Gynecological cancers: A summary of published Indian data. South Asian. J Cancer. 2016 Sep [cited 2023 Mar 30]; 05(3): 112–120. Publisher Full Text . Reference Source\n\nMatulonis UA, Sood AK, Fallowfield L, et al.: Ovarian cancer. Nat Rev Dis Primer. 2016 Aug 8 [cited 2023 Mar 30]; 2: 16061. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLoprinzi CL, Lacchetti C, Bleeker J, et al.: Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol Off J Am Soc Clin Oncol. 2020 Oct 1 [cited 2023 Mar 30]; 38(28): 3325–3348. PubMed Abstract | Publisher Full Text\n\nJohnson PM: Transcutaneous Electrical Nerve Stimulation: Mechanisms, Clinical Application and Evidence. Rev Pain. 2007 Aug [cited 2023 Mar 30]; 1(1): 7–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHindle KB, Whitcomb TJ, Briggs WO, et al.: Proprioceptive Neuromuscular Facilitation (PNF): Its Mechanisms and Effects on Range of Motion and Muscular Function. J Hum Kinet. 2012 Mar [cited 2023 Mar 30]; 31: 105–113. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPereira MP, Gonçalves M: Proprioceptive Neuromuscular Facilitation Improves Balance and Knee Extensors Strength of Older Fallers. Int Sch Res Not. 2012 Nov 14 [cited 2023 Mar 30]; 2012: 1–7. Publisher Full Text Reference Source\n\nSingh K, Arora L, Arora R: Effect of proprioceptive neuromuscular facilitation (pnf) in improving sensorimotor function in patients with diabetic neuropathy affecting lower limbs. Int J Physiother. 2016 Jun 9 [cited 2023 Mar 30]; 3: 332–336. Publisher Full Text Reference Source\n\nFernandes J, Kumar S: Effect of lower limb closed kinematic chain exercises on balance in patients with chemotherapy-induced peripheral neuropathy: a pilot study. Int J Rehabil Res Int Z Rehabil Rev Int Rech Readaptation. 2016 Dec [cited 2023 Mar 30]; 39(4). Reference Source\n\nLavoie Smith EM, Cohen JA, Pett MA, et al.: The reliability and validity of a modified total neuropathy score-reduced and neuropathic pain severity items when used to measure chemotherapy-induced peripheral neuropathy in patients receiving taxanes and platinums. Cancer Nurs. 2010 Jun [cited 2023 Mar 30]; 33(3): 173–183. PubMed Abstract | Publisher Full Text\n\nMiranda-Cantellops N, Tiu TK: Berg Balance Testing. StatPearls Publishing; 2023 [cited 2023 Mar 30]. Reference Source\n\nCalhoun EA, Welshman EE, Chang CH, et al.: sychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2003 Dec [cited 2023 Mar 30]; 13(6): 741–748. PubMed Abstract | Publisher Full Text\n\nDelgado DA, Lambert BS, Boutris N, et al.: Validation of Digital Visual Analog Scale Pain Scoring With a Traditional Paper-based Visual Analog Scale in Adults. J Am Acad Orthop Surg Glob Res Rev. 2018 Mar [cited 2023 Mar 30]; 2(3). Publisher Full Text Reference Source\n\nRELIABILITY AND VALIDITY OF SEMMES-WEINSTEIN MONOFILAMENT TE…. J Geriatr Phys Ther. [cited 2023 Mar 30]. Reference Source"
}
|
[
{
"id": "176727",
"date": "16 Aug 2023",
"name": "Rakesh Krishna Kovela",
"expertise": [
"Reviewer Expertise Physiotherapy in Paediatrics",
"Physiotherapy in adult neurological conditions",
"physiotherapy in developmental disorders"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAs its a protocol, the methodology is clear except for the objectives as they are lengthy; the authors can cut short the length of the objectives. Permissions from scale developers need to be mentioned. Permission from onco HOD to take the samples from oncology unit need to be mentioned. Overall the protocol is quite acceptable to be indexed.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-527
|
https://f1000research.com/articles/11-520/v1
|
13 May 22
|
{
"type": "Research Article",
"title": "Neonatal resuscitation: A cross-sectional study measuring the readiness of healthcare personnel",
"authors": [
"Martono Tri Utomo",
"Mahendra Tri Arif Sampurna",
"Rufina Adelia Widyatama",
"Visuddho Visuddho",
"Ivan Angelo Albright",
"Risa Etika",
"Dina Angelika",
"Kartika Darma Handayani",
"Abyan Irzaldy",
"Martono Tri Utomo",
"Rufina Adelia Widyatama",
"Visuddho Visuddho",
"Ivan Angelo Albright",
"Risa Etika",
"Dina Angelika",
"Kartika Darma Handayani",
"Abyan Irzaldy"
],
"abstract": "Background: The optimal neonatal resuscitation requires healthcare personnel knowledge and experience. This study aims to assess the readiness of hospitals through its healthcare personnel in performing neonatal resuscitation. Methods: This study was an observational study conducted in May 2021 by distributing questionnaires to nurses, midwives, doctors, and residents to determine the level of knowledge and experience of the subject regarding neonatal resuscitation. We conducted the research in four types of hospitals A, B, C, and D, which are defined by the Regulation of the Minister of Health of the Republic of Indonesia by the capability and availability of medical services. The type A hospital is the hospital with the most complete medical services, while type D hospitals have the least medical services. The comparative analysis between participants’ characteristics and the knowledge or experience score was conducted. Results: The total 123 participants are included in the knowledge questionnaire analysis and 70 participants are included in the resuscitation experience analysis. We showed a significant difference (p = 0.013) of healthcare personnel knowledge between the A type hospital (Median 15.00; Interquartile Range [IQR] 15.00–16.00) and the C type hospital (median 14.50; IQR 12.25–15.75). For the experience, the healthcare personnel of type A and type B hospitals have significantly higher experience scores than the type D hospital (p = 0.014; p = 0.007), but we did not find a significant difference between others type of hospital comparison. Conclusions: In this study, we found that the healthcare personnel from type A and type B hospitals are more experienced than the type D hospital in conducting neonatal resuscitation. We suggest more neonatal resuscitation training to improve the readiness of healthcare personnel from type C and type D hospital.",
"keywords": [
"Healthcare Personnel",
"Hospital",
"Neonate",
"Readiness",
"Resuscitation"
],
"content": "Background\n\nNeonatal mortality is one of the standards of neonatal care. Data from developing countries showed that about 4 million babies die in the neonatal period.1 As a developing country, Indonesia also contributes, with the mortality rate reaching 12.4 per 1,000 live births in 2019.2 The right strategy for neonatal referral and the readiness of the hospital must be assessed to decrease the neonatal mortality rate in Indonesia.3,4\n\nThe leading causes of neonatal mortality were prematurity, sepsis, and asphyxia.5–7 These conditions are often related to the requirement of neonatal resuscitation.8,9 Neonatal resuscitation is a series of procedures performed to prevent the morbidity and mortality associated with a hypoxic-ischemic tissue injury (brain, heart, kidney) and restore spontaneous breathing and adequate cardiac output.10,11 The appropriate neonatal resuscitation is believed to increase the survival of neonates and reduce the mortality.12\n\nThe neonatal resuscitation service and patient prognosis were strong influence factors in the success of this procedure. Essential tools also must be available and ready to use whenever needed.11,13 The healthcare personnel which play important roles on the neonatal resuscitation must be prepared by several trainings.14 The trainings are expected to increase the healthcare personnel’s capability and confidence in doing neonatal resuscitation.15\n\nTo provide optimal services, healthcare personnel must be prepared with both knowledge and experience.16–18 Therefore, the factors that are associated with the knowledge and experience of the healthcare personnel need to be discovered. This study aims to assess the readiness of hospitals by analyzing the knowledge and experience of healthcare personnel in performing neonatal resuscitation.\n\n\nMethods\n\nThis research has obtained permission from the Ethics Committee of RSUD Dr. Soetomo Surabaya (Letter of Exemption 0335/LOE/301.4.2/II/2021). The data in this study was collected in May 2021 by distributing questionnaires to nurses, midwives, doctors, and residents to determine the level of knowledge and experience of the subject regarding neonatal resuscitation. The researchers met the participants and gave the explanation about the questionnaire in the pediatrics department of each hospital. Subjects in this study have filled out a statement of consent to be involved in this study. To address potential sources of bias, we invited respondents from all types of hospitals (A-D) to participate in our study.\n\nThis study was conducted in May 2021. The participants filled out the questionnaire for knowledge and experience measurement.19,20 The questionnaire was adopted from Jukkala et al.20 study with their permission. They developed questionnaires for measuring knowledge and experience in hospital settings. The questionnaires were then translated into Indonesian. The questionnaire was validated by several experts in neonatal resuscitation, which confirmed it was comprehensible. After that, the questionnaire was disseminated to 10 nurses to assess the validity and reliability using the bivariate correlation test and alpha-cronbach reliability test.\n\nThe resuscitation knowledge questionnaire contained 25 statements which are true or false questions. The participants chose the answer by marking either “true” or “false” in the column provided. The correct answer mark is 1 point and the wrong answer mark is 0 point. We obtained the total score for each subject for further analysis. From the 148 respondents, we excluded 25 participants because they did not meet our criteria. Five respondents were excluded because they do not work at a type A to D hospital. A further 20 respondents were excluded because they were co-assistant. Leaving 123 respondents included for the knowledge analysis in this study.\n\nThe resuscitation experience questionnaire contained 23 statements regarding neonatal resuscitation. The participants were asked to choose an answer using a Likert scale from one to five indicating from rarely to often doing the job in the statement. The data from each subject was then totaled for further analysis. From the 89 respondents who filled out the experience questionnaire, 19 respondents were excluded because they did not meet our criteria. Three respondents did not work at a type A to D hospital and 16 respondents were co-assistants. Leaving 70 respondents for the resuscitation experience analysis.\n\nType A–D hospitals are defined by the Regulation of the Minister of Health of the Republic of Indonesia No. 340/MENKES/PER/III/2010.21 The hospital type is classified based on the medical service facilities and their capabilities. For the type A hospitals there must be at least 4 Basic Specialists, 5 Medical Support Specialists, 12 Other Specialists and 13 Sub Specialist Services. Type B hospitals must have at least 4 Basic Specialists, 4 Medical Support Specialists, 8 Other Specialists and 2 Subspecialist Services. Type C hospitals must have at least 4 Basic Specialists and 4 Medical Supporting Specialist Services. Type D hospitals must have at least 2 Basic Specialist Medical Services.\n\nAccording to the American Academy of Pediatrics (AAP),22 work units in neonatal care are divided into four levels, namely level 1 to level 4. Level 1 is usually carried out to stabilize the condition of term infants with physiologically stable conditions. Level 2 work units are responsible for stabilizing the premature infants and term infants who are physiologically ill. While at level 3, it is necessary to carry out continuous infant stabilization and observation.22 Although there are four levels, in this study we only divided the room into 3 levels. The level 1 consists of the emergency room, baby room, or neonate room, the level 2 consists of a perinatology room, and the level 3 were Neonatal Intensive Care Unit (NICU) or Pediatric Intensive Care Unit (PICU).\n\nWe provide tables for each answered question for the knowledge and experience questionnaire. For analysis, we use the average of the total knowledge and experience for the comparative analysis. The continuous data was presented as median and interquartile range (IQR). The Mann-Whitney U test and Kruskal Wallis test were used to compare differences of total knowledge or experiences score between the groups for each factor. The Kruskal Wallis test was used for the multi-categorical data. The Mann-Whitney U test was used for the two-categorical data and the post-hoc analysis. Statistically significant was considered using two-sided α less than 0.05. Statistical analysis was done using the IBM SPSS software (version 23, RRID:SCR_016479).\n\n\nResults\n\nThe characteristics of the participants in the study are shown in Table 1.47 For the knowledge questionnaire, the participants mostly worked at type A hospitals (64.2%) and were mostly aged below 30 years. Only one participant was educated in master’s degree and doctoral degree. The participating professions in this study were midwives (37.4%) and nurses (33.3%) and also dominated by women (91.1%). Most of the employees were contract workers, which consists of midwives, nurses, and general practitioners. For the experience questionnaire, the participants mostly worked at type A hospitals (48.6%). Most of the participant’s professions were nurses (45.7%) and the participants were dominated by females (85.7%). Most of the participants had bachelor’s degrees (60%) and the permanent worker (40%) was the most common type of worker.\n\nTable 2 showed the answers for the knowledge questionnaire. The highest number participants chose false on the statement about chest compression initiation and positive pressure ventilation (87%). Statements about the number of heart rates in infants, infant diagnosis of primary or secondary apnea, the timing of oxygen administration, and the purpose of determining the Apgar score are also considered as hard questions with a high number of participants.\n\nET: Endotracheal; HR: Heart Rate; PPV: Positive Pressure Ventilation.\n\nWe found a significant difference (p = 0.007) between male (median 17.00; IQR 15.00–18.00) and female (median 15.00; IQR 14.00–16.00) participants as shown in Table 3. The education and type of professional role are important factors on participants knowledge. The students (which is the same population as residents) (median 17.00; IQR 15.00–18.00) have higher knowledge than the permanent (median 15.00; IQR 13.00–16.50) and contract (median 15.00; IQR 15.00–15.00) workers (p = 0.001). The post-hoc analysis showed a significant difference (p = 0.013) of knowledge between the A type hospital (median 15.00; IQR 15.00–16.00) and the C type hospital (median 14.50; IQR 12.25–15.75).\n\n* p-value < 0.05.\n\nThe responses to the knowledge questionnaire were shown in Table 2. The majority of participants rarely performed pulse examinations on umbilical cord (40%). The study also revealed that several participants rarely perform endotracheal suctioning (35.7%), umbilical catheterization (34.3%), take blood through an umbilical vein catheter (47.1%), and administer drugs/fluids through an umbilical catheter (35.7%). Most of them were also not experienced in interpreting the results of neonates' blood gases (27/70; 38.6%) as shown in Table 4.\n\nPPV: Positive Pressure Ventilation.\n\nTable 5 showed the comparison between each group’s risk factors on participant resuscitation experience. Types of hospital are associated with the experience of the medical profession (p = 0.026) with type B as the highest experience option. In the post-hoc analysis, we know that there are non-significant differences between type A hospital and type B hospitals (p = 0.618). The significant differences for the experience of the healthcare personnel are between A and D hospitals (p = 0.014) and between B and D hospitals (0.007).\n\n* p-value < 0.05.\n\nWe also found asignificant difference (p = 0.022) between the ages, seemingly the older age have more experience on neonatal resuscitation. The type of profession also plays an important role in neonatal resuscitation (p = 0.002). The nurses have the highest experience score (median 89.50; IQR 78.75–96.00) and the general practitioners have the lowest experience score (median 42.00; IQR 30.00–66.00). The longer work experience tended to have a higher experience score (p = 0.006) and the second unit level was the unit level with the lowest experience score compared to the first and third level (p = 0.003).\n\n\nDiscussion\n\nA high level of knowledge and experience of neonatal care is the key to the success of the resuscitation team.12,15,20 Our study describes the knowledge and experience of the health care provider in tertiary hospitals in Indonesia. We found the readiness of healthcare personnel was associated with the type of hospital. We found that medical personnel in the type A hospital have better knowledge that the type C hospital. For the experience, the type A and type B hospitals showed more experienced healthcare personnel than the type D hospital. This study also reveals several factors that influence knowledge and experience. Hence, this study may be used as a reference in the neonatal resuscitation guidelines or policies.\n\nNeonatal resuscitation is an action that requires decisive skill which is obtained by knowledge and experience.23 The neonatal resuscitation team training must be conducted in sufficient time to ensure the capability for the healthcare personnel.11,23 The availability of tools is also an important factor of hospital readiness to perform this procedure.13 Type A or type B hospitals have more qualified facilities to perform the neonatal resuscitation. This is the reason why type A and type B hospitals have better experience in performing neonatal resuscitation than type D hospitals. This also indicates that neonatal resuscitation must be done at the type A or type B hospitals since they are more ready to perform the procedure.\n\nResidents have the highest knowledge score among other types of professions. The students also have the highest knowledge score, since they mostly consist of residents. Knowledge of neonatal resuscitation is a competency that must be mastered by residents during their education as a prospective specialist.24,25 Residents have the responsibility to plan treatment according to the patient's condition. Even with supervision, residents are actually expected to have extensive knowledge about the causes, diagnosis, prognosis, complication, and management of neonates.26,27\n\nWe found that nurses have the best experience scores among other types of professions. Nursing is a profession that is directly involved in providing services to the patients.16,28,29 In the tertiary hospitals, where there are very large numbers of patients, doctors are often more involved in planning patient management. In this study, almost all general practitioners are young doctors, who just registered as the internship doctors. That may be the reason for their lack of experience. However, the right strategy needs to be implemented to improve the experience for general practitioners, since they will help in handling the newborns later.30\n\nPrevious studies have reported the relation between the age and the experience of neonatal resuscitation.18 Experience will be gained after several times doing and practicing the procedure.31,32 This is also the reason why work experience has a significant relation to the experience score. Experienced practitioners were found to be more confident in performing actions on neonatal patients.33,34\n\nWe found a significant difference between unit level and the total experience score. Higher unit levels have higher total experience scores. This is because at the level 1 unit, the baby being treated is a normal baby, while the higher level of care is related to more complications suffered by the babies.22,35 The more difficult procedure may not be conducted at the unit level 1 and level 2, while this procedure is often held in the unit level 3.22 However, we did not find any difference in knowledge between the three unit levels. Although most of the treatment in the level one unit is a normal baby, knowledge of signs of severity and early treatment is important at all levels.36\n\nAdditional training using The Newborn Resuscitation Manual from the United Kingdom with skill demonstrations and scenarios using mannequins have been proven to increase the level of knowledge of nurses, doctors, resident doctors, and specialists in Northern Nigeria.19 To increase personal experience, the health care providers need to practice each step of resuscitation.37 Routine training may be an important indicator in determining the hospital's readiness to conduct the neonatal resuscitation.38 Training on the steps of neonatal resuscitation, especially in the steps of palpating umbilical cord pulse, endotracheal suctioning, endotracheal intubation, umbilical catheter placement, taking blood through an umbilical vein catheter, administering drugs/fluids through an umbilical catheter, and interpreting neonatal blood gas results, must be a concern and require more intense training since most of the research subjects in this study rarely perform them.39,40\n\nEndotracheal intubation in neonates is rarely done because of the high level of difficulty and high risk of an adverse event for the procedure.40,41 Even for the skilled healthcare personnel, sometimes they still need to do several attempts until the intubation can enter the trachea of the neonate.38,41 The placement of an umbilical catheter, blood collection, and administration of drugs through the umbilical vein are rarely done, possibly because of its potential to be a risk factor of sepsis.42,43 More practice with evaluation are needed to increase the healthcare personnel confidence in doing the neonatal resuscitation.44–46\n\nThese findings may provide additional information to the guidelines of healthcare personnel training and qualifications. The participants joined this research voluntarily and were given brief socialization to make sure of the comprehension of the questionnaire to decrease risk of bias. However, several limitations exist in our study. First, the number of research subjects was reduced by the COVID-19 pandemic. We did consecutive sampling rather than random sampling which is more applicable. Second, we did not assess how many times the participants have joined the neonatal resuscitation training. The previous training may be associated with the knowledge and experience score of the participants.\n\n\nConclusion\n\nThe success of neonatal resuscitation is influenced by the readiness of the hospital, which can be seen through indicators of the level of knowledge and experience of the healthcare personnel. In this study, we found that the healthcare personnel from type A and type B hospitals are more experienced than the type D hospital in conducting neonatal resuscitation. We suggest that the type D hospital or other primary care must refer the neonate if there is the need for neonatal resuscitation. Additional neonatal resuscitation training is necessary to increase the knowledge and experience of the healthcare personnel. Finally, larger observational studies with multi-center approaches need to be conducted to confirm our findings.\n\n\nData availability\n\nFigshare: Neonatal Resuscitation: Measuring The Readiness of Healthcare Personnel, https://doi.org//10.6084/m9.figshare.18865418.47\n\nThe project contains the following underlying data:\n\n• Experience.sav\n\n• Knowledge.sav\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgements\n\nWe acknowledged the contribution of Peni Indriani and Paniani as the head of the Neonatal Intensive Care Unit (NICU) in Dr. Soetomo General Hospital.\n\n\nReferences\n\nRaghuveer T, Cox A: Neonatal resuscitation: an update. Am Fam Physician. 2011; 83: 911–918. PubMed Abstract\n\nThe World Bank: Mortality rate, neonatal (per1000 live births) Indonesia. World Bank Gr; n.d.Reference Source\n\nKozuki N, Guenther T, Vaz L, et al.: A systematic review of community-to-facility neonatal referral completion rates in Africa and Asia. BMC Public Health. 2015; 15: 989. Publisher Full Text\n\nPai VV, Kan P, Bennett M, et al.: Improved Referral of Very Low Birthweight Infants to High-Risk Infant Follow-Up in California. J. Pediatr. 2020; 216: 101–108.e1. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: Newborn death and illness.n.d.Reference Source\n\nAl-Sheyab NA, Khader YS, Shattnawi KK, et al.: Rate, Risk Factors, and Causes of Neonatal Deaths in Jordan: Analysis of Data From Jordan Stillbirth and Neonatal Surveillance System (JSANDS). Front. Public Health. 2020; 8: 595379. PubMed Abstract | Publisher Full Text\n\nTri M, Sampurna A: A population-based study of neonatal deaths in Indonesia based on the Indonesian demographic health survey: what determinants play an essential role?.n.d.; 1–27.\n\nVo AT, Cho CS: Neonatal resuscitation in the emergency department. Pediatr. Emerg. Med. Pract. 2020; 17: 1–16.\n\nTe Pas AB, Sobotka K, Hooper SB: Novel Approaches to Neonatal Resuscitation and the Impact on Birth Asphyxia. Clin. Perinatol. 2016; 43: 455–467. Publisher Full Text\n\nEscobedo MB, Aziz K, Kapadia VS, et al.: 2019 American Heart Association Focused Update on Neonatal Resuscitation: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2019; 140: e922–e930. PubMed Abstract | Publisher Full Text\n\nBriggs DC, Eneh AU: Preparedness of primary health care workers and audit of primary health centres for newborn resuscitation in Port Harcourt, Rivers State, Southern Nigeria. Pan Afr. Med. J. 2020; 36: 68. PubMed Abstract | Publisher Full Text\n\nO’Currain E, Davis PG, Thio M: Educational Perspectives: Toward More Effective Neonatal Resuscitation: Assessing and Improving Clinical Skills. NeoReviews. 2019; 20: e248–e257. PubMed Abstract | Publisher Full Text\n\nWeldearegay HG, Abrha MW, Hilawe EH, et al.: Quality of neonatal resuscitation in Ethiopia: implications for the survival of neonates. BMC Pediatr. 2020; 20: 129. PubMed Abstract | Publisher Full Text\n\nSintayehu Y, Desalew A, Geda B, et al.: Basic neonatal resuscitation skills of midwives and nurses in Eastern Ethiopia are not well retained: An observational study. PLoS One. 2020; 15: e0236194. PubMed Abstract | Publisher Full Text\n\nJnah AJ, Newberry DM, Trembath AN, et al.: Neonatal Resuscitation Training: Implications of Course Construct and Discipline Compartmentalization on Role Confusion and Role Ambiguity. Adv Neonatal Care Off J Natl Assoc Neonatal Nurses. 2016; 16: 201–210. Publisher Full Text\n\nMuneer A, Bari A, Haider A, et al.: Knowledge of clinicians/pediatricians about neonatal resuscitation in a tertiary care hospital. Pakistan. J. Med. Sci. 2019; 35: 775–779. PubMed Abstract | Publisher Full Text\n\nMildenberger C, Ellis C, Lee K: Neonatal resuscitation training for midwives in Uganda: Strengthening skill and knowledge retention. Midwifery. 2017; 50: 36–41. Publisher Full Text\n\nMurila F, Obimbo MM, Musoke R: Assessment of knowledge on neonatal resuscitation amongst health care providers in Kenya. Pan Afr Med J. 2012; 11: 78.\n\nUmar LW, Ahmad HR, Isah A, et al.: Evaluation of the cognitive effect of newborn resuscitation training on health-care workers in selected states in Northern Nigeria. Ann Afr Med. 2018; 17: 33–39. Publisher Full Text\n\nJukkala AM, Henly SJ: Provider readiness for neonatal resuscitation in rural hospitals. J Obstet Gynecol Neonatal Nurs JOGNN. 2009; 38: 443–452. PubMed Abstract | Publisher Full Text\n\nMinister of Health of the Republic of Indonesia: Regulation of the Minister of Health of the Republic of Indonesia No. 340/MENKES/PER/III/2010 2010.Reference Source\n\nBarfield WD, Papile LA, Baley JE, et al.: Levels of neonatal care. Pediatrics. 2012; 130: 587–597. Publisher Full Text\n\nCaldelari M, Floris L, Marchand C, et al.: Maintaining the knowledge and neonatal resuscitation skills of student midwives 6 months after an educational program. Arch Pediatr. 2019; 26: 385–392. PubMed Abstract | Publisher Full Text\n\nGebreegziabher E, Aregawi A, Getinet H: Knowledge and skills of neonatal resuscitation of health professionals at a university teaching hospital of Northwest Ethiopia. World J Emerg Med. 2014; 5: 196–202. PubMed Abstract | Publisher Full Text\n\nBuchanan JA, Hagan P, McCormick T, et al.: A Novel Approach to Neonatal Resuscitation Education for Senior Emergency Medicine Residents. West J Emerg Med. 2020; 22: 74–76. PubMed Abstract | Publisher Full Text\n\nCormier S, Chan M, Yaskina M, et al.: Exploring paediatric residents’ perceptions of competency in neonatal intensive care. Paediatr Child Health. 2019; 24: 25–29. PubMed Abstract | Publisher Full Text\n\nGunay I, Agin H, Devrim I, et al.: Resuscitation skills of pediatric residents and effects of Neonatal Resuscitation Program training. Pediatr Int. 2013; 55: 477–480. Publisher Full Text\n\nWeyer SM, Cook ML, Riley L: The Direct Observation of Nurse Practitioner Care study: An overview of the NP/patient visit. J Am Assoc Nurse Pract. 2017; 29: 46–57. PubMed Abstract | Publisher Full Text\n\nTubbs-Cooley HL, Mara CA, Carle AC, et al.: Association of Nurse Workload with Missed Nursing Care in the Neonatal Intensive Care Unit. JAMA Pediatr. 2019; 173: 44–51. PubMed Abstract | Publisher Full Text\n\nJohnson C, Shen E, Winn K, et al.: Neonatal Resuscitation: A Blended Learning Curriculum for Medical and Physician Assistant Students. MedEdPORTAL J Teach Learn Resour. 2020; 16: 10921. PubMed Abstract | Publisher Full Text\n\nLee MO, Brown LL, Bender J, et al.: A medical simulation-based educational intervention for emergency medicine residents in neonatal resuscitation. Acad Emerg Med. 2012; 19: 577–585. Publisher Full Text\n\nCusack J, Fawke J: Neonatal resuscitation: are your trainees performing as you think they are? A retrospective review of a structured resuscitation assessment for neonatal medical trainees over an 8-year period. Arch Dis Child - Fetal Neonatal Ed. 2012; 97: F246–F248. PubMed Abstract | Publisher Full Text\n\nSurcouf JW, Chauvin SW, Ferry J, et al.: Enhancing residents’ neonatal resuscitation competency through unannounced simulation-based training. Med Educ Online. 2013; 18: 1–7. PubMed Abstract | Publisher Full Text\n\nEl F, Abusaad S, Gad G, et al.: The changes on knowledge, confidence and skills accuracy of nursing students at a simulated based setting versus traditional during neonatal resuscitation. Int J Nurs Didact. 2015; 5. Publisher Full Text\n\nShim JW, Kim MJ, Kim E-K, et al.: The Impact of Neonatal Care Resources on Regional Variation in Neonatal Mortality Among Very Low Birthweight Infants in Korea. Paediatr Perinat Epidemiol. 2013; 27: 216–225. Publisher Full Text\n\nCifuentes J, Bronstein J, Phibbs CS, et al.: Mortality in Low Birth Weight Infants According to Level of Neonatal Care at Hospital of Birth. Pediatrics. 2002; 109: 745–751. Publisher Full Text\n\nCurran V, Fleet L, White S, et al.: A randomized controlled study of manikin simulator fidelity on neonatal resuscitation program learning outcomes. Adv Health Sci Educ. 2015; 20: 205–218. PubMed Abstract | Publisher Full Text\n\nQureshi MJ, Kumar M: Laryngeal mask airway versus bag-mask ventilation or endotracheal intubation for neonatal resuscitation. Cochrane Database Syst Rev. 2018; 3: CD003314. Publisher Full Text\n\nMirkuzie AH, Sisay MM, Bedane MM: Standard basic emergency obstetric and neonatal care training in Addis Ababa; trainees reaction and knowledge acquisition. BMC Med Educ. 2014; 14: 201. PubMed Abstract | Publisher Full Text\n\nFalck AJ, Escobedo MB, Baillargeon JG, et al.: Proficiency of Pediatric Residents in Performing Neonatal Endotracheal Intubation. Pediatrics. 2003; 112: 1242–1247. PubMed Abstract | Publisher Full Text\n\nVenkatesh V, Ponnusamy V, Anandaraj J, et al.: Endotracheal intubation in a neonatal population remains associated with a high risk of adverse events. Eur J Pediatr. 2011; 170: 223–227. Publisher Full Text\n\nGoh SSM, Kan SY, Bharadwaj S, et al.: A review of umbilical venous catheter-related complications at a tertiary neonatal unit in Singapore. Singap Med J. 2021; 62: 29–33. Publisher Full Text\n\nSari TK, Irwanto I, Etika R, et al.: Association Between Sepsis Risk Calculator and Infection Parameters for Neonates With Risk of Early Onset Sepsis. Indones J Trop Infect Dis. 2020; 8: 108. Publisher Full Text\n\nSawyer T, Umoren RA, Gray MM: Neonatal resuscitation: advances in training and practice. Adv Med Educ Pract. 2017; Volume 8: 11–19. PubMed Abstract | Publisher Full Text\n\nDeorari AK, Paul VK, Singh M, et al.: Impact of education and training on neonatal resuscitation practices in 14 teaching hospitals in India. Ann Trop Paediatr. 2001; 21: 29–33. PubMed Abstract | Publisher Full Text\n\nXu T, Wang H, Ye H, et al.: Impact of a nationwide training program for neonatal resuscitation in China. Chin Med J. 2012; 125: 4398–4405. PubMed Abstract\n\nSampurna M, Visuddho V: Neonatal Resuscitation: Measuring The Readiness of Healthcare Personnel. Figshare Dataset. n.d.Publisher Full Text"
}
|
[
{
"id": "137948",
"date": "11 Jul 2022",
"name": "Elisabeth M W Kooi",
"expertise": [
"Reviewer Expertise Neonatology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study is an important attempt to receive more insight in resuscitation readiness of various levels of staff in Indonesian hospitals of several levels. A questionnaire was developed and tested in ten nurses and then send out to a large number of hospital workers in neonatal departments. The results show a better readiness and experience in higher level hospitals, and some differences between characteristics of the participants.\nI have several concerns:\nThe results are based on the responses of a relatively small part of the invited population. This low response rate may have biased the results which should be assessed and discussed in more detail. i.e.: Were certain levels of staff overrepresented?\n\nAlso the validity of both questionnaires needs a critical reflection, including the assumed clinical relevant difference: even though there may be statistical significant differences, most of the time the difference between two groups is (only?) 1 or 2 points: is this relevant? The conclusion of the manuscript is fully based on this questionnaire that may need further validation including the assessment of a minimal clinical relevant difference.\n\nAlso, are the questions based on an implemented national guideline that all neonatal caretakers should be aware of? How sure are the authors about the supposed correct answers to the questions, as some are consensus based?\nOther concerns include:\nHave the authors assessed whether differences between subject characteristics were confounded by the other characteristics, i.e. were more men working in level A hospitals with more experience? This needs further analysis.\n\nTable 4 needs legends on what the various answers mean, apart from what is written in the main text.\n\nThe abstract needs a brief explanation on the questionnaire (self-developed, ranges) in the methods section in order to be able to interpret the results section, Also, in my opinion it is not relevant to mention only p-values in the abstract results, but please include effect sizes and their uncertainties. Also response rate should be mentioned in abstract.\n\nI recognize a few language issues, i.e. what does \"divided the room into...\" mean? I would suggest to have the text reviewed on its details.\n\nIn the conclusion the authors suggest to refer infants in need of resuscitation, I would rephrase into ‘risk at need for resuscitation’, otherwise referral will be too late. Also the authors conclude that more training is needed. Although this may very well be true, it is not what was investigated in this study, which is why I would weaken this statement.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "9648",
"date": "26 May 2023",
"name": "Mahendra Tri Arif Sampurna",
"role": "Author Response",
"response": "We are very thankful for your availability and willingness to help us to become our reviewer on our manuscript entitled \"Neonatal Resuscitation: A cross-sectional study measuring the readiness of healthcare personnel\". We have revised our manuscript based point-on-point revision suggested. 1. \"The results are based on the responses of a relatively small part of the invited population. This low response rate may have biased the results which should be assessed and discussed in more detail. i.e.: Were certain levels of staff overrepresented?\" Response: Thank you for your valuable comment. We notice that our small sample may introduce the bias to our study. However, in this study we are trying to get the sample during a specific period to make sure there is no time bias. We have added mentions about this issue on the strength and limitation subsection. 2. \"The validity of both questionnaires needs a critical reflection, including the assumed clinical relevant difference: even though there may be statistical significant differences, most of the time the difference between two groups is (only?) 1 or 2 points: is this relevant? The conclusion of the manuscript is fully based on this questionnaire that may need further validation including the assessment of a minimal clinical relevant difference.\" Response: Thank you for your valuable suggestions. We use the validated questionnaire from prior publication of Jukkala et al in 2007. We confirm that the questions from that paper are suitable and relevant to our research aim. We also have added the discussion regarding the specific point of the questionnaire (in example : the lack of skill on endotracheal intubation) to enrich our discussion. 3. \"Are the questions based on an implemented national guideline that all neonatal caretakers should be aware of? How sure are the authors about the supposed correct answers to the questions, as some are consensus based?\" Response: Thank you for your valuable comment. In our country, there is a need for neonatal resuscitation certificates to become a neonatal intensive care unit health provider. They will get the training to make sure of their competency in neonatal resuscitation. We confirm that questions which we obtained from Jukkala et al were suitable to assess the knowledge and skill of neonatal intensive care unit health providers. 4. \"Have the authors assessed whether differences between subject characteristics were confounded by the other characteristics, i.e. were more men working in level A hospitals with more experience? This needs further analysis.\" Response: Thank you for your valuable suggestion. We now have analyzed that there are variables that confounded others. The Profession may be related with Education, Work Experience, Employee Status, and Care Level. Age was also related to work experience. However, because of this collinearity, we cannot perform the multivariate analysis to distinguish the effect of each variable. We are trying our best to explain this issue in the results. 5. \"Table 4 needs legends on what the various answers mean, apart from what is written in the main text.\" Response: Thank you for your valuable suggestion, we now have added the information on Table 4. 6. \"The abstract needs a brief explanation on the questionnaire (self-developed, ranges) in the methods section in order to be able to interpret the results section. Also, in my opinion it is not relevant to mention only p-values in the abstract results, but please include effect sizes and their uncertainties. Also the response rate should be mentioned in the abstract.\" Response: Thank you for your valuable suggestion, we now have added a brief explanation about the questionnaire and included effect sizes in the abstract. 7. \"I recognize a few language issues, i.e. what does \"divided the room into...\" mean? I would suggest having the text reviewed on its details.\" Response: Thank you for your valuable suggestion. We have done copy editing using the help from professional English editing services. 8. \"In the conclusion the authors suggest referring to infants in need of resuscitation, I would rephrase into ‘risk at need for resuscitation’, otherwise referral will be too late. Also the authors conclude that more training is needed. Although this may very well be true, it is not what was investigated in this study, which is why I would weaken this statement.\" Response: Thank you for your valuable comment. We agree and have revised our conclusion. Again, thank you for your help."
}
]
},
{
"id": "140368",
"date": "13 Jul 2022",
"name": "Yellanthoor Ramesh Bhat",
"expertise": [
"Reviewer Expertise Pediatrics",
"Neonatology",
"Intensive care",
"Ventilation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article ‘Neonatal resuscitation: A cross-sectional study measuring the readiness of healthcare personnel” addresses the readiness of healthcare personnel with regard to the much needed topic on neonatal resuscitation. This study used questionnaire in 4 different types of hospitals. They found significantly higher experience scores among the healthcare personnel of type A and type B hospitals than the type D hospital. This need will help the local area to plan further training of personnel in type D hospital.\nOverall the study appears reasonable. The information may help plan the policy regarding neonatal resuscitation and the target groups.\n\nThe first sentence, “Neonatal mortality is one of the standards of neonatal care”-this sentence should be modified as ‘To decrease the neonatal mortality in developing countries, there is an urgent need to improve the neonatal care”.\n\nCopyediting will be required throughout the manuscript.\n\nMinimize the repetitions especially in methods and discussion.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9649",
"date": "26 May 2023",
"name": "Mahendra Tri Arif Sampurna",
"role": "Author Response",
"response": "We are very thankful for your availability and willingness to help us to become our reviewer on our manuscript entitled \"Neonatal Resuscitation: A cross-sectional study measuring the readiness of healthcare personnel\". We have revised our manuscript based point-on-point revision suggested. 1. \"The first sentence, “Neonatal mortality is one of the standards of neonatal care”-this sentence should be modified as ‘To decrease the neonatal mortality in developing countries, there is an urgent need to improve the neonatal care”.\" Response: Thank you for your valuable suggestion. We have revised the sentence to clear our research aim. 2. \"Copyediting will be required throughout the manuscript.\" Response: Thank you for your valuable suggestion. We have done copy editing using the help from professional English editing services. 3. \"Minimize the repetitions especially in methods and discussion.\" Response: Thank you for your valuable suggestion. We now have minimized the repetitions and keep the methods and discussion concisely."
}
]
}
] | 1
|
https://f1000research.com/articles/11-520
|
https://f1000research.com/articles/12-526/v1
|
22 May 23
|
{
"type": "Research Article",
"title": "Feasibility and guidelines for the use of an injectable fiducial marker (BioXmark®) to improve target delineation in preclinical radiotherapy studies using mouse models.",
"authors": [
"Kathryn Brown",
"Mihaela Ghita",
"Kevin M Prise",
"Karl T Butterworth",
"Mihaela Ghita",
"Kevin M Prise",
"Karl T Butterworth"
],
"abstract": "Background: Preclinical models of radiotherapy (RT) response are vital for the continued success and evolution of RT in the treatment of cancer. The irradiation of tissues in mouse models necessitates high levels of precision and accuracy to recapitulate clinical exposures and limit adverse effects on animal welfare. This requirement has been met by technological advances in preclinical RT platforms established over the past decade. Small animal RT systems use onboard computed tomography (CT) imaging to delineate target volumes and have significantly refined radiobiology experiments with major 3Rs impacts. However, the CT imaging is limited by the differential attenuation of tissues resulting in poor contrast in soft tissues. Clinically, radio-opaque fiducial markers (FMs) are used to establish anatomical reference points during treatment planning to ensure accuracy beam targeting, this approach is yet to translate back preclinical models. Methods: We report on the use of a novel liquid FM BioXmark® developed by Nanovi A/S (Kongens Lyngby, Denmark) that can be used to improve the visualisation of soft tissue targets during beam targeting and minimise dose to surrounding organs at risk. We present descriptive protocols and methods for the use of BioXmark® in experimental male and female C57BL/6J mouse models. Results: These guidelines outline the optimum needle size for uptake (18-gauge) and injection (25- or 26-gauge) of BioXmark® for use in mouse models along with recommended injection volumes (10-20 µl) for visualisation on preclinical cone beam CT (CBCT) scans. Injection techniques include subcutaneous, intraperitoneal, intra-tumoral and prostate injections. Conclusions: The use of BioXmark® can help to standardise targeting methods, improve alignment in preclinical image-guided RT and significantly improve the welfare of experimental animals with the reduction of normal tissue exposure to RT.",
"keywords": [
"Fiducial marker",
"practicable guidelines",
"preclinical models",
"image-guidance",
"preclinical radiotherapy"
],
"content": "Introduction\n\nRadiotherapy (RT) remains a critical component of multidisciplinary cancer care. Progress in RT has been driven by advances in RT and imaging technologies with parallel increases in our understanding of RT response at the cell, tissue and whole organism levels. RT relies on image guidance to achieve high levels of precision and accuracy during treatment, most often using computed tomography (CT) to maximise the competing probabilities of tumour control (TCP) and normal tissue complication probability (NTCP).\n\nDuring RT, fiducial markers (FMs) are commonly used for daily alignment, tumour tracking and to improve patient positioning for treatment.1–3 FMs can enhance the differentiation of tumour and normal tissue margins in low contrast tissues4 and their use has significantly improved the accuracy of different RT techniques: intensity modulated RT (IMRT), image-guided RT, volumetric modulated arc therapy (VMAT) and hypo-fractionated stereotactic treatments.5\n\nIrradiation of tumours and tissues in mouse models requires high levels of precision and accuracy to recapitulate clinical scenarios and limit adverse effects on animal welfare. Commonly, preclinical RT set-ups are untargeted leading to mice presenting with signs of radiation injury and toxicity making studies short-lived hindering further development.6–8 However, implementation of small animal image-guided radiotherapy platforms in research has been a huge refinement, combining volumetric imaging modalities with treatment planning and delivery.9–11 These platforms have advanced previous wide field and untargeted RT set-ups, yet the localisation of small, low contrast tissue targets continues to be challenging.12 This has prevented the development of sophisticated and cutting-edge RT protocols, such as hypo-fractionation (delivering a higher dose of radiation per session in comparison to conventional RT therefore reducing the overall number of treatment sessions), due to limitations in visualisation of some soft tissue targets.13 To overcome targeting errors, lack of standardisation in treatment delivery and improve animal welfare in preclinical models of RT without the need for expensive updated platforms we propose the reverse translation of FMs.12\n\nFMs are typically composed of high-Z number materials to ensure differentiation from internal structures.14 Solid FMs, such as gold, are not suitable for preclinical RT as they result in streaking imaging artefacts on CBCT scans, decreased accuracy for dose calculations and alter dose perturbations.15–19 In addition, the surgical procedure to insert solid FMs puts mice under high levels of stress and decreases animal welfare.5,20\n\nLiquid FMs, such as BioXmark®, offer refinements over solid fiducials including ease of injection, adaptable size, reduced imaging artefacts and negligible effects on radiation dose.16,21–23 BioXmark® has the scope to increase precision and accuracy for the development of innovative preclinical RT studies. Increasing the precision of RT doses can reduce error in treatment targeting and thus reduce the need for large study numbers. In addition, reduced RT fields will prevent unnecessary dosing and RT toxicity to surrounding normal tissues, significantly improving animal welfare all within the framework of the NC3Rs.24–26 BioXmark® has been successfully evaluated and deemed advantageous compared to other solid FMs for use in RT treatment in both clinical22,27–33 and preclinical settings.34,35\n\nSuccessful refinement of radiotherapy dosing has the potential to impact over 500 mice required annually for radiotherapy studies within the Patrick G. Johnston Cancer Centre, upwards of 4,000 mice per year would benefit nationally, and over 30,000 mice per year internationally.\n\nThe purpose of this study is to demonstrate the versatility and ease of use of BioXmark® in preclinical applications. This article provides guidelines for the injection of BioXmark® in mouse models to aid visualisation of treatment targets and standardisation of treatment alignment for future preclinical RT treatment set-ups.\n\n\nMethods\n\nBioXmark® is a liquid FM produced by Nanovi A/S (Kongens Lyngby, Denmark). It is a sterile, ready-to-inject liquid composed of biodegradable sucrose acetate isobutyrate (SAIB), iodinated SAIB and ethanol. This formulation ensures that when BioXmark® is injected into soft tissue the ethanol partly diffuses out of the marker, increasing its viscosity, resulting in the formation of a semi-solid gel.36 BioXmark® is visible on magnetic resonance imaging (MRI) and ultrasonography due to the SAIB component and visible on X-ray imaging modalities due to the electron-dense iodinated SAIB component.32 Evidence of the visibility of BioXmark® on multiple imaging modalities in clinical, preclinical and phantom studies is presented in Table 1.\n\nLike other FMs, it is recommended clinically to avoid the injection of BioXmark® into necrotic tissue, highly vascularised tumour tissue or air-filled cavities.36 Preclinical injection of BioXmark® should also avoid these tissues and always be through the least invasive procedure possible and actively avoid the need for surgical implantation. Volumes over 50 μl are not recommended for use in mouse models due to negative imaging artefacts on preclinical CBCT scans. An optimum marker volume is suggested between 10-20 μl, this will allow visualisation on CBCT scans without hindering visualisation of small anatomical structures.35 Larger volumes may be more applicable for clinical use or larger animal species.\n\nAll experimental procedures were carried out in accordance with the Home Office Guidance on the Operation of the Animals (Scientific Procedures) Act 1986, and approved by the Queen’s University Belfast Animal Welfare and Ethical Review Body (PPL2813). Animals were euthanized by Schedule 1 procedures. Animal studies are reported in compliance with the ARRIVE guidelines.37\n\nAll mice were obtained from Charles River Laboratories (Oxford, UK). A mix of mice ages and genders were used due to animal availability from other ongoing studies. Female 12–15-week-old C57BL/6J mice were used for subcutaneous (n=3) and intra-peritoneal injections (n=2), male 14-18-week-old C57BL/6J mice were used for intra-tumoral study (n=21 BioXmark® injected tumours, n=21 control tumours) and male 10-15-week-old C57BL/6J mice were used for prostate injections (n=2). These numbers were used to assess the feasibility of injection types. No criteria were set to exclude animals from these studies. Mice were randomized to receive either a subcutaneous, or intra-peritoneal injections using an online random sequence generator. Blinding was not possible for intra-tumoral and prostate injections. Blinding was also not possible for image analysis as the injected FM, BioXmark®, was clearly visualized on CBCT scans.\n\nAll mice were housed under controlled conditions (12-hour light–dark cycle, 21°C) in standard caging and received a standard laboratory diet and water ad libitum. To improve the welfare of mice environmental enrichment tools were placed in all cages including cardboard tubes for exploration, softwood blocks to encourage gnawing to prevent teeth overgrowth, nesting material for comfort and mouse swings for added cage complexity and exercise. Mice were also handled gently using refined cupping methods and frequently from a young age to reduce stress.\n\nMice were anaesthetised with injectable ketamine and xylazine (100 mg/kg and 10 mg/kg) prior to BioXmark® injection and CBCT imaging. All mice were placed in a heat-box (37°C) for recovery and monitored closely after injections until conscious and returned to normal behaviour.\n\nA 1 ml micro-dose syringe (Vlow Medical, Netherlands) was used for the uptake and injection of BioXmark®. Micro-dose syringes are recommended as they ensure a controlled injection volume. A loading 18-gauge needle was used to fill the syringe slowly from the glass ampoule. BioXmark® is a viscous liquid so thinner needles may require a longer time to fill the syringe. Air bubbles were checked for through visual inspection prior to injection and were removed by gently tapping the side of the syringe and any excess or leakage BioXmark® was cleaned using ethanol wipes. The loading needle was removed after uptake into the syringe and replaced with a smaller needle (25-gauge) for each injection. Needles were replaced prior to each injection.\n\nBioXmark® was loaded into a micro-dose syringe as detailed above. For this study, we used a micro-dose syringe with options for the injection of 10, 20 and 40 μl. Mice were anaesthetised with injectable ketamine and xylazine (100 mg/kg and 10 mg/kg) before injection. A small area of fur on each flank was shaved and cleaned with an ethanol wipe for injection. 25-gauge needles were used for subcutaneous injections. The skin of the mouse was tented using the thumb and finger and a preselected volume of BioXmark® (10 μl (n=1), 20 μl (n=1) or 40 μl (n=1)) was injected under consistent pressure. Each mouse received two injections of BioXmark®, one on each flank, e.g. 10 μl on the left and 10 μl on the right. As BioXmark® is very viscous the needle was held for 30 seconds after the volume was injected and then slowly removed. All mice were placed in a heat-box for recovery (37°C) and monitored closely until fully recovered from the anaesthetic and then returned to their original cage.\n\nFor this study, we used a micro-dose syringe (20 and 40 μl) and 25-gauge needles for injections (20 μl, n=1, 40 μl, n=1). Mice were anaesthetised with injectable ketamine and xylazine (100 mg/kg and 10 mg/kg) before the study, and the injection point sterilized with ethanol before intraperitoneal injection. As BioXmark® is very viscous, the needle was held for 30 seconds following injection and then slowly removed. No mice presented with bleeding or leakage of BioXmark®, if there was leakage of BioXmark® this could be removed with an ethanol wipe. Mice were placed in a heat-box for recovery (37°C) and monitored closely until fully recovered from the anaesthetic before returning to their original cage.\n\nA previous study reported that it was not possible to mix BioXmark® with tumour cells and a solid tumour must be established prior to injection of BioXmark®.34 In this study, we trialled an intra-tumoral injection of BioXmark® as outlined in Brown et al.35\n\nTumour xenograft studies were performed using MC38 colon cancer cells (originate from James W. Hodge) cultured in DMEM media supplemented with 10% foetal bovine serum (FBS) and 1% penicillin/streptomycin. Cells were maintained at 37°C in a humidified atmosphere of 5% CO2 and subcultured every 3–4 days to maintain exponential growth.\n\nMC38 cells were cultured in vitro and prepared in PBS (1 × 105 cells per 100 μl). Subsequently, 100 μl was injected subcutaneously into the flank of each C57BL/6J mouse (n=42). Mice were anesthetized using inhalant isoflurane (0.5 – 2%) for implant and placed in a heat box for recovery. Mice were then returned to conventional housing and closely monitored. Tumour volume was determined three times a week using calliper measurements in three orthogonal dimensions. Once tumours grew to a volume of 100 mm3 mice were randomised using an online random sequence generator into control (n=21) and BioXmark® (n=21) cohorts. This injection method was used to assess the radiobiological effect of BioXmark® with tumours treated with single (16 Gy) or fractionated (2×8 Gy or 3×4 Gy) doses of RT. These mice were treated with RT as outlined in Brown et al.35\n\nFor the intra-tumoral injection of BioXmark®, the FM was loaded into a micro-syringe as detailed above and 25-gauge needles were used for injection. Mice were anaesthetised with injectable ketamine and xylazine (100 mg/kg and 10 mg/kg) and the injection point sterilized with ethanol before injection. The needle was carefully placed into the middle of the tumour (estimated through needle insertion) and 20 μl of BioXmark® injected under consistent pressure. To prevent leakage or bleeding the needle was held for 30 seconds before removal. No mice presented with bleeding or leakage of BioXmark®. All mice were placed in a heat-box for recovery (37°C) and monitored closely until fully recovered from the anaesthetic.\n\nIntra-prostate injections of BioXmark® were performed under aseptic conditions (n=2). Mice were anaesthetised using inhalant isoflurane (0.5–2%) throughout the procedure and administered analgesia (buprenorphine 0.015 mg/ml (0.05 mg/kg dose)) via IP injection before the surgical procedure and 6 hours post. Protocol adapted from Pavese et al.38 A small portion skin was shaved and the prostate exposed through a low midline abdominal incision of 5 mm (roughly 1 cm above external genitals). The anterior lobe was identified, and a 26-gauge needle was used to inject 10 μl of BioXmark® under consistent pressure and the needle held in place for 30 seconds to prevent leakage. Due to the delicate procedure, we trialled a finer gauge needle and found it feasible to inject BioXmark® effectively with a 26-gauge needle. Successful injection was confirmed by the formation of a small rounding or mound shape. The injection area was checked for bleeding or leakage of BioXmark®, none was found to leak, before carefully placing the prostate back into the abdominal cavity and the small wound was sealed with tissue glue and stitches. Mice were placed in a heat box for recovery (37°C) and healing, body weight and behaviour were closely monitored after the surgical procedure and then returned to original caging.\n\nBioXmark® uptake\n\nA. BioXmark® should be stored at room temperature in a sealed glass ampoule.\n\nB. Prepare the syringe (micro-dose injector, vlow medical 1ml) by adding a loading needle (18-gauge).\n\nC. Carefully open the BioXmark® ampoule and fill the syringe with the transparent liquid using the loading needle.\n\n- BioXmark® is a viscous liquid so thinner needles may require a longer time to fill the syringe.\n\n- Remove bubbles by gently tapping the syringe.\n\n- Clean excess or spilled BioXmark® with an ethanol wipe.\n\n- BioXmark® is single use, dispose of excess when finished.\n\nD. Once all the liquid has been taken up into the syringe change the loading needle to a new needle for injection (25-gauge or 26-gauge).\n\nE. Fill the new needle with BioXmark® liquid ensuring no air bubbles are present.\n\nF. Clean any excess BioXmark® from the needle with an ethanol wipe before injection.\n\nInjection of BioXmark®\n\nA. Place anaesthetised mouse on a clean surface and shave a small area of fur (if required) on the flank of mouse at the point of implant.\n\n- Once ready for implant suitably restrain, depending on injection route, the mouse for injection.\n\nB. Use an ethanol wipe to clean the skin.\n\nC. Insert the 25-gauge/26-gauge needle (bevel side down) and inject the volume of BioXmark® required under consistent pressure. Hold for 30 seconds before slowly removing the needle.\n\nD. Check area for bleeding or leakage of BioXmark® and carefully clean with ethanol wipe if needed.\n\n- If bleeding occurs, check the source of bleeding to ensure no internal organs have been punctured or pain caused to the animal. Apply pressure with clean gauze. If bleeding does not stop take appropriate measure e.g. additional monitoring, pain relief, remove from experiment.\n\nE. If multiple injections of BioXmark® are required, replace needle and repeat injection process.\n\nF. Place mouse in a heat-box for recovery (37°C) and monitor closely until fully recovered from anaesthetic.\n\nIntra-tumoral injection of BioXmark®\n\nA previous study trialled mixing BioXmark® with tumour cells prior to implant for targeting, this was not feasible with the tumour needing to be establish prior to BioXmark® injection.34 In this study we trialled an intra-tumoral injection of BioXmark® as outlined in Brown et al 2020.35 Mice were randomised into control of BioXmark® injected cohorts once sucutaneous tumours reached a suitable size for treatment (100 mm3). This protocol was used to determine the radiobiological effect of BioXmark® on tumour response, cytotoxicity and dose perturbation.35 For tumour targeting multiple subcutaneous injections of BioXmark® around the tumour would be more suitable (Figure 1).\n\nA. Ensure needle and syringe are loaded with BioXmark® and are prepared for injection.\n\nB. Place anaesthetised mouse on a clean surface and use an ethanol wipe to sterilise the point of injection.\n\nC. Insert the 25-gauge/26-gauge needle (bevel side down) to the middle of the tumour.\n\nD. Inject the desired volume of BioXmark® (10-25 μl) under consistent pressure and wait 30 seconds before removing the needle.\n\nE. Check area for bleeding or leakage of BioXmark® and carefully clean with ethanol wipe if needed.\n\n- If bleeding occurs, check source and apply pressure to stop. Take appropriate measures if needed e.g. additional monitoring.\n\nF. Place mouse in a heat-box for recovery (37°C) and monitor closely until fully recovered from anaesthetic.\n\nOrthotopic prostate injection of BioXmark®\n\nMice were anaesthetised using inhalant isoflurane throughout the procedure and administered analgesia (buprenorphine 0.015 mg/ml (0.05 mg/kg dose)) prior to surgical procedure and 6 hours post. Protocol adapted from Pavese et al 2013.39\n\nA. Procedure to be performed under aseptic conditions.\n\nB. Ensure needle and syringe are loaded with BioXmark® and are prepared for injection.\n\nC. Expose the prostate through a low midline abdominal incision of 5 mm (roughly 1 cm above external genitals).\n\nD. Once the prostate is exposed identify the lobes.\n\nE. Using a 26-gauge needle, inject 10 μl of BioXmark® into the anterior lobe of the prostate under consistent pressure.\n\nF. To ensure successful injection, check a small bubble had formed. Hold the needle in place for 30 seconds before removal to prevent leakage.\n\nG. Check area for bleeding or leakage of BioXmark® and carefully clean with cotton tip if needed.\n\n- If bleeding occurs, check source of bleed to ensure no internal organs have been punctured or pain caused to the animal. Use sterile cotton tip to clean the area/apply pressure. Take appropriate measures if needed e.g. additional monitoring, pain relief, remove from experiment.\n\nH. Carefully place the prostate back into the abdominal cavity.\n\nI. Use tissue glue and stiches to close the small wound.\n\nJ. Place mouse in a heat box for recovery (37°C).\n\n- Or suitable equivalent e.g. cage placed on heat mat\n\nK. Closely monitor mouse after surgical procedure.\n\n- In particular wound healing, body weight and behaviour.\n\nImaging was completed using the Small Animal Radiation Research Platform (SARRP) (Xstrahl Life Sciences, Camberley UK) onboard CBCT imaging. An imaging energy of 60 kV was used with 0.5 mm Al filtration for all in vivo models. The acquired CBCT scans were transformed into material properties by defining five discrete windows for these materials; air, lung, fat, tissue and bone.39 Imaging was completed immediately after the injection of BioXmark®, while the mice were still anaesthetised, for subcutaneous, IP and intra-tumoral injections. Mice injected with BioXmark® into the prostate were allowed to recover overnight in the home cage and imaged the following day. These mice were anaesthetised with injectable ketamine and xylazine (100 mg/kg and 10 mg/kg) for imaging.\n\nComputational Environment for Radiological Research (CERR) software (https://cerr.github.io/CERR/) was used to complete additional image analysis. Image analysis could not be blinded as BioXmark® was visible on the CBCT scans. For contouring of BioXmark®, all relevant DICOM images and structure sets were exported into CERR software within MATLAB (Version 2019b).40 Structures of interest were contoured manually using the CERR in-house contouring interface. Contours were created slice-by-slice in the coronal plane with corrections made using the sagittal and axial planes. To reduce variations in contours all structures were contoured by the same user.\n\nStatistical differences were calculated using unpaired two-tailed student t-tests, or one-way ANOVA tests where appropriate, with a significance threshold of p < 0.05 using Prism GraphPad Prism 7 (Version 7.01, GraphPad Software, Inc.). Data is presented either as the average for the entire experimental arm ± standard error (SEM).\n\n\nResults\n\nThis study has provided methods for the application of BioXmark® in small animal models. Mice of both male and female sexes were used and no behavioural or toxic side-effects due to BioXmark® were observed.\n\nFigure 1A shows CBCT scans from mice injected subcutaneously with BioXmark® at two separate points on the flank (10, 20 or 40 μl). BioXmark® is easily visualised in bright white on all CBCT scans and could be easily differentiated from anatomical structures (Figure 1A). Capsules of BioXmark® formed in the cavity under the skin with all volumes having a similar 3-D shape (Figure 1B & Supplementary Figure 1). Further analysis of the long-term (5-month) stability of BioXmark® injected subcutaneously is detailed in Brown et al.35\n\nPanel A: CBCT scans of 10 (i), 20 (ii) and 40 µl (iii) of BioXmark® (left to right) injected subcutaneously at two points on the flank of mice (n =1). Panel B: Volumes of BioXmark® on CBCT scans were contoured using CERR software and 3-D shape of each marker visualized.\n\nDue to differences in marker shape between subcutaneous (Figure 1A) and intraperitoneal injections (Figure 2A) we assume that BioXmark® moulds around anatomical structures before solidifying. There is greater diversity in the shape after injection into the intraperitoneal cavity with the most evidenced by the larger volume of 40 μl (Figure 2A & B), indicating that the intraperitoneal injection is less stable than other methods with the marker breaking up and potentially solidifying in a different area than injected.\n\nPanel A: CBCT scans of 20 µl (i) and 40 µl (ii) of BioXmark® injected via intraperitoneal injection (n=1 per dose). Panel B: 3-D visualisation of 20 µl (i) and 40 µl (ii) of BioXmark® after intraperitoneal injection.\n\nTumour volumes have different shapes and sizes and are heterogeneous causing differences in diffusion of a substance, such as drugs or contrast agents, and potentially BioXmark®. Figure 3A shows the injection of 20 μl of BioXmark® into a subcutaneous MC38 colon carcinoma tumour. This was completed to trial the feasibility of injecting BioXmark® into dense tissue. Intra-tumoral injections were visualised as a hyperdense structure in the centre of the tumour easily differentiated from the tumour tissue (Figure 3A). 3-D reconstructions of injected BioXmark® which underwent fractionated RT (3×4 Gy) are shown in Figure 3B. Minimal changes were observed in the shape of BioXmark®. No radiobiological effects of BioXmark® were determined, further detailed in Brown et al.35\n\n20 µl was injected into MC38 subcutaneous tumours once they reached a volume of 100 mm3. Panel A: Mice were imaged on CBCT at 60 kV prior to receiving radiotherapy (n=21). Panel B: Volumes of BioXmark® on CBCT scans were contoured using CERR software and the 3-D shape of each marker was visualised throughout the dose schedule.\n\nThe injection of 10 μl of BioXmark® into an orthotopic prostate model is shown in Figure 4A. This method is the most technical and clinically accurate for placement of a FM for RT treatment targeting. The orientation of the marker can be monitored through 3-D analysis providing additional information on the location of the prostate. BioXmark® can be clearly visualised from CBCT scans but also differentiated from soft tissue through CBCT values for tissue (p=0.0093), air (p=0.0072) and bone (p=0.0073) (Figure 4C). Injected BioXmark® can help to identify the prostate to improve defining a target volume for beam delivery. This model could be used for normal tissue targeting of the prostate or for targeting orthotopic prostate tumours.\n\nPanel A: Mice were imaged on CBCT at 60 kV after injection of BioXmark® (n=2). Panel B: 3-D shape of injected BioXmark®. Panel C: Viability of the marker was quantified through CBCT numbers for BioXmark®, tissue, air and bone. Data presented are mean values ± SEM; statistical significance is reported as *< 0.05, ** < 0.01.\n\n\nDiscussion\n\nThis study is the first to provide a detailed methodology for the use of the liquid FM BioXmark® in preclinical mouse models. The feasibility of multiple injection methods has been trialled for use of the marker as a reference point for submillimetre targeting and beam positioning in preclinical RT set-ups. In this study, we assessed the visibility and 3-D profile of BioXmark® for subcutaneous, intraperitoneal, intra-tumoral and orthotopic prostate injections. All injection types were feasible and easily performed with BioXmark® easily differentiated from anatomical structures on CBCT scans. However, the IP injection of BioXmark® would not be recommended for use in RT targeting due to movement through the IP cavity, it may be more applicable to use a contrast agent for IP injections. We would recommend injection volumes between 10-20 μl of BioXmark® for use in mouse models. This study complements previous experimental studies for the transferability of BioXmark® between laboratories to improve treatment targeting in preclinical models of RT.34,41\n\nWhen BioXmark® is injected into soft tissue it forms a semi-solid gel, this acts as an anchor for the FM. Stability is an essential property of FMs for treatment targeting.14 Movement or loss of a marker can lead to inaccurate dose deposition and reduces the efficiency of RT treatment which may be increasingly important during hypo-fractionated schedules.42 Other liquid FMs are not suitable for fractionated RT as they have been reported to not solidify after injection (Lipiodol) or are not stable for long periods (hydrogel).16,43 The iodine-containing contrast agent Imeron 300 has been used preclinically for contrast-enhanced CBCT scans. Dobiasch et al have compared Imeron 300 with BioXmark® for targeting pancreatic tumours in mice; whilst both were easily visualised on CBCT scans BioXmark® was concluded more suitable for targeted RT.34 Imeron 300 has to be continually administered for scanning, adding additional stress on experimental mice.44 BioXmark® biodegrades slowly with stability shown up to 6 months preclinically.35 De Blanck et al estimate that full marker degradation is up to 3 years clinically31; therefore, BioXmark® is ideal for outlining treatment parameters for fractionated RT and treatment follow-up.\n\nAs a liquid FM, BioXmark® has advantages over solid FMs with the volume more controllable making it adaptable for preclinical use. The volume of the marker can be target specific and as small as 5-10 μl (Table 1).34,35 Once injected these markers conform to complex shapes surrounding soft tissue or tumour borders for 3-D visualisation. The final shape of injected BioXmark® can provide crucial information on the shape, size and rotation of a tumour which cannot be achieved with solid FMs.16,23,45 Any changes to the shape of BioXmark® after irradiation have yet to be reported from current clinical and preclinical studies. We were able to monitor the 3-D shape of intratumorally injected BioXmark® throughout fractionated treatments (Figure 3B) and showed that the 3-D shape was not significantly affected by 4 Gy fractions of RT. Small changes observed were expected due to changes in tumour shape after irradiation. However, we would recommend using peri-tumoral injections i.e. at multiple points surrounding or adjacent to a tumour, of BioXmark® for future studies to better align with clinical set-ups and remove BioXmark® from the treatment volume.\n\nFMs or fixed contrast agents are essential to improve the targeting of tumours in the lower abdomen and prostate in small animal RT. Current set-ups have high levels of errors due to large target fields which reduce the clinical relevance of studies and cause high levels of normal tissue toxicity.44,46,47 In addition, there are significant targeting errors in fractionated treatment schedules due to a lack of stable reference points. Verginadis et al used a solid radio-opaque marker for implantation to the jejunum of a mouse to improve targeting. This study reported increased toxicity levels and blockage of the GI tract.48 BioXmark® is an alternative marker with no reports of toxic side effects preclinically.34,35 We have demonstrated the ability to use BioXmark® for the targeting of prostate tumours with clear differentiation of BioXmark® from anatomical structures (Figure 4C). This approach can be adapted to other orthotopic tumour models to improve the reproducibility of RT targeting and significantly reduce the risk of adverse effects in mice.\n\n\nConclusion\n\nDespite advances in preclinical research, only one-third of in vivo studies translate to clinical trials.49 This is largely due to preclinical studies not replicating the clinical setting, and a lack of comprehensive reporting of methods, data sharing and transferability of protocols between laboratories.50 This study shows the feasibility of using BioXmark® in preclinical models of RT, it’s use can be adapted within preclinical radiobiology centres worldwide to improve the visualisation of orthotopic tumours and the translational impact of studies. Standardising the coupling of preclinical RT platforms with targeted imaging tools such as BioXmark® is a huge step toward quality assurance, reducing targeting uncertainties and most importantly improving animal welfare.\n\n\nAuthor contributions\n\nConceptualization, K.T.B., K.M.P.; Methodology, data curation and investigation, K.H.B., M.G., K.T.B.; Writing – Original Draft Preparation, K.H.B., K.T.B.; Writing- review & editing, M.G., K.M.P. All authors have read and agreed to the published version of the manuscript.",
"appendix": "Data availability\n\nFigshare. Preclinical CBCT scans. DOI: https://doi.org/10.6084/m9.figshare.22227490.v1 52\n\nThis project contains the following data:\n\n- CBCT datasets to accompany “Feasibility and guidelines for the use of an injectable fiducial marker (BioXmark®) to improve target delineation in preclinical radiotherapy studies using mouse models.”\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare. ARRIVE checklist. DOI: https://doi.org/10.6084/m9.figshare.22227478.v1\n\n- ARRIVE checklist to accompany “Feasibility and guidelines for the use of an injectable fiducial marker (BioXmark®) to improve target delineation in preclinical radiotherapy studies using mouse models.”\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nThe authors wish to acknowledge Jesper Boysen and Michael Wrang Mortensen (Nanovi A/S, Denmark).\n\n\nReferences\n\nGoyal S, Kataria T: Image Guidance in Radiation Therapy: Techniques and Applications. Radiol. Res. Pract. 2014; 2014: 1–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBedford JL, Chajecka-Szczygielska H, Thomas MDR: Quality control of VMAT synchronization using portal imaging. J. Appl. Clin. Med. Phys. 2015; 16: 284–297. 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PubMed Abstract | Publisher Full Text\n\nde Souza Lawrence L , et al.: Novel applications of an injectable radiopaque hydrogel tissue marker for management of thoracic malignancies. Chest. 2013; 143: 1635–1641. PubMed Abstract | Publisher Full Text\n\nStegen B, et al.: Contrast-enhanced, conebeam CT-based, fractionated radiotherapy and follow-up monitoring of orthotopic mouse glioblastoma: A proof-of-concept study. Radiat. Oncol. 2020; 15: 1–10.\n\nBertholet J, Knopf A, Mcclelland J, et al.: Real-time intrafraction motion monitoring in external beam radiotherapy. Phys. Med. Biol. 2019; 64: 15TR01. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBooth C, Tudor G, Tonge N, et al.: Evidence of delayed gastrointestinal syndrome in high-dose irradiated mice. Health Phys. 2012; 103: 400–410. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTaniguchi CM, et al.: PHD inhibition mitigates and protects against radiation-induced gastrointestinal toxicity via HIF2. Sci. Transl. Med. 2014; 6: 236ra64.\n\nVerginadis II, et al.: A Novel Mouse Model to Study Image-Guided, Radiation-Induced Intestinal Injury and Preclinical Screening of Radioprotectors. Cancer Res. 2017; 77: 908–917. PubMed Abstract | Publisher Full Text\n\nHackam DG, Redelmeier DA: Translation of research evidence from animals to humans. JAMA. 2006; 296: 1727–1732. Publisher Full Text\n\nFreedman LP, Cockburn IM, Simcoe TS: The Economics of Reproducibility in Preclinical Research. PLoS Biol. 2015; 13: e1002165. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchneider S, et al.: Detectability and structural stability of a liquid fiducial marker in fresh ex vivo pancreas tumour resection specimens on CT and 3T MRI. Strahlenther. Onkol. 2019; 195: 756–763. PubMed Abstract | Publisher Full Text\n\nBrown K: Preclinical CBCT scans. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "215290",
"date": "09 Nov 2023",
"name": "Emma Biglin",
"expertise": [
"Reviewer Expertise Radiobiology",
"preclinical dosimetry"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe study by Brown et al. provides detailed guidelines for the use of the liquid fiducial marker (FM) BioXmark to help identify areas of interest within a cone-beam CT scan, with the overall aim of improving the targeting of radiation. To demonstrate the use of BioXmark, the authors tested the FM at four different injection sites. Capsules of BioXmark were easily identifiable at all injection sites, even in high density areas, however in the intraperitoneal site the FM broke down and migrated around the structure. BioXmark allows the identification of tumour sites for improved RT targeting, without impacting the image quality or inducing toxic side effects as seen with other FMs.\nImproved RT targeting will refine preclinical research by minimising potential toxicity to normal tissue and associated short- and long-term side effects. Increasing confidence in the dose delivered to the target also has the potential to reduce the numbers of animals required.\nThe article is well written and provides an easily reproducible protocol to allow this technique to be adopted into routine protocol at other institutions. Use of this technique has a huge impact on preclinical RT research to both improve the reliability of results and animal welfare. I have a few minor comments that may improve the manuscript.\nIntroduction\nThe authors include a good introduction of the use of FMs, with the limitations of using solid FMs and how liquid FMs are more suitable in the RT context. Are there any limitations to using liquid FMs?\nMethods\nTable 1 is a good summary of the current uses of BioXmark but it is quite difficult to distinguish the subheadings within the table as they blend in with the other rows.\n\nParagraph 2 line 1 – can the authors describe why it is not recommended to inject BioXmark into necrotic tissue, highly vascularised tissue or air cavities and is there a way to avoid this?\n\nIn accordance with the ARRIVE guidelines can you include:\ni) The total number of mice used for the study – how many of these were from other studies? ii) How were the sample sizes calculated? iii)Were there any animals/data points not included in the analysis?\n\nThe authors describe the optimal volume to be 10-20ul, was there a particular reason why 10ul wasn’t used for the intraperitoneal site and 40ul was used for the subcutaneous and intraperitoneal sites?\n\nCan the authors include the suppliers of all consumables: needles, cell culture reagents etc?\n\nWhat radiobiological effects were assessed in the intra-tumoral group?\n\nFor the fractionated group, could you please clarify if these were on consecutive days?\n\n“Injection of BioXmark protocol” – Is this for the subcutaneous and intraperitoneal injection sites?\n\nPreclinical imaging – what software was used to define the material properties? Have you used the right reference here?\nResults\nFigure 3B – can you clarify that the different doses in the figure are accumulations of the individual fractions.\n\nI would suggest adding details of the volume contouring to figure captions 2 and 4, to be consistent with figure captions 1 and 3.\n\nCan the last two sentences of the final paragraph be combined as there is slight repetition? Would it sound better as “normal tissue sparing of the prostate” as it currently may sound like you are looking to target the prostate with radiation rather than identify it to make sure it is out of the radiation field?\nDiscussion\nParagraph 2, sentence 3 – to avoid confusion would it be better to say “movement or loss of a marker can lead to inaccurate targeting” rather than dose deposition as this reads like the FM deposits the dose.\n\nAre the 3Rs implications of the work described accurately? Yes\n\nAre a suitable application and appropriate end-users identified? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "215285",
"date": "10 May 2024",
"name": "Jane Sosabowski",
"expertise": [
"Reviewer Expertise Preclinical radiotherapy",
"preclinical imaging"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTitle: The title of this manuscript summarises the content well: Mainly, the paper concerns development of injection protocols for a liquid fiducial marker (BioXmark) that can be used preclinically during CT imaging and radiotherapy. Abstract:. please correct:..... to ensure accuracy of beam targeting. (new sentence) This approach ..... Introduction: The Introduction does a good job of setting the scene for this study, outlining use in relation to clinical applications, describing the problems inherent in using solid FMs preclinically, and relating the study to improvements in animal welfare. However, in places, particularly paragraph 3, it is difficult to read, due to sub-optimal grammar or punctuation. This would be improved by re-reading and restructuring some of the longer sentences. Methods: In general, the detail in the Methods section is excellent. The only issue is in the section on intra-tumoral injection, which states: ‘This protocol was used to determine the radiobiological effect of BioXmark® on tumour response, cytotoxicity and dose perturbation (35). Reference 35 (Brown et al 2020), is frequently referred to throughout the text, but relates to a different tumour cell line, Lewis Lung, rather than the MC38 cell line described here. To me, there is insufficient data on how these two studies are related. It would be helpful to add a bit more information and clarification on the two studies, if appropriate, to assist the reader.\n\nPreclinical imaging method section: \"An imaging energy of 60 kV was used\" - keV is not a unit of energy Results: The Results presented are quite straightforward; firstly a characterization of BioXmark injection at subcutaneous (n=3), intra-peritoneal (n=2)and intra-prostate (n=2) sites; with methodological recommendations proposed for each location. The main contents of the Results show the appearance of the marker in whole mouse CT scans and a contour-derived representation of BioXmark distribution from within each tissue (Figures 1, 2 and 4). These sections provide useful information for other users, but did feel a bit limited. I would prefer that there was a summary of the effects of BioXmark on dose calculation at these locations, and if possible some information on the effect on measured radiation dose, or a reference to these, if indicated in an additional publication. It would be helpful to have confirmation that the Muriplan software can calculate accurate doses in regions containing the BioXmark, and that if this is an issue, how best it could be mitigated. However, this notwithstanding, the study provides a lot of detail on injection protocols that will be useful for researchers looking to use Bioxmark as an FM in pre-clinical irradiations. It is also informative as it shows the relative utility of BioXmark for injection at different sites. The remaining Results section, referring to Figure 3, details intra-tumoral injection (n=42) to demonstrate ‘the feasibility of injecting BioXmark® into dense tissue.’ and shows CT scans from one mouse and a representation of BioXmark distribution over the course of a 4x 4 Gy irradiation schedule, to highlight the minimal changes to BioXmark following irradiation. For this section, the timescale over which the 4x4 Gy fractions were delivered should be added. Also, there is a statement that ‘no radiobiological effects of the BioXmark were determined, further detailed in reference 35.’ However, reference 35 presents very limited detail on radiobiological effect, only dose calculation discrepancies and the impact that these may have on tumour growth following treatment. Therefore it might be best to restate in this current paper, the potential impact on dose calculation of BioXmark in the target volume. If there are any biological markers of radiation effect that have been analysed, in the presence/absence of BioXmark, following treatment, it would be good to mention that here. If there is n=42 data, these should be presented.\nDiscussion and Conclusion: These were very clear and concise Additional issues The text is a bit repetitive in places, also one section occurs twice, headed: ‘Intra-tumoral injection of BioXmark’ , and the first two sentences starting: ‘A previous study trialled mixing BioXmark® with tumour cells prior to implant for targeting…’ Therefore, one of the sections should be deleted. Statistical analysis is not particularly necessary but is provided to show the difference in CBCT values for radiodensity between the BioXmark and other tissues on the CT scan. In my opinion, it is not necessary to give exact p-values to multiple decimal places for these p-values, as large numbers of decimal places are harder to read. The test used to generate the p-values should be indicated. Please adjust this if possible.\n\nAre the 3Rs implications of the work described accurately? Yes\n\nAre a suitable application and appropriate end-users identified? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "274478",
"date": "23 May 2024",
"name": "Katrina Stevenson",
"expertise": [
"Reviewer Expertise Preclinical radiation studies/preclinical cancer models"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this paper the researchers aim to demonstrate the versatility and ease of use of BioXmark® in preclinical applications.\nThis study provides a good comprehensive technical overview of how BioXmark® works and how to use it into your pre-clinical imaging studies. The details of the protocols used would allow the FM to be easily incorporated into the practice in other establishments.\nThis research shows that BioXmark® would be useful in preclinical imaging to delineate the area of tumour which would improve the accuracy of dosing mice with radiation in small animal radiation systems therefore reducing normal tissue irradiation toxicity. This aligns with the use of fiducial markers in clinical practice further validating the use in preclinical imaging and radiation.\nThe study highlights the impact that using BioXmark® could make on the number of mice used in imaging and radiations studies – cutting down required amount as you are more assured of the accuracy and eliminating poorly targeted tumours. Thus, making the method interesting in terms of the NC3Rs framework.\nMethods set out how the study used BioXmark® in all injection methodologies discussed – intra-tumoral, intraperitoneal, subcutaneous and orthotopic. Detailed instruction on handling and injecting the reagents are given. Numbers of mice used is given - some experimental numbers used are low but as this is a proof of principle, technical study, are adequate. Both males and females were used, and no toxicity was seen.\nResults give a good indication of how the FM would look in preclinical models with examples for each methodology – ruling out the use of intraperitoneal injection due to the disruption in stability of BioXmark®. They have also shown the volumes of the FM using the CERR software and this shows a 3-D visualisation of the FM. Placement of the BioXmark® in the orthotopic prostate model proved the most technically challenging but would give good accuracy in dosing the prostate – helping to prove clinical relevance of using this FM in preclinical studies. Long term stability of BioXmark® has been previously discussed in Brown et. al., reference 35.\nDiscussion clearly describes how this study has shown the benefits of using this liquid FM in preclinical studies as an aide to increasing targeting accuracy.\nAn interesting area of study not covered in this research would be to look at how the BioXmark® interferes with the dose given to the to the tissue – if there was a differential in dose calculated by the preclinical imaging and radiation software – this had been touched on a little in the referenced previous study by Brown et. al., reference 35.\nIt would have been good to have details of the scheduling of the fractionated doses of radiation in the methods/results sections. Methods/protocols sections - the text is quite repetitive.\n\nAre the 3Rs implications of the work described accurately? Yes\n\nAre a suitable application and appropriate end-users identified? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-526
|
https://f1000research.com/articles/11-272/v1
|
03 Mar 22
|
{
"type": "Research Article",
"title": "Harmonisation of welfare indicators for macaques and marmosets used or bred for research",
"authors": [
"Mark J. Prescott",
"Matthew C. Leach",
"Melissa A. Truelove",
"Matthew C. Leach",
"Melissa A. Truelove"
],
"abstract": "Background: Accurate assessment of the welfare of non-human primates (NHPs) used and bred for scientific purposes is essential for effective implementation of obligations to optimise their well-being, for validation of refinement techniques and novel welfare indicators, and for ensuring the highest quality data is obtained from these animals. Despite the importance of welfare assessment in NHP research, there is little consensus on what should be measured. Greater harmonisation of welfare indicators between facilities would enable greater collaboration and data sharing to address welfare-related questions in the management and use of NHPs. Methods: A Delphi consultation was used to survey attendees of the 2019 NC3Rs Primate Welfare Meeting (73 respondents) to build consensus on which welfare indicators for macaques and marmosets are reliable, valid, and practicable, and how these can be measured. Results: Self-harm behaviour, social enrichment, cage dimensions, body weight, a health monitoring programme, appetite, staff training, and positive reinforcement training were considered valid, reliable, and practicable indicators for macaques (≥70% consensus) within a hypothetical scenario context involving 500 animals. Indicators ranked important for assessing marmoset welfare were body weight, NHP induced and environmentally induced injuries, cage furniture, huddled posture, mortality, blood in excreta, and physical enrichment. Participants working with macaques in infectious disease and breeding identified a greater range of indicators as valid and reliable than did those working in neuroscience and toxicology, where animal-based indicators were considered the most important. The findings for macaques were compared with a previous Delphi consultation, and the expert-defined consensus from the two surveys used to develop a prototype protocol for assessing macaque welfare in research settings. Conclusions: Together the Delphi results and proto-protocol enable those working with research NHPs to more effectively assess the welfare of the animals in their care and to collaborate to advance refinement of NHP management and use.",
"keywords": [
"behaviour",
"Callithrix",
"Macaca",
"non-human primate",
"refinement",
"welfare assessment",
"well-being",
"3Rs"
],
"content": "\n\n\n\nScientific benefit(s)\n\n• Harmonises welfare indicators for macaques, enabling inter-lab comparative studies and also greater data sharing to boost sample sizes for welfare-focused research.\n\n• Ranks welfare indicators and narrows the field for further investigation of those considered most important by experts.\n\n3Rs benefit(s)\n\n• Identifies context appropriate welfare indicators, that are valid, reliable and practicable, allowing better assessment of welfare, minimisation of harm and evaluation of the impact of refinement techniques.\n\n• Potentially benefits the welfare of an estimated 100,000 non-human primates (NHPs) used globally per year in biomedical research.\n\nPractical benefit(s)\n\n• Presents a practical and generalised welfare assessment protocol to support laboratory staff in assessing, monitoring and maximising the health and wellbeing of macaques.\n\nCurrent applications\n\n• Welfare assessment of macaques bred for and used in research, including in toxicology, neuroscience, infectious disease and other disciplines.\n\nPotential applications\n\n• Welfare assessment of marmosets and other NHP species.\n\n• Benchmarking of welfare standards/quality of life between facilities.\n\n\nIntroduction\n\nGlobally, an estimated 100,000 non-human primates (NHPs) are used annually in biomedical research and testing, with a far larger number housed in breeding facilities (Carlsson et al., 2004; Lankau et al., 2014; Zhang et al., 2014; Vermeire et al., 2017; Grimm, 2018). Accurate assessment of the welfare of these animals is essential for fulfilling ethical and legal obligations to minimise any harm caused by scientific or veterinary procedures, and for the effective implementation of refinement techniques such as analgesia and humane endpoints (Rennie & Buchanan-Smith, 2006; Jennings & Prescott, 2009; Hawkins et al., 2011; Descovich et al., 2019). It is also important for evaluating enhancements to animal management aimed at promoting positive welfare states and good psychological well-being, such as environmental enrichment and training for cooperation with husbandry (Chamove, 1989; Segal, 1989; Bassett et al., 2003; Lutz & Novak, 2005; Buchanan-Smith et al., 2005; Buchanan-Smith, 2010a; Coleman & Maier, 2010; Coleman & Novak, 2017). In some countries, there is a requirement for in vivo researchers to report to regulators the ‘actual severity’ experienced by the animals used in their experiments (European Union, 2010; Home Office, 2014; USDA APHIS, 2018), which is predicated on the ability to recognise and accurately measure pain and distress. Welfare assessment is also a component of the scientific method, because physiological and psychological responses to suffering can significantly affect data quality (Poole, 1997; Institute for Laboratory Animal Research, 2008). Minimising avoidable suffering is therefore necessary to ensure the validity of the scientific research performed (Novak & Petto, 1991; Graham & Prescott, 2015; Hannibal et al., 2017; Prescott et al., 2021).\n\nMost NHP facilities have dedicated and highly trained animal care staff who go to great efforts to optimise the well-being of the NHPs in their care (Coleman, 2011), and effective welfare assessment tools will enable them to better accomplish this. It is recognised that welfare assessment should encompass both physical health and psychological well-being (National Research Council, 1998; Wolfensohn & Honess, 2005; Jennings & Prescott, 2009). However, working evaluations of laboratory NHP welfare are often based on measurements of various indicators presumed to be related to the extent of failure to cope, or difficulty in coping, with the environment (Lutz et al., 1991; European Commission, 2002). Modern welfare assessments should also aim to evaluate positive as well as negative states of individuals (Hawkins et al. 2011; Wolfensohn et al., 2018). Social play, allogrooming, food sharing, exploration, and relaxed gait have been suggested as behavioural indicators of positive NHP welfare in the laboratory, though relatively few have been validated (University of Stirling, 2011; Blois-Heulin et al., 2015; NC3Rs, 2015; Ahloy-Dallaire et al., 2018; Miller et al., 2020).\n\nMost facilities that house or breed NHPs for research (i.e. laboratories, breeding centres, etc.) utilise a combination of animal-based indices, as this gives the best estimate of an individual NHP’s welfare state (Novak & Suomi, 1988; National Research Council, 1998; Jennings & Prescott, 2009). These include physical or somatic observations (e.g. susceptibility to disease; growth rate; coat and body condition), physiological measurements (e.g. heart rate; body temperature; plasma cortisol), and structured behavioural assessments (e.g. behavioural repertoire; activity budgets; presence of quantitative or qualitative behavioural abnormalities) (Poole, 1988; European Commission, 2002; Wolfensohn & Honess, 2005; Gottlieb & Pomerantz, 2021; Novak & Meyer, 2021). Some animal-based indices used in practice, such as stereotyped behaviour (e.g. pacing), have been criticised for their lack of validity or validation (Poirier & Bateson, 2017; Polanco et al., 2021) and specificity (Descovich et al., 2019). Regardless, animal-based indices can be used to assess the outcome of providing resources for animal care, such as cage space and a varied diet.\n\nA variety of resource-based indicators, which are variables measured not in the animals but in the environment, are also used to assess welfare (e.g. size and design of enclosures; provision of environmental enrichment; health monitoring programmes). These input-based, engineering criteria are attractive because they are objective, less time intensive, and easy to measure (e.g. during site inspection) (Johnsen et al., 2001; Mench 2003); however, they are often indirect measures of welfare and can be experienced differently by individuals (e.g. Izzo et al., 2011; Velarde & Dalmau, 2012). Used alone, they do not effectively evaluate the welfare state of individual animals; but used alongside animal-based outcome indices, resource-based input indices can usefully contribute to welfare assessments, and are important for standardising within and between facilities, especially if founded on validated welfare needs (Beaver & Bayne, 2014; Bennett et al., 2018) (Figure 1).\n\nDespite the importance of welfare assessment in NHP research, there are few established welfare assessment tools, and little is known about the level of consensus within the research community on whether the available indices are considered valid (i.e. genuinely measuring an aspect of an animal's welfare state), reliable (i.e. can be measured consistently across and between users), and practicable (i.e. can be measured with limited time, resources, and within facility constraints). Truelove et al. (2020) conducted a Delphi consultation to identify laboratory macaque welfare measures and their relative importance. A list of 115 potential indicators for use in welfare assessment of macaques (54 animal-based and 61 environment-based items) was provided to a panel of macaque experts, predominantly from North America. Experts indicated which indicators were valid, reliable, and practicable to measure using the provided on-site scenario (Table 1a) and a composite percentage agreement score was assigned to each indicator, allowing subsequent ranking. Among the 39 experts who completed the two rounds of the survey, resource/environment-based measures were considered better suited than animal-based ones for on-site welfare assessment, with the presence of self-harm behaviours and provision of social enrichment considered the most important indicators for assessing macaque welfare; a total of 56 indicators were selected as being valid, reliable, and practicable. The ten indicators with the highest composite respondent percentage agreement score following two rounds of ratings included only one animal-based indicator (self-harm behaviour). These 56 indicators were presented as part of the current study, in part to gauge validity of the measures found in Truelove et al. (2020), as well as to uncover any indices that a different group of experts might accept or reject as useful in assessing macaque welfare.\n\nIf there was a broader consensus on appropriate indicators of suffering and well-being in NHPs used for research, and widely applicable welfare assessment tools, then this would help researchers, veterinarians, and other animal care staff better fulfil their obligations to optimise the welfare of the animals in their care. Importantly, it could also facilitate greater collaboration and data sharing between research facilities to address welfare-related research questions, such as the impact of common procedures and putative refinements. Not only would this boost sample sizes for welfare-focused studies, especially those which must piggy-back onto ongoing scientific procedures conducted primarily for another research purpose, but it would also enable inter-laboratory comparative studies to identify how variation in management practices influence animal welfare (Bliss-Moreau et al., 2021); doing so across an international audience might also identify practices diverging due to differences in culture and research specific to a region (e.g. McMillan et al., 2017; Baker & Prescott, unpublished work). In 2017, the United Kingdom’s national 3Rs centre (NC3Rs) led an international data crowdsourcing project to establish the prevalence and potential triggers for aggression-related injury in group-housed male laboratory mice (Lidster et al., 2019) – a significant problem affecting the murine research community. In total, 143 animal technicians from 44 facilities collected aggression and husbandry data on over 137,000 mice using a common data collection framework. By comparing the prevalence of aggression and husbandry variables between facilities, the key factors that influence levels of aggression in male mice were identified, leading to recommendations for practical changes to husbandry to minimise aggressive behaviour and improve mouse welfare. This work illustrates the potential for welfare improvements when tapping into the expertise of a large group, regardless of the approach taken (e.g. crowdsourcing, Delphi).\n\nTo achieve broad consensus for NHP welfare indicators, and to develop a practical protocol for assessing macaque welfare, advantage was taken of the assembly of a group of NHP experts at the 2019 NC3Rs Primate Welfare Meeting. This international event supports laboratory and breeding centre staff working directly with NHPs to develop, share, and implement evidence-based refinements in NHP use and care. At the 2019 meeting, a hybridised Delphi consultation was undertaken to help harmonise NHP welfare assessment by gaining agreement amongst the experts on a list of welfare indices for macaque and marmosets that are valid, reliable, and practicable. Additionally, participants were surveyed about the methods used to measure each of these indices.\n\nA classical Delphi consultation is an iterative, multi-stage survey technique that involves controlled feedback to a panel of anonymous subject experts; the consultation results in statistical group consensus on a selected topic as indicated by response stability between rounds (Van Zolingen & Klaassen, 2003). This is in contrast to the group Delphi/expert workshop approach, in which a panel of experts work together, rather than independently, on a topic to arrive at consensus (Webler et al., 1991) – all other elements are identical. We integrated both approaches for this study, using a classical Delphi in one round and a group Delphi in another round. Achieving consensus between experts increases the validity of the welfare assessment protocol and ensures that it incorporates a wide range of expert opinions, so that it is not perceived as an imposition from a single group of people (Boulkedid et al., 2011).\n\n\nMethods\n\nOnline survey software from Qualtrics was used to survey the delegates of the NC3Rs Primate Welfare Meeting (8 November 2019, London) about their views on welfare indices for macaques and marmosets, as part of a hybridised Delphi consultation process. The inclusion criteria were being a delegate of the meeting and being directly involved in the care, use or breeding of NHPs for research, which all participants met. The survey was constructed and administered by the authors. Participation was voluntary and responses were submitted using personal mobile devices. The link to the survey was emailed on the day of the meeting and also displayed at the event. Participants completed a consent statement online at the start of the survey. Additionally, if any participant wished to withdraw consent at any time, they were asked to contact the NC3Rs team who would then remove the data they had supplied. All delegates provided consent and no delegates subsequently retracted consent. Quasi-anonymity was maintained: responses remained unknown to other participants but were known to the authors and response data were coded by username after receipt so that individuals’ responses could not be readily linked. Data collection procedures were approved by the Ethics Committee of the Faculty of Science, Agriculture and Engineering at Newcastle University. All data were managed according to a data management plan for NC3Rs office-led data sharing projects.\n\nParticipants were researchers, veterinarians, and animal technologists working directly with NHPs in nine countries (United Kingdom [UK], France, Germany, Hungary, Italy, Netherlands, Sweden, Switzerland, and the United States of America [USA]), with three-quarters based within the UK. Respondents were asked to identify their species of focus (macaque or marmoset) and area of specialty (neuroscience, infectious disease, toxicology, breeding, or other). In this way, we were able to actively control for species as a potential source of bias in the study. The survey method (hybridized Delphi) also addressed two potential biases (dominance effect and Von Restorff effect) through the use of multiple rounds and anonymity (Hallowell, 2009).\n\nMultiple steps were required to complete the hybridised Delphi consultation process (Figure 2). First, participants were presented with the scenario in Table 1a. They were then presented with the top ten welfare indices identified as valid, reliable, and practicable (≥70% consensus) for assessing macaque welfare in the Delphi consultation of Truelove et al., 2020 (Table 1b) and asked:\n\nQ1 “Which of the following indices do you think are the most valid and reliable for assessing NHP welfare? (select as many indices as you feel are appropriate)”\n\nQ2 “How practical are the indices you selected for assessing NHP welfare from the top ten?” (with the options: “Very impractical; Impractical; Neither; Practical; Very practical”)\n\nNext, the participants were presented with a more extensive list of 56 welfare indices from the aforementioned Delphi consultation and asked:\n\nQ3 “Of the 56 indices, which do you think are the most valid and reliable for assessing NHP welfare? (select as many indices as you feel are appropriate)”\n\nQ4 “How practical are the indices you selected for assessing NHP welfare from the 56 indices?” (with the options: “Very impractical; Impractical; Neither; Practical; Very practical”)\n\nFinally, participants had the opportunity to suggest additional indices that they considered to be valid, reliable, and practicable for assessing welfare (Q5; free text responses; 5% threshold).\n\nIn a second round of the consultation, the participants were split into pre-assigned groups according to the scientific disciplines they worked in and whether their work involved marmosets or macaques. Working as a group and bearing in mind the same scenario (Table 1a), participants were provided feedback from the first round as to which welfare indicators were considered valid and reliable, and which were considered practicable. They were asked to discuss and then define how they would measure each of the indices identified as being valid, reliable, and practicable in round 1 (i.e. at or exceeding 70% consensus, as per Truelove et al., 2020 and Leach et al., 2008). Specifically, they were asked to consider the following and then respond as a group:\n\nQ6 “Are you recording this measure at an individual, group/cage, room or unit level?” (with the option: “Other [please specify]”)\n\nQ7 “How would you record this measure? i.e. what method and equipment (if any) would you use?” (free text responses)\n\nQ8 “How long would you spend recording this measure? i.e. would you measure this intermittently, and how frequently or constantly and over what period of time etc.?” (free text responses)\n\nQ9 “What proportion of animals/groups/rooms/units would you assess in order to get a meaningful assessment?” (selected choice in 10% intervals from <10% to 100%; with the option: “Other [please specify]”)\n\nThe top ranked welfare indicators for macaques identified during the two Delphi consultations and the information obtained regarding their measurement was then used, along with the expertise of the authors, to construct a prototype protocol for assessing macaque welfare in research settings.\n\nMany Delphi studies have used percentage measures as their primary indication of consensus, despite disagreement as to whether this is adequate (Hsu & Sanford, 2007). We set an a priori agreement level of 70% or greater for consensus, as has been done in other animal welfare and healthcare studies (e.g. Leach et al., 2008; Keeney et al., 2011).\n\nDescriptive statistics were used to summarize the participants’ responses per round. For all completed surveys, there were no missing data. For those surveys started but without any collected data (i.e., no answers provided but an identifier was issued), these were removed so as to not inflate the number of participants. Data were imported into Microsoft Excel for Microsoft 365 (2021) and summarised for analysis; participant identifiers were removed to maintain anonymity. Free text comments were analysed qualitatively and were grouped by similar idea by one coder (MAT).\n\nTo complete the Delphi process, group stability (i.e. consistency of response between rounds) must be demonstrated (von der Gracht, 2012); this was achieved by Krippendorff’s alpha coefficient (α) test (Hayes & Krippendorff, 2007 ). For interpretation, a value of 0 indicates perfect disagreement whereas 1 indicates perfect agreement; a value of 0.667 or more permits (tentative) conclusions to be made (Krippendorff, 2004).\n\n\nGeneralised macaque welfare assessment protocol (GEN-MAC)\n\nOur generalised macaque welfare assessment protocol aims to offer a practical and context appropriate tool for laboratory staff caring for macaques (Table 2). It provides a quantitative set of criteria to support staff in monitoring and maximising macaque health and well-being, based on expert consensus. The tool encompasses all four domains of potential welfare compromise (i.e. nutritional, environmental, health, behavioural) identified by the Welfare Quality® project (Blokhuis et al., 2013) and Mellor et al. (2009). Taken together, the chosen indicators should provide an assessment of an individual animal’s welfare, and hence, when repeatedly measured over time, provide an assessment of its quality of life (Fraser, 2008). We acknowledge that good animal welfare is more than the mere absence of negative experiences and recognise that the tool incorporates few indicators of positive welfare state currently; however, validation of these is proving difficult (e.g. see Ahloy-Dallaire et al., 2018 for a discussion of the relationship between play and positive affective states). As new indices of positive state are validated, they can be incorporated into this tool.\n\n\n\na. A specialist in behaviour modification was involved in development of the training programme\n\nb. One person has overall responsibility for the training programme (training coordinator) to ensure a consistent approach\n\nc. Animals are trained by dedicated staff members, who possess a high degree of training knowledge and competence\n\nd. Training procedures are documented in SOPs/protocols\n\ne. Methods are predominantly based on PRT; where negative reinforcement is used, it is in combination with PRT and only where PRT alone has failed\n\nf. The training programme allows sufficient time for progressive habituation to conditions, techniques, and procedures before data collection begins\n\ng. Records of individual training performance are kept and regularly reviewed; training is tailored to individual differences in learning\n\n\n\na. Incorporates enrichment interventions that satisfy a range of needs in the social, locomotory, sensory, cognitive, and food-based domains\n\nb. Offers novelty (objects, space, activities) to stimulate and provide new challenges\n\nc. Provides animals with a degree of choice and control in their environment\n\nd. Incorporates regular monitoring for behavioural signs of distress, including prolonged withdrawal or hunched posture, prolonged expression of stereotypies, or excessive fearful behaviours\n\ne. Overseen by a dedicated individual with behavioural science or veterinary expertise\n\nf. Behavioural management strategies/procedures are documented in SOPs/protocols\n\ng. Behavioural management forms part of research protocol review\n\n\n\na. Accurate and clearly defined humane endpoints are established prior to study initiation\n\nb. Animals are monitored at an appropriate time and frequency to enable the earliest possible euthanasia decision and avoid moribundity/spontaneous death\n\nc. Humane endpoints are regularly reviewed and refined over time, as new data becomes available from studies using the model\n\nd. All personnel performing endpoint criteria assessments are able to recognise the signs of ill health\n\ne. Structured welfare assessment/humane endpoint score sheets are available and included in SOPs\n\nf. Where applicable, technologies such as telemetry, actimetry, imaging, and CCTV are used to inform endpoints decisions\n\nThis tool is not intended to replace welfare assessment protocols tailored to specific scientific disciplines, projects, procedures, and adverse effects. Rather it presents an appropriate number of valid, reliable, and practicable indicators for a generalised assessment of “wellness” that can inform and augment existing specific tools. This generalised tool is particularly suited for high level assessments of the outcome/quality of institutional behavioural management programmes and comparisons between laboratories. Where appropriate, facilities working in specific disciplines may wish to supplement this core set of indicators with additional ones listed in Figure 4 or the literature (e.g. Smith et al., 2006; Wolfensohn & Honess, 2005; Honess & Wolfensohn, 2010; Kirchner & Bakker, 2015; Descovich et al., 2019 for neurophysiology). Where physiological measurements are required, the least invasive and most refined method that will provide the necessary data should be used (e.g. Davenport et al., 2006; Rennie & Buchanan-Smith, 2006; Smiley Evans et al., 2015). Awareness of the context for the assessment is important; for example, food intake can be reduced following administration of anaesthetic and analgesic medication, as well as due to pain or illness.\n\nLike other welfare assessment tools, this one combines animal-based measures of welfare with indirect resource- and staff-based ones, which are more amenable for assessing the welfare of large numbers or groups of animals when under time constraints. There is evidence that the resource- and staff-based measures included are closely associated with outcomes indicative of good animal welfare in macaques, even if they do not guarantee that any one animal is experiencing a good quality of life (Jennings & Prescott, 2009; Schapiro et al., 2014). For example, it can be time consuming to measure affiliative social interactions, but an acceptable alternative is to check the macaques are at least socially housed with the opportunity for normal social behaviour and there is no evidence of NHP induced injury. Our approach to scoring of staff-based indicators allows a degree of flexibility and rewards programmes which incorporate elements of good practice, though users can choose to focus on the other indicator types if they wish. Most of the animal-based indicators can be directly and objectively measured after only a short-period of staff training, and they do not overly disturb the animal. The information can be gathered during site inspections, daily observations, physical exams, and other activities, such as handling for scheduled scientific procedures. Where there is the option to conduct more detailed, extended behavioural observations (e.g. analysis of closed-circuit television [CCTV] recordings), we would encourage this as it will provide greater insight into an animal’s welfare state, especially if compared against a baseline measurement of normal behaviour for individual animals during their active phase and prior to any study (Council on Animal Care, 2019). A pilot study is underway to assess the time commitment required for completion of assessments using the tool, for a variety of group and colony sizes. It is possible that emerging approaches for automated recording and analysis of NHP behaviour will help to reduce the time required in the future (Rushen et al., 2012; Witham, 2018; Bain et al., 2021).\n\nThe multi-dimensional assessment should be performed by experienced staff, ideally with a knowledge of the individual animals, so that changes in welfare status can be more readily identified. The indicators included in the protocol do not require veterinary diagnostic expertise or specialist animal behaviour knowledge to be accurately recorded, but the involvement of such experts in implementing the welfare assessment tool is encouraged, particularly in the interpretation of the findings of assessments using this tool. A team approach, with good communication among those involved and periodic testing of inter-observer reliability, will help to ensure reliable assessments and consistent use of the tool (Clingerman & Summers, 2012; Lambeth et al., 2013). Individual animal records can be combined to give an overview of the colony, which can be reviewed periodically or compared with data from other colonies. If the tool is used as part of daily health checks, then scores can be compared over time and a greater severity score assigned where there is repeated evidence of impaired welfare.\n\nTo facilitate use of the GEN-MAC protocol in practice, an Excel version is available to download. The file incorporates the formulae for calculating the welfare scores. We encourage users of the protocol to provide us with feedback, so that the tool can be enhanced; please email mark.prescott@nc3rs.org.uk. When reporting use or adaptation of GEN-MAC in the literature, please use the following citation:\n\nGeneralised macaque welfare assessment protocol (GEN-MAC) https://doi.org/10.25405/data.ncl.19106960. From: Prescott MJ, Leach MC, Truelove MA. Harmonisation of welfare indicators for macaques and marmosets used or bred for research. F1000Research 2022: X-X (https://doi.org/10.12688/f1000research.109380.1).\n\n\nResults\n\nA total of 73 participants took part in this survey (Leach et al., 2022). Of these 73 respondents, 67 (92%) worked with macaque species (rhesus macaques, Macaca mulatta, and cynomolgus/long-tailed/crab-eating macaques, M. fascicularis): 34 (47%) in neuroscience, 12 (16%) in breeding, nine (12%) in toxicology, four (5%) in infectious disease research, and eight (11%) in other disciplines. Six respondents (8%) worked with common marmosets, Callithrix jacchus: four in infectious research, one in neuroscience, and one in breeding.\n\nRound 1, Phase 1 – rating of top ten indices\n\nPercentage scores for validity and reliability, and practicability, of the top ten macaque welfare indicators in the Truelove et al. (2020) Delphi were compared with the scores for the same indices in the current Delphi (Figure 3). Considering respondents working with macaques only, there was agreement between the two consultations that presence of self-harm behaviour, provision of social, food, and physical enrichment, and health and behaviour monitoring are valid, reliable, and practicable welfare indicators for NHPs (>70% consensus). However, whilst included in the top ten indicators in Truelove et al. (2020), cage furniture, humane euthanasia, hear other NHPs, and room ventilation failed to reach the consensus criterion in the current survey.\n\nRound 1, Phase 2 – rating of 56 indices\n\nThe percentage agreement scores for the more extensive list of macaque welfare indicators presented in Round 1, Phase 2 are given in Table 3. For Table 3 (macaques) and Table 5 (marmosets), “Practical” reflects two practicability categories that have been collapsed (practical + very practical). Those indices reaching less than 70% agreement for practicability have been shaded grey. The 56 indices have also been categorised into the following symbol-coded indicator types:\n\n▪ Animal-based: behavioural#, physiological/physical##\n\n▪ Environment-based: micro^ (i.e. cage), macro^^ (i.e. ambient)\n\n▪ Staff-based: procedural and development+, husbandry++\n\n* Fewer respondents replied to Q4.\n\nAcross the 56 welfare indicators presented to the macaque respondents (n=67), only eight (14.3%) met the a priori agreement level of ≥ 70% for validity and reliability; these were also considered practicable measures. Three were animal-based (self-harm behaviour, body weight, appetite), whilst the other five were environment- or staff-based (social enrichment, cage dimensions, health monitoring, staff training, positive reinforcement training). Three of these eight indices selected by respondents are in the top ten of Truelove et al. (2020) (self-harm behaviour, social enrichment, and health monitoring) (see Extended data, Supplementary Table 1 (Leach et al., 2022)). Consensus for three additional indictors was nearly reached, with agreement levels between 65-69.99%; one was animal-based (NHP induced injuries) and the remainder were staff- and environment-based (behavioural management programme, vertical space).\n\nItems were deemed more practicable to measure than they were valid and reliable, with 48 indicators (85.7%) meeting the threshold for consensus for practicability and two additional indicators approaching consensus (room cleaning frequency, frequency of moves during lifetime). Six indicators did not meet the consensus threshold for practicability when considering the hypothetical scenario; four of these were environment- or staff-based (field of view, intentional exposure to novelty, frequency of chair restraint, cage position) and two were animal-based (fear of other NHPs, environmentally induced injuries).\n\nRound 2 – measurement of selected welfare indicators\n\nRespondents working with macaques were classified into five categories: neuroscience (n=34), toxicology (n=9), infectious disease (n=4), breeding (n=12), and other (n=8). The ‘other’ category included the disciplines of reproduction, surgery, metabolic disease, and ethology. Figure 4 shows the indicators chosen as reliable and valid by two-thirds of macaque respondents (i.e. at or approaching consensus) by discipline and indicator type. Items approaching consensus (65-69.99%) are included in these results as some of the groups had small sample sizes and items would perhaps reach consensus with additional participants. Refer to Extended data Supplementary Table 2 for a complete list of the respondent agreement scores for validity and reliability of the indices by discipline category (Leach et al., 2022).\n\nMore of the 56 welfare indices were considered valid and reliable by at least two-thirds of respondents in the infectious disease category (33 indices) and breeding category (24 indices), than in the other three categories. Whilst the number of animal-focused indices is relatively similar across the main disciplines (6-8 indices), the infectious disease and breeding categories also include procedural and developmental indices, as well as more micro-environment level indicators. Self-harm behaviour is one of the top four indices in all discipline categories but toxicology, and body weight appears as one of the top four as well in all except breeding. Provision of social enrichment appears in each discipline except toxicology and other. Potential explanations for the variation between the disciplines are given in the Discussion section.\n\nDiscipline groups discussed and reported how they would measure the potential welfare indicators deemed valid, reliable, and practicable. The top ten indices from the current survey and how they might be measured are given in Table 4. For each indicator, participants recommended that each should be measured at 91-100% of the population being assessed, whether the unit of measurement be at the individual or the facility level, to get a meaningful assessment. All indicators except staff training could be measured at the individual level, and there was a mix of methods for recording the indices, with observation, records, or both being recommended.\n\nRound 1, Phase 1 – rating of top ten indices\n\nAs was the case for macaque respondents, when presented with the top ten indices from Truelove et al. (2020), most respondents working with marmosets considered social, physical, and food enrichment to be indices that can be used to assess welfare, along with self-harm behaviours and the presence of a health monitoring programme; cage dimensions was also considered important. Hearing other NHPs and ventilation were not rated highly (selected by only 50% of respondents) (Figure 5). A smaller proportion of respondents working with marmosets considered a behavioural management programme to be useful for assessing welfare (50%), than did those working with macaques (82.6%). Of these top ten indices, eight were considered practicable by all respondents, and all ten by at least two-thirds of respondents (potentially a consequence of the small sample size; n=6).\n\nRound 1, Phase 2 – rating of 56 indices\n\nOverall, 21 of the more extensive list of 56 indicators were considered valid and reliable measures for assessing marmoset welfare (Table 5); eight met consensus, while the other 13 approached consensus. Of these 21, nine are animal-based, with the remainder comprised of environment-based (9) or staff-based (3) indicators. Of the 56 indicators, 50 (89.3%) were rated as practicable by at least two-thirds of the respondents working with marmosets.\n\nThe few respondents working with marmosets were classified into three categories: infectious disease (n=4), neuroscience (1) and breeding (n=1). Indicators chosen as reliable and valid by at least two-thirds of these respondents are shown by discipline and indicator type in Figure 6. Items approaching consensus (65-69.99%) are included in these results as the groups had very small sample sizes and items would perhaps reach consensus with additional participants. More of the 56 welfare indices were considered valid and reliable by at least 70% of respondents in the infectious disease category (21 indices) and neuroscience category (16 indices), than in breeding (9). Seven indices were selected in all three disciplines (stereotypy, body weight, mortality, NHP induced injuries, cage furniture, animal care observations, and disease surveillance) and all 16 indices in the neuroscience category were also selected by the infectious disease group.\n\nRound 2 – measurement of selected welfare indicators\n\nThe marmoset experts also discussed and reported how they would measure the potential welfare indices deemed valid, reliable, and practicable. The top eight indices from the current survey and how they might be measured for this species are given in Table 6. For each indicator, participants recommended that each should be measured at 91-100% of the population being assessed, whether the unit of measurement be at the individual or the facility level, to get a meaningful assessment. All indicators could be measured at either the individual or cage level, as appropriate, with NHP induced injuries also being assessed at the room level. There was a mix of methods for recording these indices, with observation, records, or both being recommended.\n\nMacaque and marmoset respondents\n\nConsidering both macaque and marmoset respondents (N=73), the whole group’s level of disagreement about the validity and reliability of the top ten indicators identified in Truelove et al. (2020) was high in both phases (Phase 1, α=0.1993; Phase 2, α=0.0915); however, levels remained relatively consistent between phases (Δ 0.1078), indicating group stability. The movement that occurred between phases was in the direction of disagreement (signifying divergence). Likely, this was a result of the increased options provided to the respondents between phases (i.e., more potential indices in Phase 2) and not requiring ranking of the same ten items across each phase; respondent fatigue is also a possibility. When asked to indicate which of 56 potential macaque welfare indicators are valid and reliable (Q3) for assessing NHP welfare, those ten initially presented (Q1) shifted in importance as evidenced by the proportion of respondents who selected an item as important for assessing welfare (Table 7). Across the two phases, the respondents’ average inter-rater agreement was 78%; however, there were 12 respondents who had scores below 70%.\n\nAcross the two Delphi consultations, four indicators were identified as important for both marmosets and macaques: body weight, NHP induced injuries, physical enrichment, and cage furniture (Table 8).\n\n* Top eight are valid, reliable, and practicable; NHP induced injuries and behavioural management are valid and reliable.\n\n\nDiscussion\n\nThis study aimed to achieve consensus on effective indices of welfare for macaques and marmosets bred and used for research through expert consultation about the validity, reliability and practicability of a range of potential indicators. It builds upon the previous Delphi consultation of Truelove et al. (2020) by surveying a larger population of macaque experts working within a broader range of countries (predominantly within the EU) and collecting information on how top-ranking indices should be measured. The larger population also enabled us to explore differences between disciplines (though sample sizes were small for some discipline categories). By combining data from the two consultations, we were able to develop a generalised protocol for welfare assessment of macaque species.\n\nWe chose a Delphi process owing to the ability to survey a large number of experts anonymously and independently, without the opinions of any one respondent/group dominating the discussion, and to provide controlled feedback, helping to reduce noise and converge upon quality indicators. The systematic Delphi approach is more rigorous than other group consensus approaches, like case studies or focus groups (Boulkedid et al., 2011). However, it does have limitations which impact on our interpretation of the results (outlined below).\n\nConsidering first respondents working with common marmosets, of the 56 indicators presented in Round 1 Phase 2, only 37.5% (21/56) were considered valid and reliable for assessing marmoset welfare, and 89.3% (50/56) were rated as practicable by at least two-thirds of the respondents. This is not surprising given these indicators were those furnished from the macaque literature and experts in Truelove et al. (2020). Of the six indicators rated as not practicable, five were staff-based and one was a micro-environment indicator. Of note in terms of species differences is the observation that ambient environment indicators such as humidity, room temperature, room ventilation, and light intensity were considered valid and reliable by two-thirds of marmoset respondents but not so of macaque respondents, probably reflecting the physical needs of these tropical New World monkeys, which are different to those of macaques and temperate living humans (Buchanan-Smith, 2010b).\n\nIndicators ranked important for assessing the welfare of common marmosets were body weight, NHP and environmentally induced injuries, cage furniture, huddled posture, mortality, blood in excreta, and physical enrichment. These findings should be viewed as preliminary given only six of our 73 respondents (8%) worked with this species and the indices were from Truelove et al. (2020). Nonetheless, whilst they cannot be said to be indicative of the marmoset research community, these findings have value in identifying potential effective indicators that can be further explored in a subsequent Delphi process involving a larger population of subject experts. We consider it important to conduct this exercise, given the resurgence in the use of this species in biomedical research (Colman et al., 2021). Some of the chosen indicators may reflect signs typically associated with marmoset wasting syndrome, a disease which causes morbidity and mortality in captive colonies (Ludlage & Masfield, 2003). We note also there was some inter-species application, as indicated by the percentage agreement scores of marmoset experts for seven of the top ten macaque indices in Truelove et al. (2020). It is valuable to have identified welfare assessment indicators that could be applied to multiple NHP species, particularly when conducting a limited-time, on-site assessment.\n\nWhen presented with 115 potential indicators for macaques, participants in the Truelove et al. (2020) Delphi selected 56 of these as valid, reliable, and practicable within the context of a hypothetical scenario involving 500 animals; environment-based and staff-based indicators (44) were selected more than three times animal-based indicators (12). In the current study and with the same scenario, of the 56 indices, only eight were found to be valid, reliable, and practicable by at least 70% agreement of the macaque respondents. Three of the eight were animal-based (self-harm behaviour, body weight, appetite); the remainder were either environment-based (social enrichment, cage dimensions) or staff-based (health monitoring programme, staff training, positive reinforcement training). In addition, NHP induced injuries (animal-based) and presence of a behavioural management programme (staff-based) approached consensus at 68.7%.\n\nIt is notable that no physiological indicators and only one behavioural indicator (self-harm behaviour) are included in the top ten of Truelove et al. (2020), probably reflecting the greater effort required in collecting animal-based data to assess welfare (though 12 animal-based indicators, including body weight, appetite, and NHP induced injuries did reach consensus in Truelove et al., 2020). We speculate that the predominantly European participants of the current Delphi were more open to animal-based indicators than the predominantly North American participants in Truelove et al. (2020) because European macaque colonies tend to be smaller and there is perhaps more staff resource available to obtain information requiring direct measurement. Environment- and staff-based indicators can generally be assessed with more immediacy and ease, and without specialist equipment or judgement (e.g. whether cage furniture is present in the enclosure). However, it should be noted that the mere presence of something does not give a full picture of its contribution to NHP welfare; the quality of the item, and how much it is used, and by which animals, are also important factors.\n\nOf the eight indicators selected in Phase 2, three of these also appeared in the top ten of Truelove et al. (2020) presented in Phase 1 (self-harm behaviour, social enrichment, health monitoring programme), strongly suggesting that these indicators are considered critical for the assessment of macaque welfare. Also exceeding or approaching the 70% threshold in Phase 1 were a behavioural management programme, physical enrichment, and food enrichment, suggesting their consideration as well. Social enrichment was rated the top indicator in Phase 1 (>94% of respondents), reflecting the importance of companionship for psychological well-being in these animals. Social enrichment and self-harm behaviour are well known as important indicators of good and poor welfare, respectively, in NHPs, and there is a large literature on their incidence and relevance to macaque well-being, so it is not surprising that there was consensus agreement on their importance in both Delphi consultations. Fewer than two-thirds of respondents felt a humane euthanasia programme, hearing other NHPs, cage furniture, and ventilation could be used to assess welfare. Opinion was split on how practical cage furniture and ventilation are as welfare indices for macaques. Agreement scores for practicability were generally higher in Truelove et al. (2020) than in the current study, possibly reflecting differences in expert demographics, sample size, and methodology.\n\nA greater number of the 56 indicators were considered valid and reliable by respondents working with macaques in infectious disease research and breeding, than in neuroscience, toxicology and other disciplines, perhaps reflecting a greater awareness of the impact of surgical and husbandry procedures, and the cage environment, on the welfare of these animals (Figure 4). Macaques in neuroscience also undergo frequent sedations, surgeries, and medical procedures, so it is curious these did not approach consensus in this category but did so in infectious disease. Within neuroscience, body weight and appetite are included in the top four indices, reflecting that many macaques used in neuroscience undergo food or fluid control to motivate them to work on behavioural or cognitive tasks whilst brain activity is measured. Self-harm behaviour and stereotypies are within the top seven, reflecting the practice of monitoring between experimental manipulations behavioural changes which could compromise the validity of the NHP model. Although they did not meet the set threshold for inclusion as items to rate by all participants, additional indicators suggested by respondents within this discipline included activity level (including the presence of depressive-like behaviour or non-alert inactive behaviour), engagement with and performance on experimental tasks, and water intake (again reflecting the scientific procedures involved).\n\nWithin infectious disease, more than half of the indicators (33/56) were considered valid and reliable by three-quarters of respondents, with over 40% (14/33) of these being cage-based. Appetite, body weight, and mortality are in the top five, reflecting that many of the macaques used in such studies will experience disease (Prescott et al., 2021). Additionally, to round out the top five are stereotypy and self-harm behaviour. Similar to neuroscience, these indices reflect the practice of monitoring behavioural changes between experimental manipulations over prolonged periods of time.\n\nTen indicators were selected by more than two-thirds of respondents in toxicology, drawn from a range of categories – behavioural, physiological, husbandry-based, and cage-based. Body weight and mortality checks are routinely performed as part of regulatory toxicology studies. Most animals are euthanised for pathology when assigned to toxicology studies, which might account for the appearance of a humane euthanasia programme in the top four. Huddled posture may reflect sickness due to test drug administration.\n\nWithin breeding, 24 of the 56 indices (42.9%) were selected by more than two-thirds of respondents. Of the top ten, five are cage-based and four husbandry-based, reflecting the large group sizes and number of animals to be monitored in breeding units, as well as the relative lack of need for scientific procedures and for welfare data for a scientific purpose. The inclusion of indicators such as social density, vertical space, environmental complexity, cage furniture, and visual barriers probably reflects the more spacious environments often afforded to breeding animals.\n\nThat some indices are contextualized differently across specializations is not surprising. For example, those who require chair restraint for handling of monkeys to do their research might find frequency of such restraint to be a more useful indicator than those who do not. This brings to light the difficulty in assessing animal welfare and the complexities of using indicators – they must be well defined, validated for the species for which they are applied, and need be not only practical to measure but also reliable across time and raters. Agreement on which of these is most important is coloured by culture and work experience as well as discipline perspective (Duijvesteijn et al., 2014), and when working as a group, the results of the process will also be subject to the composition of the panel. In the current study, the majority of respondents working with macaques did so in neuroscience, and most respondents were primarily from the UK and EU, whereas those in the Truelove et al. (2020) study were primarily from the USA. Differences exist between these regions in how laboratory NHPs are housed and managed, partly due to the oversight regulations. For example, minimum cage space requirements for NHPs are considerably smaller in the USA than in the UK and EU member countries. Under Directive 2010/63/EU (European Union, 2010), the minimum volume for macaques from three years of age is 1.8m3 /64ft3 per animal, reflecting the value placed on providing housing that allows for exercise and the expression of ethologically relevant behaviours, such as running, climbing, leaping and hiding from companions (NC3Rs, 2017). Under the ILAR Guide (National Research Council, 2011), the minimum volume per macaque up to 10kg is 0.25m3/9ft3, and this space allocation was not increased in the 2011 revision. One possible reason for this disparity in minimum cage space is that UK and EU NHP facilities tend to house considerably fewer animals than those in the USA. Irrespective of these regional differences, our two Delphi consultations have been able to identify critically important indices for macaque welfare.\n\n\nConclusions\n\nWe have identified context appropriate indicators that are valid, reliable, and practicable for assessing the welfare of macaques and marmosets bred and used for research, including in toxicology, neuroscience, and infectious disease, potentially benefiting far in excess of 100,000 NHPs used globally per year by improving welfare assessment, minimisation of harm and evaluation of the impact of refinement techniques. In ranking potential welfare indicators, we have identified those indicators considered the most important by experts and narrowed the field for further investigation and validation of both species-specific and general indicators. We have used the top-ranking indicators for macaques identified by experts in our two Delphi consultations, and agreement on how these should be measured, to develop a practical and generalised welfare assessment protocol to support laboratory staff in monitoring and optimising macaque health and well-being (GEN-MAC). Our work to harmonise welfare indicators and assessment should facilitate inter-lab comparative studies, data-sharing to boost sample sizes in research asking welfare-focused questions, and benchmarking of welfare standards between facilities. It would be good to build upon this momentum and achieve further consensus and harmonisation globally, involving Pacific Rim countries in addition to North America and Europe. Further validation of the proto-protocol, and of the top-ranking welfare indicators, would also be welcome. Funding opportunities are available from the NC3Rs, other bioscience organisations, and animal welfare charities.\n\n\nData availability\n\nNewcastle University research repository: Survey Data and Supplementary Tables. https://doi.org/10.25405/data.ncl.19106960 (Leach et al., 2022).\n\nThis project contains the following underlying data:\n\n▪ Survey 1 Data anonymised.xlsx (Anonymised data set generated during Survey 1)\n\n▪ Survey 2 Data anonymised.xlsx (Anonymised data set generated during Survey 2)\n\nNewcastle University research repository: Survey Data and Supplementary Tables. https://doi.org/10.25405/data.ncl.19106960 (Leach et al., 2022).\n\nThis project contains the following extended data:\n\n▪ Supplementary Table 1.doc (Comparison of validity and reliability and practicability respondent scores between two Delphi exercises, macaques, 56 welfare indices)\n\n▪ Supplementary Table 2.doc (Macaque respondent agreement scores for validity and reliability by discipline, 56 welfare indices, n=67 respondents)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
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}
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[
{
"id": "126226",
"date": "22 Mar 2022",
"name": "Augusto Vitale",
"expertise": [
"Reviewer Expertise animal behaviour",
"animal welfare",
"primatology",
"ethics of research"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe aim of this paper is to identify shared indicators for the level of welfare of macaques and marmosets in research laboratories, using a Delphi consultation during a NC3Rs meeting on primate welfare. The results pointed out at some reliable indicators for both species, with some interesting differences: self-harm behaviour and social enrichment were chosen as being important for macaques, whereas body weight for marmosets.\nI found the paper very informative and very relevant. These are the kind of studies which are really needed to improve the conditions of NHP in captivity, so I really applaud the authors' efforts. However, I have some concern about part of the article's content. In particular, although it is very informative and important for the macaques, less so for the marmosets. I don't feel that the authors have enough responses from the marmoset community to draw conclusions. There is in this paper a real unbalance when it comes to deal with the two species. I understand that this is a big ask, but I would feel more comfortable with this paper if the marmosets would be left to develop in another time, with more data available.\nIn particular:\nIn the \"Research highlights\" table, under \"Scientific benefit(s)\" and \"Current applications\" marmosets are not mentioned, supporting my general impression.\nTable 2: Some of the scoring criteria appear to be \"states\" (e.g. presence of injuries\"), other \"events\" (e.g. affiliative behaviours). Is there any possibility to have an idea on how these observations would be carried out, in terms of timing, frequency...?\n\nIn the section \"Results - Demographics\" we have 67 colleagues working with macaques, and 6 working with marmosets. It appears to me greatly unbalanced. I would then delete the responses from the marmosets' people, for later wider participation.\nTable 6 reports the results for marmosets, however it is based on a very limited sample size. For example, just one person replied in the area of neuroscience - I would suggest to delete it.\nIn the \"Conclusions\" section, there is no mention of the results on marmosets.\nTherefore, I recommend the approval of the present paper, but I consider it a \"macaque paper\", so:\ni) if the authors delete any reference to the marmoset survey;\nii) or they play down very much that part, perhaps mentioning the results in the final discussion, underlying the necessity and need to compare different species, looking at their preliminary data on marmosets.\n\nAre the 3Rs implications of the work described accurately? Yes\n\nAre a suitable application and appropriate end-users identified? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "8034",
"date": "07 Apr 2022",
"name": "Mark Prescott",
"role": "Author Response",
"response": "We thank the reviewer for his comments on the manuscript. We are pleased the importance of this work for improving non-human primate welfare has been recognised. The reviewer's comments focus on the marmoset data. We appreciate the sample size for respondents using common marmosets is small and had hoped that this would be larger at the 2019 Primate Welfare Meeting. It is important to note there was no separate marmoset survey. We considered not including the marmoset data in the paper, but decided it was important to do so for a variety of reasons: We are obligated to publish the data provided by all of the participants of the 2019 Delphi consultation. Publishing the full data (and making the data set available) is the most transparent approach, in line with contemporary good practice. Including the marmoset and macaque findings allows for comparisons to be made between species/genera, which shows some interesting differences as the reviewer acknowledges. This emphasises the importance of doing such work per species. We would therefore like to retain the marmoset data within the paper. We have already been careful to acknowledge the small sample size for marmosets in the Discussion section (which, as the reviewer has recognised, is also reflected in the Research Highlights section): These findings should be viewed as preliminary given only six of our 73 respondents (8%) worked with this species and the indices were from Truelove et al. (2020). Nonetheless, whilst they cannot be said to be indicative of the marmoset research community, these findings have value in identifying potential effective indicators that can be further explored in a subsequent Delphi process involving a larger population of subject experts. We consider it important to conduct this exercise, given the resurgence in the use of this species in biomedical research (Colman et al., 2021). We believe this text addresses the reviewer’s suggestions to mention the marmoset results in the final Discussion, consider the marmoset data preliminary, and to gather data from a larger population of marmoset experts. We also comment in the Discussion on the differences and similarities in the findings for marmosets and macaques. Our Conclusion section is high level and does refer to the common marmoset data. However, in the revised paper we now state explicitly in the Conclusion (and Methods) that there were too few common marmoset data to generate a welfare assessment protocol for this species: There were too few marmoset data to generate a welfare assessment protocol for this species, and we recommend further data are collected. Also in response to the reviewer, we have added marmosets to the second bullet under Research Highlights – Scientific benefits: Ranks welfare indicators for macaques and marmosets and narrows the field for further investigation of those considered most important by experts. Regarding the comment on Table 2 (GEN-MAC protocol) indications of how frequently the observations of behavioural states and events would be carried out are given in the table (e.g. on inspection or recorded in daily logs): these are suggestions only, to allow the GEN-MAC protocol to be adapted to local circumstances. They are based on the views of the Delphi participants, which are summarised in Table 4. We thank the reviewer again for his constructive feedback."
}
]
}
] | 1
|
https://f1000research.com/articles/11-272
|
https://f1000research.com/articles/12-523/v1
|
22 May 23
|
{
"type": "Case Study",
"title": "Digital Rock Art: beyond 'pretty pictures'",
"authors": [
"Joana Valdez-Tullett",
"Sofia Figueiredo Persson",
"Sofia Figueiredo Persson"
],
"abstract": "The term ‘Rock Art’ is loosely used in this article to refer to prehistoric carvings and paintings. Rock art research has changed profoundly in the last two decades. Partly, this is due to the introduction of more ‘scientific’ methodologies such as digital recording, to overcome the subjective nature of analogue documentation methods. Digital recording offers not only ‘pretty pictures’ but more immediate and quantifiable datasets and methods of analysis. As a result, new research implementing complex, multi-scalar and inter-relational analyses, which do not focus solely on the motifs or the landscape location, but encompass many variables of the rock art assemblages, have been successful in bringing rock art to wider narratives of prehistory. This article reflects on the interaction between rock art and digital archaeology, considering how the application of digital resources has changed the way we think, record and conduct research in this field. It will be illustrated by two main case studies from Iberia: Schematic Art in its painted form, and Atlantic Rock Art, a carving tradition.",
"keywords": [
"Digital Rock Art",
"Digital Archaeology",
"Rock Art Research",
"3D modelling",
"Imaging Analysis",
"Atlantic Rock Art",
"Schematic Paintings",
"Methodology"
],
"content": "Introduction: Image and representation\n\nImage and representation are integral to archaeology, an inherently visual discipline, with an imperative to graphically record its study objects (e.g. Moser, 1992; Montero-Ruiz et al., 2000; Jones and Bonaventura, 2011; Olsen, 2010; Opgenhaffen, 2021). The important relationship between archaeological practice and visualization was emphasised by early archaeologists (e.g. Petrie, 1904, Piggott, 1965, 1978), with Piggott stating that for Pitt Rivers a site was best described firstly through illustrations and then text (1965:174). Moreover, it has been argued that to illustrate is to intimately explore the archaeological record and that this is a fundamental step in the understanding of its complexities (Swogger, 2000). The archaeological illustrative process refers not only to different ways of presenting data, but also to the translation of ideas, theories and arguments (Moser, 1992). For example, many of us turn to drawings on our field notebooks to express specific ideas, and our work is almost always (if not always) supported by drawings of our processes and finds. It is, however, this sense of entanglement between the recorder and the study object that makes the process of drawing so interpretative and therefore subjective, dependent on individual skills and personal decision making regarding how and what to capture (Morgan and Wright, 2018).\n\nThis relationship is even more fundamental for rock art, due to the intrinsic visual character of this type of materiality. Rock art can be defined as the act of carving or painting natural hard rock surfaces in caves, shelters, some types of monuments, boulders and outcrops in open landscapes, portable blocks and plaques. In some scholar traditions the term ‘rock art’ refers only to the carved expression of the artistic manifestations, but in this paper we will use it interchangeably to designate both paintings and carvings (also known as engravings) on rock, durable surfaces. Rock art is a popular topic, but mostly side-lined by mainstream archaeology. There are many reasons that explain this alienation, in particular rock art’s own character, which does not allow for the application of methods and analyses common to other areas of archaeological research. Typically devoid of stratigraphic associations, the lack of precise dating and contextualisation make rock art a difficult subject to engage with. Besides their landscape location, the carved and painted motifs were, until recently, the only other element that researchers have available to study rock art.\n\nThe visual nature of the motifs is the most conspicuous feature of rock art sites. Recording them is fundamental for rock art research, with outputs enabling the sharing of information, which is not always accessible to all (since fixed in the landscape), the analysis of motifs and a deeper understanding of the rock art. Over time, a plethora of analogue recording methods were developed, each claiming to be more accurate and precise than the next, with clear preferences according to scholarly traditions. This variability, however, poses issues, since there is a generalized lack of representational guidelines, resulting in a heterogenous and subjective record, depending on the recorder’s judgement and experience. The democratization of digital technologies and their application to archaeology changed this scenario and, consequently, traditional methods were largely abandoned. The introduction of new digital methods and techniques have fundamentally changed practices in rock art research, increasing productivity, speed of operation, and facilitating engagement with new approaches and visualizations (e.g. Beale and Reilly, 2017; Huvila and Huggett, 2018). Rock art is now mostly documented with 3D technologies (e.g. Díaz-Andreu et al., 2006; Días-Guardamino et al., 2013, 2015; Jaillet et al., 2017; Horn et al., 2018; Valdez-Tullett, 2019) and imaging analysis methods (e.g. Mark and Billo, 2002; Harman, 2005; Rogerio-Candelera et al., 2013; Figueiredo, 2017; Defrasne et al., 2019; Challis, 2022).\n\nDigital Archaeology changed the face of rock art. Recent methodological and theoretical approaches to rock art have become increasingly more complex, engaging with computational applications such as Geographic Information Systems (GIS) and spatial statistics (e.g. O’Connor, 2006; Valdez-Tullett, 2019), physiochemical approaches to material analysis (e.g. Defrasne et al. 2019; Domingo-Sanz et al. 2021), quantitative analyses (e.g. Figueiredo, 2017; Riris and Oliver, 2019; Valdez-Tullett, 2019), archaeometry (e.g. Andreae and Andreae, 2022), network science (e.g. Riris and Oliver, 2019; Valdez-Tullett, 2019, 2021), experimental archaeology (e.g. Needham et al., 2022) or artificial intelligence (e.g. Horn et al., 2021; Horn et al., 2022). These approaches have endowed rock art research with a more robust professional scholarship and ‘academic seriousness’, due to the scientificity, technicalities and reproducibility of methods.\n\nDespite the wide-ranging impact of digital technologies in rock art, this article engages specifically with the application of recording methods, responding to a call for a more critically engaged and theoretically-driven application of technological methods within Digital Archaeology (Gillings, 2012; Perry and Taylor, 2018). It reflects on the significant shift to digital which, notwithstanding the positive transformation that it entailed within the discipline, is not without issues and further implications.\n\nWe will examine the interaction between rock art and digital archaeology, considering how the application of digital resources changed the way we think, record and conduct research in this field. Our considerations will be illustrated by two main case studies from Iberia: Schematic Art in its painted form, and Atlantic Rock Art, a carving tradition, each presenting distinct challenges. This paper offers and develops the concept of “Digital Rock Art”, based on the steady and growing relationship between rock art research and the use of digital technologies.\n\n\nArchaeology and the Digital Turn: setting the scene\n\nArchaeology lies in the intersection between ‘hard’ sciences, social sciences and humanities. For this reason, archaeology is highly interdisciplinary. This entanglement leads to the incorporation of an array of methodologies and techniques, and therefore it is not surprising that archaeology was an early adopter of digital applications (Huggett, 2015, 2021; Costopoulos, 2016; Beale and Reilly, 2017). The field has been dealing with the digital world for the last six decades and has seen its Digital Turn (Costopoulos, 2016; Huvila and Huggett, 2018; Perry and Taylor, 2018; Huggett, 2021). Digital Archaeology has become a common term, referring to a multiplicity of tools and applications incorporated in the archaeological practice (e.g. Huvila and Huggett, 2018; Huggett, 2021). The term extends beyond the use of GIS and spatial technologies, doubtless the most popular digital tool used in archaeology, to include quantitative and qualitative methods, statistical approaches, applied computational technologies, digital imaging and 3D recording methods (Perry and Taylor, 2018). This overarching presence of digital technologies in all stages of the archaeological process, from recording to data management and research, led Morgan and Eve to state that ‘we are all digital archaeologists’ (Morgan & Eve, 2012:523).\n\nDigital Archaeology is a dynamic field, rapidly evolving. The application of digital tools has changed the nature of archaeological practices, although we currently have a limited understanding of this impact, due to the lack of critical self-reflection (Huvila and Huggett, 2018). The fast development of technologies, dictated by the affordability and practicality of new methods, has led to a methodologically advanced, albeit under-theorized, use of digital applications (Huggett, 2004; Frieman and Gillings, 2007; Diaz-Guardamino and Morgan, 2019). In the last two decades there has been a general decrease of cost in specialized equipment and many pieces of dedicated software, which no longer require expensive high-powered computers to run on. More user-friendly methods have been developed, with less time-consuming processes, making the application of new technologies more accessible to all. In this context, Beale and Reilly note that ‘[o] ne only has to scan the pages of more than 40 years of the proceedings of Computer Applications and Quantitative Methods in Archaeology (CAA) to see that the introduction of new devices, techniques and theories of technology have dominated the discourse of archaeological computing’, and although ‘[t] his is not to say that innovative theoretical work has not taken place in archaeological computing’, ‘external critique of digital methods has been required in order for the theoretical underpinnings of this digital practice to be articulated in full’ (2017). Critical scrutiny of processes by those directly involved with the application of the technologies is often difficult to undertake, and the technical abilities of applications overshadow any meaningful review of their implications (Huvila and Huggett, 2018; Perry and Taylor, 2018).\n\nThe tendency to focus on technical approaches and discussions on the tools as objects of study is common (Costopoulos, 2016). Despite the lack of critically engaged discussions, it is undeniable that the overwhelming presence of digital technologies had and still have a significant impact on archaeological practices (Hacigüzeller et al., 2021). Digital Archaeology has introduced many benefits and fosters an engagement between several parties and audiences (Jeffrey, 2015), whilst also raising a number of epistemological and ethical issues related to transparency and authenticity (Rabinowitz, 2015), biases and subjectivities (Garstki, 2017), distance and separation from the archaeological object (Huggett 2015; Jeffrey 2015; Papadopoulos et al., 2019). As such, there is currently a call for a much-needed critical analysis of the use of digital technologies to assess their impact and role within the field (e.g. Huggett, 2015, 2021; Jeffreys, 2015; Perry and Taylor, 2018; Hacigüzeller et al., 2021), which is tentatively being addressed (e.g. Opgenhaffen, 2021). To progress with theoretically informed approaches, reflections on Digital Archaeology should focus on the integration of digital tools and methodologies into archaeological practice, promoting an understanding of their development and impact, and avoiding technological determinism (Huggett, 2015, 2021; Huvila and Huggett, 2018).\n\nIn line with this need for a critical engagement of digital technologies in archaeological practices, the remainder of this paper will focus on the impact of these applications in the documentation and study of prehistoric paintings and carvings.\n\n\nRecording methods for Rock Art\n\nRecording rock art, in any of its forms (painted or carved), is a hard task. The evidence is usually fragmentary and fragile, and the designs can be difficult to identify. Painted and carved motifs fade and erode with time, becoming almost invisible to the naked eye. Rock art’s location, from open landscapes to secluded shelters and deep caves, present particular challenges to the recorders, especially when documentation processes have to be carried out in the field, whether through analogue or digital methods. Portable art can generally be recorded in controlled and indoor environments.\n\nTraditional methods of rock art recording are based on Cartesian representations of panels with a 2 dimensional, flat and static perspective (Díaz-Guardamino and Wheatley, 2013; Figueiredo, 2017; Papadopoulos et al., 2019). Unlike other types of archaeological documentation, there is an obvious lack of regulations in rock art reproduction, with the topic being briefly featured only in a limited number of publications (e.g. Adkins and Adkins, 1989; Bahn and Vertut, 1997). Consequently, various analogue recording methods were developed over time, used simultaneously, with very different results.\n\nSome of the earliest illustrations of carvings and paintings date to the 17th and 18th centuries, created through sketches, drawings and paintings (e.g. Lhwyd 1659-1709 cf. Williams and Shee 2015 in Ireland; Contador de Argote 1738, after Correia 1916:117-118 in Portugal). The most famous are certainly the tracings and paintings which Abbé Henri Breuil created for European Palaeolithic cave art which, although highly subjective, had a remarkable influence in our perception and research focus of this type of prehistoric art (e.g. Altamira in 1902 and 1932).\n\nIn the late 19th century, antiquarians began to timidly use photography to document archaeological sites (e.g. Williams and Shee, 2015; Valdez-Tullett et al., 2022), a trend that was well embedded in archaeological practices in the 20th century. Rock art motifs were often enhanced before being photographed (e.g. Ramon Sobrino Buhigas and Ramon Lorenzo-Ruza in Galicia, Asociación Cultural Colectivo A Rula, 2020). Other rock art recording methods were developed and extensively applied, depending on local scholarly traditions and preferences. Some recorders preferred drawing plans with grid systems and planning frames, as well as tape and offset methods (e.g. Lorenzo-Ruza, 1953; van Hoek, 1995), others adhered to rock art specific techniques such as frottage or rubbings, a method particularly popular in England, Scandinavia and Spain (in Galicia). Making use of the depth of carved grooves, the panels were covered by paper upon which graphite was applied, sometimes combined with tracing, highlighting the motifs (Horn et al., 2019; Potter et al., 2022).\n\nA bi-chromatic method was developed in Valcamonica (Italy) in the 1960s and 1970s. Black and white colours were applied to the rock surfaces, emphasising the differences between carvings and rock surface. This method, as well as the reproduction of engravings with latex and silicone-based moulds, was extensively used in Portugal during the rescue project of the prehistoric rock art of the Tagus Valley, submerged by the Fratel dam in 1973 (Baptista and Santos, 2013:34-36). Both techniques were abandoned in favour of direct tracing, a technique that operates at a 1:1 scale. In this case, the rock surface is wrapped with transparent polyvinyl sheet(s), upon which motifs and other features (i.e. fissures, fractures, solution holes, etc.) are traced onto with markers, preferrably during the night, benefitting from artificial oblique light. This versatile method can also be applied to paintings, where the colour of the original pigments can be tentatively reproduced (e.g. Shee, 1981; Figueiredo, 2017). Direct tracing has been the preferred method used by Portuguese and Irish researchers, and was applied by Shee Twohig in her seminal work on European Megalithic Art (Shee, 1981). Direct tracing can produce very satisfying results, notwithstanding its inherent subjectivity, and fosters a privileged physical engagement between observer and decorated rock, which is absent from other approaches.\n\nPhotograph by Joana Valdez-Tullett.\n\nAlthough the methods described above are well established in rock art documentation, there is a lack of literature engaging with their methodological processes and critical assessments of techniques and results. Often taken as accurate and reliable, in reality these methods entail high degrees of subjectivity, due to the selective and interpretative exercise inherent to the data gathering process (in rock art’s case including weather, weathering and preservation, geology, etc.), as well as individual skills and interests (e.g. Díaz-Guardamino and Wheatley, 2013; Figueiredo, 2017; Morgan and Wright, 2018; Papadopoulos et al., 2019; Horn et al., 2021).\n\nRock art reproductions resulting from analogue recording methods are no longer satisfactory. The 2D outputs are often inaccurate, failing to capture the essence of the monuments, their depth, volume, micro-topography, texture and overall context, depriving researchers of vital contextual information (Díaz-Guardamino and Wheatley, 2013:189; Robin, 2015:35). Discrepancies of representation styles result in significant differences in reproductions of the same panels by different people, even when working on the same sites. For example, natural features, such as fissures and cracks, may not always be represented leaving the motifs floating on a white background; even if identified in the field, superimpositions are not always clearly marked, or there is no information regarding which motif is overlain; taphonomic processes affecting the rock surface and the integrity of the motifs are not always represented; and, of course, the inherent bias resulting from the experience of the observer, which may result in significant differences. For example, a carved rock in Culnoag (Dumfries and Galloway, Scotland) has been documented by Ronald Morris (1979) and Maarten van Hoek (1995), who worked together on numerous occasions. While Morris’ drawing features 8 circular carved motifs against a blank background, van Hoek counted 12 and added a prominent fissure dividing the rock face, against which some motifs are abutted. These substantial variations affect interpretations and are aggravated by the fact that the inaccuracies of some of these models are not immediately obvious or fully understood by late users of these outputs (Diaz-Guardamino and Wheatley, 2013:189; Horn et al., 2021:190). Consequently, it is surprising that the field has seldom reflected on recording processes and is often over-reliant on these illustrations, which shape our perception of rock art and research in general.\n\nDifferent digital recording processes are required for rock carvings and paintings. Carvings benefit from image-based modelling methods, which use multiple static images and pixel recognition to produce three-dimensional point clouds, replicating the micro-topography of the rock surfaces, high-accuracy techniques resulting in sub-millimetric 3D models (Díaz-Guardamino and Wheatley, 2013; Horn et al., 2019). Paintings require digital imaging approaches focused on colour enhancement techniques (Mark and Billo, 2002; Rogerio-Candelera et al., 2013; David et al., 2015; Le Quellec et al., 2015; Figueiredo, 2017).\n\nDigital imaging analysis and 3D modelling have been around for several decades, but the first computational techniques applied to rock art involved photographic colour enhancements, albeit their limited scope for analysis (Rip, 1989; Brady and Gunn, 2012; Robin, 2015:36; Rogerio-Candelera, 2015:69). The first photogrammetric and 3D laser scanning experiments were introduced in the 1980s (e.g. Delluc and Delluc, 1984; Aujoulat, 1987), developing more significantly since the 2000s (Robin, 2015). The democratization of digital technologies was fundamental in this process, with a variety of methods and techniques becoming more affordable and user friendly, and therefore consistently applied in the documentation of rock art (e.g. Muzquiz Perez-Seoane and Saura Ramos, 2003; Díaz-Andreu et al., 2005, 2006; Brady, 2006; Chandler et al., 2007; Fredlund and Sundstrom, 2007; Mañana-Borrazas et al., 2009; Lerma et al., 2010; Jones et al., 2011; Abbot and Anderson-Whymark, 2012; Diaz-Guardamino and Wheatley, 2013; Williams and Shee, 2015; Figueiredo, 2017; Horn et al., 2018; Valdez-Tullett, 2019; Valdez-Tullett et al., 2022).\n\nThe location and context of each decorated surface will often determine the most fitting digital recording method to use. Laser Scanning and Structure from Motion (SfM) photogrammetry are particularly well suited for the documentation of large surfaces, monuments or outcrops in open landscapes (e.g. Díaz-Andreu et al., 2005, 2006; Jones et al., 2011; Abbot and Anderson-Whymark, 2012; Díaz-Guardamino and Wheatley, 2013; William and Shee, 2015; Jaillet et al., 2017; Horn et al., 2018; Valdez-Tullett, 2019; Watson and Bradley, 2021; Valdez-Tullett et al., 2022).\n\nThe term ‘Laser Scanning’ encompasses a range of tools which collect precise and accurate point clouds through a scanner, mounted on a tripod, vehicle or aircraft (Jaillet et al., 2017; Historic England, 2018). The scanner sweeps the surroundings with a light beam that measures distances and analyses the properties of the light, reflecting this information and translating the data into a Cartesian coordinate system (Jaillet et al., 2017; Historic England, 2018). Increasingly more portable, Laser Scanning can now be applied to more challenging locations, such as the small gap between the ground and the inner surface of a capstone of a cist in Dunchraigaig Cairn (Kilmartin, Scotland), which enabled the production of a sub-millimetric high-resolution 3D digital model of Scotland’s first ever found prehistoric animal carvings (Valdez-Tullett et al., 2022). Early laser scan surveys applied to rock art were firstly carried out in a small cave in the Beune Valley (France) (Aujoulat et al., 2005) and in the very challenging and partially submerged Cosquer Cave in the Calanque de Morgiu (France) (Thibault, 2001). Given the technical expertise required for data capture and processing, as well as the cost of the equipment, Laser Scanning is still the most inaccessible digital recording technique. Conversely, SfM photogrammetry continues growing in popularity and is currently the most common 3D modelling method used in archaeology. It consists in the capturing of a series of overlapping photographs, taken from different positions, covering an object’s surface. The intersecting points of the images are identified and stitched with a dedicated software such as Agisoft Metashape® (previously known as Agisoft Photoscan®). Matching points are plotted in a three-dimensional space, representing the object’s depth, resulting in a 3D model (Miles et al., 2013; Valdez-Tullett, 2019; Horn and Potter, 2020). These models mimic the micro-topography of the study objects recreating their geometry, texture, colours and allowing for measurements (Sapirstein and Murray, 2017; Papadopoulos et al., 2019). SfM is a rather versatile technique, and can be applied to a variety of contexts from small objects to large outcrops and monuments, excavations and landscapes.\n\nReflectance Transformation Imaging (RTI) is another popular method for the documentation and analysis of carvings (e.g. Mudge et al., 2006; Earl et al., 2010; Kleinitz and Pagi, 2012; Díaz-Guardamino and Wheatley, 2013; Díaz-Guardamino et al., 2015; Jones and Díaz-Guardamino, 2019; Valdez-Tullett, 2019). It is a low-cost computational technique based on the capture of photographs from a fixed point, using the reflectance properties of the object’s surface. Although it cannot create full 3D models, it produces excellent high-resolution 2.5D isometric representations of the objects and photo-realistic visualizations, enhancing the recorded shapes and textures (Mudge et al., 2006; Díaz-Guardamino et al., 2015:41).\n\nPhotograph by Joana Valdez-Tullett.\n\nWhile not particularly useful for large surfaces, RTI is well suited for capturing small details (e.g. artefacts or individual motifs), which are then explored with controlled lighting conditions and interactive visualizations (Malzbender et al., 2000; Malzbender et al., 2001; Díaz-Guardamino and Wheatley, 2013:190-191). Recently, RTI has been pivotal in the recording and analysis of Neolithic decorated artefacts from Britain and Ireland, recovering an unprecedented understating of the sensorial manufacturing processes of the objects, phasing and chronology, leading to renewed considerations of their social and cultural roles (e.g. Jones and Díaz-Guardamino, 2019; Davis et al., 2021).\n\nRTI and rendering by Joana Valdez-Tullett.\n\nAlthough RTI’s set up poses some limitations when used outdoors, the simplicity and portability of both this and SfM photogrammetry have contributed to the generalized use of 3D modelling in all stages of rock art research. In addition to more accurate and precise reproductions of carvings, 3D modelling also offers a range of analytical possibilities to researchers, with a range of enhancement techniques which enable the manipulation of colour, texture, highlight relief of grooves, and facilitates interactive visualizations in different modes and lighting conditions (e.g. Radiance Scaling in MeshLab®, see Vergne et al., 2010).\n\nImage by Joana Valdez-Tullett.\n\nThree-dimensional technology is not particularly useful for paintings, except when used to replicate the relationship between painted motifs and the texture of the rocks, obvious for example in the painted bison of Altamira, depicted over round convexities of the rock surface, providing volume to the animals. Instead, photographic imaging enhancement methods are used to highlight paintings, enabling the visualization of faded pigments (Le Quellec et al., 2015). Enhancement techniques include infra-red (e.g. Fredlund and Sundstrom, 2007) and multispectral photography (e.g. Pires et al., 2010; Papadopoulos et al., 2019), cross-polarization (e.g. Henderson, 2002) and post-processing of images with software such as Adobe Photoshop® (e.g. Mark and Billo, 2002; Domingo-Sanz and López-Montalvo, 2002; Brady, 2006; David et al., 2015). In the last decade DStretch®, which stands for ‘decorrelation stretching’, has gained much interest. This plug-in for the free software ImageJ®, was designed by Jon Harman specifically for the digital enhancement of rock art paintings, and is based on a decorrelation algorithm which, when applied to visible spectral wavelengths, highlights colour (Harman, 2005; López-Menchero Bendicho et al., 2017). DStretch enables a more objective reproducibility of the paintings, being more reliable and less time consuming than other methods, which require expert knowledge to execute. As such, it has been adopted worldwide, and its new format as a mobile application made it highly portable and suitable to document paintings in remote and inaccessible environments (e.g. Mark and Billo, 2006; Quesada Martínez, 2008; Rogerio-Candelera et al., 2013; Gunn et al., 2014; Le Quellec et al., 2015; Figueiredo, 2017; Quesada and Harman, 2019).\n\nImage composition by Sofia Figueiredo Persson.\n\n\nDigital Rock Art is here to stay\n\nAn early adopter of digital technologies, rock art research has changed significantly in the last two decades. The first phase of Digital Rock Art occurred following the introduction of Landscape Archaeology in the 1990s, largely by the hand of Richard Bradley (e.g. 1997), a paradigm that launched new theoretical and methodological approaches, and which represented an important turning point for rock art studies. Bradley offered an alternative approach to the traditional emphasis on iconography, exploring rock art’s privileged relationship with landscape, particularly well-suited to the application of spatial analysis. In the context of 1990s emerging interest in GIS, Gaffney et al. published the first paper describing the use of viewshed analysis to rock art sites in Kilmartin (Gaffney et al., 1996). Landscape Archaeology and GIS have, since then, been important components of rock art research (e.g. Fairén, 2004; Cruz-Berrocal, 2005; O’Connor, 2006; Valdez-Tullett, 2019). Recently, other computational applications have featured in a variety of rock art studies, in addition to the expansion of digital recording methods, allowing us to conclude that we are firmly entrenched in a Digital Rock Art era. But what does this mean, beyond the production of ‘pretty pictures’? There are several components to Digital Rock Art, offering many advantages, though not without pitfalls.\n\nFieldwork directed at rock art has fundamentally changed due to the introduction of digital recording methods. Typically, this would entail a programmed incursion, operated across several days, involving multiple individuals, to firstly identify the sites and then, at a different time, record them. Regardless of the chosen technique, these processes would often require complex logistics, various pieces of heavy equipment and multiple work days. Equally, post-recording procedures were onerous, involving several steps, and often devices such as large scanners, which were not widely accessible, to scan 1:1 field drawings then digitized in software such as Adobe Illustrator®, and later published. A process which leapt from analogue to digital and back to analogue, reminiscent of Dawson and Reilly’s concept of ‘phygital nexus’ (Dawson & Reilly, 2019).\n\nImage by Joana Valdez-Tullett and Joana Teixeira.\n\nThe introduction of digital recording methods has made rock art-oriented fieldwork more economical, since it is less time consuming, requiring fewer digital appliances (e.g. camera, lens or lenses, flash, triggers, occasionally a tripod), which are more affordable and transportable, as well as cheaper software with many freeware options available (e.g. 3DF Zephyr, Visual SFM, Blender, MeshLab, etc.). Due to new technologies, paintings and carvings can now be identified and recorded in single day trips, with results of photographic surveys being processed and available the same or following day. In addition, they introduced more certainty in the identification of rock art, since it is now easy and quick to document a rock surface to later confirm or dispel if it bears any decoration. Indeed, field examination of rock art is not always straightforward and is determined by a number of factors, from the observer’s experience to the motifs' conservation and weathering, weather conditions, time of the day or year, and available lighting. In situ observation and recording of rock art often involves a ‘dance’-like performance where the observer moves around the panel to get up close to the motifs and analyse them in detail, under the best possible lighting conditions. Given the challenges, touch can be particularly valuable in the identification of carvings, revealing the soft depressions and edges of the artificial grooves, even when invisible to the naked eye (Valdez-Tullett, 2019). Similarly, the visualization of paintings may require specific types of bodily engagements, depending on their locations. Often preserved in secluded places, the observer may find themselves in awkward positions within small shelters or the corner of dark caves. Such interaction places us on the same biographical chain of the site/monument, somehow connecting us to others in the past, who have shared similar experiences (Jeffrey, 2015). In all scenarios, the observer develops an intimate sensorial relationship with the rock art that is largely absent with the application of digital recording methods and which, unlike traditional techniques, are praised for their non-contact character. Thus, we confront ourselves with a situation of tension between an irrevocable shift towards Digital Rock Art, and the realization that sensorial experiences cannot be replaced by virtual visualizations, and are pivotal for a full understanding of our study objects, but which in the case of rock art may be damaging for the integrity of their materiality and future analyses (e.g. Hamilakis, 2014; Jeffrey, 2015; Papadopoulos et al., 2019; Valdez-Tullett, 2019; Skoglund et al., 2020).\n\nPhotograph, 3D model and rendering by Joana Valdez-Tullett.\n\nhttps://sketchfab.com/3d-models/derreeny-288-iveragh-peninsula-co-kerry-0921a1e495e14647ade40f478111bf4a/embed\n\nNevertheless, digital methods reduce ambiguity in the recording process, making the distinction between natural and artificial grooves more obvious, as well as aiding in the interpretation of compositions and identification of difficult features such as superimpositions, phasing, etc.\n\nDigital recording techniques introduced the ability to reproduce study objects more faithfully, even if, as seen, they do not exclude human bias entirely. Processes still imply a certain degree of decision-making, including the selection of equipment (i.e. camera, laptops, software) to use, which in their nature are a product of human input (Huggett, 2015).\n\nCombined with an affordable and user-friendly technology, which can produce rapid results and be used in large scale projects, digital methods became the preferred tools for rock art documentation.\n\nThey facilitate the multi-scalar recording of rock art, from the small details of motifs to the landscape location of the assemblages (e.g. the use of drone LiDAR to contextualize a specific site or group of sites), as well as the landscapes themselves. RTI and SfM photogrammetry are the most popular techniques in rock art research, given their ease of use and need for minimal equipment. They are also extremely versatile and forgiving, resulting in very satisfactory 2.5D and 3D models respectively.\n\nThe digital reproduction of rock art panels has resulted in unparalleled datasets which are transforming our perception of rock art. Motifs, whether carved or painted, have never been so clearly visualized, regardless of weathering. Models of the whole surfaces, or indeed whole outcrops, can now be captured, even if situated in challenging places. We can now record the assemblages comprehensively, capturing carving techniques, details of inter-relationships between motifs within compositions, and between the former and the micro-topography of the surfaces, including natural features which are often so important. Other emerging methodologies are currently used in the analysis of colouring material applied to prehistoric paintings (e.g. Defrasne et al., 2019; Domingo and Chieli, 2021). In both cases, however, digital recording techniques have introduced new layers of nuance to relative chronology and phasing, enabling the identification of features such as superimpositions, erasure, re-carve or re-paint of motifs, which are otherwise difficult to discern. These features are indicative of moments of production, use, re-use and sometimes decommission, elucidating on the diachrony of rock art.\n\nRe-assessments of well-known sites, surveyed with digital methods, have revealed surprising new details. An emblematic example is that of Stonehenge, possibly UK’s most popular monument, which was scanned in the early 2000s revealing several Early Bronze Age axeheads carved on the trilithons, when only a few were previously known (Goskar et al., 2003; Abbot and Anderson-Whymark, 2012). More recently, the find of the first clearly prehistoric representations of animals in Kilmartin (Scotland), an emblematic region for rock art in Scotland, when Hamish Fenton quickly photographed the underside of the capstone of Dunchraigaig Cairn, and produced a 3D model revealing a group of unprecedented deer carvings (Fenton, 2021, but see Valdez-Tullett et al., 2022 for more details)1. Recent 3D modelling of other neighbouring monuments in the Bronze Age linear cemetery in Kilmartin, some of which bearing cists with decorated slabs, revealed new motifs and shed light on the biographies of the tombs, exposing superimpositions between axeheads and cupmarks at Nether Largie North cairn, highlighting phases of manufacture and modification (Watson and Bradley, 2021). Although these monuments have been known for decades, some of which excavated in the 19th century, the finding of new carvings due to the application of new technologies, demonstrates the importance of digital methods and suggests that more details can be revealed in the future, as technology evolves. Given the position of the carved stones within some of these monuments, the 3D models are the only way of clearly visualizing their decorations, without having to dismantle the structures.\n\nIn addition to the high-resolution outputs and the ‘pretty pictures’, digital surveys are enabling the capture of intricate and measurable datasets of rock art, which can then be used in complex analyses. The unprecedented level of detail provided by digital recordings is rekindling an interest in iconography, a component of rock art which was largely relegated in western rock art scholarly traditions, with the advent of Landscape Archaeology in the 1990s. Combined with landscape location, however, the motifs were certainly pivotal pieces of the messages that the rock art assemblages conveyed, and the two case studies described below – on Atlantic Rock Art and Schematic Paintings in Iberia – illustrate how multi-layered datasets can contribute decisively for the development of new research methodologies and a new understanding of relatively otherwise well-known rock art traditions.\n\nThere are three main strands of research regarding the application of digital technologies to rock art: a) the first one based on the technical application of recording and processing methods and their results (e.g. Montero-Ruiz et al., 1998; Mark and Billo, 2002; Goskar et al., 2003; Díaz-Andreu et al., 2005; Chandler et al., 2007; Fredlund and Sundstrom, 2007; Lerma et al., 2010; Abbot and Anderson-Whymark, 2012; Brady and Gunn, 2012; Díaz-Guardamino and Wheatley, 2013); b) a second group reflecting on the historiography of use of such methods (e.g. Díaz-Guardamino and Wheatley, 2013; David et al., 2015; Le Quellec et al., 2015; Robin, 2015; William and Shee, 2015; Sharpe, 2021) and finally, a more recent one, c) based on resulting datasets used to create new knowledge about rock art (e.g. Miles et al., 2013; Figueiredo, 2017; Jones and Díaz-Guardamino, 2019; Riris and Oliver, 2019; Horn et al., 2020, 2022; Valdez-Tullett, 2019, 2021; Valdez-Tullett et al., 2022; Watson and Bradley, 2021).\n\nThe first group comprises publications describing and comparing the application of specific methods and technologies to rock art recording. Robin mentions 90 references of articles and book chapters on ‘computer methods applied to the recording of various rock art contexts from around the globe’ in 2015, to which a greater number must be added, at the time of publication. The significant increase of publications on the subject is testament of the popularity of these methods, especially since the mid-2000s, from which point the diversity of techniques applied also increased. Whilst RTI and SfM are still the most commonly applied technologies, other approaches and combinations of methods are becoming commonplace (e.g. Miles et al., 2013; Vázquez Martínez et al., 2015; Horn et al., 2019; Papadopoulos et al., 2019; Peña-Villasenín et al., 2019; Carrero-Pazos et al., 2022). This group also comprises publications addressing the processing of 3D data, such as the manipulation of RTI visualizations (e.g. Díaz-Guardamino et al., 2015; Jones and Díaz-Guardamino, 2019) or the application of MeshLab’s Radiance Scaling filter (Vergne et al., 2010), one of the most popular rendering options for rock art visualization due to its potential to clearly and easily enhance depth variations, concavities and convexities across a 3D model (e.g. Vázquez Martínez et al., 2015; Peña-Villasenín et al., 2019; Valdez-Tullett, 2019; Mark and Billo, 2021).\n\nPhotograph, 3D model and rendering by Joana Valdez-Tullett.\n\nDigital datasets are dynamic, leading researchers to experiment with a range of techniques, which may not necessarily be typical of rock art research. Topographic landscape analysis techniques, such as those available in GIS for LiDAR processing and visualization, have been applied to 3D models of prehistoric carvings, resulting in high-resolution images with well-defined depth differences, which are useful to highlight chronological and spatial relationships between the motifs (e.g. Lymer, 2015; Carrero-Pazos et al., 2016; Horn et al., 2019; Valdez-Tullett et al., 2022). This growing multidisciplinarity of rock art research is leading to more complex approaches and in the last 10 years, some projects have experimented with machine learning and computer vision, such as the 3d-PITOTI pilot project in Valcamonica (Italy) (e.g. Poier et al., 2016, 2017; Seidl, 2016; Zeppelzauer et al., 2015; Zeppelzauer et al., 2016) and in Scandinavia (Horn et al., 2021; Horn et al., 2022). Developments with the use of machine learning in rock art classification have recently been explored more systematically in Scandinavia, leading researchers to question common notions of typology. Interestingly, artificial intelligence has also shown to be able to open new perspectives on motifs, even when stemming from misinterpretations of the algorithms, allowing for improvement of typologies and new avenues for interpretation. While machine learning provides new ways of addressing and augmenting data, however, Horn et al. agree that ‘there is no way we are able to interpret human-created material without a human view’ (Horn et al., 2022).\n\nMost publications which fit this first group discuss digital technologies and results produced by each method, often with little reflection on potential biases and pitfalls. Nevertheless, unlike the general trend within Digital Archaeology, rock art researchers have felt the need to consider in more depth the use and impact of digital methods, with such publications constituting the second abovementioned group. Partly, this is a reaction to the lack of guidelines in analogue recordings which led to a multiplicity of methods and reproductions of panels, whose lack of standardization failed to convey relevant information and produce satisfactory graphics, hindering rock art research. Moreover, the diversity of available documentation methods triggered the need to compare, contrast and reflect on their application, in search of accuracy and a much-needed scientific rigour to rock art studies (e.g. Domingo-Sanz, 2014).\n\nThe critical engagement of rock art researchers with their digital recording methods and the evolution of their thoughts is clear in the organization of dedicated events, two of which took place in 2014. Earlier that year Guillaume Robin ran the ‘Documenting prehistoric parietal art: recently developed digital recording techniques’ workshop at the University of Cambridge, focusing on methodologies, multi-scalar approaches and data processing for archaeological analysis and interpretation, resulting in an important edited volume (Robin, 2015). Later that year, a session organized by Joana Valdez-Tullett, Marta Díaz-Guardamino and Guillaume Robin for the Theoretical Archaeology Group (TAG) conference in Manchester, was concerned with the unwarranted ‘recording-approach’ of rock art sites and decorated artefacts prompted by the democratization of digital technologies, generating innumerable datasets worldwide but which, notwithstanding the ‘pretty pictures’, had a limited contribution in the advancement of research questions. The abstract of the session stated that presentations would ‘discuss how these innovative technologies can be used to, not only reproduce images, but also contribute to their interpretation, meet research goals and solve complex archaeological problems’. Similar issues were raised by Sara Perry and James Taylor in 2016 in the session ‘Theorising the Digital’ at the CAA conference (2018). Nevertheless, introspective publications are still not that common.\n\nThe last group mentioned above refers to the use of datasets created with the application of digital technologies, to develop innovate and pioneering rock art research. Digital models have enabled researchers to address old questions, for example the confirmation that superimpositions do exist in Atlantic Rock Art, until recently thought to be absent from this tradition, or reinforcing the idea that natural features are important parts of compositions, by clearly highlighting this relationship (e.g. Jones et al., 2011; Valdez-Tullett, 2019). The accuracy with which archaeologists can now investigate carved and painted surfaces has revealed new artistic practices and processes of manufacture, shedding light on the biographies of rock art, bringing it to central discussions of prehistory (e.g. Miles et al., 2013; Diaz-Guardamino et al., 2015; Figueiredo, 2017; Valdez-Tullett, 2019). In addition, the very detailed, and more rigorous, data capture with digital methods can easily be used in qualitative and quantitative analyses, increasing the pace of research, now beginning to be more often based on scientific methodologies. These robust datasets are pushing agendas forward and being studied with a range of computational applications such as spatial, qualitative and quantitative statistics (e.g. Figueiredo, 2017; Rodríguez-Rellán et al., 2018; Riris and Oliver, 2019; Valdez-Tullett, 2019), Agent-Based-Modelling (ABM) (e.g. Bjerketvedt et al., in prep.), network science (e.g. Riris and Oliver, 2019; Valdez-Tullett, 2019) and machine learning (e.g. Horn et al., 2021; Horn et al., 2022).\n\nThe new face of rock art research is veering away from the amateurism with which it has always been characterized (Sharpe, 2021), bringing it closer than ever to main strands of archaeological research, with rigorous and reproducible methodologies.\n\n3D model and rendering by Joana Valdez-Tullett. This 3D model shows various phases of carving, providing a sense of time depth to the composition. On some areas the surface of the rock was detached, and the new exposed surface was re-carved, with lines following those on the truncated motif, in an attempt to complete it. Other parts of the newly exposed rock surface where also decorated with motifs of similar grammar (3D model and rendering by Joana Valdez-Tullett). https://sketchfab.com/3d-models/kirkdale-house-4-f9c037034ecd4c66a1bc6ba30ed83592/embed.\n\nVisualization is an important part of rock art reproduction, pivotal for analysis and publication. For this reason, illustrations resulting from traditional recording methods present many issues. Highly subjective, they are constructs of individuals, highlighting their vision of what rock art and the media upon which it was created is about. Until recently, rock art reproductions were very heterogenous, with represented details depending on the judgement of the recorders. These could lead to the neglect of some details in determent of others, which can be pivotal for the interpretation of the panels, such as the relationship between motifs or taphonomic processes which may be reflected on the carvings and paintings. Although digital imaging is still partial, new methods eliminate a great part of this subjectivity. The resulting interactive models are now easy to share, annotate and manipulate, being open to the interpretation of each observer. Many 3D models, for example, are uploaded to online platforms such as Sketchfab, enabling others to view panels interactively and through a selected number of renderings, or to download them and explore them through other means. The versatility of digital technologies has expanded awareness of rock art and brought different publics closer to these prehistoric artistic manifestations, which can be explored through a multiplicity of dynamic systems from interactive 3D models to augmented and virtual reality (AR/VR). These approaches aim at exploring sensoriality and recreating the kind of interaction that people in the past would have with the objects, provide further understanding on their materiality and processes of fabrication (Papadopoulos et al., 2019).\n\nThe production of 3D models of carved outcrops and boulders enables a better understanding of the micro-topography of the rock surfaces, providing a sense of texture, absent in 2D reproductions. (3D model and rendering by Joana Valdez-Tullett). https://sketchfab.com/3d-models/pepperpot-white-wells-ilkley-moor-129ac9811a6a4e19b88c78b6065e0183/embed.\n\nDespite advances with digital recording methods and the added value of interactive models, publications remain fairly traditional, with only a few journals allowing for the display of interactive features. As such, publications do not take full advantage of the resources afforded by digital recording methods, and most articles are still illustrated with static images. Nevertheless, these are now more refined, high-resolution and visually relevant. These images have important repercussions, since they can be more confidently used by other researchers, who are then able to develop further investigations. As the FAIR2 principles (e.g. Wilkinson et al., 2016) gain terrain in archaeology, many projects decide to make their data and metadata available and accessible to others, who can replicate and re-use them in other contexts, a process that is pivotal for research progress.\n\nInitiatives of public and community engagement in archaeology are increasing, with shouts to ‘counteract alienation, & shallow, passive consumption’ (Moshenska, 2004: 97) of heritage, placing researchers and communities in a more equal position (e.g. Marshall, 2009; Jones et al., 2017). The benefits of active community engagement for enhancing social value of archaeology and heritage have long been acknowledged (e.g. Smith & Waterton, 2009). In this context, digital heritage emerges as a tool to connect communities with heritage research and vice-versa, with the potential to build cooperative relationships. Between 2004 and 2008 the Northumberland and Durham Rock Art Pilot (NADRAP) in England pioneered a volunteer-led project, combining data collection and rock art recording, while promoting public participation and access to heritage (Sharpe, 2021). While photogrammetry was part of the methodology, technology at the time was not particularly well-developed or user-friendly and resulting 3D models were poor in quality and resolution, except for those which were laser scanned by specialists. The project was replicated in 2010, this time in West Yorkshire (England), under the guise of the Carved Stone Investigations: Rombalds Moor (CSIRM) project (Sharpe, 2021). More than 1000 3D models for these projects can found online in Sketchfab, a platform maintained by Richard Stroud, a former volunteer. These experiences, in which digital methods were involved and used by volunteers, albeit incipiently, inspired other projects which benefitted from the development of the technology and user-friendly technical approaches. The ACCORD (Archaeology Community Co-Production of Research Data) project in Scotland, saw community groups work together with researchers to explore pre-existing relationships with heritage places, ranging from rock art to rock-climbing venues, while digitally recording them with RTI and SfM (Jeffrey et al., 2017). Nevertheless, it was with Scotland’s Rock Art Project (ScRAP)3, that the benefits of digital recording in public engagement rock art related projects reached their peak. This community co-production project ran between 2017-2021, aiming to enhance understanding and awareness of Scotland’s prehistoric carvings and research. Working with 11 community teams, comprising over 200 people, who were trained in rock art fieldwork including RTI and SfM photogrammetry, the project resulted in a comprehensive online database, comprising more than 3000 records of rock art, 1630 of which documented in situ by ScRAP’s4 staff and/or volunteers. Besides the typical data capture of textual descriptions, sketches, photographs and spatial data, each record included the production of a 3D model, then made publicly available through Sketchfab. All the data was made available through the project’s website, regularly updated throughout the duration of the project, and still live at the time of writing5. Furthermore, the availability of rock art 3D models through open and online platforms, makes the sites more available than ever and more inclusive, since field visits often cannot accommodate for all. The consistency of ScRAP’s dataset was the foundation of the research carried out by project, which changed perspectives of prehistoric rock art in Scotland (Barnett et al., 2021). The model for community collaboration and research developed by ScRAP has potential to be implemented worldwide, and was the inspiration for Rock Art Scotland and South Africa Project (RASSA)6. Considering local geographical and social prerequisites, RASSA developed an active programme of public engagement, empowering low-income and marginalised communities to find and record their rock art heritage, using the low-cost DStretch mobile application.\n\nPhotograph by Joana Valdez-Tullett.\n\nDigital recording methods have provided new tools for conservation and heritage management, although there are only a limited number of studies on this topic for rock art (e.g. Darvill and Fernandes, 2014; Agnew et al., 2015; Loubser, 2017; Fernandes et al., 2022).\n\nRock art is a vulnerable type of heritage at heightened risk, given its location in the landscape, facing natural (e.g. weather, animals, vegetation) and human threats (e.g. increasing population, extensive and intrusive agricultural practices). Rock art conservation risks are worldwide, and in many cases the main problem is the lack of logistical and human capacity to regularly monitor the many thousands of known rock art sites. Just in the area of Kilmartin there are more than 200 carved rocks, most of them of small to medium size and difficult to locate. Even in protected areas such as the Côa Valley Park (Portugal), a UNESCO site, rock art protection is challenging. In 2017, a rare depiction of a Palaeolithic human was defaced with the addition of a bicycle and a stick person, which were etched over the prehistoric motif, causing irreversible damage to a thousands year old unique image.\n\nDigital Rock Art has the potential to offer comprehensive approaches to tackle the conservation and safeguard of rock art sites, from data recording, to management and semi-automatic monitoring (Barnett et al., 2005; Ruiz López et al., 2018). Detailed data capture, encapsulated in digital databases provide information for a better reconnaissance of rock art sites and an understanding of potential changes and assessment of threats over time, as well as ensuring the digital survival of heritage. In addition, through digital imaging and modelling or surveys created at different time intervals, experts are now able to screen more effectively any weathering effects or changes that may have affected the decorated rocks. Some archives hold old photographs which are now being processed with recent software to reproduce 3D models which, whilst not high-resolution, may provide an idea of the condition of panels decades ago. Recently, ScRAP was able to compare a newly created 3D model of the impressive carving of High Banks 4 (Kirkcudbright, Dumfries and Galloway), against a 3D model, created by Hugo Anderson-Whymark7, of concrete casts which were made of this outcrop in the 1890s, revealing subtle differences between the two. Of course, this kind of monitoring relies on digital datasets, whose digital preservation raises other specific issues, but which will not be discussed here (e.g. López-Menchero Bendicho et al., 2017).\n\nThe comparison between the two 3D models shows slight differences between the casts and the current condition of the rock art. https://sketchfab.com/3d-models/high-banks-neolithic-rock-art-casts-and-reality-9a6d47eda7974b8e8294f94b71d4ac67/embed.\n\nRock art preservation can also be achieved by having a reduced number of visitors, since many sites are now available and can be ‘visited’ remotely through digital platforms, in the comfort of our homes. Equally, open-access, high-resolution models raise confidence in rock art reproductions and therefore panels do not need to be recorded so often, and be subject to several rounds of cleaning, etc, which may have a potential effect on the motifs and preservation of the rock surfaces.\n\nDigital Archaeology opens other avenues for rock art safeguarding, as exemplified by the Rock Art CARE project, who developed a free mobile app, to facilitate an accessible monitoring system of sites, while engaging with the general public (Mazel and Giesen, 2019). Through the mobile app, visitors in the north of England can download a map with the location of the rock art sites in the area, but also log the conditions of the carvings and if there are any conservation concerns. Indeed, raising awareness of rock art may well be the best strategy for its future preservation.\n\n\nMoving Rock Art research forward\n\nThis paper aimed to demonstrate that, when applied critically, and preferably as part of a multi-sensorial and multi-scalar methodology, 3D technology can provide new insights into rock art biographies and bring us closer to their makers. The following case studies illustrate how the use of digital technologies and resulting datasets inspired creative methodologies which are producing ground-breaking new knowledge.\n\nAtlantic Rock Art is a carving tradition mostly known for its circular iconography including cupmarks (small circular hollows dug onto the rock surface) and cup-and-rings (cupmarks surrounded by carvings of one or multiple circles). These motifs have been created, in open air boulders and outcrops, during the 4th and 3rd millennium BC (at least) across wide landscapes in European countries such as Britain, Ireland, Portugal and Spain. This type of rock art was firstly identified in the 19th century and since then many theories have emerged to explain the geometric motifs and their widespread distribution, which was initially highlighted when Irish scholar Eóin MacWhite compared the iconography of the carved outcrops in Galicia with those in Ireland (MacWhite, 1951). Atlantic Rock Art was the focus of Richard Bradley’s research which, as seen, resulted in an important turning point for rock art studies in general, with the introduction of Landscape Archaeology theory and methods (e.g. Bradley, 1997). However, this new paradigm largely overlooked the study of motifs, then stigmatized for being Culture History’s main focus, and consequently overshadowed by the emerging interest in rock art’s locational patterns.\n\nPhotograph by Joana Valdez-Tullett.\n\nEngaging with new theoretical paradigms of New Materialism and Assemblage Theory, Valdez-Tullett recently built on some of Bradley’s premises on connectivity, and developed a multi-scalar relational methodology to study Atlantic Rock Art across five study areas in different countries: Monte Faro (Valença, Portugal), Barbanza Peninsula (Galicia, Spain), Ilkley Moor (Yorkshire, England), Machars Peninsula (Dumfries and Galloway, Scotland) and Iveragh Peninsula (Co. Kerry, Ireland). A dataset comprising 263 carved rocks were analysed according to three scales of analysis, each deconstructed in a number of variables that characterize Atlantic Rock Art. A Graphic Scale (small) of analysis focused on the motifs (i.e. morphology, carving techniques); a Sensorial Scale (medium) of analysis on the rock media, the motif compositions and the relationships between the two (i.e. micro-topography, texture, colour, inter-relationship of the motifs and relationships of the carvings with the rock surface); and finally an Environmental Scale (large) of analysis discussed the relationship between the location of the rock art and the wider landscape in which it sits (i.e. position within the landscape, relationship with natural landmarks and other contemporary archaeological sites, visibility, mobility patterns, etc.). Data capture included spatial data and the digital recording of all carved panels with the production of high-resolution 3D models which provided very fine details of the rock art’s character. The use of digital recording methods and 3D modelling (i.e. high-resolution SfM photogrammetry and RTI) enabled the identification of 5039 individual motifs, which were classified according to an extensive categorical scheme. However, unlike previous typologies, this was a relational exercise which combined the motifs with other inter-connected elements of the rock art such as carving techniques, associated micro-topographic features of the rock surfaces, relationships between motifs, the surrounding landscape, other types of contemporary archaeological sites, audience experience, etc. The approach enabled the identification of processes of manufacture that had not been recognized before. For example, minute details in the motifs’ morphology were identified in the five case studies simultaneously, suggesting that the wide distribution of the rock art resulted from intentional teaching facilitated by an extensive systematic network of exchange and cultural transmission in place during the Neolithic (Valdez-Tullett, 2019). These details on the making of rock art were crossed with results of spatial and statistical analysis for a better understanding of locational patterns. These analyses were also used to confirm or dispel long lasting assumptions of Atlantic Rock Art, such as its relationship with routeways or extensive visibilities, resulting from uncritical approaches and the direct transposition of Bradley’s conclusions to other geographic regions, often with very little supporting evidence.\n\nRTI and rendering by Joana Valdez-Tullett.\n\nPhotograph, 3D model and rendering by Joana Valdez-Tullett.\n\nValdez-Tullett pioneered the use of network science methods to the study of rock art. This approach enabled an effective relational analysis of all the components of Atlantic Rock Art, described and recorded at all scales, and a dynamic assessment of a complex dataset. While Atlantic Rock Art was perceived as a homogenous tradition given the standardized character of the motifs and its use in open landscapes across western Europe, this in-depth analysis composed of different inter-related elements, allowed for the identification of significant regional preferences, albeit more obvious in the small details. Notwithstanding the fine variations, it is clear that Atlantic Rock Art was part of a system of beliefs common to distant communities. A concept that was important enough to be adopted and adapted by each society in different points of the Atlantic, who recreated it according to their own preferences, determined by their cultural and social views (Valdez-Tullett, 2019, 2021). Valdez-Tullett’s approach was the first systematic study to effectively demonstrate Atlantic prehistoric connectivity and networks of exchange through rock art. This research was successful in placing the creation of Atlantic Rock Art in the context of the Neolithic period, tying it with other contemporary practices, and bringing the tradition into mainstream discussions and current narratives of European prehistory (see Valdez-Tullett, 2019, 2021).\n\nNeolithic Schematic rock paintings can be found across an extensive territory from the Iberian Peninsula to Italian Piedmont (e.g. Defrasne et al., 2019). In Iberia, this rock art tradition was firstly recognized in the beginning of the 20th century with the discovery of Roca de los Moros in the Cogul caves complex in Cataluña (Spain) (Rocafort, 1908; Cabré, 1915). Schematic paintings can be found across most of Iberia, with notable concentrations in the Spanish regions of Jaén, Cádiz, Alicante and Salamanca (e.g. Sanchidrián, 2005), and the Portuguese region of Trás-os-Montes.\n\nIn Iberia, the terms ‘Schematic Rock Art’ and ‘Schematic Paintings’ are unhelpfully widely used to designate any motifs which do not fall within other well established prehistoric artistic traditions. However, their classical meaning refers to parietal paintings, produced between the local Neolithic and the Late Chalcolithic (6000-2000 BC). The iconography is rather schematized, characterized by a simplification of shapes devoid of realism (Figueiredo, 2015, 2017). The motifs are mostly representations of humans and animals, as well as geometric and abstract figures. These are typically created with red pigments, but images can also be found in black, yellow or white colours. Schematic paintings were generally created in shelters and overhangs in secluded and conspicuous places of the landscape. This rock art tradition has often been interpreted as highly symbolic, lacking any realistic or naturalist characteristics, being instead reduced to schemas (Figueiredo, 2017).\n\nPrevious sections have mentioned that rock paintings were at the forefront of the development of Digital Archaeology, namely with imaging enhancement techniques. Schematic Art played an important role in this new approach to recording in Iberia. In 2017, a study by Figueiredo was published with results of an investigation carried out between 2007 and 2013, focusing on the Schematic Paintings of northeast Portugal. It featured data gathered from 26 rock art sites, comprising 77 panels and 500 individual painted motifs. Digital photography, artificial lighting and diffusers were used to document the paintings, overcoming limitations imposed by weather conditions and enabling an effective control over the recording environment. All files were obtained in \"RAW\" format, thus making the record as wide and flexible as possible for digital editing and image analysis. The images were subsequently processed with two digital enhancement methods. In Serra de Passos (Mirandela, Bragança) the use of DStretch enabled the identification of new painted panels in well-known sites, as well as a more accurate re-classification of motifs. For example, panel A of Shelter 1 of Regato das Bouças had been described for decades as bearing representations of bars and dots (Sanches, 1997:266), but the new digital approach revealed that in reality it had two sets of bars and an idol, a typical motif of the Chalcolithic period (Figueiredo, 2017). Idols are widespread figures in the Iberian Peninsula at this time, commonly represented in a two-dimensional (rock art, ceramics) and three-dimensional (stone, bone, ceramics) way. They bear anthropomorphic features, and the prominent depiction of their wide eyes is particularly defining of their type. In Serra de Passos, we find complex anthropomorphic idols with the representation of the body, but also other more typical idols, only featuring a face or mask, often with wide eyes (e.g. Bueno-Ramirez and Soler-Díaz, 2020). This reinterpretation of the motifs is highly significant and places the site in a specific cultural and chronological context. In Cachão da Rapa (Carrazeda de Ansiães, Bragança) the application of image decorrelation techniques using the software package HyperCube (Rogerio-Candelera et al., 2013) revealed striking differences from previous reproductions of the paintings. While the available published tracings described 63 painted motifs of schematic style, after the image analysis a much richer and complex panel was uncovered, with the discovery of new figures and superimpositions, previously invisible to the naked eye (Rogerio-Candelera et al., 2013; Figueiredo, 2017).\n\nPhotograph by Sofia Figueiredo-Persson.\n\nThe Chalcolithic idol is at the centre of the image, with its eyes - a distinctive feature - outlined above the red circular mark. Photograph and DStretch rendering by Sofia Figueiredo-Persson.\n\nThe data captured throughout the project was organized according to a set of variables and three levels of analysis: the painted motifs, the panels (whether in shelters or overhangs), their location in the rock media, and the rocks in the landscape. The dataset was used to develop the first comprehensive statistical study of schematic painted rock art in Iberia (Figueiredo, 2017). The analysis of Correlation Coefficients enabled the establishment of two different groups of paintings, distinctive in terms of chronology, represented motifs, rock media and landscape locations, corresponding to the vision of two different prehistoric communities. The first group dated to the Neolithic and comprised a small number of motifs composed mostly of simple human figures and animals such as deer, but also some examples of geometric imagery such as bars, grids and ramiforms (i.e. figures resembling tree branches, usually depicted with a vertical line and small parallel diagonal lines on both sides). These sites are typically found in small valleys and near watercourses. A second group of paintings dated to the Chalcolithic, had an increased number of motifs and a repertoire composed of human figures, and geometric and abstract images which now became more complex. The latter expanded significantly in number at the expense of animal representations, which tend to disappear. These sites are now found in mountains or hilltops.\n\nFigueiredo-Persson’s approach moved beyond the static analysis of the images and the micro-context of the paintings (i.e. a shelter or an overhang), and was successful in the articulation of a number of variables that, when studied relationally, offered a renewed glimpse of Schematic painting and its place within Iberian Neolithic and Chalcolithic societies.\n\n\nConclusion\n\nThis article presented the concept of Digital Rock Art, based on the prevalence of digital practices in current rock art research. It has mused on the role of digital technologies within archaeology and rock art studies, briefly referring to the impact of the former in the latter, while focusing on recording methods. Clearly, the introduction of digital technologies, whether 3D or imaging analysis and enhancement, have revolutionized rock art research, not only resulting in more accurate and less biased ‘pretty pictures’, but creating new tools for analysis and interpretation.\n\nThe democratization of digital technologies has led to a generalized application of various methods to rock art documentation, management and research. The array of available digital resources has significantly changed the course of rock art studies, being a ‘catalyst for innovation’ (Beale and Reilly, 2017). However, there is a need to reflect on this stark shift in rock art research practices, considering the benefits, but also potential consequences.\n\nRecording methods are the more noticeable facet of Digital Rock Art. Contrasting the practicalities of traditional documentation with new digital technologies, clearly highlights the benefits of the latter. Ultimately, analogue methods are highly dependent on human judgement, making them subjective and ambiguous. It is clear that digital recording methods are excellent for rock art documentation, and it is not surprising that traditional techniques were largely abandoned in face of the rapid development of digital technologies, associated equipment and software. Documenting rock art has become easier and less time consuming in all its phases, from the field to the lab. In addition, digital methods are largely non-invasive, when compared to traditional processes, and are therefore preferred in the context of rock art preservation.\n\nAlthough the use of digital technologies and methods in the recording, processing and analysis of rock art aims to establish a more scientific approach, devoid of subjectivity, the result is still a construct, or what Papadopoulos et al. designated of ‘sensorial assemblage’ (Papadopoulos et al., 2019). An entanglement of interactions between the study objects, the observations, the tools used, and the outputs, a relational process of which the observer is also part of, introducing their personal context and biases to the process, as well as their sensorial and affective experiences (as in Barad, 2007; but see also Beale and Reilly, 2017; Papadopoulos et al., 2019; Opgenhaffen, 2021). Nevertheless, the lack of sensorial experiences attached to digital recording methods is one of the issues of these approaches. While analogue recording methods typically require a deeper bodily engagement with the panels, making the recorder more sensorially aware of the study object and its characteristics (e.g texture, colour, dimension of things, temperature), digital modelling promotes a sense of distance and separation between observer and the study object, limiting this experience (Huggett, 2015; Jeffrey, 2018; Papadopoulos et al., 2019). Visualizations are not a satisfactory substitute for direct, embodied experiences (Jeffrey, 2018). As such, Papadopoulos et al. have argued that the ideal solution is an approach combining a range of techniques which ‘despite the vision-centre basis have the potential to advance discussion on sensoriality by foregrounding 3D properties and evoking corporeality, multisensorial and kinaesthetic affective experiences’ (Papadopoulos et al., 2019:3). The authors of this paper suggest that research should not depend solely on digital images, as useful as they may be, but instead should be undertaken through a combination of in situ observations, sketches on a notebook, photographs, 3D models and other digital images processed with various methods, providing a more comprehensive picture of the rock art and enabling more detailed interpretations.\n\nThe intensity with which digital technologies have taken over rock art research, particularly regarding recording, is partly due to the potential that these methods offer in the reproduction of more accurate models, which are more tightly controlled and less subjective than analogue alternatives. They enable the multi-scalar digital and 3D documentation of rock art - from very fine details of the motifs to the rock medium upon which they were created, and the landscape where they are located – and therefore datasets that are suitable for more comprehensive and holistic approaches. Rock art reproductions have never been so accurate. More precise methods, which produce extensive, detailed and measurable datasets bring rock art investigation closer to the scientific rigour that is expected of archaeological work (Domingo-Sanz, 2014). The new facet of rock art research, largely promoted by the introduction of more scientific approaches facilitated by digital technologies, have been contributing to a detachment of rock art with its reputation of amateurism. This is an important transformation in the perception of rock art, slowly changing in the eyes of the wider archaeological community. It contributes decisively to bring rock art to mainstream discussions, a plea that has been made decades ago by Richard Bradley (1997). Hopefully, rock art will no longer feature only the covers of books, but will in the future be effectively incorporated into their pages, weaved in narratives of past societies. Indeed, rock art was an important feature of the past, otherwise it would not have been replicated in hundreds and thousands of outcrops, boulders, caves and shelters across vast landscapes, and therefore it should be included in mainstream and current discussions.\n\nIn summary, this paper contemplated the use of Digital Rock Art, aiming to emphasise the importance of understanding techniques, how and why to apply them to meet specific objectives and the need to theorize and reflect upon their use, steering away from what Huggett called ‘technological fetishism’ (Huggett, 2004) and the production of mere ‘pretty pictures’.\n\n\nAuthor contributions\n\nJoana Valdez-Tullett and Sofia Figueiredo Persson are responsible for the conceptualization, evolution and overarching research goals and aims of their individual research projects which feature this article as the case studies. They were responsible for the development of the methodologies, the application of any digital recording methods as well as statistical, computational and formal techniques to analyse the data. Both projects were funded by the Portuguese Foundation for Science and Technology (FCT) as doctoral grants.\n\nInitial draft was written by Joana Valdez-Tullett. Article was revised by Sofia Figueiredo and Andy Valdez-Tullett.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nAcknowledgements\n\nThe authors are indebted to the Portuguese Foundation for Science and Technology for funding their doctoral research projects. We are also grateful to the F1000Research team to invite us to contribute to the New Digital Archaeologies collection, and covering our open access fees. Finally, we would like to thank Andy Valdez-Tullett for reviewing an early draft of this paper.\n\n\nReferences\n\nAbbot M, Anderson-Whymark H: Stonehenge Laser Scan Archaeological Report. English Heritage. 2012; 32: 1–71.\n\nAdkins L, Adkins RA: Archaeological Illustration. Cambridge: Cambridge University Press; 1989.\n\nAgnew N, Deacon J, Hall N, et al.: Rock Art: a cultural treasure at risk. 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Manag. Archaeol. 2019; 21(3): 160–183. Publisher Full Text\n\nMiles J, Pitts M, Pagi H, et al.: Photogrammetry and RTI Survey of Hoak Hakananai’a Easter Island Statue. Across Space and Time: Papers from the 41st Conference on Computer Applications and Quantitative Methods in Archaeology. 2013; pp. 144–155.\n\nMontero-Ruiz I, Rodrígurz Alcalde ÁL, Vincent García JM, et al.: Técnicas digitales para la elaboración de calcos de Arte Rupestre. Trab. Prehist. 1998; 55(1): 155–169. Publisher Full Text\n\nMontero-Ruiz I, Rodríguez Alcalde AL, e Cruz Berrocal, M.: Técnicas Analíticas Baseadas en el Proceso de Imágenes Digitales Multiespectrales. In Ana Rosa Cruz e Luiz Oosterbeek (coord.), Arte Pré-Histórica Europeia- O Método, ARKEOS: Perspectivas em diálogo. n. 7. , CEIPHAR, Tomar; 2000; pp. 13–34.\n\nMorgan C, Eve S: DIY and Digital Archaeology: what are you doing to participate? World Archarol. 2012; 44(4): 521–537. Publisher Full Text\n\nMorgan C, Wright H: Pencils and Pixels: Drawing and Digital Media in archaeological Field Recording. J. Field Archaeol. 2018; 43(2): 136–151. Publisher Full Text\n\nMorris R: The Prehistoric Rock Art of Galloway and the Isle of Man.Poole, Dorset: Blandford Press; 1979.\n\nMoser S: The visual language of archaeology: a case-study of the Neanderthals. Antiquity. 1992; 66: 831–844. Publisher Full Text\n\nMoser S: Making Expert Knowledge through the Image: Connections between Antiquarian and Early Modern Scientific Illustration. Isis. 2014; 105(1): 58–99. PubMed Abstract | Publisher Full Text\n\nMoshenska G: The archaeological uncanny. Publ. Arch. 2004; 5: 91–99.\n\nMudge M, Malzbender T, Schroer C, et al.: New Reflection Transformation Imaging Methods for Rock Art and Multiple-Viewpoint Display. The 7th International Symposium on Virtual Reality Archaeology and Cultural Heritage VAST2006. 2006; pp. 195–202.\n\nMuzquiz Pérez-Seoane M, Saura Ramos PA: El facsímil del techo de los bisontes de Altamira.Lasheras Corruchaga JA, editor. Redescubrir Altamira. Madrid: Turner; 2003; pp. 219–242.\n\nNeedham A, Wisher I, Langley A, et al.: Art by firelight? Using experimental and digital techniques to explore Magdalenian engraved plaquette use at Montastruc (France). PLoS One. 2022; 17(4): e0266146. PubMed Abstract | Publisher Full Text | Free Full Text\n\nO’Connor B: Inscribed landscapes: contextualising prehistoric rock art in Ireland. 2 vols. PhD Thesis submitted to University College Dublin. 2006.\n\nOlsen B: In defence of things.Plymouth: Altamira Press; 2010.\n\nOpgenhaffen L: Tradition in transition: Technology and change in archaeological visualisation practice. Open Archaeol. 2021; 7: 1685–1708. Publisher Full Text\n\nPapadopoulos C, Hamilakis Y, Kyparissi-Apostolika N, et al.: Digital Sensoriality: the Neolithic Figurines from Koutroulou Magoula, Greece. Camb. Archaeol. J. 2019; 29(4): 625–652. Publisher Full Text\n\nPeña-Villasenín S, Gil-Docampo M, Ortiz-Sanz J: Professional SfM and TLS vc s simple SfM photogrammetry for 3D modelling of rock art and radiance scaling shading in engraving detection. J. Cult. Herit. 2019; 37: 238–246. Publisher Full Text\n\nPerry S, Taylor J: Theorising the Digital: A call to Action for the Archaeological Community.Matsumoto M, Uleberg E, editors. Oceans of Data: Proceedings of the 44th conference on Computer Applications and Quantitative Methods in Archaeology. Oxford: Archaeopress; 2018; pp. 11–22.\n\nPetrie WMF:Methods and aims in Archaeology.London: Macmillan & Co; 1904.\n\nPiggott S: Archaeological draughtsmanship: Principles and practice part I: Principles and retrospect. Antiquity. 1965; 39(155): 165–176. Publisher Full Text\n\nPiggott S: Antiquity Depicted: Aspects of archaeological illustration.London: Thames and Hudson; 1978.\n\nPires H, Lima P, Pereira LB: Novos métodos de registo digital de arte rupestre: digitalização tridimensional e fotografia multispectral. Actas das Jornadas Raianas. 2010; 2009.\n\nPoier G, Seidl M, Zeppelzauer M, et al.: PetroSurf3D: A high-resolution 3D dataset of rock art for surface segmentation. arXiv preprint.2016.\n\nPoier G, Seidl M, Zeppelzauer M, et al.: The 3D-Pitoti dataset. In ACM (Ed.), The 15th International Workshop, Florence, Italy, 19.06.2017 (pp. 1–7, ICPS). The Association for Computing Machinery; 2017. Publisher Full Text\n\nPotter R, Horn C, Meijer E: Bringing it all together: a multi-method evaluation of Tanum 247:1. Dan. J. Archaeol. 2022; 11: 1–12. Publisher Full Text\n\nQuesada-Martinez E: Aplicación DStretch del software Image-J. Avance de resultados en el Arte Rupestre de la Región de Murcia. Cuadernos de Arte Rupestre. 2008; 5: 14–47.\n\nQuesada E, Harman J: A step further in rock art digital enhancements. DStretch on Gigapixel imaging. Digital Applications in Archaeology and Cultural. Heritage. 2019; 13: e00098.\n\nRabinowitz A: The work of archaeology in the age of digital surrogacy.Olson B, Caraher W, editors. Visions of Substance: 3D imaging in Mediterranean Archaeology. Grand Forks (ND): The Digital Press at the University of North Dakota; 2015; pp. 27–42.\n\nRip MR: Colour space transformation for the enhancement of rock art images by computer. Rock Art Res. 1989; 6(1): 12–14.\n\nRiris P, Oliver J: Patterns of Style, Diversity, and Similarity in Middle Orinoco Rock Art Assemblages. Arts. 2019; 8: 48. Publisher Full Text\n\nRocafort: Les pintures rupestres de Cogul. Bulletí del Centre Excursionista de Catalunya. 1908; 158: 65–73.\n\nRobin G: Editorial. Digital Applications in Archaeology and Cultural Heritage. 2015; 2(2–3): 35–40. Publisher Full Text\n\nRogerio-Candelera M: Digital image analysis based study, recording, and protection of painted rock art. Some Iberian experiences. Digit. Appl. Archaeol. Cult. Heritage.2015; 2: 68–78.\n\nRodríguez-Rellán C, Vázquez-Martínez A, Fábregas-Valcarce R: Cifras e imágenes: una aproximacióm cuantitative a los petoglifos Gallegos. Trab. Prehist. 2018; 75(1): 109–127. Publisher Full Text\n\nRogerio-Candelera MA, Figueiredo SS, Borges AF: Cachão da Rapa prehistoric rock art paintings revisited: digital image analysis approach for the assessment of Santos Júnior’s tracings.Rogerio Candelera MA, Lazzari M, Cano E, editors. Science and Technology for the Conservation of Cultural Heritage. London: CRC Press; 2013; pp. 261–264.\n\nRuiz-López JF, Quesada Martínez E, Pereira Uzal JM: Diagnosis and monitoring of rock art sites in “4D arte rupestre” projects. Les Nouvelles de l’archéologie. 2018; 154: 63–68. Publisher Full Text\n\nSanches MJ: Pré-história recente de Trás-os-Montes e Alto douro (O abrigo do Buraco da Pala no Contexto Regional).Porto: Sociedade Portuguesa de Antropologia e Etnologia; 1997.\n\nSanchidrián JL: Manual de Arte Prehistorico. Barcelona: Ariel Prehistoria; 2005.\n\nSapirstein P, Murray S: Establishing Best Practices for Photogrammetric Recording During Archaeological Fieldwork. J. Field Archaeol. 2017; 41(4): 337–350.\n\nSeidl M: Computational analysis of petroglyphs. PhD thesis submitted to the Technische Universität Wien, Vienna.2016.\n\nSharpe K: Documenting English rock art: a review of the ‘big picture’.Hey G, Frodham P, editors. New Light on the Neolithic of Northern England. Oxford: Oxbow Books; 2021; pp. 73–81.\n\nShee Twohig E: The Megalithic Art of Western Europe.Oxford: Clarendon Press; 1981.\n\nSkoglund P, Persson T, Cabak Rédei A: A Multisensory Approach to Rock Art: Exploring Tactile and Visual Dimensions in the Southern Scandinavian Rock Art Tradition. Proceedings of the Prehistoric Society. 2020; 86: 95–110. Publisher Full Text\n\nSmith L, Waterton E: Heritage, Communities and Archaeology.London: Duckworth; 2009.\n\nSwogger J: Image and interpretation: the tyranny of representation?Hodder I, editor. Towards Reflexive Method in Archaeology: the example of Ćatalhöyük. Cambridge: McDonald Institute for Archaeological Researcher; 2000; pp. 143–152.\n\nThibault G: Modélisation 3-D de la grotte Cosquer par relevé laser. International Newsletter on Rock Art. 2001; 28: 25–29.\n\nValdez-Tullett J: Design and Connectivity: The Case of Atlantic Rock Art.Oxford: BAR Publishing; 2019.\n\nValdez-Tullett J: An integrated methodology for the study of Atlantic Rock Art. Quat. Int. 2021; 572: 139–150. Publisher Full Text\n\nValdez-Tullett J, Barnett T, Robin G, et al.: Revealing the earliest animal carvings in Scotland: the Dunchraigaig Deer, Kilmartin. Camb. Archaeol. J. 2022; 1–27. Publisher Full Text\n\nvan Hoek M : Morris’ Prehistoric Rock Art of Galloway.Privately Published; 1995.\n\nVázquez-Martínez A, Vilas-Estevez B, Carreo-Pazos M: Sobre as Tecnicas de Reproducion dos Gravados Rupestres Galaicos ao Aire Libre. Fervedes.2015; 8: 17–24.\n\nVergne T, Pacanowski R, Barla P, et al.: Improving Shape Depiction under Arbitrary Rendering. IEEE Trans. Vis. Comput. Graph. 2010; 17(8): 1071–1081.\n\nWatson A, Bradley R: A New Study of the Decorated Cists in Kilmartin Glen, Argyll, Scotland. Proceedings of the Prehistoric Society. 2021; 87: 219–230. Publisher Full Text\n\nWilkinson MD, et al.: The FAIR Guiding Principles for scientific data management stewardship. Scientific Data. 2016; 3: 160018. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWilliams K, Shee Twohig E: From sketchbook to structure from motion: Recording prehistoric carvings in Ireland. Digital Applications in Archaeology and Cultural Heritage. 2015; 2(2-3): 120–131. Publisher Full Text\n\nZeppelzauer M, Poier G, Seidl M, et al.: Interactive segmentation of rock-art in high-resolution 3D reconstructions. Digital Heritage – IEEE. 2015; 2: 37–44.\n\nZeppelzauer M, Poier G, Seidl M, et al.: Interactive 3D segmentation of rock-art by enhanced depth maps and gradient preserving regularization. J. Comput. Cult. Herit. 2016; 9(4): 1–30. Publisher Full Text\n\n\nFootnotes\n\n1 A 3D model of these carvings, created by Historic Environment Scotland, can be viewed on Sketchfab: https://sketchfab.com/3d-models/dunchraigaig-cairn-rock-art-untextured-view-4a275e4335fb43a68a0449724b61334e.\n\n2 Findability, Accessibility, Interoperability, Reusability (FAIR).\n\n3 A project funded by the UK's Arts and Humanities Research Council (AHRC) and hosted by Historic Environment Scotland, in collaboration with the University of Edinburgh and the School of Simulation and Visualization of the Glasgow School of Arts.\n\n4 For which Joana Valdez-Tullett was the Post-doctoral Researcher.\n\n5 www.rockart.scot\n\n6 A partnership between the University of Edinburgh, the University of Witwatersrand and ScRAP.\n\n7 National Museum of Scotland."
}
|
[
{
"id": "174848",
"date": "19 Jul 2023",
"name": "Eleni Kotoula",
"expertise": [
"Reviewer Expertise Digital heritage",
"digital research"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article provides insights into the use of digital recording techniques in rock art studies. As an introductory note, the authors highlight how different forms of visualization, from sketches and drawings to images and 3D models, have been used in the discipline historically, paying particular attention to the shift to digital archaeology approaches. Then the role of these techniques in fieldwork and a comparative discussion between digital and traditional approaches offers the opportunity for the author to reflect critically on the relevant literature. The categorization of research into three groups; techniques and applications (1), historiography (2) and data/new knowledge generation (3) is particularly interesting and sets the scene for the two case studies included in this paper. Issues around visualization, publications, preservation and heritage management are also mentioned, offering a holistic approach to all the different dimensions of rock art studies methodological approaches. A critique, really well evidenced in the paper, is a large number of data generated and the relatively limited contribution to the advancement of research questions. The frameworks proposed in case studies partly address this issue. In their concluding remarks, the authors support the use of both conventional and digital approaches, which appears a good balance but raises a few questions about the planning of research projects and might be a challenging exercise for researchers and practitioners.\nIn the era of big data, there is a trend across disciplines and domains, as a result of the technological advancement in the field of data acquisition. Social media data, synthetic data or data extracted via web scraping are largely used in arts, humanities and social sciences. Archaeology, and rock art in particular for the context of this paper, is another depiction of this phenomenon. It might be worth addressing this. Another suggestion is the addition of references to the software beyond Agisoft available on the market, including freeware. Also, I strongly encourage authors to review whether stratigraphic approaches have been applied in rock art studies.\n\nThis paper is ideal for a reading group at postgraduate research level and beyond between aspiring digital archaeologists, since it highlights relevant literature and incorporates discussion on both practice and research, an excellent brief summary of digital methods applied so far, and a wonderful opportunity for workshop style framework evaluation. It prompts so many crucial questions!\nExpanding the proposed frameworks might be an exciting project for future consideration.\nI am not in a position to reflect critically on specific rock art traditions, due to my limited experience on this.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Not applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Yes",
"responses": []
},
{
"id": "193693",
"date": "09 Aug 2023",
"name": "Sven Ouzman",
"expertise": [
"Reviewer Expertise Archaeology",
"Rock Art",
"Heritage",
"Indigneous Knowledge",
"Museums",
"Contemporary Archaeology",
"Graffiti",
"Homelessness"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary\n\nThank you for the opportunity to review this interesting and consequential manuscript. I think it should be published - paying attention to the comments and suggestions below. Primarily, my suggestions are around a more effective structure – integrating the two case studies at the end into the main body of the article; by considering more closely concepts of ‘accuracy’, and non-visual data. I enjoyed the section on conservation and some visualisations here would be great, and also on ‘democratisation’ but the authors may want to consider how ‘democratisation’ is not yet universal and indeed, that the digital sometimes encroaches on people’s data and other sovereignty. Also, a bit more explicit theory on how recordings are governed by the aims of that recording as well as by the very instruments we use. The paper does come across as quite Euro-centric – and could be rescoped as a paper on European rock art – but this does mean some European issues are universalised; especially with regard to covering the history of rock art recording and state of digital recording. The conclusion could be developed to include how rock art recording could be a vehicle for integration with other archaeologies. In any event, a very productive and enjoyable read on a great job of summarising the state of digital rock art research, thank you.\nIf I have misread anything or been unfair, please do get in touch and we can chat.\nResearch article Criteria Is the work clearly and accurately presented and does it cite the current literature? - Mostly Is the study design appropriate and does the work have academic merit? - Yes Are sufficient details of methods and analysis provided to allow replication by others? - N/A If applicable, is the statistical analysis and its interpretation appropriate? - N/A Are all the source data underlying the results available to ensure full reproducibility? - No Are the conclusions drawn adequately supported by the results? - Mostly\nStructure and Content\nBody and case studies: The segue from the literature survey and overview of digital rock art recording and the two case studies is quite abrupt. It would be good if in the intro the authors provide reasons for why the two case study areas were chosen with respect to digital recording, provide a map early on of where the case studies are – and also of the images up to Figure 14, which may or may not be from those case study areas. Figure 16 comes rather late and should be more clearly annotated with the names of the two case study regions. Indeed, rather have one map rather than a map each for the case studies, as the two maps are quite different in scale, representational conventions. Alternatively – and probably more effectively - mix the end case studies within the lit review section, with a short intro to each and then explain how a particular digital recording furthered particular regional project aims. The ’connectivity’ enabled by the first case study doesn’t have a supporting visualisation of work, for example. Ditto the second case study’s association with watercourses. A third option is just to have this as review article, without the case studies (or without them as separate sections). As a final suggestion – neither case study mentions dating and a sentence or two on broad temporal context would be useful.\n\nGaps\nRock art: There are some gaps in the coverage of the historical use of the term ‘rock art’ and variants – such as Taçon and Chippindale 19981; and Rosenfeld 19992. It would be very useful to quote a series of definitions of ‘rock art’ over the last 100 years or so to chart our understanding of the term. A Table here could do the job and be very effective.\n\nRecording methods early 18th and 19th century recordings are said the be ‘flat’, yet often the pencil and ink sketches and lithographs display a volume and 3D-ness that later analogue scientific recordings lack. So, it is not a case of recordings techniques improving at a steady rate; it is much more variable. See also Hodder’s classic ‘Site reports in context’ for the immediacy of some earlier writings/sketchings3.\n\nHistory of recording methods makes universal statements but is restricted to Europe and does not include work like Pat Vinnicombe’s that did record cracks, colour etc. – as did Harald Pager’s both in southern Africa; the Frobenius expeditions to various parts of the world – and interesting gendered nature of rock art recordings they did. So maybe make clearer it is a history of European rock art recording techniques. No references for machine learning are provided – Jalandoni et al. 2022 would be a useful addition4.\n\nIntellectual (and cultural property): In an age of big and small data it is vital to consider also the IP, ICIP and cultural safety associated with rock art recordings and who is authorised to access and use these. In some parts of the world, strict protocols on recording and using what we call ‘images’ are in place – especially where Indigenous groups work with archaeologists. So, a section on this would be very useful, indeed, essential, a sit will vary across the world but is something all practitioners need to be aware of. Here a discussion of law and ethics would really add to the utility of this article, especially where it talks about the lack of standardisation and approaches – a clear gap in the field open to abuse or simply bad practice. Discussion of the FAIR principles – just a few sentences – would address this gap. Finally, some thoughts on long-term data storage and sovereignty here are needed – we go to a large expense in time, effort, resources on digital models, but how durable and transferrable will they be? IP can both democratise – and threaten sovereignty.\n\nOnly visual? The assertion that archaeology and rock art are ‘inherently visual’ is not incorrect and there is good critical exploration of how understanding visuality advances our knowledge and in pointing out the under-theorisaion of the ‘digital turn’ - but there is a school that deals with non-visual uses (e.g. Ouzman 20015, and the corpus on sound produced by Margarita Díaz-Andreu’s team), which are equally useful and a valuable check and balance to ocularcentrism which may exclude rock art recordings from recording non-visual criteria/aspects/data. The authors do mention the ‘sensorial’ engagement digital recording allows, so this could be signalled earlier and then built on.\n\nDemocratic? The ‘democratic’ nature of digital technologies is valid with regards to recording per se, but displays a certain privilege by not considering how digital technologies can be beyond the finances and capabilities of scholars who work in less well-resourced environments. Yes, costs have come down, but access is not yet universal. On the plus side, many digital technologies serve to engage Indigenous and other stakeholders in the archaeological process, increasing involvement, awareness and the like.\n\nDefinitions: It would be useful to have a definition of ‘digital archaeology’ and, indeed, ‘rock art’ to chart where our current understanding of these terms are, and in this article. ‘Accuracy’ also needs to be defined.\n\nLandscape? Mention is made of how digital recording helps situate rock art in a wider physical topography – but the recordings shown are all of just the rock art - and some examples of how landscape can be incorporated/visualised would be very useful. One step would be to have a map showing where the sites recorded and reported on in this project are (most readers won’t know where the two rock art study regions are with any precision), another step would be visualisations of rock art in landscape.\nReasoning\nWhat is ‘accuracy’? I think it would be useful to have a section on ‘accuracy’. No single method is a priori more or less accurate than another – it depends on what research questions, conservation imperatives, stakeholder wishes etc are being addressed. More variables, digital or analogue, do not necessarily make for a more ‘accurate’ recording – indeed, they may obscure detail. All recordings are made with certain goals in mind (be they implicit or explicit), and how these affect what is and is not recorded. So there can be no universally valid recording – though some are certainly more widely applicable than others. Possibly a Table listing the things typically captured by Digital and Analogue means, side-by-side would effectively portray the reach and limitations of each approach. Human bias is mentioned in ‘digital rock art recording’ but not developed; but it is really the need to articulate that what we do and how we do it is not neutral and universal, but pre-determined by what we want to know. In this vein it would also be very useful at the end for the authors to give their thoughts on where rock art recording will go into he future, especially to integrate it with other archaeologies. Here some Actor Network Theory could be useful in showing awareness that it is not just humans selecting recording tools, but a recursive relationship between the two exists.\nImages:\nPlacement? These are mostly good but not always placed optimally. For example, Figure 4 would seem to need to come earlier when Morris and van Hoek’s copies are being discussed. The text also has no reference to figures in it, making the association of images with specific text difficult or uncertain.\n\nComparisons? Also, there is definitely scope for more comparative pics comparing say a phot/sketch of rock art, with a digital rendering. Or even one rock art, with 3 or more different copyings. Figure 6 is a good example though calibrating left and right hand images is a bit difficult. Figs 20 and 21 could be combined to increase effective visual ‘reading’.\n\nScales? Some of the digital renderings lack scales – e.g. Figs 8, 9, 11, 14, 17. Others, like Figs 10, 12, 18 have a scale bar but do no say what the scale/increments is/are.\nOther\n\nPrehistoric? I know this is normal in European archaeology but the term ‘prehistoric’ is less-and-less used because of it’s privileging of history. As a decolonial practice it would be useful to dispense with this term. It will also remove confusion about the applicability of digital archaeology, to all rock art. Especially in cases where a site has palimpsests from different time periods.\n\nFixity? Not all ‘rock art’ is fixed in the landscape – consider mobiliary art, for example (or is this not included in the authors’ understanding of ‘rock art’; though it is mentioned in ‘Recording Methods’)? Also, the motif may be fixed but the constituent ingredients for paintings and even the tools for engraving, may come from some distance away.\n\nI know I suggest Tables a lot – but a Table listing the main digital recording methods currently used, how they work, and their strong and weak points would be very useful for the reader to have ‘at-a-glance’.\n\nThe observations about rock art’s marginality within archaeology is only partly true. In many parts of the world – Australia, southern Africa, it does not hold and huge strides are being made in South and Meso America, for example. So perhaps gloss this as more a European and North American circumstance.\nCongratulations to the authors and I look forward to reading the final article. If any of the above is unclear I would be happy to discuss.\nReferences\nHodder, I. (1989). Writing archaeology: Site reports in context. Antiquity, 63(239), 268-274. doi:10.1017/S0003598X00075980\nJalandoni, Y Zhang, NA Zaidi – 2022. On the use of Machine Learning methods in rock art research with application to automatic painted rock art identification Journal of Archaeological Science.\nOuzman, S. 2001. Seeing is deceiving: rock-art and the non-visual. World Archaeology, 33(2), 237-256. https://doi.org/10.1080/00438240120079271\nRosenfeld, A. 1999 Rock art and rock markings. Australian Archaeology 49:28–33.\n\nTaçon, P. S. C. & Chippindale, C., 1998. An Archaeology of rock-art through informed methods and formal methods. In: P. S. C. Taçon & C. Chippindale, eds. The Archaeology of Rock-Art. Cambridge: Cambridge University Press, pp. 1-10.\n\nYours sincerely\nSven Ouzman Archaeologist and Heritage Specialist School of Social Sciences\n\n• M257, Perth WA 6009 Australia\n\n+61 8 6488 2863 • +61 49 793 8486 • sven.ouzman@uwa.edu.au\n\nW Archaeology & Centre for Rock Art Research + Management\n\nORCID\n\nhttp://orcid.org/0000-0002-9379-2996\n\nSenior Fellow\n\nHigher Education Academy Research Fellow\n\nUWA Africa Research + Engagement Centre Research Associate\n\nAnthropology & Archaeology, University of South Africa, Archaeology,\n\nIziko Museums of South Africa, Rock Art Research Institute,\n\nUniversity of the Witwatersrand\n\nI pay my respects and acknowledgements to all traditional custodians on whose land I live, work and travel, in Australia and overseas\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Not applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Yes\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Partly",
"responses": []
},
{
"id": "189126",
"date": "14 Sep 2024",
"name": "Iñaki Intxaurbe",
"expertise": [
"Reviewer Expertise Rock Art",
"Digital Methodologies",
"Palaeolithic",
"Cave Geomorphology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe work presented by the researchers Joana Valdez-Tullett and Sofia Figueiredo Persson presents an interesting debate and reflection on what the intrusion of what some have called \"digital humanities\" has meant, a set of interdisciplinary approaches that encompass the use of new documentation techniques and data analysis, in the field of rock art research (of which they also make an interesting point regarding its definition).\nThe article focuses on two specific cases, more linked to the study of rock art from Holocene chronology.\nIn my opinion, the article deserves to be approved with some changes that should be considered by the authors.\nAccording to the \"ARTICLE GUIDELINES\" of the journal, in 15th point, referring to “figures and tables”, it states that \"All figures and tables should be cited and discussed in the article text\".\nIn this sense, I address the authors to comply with this point, adding the references to the figures within the main text, so that it can be followed in an orderly and more understandable way.\nOn the other hand, on page 7, they cite an article by Aujoulat et al., 2005 to refer to “Early laser scan surveys applied to rock art were firstly carried out in a small cave in the Beune Valley (France)”. I require authors to add the name of the cave (Vielmouly) in their sentence, as it is important to know which site they are talking about. I would also add that this test was subsequently used in the famous Chauvet Cave, since as the authors they cite point out, “Dans ce contexte particulier de Chauvet-Pont-d'Arc, les conditions de conservation des sols archéologiques impliquent une déambulation limitée aux secteurs équipés de passerelles métalliques. Cette contrainte met de nombreux panneaux hors de portée de l'observateur. L'approche 3D favorise, dans une très large mesure, l'enregistrement de ces témoignages en contournant cette difficulté suite à une restitution de l'image telle qu'elle peut apparaître dans des conditions normales d'observation” (Aujoulat et al., 2005).\nAlso, I find the title of “Case study 2: Schematic Art, a Neolithic painting tradition” shocking, since the same authors argue the presence of Neolithic schematic art in the base, under the Chalcolithic rock art motifs. So, I would put “Holocene painting tradition” or something similar.\nFinally, there are a series of publications that I think may be interesting to complete this debate, so I encourage the authors to consider including them in their work.\nThe first two could be included in the third paragraph of the section “Digital recording methods” on page 7, mentioning the case they occupy (petroglyphs and caves).\nDespite the fact that the authors cite a couple of articles by these researchers, I miss this reference, since it deals with the same subject (and uses the same techniques) that the researchers use as one of the example cases in their discussion (rock art Atlantic, although in this case they attribute it to the Bronze Age):\nCarrero-Pazos, M., et al., 2018 (Ref 1)\nI think that the particular case of the documentation of fine incised lines in deep caves deserves a mention in this article that deals with \"Digital Rock Art\":\nRivero, O., et al., 2019 (Ref 2)\nIn this sense, two other cases could enrich the mentions of the use of new documentation and study techniques. All these works could be cited in the first paragraph of the section “Digital Rock Art is here to stay” on page 10.\nGIS, and particularly the case of caves, three-dimensionally complex environments, and therefore exceptional in the discipline of rock art study:\nIntxaurbe, I., et al., 2022 (Ref 3)\nGIS in the open air, to understand the situation of the “macro-schematic” style in Iberian levant, according to their visibility and acoustic features:\nGarcía Atiénzar, G., et al., 2022 (Ref 4)\nGIS for the realization of predictive models that help locate rock art in caves:\nGarate, D., et al., 2020 (Ref 5)\nGIS for the realization of predictive models that help locate rock art in the open air:\nAubry, T., et al., 2012 (Ref 6)\nVirtual reality in caves with rock art:\nWisher, I., et al., 2023 (Ref 7)\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Not applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-523
|
https://f1000research.com/articles/12-521/v1
|
19 May 23
|
{
"type": "Clinical Practice Article",
"title": "Successful use of conjunctival flaps to prolong survival of type I keratoprosthesis in severe bilateral chemical burns: two case reports",
"authors": [
"Sheetal Mahuvakar",
"Neha Jain",
"Sayan Basu",
"Sheetal Mahuvakar",
"Neha Jain"
],
"abstract": "Introduction: This report describes the use of conjunctival flaps to enable the survival of type I keratoprosthesis (KPro) in two cases of bilateral severe total limbal stem cell deficiency (LSCD) following chemical burns. Presentation of case: Two patients had a history of bilateral chemical injury with lime. On examination, the presenting vision was light perception to hand motions and both cases had conjunctivalized ocular surfaces with symblepharon. A modified technique of type I keratoprosthesis was used, where the conjunctivalized corneal pannus was dissected and lifted off as an inferior fornix-based conjunctival flap. This was followed by a standard surgical technique of type I KPro. The flap was then secured over the device and optical opening was made two weeks later. Both the patients had stable ocular surfaces with visual acuity of 20/20 at 2–7 years of follow-up. Discussion: In patients with total LSCD with adnexal involvement, type I KPro has unsatisfactory long-term survival because of the risk of repeated epithelial breakdowns and stromal ulceration. With the innovative approach described in this report, type I KPro can be successfully used for sustainable visual improvement in the presence of severe ocular surface disease and symblepharon. Conclusion: Conjunctival flaps can be used along with type I KPros to improve long-term survival and give sustainable visual outcomes in cases of bilateral corneal blindness due to advanced ocular surface damage.",
"keywords": [
"Chemical injury",
"Bilateral limbal stem cell deficiency",
"Keratoprosthesis",
"Type I keratoprosthesis"
],
"content": "Introduction\n\nA keratoprosthesis (KPro), or artificial corneal prosthesis, is preferred for visual rehabilitation in total limbal stem cell deficiency (LSCD) and corneal opacification, where penetrating corneal grafts are unlikely to survive long term due to the presence of extensive stromal vascularization, and poor ocular surface.1–3 The type I KPro is used in wet eyes with normal lid anatomy and blink function.4 With continuous modification in the structure of the type I device, complications like retro-prosthetic membrane, extrusion, etc. have reduced especially for non-immune etiology.2,5 To prevent recurrent epithelial breakdown over the donor corneal graft and sterile corneal necrosis, a soft bandage contact lens (BCL) is placed after the KPro surgery.6,7 In patients with dry eyes, abnormal lid function, extensive keratinization or symblepharon, such as in Stevens-Johnson syndrome (SJS), mucous membrane pemphigoid (MMP) or severe ocular burns where the risk of corneal graft melt is high or it is difficult to retain a BCL, a more complicated type II KPro needs to be performed.4,5 Thus, to overcome the limitations of a type I KPro in severe ocular surface disease and avoid the need for a type II KPro, we describe a new approach of type I KPro in two cases of chemical injury sequelae with bilateral total LSCD with corneal pannus and extensive ocular surface involvement. This report is as per the SCARE-2020 guidelines.8\n\n\nCase series\n\nA 26-year-old male student from the Indian north-east presented with a history of chemical injury with lime in both eyes one year ago. There was no relevant family history. An amniotic membrane grafting (AMG) with symblepharon release was done in both eyes at another hospital. At presentation, visual acuity was hand motions in both eyes. On examination, lid margin in both eyes were thickened with diffuse bulbar conjunctival congestion and 360 degree corneal conjunctivalization. In the right eye, symblephara were present superiorly and temporally. In the left eye, symblepharon were present temporally. A pyogenic granuloma was present at 1 o’clock with a descemetocele in the visual axis in the left eye. The rest of the anterior segment details could not be visualized. Both eyes had some wetness, but the Schirmer’s test was recorded as 5 mm of wetting at 5 minutes. Digital intra-ocular pressure (IOP) and B-scan was normal in both eyes. He was diagnosed with bilateral total LSCD with left eye descemetocele. A type I KPro implantation was planned for the right eye. Because of the severity of the ocular surface damage and the high risk of post-operative surface complications a different approach was taken.\n\nThe surgery was done under local anesthesia. Conjunctival peritomy was done superiorly. The conjunctivalized pannus covering the corneal surface was separated from the underlying adhesions by blunt dissection and lifted off the cornea as a single flap with an inferior hinge. Excess fibrovascular proliferation in the undersurface of the reflected flap was excised to make it thin. The host cornea was then trephined with 8.5 mm hand-held trephine and donor cornea with 9.0 mm hand-held trephine. Aurolab keratoprosthesis of +59.0 dioptre was assembled. the graft–host junction was sutured with 16 interrupted sutures with 9-0 nylon. The pannus was replaced back and secured into position with fibrin glue (Tisseel Kit, Baxter AG, Vienna, Austria).\n\nOn first post-operative day, mild lid edema was present along with diffuse conjunctival congestion. The anterior surface of the keratoprosthesis was covered by pannus. The patient was started on topical corticosteroid (prednisolone acetate 1%, 6 times per day), antibiotic (moxifloxacin 0.5%, 4 times per day), anti-glaucoma (timolol 0.5%, twice daily) eyedrops along with oral acetazolamide 250mg (once daily at bedtime). An opening in the conjunctival flap, just large enough to expose the underlying optical cylinder, was made 2 weeks later after which the vision improved to 20/50P. The keratoprosthesis was present in place and the ocular surface was stable. Fundus examination was normal. At last follow-up at 82 months, visual acuity in the right eye with −1.25D of spherical correction was 20/20. The ocular surface was stable with conjunctivalized corneal graft and keratoprosthesis in place (Figure 1, 2). Mild posterior capsular opacification was noted. Topical corticosteroids were continued along with topical antibiotic and anti-glaucoma eyedrop.\n\n(A) The right eye of the first patient with total limbal stem cell deficiency with granuloma over the cornea. Superior and inferior symblephara are present. Anterior segment cannot be visualized.\n\n(B) Left eye of the same patient with distichiasis and trichiasis in upper and lower lid. Granuloma is present in the central upper lid. Total limbal stem cell deficiency in present with extensive symblephara. (C) In the right eye, the area of accidental cut supero-nasally was meticulously sutured. The area has healed well with no defect.\n\n(D) Right eye of the first patient, 3 days after the central opening was made. The carrier graft is conjunctivalized. The keratoprosthesis is in place with clear visual axis. The peripheral iridotomy can be seen supero-nasally. (E) The left eye of the second patient. Symblephara are present temporally. Cornea in conjunctivalized completely with a descemetocele in the visual axis. Pyogenic granuloma is present at 1 o clock. The right eye of the patient had similar clinical features on presentation. (F) Right eye of the second patient at 15 months post-surgery. The keratoprosthesis is in place with the carrier graft well conjunctivalized. The ocular surface with healthy with no corneal melt. The visual axis is clear with mild posterior capsular opacification.\n\nA 45-year-old male carpenter from north India presented with a history of injury to both eyes with toilet cleaning solution two months ago. There was no relevant family history. He had undergone AMG twice at another hospital. At presentation he had total LSCD with persistent epithelial defects (PED) in both eyes for which AMG with tarsorrhaphy was repeated. Over 3 months, thick fibrotic pannus with granuloma covering cornea and symblepharon was noted in both eyes. Living-related allogeneic simple limbal epithelial transplantation (SLET) was done in the right eye which eventually failed. A Boston type I KPro was done for the left eye which later developed microbial keratitis due to which it had to be explanted.\n\nAfter 9 months, visual acuity was light perception with accurate projection of rays in both eyes. On slit lamp examination, both eyes had thickened lid margins and distichiasis. Both eyes had thick fibrotic pannus over the cornea, with superior and inferior symblepharon. A granuloma covering the cornea was present in the right eye (Figure 1). Both eyes were relatively wet. B-scan in both eyes had anechoic vitreous. He was planned for a type I aphakic KPro implantation in the right eye. However, with the hindsight of epithelial healing issues and infection in the left eye, and the encouraging outcome seen in the previous case, a decision to use a conjunctival flap was made.\n\nThe surgery was done under local anesthesia. The conjunctival flap was raised in a manner similar to the previous case, however there was an inadvertent buttonhole created supero-nasally. Host cornea was trephined with 8.75 mm hand-held trephine and removed. Open sky cataract extraction was performed leaving intact posterior capsule. Two peripheral button iridectomies were done in superior quadrant. Donor cornea was trephined with 9 mm hand-held trephine followed by central 3 mm trephination and Aurokpro was assembled. The graft–host junction was sutured with 16 interrupted sutures with 10-0 nylon. The pannus was replaced in its original position covering the whole ocular surface including KPro and sutured to episcleral tissue with 8-0 vicryl sutures. The inadvertent cut was also sutured meticulously.\n\nOn the first post-operative day, topical antibiotic (gatifloxacin 0.5%, 4 times per day) was started along with anti-glaucoma (timolol maleate + brimonidine tartarate, twice per day) eyedrops. Topical corticosteroids (prednisolone acetate 1%, 6 times per day) were started and tapered over 3 weeks to a maintenance dose of 3 times per day. An optical opening was made after 12 days following which the vision was 20/40. After 4 months vision dropped to 20/120. On examination, posterior capsular opacification was noted. On OCT, macular edema was seen. YAG capsulotomy was done along with sub-tenon’s triamcinolone acetanoid injection. At the last follow-up at 24 months, vision was 20/20. On examination, the KPro was noted to be in place and the ocular surface was stable. Resolution of macular edema was seen on OCT. Topical corticosteroid, antibiotic and anti-glaucoma eyedrop were continued.\n\n\nDiscussion\n\nIn cases with severe ocular surface disease and adnexal involvement, the risk of surface breakdown, peri-optical cylinder melting, and infection is high with the use of the type I KPro. It is also often difficult to retain the BCL because of symblephara and forniceal shortening, which further contributes to the threat of surface complications. These cases are more amenable to the type II KPro.4,5 However, the surgical procedure of the type II KPro is complex and carries many disadvantages like poor cosmesis, restricted visual fields, in addition to complications of type I KPro. A multidisciplinary team is required as vitrectomy and glaucoma surgery is done concurrently, restricting it’s availability at few centers worldwide.9,10 To overcome these disadvantages, the surgical technique of type I keratoprosthesis was modified to improve the survival in eyes with cicatrizing ocular surface disease that are prone to sterile corneal melting.\n\nThe use of conjunctival flaps in KPros in not new. Conjunctival flap was reported to be mobilized and positioned on the KPro followed with delayed opening.11–13 In another technique for patients with inferior fornix foreshortening, the superior tarsal and palpebral conjunctiva was mobilized to cover the KPro entirely and optical opening was made 3 months later. Although the KPro was retained on long-term follow-up, it predisposed the patients to develop ptosis due to advancement of forniceal tissue over the cornea.5 Conjunctival flap or oral mucous membrane graft has also been used to salvage an isolated area of device exposure.14,15 In all above techniques, the conjunctiva was freely mobile and could easily cover the device entirely.\n\nIn the present cases, along with total LSCD, ocular surface was extensively involved with conjunctival cicatrization, granuloma, and symblepharon. The above-mentioned techniques of conjunctival mobilization were not possible due to extensive adhesions as it would have been difficult to advance the conjunctiva to cover the device entirely. This report describes a novel way of using conjunctival coverage to overcome the possibility of sterile keratolysis and eliminate the need for BCL usage, while retaining the technical ease of implanting a type I KPro. The advantage is that it can be done in cases where symblepharon and fibrosis restricts the advancement of conjunctiva. Repositioning of the conjunctivalized corneal pannus over the KPro helps in faster conjunctivalization of the carrier graft, thus increasing the retention of the KPro and decreasing the probability of extrusion and corneal melt despite avoiding the use of a BCL. As lid anatomy is not distorted, there is no possibility of ptosis later. The surgery is comparatively simpler and less disfiguring, thus can have more widespread acceptability as well.\n\n\nConclusion\n\nIn chemical injury sequelae with ocular surface involvement, type I KPro implantation under the corneal pannus followed by creation of an optical opening, provides a stable ocular surface and sustainable visual recovery in the long-term.\n\n\nConsent\n\nWritten informed consent was obtained from the patients for publication of this case series and accompanying images.\n\n\nEthical approval\n\nEthics committee approval was not required for this manuscript because it is a clinical case report\n\n\nAuthor contribution\n\nStudy concept or design: SM, SYB\n\nWriting and revising the paper: SM, SYB, NJ\n\n\nResearch registration\n\nNot applicable",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nShanbhag SS, Saeed HN, Paschalis EI, et al.: Boston keratoprosthesis type 1 for limbal stem cell deficiency after severe chemical corneal injury: A systematic review. Ocul. Surf. 2018 Jul; 16(3): 272–281. PubMed Abstract | Publisher Full Text\n\nKoo EH, Hannush SB: Challenges in management of the Boston Keratoprosthesis Type 1. Curr. Opin. Ophthalmol. 2021; 32: 385–388. PubMed Abstract | Publisher Full Text\n\nSalvador-Culla B, Kolovou PE, Arzeno L, et al.: Boston Keratoprosthesis Type 1 in Chemical Burns. Cornea. 2016; 35: 911–916. PubMed Abstract | Publisher Full Text\n\nVazirani J, Mariappan I, Ramamurthy S, et al.: Surgical Management of Bilateral Limbal Stem Cell Deficiency. Ocul. Surf. 2016; 14: 350–364. Publisher Full Text\n\nEghrari AO, Ahmad S, Ramulu P, et al.: The Usage of a Conjunctival Flap to Improve Retention of Boston Type 1 Keratoprosthesis in Severe Ocular Surface Disease. Ocul. Immunol. Inflamm. 2016; 24: 555–560. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSejpal K, Yu F, Aldave AJ: The Boston keratoprosthesis in the management of corneal limbal stem cell deficiency. Cornea. 2011; 30: 1187–1194. PubMed Abstract | Publisher Full Text\n\nChew HF, Ayres BD, Hammersmith KM, et al.: Boston keratoprosthesis outcomes and complications. Cornea. 2009; 28: 989–996. Publisher Full Text\n\nAgha RA, Franchi T, Sohrabi C, et al.: The SCARE 2020 Guideline: Updating Consensus Surgical CAse REport (SCARE) Guidelines. International journal of surgery (London, England). 2020; 84: 226–230. PubMed Abstract | Publisher Full Text\n\nNanavaty MA, Avisar I, Lake DB, et al.: Management of skin retraction associated with Boston type II keratoprosthesis. Eye (Lond.). 2012; 26: 1384–1386. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGomaa A, Comyn O, Liu C: Keratoprostheses in clinical practice - a review. Clin. Exp. Ophthalmol. 2010; 38: 211–224. PubMed Abstract | Publisher Full Text\n\nAl-Merjan J, Sadeq NDC: Temporary tissue coverage in keratoprosthesis. Middle East J Ophthalmol. 2000; 12–18.\n\nGirard LJ, Moore CD, Soper JW, et al.: Prosthetosclerokeratoplasty-implantation of a keratoprosthesis using full-thickness onlay sclera and sliding conjunctival flap. Transactions - American Academy of Ophthalmology and Otolaryngology American Academy of Ophthalmology and Otolaryngology. 1969; 73: 936–961.\n\nDohlman CH, Jamal Al-Merjan NS: Total Conjunctival Flap in KPro Surgery. Boston KPro Newsletter.2016.\n\nAdesina OO, Vickery JA, Ferguson CL, et al.: Stromal melting associated with a cosmetic contact lens over a Boston keratoprosthesis: treatment with a conjunctival flap. Eye Contact Lens. 2013; 39: e4–e6. Publisher Full Text\n\nZiai S, Rootman DS, Slomovic AR, et al.: Oral buccal mucous membrane allograft with a corneal lamellar graft for the repair of Boston type 1 keratoprosthesis stromal melts. Cornea. 2013; 32: 1516–1519. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "183670",
"date": "27 Jul 2023",
"name": "Amit Raj",
"expertise": [
"Reviewer Expertise Ocular surface and Cornea and anterior segment"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nCongratulations to the authors for giving insight into the use of conjunctival flap in cases of type 1 Keratoprosthesis. Definitely, the procedure gives an added advantage of a more stable ocular surface with lesser surface-related complications; however, the absence of a flange/collar in the anterior-most part of the optic results in repeated conjunctival growth over the optic obscuring visual axis. This needs frequent excision of the overgrown conjunctiva. This complication can be overcome with designs of type 1 keratoprosthesis with an added flange/collar. The conjunctiva can be tucked in beneath this collar/flange with other advantages and ease of type 1 keratoprosthesis.\n\nIs the background of the cases’ history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the conclusion balanced and justified on the basis of the findings? Yes",
"responses": []
},
{
"id": "214602",
"date": "31 Oct 2023",
"name": "Jiaqi Chen",
"expertise": [
"Reviewer Expertise Cornea disease"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article reports the use of conjunctival flaps in patients with type I KPro implantation. This surgical procedure is useful and enables patients with symblepharon and forniceal shortening to receive a type I KPro, which is usually indicated for the type II KPro. In patient 2, the symblephron is comparatively modest from the images. One alternative method may be the symblepharon lysis and buccal mucosa implantation to reconstruct the ocular surface as we used before, which may ameliorate the blink-related microtrauma to the cornea and chronic inflammation (Zhang et al., 20201).\n\nIs the background of the cases’ history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the conclusion balanced and justified on the basis of the findings? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-521
|
https://f1000research.com/articles/12-520/v1
|
19 May 23
|
{
"type": "Data Note",
"title": "Dataset: A consolidated and harmonised Verbal Autopsy dataset from Health and Demographic Surveillance Sites in South Africa",
"authors": [
"Eilidh Cowan",
"Lucia D'Ambruoso",
"Jessica Price",
"Edward Fottrell",
"Kobus Herbst",
"Lucia D'Ambruoso",
"Jessica Price",
"Edward Fottrell",
"Kobus Herbst"
],
"abstract": "This data note provides details of the development of a Verbal Autopsy (VA) dataset produced with the South African Population Research Infrastructure Network (SAPRIN) drawing on datasets from health and socio-demographic surveillance sites’ (HDSS) ‘ covering a population of over 250,000 in two rural provinces in South Africa for the period 2012-2019. The purpose of the data set was to refine an analytical tool within VA, which provides unique information on care seeking and utilisation at and around the time of death complementary to that of medical cause of death. On an individual basis, the dataset includes demographic data, probable cause of death data, and data on care seeking and utilisation at or around the time of death drawn from longitudinal population cohorts. The purpose of this publication is to describe both the dataset and methods in formatting and processing the data for other researchers who may be interested in similar data. The data described in this paper are available to be requested from the respective HDSS repositories.",
"keywords": [
"South Africa",
"Verbal Autopsy",
"Cause of death",
"Circumstances of Mortality"
],
"content": "Introduction\n\nEvery year, the medical causes of approximately 30 million deaths, half of all deaths worldwide, are not formally registered1. These deaths occur predominantly in low- and middle-income countries where there is a lack of complete and functioning civil registration and vital statistics (CRVS) systems2. Verbal autopsy (VA) is currently the only realistic alternative to medical certification of deaths in settings where CRVS is incomplete or absent. VA is a pragmatic survey-based method in which trained fieldworkers gather information from final caregivers on signs and symptoms of the deceased prior to death. VA data are then interpreted, by physicians or computer models, to determine probable cause(s) of death3. The method is used to quantify levels and causes of death in otherwise unregistered populations. The World Health Organization (WHO) leads the development of international standards for VA.\n\nThis data note provides details of the development of a Verbal Autopsy dataset produced with the South African Population Research Infrastructure Network (SAPRIN) drawing on datasets from health and socio-demographic surveillance sites’ (HDSS. The purpose of the data set was to refine an analytical tool within VA, which provides unique information on care seeking and utilisation at and around the time of death complementary to that of medical cause of death.\n\nAcknowledging the social determinants of heath as the fundamental causes of avoidable mortality and health inequalities, we sought to develop a systematic and scalable categorization system for circumstantial drivers of deaths4. We previously devised an approach within VA tools called Circumstances of Mortality Categories (COMCAT)5. The system is designed for large scale population assessment of burden of disease inclusive of the needs and behaviours of individuals and the responsiveness of the health system towards these6. For example, a woman whose cause of death is assigned as obstetric haemorrhage might have died at home, while another woman with the same cause of death might have been inadequately managed despite reaching a facility. Measuring these scenarios at population level will provide important information for health services and reducing avoidable mortality.\n\nThe development of the COMCAT model began with the supplementation of existing interview questions on medical causes of death, to include input questions on care seeking and utilisation at and around the time of death, which were taken up in the 2012 WHO VA standard7. From this, models were developed within existing automated VA data interpretation tools to assign likelihoods to circumstantial categories for each death on: emergencies, recognition of illness severity, use of traditional medicine, accessing care, and perceptions of poor quality of care5.\n\nThis paper describes the collation and formatting of a mortality dataset from Health and Demographic Surveillance Sites (HDSS) in South Africa for use in refining the COMCAT system. HDSS are geographically defined populations that undergo continuous demographic monitoring. All vital events, such as births and deaths, are regularly recorded to track population change and highlight health and social care priorities8. The dataset harmonises and links routinely collected VA data from the South African Population Research Infrastructure Network (SAPRIN). SAPRIN is a national research infrastructure funded by the National Department of Science and Innovation that aims to harmonise and integrate South Africa’s HDSSs.\n\n\nMethods\n\nEach HDSS had a specific VA questionnaire that, since 2012, is broadly based on the WHO-2012 or WHO-2016 standard. VA data are collected electronically at household level by trained fieldworkers. Trained fieldworkers select responses to the questions from a specified set of answers, with logical skips and validation rules consistent with the WHO standard. Data quality control is carried out on al captured questionairres by specific HDSS team supervisors using either RedCap or Survey Solutions. We obtained all VA data, from the three HDSS’ included in the SAPRIN Network that had been collected on deaths that occurred from 2012 onwards. This was in order to increase the likelihood of inclusion of the COMCAT data, which were included in the WHO standard since 2012.\n\nAs each HDSS has a unique VA questionnaire, we aligned each of the HDSS’ questionnaires and potential responses to the WHO-2016 standard. As the VA interpretation tools are based on the WHO standard, in doing this we ensured the required indicators were available to utilise both a VA data formatting packages (PyCrossVA) and one of the automated VA interpretation tools to generate probable cause of death. A common data specification was developed that would retain maximum information but allow us to utilise one of the VA interpretation tools. VA interpretation tools use mathematical formulae, such as Bayes theorem, to calculate the probability of cause of death from a prior set of probabilities relating to input indicators, from the VA questionnaire9.\n\nAfter formation of the data specification, data were examined, as detailed above, to ensure the dataset included the indicators required to be processed in a VA interpretation tool to output both a reliable probable cause of death and COMCATs. A variety of additional indicators to the WHO standard had been included in the different sites’ questionnaires. These indicators were not included in the consolidated dataset as they are not required for the automated VA tool. However, individual case ID remained consistent throughout and these additional indicators could be included from the original dataset if of interest after the data had been processed by the VA interpretation tool. At this stage, we excluded one of the HDSSs, DIMAMO, as they did not have relevant data on the COMCAT input indicators. Data were then recoded and renamed in line with the newly developed data specification, this was done in pyCrossVA, a Python package (Python Programming Language, RRID:SCR_008394) developed to format VA data from WHO standard into the format for use in the desired VA interpretation tools. At this stage, we processed the data using the InterVA-5.1 interpretation tool in R 3.61 (R Project for Statistical Computing, RRID:SCR_001905). InterVA-5 was selected as this is currently the only tool that will output COMCATs, and refining these was the objective for the use of the data.\n\nAt all stages, data were processed individually by HDSS’. After the data had been processed through InterVA-5.1 we then added an additional variable of HDSS name to allow us to differentiate these by location before appending the two datasets. The final data set included records of 7980 deaths, 5924 and 2056 from Agincourt and AHRI HDSS respectively, for the period of 2012–19, and consisted of 25 variables detailing, basic demographics, probable cause of death, COMCAT and COMCAT input indicators.\n\nThe data were subject to consistency checks in InterVA-5.1. These are carried out before probable causes of death are determined for each individual death, where possible errors will be adjusted by InterVA-5.1 using other questions. These generate warning messages that can be interpreted by researchers. For example, a record of a male that has identified as pregnant will generate a warning message and, depending on the other information available, one of these inputs (i.e. male or pregnant) will be deemed an error and corrected by InterVA-5.1. Further to this, we excluded those aged over 100 years due to the unreliability of the data given the average life expectancy in the region.\n\n\nSoftware availibility\n\nSoftware packages used to both format and process VA data are all open source and are available from the following ‘https://github.com/verbal-autopsy-software’. These packages also contain functions to analyse VA data.\n\n\nData availability statement\n\nThe data described in this study cannot be made available to the public in an open repository due to the sensitive nature of the data. However, the data are available to be requested from SAPRIN or the respective HDSS repositories. Requests for the data can be made at the following link https://saprindata.samrc.ac.za/index.php/catalog/33.",
"appendix": "Acknowledgements\n\nThe authors acknowledge the South African Population Research Infrastructure Network (SAPRIN), the African Health Research Institute (AHRI) and the MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt) for their support. The authors gratefully acknowledge Chodwizadziwa Kabudula, Daniel Mahlangu, Dickman Gareta, Siyabonga Nxumalofrom and Joseph Tlouyamma from the Agincourt, AHRI and DIMAMO HDSSs who supported with data, and individuals who supported the development and maintenance of the OpenVA software.\n\n\nReferences\n\nSetel PW, Macfarlane SB, Szreter S, et al.: A scandal of invisibility: making everyone count by counting everyone. Lancet. 2007; 370(9598): 1569–1577. PubMed Abstract | Publisher Full Text\n\nMarinda E, Simbayi L, Zuma K, et al.: Towards achieving the 90-90-90 HIV targets: Results from the south African 2017 national HIV survey. BMC Public Health. 2020; 20(1): 1375. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBasera TJ, Schmitz K, Price J, et al.: Community surveillance and response to maternal and child deaths in low- and middle-income countries: A scoping review. PLoS One. 2021; 16(3): e0248143. PubMed Abstract | Publisher Full Text | Free Full Text\n\nD’Ambruoso L, Byass P, Qomariyah SN, et al.: A lost cause? Extending verbal autopsy to investigate biomedical and socio-cultural causes of maternal death in Burkina Faso and Indonesia. Soc Sci Med. 2010; 71(10): 1728–38. PubMed Abstract | Publisher Full Text\n\nHussain-Alkhateeb L, D'Ambruoso L, Tollman S, et al.: Enhancing the value of mortality data for health systems: adding Circumstances Of Mortality CATegories (COMCATs) to deaths investigated by verbal autopsy. Glob Health Action. 2019; 12(1): 1680068. PubMed Abstract | Publisher Full Text\n\nD’Ambruoso L: Care in obstetric emergencies : quality of care, access to care and participation in health in rural Indonesia. PhD Thesis University of Aberdeen. University of Aberdeen, Aberdeen, 2011.\n\nD’Ambruoso L, Kahn K, Wagner RG, et al.: Moving from medical to health systems classifications of deaths: extending verbal autopsy to collect information on the circumstances of mortality. Glob Health Res Policy. 2016; 1(1): 2. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKahn K, Tollman SM, Collinson MA, et al.: Research into health, population and social transitions in rural South Africa: Data and methods of the Agincourt health and demographic surveillance system. Scand J Public Health Suppl. 2007; 69: 8–20. PubMed Abstract | Publisher Full Text | Free Full Text\n\nInterVA - software for verbal autopsy. [Accessed: 09-Jul-2021]. Reference Source"
}
|
[
{
"id": "174908",
"date": "21 Jun 2023",
"name": "Tathagata Bhattacharjee",
"expertise": [
"Reviewer Expertise data integration",
"ETL",
"record linkage",
"data standardization",
"OMOP /OHDSI"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper brings out an important aspect for the need to prepare datasets for VA analysis. The method is crisply explained. However, sharing a sample anonymized dataset would have been more appreciated along with some sample code implementations for more clarity on the implementation which would help researchers to replicate or derive guidance on the processes in preparation of such datasets.\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
},
{
"id": "237763",
"date": "06 Feb 2024",
"name": "Bruno Masquelier",
"expertise": [
"Reviewer Expertise Demography",
"child and adult mortality estimation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI read this short article with interest, as it deals with an important subject. I agree with the authors on the importance of complementing traditional verbal autopsies with additional, standardized information on the circumstances surrounding death, regarding the social determinants of health and care-seeking. The COMCAT tool is a significant contribution in this respect. It is also important to acknowledge the heavy work done on standardizing and pooling together datasets from different HDSS. However, I don't quite see the point of this article specifically, as it doesn't provide results, it doesn't document a database in the public domain, and it doesn't specify how the consolidated database can be acquired, and under what conditions. The article looks more like a deliverable for a project, but the contribution to scientific literature is not obvious to me at this stage. I would invite the authors to provide a sample anonymized dataset, as suggested by another reviewer, or to detail the procedures required to access the dataset. More info on the variations in data quality or response rates across HDSS sites concerning the COMCAT questions would also strengthen the paper.\n\nMinor comments - In the introduction, the authors mention that the cause of death of 30 million deaths is not formally recorded in a CRVS system. But they base this assertion on a 2007 article by Setel and colleagues. I imagine the situation has changed over the past 15 years, and more recent estimates are available. - In the \"methods\" section, the authors mention additional indicators and indicate that they could be associated with this database based on individual IDs. Could you give some examples? - small typo=\"al captured questionnaires\"\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? No",
"responses": []
},
{
"id": "174907",
"date": "13 Sep 2024",
"name": "Tom Smith",
"expertise": [
"Reviewer Expertise Epidemiology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article provides a well written description of the rationale for the dataset. If anything, the importance of this is understated, since analysis of such dataset is crucial for understanding how to reduce mortality across the world.\nUnfortunately the authors do not actually provide the data, stating instead that \"the data are available to be requested from SAPRIN or the respective HDSS repositories\", a statement which the reader must take on trust.\nI noted a few minor typos:\n(HDSS should read (HDSS).\n\"The purpose of the data set was ... \" should be \"... is... \" I think.\nCitations should be provided for the software used (e.g. Red Cap)\n\nIs the rationale for creating the dataset(s) clearly described? Yes\n\nAre the protocols appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and materials provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-520
|
https://f1000research.com/articles/12-129/v1
|
02 Feb 23
|
{
"type": "Research Article",
"title": "Effect of vital bleaching on surface roughness and microhardness of nanofilled and nanohybrid composite resins",
"authors": [
"Anindita Chakraborty",
"Tina Puthen Purayil",
"Kishore Ginjupalli",
"Kalyana-Chakravarthy Pentapati",
"Neetha Shenoy",
"Anindita Chakraborty",
"Kishore Ginjupalli",
"Kalyana-Chakravarthy Pentapati",
"Neetha Shenoy"
],
"abstract": "Background: To compare the surface roughness and microhardness of Ceram.x® SphereTEC™ one and Filtek Z350 XT after in-office vital bleaching with Pola office. Methods: A total of 20 samples of 10 mm diameter and 2 mm height of Ceram.x® SphereTEC™ one and Filtek Z350 XT were prepared. The samples were subjected to two bleaching sessions with 35% hydrogen peroxide (Pola office) with a seven-day interval between each session. Surface roughness and microhardness of the prepared samples prior to and after the bleaching regimen were measured using a profilometer and Vickers hardness tester, respectively. Results: A significant reduction (p <0.001) in the surface hardness of Filtek Z350 XT from 26.67 ± 2.10 to 17.83 ± 1.36 Vickers hardness number (VHN) was observed after the bleaching whereas no significant reduction in surface hardness was observed with Ceram.x® SphereTEC™ one. However, in-office bleaching of these materials did not significantly alter their surface roughness. Conclusions: The effect of in-office bleaching on the surface hardness of resin composites seem to vary due to variations in the composition of dental composites such as filler loading. Among the composites tested, in office bleaching of Ceram.x® SphereTEC™ did not result in significant changes in its surface hardness and roughness.",
"keywords": [
"restorative resin",
"microhardness",
"surface roughness",
"in-office bleaching"
],
"content": "Introduction\n\nBleaching removes intrinsic and extrinsic stains from the dental tissues.1,2 Although the procedure is complex the vast majority work by oxidation, a chemical process that converts organic materials into carbon dioxide and water. The outcome depends on the concentration and the ability of the bleaching agent to reach the chromophore molecules coupled with duration and frequency of contact.\n\nDental bleaching can be either in-office (under clinical supervision) or at-home bleaching. Bleaching is effective in improving esthetics, but there has been a growing concern in the recent past on the effect of bleaching materials and techniques on existing restorative materials in the oral cavity. With ever-increasing demand for esthetics, there has been an increase in the use of direct esthetic restorative materials, especially dental composites. A dental composite restorative material mainly consists of a polymerizable resin matrix, reinforcing fillers, and a coupling agent that bonds resin with the fillers. The vast majority of dental composites are commercially available for clinical use mainly differ in terms of the resin matrix materials and the fillers used. The clinical performance of these materials significantly vary depending on the type, size, distribution, and concentration of fillers used in the composites.\n\nCeram.x® SphereTEC™ one (Dentsply, Konstanz, Germany) is a light-curable nanoceramic, radiopaque restorative material with a granulated filler technology (SphereTEC™). It consists of a blend of pre-polymerized fillers of a size equivalent to 15 μm, non-agglomerated glass of 0.6 μm, and Ytterbium fluoride of 0.6 μm. It has distinctive handling characteristics, natural-looking gloss, and effortless polishing. Its resin matrix consists of a reformed version of the polysiloxane comprising matrix from the original Ceram.x® mono+/duo+. It is combined with a well-established polyurethane methacrylate, bis-EMA, and TEGDMA to increase its mechanical strength.\n\nFiltek™ Z350 XT (3M, ESPE, St. Paul, USA) universal nanocomposite restorative is a light-activated composite designed for use in anterior and posterior restorations. The nanofillers consist of 20 nm silica and 4–11 nm zirconia, both in combination of non-agglomerated/non-aggregated and aggregated forms. The presence of nanofillers in agglomerated or clustered forms with a broad distribution in the size of the clusters permits higher filler loading as well as superior polishing ability and thus the esthetic characteristics. Both Ceram.x® SphereTEC™ one and Filtek™ Z350 XT contain fillers in the nanometer range; however, their particle size and distribution is different.\n\nMany studies have reported the action of bleaching agents on restorative materials.3–7 The observed changes after bleaching of composite resin materials are alterations in smoothness, hardness and reduction in bond strength.8,9 Such observed changes could be due to the differences in the concentration and type of bleaching agent used. In addition, compositional changes in composites in terms of the resin matrix, filler content, size, and distribution may also affect their susceptibility to bleaching.10 Hence, it is essential to investigate the effect of bleaching on the properties of composites, especially those with newer fillers. The use of hybrid composites as universal composites for anterior and posterior restoration is common during the regular dental practice. In this regard, the present study aimed to compare the surface roughness and microhardness of nanofilled and nanohybrid composite restorative materials subjected to in-office bleaching.\n\n\nMethods\n\nA customized split mold was used to fabricate twenty disc-shaped specimens of 10 mm diameter and 2 mm height of Ceram.x® SphereTEC™ one (Dentsply, Sirona) and Filtek Z350 XT (3M ESPE, St. Paul, USA). Table 1 summarizes information regarding the composition and manufacturers’ details of composite resin materials.\n\n\n\n• Spherical, prepolymerized SphereTEC™ fillers (d3,50 ≈ 15 μm)\n\n• Non-agglomerated barium glass (d3,50 ≈ 0.6 μm) and ytterbium fluoride (d3,50 ≈ 0.6 μm)\n\n\n\n• Non-aggregated 20 nm silica, 4–11 nm zirconia\n\n• Aggregated zirconia/silica clusters\n\nAfter the composite material was packed into the mold, mylar strip was used both on top and bottom surfaces to obtain a smooth surface on the composite. Subsequently, the composite material was cured for 20 seconds on both sides using a visible light curing unit (3M ESPE Elipar, St Paul, USA).\n\nThe prepared discs were subjected to in-office bleaching using 35% hydrogen peroxide (Pola office, SDI Limited, Australia) as per the manufacturer’s instructions. The procedure involved applying a bleaching agent two times with one-week interval between the applications. The bleaching protocol involved the application of a bleaching agent three times onto the surfaces of each disc for 15 mins. The discs were rinsed with distilled water for one minute between each application. After the bleaching process, all the discs were stored in distilled water.\n\nThe surface hardness of the discs before and after the bleaching was measured using the Vickers hardness testing machine (MMT X7, Matsuzawa Company, Japan). The specimens were mounted on a platform of the device, and a load of 200 g was applied for 30 seconds. The load was removed after dwell time, and the length of the diagonal of the indentation was measured. Three measurements of each sample were carried out and an average length of the indentation was used for the computation of hardness. The surface hardness was calculated by dividing the load by the area of the indention and was reported as Vickers hardness number (VHN).\n\nSurface roughness of the specimens pre- and post-bleaching was measured using a surface profilometer (Surtronics 3+, Taylor Hobson, UK). The samples were placed on a flat stable surface. The stylus of the profilometer was passed over the surface of the specimen perpendicularly to a distance of 0.8 mm. The experiment was carried out in triplicate on each disc, and average surface roughness, as Ra, was recorded in microns.\n\nAll the analyses were done using SPSS version 20 (RRID:SCR_019096). A p-value of < 0.05 was considered statistically significant. Normality was tested using the Kolmogorov Smirnov test. Comparison of mean surface roughness and microhardness before and after the bleaching was done using the Paired t-test. ANCOVA was used to evaluate the significant differences in the surface roughness and microhardness between the materials after adjusting the baseline values. Data for this study can be accessed at Mendeley Data.11\n\n\nResults\n\nThere was no significant difference in mean microhardness before and after bleaching (p = 0.954) in Ceram.x® SphereTEC™ one. However, Filtek Z350 XT showed a significant reduction in the surface hardness after bleaching (p < 0.001). There were no significant differences in the mean surface roughness before and after bleaching in both the composite resin materials (p = 0.153 and 0.199), respectively (Table 2).\n\n* Denotes statistically significant (p < 0.05), paired t test.\n\nANCOVA evaluated the difference in microhardness and surface roughness between Ceram.x® SphereTEC™ one and Filtek Z350 XT after bleaching while adjusting for before bleaching values. The adjusted mean (estimated marginal mean) microhardness after bleaching for Ceram.x® SphereTEC™ one (35.79 ± 1.45) was significantly higher than Filtek Z350 XT (19.538 ± 1.45) (p < 0.001). However, no significant difference in the adjusted mean (estimated marginal mean) surface roughness after bleaching was seen between Ceram.x® SphereTEC™ one (2.13 ± 0.2) and Filtek Z350 XT (2.5 ± 0.2) (p = 0.21).\n\n\nDiscussion\n\nThe main objective of the present study was to assess the effect of in-office bleaching on two nanohybrid composites with variations in filler size and loading. As the bleaching process generally affects the surface characteristics of dental composites, both surface roughness and microhardness of Ceram.x® SphereTEC™ one and Filtek Z350 XT were measured prior to and after bleaching using Pola office. The bleaching agent consisted of hydrogen peroxide/sodium perborate/carbamide peroxide that generally oxidizes the chromophores and improves the shade of the discolored tooth. Exposure of these bleaching materials can also potentially affect the existing restorative materials due to their strong oxidizing ability.\n\nSome of the previous investigations have reported an increase in microhardness of composites after bleaching treatment with carbamide peroxide.12 In contrast, other research studies have indicated a reduction in surface hardness.13 Our study did not show any significant changes in the microhardness and surface roughness concerning nanohybrid composite [Ceram.x® SphereTEC™ one] which was in accordance with previous reports.14,15 There was a significant reduction in microhardness of Filtek Z350 XT, whereas the surface roughness remained unaffected. These observations were in agreement with previous research.16 An increase in the surface roughness of restorative materials will facilitate the plaque accumulation on the surface thus affecting the esthetics.17 Similarly, a decrease in the surface hardness makes the material more vulnerable to wear during masticatory force application.18\n\nHydrogen peroxide tends to cause oxidation, thereby facilitating the generation of free radicals.19 The unreacted double bonds in the polymer resin are prone to oxidative cleavage by peroxides. The by-products of this reaction may bring about a reduction in microhardness. Moreover, the free radicals generated by the peroxides are capable of causing hydrolytic degradation of composite resin at the resin-filler interface, thereby paving the way for filler-matrix debonding, leading to microscopic cracks and thus increasing surface roughness.20\n\nCeram.x® SphereTEC™ has a high proportion of filler particles with advanced granulated filler technology. The nanohybrid composition with advanced filler technology ensures a higher filler loading and hence superior flexural strength, compressive strength, and low water sorption. Higher filler loading and reduced resin matrix content reduces the chance of resin matrix oxidation by hydrogen peroxide, making them resilient to acidic bleaching agents. On the other hand, resin composite Filtek Z350 is a nanoparticulated composite compounded by BisGMA, UDMA, BisEMA, and minor proportions of TEGDMA. The overall inorganic filler loading in these composites is about 72% by weight, which is less than Ceram.x® SphereTEC™ composites with an inorganic filler loading of 77–79% by weight. A low filler loading with a large resin matrix volume makes these composites more prone to oxidation or degradation by bleaching agents, hence a significant reduction in microhardness after bleaching.21\n\nFree radicals induced by peroxides may impact the resin–filler interface and cause a filler–matrix debonding.22 The microhardness of the composites is highly influenced by the amount and type of the inorganic fillers.23 Hence, a reduction in the surface microhardness for Filtek Z350 XT may be due to the inorganic filler loss on the surface. Ceram.x® SphereTEC™ one has pre-polymerized filler particles of non-agglomerated barium glass and ytterbium fluoride and a resin matrix with highly dispersed methacrylic polysiloxane nanoparticles that are chemically similar to glass or ceramics. Such filler composition is more resistant to abrasion and inorganic filler loss at the surface. Hence no significant changes in microhardness and surface roughness were observed.\n\n\nConclusions\n\nThe results of the present study indicate that the effect of in-office bleaching on dental composites vary significantly depending on the type of dental composite. Variations in the composition such as filler size and loading may alter their resistance to bleaching. Hence, the effect of the bleaching agent on the existing composite resin restorations must be considered at the time of selection of the bleaching agent and the regimen for clinical use.",
"appendix": "Data availability\n\nMendeley Data: Underlying data for ‘Effect of vital bleaching on surface roughness and microhardness of nanofilled and nanohybrid composite resins’, https://www.doi.org/10.17632/5fjyt8z6vc.1. 11\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nHaywood VB, Sword RJ: Tooth bleaching questions answered. Br. Dent. J. 2017; 223: 369–380. PubMed Abstract | Publisher Full Text\n\nJoshi S: An overview of vital teeth bleaching. J. Interdiscip. Dent. 2016; 6(1): 3. Publisher Full Text\n\nSharafeddin F, Jamalipour G: Effects of 35% carbamide peroxide gel on surface roughness and hardness of composite resins. J. Dent (Tehran). 2010; 7(1): 6–12.\n\nHafez R, Ahmed D, Yousry M, et al.: Effect of In-Office Bleaching on Color and Surface Roughness of Composite Restoratives. Eur. J. Dent. 2010 Apr; 04(02): 118–127. Publisher Full Text\n\nAtali PY, Topbaşi FB: The effect of different bleaching methods on the surface roughness and hardness of resin composites. J. Dent. Oral Hyg. 2011; 3(2): 10–17.\n\nYu H, Li Q, Cheng H, et al.: The effects of temperature and bleaching gels on the properties of tooth-colored restorative materials. J. Prosthet. Dent. 2011 Feb; 105(2): 100–107. PubMed Abstract | Publisher Full Text\n\nHubbezoglu I, Akaoǧlu B, Dogan A, et al.: Effect of bleaching on color change and refractive index of dental composite resins. Dent. Mater. J. 2008; 27(1): 105–116. PubMed Abstract | Publisher Full Text\n\nÖzduman ZC, Kazak M, Fildisi MA, et al.: Effect of Polymerization Time and Home Bleaching Agent on the Microhardness and Surface Roughness of Bulk-Fill Composites: A Scanning Electron Microscopy Study. Scanning. 2019 Jun 2; 2019(6): 1–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVieira I, Ferraz LN, Vieira Junior WF, et al.: Effect of at-home bleaching gels with different thickeners on the physical properties of a composite resin without bisphenol A. J. Esthet. Restor. Dent. 2022 Sep; 34(6): 969–977. PubMed Abstract | Publisher Full Text\n\nRastelli ANS, Jacomassi DP, Bagnato VS: Chemical and Physical Analysis of the Effect of In-Office Tooth Bleaching Agent on Three Esthetic Composite Resin Restorations. Mathews J. Dent. 2016 Dec 28; 2(1): 1–13.\n\nPuthen Purayil T, Pentapati K:Effect of vital bleaching on surface roughness and microhardness of nanofilled and nanohybrid composite resins. [Dataset]. Mendeley Data. 2022; V1. Publisher Full Text\n\nEsmaeili B, Abolghasemzadeh F, Gholampor A, et al.: The effect of home bleaching carbamide peroxide concentration on the microhardness of dental composite resins. Gen. Dent. 2018; 66(1): 40–44. PubMed Abstract\n\nOnwudiwe UV, Umesi DC, Orenuga OO, et al.: Clinical evaluation of 16% and 35% carbamide peroxide as in-office vital tooth whitening agents. Nig. Q. J. Hosp. Med. 2013; 23(2): 80–84. PubMed Abstract\n\nYap AUJ, Wattanapayungkul P: Effects of in-office tooth whiteners on hardness of tooth-colored restoratives. Oper. Dent. 2002; 27(2): 137–141. PubMed Abstract\n\nMourouzis P, Koulaouzidou EA, Helvatjoglu-Antoniades M: Effect of in-office bleaching agents on physical properties of dental composite resins. Quintessence Int. 2013; 44(4): 295–302. PubMed Abstract | Publisher Full Text\n\nLangsten RE, Dunn WJ, Hartup GR, et al.: Higher-concentration carbamide peroxide effects on surface roughness of composites. J. Esthet. Restor. Dent. 2002; 14(2): 92–96. PubMed Abstract | Publisher Full Text\n\nKumari C, Bhat K, Bansal R: Evaluation of surface roughness of different restorative composites after polishing using atomic force microscopy. J. Conserv. Dent. 2016 Jan 1; 19(1): 56–62. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPadovani G, Fúcio S, Ambrosano G, et al.: In Situ Surface Biodegradation of Restorative Materials. Oper. Dent. 2014 Jul 1; 39(4): 349–360. Publisher Full Text\n\nAnagnostou M, Chelioti G, Chioti S, et al.: Effect of tooth-bleaching methods on gloss and color of resin composites. J. Dent. 2010; 38: p. e129–36. Elsevier. Publisher Full Text\n\nWattanapayungkul P, Yap AUJ: Effects of in-office bleaching products on surface finish of tooth-colored restorations. Oper. Dent. 2003; 28(1): 15–19. PubMed Abstract\n\nTorabi K, Rasaeipour S, Ghodsi S, et al.: Evaluation of the effect of a home bleaching agent on surface characteristics of indirect esthetic restorative materials-part II microhardness. J. Contemp. Dent. Pract. 2015; 15(4): 438–443.\n\nEl-Murr J, Ruel D, St-Georges AJ: Effects of external bleaching on restorative materials: a review. J. Can. Dent. Assoc. 2011; 77(7): b59.\n\nJun SK, Kim DA, Goo HJ, et al.: Investigation of the correlation between the different mechanical properties of resin composites. Dent. Mater. J. 2013; 32(1): 48–57. Publisher Full Text"
}
|
[
{
"id": "162247",
"date": "20 Feb 2023",
"name": "Rama Krishna Alla",
"expertise": [
"Reviewer Expertise Dental Materials",
"Nanoparticles in dentistry",
"fibre-reinforced composites."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript compared the surface roughness and microhardness of Ceram.x® SphereTEC™ one and Filtek Z350 XT after in-office vital bleaching with Pola office. A total of 20 composite discs with 10 x 2 mm were fabricated with Ceram.x® SphereTEC™ one and Filtek Z350 XT. The samples were subjected to two bleaching sessions with 35% hydrogen peroxide (Pola office) with a seven-day interval between each session. Surface roughness and microhardness of the prepared samples prior to and after the bleaching procedures were measured using a profilometer and Vickers hardness tester, respectively. This study reported a significant reduction (p <0.001) in the surface hardness of Filtek Z350 XT after the bleaching and no significant decrease in surface hardness with Ceram.x® SphereTEC™ one. However, in-office bleaching of these materials did not report a significant change in their surface roughness.\nThe detailed report is as follows.\nThis manuscript was well-written and adhered to the standards.\nThe introduction was adequate and described the objectives of the study clearly. In the second paragraph, a few references should have been cited to substantiate the information presented.\n\nThe methodology was clearly described. The methodology can include information about the curing lamp specifications and the radiation/wavelength employed.\n\nResults described well based on the statistical analysis performed.\n\nThe discussion is adequate and consistent with the results. The reasons for varying the surface hardness and roughness were discussed. The outcomes of the current study were compared with those of other comparable investigations. The limitations and the future scope of this study could have been emphasized.\n\nThe conclusions were appropriate based on the results.\n\nThe references were appropriate and mentioned the most recent studies.\nThe data presented in the current study is useful to the scientific community and clinicians. This study reported a significant decrease in the surface hardness of the composites with the bleaching procedures. This decrease in hardness was dependent on the filler loading to resin ratio. Therefore, the data presented in this study is handy to clinicians for selecting an appropriate composite for their patient's needs.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9674",
"date": "18 May 2023",
"name": "Tina Purayil",
"role": "Author Response",
"response": "Query 1 The introduction was adequate and described the objectives of the study clearly. In the second paragraph, a few references should have been cited to substantiate the information presented. Response 1 References has been added to the second paragraph. Abouassi T, Wolkewitz M, Hahn P. Effect of carbamide peroxide and hydrogen peroxide on enamel surface: an in vitro study. Clin Oral Investig. 2011;15(5):673–80. De Geus JL, Wambier LM, Kossatz S, Loguercio AD, Reis A. At-home vs In-office Bleaching: A Systematic Review and Meta-analysis. Oper Dent. 2016 Jul 1;41(4):341–56. Query 2 The methodology was clearly described. The methodology can include information about the curing lamp specifications and the radiation/wavelength employed. Response 2 The composite material was cured for 20 seconds on both sides using a visible light curing unit (3M ESPE Elipar, St Paul,MN, USA ) having a light intensity of 1200 wM/cm2. Query 3 The limitations and the future scope of this study could have been emphasized. Response 3 The results of the present study indicate that compositional variations influence the susceptibility of dental composites to bleaching. However, the present study selected only two types of dental composites. Additional studies on large number of composites and their types (microfilled, nanofilled, hybrid composites etc) may provide more insights on the effect of bleaching on composites restorative materials."
}
]
},
{
"id": "168376",
"date": "17 Apr 2023",
"name": "Olivia A. Osiro",
"expertise": [
"Reviewer Expertise Dental Biomaterials Science"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article is coherent and addresses a relevant topic. The study design and methodology are suitable to answer the research question.\nIn the introduction, although a clear description of the relevance of the study is provided together with a description of the composite materials, very little information is covered on bleaching materials and techniques and how these can specifically affect the material properties. For example, where this is attempted in the first two paragraphs, the information is scanty and supported by only two citations. Likewise, in the final paragraph, a general statement is made on the effect of the bleaching agents and suspected attributes regarding the material composition but no specific explanation and corresponding examples which would be helpful in justifying the need for this study. A clear distinction should be made between the nanofilled and the nanohybrid composite.\nIn the methods, the manufacture of Ceram.X SphereTec One in Table 1 is different from that stated in the introduction. The description of the specimens is also lacking important detail - how many specimens were prepared for each composite material? This should also be clarified in the abstract. What was the total sample size and was this calculated based on a determined statistical power?\nWhat material was the split mould made of? Where was the mylar strip sourced from?\n\nHow much bleaching agent was applied on the discs? Was it the same quantity for all discs at all times? Were the discs dry at the initial bleaching application, before they were stored in distilled water?\nFor the hardness test, the length of indentation was measured but the calculation was derived from the area of indentation. This description should be clarified.\n\nThe description of the surface roughness measurement is also unclear, specifically, '...passed over the surface of the specimen perpendicularly to a distance of 0.8mm...'\nIn the results, it would be useful to also report the t-values in Table 2 and F or relevant test values for ANCOVA, as well as the 95% CI.\nTable 2 shows paired t-test results within the same material, that is, before and after for the same material (within) not between the two materials.\n\nA statement on the significant difference on microhardness between the two materials should also be captured in the abstract.\nIn the discussion, reference is made to a study on two nanohybrid composites in the first paragraph - this should be clarified as the title talks of a nanofilled and a nanohybrid.\n\nThe description of the bleaching agent in the discussion is different from that presented in the methodology - can this have any influence on the outcome observed?\nAlthough clear arguments are presented in the discussion, some paragraphs lack supporting citations e.g only one in paragraph 4.\nWere there any limitations in this study? Are the conclusions generalizable? Can the observations be accurately and undoubtedly attributed to the type of composite as implied in the conclusion? Do the authors believe that this study was able to show the effect of the bleaching agent on the composite due to the filler type and load?\nThroughout the MS, some minor grammatical errors should also be addressed to improve clarity e.g In the title and objective, is the use of 'vital' correct considering that this was an in vitro study?; In the abstract conclusion, '...seems to vary due to variations...'; In the introduction, the second statement in the first paragraph, '..the majority of bleaching agents...' could improve clarity; in the second paragraph, third statement, '...ever-increasing demand...there has been an increase....'\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "9675",
"date": "18 May 2023",
"name": "Tina Purayil",
"role": "Author Response",
"response": "Reviewer 2 Query 1 In the introduction, Although a clear description of the relevance of the study is provided together with a description of the composite materials, very little information is covered on bleaching materials and techniques and how these can specifically affect the material properties. For example, where this is attempted in the first two paragraphs, the information is scanty and supported by only two citations. Likewise, in the final paragraph, a general statement is made on the effect of the bleaching agents and suspected attributes regarding the material composition but no specific explanation and corresponding examples which would be helpful in justifying the need for this study. A clear distinction should be made between the nanofilled and the nanohybrid composite. Response 1 The introduction has been revised. Although a clear description of the relevance of the study is provided together with a description of the composite materials, very little information is covered on bleaching materials and techniques and how these can specifically affect the material properties- The most commonly used bleaching agents are hydrogen peroxide and carbamide peroxide. These bleaching agents can be applied at-home and in-office and are considered to be effective and relatively safe when supervised by a dentist. Many studies have reported the action of bleaching agents on restorative materials. The observed changes after bleaching of composite resin materials are alterations in smoothness, hardness and reduction in bond strength. A clear distinction should be made between the nanofilled and the nanohybrid composite. Filtek™ Z350 XT (3M, ESPE, St. Paul, USA) is a universal nanocomposite consisting of nanometer-sized filler particles in the composite matrix. Ceram.x ® SphereTEC™ one (Dentsply, Konstanz, Germany) is a light-curable nanohybrid composite consisting of nanometer and micrometer-sized fillers with a granulated filler technology (SphereTEC™). Query 2 In the methods, the manufacture of Ceram.X SphereTec One in Table 1 is different from that stated in the introduction. Response 2 Manufacturer details of Ceram X Sphertec One in Table 1 has been changed to Dentsply, Konstanz, Germany Query 3 The description of the specimens is also lacking important detail - how many specimens were prepared for each composite material? This should also be clarified in the abstract. Response 3 20 samples each of (10 mm diameter and 2 mm height) Ceram.x® SphereTEC™ one and Filtek Z350 XT were prepared. It has been revised both in abstract and also in the main text. Query 4 What was the total sample size and was this calculated based on a determined statistical power? Response 4 Total sample size is 40. Sample size was estimated based on the microhardness values reported by Sharafeddin and Jamalipour which yielded an effect size of 1.42. With a power of 80% and 95% confidence interval, the sample size was estimated to be nine per group Query 5 What material was the split mould made of? Where was the mylar strip sourced from? Response 5 Split mould was made of stainless steel. Manufacturing detail of mylar strip is (SS White Co, Philadelphia, PA, USA) and its been added to the main text Query 6 How much bleaching agent was applied on the discs? Was it the same quantity for all discs at all times? Were the discs dry at the initial bleaching application, before they were stored in distilled water? Response 6 The prepared discs were subjected to 0.1 ml of 35% hydrogen peroxide (Pola office, SDI Limited, Australia) Same quantities were used for all the discs. Yes, the discs were dry at the initial bleaching application. Query 7 For the hardness test, the length of indentation was measured but the calculation was derived from the area of indentation. This description should be clarified. Response 7 Using the length of the diagonal of the indentation, area of the indentation [square-shaped indentation] was measured as follows: area of indentation = ½ x length of the diagonal2 Query 8 The description of the surface roughness measurement is also unclear, specifically, '...passed over the surface of the specimen perpendicularly to a distance of 0.8mm...' Response 8 The word perpendicular was used in the context that the stylus was moving over the surface We have removed the word “perpendicularly” from the text. Surface roughness of the specimens pre- and post-bleaching was measured using a surface profilometer (Surtronics 3+, Taylor Hobson, UK). The samples were placed on a flat stable surface. The stylus of the profilometer was passed over the surface of the specimen to a distance of 0.8 mm. The experiment was carried out in triplicate on each disc,and average surface roughness, as Ra, was recorded in microns Query 9 In the results, it would be useful to also report the t-values in Table 2 and F or relevant test values for ANCOVA, as well as the 95% CI. Response 9 t-values ,F values and 95% CI have been added to the table 2 and text. Query 10 Table 2 shows paired t-test results within the same material, that is, before and after for the same material (within) not between the two materials. Response 10 It has been included in the Table 2 Query 11 A statement on the significant difference on microhardness between the two materials should also be captured in the abstract. Response 11 This statement is added to the abstract: The adjusted mean (estimated marginal mean) microhardness after bleaching for Ceram.x ® SphereTEC™ one (35.79 ± 1.45) was significantly higher than Filtek Z350 XT (19.54 ± 1.45) (p < 0.001). Query 12 In the discussion, reference is made to a study on two nanohybrid composites in the first paragraph - this should be clarified as the title talks of a nanofilled and a nanohybrid. Response 12 It has been revised in the first paragraph of the discussion: The main objective of the present study was to assess the effect of in-office bleaching on nanohybrid and nanofilled composites Query 13 The description of the bleaching agent in the discussion is different from that presented in the methodology - can this have any influence on the outcome observed? Response 13 The active ingredient of majority of bleaching agents is hydrogen peroxide and generally oxidizes the chromophores and improves the shade of the discolored tooth. It has been revised in the second paragraph of the discussion Query 14 Although clear arguments are presented in the discussion, some paragraphs lack supporting citations e.g only one in paragraph 4. Response 14 Supporting study has been included in paragraph 4 : Preethy NA, Jeevanandan G, Govindaraju L, Subramanian EMG. Comparison of Shear Bond Strength of Three Commercially Available Esthetic Restorative Composite Materials: An In Vitro Study. Int J Clin Pediatr Dent. 2020 Nov 1;13(6):635–9. Query 15 Were there any limitations in this study? Response 15 The results of the present study indicate that compositional variations influence the susceptibility of dental composites to bleaching. However, the present study selected only two types of dental composites. Additional studies on large number of composites and their types (microfilled, nanofilled, hybrid composites etc) may provide more insights on the effect of bleaching on composites restorative materials. Query 16 Are the conclusions generalizable? Can the observations be accurately and undoubtedly attributed to the type of composite as implied in the conclusion? Do the authors believe that this study was able to show the effect of the bleaching agent on the composite due to the filler type and load? Response 16 From the results of the present study, we conclude that the variations in formulation of dental composites can influence their susceptibility to bleaching. In that sense, variations in filler size and loading would also alter the ratio between resin matrix to filler. Hence, the findings of the present study can be generalized to the extent that variations in composition changes their susceptibility to bleaching Query 17 Throughout the MS, some minor grammatical errors should also be addressed to improve clarity e.g In the title and objective, is the use of 'vital' correct considering that this was an in vitro study?; In the abstract conclusion, '...seems to vary due to variations...'; In the introduction, the second statement in the first paragraph, '..the majority of bleaching agents...' could improve clarity; in the second paragraph, third statement, '...ever-increasing demand...there has been an increase....' Response 17 In the title and objective, is the use of 'vital' correct considering that this was an in vitro study?:Title has been rephrased to “Effect of in-office bleaching agent on the surface roughness and microhardness of nanofilled and nanohybrid composite resins” In the abstract conclusion, '...seems to vary due to variations..: Abstract has been revised to -In office-bleaching with 35% hydrogen peroxide can reduce the microhardness of nanofilled composite. However, the surface roughness was not influenced by the bleaching procedure in both nanohybrid and nanofilled composite resin materials. In introduction-the majority of bleaching agents: Second statement in the first paragraph has been revised to :This procedure involves diffusion of bleaching agent which alters the structure of chromophore molecules present in enamel and dentin , thereby promoting tooth whitening ever-increasing demand...there has been an increase -third statement in the second paragraph has been revised to With greater demand for esthetics, there has been an increase in the use of direct esthetic restorative materials, especially dental composites"
}
]
}
] | 1
|
https://f1000research.com/articles/12-129
|
https://f1000research.com/articles/12-513/v1
|
18 May 23
|
{
"type": "Research Article",
"title": "HIV preventive behavior scale for Thai men who have sex with men (MSM): development and psychometric properties",
"authors": [
"Passakorn Koomsiri",
"Nanchatsan Sakunpong",
"Passakorn Koomsiri"
],
"abstract": "Background: There are several ways to measure HIV prevention behavior. The simplest is self-assessment. In foreign countries, many scales have been developed. However, there are only a few developed scales among MSM in Thailand and they are not up to date. The objective of this study is to investigate the psychometric features of the HIV preventative behavior measure in Thai men who have sex with men (MSM).\n\nMethods: The sample consisted of 424 Thai MSM individuals aged 25 or older who had at least one sexual encounter using any method in the previous six months. Test the sample by dividing it in half. Analysis’s construct validity via Exploratory and Confirmatory Factor analysis, reliability using Cronbach's reliability coefficient. Tests of convergent and discriminant validity based on Pearson correlation coefficients. Results: This metric consists of nine items, each comprised of two components: 1) denial and avoidance of the risk of obtaining HIV, and 2) self-protective actions before and during sexual activity. Both components of the CFA were in excellent agreement with the empirical data (χ2 = 36.56, p =.06, χ2/df = 1.46, GFI = 0.96, CFI = 0.98, AGFI = 0.94, RMR = 0.07, RMSEA = 0.05, TLI = 0.96). Cronbach's reliability coefficient is .77, and the HIV Preventive Behavior Scale was significantly linked with the AIDS risk behavior avoidance scale and the AIDS prevention scale (r = 0.21 and 0.16, p < 0.01). There was no correlation with the Thai Language Learning Attitude Scale.\n\nConclusions: The psychometric qualities are satisfactory and can be used to identify individuals at risk for psychological interventions to enhance HIV preventive behavior among Thai MSM.",
"keywords": [
"HIV",
"MSM",
"Preventive Behavior",
"Psychometric Properties",
"Scale"
],
"content": "Introduction\n\nMen who engage in sexual relations with other men are regarded as a sexual minority that is persecuted and discriminated against by society. The minority stress model says that men who have sex with other guys are more likely to experience stress due to characteristics that differ from those of the majority. In other words, gender rules that are perceived as alienating have little effect on mainstream society. The resultant bias influences the establishment of minority identities by instilling a sense of alienation, self-loathing, and unacceptability in those who recognize that they have a different gender status and identity than the majority population. This results in a negative self-image, which generates immediate stress and physical or mental health issues.1,2 The prevalence of sexually transmitted diseases (STDs) was reported to be 35.4% among MSM in Thailand in 2018, with an average sample age of 26 years old.3 In Thailand in 2018, the epidemiological characteristics of HIV infection in men in intimate relationships with men who got treatment and long-term follow-up revealed a prevalence of 15 percent.4 Recent studies reveal that HIV prevalence is high among men who engage in sexual activity with other men. This may be related to the minority stress model described above.\n\nHuman Immunodeficiency Virus (HIV) is the virus responsible for acquired immunodeficiency syndromes (AIDS). When it enters the body, it will undergo an incubation period. There may be years without symptoms. After HIV multiplies, it destroys CD4 white blood cells. When white blood cells are depleted, the body lacks immunity, resulting in diseases such as pulmonary tuberculosis and meningitis, as well as fungal infections in various parts of the body, etc. Immunodeficiency syndrome is referred to as AIDS. Patients with advanced AIDS typically die within two to four years if they are not treated early. However, early HIV infection may not necessarily result in AIDS. HIV prevention behaviors should be emphasized in both people living with HIV and those at risk of transmitting the infection to others, including those who are HIV-negative, if the infection has not destroyed the immune system at the onset of various symptoms.5,6\n\nFrom the review of concepts related to HIV prevention behaviors, the health belief model concept asserts that perceptions and beliefs of individuals will influence one’s practice to avoid the occurrence of that disease because they believe they are at risk of the disease, have a penalty, and have obstacles that can be severe and affect daily life. Theory of rational action that explains the relationship between attitudes and behavior.7 The notion of self-efficacy and health behaviors that explain an individual’s capacity to control sexual activity related to risky sexual behavior. Low perception of self-control is related to an increased likelihood of engaging in sexual practices that result in HIV infection.8 HIV infection prevention behavior will occur when a person acts or behaves to avoid contracting HIV as because of assessment. A person’s perspective on their odds of contracting HIV and the severity of AIDS, the perceived benefits and hurdles of self-defense, and the presence of a role model or reference group may influence their ability to manage and consistently display HIV prevention practices.\n\nHIV prevention behavior is a health behavior that can be measured or evaluated in a variety of ways, particularly the self-assessment scale at various levels, for which many countries have developed and studied numerous psychological properties, including the AIDS Prevention Questionnaire, the Perceived Risk of HIV Scale, and the Scales to Assess Knowledge, Motivation, and Self-Efficacy for HIV PrEP.9–12 In Thailand, HIV preventive behavior scale are not being updated. Since 2011, Pimthong and Bhanthumnavin13,14 have established the AIDS risk behavior avoidance scale and the AIDS preventative behavior scale. Such metrics have been developed for quite some time.15–17 Therefore, the researcher created a new HIV preventive behavior scale, which led to the purpose of this study, which was to examine the psychometric properties among Thai MSM. This study was conducted within the framework of Thai society by utilizing the cognitive interview technique. Convergent and discriminant validity were also investigated. The researcher believes that this scale can be used to assess the level of HIV prevention behaviors for self-prevention and that multidisciplinary studies can be used as a search engine for sex risk behaviors, leading to counseling or psychological activities to promote and prevent HIV risk behaviors among men who have sex with other men in the future.\n\n\nMethods\n\nThis study was a cross-sectional study to examination of the psychometric properties of the HIV Prevention Behavior Scale among males who engage in sexual relations with other men. In total, 424 participants responded to an online questionnaire between August and November 2022. On January 19, 2022, the Srinakharinwirot University, Human Research Ethics Committee gave its approval for this study, giving it the approval number SWUEC-G-512/2564E. January 19, 2022.\n\nThe subjects are aged 25 years and older, identified themselves as men who had sex with men at least once within the previous six months, and were willing to answer the online HIV preventive behavior scale using a Google form, which required a minimum sample size of 200 based on the Central Limit Theorem, which states that the sample group tends to be normally distributed.18 The Snowball selection sample group was picked, where the sample group introduced a group of persons with comparable qualities and who voluntary selection, obtained a total of 424 samples.\n\nHIV preventive behavior scale, consisting of 9 items, was the instrument utilized in this investigation. The response was a five-level self-assessment scale: 1 = never practiced, 2 = rarely practiced, 3 = occasionally practiced, 4 = frequently practiced, and 5 = routinely practiced.19 Average acts or behaviors over the preceding six months. All inquiries were positive. A high total score indicates an elevated level of HIV-preventive behavior. Tool development: From literature studies and research on HIV prevention behavior in Thailand and overseas, instruments were created. The researcher brought the Pimthong and Bhanthumnavin measurements as a model to further build,13,14 which was developed within the context of the Thai people. First, we are beginning with the development of the model through cognitive interviewing.20 The cognitive interview is a questioning approach based on the respondent’s capacity for recognition and comprehension. This study questioned three specialists with more than five years of expertise in HIV prevention. The substance of the data was evaluated to categorize activities with similar meanings. Afterward, the gathered data was utilized to develop a questionnaire and determine the validity of the content by analyzing the responses. Index of item congruence (IOC) from 3 specialists.21,22 Including researchers on gender diversity, HIV-related research, and university professors. By eliminating questions with a content validity of less than .60, the items were chosen, with an adjusted item-total correlation below .30. The definition of the entire assessment can be summed up as follows: \"In males who have sex with men and exhibit self-protective actions before and during sex, including effectively responding to or managing sexual emotions.\"\n\nAIDS risk behavior avoidance scale, developed by Pimthong in 2011, it measures behavioral intent or a person’s readiness to attempt to avoid actions or activities that lead to AIDS risk. By choosing to act or not to act, such as changing sexual partners often taking drugs or intoxicants watching porn, and choosing places that should or should not go, such as entertainment venues, and gay saunas, a total of 12 items, with 7 positive items and 5 negative items. The responses are rated on a 6-point scale ranging from the truest to not true at all. Scores were calculated using a total score of 12-72. If the score was high, it indicated that there was a high risk of AIDS avoidance behavior. For the psychometric characteristics, the discriminant power ranged from 4.74 to 8.93, the item correlation coefficient with the total score was .32 to.64, and the reliability for the whole version with the alpha coefficient was .83. with empirical data with a χ2 = 34.70, df = 46, p-value = .89, NFI = .94, GFI = .95, AGFI = .91, SRMR = .049, CFI = 1.00, and RMSEA = 0.0.14\n\nAIDS prevention scale, developed by Pimthong in 2011, it is a model to measure a person’s sexual behavior. By considering the method of sexual intercourse, such as using a condom with lubricant every time you have anal sex. Not swallowing partner’s semen, etc. There were a total of 10 items, 4 positive and 6 negative items. Each item had a 6-point evaluation scale ranging from very true to absolutely false by measuring 3 behavioral components. The aspects related to the risk of HIV infection during sex were 1) no risk, 2) moderate risk, and 3) high risk. The score is calculated using a total score of 10-60. If the score is high, it indicates that AIDS prevention behaviors while having sex are high. For the psychometric characteristics, the discriminant power ranged from 4.09 to 9.90, the item correlation coefficient with the total score was .20 to.62, and the reliability for the whole version with the alpha coefficient was .77. with empirical data with a χ2 = 23.52, df = 30, p-value = .70, NFI = .93, GFI = .96, AGFI = .92, SRMR = .049, CFI = 1.00, and RMSEA = 0.0.14\n\nThai Language Learning Attitude Scale, developed by Samrongthong in 2011 as a model to measure the attitude towards learning the Thai language. There are a total of 20 items. Answers are self-exploratory. Questions are both positive and negative items. Then choose a response from 5 levels: strongly disagree, disagree, not sure, agree, and strongly agree. There was reliability from internal consistency analysis with Cronbach’s reliability coefficient of .85.23\n\nAfter acquiring a draft of the HIV Preventive Behavior Scale, its psychometric properties were tested using corrected item-total correlation analysis, and the internal consistency was evaluated using Cronbach’s reliability coefficient. The construct validity was analyzed by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), including the examination of convergent and discriminant validity by analyzing Pearson product-moment correlation coefficients with the AIDS risk behavior avoidance scale and the AIDS preventative behavior scale, and the Thai Language Learning Attitude Scale.\n\nData collection for this study was on an online scale. When the sample reads the statement well if they are willing to provide information, their consent was written. The statement will be described the purpose of the data collection, research procedures, and analysis. The collection of data will not identify the identity of the sample.\n\nIf the sample does not agree to answer the survey, they can choose to decline to participate in the research and will immediately stop taking the survey. For experts who were cognitive interviewed. The researcher made a letter requesting an interview with the affiliation. The experts can either accept or decline the interview according to their preferences.\n\n\nResults\n\nBased on the cognitive interviewing technique, the researcher examined the content and categorized the HIV-preventive activities of men who have sex with males into three broad categories.\n\nGroup 1 Denial and avoidance of HIV risk Behaviors, is the attempt by men who engage in sexual activity with other men to avoid or reject the stimuli that increase the risk of contracting or transmitting HIV.\n\n\"… avoid holding the gathering outdoors. In the absence of prior acquaintances, when one meets someone, they like, they will poke each other…\" 1st participant.\n\n\"The majority of males who have sex with other men have transient sex partners. There are few consistent sexual partners. Too frequent mate switching poses a risk of illness.\" 2nd participant.\n\nGroup 2 Self-protective actions before and during sexual activity, is the behavior of males who engage in sex with other males to avoid contracting or transmitting HIV before and during sexual activity.\n\n\"If you want to know about protection, you can ask whether or not he used a condom during sexual activity.\" 1st participant.\n\n\"Taking drugs during intercourse… will make you inebriated… will cause you to forget to take medications or wear a condom… is an additional factor in the decline of HIV infection.\" 3rd participant.\n\nGroup 3 Appropriate sexual response: in which males who have sex with other guys express their sentiments, sexual emotions, or sexual feelings about themselves or their partners without negatively impacting themselves or others. The promotion of health, spirituality, and self-love\n\n“… less focus on sexual cues and more focus on other life pleasures… having a mental anchor may reduce sexual preoccupation… ” 1st participant (further interviews)\n\n“Various activities, such as aerobic dance, exercising, and running, can be used to reduce sexual desire; this helps… educate people to be safe in love… with acceptable sexual arousal.” 2nd participant.\n\nDemographic data, the sample used in the study of psychometric properties all 424 people who were men and had sex with a man in the past six months, regardless of their sexual orientation. On average, they were 32.08 (SD = 6.42) years old. IOC was analysed from 3 consensus experts, 19 questions with content validity between .66 and 1.00, then analysed the corrected item-total correlation (CITC) in a sample group of 424 individuals by selecting questions with a value of .30 or greater.24,25 Skewness and kurtosis were not greater than ±2 when analyzing the normal distribution of the data for the 9 questions with CITC scores between .33-.47,18,26 which can be utilized to study the data further.\n\nThe researcher used a sample of 424 people to look at the Pearson product-moment correlation coefficients between all nine questions. Each question was found to have a statistically significant association with 35 pairs at the .05 level, at .11-.58, but no higher than .90.27 There was only one set of uncorrelated questions between items 2 and 4. Kaiser-Meyer-Olkin Evaluation of Sampling Efficacy (KMO) = .78, which is close to one and indicates that the model explains 78% of the variance for Bartlett’s Test of Sphericity; χ2 = 843.73, df = 36, sig. = .00,28 indicating that the correlation matrix is not equal to zero. Consequently, it can be studied further for EFA and CFA.\n\nPrincipal Component Analysis with Varimax and Kaiser Normalization-based EFA results from the first half of a sample of 212 individuals (Convergence occurred after 5 cycles of rotation.) The HIV Preventive Behavior Scale has three Eigenvalues greater than 1 after five rounds29 in three components. The first component was denial and avoidance of HIV risk. The factor weight (factor loading) for each of the three items ranged from .75 to .83.30 Component 2 consisted of self-protective conduct before and during sexual contact. Consisting of items 5 through 9, the weight of each element ranges from .46 to .73.30 However, just item 4 was categorized independently in component 3. Therefore, the number of items is insufficient to be categorized as component 3,31 and after examining the considerate content of item 4, it is determined that it overlaps with component 2, so it is suggested that such questions be included in component 2. As demonstrated in Table 1, the researcher concludes that this measure comprises only two components: denial and risk avoidance of HIV infection and self-protective conduct before and during sexual activity.\n\nThe second half of the 212 participants were utilized to conduct a confirmatory factor analysis to validate the HIV Preventive Behavior Scale against empirical data. The two-component confirmation analysis demonstrated that the model was in good agreement with the empirical data. Component 1: denying and avoiding HIV risk consisted of questions 1-3 with factor loading (b); each question is between .60 to .85,30 the standard error (SE) is between .15 to .20, the statistically significant test values (t) are between 7.32 and 7.55 with statistical significance (p < .01), and the coefficient of determination (R2) in each item ranges from .36 to 73, and component 2 is self-protective conduct before and during sexual contact consisted of questions 4-9 (b = .41-74; SE = .17-.26; t = 4.15-6.29; p < .01; R2 = .13-.54). Including have factor correlation between component 1 and 2 at .58, see Table 2 (also see Figure 1).\n\n** p < .01.\n\nConsistent with empirical data, the following two components of the HIV Preventive Behavior scale model were identified by CFA: Chi-square: χ2 = 36.56, p = .06, Relative Chi-square: χ2/df = 1.46, Goodness of Fit Index: GFI = .9, 6, Comparative Fit Index: CFI = .8, Adjusted goodness of fit index: AGFI = .94, Root Mean Square Residual: RMR = .07, Root Mean Square Error of Approximation: RMSEA = .05, Root mean square residual: TLI = .96. Overall, the model matches the empirical data well (good fit).27,32,33\n\nInternal consistency from Cronbach’s reliability coefficient was used to determine that the 9-item HIV Preventive Behavior Scale’s reliability was equivalent to .77 Pearson product-moment correlation coefficients, which were used to examine convergent and discriminant validity among 424 individuals Thai MSM. There are positive correlations between the HIV Preventive Behavior Scale (SUMPHIV) with the AIDS risk behavior avoidance scale (SUML), and the AIDS prevention scale (SUMA) were statistically significant at the .01 level, with correlations of .21 and .26, respectively. There was no correlation between the HIV Preventive Behavior Scale and the Thai Language Learning Attitude Scale (SUMT) (see Table 3).\n\n** p < .01.\n\n\nDiscussion\n\nThe purpose of this study was to examine the psychometric properties of the HIV prevention behavior test in Thai MSM. It was determined that this measure had two elements: 1) denial and avoidance of HIV risk and 2) self-protective conduct before and during sexual activity, like previous studies by Pimthong and Bhanthumnavin.13 It was discovered that the AIDS-preventive behaviors of males who engage in sex with other men can be separated into two categories: risk avoidance of HIV infection and self-protective conduct during sex. According to the CFA analysis, nine items of the HIV Preventive Behavior Scale were compatible with empirical evidence.9,10,34 χ2 = 36.56, p = .06, χ2/df = 1.46, GFI = .96, CFI = .98, AGFI = .94, RMR = .07, RMSEA =.05, TLI = .96.27,32,33 The component factor correlation was moderate, with a value of .58 and not exceeding .85, indicating discriminating validity35 and that the components were separated. This study’s findings are comparable to the Two-Dimensional Sexual Sensation Seeking Scale of Ferrer-Urbina et al., 2020, who believed that risky sexual behaviors have been associated with sexual sensation seeking. The researcher and colleagues developed the Sexual Sensation Seeking Scale with nine questions and two components: 1) sexual emotion seeking and 2) sexual boredom. The first section of the questionnaire concerned dangerous behavior, while the second section addressed sexual feelings. There were a total of 770 Latin American adolescents and adults enrolled in the study. Using CFA and ESEM, the researchers determined that structure delivers high levels of reliability and validity, depending on the internal structure of the test.36 It is also consistent with a two-component HIV-related behavioral scale, such as Mena-Chamorro et al.’s11 development and proof of the validity of the HIV risk perception scale for young adults in a Hispanic American context. A sample of 524 participants, ages 18 to 33, comprised 49% men and 49% women. 51.84% of those polled identified as heterosexual. There were nine components on the scale. The results indicated that the scale was divided into two components: perceived risk susceptibility and perceived risk severity; however, the focus of this study component is on the perceived risk of HIV infection, and the 2022 study by Sao et al. on the development and psychometric evaluation of the HIV stigmatizing attitudes scale in Tanzania. The measure is separated into two components with strong reliability and validity: moral judgment and interpersonal distance.37\n\nAccording to the examination of the psychometric properties of nine HIV preventive behavior scales, there are nine HIV preventive behavior scales. It was determined to be content valid, structurally valid with discrimination, and to have adequate reliability (Cronbach’s reliability coefficient = .77), which may explain the group homogeneity of the data in the risk condition of 6 months, resulting in consistent measurement.27 In addition, it was six items more confident than the PrEP self-efficacy measure (Cronbach’s alpha coefficient = .62) examined by Mueses-Marn et al., 202112 are just as reliable as the original measurement (Cronbach’s alpha = .77).13 Considering the convergent and discriminant validity of the HIV Preventive Behavior Scale, the nine items can be viewed as evidence of the structural validity of the scale. The HIV Preventive Behavior Scale correlates with the HIV Preventive Behavior Scale and can also be examined in terms of self-protective behaviors during sexual encounters.13 It can be shown that this study is comparable to the score on the Perceived Risk of HIV Scale, which is positively related to the score on the Risk Behavior Assessment (rxy = .63, p ≤ .001).9 In addition, there was no correlation between the 9-item HIV Preventive Behavior Scale and the Thai language learning attitude scale. This is because the HIV-preventive behavior measurement content is unrelated to the perception of learning Thai. This demonstrates the instrument’s discriminant validity.\n\nThe primary limitation of this study was the questionnaire response rate of the sample. This research was conducted using an online survey, which made it difficult to distinguish between the MSM group and those with risk behaviors for HIV infection during the prior six months. This may result in erroneous study results. Next, question number 4, the use of condoms when having sex, this topic was eliminated from the EFA analysis as component 3, but the researcher explored integrating it with component 2, which relates to HIV-preventative behaviors. Since the content of the question was primarily evaluated, it was determined that the content was compatible with the question in the element of group component 2 without starting with the EFA analysis results.39 However, the CFA analysis revealed that the measurement models were coherent when Question 4 and Component 2 were joined.\n\n\nConclusions\n\nThe HIV Preventive Behavior Scale was discovered to have two components: rejecting and avoiding the risk of HIV infection and preventative behaviors before and during sexual activity. The measurement model was well consistent with the empirical data when assessing the CFA from nine items. In this regard, the full version of the exam has a specific amount of confidence that it is acceptable. However, further research is required on convergent and discriminant validity, as the correlation between comparable and dissimilar measures remains poor, as well as on the components of evaluating HIV prevention behavior in men. This is because many studies failed to differentiate between denial and avoidance behaviors at risk of HIV infection and protective behaviors before and during sex.38",
"appendix": "Data availability\n\nFigshare: Raw data of psychometric properties’ HIV Preventive Behavior Scale among Thai MSM, https://doi.org/10.6084/m9.figshare.22491319.v6. 40\n\nThis project contains the following underlying data:\n\n1. CFA 9 item.docx (CFA analysis results)\n\n2. EFA.docx (EFA analysis results)\n\n3. Reli_corre.docx (analysis results of reliability, convergent and discriminant validity)\n\n4. Raw data.sav (raw data file)\n\n5. Questionnaire.docx (questionnaire file and google form: https://docs.google.com/forms/d/e/1FAIpQLSfzsgYqrNlWYVwUCOkRuRDRGjHipVFHQ6Hf44IBUvOKKPqiww/viewform?usp=sf_link)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC BY 4.0).\n\n\nAcknowledgments\n\nThank you to everyone who participated in this study by completing the questionnaire. Thank you to the personnel of the AIDS Study Center, the Thai Red Cross Society, and Mplus Thailand for assisting with the collection of research data. Including data verification experts and supplying important information for the measure’s development. And thank you to everyone who has contributed but is not listed here.\n\n\nReferences\n\nMeyer IH: Prejudice, social stress, and mental health in lesbian, gay, and bisexual populations: conceptual issues and research evidence. Psychol. Bull. 2003; 129(5): 674–697. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKittiteerasack P: Minority stress model (MSTM): A Conceptual framework of mental health risk in sexual and gender minority populations. J. Psychiatr. Nurs. Ment. Health. 2019; 33(1): 1–17.\n\nBarisri S, Sujirarat D, Tipayamongkholgul M: Prevalence and Factors Associated with Sexually Transmitted Infection (Chlamydia trachomatis, Neisseria gonorrhea and Syphilis) among Men Who Have Sex with Men and Transgender Women in Thailand. Health Literacy for Sustainable Development Goal: Human Resource Development, 16th MUPH Conference. 2018; pp. 275–283.\n\nSeekaew P, Pengnonyang S, Jantarapakde J, et al.: Characteristics and HIV epidemiologic profiles of men who have sex with men and transgender women in key population-led test and treat cohorts in Thailand. PLoS One. 2018; 13(8): e0203294. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDamrongkwan K: AIDS…the beginning of learning from Bamras Hospital in the past. Nonthaburi, Thailand: Knowledge Management Research Institute and disease control standards, Department of Disease Control, Ministry of Public Health; 2018.\n\nKaewdang K, Rachaniyom S: Nurses and Holistic Nursing Care in AIDS Patient. Journal of Phrapokklao Nursing College. 2015; 26(suppl.1): 128–135.\n\nUNAIDS: Listen Learn Live World AIDS Campaign with Children and Young People. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nMueses-Marín HF, Alvarado-Llano B, Torres-Isasiga J, et al.: Scales to Assess Knowledge, Motivation, and Self-Efficacy for HIV PrEP in Colombian MSM: PrEP-COL Study. AIDS Res. Treat. 2021; 2021: 1–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPimthong S, Bhanthumnavin D: Psycho-Social Factors Correlated with HIV/AIDS Preventive Behavior in Men Who Have Sex with Men: A Structural Equation Model. J. Behav. Sci. 2012; 18(2): 90–107.\n\nPimthong S: Psycho-Social Factors Correlated with HIV/AIDS Preventive Behavior in Men Who Have Sex with Men. Bangkok, Thailand: National Institute of Development Administration; 2011. Dissertation (Social and Environmental Development).\n\nGrant RM, Lama JR, Anderson PL, et al.: Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N. Engl. J. Med. 2010; 363(27): 2587–2599. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLin SY, Lachowsky N, Hull M, et al.: Awareness and use of nonoccupational post-exposure prophylaxis among men who have sex with men in Vancouver, Canada. HIV Med. 2016; 17: 662–673. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRamautarsing RA, Meksena R, Sungsing T, et al.: Evaluation of a pre-exposure prophylaxis programme for men who have sex with men and transgender women in Thailand: learning through the HIV prevention cascade lens. J. Int. AIDS Soc. 2020; 23 Suppl 3: e25540. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHair JF, Black WC, Babin BJ, et al.: Multivariate data analysis. Upper Saddle River, New Jersey, United State of America: Prentice Hall; 2006.\n\nLikert R: A technique for measurement of attitudes. Arch. Psychol. 1932; 07(140): 161–176. Publisher Full Text\n\nWillis GB: Analysis of the Cognitive interview in questionnaire design. New York, United State: Oxford University Press; 2015.\n\nMarshall B, Cardon P, Poddar A, et al.: Does sample size matter in qualitative research? A review of quality interviews in IS research. J. Comput. Inf. Syst. 2013; 54: 11–22. Publisher Full Text\n\nNastasi BK, Schensul S: Contributions of qualitative research to the validity of intervention research. J. Sch. Psychol. 2005; 43(3): 177–195. Publisher Full Text\n\nSamrongthong P: A Study of the Achievement and Attitude in Thai of Mathayomsuksa v Students Though the Electronic Book and the Teacher’s Manual. Bangkok, Thailand: Srinakharinwirot University; 2011. Thesis (Secondary Education).\n\nPengruck L, Boonphak K, Sisan B: Early childhood education: A confirmatory factor analysis concerning Thai administrators’ creative administration. Asia Pac. Soc. Sci. Rev. 2019; 19(1): 17–32.\n\nStreiner DL, Norman GR: Health measurement scales. A practical guide to their development and use. Oxford, England: Oxford University Press; 2003.\n\nKline RB: Principles and practice of structural equation modeling. New York, United State of America: Guilford Press; 2005.\n\nHair JF, Black WC, Babin BJ, et al.: Multivariate data analysis: a global perspective. New York, United State of America: Pearson Prentice-Hall; 2010.\n\nJoreskog KG, Sorbom D: LISREL 8: User’s reference guide. Chicago, United State of America: Scientific Software; 1996.\n\nPinyo T: Techniques for interpreting the results of factor analysis in research work. Panyapiwat Journal. 2018; 10: 192–304.\n\nStevens J: Applied Multivariate Statistics for the Social Sciences. 3rd ed.New Jersey, United State of America: Lawrence Erlbaum Associates Mahwah; 1996.\n\nTayraukham S: Factor Analysis: FA. Journal of Educational Measurement Mahasarakham University. 2018; 10: 15–28.\n\nKelloway EK: Using Mplus for Structural Equation Modeling; A Researcher’s Guide. United State of America: SAGE Publications; 2015.\n\nHu L, Bentler PM: Fit indices in covariance structure modeling: Sensitivity to under parameterized Model misspecification. Psychol. Methods. 1998; 3(4): 424–453. Publisher Full Text\n\nLi J, Liu H, Liu H, et al.: Psychometric assessment of HIV/STI sexual risk scale among MSM: A Rasch model approach. BMC Public Health. 2011; 11: 1–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee J, Cagle JG: Validating the 11-Item R-UCLA Scale to Assess Loneliness among Older Adults: An Evaluation of Factor Structure and Other Measurement Properties. Am. J. Geriatr. Psychiatry. 2017; 25(11): 1173–1183. PubMed Abstract | Publisher Full Text\n\nFerrer-Urbina R, Mena-Chamorro P, Zambrana P, et al.: Development and validity evidence of the Two-Dimensional Sexual Sensation Seeking Scale. Revista Latinoamericana de Psicología. 2020; 52: 176–183. Publisher Full Text\n\nSao SS, Minja L, Vissoci JRN, et al.: The Development and Psychometric Evaluation of the HIV Stigmatizing Attitudes Scale (HSAS) in Tanzania. AIDS Behav. 2022; 26: 1530–1543. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKoh KC, Yong LS: HIV Risk Perception, Sexual Behavior, and HIV Prevalence among Men-Who-Have-Sex-with-Men at a Community-Based Voluntary Counseling and Testing Center in Kuala Lumpur, Malaysia. Interdiscip. Perspect. Infect. Dis. 2014; 2014: 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPlucker JA: Exploratory and Confirmatory Factor Analysis in Gifted Education: Examples with Self-Concept Data. J. Educ. Gift. 2003; 27(1): 20–35. Publisher Full Text\n\nKoomsiri P, Sakunpong N: Raw data of psychometric properties’ HIV Preventive Behavior Scale among Thai MSM. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "353209",
"date": "30 Dec 2024",
"name": "Roghieh Nooripour",
"expertise": [
"Reviewer Expertise MindfulnessAdolescent Mental HealthStressEmotionCyberpsychology"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nAbstract\nThe objective stated in the abstract should be more precise. Instead of stating that the study “investigates the psychometric features,” specify the particular psychometric features you aim to assess (e.g., reliability, construct validity, etc.). This will provide the reader with a clearer understanding of the study's purpose. The description of the methods is very brief. Mention how the two-part division of the sample (for exploratory and confirmatory factor analysis) is executed, and clarify the rationale for using Cronbach’s alpha as the primary reliability measure. Also, explain the choice of convergent and discriminant validity tests, and how they are relevant to the study's goals. In the results section, the statistical values (e.g., χ2, p-values, CFI) should be explained more thoroughly. Indicate the significance level of the tests and whether the statistical results align with the expectations for a valid psychometric tool. Adding clarity on how these results support the psychometric validity of the scale would strengthen this section. The conclusion in the abstract is appropriate, but it could be more concise by directly stating that the scale is not only psychometrically valid but also relevant for future interventions. It is important to emphasize how the study’s findings can lead to practical applications in HIV prevention.\nIntroduction\nintroduction presents various pieces of information (minority stress, HIV prevalence, etc.), but the connection between these elements and the study’s focus on HIV prevention behavior could be more explicitly stated. Ensure the flow logically progresses from the introduction of the problem (HIV among MSM) to the significance of the psychometric tool being studied. The transition between the introduction of MSM as a vulnerable group and the prevalence of HIV among them could be more seamless. Focus on the significance of the HIV prevention behavior scale for MSM in Thailand specifically, and state why this research is necessary. The issue of outdated scales should be more directly tied to the need for an updated measure that aligns with current challenges and social contexts. Concepts like the \"minority stress model,\" \"HIV prevention behavior,\" and other theories mentioned should be introduced with clearer definitions. Present these theories within the context of the study, making it clear why they are central to understanding the behavior of MSM in Thailand, specifically in relation to HIV prevention. Although the introduction introduces relevant theories such as the Health Belief Model and Theory of Rational Action, it would benefit from a clearer integration of how these theories relate to the study's objectives. Expanding on the link between these theoretical frameworks and the HIV prevention behaviors in MSM would create a more robust narrative. While the introduction mentions the absence of updated scales for HIV prevention behavior in Thailand, further emphasize the gap in the literature and how this study contributes to filling that gap. It would be helpful to discuss briefly why existing scales are inadequate in the context of Thai MSM and what this study hopes to improve or provide.\nMethods\nWhile the cross-sectional design is stated, more information is needed on why this design is suitable for the study’s objectives. For example, explain how cross-sectional data can be used to examine psychometric properties and why longitudinal data might not have been necessary for this particular research question. The sampling method (snowball sampling) is described, but the rationale for using this method should be elaborated. Discuss the potential limitations of snowball sampling (e.g., selection bias, homogeneity of sample) and how these limitations are addressed. Moreover, clarify the justification for selecting individuals aged 25 and older, and explain if this age range reflects the target population for the HIV preventive behaviors scale. The sample size calculation based on the Central Limit Theorem and the need for a minimum of 200 participants is mentioned but needs more explanation. Why specifically was this size chosen? It would be beneficial to present the power analysis or any other statistical justification for the sample size. The section detailing the HIV Preventive Behavior Scale and other tools needs more specificity. For example, describe why the 9-item scale was developed, how the items were selected, and how they were related to the key HIV prevention behaviors. A more detailed explanation of the cognitive interview method would also be helpful, including the role of expert feedback and how this method enhanced the validity of the scale. While the statistical methods (EFA, CFA, reliability analysis) are listed, more details should be provided about the specific steps and decisions made during these analyses. For instance, explain the criteria used for determining construct validity in the CFA, the thresholds for good model fit, and how these criteria relate to the goals of the study. Discuss how you handled potential issues like multicollinearity or cross-loadings in the factor analysis. Provide more details about how participants’ consent was obtained, particularly in terms of the online survey. Discuss how anonymity was maintained, how the confidentiality of participants was ensured, and how the study complied with ethical guidelines for research with vulnerable populations. How were participants recruited, and were there any specific challenges in obtaining a diverse sample? Also, describe how the data was stored and managed to ensure integrity.\nResults\n\nThe categorization of the HIV-preventive behaviors into three broad groups (denial and avoidance, self-protective actions, and appropriate sexual response) should be more explicitly defined. The terms “denial,” “avoidance,” and “self-protective” need to be clearly operationalized, as their meaning could vary among different readers. For example, the term “self-protective” requires further elaboration to ensure that it is understood in a way that aligns with the research context. A more detailed explanation of how these categories were derived would improve clarity. While the inclusion of participant quotes helps illustrate the themes, it would be beneficial to more systematically explain how these quotes were selected and their significance in relation to the overarching research questions. It is crucial to link the quotes directly to the themes identified in the categories (e.g., how does each participant’s quote specifically inform the \"denial and avoidance\" or \"self-protective actions\"?). Additionally, ensure that the formatting of these quotes is consistent, particularly when indicating direct statements. The details of the factor analysis (e.g., PCA, EFA, CFA) should be more transparent. Specifically, while it is stated that \"the first component was denial and avoidance of HIV risk,\" it is not clear how the decision was made to group certain items together in this category. More explanation should be given about the thresholds or criteria used for factor loadings and why certain items (like question 4) were moved between components. Additionally, clarify how you determined the adequacy of the model fit based on the indices presented (e.g., χ², GFI, RMSEA) and how these compare to established benchmarks in the literature. The integration of demographic data with the psychometric analysis is lacking. To enhance the interpretation, demographic variables (such as age, sexual orientation, and frequency of sexual encounters) could be incorporated into the factor analyses or reliability tests to investigate whether certain variables influence the HIV preventive behavior scores.\n\nDiscussion\n\nThe discussion should better articulate how the study's findings build upon or diverge from previous research. For instance, while references to studies by Pimthong and Bhanthumnavin are made, the specific ways in which this study either aligns or contrasts with their findings are not clearly outlined. You should highlight the significance of the two-factor model in this study and compare it in depth with similar models used in HIV prevention research, including contrasting findings from different cultural or regional contexts. The two-component structure identified in the CFA (denial and avoidance, self-protective conduct) should be further examined in relation to the overall theory of HIV prevention behavior. How do these components relate to theoretical frameworks in sexual health and HIV prevention? Providing a more detailed theoretical underpinning for the categories would allow readers to better understand the broader implications of the findings. In particular, it would be valuable to explore whether these two components align with broader psychological theories of health behavior or HIV-related stigma. The discussion should provide more practical recommendations for HIV prevention programs. While the findings are connected to previous studies, there is less focus on how the research results can inform interventions or policies targeting MSM. More concrete suggestions on how to integrate the two components of HIV prevention behavior into public health strategies would strengthen the relevance of the study. The limitations section is briefly mentioned but should be expanded. It is essential to include a critical examination of the study’s limitations, such as the potential biases in the sampling process due to the use of online surveys, which could affect the generalizability of the findings. You should also discuss the limitations of relying solely on self-reported data, as this may introduce response biases, and the potential effects of social desirability or recall bias on the results. Additionally, the issue of sample homogeneity in terms of age or sexual orientation should be discussed, as it might limit the applicability of the findings to broader populations. While the limitations section touches on some areas for improvement, the discussion should provide a more thorough outline of potential future research. Consider recommending further studies that examine the cultural nuances in HIV preventive behaviors among MSM in other regions or countries. Also, explore how different prevention interventions might be tailored to the specific behaviors identified in this study, such as targeting denial and avoidance or enhancing self-protective behaviors. In line with the limitations, it would be beneficial to suggest methodological refinements for future studies, such as the inclusion of qualitative interviews to gain deeper insights into the underlying psychological mechanisms behind the two components identified. This would complement the quantitative data and provide a more comprehensive understanding of MSM’s HIV prevention behaviors. The discussion would benefit from a more in-depth exploration of the cultural context within Thailand, and how it might influence the reported HIV preventive behaviors. For instance, consider discussing how societal views on sexuality, masculinity, and HIV risk might shape the denial/avoidance and self-protective behavior categories identified in this study. This would provide a more nuanced understanding of the findings and their implications for HIV prevention within this specific cultural setting.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-513
|
https://f1000research.com/articles/12-508/v1
|
17 May 23
|
{
"type": "Research Article",
"title": "Exercises on a balancе cushion to influence of lumbar vertebral syndrome",
"authors": [
"Krasimira Zlatkova",
"Yuliyan Zlatkov",
"Yuliyan Zlatkov"
],
"abstract": "Background: The pain in the lumbar region is common. One of the causes of low back pain is lumbar vertebral syndrome. There is a wide range of options for treating low back pain. The purpose of the study is to describe exercises on a balance cushion to influence the pain in lumbar vertebral syndrome and to track the effect of their application. Methods: We studied 20 participants with low back pain. We applied the following tests to the patients: visual analogue scale, Schober test, measurement of lateral flexion and Straight leg raise test. The methodology includes exercises on a balance cushion. We performed manual manipulation techniques on each patient by treating trigger points in the lower back and buttocks once a week. Results: We achieved an improvement in the studied indicators after the applied therapy, which was expressed in a reduction of pain and restoration of normal mobility in the lumbar region. Conclusions: The application of exercises on a balance cushion allows in a short time to affect the pain and mobility in the lumbar spine to fully perform their work and professional activities.",
"keywords": [
"exercises",
"balance cushion",
"low back pain",
"lumbar vertebral syndrome"
],
"content": "Introduction\n\nMany authors work in the area of low back pain, defining it as a health problem with a large social economic impact (De Castro et al., 2020). According to Botov, Shnyakin, Osipov and Zhavner (2018) today, it is generally accepted that most people experience low back pain (LBP) throughout their lives and this pain becomes chronic with age (Botov, Shnyakin, Osipov and Zhavner, 2018). Janura et al. (2015) noted that LBP is a painful disease which results in limitations on normal daily physical activities related to self-care, social contact and communication (Janura et al., 2015). In 2015 Gotova, Filipova and Popova ported that approximately 75-85% of the elite female rhythmic gymnasts worldwide have had at least one episode of lumbar spine pain during their racing career (Gotova, Fillipova and Popova, 2015).\n\nLower back pain can occur or develop by many kinds of factors like age, gender, height, weight, body mass index (BMI) and general health (Alperovitch-Najenson et al., 2010). Zlatkov (2019a) shares that the pain in this region can be of a different nature – neurological, traumatic, psychological, etc. Determining the type and location of pain in the lumbosacral region helps to diagnose correctly, which aids to choose the right treatment (Zlatkov, 2019a). Konstandinu et al. (2016), studying tennis players, report that the causes of lumbar pain are various – single or multiple external injuries, osteoporosis, static overload, muscle strain, as well as stress (Konstandinu et al., 2016). According to Zlatkov (2020) one of the reasons for the distribution of lumbar pain is lifestyle – the lack of physical activity, which leads to detraining of the muscles that support the spine (Zlatkov, 2020).\n\nZlatkov (2019b) reports that one of the causes of pain in the lumbar region is vertebral syndrome, which can affect people of different ages (Zlatkov, 2019b). According to Todorova, Georgieva and Gavrailov (2015) vertebral syndrome is characterized by smoothed physiologic lordosis, functional scoliosis, rigid paravertebral musculature, hypomobility, button symptom, impaired posture and locomotion (Todorova, Georgieva and Gavrailov, 2015).\n\nStoyanov, Avamova, Mitova and Gramatikova in 2020 summarize that low back pain leads to a loss of full life, which negatively affects the quality of life of patients. The authors report that there are various methods of treating chronic spine pain syndrome (Stoyanov, Avramova, Mitova and Gramatikova, 2020). There is a wide range of options for treating low back pain. According to Pappas, Panou and Souglis (2013) these interventions can be categorized as active or passive (Pappas, Panou and Souglis, 2013).\n\nLowe, Swanson, Hudock and Lotz (2015) share that use of a backrest support surface for the lumbar spine reduces activation of trunk muscles and aligns the spine in a more optimal lordosis, or “S-shaped”, posture. The unstable (stability ball) seating practice is predicated on deliberately inducing a trunk muscle (or “core activation”) challenge to create an exercise stimulus and a beneficial physiological response for the individual (Lowe, Swanson, Hudock and Lotz, 2015).\n\nWang, Weiss, Haggerty and Heath (2014) note that active seating is classified as the use of an unstable seating surface that requires the user to engage in more movement of the carcass to maintain an upright sitting posture. According to the authors this type of seating can be performed on an extremely compatible surface such as a stability ball or a moderately compatible air cushion placed on the seat of the chair (Wang, Weiss, Haggerty and Heath, 2014).\n\nLee, Lim, Won and Kim (2018) administered to drivers with low back pain therapy with a gel cushion for a period of three months and found that their condition improved (Lee, Lim, Won and Kim, 2018).\n\nWe suggest that patients suffering from low back pain exercise on a balance cushion. Exercises improve the condition of patients by influencing the mobility of the lumbar spine, reducing pain and relaxing the muscles. As the mobility in the lumbar region improves, the trophism of the nucleus pulposus also improves.\n\nFrom the literature reference we did not find authors who indisputably prove the effectiveness of the application of a balance cushion in patients with low back pain. Therefore, we believe that our article is important and original and should enrich the means used to affect low back pain.\n\nThe purpose of the study is to describe exercises on a balance cushion to influence the pain in lumbar vertebral syndrome and to track the effect of their application.\n\nThe research objectives are:\n\n1. to improve the general condition of patients;\n\n2. to reduce pain;\n\n3. to improve mobility in the lumbar region.\n\nExercises with a balance cushion are intended for all low back pain sufferers and especially for people with sedentary occupations. They enrich the means that can be applied to deal with this type of pain. After the pain subsides, patients can apply sitting on a balance cushion for prophylaxis.\n\nWe are of the opinion that the application of exercises on a balance cushion will lead to a reduction in muscle stiffness and improve the movements in the lumbar region.\n\n\nMethods\n\nThe study was conducted in the Eighth Academic Building of Southwest University “Neofit Rilski”, Blagoevgrad for the period January-June 2021. In the present study included 20 subjects with low back pain, aged 25-35 years. The Commission for Ethics of Scientific Research at South-West University “Neofit Rilski” – Blagoevgrad provided ethical approval (No: 2012-1/10 December 2020) for this research to carry out in accordance with the Declaration of Helsinki. After getting acquainted with the nature of the study and obtaining written informed consent, we proceeded to conduct the study.\n\nThe inclusion criteria were:\n\n✓ Аge between 25 and 35 years;\n\n✓ Low back pain;\n\n✓ Patients should be dissatisfied with the condition and want to change it.\n\nТhe exclusion criteria were:\n\n✓ Pregnancy;\n\n✓ Recent operations;\n\n✓ Cauda equina syndrome.\n\nThe following studies were performed on patients:\n\n✓ Evaluation of pain using a visual-analogue scale - Visual analog scala (VAS) is used to evaluate pain objectively (Sanioglu, Yerebakan and Farsak, 2017);\n\n✓ Shober test- this is a test to determine mobility in the lumbar region. This test measures the flexion in the lumbar spine (Zlatkov, 2019b);\n\n✓ Measurement of lateral flexion - used to assess lateral mobility;\n\n✓ Straight leg raise test - this is one of the main tests to determine disc herniation and protrusion, especially in cases of root compression (Zlatkov and Popov, 2019).\n\nThe dynamics of the studied indicators were monitored before and after the kinesitherapy.\n\nWe introduced patients to the nature of the study. After receiving informed consent and approval from the Commission for Ethics of Scientific Research at South- West University “Neofit Rilski”, Blagoevgrad, we proceeded to conduct the study. Written informed consent for publication of their details was obtained from the study participant. We applied exercises on a balance cushion for a period of one month. After conducting research (VAS, Schober test, measurement of lateral flexion and Straight leg raise test) on the participants in the study and determining their condition, the therapy was started. At the beginning of the procedures, each participant was given a manipulative massage and treatment of trigger points in the back, lumbar region, buttocks and lower limbs. They then proceeded to perform the exercises on a balance cushion. Each exercise was demonstrated by us in order for it to be learned correctly and to be performed independently at home. The exercises were the following:\n\nExercise 1. Sitting on the balance cushion. Inclination and declination of the pelvis (Figure 1). Performed 8-10 times.\n\nExercise 2. Seat on a balance cushion. Elevation of the pelvis to the left and right. It was performed 7-8 times for each country (Figure 2).\n\nExercise 3. Seating on a balance cushion. Circles of movements with the pelvis. They were performed 7-8 times for each side (Figure 3).\n\nThe duration of the exercises was approximately 10 minutes altogether. They should be performed several times a day. Subjects who had been in a sitting position at work for a long time were advised to use a balance cushion there as well. The duration of the study period was one month, during which patients strictly performed the exercises at home and once a week we applied manual manipulative techniques on our part.\n\n\nResults\n\nThe dynamics of the studied indicators were monitored before and after the kinesitherapy. The evaluation of research results were realized by statistical and mathematical methods and procedures using Graph Pad Prism 3.0. We calculated the mean and standard deviation of the studied indicators. In term to calculate statistically, significant differences we use Wilcoxon signed-rang test to compare independent quantitative variables.\n\nThe mean age of the participants in our study was 29.8 ± 3.89 years. Participants in our study were men (n = 10) with a mean age of 29.4 ± 4.69 years and women (n = 10) with a mean age of 30.2 ± 3.08 years.\n\nThe degree of pain is measured with a visual-analogue scale. Before our treatment, the mean values (X¯ ± SD) of the degree of pain in the participants were 6.7 ± 1.08, and after it - 0.4 ± 0.75. Prior to kinesitherapy, 12 subjects reported severe pain and 7 had moderate pain. At the end of therapy, 15 of the patients indicated that they were without pain and 5 with mild pain.\n\nThe mean values of the measured mobility in the lumbar region according to the Schober test are 1.87 ± 0.23 cm before the therapy with a balance cushion and 3.035 ± 0.15 cm after it. We compared the mean values for statistical reliability by Wilcoxon test at p ˂ 0.05.\n\nIn Table 1 we present the mean (X¯) ± standard deviation (SD) of the measured lateral flexion before and after the exercises with a balance cushion. The measured values are in cm. We see an improvement of 3.27 cm to the left and 2.88 cm to the right.\n\n⁎ We found statistically differences in Wilcoxon test at p < 0.05 before and after therapy.\n\nBefore and after applying the exercises with a balancе cushion, we measured the degrees reached from the Straight leg raise test. Before treatment, the mean values (X¯ ± SD) of the test were 48.45 ± 5.94 °, and after it - 76.25 ± 3.34 °. We compared the mean values of the Wilcoxon signed - rang test for statistical reliability at p ˂ 0.05.\n\n\nDiscussion\n\nIn recent years, there has been a decline in the age of those affected by disc herniation. In our practice, we are seeing younger people with lumbar spine problems.\n\nWhen assessing the degree of pain through the visual-analog scale (VAS), we clearly see improvement in patients after a month of therapy with a balance cushion. 75% of participants reported no pain at the end of the study, and 25% reported mild pain, which indicates how effective it is to exercise on a balance cushion. Islam et al. (2020) assessed the degree of VAS pain in motorcyclists with low back pain divided into two groups. At the beginning of the study, she had grades 7 and 8 in the VAS. After 6 weeks of middle assessment performance, successful progressions were observed at 37.1% and 40.0% to the respective participants persisted at the range of 4 and 5 into VAS (Islam et al., 2020).\n\nThe measured values from the Shober test after the therapy show a clear improvement in lumbar mobility. It is normal for the measured distance to be increased from 3.5 to 4 cm (Pashkunova, 2015). The mean obtained at the end of balancе cushion therapy approaches normal values. The observed improvement from the application of exercises on a balance cushion proves their applicability in patients with lumbar vertebral syndrome. Yen et al. (2015) examined healthy subjects and found that the rate of decrease in lumbar mobility, as measured by the Schober test in men, was very significant from an average of 5.0 cm in the youngest group to 3.1 cm in the oldest group and 3.6 cm to 2.4 cm among women (Yen et al., 2015).\n\nMeasurement of lateral flexion shows a significant improvement in the patient’s condition immediately after performing exercises on a balancе cushion. It was essential for us to keep this improvement. Therefore, we recommended that you exercise several times a day for 5-7 minutes, for a long time (1 month). For the same time period in 2011, Krastev, Nikolovska, Stratorska, and Vasileva noted an improvement in the lateral flexion of 1.7 cm and 1 cm to the left and 1.8 cm and 0.8 cm to the right by applying manual therapy and classic therapeutic massage, analytical exercises in patients with chronic lumbosacral pain (Krastev, Nikolovska, Stratorska, and Vasileva, 2011).\n\nThe improvement in test values Straight leg raise test at the end of a balancе cushion therapy indicated an effect on neurological symptoms in study participants. The distinction between muscular and nerve root pain causes many clinicians to use various additional confirmatory tests (e.g., the Bragard test). According to Hall and McIntosh (2014), the use of additional tests is not required in the correct application and interpretation of the Straight leg raise test (Hall and McIntosh, 2014). By measuring the values of the Straight leg raise test, we prove digitally the effectiveness of our methodology for responding to lumbar vertebral syndrome.\n\n\nConclusions\n\nThe lumbar vertebral syndrome, as a result of various causes, is increasingly common in the younger population. The use of various conservative methods to influence them aims to improve the quality of life of those affected. The application of exercises with a balance cushion enriches the kinesitherapeutic practice. Their implementation in the daily lives of those affected by this problem allows in a short time to affect the pain and mobility in the lumbar spine to fully perform their work and professional activities.",
"appendix": "Data availability\n\nDryad: Exercises on a balance cushion to influence of lumbar vertebral syndrome, https://doi.org/10.5061/dryad.b8gtht7hh (Zlatkova and Zlatkov, 2023).\n\nThis project contains the following underlying data:\n\n- Lumbar_vertebral_syndrome.xlsx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nReferences\n\nAlperovitch-Najenson D, Santo Y, Masharawi Y, et al.: Low back pain among professional bus drivers: ergonomic and occupational-psychosocial risk factors. The Israel Medical Association journal: IMAJ. 2010; 12: 26–31. PubMed Abstract\n\nBotov A, Shnyakin P, Osipov A, et al.: Search for effective treatment techniques for professional athletes with lower back pain. Journal of Physical Education and Sport. 2018; 18: 17–22.\n\nDe Castro JBP, Lima VP, Dos Santos AOB, et al.: Correlation analysis between biochemical markers, pain perception, low back functional disability, and muscle strength in postmenopausal women with low back pain. Journal of Physical Education and Sport. 2020; 20: 24–30.\n\nGotova J, Filipova M, Popova D: Study of the therapeutic effect of auriculotherapy in the acute period of lumbar spine pain syndrome in female athletes. Physics Journal. 2015; XII: 30–32. (in Bulgarian language).\n\nHall H, McIntosh G: Passive Straight Leg Lift Test: Definition, Interpretations and Utilization. Journal of Current Clinical Care. 2014; 4: 24–32.\n\nIslam A, Ahmed S, Kamrujjaman M, et al.: Effect of physical exercise and routine intervals on LBP assessment using VAS, OLBPDQ, and RMQ among professional motorbike riders in Dhaka city. Journal of Physical Education and Sport. 2020; 20: 1747–1753.\n\nJanura M, Gallo J, Svoboda Z, et al.: Effect of physiotherapy and hippotherapy on kinematics of lower limbs during walking in patients with chronic low back pain: A pilot study. Journal of Physical Education and Sport. 2015; 15: 663–670.\n\nKonstandinu A, Megova T, Mihaylova N, et al.: Physiotherapy for Back Injuries Prophylaxis of Tennis Players. International Journal of Sports and Physical Education (IJSPE). 2016; 2: 16–19.\n\nKrastev T, Nikolovska, Stratorska T, et al.: Kinesitherapy for chronic pain syndrome in the lumbar-sacral region, Optimization of the combination of modern manual techniques in the treatment of musculoskeletal dysfunctions. NSA Press; 2011; pp. 94–102. (in Bulgarian language)\n\nLee JW, Lim YH, Won YH, et al.: Effect of gel seat cushion on chronic low back pain in occupational drivers: A double-blind randomized controlled trial. Medicine. 2018; 97: e12598. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLowe BD, Swanson NG, Hudock SD, et al.: Unstable sitting in the workplace–are there physical activity benefits? American Journal of Health Promotion: AJHP. 2015; 29: 207–209. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPappas E, Panou H, Souglis A: The effect of a pilates exercise programme using fitball on people suffering from chronic low-back pain in terms of pain reduction and function improvement. Journal of Physical Education and Sport. 2013; 13: 606–611.\n\nPashkunova Y: Analysis of the applied complex physiotherapy program in adults with chronic thoraco-lumbar pain. Scientific Papers of the University of Ruse. 2015; 54: 127–132. (in Bulgarian language).\n\nSanioglu S, Yerebakan H, Farsak MB: Effects of Two Current Great Saphenous Vein Thermal Ablation Methods on Visual Analog Scale and Quality of Life. BioMed Research International. 2017; 2017: 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStoyanov G, Avramova M, Mitova S, et al.: Frequency and prevalence of chronic pain syndrome in the spine. Knowledge - International Journal. 2020; 42: 777–783.\n\nTodorova G, Georgieva S, Gavrailov Y: Differential kinesitherapeutic approach in lumbo-sacral pathologies. Scientific works of Ruse University. 2015; 54: 41–45. (in Bulgarian language).\n\nWang H, Weiss KJ, Haggerty MC, et al.: The effect of active sitting on trunk motion. Journal of Sport and Science. 2014; 3: 333–337.\n\nYen YR, Luo JF, Lui ML, et al.: The anthropometric measurement of Schober’s test in the normal Taiwanese population. BioMed Research International. 2015; 2015: 1–5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZlatkov Y, Popov N: Tracing the role of Straight leg raise test in patients with lumbar vertebral syndrome. Sport & Science. 2019; 212–217. (in Bulgarian language).\n\nZlatkov Y: Differentiation of the pain in the lumbosacral region. Knowledge. Int. J. 2019a; 35: 1185–1187.\n\nZlatkov Y: Application of own methodology in the treatment of lumbar vertebral syndrome. Sport & Science. 2019b; 218–227. (in Bulgarian language).\n\nZlatkov Y: Characteristics of lumbar pain. Knowledge International Journal. 2020; 41: 545–550.\n\nZlatkova K, Zlatkov Y: Exercises on a balance cushion to influence of lumbar vertebral syndrome. [Dataset]. Dryad. 2023. Publisher Full Text"
}
|
[
{
"id": "306744",
"date": "06 Aug 2024",
"name": "Aysegul Ketenci",
"expertise": [
"Reviewer Expertise Low back pain",
"exercise"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIntroduction The introduction of this article is not well-organized and fails to effectively correlate the previous literature with the objectives of this study. Although various studies and statistics related to low back pain (LBP) are mentioned, the narrative lacks a coherent flow that connects these findings to the current research focus. Although several relevant studies are cited, the discussion does not establish a clear connection between these previous findings and the specific aims of this study. For example; the sentence “In 2015 Gotova, Filipova and Popova ported that approximately 75-85% of the elite female rhythmic gymnasts worldwide have had at least one episode of lumbar spine pain during their racing career (Gotova, Fillipova and Popova, 2015).” Is not related and necessary. It was written “According to Todorova, Georgieva and Gavrailov (2015) vertebral syndrome is characterized by smoothed physiologic lordosis, functional scoliosis, rigid paravertebral musculature, hypomobility, button symptom, impaired posture and locomotion (Todorova, Georgieva and Gavrailov, 2015).” But different kind of pathologies for example; disc herniation, facet joint osteoarthritis, disc degeneration, spondylolisthesis etc can make this kind of symptoms and signs. Differential diagnosis of these pathologies should be made and appropriate treatments should be applied. Notably, the study by Lee et al. (2018) is mentioned, which has similar objectives related to the use of cushions for low back pain relief. However, there is no detailed explanation of how the current study differentiates itself from Lee et al.'s research, which is crucial for understanding its unique contributions.\nStudy Design and Inclusion/Exclusion Criteria To accurately assess the effectiveness of the balance cushion exercises, the study should include a control group that receives either no intervention or an alternative standard treatment. This would allow for a clearer comparison and better isolation of the effects of the balance cushion exercises from other variables, such as the manual manipulation techniques that were also administered to participants. While the inclusion criteria mention age and the presence of low back pain, the duration of low back pain and whether radiation of pain should be specified to distinguish between acute and chronic cases, which may respond differently to the intervention. For example, stating that participants must have experienced low back pain for at least three months would clarify the study's focus on chronic conditions. Previous treatments and exercise habits should be noted. The exclusion criteria should be expanded to include individuals with neurological, rheumatological diseases and comorbidities. These conditions can significantly influence pain perception and response to treatment, thereby introducing potential confounding variables that could affect the study's outcomes. The mention of subjects who had been sitting for long periods using a balance cushion introduces heterogeneity into the study group. This subgroup, who use the cushion longer and more frequently than specified, should be clearly defined and analyzed separately if needed to avoid confounding the results. Including specific numbers and conducting different analyses for this subgroup would help maintain the study’s internal validity. The current methodology also lacks clarity on how the efficacy of the intervention was assessed. While several tests, such as the visual analogue scale (VAS), Schober test, lateral flexion measurement, and Straight leg raise test, are mentioned, the criteria for evaluating success are not well-defined. Detailed descriptions of the assessment tools, their application, and the interpretation of results would improve the robustness of this section. Additionally, some problems are observed in the selection of literature. For example, the literature given for VAS is about “comparing two current great saphenous vein thermal ablation methods on VAS and QL”. One of the literature describing different pain assessment scales should be used. Procedures The authors said that “They should be performed several times a day” Do we know how many times a day patients do it? Is there a cut-off number?\nResults The statistical tests used are mentioned, but the results lack p-values, which are essential for interpreting the significance of the findings. More comprehensive statistical analysis, including confidence intervals and effect sizes, would provide a deeper understanding of the intervention's impact and the reliability of the results. Additionally, there are minor grammatical errors, such as \"Wilcoxon signed-rang\" which should be \"Wilcoxon signed-rank\" test, and it should be noted that this test is for paired quantitative variables, not independent ones. Furthermore, the tables provided are not sufficient. More descriptive tables, including baseline characteristics of the study population and detailed results of the different assessments, would improve the clarity and comprehensiveness of the paper. Discussion It was written “In recent years, there has been a decline in the age of those affected by disc herniation. In our practice, we are seeing younger people with lumbar spine problems.” At the beginning of the discussion section. The aim of this study is “ Exercises on a balancе cushion to influence of lumbar vertebral syndrome”. The study group includes patients with lumbar vertebral syndrome, not disc herniation patients. So this first sentence is not relevant with the study. The discussion section should more thoroughly address the potential biases and limitations of the study. These include the small sample size, short duration of the intervention, and the absence of a control group. Acknowledging these limitations would provide a more balanced interpretation of the findings and highlight areas for future research. Most important thing, you said that “We performed manual manipulation techniques on each patient by treating trigger points in the lower back and buttocks once a week.” How results can be attributed to exercise?? How can you say that the improvement is not due to manual therapy? Moreover, the discussion should explore the broader implications of the results within the context of existing literature. This includes comparing the findings with those of similar studies, such as Lee et al. (2018), and discussing possible mechanisms through which balance cushion exercises might influence pain and mobility in individuals with lumbar vertebral syndrome. Additional comments There is no need to say \"Zlatkova (2019) states this and that (Zlatkova ,2019).\"; only one of them is enough.\nIt says “each country” after the exercise 2. It is not clear what it means, may need to be revised.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
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https://f1000research.com/articles/12-508
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