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https://f1000research.com/articles/11-298/v1
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10 Mar 22
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{
"type": "Brief Report",
"title": "Rice straw decomposition in paddy surface water potentially reduces soil methane (CH4) emission",
"authors": [
"Huynh Van Thao",
"Masato Oda",
"Nguyen Huu Chiem",
"Huynh Van Thao",
"Masato Oda"
],
"abstract": "Background: Rice cultivation is a significant methane (CH4) emission source. Rice straw (RS) incorporation into the soil is a key factor that produces higher CH4 emission. The RS waterlogging approach on the soil surface possibly reduces CH4 emission due to not being buried into the soil. However, evaluation of CH4 emission by this approach has not been determined. The objective of this study was to examine CH4 emission under RS waterlogging on surface water compared with RS incorporation into the soil. Methods: We carried out a microcosm experiment in a screen-house with two treatments, including (i) RS incorporation into the soil and (ii) RS waterlogging on the soil surface in triplicates. We compared the CH4 emissions and CH4 accumulation for the rice-growing and off-sowing periods. Yield-scaled CH4 emission was assessed based on total methane emission and rice yield. Results: The results demonstrated that RS waterlogging reduced CH4 emission by 16.9% compared to RS incorporation into the soil. During the rice-growing period, total CH4 emission from RS waterlogging accounted for 36% of the incorporation treatment. However, RS waterlogging is caused by high emissions during the off-sowing stage. The difference between yield-scaled CH4 emissions was insignificant. Conclusions: This study demonstrated that the treatment of RS by waterlogging is an appropriate alternative to conventional RS practices known as incorporation, which increases greenhouse CH4 emission. However, high CH4 emission during the off-sowing period, and RS accumulation in the field are key drivers that possibly contribute to greenhouse gas emissions. Therefore, further evaluation is needed to determine the long-term effects of this approach.",
"keywords": [
"greenhouse gas emission",
"rice straw incorporation",
"methane emission",
"organic rice",
"water management",
"the Vietnamese Mekong Delta"
],
"content": "Introduction\n\nThe agricultural sector contributes approximately 10–12% of global anthropogenic emissions. Of these emissions, 47% of methane (CH4) emission has been attributed to agriculture production (Smith et al., 2007). Rice fields have been considered an important source of atmospheric CH4, accounting for 15–20% of the global total anthropogenic CH4 emission (Sass & Fisher, 1997). Rice straw (RS) plays a vital role in contributing to CH4 emission from paddy fields. Several field experiments have shown that RS incorporation significantly increases CH4 emissions in rice fields (Hoa et al., 2019; Jiang et al., 2019; Liu et al., 2015; Wang et al., 2019). In the Mekong Delta of Vietnam, the intensification of rice cultivation is a great contributor to CH4 emission (Oda & Chiem, 2019). Several studies have explored decomposing RS in paddy surface water as an effective pathway to reduce CH4 emission (Boateng et al., 2017; Oda & Chiem, 2019; Tariq et al., 2017). For example, Thao et al. (2019) demonstrated a field experiment on RS decomposing in field surface water 20 days before sowing as a suitable possibility for developing a double-cropping pattern in the Mekong Delta. However, the research did not determine how much this process reduced CH4 emissions. In addition, Oda & Chiem (2019) suggested that the strategy of decomposing RS on surface water effectively reduces CH4 emission from the paddies. To the best of our knowledge, CH4 emission from the RS decomposition process in water has not been thoroughly studied. Therefore, we conducted a microcosms experiment to clarify whether RS waterlogging reduces CH4 emission, and the results found that this approach did decrease the CH4 emission from the paddy field.\n\n\nMethods\n\nThis study was conducted in an experimental screen house at Can Tho University (Cantho City, Vietnam) from April to August 2019. The screen-house consisted of a translucent white roof and rat-proof wire screens. The inner humidity in the experimental house is relatively similar compared with outdoors. We used plastic containers (38 cm × 58 cm × 30 cm high) filled to 20 cm with paddy field soil (10°18′N, 105°54′E). The soil was classified as Thionic Glycesol (International Union of Soil Sciences (IUSS) working group World Reference Base (WRB), 2015) (Dong et al., 2012).\n\nEffects of RS waterlogging and RS incorporation into the soil on methane emission were evaluated following a conventional rice cultivation experiment (first crop). The first experiment set essential conditions (rice straw, soil) for implementing the second experiment. In the first crop, a short-duration variety of rice was used (IR50404 cultivar, 85–90 days) which is a typical rice variety of Vietnam, provided by Cuu Long Delta Rice Research Center (CLRRI). Pre-germinated seeds were sown at an equivalent rate of 250 kg ha-1 on wet-leveled soil. Water irrigation was managed as alternative wetting and drying (AWD) technology which reflood 5 cm when the surface water level naturally declined to 10 cm below the soil surface. The technology is known as multiple aerations developed by International Rice Research Institute (IRRI) to reduce water consumption for rice cultivation (Hoa et al., 2018). In the second crop, we used RS and soil from containers in the first crop to examine the effects of rice straw incorporation and waterlogging on methane emission. Fresh RS (above-surface biomass) in the first crop was collected and cut into 5 cm in length. Then it was immediately scattered onto the soil surface as well as incorporated into the soil, correspondingly. The IR50404 variety was also sown at a rate of equivalent to 250 kg ha-1. Water irrigation was managed as a continuously flooding management method during the rice-growing period. Fertilizers were not applied for either experiment.\n\nThere were two treatments, comprising (i) RS waterlogging on the soil surface and (ii) RS incorporation into the soil. Each treatment was set up in triplicate. A total of six microcosms were laid out closely in an array of two columns and three rows. Both treatments were performed one day after harvesting the first crop.\n\nIn the waterlogging treatment, RS was scattered on the soil surface and irrigated to 10 cm in-depth for the waterlogging treatment. Then, the RS was gently pressed into water. It was left for a 20-day stage without disturbing (off-sowing period). This timing was followed by a field demonstration recommended by Thao et al. (2019) that RS was well-fermented in water within 20 days, and the rice field has suitable conditions for broadcasting rice seeds. In the RS incorporation treatment, RS was incorporated into the soil by a shovel and immediately irrigated to 2 cm in-depth for a 5-day period (off-sowing period), a typical treatment pattern for a triple-cropping rice production system in the Vietnamese Mekong Delta.\n\nOn the sowing day, we drained the field and leveled it by hand. The soil was not reincorporated. We started irrigation on day 7 with 3–5 cm of water and maintained the water level during the rice-growing period. The water level was drained seven days before harvesting.\n\nThe closed chamber method was used to measure CH4 following the guidelines recommended by Minamikawa et al. (2015). The chamber (58 cm in length × 38 cm in wide and 90 cm in height) was equipped with a vent to allow equilibration of the pressure, a thermometer, a sampling port, and a fan to ensure well-mixed air inside the chamber while taking the gas sample. Gas sampling was flushed five times with chamber air before collecting. Gas samples were collected with a propylene syringe 50mL at 3, and 23 min after the chamber placement, and each gas sample was immediately injected to 15 mL in vacuumed vials. During the off-sowing period (rice straw treated before harvesting), gas sampling was taken on days 3, 6, and 13 for the rice straw waterlogging treatment, while RS incorporation treatment was sampled on day 3. After sowing, sampling frequently intensified every three days during the first 21 days when the high fluxes were characteristically observed. Then, the process was carried out once a week until the day of harvest. All gas samples were taken between 07:00, and 10:00 am. The CH4 concentration was analyzed by gas chromatography (Shimadzu GC2014, Japan) equipped with a flame ionization detector, using 60/80 Carboxen® 1000 column at temperature 180 °C. Nitrogen (99.99%) as a carrier gas at a flow rate of 30 ml min−1.\n\nTap water was directly irrigated for rice containers. Water levels were checked by a 50-cm ruler (1-mm scale). Grain yield was detected by harvesting all rice in each pot and removing all unfilled grains using tap water. Grains were sundried at ambient temperature. The presented grain yield was adjusted to 14% of moisture by a grain moisture tester (Riceter f2, Kett Electric Laboratory, Tokyo, Japan).\n\nThe cumulative CH4 emissions were calculated using a trapezoidal integration method with linear interpolation and numerical integration between sampling times. The calculation was done as follows: (i) calculate the daily gas flux by multiplying the daily mean hourly gas flux by 24, (ii) calculate the emission between every two consecutive measurements using the trapezoidal rule, and (iii) sum up the areas of all the trapezoids. Yield-scale CH4 emission was calculated by dividing total methane emission by grain yield. Detailed guidance can be found at Minamikawa et al. (2015). All measurements were carried out with three repetitions. Data processes were performed using Microsoft Excel 2019.\n\nData analysis was performed using IBM SPSS Statistics 22.0 (RRID:SCR_016479). The independent sample t-test comparison was used to compare the CH4 emission in rice-growing and off-sowing periods as well as yield-scaled CH4 emission. The statistical significance was done with a confident level of 95%.\n\n\nResults\n\nWe assessed the effects of rice straw management via waterlogging and incorporation on CH4 emission using a container experiment. The results showed that the CH4 emission from waterlogging accounted for 36% of the incorporation treatment during the rice-growing period (Figure 1a) (Oda et al., 2020). However, high emissions were found in the off-sowing stage (Figure 1b). The total CH4 emissions from the waterlogging and incorporation treatments were 502 ± 111.4 kgCH4.ha-1.crop-1 and 604 ± 41.9 kgCH4.ha-1.crop-1, respectively. In general, the magnitude of seasonal CH4 emission that was observed in our study was lower than what was found in previous studies on triple-cropping in the central Mekong Delta of Vietnam, which ranged between 710 and 1,789 kgCH4.ha-1.crop-1 (Oda & Chiem, 2019; Vo et al., 2018). The CH4 emission for the decomposing RS subject to waterlogging was 16.9% lower than that of the straw in the incorporation approach, even though the total timing of the off-sowing and rice-growing period was 30% longer. For the yield-scaled CH4 emission from straw, the waterlogging and incorporation models were 0.21 ± 0.02 kg CH4.kg grain-1 and 0.3 ± 0.08 kg CH4. kg grain-1, respectively. The difference between yield-scaled CH4 emissions was insignificant (P>0.05) (Figure 2).\n\nCH4 emission accumulation of rice strawy (RS) waterlogging and RS incorporation in the periods of rice-growing (a), and off-sowing (b).\n\nCH4 emission peaked one week after the prior crop's harvest. The peak of waterlogging was 3.82 times higher than the peak of the incorporation approach (Figure 3). After sowing, the CH4 emission of the incorporation approach was always higher when compared with the waterlogging method. The first peak was in line with a previous study (Oda & Chiem, 2019).\n\n\nDiscussion\n\nConventional rice cultivation based on rice straw incorporation of paddy fields is a substantial source of CH4 emissions. Modification of rice straw practices is undoubtedly necessary to reduce CH4 flux when the rice straw incorporated into the soil. In other words, rice straw incorporation will be the most detectable substrate source to contribute to higher CH4 emission from rice paddy fields. Although rice straw amendment enriches soil organic carbon and improves soil fertility (Bjoern et al., 2014; Liu et al., 2014), it increases the availability of organic carbon and simultaneously intensifies strict anaerobic conditions to stimulate CH4 formation on the rice paddy field (Sass et al., 1991). Waterlogging rice straw management strategy instead of incorporation demonstrates less methane emission 12%, even though rice straw applied during the fallow period decreased CH4 emission by 11% compared to the same amount rice straw applied during rice filed preparation (Lu et al., 2000). In this study, we reached similar results in mitigation of emission from the rice straw practice with regards to non-incorporation reduced 16.9% for the whole period. The efficiency of CH4 emission from rice straw waterlogging on the field surface promotes aerobic decomposition, resulting in reducing CH4 emission.\n\nThis study showed the effects of rice straw management on CH4 emission in the rice-growing period. Total CH4 emission of rice straw after waterlogging was lower than that of the incorporation approach. These findings suggest that when rice straw was decomposed in water generated less CH4 emission than when it was buried in the soil. This can be explained by decomposition via soil-flooding management, which blocks oxygen penetration into the soil and creates a stable anaerobic condition, allowing bacteria capable of producing CH4 to thrive (Conrad, 2007). In the decomposition of rice straw in water, which is generally affected by dissolved oxygen, methanogenesis fermentation can be limited by high O2 concentrations (Jiang et al., 2019). In addition, the low yield-scaled CH4 emission from waterlogging demonstrates that this method effectively increases agricultural production and improves environmental protection.\n\nAs observed in this study, when waterlogging is used during the off-sowing period, CH4 emission is more concentrated than incorporation because the rice straw decomposition period is longer than that of rice straw incorporation treatment. Specifically, the off-sowing period was conducted for 20 days, while the rice straw incorporation treatment was performed for five days only. Subsequently, the total CH4 emission during the RS waterlogging is more significant than rice straw incorporation. Rice straw CH4 emission sources generate from rice straw decomposing. During off-sowing, rice straw waterlogging decomposes faster than incorporation and produces much more readily available carbon. The decomposing process consumes dissolved oxygen in the water, creating an anaerobic condition, contributing to the CH4 generation.\n\nThe development of agricultural technologies to reduce CH4 emission during off-sowing should be performed in future research. For instance, alternative wetting and drying (AWD) or intermittent irrigation could be a suitable option for reducing CH4 emission during the waterlogging period because it transmits the surface condition of the paddy field from reduction condition to oxidation condition by frequent contact with the air. Furthermore, the effects on the proportion of rice straw returning and seasonal carbon accumulation have not been deduced. Thus, future works should continuously examine their effects on CH4 emission in the long-term run.\n\n\nConclusions\n\nWe evaluated effects of RS treatment measures on CH4 emissions under waterlogging and incorporation. Our results indicated that RS decomposition under the waterlogging approach reduces CH4 emission compared to the incorporation approach, confirming the feasibility of rice straw waterlogging as a mitigation option for paddy CH4 emission in the Vietnamese Mekong Delta. However, waterlogging significantly contribute to CH4 emission during the off-sowing period. Thus, we recommend that reducing CH4 emission using RS decomposition during off-showing should be examined for further studies.\n\n\nData availability\n\nFigshare: Methane emission in waterlogging double cropping. https://doi.org/10.6084/m9.figshare.11987628.v1 (Oda et al., 2020).\n\nThis project contains the following underlying data:\n\n- Methane concentration and GHG_12 March 2020_17h25.xlsx (This file provides raw data that collected during experimental operation used for calculating CH4 emission (mgCH4.m-2.h-1) and cumulative methane emission (kgCH4.ha-1.crop-1), and yield-scaled CH4 emission (kg CH4 grain-1)).\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\nWe would like to thank Ms. Nguyen Ngoc Ngan, Mr. Ta Quang Khoi, and Mr. Nguyen Thien Thanh, students in Can Tho University, for their support of the study. We also thank Dr. Nigel Downes for proofreading the manuscript.\n\n\nReferences\n\nBjoern OS, Marianne S, Roland JB: Methane and nitrous oxide emissions from flooded rice fields as affected by water and straw management between rice crops. Geoderma. 2014; 235–236: 355–362. Publisher Full Text\n\nBoateng KK, Obeng GY, Mensah E, et al.: Rice Cultivation and Greenhouse Gas Emissions: A Review and Conceptual Framework with Reference to Ghana. Agriculture. 2017; 7(1): 7. Publisher Full Text\n\nConrad R: Microbial ecology of methanogens and methanotrophs. Adv Agron. 2007; 96: 1–63. Publisher Full Text\n\nDong NM, Brandt KK, Sørensen J, et al.: Effects of alternating wetting and drying versus continuous flooding on fertilizer nitrogen fate in rice fields in the Mekong Delta, Vietnam. Soil Biol Biochem. 2012; 47: 166–174. Publisher Full Text\n\nHoa DT, Nghia TH, Tokida T, et al.: Impacts of alternate wetting and drying on greenhouse gas emission from paddy field in Central Vietnam. Soil Science and Plant Nutrition. 2018; 64(1): 14–22. Publisher Full Text\n\nHoa HTT, Do DT, Giang TTT, et al.: Incorporation of rice straw mitigates CH4 and N2O emissions in water saving paddy fields of Central Vietnam. Archives of Agronomy and Soil Science. 2019; 65(1): 113–124. Publisher Full Text\n\nJiang Y, Qian H, Huang S, et al.: Acclimation of methane emissions from rice paddy fields to straw addition. Sci Adv. 2019; 5(1): eaau9038. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLiu C, Lu M, Cui J, et al.: Effects of straw carbon input on carbon dynamics in agricultural soils: A meta-analysis. Glob Chang Biol. 2014; 20(5): 1366–1381. PubMed Abstract | Publisher Full Text\n\nLiu G, Yu H, Ma J, et al.: Effects of straw incorporation along with microbial inoculant on methane and nitrous oxide emissions from rice fields. Sci Total Environ. 2015; 518–519: 209–216. PubMed Abstract | Publisher Full Text\n\nLu WF, Chen W, Duan BW, et al.: Methane emission and mitigation options in irrigated rice field in southeast China. Nutr Cycl Agroecosys. 2000; 58: 65–73. Publisher Full Text\n\nMinamikawa K, Tokida T, Sudo S, et al.: Guidelines for measuring CH4 and N2O emissions from rice paddies by a manually operated closed chamber method. National Institute for Agro-Environmental Sciences, Tsukuba Japan. Version 1 August. 2015. Reference Source\n\nOda M, Chiem Nguyen H: Methane emissions in triple rice cropping: patterns and a method for reduction [version 3; peer review: 1 approved, 2 approved with reservations]. F1000Res. 2019; 8: 1675. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOda M, Huynh VT, Chiem Nguyen H: Methane emission in waterlogging double cropping. figshare. Dataset. 2020. http://www.doi.org/10.6084/m9.figshare.11987628.v1\n\nSass RL, Fisher FM, Harcombe PA, et al.: Mitigation of methane emissions from rice fields: Possible adverse effects of incorporated rice straw. Glob Biogeochem Cycles. 1991; 5(3): 275–287. Publisher Full Text\n\nSass RL, Fisher FM: Methane emissions from rice paddies: a process study summary. Nutr Cycl Agroecosyst. 1997; 49: 119–127. Publisher Full Text\n\nSmith P, Martino D, Cai Z, et al.: Greenhouse gas mitigation in agriculture. Philos Trans R Soc Lond B Biol Sci. 2007; 363(1492): 789–813. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTariq A, Vu QD, Jensen LS, et al.: Mitigating CH4 and N2O Emissions from Intensive Rice Production Systems in Northern Vietnam: Efficiency of Drainage Patterns in Combination with Rice Residue Incorporation. Agriculture Ecosystems & Environment. 2017; 249: 101–11. Publisher Full Text\n\nThao HV, Oda M, Chiem Nguyen H, et al.: Effects of herbicide application (Sofix 300 EC) and waterlogged rice straw degradation on organic rice yield in the double-cropping pattern. J Viet Env Spec Iss. APE2019, 2019; 68–74. Reference Source\n\nVo TBT, Wassmann R, Tirol-Padre A, et al.: Methane emission from rice cultivation in different agro-ecological zones of the Mekong river delta: seasonal patterns and emission factors for baseline water management. SSPN. 2018; 64(1): 47–58. Publisher Full Text\n\nWang H, Shen M, Huic D, et al.: Straw incorporation influences soil organic carbon sequestration, greenhouse gas emission, and crop yields in a Chinese rice (Oryza sativa L.) wheat (Triticum aestivum L.) cropping system. Soil and Tillage Research. 2019; 195: 104377. Publisher Full Text"
}
|
[
{
"id": "135051",
"date": "16 May 2022",
"name": "Yosei Oikawa",
"expertise": [
"Reviewer Expertise My area of expertise is technical improvements and extension of sustainable agricultural and agroforestry 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\nThis study investigated the effects of rice straw waterlogging and rice straw incorporation into the soil on methane emission through a microcosm experiment. The results showed significant differences between those treatments and seem to contain some suggestive points to reduce methane emissions in paddy fields. However, there are unclear points in the study. To improve the current version 1, I would like to suggest or recommend the following questions and comments:\n\nPlease define \"off-sowing periods\" in Methods. \"Thao et al. (2019) demonstrated a field experiment on RS decomposing in field surface water 20 days before sowing as a suitable possibility for developing a double-cropping pattern in the Mekong Delta.\" It is difficult for me to understand this sentence, especially \"suitable possibility\". Some descriptions in sub-chapters \"Study setting and materials\", \"Rice cultivation\", \"Experimental design\", and \"Measurements\" can be moved to more appropriate places. I recommend the authors to briefly explain the reason of no fertilizer application. Is \"no fertilizer cultivation\" commonly practiced in the Mekong Delta? If any fertilizer was applied, what would happen in the experiment except yield increase? Can local farmers practice both \"no fertilizer cultivation\" and fertilizer application for their profit? I recommend the authors to elaborate the microcosms used in the experiment such as size and shape. I recommend the authors to elaborate \"RS incorporation into soil\" such as the soil depth and the amount of rice straw (that must be the same amount as that of harvested from the first cropping and that of waterlogged treatment). Is the RS incorporation into soil a conventional method in the Mekong delta? An additional sentence would be appreciated to explain the reason why this treatment can be the control to RS waterlogged treatment. \"Rice-growing period\" and \"off-sowing period/stage\" need to be more clearly defined. Are off-sowing periods 20 days for waterlogged treatment, 5 days for incorporation treatment? Significant digits of some data need to be confirmed. For example, on \"0.21 ± 0.02 kg CH4.kg grain-1 and 0.3 ± 0.08 kg CH4. kg grain-1\", 0.3 might be 0.30. Data Fig.1 and Fig. 2 were summed to describe the total CH4 emission. It would be better to kindly add the data in figure to the descriptions on Fig. 1a and Fig. 1b before showing the total CH4 emission, \"502 ± 111.4 kgCH4.ha-1.crop-1 and 604 ± 41.9 kgCH4.ha-1.crop-1\". It is recommended that \"rice-growing period\" and \"off-sowing period\" are shown in Figure 3a and 3b. I think the data on rice yields of both treatments are necessary for further discussion, as well as rice straw inputs. \"The efficiency of CH4 emission from rice straw waterlogging on the field surface promotes aerobic decomposition, resulting in reducing CH4 emission.\" Does it mean that other carbon sources such as CO2 and organic carbon increased or released? \"when waterlogging is used during the off-sowing period, CH4 emission is more concentrated than incorporation because the rice straw decomposition period is longer than that of rice straw incorporation treatment.\" The reason is not clear to me. Does it mean that rice straw in water is slowly decomposed in an anaerobic condition as compared to that incorporated with soil? I would appreciate it if you could kindly explain the reason of high methane emission during the off-sowing period (and if any possible countermeasures to avoid it).\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? Yes\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",
"responses": [
{
"c_id": "8392",
"date": "17 Jun 2022",
"name": "Thao Huynh Van",
"role": "Author Response",
"response": "Thank you very much for giving us constructive comments that helped us improve this paper immensely. All your comments have been carefully read and revised to elucidate underlying aspects. Our responses to your comments are as follows: Comment 1: Please define \"off-sowing periods\" in Methods. Reply 1: We added the term in the methods. Please find out in the experimental design. Comment 2: \"Thao et al. (2019) demonstrated a field experiment on RS decomposing in field surface water 20 days before sowing as a suitable possibility for developing a double-cropping pattern in the Mekong Delta.\" It is difficult for me to understand this sentence, especially \"suitable possibility\". Reply: We revised this sentence to make it more apparent to readers. The revision is as follows “In a field experiment, Thao et al. (2019) reported that a 20-day period of RS decomposition in surface water (off-sowing) was suitable for growing rice in the VMD's double-cropping pattern”. Please find out in the introduction section. Comment 3: Some descriptions in sub-chapters \"Study setting and materials\", \"Rice cultivation\", \"Experimental design\", and \"Measurements\" can be moved to more appropriate places. Reply: We appropriately revised the method, these subitems in the methods have been rearranged more appropriate. Please find out in the methods section. The title of “Study setting and materials” has been changed to “Experimental site and materials” and the “rice cultivation” was integrated into the “Experimental design”. Comment 4: I recommend the authors to briefly explain the reason of no fertilizer application. Is \"no fertilizer cultivation\" commonly practiced in the Mekong Delta? If any fertilizer was applied, what would happen in the experiment except yield increase? Can local farmers practice both \"no fertilizer cultivation\" and fertilizer application for their profit? Reply: Our study set the study’s aim of examining the effect of the rice straw treating approach by waterlogging and incorporation to methane emission patterns. Fertilizers are known as a primary factor that could significantly change the CH4 emission patterns. Therefore, we did not apply fertilizers for the treatments to eliminate unexpected impacts on the findings. We added a brief explanation in the method section for the updated version. As you inquired, it is acknowledged that fertilization has a common practice of most farmers in the Vietnamese Mekong Delta with expect to increase rice yield; no fertilization is also considered for organic rice practices in VMD. However, comparing the practice of no fertilizer cultivation\" and fertilizer application in the same pattern has not been disclosed. Comment 5: I recommend the authors to elaborate the microcosms used in the experiment such as size and shape. Reply: It was added in the material section of the Methods. Comment 6: I recommend the authors to elaborate \"RS incorporation into soil\" such as the soil depth and the amount of rice straw (that must be the same amount as that of harvested from the first cropping and that of waterlogged treatment). Is the RS incorporation into soil a conventional method in the Mekong delta? An additional sentence would be appreciated to explain the reason why this treatment can be the control to RS waterlogged treatment. Reply: Thank you so much for your recommendation. Your recommendations have been adopted. We added 2 additional sentences to make it more straightforward for readers. It is as follows “The soil depth was mixed approximately 20 cm in depth. Then, it … (off-sowing period). RS incorporation into the soil treated for 5 days was a typical treatment pattern for a triple-cropping rice production system in the VMD. The amount of RS applied for treatments was the same amount collected in the container, correspondingly.” We added the measured data to the methods as well as discussion section. Comment 7: \"Rice-growing period\" and \"off-sowing period/stage\" need to be more clearly defined. Are off-sowing periods 20 days for waterlogged treatment, 5 days for incorporation treatment? Reply: We clarified the term of off-sowing period in the method section. It is as follows “The term of off-sowing used indicates a period that RS treated before sowing, which was 20 days for the RS waterlogging treatment and 5 days for the RS incorporation treatment.” Comment 8: Significant digits of some data need to be confirmed. For example, on \"0.21 ± 0.02 kg CH4. kg grain-1 and 0.3 ± 0.08 kg CH4. kg grain-1 \", 0.3 might be 0.30. Reply: We confirm the number of digits after the decimal point as commented. Comment 9: Data Fig.1 and Fig. 2 were summed to describe the total CH4 emission. It would be better to kindly add the data in figure to the descriptions on Fig. 1a and Fig. 1b before showing the total CH4 emission, \"502 ± 111.4 kg CH4.ha-1.crop-1 and 604 ± 41.9 kg CH4.ha-1.crop-1\". Reply: Your suggestion has been adopted. Please find put these Figures. Comment 10: It is recommended that \"rice-growing period\" and \"off-sowing period\" are shown in Figure 3a and 3b. Reply: Your suggestion has been adopted. Revision has been shown in the Figure. Comment 11: I think the data on rice yields of both treatments are necessary for further Discussion, as well as rice straw inputs. Reply: AS mentioned, the brief report aimed to test the hypothesis of whether the rice straw waterlogging method could reduce methane compared with conventional RS treatment by incorporation or not. Previously, it was suggested that discussion should emphasize the methane emissions rather than rice yield and rice straw application, although rice yield and amount of rice straw added were also recorded in this study. However, your recommendations have been adopted to elucidate underlying aspects to readers. We added Figure 2a to show the yield between 2 treatments. Also, the amount of rice straw also added to the discussion section. Comment 12: \"The efficiency of CH4 emission from rice straw waterlogging on the field surface promotes aerobic decomposition, resulting in reducing CH4 emission.\" Does it mean that other carbon sources such as CO2 and organic carbon increased or released? Reply: It is well known that decomposing of organic matters in aerobic conditions produces much more CO2 due to microbial heterotrophic respiration. To clarify, we revised that sentence as follows: “The efficiency of CH4 emission mitigation from RS waterlogging on the field surface was more likely attributed to the RS decomposition in an aerobic environment because CH4 formation is more favourable in anaerobic conditions”. Comment 13: when waterlogging is used during the off-sowing period, CH4 emission is more concentrated than incorporation because the rice straw decomposition period is longer than that of rice straw incorporation treatment.\" The reason is not clear to me. Does it mean that rice straw in water is slowly decomposed in an anaerobic condition as compared to that incorporated with soil? I would appreciate it if you could kindly explain the reason of high methane emission during the off-sowing period (and if any possible countermeasures to avoid it). Reply: thank you so much for your question as well as your recommendation. We revised and added additional explanations to make it clearer to readers. The revision is as follows: “As observed, high CH4 emissions were found during the off-sowing period compared to the rice-growing period under RS water logging. Though the methanogenesis fermentation can be limited by high O 2 concentrations ( Mowjood & Kasubuchi, 1998), the root mass of the first crop could generate methanogenesis ( Jiang et al., 2019). This could be partly explained by the high CH4 emissions during off-growing”. Thank you so much for all your comments. Looking forward to hearing from you. Best regards, Authors."
}
]
},
{
"id": "129417",
"date": "23 May 2022",
"name": "Azeem Tariq",
"expertise": [
"Reviewer Expertise sustainable crop production",
"Greenhouse gas emissions",
"climate change mitigation",
"nutrient cycling"
],
"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 of 'Rice straw decomposition in paddy surface water potentially reduces soil methane (CH4) emission' present an effort in assessing the effects of two rice straw amendments on soil CH4 emissions during the crop growing period and during the straw decomposition.\nIn general the paper has a major issue with respect to the methodological approach used for sampling and comparing the two treatments of rice straw amendments. Authors did not use the uniform pattern for sampling in both treatments which could lead to overestimate/underestimate of emission in treatments. For example, in comparison for off sowing periods, authors just took one sample in soil incorporated treatment, while three in flooded treatment. Further, sampling was continued for 125 days in waterlogging, but 90 days in soil incorporated treatment. The comparison between treatments will be biased if they don’t follow the similar pattern of sampling and analysis.\nLast two sentences of method section in Abstract are not clear. E.g. “However, RS waterlogging is caused by high emissions during the off-sowing stage. The difference between yield-scaled CH4 emissions was insignificant.” It is not clear what the authors want to explain here and what they are comparing?\nIntroduction section lacks clear objectives and state-of-the-art of the study. Authors also explain the results already in the introduction.\nSpace between words is missing at the number of places, e.g. “decomposingRS” in Introduction, units in results section etc.\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? Partly\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": "8393",
"date": "17 Jun 2022",
"name": "Thao Huynh Van",
"role": "Author Response",
"response": "Thank you very much for giving us constructive comments that helped us improve this paper immensely. All your comments have been carefully read and revised to elucidate underlying aspects. Our responses to your comments are as follows: Comment 1: In general, the paper has a major issue with respect to the methodological approach used for sampling and comparing the two treatments of rice straw amendments. Authors did not use the uniform pattern for sampling in both treatments which could lead to overestimate/underestimate of emission in treatments. For example, in comparison for off sowing periods, authors just took one sample in soil incorporated treatment, while three in flooded treatment. Further, sampling was continued for 125 days in waterlogging, but 90 days in soil incorporated treatment. The comparison between treatments will be biased if they don’t follow the similar pattern of sampling and analysis. Reply: We thank you for your comments. Actually, rice straw waterlogging is a method that could be used for a double rice cropping season in the Vietnamese Mekong Delta (VMD), while Rice straw incorporation treatment is a typical rice cultivation practice in the triple cropping season. Triple rice cropping season requires a short-time treatment of rice straw (5 days after harvesting the previous crop), while the double-cropping season has more time to treat rice straw. Thus, our study recommended 20 days of rice straw treatment for double rice cropping season. Moreover, the suggestion is based on our previous study (Thao et al. 2019, shown in the reference) conducted at a rice paddy field. It showed that 20 days were suitable for starting the second crop. Moreover, our study was conducted to test the hypothesis of whether rice straw treatment by waterlogging could be a feasible method that could be applied for the double cropping season or not. Because the primary difference of the 2 methods was the timing of the rice straw to be treated. Thus, we could accept the temporal disparity for evaluating the CH4 emission because the comparison is carried for 2 patterns that are not similar to common ones. The difference in gas samples collected during the off-showing period depends on the time that RS was treated. We discussed deciding the frequency of samples to be taken during off-growing based on our real experiment, although there was no specific instruction for sampling during the off-growing period. We acknowledged that more frequent gas sampling could increase accuracy and reduce biases when examining methane emissions. Based on your comments and another reviewer, we adopted them and significantly revised/rearranged them logically so that it could offer a clearer version to the readers. Please find out in the Methods section. Comment 2: Last two sentences of method section in Abstract are not clear. E.g. “However, RS waterlogging is caused by high emissions during the off-sowing stage. The difference between yield-scaled CH4 emissions was insignificant.” It is not clear what the authors want to explain here and what they are comparing? Reply: We thank you for the comment. It has just been revised to make it clearer to readers. The revision is as follows “RS waterlogging is a feasible option to alternate conventional RS incorporation toward lower CH4 emissions from rice production. Ameliorating CH 4 emission mitigation by RS waterlogging during off-sowing is recommended for future works.” Comment 3: Introduction section lacks clear objectives and state-of-the-art of the study. Authors also explain the results already in the introduction. Reply: Thank you so much. We revised the introduction to offer clear objectives and ameliorate the study's significance. Comment 4: Space between words is missing at the number of places, e.g. “decomposingRS” in Introduction, units in results section etc. Reply: We corrected it through the paper. Thank you so much for all your comments. Looking forward to hearing from you. Best regards, Authors."
}
]
}
] | 1
|
https://f1000research.com/articles/11-298
|
https://f1000research.com/articles/11-425/v1
|
14 Apr 22
|
{
"type": "Research Article",
"title": "Factors associated with knowledge and awareness of stroke among the Lebanese population: A cross-sectional study",
"authors": [
"Diana Malaeb",
"Nada Dia",
"Chadia Haddad",
"Souheil Hallit",
"Hala Sacre",
"Muna Barakat",
"Sara Mansour",
"Pascale Salameh",
"Hassan Hosseini",
"Chadia Haddad",
"Souheil Hallit",
"Hala Sacre",
"Muna Barakat",
"Sara Mansour",
"Pascale Salameh",
"Hassan Hosseini"
],
"abstract": "Background: Evaluation of the knowledge about stroke in the general population is extremely vital as it prevents stroke development, limits complications, and achieves better quality of life. We assume that the general Lebanese population lacks awareness about stroke and its associated complications. This study aims to evaluate stroke knowledge and determine the factors associated with stroke awareness among the general Lebanese population. Methods: This cross-sectional study assessed respondents’ sociodemographic characteristics and the identification of risk factors, warning signs, stroke consequences, and early response to stroke symptoms. A total of 551 Lebanese adults without a history of stroke filled in an online self-reported questionnaire publicly shared on social applications. Logistic regression analysis was performed to identify the factors associated with poor knowledge of stroke. Results: Among the 551 participants enrolled, 403 (74.2%) were females and 312 (56.7%) were under 30 years of age. Females compared to males and employed compared to unemployed had significantly higher odds of identifying at least one risk factor (OR=4.3 [95%CI=1.1;16.8] and 6 [95%CI=1.2;29.6], respectively). Also, when compared to unemployed, employed participants had significantly higher odds of recognizing at least one of the early stroke symptoms (OR=3.3 [95%CI=1.2;8.9]) and identifying at least one of the stroke consequences (OR=5.3 [95%CI=1.1;25.9]). Reaching a university level of education compared to a school level was associated with significantly higher odds (OR=2.3 [95%CI=1.1;4.8]) of taking a patient to a hospital. Conclusion: Well-educated, employed, and female participants were more knowledgeable about stroke. Tailored interventions focusing on individuals with inadequate stroke literacy are needed. Further studies, more representative of the general Lebanese population with a larger sample size, are necessary to confirm our findings.",
"keywords": [
"stroke",
"knowledge",
"awareness"
],
"content": "Introduction\n\nIschemic stroke is neurologic dysfunction caused by sudden embolic occlusions in the cerebral vessel.1,2 It accounts for around 87% of all cases of stroke worldwide and is a major contributing cause of mortality and a significant factor of disability in adults.3,4 In Lebanon, the adjusted prevalence of stroke is 0.5%, and the cumulative mortality rates are 14.1% at one month.5,6\n\nPrimary prevention against stroke is considered a cornerstone in minimizing stroke development. It is reached through a variety of strategies that focus on identifying related risk factors, implementing preventative measures, and educating patients. Awareness programs should aim to increase community knowledge, which is one of the most effective prevention measures; this raises the need for an accurate assessment of stroke knowledge and its related triggers.7–11 Moreover, knowledge will not only improve patients’ quality of life but can also prevent health care professionals from being overwhelmed when stroke cases arrive in the hospital at an early stage.12 This is noteworthy as 80% of stroke cases are preventable if adequate precautions and measures are taken promptly.13\n\nTherefore, it is essential to explore features such as lifestyle, behavior,14 educational background, smoking history,15 and socioeconomic status15,16 to understand the disparities in stroke knowledge between different sociodemographic groups. Since stroke risk factors (e.g., history of hypertension, diabetes) are identifiable in individuals with low socioeconomic, past medical history is also an important factor to investigate. Educational level, personal history of smoking, and high-income status have been associated with increased stroke knowledge.17 With regard to gender, there are conflicting results. Some studies reported that females are more likely than males to present non-traditional stroke warning signs, develop stroke, and arrive late to the hospital18–20; on the contrary, other studies showed that females are able to identify all the five conventional warning signs of a stroke and quickly call the emergency line.21\n\nIn Lebanon, various studies were conducted that assessed stroke risk factors, prevalence, adherence to post-discharge medications, and acute hypertension treatment.5,6 However, no nationwide study has been conducted yet. Only one study assessed the public awareness towards stroke but examined a small population, as it was limited to the capital city.22 Thus, this study aims to evaluate stroke knowledge and determine the factors associated with stroke awareness among the general Lebanese population.\n\n\nMethods\n\nThe study was conducted based on the declaration of Helsinki and was approved by the ethics committee at the School of Pharmacy of the Lebanese International University (202ORC-035-LIUSOP). Written informed consent was obtained from all participants before inclusion in the study.\n\nThis descriptive observational cross-sectional study was carried out from September 2020 through January 2021 on the Lebanese population from all Governorates (Beirut, Mount Lebanon, North, South, and Beqaa), using an anonymous online survey. A snowball sampling method was used to abide by the lockdown restrictions enforced by the Lebanese Government. An electronic survey was developed using Google forms platform and was distributed through different social media platforms (i.e., WhatsApp, LinkedIn, and Facebook). The link to the questionnaire was posted by the authors on each platform and made available to all the users, who are given the right to share. No particular group was targeted. Participation in this survey was voluntary and free of charge. Participants over the age of 18 were eligible, while those with a history of stroke were excluded. The anonymity of the participants was guaranteed during the data collection process.\n\nBased on another study, which concluded that around 71.8% of the participants were able to identify at least three out of five stroke risk factors,23 and in the absence of similar studies in Lebanon, the Epi Info software version 7.2 (population survey; https://www.cdc.gov/epiinfo/index.html) calculated a minimum sample of 312 participants at a confidence level of 95%. The purpose for oversampling is to take into account patients’ refusal.\n\nThe questionnaire was distributed in Arabic, the native language of Lebanon.24 The questionnaire was structured initially in the English language and then translated by a single bilingual translator, whose native language is Arabic and fluent in English. An expert committee formed by healthcare professionals and a language professional verified the Arabic-translated version. A backward translation was then performed by a native English speaker translator, fluent in Arabic and unfamiliar with the concepts of stroke. The back-translated English questionnaire was subsequently compared with the original English one, by the expert committee, aiming to discern discrepancies and to solve any inconsistencies between the two versions. The process of forward-back translation was repeated until all ambiguities disappeared. It was self-administered and required approximately 20 minutes to be completed.\n\nThe questionnaire is similar to those used in the literature.22,23,25–32 The current questionnaire, methods, and tools used in this study was mainly adapted from a study conducted in Jordan in which the general knowledge about stroke was assessed.33 The questionnaire was structured similarly to the one of Jordan in all the aspects that covered stroke knowledge except for the sociodemographic factors (i.e., economic status and residence area) because of the discrepancy between the two countries. However, differences were only in the sociodemographic characteristics due to the slight variation between the two countries. The questionnaire was structured to collect information about stroke in terms of symptoms, risk factors, early warning signs, and complications. Participants completed it without the assistance of investigators to avoid any potential influence when responding to questions. The opening section of the questionnaire covered the sociodemographic characteristics, including age, marital status, smoking status (positive when participant smoked for at least a year), employment status (employed versus unemployed), monthly income, residence (urban versus rural), educational level, and past medical history determined by self-report such as ever being diagnosed with the medical condition by a healthcare professional (e.g., hypertension, diabetes mellitus, dyslipidemia). Age was classified into four categories (18-29, 30-49, 50-70, and above 70 years) while family income was divided into three categories: low (<1,500,000 Lebanese Lira (LL)), intermediate (1,500,000-3,000,000 LL), and high (>3,000,000 LL).24,29\n\nThe second section evaluated the general knowledge related to stroke. Participants responded to whether stroke is a disease that: 1) affects the brain, 2) is an old person disease, 3) is contagious, 4) is hereditary, and 5) and can be prevented. Also, this section assessed awareness of the risk factors of stroke, including old age, hypertension, diabetes mellitus, heart disease, high cholesterol, smoking, alcohol consumption, physical inactivity, obesity, and stress. Furthermore, this section focused on participants’ knowledge of early stroke warning signs including: 1) sudden numbness or weakness of the face, arms, or legs, 2) sudden difficulty speaking or understanding speech, 3) sudden blurry vision or visual impairment in one or both eyes, 4) sudden dizziness, or loss of balance or coordination, and 5) sudden severe headache. Additionally, participants reported potential consequences of stroke: 1) movement and functional problems (i.e., one-sided paralysis, loss of ability to walk, tiredness, fatigue), 2) Cognitive and memory problems (i.e., loss of ability to speak, write, read, remember or understand), 3) visual problems (i.e., loss of sight or blurred vision), 4) emotional and personality changes (i.e., depression, anger, mood changes), and 5) long-term disabilities. Three questions assessed the attitude and the reaction of people towards a patient experiencing stroke (e.g., willingness to take a patient to hospital care); two others were on the curiosity and self-assessment while the last one was to determine the sources of information of knowledge about stroke. Participants were given one point for each correct response to the above statements (see extended data – date key).24 Missing answers were not counted.25 Sometimes, multiple answers were allowed; that is why the total score was higher than the total number of questions.\n\nData collected were analyzed using the Statistical Package for Social Sciences version 25.0 (SPSS; https://www.ibm.com/be-en/products/spss-statistics). A freely accessible software alternative software to run this analysis is RStudio (https://www.rstudio.com/products/rstudio/download/). Continuous variables were presented as mean standard deviation and 95% confidence interval. Categorical and ordinal variables were shown as frequencies (n) and percentages (%). Correlations between risk factors, early symptoms, and consequences of stroke with the socio-demographics and past medical history were determined by the Pearson chi-square or Fisher’s exact test if the cell count was less than five.\n\nLogistic regressions models were used to assess the association between sociodemographic factors, the medical history that showed a P<0.2 in the bivariate analysis and identified a total number of risk factors, identified a total number of early symptoms, identified a total number of consequences, and willingness to take a patient to a hospital. Potential confounders were eliminated if P>0.2 to protect against residual confounding.\n\nThe results were presented in the form of odds ratios (OR) and 95% confidence interval. Statistical tests were two-tailed and indicated statistical significance at P<0.05.\n\n\nResults\n\nOut of the total 551 participants enrolled in the study, 403 (74.2%) were females, 312 (56.7%) were under 30 years of age, and almost half were single and residing in rural areas. The most common concomitant disease was dyslipidemia (17.6%), followed by obesity (16.8%) and peptic ulcer (16.2%). The sociodemographic factors results are displayed in Table 1.24 Almost all the participants had heard of stroke (93.6%); 69.1% know about stroke if someone around had the disease.\n\n* LL, Lebanese Lira.\n\nOur sample revealed a variable level of knowledge about stroke (Figure 1 and Table 2). The majority were aware that stroke is a brain disease and that it can be prevented (80% and 90%, respectively). Approximately half of the participants could identify four out of five correct answers related to stroke knowledge. Furthermore, 90% believed that psychosocial stress was the most common risk factor of stroke, followed by hypertension and dyslipidemia. The most common warning signs were ‘Sudden difficulty in speaking or understanding speech’ and ‘Sudden weakness/numbness of the arms/face/legs’, accounting for 85%. Only 26% identified all the risk factors, 22.7% recognized all the symptoms, and 44% stated all possible stroke consequences. Internet/social media (30%), health-care professionals (30%), and family/relatives (18.9%) were the main sources of information of knowledge about stroke. It is noteworthy that missing answers were not counted in the analysis.\n\n* Missing answers were not included in the analysis.\n\nA significantly higher percentage of females versus males (74.9% vs. 25.1%), residents of the rural versus urban areas (53.8 % vs. 46.2%), and employed versus unemployed (99% vs. 96.3%) correctly identified risk factors. Moreover, a significantly higher percentage of participants who had a job versus unemployed (97.7% vs. 93.7%) recognized at least one warning symptom of stroke. A significantly higher percentage of subjects with university level of education compared to school level (91.5 % vs. 8.5%) and those employed versus unemployed (99% vs. 96.2%) correctly identified the consequences emerging from stroke (Table 3).\n\n° Fisher’s exact test was used when the cell counts were less than 5.\n\n† Significant P-values.\n\n* LL, Lebanese Lira\n\nA significantly higher number of correct answers was associated with university compared to school level of education (91.8% vs. 8.2%), no history of dyslipidemia compared to having dyslipidemia (83.8% vs. 16.2%), and no history of depression versus having depression (87.2% vs. 12.8%) (Table 4).\n\n° Fisher’s exact test was used when the cell counts were less than 5.\n\n† Significant p-values.\n\n* LL, Lebanese Lira\n\nWhen considering the identification of at least one risk factor as the dependent variable, our analysis showed that females compared to males and employed compared to unemployed had significantly higher odds (OR 4.3 [95% CI 1.1;16.8] and 6 [95% CI 1.2;29.6], respectively).\n\nWhile when considering the identification of at least one early stroke symptom as the dependent variable, employed compared to unemployed had significantly higher odds (OR 3.3 [95% CI 1.2;8.9]).\n\nAlso, when considering the identification of at least one stroke consequence as the dependent variable, employed compared to unemployed had significantly higher odds (OR 5.3 [95% CI 1.1;25.9]).\n\nWhen taking the identification of at least one stroke symptom as the dependent variable, university level compared to school level of education had significantly higher odds (OR 2.3 [95% CI 1.1;4.8]) (Table 5).\n\n† Significant P-values.\n\n* Reference.\n\n\nDiscussion\n\nThe current study evaluated factors related to knowledge about stroke risk factors, early symptoms, and consequences in a sample of the general Lebanese population without a history of stroke. The results indicated that the majority of participants identified at least one stroke related risk factor, symptom, and consequence. Our percentages are higher than those reported in the literature, showing that at least one stroke risk factor may be identified by more than half of the sample, probably as most of our participants had a university degree.7,34–36 A Lebanese study among 390 participants showed that 68% could spontaneously recall at least one stroke symptom, and 85.4% spontaneously recalled at least one risk factor.22 A study done in Spain has found that 60% of the sample identified at least one risk factor,37 and an Australian study revealed that 76% could name at least one risk factor.7 However, other studies have demonstrated a low knowledge of stroke risk factors and symptoms in the general population.38–40\n\nOur results revealed that hypertension and psychological stress were the most known risk factors, with a percentage close to 80%. A previous study in Lebanon had found that the most recalled risk factor was hypertension (48.2%), followed by stress (43.1%).22 A study in Morocco among 469 participants has found similar results, with a percentage close to 50%. These findings are in line with those of several surveys conducted in different countries. Although diabetes is a major risk factor for stroke,41 it was the least reported in our study. Similarly, another study found that more than half of the sample did not recognize diabetes or hypercholesterolemia as risk factors for stroke.42\n\nAlso, our results showed a higher percentage of participants recalling at least one stroke early symptom compared to those studies in Portugal (74.2%),43 Norway (70.7%),44 Oman (68%),45 Korea (65%),46 and Jordan (95.5%).33 Sudden loss of speech was the most frequently reported stroke symptom in our study compared to studies in Jordan (54.7%), Ireland (54%),47 and Australia (60.1%).7 However, other studies reported sudden weakening of one side of the body to be the most prevalent symptom, as in the Omani (65 %)45 and Nigerian (55 %) populations.48\n\nIn our study, most of the sample was aware of the importance of going to a hospital emergency as early as possible after a stroke is identified, in agreement with previous findings showing that a high percentage of participants recognized the need for immediate medical care.22 A study in Oman among 400 participants found that 73% would go immediately to the hospital if they knew they had a stroke.45 However, the percentage found in international studies was lower, with only 47% claiming they would go to a hospital if they suspected they had a stroke.38\n\nThe adequate knowledge of stroke risk factors, symptoms, and consequences in our sample could be explained by the young age of the participants and the high level of education, which might be related to better awareness of these aspects of the stroke.\n\nOur results showed that females had better knowledge about stroke risk factors than males, in agreement with other findings.36,49,50 However, some studies did not detect any gender differences51,52 in risk factors awareness, and others showed a better knowledge among men.37,48 Women tend to be more knowledgeable and might be more interested in health topics than men and take more time to seek related information.53 In this regard, the country of origin is an essential factor to consider because of cultural gaps in gender distribution, access to education, and information in each country.39\n\nMoreover, our results revealed that being employed was significantly associated with better awareness of stroke risk factors, early symptoms, and consequences. Similarly, a study in Spain among 2,411 persons has found that actively employed individuals have a better knowledge of stroke than unemployed.54 One possible explanation could be that employed people might have the financial capacity to access information or visit their physician more regularly for check-ups. Our results also showed that higher education levels were a significant factor associated with the need for immediate medical intervention and direct transfer to the hospital after warning signs of stroke. Expectedly, the more literate the participants, the more health-related knowledge they have, making them more ready to respond to any stroke condition.\n\nThis study has several limitations. The results could not be representative of the entire Lebanese population as the majority of participants were females, well-educated with computer literacy and internet access; thus, less-educated people and those who did not have access to a computer or mobile or internet were not assessed. Additionally, its cross-sectional design cannot infer causality. Information bias could also exist as the study questionnaire was online and answers were self-reported. The answers to stroke awareness might be overestimated because the questionnaire used consisted of multiple-choice questions with limited options available; thus, the participants could have guessed the answers. Selection bias might have also occurred since the sample was not randomly selected but rather gathered using the snowball sampling technique. Residual confounding bias is also possible since there might be factors related to stroke awareness that were not measured in this study.\n\n\nConclusion\n\nThe evaluation of stroke knowledge among the general Lebanese population showed that well-educated, employed, and female participants were more knowledgeable about stroke. Tailored interventions focusing on individuals with inadequate stroke literacy are needed to improve stroke awareness.\n\nFurther studies, more representative of the general Lebanese population and with a larger sample size, are necessary to confirm our findings.\n\n\nData availability\n\nOSF: Factors Associated with Knowledge and Awareness of Stroke Among the Lebanese Population: A Cross-Sectional Study. https://doi.org/10.17605/OSF.IO/Y2DAP.24\n\nThis project contains the following underlying data:\n\n- Anonymous data_Stroke Education Article_Dr Diana Malaeb.sav\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nOSF: Factors Associated with Knowledge and Awareness of Stroke Among the Lebanese Population: A Cross-Sectional Study. https://doi.org/10.17605/OSF.IO/Y2DAP.24\n\nThis project contains the following extended data:\n\n- Questionnaire_Stroke Education Article_Dr Diana Malaeb.doc. (English version of the questionnaire).\n\n- Questionnaire_Stroke Education Article_Dr Diana Malaeb.Arabic.doc. (Arabic version of the questionnaire).\n\n- Data key_Stroke Education Article_Dr Diana Malaeb.docx.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgments\n\nWe thank all the participants for their participation and contribution to this study.\n\n\nReferences\n\nAdams HP Jr, Bendixen BH, Kappelle LJ, et al.: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24(1): 35–41. PubMed Abstract | Publisher Full Text\n\nSacco RL, Kasner SE, Broderick JP, et al.: An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013; 44(7): 2064–2089. PubMed Abstract | Publisher Full Text\n\nRosamond W, Flegal K, Furie K, et al.: Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2008; 117(4): e25–e146. 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PubMed Abstract | Publisher Full Text\n\nRamírez-Moreno JM, Alonso-González R, Peral Pacheco D, et al.: Effect of socioeconomic level on knowledge of stroke in the general population: A social inequality gradient. Neurologia (Barcelona, Spain). 2016; 31(1): 24–32. PubMed Abstract | Publisher Full Text\n\nLisabeth LD, Brown DL, Hughes R, et al.: Acute stroke symptoms: comparing women and men. Stroke. 2009; 40(6): 2031–2036. Publisher Full Text\n\nMandelzweig L, Goldbourt U, Boyko V, et al.: Perceptual, social, and behavioral factors associated with delays in seeking medical care in patients with symptoms of acute stroke. Stroke. 2006; 37(5): 1248–1253. PubMed Abstract | Publisher Full Text\n\nRoger VL, Go AS, Lloyd-Jones DM, et al.: AHA statistical update. Heart disease and stroke statistics–2012 Update A report from the American Heart Association. Circulation. 2012; 125(1): e2–e20. PubMed Abstract | Publisher Full Text\n\nFocht KL, Gogue AM, White BM, et al.: Gender differences in stroke recognition among stroke survivors. J. Neurosci. Nurs. 2014; 46(1): 18–22. PubMed Abstract | Publisher Full Text\n\nKhalil HM, Lahoud N: Knowledge of Stroke Warning Signs, Risk Factors, and Response to Stroke among Lebanese Older Adults in Beirut. J. Stroke Cerebrovasc. Dis. 2020; 29(5): 104716. PubMed Abstract | Publisher Full Text\n\nSadighi A, Groody A, Wasko L, et al.: Recognition of Stroke Warning Signs and Risk Factors Among Rural Population in Central Pennsylvania. J. Vasc. Interv. Neurol. 2018; 10(2): 4–10. PubMed Abstract\n\nDia N: Factors Associated with Knowledge and Awareness of Stroke Among the Lebanese Population: A Cross-Sectional Study. Open Science Framework (OSF). 16 Jan. 2022. Publisher Full Text\n\nHan CH, Kim H, Lee S, et al.: Knowledge and Poor Understanding Factors of Stroke and Heart Attack Symptoms. Int. J. Environ. Res. Public Health. 2019; 16(19). PubMed Abstract | Publisher Full Text\n\nKrishnamurthi RV, Barker-Collo S, Barber PA, et al.: Community Knowledge and Awareness of Stroke in New Zealand. J. Stroke Cerebrovasc. Dis. 2020; 29(3): 104589. PubMed Abstract | Publisher Full Text\n\nArnett DK, Blumenthal RS, Albert MA, et al.: 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 140(11): e596–e646. PubMed Abstract | Publisher Full Text\n\nZafar A, Albakr AI, Shahid R, et al.: Stroke literacy in the population of the Eastern Province of Saudi Arabia; immediate steps are essential to bridge the gap. Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association. 2020; 29(10): 105088. Publisher Full Text\n\nAhmed AAA, Al-Shami AM, Jamshed S, et al.: Development of questionnaire on awareness and action towards symptoms and risk factors of heart attack and stroke among a Malaysian population. BMC Public Health. 2019; 19(1): 1300. PubMed Abstract | Publisher Full Text\n\nDar NZ, Khan SA, Ahmad A, et al.: Awareness of Stroke and Health-seeking Practices among Hypertensive Patients in a Tertiary Care Hospital: A Cross-sectional Survey. Cureus. 2019; 11(5): e4774. PubMed Abstract | Publisher Full Text\n\nChang T, Ibrahim S, Ranasinghe HM, et al.: Knowledge of Stroke, Its Warning Symptoms, Risk Factors and Treatment among the General Public and General Practitioners in a South Asian Population. J. Stroke Cerebrovasc. Dis. 2020; 29(5): 104760. PubMed Abstract | Publisher Full Text\n\nMadae’en SS, Bulatova NR, Al-Qhewii A, et al.: Stroke awareness in the general population: A study from Jordan. Trop. J. Pharm. Res. 2013; 12(6): 1071–1076.\n\nBarakat M, AlSalamat HA, Jirjees F, et al.: Factors Associated with Knowledge and Awareness of Stroke Among the Jordanian Population: A Cross-Sectional Study. F1000Res. 2021; 10: 1242. Publisher Full Text\n\nPancioli AM, Broderick J, Kothari R, et al.: Public perception of stroke warning signs and knowledge of potential risk factors. JAMA. 1998; 279(16): 1288–1292. PubMed Abstract | Publisher Full Text\n\nCroquelois A, Bogousslavsky J: Risk awareness and knowledge of patients with stroke: results of a questionnaire survey 3 months after stroke. J. Neurol. Neurosurg. Psychiatry. 2006; 77(6): 726–728. PubMed Abstract | Publisher Full Text\n\nReeves MJ, Rafferty AP, Aranha AA, et al.: Changes in knowledge of stroke risk factors and warning signs among Michigan adults. Cerebrovasc. Dis. 2008; 25(5): 385–391. PubMed Abstract | Publisher Full Text\n\nSegura T, Vega G, López S, et al.: Public perception of stroke in Spain. Cerebrovasc. Dis. 2003; 16(1): 21–26. PubMed Abstract | Publisher Full Text\n\nJones SP, Jenkinson AJ, Leathley MJ, et al.: Stroke knowledge and awareness: an integrative review of the evidence. Age Ageing. 2010; 39(1): 11–22. Publisher Full Text\n\nStroebele N, Mueller-Riemenschneider F, Nolte CH, et al.: Knowledge of risk factors, and warning signs of stroke: a systematic review from a gender perspective. Int. J. Stroke. 2011; 6(1): 60–66. PubMed Abstract | Publisher Full Text\n\nNicol MB, Thrift AG: Knowledge of risk factors and warning signs of stroke. Vasc. Health Risk Manag. 2005; 1(2): 137–147. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTun NN, Arunagirinathan G, Munshi SK, et al.: Diabetes mellitus and stroke: A clinical update. World J. Diabetes. 2017; 8(6): 235–248. PubMed Abstract | Publisher Full Text\n\nKharbach A, Obtel M, Achbani A, et al.: Level of Knowledge on Stroke and Associated Factors: A Cross-Sectional Study at Primary Health Care Centers in Morocco. Ann. Glob. Health. 2020; 86(1): 83. PubMed Abstract | Publisher Full Text\n\nDuque AS, Fernandes L, Correia AF, et al.: Awareness of stroke risk factors and warning signs and attitude to acute stroke. Int. Arch. Med. 2015; 8. Publisher Full Text\n\nSundseth A, Faiz KW, Rønning OM, et al.: Factors related to knowledge of stroke symptoms and risk factors in a Norwegian stroke population. J. Stroke Cerebrovasc. Dis. 2014; 23(7): 1849–1855. PubMed Abstract | Publisher Full Text\n\nAl Shafaee MA, Ganguly SS, Al Asmi AR: Perception of stroke and knowledge of potential risk factors among Omani patients at increased risk for stroke. BMC Neurol. 2006; 6: 38. PubMed Abstract | Publisher Full Text\n\nKim JS, Yoon SS: Perspectives of stroke in persons living in Seoul, South Korea. A survey of 1000 subjects. Stroke. 1997; 28(6): 1165–1169. PubMed Abstract | Publisher Full Text\n\nHickey A, O’Hanlon A, McGee H, et al.: Stroke awareness in the general population: knowledge of stroke risk factors and warning signs in older adults. BMC Geriatr. 2009; 9: 35. PubMed Abstract | Publisher Full Text\n\nWahab KW, Okokhere PO, Ugheoke AJ, et al.: Awareness of warning signs among suburban Nigerians at high risk for stroke is poor: a cross-sectional study. BMC Neurol. 2008; 8: 18. PubMed Abstract | Publisher Full Text\n\nPark MH, Jo SA, Jo I, et al.: No difference in stroke knowledge between Korean adherents to traditional and western medicine – the AGE study: an epidemiological study. BMC Public Health. 2006; 6(1): 153. PubMed Abstract | Publisher Full Text\n\nRüdiger R, Mensink Monika HB: Schlaganfallwissen der Bevolkerung Survey im Kreis Wesel. Bundesgesundheitsbl. Gesundheitsforsch. Gesundheitsschutz. 2002; 2006(49): 450–458.\n\nKoçer A, İnce N, Koçer E, et al.: Factors influencing treatment compliance among Turkish people at risk for stroke. J. Prim. Prev. 2006; 27(1): 81–89. PubMed Abstract | Publisher Full Text\n\nPontes-Neto OM, Silva GS, Feitosa MR, et al.: Stroke awareness in Brazil: alarming results in a community-based study. Stroke. 2008; 39(2): 292–296. Publisher Full Text\n\nHorch K, Wirz J: People’s interest in health information. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2005; 48(11): 1250–1255. PubMed Abstract | Publisher Full Text\n\nRamirez-Moreno J, Alonso-González R, Pacheco DP, et al.: Effect of socioeconomic level on knowledge of stroke in the general population: A social inequality gradient. Neurología (English Edition). 2016; 31(1): 24–32. Publisher Full Text"
}
|
[
{
"id": "135286",
"date": "22 Apr 2022",
"name": "Mohammad Al-Shorbagy",
"expertise": [
"Reviewer Expertise Neuropharmacology"
],
"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 current cross-sectional study highlights the factors associated with the knowledge and awareness of stroke among a sample of the Lebanese population. Motives to initiate the study in that population seem logical and the stratification of the population groups serves the purpose of the study. Results are coherent and neatly described with appropriate statistical analysis. The conclusions drawn are not overly expressed and are matching with the obtained results and can drive action to population awareness as well as feed future research in that particular setup.\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": "8356",
"date": "28 Jun 2022",
"name": "Nada Dia",
"role": "Author Response",
"response": "Dear Prof. Mohammad Al-Shorbagy Thank you for reviewing our article. We look forward to hearing from you in due time regarding our second version and to responding to any further questions and comments you may have. Sincerely, Nada Dia"
}
]
},
{
"id": "135285",
"date": "01 Jun 2022",
"name": "Ammar Ali Saleh Jaber",
"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\nThis research assesses the knowledge and awareness of the Lebanese population regarding stroke in a cross-sectional study. The methodology is scientifically founded. The article is well-written and raises an interesting question. The results are represented adequately. The study paves the road for awareness campaigns about stroke. This article is of good quality, fit for indexing and citation.\n\nHowever, I have some minor points for revision before final indexing:\nState the objectives of the study in a clearer manner.\n\nThe real questionnaire should be attached as supplement material for reproducibility.\n\nSome of the English writing in the intro needs to be revised before submission.\n\nIn the 4th paragraph of the intro, a very brief comparison of Lebanon people to a neighbouring country might be needed.\n\nOverall, this manuscript will be very interesting after doing the above recommendations and insertion of the recommended citations.\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",
"responses": [
{
"c_id": "8355",
"date": "28 Jun 2022",
"name": "Nada Dia",
"role": "Author Response",
"response": "Dear Prof. Ammar ali saleh Jaber, Thank you for reviewing our article. Our reply is stated below each question: State the objectives of the study in a clearer manner. Thank you for pointing this out. We have stated the objectives clearly, as requested, in the second version. The real questionnaire should be attached as supplement material for reproducibility. Thank you for this suggestion. Abiding by the policy of the journal, the questionnaire is accessible online via the link provided in the section on data availability. Some of the English writing in the intro needs to be revised before submission. Thank you for pointing this out. English writing was revised and corrected. In the 4th paragraph of the intro, a very brief comparison of Lebanon people to a neighboring country might be needed. Thank you for raising an important point here. The introduction was expanded to cover neighboring countries. We look forward to hearing from you in due time regarding our second version and to respond to any further questions and comments you may have. Sincerely, Nada Dia"
}
]
}
] | 1
|
https://f1000research.com/articles/11-425
|
https://f1000research.com/articles/11-768/v1
|
11 Jul 22
|
{
"type": "Research Article",
"title": "Analysis of the influence of asset allocation policy, investment manager performance, and risk level on the performance of Sharia money market mutual funds in Indonesia",
"authors": [
"Anisah Firli",
"Risris Rismayani",
"Dinna Miftahul Jannah",
"Risris Rismayani",
"Dinna Miftahul Jannah"
],
"abstract": "Background: Islamic money market mutual funds have become an alternative to conventional investment instruments. This research has novelty in determining the variables of mutual fund performance by combining risk and return factors, asset allocation policy variables, and investment manager performance, which have a high impact on the return and risk level in reducing the risk of loss on investment. In addition, this research was conducted on the performance of Islamic money market mutual funds that have not been studied before. Methods: This research uses data on Islamic money market mutual funds registered with the Financial Services Authority in Indonesia. The performance of Islamic money market mutual funds was calculated using the Sharpe Method and tested using multiple regression analysis. Results: The results showed that the asset allocation policy, investment manager performance, and the level of risk simultaneously have a significant effect on the performance of Islamic money market mutual funds in Indonesia; however, partially, there is no significant effect between (1) the asset allocation policy on the performance of Islamic money market mutual funds in Indonesia: (2) investment manager performance on the performance of Islamic money market mutual funds in Indonesia, and (3) the level of risk on the performance of Islamic money market mutual funds in Indonesia.\n\nConclusions: The results indicated that optimization of returns and risks was needed by considering the composition of asset allocation, choosing the right investment manager, and conducting a good risk level analysis to obtain optimal Islamic money market mutual fund performance.",
"keywords": [
"Asset Allocation",
"Investment Manager",
"Risk Level",
"Performance",
"Money Market",
"Mutual Fund"
],
"content": "Introduction\n\nThe Otoritas Jasa Keuangan (OJK/Financial Services Authority) stated that Islamic mutual funds in Indonesia had developed significantly from year to year. Initially, in 2013 there were only 50 products, and in 2018 there were 198 products.1 Numerous investors choose sharia mutual funds as an alternative to conventional mutual funds because the benefits are great, yet the risks received are not higher than conventional mutual funds.2 Amid negative sentiment hitting Indonesia's stock and bond markets, money market mutual funds experienced positive performance in 2018, which grew 4.18%.3 Basic assets in deposits and increased interest rates increase the likelihood that returns on money market mutual funds will also rise.4 The performance of money market mutual funds will be stable at a positive level if the benchmark interest rate does not decline.5 Moreover, money market mutual funds have a smaller risk value than other mutual funds.6\n\nA mutual fund has good asset performance with a high asset allocation value.7 Researchers have examined the effect of asset allocation policy variables on mutual fund performance in Islamic equity mutual funds,8,9 tested the variables of mutual fund investment manager performance,10 and examined the level of risk as a variable that affects equity fund performance.11,12 This current research was conducted using more complete variables by combining the risk and return factors (asset allocation policy, investment manager performance, and risk level). It was carried out on a new object, namely Islamic money market mutual funds, which have not been the focus of previous research.\n\nBased on the phenomenon and literature review, to determine that the optimal performance of a mutual fund can be influenced by asset allocation policies, investment manager performance, and the level of risk, hypothesis testing was carried out on the performance of money market mutual funds. Figure 1 illustrate the relationship between the variables. The arguments that drive the relationships of studied research variables are as follows:\n\n(1) Asset allocation policy\n\nAsset allocations refer to various asset classes (e.g., money market securities, bank accounts, long-term bonds, stocks, tangible assets, and others) that are allocated in investment portfolios.13 Asset allocation is also defined as various asset classes invested according to their composition and proportion. Hence, performance depends on the allocation of the funds.14 The Asset Class Factor Model15 can measure the effectiveness of the asset allocation policy. To gain a greater return for investors, the appropriate allocation of funds is carried out to encourage the performance of Islamic equity funds.16,17 The notion of allocation funds is also supported by research that found that stock mutual funds have positive and significant results influenced by policy.18-20 Moreover, findings from another empirical study explained that the asset allocation policy affects the performance of equity funds.11,21\n\nAsset allocation policy has a significant effect on the performance of Islamic money market mutual funds that are registered with the OJK.\n\n(2) Investment manager performance\n\nPrior research affirmed that the measurement of investment manager performance includes assessing the ability to manage investor funds, asset selection, investment timeliness, and diversification through portfolios.11 Investment manager performance can be measured through two abilities, namely the market timing ability (an investment manager’s ability to invest according to the market conditions) and Stock Selection Ability (an investment manager’s ability to determine asset choices and manage investor funds).7 Furthermore, empirical research also showed that the investment managers’ abilities include decomposing assets, estimating the predictability of asset performance, market timing, and the portfolio of asset selection.22\n\nTo optimize mutual fund performance and returns, one of the supporting indicators is the performance of investment managers, which includes a composition of market timing abilities and stock selection abilities.7 In line with that, further research found that the performance of investment managers has a significant effect on the performance of equity funds.10\n\nInvestment managers’ ability significantly affects the performance of Islamic money market mutual funds registered with the OJK.\n\n(3) Risk level\n\nA risk is a form of uncertainty about things that will occur later in investment decisions and include interest rate, market risk, inflation risk, business risk, financial risk, liquidity risk, currency exchange risk, and country risk.23 Risk is also defined as a difference between the expected and actual returns; the greater the difference, the greater the risk.24 According to empirical research, every investment of funds in the form of a portfolio has a risk,25,26 which means that an investment has a risk that affects the performance of Islamic mutual funds.16 Further research also concluded that the level of risk influences the performance of equity funds.7\n\nRisk level has a significant effect on the performance of Islamic money market mutual funds that are registered with the OJK.\n\nAsset allocation policy, investment manager performance, and risk level simultaneously affect the performance of Islamic money market mutual funds registered with the OJK.\n\n\nMethods\n\nThis study used the quantitative method. The unit of analysis was the organization, and the study object was the shares of companies registered with the OJK. The time dimension used was time series, which involves data collected over several years (2015-2018) that provides an overview of the development of an activity or situation. This research took place in 2019 and was conducted on Islamic money market mutual funds registered with the OJK between 2015 and 2018, with a total sample of 36 Islamic money market mutual funds.\n\nThis study used purposive sampling with the following criteria: Islamic money market mutual funds operating between January 2015 and December 2018 that their respective investment managers actively manage. The total sample obtained in this study was 36 Islamic money market mutual funds.\n\nThere is one dependent variable in this research, namely the Islamic money market mutual funds’ performance, and three independent variables: asset allocation policy, investment manager performance, and risk level. Data from funds used in this study were obtained from the official website of the OJK www.ojk.go.id by searching the financial reports, annual reports, and prospectus’ of each mutual fund registered with OJK between 2015-2018.\n\nMutual fund performance data collected included:\n\n1. Asset allocation, obtained from data on the proportion of assets, including sharia, Sukuk, and mudhabarah deposits, as well as return data from each asset\n\n2. Investment manager performance, obtained from data on return of the portfolio, risk-free assets, and the stock market, as well as regression coefficient data of excess market return or slope when the market is down and regression coefficient that indicates the ability of market timing from the investment manager\n\n3. The level of risk obtained from the return and expected return\n\n4. Performance of Islamic money market mutual funds obtained from the average performance of a certain sub-period Mutual Fund and the average risk-free investment performance of a certain sub-period\n\nWe accessed the website https://www.pasardana.id/fund/search and then filtered the type of “sharia”, currency “IDR”, and date (each month of 2015, 2016, 2017, and 2018). The search list was narrowed again by typing the specific name of mutual funds, which were:\n\n• BNI-AM Dana Lancar Syariah\n\n• BNI-AM Dana Pasar Uang Syariah Amerta\n\n• Bahana Likuid Syariah\n\n• Mandiri Kapital Syariah\n\n• Mega Dana Kas Syariah\n\n• PNM Pasar Uang Syariah\n\n• EMCO Barokah Syariah\n\n• Insight Money Syariah\n\n• Trimegah Pundi Kas Syariah\n\nFrom this search, we obtained the “managed fund” and “participation unit” data for each month of 2015, 2016, 2017, and 2018 for every mutual fund that we listed.28\n\nThese obtained data were then tabulated in Excel and then calculated using SPSS. The asset allocation policy variable was measured using Sharpe’s Asset Class Factor Model, the investment manager performance using the Treynor-Mazuy Model, the level of risk using the Standard Deviation Formula, and the performance of the Islamic money market mutual funds using the Shape Ratio (Table 1).\n\nData were tabulated for asset allocation policy variables by calculating the proportion of mutual fund allocation, the rate of return for each mutual fund, and error terms. Tabulated data for investment manager performance was obtained by calculating the return of the portfolio, return of risk-free assets, return for the stock market, and intercept that indicates stock selection from the investment manager. Tabulated risk level data was obtained by calculating return period-i, expected return, and the number of observations. Tabulated mutual fund performance data was obtained by calculating the Sharpe ratio value, the average performance of a certain sub-period Mutual Fund, the average risk-free investment performance of a certain sub-period, and the Mutual Fund standard deviation for a certain sub-period.\n\nData collection was carried out using the following stages: 1. Calculate the Asset Allocation Method with the following formula\n\nClass Factor Model (Sharpe, 1995) Asset allocation policies were analyzed\n\nRit = asset return i for t period\n\nbi1 = proportion for mutual fund i for asset allocation 1, namely syariah\n\nbi2 = proportion for mutual fund I for asset allocation 2, namely Sukuk\n\nbi3 = proportion for mutual fund I for asset allocation 3 yaitu mudhabarah deposits\n\nF1t = return obtained from asset class index 1, namely ISSI in period t\n\nF2t = return obtained from asset class index 2, namely the 12-month deposit interest rate in period t\n\nF3t = return obtained from asset class index 3, namely the 3-month deposit interest rate in period t\n\nεit = error term (selecting process) including timing and stock picking\n\n2. Calculate Investment Manager Performance using Treynor-Mazuy Model:\n\nRp = Return of portfolio\n\nRf = Return of risk-free assets\n\nRm = Return for stock market\n\nα = Intercept that indicates stock selection from investment manager\n\nβ = Regression coefficient of excess market return or slope when the market is down\n\nγ = Regression coefficient that indicates the ability of market timing from investment manager\n\nεp = error term\n\n3. Calculate Risk Level using standard deviation:\n\nσi = Standard Deviation\n\nRi = Return period i\n\nERi = Expected return\n\nN = number of observations\n\n4. Performance of Islamic money market mutual funds\n\nSharpe Ratio:\n\nSRD= Sharpe ratio value\n\nPerformanceRD = the average performance of a certain sub-period Mutual Fund\n\nPerformanceRF = the average risk-free investment performance of a certain sub-period\n\nσ= Mutual Fund standard deviation for a certain sub-period\n\nHypothesis testing was carried out using Multiple Linear Regression Analysis (F test and t-test) to test the effect simultaneously and partially between variables. The data were tested using classical assumption tests (normality using the Kolmogorov-Smirnov test, multicollinearity using the VIF test, autocorrelation, and heteroscedasticity). The data were processed using SPSS software version 26.\n\n\nResults and discussion\n\nThe asset allocation policy for Islamic money market mutual funds increased from 2015 to 2016 and from 2017 to 2018. During these years, five out of nine sharia money market mutual funds experienced a significant decrease in the average value of their asset allocation policies, while four out of nine Islamic money market mutual funds experienced an average increase of around one point. Meanwhile, from 2016 to 2017, there was a decline. The overall decline in that year is presented in Table 2 below.\n\nThe performance of Islamic money market investment managers increased on average in three years but decreased in the last year (2017-2018). In that period (2017-2018), the performance of almost all sharia money market mutual fund investment managers experienced a decline except for one company with an increase of 1 point. Thus, this resulted in an overall decline (see Table 3).\n\nThe level of risk in the Islamic money market increased in three years but decreased last year (2017-2018) (Table 4). This result is similar to the average value of investment managers. The decrease in the average value of investment managers for one year was also in line with the increased level of risk.\n\nThe performance of Islamic money market mutual funds was proxied using a shape ratio, the calculation result of the return, the Bank Indonesia Certificate, and standard deviation. The performance of Islamic money market mutual funds decreased from 2015 to 2018 (see Table 5).\n\nThe normality test was carried out using the Kolmogorov-Smirnov test with a result of 0.2, which is higher than 0.05. It can be concluded that the data is normally distributed. The multicollinearity test showed that all independent variables have VIF results of less than 10. It can be concluded that there is no multicollinearity. The autocorrelation test was carried out by looking at the obtained Durbin-Waston value of 1.484, within the range of 1.654 and 2.346. Therefore, it can be concluded that there is no autocorrelation. The Heteroscedasticity test was performed using the Glejser test and showed a number greater than 0.05, namely 0.345 for asset allocation, 0.635 for operations manager performance, and 0.886 for the level of risk. Hence, heteroscedasticity did not occur.\n\nThe result of multiple linear analysis in this research is as follows:\n\nin which:\n\nKR = Mutual Fund Performance\n\nAA = Asset Allocation\n\nKMI = Investment Manager Performance\n\nTR = Risk Level\n\ne = error\n\nTable 6 shows the results of the F test (simultaneous), which gains the significance value of 0.031. It can be concluded that the asset allocation policy, investment manager performance, and risk level simultaneously affect the performance of Islamic mutual funds on the Islamic money market registered with the OJK.\n\na Dependent Variable: Mutual Fund Performance.\n\nb Predictors: (Constant), Risk Level, Investment Manager Performance, Asset Allocation.\n\nBased on Table 7, the results of the t-test (partial) show that the significance value of the asset allocation policy is 0.9, the investment manager's performance is 0.156, and the risk level is 0.156. All variables have a significant value above 0.05; hence the asset allocation, investment manager performance, and risk level partially do not have a significant effect on the performance of sharia mutual funds registered with the OJK.\n\na Dependent Variable: Mutual Fund Performance.\n\nThe asset allocation policy does not have a significant effect on the performance of Islamic money market mutual funds. This result aligns with prior research on stock market investment7 while contradicting another study that showed that the allocation asset policy and risk level have no significant partial effect on the performance of money market mutual funds in Indonesia.8\n\nThe investment manager's performance does not have a significant effect on the performance of Islamic money market mutual funds. Changing market conditions can cause investment managers to have no consensus in predicting the future. Therefore, improving investment management performance may not necessarily improve the expected investment performance. This result aligns with prior research conducted in other markets.16,27 In contrast, another study regarding the influence between investment manager performance and allocation of assets on money market mutual funds performance in Indonesia conducted by Paramitha and Purnawati (2017) provided a different view, arguing that investment manager performance has a significant effect on the performance of money market mutual funds in Indonesia.10\n\nThe risk level does not have a significant effect on the performance of Islamic money market mutual funds. Previous research conducted by Hariyono & Tamsil (2015) that showed the risk level has a significant impact on money market mutual funds performance supported this result,9 while Handayani et al. (2015) found there is a significant impact between risk level and Islamic money market mutual funds.16\n\nTable 8 shows that the R Square value is 0.239. Viewed in a percentage, the asset allocation variable, the investment manager performance, and the risk level have a 23.9% contribution or effect on the performance of mutual funds. The remaining 76.1% is influenced by other factors not examined in this research.\n\na Predictors: (Constant), Risk Level, Investment Manager Performance, Asset Allocation.\n\nb Dependent Variable: Mutual Fund Performance.\n\n\nConclusions\n\nAsset allocation policy, investment manager performance, and risk level simultaneously have a significant effect on the performance of Islamic money market mutual funds in Indonesia, but partially there is no significant effect. These results imply that the produce a high performance of the Islamic money market is affected by the combination of optimized asset allocation policies, the right investment manager, and a suitable risk level analysis. If one of these variables (asset allocation policies, the right investment manager, and a suitable risk level analysis) is not applied, the desired Islamic money market mutual performance will not be achieved effectively. The actual influence of the dependent variable on the independent variable is 23.9%. Further research is expected to add other variables such as mutual fund size, mutual fund age, portfolio turnover, stock price index, mutual fund operating costs, and total mutual fund assets on the Islamic money market to enrich the research results.\n\nA strength of this study is its use of a different object from previous works of literature. This study uses Islamic money market mutual funds, focusing on Indonesia. Using a complete combination of variables compared to previous research can contribute to the existing literature, namely that asset allocation policy, investment manager performance, and the level of risk simultaneously have a significant effect on the performance of Islamic money market mutual funds in Indonesia. Investors, companies, and governments are expected to focus on asset allocation policies, investment manager performance, and the level of risk in order to improve the performance of Islamic money market mutual funds in Indonesia. A limitation of this study is the low number of samples because Islamic mutual funds only started in 2015.1 To analyze data using the regression method, we need to reach a minimum of 30 samples. The Financial Services Authority of Indonesia stated that Islamic mutual funds in Indonesia had only a variety of 50 products in 2013 and increased to 198 products in 2018.1 Based on our data collection, we only have a total sample of 36 Islamic money market mutual funds conducted during 2019. However, the study results can be generalized for Islamic mutual funds' performance in Indonesia.\n\n\nData availability\n\nFigshare: Dataset - F1000-109708.xlsx. https://doi.org/10.6084/m9.figshare.19241982.v228\n\nThis project contains the following underlying data:\n\n• Dataset - F1000-109708.xlsx\n\n(Data of Indonesian Sharia Mutual fund asset allocation, risk level, mutual fund performance, and investment manager performance for the last four years).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAuthor contributions\n\nConceptualization, A.F., R.R., D.M.J.; methodology, A.F., D.M.J.; software, D.M.J.; data curation, A.F., D.M.J.; visualization, D.M.J.; validation, A.F., R.R.; analysis, A.F., D.M.J.; writing – original draft preparation, R.R., D.M.J.; writing – review & editing, A.F., R.R., D.M.J.; project administration, R.R.; supervision, A.F. All authors have read and agreed to the published version of the manuscript.",
"appendix": "References\n\nOtoritas Jasa Keuangan Indonesia: Statistik Reksa Dana Syariah 2018 Juni. Otoritas Jasa Keuangan Indonesia. 2018.Reference Source\n\nKontan: Dana kelolaan reksadana syariah makin merekah. Kontan.co.id. 2018.Reference Source\n\nHendrayana W: Kilas Balik Industri Reksadana 2018. Infovesta. 2019. Reference Source\n\nKontan: Per September, kinerja reksadana campuran paling rendah. Kontan.co.id. 2018.Reference Source\n\nKontan: Reksadana pasar uang berpotensi membukukan return 6% di tahun ini. Kontan.co.id. 2019.Reference Source\n\nWardhani RT, Juanda A, Syam D: Analisis Kinerja Reksadana Syariah di Pasar Modal Indonesia Menggunakan Metode Sharpe. Jurnal Akademi Akuntansi. 2018; 1(1). Publisher Full Text\n\nSari APN, Purwanto A: Analisis Kebijakan Alokasi Aset, Kinerja Manajer Investasi dan Tingkat Risiko terhadap Kinerja Reksadana Saham di Indonesia. PhD Thesis, Fakultas Ekonomika dan Bisnis.2012.\n\nYanti NI: Pengaruh Kebijakan Alokasi Aset, Pemilihan Saham Dan Tingkat Risiko Terhadap Kinerja Reksadana Campuran Periode 2010-201. Jurnal Ilmu Manajemen (JIM). 2017; 5(4).\n\nHandoyo S, Tamsir Y: Pengaruh Kebijakan Alokasi Aset, Tingkat Risiko, Pemilihan Saham Dan Market Timing Terhadap Kinerja Reksa Dana Saham Syariah Di Indonesia.2015. Accessed: Jan. 10, 2022.Reference Source\n\nParamitha ASPP, Purnawati NK: Pengaruh Kinerja Manajer Investasi dan Kebijakan Alokasi Aset terhadap Kinerja Reksa Dana Saham di Indonesia, PhD Thesis, Udayana University.2017.\n\nNurcahya Enka GP: Reksadana di Indonesia: Analisis Kebijakan Alokasi Aset, Pemilihan Saham dan Tingkat Risiko. Universitas Jendral Soedirman Purwokerto. Simposium Nasional Akuntansi XIII. Purwokerto. 2010.\n\nYolanda P, Anggraini F, Darmayanti Y: Analisis Pemilihan Saham dan Tingkat Risiko terhadap Kinerja Reksa Dana Saham. Jurnal Kajian Akuntansi dan Auditing. 2019; 14(2): 113–121. Publisher Full Text\n\nBodie Z, Kane A, Marcus AJ: Manajemen Portofolio dan Investasi. Salemba Empat;2014.\n\nPratomo EP: Reksa dana: solusi perencanaan investasi di era modern. Gramedia Pustaka Utama;2001.\n\nSharpe WF: The sharpe ratio. Journal of Portfolio Management. 1994; 21(1): 49–58. Publisher Full Text\n\nHandayani W, Yuhelmi Y, Desiyanti R: Analisis Kebijakan Alokasi Aset, Kemampuan Manajer Investasi, Dan Tingkat Risiko Terhadap Kinerja Reksadana Saham Syariah Yang Terdaftar Di Bursa Efek Indonesia. Abstract of Undergraduate Research, Faculty of Economics, Bung Hatta University. 2015; 6(2).\n\nAlexandri MB, Laiela F: PERFORMANCE OF ISLAMIC MUTUAL FUNDS IN INDONESIA. Jurnal Masyarakat dan Filantropi Islam. 2019; 2(1): 37–43.\n\nAgung J, Wirasedana IWP: Analisis Kinerja Reksadana Saham di Indonesia. E-Jurnal Akuntansi Universitas Udayana. 2014; 7(1): 250–265.\n\nDrobetz W, Köhler F: The contribution of asset allocation policy to portfolio performance. Financial Markets and Portfolio Management. 2002; 16(2): 219–233. Publisher Full Text\n\nTokat Y, Wicas N, Kinniry FM: The asset allocation debate: A review and reconciliation. Journal of Financial Planning-Denver. 2006; 19(10): 52.\n\nBaş NK, Sarıoğlu SE: The Importance of Asset Allocation, Investment Policy and Active Management in Explaining Turkish Pension Fund Return Variations. IJBSS. 2018; 9(8). Publisher Full Text\n\nRamayanti TP, Purnamasari K: Kemampuan Pemilihan Saham dan Penetapan Waktu Pada Manajer investasi Reksa Dana Saham di Indonesia. Esensi: Jurnal Bisnis dan Manajemen. 2018; 8(1). Publisher Full Text\n\nFahmi I: Pengantar teori portofolio dan analisis investasi. 1st ed.Bandung:Alfabeta;2015.\n\nTandelilin E: Analisis investasi dan manajemen portofolio. Yogyakarta:BPFE-Yogyakarta;2001.\n\nDangl T, Randl O, Zechner J:Risk control in asset management: Motives and concepts. Innovations in Quantitative Risk Management. Cham:Springer; 2015; pp. 239–266.\n\nConnor G, Korajczyk RA: Risk management in asset management. The Growth of Risk Management: A History. 2003.\n\nAnita A: KINERJA MANAJER INVESTASI REKSADANA SAHAM SYARIAH DI INDONESIA. Al-Masraf: Jurnal Lembaga Keuangan dan Perbankan. 2019; 4(1): 1–6. Publisher Full Text\n\nFirli A, Rismayani R, Jannah DM: Dataset - F1000-109708.xlsx. figshare. Dataset. 2022. Publisher Full Text"
}
|
[
{
"id": "151773",
"date": "23 Dec 2022",
"name": "Muhammad Najib Razali",
"expertise": [
"Reviewer Expertise Investment and Finance"
],
"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\nSince this is a quantitative analysis, hypothesis number two does not sound legit. We cannot measure the manager’s ability by assessing the market or company’s performance.\n\nThe phrase \"registered with the OJK\" can be deleted for all hypotheses. It is sufficient to mention this in the introduction as well as in the methodology.\n\nThe sampling technique is not relevant here as the study uses time series data. All data in the time series have the same characteristics.\n\nTo correlate investment manager performance to the risk-free rate, return, and the stock market is wrong. Please have more readings regarding this topic.\n\nThis paper needs some significant corrections in terms of methodology and purpose. Please read more academic articles on this research topic.\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?\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/11-768
|
https://f1000research.com/articles/11-511/v1
|
12 May 22
|
{
"type": "Case Report",
"title": "Case Report: Open biopsy and drainage for breast abscess caused by cholesterol granuloma is beneficial rather than breast core biopsy",
"authors": [
"Freda Halim",
"Ricarhdo Valentino Hanafi",
"Eka Julianta Wahjoepramono",
"Ricarhdo Valentino Hanafi",
"Eka Julianta Wahjoepramono"
],
"abstract": "Cholesterol granuloma is a rare non-infectious disease. Currently, there are no established guidelines, leaving the clinician to decide the best practice for each patient. A 43-year-old woman presented to the Surgery Clinic at Siloam General Hospital, Tangerang, Banten, Indonesia, with the primary complaint of a painful mass located in her left breast over the previous week before being admitted to the hospital. The mass was found abruptly and was accompanied by severe pain and fever. On inspection, peau d’orange, nipple retraction, tenderness, and warmth of the skin were observed. Ultrasonography suggested a malignant mass. The primary diagnosis was breast cancer, with a secondary differential diagnosis of breast abscess. An open biopsy was chosen because a breast abscess was the possible diagnosis. The biopsy results showed characteristics of cholesterol granuloma. Following the operation, the pain score was notably reduced as the operation showed a satisfactory result. The primary purpose of this case report was to illustrate a case of breast abscess caused by cholesterol granuloma, in which open excisional biopsy and drainage was superior for pain reduction and faster recovery.",
"keywords": [
"Breast Abscess",
"Cholesterol Granuloma",
"Open Excisional Biopsy"
],
"content": "Introduction\n\nCholesterol granuloma is a chronic inflammatory granulomatous disease caused by cholesterol crystals that have been released into the tissue.1 This disease is mainly found in the middle ear cavity or mastoid process but rarely in the breast.2,3 The incidence rate of cholesterol granuloma in the ear is 0.6 cases per one million population. While the incidence rate of cholesterol granuloma in the breast has never been published, it is estimated to be far less than the incidence rate of cholesterol granuloma in the ear.4\n\nCholesterol granuloma of the breast is a rare and benign disease. The etiology of this disease in the breast is unclear. However, some reports mentioned the terminal stage of ductal ectasia, which is responsible for the ruptures of the terminal duct, and its lipid-rich material, such as cholesterol crystal escapes the broken luminal structure of the terminal duct. The further inflammatory process surrounds this cholesterol crystal, then forms an encapsulated lesion. The cholesterol crystal is also resistant to resorption by giant cells, creating a problematic situation for the inflammatory process to subside by itself.5,6 However, this theory is still debatable as not all ruptured ductal ectasia will lead to the leak of cholesterol crystals.5\n\nBreast cancer is still a leading cause of newly diagnosed cancer cases in Indonesian women. As most of the patients (80%) are diagnosed in locally advanced stages, breast cancer holds a high mortality rate in Indonesia.7–9 The delay of women seeking medical attention is often the main reason for this highly advanced stage presentation. This is due to the patient’s neglect, inadequate knowledge, and other socio-economic problems.8,9 Sub-urban areas, such as our current practice location in Tangerang, are no exceptions. Clinicians can easily find new cases of locally advanced breast cancer with a classical clinical presentation, such as ulceration, peau d’orange, and multiple regional and distant metastases, with poor prognosis.10 However, in some patients with ambiguous clinical presentation, the clinician needs to consider other differential diagnoses other than breast cancer, such as a case of breast abscess caused by cholesteatoma granuloma, as depicted in this case report.\n\n\nCase report\n\nA 43-year-old Javanese housewife woman presented to the Surgery Clinic at Siloam General Hospital, Tangerang, Banten, Indonesia, with the primary complaint of a painful mass located in her left breast over the previous week before being admitted to the hospital. The mass was found abruptly in the patient, and she showed severely progressive pain (Visual Analog Score 7/10)11 and a slight fever. Initially, the patient didn’t notice any lumps on either of her breasts. A retracted nipple accompanied this complaint but without any edema and redness on the skin.\n\nOn inspection during the physical examination, peau d’orange and nipple retraction were found prominently (Figure 1). A painful mass of approximately 5 × 7cm was found on palpation. The mass had an irregular border, hard consistency, and no fluctuation. Moreover, the attending clinician noted prominent tenderness and warmth of the skin, which is unusual for such breast cancer cases.\n\nThe red line illustrates the location of the mass. The skin of the left breast was consistent with peau d’orange, the classical sign of locally advanced breast cancer.\n\nPreliminary ultrasonography was conducted to further investigate the diagnosis, which showed a solid mass at the left breast with an irregular border and multiple enlarged lymph nodes in the left axillary region (Figure 2). These findings suggest a malignant mass at the left breast with regional metastasis to the left axillary region. The laboratory exam was unremarkable, without elevation in systemic inflammatory markers such as leucocytes and neutrophils.\n\nA solid mass with an irregular border is shown in the left picture. The right image shows multiple enlarged lymph nodes in the left axillary region.\n\nSince neglected breast carcinoma is prevalent in our daily clinical practice, the primary working diagnosis was breast cancer with a secondary differential diagnosis of breast abscess. These differential diagnoses were made due to the abrupt incidence of the mass, accompanied by severe pain and warmth of the surrounding skin of the affected breast, which is unusual for patients with breast cancer. Typically, breast cancer requires a core biopsy as a further diagnostic procedure. However, the clinician felt the urge for an open biopsy because the breast abscess was the possible secondary diagnosis.\n\nOpen biopsy and drainage were performed under general anesthesia. An abscess cavity was found within the left breast, with size and location in accordance with the mass previously palpated in pre-operative clinical examination. There was approximately 15cc purulent material found with much necrotic tissue and a hard, solid abscess wall. The surgeon decided to do a biopsy of the abscess wall, followed by debridement of the abscess cavity, and left the wound open, thus permitting secondary wound healing while awaiting the biopsy result. Culture of the purulent material was done, but no bacteria were found, further proving that this is a “sterile abscess”.\n\nFollowing the operation, the patient’s pain scores were notably reduced to only 3/10. This low pain level was easily managed by oral analgesics such as paracetamol (500 mg per oral solution). The patient was discharged on the first day after the operation. A follow-up meeting was scheduled two weeks, four weeks, and six months after the surgery. The patient did not complain of any pain. The scar healed entirely within four weeks and was observed for six months with satisfactory results (Figure 3).\n\nPeau d’orange and necrotic tissue or purulent material were absent. The scar was partially healed.\n\nAt one-month post-surgery, a follow-up with the patient was scheduled. At this follow-up, the patient reported no complaints at her surgical site. The pain score was reduced to zero points, and the wound showed an improvement without any secondary infection (Figure 4).\n\nThe scar was nearly healed without any infection.\n\nBiopsy of the abscess wall showed dilated duct lumen containing needle-like cholesterol crystal, with surrounding chronic inflammatory infiltrate and foreign body type multinucleated giant cells (Figure 5). Some areas showed cholesterol crystals being engulfed by multinucleated giant cells (Figure 6). Thus, the biopsy confirmed cholesterol granuloma of the breast as the diagnosis, and a malignant lesion of the breast was not found.\n\nA dilated duct lumen contains needle-like cholesterol crystals, with surrounding chronic inflammatory infiltrate and foreign body type multinucleated giant cells (H&E, magnification ×10). H&E, hematoxylin and eosin.\n\nCholesterol crystals engulfed by multinucleated giant cells (H&E, magnification ×40). H&E, hematoxylin and eosin.\n\n\nDiscussion\n\nThe management of breast carcinoma and breast abscess are entirely different. Typically, the difference is prominent in clinical pictures and imaging, so clinicians will not consider these two entities as differential diagnoses.12\n\nThe primary diagnostic assessments for breast cancer are clinical examination, radiology, and core biopsy of the mass.9,13 However, the experience of both the clinician and radiologist is also a dominant factor in determining whether a mass is benign or malignant.13 A report of two cases of cholesterol granuloma on the breast showed that both mammography and ultrasonography were suggestive of carcinoma of the breast, but open biopsy showed cholesterol granuloma.14 While some reports find this is an accurate tool to get a definitive diagnosis for invasive breast cancer with sensitivity reported 90-99%, reports in Indonesia show its sensitivity is only 78% in early breast cancer.15–17 The last fact, combined with the plausibility of breast abscess as the diagnosis in this case report, led the surgeon to choose open biopsy instead of core biopsy for the patient.\n\nDue to its rarity and similarity to breast cancer signs and symptoms, treatment guidelines for breast abscess due to cholesterol granuloma have not yet been established. A report by Jeong et al., 2016 indicated that core biopsy was sufficient to diagnose breast abscess, and afterward, the follow-up showed a decrease in size.18 But serial cases from Nam et al., 2019 of 12 cases of cholesterol granuloma of the breast showed that the more suitable treatment for breast abscess was an excisional biopsy.5 Reports from Osada & Kitayama, 2002 and Fujii et al., 2013 stated that open and excisional biopsies provided satisfying results and no recurrence.6,19 In most cases, diagnosis based on microscopy is precise, but some conditions may mimic malignancy in fragmented core biopsy samples. Conversely, some malignancies can also simulate benign inflammatory or reactive conditions.20\n\nDue to its consideration as a breast abscess, open biopsy and drainage were preferable, which acted as diagnostic and curative procedures. On the other hand, core biopsy simply is less suitable in many cases because of cholesterol granuloma present in other body regions, such as the ovarium, middle ear cavity, brain, and testis, which also require resection of the affected tissue and removal of the inflammatory tissue.1,2,21,22\n\nThis case report has many strengths; the physical, laboratory, and radiography examinations were done thoroughly, which support the diagnosis, and definitive treatment of surgery was performed with a satisfactory result with no complications and complete scar healing. Moreover, the complete patient follow-up during the hospitalization and post-hospitalization were comprehensively collected. In addition, most previously reported cases didn’t report or evaluate post-procedure pain scores. However, in this case report, the pain score was dramatically reduced.\n\n\nConclusions\n\nAlthough it could be very similar in presentation, an experienced clinician should be wary and consider some entities that could mimic carcinoma of the breast, such as cholesterol granuloma. An excisional biopsy is essentially required to eradicate inflammatory tissue to ensure the healing process.\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.\n\n\nAuthor contributions\n\nFH worked on the Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Resources, Software, Visualization, Writing – Original Draft Preparation. RVH was involved in Conceptualization, Formal Analysis, Methodology, Software, Visualization, Writing-Review & Editing. EJW was involved in Project Administration, Supervision, Writing – Review & Editing. FH wrote the draft of the article, RVH and EJW helped with the final manuscript preparation. All figures are original to this manuscript and permission from the patient to publish such an image is obtained. All authors read and approved the final manuscript.",
"appendix": "Acknowledgments\n\nThe authors would like to thank Patricia Diana MD from the Faculty of Medicine, Pelita Harapan University for her detailed explanation of the pathology result and picture.\n\n\nReferences\n\nSagnic S, Bakir MS, Birge Ö, et al.: Case Report Cholesterol granuloma mimicking ovarian cancer. Int. J. Clin. Exp. Pathol. 2021; 4(6): 741–745.\n\nKuruma T, Tanigawa T, Uchida Y, et al.: Case Report Large Cholesterol Granuloma of the Middle Ear Eroding into the Middle Cranial Fossa. Case Rep. Otolaryngol. 2017; 2017: 1–5. Publisher Full Text\n\nKhan R, Narula V, Jain A, et al.: Cholesterol granuloma of the breast mimicking malignancy. Case Reports. 2013; 2013: bcr2013200108. Publisher Full Text\n\nIsaacson B: Cholesterol granuloma and other petrous apex lesions. Otolaryngol. Clin. N. Am. 2015 Apr; 48(2): 361–373. PubMed Abstract | Publisher Full Text\n\nNam G, Singer TM, Lourenco AP, et al.: Cholesteroloma of the breast: A 10 year retrospective review of 79 cases with radiology correlation. Breast J. 2019; 25(6): 1177–1181. PubMed Abstract | Publisher Full Text\n\nOsada T, Kitayama J, Nagawa H: Cholesterol granuloma of the breast mimicking carcinoma: report of a case. Surg. Today. 2002; 32(11): 981–984. Publisher Full Text\n\nWHO: GLOBOCAN 2020: New Global Cancer Data.2020.Reference Source\n\nNasional IPDB dan JK: Profil Kanker Timja Payudara RS Kanker Dharmais.2020. Reference Source\n\nMinistry of Health: Panduan Penatalaksanaan Kanker Payudara (Breast Cancer Treatment Guideline). Ministry of Heatlh, editors. Panduan Penatalaksanaan Kanker Payudara (Breast Cancer Treatment Guideline). 1st Ed.J Kesehat Masy; 2019; p. 1–50.\n\nAgus AMC, Halim FS: Perbedaan usia, onset, dan ukuran tumor pasien kanker payudara baru sebelum dan selama pandemi SARS-CoV-2 di Siloam Hospital Lippo Village periode April 2019 - Desember 2020.2021. Reference Source\n\nBushnik T: Visual Analog Scale. Encyclopedia of Clinical Neuropsychology. New York: Springer; 2011; 2626–2626. Publisher Full Text\n\nChamie K, La Rochelle J, Shuch B, et al.: Schwartz’s Principles of Surgery. Chamie K, La Rochelle J , editors. 10th Ed.United States of America: McGraw-Hill Education; 2015; p 1660.\n\nKarim MO, Khan KA, Khan AJ, et al.: Triple Assessment of Breast Lump: Should We Perform Core Biopsy for Every Patient? Cureus. 2020; 12(3): e7479. PubMed Abstract | Publisher Full Text\n\nIshizaki M, Ohsumi S, Takashima S, et al.: Two cases of cholesterol granuloma of the breast. Breast Cancer. 2001; 8(2): 158–161. PubMed Abstract | Publisher Full Text\n\nDillon MF, Quinn CM, McDermott EW, et al.: Diagnostic accuracy of core biopsy for ductal carcinoma in situ and its implications for surgical practice. J. Clin. Pathol. 2006; 59(7): 740–743. PubMed Abstract | Publisher Full Text\n\nKartini D, Megatia I, Darmiati S, et al.: Triple Diagnostic Accuracy on Early Stage Breast Cancer at Cipto Mangunkusumo Hospital and Persahabatan Hospital. New Ropanasuri J. Surg. 2018; 3(2): 20–24. Publisher Full Text\n\nBrancato B, Crocetti E, Bianchi S, et al.: Accuracy of needle biopsy of breast lesions visible on ultrasound: Audit of fine needle versus core needle biopsy in 3233 consecutive samplings with ascertained outcomes. Breast. 2012; 21(4): 449–454. PubMed Abstract | Publisher Full Text\n\nJeong SH, Lee EH, Hong HS, et al.: Cholesterol Granuloma of the Breast Incidentally Detected on Dynamic Abdominal CT: A Case Report. J. Korean Soc. Radiol. 2016; 74(1): 22. Publisher Full Text\n\nFujii T, Yajima R, Morita H, et al.: Cholesterol granuloma of the breast suspected as breast carcinoma. Int. J. Case Reports Images. 2013; 4(12): 723. Publisher Full Text\n\nD'Alfonso TM, Ginter PS, Shin SJ: A Review of Inflammatory Processes of the Breast with a Focus on Diagnosis in Core Biopsy Samples. J. Pathol. Transl. Med. 2015; 49(4): 279–287. PubMed Abstract | Publisher Full Text\n\nMendonça R, Peron CS, Stefani MA, et al.: Cerebral cholesterol granuloma: Case report. Arq. Neuropsiquiatr. 2007; 65: 540–541. Publisher Full Text\n\nUnal D, Kilic M, Oner S, et al.: Cholesterol granuloma of the paratesticular tissue: A case report. J. Can. Urol. Assoc. 2015; 9(6): 390–392. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "137614",
"date": "16 May 2022",
"name": "Tommy Supit",
"expertise": [
"Reviewer Expertise General surgery",
"biomolecular aspects of wound healing"
],
"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\nCase history and progression (partly)\nPlease provide/mention information on the patient's BC risk factors\nDetails on PE, diagnostics & treatments (partly)\nPlease provide breast US images with higher resolution\n\nAny information on the BIRADS score for this patient?\n\nCan the authors provide macroscopic photographs of the excised tissue?\n\nAny antibiotic given pre- or post-operation?\nGeneral comments\nOverall a succinct and informative case report.\n\nRequires minor grammatical corrections\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? Yes",
"responses": [
{
"c_id": "8294",
"date": "14 Jun 2022",
"name": "Freda Halim",
"role": "Author Response",
"response": "Thank you for your feedback. We appreciate the effort you and the reviewers have dedicated to providing your valuable feedback on my manuscript. We have highlighted the changes within the manuscript. Here is a point-by-point response to the reviewer's comments and concerns. REVIEWER 1 1. Please provide/mention information on the patient's BC risk factors Author's comment: Thank you for the suggestion. In the revised manuscript, I have incorporated the patient’s breast cancer risk factors, including age above 40 years old, a weight of 78 kg, a height of 168 cm, and a BMI of 27.63 kg/m2 (overweight). On the other hand, the patient did not has prior hormonal therapy, history of alcohol consumption, and cancer-related family history. 2. Please provide breast US images with higher resolution Author’s comment: Thank you for your concern. I have upgraded the breast ultrasound images to a higher resolution. 3. Any information on the BIRADS score for this patient? Author’s comment: The BIRADS score of this patient was five points from ultrasonography which are highly suggestive of breast malignancy. 4. Can the authors provide macroscopic photographs of the excised tissue? Author’s comment: Yes, we can. I have added the macroscopic picture of the excised tissue in the manuscript. 5. Any antibiotic is given pre- or post-operation? Author’s comment: The patient was continuously given ceftriaxone 2 gr once daily from preoperative until postoperative day one. As the patient was discharged at POD 1, Clindamycin 300mg tablet twice daily per os was given for seven days. We look forward to hearing from you regarding the submission, responses, further questions, and comments you may have. Sincerely, Freda Halim"
}
]
}
] | 1
|
https://f1000research.com/articles/11-511
|
https://f1000research.com/articles/11-639/v1
|
10 Jun 22
|
{
"type": "Research Article",
"title": "Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study",
"authors": [
"Refat M. Nimer",
"Omar F. Khabour",
"Samer F. Swedan",
"Hassan M. Kofahi",
"Omar F. Khabour",
"Samer F. Swedan",
"Hassan M. Kofahi"
],
"abstract": "Background: Managing coronavirus disease 2019 (COVID-19) using available resources is essential to reduce the health burden of disease. The severity of COVID-19 is affected by nutritional status. In this study the effect of natural product use prior to infection with COVID-19 on disease severity and hospitalization was explored. Methods: This was a cross-sectional study. Between March and July 2021, a self-administered survey was conducted in Jordan. Individuals who recovered from COVID-19 and were ≥18 years old were the study population. Study measures included the use of natural products, COVID-19 severity, and hospitalization status. A multivariate regression model was used for statistical analysis. Results: The mean age (mean ± SD) of the study sample (n=2,148) was 40.25 ± 15.58 years old. Multivariate logistic regression showed that the regular intake of carnation (OR [0.56], CI [0.37–0.85]), onion (OR [0.69], CI [0.52–0.92]), lemon (OR [0.68], CI [0.51–0.90]), and citrus fruits (OR [0.66], CI [0.50–0.89]) before infection were associated with a substantial reduction in COVID-19 severity (P<0.01). Also, the consumption of carnation (OR [0.55], CI [0.34–0.88]), lemon (OR [0.57], CI [0.42–0.78]), and citrus fruits (OR [0.61], CI [0.44–0.84]) were associated with a significant decrease in the frequency of COVID-19-induced hospitalization (P<0.01). Conclusions: Regular consumption of carnation, lemon, and citrus fruits before infection was associated with better outcomes for COVID-19. Studies on other populations are required to confirm these findings.",
"keywords": [
"COVID-19",
"natural products",
"carnation",
"onion",
"lemon",
"citrus",
"hospitalization",
"severity"
],
"content": "Introduction\n\nCoronavirus disease 2019 (COVID-19) is a global pandemic due to the SARS-CoV-2 that causes severe acute respiratory syndrome.1,2 Since the World Health Organization (WHO) declared the pandemic in March, 2020, the mortality toll from COVID-19 worldwide has passed six million by April 2022.3 SARS-CoV-2 can cause a wide variety of symptoms, from asymptomatic infection to severe acute respiratory syndrome and death.4,5\n\nMaintaining a healthy diet has been suggested as a way to boost immune functions and protect against severe infections.6 Certain foods and natural products contain bioactive constituents that have immunomodulating, anti-inflammatory, antioxidant, antibacterial, and antiviral properties. Hence, they can be used for pre- and post-exposure prophylaxis to enhance the activity and quantity of cytokines and different types of white blood cells.7 Therefore, natural products may enhance viral infection outcomes by reducing inflammation and respiratory symptoms.8\n\nMost people in the Middle East region still consume traditional medicinal herbs, immune-boosting foods, and drinks as part of their diet.9–11 During the pandemic, increased demand on medicinal natural products certain foods, drinks, and medicinal herbs such as ginger, garlic, turmeric, and citrus fruits, has been observed.12,13\n\nSeveral studies have examined the effect of consumption of certain foods, drinks, and medicinal herbs on COVID-19 progression.14,15 However, the method of preparing and consuming these natural products may vary for different populations, which may affect the desired benefits of these products. In addition, each geographical area or country may have unique medicinal herbs and immunomodulatory foods. In Jordan, the effect of regular consumption of certain immune-boosting foods and medicinal herbs prior to infection with COVID-19 on the clinical course has not yet been investigated. Due to the seriousness of COVID-19 infection, we hypothesized that an increase in the use of some immune-boosting foods and medicinal herbs would be associated with a less severe form of COVID-19 infection. Therefore, the current study examined the association between the use of many natural products and foods that boost the immune system (green tea, black caraway, Indian costus, cumin, turmeric, anis, chamomile, propolis, honey, carnation, star anis, onion, garlic, lemon, and citrus fruits) before infection with the risk of COVID-19 severity and hospitalization in Jordan.\n\n\nMethods\n\nThis cross-sectional survey was carried out in Jordan (between March and July 2021) as part of the Jordanian COVID-19 survey project (JCSP).16 The Institutional Review Board of Jordan University of Science and Technology granted ethical approval for the project (Ref.: 3/139/2021, dated 30/03/2021). Adults who recovered from COVID-19 were included in the current investigation. Exclusion criteria included current COVID-19 infection and vaccination prior to contracting the virus. Persons previously vaccinated were excluded since vaccination has a considerable influence on disease severity and may mask the potential benefits of the consumption of medicinal herbs and immune-boosting foods on the dependent variables of the study. This cross-sectional study was designed as recommended by the STROBE checklist.17\n\nThe current study used a self-administered questionnaire in Arabic, which can be found translated into English as Underlying data.64 Participants were asked about their demographics (age, gender, body mass index (BMI), and education), comorbidities, and consumption of medicinal herbs and immune-boosting foods before infection with COVID-19. Furthermore, infection symptoms and admission to hospital data were gathered. A panel of area specialists validated the questionnaire, which was then piloted on a limited number of participants. The opinions of experts and participants were gathered and utilized to assess and enhance the clarity of the questionnaire. Results of the first draft of the questionnaire were excluded from the final analysis. The principal investigators’ involvement in data collection was minimized to reduce sources of bias. Participants were chosen to represent various Jordanian geographical regions, and information was gathered from them through an online questionnaire supplied to participants by trained research assistants. We used specific techniques to reduce response bias as much as possible. First, the researcher did not interpret the questionnaire because it was self-administered. Second, we double-checked the items’ clarity by translating them into Arabic. Finally, all duplicate entries were eliminated.\n\nThe sample size for our study was calculated using the online Raosoft sample size calculator (Raosoft Inc., Seattle, WA, USA). According to the world meter elaboration of the most recent United Nations data, Jordan’s population is around 10 million people. The confidence level was set at 95%, the margin of error was set at 3%, and the response distribution was set at 50%. With 770,712 confirmed cases reported by the end of July 2021,18 the recommended sample size was 1067.\n\nA convenient sampling procedure was used in the study. “Google Forms” was used to create and administer the survey. To ensure anonymity, the study did not collect identifying information, such as participants’ names and places of work. In addition, the data were saved in encrypted digital format that required a password to access. The first section of the questionnaire sought informed consent and confirmed recovery from COVID-19. All paricipants provided informed consent. Anyone could opt out and withdraw from the survey by not submitting their answers, so participation was entirely voluntary. To ensure that the Jordanian population is adequately represented, trained researchers recruited participants from various Jordanian governorates. The questionnaire was completed by a total of 2,148 participants.\n\nBased on symptoms, the severity of COVID-19 infection was classified into two categories; severe and non-severe (asymptomatic, mild symptoms, and moderate), as previously reported.19 Fever, sore throat, body pains, and nausea, with no signs or symptoms of pneumonia, were considered mild cases. Pneumonia (persistent fever and cough) but no hypoxemia (arterial oxygen saturation measured by pulse oximetry (SpO2) ≤ 92%) were considered moderate cases.19 Confirmed severe pneumonia and hypoxemia were considered severe cases. It is worth noting that during peak COVID-19 waves, several patients were not admitted to hospitals because of the increased burden on hospitals.16 As a result, such cases received medical care at home through private doctor visits, and some used medical oxygen supply systems in their homes.\n\nIn this study, the independent variables were the use of natural products (medicinal herbs, immune-boosting foods), whereas the dependent variables were COVID-19 severity and hospitalization. All data with missing values were excluded from the analysis. For different variables, percentages, frequencies, means, and standard deviations (SD), were used as appropriate. The Chi-squared test was utilized to determine any differences in severity/hospitalization between users of natural products. Multivariate logistic regression was applied to examine the impact of natural food use on the severity/hospitalization while controlling for different confounders. The adjusted odds ratios (OR) and 95% confidence interval (CI) were presented. P<0.05 indicates statistical significance. The data were analyzed using IBM SPSS Statistics v23 (RRID:SCR_016479).\n\n\nResults\n\nThe questionnaire was completed by 2,148 participants. The demographics of the sample are summarized in Table 1.64 Women comprised 58.2% of participants. The participants’ mean age was 40.25±15.58 years. The majority of participants had non-severe COVID-19 infection and were not admitted to hospitals (87.9% and 89.8%, respectively). Among the participants, 16.9% were smokers, and 23.1% had at least one comorbidity (Table 1).\n\n* Expressed as: mean ± SD.\n\n# Expressed as N (%). COVID-19, coronavirus disease 2019.\n\nCOVID-19 severity/hospitalizations were investigated in relation to the use of medicinal herbs and immune-boosting foods (Table 2). Lemon and citrus fruits were associated with lower incidence of severe COVID-19 and hospitalization (P<0.01). Moreover, intake of ginger and green tea was associated with reduced disease severity (P=0.018 and P=0.036, respectively). However, no significant effects on severe COVID-19 and hospitalization outcomes were observed due to consumption of anise, chamomile, propolis, honey, onions, garlic, carnation, star anise, black caraway, Indian costus, and turmeric, prior to infection.\n\n* P≤0.05.\n\nThe multivariate logistic regression model was performed to account for potential confounders and comorbidities. The data are shown in Table 3 for two outcomes: COVID-19 severity and hospitalization status with the use of each natural product. After controlling for covariates, the findings (Table 3) showed that consumption of carnation (P<0.01), onion (P<0.01), lemon (P<0.01), and citrus fruits (P<0.01) were predictors of lower disease severity. In addition, the consumption of carnation (P<0.01), lemon (P<0.001), and citrus fruits (P<0.01), were predictors of reduced hospitalizations due to COVID-19 infection (Table 3).\n\n* P≤0.05.\n\n\nDiscussion\n\nCOVID-19 can show a spectrum of clinical symptoms from mild to severe respiratory distress and death. It is suggested that the nutritional status of people may influence COVID-19 clinical severity.20 In the current study, the effects of using natural products prior to infection with COVID-19 on disease severity and hospitalization were examined. Previous studies have examined the associations between the severity of infection with the intake of immune-boosting foods and medicinal herbs.12,21,22 According to the literature, there is no evidence that natural products and medicinal herbs impart protection from or cure COVID-19.23 However, consumption of natural products before becoming infected with COVID-19 may boost the immune system and lead to favored disease outcomes. The current study found that regular consumption of carnation, lemon, and citrus fruits, before infection was associated with better outcomes for COVID-19.\n\nThis study found that carnation use by the participants reduced COVID-19 hospitalizations and disease severity. Due to its therapeutic uses, carnation is nominated as a candidate for the management of COVID-19.24–27 During the COVID-19 pandemic, the consumption of carnation to relieve throat pain has increased.28 A randomized clinical trial of a blend that contains carnation buds demonstrated a boost in energy levels among post-COVID-19 female patients.29 In addition, carnation has antibacterial, antiviral, and antifungal effects, and is used to kill germs in dental creams, toothpaste, mouthwash formulations, and throat sprays.22,30 The mechanism by which carnation may reduce the severe form of COVID-19 involves interference of SARS-CoV-2 S1-protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor.31 Moreover, carnation has been shown to increase the availability of oxygen by improving blood supply to both the heart and the brain.32 Carnation has also been reported to be beneficial for the management of chronic coughs, shortness of breath, and maintaining a normal heart rate.33\n\nThe current study also showed a significant decrease in the frequency of the severe form of COVID-19 and hospitalization due to the consumption of lemon and citrus. Citrus fruits are known to contain a variety of bioactive constituents, including vitamin C, anthocyanin, and flavanones,34 which offer a variety of health benefits, such as the normalization of oxidants and inflammation.35,36 Furthermore, citrus fruits, such as oranges and grapefruits, are grown in Jordan, making them a readily available natural source of vitamin C.37 Citrus fruits are commonly used by Jordanians to improve the body’s immunity against COVID-19 infection.11 Similar to carnation, active ingredients in citrus fruits can interfere with binding of SARS-CoV-2 to the ACE2 receptor.38,39 Moreover, naringin of citrus fruits has been shown to suppress the expression of proinflammatory cytokines during the inflammatory response.38,40 Furthermore, hesperidin, a biologically active molecule in orange fruit, was shown to inactivate the SARS-CoV-2 RNA polymerase complex.41,42 The antioxidant components of citrus fruits can also protect against oxidative stress associated with COVID-19 infection.43\n\nOnion has been shown to significantly reduce the frequency of severe illness among participants who consumed it regularly. Onion has antiviral, antifibrotic, antioxidant, and anti-inflammatory bioactive compounds, such as quercetin, apigenin, and selenium.36,44 In several studies, onion and its bioactive components reduced inflammation in the lungs and protected against various respiratory illnesses.45–47 It is suggested that phytochemicals derived from onions can interfere with the function of the main protease of SARS-CoV-2.48–50 In addition, anti-inflammatory diets that incorporate onions were recommended to reduce the severity of COVID-19.12,51,52\n\nAlthough honey and ginger were among the most consumed natural products for the prevention or mitigation of COVID-19 symptoms in Jordan,11 results showed no impact of ginger and honey on the rate of hospitalization and disease severity. Ginger is suggested as a natural product for the management of COVID-19.53 In contrast to the current findings, Aldwihi et al., showed that patients who consumed ginger were less likely to be hospitalized.54 Moreover, a decrease in COVID-19 severity was observed among patients who consumed ginger as treatment.55 According to clinical trials, honey (propolis), a resinous substance made by bees, may help reduce viral clearance time and improve clinical COVID-19 outcomes by interfering with viral replication and entry.56–58 However, the effects of honey were observed in a limited number of studies involving small sample sizes.59 Thus, more investigations are required to confirm the role of bee products in the management of COVID-19.\n\nAccording to the logistic regression analysis, no associations were observed due to consumption of green tea, black caraway, Indian costus, cumin, turmeric, anis, chamomile, star anis, and garlic with COVID-19 hospitalizations and severity. While several studies have revealed the anti-inflammatory and antiviral effects of many of these natural products,60–62 their contribution toward reducing COVID-19 severity is highly controversial, and requires preclinical and clinical trial evaluations, and validation using models of the disease.8,63\n\nAmong the study limitations is that the total number and quantity of natural products used by the subjects were unknown. Furthermore, data on the duration of COVID-19 and hospitalization were not collected. Finally, since the study collected retrospective data, the data may be subject to recall bias. As a result, more studies are required to verify the study findings.\n\n\nConclusions\n\nThe study findings showed that the regular consumption of lemon, citrus fruits, and carnation lowers the rates of COVID-19 severity and hospitalization. Studies in other populations are required to confirm these findings.\n\n\nData availability\n\nFigshare: Natural Products Raw Data. https://doi.org/10.6084/m9.figshare.19758820.64\n\nThis project contains the following underlying data:\n\n- Natural products Raw Data.xlsx (survey responses from all participants)\n\n- Questionnaire in English.docx\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": "140507",
"date": "22 Jun 2022",
"name": "Fatin Y. Atrooz",
"expertise": [
"Reviewer Expertise Behavioral neuroscience",
"cytogenetics",
"public health 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\nSummary: The study explored the association between using specific natural products prior to COVID-19 infection and the severity of the disease and hospitalization status in a sample of Jordanian adults.\nTitle: This is a retrospective study, the study design included a survey about prior COVID-19 infection and natural products consumption prior to infection.\nMethods: - Recruitment method is not clear, how the investigators reached out to the potential participants is not stated. The study suggests that only people who were previously infected with COVID-19 were included in the study. This assumption should be discussed in the inclusion criteria. - Calculation of the study sample assumed that the total population is the number of COVID-19 infected people as reported by the end of July 2021. Does this report include only adults or total confirmed cases? As the survey targeted only adults, the authors should identify precisely the study population as a reference for sample size calculation.\nResults: - Why is lemon considered a separate category from citrus? I suggest including all citrus fruit, including lemon as one category. - In table 1, the results were expressed in a different format, I suggest having all the results expressed as N (%). For this purpose, age can be categorized into 2-3 categories, and same for BMI. - In the multivariate logistic regression, the authors mentioned that after controlling for covariate, the findings... What are the covariates? The authors should list the covariates here, and if that includes controlling for age and gender.\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": [
{
"c_id": "8464",
"date": "06 Jul 2022",
"name": "Refat Nimer",
"role": "Author Response",
"response": "We would like to thank the reviewers for careful and thorough reading of this manuscript and for the thoughtful comments and constructive suggestions, which helped to improve the quality of this manuscript. Please find attached a point-by-point response to reviewers’ concerns. We hope that you find our responses satisfactory and that the manuscript is now acceptable for publication. Reviewer #1 (Comments to the Author): - Recruitment method is not clear, how the investigators reached out to the potential participants is not stated. The study suggests that only people who were previously infected with COVID-19 were included in the study. This assumption should be discussed in the inclusion criteria. Authors’ response: The recruitment method has now been illustrated in the revised manuscript. In the cover page for the questionnaire, we outlined the criteria for participation in the study, which includes infection with COVID-19 and recovery from illness. The research assistance emphasized that participants' infection should have been confirmed by polymerase chain reaction (PCR). Participants were approached in public places such as bus stations, parks, religious places, universities and restaurants. - Calculation of the study sample assumed that the total population is the number of COVID-19 infected people as reported by the end of July 2021. Does this report include only adults or total confirmed cases? As the survey targeted only adults, the authors should identify precisely the study population as a reference for sample size calculation. Authors' response: The sample size for our study was calculated using Raosoft Online Sample Size Calculator (Raosoft Inc., Seattle, WA, USA). 770,712 is the total confirmed cases reported by the end of July 2021, and the recommended sample size was 1067. However, this calculation is to check whether the sample size in our study is sufficient and representative. The number of cases under 18 years of age during the time of sample collection (before the emergence of the Omicron variant) was expected to be small compared to the adult cases (no data available). Therefore, if patients under 18 years are subtracted from the total cases, this would lead to a negligible change in the sample size. Nonetheless, the study sample size was larger than required (n= 2,148) even if child cases are considered. This point is now clarified in the Method section. - Why is lemon considered a separate category from citrus? I suggest including all citrus fruit, including lemon as one category. Authors’ response: Thank you for your comment. We prefer to keep lemon as a separate category from citrus because some studies showed variations in their nutritional values. This was clarified in the revised manuscript. - In table 1, the results were expressed in a different format, I suggest having all the results expressed as N (%). For this purpose, age can be categorized into 2-3 categories, and same for BMI. Authors' response: Done as suggested. - In the multivariate logistic regression, the authors mentioned that after controlling for covariate, the findings... What are the covariates? The authors should list the covariates here, and if that includes controlling for age and gender. Authors' response: The point raised by the reviewer is now incorporated in the revised manuscript."
}
]
},
{
"id": "140506",
"date": "28 Jun 2022",
"name": "Caterina Vicidomini",
"expertise": [
"Reviewer Expertise Environmental chemistry & human health. Computational studies. Synthesis of small molecules"
],
"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 paper, the authors retrospectively explored the effect of a series of natural products use prior to infection with COVID-19 on disease severity and hospitalization. The authors hypothesized that an increase in the use of some immune-boosting foods and medicinal herbs would be associated with a less severe form of COVID-19 infection. Study measures included the use of selected natural products, COVID-19 severity, and hospitalization status. A multivariate regression model was used for statistical analysis.\nIn my opinion, this paper has some limitations including those the authors have described in the text. The total number and quantity of natural products used by the subjects were unknown, and also, I didn't find any information on whether the participants consumed these natural products as commercial supplements, or if they prepared them from natural sources at home, for example.\nIn any case, the work seems interesting and provides ideas for research insights. In my opinion it is therefore worthy of indexing.\nI have just a few suggestions:\nProvide some information on the recruitment method adopted.\n\nSpecify, at least for the most active products such as carnation, how it is usually consumed.\n\nReading the questionnaire, I saw that the authors collected data on potential confounders and comorbidities, but they didn't specify anything on this aspect. Please, add what they considered confounders. If possible, it would be interesting to evaluate whether, for example, the cigarette smoking modified the beneficial effect of natural substances intake.\n\nI know that there are other natural substances traditionally used to boost the immune system, but they were not mentioned or considered in the study. Please add a comment in the text and cite at least the following reference.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? 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": "8463",
"date": "06 Jul 2022",
"name": "Refat Nimer",
"role": "Author Response",
"response": "We would like to thank the reviewers for careful and thorough reading of this manuscript and for the thoughtful comments and constructive suggestions, which helped to improve the quality of this manuscript. Please find attached a point-by-point response to reviewers’ concerns. We hope that you find our responses satisfactory and that the manuscript is now acceptable for publication. Reviewer #2 (Comments to the Author): In my opinion, this paper has some limitations including those the authors have described in the text. The total number and quantity of natural products used by the subjects were unknown,.. Authors' response: We agree with the reviewer that the rate of consumption of these natural products was unknown. However, this point was mentioned in the limitations (highlighted in red). And also, I didn’t find any information on whether the participants consumed these natural products as commercial supplements, or if they prepared them from natural sources at home, for example. Authors’ response: This study focuses on natural products, not commercial supplements. However, the point raised by the reviewer is now incorporated in the revised manuscript. Provide some information on the recruitment method adopted. Authors' response: More information was added at “Study design and subjects” section. Specify, at least for the most active products such as carnation, how it is usually consumed. Authors’ response: Your suggestion is now incorporated in the updated version of the manuscript. Reading the questionnaire, I saw that the authors collected data on potential confounders and comorbidities, but they didn't specify anything on this aspect. Please, add what they considered confounders. If possible, it would be interesting to evaluate whether, for example, the cigarette smoking modified the beneficial effect of natural substances intake. Authors’ response: COVID-19 was reported to be more severe in people having high BMI or comorbidities. However, the aim of this study was to explore the effect of using natural products on the severity of the disease, regardless of the confounding factors. Therefore, multivariate regression analysis was applied to control for possible confounding factors such as age, gender, cigarette smoking, and the number of comorbidities (Table 3). The analysis without adjusted confounding factors is shown in Table 2. The point raised by the reviewer is now discussed in the revised manuscript. I know that there are other natural substances traditionally used to boost the immune system, but they were not mentioned or considered in the study. Please add a comment in the text and cite at least the following reference. PMID: 33511704 Authors’ response: We agree with the reviewer's comment. However, this study covered the broadest range of natural products used by the Jordanian population. The point raised by the reviewer is now incorporated in the revised manuscript the last sentence in the introduction) and the proposed reference was added (ref no. 14)."
}
]
}
] | 1
|
https://f1000research.com/articles/11-639
|
https://f1000research.com/articles/10-752/v1
|
04 Aug 21
|
{
"type": "Data Note",
"title": "High-risk human-caused pathogen exposure events from 1975-2016",
"authors": [
"David Manheim",
"Gregory Lewis",
"Gregory Lewis"
],
"abstract": "Biological agents and infectious pathogens have the potential to cause very significant harm, as the natural occurrence of disease and pandemics makes clear. As a way to better understand the risk of Global Catastrophic Biological Risks due to human activities, rather than natural sources, this paper reports on a dataset of 71 incidents involving either accidental or purposeful exposure to, or infection by, a highly infectious pathogenic agent.\nThere has been significant effort put into both reducing the risk of purposeful spread of biological weapons, and biosafety intended to prevent the exposure to, or release of, dangerous pathogens in the course of research. Despite these efforts, there are incidents of various types that could potentially be controlled or eliminated by different lab and/or bioweapon research choices and safety procedures.\nThe dataset of events presented here was compiled during a project conducted in 2019 to better understand biological risks from anthropic sources. The events which are listed are unrelated to clinical treatment of naturally occurring outbreaks, and are instead entirely the result of human decisions and mistakes. While the events cover a wide range of cases, the criteria used covers a variety of events previously scattered across academic, policy, and other unpublished or not generally available sources.",
"keywords": [
"Laboratory Acquired Infection",
"Biosafety",
"Biosecurity",
"Laboratory Safety",
"Laboratory Accidents",
"Biological Warfare",
"Global Catastrophic Biological Risk"
],
"content": "Listing events relevant to human-caused biocatastrophes\n\nWhile there are certainly large-scale risks from natural pathogens1, there is a likely far larger risk that emerges from various intentional human uses of pathogens2, especially pathogens that have bioweapon or pandemic potential. This paper attempts to provide a list of all recent publicly known events that occurred due to research into or use of pathogens that could cause widespread damage. This includes any which are likely covered by the US Select Agents program, as well as other pathogens known to be capable of pandemic spread. This section begins with a discussion of inclusion criteria, then reviews issues with incompleteness of records, and finally discusses related prior literature, before presenting the list of events.\n\nThe time period and other inclusion criteria are necessarily somewhat arbitrary, but these events are thought to best illustrate the current risks of what researchers have referred to as human-caused Global Catastrophic Biological Risks (GCBRs). Because the events differ greatly, the list is split into separate categories with slightly different criteria. For biological weapons and related incidents, the list is restricted to events that occurred after the passage of the 1975 Biological Weapons Convention (BWC). This time period excludes both intentional spread of disease throughout human history, as well as somewhat recent events more closely associated with risks considered here, though the latter will be briefly mentioned.\n\nFor laboratory accidents, the time frame is identical, both for consistency, and because the modern era of lab safety began with significant changes after the first Asilomar conference in 1973 that identified a variety of risks and important needed changes to safety protocol. While the Asilomar conference was specific to recombinant DNA research, it led to changed practices more widely. Among other critical biosafety advances, this included the explicit identification of the dangers of ”mouth pipetting”3, and following this, the 1975 conference focused in part on laboratory safety.\n\nTo focus on high-risk events, the inclusion criteria used is that the event involved a pathogen (either wild-type or a enhanced or weaponized variant) that is usable as a bioweapon, or that requires similar safeguards. Most events identified, therefore, involve agents that Pal et al. include as having a “probability to be used as bio-weapons”4. This excludes, for example, laboratory HIV infections due to mishandled specimens5, the seemingly frequent incidents of laboratory-acquired Brucellosis6, and many other such events reported in the literature which pose important risks, but are far more limited in their impact than the events considered in this paper.\n\nIn listing events, we note that risks from potentially weaponisable pathogens can arise from a) their use in a biological attack, b) accidents involving their use within a biological weapons program, c) accidents involving their use within research for research purposes. As discussed below, laboratory acquired infections (LAIs), i.e. accidental exposure and infection during research, is the most common of the publicly known type of event. At the same time given secrecy and incomplete reporting, while we have moderate confidence that they are the most common, it seems far less likely that they are the most worrisome.\n\nA non-systematic search for laboratory accidents, use of biological weapons, and other related anthropic sources of risk was conducted. The search collated extant reviews and compilations from both academic literature, grey literature, and press articles, as well as finding additional events from each source. In each case, where possible the original sources and lists of additional events were investigated. The sources and source types are discussed in more detail below.\n\nIt is near-certain that there are events involving biological weapons that are, and will remain, unknown. Even research and development of biological weapons is forbidden by the BWC, so that violations of this convention, and any attendant accidents, would be expected to be kept secret. Furthermore, any deliberate release of a biological weapon would constitute a flagrant violation of international law, and a moral outrage. Such events are likely war crimes or crimes against humanity, and excepting rare cases like the truth and reconciliation commission in South Africa, it is unlikely that perpetrators will document their crimes or provide evidence to the public.\n\nWhere the BWC is not relevant, in the case of accidents in academic or permitted defensive research, there are still clear incentives at the individual actor, research, and national levels not to report. Individual workers are likely to be blamed for accidents, and may be hesitant to report them even when all proper precautions were taken. Laboratories and research projects where accidents occur are likely to be reprimanded, lose funding, or worse. The programs and governments that sponsor such research also have reputational risks when news of such incidents leak. In addition, Kahn suggests that the claim that secrecy is helpful makes failure to report accidents easy7. For all of these reasons, it is unsurprising that the vast majority of known incidents are known only in retrospect, often after other parties reveal them - and this dynamic is made clear by the sources of reports included in this paper.\n\nDespite all of these incentives, incidents become known through a variety of channels. This paper is an attempt to capture all such currently publicly known events, based on a review of news stories, books, gray literature, and academic journal articles on high-risk pathogen accidents and purposeful exposures. The broad scope is necessary because of the fragmentary reporting of such events.\n\nSearches restricted to academic literature are notoriously incomplete. For example, of the 71 events identified in this paper, Su et al.’s 2019 review of Pubmed papers found only three reports - one Brucellosis infection, the 2009 death of Malcolm Casadaban due to Plague, and one case, reported by McCollum et al. but not included in other lists, of a laboratory worker that contracted Cowpox8,9. The lack of overlap seems to be a clear indication that most cases that occur are not reported in the medical or academic literature.\n\nSimilarly, incidents reported in the press are limited to those that are newsworthy in some sense. This list includes events that were uncovered via later investigative reporting or other means, but many events are reported properly to authorities but never noted publicly1. The press sometimes covers these events when there is a death, or when there is some issue that points to negligence or irresponsible behaviour, as occurred at Boston University in 2005 where an infection was not properly reported10.\n\nThis list, or any other compiled in a similar fashion, will be at best a generously underestimated lower bound on the historical rate of incidents in the United States. Further, given the paucity of non-US events, the list is plausible a far greater underestimation of the risk outside of the US. It is very likely that non-public records exist that will be uncovered in the future due to investigation, or will be declassified by governments based on public pressure. Not only should it be expected that the list will need to be revised in the future to account for new revelations and future events, but we should expect that some events will never be known to the public, perhaps including major accidents or intentional acts.\n\nThere have been many prior lists of events, but while sources reviewed vary, none are complete. Even if reports were intended to be comprehensive, they become outdated as additional historical events become known, and as additional events occur. Along with mention of key sources, we will note issues with both academic sources and gray literature, as well as the limitations of news reporting on such events.\n\nAcademic literature. In the academic literature, many accounts are case studies and descriptions rather than attempts to provide a catalogue of events, but these have been compiled in several review articles. Unfortunately, the focus differs markedly and while they cover lab accidents of various types, most focus on clinical accidents. (Healthcare workers are known to be at high risk of exposure to these pathogens when they occur11, but these infections are due to necessary clinical work and so are unrelated to bioweapons or research, thus are excluded here.) They also are incomplete, at least in part because the source case studies rely on self-reporting.\n\nEarly work compiling accidental exposures includes Hanson et al.’s 1967 paper that attempted to catalogue laboratory acquired infections12, which was updated by Pike to cover up until 197513, though this almost entirely predates the time period being considered. Richardson also presented a summary of 109 LAIs that occured at the Centres for Disease Control (CDC) from 1947–1973 at the 16th Annual Biosafety Conference, though this seems not to have been published14. More recently, Harding and Byers surveyed case report and other academic literature from 1979–2004, and Harding and Byers later extended the dataset to 201515. Both of these lists did not fully split out infections between research, clinical, and diagnostic laboratories, but the earlier review noted that most reported bacterial infections occurred in clinical laboratories (84 vs. 471) while most reported viral infections occurred in research facilities (418 vs. 181). The later review similarly found that ”Sixty-seven percent of the viral LAIs occurred in research facilities”, while less than 10% of bacterial infections were in research laboratories.\n\nMany or most of the laboratory-acquired infections reviewed in Harding and Byers were related to the accidental use of or exposure to infected animals, rather than intentional work with the pathogens, and many were low-consequence infections. While this makes many cases not relevant for the current review, the initial paper found 155 cases and one death from Hantaviruses, 143 cases of Brucella2, 5 cases of Chikangunya (2 asymptomatic), 4 cases of Dengue, and 6 cases of SARS-CoV. The update to this work in 2017 by Harding and Byers15 extended the dataset to 2015, and included another death and 108 additional clinical and subclinical infections from Hantavirus, 235 additional cases of Brucella, 3 additional cases of Dengue, and no new cases of Chikangunya or SARS-CoV. Importantly, it seems the overall direction in number of such infections is ambiguous. A related effort, assisted by Byers, is the Association for Biosafety and Security (ABSA)’s searchable LAI database16, which has been updated at least once since the initial release in 2016, and is currently publicly accessible. This seems to be an ongoing project to compile events, though the list is restricted to ”peer-reviewed published LAIs” and based on this review, seems to be unfortunately far from complete. (Note that a single event was found in this database which was not listed elsewhere, a potential exposure to Anthrax in a BSL-4 laboratory due to a ripped suit17. Incidentally, the event was sourced to a newpaper article rather than a peer reviewed source.)\n\ngray literature. Some more recent work is gray literature that has focused more directly on some classes of research-related risk discussed here. For example, the 2008 Environmental Impact Statement (EIS) for the National Bio and Agro-defense Facility (NBAF) opened by the US government in Manhattan, Kansas had an appendix that detailed biocontainment lapses and LaIs relevant to research18. Given more recent revelations, this is still somewhat dated, but it contains an attempt at a comprehensive list of relevant events. A recent paper in the Bulletin of Atomic Scientists discussed human error events and associated risks, and the appendix included two event lists for more recent events based on Federal Select Agent Program (FSAP) reports obtained via a Freedom Of Information Act (FOIA) request by John Greenewald, Jr. These reports, by the US Department of Agriculture and Health and Human Services to the US Congress, cover the years 2003–201519. These lists unfortunately do not clearly distinguish between research accidents and clinical or diagnostic accidents, though for this paper we have inferred which events fit the criteria outlined below. It also has insufficient information to know what events are being reported, including where the event occurred or when. Another sources is a set of publicly released FOIA requests by the Sunshine Project covering 2003–200620, discussed in more detail below.\n\nEach of these sources are incomplete, and overlap in some places but not others. Many of the events found by the Sunshine Project are missing from the FSAP reports covering that period. The Select Agent report also misses several events in the United States that were reported publicly elsewhere. One recent report listing lab accidents in research is Silver’s 2015 in-depth review of five cases of laboratory-acquired lethal infections by potential bioweapon pathogens, which also mentions several other events. Silver includes several events that were included in neither the Select Agents program reports, nor the Sunshine Project work, nor the 2008 EIS. At the same time, Silver’s list does not claim to be comprehensive, and excludes many events that are listed elsewhere21.\n\nIntentional use. All of these reports exclude intentional use a biological warfare as unrelated to laboratories. While this makes sense for research considering only LAIs, it ignores other risks, such as the fact that some intentional uses were only possible because of research being done. Misappropriation of the Anthrax used in the 2001 attacks was possible because of access to samples in a research laboratory, and training and experience in cultivating anthrax in the course of doing research.\n\nEven more directly implicated are deaths due to intentional use in warfare. Frischknecht provides a very useful and comprehensive review of the history of biological warfare. Unfortunately, this includes little about of post-WWII biological warfare, many examples of which have come to light after that publication in 200322. The literature on these is small, and scattered, with many more allegations than known cases, but events from several recent books and news articles on these events are included.\n\n\nEvents\n\nSome events involve human deaths, others involve either active infections or seroconversions (i.e. post-hoc detection of antibodies that indicate an infection occurred,) and some involve spread to animals, or a failure to spread despite definite exposure. Not included in the event counts are suspected but nonconfirmed exposures during research, or clinical laboratory accidents that occur during the treatment of natural outbreaks or diagnostics of naturally occurring disease, though both are also discussed briefly.\n\nIn the list, it is critical to differentiate between purposeful deployment of bioweapons and accidental events, and both Table 1 and the below discussion does so. It is also useful to further distinguish different classes of events. In addition to malicious intentional use, there is a range of purely defensive research - though this does not preclude risks due to accidents or misuse. Purposeful usage includes both misuse by rogue actors, testing of biological weapons, and purposeful deployment by state actors. Accidental exposures include both straightforward research lab accidents, exposure due to incomplete safety precautions, and accidental exposure due to confusion of dangerous pathogens with less-dangerous or inert samples.\n\nSources:\n\nA National Bio-and Agro-Defense Facility's Environmental Impact Statement18\n\nB FSAP reports to Congress19\n\nC Reports uncovered by the Sunshine Project20\n\nD Individual reports and news articles\n\no Many agricultural infections that infect animals outside of laboratories are not fully traced, but all livestock potentially exposed or infected are slaughtered. In such cases, the exact extent is unknown.\n\n+ These are credible allegations, albeit with various degrees of support from published epidemiological research or documentation of the events.\n\n×Discussed in DHS Select Agent reports, further details are unavailable.\n\nAs an introduction to the list of events, it is worth noting that even for events that are known and documented, there can be significant uncertainty. One useful example is the 1977 influenza epidemic, discussed by Rozo and Gronvall23. There is now near-certainty that the influenza virus was introduced by human action, but the details of how this occurred are unclear. Reasonable theories include purposeful deployment, accidental release from bioweapons or related research, or accidental infection due to a live vaccine24. Furthermore, details of the escape may not be known even to those involved. If the pathogen escaped from lab, the lab may not have been aware, and the connection to the live vaccine trials were made only decades later. In other cases, including events that are included in the list but not detailed in FSAP reports to the US Congress, the details of the events are potentially known and/or documented, but any known details are not available publicly.\n\nTable 1 summarizes the events that qualify given the criteria listed above. The various classes of programs and events, along with illustrative examples from the list, are detailed later in the paper. Note that while details of programs are typically unavailable. Because of this, accidents in locations known to be working on state bioweapons programs are listed as such, while accidents in laboratories and military locations openly working on bioweapons defense as such. Any other research not conducted as state biodefense work, or where details are unknown, is listed as (academic) research.\n\nAs noted in the notes Table 1, the primary sources for these incidents include the National Bioand Agro-Defense Facility’s Environmental Impact Statement18, FSAP reports to Congress19, reports uncovered by the Sunshine Project20, and individual reports and news articles which are individually cited in the table.\n\n\nDiscussion\n\nThe sources for the above events are both varied, and incomplete. Despite limitations, however, the events and the details that are known do allow a limited degree of insight into the historical risks. Given that, we review some of the events and make observations for each class of event. This review starts with intentional use, then accidents in bioweapons programs, and finally research laboratories. For each, we discuss the likely missing data, overall trends, and the various changes made to reduce risk, and some implications of the risk that remains.\n\nIntentional use of bioweapons is rare, and there are few recorded cases since the passage of the BWC, but the extent of devastation possible from such use makes them an important part of the overall risk. Several known purposeful uses of bioweapons, and allegations of such use exist3, and these illustrate different sub-categories of risk; (1) intentional military use of biological weapons, including the alleged uses of various biological weapons by Rhodesia in the late 1970s, and the alleged use of Cholera by the South African military, (2) intentional testing of biological weapons on humans, as alleged in the Iraqi and North Korean bioweapons programs, and (3) misuse by a rogue and non-state actors, as in the 2001 Anthrax attacks in the United States, or the failed anthrax attacks by Aum Shunrikyo.\n\nThe clear trend away from large states pursuing biological weapons after the passage of the BWC is the subject of an extensive literature. Given that a key purported factor is norms, it is worth noting several notable events prior to the passage of the BWC, but well after the widespread recognition of the unacceptability of intentional or negligent exposure of civilians to bioweapons. These include the US government’s Tuskegee and Guatemalan syphilis experiments that ended by the early 1970s, and the various biological weapons programs during World War II.\n\nThe first alleged intentional deployment of biological weapons after the passage of the BWC was the use of various biological weapons by the Rhodesian government26,34. This is perhaps best thought of as a series of events, the largest of which was the use of anthrax during the Rhodesian insurgency in 1978–9. While there is some dispute about the causes of this outbreak, recent analyses of the outbreak pattern strongly imply that it was not of natural origin26,35. In addition, Cross details the extensive use of various chemical and biological weapons during the Rhodesian wars by the government. Specifically, Cholera was intentionally released at least twice into rivers in order to infect black South African villages, and Anthrax was released at least once36.\n\nClosely related to, and partially allowing the Rhodesian incidents, South Africa developed and stockpiled a number of chemical and biological weapons. There have been at least some allegations that South Africa used the biological weapons they developed, but if any such use occurred, it was not documented by the extensive later investigations36.\n\nThese types of intentional events are worrying, as states undergoing nationally existential crises, as Rhodesia did, could make similar decisions now or in the future37. Thankfully, the rate of such wars and insurgencies has been declining38,39.\n\nIn addition to intentional attacks using developed biological weapons, it seems that various biological weapons programs have tested weapons on human subjects. Included in this are allegations that there was an Iraqi program that involved human testing of Anthrax in the 1980s40. Similarly, there have been allegations that North Korea tested bioweapons on prisoners41. This class of testing is itself a crime against humanity, and can pose further risks if the pathogen spreads. However, no such testing has been proven or more clearly documented as having occurred in any of these cases.\n\nBioterrorism and misuse by rogue actors is an oft-mentioned concern, albeit with few examples of even attempted attacks4 An earlier and more successful event was the 1984 Rajneeshee attack, a food-poisoning attack with Salmonella that led to 751 infections and 45 hospitalizations, but no fatalities. It is noteworthy, but does not involve a pathogen with biowarfare potential, per Pal et al.4, and was intended as a method of short-term incapacitation rather than as a mass casualty attack42. In addition to this attack, Carus lists a number of other attempts and actual attacks during the time period in question involving chemical agents and pathogens of minimal concern that do not qualify. The single exception was Aum Shinrikyo, which attempted both an anthrax attack and an attack using botulinum toxin (”botox”) against downtown Tokyo in the 1990s, which failed for a variety of reasons. Regarding Anthrax, Olson explains that “the cult may not have had the right agents or the right technologic facilities; they could have overcooked the bioagents or not known how to use them”28.\n\nThe only bioterrorism attack involving a highly-dangerous pathogen that was successful involved the 2001 mailing of a series of envelopes with weaponized anthrax spores to a number of prominent US politicians. The attack was later determined to have been carried out by a US bioweapons researcher who stole an anthrax sample from the lab he was working in, then cultured it. One point that is perhaps notable for other reasons, despite the purely defensive nature of the research, the transition from defensive to offensive work is possible in at least some cases. The reaction to this event included numerous recommendations for better managing risks from Anthrax attacks, including Inglesby et al.’s summary43, but these all focused on response and risk mitigation.\n\nIt is noteworthy that there has been little emphasis on mitigating risks by choosing not to train and employ scientists to cultivate samples of weaponized strains of anthrax or other bioweapon-capable organisms. This suggestion may seem naive, but there are a variety of reasons to think it is both viable, and would be effective. First, the difficulty of preventing insider threats is well documented45. Second, not only is such cultivation complex (despite clear interest46,47), dangerous potential biological weapon pathogens have never been successfully used by terrorist groups. In fact, many such groups have attempted to develop and use pathogenic agents42, so a large corpus of biodefence activity may pose a greater bioterrorist threat than the one it is trying to combat.\n\nFor example, the attempt by Aum Shinrikyo discussed above, along with their abortive attempts to acquire and culture other pathogens including Ebola, were only discovered in retrospect. Note that Aum Shinrikyo has access to far more money and resources than all but the most successful terrorist groups. Despite these resources, and the near-complete lack of effort devoted to stopping their work, their attempts and failure would still be unknown if not for their successful chemical weapon attack and subsequent investigation and prosecution. As noted earlier, the only recorded deaths from bioterrorism involved pathogens from a state bioweapons program, cultured by a researcher in that program.\n\nThere have been several classes of releases that could pose a threat of spread. First, there are accidents related to biological warfare program research. Second, there are accidental exposures during scientific research, including both accidental laboratory exposure, and exposures where the exact method of transmission is less clear. Third, there are exposures due to due to the incorrect labelling or distribution of a pathogen. Excluded from the list and counts in this paper, but discussed briefly, are infections of healthcare workers in the course of clinical work related to natural outbreaks.\n\nState bioweapon program accidents. Accidents involving (illegal) State-sponsored biowarfare research have occurred at least once, and near-certainly several other times since the enactment of the BWC in 1975. The first and only well documented case was the 1979 Sverdlovsk Anthrax Leak, in which anthrax being cultivated and processed for use in missiles was accidentally released due to a mis-communication about a filter which was removed for cleaning25. A second event allegedly occurred in 1999, in Oblivskaya. At that time, Alexander Kouzminov notes that there was “an accidental release of a synthesized virus” that is similar to Crimean-Congo hemorrhagic fever, which caused a small outbreak, and infers that there was a cover-up29.\n\nAn earlier event in the USSR, in what is now Kazakhstan, is the Aral smallpox incident. This occurred in 1971 and so predates the BWC, but despite being excluded form the list, it illustrates the potential for spread. Zelicoff and Bellomo48 explains that the incident started due to a dispersal test of an enhanced strain of smallpox, which subsequently accidentally spread off of the island being used for the weapons test to a nearby ship, which docked, after which the infected individuals spread the infection further. This nearly led to a large-scale epidemic, and was stopped only by quarantining thousands of people for several weeks, incinerating several properties, halting all traffic in and out of a city, and launching a mass vaccination campaign including over 50,000 people.\n\nAlso prior to the time period discussed, it is worth mentioning the deaths of William Boyles, Joel Willard, and Albert Nickel. Per Shane49, and per Treaster50, all three were accidentally infected in the course of US bioweapons research at Fort Detrick in separate incidents in 1951, 1959, and 1964, respectively. Rusnak et al.51 reviewed records from the US bioweapons program at USAMRIID from 1943 to 1969, starting before the routine use of modern biosafety equipment and the availability of vaccines, and found 423 infections during that period. While similar events are not known about various other countries’ Bioweapons programs, it would seem likely they occurred, despite the fact that such accidents are unknown, given that accidents in the course of pursuing bioweapons are unlikely to be publicised.\n\nThe lack of current events makes it tempting to conclude that the risk is now low, but the logic behind such a conclusion is faulty. The events mentioned here are limited to the US program and exposure of the public in the Russian program, and in each case, the events were kept classified, and the incidents were only revealed in retrospect. In the US, the fatalities were first uncovered due to congressional pressure on the US Army towards the end of the Vietnam war, and the much later paper by Rusnak et al. reviewing (still non-public) medical records revealed the hundreds of nonfatal cases. In Russia, the few events are known mostly due to defectors from the biological warfare program. But-for these reasons, it seems likely the US program, and the non-public infections and fatalities in Russia, would not have been uncovered - and it seems near-certain that accidents in other countries that pursued bioweapons occurred but remain undisclosed.\n\nA more reasonable conclusion would be to consider this risk to be proportional to the (unknown) number and size of extant bioweapons programs. The risk of accidents in such laboratories is almost certainly lower than it once was, due to improved understanding of safety. How this compares to other laboratories is unknown.\n\nThe largest category of known events are accidents in laboratories doing research on bioweapon relevant pathogens5. While incidents that are known mostly occurred in the United States, it seems likely that this is due to a combination of the relatively large amount of research into these pathogens done there, and the ability for investigators to file FOIA and similar requests6.\n\nMost of the incidents have straightforward causes, such as accidental skin punctures from needles or otherwise, or exposure to aerosolized pathogens In other cases, however, it is unclear how transmission occurred. Kimman et al. notes that ”For the majority of LAIs there appears to be no direct cause”52 - that is, exposures occur even in laboratories that follow standard safety precautions, without obvious accidents.\n\nLaboratory accidents and known causes. A large portion of events involve needle-sticks or other skin punctures. For example, a 2002 event discussed by the NBAF report at an unknown location involving West Nile Virus was an accidental puncture when a researcher was extracting material from a mouse brain. Accidents do not always seem to improve practice, as even after a 2003 anthrax incident involved a University of New Mexico (UNM) researcher, another event, with the pathogen involved redacted, occurred in the same laboratory the following year, 200420. Further, not all such accidents are minor - even when an event is known, the infection can be fatal, as in another 2004 event, where Antonina Presnyakova, a researcher at the Russian Vector lab, died after being accidentally stuck by a needle contaminated with Ebola virus21.\n\nMany other diseases are contracted due to insufficient safety procedures around aerosolization. For example, in 2006, at Texas A&M, three students were also infected with Q-fever, presumably due to aerosol challenges done involving livestock. Further safety measures and greater care seem unlikely to fully address this risk. For example, also in 2006, at the same university, a professor at the same university invented a ”foolproof” aerosolization chamber, but during cleaning a researcher contracted Brucella. Compounding the concern, the same chamber was involved in exposures of non-bioweapons pathogens at two other universities the same year20.\n\nSomewhat differently, though still accidental, one laboratory-acquired Dengue event was due to a mosquito bite in a research laboratory in Australia in 2011. This occurred despite wearing proper personal protective equipment, and seemingly involved no mistake on the part of the researcher32.\n\nSafety procedures around facilities and maintenance are another issue that has lead to accidents. In addition to the 1979 Sverdlovsk Anthrax Leak discussed above where a filter was not replaced correctly, a 2007 outbreak of Foot-and-Mouth disease in the UK was with high likelihood traced to aging pipes between two laboratories. In that case, there was a citric acid disinfection procedure in the first laboratory that was known to be insufficient, and the effluent was still categorised as requiring Category 4 containment. Despite this, the pipes leading to the final disinfection stage were not properly inspected or maintained, and a later independent review of the accident found that they very likely leaked53. The result was an outbreak that required the slaughter of herds at four locations, and restricted the export of meat from the UK for several months - with massive economic costs.\n\nIt is worth noting that a large number of cases with known details were uncovered due to work by the Sunshine project. This now-defunct project filed requests for non-public records at a large number of universities, only a fraction of which were ever filled. The requested records seem to have covered only the time period between 2003 and the time the records were requested, in 2006. Given that many of these events would presumably have remained unknown without their work, it seems extremely unlikely that the list is complete, and very likely that further such work would expand it.\n\nIn a similar vein, the relative paucity of events pre-2003 seems more likely attributable to incomplete records and a lack of public reporting rather than to a lack of events. On the other hand, it seems unlikely that the later time period is representative of the earlier accident rate. This is because there was a significant post-2001 expansion of work related to pathogens that could be used for bioterrorism. While the causes are unclear, it seems plausible both that safety standards were followed less closely in the rush to expand research, and that the relevant class of research was undertaken at a greater pace than earlier, making the same rate of accidents lead to more events.\n\nAccidents due to unknown causes. In some incidents, the cause of infection is less clear, even after later investigation. Janet Parker, the last person to contract Smallpox, died in 1978 due to an escaped pathogen. She was a medical photographer who seemingly never entered the laboratory which worked with Smallpox, but worked a floor above that laboratory. How transmission occurred remains the subject of conjecture.\n\nMore recently, in 2009, Dr. Malcolm Casadaban at the University of Chicago died of plague. It is unclear how the infection occurred, but (despite colleague’s claims to the contrary), the University claimed it was due to lax laboratory practices with coats and gloves. Perhaps supporting the claim that the lab did not require sufficient safety precautions, a cutaneous Anthrax infection occurred in the same laboratory in 2011, presumably due to contact with a sample. This was thankfully quickly recognised, perhaps partly due to the earlier death of Casadaban, but it remains unclear when or how exactly the disease was contracted21.\n\nIn addition to these cases, there are a number of cases where routine blood testing of laboratory workers uncovered seropositives - indicating that the individual was infected at some point. These infectious are likely subclinical, and (if so) these cases posed minimal risks of spread, but they indicate the existence of many exposure incidents that do not have a known cause, and are only found in retrospect. Given clear reason to believe that not all accidents have known causes, it seems dubious to claim that typical practice is sufficient to eliminate these risks.\n\nPathogen mix-ups. There have been a number of events where the exposure was due to the accidental presence of a bioweapons pathogen. The Select Agent Program reports also note that there are on the order of one and two hundred events each year where pathogens are lost in transit, misplaced, not properly accounted for in inventories, accidentally destroyed, or otherwise cannot be accounted for, but in general these seem not to have led to exposures or infections. In some cases, however, there were infections or more clear indication of exposure. In 2004, Miller54 reports research on a possible vaccine for anthrax that was supposedly using heat-inactivated Bacillus anthracis. When 49 of the 50 injected mice quickly died, it was realised that the anthrax was not, in fact, inactive, and that the researchers had been exposed - thankfully, none were infected.\n\nIn other cases, the pathogen was not supposed to be present at all. In 2005, Johnson18 notes that an event at University of California Berkeley involved accidental exposure to aerosolized Rocky Mountain Spotted Fever instead of the more harmless pathogen they expected. A second similar incident in 2005 involved lab workers at Boston University who were infected with a dangerous variant of Tularemia after working with what they thought was a harmless variant. This seems to be the case referred to in the DHS Select Agent Report, 2003–2006. Prior to the much later revelation of that report due to a FOIA request, this event was publicized by Smith10 due to a scandal involving illegally delayed reporting of Tularemia - and if the reporting had not been delayed, or had never occurred, it seems unlikely that any notice would have been paid, other than (perhaps) the select agent reporting.\n\nLastly, there have been a number of transit accidents, where a pathogen exposure occurs in transit, or due to a mix-up. For example, there was a dry-ice explosion involving a sample of West Nile Virus being sent by a research group in Columbus, Ohio. Reporting by 30 noted that as many as 50 Federal Express workers may have been exposed.\n\nThe reports used for sourcing the events in the above list are clearly incomplete, especially for older and undetected events, and international events. There is (unfortunately non-public) reporting of events in the United States, and while it is possible that the greater amount of research in the US means events elsewhere are rarer, it seem hard to believe that international safety standards which for many countries have lagged those in the US - have ensured that no such events occurred.\n\nEvidence that there is under-reporting is scant, for obvious reasons. Despite this, an anonymous survey on biosecurity and accidents was conducted in Belgium provides clear reason to assume such events are common. The survey covered the five-year period from 2007–2012, but these events were not detailed enough for inclusion in the above list. The study uncovered many previously-unknown events, and extrapolated an overall yearly rate of approximately 1,000 bio-accident “possible events,” to adapt the DHS terminology. The survey covered all pathogens, across both research and clinical laboratories, rather than only research, but focused on high risk pathogens. To assist comparison to the above list, only a quarter of respondents worked in BSL-3 laboratories (there are no BSL-4 laboratories in Belgium), and just over half were involved in research and development, rather than clinical work.\n\nOne strong piece of evidence of under-reporting is that none of the three previously publicly reported LAIs in Belgium were of Class-3 pathogens, but of the ”74 to 95” additional LAIs reported in Wytsmanstraat’s (anonymous) survey, 19 to 26 involved Class-3 pathogens, including Tuberculosis, Brucella, and Rabies55. These results point to both the obvious under-reporting discussed previously, but also the relatively high prevalence of dangerous pathogen infections.\n\nThis leaves the (plausible) possibility that reports of such events were publicly reported but not found in this review of (primarily English-language) reports, or that these incidents are not being publicly reported. On the other hand, there has been work done since the late-aughts to improve biosafety standards.\n\nThe Select Agent reports that have been made available via FOIA requests still show a very worrying continuation of 1–2 infection events per year. Reports since 2008 show hundreds of “possible release” events per year, where an exposure may have occurred. This is very relevant for risk analysis involving near-misses and understanding of lab safety. On the other hand, improved reporting should not be taken to imply a greater rate of such events. In fact, the opposite is likely, and better reporting of non-exposure accidents implies that while the number of reported possible events has increased, the number of events has stayed fairly steady or dropped. In recent data, only approximately 1% of reported possible events lead to infections, and a significant and growing portion of these events were sero-conversions with no clinical manifestation, and would have remained unknown without testing - supporting the hypothesized decrease in events.\n\nNot all of the relevant risks are captured by reviewing events. In addition to accidents risks for new types of research recently highlighted by 19, and the info-hazard risks discussed by 56, there are the more general temptation hazard discussed in 57, including the plausible eventuality where something dangerous is done “against our better judgment”, or the even broader risks imposed on humanity from self-interested actors that might rationally choose to deploy biological weapons despite the risks.\n\nThe available information about events point to a clear but small risk from laboratory accidents, and a hard-to-quantify risk from both the development of biological weapons, and from research into these pathogens. Even productive basic research, which is demonstrably valuable in mitigating risks, has unfortunately too little attention paid to the risks, which can be significant19.\n\nGiven the occasional failure of precautions and safety standards than already exist, the risk posed by the research process itself may in certain cases even outweigh the benefits. Beyond extrapolations from these known events, Howard et al.58 argues that it is clear that future directions in laboratory research, including synthetic biology, will pose additional poorly-understood risks of the types reviewed. Even in the present, however, many argue that the risks of research involving gain-of-function for easily spread pathogens is likely to outweigh the benefits, as 59–61 and others recently suggested regarding gain-of-function work for novel influenza viruses.\n\nPossible consequences - comparing to influenza accidents. None of the historical events listed in the paper involving the highest-risk pathogens created an uncontrolled spread, though one bio-warfare research accident killed more than a hundred people. The same cannot be said for research into influenza, as the 1977–78 Influenza accident showed.\n\nAs noted above, Rozo and Gronvall23 detail an event in 1977 that accidentally released the strain of H1N1 influenza that circulated in 1950, and this spread widely. It is still somewhat unclear where or how this event started, but since much of the population had latent immunity due to strains of H1N1 that circulated in 1943 and 1947, the release caused minimal impact on those older than 20, and was thankfully limited.\n\nA worryingly similar event in 2004–5 was reported in 18,62 and involved the distribution of thousands of what should have been a harmless strain of influenza to labs across the world. This was done as part of testing labs’ ability to identify strains of influenza. Unfortunately, the private company that made the kits included the 1957 Asian influenza instead of a harmless strain. It is plausible that if this strain had escaped, it could have had much more serious consequences there had not been a recently circulating strain of H2N2, and presumably most under the age of 50 were vulnerable. Simulations by Merler et.al. have shown that this risk is non-negligible63, and based partly on this, the report by Klotz in the Bulletin of the Atomic Scientists speculated that “a release into the community of [an avian flu like] pathogen could seed a pandemic with a probability of perhaps 15 percent19.\n\n\nConclusions\n\nThe report presents three classes of program, offensive, defensive, and academic research. Each poses risks, and examples of each are available in the recent past.\n\nWhile this dataset of biological exposure events is nearly certainly incomplete, it is a step towards the needed understanding for assessing the risks of larger scale events. Potentially more importantly, it contributes to building a lower bound for this risk, and points to how much uncertainty remains due to both lax reporting standards and unknowable events.\n\n\nData availability\n\nTable 1 contains the underlying data.",
"appendix": "Footnotes\n\n1This research included no further efforts to uncover previously unknown events, though this is likely a useful approach to better understanding the risk.\n\n2There were several aborted fetuses due to these infections, but no other deaths.\n\n3The incidents of human testing and purposeful use are included in the paper, but given the sensitive nature of these alleged war crimes and/or crimes against humanity, and the inability for those alleging the events to provide inarguable proof, no position is taken on what actually occurred.\n\n4A pair of non-attempted “attacks” involving a former white nationalist microbiologist occurred in 1995 and 1998, but the attacker was interested in boasting about his importance rather than planning an attack, and there seems to have been no possibility of any infections at any point44.\n\n5As noted earlier, clinical accidents are even more common, but are not the consequence of decisions made about what research to engage in, and the class of accident is very different.\n\n6These requests will uncover research accidents, but are not granted for information ”properly classified in the interest of national security,” which could include any events related to (even defensive) biowarfare.\n\n\nReferences\n\nManheim D: Questioning Estimates of Natural Pandemic Risk. 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PubMed Abstract | Publisher Full Text\n\nLipsitchand M, Inglesby T: The U.S. is funding dangerous experiments it doesn’t want you to know about. February 27, 2019. Reference Source\n\nPiper K: Biologists are trying to make bird flu easier to spread. Can we not? Vox.com, 2019. Reference Source\n\nSalzberg S: Scientists Resume Efforts To Create Deadly Flu Virus, With US Government's Blessing. Forbes, 2019. Reference Source\n\nMacKenzie D: Pandemic-causing 'Asian flu' accidentally released. New Scientist. 2005. Reference Source\n\nMerler S, Ajelli M, Fumanelli L, et al.: Containing the accidental laboratory escape of potential pandemic influenza viruses. BMC Med. 2013; 11(1): 252. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "94609",
"date": "18 Oct 2021",
"name": "Sam Weiss Evans",
"expertise": [
"Reviewer Expertise As relevant to this article",
"I study the processes through which biosecurity governance mechanisms come into being and are seen as legitimate",
"how they create zones of vision and absence",
"and how those mechanisms change over time."
],
"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 Data Note that describes a dataset of 71 incidents involving either accidental or purposeful exposure to, or infection by, a highly infectious pathogenic agent. Building a dataset like this is necessarily non-exhaustive, sporadic, and time-consuming. This paper did not seek to uncover previously unknown events, just gather those that are so far known.\nIs the rationale for creating the dataset(s) clearly described? Response: Yes. It helps provide evidence for a lower bound on the levels of accidents or purposeful exposure to highly infectious pathogenic agents.\n\nAre the protocols appropriate and is the work technically sound? Response: It is. There are numerous reasons why a dataset like this is necessarily incomplete, which are articulated clearly in the paper.\n\nAre sufficient details of methods and materials provided to allow replication by others? Response: Yes.\n\nAre the datasets clearly presented in a useable and accessible format? Response: Yes, though having an ability to access the table in a more database-friendly manner (e.g. CSV file) would be helpful.\n\nSpecific comments:\np.3 “there is a likely far larger risk that emerges from various intentional human uses of pathogens, especially pathogens that have bioweapon or pandemic potential”: This claim is not supported by the in-text citation, which explicitly notes its comments on anthropogenic extinction causes is highly speculative.\n\nInclusion criteria:\n\n“what researchers have referred to as human-caused Global Catastrophic Biological Risks (GCBRs).” Which researchers? Provide citation.\n\n“the event involved a pathogen (either wild-type or a enhanced or weaponized variant) that is usable as a bioweapon.” Surely this does not mean that the pathogen was fully weaponized? Please clarify. You could just combine with the following sentence.\n\nRegarding South Africa: this would be an opportune spot to mention how, even with South Africa’s inclusion in the BTWC, there was still significant absences with their disclosure of their bio weapons program. See, e.g. Rappert & Gould (2016) “Dis-eases of secrecy.” Jacana Media.\n\nThere should be a different numbering system for footnotes vs endnotes.\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": "121971",
"date": "22 Feb 2022",
"name": "Gamal Wareth",
"expertise": [
"Reviewer Expertise Bioterrorism Agents/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 of Manheim D and Lewis G titled “High-risk human-caused pathogen exposure events from 1975-2016” is interesting and scientifically accepted. The report included a dataset of 71 incidents involving either accidental or purposeful exposure to, or infection by, a highly infectious pathogenic agent. The article is very well written and I recommend indexing it. However, there are minor enquires that need to be addressed before considering indexing.\nThe information in table 1 is arranged chronically from the past to the recent while two events (cholera and Anthrax in the 1970s) come later after 1979 and not clear if they have to be listed first in the table as the exact year of the event is not determined.\n\nIn the discussion, section Accidental release, please remove one “due to”, as it repeated two times in the 7th line of the paragraph.\n\nHighlighting the accidental infection of men from vials containing live vaccine candidates during immunization of animals is missing in the report such as what happened in the case of brucellosis.\n\nShort hints about the COVID-19 story are required which is not clear whether it is a laboratory accident of wildlife acquired infection. Even though all events were included in the table, I expected to see the events classified according to pathogen category e.g. bacterial, viral, to be more clear for the reader.\n\nOutlooks and recommendations are missing in the conclusion.\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? Partly",
"responses": [
{
"c_id": "8205",
"date": "10 May 2022",
"name": "David Manheim",
"role": "Author Response",
"response": "Thank you for your helpful suggestions! In the forthcoming revision, I have added notes addressing the relevance due to COVID-19, and regarding brucellosis from live vaccines. The absence of outlooks and recommendations in the conclusions is due to the requirements for the journal article type, \"data note,\" intended to describe a dataset rather than make substantive conclusions. If we were called upon to do so, I would note that first, the risks from accidental and deliberate events are very worrying, and require more international cooperation and coordination, and second, the trend towards greater safety is encouraging, but there is significant work remaining for both transparency around accidents and substantive laboratory safety measures which can be decided on the basis of better data, and we hope improvements in laboratory monitoring and safety will continue. Regarding chronology, while the dates of some events in the 1970s are unclear, it seems reasonable to put the events which are likely to have occurred or continued later than most of the events during the 1970s at the end of that decade rather than the beginning. (The war in Rhodesia ended in late 1979, while the Sverdlovsk Anthrax event was in April 1979.) Finally, thank you for the suggestion to add pathogen types to the data, which I agree can be helpful for those using the dataset. My current professional work involves advocacy related to laboratory safety and biorisk policy, and is therefore related to the topic of the research."
}
]
}
] | 1
|
https://f1000research.com/articles/10-752
|
https://f1000research.com/articles/11-761/v1
|
08 Jul 22
|
{
"type": "Research Article",
"title": "A simple approach for extending up to the ultra-relativistic limit the theory of a non-relativistic Fermi gas",
"authors": [
"Luis Grave de Peralta"
],
"abstract": "Background: The theory of a Fermi gas constitutes a useful physical model with multiple applications from solid state to stellar physics. The theory of a non-relativistic Fermi gas is relatively simple when compared with the one for a relativistic Fermi gas. Therefore, it would be useful if a rigorous theory of a relativistic Fermi gas could be constructed like the theory of a non-relativistic Fermi gas.\nMethods: Such a theory, for T > 0 K, is presented here. It is based on using a recently reported formula for the energies of a relativistic spin-0 particle in a three-dimensional infinite well. The Pauli exclusion principle is used for taking care of the fermion nature of the particles forming a Fermi gas.\nResults: A unified description of a Fermi gas at low temperatures is presented. This description is valid from the non-relativistic to the ultra-relativistic limits. Moreover, it is simple. The theory follows the relatively simple approach often used for constructing the theory of a non-relativistic Fermi gas.\n\nConclusions: The ultra-relativistic results reported here are often obtained using a different approach than the one used in this work. These results are not new, but they corroborate the correctness of the presented approach. In addition, the relative simplicity of the approach presented in this work allows for teaching the theory of a relativistic Fermi gas in introductory quantum mechanics courses.",
"keywords": [
"Quantum Mechanics",
"Relativistic Quantum Mechanics",
"Fermi Gas"
],
"content": "I. Introduction\n\nThe theory of a Fermi gas constitutes a useful model with multiple applications from solid state to stellar physics.1–3 The theory of a non-relativistic Fermi gas is relatively simple when compared with the one for a relativistic Fermi gas.1–4 Therefore, it would be useful if a rigorous theory of a relativistic Fermi gas could be constructed like the theory of a non-relativistic Fermi gas.1,2 Building on recently published results for a relativistic Fermi gas at T = 0 K,5 in this work we present such a theory for T > 0 K for the first time.\n\nThe theory of a non-relativistic Fermi gas is built from a well-known analytical expression, which gives the energies of a non-relativistic spin-0 particle in a three-dimensional infinite well (particle in a box).1,2 The Pauli exclusion principle is used, in the non-relativistic theory of a Fermi gas at 0 K, for taking care of the fermion nature of the particles forming a Fermi gas.1,2 However, this relatively simple theory cannot be directly extended to the relativistic domain.3,4 This is because no such analytical expression was known, until recently, for the energies of a relativistic spin-0 particle in a box.5–9 In what follows, first, in Section II is presented a discussion about the energy of a relativistic spin-0 particle in a box when the particle is in a quantum state with positive kinetic energy. In Section III, it is summarized how the energy formula presented in Section II was used for constructing the theory of a relativistic Fermi gas at T = 0 K.5 In Section IV, it is shown that it is possible to construct a theory of a relativistic Fermi gas at T > 0 K but using the same approach often used for constructing the theory of a non-relativistic one. We are then presenting a simple approach for constructing a theory of a Fermi gas valid from the non-relativistic to the ultra-relativistic limits. Finally, the conclusions of this work are given in Section V.\n\n\nII. Positive energies of a spin-0 particle in a box\n\nA relativistic spin-0 particle with mass m, which is completely confined in a cubic box of size L, only has kinetic energy. The possible positive values of the particle’s energy can be found by solving a special case of the spinless Salpeter equation10,11:\n\nIn Eq. (1), c is the speed of the light in vacuum and the wavefunction (ψ) must satisfy null boundary conditions. As it will be shown below, after discounting the energy of the particle associated with its mass (mc2), Eq. (1) can be rewritten as the Poirier-Grave de Peralta equation6,12:\n\nWhen a particle in a box is in a stationary state, it has a constant kinetic energy value, thus a constant value of the square of its linear momentum (p2). Therefore, the solutions of Eq. (2) are exactly equal to the solution of the Grave de Peralta (GdeP) equation6–9,12:\n\nEquation (3) differs from Eq. (2) in that γ is not an operator but a parameter equal to the classical value of the Lorentz factor of special theory of relativity.13 Clearly, Eq. (3) reduces to the Schrödinger equation when γ = 1.1 The infinite-well potential does not interact with the spin degree of freedom; therefore, the energies of a spin-0 and spin-1/2 particle in a cubic box are the same and equal to5,6,14:\n\nIn Eq. (4), ℏ is the reduced Plank constant,1 and γ is given by the following equation5–6:\n\nIn the non-relativistic limit, the reduced Compton wavelength λ/2π << L, thus γ = 1 and Eq. (4) reduces to the well-known formula1,2:\n\nThe theory of a non-relativistic Fermi gas, formed by N non-interacting fermions with spin-½, is based on using Eq. (6). The fermion nature of the particles is included by considering the Pauli exclusion principle.1,2 The correct relativistic formula, Eq. (4), was only recently reported.5–9 Consequently, it can be now used for constructing a theory of a relativistic Fermi gas like the well-known one for a non-relativistic Fermi gas.1,2 This project was started recently.5\n\nIt could be helpful noting that Eq. (1) can be obtained by applying the formal first-quantization substitution1,3:\n\nIn Eq. (8), γ is the classical Lorentz factor given by Eq. (3). Alternatively, we could start from the following equation, which is equivalent to Eq. (8)6:\n\nApplying the formal first-quantization substitution to Eq. (9), we obtain6:\n\nIn Eq. (10), γ is the operator given by Eq. (1). Now, it is well known in quantum mechanics that applying a constant energy shift to the Hamiltonian gives way to an immaterial time-evolving phase factor in the solution wavefunction. Therefore, Eq. (2) can be obtained from Eq. (10), after replacing Ω as follows6:\n\nFor a particle in a box, the solutions of Eq. (2) and (3) are identical. This is because a particle in a box has a constant kinetic energy value when it is in a stationary state; therefore, the particle must also have constant value of the square of its linear momentum (p2) and thus a constant value of γ. Consequently:\n\nFor instance, if a particle trapped in a one-dimensional box is in a stationary state, then γ is equal to6:\n\nIn Eq. (13), ESch is the well-known energy of the corresponding non-relativistic problem1,6:\n\nNote that for a particle in a box the possible values of k are determined by the boundary conditions; thus, k is the same for a non-relativistic and a relativistic particle in a box.6 Consequently, for a particle in a one-dimensional box6:\n\nAnd:\n\nEquations (4) and (5) are the tridimensional versions of Eqs. (16) and (15), respectively.\n\nThe above discussion is enough for justifying the validity of our approach, which is based on using Eqs. (3) to (5) for constructing a theory of a relativistic Fermi gas. Moreover, it is easy to show that the GdeP equation for any time-independent scalar potential (V):\n\nConsequently, the classical value of the Lorentz factor (γ) is in general not constant:\n\nUsing Eqs. (7) and (19), we can rewrite the time independent GdeP equation corresponding to Eq. (17) in the following way:\n\nThe above equation is an appealing Schrödinger-like form of the time-independent Klein-Gordon equation. Indeed, it is easy to show that by making E′ = E - mc2, Eq. (20) reduces to the well-known expression for the corresponding stationary Klein-Gordon equation (15).\n\n\nIII. Relativistic Fermi gas at T = 0 K\n\nIt was recently obtained, using Eq. (4), that the Fermi energy (EF) of a relativistic gas formed by N fermions occupying a volume V is given by the following equation (5):\n\nIn the non-relativistic limit (γ ≈ 1) Eq. (21) gives the well-known formula1–2:\n\nThis is hardly a surprise because Eq. (21) and Eq. (22) were obtained using the same approach.2,5 However, Eq. (21) also gives the correct result in the ultra-relativistic limit (γ >>1)3,4:\n\nThis is a well-known formula for a relativistic Fermi gas that was originally obtained following a different approach.3,4 This suggests that a correct theory of a relativistic Fermi gas can be constructing using Eq. (4) and following the relatively simple approach often used for constructing a theory of a non-relativistic Fermi gas.1,2 We will see over and over in this work that it is always the case. For instance, the total energy of a relativistic Fermi gas at 0 K can be obtained from Eq. (4) in the following way5:\n\nIn the non-relativistic limit Eq. (24) gives the well-known formula2,5:\n\nIn Eq. (25) EF is given by Eq. (22). As expected, Eq. (24) also gives the correct result in the ultra-relativistic limit3–5:\n\nIn Eq. (26) EF is given by Eq. (23). Consequently, the degeneracy pressure of a non-relativistic (nr) and an ultra-relativistic (ur) Fermi gas at 0 K are1–5:\n\nThe possibility of obtaining correct non-relativistic and ultra-relativistic formulas, while using the same theoretical approach, allows for illustrating the effects of the inclusion of special theory of relativity in quantum mechanics. A dramatic example of this is the use of Eqs. (25) and (26) for explaining why Fermi gas stars gravitationally collapse when their masses surpass the Chandrasekhar mass limit.5,16,17\n\n\nIV. Electronic heat capacity of a relativistic Fermi gas\n\nOften in solid state physics, the non-relativistic theory of a Fermi gas is developed for calculating the electronic heat capacity (Cel) of solids at low temperatures, i.e., when 0 < T < EF/KB, where KB is the Boltzmann constant2:\n\nIn Eq. (28), D (EF) is the density of states at E = EF2:\n\nN is obtained from Eq. (21); therefore, using Eqs. (22) and (23) in the non-relativistic and ultra-relativistic limits, respectively; we obtain:\n\nTherefore, from Eqs. (28) and (30) follows:\n\nAgain, in both limits, Eq. (31) gives known equations.2–4 Substituting Eq. (22) in Eq. (31), one obtains2–4:\n\nWhile substituting Eq. (23) in Eq. (31), we obtain4:\n\nTherefore, in both limits Cel/NKB is proportional to T but the dependence on the density of the gas (ρ) is different.\n\n\nV. Conclusions\n\nWe presented a unified description of a Fermi gas at low temperatures. This description is rigorously valid from the non-relativistic to the ultra-relativistic limits. Moreover, it is simple. The presented theory is based on a recently reported formula for the energies of a relativistic spin-0 particle in a box. The theory follows the relatively simple approach often used for constructing the theory of a non-relativistic Fermi gas. However, the theory outlined here does not include the formation and destruction of particle-antiparticle pairs at energies large than 2mc2. It is then limited to cases where the number of particles can be considered constant.\n\nIt is worth noting that the ultra-relativistic results given by Eqs. (23), (26), (27), and (31) are often obtained using a different approach than the one used in this work. These results are not new but, together with the correct deduction of the Chandrasekhar mass limit reported in Ref. [5], they corroborate that the recently reported Eq. (4) is correct and illustrate the practical utility of Eqs. (3) and (17). In addition, the approach presented in this work allows for teaching the theory of a relativistic Fermi gas in introductory quantum mechanics courses.18\n\n\nData availability statement\n\nNo data are associated with this article.",
"appendix": "References\n\nGriffiths DJ: Introduction to Quantum Mechanics. 3rd ed.USA:Prentice Hall;2018.\n\nKittel C: Introduction to Solid State Physics. 8th ed.New York:J. Wiley & Sons;2005.\n\nGreiner W, Neise L, Stöcker H: Thermodynamic and Statistical Mechanics. New York:Springer-Verlag;1997.\n\nLandau L, Lifshits EM: Statistical Physics. 2nd ed.Oxford:Pergamon Press;1970.\n\nLopez-Boada R, Grave de Peralta L: Some Consequences of a Simple Approach for Constructing a Theory of a Relativistic Fermi Gas. J. Modern Phys. 2021; 12: 1966–1974. Publisher Full Text\n\nGrave de Peralta L, Poveda L, Poirier B: Making relativistic quantum mechanics simple. Eur. J. Phys. 2021; 42: 055404. Publisher Full Text\n\nGrave de Peralta L: Did Schrödinger have other options? Eur. J. Phys. 2020; 41: 065404. Publisher Full Text\n\nGrave de Peralta L: Res. Phys. 2020; 18: 103318.\n\nGrave de Peralta L: Natural Extension of the Schr&ouml;dinger Equation to Quasi-Relativistic Speeds. J. Modern Phys. 2020; 11: 196–213. Publisher Full Text\n\nJacobs S, Olsson MG, Suchyta C III: Comparing the Schrödinger and spinless Salpeter equations for heavy-quark bound states. Phys Rev. D. 1986; 33: 3338–3348. PubMed Abstract | Publisher Full Text\n\nLucha W, Schöberl FF: Semirelativistic Hamiltonians of apparently nonrelativistic form. Phys. Rev. A. 1995; 51: 4419–4426. PubMed Abstract | Publisher Full Text\n\nPoveda LA, Grave de Peralta L, Pittman J, et al.: A Non-relativistic Approach to Relativistic Quantum Mechanics: The Case of the Harmonic Oscillator. Found. Phys. 2022; 52: 29. Publisher Full Text\n\nChristodeulides C: The Special Theory of Relativity. New York:Springer;2016.\n\nRuiz-Columbie A, Farooq H, Grave de Peralta L: Direct Relativistic Extension of the Madelung-de-Broglie-Bohm Reformulations of Quantum Mechanics and Quantum Hydrodynamics. J. Modern Phys. 2021; 12: 1358–1374. Publisher Full Text\n\nGreiner S: Relativistic Quantum Mechanics: wave equations. New York:Spring-Verlag;1990.\n\nMorison I: Introduction to Astronomy and Cosmology. U. K.:Wiley;2008.\n\nKutner ML: Astronomy, a Physical Perspective. 2nd ed.Cambridge:Cambridge University Press;2003.\n\nGrave de Peralta L, Webb KC, Farooq H: A pedagogical approach to relativity effects in quantum mechanics. Eur. J. Phys. 2022; 43: 045402. Publisher Full Text"
}
|
[
{
"id": "147128",
"date": "11 Aug 2022",
"name": "Niels Benedikter",
"expertise": [
"Reviewer Expertise mathematical and theoretical physics",
"many-body quantum systems",
"Fermi gas"
],
"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 considers a semi-relativistic Schrödinger equation (of square-root type) for fermionic particles in a box, computing the heat capacity in the non-relativistic and ultrarelativistic limit.\nThe work does not represent the state of knowledge completely: the problem considered is trivial, namely on the level of a student exercise in an advanced quantum mechanics course.\nFor example, the claim \"no such analytical expression was known, until recently, for the energies of a relativistic spin-0 particle in a box\" is wrong. The formula is completely elementary and should be obvious to any theoretical physicist.\nEquation (2) is a trivial rewriting of eq. (1). It irritates that the author tries to put his name on this equation.\nEquation (3) is trivial, because an operator can always be replaced by its eigenvalue when acting on an eigenstate. Again, it irritates that the author tries to put his name on this trivial equation.\nThe paper continues like that.\nA complete thermodynamical description may be explicitly computed looking at the grand canonical potential (as done already, e.g., by ref. 1 from the year 1942).1\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?\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? No",
"responses": [
{
"c_id": "8638",
"date": "25 Aug 2022",
"name": "Luis Grave de Peralta",
"role": "Author Response",
"response": "The author appreciates the “Yes” response of the reviewer to the question “Is the study design appropriate and is the work technically sound? This is because as stated in the Conclusions, the author does not claim that the results presented in this work are originals. The author also appreciates the reviewer opinion that “the problem considered is … on the level of a student exercise in an advanced quantum mechanics course.” This is because, as stated in the Conclusions, the author considers that “the relative simplicity of the approach presented in this work allows for teaching the theory of a relativistic Fermi gas in introductory quantum mechanics courses,” which is not a common practice due to the relative complexity of relativistic quantum mechanics. The author respectfully disagrees with the reviewer in the following: Eqs. (4) and (5) give the energies of a relativistic spin-0 particle completely confined in a cubic box. These formulas are a three-dimensional generalization of the one-dimensional infinite well case. The formulas corresponding to the one-dimensional case were recently published for the first time (see Refs. (6) to (8)). Certainly, Eqs. (4) and (5) are simple; thus, it could be surprising that they were reported recently. The reason for this is that there are a lot of technical difficulties for solving the Klein-Gordon and the Dirac equations for a one-dimensional infinite well (see for instance, P. Alberto, C. Fiolhais, and V. M. S. Gil, Eur. J. Phys, 17, 19 (1996)). The originality of the approach presented in this work is that starting from Eqs. (4) and (5), we can arrive to well-known relativistic results using the same approach commonly followed in Introductory Quantum Mechanics and Solid-State courses for studying a non-relativistic Fermi gas (see for instance Refs. (1) and (2)). The author also respectfully disagrees with the reviewer in the following: at a first look, Eq. (3) could be seemed like a trivial relativistic extension of the Schrödinger equation, but Eq. (3) is a very interesting and reach equation that only recently has been intensively studied (see for instance Refs. (6), (7), and (12)). Note that in many interesting cases (for instance, the relativistic harmonic oscillator and the Coulomb potential) the eigenfunctions of the energy operator are not eigenfunctions of the γ operator. Fortunately, as the reviewer cleverly pointed out, the eigenfunctions of the energy operator are eigenfunctions of the γ operator for a relativistic spin-0 particle completely confined in a cube. This simplifies the solution of Eq. (3) for this specific case (see Refs. (6) to (8)). Also note that Eq. (3) describes a constant number (one) of spin-0 particles; therefore, in contrast with the Klein-Gordon equation, there are not paradoxes associated to Eq. (3) for an infinite well. Equation (2) is as least as interesting and reach as Eq. (3). The author suggests to the readers to go carefully over Refs. (6) and (12). There is a lot of original work there."
},
{
"c_id": "8680",
"date": "09 Sep 2022",
"name": "Niels Benedikter",
"role": "Reviewer Response",
"response": "Equation (1) and its trivial rewriting (2) have already been given by Dirac, Klein, and Fock. As early as 1964, this equation has been given in the textbook on relativistic quantum mechanics by Bjorken and Drell. Mathematically it does not present any difficulty, as may be learned for example from the textbook \"Analysis\" by Lieb and Loss. In fact, the equation has been widely studied in mathematical physics, and its solution as discussed in the paper is obvious to any researcher with some basic knowledge of Fourier analysis. Equation (3) constitutes a naive and uncontrolled approximation, that, except for the treated trivial case, cannot be expected to yield a correct result."
}
]
},
{
"id": "171501",
"date": "14 Aug 2023",
"name": "J. P. W. Diener",
"expertise": [
"Reviewer Expertise Theoretical nuclear physics",
"magnetised dense nuclear matter"
],
"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 aims to demonstrate an alternative approach to description of a non-relativistic and relativistic Fermi gas. In the conclusion, it is further stated that \"...approach presented in this work allows for teaching the theory of a relativistic Fermi gas in introductory quantum mechanics courses.\"\n\nDue to the format of the journal, this reviewer is privy to the responses of the other reviewer as well as the author's response to the previous reviewer's comments. In order to provide a constructive contribution, I will consider the implied pedagogical aim of the article.\n\nIn this regard, the effort of the author to present alternative approaches to what could be considered a standard problem is appreciated. However, in order to assist with alternative approaches to teaching the subject matter, a direct comparison between approaches would have been appreciated, thereby illuminating additional physical insights as well as the pros and cons of the different approaches (simply stating that one is \"simpler\" is of limited use). Unfortunately the article heavily directly references previous results (in other publications), with which the reader might or might not be familiar, with limited context given in this article. This detracts from the readability of the article.\nDue to these shortcomings, I unfortunately find the article of limited pedagogical interest.\n\nI also concur with the objections raised by the previous reviewer and note the responses by the author. However, in my opinion, the author's responses do not address the valid concerns raised by the previous reviewer.\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?\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? No",
"responses": [
{
"c_id": "10065",
"date": "16 Nov 2023",
"name": "Luis Grave de Peralta",
"role": "Author Response",
"response": "The author appreciates the reviewer opinion, cite \"the effort of the author to present alternative approaches to what could be considered a standard problem is appreciated.\" The author also agrees with the reviewer in that a direct comparison between approaches would have been appreciated. However, the author consider that it is outside of the scope of this article. There are references in the manuscript (Ref. 3-4) where a reader can find the statistical approach often used for describing a relativistic Fermi gas."
}
]
},
{
"id": "171496",
"date": "14 Aug 2023",
"name": "E.F. El-Shamy",
"expertise": [
"Reviewer Expertise theoretical plasma physics and its applications"
],
"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 have carefully reviewed this manuscript. The author presents a unified description of a Fermi gas at low temperatures that remain valid from the nonrelativistic to the ultra-relativistic regimes. The theory developed follows a relatively simple approach commonly used for constructing the theory of a non-relativistic Fermi gas. However, it should be noted that the theory outlined in this work does not account for the formation and destruction of particle-antiparticle pairs at energies greater than 2mc2 . As a result, it is limited to cases where the number of particles can be considered constant. Nevertheless, I have concerns regarding the suitability of this paper being indexed, and I have provided detailed comments below:\n\nFirst of all, the work appears to be more of a straightforward mathematical exercise rather than a comprehensive exploration of the current state of knowledge. The problem addressed is relatively straightforward, close to a student exercise in an advanced quantum mechanics course.\n\nThe author's mathematical treatment simplifies the problem but overlooks the true physical intrinsic of relativistic quantum mechanics. For instance, the author's approach is based on the hypothesis that a particle in a stationary state within a box possesses a constant kinetic energy value, thus a constant value of the square of its linear momentum (p2 ). However, this assumption is not valid in the relativistic Fermi gas model.\nIn the Fermi gas model, it is well-established that the energy levels of particles are filled up to the Fermi energy level, which depends on the system's temperature and density. The Fermi energy represents the maximum energy level occupied by fermions at absolute zero temperature. Therefore, assuming a constant kinetic energy value (i.e., a particle in a box being in a stationary state with constant kinetic energy) would imply that all particles have the same momentum, contradicting the principles of special relativity. In the relativistic Fermi gas model, the distribution of particle momenta is determined by the Fermi-Dirac statistics and the Fermi-Dirac distribution function. These considerations account for the relativistic energy-momentum relation and the exclusion principle, enabling an accurate description of the system.\nBased on the above-mentioned points, I am of the opinion that this manuscript is not suitable 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? 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? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "10066",
"date": "16 Nov 2023",
"name": "Luis Grave de Peralta",
"role": "Author Response",
"response": "The author appreciates the opinion of the reviewer, cite \"the work appears to be more of a straightforward mathematical exercise rather than a comprehensive exploration of the current state of knowledge. The problem addressed is relatively straightforward, close to a student exercise in an advanced quantum mechanics course,\" this is because this supports the author claims about the simplicity of the proposed description of a relativistic Fermi gas. The author disagrees with the reviewer in the following point, cite \"assuming a constant kinetic energy value (i.e., a particle in a box being in a stationary state with constant kinetic energy) would imply that all particles have the same momentum, contradicting the principles of special relativity.\" This is because the Pauli's exclusion principle was used. Consequently, only two fermions have the same momentum at 0 K. There is no reason for the reviewer to answer NO to the question, cite \"Are all the source data underlying the results available to ensure full reproducibility? The correct answer should be \"Not applicable.\" (See other reviewers)"
}
]
}
] | 1
|
https://f1000research.com/articles/11-761
|
https://f1000research.com/articles/10-110/v1
|
15 Feb 21
|
{
"type": "Brief Report",
"title": "Importance of respiratory syncytial virus as a predictor of hospital length of stay in bronchiolitis",
"authors": [
"Jefferson Antonio Buendia",
"Diana Guerrero Patino",
"Diana Guerrero Patino"
],
"abstract": "Introduction: Bronchiolitis is the leading cause of hospitalization in children. Estimate potentially preventable variables that impact the length of hospital stay are a priority to reduce the costs associated with this disease. This study aims to identify clinical variables associated with length of hospital stay of bronchiolitis in children in a tropical middle-income country Methods: We conducted a retrospective cohort study in 417 infants with bronchiolitis in tertiary centers in Colombia. All medical records of all patients admitted to the emergency department were reviewed. To identify factors independently associated we use negative binomial regression model, to estimate incidence rate ratios (IRR) and adjust for potential confounding variables Results: The median of the length of hospital stay was 3.68 days, with a range of 0.74 days to 29 days, 138 (33.17%) of patients have a hospital stay of 5 or more days. After modeling and controlling for potential confounders age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, RSV isolation, and C-reactive protein were independent predictors of LOS Conclusions: Our results show that in infants with bronchiolitis, RSV isolation, age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, and C-reactive protein were independent predictors of LOS. As a potentially modifiable risk factor, efforts to reduce the probability of RSV infection can reduce the high medical cost associates with prolonged LOS in bronchiolitis.",
"keywords": [
"Bronchiolitis",
"Colombia",
"respiratory syncytial virus",
"length of hospital stay",
"chest indrawing"
],
"content": "Introduction\n\nBronchiolitis is the most frequent lower respiratory tract infection in infants1,2. One of the variables with more incidence in the financial burden of this disease is the hospital length of stay (LOS). Among inpatients with bronchiolitis, approximately a quarter undergo a prolonged length of stay (LOS)3. The hight medical cost associates with prolonged LOS in bronchiolitis imposes an economic burden, especially in tropical middle-income countries4. LOS is a direct measure of the quality of health service5.\n\nSome models have identified predictors of LOS such as age, underlying conditions (congenital heart disease, chronic lung conditions, immunocompromised states), low weight, male gender, clinical characteristics at admission, prematurity, RSV isolation6. However, many of these models lack accuracy7 or were made in patients without significant comorbidities8. Otherwise, in tropical areas in addition to genetic differences, the respiratory syncytial virus (RSV), generates differences in the burden of morbidity and mortality given the non-seasonality of these areas9. In this context, there is a critical need to explore predictors of LOS, especially in tropical areas, improving their accuracy of current models .This information will allow risk management for healthcare and prioritize care strategies in groups with a high probability of prolonged hospital stay to reduce their impact on hospital costs and morbidity. This study aims to identify clinical variables associated with LOS of bronchiolitis in children in a tropical middle-income country.\n\n\nMethods\n\nWe conducted a retrospective cohort study that included all infants with bronchiolitis younger than two years of age in tertiary centers in Rionegro, Colombia, from January 2019 to December 2019. The municipality of Rionegro had a total population of 101,046 inhabitants, with two tertiary referral hospitals10. Inclusion criteria were defined as children younger than two years of age admitted to the pediatric ward diagnosed with bronchiolitis, according to the national clinical guideline of bronchiolitis (first wheezing episode younger than 24 months of age)11. Patients without lower respiratory compromise, with positive bacterial cultures on admission, confirmed whooping cough (culture or PCR) were excluded. The study protocol was reviewed and approved by the Institutional Review Board of the University of Antioquia (No 18/2015).Informed consent was obtained from all parents or caregivers of the patients included in the study, following the clinical research standards in Colombia, and prior approval by the ethics committee.\n\nWe collected the following variables: age, sex, weight, height, signs, and symptoms on admission (including fever, chest indrawing, chest auscultation, %SpO2), vaccination scheduled chart for age, exposure to cigarette smoking, history of prematurity and bronchopulmonary dysplasia confirmed by a neonatologist at the time of discharge from the NICU, comorbidities (congenital heart disease, neurological disease), diagnostic tools as chest X rays, hemograms, etc. Additionally, we collected variables related to outcomes of care or disease-severity parameters such as length of hospital stay. In our hospitals, bronchodilators and systemic steroids are used at the discretion of attending physicians according to national clinical guidelines of bronchiolitis11. Nasopharyngeal aspirate (NPA) was taken immediately upon admission to the emergency department within 48 hrs of admission using standardize technique. RSV was confirmed using direct immunofluorescence (Light Diagnostics TM Respiratory Panel 1 DFA, Merck-Millipore Laboratory).NPA data for other viruses were no available in our institution consistently.\n\nContinuous variables were presented as mean ± standard deviation (SD) or median (interquartile range [IQR]), whichever appropriate. Categorical variables are shown as numbers (percentage). Differences between continuous variables were analyzed using the unpaired t-test or Wilcoxon's signed-rank test, whichever was appropriate. Associations between categorical variables and the outcome variable were analyzed using the chi-square test or Fisher's exact test, as needed. To identify factors independently associated with length of hospital stay, we used a Poisson regression model, or negative binomial regression model in case of the presence of overdispersed count data, to estimate incidence rate ratios (IRR) and adjust for potential confounding variables. We only include initially variables associated with LOS with values of p <0.2 or that change the effect estimate by more than 10% after their inclusion. The variable selection and modeling processes were made following the recommendations of Greenland12. The goodness of fit of the model was evaluated using Hosmer–Lemeshow test and area under curve in Poisson regression or Akaike information criterion (AIC), Bayesian information criterion (BIC) in negative binomial regression. All statistical tests were two-tailed, and the significance level used was p < 0.05. The data were analyzed with Stata v15.0 (Stata Corporation, College Station, TX).\n\n\nResults\n\nDuring the study period, 417 cases of bronchiolitis were included. A total of 66% of the patient was less than 6 month, most of them males (60%), with supportive O2 (83%). RSV was isolated in 200 patients (48%). Of these, 81 patients had a history of premature birth and 17 of them with BPD. A total of 20 patients had some cardiac or neurological disease and 10 of them with a history of use of palivizumab. Table 1 presents the clinical characteristics of the population. Deidentified individual-level raw data are available from Zenodo13.\n\n*Atelectasis (n=7), alveolar(n=16) or interstitial (n=48) infiltrates, hyperinflation(n=38)\n\nCHD : Congenital heart disease, BPD: Bronchopulmonary dysplasia, RSV: Respiratory syncytial virus\n\nThe median of the length of hospital stay was 3.68 days, with a range of 0.74 days to 29 days and an interquartile range of 4.06 days. Among all 417 patients, 138 (33.17%) have a hospital stay of 5 or more days\n\nDue to the significative presence of overdispersed count data was detected (Likelihood-ratio test of alpha=0, χ2= 203.97, p=0.000), a negative binomial regression model was used to adjust for potential confounding variables. The predictive variables included in the complete model were age, sex, premature birth, comorbidities, BPD, atopy, previously hospitalization by bronchiolitis, %SpO2, fever, signs of respiratory distress, RSV, Leucocytosis (>15.000/mm3) and increased C-reactive protein (>4 mg/lit.). After modeling and controlling for potential confounders in the negative binomial regression: age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, RSV isolation, and C-reactive protein were independent predictors of LOS (Table 2).\n\n\nDiscussion\n\nThe main purpose of this study was to determine the independent clinical variables associated with LOS of bronchiolitis in children in tropical middle-income countries. Our study shows that RSV, age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, and C-reactive protein were independent predictors of LOS\n\nOur results emphasize the importance of knowing the presence of RSV. While some predictors of LOS, such as age, comorbidities, and potentially initial signs of respiratory distress, can not be modified, others as RSV isolation are potentially modifiable by interventions such as futures vaccines or palivizumab in a high-risk population. Previous studies in populations with seasonality had revealed the importance of RSV as a predictor of hospital stay. DeVicenzo et al., in a sample of 141 infants <24 months old without previous chronic cardiac or lung disease or prematurity, in Tennessee found that higher nasal RSV load was an independent predictor of longer hospitalization. A 1-log higher RSV load predicted a 0.8-day longer hospitalization, reflects the higher RSV load that occur earlier in the disease14. Mansbasch et al., in a prospective cohort of 2207 infants of 16 US hospital without excluding patients previous chronic cardiac or lung disease or prematurity, also found that patients with RSV have a higher proportion of patient with prolonged LOS (>3 days) than patients with only HSV infection, but less than RSV+HRV co-infection (48% vs 28% vs 54%, p<0.00115. Rodríguez-Martínez, in 303 infants with acute bronchiolitis in Bogota, also found that RSV isolation correlated with a hospital stay of 5 or more days (OR 1.92, CI 95% 1.02 to 3.73)3. In Qatar, Janahi et al., , detected RSV in 51.2% of in 369 patients admitted to the pediatric ward for bronchiolitis, but no association was found between RSV and LOS16. Additionally, Masarweh et al., in a retrospective study of 4793 infants with bronchiolitis in a single tertiary medical center in Israel between 2001–2009, found that RSV isolation did not correlate with LOS17. In this evidence, only the Mansbach study used the PCR assay for viral detection, but the results with immunofluorescence assay with respect to the predictive value of RSV were similar to the PCR assay. Indeed, the main problem of the studies mentioned above was the serious statistical mistakes of analyzing the LOS. While we used a negative binomial regression model, due to the presence of overdispersed count data, to adjust for potential confounding variables to analyze LOS, studies by Rodriguez, Devicenzo, and Mansbach dichotomize the LOS to perform logistic regression, while Masarweh's study performed a linear regression; being both approaches not completely correct. The loss of information from dichotomizing a continuous outcome is well documented in the literature, and even worse, analyzing a variable that does not have a normal distribution with a linear regression invalidates this method of analysis18. These pitfalls in statistical analysis can explain the lack of accuracy of predictive models6. The regression models recommended are median, gamma, or Poisson regression; which have some type I error but avoid the mistakes previously mentioned with the logistic or linear regression model.\n\nOthe variable potentially modifiable associated with LOS was age <6 months. Our findings are consistent with previous results reported in the literature and provide further evidence that younger infants are at a greater risk of requiring prolonged LOS3. This can be explained because the smaller caliber of the airways in younger infants and poor innate immune response to RSV in newborns, making younger infants more susceptible to severe forms of viral infections and prolonged LOS19,20. Preventive strategies such as the use of palivizumab in a high-risk population or the use of future vaccines that confer immunity in children under 6 months against RSV; will constitute possibly effective interventions in reducing the economic burden of this disease.\n\nSeveral predictive models had reports consistently the chest indrawing as predictive of prolonged LOS that is which is biologically plausible and expected due that this sign also is a universal marker of severity of the disease, as well as the presence of underlying conditions (congenital heart disease, chronic lung conditions, immunocompromised states)3,6–8,21–23 or C-reactive protein (CRP) as a biomarker of severity and bacterial co-infection in patients hospitalized for bronchiolitis24–26\n\nOur study has limitations. First, since this study was based on medical records review, we cannot include other variables such as environmental pollution and genetic factors, and residual confounding cannot be excluded. Second, the study was conducted in a tertiary referral hospital, and therefore the patients included represent the high spectrum of severity, limiting the generalization of results to other contexts. However, the similarity of our population in terms of clinical characteristics, risk factors, and seasonality of bronchiolitis in our country with previous reports suggest strength and consistency in our results3,4\n\n\nConclusion\n\nOur results show that in infants with bronchiolitis, RSV, age <6 months, comorbidities (CHD or neurological), BPD, chest indrawing, and C-reactive protein were independent predictors of LOS in a tropical middle-income country. As a potentially modifiable risk factor, efforts to reduce the probability of RSV infection can reduce the hight medical cost associates with prolonged LOS in bronchiolitis.\n\n\nData availability\n\nZenodo: Importance of respiratory syncytial virus as a predictor of hospital length of stay in Bronchiolitis. http://doi.org/10.5281/zenodo.443243413.\n\nThis project contains the raw data for each patient assessed in the present study.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nDeclarations\n\nThe study protocol was reviewed and approved by the Institutional Review Board of Clinica Somer (No 281015) and the University of Antioquia (No 18/2015).\n\nAll authors consent this paper for publication\n\n\nAbbreviations\n\nincidence rate ratios (IRR)\n\nhospital length of stay (LOS)\n\nrespiratory syncytial virus (RSV)\n\nNasopharyngeal aspirate (NPA\n\nBronchopulmonary dysplasia (BPD)\n\nChronic heart disease (CHD)",
"appendix": "Authors' contributions\n\nAll the authors contributed in the same way from conception of the work to the publication of results. All Authors read and approved the manuscript.\n\n\nReferences\n\nNair H, Nokes DJ, Gessner BD, et al.: Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010; 375(9725): 1545–55. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBuendía JA, Patiño DG: Costs of Respiratory Syncytial Virus Hospitalizations in Colombia. Pharmacoecon Open. 2020. PubMed Abstract | Publisher Full Text\n\nRodríguez-Martínez CE, Sossa-Briceño MP, Nino G: Predictors of prolonged length of hospital stay for infants with bronchiolitis. J Investig Med. 2018; 66(6): 986–91. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRodriguez-Martinez CE, Sossa-Briceño MP, Castro-Rodriguez JA: Direct medical costs of RSV-related bronchiolitis hospitalizations in a middle-income tropical country. Allergol Immunopathol (Madr). 2020; 48(1): 56–61. PubMed Abstract | Publisher Full Text\n\nAnderson ME, Glasheen JJ, Anoff D, et al.: Understanding predictors of prolonged hospitalizations among general medicine patients: A guide and preliminary analysis. J Hosp Med. 2015; 10(9): 623–6. PubMed Abstract | Publisher Full Text\n\nLuo G, Nkoy FL, Gesteland PH, et al.: A systematic review of predictive modeling for bronchiolitis. Int J Med Inform. 2014; 83(10): 691–714. PubMed Abstract | Publisher Full Text\n\nCorneli HM, Zorc JJ, Holubkov R, et al.: Bronchiolitis: clinical characteristics associated with hospitalization and length of stay. Pediatr Emerg Care. 2012; 28(2): 99–103. PubMed Abstract | Publisher Full Text\n\nWeisgerber MC, Lye PS, Li SH, et al.: Factors predicting prolonged hospital stay for infants with bronchiolitis. J Hosp Med. 2011; 6(5): 264–70. PubMed Abstract | Publisher Full Text\n\nRodriguez-Martinez CE, Sossa-Briceño MP, Acuña-Cordero R: Relationship between meteorological conditions and respiratory syncytial virus in a tropical country. Epidemiol Infect. 2015; 143(12): 2679–86. PubMed Abstract | Publisher Full Text\n\nEstadisticas DAN: Proyecciones de poblacion. 2018. Reference Source\n\nColciencias MdSyPS: Guía de Práctica Clínica Para el diagnóstico, atención integral y seguimiento de niños y niñas con diagnóstico de Asma. Guía No. 01 2014. Reference Source\n\nGreenland S: Modeling and variable selection in epidemiologic analysis. Am J Public Health. 1989; 79(3): 340–9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBuendía J: Importance of respiratory syncytial virus as a predictor of hospital length of stay in Bronchiolitis (Version 1) [Data set]. Zenodo. 2021. http://www.doi.org/10.5281/zenodo.4432434\n\nDeVincenzo JP, El Saleeby CM, Bush AJ: Respiratory syncytial virus load predicts disease severity in previously healthy infants. J Infect Dis. 2005; 191(11): 1861–8. PubMed Abstract | Publisher Full Text\n\nMansbach JM, Piedra PA, Teach SJ, et al.: Prospective multicenter study of viral etiology and hospital length of stay in children with severe bronchiolitis. Arch Pediatr Adolesc Med. 2012; 166(8): 700–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJanahi I, Abdulkayoum A, Almeshwesh F, et al.: Viral aetiology of bronchiolitis in hospitalised children in Qatar. BMC Infect Dis. 2017; 17(1): 139. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMasarweh K, Gur M, Leiba R, et al.: Factors predicting length of stay in bronchiolitis. Respir Med. 2020; 161: 105824. PubMed Abstract | Publisher Full Text\n\nAggarwal R, Ranganathan P: Common pitfalls in statistical analysis: Linear regression analysis. Perspect Clin Res. 2017; 8(2): 100–2. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSimon AK, Hollander GA, McMichael A: Evolution of the immune system in humans from infancy to old age. Proc Biol Sci. 2015; 282(1821): 20143085. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlvarez AE, de Lima Marson FA, Bertuzzo CS, et al.: Epidemiological and genetic characteristics associated with the severity of acute viral bronchiolitis by respiratory syncytial virus. J Pediatr (Rio J). 2013; 89(6): 531–43. PubMed Abstract | Publisher Full Text\n\nHasegawa K, Tsugawa Y, Brown DFM, et al.: Trends in bronchiolitis hospitalizations in the United States, 2000-2009. Pediatrics. 2013; 132(1): 28–36. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcCallum GB, Chatfield MD, Morris PS, et al.: Risk factors for adverse outcomes of Indigenous infants hospitalized with bronchiolitis. Pediatr Pulmonol. 2016; 51(6): 613–23. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDavies CJ, Waters D, Marshall A: A systematic review of the psychometric properties of bronchiolitis assessment tools. J Adv Nurs. 2017; 73(2): 286–301. PubMed Abstract | Publisher Full Text\n\nFares M, Mourad S, Rajab M, et al.: The use of C-reactive protein in predicting bacterial co-Infection in children with bronchiolitis. N Am J Med Sci. 2011; 3(3): 152–6. PubMed Abstract | Free Full Text\n\nCebey-López M, Pardo-Seco J, Gómez-Carballa A, et al.: Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection. PLoS One. 2016; 11(2): e0146599. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLamarão LM, Ramos FL, Mello WA, et al.: Prevalence and clinical features of respiratory syncytial virus in children hospitalized for community-acquired pneumonia in northern Brazil. BMC Infect Dis. 2012; 12: 119. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "85075",
"date": "28 Jun 2021",
"name": "Mauricio T. Caballero",
"expertise": [
"Reviewer Expertise Respiratory virus infection in children."
],
"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\nImportance of respiratory syncytial virus as a predictor of hospital length of stay in bronchiolitis is an interesting retrospective study conducted in tertiary centers in Rionegro, Colombia, from January 2019 to December 2019. The study explores variables associated with length of stay due to bronchiolitis in children under two years old. I have few comments regarding the study methods and results.\nRespiratory syncytial virus was confirmed using direct immunofluorescence, which may underestimate the real burden of viral infection. How do authors estimate this could impact the results?\n\nAuthors did not mention if other respiratory viruses were explored and compared as associated to length of hospital stay.\n\nUnivariable analysis should be shown in an extra 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? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Partly\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": "6857",
"date": "20 Dec 2021",
"name": "Jefferson Buendia",
"role": "Author Response",
"response": "We appreciate your valuable comments. Respiratory syncytial virus was confirmed using direct immunofluorescence, which may underestimate the real burden of viral infection. How do authors estimate this could impact the results? Response: Corrected. This limitation was added to the discussion of the paper. Authors did not mention if other respiratory viruses were explored and compared as associated to length of hospital stay. Response: Corrected. This limitation was added to the discussion of the paper. Univariable analysis should be shown in an extra table. Response: Corrected. Added a new table with the univariate analysis."
}
]
}
] | 1
|
https://f1000research.com/articles/10-110
|
https://f1000research.com/articles/11-759/v1
|
07 Jul 22
|
{
"type": "Case Study",
"title": "MRI data harmonization across sites using ComBat enhances classification of meningioma and glioma brain-tumors in dogs: a case study",
"authors": [
"Debmalya Nandy",
"Xinyi Yang",
"Xin Jin",
"Lynn Griffin",
"Katerina Kechris",
"Fuyong Xing",
"Xinyi Yang",
"Xin Jin",
"Lynn Griffin",
"Katerina Kechris",
"Fuyong Xing"
],
"abstract": "Background: Magnetic resonance imaging (MRI) in clinical patients is often evaluated for diagnostic purposes. However, to develop a disease classifier, imaging data can be “noisy”, as in being heterogeneous (e.g., obtained from multiple sites), having significant crossover between normal and pathological processes, being highly imbalanced for the outcome variable (i.e., unequal numbers of cases and controls), or due to a lack of accurate quantitative analysis tools that are transferable, easily usable, and accurate to generate the final image variables for machine learning analyses.\nMethods: In this article, we demonstrate the effectiveness of ComBat harmonization of heterogeneous MRI data on dogs’ brains, collected across multiple sites, prior to using them in the random forest (RF) classifier to attempt to differentiate the meningioma and the glioma tumor-types. We consider three image variables generated from each of the brain scans and three clinical covariates – age, sex, and breedtype – for each subject. The scans are generated either at Colorado State University (CSU) or outside CSU. We compare the RF classifier performance in identifying the two tumor types, with and without preprocessing the data with ComBat site-specific harmonization.\nResults: The post-ComBat disease classification accuracy measures – sensitivity, specificity, and total accuracy – indicate an overall significant edge in the RF performance compared to their without-ComBat counterparts across different scenarios. Moreover, incorporating both the image variables and the clinical covariates in the RF model results in the highest total accuracy.\nConclusions: Use of MRI data in combination with clinical covariates is more informative than using only clinical covariates in classifying meningioma and glioma brain-tumors in dogs. Moreover, as a preprocessing step for MRI data, we recommend adjusting for the site-specific variability using ComBat harmonization prior to performing downstream analyses, such as disease classification.",
"keywords": [
"Brain MRI",
"Canines",
"ComBat",
"Data harmonization",
"Multiple sites",
"Meningioma",
"Glioma",
"Random forest classification"
],
"content": "Introduction\n\nMagnetic resonance imaging (MRI), a powerful technology to detect abnormalities in human and animal organs,1–9 can be challenging for clinically differential diagnosis.10–14 In omics sciences, data normalization (henceforth, “harmonization”) is a crucial preprocessing step prior to downstream analyses,15–21 mitigating any spurious effects on the scientific conclusions incorporated due to undesired sources of variation, such as batch effects, intrinsic factors within the subjects, and scanning sites. Such harmonization is also essential for MRI data, as the signal intensities in these data are measured in arbitrary units that vary across study-visits and patients.22–25\n\nIn this study, we demonstrate the effectiveness of a batch-effect correction tool, ComBat,26 widely used in transcriptomics27,28 but also adopted for radiomics data,29,30 in adjusting for undesirable effects of multiple sites on MRI signal intensities (SIs). We chose ComBat due to its superior performance in removing site-specific unwanted variations from fractional anisotropy and mean diffusivity maps in diffusor tensor MRI.29 In their study, the authors considered only controls, used data that were from two “pure” sites, and implemented a sophisticated image-processing pipeline to generate the tissue outcome labels, which resulted in final measurements on the image variables (voxels) having dimensions in the order of 10,000’s. In our case, however, each subject is diseased (meningioma/glioma) and the data come from two “impure” sites, i.e., the “outside” site consists of multiple non-CSU sites, the data thus potentially being noisy due to heterogeneous MRI scanners/protocols used. Notably, such site-heterogeneity can be commonplace to ensure a sufficient sample size. Additionally, we use only three manually recorded image variables, available for all subjects across the sites. Via the downstream performance of the ensemble machine learning classification tool, random forest31–34 (RF), our study thus aims to demonstrate the utility of ComBat harmonization in a “non-ideal” yet practical scenario.\n\n\nMethods\n\nWe use n = 244 subjects (dogs) in our study, belonging to one of the following four subpopulations: 1) glioma, scanned at the Colorado State University – Veterinary Teaching Hospital (CSU-VTH), n = 39; 2) glioma, obtained from a site outside CSU, n = 20; 3) meningioma scanned at the CSU-VTH, n = 106; and 4) meningioma, obtained from a site outside CSU, n = 79. Note that we treat the subjects as coming from only two sites -- CSU and “outside”. However, the “outside” site actually consists of 36 unique sites (Table 1).\n\nDN and XY, the two “processors”, generate the data used in the final analyses. DN scans through the conclusion of each patient’s brain MRI diagnostic report stored in the CSU-VTH Philips IntelliSpace PACS (picture archiving and communication system) Radiology software (henceforth referred to as “PACS”) database, labeling the associated brain tumor-type as either “glioma” or “meningioma” based on the radiologist’s/principal interpreter’s conclusion including terms such as “likely”/“most likely”/“most consistent”, etc. Therefore, these binary tumor-type labels are not based on surgical, histopathological evidence and are used as the outcome variable in the downstream RF classification (see the “Statistical analysis” section). Since we do not have access to the diagnostic reports for the subjects from the “outside” site, we consider instead the corresponding ones from the CSU PACS database that are closest to their original exam dates.\n\nFor each patient, we only consider the transverse/axial section, T1-weighted, post-contrast scans (typically labeled as “Trans T1 +C”). The processors scan through all the slices within each patient’s respective DICOM file and select up to three representative slices in which the cancerous lesions are most prominently visible (i.e., highest contrast) by naked eye. Note that, among the 244 subjects, we settle with only one suitable slice for seven subjects and two for six subjects (Extended data: Table S1).47 Then, within each chosen slice, two circular regions of interest (ROIs) are drawn encompassing the densest parts visually examined, one each on the lesion and on the “normal” tissue, using the PACS software in-built “drawing” tool. Also note that, as “normal” tissue, we choose facial muscle for seven meningioma subjects and muscle of mastication for the rest (Extended data: Table S2).48 From each of these two ROIs, three statistics for the SIs are noted: mean, standard deviation, and the central point-value. See Figure 1 for an example.\n\nThis subject (dog) belongs to the “meningioma outside” subpopulation, i.e., its brain MRI is performed at a non-CSU site and diagnosed with meningioma tumor-type. The normal tissue chosen in (B) is muscle of mastication. The means and the standard deviations of the SIs within the two ROIs are indicated beside the circles drawn and the central point-value SIs are indicated at the bottom of the slides, outside of the parentheses.\n\nBesides the three MRI variables, for each patient we also record the following covariates: three clinical – age (in months) at the time of MRI scan, sex (male, female, male castrated, female spade/spayed), and breedtype; six related to MRI scanner – repetition time (TR), echo time (TE), number of excitations (NEX), slice thickness (mm), frequency phase (X x Y), and field-of-view reconstruction (FOV recon; cm); and one technical – processor.\n\nNote that, for the final analysis, we use both sex and breedtype as binary variables: sex (female/male) and breedtype (non-brachycephalic/brachycephalic). Data on frequency phase are used as two independent scanner covariates. Due to the presence of missing data, we eventually omit the “FOV Recon” scanner covariate from the final analysis. Thus, we have three binary covariates – sex, breedtype, and processor, coded as 0/1; the rest are treated as continuous variables. See Table 2 for a summary of all of the final variables used in our analyses.\n\nThe data are grouped based on the four subpopulations as indicated in the columns. Apart from the three binary covariates – sex, breedtype, and processor – that are coded as 0/1, the rest are treated as continuous variables; each cell-value indicates the range in the top line and the median (median absolute deviation in parentheses) in the bottom line.\n\nPreprocessing of the data and final variables\n\nFor each of up to three selected slices corresponding to each sample, we first normalize the mean, the standard deviation, and the central point-value of the SIs within the diseased ROI by taking respective ratios to the normal ROI within that same slice (Figure 1). We call these three measures adj-mean (SI), adj-SD (SI), and adj-cent (SI), respectively. Next, for each sample, we compute the means of these adjusted measures across the selected slices. These three summarized measures, respectively referred to as μ (adj-mean (SI)), μ (adj-SD (SI)), and μ (adj-cent (SI)), are used as the final three image variables in the subsequent analyses (Figures S1 and S2).50–55 The intercorrelations among the three continuous image variables and the disease labels (0 = glioma, 1 = meningioma) are shown in Figure S3.56,57 We note that, for both CSU and outside sites μ (adj-mean (SI)) and μ (adj-cent (SI)) are maximally correlated with the disease labels and the correlations among the μ (adj-SD (SI)) and disease labels are negligible. Among the continuous covariates across both sites, while age (in months), μ (adj-mean (SI)), and μ (adj-cent (SI)) resemble a Gaussian distribution, those of others deviate greatly from it (data not shown).\n\nFor the classification of meningioma and glioma brain-tumors (glioma treated as the “positive” class), we apply RF31–34 and evaluate classification performance based on sensitivity, specificity, and total accuracy, benchmarked via “lower” and “upper” bounds (Table 3). Using the same site for training and test sets, we expect better RF classification performance (upper bound) compared to when using different sites (lower bound).\n\nM: Meningioma, G: Glioma. For “lower” bound computations, we use all the samples within the outside site (n = 99, M/G = 79/20) to train the RF model, and randomly subsample n = 38 subjects from the CSU population, ensuring M/G = 19/19 representation, for the test set. For “upper” bound computations, we randomly subsample n = 79 meningioma CSU subjects from the remaining 87 for the training sets and use the same test sets as those used for the lower bounds.\n\nFor the “lower” bound calculations, we use all the samples within the outside site (n = 99, M/G = 79/20) to train the RF classifier, and randomly subsample n = 38 subjects from the CSU population, ensuring M/G = 19/19 representation, for the test set. Note that, the training set for the lower bound have 4:1 imbalanced class distribution in the outcome, which we adjust for using the Synthetic Minority Oversampling TEchnique (SMOTE),35 using arguments perc.over = 3 and perc.under = 1.45 within the smote() function. The size of a final training set is thus increased to n = 159 (M/G = 79/80). We use the original n = 79 meningioma samples and the n = 80 glioma cases that are generated using SMOTE. Within this training set, we tune the parameters of the RF classifier using 5-fold cross-validation repeated 25 times, and using all possible combinations of predictor variables in the model via the mtry argument in the train() function. For the “upper” bound calculations, we keep the identical test set compositions as in lower bound computations, and form the training set by randomly subsampling n = 79 “meningioma CSU” subjects from the remaining 87. We repeat this exercise of computing lower and upper bounds 75 times, each time with a different training-test split. Finally, we report the medians (and median absolute deviations) of the classification metrics across these 75 random samples; see Table 5 for an example.\n\nWe investigate the RF classifier performance at the lower and upper bounds for the following scenarios:\n\n• [Case 0: one scenario] We examine the effectiveness of using three clinical covariates only in classifying the tumor types. No image, technical, and scanner covariates are used, and therefore, no ComBat harmonization is involved.\n\n• [Case 1: four scenarios] We use the three image variables in ComBat. Besides, we either use the three clinical covariates or not in ComBat and in subsequent RF, thus giving rise to four scenarios (a – d; Table 4). We do not use any technical and scanner covariates in ComBat.\n\nTo assess the impact of ComBat harmonization on RF classification performance, we conduct nonparametric tests (Wilcoxon’s signed-rank paired one-sided tests with continuity correction) to examine whether a post-ComBat classification metric lower bound is: (1) significantly greater than that for its pre-ComBat counterpart, and (2) significantly lower than the corresponding upper bound (Table 5). Glioma is treated as the “positive” class in classification and, therefore, sensitivity measures the proportion of true glioma cases correctly identified, specificity measures the proportion of true meningioma cases correctly identified, and total accuracy measures the total proportion of true meningioma and glioma cases correctly identified.\n\nThe medians and median absolute deviations of the classifiation metrics are computed based on 75 repetitions of random training/test splits. Values closer to 1 indicate better performance. For post-ComBat lower bounds: 1) bold indicates significantly greater value (p-value < 0.05, Wilcoxon’s signed-rank paired one-sided test with continuity correction) compared to the corresponding pre-ComBat lower bound; 2) underline indicates corresponding upper bound is not significantly higher. Therefore, bold and underline together indicate the best results using ComBat.\n\n\nResults\n\nBelow we discuss the full set of results for the scenarios in Cases 0 and 1.43–46,50–57 Note that, besides these two cases, we also examine the results of another case (Case 2) in which, alongside the three image variables, we include one technical covariate and six scanner covariates (see the “Study population and data generation” section) in the ComBat step. However, since the essence of these results is mostly similar to that of Case 1, we set them aside as “Extended data” (Extended data: Table S3).49\n\nUsing only the clinical covariates of the subjects in the RF model (Case 0), the lower bound total accuracies are not significantly lower than those for upper bounds: both medians = 57.9%; p-value = 0.332 (Figure 2). The lower bounds of the sensitivity and the specificity measures are also not significantly lower than those for the upper bounds: p-values 0.133 and 0.884 respectively. Thus, the distributions of the age/sex/breed-type between meningioma/glioma subjects do not vary significantly across sites. For example, exact p-values corresponding to the Pearson’s chi-squared tests (with Yates’ continuity correction) on the two 2×2 contingency tables for sex and breed-type distributions across CSU and Outside sites are 0.762 and 0.604, respectively. Also, among all scenarios, RF achieves the lowest medians of total accuracy and sensitivity in this case, which indicates an overall poor predictive strength of using only clinical covariates in the RF model (Figures 2 and 3).\n\nL, U: lower bound (black) and upper bound (blue) obtained from RF models using only three clinical covariates.\n\nL.c0, U.c0: lower bound (black) and upper bound (magenta) obtained from RF models using only three clinical covariates; no ComBat harmonization involved; L, L.CB, U: pre-ComBat lower bound (red), post-ComBat lower bounds (green, 1a; blue, 1b), and upper bound (cyan) obtained from RF models using only three image variables.\n\nPre-harmonization\n\nTotal accuracy: Using only the image variables in the RF model, the lower bound total accuracy (pre-ComBat) does not differ significantly from that using only three clinical covariates (Case 0): medians 60.5% vs. 57.9%; p-value = 0.270. However, the upper bound total accuracy is significantly higher than that in Case 0: medians 65.8% vs. 57.9%; p-value = 4.06 E-07 (Figure 3-A).\n\nSensitivity: Using only the image variables in the RF model, the lower bound sensitivity (pre-ComBat) is significantly higher than that using only three clinical covariates (Case 0): medians 47.4% vs. 42.1%; p-value = 9.68 E-04. Similarly, the upper bound sensitivity is also significantly higher than that in Case 0: medians 52.6% vs. 47.4%; p-value = 6.58 E-04 (Figure 3-B).\n\nSpecificity: Using only the image variables in the RF model, interestingly, the lower bound specificity (pre-ComBat) is significantly lower than that using only three clinical covariates (Case 0): medians 68.4% vs. 73.7%; p-value = 3.31 E-03. However, the upper bound specificity is significantly higher than that in Case 0: medians 78.9% vs. 73.7%; p-value = 5.67 E-05 (Figure 3-C).\n\nPost-harmonization\n\nTotal accuracy: Using post-ComBat harmonization (scenarios a, b), the total accuracy lower bounds are significantly higher compared to their pre-ComBat and Case 0 counterparts. For example, post-ComBat with only three image variables (scenario a): (1) vs. pre-ComBat: medians 65.8% vs. 60.5%; p-value = 2.64 E-08 (Table 5, Figure 3-A) and (2) vs. using only the clinical covariates (Case 0): medians 65.8% vs. 57.9%; p-value = 4.98 E-08 (Figure 3-A).\n\nSensitivity: Using post-ComBat harmonization (scenarios a, b), the sensitivity lower bounds are significantly higher compared to their pre-ComBat and Case 0 counterparts. For example, post-ComBat with only three image variables (scenario a): (1) vs. pre-ComBat: medians 57.9% vs. 47.4%; p-value = 4.33 E-08 (Table 5 and Figure 3-B) and (2) vs. using only the clinical covariates (Case 0): medians 57.9% vs. 42.1%; p-value = 7.88 E-11 (Figure 3-B).\n\nSpecificity: Using post-ComBat harmonization (scenarios a, b), the specificity lower bounds are significantly higher compared to their pre-ComBat counterparts. For example, post-ComBat with only three image variables (scenario a) vs. pre-ComBat: medians 73.7% vs. 68.4%; p-value = 1.16 E-03 (Table 5 and Figure 3-C). Interestingly though, these post-ComBat lower bounds are not significantly higher than that using only the clinical covariates (Case 0): all three medians 73.7%; p-values (scenarios a and b vs. Case 0) = 0.347 and 0.359, respectively (Figure 3-C).\n\nThese results confirm that using just the three image variables in the RF model, ComBat harmonization enhances the RF classification performance (except for specificity) compared to that in pre-ComBat and when using only the clinical covariates.\n\nPre-harmonization\n\nTotal accuracy: Using the image variables and the clinical covariates in the RF model, the lower bound total accuracy (pre-ComBat) is significantly higher than that using only three image variables in RF: medians 68.4% vs. 60.5%; p-value = 7.48 E-09. Similarly, the upper bound total accuracy is also significantly higher: medians 71.1% vs. 65.8%; p-value = 3.64 E-07 (Table 5, Figure 4-A).\n\nL3, U3: pre-ComBat lower bound (black) and upper bound (magenta) obtained from RF models using only three image variables; L6, L6.CB, U6: pre-ComBat lower bound (red), post-ComBat lower bounds (green, 1c; blue, 1d), and upper bound (cyan) obtained from RF models using three image variables and three clinical covariates.\n\nSensitivity: Using the image variables and the clinical covariates in the RF model, the lower bound sensitivity (pre-ComBat) is significantly higher than that using only three image variables in RF: medians 52.6% vs. 47.4%; p-value = 8.77 E-04. Similarly, the upper bound sensitivity is also significantly higher: medians 63.2% vs. 52.6%; p-value = 1.76 E-06 (Table 5, Figure 4-B).\n\nSpecificity: Using the image variables and the clinical covariates in the RF model, the lower bound specificity (pre-ComBat) is significantly higher than that using only three image variables in RF: medians 78.9% vs. 68.4%; p-value = 2.33 E-10. Similarly, the upper bound specificity is also significantly higher: medians 84.2% vs. 78.9%; p-value = 2.90 E-03 (Table 5, Figure 4-C).\n\nPost-harmonization\n\nTotal accuracy: Using post-ComBat harmonization (scenarios c, d), the total accuracy lower bounds are significantly higher compared to their pre-ComBat and post-ComBat with only image variables in RF counterparts. For example, post-ComBat using three image variables and three clinical covariates (scenario c): (1) vs. pre-ComBat: medians 71.1% vs 68.4%; p-value = 8.80 E-04 and (2) vs. using only image variables in the RF model (scenario b): medians 71.1% vs. 65.8%; p-value = 1.84 E-04. Moreover, comparing between post-ComBat scenarios c and d: medians 71.1% vs 68.4%, p-value = 6.97 E-03 (Table 5, Figure 4-A).\n\nSensitivity: Using post-ComBat harmonization (scenarios c, d), the sensitivity lower bounds are not significantly higher compared to their pre-ComBat counterparts. For example, post-ComBat using three image variables and three clinical covariates (scenario c) vs. pre-ComBat: both medians 52.6%; p-value = 0.953 (Table 5, Figure 4-B). However, this post-ComBat sensitivity lower bound in scenario c is significantly higher than that using only image variables (scenario d): both medians 52.6%; p-value = 0.0177. Interestingly, post-ComBat sensitivity in scenario c (and d) deteriorates significantly compared to those when not using the clinical covariates in the RF model in scenario b (and scenario a): medians 52.6% vs. 63.2% (52.6% vs. 57.9%); p-value = 2.07 E-05 (6.93 E-05; Table 5).\n\nSpecificity: Using post-ComBat harmonization (scenarios c, d), the specificity lower bounds are again significantly higher compared to their pre-ComBat counterparts. For example, post-ComBat specificity lower bound using three image variables and three clinical covariates (scenario c) vs. pre-ComBat: medians 84.2% vs. 78.9%; p-value = 9.44 E-10 (Table 5, Figure 4-C). This post-ComBat specificity lower bound in scenario c is also significantly higher than that using only image variables (scenario d): both medians 84.2%; p-value = 2.69 E-03 (Table 5, Figure 4-C) and compared to those when not using the clinical covariates in the RF model (scenario b): medians 84.2% vs. 73.7%; p-value = 3.05 E-12 (Table 5).\n\nThese results confirm that using the image variables and clinical covariates together in the RF model, with or without ComBat harmonization, results in better RF classification performance (except for sensitivity) than using only the image variables. Furthermore, using the image variables as well as the clinical covariates in both ComBat harmonization and the RF model provides the highest total accuracy and specificity across all scenarios.\n\n\nDiscussion\n\nIn this case-study, we demonstrate the efficacy of MRI data harmonization using ComBat in enhancing the downstream RF classification performance. Utilizing the clinical covariates along with the image variables both in ComBat and RF (Case 1, scenario c) results in the highest total accuracy. When adjusting for the technical and scanner covariates in ComBat (Case 2), we only notice significant improvements in specificity (correct identification of true meningioma cases; scenarios c, d) compared to when not using them (Case 1; Tables 5 and S3). For both cases, RF achieves the highest specificity with the clinical covariates included in the model, irrespective of including them in ComBat (e.g., maximum median value for Case 1 is 84.2%, scenarios c, d; Table 5). Of all cases and scenarios, RF attains the highest sensitivity (correct identification of true glioma cases) when we include the clinical covariates in ComBat but not in the classification model in Case 1 (maximum median value is 63.2%, scenario b; Table 5).\n\nIn summary, we confirm the overall effectiveness of ComBat harmonization in adjusting for the site-specific variability even for our “non-ideal” as a practically feasible, noisy, low-dimensional, manually processed MRI dataset.\n\nThe highest median total accuracy we obtain is 71.1% (Case 1, scenario c). However, among the 75 repetitions, we do notice up to a maximum of 84.2%. The challenge in attaining any higher total accuracy is mainly poised by low sensitivity, i.e., correct identification of true glioma cases, possibly due to: 1) insufficient predictors – we have used three available, manually generated image variables and three covariates for our analyses; 2) the possible minor mislabeling of the tumor-types or imprecise ROIs because the labels are based on the visual inspection and subjective, expert conclusion of the examining radiologists at the CSU-VTH and not confirmed via surgical histopathology, or because the ROIs in each scan-slice are drawn by two non-radiologists, and hence can possibly incur imprecise diseased/normal ROIs; 3) non-homogeneous sites – ComBat performance can potentially sharpen further with more homogeneous composition of the “outside” site; 4) an imbalanced outcome classes – although we address the severe class imbalance, a more balanced distribution in the original data may enhance RF performance36; and 5) the choice of class imbalance adjustor and classifier – one may choose a different class-imbalance adjustment, such as “over-sampling”,37 or a different classifier, such as logistic regression.38 However, our initial exploration suggests that the SMOTE-RF combination provides better results than those of some other alternatives (data not shown).\n\n\nData availability\n\nFigshare: Image and Covariates Data on CSU-Meningioma Subjects. https://doi.org/10.6084/m9.figshare.19497671.v1.43\n\nFigshare: Image and Covariates Data on CSU-Glioma Subjects. https://doi.org/10.6084/m9.figshare.19497683.v1.44\n\nFigshare: Image and Covariates Data on Outside-Meningioma Subjects. https://doi.org/10.6084/m9.figshare.19497686.v1.45\n\nFigshare: Image and Covariates Data on Outside-Glioma Subjects. https://doi.org/10.6084/m9.figshare.19497692.v1.46\n\nFigshare: Table S1: Number of Subjects with Less Than Three Image Slices Selected. https://doi.org/10.6084/m9.figshare.19497701.v3.47\n\nFigshare: Table S2: Number of Subjects for Whom Facial Muscle is Used as Normal Tissue. https://doi.org/10.6084/m9.figshare.19497707.v2.48\n\nFigshare: Table S3: Case 2 Full Results. https://doi.org/10.6084/m9.figshare.19498832.49\n\nFigshare: Figure S1-A. https://doi.org/10.6084/m9.figshare.19498934.v1.50\n\nThis project contains the following extended data:\n\n• New_CSUOut-MeninGlio_boxplot_final_meanSI.png (Boxplots of means [across up to three slices] of normalized mean of signal intensities measured on 244 subjects distributed across four subpopulations).\n\nFigshare: Figure S1-B. https://doi.org/10.6084/m9.figshare.19498937.v1.51\n\nThis project contains the following extended data:\n\n• New_CSUOut-MeninGlio_boxplot_final_sdSI.png (Boxplots of means [across up to three slices] of normalized standard deviation of signal intensities measured on 244 subjects distributed across four subpopulations).\n\nFigshare: Figure S1-C. https://doi.org/10.6084/m9.figshare.19498940.v1.52\n\nThis project contains the following extended data:\n\n• New_CSUOut-MeninGlio_boxplot_final_centSI.png (Boxplots of means [across up to three slices] of normalized central point-value of signal intensities measured on 244 subjects distributed across four subpopulations).\n\nFigshare: Figure S2-A. https://doi.org/10.6084/m9.figshare.19498943.v1.53\n\nThis project contains the following extended data:\n\n• Processors_allGroups_boxplot_final_meanSI.png (Boxplots of means [across up to three slices] of normalized mean of signal intensities measured by two processors [“XY” and “DN”] on 244 subjects distributed across four subpopulations: GC = “Glio-CSU”, MC = “Menin-CSU”, GO = “Glio-Out”, MO = “Menin-Out”).\n\nFigshare: Figure S2-B. https://doi.org/10.6084/m9.figshare.19498946.v1.54\n\nThis project contains the following extended data:\n\n• Processors_allGroups_boxplot_final_sdSI.png (Boxplots of means [across up to three slices] of normalized standard deviation of signal intensities measured by two processors [“XY” and “DN”] on 244 subjects distributed across four subpopulations: GC = “Glio-CSU”, MC = “Menin-CSU”, GO = “Glio-Out”, MO = “Menin-Out”).\n\nFigshare: Figure S2-C. https://doi.org/10.6084/m9.figshare.19498949.v1.55\n\nThis project contains the following extended data:\n\n• Processors_allGroups_boxplot_final_centSI.png (Boxplots of means [across up to three slices] of normalized central point-value of signal intensities measured by two processors [“XY” and “DN”] on 244 subjects distributed across four subpopulations: GC = “Glio-CSU”, MC = “Menin-CSU”, GO = “Glio-Out”, MO = “Menin-Out”).\n\nFigshare: Figure S3-A. https://doi.org/10.6084/m9.figshare.19498952.v1.56\n\nThis project contains the following extended data:\n\n• meninglioCSU_corr_final_3img_dislab.png (Pearson’s correlations among the three image variables and the disease labels [“dis.lab”; meningioma = 1, glioma = 0] within CSU subjects).\n\nFigshare: Figure S3-B. https://doi.org/10.6084/m9.figshare.19498964.v1.57\n\nThis project contains the following extended data:\n\n• meninglioOut_corr_final_3img_dislab.png (Pearson’s correlations among the three image variables and the disease labels [“dis.lab”; meningioma = 1, glioma = 0] within “Outside” subjects).\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\nSoftware availability\n\nSource code available from: https://github.com/KechrisLab/ComBat_dogBrainMRI/tree/MRI\n\nArchived source code at time of publication: https://doi.org/10.5281/zenodo.6632525.58\n\nLicense: GNU General Public License v3.0\n\nWe generated all imaging data using the Philips IntelliSpace PACS Radiology software v4.4 (Philips Healthcare Informatics, Inc, 4100 East Third Avenue, Suite 101, Foster City, CA 94404, USA); license purchased by the CSU-VTH. We performed all of the statistical analyses and generate all of the figures using the R statistical software, version 4.1.0.39 We implemented the ComBat data harmonization using the neuroCombat R software package, which is publicly available in Jean-Philippe Fortin’s GitHub: https://bit.ly/fortin-ComBat-git, and the SMOTE imbalanced class adjustment using the smote() function within the performanceEstimation CRAN package.40 For the RF classifier, we use method = “rf” input argument in the train() function and compute the classification performance evaluation metrics using the confusionMatrix() function, both within the caret CRAN package.41,42 As a freely available alternative to PACS for a DICOM viewer and imaging data generator, we suggest Horos.\n\n\nEthical approval\n\nApproval of VCS #2018-162 “Lymphotropic Nanoparticle Enhanced MRI for Diagnosis of Metastatic Disease in Canine Head and Neck Tumors” was obtained by Dr. Lynn Griffin on June 4, 2018, and subsequently on August 8, 2019 (for amendment to increase the approved animal numbers), from the Colorado State University Veterinary Teaching Hospital Clinical Review Board. The Clinical Review Board consists of 14 faculty members (as of August 8, 2019) from the College of Veterinary Medicine and Biomedical Sciences including a standing member of IACUC, the Hospital Director, and the Chair of the Department of Clinical Sciences.\n\nClient consent was obtained from the respective owners of all dogs included in this study to use all obtained images and medical data for the purposes of research. Consent for publication is not applicable.",
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Publisher Full Text\n\nHastie T, Tibshirani R, Friedman J: The Elements of Statistical Learning: Data Mining, Inference, and Prediction, Second Edition. Springer Science & Business Media;2009.\n\nChawla NV, Bowyer KW, Hall LO, et al.: SMOTE: Synthetic Minority Over-sampling Technique. J. Artif. Intell. Res. 2002; 16: 321–357. Publisher Full Text\n\nTharwat A: Classification assessment methods. Applied Computing and Informatics. 2021; 17: 168–192. Publisher Full Text\n\nYap BW, et al.: An Application of Oversampling, Undersampling, Bagging and Boosting in Handling Imbalanced Datasets. Lecture Notes in Electrical Engineering. 2014: 13–22. Publisher Full Text\n\nHosmer DW Jr, Lemeshow S, Sturdivant RX: Applied Logistic Regression. John Wiley & Sons;2013.\n\nR Core Team: R: A Language and Environment for Statistical Computing. 2021.\n\nTorgo L: An Infra-Structure for Performance Estimation and Experimental Comparison of Predictive Models in R. CoRR. 2014; abs/1412.0436.\n\nKuhn M: caret: Classification and Regression Training. 2021.\n\nIrizarry RA: The caret package. Introduction to Data Science. 2019: 523–528. Publisher Full Text\n\nNandy D: Image and Covariates Data on CSU-Meningioma Subjects. figshare. [Dataset].2022. Publisher Full Text\n\nNandy D: Image and Covariates Data on CSU-Glioma Subjects. figshare. [Dataset].2022. Publisher Full Text\n\nNandy D: Image and Covariates Data on Outside-Meningioma Subjects. figshare. [Dataset].2022. Publisher Full Text\n\nNandy D: Image and Covariates Data on Outside-Glioma Subjects. figshare. [Dataset].2022. Publisher Full Text\n\nNandy D: Table S1: Number of Subjects with Less Than Three Image Slices Selected. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Table S2: Number of Subjects for Whom Facial Muscle is Used as Normal Tissue. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Table S3: Case 2 Full Results. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Figure S1-A. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Figure S1-B. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Figure S1-C. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Figure S2-A. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Figure S2-B. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Figure S2-C. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Figure S3-A. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: Figure S3-B. figshare. [Extended data].2022. Publisher Full Text\n\nNandy D: KechrisLab/ComBat_dogBrainMRI: ComBat for Dog-Brain MRI Data Harmonization (MRI). Zenodo. [Software]. 2022. Publisher Full Text"
}
|
[
{
"id": "207729",
"date": "16 Oct 2023",
"name": "Nick Jeffery",
"expertise": [
"Reviewer Expertise Veterinary clinical research",
"bench research in neuroscience"
],
"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\nGeneral comments\nIt is an interesting and important idea to apply data normalization to veterinary MR images, so as to be able to accumulate data from many sources. This manuscript does achieve a demonstration of this process reasonably well but it might be dependent on who the authors consider their target audience to be. This is not an easy manuscript to read and understand to readers who are not specialist data analysts (I am not a specialist data analyst). I think i just about understand the gist of what the authors have done but don't fully understand the methods for sure.\nIt would help to explain some of the methods in non-technical jargon, and use fewer abbreviations. One aspect that is not clear to me is how the test and training set results have been used to produce the results displayed in Table 5 & Figures 2-4. Another aspect is that although ComBat is introduced in the introduction it is not described what it does in this context (and - roughly - how it works).\n\nFrom a veterinary clinical perspective, 'Case 0' is a bit of a straw man - since few clinicians would consider those clinical covariates sufficient to distinguish the type of tumor. Also, the overall diagnostic ability - albeit against a poor gold standard (clinician opinion on images) is very poor. Anything less than about 95% sensitivity and specificity severely limits the clinical utility of a diagnostic test. I realize that the purpose of the manuscript is to examine ComBat - and it does show some benefit, but there is a need for further refinement - that perhaps could be alluded to in the discussion section.\n\nSpecific comments\nMore information / background required about ComBat\n\nMore information required about SMOTE. It is not 100% clear what this is doing.\n\nNeeds better explanation of the relationship between training and test sets and the displayed results.\n\nMore information on the selection of the disease ROIs. How big were they? How were they selected by the investigator? In clinical diagnosis the differentiation of these tumor types usually relies quite heavily on the pattern of contrast enhancement (plus localization) and so if investigators were only selecting regions of homogenous enhancement it would seem unlikely that ANY RF investigation would permit differentiation.\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? I 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\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Partly",
"responses": []
},
{
"id": "276291",
"date": "28 May 2024",
"name": "Abbe Crawford",
"expertise": [
"Reviewer Expertise This article covers methods and data analysis that are outwith my area of expertise (which is in veterinary clinical neurology and basic cellular neuroscience)."
],
"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 uses a tool to “normalise”/reduce heterogeneity in MRI data from multiple institutes prior to analysis with a Random Forest classifier. As a proof of principle this study provides useful information and has a valuable goal, but evaluation in a population of confirmed tumour types (rather than presumptive diagnoses) is encouraged.\n\nI struggled to grasp exactly what the ComBat harmonization entails? How was this performed? I assume it is more than your manual comparison of the lesion and “normal” ROIs? This should be clarified in the methods.\nI do not have relevant experience with computer learning and so cannot interrogate the RF methodology and data interpretation.\nAbstract- You conclude that “Use of MRI data in combination with clinical covariates is more informative than using only clinical covariates in classifying meningioma and glioma brain-tumors in dogs” – this seems fairly intuitive and perhaps not the strongest conclusion from your study?”\nMethods: Can you explain the justification and potential limitations of your decision to compare 1 site with 36 others?\n\nWhy were only T1W+C sequences used for analysis?\n“encompassing the densest parts visually examined” – please explain what you mean by densest, also why and how this was selected? And why did you compare brain tumour to muscle, rather than normal brain parenchyma? How large was the selected ROI and was this standardised?\nI am struggling to understand how the SMOTE option allows you to “generate” more gliomas than you had in your starting population? This might be obvious to those using this technique but would be helpful to explain for a broader readership.\nCould you label each box on the boxplots to improve readability/interpretation?\nI think that the manuscript would be strengthened by expanding the discussion to consider the clinical application of this and how the work could be developed in the future, also potential options for improvement (particularly considering the poor sensitivity and specificity documented). Presumably incorporation of more imaging sequences (other than T1+C) and additional clinical variables could improve accuracy?\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? I 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\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-759
|
https://f1000research.com/articles/11-198/v1
|
16 Feb 22
|
{
"type": "Research Article",
"title": "Estimated number of deaths directly avoided because of COVID-19 vaccination among older adults in Colombia in 2021: an ecological, longitudinal observational study",
"authors": [
"Maylen Liseth Rojas-Botero",
"Julián Alfredo Fernández-Niño",
"Leonardo Arregocés-Castillo",
"Fernando Ruiz-Gómez",
"Maylen Liseth Rojas-Botero",
"Leonardo Arregocés-Castillo",
"Fernando Ruiz-Gómez"
],
"abstract": "Background: Colombia’s national COVID-19 vaccination plan began in February of 2021. It gave priority to older adults, who constituted 77.7% of deaths from this illness in the year 2020. The main goal of the plan is to decrease specific mortality and the number of serious COVID-19 cases, however, the number of deaths avoided by this strategy is unknown. The objective of this study was to estimate the number of avoided deaths in Colombia by fully vaccinating older adults against COVID-19, during the first year of the implementation of the national vaccination plan. Methods: This study took on the design of an ecological, longitudinal study. Full vaccination coverage for older adults was calculated for each epidemiological week and age group from March to December 2021, based on which the number of avoided COVID-19 deaths was estimated. A sensitivity analysis was performed taking into account variations in the vaccines’ effectiveness by age group. Results: In Colombia, over 5.3 million adults 60 years of age and older received full COVID-19 vaccinations between March and December 2021. During that same period, nearly 46,000 deaths of older adults from this cause were registered. We estimated that vaccination has avoided around 22,000 more older adults from dying from COVID-19 in Colombia, that is, 32.4% of expected deaths in 2021. According to the sensitivity analysis, the number of lives saved ranged from 19,597 to 36,507. Conclusions: Colombia’s strategy to vaccinate older adults against COVID-19 has avoided mortality for this age group from being 48.0% higher than what was observed during the study period. Even more lives have been saved when taking into account the parameters that were defined and the omission of the contribution from partial vaccinations.",
"keywords": [
"SARS-CoV-2",
"COVID-19",
"COVID-19 Vaccines",
"Aged",
"Mortality",
"Colombia."
],
"content": "Introduction\n\nThe COVID-19 pandemic has caused some of the worst social, economic and health crises in recent history, which poses unprecedented challenges for public health worldwide.1 The number of people affected by the SARS-CoV-2 virus increased rapidly, with 297.4 million cases having been registered globally as of December 2021, and at least 5.4 million deaths.2 In the case of Colombia, 5.1 million cases and roughly 130,000 deaths were reported during this same period.3\n\nWhile this illness can occur at any age, it has been found that older adults have an increased risk of negative outcomes from COVID-19, such as serious illness, hospitalization and death.4,5 In fact, 77.7% of the deaths registered in Colombia during the year 2020 were adults 60 years of age and older.3 Given the recognition of the greater load of serious morbidity and death, it has been recommended to prioritize older adults when implementing prevention measures.6\n\nThanks to global efforts and academic, industry and government groups, successful vaccines have been developed at an unprecedented rate. Given these advances, current vaccinations, along with non-pharmacological measures, have become the best strategy for sustainably controlling the COVID-19 pandemic.7\n\nColombia’s national COVID-19 vaccination plan was implemented on February 17, 2021.8 Since it was first proposed, the Ministry of Health prioritized older adults, beginning with those 80 years of age and older, and making access to the vaccines progressively available based on higher risks of complication and death caused by COVID-19.8\n\nThe first full vaccinations of older adults in Colombia were registered as of the second week of March, 2021 (epidemiological week 10) after the first vaccines to this age group were administered by the end of February, 2021.9 As part of the evaluation, Esperanza cohort, a population-based-study estimated the effectiveness of the COVID-19 vaccines in older adults according to laboratory and age group.10 Nevertheless, the number of deaths that were avoided among older adults in Colombia was still unknown at the end of the year.\n\nTherefore, the purpose of this study was to estimate the number of deaths that were avoided by fully vaccinating the population of adults 60 years of age and older in Colombia in 2021, between epidemiological weeks 10 and 52.\n\n\nMethods\n\nAn observational, ecological, population-based longitudinal study was performed. The unit of analysis corresponded to the country during the time between epidemiological weeks 10 and 52, in the year 2021. This analysis only considers the coverage of complete vaccination schedule (we excluded those partially vaccinated) among all older adults (aged 60 years and over) residing in Colombia in 2021. No other exclusion criteria were applied.\n\nThis analysis included information from 5340863 older adults registered as fully vaccinated in Colombia during 2021. Given the lags in reporting to information systems, the actual number of vaccinated would be higher.\n\nThis study used the weekly number of full COVID-19 vaccinations for adults ages 60 to 110 years old, according to age group. These data were managed by the PAIWEB information system of the Ministry of Health and Social Protection (MinSalud in Spanish).PAIWEB records the application of the doses since the beginning of the distribution of the vaccines against COVID-19 in Colombia. The study also used the number of weekly COVID-19 deaths according to simple ages, made available by the Integrated Social Protection Information System (SISPRO) and it is publicly available through the Colombian government's open data page. In addition, population projections for the year 2021 were used, available through DANE,11 as was the vaccines’ effectiveness in preventing deaths by age group, as reported for Colombia.10\n\nThe results are presented with texts and figures. The analysis was performed with Excel® (Microsoft corporation, 2019) (RRID:SCR_016137) and STATA® 16.1 for Mac (StataCorp. 2019) (RRID:SCR_012763).\n\nFirst, the evolution of full vaccination coverage among older adults was presented by age groups: 60-69, 70-79 and 80 and older. Coverage was calculated using the population projection at the midpoint of the period as the denominator, for each age group. Full vaccination was defined as one dose of Ad26.COV2.S (Johnson & Johnson) or two doses of BNT162b2 (Pfizer), ChAdOx1 (AstraZeneca) nCoV-19, CoronaVac (Sinovac) or mRNA-1273 (Moderna).12\n\nThe number of COVID-19 deaths that were avoided for fully vaccinated adults 60 years and older was then estimated for epidemiological weeks 10 through 52 of 2021 using the methodology proposed by Machado et al.13 The number of avoided deaths was estimated as follows:\n\nAs mentioned previously, the national vaccination plan was implemented on February 17, 2021.14 Therefore, the first full vaccinations were observed beginning on March 7.9 Thus, i ranges between epidemiological weeks 10 and 52 of the year 2021.\n\nIn addition, the time it takes for the vaccines to generate immune protection was considered, in this case, approximately 14 days. Thus, week i−2 corresponds to the lag time between vaccination coverage and the clinically relevant time for vaccine protection.\n\nThe effectiveness of the vaccines in preventing death was based on the Esperanza cohort study,10 which reported 87.6% for adults ages 60 to 69 years old, 78.9% for those ages 70 to 79 years, and 61.2% for adults 80 years of age and older. These effectiveness rates are lower than those found for preventing death after hospitalization10 and were selected in order to obtain conservative estimates of the number of avoided deaths.\n\nAfter estimating the avoided deaths with the strategy, the number of expected deaths Dexp was calculated for an unvaccinated scenario, as follows13:\n\nThis information was used to graph expected versus observed mortality rates per 100,000 using, as the denominator, the population projection as of the midpoint of the period for each age group. In addition, the preventable fraction was calculated as the proportion of the number of deaths observed with respect to expected deaths.\n\nFollowing on from Machado’s et al. study, the number needed to be vaccinated (NNV) to avoid a death was estimated as13:\n\nSensitivity analysis\n\nThe analysis was replicated from the Esperanza cohort’s report9 of the lowest and highest effectiveness rates for preventing death without prior hospitalization, for each age group. The age groups were based on those defined originally in the Esperanza cohort.9 The number of avoided deaths was calculated for an effectiveness of 82.5% and 95.0% for the 60–69-year-old group, an effectiveness of 70.7% and 95.7% for the 70–79-year-old group, and 59.1% and 83.4% for the 80 years and older age group.10\n\nThis investigation meets the scientific, technical, administrative, and ethical considerations stipulated by existing regulations for research with human beings in Colombia. In accordance with 1993 resolution 8430, this investigation is classified as no risk given its exclusive use of aggregated and secondary information sources. None of the study researchers accessed the databases with the original personal identifiers, and only the anonymized databases. All information handling standards were followed. Due to these characteristics, this study did not require review or approval by a research ethics committee.\n\nThe Ministry of Health and Social Protection is governed by national legislation on information management, habeas data laws, and institutional manuals of good practices. All information sources are directly managed by the Ministry, and the bases are anonymized, joined, and consolidated by an independent technician, through the generation of their own encrypted key code that allows the sources to be linked without using the original personal citizen identification. In this way it is not possible for researchers or external agents to recover the original identity numbers or personal data.\n\n\nResults\n\nBetween March and December of 2021 (epidemiological weeks 10 through 52), over 5.3 million adults 60 years and older in Colombia received full COVID-19 vaccinations. As the vaccination strategy progressed (Figure 1) 3,45,983 COVID-19 deaths were recorded for this population, for a specific mortality rate of 646.9 per 100,000 for that epidemiological period16 (Table 1).\n\nColombia. Epidemiological weeks 10 to 52, of 2021.\n\nColombia. Epidemiological weeks 10 to 52 of 2021.\n\nAs seen in Figure 1, the population 80 years and older was vaccinated more quickly, with over 70% full vaccination coverage for this age group by epidemiological week 19 (May 9-15, 2021). In contrast, adults 60 to 69 years old reached that level of coverage on epidemiological week 41 (October 10-16, 2021).20\n\nThe weekly number of avoided deaths by full vaccination of adults 60 years and older was estimated. Using effectiveness indicators for each age group, it was estimated that 32.4% of the total expected deaths of adults 60 years of age and older was avoided by full vaccinations during the study period (a total of 22,078 lives saved), ranging from 21.7% of deaths avoided in the population 60 to 69 years old to 40.6% in those 80 years and older (Table 1).\n\nThe largest preventable fraction was found among adults 80 years of age and older. In a scenario without COVID-19 vaccinations, the expected mortality rate would be 2,254.7 deaths from COVID-19 per 100,000 inhabitants for this age group during the observation period. Nevertheless, the observed rate was 40.6% lower, with 1,338.3 deaths per 100,000. As shown in Figure 2, the number of observed deaths is lower than the number of expected deaths as of epidemiological week 17.\n\nAvoided deaths for adults 60 years of age and older as of vaccination. Colombia, 2021.\n\nLastly, the number needed to be vaccinated to prevent a death was estimated at 166 for the 60- to 69-year-old group, 136 for those between 70 to 79 years old and 77 for adults 80 years of age and older.\n\n\nDiscussion\n\nThe results of this preliminary analysis suggest that Colombia’s national COVID-19 vaccination plan has avoided at least 22,000 deaths of older adults between epidemiological weeks 10 and 52 in its first year of implementation.\n\nColombia designed a plan based on risk prioritization criteria, in which the first two stages included adults 60 years of age and older, beginning with those who were at least 80 years old—along with health personnel.8 The strategy that was defined made it possible to attain a high vaccination coverage more quickly for this age group than for younger people. As a result of this decision, which was based on ethical and epidemiological principles,7 a greater number of lives could be saved given that older adults constitute the group with the greatest mortality load.11 Protecting them first optimized the benefits that immunization provides for specific mortality. In addition, this initial prioritization led the way for this group to be the first to receive the booster dose.\n\nOf the 22,078 deaths that were prevented among adults 60 years of age and older, 43.6% were avoided among those who were 80 years old and over. Similar results were reported by Meslé et al.12 who found that adults 80 years and older constituted 57.1% of the deaths that were avoided in 30 countries in Europe due to partial and full COVID-19 vaccinations. These findings affirm the importance of prioritizing older adults when implementing prevention measures.\n\nIn the same study,12 the researchers found that between December 2020 and November 2021, COVID-19 vaccinations prevented 469,186 deaths of older adults (51.5% of expected deaths) in 33 countries in Europe, with preventable fractions ranging from 5.6% in Ukraine to as much as 92.9% in Iceland. These results are related with the speed with which the countries achieved high vaccination coverage for adults 60 years of age and older. Specifically, in Moldova, Romania and Ukraine, where full coverage was under 60.0%, the highest preventable fraction was 19.9%, whereas countries that quickly achieved full coverage for over 95.0% of their population (Iceland and England) prevented at least 85.8% of expected deaths.12\n\nWhile the number of deaths that were found to have been prevented in Europe is greater than that reported for Colombia, this comparison should be made cautiously. There are several reasons the studies may not be directly comparable for example, that study used effectiveness measures that were higher than what has been previously reported for older adults (60.0% for partial and 95.0% for full vaccinations). The estimates used in the present work are more precise since they take into account differences in the effectiveness of the vaccines by age group, although partial vaccinations are not included. If an estimate of 95.0% were to be used for protection from death with full vaccinations—such as in the study mentioned—then the number of avoided deaths in Colombia would double, reaching 46,214 lives saved.\n\nThis research offers a conservative measurement of the number of avoided deaths by vaccinating older adults in Colombia, given that it only included lives saved by full vaccinations and it used the lowest available effectiveness measures for each age group, which corresponded to the deaths without prior hospitalization that were reported in the Esperanza cohort.9 In addition, the effectiveness of boosters was not considered, nor was a significant proportion of older adults who had hybrid immunity, whose protection would be greater.13 Thus, the number of avoided deaths with the implementation of the national vaccination plan could be much higher than the estimates reported herein.\n\nThe limitations of this study include those that are inherent to the use of secondary information sources, such as the lag between registering events such as vaccinations and deaths. In addition, since this is an ecological analysis, the results could vary when considering individual variables with which counterfactual scenarios are projected.14 In addition, in Colombia, the coverage with boosters only began at the end of November, so its effects on the prevention of deaths could not be estimated in this first analysis.\n\nNevertheless, this approach enables comparisons with previous analyses of other countries, and constitutes one of the components in the comprehensive evaluation of the national vaccination plan, which has as one of its main objectives as the reduction of specific mortality.15 Another strength of this work is the use of vaccine effectiveness measures estimated in real-life conditions for Colombia’s older adult population for each of the age groups,9 thereby providing results that are closer to the specific situation of the country.\n\nFuture studies could evaluate the number of avoided deaths for the entire population or for special groups, such as children, across the different stages of implementing the national vaccination plan, which is continuing into the year 2022. The scientific and academic communities are encouraged to use other approaches to evaluate and compare the consistency of the conclusions. Lastly, this work serves as input for continuing to promote vaccinations as one of the key strategies for overcoming the COVID-19 pandemic, especially in the older adult population.\n\n\nData availability\n\nAll the original data used to build the final dataset of this study are of public access and can be downloaded from the official websites. The links to access them are shown below:\n\nThe dataset with all the COVID-19 confirmed cases and deaths in Colombia at an individual level is public available at the following link: https://www.datos.gov.co/widgets/gt2j-8ykr?mobile_redirect=true.\n\nThis database has individual and anonymous information on each confirmed case of COVID-19 in Colombia. For each case, the date of onset of symptoms, the date of report, sex, age, and final clinical status (dead or alive) are presented.\n\nBoard that allows consultation of vaccination coverage for COVID-19 by epidemiological week, municipality and age group in Colombia.\n\nFigshare: Dataset of Study: Estimated number of deaths directly avoided because of COVID-19 vaccination among older adults in Colombia. https://doi.org/10.6084/m9.figshare.1912253020\n\nThis project contains the following extended data:\n\n- Dataset Avoided Deaths (aggregated data used for final analysis)\n\nThe authors have permission to publish data from the databases used or if the data were under open licenses that allowed republication.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nThe Lancet: COVID-19 in Latin America: a humanitarian crisis. Lancet. 2020; 396: 1463. PubMed Abstract | Publisher Full Text\n\nJohns Hopkins University & Medicine: Coronavirus Resource Center. Global Map. Johns Hopkins Coronavirus Resource Center; 2021; Reference Source\n\nInstituto Nacional de Salud (INS): Coronavirus Colombia.2021 [cited 2021 Jun 18]. Reference Source\n\nLiu Y, Mao B, Liang S, et al.: Association between ages and clinical characteristics and outcomes of coronavirus disease 2019. Eur. Respir. J. 2020 Apr 20; 55(5): 2001112. PubMed Abstract | Publisher Full Text\n\nBonanad C, García-Blas S, Tarazona-Santabalbina F, et al.: The Effect of Age on Mortality in Patients With COVID-19: A Meta-Analysis With 611,583 Subjects. J. Am. Med. Dir. Assoc. 2020 Jul; 21(7): 915–918. PubMed Abstract | Publisher Full Text\n\nOMS: WHO Sage roadmap for prioritizing uses of COVID-19 vaccines in the context of limited supply: An approach to inform planning and subsequent recommendations based upon epidemiologic setting and vaccine supply scenarios. Version 1.1. OMS; 2020 [cited 2020 Dec 16]. Reference Source\n\nOmer SB, Benjamin RM, Brewer NT, et al.: Promoting COVID-19 vaccine acceptance: recommendations from the Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA. Lancet. 2021 Dec; 398(10317): 2186–2192. PubMed Abstract | Publisher Full Text\n\nMinisterio de Salud y Protección Social: Plan Nacional de Vacunación contra el COVID-19. Documento técnico, v2. : MinSalud; 2021 [cited 2022 Jan 6]. Reference Source\n\nMinisterio de Salud y Protección Social: Resolución 195. Minsalud; 2021 [cited 2022 Jan 6]. Reference Source\n\nArregoces Castillo L, Fernández-Niño JA, Rojas-Botero ML, et al.: Effectiveness of COVID-19 Vaccines in Older Adults in Colombia: First Report of the Esperanza Cohort. A Matched-Pair, National Study. SSRN Journal. 2021 [cited 2022 Jan 6]. Publisher Full Text Reference Source\n\nDANE: Proyecciones de población a nivel departamental. Periodo 2018-2050. DANE; 2020.\n\nMinisterio de Salud y Protección Social: Resolución 1151. Minsalud; 2021 [cited 2022 Jan 6]. Reference Source\n\nMachado A, Mazagatos C, Dijkstra F, et al.: Impact of influenza vaccination programmes among the elderly population on primary care, Portugal, Spain and the Netherlands: 2015/16 to 2017/18 influenza seasons. Eurosurveillance. 2019 Nov 7 [cited 2022 Jan 6]; 24(45). PubMed Abstract | Publisher Full Text\n\nMinisterio de Salud y Protección Social: Resolución 168. Minsalud; 2021 [cited 2022 Jan 6]. Reference Source\n\nYanez ND, Weiss NS, Romand J-A, et al.: COVID-19 mortality risk for older men and women. BMC Public Health. 2020 Dec; 20(1): 1742. PubMed Abstract | Publisher Full Text\n\nMeslé MM, Brown J, Mook P, et al.: Estimated number of deaths directly averted in people 60 years and older as a result of COVID-19 vaccination in the WHO European Region, December 2020 to November 2021. Eurosurveillance. 2021 Nov 25 [cited 2022 Jan 6]; 26(47). PubMed Abstract | Publisher Full Text\n\nKeeton R, Richardson SI, Moyo-Gwete T, et al.: Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner. Cell Host Microbe. 2021 Nov; 29 (11): 1611–1619.e5. PubMed Abstract | Publisher Full Text\n\nVanderWeele TJ: Invited Commentary: Counterfactuals in Social Epidemiology—Thinking Outside of “the Box.”. Am. J. Epidemiol. 2020 Mar 2; 189(3): 175–178. PubMed Abstract | Publisher Full Text\n\nMinSalud: Decreto 109 de 2021. Por el cual se adopta el Plan Nacional de Vacunación contra el COVID-19 y se dictan otras disposiciones. Ministerio de Salud y Protección Social; 2021 [cited 2021 Jul 13]; Reference Source\n\nFernández-Niño JA, Botero R, Liseth M, et al.: Dataset of Study: Estimated number of deaths directly avoided because of COVID-19 vaccination among older adults in Colombia. figshare. Dataset. 2022. Publisher Full Text"
}
|
[
{
"id": "128107",
"date": "11 May 2022",
"name": "B. Piedad Urdinola",
"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 research question is a very important one that will allow us to understand the effects of vaccination on mortality for the most affected age group by the disease in Colombia and the proposed methods lead to a conservative estimation, however it can be further refined by adding the following comments:\nThe methods the authors proposed follow closely Machado et al.’s, that article explicitly exposes that they are accounting for the number of medically attended influenza-confirmed cases (MAICC). I believe this is also the case for the article at hand, accounting for medically attended cases, however it is not explicit in the document, and it makes an important difference to mention it. Because a part of the Colombian population inhabits low density municipalities with little or hard to reach health facilities where could be properly attended by a medical doctor. Besides other reasons why people pass unattended even with access to medical assistance, such as congestion due to the pandemic, postponement to visit MDs due to fear of contagion and the like.\n\nOn the same note, please make explicit if the paper is accounted deaths are all confirmed deaths or if they also include suspicious cases as well.\n\nFinally, there could also be confounding with other government policies or self-imposed habits that reduce the mortality in the group under study. Particularly in Colombia, lockdowns were prolonged for elderly, and many may have changed their behavior even after the restrictions were removed. Also, the national protests occurred during the period under analysis and made very hard to move across some towns and even within certain towns such as Cali and Bogota, particularly for elderly who mostly were not involved in them. Authors could be inspired by the following work: Arbel, R., Moore, C. M., Sergienko, R., & Pliskin, J. (2022). How many lives do COVID vaccines save? Evidence from Israel. American journal of infection control, 50(3), 258-261.1\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "8254",
"date": "19 May 2022",
"name": "Julián Alfredo Fernández-Niño",
"role": "Author Response",
"response": "We thank Dr. Urdinola for reviewing our manuscript. We present our responses below each comment as well as a new version of our manuscript (Version #2). The methods the authors proposed follow closely Machado et al.’s, that article explicitly exposes that they are accounting for the number of medically attended influenza-confirmed cases (MAICC). I believe this is also the case for the article at hand, accounting for medically attended cases, however it is not explicit in the document, and it makes an important difference to mention it. Because a part of the Colombian population inhabits low density municipalities with little or hard to reach health facilities where could be properly attended by a medical doctor. Besides other reasons why people pass unattended even with access to medical assistance, such as congestion due to the pandemic, postponement to visit MDs due to fear of contagion and the like. Response: Our analysis only included confirmed COVID-19 deaths. These deaths included some that were surely medically treated (the majority) and some that were not. We use confirmed deaths obtained from the official national registry called RAUF-ND. Confirmed deaths includes deaths certified by a medical doctor regardless of whether the person was able to receive medical care before they died. COVID-19 death was defined as a death resulting from clinically compatible illness in a confirmed case of COVID-19, unless there was a clear alternative cause of death that could not be related to COVID-19. In this sense, Colombia uses the definitions recommended by the WHO for surveillance of COVID-19 (Pan American Health Organization Case definitions for COVID-19 surveillance. https://www.paho.org/en/case-definitions-covid-19-surveillance-16-december-2020). Certainly, we know that some COVID-19 deaths went undetected as some people might not have had access to a diagnostic test before or after they died. (Although, according to national guidelines, applying a diagnostic test for clinical suspicious deaths (including post-mortem test) is mandatory in Colombia). Furthermore, for any cause of death, there will always be issues related to the final classification of the leading cause of death or even the previous clinical diagnosis, as it also depends on access to medical care, clinical judgment, and ultimately the quality of death certificates. In addition, it is important to distinguish “deaths with COVID-19” from “deaths from COVID-19”, and as matter of fact for some deaths it may be difficult to identify the actual causal chain that led to death even when there is a positive diagnostic test. We agree with the reviewer that this could be a big limitation of the study. To address this, we need some adjustments that are not possible now considering the COVID death reclassification is a process that is still in progress. Colombia, like other countries in the world, is still advancing the process of reclassifying COVID-19 deaths by carrying out clinical algorithms, verbal autopsies, and the search for unidentified diagnostic tests. This is a process that takes months and ends in a process of statistical amendment. Therefore, we are thinking of repeating this same analysis when final classification is available. We added this as a limitation in our discussion. On the same note, please make explicit if the paper is accounted deaths are all confirmed deaths or if they also include suspicious cases as well. Response: Only confirmed deaths from COVID-19 were considered in our analysis as in previous studies. Suspicious deaths include deaths where the cause cannot be confirmed to be associated with a SARS-Cov-2 infection, certainly this may include a proportion of real deaths from COVID-19, but also probably includes an important share of syndromatically similar deaths from other causes such as Influenza. The use of suspicious deaths would imply making some risky assumptions about the proportion of suspicious deaths that would be COVID-19 deaths, which varies at the territorial level. This may be a later analysis as soon as we have the final reclassification of deaths in Colombia. Now, that is mentioned in the discussion of the manuscript. Finally, there could also be confounding with other government policies or self-imposed habits that reduce the mortality in the group under study. Particularly in Colombia, lockdowns were prolonged for elderly, and many may have changed their behavior even after the restrictions were removed. Also, the national protests occurred during the period under analysis and made very hard to move across some towns and even within certain towns such as Cali and Bogota, particularly for elderly who mostly were not involved in them. Authors could be inspired by the following work: Arbel, R., Moore, C. M., Sergienko, R., & Pliskin, J. (2022). How many lives do COVID vaccines save? Evidence from Israel. American journal of infection control, 50(3), 258-261.1 Response: The estimate of avoided deaths made in this study is a conservative measure for reasons explained in the manuscript. However, the prevention of deaths is certainly multifactorial, and non-pharmacological interventions (NPI) likely also played a role, especially during the early phases of the pandemic as we showed before: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289626/ In Colombia, the differential measures for older adults lasted only a few weeks after being suspended by the Colombian Constitutional Court in June of 2020 before of the beginning of the National Vaccination Plan in Colombia during 2021. (https://www.elespectador.com/salud/corte-constitucional-amparo-los-derechos-de-participantes-de-la-revolucion-de-las-canas/) The impact of these other measures (NPI) is not evaluated in this study, and to do so would require another and more complex approach, which is beyond our objectives. However, we can affirm that the NPI (as national lockdowns) affected the entire population, although certainly in real life, some social groups could have different responses, for example to isolation whose adherence depends on employment or housing conditions (as well as other social determinants), however these factors are likely more important for the risk of infection than for the risk of death. Certainly, this study is a rough approximation from an ecological level, and it is not intended to evaluate the effect of other measures, nor their interaction with other factors. Regarding the impact of the protests, it is certainly something very difficult to evaluate. We tried to explore this impact in one previous study: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3899602 We added a comment in our discussion."
}
]
}
] | 1
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https://f1000research.com/articles/11-198
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https://f1000research.com/articles/11-757/v1
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07 Jul 22
|
{
"type": "Study Protocol",
"title": "A scoping review protocol on food handlers’ knowledge, attitude, and practices towards food hygiene and safety in low and middle-income countries",
"authors": [
"Paritosh Dabral",
"Senthil Kumaran Piramanayagam",
"Keith Nigli",
"Vijay Shree Dhyani",
"Paritosh Dabral",
"Keith Nigli",
"Vijay Shree Dhyani"
],
"abstract": "Background: Food safety and hygiene has emerged as the foremost cause of concern in recent time, especially post-pandemic and has changed the eating out behaviour of the consumers. Consumers often consider food safety and hygiene as one of the most prominent factors and hence it is important for food handlers to have adequate knowledge and the right attitude towards food safety and food hygiene. The review will summarise the evidence on food handlers’ behaviours towards food safety and hygiene and associated factors that inhibit positive behaviour towards following food safety protocols and standards. Methods: This scoping review protocol is guided by updated methodology from Joanna Briggs Institute (JBI). The search will be conducted on Medline (PubMed), Scopus and Web of Science. Google Scholar will be used to locate pertinent grey literature. A citation search will also be employed for identifying additional relevant studies. Quantitative and qualitative studies published from 2011- present will be included. Two reviewers will independently screen and extract the data. A third reviewer will be involved in resolving disagreements between reviewers. A two-stage screening including title/abstract and full-text will be conducted. Data extraction will be done using a pilot-tested data extraction form. The data extracted from included studies will be organised and presented using narrative synthesis. The review will also attempt to identify the unaddressed gaps in the literature with the available evidence. Ethics and dissemination: An ethical clearance is not required for this scoping review as findings from existing published literature will be summarised. The review findings will be disseminated through conference presentations and journal publications.",
"keywords": [
"Food Hygiene",
"Food Safety",
"Food handlers",
"Knowledge",
"Attitude",
"Practices",
"KAP"
],
"content": "Introduction\n\nFood is an integral and indispensable part of all cultures. However, illness—or even death—may result if contaminated food is consumed. Measures that prevent contamination of food during processing, preparation, and food handling thereby ensuring that the food is safe to consume are termed as food safety. “Any disease of an infectious or toxic nature caused by, or thought to be cause by, the consumption of food or water” is how the World Health Organization (WHO) defines foodborne diseases (FBDs).1 FBDs continues to be the foremost public health challenge contributing to 420,000 mortalities and 600 million cases FBDs in 2010.2 This makes the impact of FBD comparable to diseases such as malaria, tuberculosis, and HIV/AIDS. Although the complete economic and social impacts of FBD are not fully known, they are estimated to be enormous and considerable.3 Instances of FBD have been reported from many countries around the world. LMICs have been hit particularly hard by instances of FBD4,5 as access to clean water is scarce and the foodservice sector in these countries is mostly unorganised and informal. The Federation of Indian Chambers of Commerce and Industry (FICCI) in its report of 20176 has indicated that about 66% of the foodservice establishments in India are in the unorganised sector. On the other hand, the possibility of wide-spread outbreak of FBD in high-income nations cannot be dismissed. In such countries, the highly consolidated structure of the foodservice industry with extensive and long supply chains has the potential to effect wide-spread occurrence of FBD as number of patrons frequenting such establishments is considerable.\n\nThe rise in eating out venues and accessibility to different cuisines are helping the food industry to post strong and sustained—except for a few periods of exception—growth for last two decades.7 The dining-out behaviour has seen continuous increase due to factors such as convenience, higher income, working women, nuclear families, and globalisation.8 The Indian domestic food service market is projected to be worth about INR 5 trillion with a CAGR of 10%.9\n\nEvidence from many research studies10–15 suggest that food safety is an important consideration when selecting a dining-out destination. Czarniecka-Skubina, 2021 has reported an increased awareness amongst consumers about food safety and hygiene due to the ongoing COVID-19 pandemic.13 Overall impression of the establishment, inspection ratings, grooming and attire of staff members, and observed cleanliness are the elements identified by Henson et al. (2006) that influence customers’ perception of an establishment’s food safety.16 In their study, Sohn and Lee (2018) attribute the increase in number of restaurants and other foodservice operations that have an “open” kitchen design where patrons can observe the kitchen operations to patrons’ perception of offering better food quality and cleanliness.17 Consequently such establishments are becoming popular amongst patrons who value food safety and cleanliness.17,18\n\nMany studies19–21 identify insufficient among food handlers on Knowledge, Attitude and Practices (KAP) as the reason behind instances of FBD. A study by Knight et al. (2007) found that a majority of consumers believed that the food safety aspect at restaurants is significantly lower than—amongst others—grocery stores or supermarkets.10 This perception of poor food safety at foodservice establishments in general and restaurants in particular has assumed significance as an instance of FBD at a foodservice business operation can have serious financial, societal, and economical implications. Grover and Dausch (2000) listed reduction in number of customers, adverse publicity, cost of litigation, and erosion of trust as the effects of a foodservice establishment being identified as the source of FB illness.22\n\nThe instances of FBD are highest—3 out of every 5 cases—for food served in foodservice settings like restaurants, cafés, bistros etc.23 Hedberg (2006) estimated that about 60% of these cases are due to unsafe food handling.24 However, these figures are significantly lower than the actual number of cases as only about 7% of the customers who became ill due to FBD informed the health authorities.16,25 The annual cost of illness in USA is about USD 6.9 billion for top five and between USD 51 to USD 77.7 billion for all foodborne pathogens.26,27 This economic burden coupled with the top five factors recognised by FDA28—poor personal hygiene, contaminated equipment, unsafe food sources, inadequate cooking, and incorrect holding temperature—for occurrence of FBD, indicate the significant contribution of foodservice establishments towards FBD and indicate the scope for limiting occurrences of FBD by engaging foodservice workers in the control of FBD by imparting relevant training.\n\nFood hygiene practices such as keeping and cooking raw and cooked food separately at safe temperatures, using clean water for cooking are some of the ways to ensure food safety.29 Thus it is important for food handlers to have adequate knowledge and right attitude towards food safety and they should also ensure practicing proper food hygiene and safety while handling the food.30\n\nFew systematic reviews of consumer’s Knowledge, Attitude and Practices (KAP) have been done previously.31–33 However, there is scant and insufficient synthesis of various studies on KAP of food handlers. Thus, there is a necessity of synthesizing evidence on KAP of food handlers with regard to food safety and hygiene. To cater to this need, a scoping review of peer and non-peer-reviewed articles and grey literature is planned.\n\nThe objective of this review is to find out the KAP of food handlers in food facilities as well as potential factors affecting it. The review will also attempt to identify the unaddressed gaps in the literature.\n\n\nMethods\n\nUpdated methodological guidance by JBI was followed for preparing the scoping review protocol.34 Additionally, PRISMA Extension for Scoping Reviews35 and scoping review methodology by Arksey and O’Malley’36 was also referred.\n\nThe scoping review will be conducted in five different stages.\n\nThis review will address the following questions\n\n(i) What is the level of food handlers’ KAP towards food hygiene and safety in LMICs?\n\n(ii) What are the determinants that affects food handlers’ KAP in LMICs?\n\n(iii) What are the gaps in the existing literature with respect to food handlers’ KAP?\n\nInclusion criteria\n\nThe English language articles from the year 2011 year onwards will be considered for this review. Population, concept, context (PCC) mnemonic will guide the inclusion/exclusion criteria for this review.\n\nPopulation\n\nThe review will include food handlers above 18 years of age. Food handlers working in restaurants and in other food establishments such as street food handlers, food processing units, school canteens, food courts will be considered for inclusion. The review will also consider studies where consumer’s perception of food handler’s KAP is provided. Food handlers in hospital settings will be excluded.\n\nConcept\n\nFood hygiene and safety is increasingly assuming importance in today’s dining out environment. Customers are increasingly and critically examining the hygiene and safety scores—whether formal or informal—to determine their eating-out venue. Recognising this, many foodservice businesses are now getting their business audited and displaying scores prominently to attract customers. While examining factors that influence choice of eating-out venue; consumers often consider, food safety and hygiene as one of the most prominent factor. Thus it is very important for the food handler’s to have apt KAP and they should develop positive food handling behaviours. Some definitions related to the concept of this review are mentioned below.\n\n“Food safety is about handling, storing and preparing food to prevent infection and help to make sure that our food keeps enough nutrients for us to have a healthy diet”.37\n\n“Food hygiene is defined as the measures and conditions necessary to control hazards and to ensure fitness for human consumption of a foodstuff taking into account its intended use”.38\n\n“A KAP survey is a quantitative method (predefined questions formatted in standardized questionnaires) that provides access to quantitative and qualitative information. KAP surveys reveal misconceptions or misunderstandings that may represent obstacles to the activities that we would like to implement and potential barriers to behaviour change”.39\n\nStudies from LMICs will be included in this review.\n\nStudies involving different designs such as quantitative, qualitative and mixed method research designs will be considered for this review. We will also be including conference papers. However, letters to the editor, editorials, commentaries perspectives and reviews will be excluded.\n\nStudies published in English, conducted between 2011 and 2022 (both years included), and relevant to the review will be identified by conducting the search on Medline (PubMed), Global Index Medicus, Web of Science, Scopus, ProQuest and Google Scholar. The keywords guiding the search will include “Food handlers”, “Knowledge”, “Practices”, “Attitude”, “KAP”, “Food Hygiene, “Food Safety”, “Restaurant”, “Food safety training”, “Food Hygiene training”, “Food service establishment”, “Behavior”, “Facilitators, “factors” “and “Barriers”. PCC mnemonic described in JBI methodology will guide the search. Also, the references of included articles included in the review will be hand searched to locate and include any relevant study that meet the inclusion criteria. The preliminary search conducted on PubMed (Table 1) combining keywords with Boolean operators will be refined and customized for other databases in consultation with the librarian.\n\nAll the citations from the databases search will be imported to Rayyan software. Records after removing duplicates will undergo title, abstract and full-text screening. A two stage identical screening process will be followed, where every article will be independently reviewed by two reviewers following pre-defined inclusion and exclusion criteria. A consensus approach will be used to resolve discrepancies among the reviewers. If the disagreement cannot be resolved this way, a third reviewer will be asked to adjudicate. Conclusively relevant sources will be retrieved in full. The selected full text will be reviewed in minute detail against the eligibility criteria independently. In case of further ambiguities about the eligibility of an article, it will be labelled and discussed with the third reviewer. Search results indicating the number of articles included and excluded at different screening stage and exclusion reasons at full text screening stage will be depicted in PRISMA flow chart.40\n\nA piloted data extraction form will be used to collect the data relevant to research questions. Specific information on citation details, methodological characteristics and associated outcome measures of significance will be included in data extraction form. To ensure that the data is adequately extracted, the form will be pilot tested before final data extraction starts. Modifications will be incorporated as a result of piloting the extraction and will be documented in the scoping review. Two reviewer will independently extract the data from included studies. The discrepancies between reviewers will be discussed with a third reviewer. A request will be made to the authors of studies included in the review to obtain the required missing information. Preliminary data extraction/charting sheet is presented in Table 2.\n\nData extraction will be followed by a narrative summary supported by descriptive statistics. Synthesising data will involve study characteristics such as study type, participant characteristics, setting, results, outcome variables etc. Quantitative studies will be analysed using descriptive statistics, such as frequencies, percentage, measures of central tendency and standard deviation. Analysis will be conducted based on population (food handlers), study designs, theoretical approaches and methods, geographical location, year wise distribution of the studies, association measured with respect to KAP, factors associated with KAP and food service setting. Moreover, for qualitative studies, thematic analysis will be assimilated for the analysis.\n\n\nDiscussion\n\nThis will be the first scoping review to provide aggregate summary of evidence on food handlers’ knowledge, attitude and practices in LMICs. It will map the coverage of the evidence available and existing gaps on the topic. The scoping study will employ a comprehensive search strategy which will be conducted on five electronic databases. Grey literature search on Google Scholar and citation search will also conducted to include all possible relevant articles. However, there are limitations to the search with respect to the language and number of databases covered. Non-English articles will be excluded due to lack of resources (human and monetary) to translate in English. Quality assessment of the included in scoping review will not be undertaken as it is not the mandatory requirement of the scoping review.\n\nThe review is in its initial phase of conceptualisation wherein the research question and eligibility criteria have been finalised. Currently team is working on finalising the search terms and search strategy.\n\n\nData availability\n\nNo underlying or extended data are associated with this article.\n\n\nReporting guidelines\n\nFigshare. PRISMA-P checklist. DOI: https://doi.org/10.6084/m9.figshare.20055176.v1\n\n\nAuthor contributions\n\nPD is the guarantor of this review protocol. PD, SK, KSN and VSD contributed to the title and concept genesis. PD drafted the protocol manuscript. All the authors have critically reviewed, proofread and given the final approval of the protocol version to be published.",
"appendix": "Acknowledgements\n\nThe authors would like to thank Manipal Academy of Higher Education for providing the logistics and administrative support.\n\n\nReferences\n\nSchmidt K: WHO surveillance programme for control of foodborne infections and intoxications in Europe. Sixth Report 1990-1992.1995.\n\nWHO: WHO estimates of the global burden of foodborne diseases: foodborne disease burden epidemiology reference group 2007-2015. Geneva PP - Geneva:World Health Organization;Accessed 22 Dec 2021.Reference Source\n\nDevleesschauwer B, Haagsma JA, Mangen M-JJ, et al.: The Global Burden of Foodborne Disease BT - Food Safety Economics: Incentives for a Safer Food Supply. Roberts T, editor.Cham:Springer International Publishing; 2018; p. 107–122. Publisher Full Text\n\nUNICEF, WHO: Health in the post-2015 development agenda: need for a social determinants of health approach: joint statement of the UN Platform on Social Determinants of Health. In: Health in the post-2015 development agenda: need for a social determinants of health approach: joint statement of the UN Platform on Social Determinants of Health.2013; p. 18.\n\nKäferstein F: Foodborne diseases in developing countries: aetiology, epidemiology and strategies for prevention. Int. J. Environ. Health Res. 2003 Jun; 13 Suppl 1: S161–S168. PubMed Abstract\n\nJaisani L, Shukla A, Malik R: Indian food services industry: engine for economic growth & employment. A Rep Unlocking Growth Oppor New Delhi FICCI.2017.\n\nNaska A, Katsoulis M, Orfanos P, et al.: Eating out is different from eating at home among individuals who occasionally eat out. A cross-sectional study among middle-aged adults from eleven European countries. Br. J. Nutr. 2015 Jun; 113(12): 1951–1964. PubMed Abstract | Publisher Full Text\n\nde Rezende DC , de Avelar AES : Factors that influence the consumption of food outside the home in Brazil. Int. J. Consum. Stud. 2012 May 1; 36(3): 300–306. Publisher Full Text\n\nKPMG: India’s Food Service Industry: Growth Recipe. KPMG and FICCI;2016.\n\nKnight AJ, Worosz MR, Todd ECD: Serving food safety: Consumer perceptions of food safety at restaurants. Int. J. Contemp. Hosp. Manag. 2007; 19: 476–484. Publisher Full Text\n\nLiu P, Lee YM: An investigation of consumers’ perception of food safety in the restaurants. Int. J. Hosp. Manag. 2018; 73: 29–35. Publisher Full Text Reference Source\n\nJones TF, Angulo FJ: Eating in restaurants: a risk factor for foodborne disease? Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2006 Nov; 43(10): 1324–1328.\n\nKim HJ, Park J, Kim M-J, et al.: Does perceived restaurant food healthiness matter? Its influence on value, satisfaction and revisit intentions in restaurant operations in South Korea. Int. J. Hosp. Manag. 2013; 33: 397–405. Publisher Full Text Reference Source\n\nWei Y-P: The Effect of Food Safety-Related Attributes on Customer Satisfaction of Ready-to-Eat Foods at Hypermarkets. Sustainability. 2021; 13. Publisher Full Text\n\nUngku Fatimah UZA, Boo HC, Sambasivan M, et al.: Foodservice hygiene factors—The consumer perspective. Int. J. Hosp. Manag. 2011; 30(1): 38–45. Publisher Full Text Reference Source\n\nHenson S, Majowicz S, Masakure O, et al.: Consumer assessment of the safety of restaurants: The role of inspection notices and other information cues. J. Food Saf. 2006; 26(4): 275–301. Publisher Full Text\n\nSohn E-M, Lee K-W: The effect of chefs’ nonverbal communication in open kitchens on service quality. J. Foodserv. Bus. Res. 2018; 21(5): 483–492. Publisher Full Text\n\nChow AJ, Alonso AD, Douglas AC, et al.: Exploring open kitchens’ impact on restaurateurs’ cleanliness perceptions. J. Retail. Leis. Prop. 2010; 9(2): 93–104. Publisher Full Text\n\nBaş M, Şafak Ersun A, Kıvanç G: The evaluation of food hygiene knowledge, attitudes, and practices of food handlers’ in food businesses in Turkey. Food Control. 2006; 17(4): 317–322. Publisher Full Text Reference Source\n\nda Vitória AG , de Souza Couto Oliveira J , de Almeida Pereira LC , et al.: Food safety knowledge, attitudes and practices of food handlers: A cross-sectional study in school kitchens in Espírito Santo, Brazil. BMC Public Health. 2021; 21(1): 349. PubMed Abstract | Publisher Full Text\n\nAl Banna MH, Disu TR, Kundu S, et al.: Factors associated with food safety knowledge and practices among meat handlers in Bangladesh: a cross-sectional study. Environ. Health Prev. Med. 2021; 26(1): 84. PubMed Abstract | Publisher Full Text\n\nGrover SF, Dausch JG: Hepatitis A in the foodservice industry. Food Manage. 2000; 81: 80–86.\n\nLynch M, Painter J, Woodruff R, et al.: Surveillance for foodborne-disease outbreaks–United States, 1998-2002. Morb Mortal Wkly report Surveill Summ (Washington, DC 2002). 2006 Nov; 55(10): 1–42.\n\nHedberg CW, Smith SJ, Kirkland E, et al.: Systematic environmental evaluations to identify food safety differences between outbreak and nonoutbreak restaurants. J. Food Prot. 2006 Nov; 69(11): 2697–2702. PubMed Abstract | Publisher Full Text\n\nGreen LR, Selman C, Scallan E, et al.: Beliefs about meals eaten outside the home as sources of gastrointestinal illness. J. Food Prot. 2005 Oct; 68(10): 2184–2189. PubMed Abstract | Publisher Full Text\n\nCrutchfield SR, Roberts T: Food safety efforts accelerate in the 1990’s. FoodReview. 2000 Jan 1; 23(3): 44–49.Reference Source\n\nScharff RL: Economic burden from health losses due to foodborne illness in the United States. J. Food Prot. 2012 Jan; 75(1): 123–131. PubMed Abstract | Publisher Full Text\n\nAdministration USF, D.: FDA report on the occurrence of foodborne illness risk factors in selected institutional foodservice, restaurant, and retail food store facility types. Public Heal. Serv. 2009.\n\nPrevention C for DC and. Four steps to food safety: clean, separate, cook, chill.2020.\n\nAkabanda F, Hlortsi EH, Owusu-Kwarteng J: Food safety knowledge, attitudes and practices of institutional food-handlers in Ghana. BMC Public Health. 2017; 17(1): 40. PubMed Abstract | Publisher Full Text\n\nYoung I, Thaivalappil A: A systematic review and meta-regression of the knowledge, practices, and training of restaurant and food service personnel toward food allergies and Celiac disease. PLoS One. 2018 Sep 4; 13(9): e0203496. PubMed Abstract | Publisher Full Text\n\nYoung I, Waddell L: Barriers and Facilitators to Safe Food Handling among Consumers: A Systematic Review and Thematic Synthesis of Qualitative Research Studies. PLoS One. 2016 Dec 1; 11(12): e0167695. PubMed Abstract | Publisher Full Text\n\nZanin LM, da Cunha DT , de Rosso VV , et al.: Knowledge, attitudes and practices of food handlers in food safety: An integrative review. Food Res. Int. 2017 Oct; 100(Pt 1): 53–62. PubMed Abstract | Publisher Full Text\n\nPeters MDJ, Marnie C, Tricco AC, et al.: Updated methodological guidance for the conduct of scoping reviews. JBI Evid. Synth. 2020 Oct; 18(10): 2119–2126. PubMed Abstract | Publisher 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 Oct; 169(7): 467–473. PubMed Abstract | Publisher Full Text\n\nArksey H, O’Malley L: Scoping studies: towards a methodological framework. Int. J. Soc. Res. Methodol. 2005 Feb 1; 8(1): 19–32. Publisher Full Text\n\nFAO: Food safety.Accessed 22 Dec 2021.Reference Source\n\nHolah J, Lelieveld H: Hygienic design of food factories. Elsevier;2011.\n\nGumucio S, Luhmann N, Fauvel G, et al.: The KAP survey model: knowledge, attitude, and practices. Saint-Etienne Fr. 2011; 4–5.\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"
}
|
[
{
"id": "147952",
"date": "01 Sep 2022",
"name": "Christopher J Bailey",
"expertise": [
"Reviewer Expertise Food literacy and nutrition literacy",
"adolescent health",
"systematic reviews",
"narrative reviews",
"qualitative research",
"quantitative research",
"mixed methods"
],
"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 provide a scoping review protocol on food handlers' knowledge, attitude, and practices towards food hygiene and safety in low and middle-income countries. The paper is well-written and methodologically sound. The authors have identified an important research gap in the literature. The reviewer has only two questions for the authors:\nOn page 5 of the Data extraction and charting section, the authors state: “to ensure that the data is adequately extracted, the form will be pilot tested before final data extraction starts.\" It could be possible that the authors might identify significant large numbers of papers as they have included qualitative, quantitative, mixed methods, and grey literature.\n\nThe following question relates to if a large number of papers are identified - how many abstracts will the authors be extracting before data extraction? Will there be an agreed agreement or percentage for agreement, e.g., Kappa agreement >0.80 for relevant screening? Will there be a search string used for Google Scholar? (e.g., Food handlers’ knowledge, attitudes, and practices)\nThe reviewer has provided a reference regarding best practices for using Google Scholar and grey literature for grey literature. Although the author Haddaway et al. (2015)1 discusses how the role of Google Scholar is used in evidence synthesis for systematic reviews, the authors could consider discussing this with their academic librarian regarding their scoping review.\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": "147956",
"date": "21 Sep 2022",
"name": "Hibbah Osei-Kwasi",
"expertise": [
"Reviewer Expertise Nutrition",
"Public health",
"systematic reviews."
],
"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 focusing on a very important topic. As a scoping review, the methodology is transparent and robust and makes reference to existing guidelines which is always good practice.\n\nI have a few minor suggestions:\nCan the authors provide a justification for the time frame for the searches? Why focus on that range?\n\nI also recommend including the LMIC countries in the search strategy.\n\nAlso, the paper will benefit from a final proofread. A few points include consistency in some words: e.g. amongst/among... Authors should not mix British with American English.\n\nFinally, can authors check the in-text citation for consistency as well.\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/11-757
|
https://f1000research.com/articles/11-756/v1
|
07 Jul 22
|
{
"type": "Research Article",
"title": "Pediatric malaria incidence and risk mapping in Sussundenga Municipality, Mozambique",
"authors": [
"Joao Ferrao",
"Roberto Mendes",
"Alberto Tungadza",
"Bernardo Bernardo",
"Kelly Searle",
"Roberto Mendes",
"Alberto Tungadza",
"Bernardo Bernardo",
"Kelly Searle"
],
"abstract": "Background: Malaria is a parasitic borne disease that affects red blood cells. The disease is preventable, detectable and treatable and more common in poor resource settings. Malaria is undoubtedly one of the main public health concerns impacting families and the economy in Mozambique. Age category plays a significant important role in malaria occurrence and can affect the course and progression of the disease and correct treatment. Very few studies on pediatric malaria exists in Mozambique and the existing ones use a simplistic and coarse grouping. The knowledge of malaria pediatric incidence and, the need to evaluate the local heterogeneity by generating malaria risk maps can improve the understanding of pediatric malaria being the objective of this study. Methods: A retrospective study was conducted using existing malaria positive data from 2018 to 2019 at Rural Sussundenga Hospital (RSH) in Sussundenga municipality. Attributable factors of the disease and incidence were calculated. Proportion of gender, age category and location were tested using G test. For malaria risk mapping, ten malaria factors (anthropic, sociodemographic, climatic and clinic) were used to produce two maps: one using malaria incidence and other without. Bioclimatic, Diva GIS 7.4.0 and, Landsat 8 image were used to produce the map. Results: The findings revealed that of the 42,248 patients who visited the local hospital f, 51.2% tested positive for malaria with an incidence of 45.7 per 100 persons. There is a difference between residential areas in malaria incidence, with both maps showing malaria risk in Nhamazara, Nhamarenza and Unidade communities.\n\nConclusions: This implies that malaria high risk areas seem to be located in high populated areas and areas close to water bodies. Relevant information is provided for effective planning in malaria intervention.",
"keywords": [
"Pediatric malaria",
"incidence",
"mapping",
"Sussundenga",
"Mozambique"
],
"content": "Introduction\n\nMalaria is a parasitic-borne disease that affects red blood cells. The World Health Organization (WHO) recorded 229 million malaria cases in 2019 and, of these, there were 409,000 deaths in 87 endemic countries and 67% of these occurred in children under five years. Worldwide, 95% of malaria cases occurred in 29 countries.1\n\nMozambique is among the six countries that account for half of all malaria cases and deaths globally and has the fifth highest number of cases. Due to the control programs, malaria prevalence and incidence decreased by 50 and 40%, respectively. In Southern Africa, the malaria decrease was between 50 to 91%. In Mozambique, the reduction is slow, and between 2015 and 2018, cases reduced only by 14%.2,3\n\nThe disease is preventable, detectable, treatable, and more common in poor regions. It has socioeconomic impacts, representing a significant burden on countries' revenue where it is endemic.\n\nIn Mozambique, malaria is undoubtedly one of the main public health concerns impacting families and the economy. In 2020 the country reported 8,921,081 cases and 1,114 deaths.1 Although the entire population of Mozambique is at risk, children and pregnant women are at higher risk owing to lower immunity. In the Chimoio region/province, children under five years old are three times more prone to malaria than adults.4\n\nMalaria transmission in Mozambique occurs all year round, and peaks between January and March. Malaria transmission strongly correlates with rainfall temperature, with relative humidity accounting for 72 to 80% of the cases.5–7\n\nDespite those weather conditions, malaria occurrence is also influenced by socio-demographic determinants such as age, gender, level of education, residence type (rural and urban).8–10 Age can affect the course and progression of the diseases and correct treatment.11 Very few studies in pediatric malaria exist in Mozambique, and the existing ones use a simplistic and coarse grouping of 0 to 4 and over 5 years, not reflecting stages of development and the current standard age categories.\n\nThe malaria environmental dependency results in a complex pattern of geographical variation in transmission at almost every scale. Malaria risk is rarely uniform, whether between households in a village, villages in a district, or districts in a country. The knowledge of the spatial distribution of malaria and the evaluation of local heterogeneity by generating malaria risk maps can improve the understanding of pediatric malaria, especially in children.\n\nHence, this study intends to determine the malaria determinants and map the risk of malaria in children with and without clinical data. The knowledge generated by the present research can help formulate malaria control programs and policy strategies for malaria control in under 14 age categories in Mozambique.\n\n\nMethods\n\nThis is a pilot study to determine malaria prevalence, risk factors, and health seeking behaviors in Sussundenga to map the risk of malaria in children. Retrospective data were collected from Sussundenga Health Center from January to May 2020.\n\nSussundenga village is a rural municipality in the center of Manica Province, Mozambique (33°29′52″ and -19°41′30″), administratively divided into 17 residential areas within 156.9 km2 (Figure 1).\n\nIt has a population of 41,354 inhabitants, 52% female and 48% male, with a 2.5% annual growth rate. The pediatric population (0 to 14 years) comprises 45.6% of the total population, being 4.4% less than 1 year, 11% from 1 to 4 years, and 30.2% from 5 to 14 years old.12 The livelihood of the inhabitants is based on subsistence agriculture.\n\nThe hydrographic network comprises six main rivers with a permanent flow. Most of the population has deficient access to health services in the municipality since there is only one public hospital.\n\nThe climate is warm-temperate with dry winters from April to July, hot and dry summers from August to October, and hot, humid summers from November to March. The average rainfall is 1,067.6 mm, varying significantly in the amount and distribution within and between October and November are the hottest months recording averages of 30°C. July is the coldest month with averages of 12°C. The predominant vegetation is associated with open, deciduous forests, evergreen forests, prairie, shrubs, and savanna.13\n\nIn public hospitals, all patients are registered in a record book upon arrival. A malaria test at Sussundenga District Hospital (SDH) uses a rapid diagnostic test (RDT) and a few microscopic tests for confirmation. Patient daily data were collected from 24 book records of the Pediatric Department of SDH from November 2018 to October 2020. The dataset can be found under Underlying data.49 The following variable data were recorded for the positive malaria cases: date, sex, origin, and age category. The age was grouped into five pediatric age categories: 0 to 5, 6 to 11, 12 to 23, 24 to 59 months, and 5 to 14 years old. Missing data comprised only 1.2% and were removed from the study.\n\nThe disease's weight was calculated by dividing the positive malaria cases by the total patient visits. The malaria incidence per 100 persons in each neighborhood was calculated by dividing the total number of cases occurring in each Bairro by the total population of the Bairro and then multiplied by 100.14 Chi-Square and G test tests for the proportion of gender and age category were used to test statistical significance.\n\nFor malaria risk mapping. Bioclimatic (WorldClim),15 Diva GIS 7.4.0,16 Landsat 8 image,17 accessed on September 29, 2019 with a resolution of 30 m × 30 m and, Digital Elevation Model (DEM)18 of 30 m × 30 m were used.\n\nA three-step strategy was applied to develop the map: Step 1. Malaria risk factors identification, Step 2. Determining risk factor weights (Analytical Hierarchical Process and consistency check), Step 3, Mapping risk of malaria and accuracy assessment of the produced map.\n\nStep 1. Malaria risk factors identification\n\nTen risk factors used in the weights, classes, and rank are in Table 1.\n\ni) Population density (Inhabitants/km2)\n\nTo calculate population density, Mozambique national statistics projections for 2020 was used and, data were related to the neighborhood administrative units.19 Density lower than 2,000 inhabitants per km2 was considered low risk; from 2,001 to 4,000 was considered moderate risk while over 4001 was considered high malaria risk.\n\nii) Malaria Incidence per 100 persons per residential area\n\nThe malaria incidence per 100 persons in each neighborhood was calculated. Incidence from 0 to 40 per 100 persons was considered low risk, 41 to 80 was considered moderate risk, and over 80 was considered high risk of malaria occurrence.\n\niii) Altitude (m)\n\nTo estimate altitude, a digital elevation model (DEM) at 30-meter × 30-meter resolution was used. Altitude lower than 200 meters was considered to have high malaria risk, from 201 to 1000 meters was considered to have moderate malaria risk, and over 1000 meters was considered to have a low malaria risk.20\n\niv) Average temperature (°C)\n\nThe surface temperature in degrees Celsius was extracted in the terminal infrared range of the TIRIS/Landsat-8 sensor in Band 10.21 The formula for temperature calculation was:\n\nTemperatures ranging 22 and 32°C were classified as high risk, while less than 22°C were considered low malaria risk and, above 32°C was considered moderate malaria risk.20\n\nv) Rainfall (mm)\n\nRainfall data were extracted from worldclim 2-5m.cli data and processed in Diva GIS.\n\nAreas that received an amount of rain less than 450 mm were considered to have low malaria risk, those that received an amount of rain ranging 450 to 700 mm were considered moderate malaria risk and above 700 mm of rain were considered high malaria risk.20\n\nvi) Slope (degrees)\n\nThe slope was derived from the 30 m × 30 m DEM obtained from the ArcGIS spacial analysis tool. Areas ranging 0 to 5 degrees were considered to have high malaria risk, from 5 to 15 degrees were considered to have moderate malaria risk and, above 15 degrees were considered to have lower malaria risk.20\n\nvii) Normalized Difference Vegetation Index (NDVI)\n\nThe Landsat Normalized Difference Vegetation Index is used to quantify vegetation greenness, and greater amounts of green vegetation in the soil indicate greater NDVI. The NDVI was extracted from a Landsat image and calculated by the following formula:\n\nWhere:\n\nNIR = Reflectance in the near infrared band.\n\nRED = Reflectance in the red range of the spectrum.\n\nThe NDVI from -0.288 to 0 was considered as low malaria risk, from 0 to 0.25 was considered as moderate malaria risk and from 0.255 to 0.986 was considered as high malaria risk.20\n\nviii) Distance from the road (km)\n\nThe Euclidian distance to the nearest road determines accessibility and malaria interventions capability and, was calculated using the measuring distance function in ArcGIS 10.2.2 software from a Landsat image 30 m × 30 m from September 2019. Distances less than 2.5 Km from the nearest road were considered as low malaria risk, from 2.5 to 5 Km considered as moderate malaria risk and more than 5 km considered high malaria risk.20\n\nix) Distance to water bodies (km)\n\nStagnant water bodies constitute mosquito breeding sites. ArcGIS was used to calculate the nearest waterbody by classifying a 30 m × 30 m Landsat 8 image from 2019 for water and in defined areas. The measurement distance function of ArcGIS software was employed. Areas above 1.5 km were considered as low malaria risk, from 0.5 to 1.5 km considered moderate malaria risk and lower than 0.5 km low malaria risk.20\n\nx) Land use and cover (LULC)\n\nLandsat 8 satellite image (September 2019) was used to retrieve LULC data. The reclassification of the image into different classes was carried out using the manual training sampling technique and the maximum likelihood algorithm. Areas with crops, grass and waterbodies were considered as high malaria risk, Shrub and mosaic cover areas were considered moderate malaria risk while forest, bare and urban settlements were considered low malaria risk.20\n\nLULC Classes\n\n1. Agricultural crop area, grass and water body.\n\n2. Shrub area and mosaic cover vegetation\n\n3. Forest, nude and urban settlement areas21\n\nStep 2. Determining risk factor weights (Analytical Hierarchical Process) and consistency check.\n\nThe analytical hierarchic process was determined as previously described.20 To check for consistency, an actual consistency ratio for the corresponding matrix was calculated by dividing the consistency index for the set of judgments by the index for the corresponding random matrix. Saaty suggests that if that ratio exceeds 0.1, the judgments may be too inconsistent to be reliable.22\n\nStep 3. Mapping risk of malaria risk and accuracy check\n\nTwo risk maps were produced using spatial, anthropic, and environmental variables; one risk map used ten risk factors, while the other excluded the incidence data. Figure 2 presents the spatial analyses carried out.\n\nA raster dataset was created using the variables. The reclassification was done, with all the measures given equal numeric scale, assigning them the same level of importance. For model suitability, reclassified outputs of the variables were combined assigning them weights. For the comparison of class values among layers and, numeric values of classes within each map layer, the variables were assigned values from 1 to 3, representing low, moderate and high malaria risk.\n\nApplying the overlay method, where each of the input maps is allocated a weight and every class and spatial unity existed in each variable map, different classes on a single map presented different weights and each variable map also had its own weight.\n\nBy summing all of the input variable maps after each had been multiplied by its overall weight, two final maps of risk were produced, one using the incidence variable and other without as presented in the equation:\n\nWhere:\n\nWi = weight of i-th variable map,\n\nSij = the i-th spatial class weight of j-th\n\nS = is the spatial unit value in the output map.\n\nAs a result, a new raster surface was generated representing different levels of risk of malaria based on the variables.20\n\nTests were performed using SPSS IBM version 2023 and for mapping ArcGIS 10.7.3.24\n\n\nResults\n\nFrom November 2018 to October 2020, 42,248 patients visited the pediatric department of SDH, and 21,663 (51.2%) were positive for malaria. Of the malaria-positive patients, 89.9% were from the Sussundenga municipality. The incidence per 100 persons was 45.7 for the year 2019. As per gender, the positive malaria patients were equally distributed, 48.4% male and 51.6% female.\n\nThe average age of pediatric malaria patients was 5.7 SD (Standard deviation) = 1.38 years. Figure 3 presents age group distribution, and the age group 0 to 5 months showed the most negligible percentage of cases (3.3%), while the age group 5 to 14 years old presented the highest rate of patients (45.6%). No difference was found between sex among the age categories. The full dataset can be found in the Underlying data.49\n\nMalaria incidence by residential areas\n\nThe incidence per residential area varied from 6.6 per 100 persons to 118 per 100 persons. There is a difference between residential areas in malaria incidence G = 377.38, P = 0.0001, DF = 16 and, Nhamarenza present the highest incidence, 118 per 100 persons, and the most negligible incidence was given in residential areas Chizizira and Tave with 6.6 and 6.7 per 100 persons respectively (Figure 4).\n\nMalaria cases by month\n\nThe percentage of pediatric malaria cases for 2019. January showed the highest rate of patients (19.7%), followed by May (19.6%), and the most negligible percentage of cases occurred in September (0.1%) (Figure 5).\n\ni Analytical Hierarchical Process and consistency check\n\nThe comparison matrix of 1 × 10 and 9 × 9 risk factors was used in this study. A value of 1 means that the malaria risk factors being compared have the same weight. A value of one means that variables being compared have the same weight in terms of malaria risk. A value of four for example, means that the variable in the column is four times more important in malaria risk than the comparison in the row (Tables 2 & 3). The consistency ratio was 0.081 and 0.096 for 10 × 10 and 9 × 9 matrix, respectively, which was considered good enough.\n\nMapping risk of malaria and accuracy check\n\nThe risk factor maps before reclassification are presented in Figure 6: the average temperature in the area ranges from 20.14 to 21.17 °C, and rainfall ranges from 1028 to 1,082.24 millimeters, altitude ranges from 459 to 791 meters, slope ranges from 0 to 37.5°, distance to water bodies ranges from 0 to 15,134 meters, NDVI ranges from -0.14 to 0.5, population density ranges from 41 to 59,091 people per km2, malaria incidence ranges from 2.9 to 118.\n\n(A). Temperature. (B) Rainfall (C). Altitude. (D). LULC, (E) Slope (F). Distance to water bodies. (G) NDVI for Sussundenga Village (H). Pop. Density. (I). Malaria incidence. (J) Distance to roads.\n\nFigure 7 presents the maps for the reclassified risk factors and the malaria risk in percentage. Rainfall (100%) and slope (73%) have the highest chance, altitude (100%), and NDVI (92%) have moderate risk in the municipality.\n\nThe spatial model derived to produce the two malaria risk maps from the risk factors are presented in formulas 4 and 5.\n\nFigure 8A and Figure 8B present the final malaria risk maps for Sussundenga municipality after the consolidation and the weighting using the incidence data and excluding the incidence data. The entire Sussundenga municipality is at risk of malaria, varying from moderate to high risk. Malaria's high risk coincides with the highly populated area and surrounding water bodies.\n\nA. Including incidence. B. Excluding incidence.\n\nTable 4 presents the percentage of malaria risk in Sussundenga, and there is no difference in the risk areas using and excluding the clinical data (incidence data).\n\nTable 4A and B present the area of the high and moderate malaria risks.\n\n\nDiscussion\n\nIn this study, the pediatric weight of malaria was 51.2%. In 2015 malaria was responsible for 45% of outpatient visits and 56% of pediatric admissions in Mozambique,2 consistent with these results. A study in Manhiça, a rural area in the south of Mozambique in 200825 indicated 30.5% had malaria, lower than the results of the present study, and this can be related to environmental conditions since the south of Mozambique is drier. In Malawi, a neighboring country, the weight of the disease ranged from 26% in Salima to 64% in Mwanza.26\n\nIn this study, the malaria incidence in pediatric malaria was 45.7 per 100 persons. A 2018 study reported an incidence of 39 per 100 in children under 10 years in the Central region of Mozambique.27 A study in Malawi indicated 35 to 37 per 100-person incidence in children under 15 in 2017.9 In Zimbabwe, significant progress was made in malaria cases reduction, and the incidence is 2.5 per 100 persons, while in Zambia is 20 per 100 persons.28,29\n\nThe mean age of malaria patients in this study was 5.6 SD 1.3 years. In Southern Africa, 29 studies in 2010 reported a median age of clinical malaria of 32 months highly intense and not markedly seasonal transmission areas and 72 months in low-intensity and markedly seasonal transmission areas consistent with this study.30 In China, the mean average of most childhood diseases was reported to range from 20 to 80 months and, for high incidence pediatric disease approximately 3 years.31\n\nIn this study, the age group 5 to 14 years presented the highest percentage of cases, 45.6%, while this category comprises 30.2% of the municipality inhabitants. A community study in the same municipality in 2021 reported 50% of positive malaria cases in children aged 5 to 14 years,32 consistent with these results. A study in Manhiça Mozambique22 reported 36% of cases among age group 5 to 14 in 2008 less than in this study, while, in Inhambane, Mozambique33 in 2015, reported a higher figure of 67.7%. In Malawi and Kenya, results consistent with the present findings were reported.34,35\n\nA shift in the peak age of cases from 1 to 4 years old to 5 to 9 years old was reported in 2009 in a study in Inhambane, Mozambique.36 In many malaria-endemic areas, successful control programs have substantially reduced transmission levels. Consequently, in such communities, the peak age of clinical attacks of malaria is shifting from very young to older children.37–39\n\nThe most minor malaria cases in this study occurred in children aged 0 to 5 months. For approximately six months after birth, antibodies acquired from the mother during pregnancy protect the child. This maternal immunity is gradually lost as the child develops their immunity to malaria. In areas where malaria is endemic, children are believed to achieve a high level of immunity up to 5 years of age.40,41 Higher usage of bed nets was also reported in pregnant mothers and children less than one year than in children 5 to 14 years.30,42\n\nThis study showed a difference in malaria incidence between residential areas varying from 6.6 to 118 per 100 persons. The results are consistent with Chimoio, Sussundenga, and Mozambique.4–6 In Ethiopia and Kenya, spatial variation of malaria incidence in a geographically homogeneous area was also reported,41,43 and this can be a result of high endemicity. Heterogeneous rates from 2.5 to 10.5 episodes per 100 children per year were also reported in Senegal.44 In Malawi, geographical groups of households where children experienced repeated malaria infections overlapped with high mosquito density areas.45 In Brazil, the high incidence of malaria at a low scale was due to the heavily modified landscape.46\n\nMost malaria cases occur from January to March in Mozambique.5,6 For 2019, the high number of malaria cases continued from January to May. This is a result of the Cyclone Idai that occurred in March 2019 and resulted in heavy rain and floods in the region. The malaria temporality was also reported in other countries in Africa.47,48\n\n\nConclusion\n\nThe age of pediatric malaria is shifting from 0 to 4 to the age category 5 to 14 years, and targeting this to combat malaria should be addressed. Mapping malaria risk at a low scale is feasible without using clinical data and can provide tools to improve the strategy of malaria combat in children. Malaria eradication needs to involve medical disciplines and other fields such as economics, geography and ecology, and social sciences. The use of GIS and mapping can contribute to the design and implementation of control malaria strategies by defining precisely the pattern of malaria occurrence.\n\nThis study used retrospective data to calculate pediatric malaria incidence. With climate change and extreme events such as Cyclone Idai, different results may occur in the future due to different circumstances. Previous mapping of Sussundenga was carried out using clinical data. This study aimed to prove that, even without clinical data, malaria risk can be forecasted.\n\n\nData availability\n\nThe retrospective data were collected at Centro de Saude de Sussundenga, EN216, 2207 Sussundenga, Mozambique. Coordinates: -1940954, 33.29355. Permission was granted by the District Director of Health of Sussundenga for the use of this data.\n\nHarvard Dataverse: Replication data for: Pediatric malaria incidence and risk mapping in Sussundenga Municipality, Mozambique, https://doi.org/10.7910/DVN/UL1CW7.49\n\nThis project contains the following underlying data:\n\n- Pediatric malaria data.tab\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\nEthics and consent\n\nThis study is part of the Malaria Risk, Prevention, and Health Seeking Behaviors in Sussundenga, Mozambique Project. Ethical review and approval for the study was completed by the Institutional Review Board (IRB) at the University of Minnesota [STUDY00007184] and from A Comissão Nacional de Bioética em Saúde (CNBS) at the Ministry of Health of Mozambique [IRB00002657].",
"appendix": "Acknowledgments\n\nWe would like to thank the Provincial and district directorates of health for granting permission to carry out this study, especially Dr. Firmino Jaqueta, Dr. Serafina Benesse, Dr. Filipe Murgorgo and Mrs. Elsa Trabuco. We thank Mrs Jesca Mutowo for the English revision. An earlier version of this article can be found on Research Square (https://orcid.org/0000-0002-3543-6459).\n\n\nReferences\n\nWorld Health Organization: World malaria report 2020: 20 years of global progress and challenges. Geneva: WHO; 2020. (Accessed on 10/8/2021). Reference Source\n\nMozambique malaria facts: Severe Malaria Observatory.2021. (Accessed on 10/8/2020). Reference Source\n\nO’Meara WP, Mangen JN, Steketee R, et al.: Changes in the burden of malaria in sub-Saharan Africa. Lancet Infect. Dis. 2010; 10: 545–55. (Accessed on 10/8/2020). 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Reference Source\n\nCDC: Principles of Epidemiology in Public Health Practice. Third Edition.Centre for Disease Control; 2011. accessed on 10 July 2020. Reference Source\n\nBIOCLIM: WorldClim Bioclimatic Variables: 2000. (20, 50, 80). (Accessed on10/10/2020). Reference Source\n\nDIVA-GIS: (Accessed on 15/10/2020). Reference Source\n\nLansat 8: Landsat-8 Imagery in the Period 2019. (Accessed on 15/10/2020). Reference Source\n\nUSCGS: Digital Elevation Models (DEMs). (Accessed on 15/10/2020). Reference Source\n\nInstituto Nacional de Estatística: Projecções da População 2017-2050.Reference Source\n\nFerrao JL, Niquisse S, Mendes JM, et al.: Mapping and Modelling Malaria Risk Areas Using Climate, Socio-Demographic and Clinical Variables in Chimoio, Mozambique. IJERPH. 15: 15. Publisher Full Text Reference Source\n\nTeixeira DLS, Morais TS, Silva LT, et al.: Uso de Geoecologias em Estudos Ambientais.Reference Source\n\nCoyle G: The Analytical Hierarchical Process.2004. (Accessed on 10/11/2020). Reference Source\n\nIBM: SPSS Statistics 20.\n\nArcGIS Desktop 10.7.1 Quick Start Guide: (Accessed on 10/10/2020). Reference Source\n\nGuinovart C, Bassat Q, Sigaúque B, et al.: Malaria in rural Mozambique. Part I: Children attending the outpatient clinic. Malar. J. 2008; 7: 36. PubMed Abstract | Publisher Full Text\n\nOkiro EA, Kazembe LN, Kabaria CW, et al.: Childhood Malaria Admission Rates to Four Hospitals in Malawi between 2000 and 2010. PLoS One. 2013; 8(4): e62214. PubMed Abstract | Publisher Full Text\n\nMabunda S, Casimiro S, Quinto L, et al.: A country-wide malaria survey in Mozambique. I. Plasmodium falciparum infection in children in different epidemiological settings. Malar. J. 2008; 7: 216. PubMed Abstract | Publisher Full Text\n\nSande S, Zimba M, Mberikunashe J, et al.: Progress towards malaria elimination in Zimbabwe with special reference to the period 2003–2015. Malar. J. 2017; 16: 295. PubMed Abstract | Publisher Full Text\n\nSevere Malaria Observatory: Malaria in Zâmbia.Reference Source\n\nCarneiro I, Roca-Feltrer A, Griffin JT, et al.: Age-Patterns of Malaria Vary with Severity, Transmission Intensity and Seasonality in Sub-Saharan Africa: A Systematic Review and Pooled Analysis. PLoS One. 2010; 5(2): e8988. PubMed Abstract | Publisher Full Text\n\nLi H, Yu G, Dong C, et al.: PedMap: a pediatric diseases map generated from clinical big data from Hangzhou, China. Sci. Rep. 2019; 9: 17867. PubMed Abstract | Publisher Full Text\n\nFerrao JL, Earland D, Nvela A, et al.: Modelling Sociodemographic factors that affects Malaria prevalence in Sussundenga Mozambique. Researchsquare. 2020; Reference Source\n\nCharlwood JD, Tomás EV, Bragança M, et al.: Malaria prevalence and incidence in an isolated, meso-endemic area of Mozambique. PeerJ. 2015; 3: e1370. Published 2015 Nov 5. PubMed Abstract | Publisher Full Text\n\nWalldorf JA, Cohee LM, Coalson JE, et al.: School-Age Children Are a Reservoir of Malaria Infection in Malawi. PLoS One. 2015; 10(7): e0134061. Published 2015 Jul 24. PubMed Abstract | Publisher Full Text\n\nKhagayi S, Desai M, Amek N, et al.: Modelling the relationship between malaria prevalence as a measure of transmission and mortality across age groups. Malar. J. 2019; 18: 247. PubMed Abstract | Publisher Full Text\n\nPemberton-Ross P, Smith TA, Hodel EM, et al.: Age-shifting in malaria incidence as a result of induced immunological deficit: a simulation study. Malar. J. 2015; 14: 287. PubMed Abstract | Publisher Full Text\n\nTouré M, Sanogo D, Dembele S, et al.: Seasonality and shift in age-specific malaria prevalence and incidence in Binko and Carrière villages close to the lake in Selingué, Mali. Malar. J. 2016; 15: 219. PubMed Abstract | Publisher Full Text\n\nGriffin J, Ferguson N, Ghani A: Estimates of the changing age-burden of Plasmodium falciparum malaria disease in sub-Saharan Africa. Nat. Commun. 2014; 5: 3136. PubMed Abstract | Publisher Full Text\n\nWhite M, Watson J: Malaria: Age, exposure and immunity. elife. 2018; 7. PubMed Abstract | Publisher Full Text Reference Source\n\nWorld Bank: Inquérito Nacional sobe indicadores de Malaria 2018. World Bank; 2019. (Acessed on 8/8/2021). Reference Source\n\nGeostatistical analysis and mapping of malaria risk in children of Mozambique Bedilu Alamirie EjiguID* Department of Statistics, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, Ethiopia * mailto:bedilu.alamirie@aau.edubedilu.alamirie@aau.edu.\n\nBejon P, Williams TN, Nyundo C, et al.: A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots. elife. 2014; 3: e02130. PubMed Abstract | Publisher Full Text\n\nGeifman N, Cohen R, Rubin E: Redefining meaningful age groups in the context of diseases. AGE. 2013; 35: 2357–2366. PubMed Abstract | Publisher Full Text\n\nEspié E, Diene Sarr F, Diop F, et al.: Spatio-Temporal Variations in Malaria Incidence in Children Less than 10 Years Old, Health District of Sokone, Senegal, 2010-2013. PLoS One. 2015; 10(9): e0137737. Published 2015 Sep 18. PubMed Abstract | Publisher Full Text\n\nKabaghe AN, Chipeta MG, Gowelo S, et al.: Fine-scale spatial and temporal variation of clinical malaria incidence and associated factors in children in rural Malawi: a longitudinal study. Parasites Vectors. 2018; 11: 129. PubMed Abstract | Publisher Full Text\n\nde Oliveira Padilha MA , de Oliveira Melo J , Romano G, et al.: Comparison of malaria incidence rates and socioeconomic-environmental factors between the states of Acre and Rondônia: a spatio-temporal modelling study. Malar. J. 2019; 18: 306. PubMed Abstract | Publisher Full Text\n\nDalrymple U, Mappin B, Gething PW: Malaria mapping: understanding the global endemicity of falciparum and vivax malaria. BMC Med. 2015; 13: 140. PubMed Abstract | Publisher Full Text\n\nEspié E, Sarr FD, Diop F, et al.: Spatio-Temporal Variations in Malaria Incidence in Children Less than 10 Years Old, Health District of Sokone, Senegal, 2010–2013. PLoS One. 2015; 10: e0137737. PubMed Abstract | Publisher Full Text\n\nFerrao J: Data: Pediatric malaria incidence and risk mapping with and without clinical data in Sussundenga Municipality, Mozambique.2021. Publisher Full Text"
}
|
[
{
"id": "203805",
"date": "12 Oct 2023",
"name": "Olayinka Rasheed Ibrahim",
"expertise": [
"Reviewer Expertise Pediatric Infectious disesase: Malaria",
"Tuberculosis"
],
"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\nPediatric malaria incidence and risk mapping in Sussundenga Municipality, Mozambique\nAbstract\nResults: Scanty, more like summary, this should be expanded with main findings of the study.\nConclusion: The information used to arrive at this conclusion is missing in the abstract\nKeywords: Sussundenga, Mozambique (delete one of these two words)\nIntroduction\nThe second and third paragraphs are not linking up? No mentioning of COVID-19 despite the fact that the study involved early part of COVID-19 (2020), and its potential impact?\nMethods\nRetrospective data were collected from Sussundenga Health Center from January to May\n2020: This is confusing and may not be necessary that five months was used to extract a retrospective data collection! Besides, the data for 2020 stopped in October? So what happened?\nThe pediatric population (0 to 14 years) comprises 45.6% of the total population, being 4.4% less than 1 year, 11% from 1 to 4 years, and 30.2% from 5 to 14 years old: This percentages should have n after then for interpretation\nMost of the population has deficient access to health services in the municipality since there is only one public hospital: This statement is unclear? a single pubic hospital and deficient access??? Are there private health facilities?\n“The climate is warm-temperate with dry winters from April to July, hot and dry summers from August to October, and hot, humid summers from November to March. The average rainfall is 1,067.6 mm, varying significantly in the amount and distribution within and between October and November are the hottest months recording averages of 30°C. July is the coldest month with averages of 12°C” Insert appropriate references\n“In public hospitals” You mentioned before that the district has a single public hospital?\n“Patient daily data were collected from 24 book records of the Pediatric Department of SDH from November 2018 to October 2020” Unclear\n“Missing data comprised only 1.2% and were removed from the study” Insert n\n“G test tests” add a line of what its entails in bracket.\n” Ten risk factors used in the weights, classes, and rank are” how were determined and the weight (%) appropriate for each risk factors? Kindly provide details\nTable 1: Add the meaning of abbreviations in the Table as footnotes\n“The malaria incidence per 100 persons in each neighborhood was calculated. Incidence from 0 to 40 per 100 persons was considered low risk, 41 to 80 was considered moderate risk, and over 80 was considered high risk of malaria occurrence” Kindly insert reference\nResults\n“Malaria incidence per age group in children 0 to 14 years old” while you may not be to calculate the incidence per 100 population for 2018 and 2020, kindly give the incidence (weight separately) before combining them.\n“while the age group 5 to 14 years old presented the highest rate of patients (45.6%)” this information is incorrect and a miss-interpretation, we talked of under-five and five above, the under-five is more than those above 5\n“Figure 3. Percentage of malaria cases by age category and sex in Sussundenga incidence” this figure is confusing and difficult to understand, kindly revise and present the data in a simple un-ambiguous way\n“Figure 5. Pediatric malaria cases (%) per month in Sussundenga Municipality, 2019” what is the rational for limiting this to one year, most especially when 2020 data was up to October.\nDiscussion\n“In Southern Africa, 29 studies in 2010 reported a median age of clinical malaria of 32 months highly intense and not markedly seasonal transmission areas and 72 months” Convert the months to years for easy of interpretation\nThird paragraph? Add import/implications of your findings\n“In this study, the age group 5 to 14 years presented the highest percentage of cases, 45.6%” this statement is incorrect, see earlier reasons raised “A shift in the peak age of cases from 1 to 4 years old to 5 to 9 years old was reported in 2009 in a study in Inhambane, Mozambique.36 In many malaria-endemic areas, successful control programs have substantially reduced transmission levels. Consequently, in such communities, the peak age of clinical attacks of malaria is shifting from very young to older children” wrong discussion from faulty interpretation of results\n“For 2019, the high number of malaria cases continued from January to May. This is a result of the Cyclone Idai that occurred in March 2019 and resulted in heavy rain and floods in the region. The malaria temporality was also reported in other countries in Africa” difficult to accept as your data did not show a lesser incidence of malaria before the period?\nOverall comments on discussion: This is the did not capture your objectives (Hence, this study intends to determine the malaria determinants and map the risk of malaria in children with and without clinical data) rather you focused on only the age distributions? Where are the other determinants? Besides, you did not proffer enough reasons for your findings? Implications of your findings? The whole discussion need to re-written with your objectives in focus? Conclusion\n“Mapping malaria risk at a low scale is feasible without using clinical data and can provide tools to\nimprove the strategy of malaria combat in children. Malaria eradication needs to involve medical disciplines and other fields such as economics, geography and ecology, and social sciences. The use of GIS and mapping can contribute to the design and implementation of control malaria strategies by defining precisely the pattern of malaria occurrence” Even though capture in your results, these were completely missing in your discussion and as such you cannot conclude as such.\nLimitations\n“Previous mapping of Sussundenga was carried out using clinical data. This study aimed to prove that, even without clinical data, malaria risk can be forecasted” unfortunately, you fail to compare with the previous study that used clinical data? General comments:\nNo mentioning of COVID-19 despite the fact that the study involved early part of COVID-19 (2020), and its potential impact? Could this have influenced the malaria cases in 2020 directly or indirectly (see reference Outcomes of childhood severe malaria: a comparative of study pre-COVID-19 and COVID-19 periods. https://pubmed.ncbi.nlm.nih.gov/37061668/#:~:text=BMC%20Pediatr,023%2D03985%2D4.\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": []
},
{
"id": "208930",
"date": "18 Oct 2023",
"name": "Balram Ji Omar",
"expertise": [
"Reviewer Expertise Infectious Disease",
"MDR",
"Congenital Malaria",
"Nanotechnology & Microbes",
"Candidemia",
"Bacteriology",
"ESS & section systems",
"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\nWhich type of agriculture is more common in area -Specify (Rice and some crops require more water )\n\nWas only Rapid Card test performed for Designating it as a case of malaria . Which type of RDT /ICT used will add value to manuscript by getting known for its specificity & Sensitivity\n\nAny test was done to identify species of malaria prevalent in that are (this also helps to deal and manage type of Malaria & also help for its control by recent discovery of Vaccination and medicine )\n\nHow many cases were designated as congenital malaria and malaria under Age of 1 year (important data )\n\nReference of Paediatric malaria shifting (Conclusions)\n\nArticle written is well connected ,few suggestion and comments are written above -which may be addressed\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "212302",
"date": "24 Oct 2023",
"name": "Samuel Kofi Tchum",
"expertise": [
"Reviewer Expertise Micronutrients",
"malaria",
"anaemia and food fortification or supplementation are my areas of research. I am also involved in clinical trials",
"especially among infants and young children"
],
"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 did not cite most of the literature in the manuscript during the introduction section and other sections of the manuscript.\nThe rationale for the study was not so clear though I made suggestions in the track changes version of the manuscript.\nThe data presented in some of the tables and figures were not consistent. Some were missing too.\nThe manuscripts discussed not strongly and appropriately did not compare their findings with others. They did not state why they agreed or disagreed with others.\n\nHowever, if corrections made in the track changes version of the manuscript are adhered to, this paper will be good\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-756
|
https://f1000research.com/articles/11-753/v1
|
06 Jul 22
|
{
"type": "Research Article",
"title": "The role of biomarkers in the prediction of mortality in hospitalized patients for COVID-19",
"authors": [
"Gustavo Alexandre Cruz",
"Henrique Pott-Junior",
"João Paulo Gregorio 2",
"Erica Leticia Angelo Liberato",
"Glieb Slywitch Filho",
"Thais B. Boteon",
"Sigrid de Sousa dos Santos",
"Fabiola P. G. Rizzatti",
"Fernanda de Freitas Anibal",
"MELIZA GOI ROSCANI",
"Gustavo Alexandre Cruz",
"Henrique Pott-Junior",
"João Paulo Gregorio 2",
"Erica Leticia Angelo Liberato",
"Glieb Slywitch Filho",
"Thais B. Boteon",
"Sigrid de Sousa dos Santos",
"Fabiola P. G. Rizzatti",
"Fernanda de Freitas Anibal"
],
"abstract": "Background: Despite the advances in the prognostic determinants in patients with COVID-19, it is not well known which hospitalized patients may course with an adverse outcome. The aim of this study was to identify biomarkers at hospital admission associated with increased risk of death in hospitalized patients with COVID-19. Methods: Prospective study in patients with COVID-19 admitted to a hospital and followed until discharge or death. All patients underwent clinical evaluation and laboratory tests on the first day of admission. Results: 100 patients were included, with a mean age of 57 years and 19 died. The variables associated with higher mortality were age), platelet count, D-dimer and troponin. Platelet count was independently associated with mortality, with area under the curve: 0.74 [95% CI: 0.62 - 0.86; p = 0.001]. The area under the curve of D-dimer for death was 0.74 [95% CI: 0.62 - 0.86; p= 0.001]. Considering the Kaplan Meier curves for survival in the hospitalization, there was a significant difference in the curves for D-dimer cutoff point above or below 1.1 mg/L (Log-Rank, p=0.03). Conclusion: The levels of D-dimer and platelet count have good accuracy in the detection of increased risk of death in hospitalized patients with COVID-19.",
"keywords": [
"mortality",
"biomarkers",
"pandemics",
"hospitalization",
"COVID-19",
"Infection",
"Cardiovascular disease",
"Respiratory disease"
],
"content": "Introduction\n\nThe past years have been marked by the emergence of a novel coronavirus (called SARS-CoV-2) and its global spread (Yi et al., 2020). The coronavirus disease 2019 (COVID-19) has a broad spectrum of clinical manifestations, ranging from no or mild symptoms to severe pulmonary involvement requiring hospitalization for respiratory support (Hazra et al., 2020; Mao et al., 2020). Older adults, immunocompromised subjects, and those with high comorbidity burden are more prone to severe illness, although the reasons are not yet fully understood (Pott Junior and Cominetti, 2021; Maquet et al., 2020; Richardson et al., 2020).\n\nSeveral studies have shown an association between severe illness and elevated serum levels of inflammatory markers such as erythrocyte sedimentation rate, C-reactive protein (CRP), ferritin, procalcitonin, interleukin-6 (IL-6), and interleukin-10 (IL-10), among others (Shu et al., 2020; Samprathi and Jayashree, 2021). This evidence has led to the assumption that disease severity is somehow related to an immune response shifts towards a systemic inflammatory state caused by unknown driving factors (Foo et al., 2021). Recently other markers have also been associated with disease severity, including N-type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, myocardial creatine kinase band (CK-MB), and cardiac troponin I (cTnI) (Qin et al., 2020). In particular, there seems to exist an association between COVID-19 severity and cardiovascular injury, especially among those experiencing longer lengths of hospitalization (Wang et al., 2020).\n\nSevere cases of COVID-19 often present elevated serum levels of D-dimer and cTnI, which have been associated with respiratory failure, thrombotic events, hospitalization, ICU admission, and mortality (Rajendran et al., 2021; Wibowo et al., 2021). In addition to the systemic inflammatory process, studies have shown that SARS-CoV-2 infects endothelial cells, cardiomyocytes, and cardiac endothelial cells (Liu et al., 2021; Lei et al., 2021). Thus, there are two possible concurrent mechanisms for cardiovascular involvement, including a direct effect of the virus on target cells and cell injury secondary to the systemic inflammatory process. These mechanisms are not mutually exclusive and probably act on each other (Balse and Hatem, 2021; Ho et al., 2021).\n\nThe objectives of this study were to examine (i) whether admission cardiovascular diagnostic testing with D-dimer and troponin measurement predicted early mortality among adults with COVID-19 and (ii), if so, how the disease severity influenced the association between these laboratory parameters and mortality.\n\n\nMethods\n\nThis study is a prospective cohort of adults admitted to the COVID-19 Unit of University Hospital at the Federal University of São Carlos (HU-UFSCar). This study was carried out according to the recommendations of the STROBE statement.\n\nThe study population included individuals aged ≥18 years diagnosed with COVID-19 when admitted to the COVID-19 Unit between June and January 2021, before the period of vaccination against the disease. All individuals must have had their diagnosis of COVID-19 confirmed by RT-PCR technique in at least 72h of the beginning of the symptoms. Exclusion criteria included a previous diagnosis of heart failure with known left ventricular (LV) reduced ejection fraction (LVEF<0.5); diagnosis of interstitial pulmonary fibrosis or known severe pulmonary disease that courses with fibrosis on chest tomography; and a previously known diagnosis of supraventricular or ventricular arrhythmias. Individuals' follow-up status was determined through hospital records; time-to-outcome was recorded in days.\n\nThe study followed the guidelines laid down in the Declaration of Helsinki, and all procedures involving research study participants were approved by the UFSCar's Research Ethics Committee (Number: CAAE: 34344520.8.0000.5504).\n\nData collection occurred through face-to-face interviews at hospital admission and included sociodemographic and clinical data, chronic comorbidities, and disease severity. Within the first 12 hours of admission, venous blood was sampled to analyze laboratory parameters. After admission, a professional involved in this study accompanied the clinical course of each participant until their discharge or death.\n\nMeasurements\n\nClinical evaluation. The following data were obtained: sex (male, female), age (years), systolic and diastolic blood pressure (mmHg), heart rate (bpm), respiratory rate (bpm), peripheral oxygen saturation (%), smoking habit (never, current), history of hypertension (yes, no), diabetes mellitus (yes, no), stroke (yes, no), myocardial infarction or known coronary artery disease (yes, no), and chronic obstructive pulmonary disease (yes, no). Medications in use and respectively diary dosage were also registered.\n\nLaboratory tests. The following tests were performed, in accordance with institutional protocol: complete blood count, PT/INR, D-dimer (mg/L), cTnI (ng/mL), c-reactive protein (mg/dL), urea (mg/dL), creatinine (mg/dL), sodium (mEq/L) and potassium mEq/L).\n\nQuantitative variables are presented as mean ± standard deviation or median (interquartile range) according to the Shapiro-Wilks normality test. The Mann-Whitney Wilcoxon test compared quantitative variables between groups. Categorical variables are presented as frequencies (percentages), and the Pearson's Chi-square test compared categorical variables between groups.\n\nKaplan-Meier analysis estimated overall survival probability and compared it between groups using the log-rank test. Cox proportional hazards regression models estimated each outcome's hazard risk (HR) and the 95% confidence interval (CI). Youden Index determined optimal cutoffs, while sensitivity, specificity, accuracy, and ROC curves assessed each model's diagnosis performances.\n\nStatistical significance was assessed at a two-sided p-value < 0.05. R version 4.0.3 (The R Foundation for Statistical Computing, Vienna, Austria) in R-Studio 1.3.1093 (RStudio Inc., Boston, USA) was used for all analyses.\n\n\nResults\n\nThe total of 105 patients met the inclusion criteria, but the analysis of the biomarkers was not possible in five patients, due to the temporary lack of kits. The final sample consisted of 100 hospitalized patients with COVID-19, as illustrated in the Figure 1.\n\nThe basal and clinical characteristics of the included patients are presented in the Table 1. Half of these patients needed admission in ICU and 19% died during the hospitalization. It is noteworthy that about 46% of hospitalized patients SAH, 23% had DM-2 and 16% known CAD.\n\nThe comparison of clinical and laboratory characteristics of survivors (N = 81) or non-survivors (N = 19) for COVID-19 during the hospitalization are shown in the Table 2. The patients who died were older (p > 0.001), predominantly of male gender (p = 0.02) and had lower platelet count (p < 0.001) and higher levels of cTnI (p = 0.003) and D-dimer (p = 0.002) dosed in the first 24 hours of admission compared with the survivors. There were no differences between the oxygen saturation in the admission and prevalence of comorbidities in the groups.\n\nRegarding other signals and symptoms in the admission, patients who died during hospitalization had more dyspnea sensation in the admission (p = 0.03). There was no difference between survivors and non-survivors in the following signals and symptoms: cough (p = 0.36) temperature (p = 0.90), systolic arterial pressure (p = 0.45) and heart rate (p = 0.35). In addition, there were no differences in the other laboratory markers between the groups.\n\nIn a multiple logistic regression model adjusted for age and oxygen saturation in the admission, including the biomarkers, platelets count was independently associated with death during the hospitalization (p = 0.019). The ROC curve showed area under the curve (AUC) of 0.74 [95% CI: 0.62-0.86; p = 0.001] and cutoff point < 185000/μL, sensitivity of 63% and specificity of 80% for mortality during hospitalization.\n\nRegarding other biomarkers, D-dimer had AUC of 0.74 [95% CI: 0.62-0.86; p = 0.001] and cutoff point ≥ 1.1 mg/L, sensitivity of 83% and a specificity of 65% for the prediction of mortality during hospitalization for COVID-19. These results are presented in Figure 2. The cTnI had not a good accuracy for mortality in this analysis, with AUC = 0.6 [95% CI: 0.44-0.77; p = 0.18].\n\nLegend. ROC: Standard operating curve.\n\nConsidering the Kaplan-Meier curves, as shown in Figure 3, hospitalized patients for COVID-19 and D-dimer ≥ 1.1 mg/L have a higher mortality when compared to those with D-dimer < 1.1 mg/L, dosed in the first day of the hospital admission. The curves of survival differed significantly in the log-rank test (p = 0.04).\n\nD-dimer values greater than or equal 1.1 mg/L were predictors of mortality during hospitalization. Log-Rank; p = 0.04.\n\n\nDiscussion\n\nThe great contribution of this manuscript is the possibility to identify hospitalized patients with infection by COVID-19 with higher risk of death during hospital stay. Lower platelets counts and higher levels of D-dimer showed good accuracy to detect unfavorable outcomes in these patients, in the pre-vaccination period. Values of D-dimer above or equal to 1.1 mg/L were predictors of in-hospital mortality in these patients.\n\nPlatelets are small cells without a nucleus, with a disc shape and are considered the smallest cell units synthesized by bone marrow megakaryocytes. The release of platelets are mediated by cytokines and chemokines (Ghoshal and Bhattacharyya, 2014). These cells play a role in blood clotting, wound healing, inflammation, tumor homeostatic balance, with an average life span between seven to ten days (Jurk et al., 2005; ((Lyn) Greenberg and (Sue) Kaled, 2013). Platelet count is also used as a biomarker in the identification of several diseases, especially those with a large acute inflammatory response, due to their ability to modulate the inflammatory response (Wu et al., 2020). Currently, one of the phenomena identified in patients hospitalized with COVID-19 is thrombocytopenia (Stasi, 2012). Our results corroborate with the literature and add new information: platelets count in the first hours of admission, in a model adjusted for age and risk factors, were independently associated with death in patients infected by COVID-19. Therefore, patients with thrombocytopenia need to be closely medically monitored, because of their increased risk of death during the hospitalization.\n\nAlthough the exact mechanism leading to thrombocytopenia related to patients hospitalized with COVID-19 is not known, there are studies that already showed a relationship between low platelet count and death for severe acute respiratory syndrome (SARS-CoV). The mechanism of SARS-COV-2 is very similar to SARS-COV: the inhibition of hematopoiesis in the bone marrow occurs through the interaction with certain receptors that cause a decrease in platelet formation and, consequently, thrombocytopenia (Xu, Zhou and Xu, 2020; Maquet et al., 2020). It is also described more aggregation of megakaryocytes and platelets and increased expression of P-selectin and CD40 that alter transcriptomes, changing the size, maturity and number of platelets that become more reactive to the organism itself. This leads to increased mortality in hospitalized patients with COVID-19 (Barrett et al., 2021). Furthermore, there is the release of mature megakaryocytes that cause a decrease or morphological alternation in the pulmonary capillary bed, leading to morphological destruction of platelet cells (Lei et al., 2021).\n\nLymphocytopenia was recently identified in association with SARS-COV-2, being considered an indicator of severity and hospitalized patients with COVID-19, in addition to having a direct association with the mortality rate (Tan et al., 2020; Zhao et al., 2020). In the present study, there was no significant association with low lymphocytes count and higher mortality. This probably occurred because of the limitation of the small sample.\n\nD-dimer levels are related to COVID-19 infection, mainly with disease severity and mortality during hospitalization (Zhang et al., 2020). Values of D-dimer above 1 mg/L are associated with changes in coagulation and inflammatory response (Yu et al., 2020). Patients with mild symptoms had lower levels than those with more severe symptoms (Logothetis et al., 2021). Thus, due to the cytokine storm caused by the acute infection of COVID-19, together with hypoxia secondary to lung injury and diffuse intravascular coagulation, it causes venous thromboembolism due to coagulopathy (Rostami and Mansouritorghabeh, 2020). Interestingly, in our study, mild elevation of D-dimer in the first hospital day (cutoff point 1.1 mg/L), even with no direct association with thromboembolic phenomenon, had a good accuracy for prediction of death during the days of hospitalization (Nadeem et al., 2021). Recent studies directly have described high levels of D-dimer during hospitalization as a predictor of mortality, especially in patients with DM and the elderly (Soni et al., 2020; Mouhat et al., 2020). Elevation of the D-dimer is usually due to a cytokine storm, and the increase in pro-inflammatory cytokines causes an imbalance in the coagulation system. Consequently, this leads to hypoxia through activation of the hypoxia-inducible transcription factor-dependent signaling pathway, favoring the onset of thrombosis (Poudel et al., 2021). Hypercoagulability is a direct factor related to increase D-dimer, being present in higher levels in hospitalized patients who died for lung tissue damage (Chocron et al., 2021). In addition, individuals with increased D-dimer often have myocardial injury and disseminated intravascular coagulation (DIC) on radiological examinations (Varikasuvu et al., 2021).\n\nCurrently, cTnI has been used as a biomarker related to COVID-19 infection. It is released mainly because of the myocardial injury caused by excessive inflammatory reaction through cytokine storms. Thus, these cardiac injuries are also related to increased mortality and hospitalizations, including respiratory complications (Liao et al., 2020). In our study, higher cTnI levels were more prevalent in non-survival patients. Nevertheless, cTnI had no good accuracy to identify patients with adverse outcomes. Despite this, one study pointed out that cTnI is a great predictor of 30-day mortality (Tersalvi et al., 2020).\n\nThe limitation of the study was the small sample size and limited kits for biomarkers analysis. The great relevance of this study was to identify biomarkers associated with more in-hospital mortality in the natural history of COVID-19, in the pre-vaccination period and without specifically aimed at the effective cure of this disease.\n\nFuture clinical perspectives implicate the comparison of the behavior of these markers in completely vaccinated hospitalized patients and how new advanced treatments may influence the inflammatory response.\n\n\nConclusion\n\nD-dimer high levels and platelet count at the first 24 h of admission have good accuracy in the detection of increased risk of death in hospitalized patients with COVID-19. These findings are important to identify in the first hours of hospitalization which patients have more risk of death and need a more intensive medical approach.\n\n\nData availability\n\nThe role of biomarkers in the prediction of mortality in hospitalized patients for COVID-19. DOI: https://doi.org/10.17605/OSF.IO/ND9QS (Cruz et al., 2022).\n\nThis project contains the following underlying data:\n\n- This supplementary material refers to the data of the study participants. Through these results of the attached spreadsheet, the analyzes were carried out and support the results of the manuscript under analysis for publication.",
"appendix": "Acknowledgments\n\nThe authors thank the entire medical, nursing and multidisciplinary team of the university hospital that dedicated themselves to the care of patients with COVID-19 included in this study.\n\n\nReferences\n\nBalse E, Hatem SN: Do Cellular Entry Mechanisms of SARS-Cov-2 Affect Myocardial Cells and Contribute to Cardiac Injury in COVID-19 Patients?. Front. Physiol. 2021; 12: 630778. Frontiers Media S.A. PubMed Abstract | Publisher Full Text\n\nBarrett TJ, et al.: Platelets contribute to disease severity in COVID-19. J. Thromb. Haemost. 2021; 19(12): 3139–3153. 2021/09/29. John Wiley and Sons Inc. PubMed Abstract | Publisher Full Text\n\nChocron R, et al.: D-dimer at hospital admission for COVID-19 are associated with in-hospital mortality, independent of venous thromboembolism: Insights from a French multicenter cohort study. Arch. Cardiovasc. Dis. 2021; 114(5): 381–393. 2021/03/09. Published by Elsevier Masson SAS. PubMed Abstract | Publisher Full Text\n\nCruz GA, Junior HP, Gregorio JP, et al.: The role of biomarkers in the prediction of mortality in hospitalized patients for COVID-19. [dataset].2022, June 28. Publisher Full Text\n\nFoo S-S, et al.: The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2. Cell Rep. Med. 2021; 2(11): 100453. 2021/10/27. Elsevier. PubMed Abstract | Publisher Full Text\n\nGhoshal K, Bhattacharyya M: Overview of Platelet Physiology: Its Hemostatic and Nonhemostatic Role in Disease Pathogenesis. Sci. World J. 2014; p. 781857. Edited by E. J. Benz, M. de F. Sonati, and L. Olcay. Hindawi Publishing Corporation. Publisher Full Text\n\n(Lyn) Greenberg EM, (Sue) Kaled ES: Thrombocytopenia. Crit. Care Nurs. Clin. North Am. 2013; 25(4): 427–434. Publisher Full Text\n\nHazra A, et al.: Coinfections with SARS-CoV-2 and other respiratory pathogens. Infect. Control Hosp. Epidemiol. 2020; 41(10): 1228–1229. 2020/07/03. Cambridge University Press. PubMed Abstract | Publisher Full Text\n\nHo HT, et al.: Myocardial Damage by SARS-CoV-2: Emerging Mechanisms and Therapies. Viruses. MDPI. 2021; 13(9): 1880. PubMed Abstract | Publisher Full Text\n\nJurk K, et al.: Platelets: Physiology and Biochemistry.2005; 1(212): 381–392.\n\nLei Y, et al.: SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2. Circ. Res. 2021; 128(9): 1323–1326. 2021/03/31. Lippincott Williams & Wilkins. PubMed Abstract | Publisher Full Text\n\nLiao D, et al.: Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Haematol. 2020; 7(9): e671–e678. 2020/07/10. Elsevier Ltd. PubMed Abstract | Publisher Full Text\n\nLiu F, et al.: SARS-CoV-2 Infects Endothelial Cells In Vivo and In Vitro. Front. Cell. Infect. Microbiol. 2021; 11: 701278. Frontiers Media S.A. PubMed Abstract | Publisher Full Text\n\nLogothetis CN, et al.: D-Dimer Testing for the Exclusion of Pulmonary Embolism Among Hospitalized Patients With COVID-19. JAMA Netw. Open. 2021; 4(10): e2128802–e2128802. American Medical Association. PubMed Abstract | Publisher Full Text\n\nMao R, et al.: Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol. Hepatol. 2020; 5(7): 667–678. 2020/05/12. Elsevier Ltd. PubMed Abstract | Publisher Full Text\n\nMaquet J, et al.: Thrombocytopenia is independently associated with poor outcome in patients hospitalized for COVID-19. Br. J. Haematol. 2020; 190(5): e276–e279. 2020/08/31. John Wiley and Sons Inc. Publisher Full Text\n\nMouhat B, et al.: Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients. Eur. Respir. J. 2020; 56(4): 2001811. European Respiratory Society. PubMed Abstract | Publisher Full Text\n\nNadeem I, et al.: Relationship of D-dimer and prediction of pulmonary embolism in hospitalized COVID-19 patients: a multicenter study. Future Microbiol. 2021; 16: 863–870. 2021/07/28. Future Medicine Ltd. PubMed Abstract | Publisher Full Text\n\nPott Junior H, Cominetti MR: Comorbidities predict 30-day hospital mortality of older adults with COVID-19. Geriatr. Nurs. (New York, N.Y.). 2021; 42(5): 1024–1028. 2021/06/19. Elsevier Inc. PubMed Abstract | Publisher Full Text\n\nPoudel A, et al.: D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19. PLoS One. 2021; 16(8): e0256744–e0256744. Public Library of Science. PubMed Abstract | Publisher Full Text\n\nQin J-J, et al.: Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19. Hypertension (Dallas, Tex.: 1979). 2020; 76(4): 1104–1112. 2020/07/14. Lippincott Williams & Wilkins. PubMed Abstract | Publisher Full Text\n\nRajendran V, et al.: Course of COVID-19 Based on Admission D-Dimer Levels and Its Influence on Thrombosis and Mortality. J. Clin. Med. Res. 2021; 13(7): 403–408. 2021/07/28. Elmer Press. PubMed Abstract | Publisher Full Text\n\nRichardson S, et al.: Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020; 323(20): 2052–2059. American Medical Association. PubMed Abstract | Publisher Full Text\n\nRostami M, Mansouritorghabeh H: D-dimer level in COVID-19 infection: a systematic review. Expert. Rev. Hematol. 2020; 13(11): 1265–1275. Taylor & Francis. PubMed Abstract | Publisher Full Text\n\nSamprathi M, Jayashree M: Biomarkers in COVID-19: An Up-To-Date Review. Front. Pediatr. 2021; 8. PubMed Abstract | Publisher Full Text\n\nShu T, et al.: Plasma Proteomics Identify Biomarkers and Pathogenesis of COVID-19. Immunity. 2020; 53(5): 1108–1122.e5. 2020/10/20. Elsevier Inc. PubMed Abstract | Publisher Full Text\n\nSoni M, et al.: D-dimer level is a useful predictor for mortality in patients with COVID-19: Analysis of 483 cases. Diabetes Metab. Syndr. 2020; 14(6): 2245–2249. 2020/11/17. Diabetes India. Published by Elsevier Ltd. PubMed Abstract | Publisher Full Text\n\nStasi R: How to approach thrombocytopenia. Hematology. 2012; 2012: 191–197. Publisher Full Text\n\nTan L, et al.: Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct. Target. Ther. 2020; 5(1): 33. Nature Publishing Group UK. PubMed Abstract | Publisher Full Text\n\nTersalvi G, et al.: Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J. Card. Fail. 2020; 26(6): 470–475. 2020/04/18. Elsevier Inc. PubMed Abstract | Publisher Full Text\n\nVarikasuvu SR, et al.: D-dimer, disease severity, and deaths (3D-study) in patients with COVID-19: a systematic review and meta-analysis of 100 studies. Sci. Rep. 2021; 11(1): 21888. Nature Publishing Group UK. PubMed Abstract | Publisher Full Text\n\nWang Y, et al.: Electrocardiogram analysis of patients with different types of COVID-19. Ann. Noninvasive Electrocardiol. 2020; 25(6): e12806–e12808. PubMed Abstract | Publisher Full Text\n\nWibowo A, et al.: Prognostic performance of troponin in COVID-19: A diagnostic meta-analysis and meta-regression. International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases. 2021; 105: 312–318. 2021/03/02. The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. PubMed Abstract | Publisher Full Text\n\nWu C, et al.: Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern. Med. 2020; 180(7): 934–943. PubMed Abstract | Publisher Full Text\n\nXu P, Zhou Q, Xu J: Mechanism of thrombocytopenia in COVID-19 patients. Annals of hematology. 2020; 99(6): 1205–1208. 2020/04/15. Springer Berlin Heidelberg. PubMed Abstract | Publisher Full Text\n\nYi Y, et al.: COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int. J. Biol. Sci. 2020; 16(10): 1753–1766. Ivyspring International Publisher. PubMed Abstract | Publisher Full Text\n\nYu B, et al.: Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis. J. Thromb. Thrombolysis. 2020; 50(3): 548–557. Springer US. PubMed Abstract | Publisher Full Text\n\nZhang L, et al.: D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J. Thromb. Haemost. 2020; 18(6), 1324–1329. John Wiley and Sons Inc. PubMed Abstract | Publisher Full Text\n\nZhao Q, et al.: Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis. International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases. 2020; 96: 131–135. 2020/05/04. The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "281046",
"date": "04 Jun 2024",
"name": "Motoi Ugajin",
"expertise": [
"Reviewer Expertise My specialty is respiratory medicine",
"especially infectious diseases such as pneumonia and tuberculosis."
],
"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 intend to describe the promising biomarkers for predicting the prognosis in patients with COVID-19 infection through this study. They concluded that platelet count and D-dimer are the useful biomarkers. However, from my view point, there are several flaws to reach the conclusion.\n1) In Page 3, the mentioned study duration is unclear. From June 2020 to January 2021?\n2) The authors could not include five patients in this study due to the lack of the measurement kits and underscored the importance of D-dimer through this study. Please provide the information on what kit was used to measure these biomarkers.\n3) Half of included patients required the admission in the intensive care unit. However, the vital signs of included patients on admission are missing. In order to clarify the patients’ characteristics, vital signs such as blood pressure, respiratory rate, and body temperature should be described.\n4) The variables included in the multiple logistic analysis are vague. Please provide the concrete information on the variables included into the multiple logistic analysis and the result of multiple logistic regression analysis as a separate table.\n5) In Page 5, the authors mentioned the adjustment of the multiple logistic regression model analysis using age and oxygen saturation. Please clearly describe the method of the adjustment. Otherwise, we cannot utilize the result into our daily clinical practice.\n6) Through the study, D-dimer was not the independent prognostic biomarker. Nevertheless, why do the authors pick up D-dimer for the prognostic biomarker in the ROC curve analysis and Kaplan-Meier model?\n7) What is the new finding through this study? What information can be added to the existing severity assessment scales such as Pneumonia Severity Index or CURB-65? Please describe that 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? 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? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "305695",
"date": "24 Jul 2024",
"name": "Sivananthan Manoharan",
"expertise": [
"Reviewer Expertise Systematic review and meta-analysis for COVID-19-related treatment."
],
"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\nGood day to the authors. Thank you for submitting and publishing your article in F1000 Research. I have read the article, and the authors should feel very proud for contributing an article addressing COVID-19. Although I am one of the reviewers, my role here is more like that of a reader than a reviewer. Here are my observations from the perspective of a reader.\nPage 1-method: Please add the duration of the study in the abstract to make the readers follow the work presented in this paper easily. Page 1-results: Please type 100 as a hundred when newly starting a sentence instead of writing it as 100. Page 2: Why does the corresponding author supply Gmail as a corresponding email address when the author has a valid institutional email address as traced in Google Scholar (Verified email at ufscar.br)? Page 3-method: Please provide the full term for STROBE with one or 2 sentence/s of brief explanation regarding this guideline to connect the readers to this article. Please add the name of the used kit. It is an essential information which is missing. Page 3-method: The authors mentioned as June-January 2021. Is it June 2020-January 2021? Page 3-method: There is no sample size calculation. How did the authors conclude that 100 patients’ samples are enough to derive the conclusion? Page 4-method: Given the abundance of other laboratory tests available to detect the biomarker(s), what justifies the selection of the ones listed on page 4? Page 4-results: State full term for SAH, DM, CAD abbreviations. The full terms are only available on page 5 (table 2). This may create difficulty for the readers. Page 5- Within survivors, how many of them are classified as mild, medium, and severe severity of COVID-19 disease? Did the authors pool all these patients without taking into account the severity of the disease, or was there any consideration for this? Why am I asking? Because there were 35 patients (43%, a huge number) admitted to the ICU (this is possibly the surviving most severe group). Although the patients survived, if the patients are categorized as severe COVID-19 patients, there may not be much statistical difference between the biomarkers’ readings between the surviving severe group (ICU group) and the non-survivors group. The outcome may be affected by simply pooling the data if disease severity is not considered. This statement is missing in the article. Having this statement will make us understand better regarding the risk of bias in the data analysis. Page 5: Table 2: Grouping the D-dimer data according to the severity of the disease would be more meaningful. As stated in point 9, the severity of the disease will cause an increase in blood D-dimer levels, resulting in blood thickening effect. Adding data from mild and medium severity groups could potentially 'dilute' the D-dimer data for survivors when combined without considering the severity of the disease. The authors have discussed the disease severity and level of D-dimer in COVID-19 patients on page 7 (last paragraph), but they are missing in their analyses. The authors have included more than 80% of good quality of references in the reference list.\n\nThank you.\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/11-753
|
https://f1000research.com/articles/11-752/v1
|
06 Jul 22
|
{
"type": "Research Article",
"title": "Seroprevalence of herpes simplex virus type-2 among pregnant women in Wad Madani-Sudan: a cross sectional study",
"authors": [
"Hind Ahmed",
"Nuha Abbu",
"Samar Saeed",
"Wafaa Abdalla",
"Kawthar MohammedSalih",
"Ahmed Abd Alla",
"Ahmed Hashim",
"Nuha Abbu",
"Samar Saeed",
"Wafaa Abdalla",
"Kawthar MohammedSalih",
"Ahmed Abd Alla",
"Ahmed Hashim"
],
"abstract": "Background: Sexually transmitted diseases are known to pose a significant public health threat. Herpes simplex virus type 2 (HSV-2) is a viral infection with high prevalence in Sudan, particularly among pregnant women. The aim of this study was to determine the seroprevalence of HSV-2 among pregnant women as well as their associated potential risk factors in Wad Madani-Sudan. Methods: In total, 92 pregnant women who attended the Maternity Hospital and Dr. Altigani Sedeeg Fertility Center at Wad Madani, AL-Gezira State, between April and August 2018 were included in this study. HSV-2 Immunoglobulins (IgG and IgM) were assayed by the enzyme-linked immunosorbent assay technique. Results: The seroprevalence of HSV-2 IgM and IgG were 35(38%) and 90(97.8%), respectively. A Higher prevalence of HSV-2 IgG 45(48.9%) and 13(14.1%) for IgM was detected in pregnant women aged 15-24 years old with a significant association between HSV-2 IgM and age distribution group (p-value=0.001). HSV-2 IgM and IgG seropositivity were highest in the first trimester; 26(34.2%), and 75(81.5%), respectively. The highest rate of HSV-2 IgM was detected in 19 (20.7%) women with a history of abortion, while the highest rate of HSV-2 IgG was seen in 50 (54.3%) women without a history of abortion. The statistical analysis results did not reveal significant differences between gestational stages and history of abortion with the presence of HSV-2 antibodies. Conclusion: The prevalence of HSV-2 was significant among pregnant women in Wad Madani- Sudan. There was a strong association between HSV-2 IgM seropositivity and the age of pregnant women.",
"keywords": [
"HSV-2",
"IgM",
"IgG",
"ELISA",
"pregnant women",
"Wad Madani",
"Sudan"
],
"content": "Introduction\n\nHerpes viruses are double-strand DNA viruses that belong to the family herpesviridae, subfamily Alpha herpesvirinae.1 Infection with herpes simplex virus (HSV) is one of the world’s most common viral sexually transmitted diseases2 that is categorised into HSV-type 1 (HSV-1) transmitted through oral contact, and HSV-type 2 (HSV-2) which is transmitted through sexual contact.3 Although there are a lot of undiagnosed cases as most infected persons are either asymptomatic or have genital symptoms that remain unrecognized,4 HSV-2 is the most leading cause of genital herpes, particularly in third world countries.5\n\nThe seropositivity of HSV-2 is increasing in individuals between the ages of 27-28 years worldwide.6 The seroprevalence of HSV-2 is higher in developing countries than in developed ones.7 Substantially greater HSV-2 levels have been observed in sub-Saharan Africa, where the prevalence in adults ages ranging from 10 to 50% in men and 30 to 80% in women.8 Females are more susceptible to HSV-2 (30%-80%) than males (10%-50%),9 because male-to-female transmission is easier than female-to-male transmission.10 The prevalence of Asian countries’ overall population indicates elevated values, from 10% to 30%.11 In developing nations, it is unusual to have regular health checks unless there is a sign and symptom of the disease, which contributes to the increasing rate of this disease. The frequency of HSV-2 infection among commercial female sex workers is above 80% in some African countries.9\n\nAs a prevalent pathogen, HSV also contributes to lifelong latent infection, and it is possibly associated with mother-to-fetus transmission involving the feto-placental unit.11,12 As such, this infection can cause considerable miscarriage among pregnant women and a higher risk to their infants leading to serious complications including intrauterine growth retardation, intrauterine fetal death, preterm labour, miscarriage, congenital and neonatal herpes infections13\n\nThe mortality rate for neonatal herpes (both HSV1 and 2) is 60% when left untreated.14 The risk of neonatal infection is 30% to 50% when HSV infection is acquired in the last trimester, although the risk in early pregnancy is only 1%.15 Approximately, 90% of all neonates’ HSV infections are transmitted during delivery and at least 5% are transmitted in utero.16 Despite the burden caused by these viruses, there are limited epidemiological data regarding these infections in Sudan. Therefore, the aim of this study was to assess the seroprevalence of HSV-2 and associated risk factors among pregnant women in Wad-Madani at Al Gezira State-Sudan.\n\n\nMethods\n\nThis descriptive cross-sectional study was conducted in Wad-Madani Maternity Hospital and Dr. Altigani Sedeeg Fertility Center in Al Gezira State in Sudan between April and August 2018. Data was collected through a questionnaire from pregnant women. Additionally, blood specimens were taken from selected pregnant women who had given consent after the aims and significance of the study had been explained.\n\nThe study was approved by the Ethical Committee of the College of Medical Laboratory Science, Sudan University of Science and Technology ethical approval No: (ECC-MLS-01-18).\n\nWritten informed consent was obtained from each participant before data collection and publication.\n\nBlood samples for antibody detection were collected from 92 randomly selected pregnant women and centrifuged at 3000 rpm for 5 minutes to obtain serum then stored at -20°C until tested.\n\nThe ELISA technique (Chemux BioScience, USA) (HSV2 IgM Kits Lot No: 18-D4-061 HSV2 IgG Kits Lot No: 18-D4-018) was done according to the instruction sheet. The samples were left to reach room temperature for at least 30 minutes after which they were mixed thoroughly by the vortex, prior to use. Dilutions (1:40) were prepared by adding 5 μL of the sample (added once), negative control, positive control, and calibrator, to 200 μL of sample diluent. 100 μL of diluted sera, calibrator, and controls were added to a flat-bottom 96-well plate. The plate was incubated at room temperature for 30 minutes. A 100 μL of enzyme conjugate was added to each well and incubated for further 30 minutes at room temperature, then the enzyme conjugate from all wells were removed, and the plate was washed three times with washing buffer. A 100 μL of 3,3′5,5′-Tetramethylbenzidine (TMB) chromogenic substrate was added to each well and incubated for 15 minutes at room temperature, followed by 100 μL of stop solution. The plate was read on a microplate reader at 450 nm (the sample added once). HSV-2 IgM/IgG Index less than 0.90 was considered negative for IgM/IgG antibody, while HSV-2 IgM/IgG Index between 0.91-0.99 were considered as equivocal. HSV-2 IgM/IgG Index of 1.00 or greater is positive for IgM/IgG antibody.\n\nThe data were analyzed by Statistical Package for Social Sciences (SPSS) software version 11.5. Frequencies, means and standard deviations (SD) were calculated. Pearson Chi-square test was performed between qualitative variables. A p.value of ≤ 0.05 was considered as significant for all statistical tests in this study.\n\n\nResults\n\nIn this study, 92 pregnant women aged between 15 till 44 years (26+ 6.103 SD) were included. In total, 46 of pregnant women were 15-24 years old, 35 were 25-34 years old, and 11 were 35-45 years old.\n\nIt was observed that the seroprevalence of HSV-2 IgM antibodies was 35(38%), while for HSV-2 IgG it was 90(97.8%) (Figure 1. When considering the age group, ut of the 92 pregnant women; HSV-2 IgM was detected in 13 (14.1%) and IgG in 45 (58.9%) among age group15–24 years; 12(13%) for IgM, and 34(36.9%) for IgG among (25-34) years; and 10(10.9%) for IgM and 11(12%) for IgG among (35-44) years. Furthermore, the seropositivity of HSV-2 IgM/IgG during gestational stages were: 26/35 (34.2%), 75/90 (81.5%) in the first trimester, and 9/35 (9.8%), 15/90 (16.3%) in the second trimester for IgM and IgG, respectively. The seroprevalence of HVS-2 IgM among pregnant women with a history of abortion was 19 (20.7%), while HSV-2 IgG was 40 (43.5%). In addition, 16 (17.4%) cases of IgM and 50 (54.3%) cases of IgG were detected among pregnant women without a history of abortion. In this study, the seroprevalence of HSV-2 IgM showed a high association with the age of pregnant women (p.value=0.001), while gestational stage and history of abortion showed no association with seroprevalence of both HSV-2 IgM and IgG (p.value >0.05) as shown in Table 1.\n\n\nDiscussion\n\nHSV is a common sexually transmitted infection, and the prevalence of this infection has increased significantly over the last two decades in many developed and developing countries.17 In the reproductive age group, it is an important cause of intra-uterine fetal and neonatal infection when transmitted from mother to fetus.17\n\nThe results of this study indicated that the seroprevalence of HSV-2 IgM among pregnant women was 38% and 97.8% for IgG. Slightly similar results were observed by Alshareef et al. (2017) in Sudan, who reported 87.8% of pregnant women were HSV-2 IgG positive.18 Another study conducted by Zaki and Goda (2007), in Egypt showed that 40% of pregnant women were positive for IgM,19 while a study conducted in Cote D’Ivoire by Cisse et al. (2015) indicated that 96.5% tested positive for HSV-2 IgG.20\n\nThe obtained results were relatively high when compared with similar studies carried out in other Sudan states and other countries.21,22 The reason for this difference could be related to the rate of virus exposure, the virus’s presence in a certain region, the virus’s susceptibility rate, and people’s immunological condition. Unlike the mentioned studies, lower results were obtained by Hussan (2014) in Baghdad, who reported that the prevalence of HSV-2 IgM was 4.76% among pregnant women.23\n\nThe present study found an increase in HSV-2 seroprevalence in the age groups 15–24 years 12(34. 2%), this was consistent with many studies done in Sudan such as Edress and Elhag (2015) and El-Amin et al. (2013).21,22 Also, the similar result was found in a study by Tiwari et al. (2016) in New Delhi, India.24 There are many reasons that may explain the high incidence of HSV-2 in women in this age group, especially individuals aged 20 to 29 years, as these women are highly reproductive in this age range and are more susceptible to chronic infections such as HSV-2, and the prevalence of primary or recurrent HSV-2 infection peaks during this time period.\n\nAccording to the gestational stage, HSV-2 IgM and IgG were the highest in the second trimester (52.9%) followed by the first trimester (34.6%). These findings agreed with Edress and Elhag (2015), who reported the percentage of IgM to be 1.7% in the first trimester and 3.7% in the second trimester21 and Mezher et al. (2018) in Iran found that HSV-2 seropositivity was (16.7%), (29.2%) in the first trimester, and (45.8%), (8.3%) in the second trimester for aborted and pregnant women, respectively.25 While, Mohammad and Salman showed a maximum rate of HSV-2 infection at second trimester,26 and Amar et al. (2015) in India showed that the seropositivity of IgM were 3.3% in the first, and 1.1% in the second trimester.27\n\nThe prevalence of HSV-2 IgG, IgM antibody among women who have had a history of abortion was not significant (p value>0.05) compared to women without a history of abortion. These finding was not in line with Assayaghi et al. (2017) in Yemen (p-value 0.6, 0.4) and Oluwapelumi et al. (2020).28,29 Another study by Mezher et al. (2018) indicated that the detection of HSV-2 in women who had a history of abortion was higher than in pregnant, and that may improve the probability of this virus as one of the main viral agents that cause abortion. Many studies have suggested that HSV-2 infection may be a risk factor for miscarriage abortion; nevertheless, HSV-2 infection was detected in a small percentage of women with a history of abortion, suggesting that HSV infection is unlikely to be a major factor in abortion.25\n\nThe variation in the obtained results may be due to geographical regions where the studies were conducted, the sample size technique used for analysis, and the limited period which those studies were carried out.\n\n\nConclusion\n\nTo the authors’ knowledge, there is no published data about the prevalence of HSV-2 among pregnant women in Wad-Madani, Al Gezira State, Sudan. As a result of this study there was a significant frequency of HSV-2 infection among pregnant women in Wad-Madani, particularly among those aged 15 to 24 years.\n\nThere was a significant relationship between HSV-2 IgM seropositivity and the age of the pregnant woman. However, the differences between HSV-2 IgG and IgM seropositivity rates in other socio- epidemiological data (gestational trimester and history of abortion) didn’t display statistical significance.\n\nFurther studies were recommended.\n\n\nLimitations\n\nIt is necessary to analyze these findings with more advanced techniques and study the role of HSV-2 in abortion with a larger sample size in order to fully support these conclusions. Also, the analytical study designs can give more accurate results. As this was a cross-sectional study, no assessments were done for pregnant women for subsequent miscarriage or neonatal death. Case control or cohort’s studies will obtain more accurate results and the relation between risk factors and outcomes will be highlighted clearly.\n\n\nData availability\n\nFigshare: Herpes simplex virus, https://doi.org/10.6084/m9.figshare.19375088.v4\n\nThis project contains the following underlying data:\n\nData file 1. Study questionnaire\n\nData file 2. ELISA data\n\nNuha.xls (HSV-2 raw Data)\n\nNuha dictionary.docx. (HSV-2 data dictionary)\n\nData are available under the terms of the Attribution 4.0 International (CC BY 4.0)",
"appendix": "References\n\nCarter J, Saunders V, Saunders VA: Virology: principles and applications. John Wiley & Sons;2007 Aug 15.\n\nAnzivino E, Fioriti D, Mischitelli M, et al.: Herpes simplex virus infection in pregnancy and in neonate: status of art of epidemiology, diagnosis, therapy and prevention. Virol. J. 2009 Dec; 6(1): 40. PubMed Abstract | Publisher Full Text\n\nWHO: Herpes simplex virus. Key fact.March 2022.Reference Source\n\nMnisi HP, Samie A: Prevalence of HSV1 and HSV2 among HIV and AIDS patients in the Limpopo Province by real time PCR using urine samples. Int. J. Infect. Dis. 2014 Apr 1; 21: 148. Publisher Full Text\n\nSen P, Barton SE: Genital herpes and its management. BMJ. 2007; 334(7602): 1048–1052. PubMed Abstract | Publisher Full Text\n\nWhitley RJ: Herpes simplex encephalitis: adolescents and adults. Antivir. Res. 2006 Sep 1; 71(2-3): 141–148. Publisher Full Text\n\nLooker KJ, et al.: An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection. Bull. World Health Organ. 2008; 86(10): 805–812. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDaniels B, Wand H, Ramjee G: Prevalence of herpes simplex virus 2 (HSV-2) infection and associated risk factors in a cohort of HIV negative women in Durban, South Africa. BMC. Res. Notes. 2016 Dec; 9(1): 1–8. Publisher Full Text\n\nWeiss H: Epidemiology of herpes simplex virus type 2 infection in the developing world. Herpes. 2004 Apr; 11 Suppl 1: 24A–35A. PubMed Abstract\n\nDerSarkissian C: How Common Is Genital Herpes?March 09, 2022.Reference Source\n\nCusini M, Ghislanzoni M: The importance of diagnosing genital herpes. J. Antimicrob. Chemother. 2001 Feb 1; 47(suppl_1): 9–16. Publisher Full Text\n\nNigro G, Mazzocco M, Mattia E, et al.: Role of the infections in recurrent spontaneous abortion. J. Matern. Fetal Neonatal Med. 2011 Aug 1; 24(8): 983–989. PubMed Abstract | Publisher Full Text\n\nHaider M, Rizvi M, Khan N, et al.: Serological study of herpes virus infection in female patients with bad obstetric history. Biol. Med. 2011; 3(2): 284–290.\n\nLooker KJ, Magaret AS, May MT, et al.: First estimates of the global and regional incidence of neonatal herpes infection. Lancet Glob. Health. 2017 Mar; 5(3): e300–e309. PubMed Abstract | Publisher Full Text\n\nChauhan AR, Patel A, Jamdade K, et al.: Journal of Postgraduate Gynecology & Obstetrics. Herpes. 2014 Jun; 1(6).\n\nCiavattini A, Vichi M, Rinci A, et al.: Infezioni virali in gravidanza: gestione e raccomandazioni. La Colposcopia in Italia. 2007; 2: 11–16.\n\nPaz-Bailey G, Ramaswamy M, Hawkes SJ, et al.: Herpes simplex virus type 2: epidemiology and management options in developing countries. Sex. Transm. Infect. 2007 Feb 1; 83(1): 16–22. PubMed Abstract | Publisher Full Text\n\nAlshareef SA, Eltom AM, Nasr AM, et al.: Rubella, herpes simplex virus type 2 and preeclampsia. Virol. J. 2017 Dec; 14(1): 1–4. Publisher Full Text\n\nZaki ME, Goda H: Relevance of parvovirus B19, herpes simplex virus 2, and cytomegalovirus virologic markers in maternal serum for diagnosis of unexplained recurrent abortions. Arch. Pathol. Lab. Med. 2007 Jun; 131(6): 956–960. PubMed Abstract | Publisher Full Text\n\nCisse C, Zaba F, Meite S, et al.: Seroprevalence of herpes simplex virus 2 infection among pregnant women in urban health training Yopougon-Attie (Cote Divoire). J. Med. Lab. Diagn. 2015 Apr; 6(3): 17–21. Publisher Full Text\n\nEdress HE, Elhag WI: Seroprevalence of herpes simplex virus type 2 among pregnant women attending Ibrahim Malik Teaching Hospital, Khartoum State, Sudan. Am. J. Res. Commun. 2015; 3(11): 149–160.\n\nEl-Amin EO, Elamin OE, Ahmed RA, et al.: Sero-prevalence of herpes virus infection in Sudanese pregnant women. Trop. Med. Surg. 2013 Sep 1.\n\nHussan BM: Study the prevalence of ACL, APL, CMV, HSV, Rubella and Toxoplasma gondii in aborted women in Baghdad. Med. J. Babylon. 2013; 10(2): 455–464.\n\nTiwari S, Arora BS, Diwan R: TORCH IgM seroprevalence in women with abortions as adverse reproductive outcome in current pregnancy. Int. J. Res. Med. Sci. 2016 Mar; 4(3): 784–788. Publisher Full Text\n\nMezher MN, Mejbel FA, Hussein HK: Detection of Herpes Simplex-2 Virus in Women with Spontaneous Abortion in Al-Najaf City/Iraq. J. Pharm. Sci. Res. 2018; 10(5): 0975.\n\nMohammad EA, Salman YJ: Study of TORCH infections in women with Bad Obstetric History (BOH) in Kirkuk city. Int. J. Curr. Microbiol. App. Sci. 2014; 3(10): 700–709.\n\nAmar OA, Bajaj HK, Gupta N, et al.: Prevalence of herpes simplex virus in pregnant women from gangetic plain region of Allahabad, India. Adv. Microbiol. 2015; 05(06): 404–408. Publisher Full Text\n\nAssayaghi RM, Al-Jaufy AY, Al-Robasi AA: Seroprevalence and Risk Factors for Herpes Simplex Virus Type 1 and 2 among Women Attending Antenatal and Gynecology Clinics in Sana’a City-Yemen. J. Hum. Virol. Retrovirol. 2017; 5(4): 00163. Publisher Full Text\n\nOluwapelumi OB, Peace FO, Yomi AR, et al.: Prevalence of herpes simplex virus type 2 antibodies among pregnant women attending Federal Teaching Hospital, Ido-Ekiti, Nigeria. World J. Adv. Res. Rev. 2020; 6(1): 200–206."
}
|
[
{
"id": "143500",
"date": "28 Jul 2022",
"name": "Wafa Ibrahim Elhag",
"expertise": [
"Reviewer Expertise Medical microbiology (virology",
"bacteriology",
"mycology)",
"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\nA very good research topic.\nIt needs editing and summarizing repeated words, especially in the abstract.\n\nThe data collection method, tools, and analysis must be very clear and stated in the abstract.\n\nIn the abstract, the results can be presented in a summary to highlight the important results as it was already in the result section as text and tables.\n\nIn the first paragraph of the discussion: \"HSV is a common sexually transmitted infection\", this can be replaced with \"HSV causes a common sexually transmitted infection.\"\n\nMost of the references are old.\n\nWhat about gravidity?\n\nSample size: why 92, did it represent the community?\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": "160948",
"date": "09 Feb 2023",
"name": "Oksana Debrah",
"expertise": [
"Reviewer Expertise Biomarkers",
"infectious disease (HIV",
"HPV",
"HSV)",
"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 selected a very important topic, as herpes simplex virus infection is a public health problem globally and particularly in developing populations. Due to the high incidence of genital herpes in the population, it is important to focus on the herpes simplex viruses and their potential impact on pregnancy. It is very important to identify the prevalence of this infection among the population of pregnant women and associated risk factors in the country to notify the public.\nThe manuscript contains some grammatical and punctuation errors. Please, revise the manuscript to conform to scientific English.\nBelow are more specific comments by section:\nAbstract: It is advised to revise the structure of the 'Abstract' to improve the quality of the paper (for example, background, methodology etc.). Clarification is needed regarding the justification. Authors mentioned that the prevalence of HSV-2 among pregnant women is high in Sudan. So what was the reason to conduct this study?\n\nIntroduction: The structure of the introduction is very poor. In consideration of the importance of the introduction and literature review for academic articles, I advise that the introduction should be complemented in the paper to make research meaning, purpose, progress clearer. Please, supplement in the paper.\n\nMethodology: The method used is appropriate, but not detailed. Please, provide sufficient details to allow the work to be reproduced by an independent researcher. Clearly state inclusion and exclusion criteria, more details on questionnaire and data collectors. State the data protection plan.\n\nResults: Results should be clear and concise. I suggest that the authors should look at the structure of this section and improve scientific English. Presentation of tables should be improved. The sample size is small to represent the population.\n\nDiscussion: This section should explore the significance of the results of the work, not repeat them. The discussion of the paper is a bit simple and mainly compares the results from different publications. The results should be discussed from different angles and placed into context without being over-interpreted. Authors may add the recommendations.\n\nConclusion: I suggest the authors draw a more meaningful conclusion for the study from different aspects.\n\nReviewer's Conclusion: Approved with reservations\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": []
},
{
"id": "160944",
"date": "15 Feb 2023",
"name": "David A. Leib",
"expertise": [
"Reviewer Expertise Pathogenesis and immunity to HSV"
],
"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 their manuscript, Ahmed et al. sought to assess HSV-2 seroprevalence and hypothesized risk factors among a sample of pregnant women in Sudan. This study is clinically important and of interest to herpesvirus researchers. However, the data analysis and presentation are not optimally designed to communicate population risk, and the discussion and conclusion reached do not fully agree with the data shown. The data included is of high value, but multiple methodological improvements would reinforce the authors’ conclusions.\nThe strengths of the study are primarily found in its novelty and global importance. Very little data is available about HSV-2 prevalence in pregnant women, and even less is available regarding HSV-2 prevalence in Africa. An understanding of baseline population rates is critical clinically and has the potential to eventually improve care of conditions causing substantial morbidity and mortality, such as neonatal herpes infection. Weaknesses of this study are related to methodology, including the lack of inclusion of the clinically-relevant third trimester. Most importantly, they include the sampling method, data analysis, and conflicting data interpretation between the results and discussion sections. Overall, the impact of the manuscript may be increased through the addition of data from the third trimester, additional data analysis, and discussion regarding the unexpected results given the chronic nature of the infection.\nMajor Comments\nThe results presented in the abstract and results section do not completely agree with the data referenced in the discussion.\n\nWe suggest reporting % positivity according to gestational age using the proportion of the sample in the given trimester as a denominator instead of the total number of positives for the antibody isotype (number of positives/number of women in trimester). This may be more meaningful at the population level by indicating a baseline prevalence, as opposed to reporting solely the proportion of known positives by trimester without the context of the total sample.\n\nPerform a power analysis or increase study size, the results are surprising for a chronic infection and the sample may not be representative of the population.\n\nGiven the cumulative nature of a chronic infection and exposure over time, the finding of the highest % positivity in young women is unexpected and may be indicative of a sample that is not representative of the population\n\nSimilarly, higher % positivity in the first trimester compared to the second is unexpected.\n\nWhat data was collected in the questionnaire? Was it self-reported?\n\nIs medical history self-reported? Can it be chart-linked?\n\nWhat population sampling strategy was used? Did it result in a representative sample? How was this determined? What were the inclusion criteria?\n\nWhy was the third trimester not included? If this data is available, it would be an extremely helpful addition. This is the most clinically-relevant trimester with regard to neonatal herpes acquisition.\n\nThe results and discussion sections do not agree (the data indicate highest % positivity in the first trimester, the discussion references higher % positivity in the second trimester).\n\nMinor Comments\nThere are some typographical errors in figure and text.\n\nThe y-axis in Figure 1 needs a label.\n\nClarify miscarriage (or spontaneous abortion) vs. induced abortion.\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/11-752
|
https://f1000research.com/articles/11-748/v1
|
06 Jul 22
|
{
"type": "Software Tool Article",
"title": "MAFDash: An easy-to-use dashboard builder for mutation data",
"authors": [
"Ashish Jain",
"Mayank Tandon"
],
"abstract": "Characterizing the somatic mutation landscape of a cohort of patients has become a routine task in cancer research in recent years. Such studies are often highly interdisciplinary, requiring iterative analysis that must be evaluated at each step by many researchers. Therefore, there is a growing need for reporting tools that can easily generate interactive reports for sharing data and results with collaborators. Here we present an R package, MAFDash, that tries to simplify summarization and visualization of mutation data from Mutation Annotation Format (MAF) files. The output HTML dashboard is a self-contained report that can be used for downstream analysis and sharing results. MAFDash is freely available on Github (https://github.com/CCBR/MAFDash).",
"keywords": [
"MAF",
"Mutation",
"Single Nucleotide Variants",
"Visualization",
"Dashboard",
"WES",
"WGS"
],
"content": "Introduction\n\nIn the last decade, the cost of next-generation sequencing (NGS) has gone down exponentially as both throughput and novel methods continue to advance.1 For human clinical research, this has been reflected in an ever-growing number of datasets describing genomic variation among both normal and disease cohorts, including the 1000 Genomes Project Consortium,2 and the more recent gnomAD project,3 which still serve as important benchmarks of normal genomic variation in humans. Similar efforts for characterizing somatic mutations in cancer research have been completed for 33 tumor types by The Cancer Genome Atlas (TCGA) consortium,4 and over 1,700 cancer cell lines in the Cancer Cell Line Encyclopedia (CCLE) project from the Broad Institute.5 Although both TCGA and CCLE provide mult-omics data, single nucleotide polymorphisms (SNPs) and small insertion/deletions (Indels) from NGS data are often used as starting points for downstream analyses diving deep into the biological pathways and identifying drug target genes in these cancers.6\n\nBoth TCGA and CCLE provide somatic mutations freely as Mutation Annotation Format (MAF) files. This format is used to report high quality somatic variants for cohorts of cancer patients as it is more readable and portable than the traditional variant call format (VCF), and is therefore a common starting point for downstream analysis of somatic SNP/Indel data. R packages like ‘maftools’7 are frequently used by bioinformaticians to read, summarize, and perform statistical tests on data from MAF files, and they provide excellent functions for basic visualization, and flexible manipulation of the underlying data.\n\nSince MAF files can contain a large number of annotations (e.g. the vcf2maf tool from MSKCC8 produces 136 columns of annotations with a default installation of Variant Effect Predictor9), selecting useful information and preparing it for discussion with researchers requires expertise. To simplify this task, we have developed MAFDash, an R package that helps to quickly create HTML dashboards for summarizing and visualizing data from MAF files. The resulting HTML file serves as a self-contained report that can be used to explore and share the results. MAFDash provides preset functions for extracting and organizing somatic variant data into interactive tables and figures. The goal of this package is to provide a simplified interface to filter and present data from MAF files suitable both for highly customized reports, as well as routine output from variant calling pipelines. The package also provides functions to generate individual plots as a ggplot210 or ComplexHeatmap11 object giving users more flexibility.\n\n\nMethods\n\nMAFDash is a package intended for use with the R programming language.12 The report is generated with a parameterized R Markdown script to arrange all the information. If a MAF object is provided, an interactive table is generated to provide client-side, dynamic filtering of the variant data. In addition to the dashboard generation, it also consists of a variety of functions to generate high quality figures to visualize mutation data. We also provided detailed documentation and a test dataset to demonstrate usage of these functions. Static plots are generated using the R packages ‘maftools’,7 ComplexHeatmap,11 ‘circlize’,13 and ‘ggplot2’.10 Interactive visualizations are implemented using ‘canvasXpress’14 and ‘plotly’.15\n\nMAFDash was developed and tested on 2019 Macbook Pros with 2.4GHz 8-core Intel Core i9 processors and 16 Gb of memory, running Mac OS X 10.15.7 (Catalina). The source code and documentation is hosted on Github (https://github.com/CCBR/MAFDash).\n\nThe function getMAFdataTCGA(…) retrieves TCGA mutation data in MAF format. This function takes the cancer code(s) as input and outputs the TCGA mutation data called from Mutect2,16 or other callers as available. This function internally uses the ‘TCGAbiolinks’ R package17 to download the data and then uses internal processing to output the mutation data in a clean format. For annotation information, the getTCGAClinicalAnnotation(…) function extracts and processes common clinical features provided with the TCGA data including pathological state, tissue site, age, gender, race, and vital status, and generates reasonable preset colors suitable for use with ‘ComplexHeatmap’. The processed mutation data along with the clinical annotations can be further analyzed by utilizing the various visualization functions in MAFDash.\n\nThe filterMAF(…) function in MAFDash automatically detects the presence of relevant columns and re-casts them appropriately for numeric or text-based filtering. These include tumor read frequency and depth, frequency in population databases (gnomAD18 and ExAC19), and consensus mutation calls from multiple variant callers. Such criteria are frequently used for determining tumor mutational burden (TMB) from whole-exome sequencing data.20\n\nThis function also can also remove a preset list of commonly mutated genes,21 or a custom set of genes. Finally, data is processed in definable chunks of lines (default of 10,000 lines), which is intended to help filter large MAF files without getting “out of memory” issues.\n\nMAFDash consists of various functions for visualizing summarized mutation data across a cohort of samples. Below are the different functions that are provided.\n\n• generateBurdenPlot(…): It generates a dotplot and a barplot to show the comparison of the total number of mutations across the samples. The mutations are also grouped based on its type.\n\n• generateMutationTypePlot(…): It generates a barplot showing the distribution of the silent and non-silent mutations across the input samples.\n\n• generateOncoPlot(…): It generates a heatmap that summarized the top mutated genes across the input samples.\n\n• generateOverlapPlot(…): It generates a circular plot to show the common mutations across the input samples.\n\n• generateRibbonPlot(…): It generates a heatmap to show the cosine similarity between the mutated genes using the result from maftools’ somaticInteractions(…) function.\n\n• generateTiTvPlot(…): It plots the frequency of transitions and transversions of the gene mutations in the input datasets.\n\n• generateTCGAComparePlot(…): It computes and plots the mutation load of the input MAF against all 33 of the TCGA cohorts derived from MC3 project. It also calculates the significant mutational load differences between the cancers.\n\nMutational signature matrix for single-base substitutions (SBS) were retrieved from COSMIC v3.2.22 Text in the “Acceptance criteria” section of each signature page was retrieved from the COSMIC website using R scripts. This free text was lightly filtered and manually curated yielding 25 broad categories for 78 total signatures and is provided with the package repository in tabular format (Table 1).\n\nTo aid interpretation of mutational signature analysis, we have curated COSMIC signatures etiologies from COSMIC v3.2.22 Specifically, we scraped the COSMIC website to retrieve the proposed etiology for all 78 COSMIC single-base substitution (SBS) signatures, yielding 36 unique etiologies, which we further manually curated into 25 broad categories. The generateCOSMICMutSigSimHeatmap(…) function shows these categorized proposed etiologies as colored row annotations, aimed at quickly identifying distinct or common etiologies across a cohort. Figure 1 shows the SBS signature in each sample in columns, COSMIC mutation signatures in rows, and each cell is colored to indicate the level of similarity between the two.\n\n\nUse cases\n\nMAFDash has a function (getMAFDashboard(…)) that generates an HTML dashboard for visualization and analysis of mutation data in MAF format. The dashboard consists of arbitrarily defined or preset interactive plots describing the data. By default, if MAF data is provided, the dashboard visualizes the mutations data in five different tabs.\n\n• Summary plots: Static multi-part figure describing cohort summaries of variant classification, variant type, number of variants per samples and nucleotide change (from ‘maftools’).\n\n• Burden plots: Interactive plots showing the number of variants per samples in the form of a dotplot and barplot, with hover text containing sample and mutation information.\n\n• Oncoplot: Plot summarizing the top mutated genes across the samples.\n\n• Co-occurrence of mutated genes: A circular ribbon plot showing co-occurrence of the mutations, inspired by the somaticInteractions(…) function in ‘maftools’.\n\n• Interactive heatmap: An interactive version of the oncoplot with hover text showing the number of mutations in a gene for a particular sample.\n\nIn addition to these plots, an interactive table is generated using the DT23 and crosstalk24 R packages to provide client-side, dynamic filtering of the variant data. The generated dashboard is self-contained for sharing with collaborators. MAFDash will automatically account for missing data and also provides reasonable defaults for filtering mutation data. Figure 2 shows the dashboard output for Adrenocortical carcinoma (ACC) downloaded from TCGA.6\n\nEven without MAF data, MAFDash can be used to generate an HTML report with user generated plot objects. Users can pass any ‘ggplot2’, ‘ComplexHeatmap’, or ‘plotly’ objects, or the location of an image file to include it in the dashboard as a list, and have it rendered as a dashboard with each element as a tab in the report. Figure 3 shows an example dashboard using the iris dataset provided with R.\n\n\nConclusions\n\nWe developed MAFDash to simplify the process of generating interactive reports for somatic mutation analysis. The ‘maftools’ R package already provides a comprehensive toolkit for organizing and analyzing MAF data, but it exclusively uses base R graphics for plotting, which is not amenable to further modification or interactivity. For example, the tcgaCompare(…) function is an excellent visual comparison of mutation burden with all cancer types in TCGA. To allow interactivity in MAFDash, we implemented the same visualization using ‘ggplot2’, which can trivially be converted to an interactive HTML widget using ‘plotly’. Finally, the self-contained nature of the HTML report, as well as a range of choices for interactive plots, is aimed at easily sharing data and interpretations. Overall, we hope that MAFDash will allow for quick iterations of analysis during collaborations between bioinformaticians and bench scientists.\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\nSoftware availability\n\n\n\n• Source code available at: https://github.com/CCBR/MAFDash\n\n• Archived source code at time of publication: https://doi.org/10.5281/zenodo.642183325\n\n• License: MIT License",
"appendix": "Acknowledgements\n\nWe would like to thank CCR Collaborative Bioinformatics Resource (CCBR) members for their feedback.\n\n\nReferences\n\nKris A: Wetterstrand. The cost of sequencing a human genome.2022.Reference Source\n\nConsortium Genomes ProjectAuton A, Brooks LD, et al.: A global reference for human genetic variation. Nature. 2015; 526(7571): 68–74. ISSN 1476-4687 (Electronic) 0028-0836 (Linking). PubMed Abstract | Publisher Full Text\n\nGudmundsson S, Singer-Berk M, Watts NA, et al.: Variant interpretation using population databases: Lessons from gnomad. Hum. Mutat. 2021. ISSN 1098-1004 (Electronic) 1059-7794 (Linking). Publisher Full Text Reference Source\n\nCancer Genome Atlas Research NetworkWeinstein JN, Collisson EA, et al.: The cancer genome atlas pan-cancer analysis project. Nat. Genet. 2013; 45(10): 1113–1120. ISSN 1546-1718 (Electronic) 1061-4036 (Linking). PubMed Abstract | Publisher Full Text\n\nBarretina J, Caponigro G, Stransky N, et al.: The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483(7391): 603–607. ISSN 1476-4687 (Electronic) 0028-0836 (Linking). PubMed Abstract | Publisher Full Text\n\nZheng S, Cherniack AD, Dewal N, et al.: Comprehensive pan-genomic characterization of adrenocortical carcinoma. Cancer Cell. 2016; 29(5): 723–736. ISSN 1535-6108. PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nMayakonda A, Lin DC, Assenov Y, Plass C, et al.: Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 2018; 28(11): 1747–1756. ISSN 1549-5469 (Electronic) 1088-9051 (Linking). PubMed Abstract | Publisher Full Text\n\nMemorial Sloan Kettering Cancer Center: vcf2maf.2013.Reference Source\n\nMcLaren W, Gil L, Hunt SE, et al.: The ensembl variant effect predictor. Genome Biol. 2016; 17(1): 122. ISSN 1474-760X (Electronic) 1474-7596 (Linking). PubMed Abstract | Publisher Full Text\n\nWickham H: ggplot2: Elegant Graphics for Data Analysis. New York:Springer-Verlag;2016. ISBN 978-3-319-24277-4.Reference Source\n\nGu Z, Eils R, Schlesner M: Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics. 2016; 32 (18): 2847–2849. ISSN 1367-4811 (Electronic) 1367-4803 (Linking). PubMed Abstract | Publisher Full Text\n\nR Core Team: R: A language and environment for statistical computing.2020.\n\nGu Z, Gu L, Eils R, et al.: circlize implements and enhances circular visualization in r. Bioinformatics. 2014; 30(19): 2811–2. ISSN 1367-4811 (Electronic) 1367-4803 (Linking). PubMed Abstract | Publisher Full Text\n\nNeuhaus I, Brett C: canvasXpress: Visualization Package for CanvasXpress in R. 2022. R package version 1.37.4.Reference Source\n\nSievert C: Interactive web-based data visualization with r, plotly, and shiny.2020.Reference Source\n\nBenjamin D, Sato T, Cibulskis K, et al.: Calling somatic snvs and indels with mutect2. bioRxiv. 2019. Publisher Full Text Reference Source\n\nColaprico A, Silva TC, Olsen C, et al.: Tcgabiolinks: an r/bioconductor package for integrative analysis of tcga data. Nucleic Acids Res. 2016; 44(8): e71. ISSN 1362-4962 (Electronic) 0305-1048 (Linking). PubMed Abstract | Publisher Full Text\n\nKarczewski KJ, Francioli LC, Tiao G, et al.: The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020; 581(7809): 434–443. ISSN 1476-4687 (Electronic) 0028-0836 (Linking). PubMed Abstract | Publisher Full Text\n\nKarczewski KJ, Weisburd B, Thomas B, et al.: The exac browser: displaying reference data information from over 60 000 exomes. Nucleic Acids Res. 2017. 45(D1): D840–D845. ISSN 1362-4962 (Electronic) 0305-1048 (Linking). PubMed Abstract | Publisher Full Text\n\nVilimas T: Measuring tumor mutational burden using whole-exome sequencing. Methods Mol. Biol. 2020. 2055: 63–91. ISSN 1940-6029 (Electronic) 1064-3745 (Linking). PubMed Abstract | Publisher Full Text\n\nShyr C, Tarailo-Graovac M, Gottlieb M, et al.: Flags, frequently mutated genes in public exomes. BMC Med. Genet. 2014; 7: 64. ISSN 1755-8794 (Electronic) 1755-8794 (Linking). PubMed Abstract | Publisher Full Text\n\nAlexandrov LB, Kim J, Haradhvala NJ, et al.: The repertoire of mutational signatures in human cancer. Nature. 2020; 578(7793): 94–101. ISSN 1476-4687 (Electronic) 0028-0836 (Linking). PubMed Abstract | Publisher Full Text\n\nXie Y, Cheng J, Tan X: DT: A Wrapper of the JavaScript Library’DataTables’. 2022. R package version 0.21.Reference Source\n\nCheng J, Sievert C: crosstalk: Inter-Widget Interactivity for HTML Widgets. 2021. R package version 1.2.0.Reference Source\n\nJain A, Tandon M: MAFDash: An easy-to-use dashboard builder for mutation data (0.2.2). Zenodo. 2022. Publisher Full Text"
}
|
[
{
"id": "143350",
"date": "21 Jul 2022",
"name": "Sigve Nakken",
"expertise": [
"Reviewer Expertise Genomics",
"translational bioinformatics",
"precision cancer 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\nJain and Tandon have created a tool for visualization and analysis of cancer mutation data represented through the MAF format. The tool generates a dashboard as its output, hence the name, MAFdash. The tool offers multiple features to analyse mutation data from a cohort of cases/samples, exemplified through oncoplots (highly mutated genes), burden plots, mutational signature analysis, etc.\nCurrently, the tool suffers from some key limitations that I encourage the authors to handle in a revised version.\nMajor points\nThe tool is intended for analysis of MAF data, and the authors exemplify this through data from TCGA. However, most users will primarily be interested in using MAFdash on their own data rather than TCGA/CCLE. Importantly, users who have done cancer genome sequencing typically end up with VCF files after calling (I am not aware of any somatic variant callers that produce MAF?). If the tool does not support any transformation of VCF towards MAF, I am afraid the tool will not be used according to the intentions outlined by the authors, that is to support users with analysis/visualization of mutation data. In other words, the whole premise of the tool is to have a MAF file at hand, but obtaining this from a large-scale sequencing project is not covered by the tool, nor does the tool provide pointers/workflows to how this can be accomplished. Showcasing a complete workflow from variant calling towards MAF towards MAFdash would be helpful for the users, and strengthen the tool significantly. Based on the reasoning above, I think the slogan \"Once you call the variants, it's a MAFDash to the finish line\" is in my opinon somewhat misleading.\n\nTechnically, the tool suffers from multiple issues:\n1. https://github.com/CCBR/MAFDash contains a number of pointers to https://github.com/ashishjain1988/MAFDash, this needs to be cleaned up. Similarly, the documentation site https://ashishjain1988.github.io/MAFDash/ contains links to https://mtandon09.github.io/MAFDashRPackage/. Please clean up the GitHub page and the accompanying documentation site. Most importantly, links to the the example reports are non-functioning, which are critically important to showcase the output of the tool. Currently, I am unable to explore any output examples from the tool.\n2. The installation procedure is not working properly, the DESCRIPTION file needs cleaning: - Addition of biocViews: (for Bioconductor packages) - Move the (large) BSgenome package to Suggests - Clean out the Depends stuff, just keep R there. Rest go into Suggests/Imports. - Remove most of the version pinning in the Imports - Make sure the installation works both on Mac OSX and Linux\n- Looking at the function reference (https://ashishjain1988.github.io/MAFDash/reference/index.html), there are a number of misleading elements, i.e.\ngenerateOncoPlot() - Function to generate a dashboard from a MAF file? filterMAF() and filterMAF2()? compute_exome_coverage() - is this relevant function for MAFdash?\n\nMinor points\nThe example case for arbitrary plots using the iris dataset is misleading, please provide a relevant dataset.\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? No\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? No\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? No",
"responses": []
},
{
"id": "147677",
"date": "02 Sep 2022",
"name": "Heiko Brennenstuhl",
"expertise": [
"Reviewer Expertise human genetics",
"inborn errors of metabolism"
],
"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\nIn their manuscript \"MAFDash: An easy-to-use dashboard builder for mutation data\" Jain and Tandon report an R package which allows processing and visualization of mutation data from standardized and widely available MAF files and displays the results in an HTML dashboard. Various forms of presentation are generated automatically (tables, burden plots, OncoPlots, interactive heat maps, etc.), which should enable an analysis of the data set through sophisticated visualizations.\n\nThe manuscript is well written in an understandable manner and all considerations are clearly and convincingly presented.\n\nNevertheless, I have some small points of criticism:\nMAF files are extremely impractical to handle and can be a great challenge, especially for researchers with limited experience in bioinformatics. In my experience, VCF files are much more common and should therefore be included in the workflow of this tool.\n\nSome of the links within the documentation on github are broken (e.g. https://mtandon09.github.io/MAFDashRPackage/examples/LAML.mafdash.html and https://mtandon09.github.io/MAFDashRPackage/examples/articles/Quick_Start.html)\n\nLocal installation does not work (at least in my application): Some dependencies are not available for MAFDash according to my R version (including 'TCGAbiolinks', 'maftools', 'ComplexHeatmap', 'BSgenome-Hsapiens.UCSC.hg38'), the installation is aborted with the remark 'MAFDash_0.2.2.tar.gz' had non-zero exit status'\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? 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": []
}
] | 1
|
https://f1000research.com/articles/11-748
|
https://f1000research.com/articles/11-747/v1
|
06 Jul 22
|
{
"type": "Clinical Practice Article",
"title": "Dengue and SARS-COV-2 co-infection in pregnancy: decision making dilemma",
"authors": [
"Vindya Wijesinghe",
"Diluk Senadeera",
"Indunil Piyadigama",
"Sriyani Nanayakkara",
"Diluk Senadeera",
"Indunil Piyadigama",
"Sriyani Nanayakkara"
],
"abstract": "Background: Dengue virus (DENV) and coronavirus disease 2019 (COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) are two viral illnesses that require very distinct management protocols. Missed diagnosis and under reporting of DENV is predicted due to COVID-19 pandemic. Pregnancy is associated with increased fetal and maternal morbidity and mortality due to both illnesses. Co-infection need to be reported and studied to optimize the outcomes. Methods: This is a retrospective study on pregnant patients with COVID-19 and DENV co-infection conducted from the medical records from 1st of April 2021 to 1st of September 2021. Results: In this series four patients are described. Patient 1 is a diagnosed patient with immune thrombocytopenic purpura who was in remission. She developed DENV infection during recovery of SARS-CoV-2. She received intensive care unit (ICU) care during the leaking phase. Patient 2 had an uncomplicated miscarriage during the co-infection. Patient 3 was a patient with advanced maternal age with multiple co-morbidities. She did not progress into the leaking phase. Diagnosis of DENV was missed in patient 4 and she had a fetal death. Conclusions: SARS-CoV-2 and DENV co-infection in pregnancy can be life threatening to the mother and can lead to adverse fatal outcomes. Timely diagnosis and multidisciplinary management are essential for better outcomes. Continuous data collection and reporting is advisable till the guidance is formed.",
"keywords": [
"SARS-CoV-2",
"DENV co-infection",
"Maternal and fetal mobidity and mortality"
],
"content": "Introduction\n\nSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has affected 239 million people causing 4.8 million of deaths worldwide by the year 2020/21. DENV (Dengue virus) is estimated to infect 3.9 billion people annually, with 96 million having severe and life-threatening illness and 70% of DENV infections are reported from Asia. Both DENV and SARS-CoV-2 lead to increased mortality and morbidity in pregnancy.1–5 Healthcare providers in Asia are facing an unprecedented challenge in managing co-infections with DENV during this COVID-19 pandemic.\n\nSri Lanka is a tropical country where DENV is endemic. The first DENV outbreak was in 1965 with 26 patients and six deaths. The worst out-break was experienced in 2017.6 Colombo Municipal Council (CMC) take up 25% of the case load every year. Dengue outbreak was experienced in the De Soysa maternity hospital (DMH) during the COVID-19 pandemic threatening maternal and fetal lives. We experienced four cases of co-infections from April to September 2021.\n\nDENV and SARS-CoV-2 shares similar presenting symptoms. Hence, diagnosis could be delayed and may be missed, leading to life-threatening complications. Although DENV is endemic to south Asia, during this pandemic there is only one case of SARS-CoV-2/DENV co-infection reported in the literature.7 We were able to identify four patients with SARS-CoV-2/DENV co-infection during the period from 1st of April 2021 to 1st of September 2021 in the De Soysa Hospital for Women in Colombo, Sri Lanka. We believe that it is timely to report this case series, which may aid to raise awareness and management.\n\n\nMethods\n\nThis is a retrospective analysis of the medical records of pregnant women admitted to DMH (a tertiary care maternity hospital in CMC area, Colombo, Western province) during 1st of April 2021 to 1st of September 2021 during the SARS-CoV-2 pandemic. Ethical clearance was obtained from the ethical review committee on 17th of December 2020, Faculty of medicine Colombo (Protocol number EC-20-EM17).\n\nPatient 1\n\nA 24-year-old female Sri Lankan housewife presented at 33 weeks of gestation with arthralgia, fever, shortness of breath, and sore throat in her third pregnancy. She was a diagnosed patient with immune thrombocytopenic purpura (ITP) and was in remission. She previously had a 1st trimester miscarriage followed by a neonatal death due to a ruptured hemangioma. On admission the patient had a positive polymerase chain reaction (PCR) result for SARS-CoV-2. She complained of itchy palms and soles. She had normal platelet counts and aspartate aminotransferase (AST) and alanine aminotransferase (ALT). She was anticoagulated with subcutaneous enoxaparin 40 mg daily subcutaneously for 10 days. On the tenth day of the hospital stay, she developed a fever with positive dengue non-structural protein 1 (NS1) antigen. The patient was monitored with full blood count (FBC) every 8 hours. She was sent to the ICU on day 13 of hospital admission when her platelet count dropped to 8000/mm3. She was started on oral Prednisolone 20 mg daily (continued for 7 days) and intravenous (IV) hydrocortisone 100 mg every 8 hours (for 3 days). An ultrasound scan done on day 13 revealed gallbladder wall oedema and bilateral pleural effusions. Critical phase in dengue hemorrhagic fever was diagnosed and managed as per guidelines. She was transfused 250 cc of red cell concentrate (RCC) due to a drop in pack cell volume (PCV). Due to steroids, she had elevated blood sugars, which was controlled with subcutaneous soluble insulin according to the sliding scale three times daily (daily dose of 24 units to 30 units). Her SARS-CoV-2 antibodies were also positive on day 13 of the hospital stay. Her platelets started to rise on day 14 of hospital admission. She had an unremarkable recovery and was transferred back to the ward on day 17 of admission. Her steroids were tailed off. She underwent an elective caesarean section at 37 weeks (birth weight 2.6 kg). The post-partum period was uneventful. Cord blood was sent for platelet count and the newborn platelet count was monitored on day 3.\n\nPatient 2\n\nA 31-year-old female Sri Lankan management assistant in her sixth pregnancy presented with per-vaginal bleeding at 8 weeks of period of amenorrhea (POA). She had three previous uncomplicated vaginal deliveries with a neonatal death at 4 months due to sepsis and a 1st trimester miscarriage. On admission, the patient also had dizziness, a headache and a temperature of 100 °F. Her Dengue NS1 antigen and SARS-CoV-2 PCR was positive, with PCR CT value of 29. Transvaginal ultrasound was suggestive of a complete miscarriage with empty uterine cavity. Her serum beta human chorionic gonadotrophin (β HCG) dropped from 300IU to 33IU over 48 hours. She had a platelet nadir of 101000/cm3 which started to rise from day three of the hospital admission. She was discharged on day 10 of hospital admission without further complications.\n\nPatient 3\n\nA 41-year-old female Sri Lankan teacher was admitted at 30 weeks of gestation for optimization of her preexisting medical conditions in her second pregnancy. She had a previous emergency caesarean section for placenta previa. She was a diagnosed patient with type 2 diabetes for two years with nephropathy and retinopathy. She also had chronic hypertension with the blood pressure of 140/90 mmhg. She was on insulin, methyldopa, nifedipine and Aspirin at the time of admission. The PCR for COVID-19, which was done prior to admission, was positive. She had uncontrolled blood sugar around 16 mmol/l at the time of admission for which insulin doses were titrated. On the fourth day from the positive PCR test she developed shortness of breath and her saturation deteriorated reaching 94% on air. Chest x-ray revealed bilateral patchy infiltrates. She was started on IV ceftriaxone (1 g two times daily for 5 day), oral clarithromycin (500 mg twice daily for 14 days), oral dexamethasone (2 g twice daily for 7 days) and subcutaneous enoxaparin 40 mg subcutaneously for 18 days. She also had low Hemoglobin (Hb) of 9.0 g/dl and 1.0 unit of RCC was transfused. The patient was oxygen dependent for four days. She had an uncomplicated recovery from COVID-19, and her antibiotics and dexamethasone were continued for seven days. Following the recovery of SARS-CoV-2, the patient had persistent nephrotic range proteinuria and was on evaluation. On the 20th day of the hospital admission, she developed a fever with body aches. The dengue NS1 antigen was positive. She had a further 2.0 units of RCC transfusion to correct anemia, which had been diagnosed as anemia of chronic disease. Her vital parameters, PCV and FBC’s were monitored regularly with focused assessment with sonography for trauma (FAST) scans to detect early critical phase. Her platelet count dropped to 109000/cm3. She did not develop dengue hemorrhagic fever and had a recovery after four days. She underwent an elective caesarean section at 37 weeks due to transverse lie. The newborn developed weight loss (birth weight was 2.9 kg) due to feeding issues and developed jaundice, which was treated with phototherapy. Both were discharged after the 11th day of post-partum with the necessary referrals.\n\nPatient 4\n\nA 32-year-old female Sri Lankan legal apprentice in her 1st pregnancy with an uncomplicated antenatal period was admitted with fever, arthralgia, and myalgia at 28 weeks of gestation. Her SARS-CoV-2 rapid antigen test was positive, but the NS1 was negative. FBC showed Hb of 11 g/dl with platelet of 213000/mm3. Her last fetal growth scan done at 28 weeks of gestation was normal. She was home quarantined. Her fever settled within a day, and she was asymptomatic afterwards. She developed reduced fetal movement on day seven of the illness and was admitted to the hospital on day eight. Intrauterine death was confirmed at the time of the admission.\n\nHer FBC, liver function test, renal function test, NS1 dengue antibodies, blood picture and urine full report (UFR) was performed. On admission she had a platelet count of 74000/mm3 and elevated liver enzymes (AST-157U/L, ALT-99U/L). She was normotensive and did not have urine proteins. She had positive dengue IgM antibody and negative IgG. She was carefully observed with fluid management, and she recovered without further complications. She was induced after one week from stabilization of platelets.\n\nShe delivered a morphologically normal fetus with clear liquor and without evidence of fetal growth restriction (fetal weight was 1.1 kg). No abnormalities were detected in the placenta and cord macroscopically. The couple did not consent for the pathological post-mortem. Placental histology showed extensive placental infarctions with chorionic villi with syncytial knots. The membranes showed dense aggregates of acute inflammatory cells compatible with acute chorioamnionitis.\n\n\nDiscussion\n\nApproximately one third of the patients with COVID-19 are asymptomatic.8 Furthermore, 50–85% of patients infected with DENV are asymptomatic.9 Both illnesses have a spectrum of severity varies from mild to critical.10 Moreover, they share biochemical features such as leucopenia, thrombocytopenia and deranged liver enzyme level, which make the identification of the disease further demanding.11–13\n\nMorbidity and mortality are higher during pregnancy for mother and fetus in both infections. DENV has been reported to cause fetal, neonatal and maternal death, low birth weight and preterm delivery,2–4 whereas COVID-19 can lead to preterm delivery, low birth weight, higher rate of oxygen dependency, higher ICU admissions, neonatal mortality and morbidity.14\n\nSensitivity and specificity of dengue NS1 test affect the diagnosis of DENV. The DENV antigen test was negative in the fourth patient of our case series, and she was discharged for home-based care. Even sore throat, a symptom usually associated with COVID-19, is being commonly reported in DENV cases.15\n\nDENV and SARS-CoV-2 infections require different clinical interventions, and incorrect or delayed diagnosis can have serious consequences. Anticoagulation is generally used for SARS-Cov-2 in our population after assessment of other risk factors for thrombosis, severity of illness and mobility. It has been advised to avoid anticoagulation in DENV as it can increase the risk of thrombocytopenia and even trigger Reyes syndrome, a rare condition characterized by hepatitis and encephalopathy.16\n\nDexamethasone was used in patients with severe symptoms of COVID-19 (patient 4). However, there is no evidence for dexamethasone to alleviate the course of DENV. It is advisable to deliver the fetus in cases with COVID-19 depending on the case-based evaluation of risk factors and severity of the illness. In contrary, the delivery should be delayed in mothers with DENV as it can cause life threatening bleeding and lead to leaking. This dilemma was considered in management of case number 3 and 4. Immediate multidisciplinary meetings were conducted for case 3 and 4 for the management of labor. Fortunately, the course of COVID-19 was asymptomatic to mild in those patients.\n\nIt is paramount to highlight the fact that all four patients were unvaccinated at the time of admission. The authors believe the personal preference and delay in initiating the vaccination program led to this situation.\n\nThe outcomes of the patients with co-infection were unfavorable. Out of the four patients in our sample, one patient had a miscarriage, one had a fetal death and the other two patients had caesarean sections. This is comparable with non-pregnant counterparts with co-infection.17 We had no maternal death in our population due to co-infection. Cytokine storm was proved by laboratory investigations in one case report. However, we were unable to conduct such investigations due to unavailability of tests.7\n\nCross reactivity between the antibodies formed in both illnesses had been reported.18 Hence, confirmatory diagnosis via RT-PCR for DENV would be ideal. However, this facility is not available in Sri Lanka. Clinical management of dengue fever is decided primarily on signs and symptoms and NS1 assay. An NS1 assay has moderate sensitivity and high specificity.19 However, IgM ELISA or NS1 tests are often preferred as they are more available, and more affordable. During this case series, all patients admitted with symptoms were tested for both infections, however delays occurred when the DENV antigen was falsely negative. Further, during the pandemic, collaboration between healthcare professionals (physician, microbiologist, hematologist, anesthetist, and obstetrician) in providing the care has minimized the missing cases.\n\nPlacental histology was performed in patient number 4 which showed changes comparable with the placental histology DENV infection as in Figure 1A and B.20 We believe further studies on placental histology in COVID-19 and DENV might yield more information on direct inflammation of placenta due to these viral illnesses.\n\nMembranes show dense aggregates of acute inflammatory cells compatible with acute chorioamnionitis.\n\nLack of identification of the dengue and SARS-CoV-2 serotypes is a limitation of this study as it has clinical and epidemiological significance. The authors believe that multinational collaborative studies are required to improve the quality of data and availability of data on co-infection.\n\n\nConclusions\n\nDue to the SARS-CoV-2 pandemic, the DENV cases are under diagnosed and underreported. Public health care systems are overloaded with managing the COVID-19 pandemic. This study presented a few cases of co-infections in a leading maternity hospital in Sri Lanka. This is the first case series from Sri Lanka to elaborate the co-infection during pregnancy. We believe the above information will enlighten clinicians in the management of co-infection. Both diseases could be more lethal among the pregnant population. Hence, continuous collection of information and discussion about co-infections might mitigate diagnosis and clinical management.\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 was obtained from the patients included in the article.",
"appendix": "Acknowledgements\n\nI thank all the patients participated for the study and all healthcare workers helped us to carry out patient care during COVID-19 pandemics. Patient number 4 is presented in 54th annual scientific sessions as an abstract. 21\n\n\nReferences\n\nChinn J, Sedighim S, Kirby KA, et al.: Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic. JAMA Netw. Open. 2021 Aug 11 [cited 2021 Oct 18]; 4(8): e2120456–e2120456. Publisher Full Text\n\nPaixão ES, Campbell OM, Teixeira MG, et al.: Dengue during pregnancy and live birth outcomes: a cohort of linked data from Brazil. BMJ Open. 2019 Jul 1 [cited 2021 Oct 18]; 9(7): e023529. PubMed Abstract | Publisher Full Text Reference Source\n\nTien Dat T, Kotani T, Yamamoto E, et al.: Dengue fever during pregnancy. Nagoya J. Med. Sci. 2018 May [cited 2021 Oct 18]; 80(2): 241–247. PubMed Abstract | Publisher Full Text Reference Source\n\nSondo KA, Ouattara A, Diendéré EA, et al.: Dengue infection during pregnancy in Burkina Faso: a cross-sectional study. BMC Infect. Dis. 2019 Nov 27 [cited 2021 Oct 18]; 19(1): 997. PubMed Abstract | Publisher Full Text\n\nWei SQ, Bilodeau-Bertrand M, Liu S, et al.: The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis. CMAJ Can. Med. Assoc. J. 2021 Apr 19; 193(16): E540–E548. PubMed Abstract | Publisher Full Text\n\nMalavige GN, Jeewandara C, Ghouse A, et al.: Changing epidemiology of dengue in Sri Lanka—Challenges for the future. PLoS Negl. Trop. Dis. 2021 Aug 19 [cited 2021 Oct 18]; 15(8): e0009624. PubMed Abstract | Publisher Full Text Reference Source\n\nIrwinda R, Wibowo N, Prameswari N: Cytokines storm in COVID-19 with dengue co-infection in pregnancy: Fatal maternal and fetal outcome. IDCases. 2021 Sep 6 [cited 2021 Oct 18]; 26: e01284. PubMed Abstract | Publisher Full Text Reference Source\n\nOran DP, Topol EJ: The Proportion of SARS-CoV-2 Infections That Are Asymptomatic: A Systematic Review. Ann. Intern. Med. 2021 May; 174(5): 655–662. PubMed Abstract | Publisher Full Text\n\nDuong V, Lambrechts L, Paul RE, et al.: Asymptomatic humans transmit dengue virus to mosquitoes. Proc. Natl. Acad. Sci. U. S. A. 2015 Nov 24; 112(47): 14688–14693. PubMed Abstract | Publisher Full Text\n\nDeen JL, Harris E, Wills B, et al.: The WHO dengue classification and case definitions: time for a reassessment. Lancet Lond Engl. 2006 Jul 8; 368(9530): 170–173. PubMed Abstract | Publisher Full Text\n\nWang D, Hu B, Hu C, et al.: Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan. China. JAMA. 2020 Mar 17; 323(11): 1061–1069. PubMed Abstract | Publisher Full Text\n\nGuan WJ, Ni ZY, Hu Y, et al.: Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020 Apr 30; 382(18): 1708–1720. PubMed Abstract | Publisher Full Text\n\nCobra C, Rigau-Pérez JG, Kuno G, et al.: Symptoms of dengue fever in relation to host immunologic response and virus serotype, Puerto Rico, 1990-1991. Am. J. Epidemiol. 1995 Dec 1; 142(11): 1204–1211. PubMed Abstract | Publisher Full Text\n\nAllotey J, Stallings E, Bonet M, et al.: Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020 Sep 1; 370: m3320. Publisher Full Text\n\nCheng NM, Sy CL, Chen BC, et al.: Isolation of dengue virus from the upper respiratory tract of four patients with dengue fever. PLoS Negl. Trop. Dis. 2017 Apr 5 [cited 2021 Oct 18]; 11(4): e0005520. PubMed Abstract | Publisher Full Text Reference Source\n\nGamakaranage C, Rodrigo C, Samarawickrama S, et al.: Dengue hemorrhagic fever and severe thrombocytopenia in a patient on mandatory anticoagulation; balancing two life threatening conditions; a case report. BMC Infect. Dis. 2012 Oct 26 [cited 2021 Oct 18]; 12(1): 272. PubMed Abstract | Publisher Full Text\n\nTsheten T, Clements ACA, Gray DJ, et al.: Clinical features and outcomes of COVID-19 and dengue co-infection: a systematic review. BMC Infect. Dis. 2021 Aug 2 [cited 2021 Oct 18]; 21(1): 729. PubMed Abstract | Publisher Full Text\n\nSantoso MS, Masyeni S, Haryanto S, et al.: Assessment of dengue and COVID-19 antibody rapid diagnostic tests cross-reactivity in Indonesia. Virol. J. 2021 Mar 11 [cited 2021 Oct 18]; 18(1): 54. Publisher Full Text\n\nGuzman MG, Jaenisch T, Gaczkowski R, et al.: Multi-country evaluation of the sensitivity and specificity of two commercially-available NS1 ELISA assays for dengue diagnosis. PLoS Negl. Trop. Dis. 2010 Aug 31; 4(8): e811. PubMed Abstract | Publisher Full Text\n\nRibeiro CF, Lopes VGS, Brasil P, et al.: Dengue infection in pregnancy and its impact on the placenta. Int. J. Infect. Dis. 2017 Feb 1 [cited 2021 Oct 18]; 55: 109–112. Publisher Full Text Reference Source\n\nWijesinghe PVN, Attapattu H: Dengue and COVID co-infection leading to Fetal demise. 54th Annual scientific sessions. Sri Lanka College of Obstetricians and Gynecologists."
}
|
[
{
"id": "228625",
"date": "22 Dec 2023",
"name": "Darwin A. León Figueroa",
"expertise": [
"Reviewer Expertise Infectious and transmissible 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\nI have reviewed with great interest the article entitled \"Dengue and SARS-CoV-2 co-infection in pregnancy: a decision-making dilemma\" proposed by Wijesinghe V. et al. The authors raise a very interesting issue. In the following, I present the necessary observations to improve the quality and scientific rigor of the article. Abstract- It presents a detailed structure. Key words- Check that these words are MeSH terms. Introduction I suggest that the COVID-19 data be updated to 2023 (https://covid19.who.int/). The authors should briefly present the relevance of dengue and SARS-CoV-2 coinfection in the context of pregnancy. In addition, highlight the importance of understanding the risks and implications of coinfection in this vulnerable population. Provide data on the prevalence of dengue and SARS-CoV-2 coinfection in different regions worldwide. Methods- This section provides a detailed overview of the study design, the population analyzed, the study period, the temporal context, ethical clearance, and associated ethical considerations. However, it is important to detail that this is a descriptive retrospective study based on a series of cases extracted from medical records, which would provide greater specificity to the research approach. Patient 1 The clinical case description should be improved. It is important to design a figure of a timeline where the symptomatologies of coinfection are captured. Patient 2 Specify in parentheses the normal CRP values that were taken into account. Was the patient vaccinated against COVID-19? Provide information on the treatment administered. Specify her therapeutic management. Patient 3 It would be important to design a timeline figure showing the symptoms of the coinfection. Patient 4 Specify history and therapeutic management. Discussion- The authors should summarize the specific cases in the study. Based on this address, compare it with scientific publications. The possible consequences of coinfection on maternal and fetal health should be highlighted. In addition, include relevant data on obstetric complications and perinatal outcomes associated with coinfection. Mention possible gaps in current understanding and the need for specific data to guide clinical practice. Finally, particular challenges associated with the diagnosis and management of coinfection during pregnancy should be addressed. Establish the strengths of this research and future recommendations.\n\nIs the background of the cases’ 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 conclusion balanced and justified on the basis of the findings? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/11-747
|
https://f1000research.com/articles/11-486/v1
|
03 May 22
|
{
"type": "Research Article",
"title": "Module intervention to improve involvement and practices of fathers towards infant and young child feeding (IYCF) in Coastal South India - a randomized controlled trial",
"authors": [
"Prasanna Mithra",
"Bhaskaran Unnikrishnan",
"Rekha T",
"Nithin Kumar",
"Ramesh Holla",
"Priya Rathi",
"Bhaskaran Unnikrishnan",
"Rekha T",
"Nithin Kumar",
"Ramesh Holla",
"Priya Rathi"
],
"abstract": "Background: Overall child health depends on nutrition and its related practices. At the family level, responsibility of child feeding lies with both parents. There is no uniform and systematic way to determine and assess the practices of fathers in infant and young child feeding (IYCF). Also, there is a paucity of evidence related to interventions for fathers in improving their practices and involvement in the feeding of their infant or young child (aged less than two years). Methods: This was a community-based randomized control trial, conducted among 120 fathers with infants and/or young children in Dakshina Kannada District of Karnataka. Fathers with poor level of involvement and practices towards IYCF, during the initial assessment, were included as the study participants. For the intervention, a module in the flipchart format was developed. Simple randomization technique was used to allot the participants into two groups - intervention and control. Participants in the intervention group received module intervention, in addition to the care which they received routinely, and the control group received only routine care. The participants in the intervention group were paid a monthly visit to implement the module, for six months. The post-intervention assessment was done at the end of 6 months. Results: A total of 117 participants provided post-intervention data. The mean age was 34.7 (+/- 5.48) years in the intervention group and 34.36 years (+/- 5.26) in the control group. The intervention group had a significant improvement in knowledge, attitude, and practice components at 6 months. We noted higher change scores for the intervention group (p<0.05). Conclusions: The extent of increase in practice and involvement in child feeding was clearly higher among the intervention group. The module developed was successful in improving the practices of fathers in feeding their infants and young children. Clinical Trials Registry India: CTRI/2017/06/008936 (29/06/2017)",
"keywords": [
"Paternal",
"IYCF",
"involvement",
"module",
"trial"
],
"content": "Introduction\n\nThe health of the children reflects the overall health of a community and country. However, child health is affected and influenced by several factors such as nutrition and feeding practices. These are also important determinants of children’s health, growth, and survival.1,2 Although the responsibility of a child’s feeding lies with both the parents, much of the emphasis and stress has been on mothers. When both parents put their efforts together for the child’s feeding practices, the child has a higher chance of receiving better nutrition.3–6\n\nThe important role and influence that fathers can have in shaping their children’s eating patterns have been documented.7 Paternal feeding practices towards their young children also reflect the way of time management done by the fathers.8 Despite this established paternal role in child-rearing, most of the research and policies related to child feeding, have not given importance to fathers.9,10 Several strategies using media, healthcare providers, and peer-to-peer interventions have been implemented to improve child nutrition. However, all these were keeping mothers as main recipients.11,12 But support from the father of the child, coupled with a change in attitude and knowledge even at the stage of breastfeeding has given promising results in terms of the success of breastfeeding and overall nutrition of the child.11,13 However, in many instances, fathers possess the knowledge and positive attitude towards infant and young child feeding (IYCF), but it may not be reflected in their practices.6\n\nMany factors have a role to play in determining the level and extent of paternal practices in infant and child feeding practices. Still, there is a paucity of evidence related to these practices.14–17 Given the culturally diverse Indian population, no modular interventions for fathers to improve their IYCF practices have been evaluated so far.\n\nThus, this trial was carried out to develop and test the effectiveness of a module, targeting fathers with either infants or young children aged less than 2 years, in improving their involvement in IYCF.\n\n\nMethods\n\nApproval was obtained from the Institutional Ethics Committee (IEC) of Kasturba Medical College, Mangalore (approval number IEC KMC MLR 06-17/111 dated 21st June 2017). After obtaining the approval, data collection commenced. A participant information letter was provided and written informed consent was taken from each participant, after assuring anonymity and confidentiality for the information they provided. This article is reported in line with the Consolidated Standards of Reporting Trials (CONSORT) guidelines.18\n\nThis community-based randomized controlled trial was carried out among 120 fathers of infants and young children aged 12 to <24 months in Dakshina Kannada District (Karnataka State), India, between January and December 2020. The sample size calculation, recruitment of study participants, sampling techniques followed, methodology of randomization, intervention procedures have been described earlier.19 The Template for Intervention Description and Replication (TiDier) was used for the description of the methodology.20 Sample size for this trial was calculated using an assumption of 15% improvement in the paternal practices related to IYCF after module-based intervention, 80% power, 5% alpha-error, 1:1 allocation and adding 20% non-response error, as 60 participants in each group.\n\nThe eligible participants for this trial were selected using stratified multistage random sampling technique; wherein we did the stratification at subdistrict level. At each stratum, the health centers of the public health system were chosen using simple random sampling done with the help of lottery technique, with probability proportionate to size, keeping the population covered by the centres as benchmark. Each center caters to several wards (administrative sub-unit) and again using lottery technique, a ward was selected from the health center area. From the health centers, we could collect the list of infants and young children in selected wards and visit their fathers who were selected using convenient sampling method, on a pre-approved, mutually convenient time in their houses. A total of 450 eligible fathers were assessed.21 The registration of this trial was done in Clinical Trials Registry- India (CTRI/2017/06/008936) on 29 June 2017.22\n\nThe fathers with at least one infant or a child aged less than 2 years were eligible for inclusion in the initial assessment. After the initial assessment of the eligible fathers in their involvement in IYCF,21 they were classified as having either good or poor involvement in IYCF. This assessment included the knowledge, attitude and practice aspects of IYCF, in the form of an investigator administered questionnaire.18 In case of participants with more than 1 child, the domains were assessed as applicable to the youngest child. The questionnaire consisted of scores for each of the three above mentioned domains as five-point likert scale and the total scores for practice domain were computed. Since there is no pre-existing cut-off for the score, we chose to use the median score as the cut-off to determine the number of fathers with less than 50th centile practice score to depict poor involvement.\n\nThose fathers with poor involvement were the eligible participants for this trial. Their list was arranged according to the Taluks (a sub-District administrative unit in India) of their residence and simple random sampling was used to select the Taluks. The participants from each of these Taluks were selected using simple random sampling. A total of 130 eligible participants were approached to meet the target sample size of 120. They were visited and explained about the objectives and nature of the intervention in the local language. In total, 10 eligible participants declined the invitation. Written informed consent was taken from all the participants who agreed to be part of this trial. The selected fathers were randomized into intervention & control groups. We used simple randomization technique with lottery method, using Microsoft Excel software. The generated sequence was converted to 120 opaque containers and arranged by principal investigator (PM). Another author (NK) performed sequential enrolment of participants. Following this, third author (RT) ensured the assignment of participants to the appropriate interventions. Final implementation of the intervention was done by research assistants.\n\nBaseline and post-intervention assessments at the end of 6 months were done using a content validated questionnaire, which included demographic component, awareness, attitude, and practices related to IYCF. This questionnaire was developed by the authors and tested for internal consistency along with inter-rater reliability. Minor revisions were then done to reach acceptable level of reliability. The questionnaire and other intervention materials can be found as Extended data18) At the end of 6 months, due to the coronavirus disease 2019 (COVID-19) pandemic lockdown situation, the post-intervention assessment was conducted over the telephone and google form-based blended approach due to the inability to travel to the field and to avoid personal contact with the participants.\n\nFor the intervention arm, the IYCF module was developed towards the improvement of paternal involvement in IYCF, as a pictorial-explanation flip-chart form based on extensive literature review and existing knowledge in the field.18 The module included information on feeding the baby from the time of birth, ways in which a father can support the mother in breastfeeding, significance of paternal decision in child feeding practices, when and how weaning has to be started for the baby and ways of father’s involvement in general childcare. The IYCF module was implemented in Kannada (the local language) after it was pilot tested for operational feasibility. Pilot testing was done in the field among five fathers with poor involvement in IYCF, but not part of the main trial. The interactions were documented, difficulties in communications, usage of terms were addressed. Also, feedback was taken from the participants. Finally, revision of the module was undertaken.\n\nThe intervention was done by two research assistants from the Medical Social Work background, who were trained in implementing the module in the community. They visited the participants on pre-informed dates at their homes or a convenient location and at a convenient time. The module was implemented to the intervention arm on a one-to-one interaction basis. Each interaction lasted for 20 to 30 minutes including the question-and-answer sessions. During this interaction, only the participant father was present along with the research assistant, to avoid any intervention contamination. The administration of the same module was done once a month for 6 months. Participants in the control group received their regular care in the health centers, whenever they visited with their child and during regular visits to them by the health workers.\n\nWe analyzed the data using IBM SPSS Statistics for Windows, Version 25.0 (RRID:SCR_016479). Data management was done at the central coordinating site, located in the study institute. Results were arranged as proportions, mean (with standard deviation) using the tables. Individual scores of knowledge, attitude and practice components were added from the Likert scale response of each component and a total score was obtained. These total scores were used to compare the intervention and control groups. The comparison for the knowledge, attitude, and practice scores across the groups was done using chi-square test, paired & independent sample ‘t’ tests. Intention to treat analysis was followed. A p-value < 0.05 was considered statistically significant.\n\n\nResults\n\nIn total, 130 fathers were assessed for eligibility of which 120 were randomized. All the selected participants completed the monthly modular interventions. In total, two participants in the intervention and one in the control group could not be accessible after several attempts to provide follow up information on IYCF practices. Finally, 117 participants (n=58 for intervention, n= 59 for control) were included in the analysis.18 The flow of study as per the CONSORT format is provided in Figure 1.23,24\n\nIYCF=Infant and Young Child Feeding.\n\nThe mean age of the intervention group was 34.7 (±5.48) years and the control group was 34.36 years (±5.26) (p=0.711). Both the study groups were similar concerning their demographic characteristics (age group, educational status, being first-time father or experienced father, attitude, and practice scores). The two groups were significantly different concerning the occupation categories and knowledge scores (p=0.03 and <0.0001, respectively) at the baseline (Table 1).\n\n* p-value significant at 0.05 level.\n\n# SD=Standard Deviation.\n\nThe before and after comparisons of the scores are described in Table 2. The intervention group showed statistically significant (p<0.0001) improvement in all three scores, i.e., knowledge, attitude and practice scores. In the control group, there was a decline in the knowledge scores at 6 months. We found this difference to be statistically significant (p<0.0001).\n\n* p-value significant at 0.05 level.\n\n# SD=Standard Deviation, IYCF=infant and young child feeding.\n\nThere was also improvement in the attitude; however, the difference was not found to be statistically significant (p=0.061). Also, there was a statistically significant improvement in practice scores in the control group (p=0.005). When the change scores were compared across the two groups between pre-intervention and post-intervention scores, all the three change scores (knowledge, attitude and practice) were higher for the intervention group. These differences were found to be statistically significant (p<0.0001). The details of the change score comparisons are given in Table 3. The correlation test between change scores of knowledge and practice aspects of IYCF revealed significant association.\n\n* p-value significant at 0.05 level.\n\n# SD=Standard Deviation, IYCF=infant and young child feeding.\n\n\nDiscussion\n\nFather’s support can greatly improve the status of mother and child health in the community, by bringing positive change in feeding practices of children right from birth.5 Also, the fathers’ parenting skills, feeding practices may the nutritional behaviour and overall growth and development of the child.9,25,26 Although, because of several changes in society, fathers’ involvement in childcare has been witnessing an upward trend over time, it is still influenced by a multitude of factors.5,7,27 Being a father is challenging in terms of overall childcare and the child’s diet.28 These challenges could be in terms of influence of other elderly family members in deciding the IYCF, lack of experience in childcare, absence of felt need of their involvement and many hidden factors. Neha Khandpur et al, in 2014, in their systematic review, reported that feeding practices varied in mothers and fathers. Fathers’ feeding practices towards children contributed significantly to the nutritional status of children.9 This review also highlighted the shortage of literature and thereby information on child feeding practices of fathers. The current situation of limited fathers’ involvement in IYCF and influencing factors have been reported in our earlier paper.21 We reported a 40.9% of fathers of infants or young children having poor involvement in IYCF and the same was higher among fathers belonging to urban area. Younger age and having education above graduation was associated with better involvement in IYCF. Occupation did not have a direct influence on involvement of fathers in IYCF. Also, these fathers had favourable attitude towards receiving education and training on handling babies and children, so that overall growth of their children would not be compromised.\n\nBetter paternal involvement in IYCF is possible with provision of adequate knowledge to the fathers of young children, in addition to prospective fathers.27 Considering the current Indian scenario, wherein most of the child nutrition and care-related interventions have been focusing on mothers,25 we developed a unique and simple father-oriented module.18 This module targeted an increase in knowledge, improvement in attitude and practices towards IYCF. As reported by Han et al in 2019,29 behaviour change communication (BCC) strategies are important in enhancing involvement in child feeding. However, they also noted that only knowledge gain would have a limited impact on IYCF practices. They involved mothers of children along with fathers in their community-based trial.\n\nIn our trial, the group of fathers, after receiving the modular intervention in addition to the standard care, had significant improvement in knowledge, attitude and involvement towards their IYCF. Also, the control group which received standard care showed a decline in their knowledge, a mild increase in attitude, and a significant increase in practice. However, the change scores reflected a higher difference due to the implementation of this module. Several varieties of interventions have been tried, both in developing and developed parts of the world. A trial by Pisacane A et al in Italy, conducted in 2005 towards teaching the fathers on handling and managing lactational problems showed better breastfeeding practices till 6 months.11 Similarly, Han et al in 2019,29 assessed the impact of both-parent behavior change programs through communication on IYCF practices compared to the maternal program alone. They noted that father’s IYCF knowledge increase was highest when it was clubbed with maternal BCC as compared to paternal BCC alone. However, they also reported that additional gain in knowledge did not translate to further enhancement in practices of IYCF. Elizabeth Sloand et al in Haiti30 evaluated a public health nursing strategy using village-based fathers clubs. The post-intervention opinion from the participants revealed that childcare and health improved because of this intervention. A quasi-experimental study by Faith Thuita et al, in Kenya, in 2015, studied the impact of involving fathers and/or grandmothers on diets of mothers and IYCF practices in a rural setting and they found this model successful.12\n\nThere have also been attempts to enhance paternal involvement in IYCF, right from the antenatal period of their spouses. Jenny Tohotoa et al in Perth, Australia, in 2009, carried out antenatal sessions for fathers from different socio-economic strata and reported that a father-oriented approach was successful in terms of acceptance of the education material and involvement in baby feeding following the delivery of their spouse.28 Bruce Maycock et al in Australia, in their fathers infant feeding initiative (FIFI Study), provided antenatal education sessions and postnatal support targeted to fathers and they reported that higher age and socioeconomic status of fathers had better breastfeeding rates.31\n\nAnother quasi-experimental study carried out by Abdullahi et al, in Somalia, in 2019, aimed at assessing the peer counselling effects by either mother or father as a support group on IYCF practices. They noticed a positive trend in knowledge, breastfeeding practices, and diet diversity among intervention arms.32 Shorey et al in Singapore in 2017, noted that enforcement of paternal involvement throughout the perinatal period by healthcare professionals had a positive response.17\n\nAll the previous studies showed improvement in paternal practices towards IYCF to a variable extent. However, the applicability to the wider population, the need for a professional to provide the interventions, and accessing the fathers at the right time have been some of the challenges faced by these studies. But the current module has been made simple to use by a grass-root level health worker and is made culturally neutral. Similar modular intervention-based approaches could be implemented in wider populations. The current study was carried out in a District which is having high literacy rates and better health-seeking behaviors. Thus, further effects in other regions of the country and outside regions remain to be tested. Also, the long-term effect of this module intervention, which could not be assessed in this study, would signify the need for re-enforcement of relevant information on paternal involvement in IYCF. Consequently, it would benefit the health care practitioners and policymakers in improving child growth and development through the strengthening of paternal involvement in IYCF and suitably planned interventions.\n\n\nConclusions\n\nThe participating intervention and control groups were similar to each other concerning most of the demographic characteristics. Both the groups had significant improvement in attitude and practice components at the end of 6 months, but the change scores were significantly higher for the intervention group. Also, concerning knowledge related to IYCF, the control group had a decline, and the intervention arm showed significant improvement. Thus, the module developed was successful in improving the overall involvement of fathers in their infant and young child feeding.\n\n\nData availability\n\nOpen Science Framework: Effectiveness of a module-based intervention on paternal involvement in Infant and young child feeding (IYCF) practices in Coastal South India - A Randomized Controlled Trial. https://doi.org/10.17605/OSF.IO/D9GZ5.18\n\nThis project contains the following underlying data:\n\n- RCT final with all raw data.xlsx (this dataset includes the compiled scores in knowledge, attitude and practice domains at baseline and post-intervention; 1A1-1C14 reflect pre and 2A1-2C14 reflect post intervention data)\n\nOpen Science Framework: Effectiveness of a module-based intervention on paternal involvement in Infant and young child feeding (IYCF) practices in Coastal South India - A Randomized Controlled Trial. https://doi.org/10.17605/OSF.IO/D9GZ5.18\n\nThis project contains the following extended data:\n\n- CONSORT-Final-RCT.png (CONSORT flowchart)\n\n- Informed consent-F1000.docx (Participant information sheet and consent form)\n\n- IYCF module.pdf (intervention material)\n\n- Questionnaire-F1000.docx\n\nOpen Scientific Framework: CONSORT checklist33 for ‘Module intervention to improve involvement and practices of fathers towards infant and young child feeding (IYCF) in Coastal South India - a randomized controlled trial’. https://doi.org/10.17605/OSF.IO/D9GZ5.18\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgments\n\nThe authors express sincere gratitude to Manipal Academy of Higher Education, Manipal and, the Indian Institute of Public Health, Gandhinagar, India for all the support extended towards this study. Also, authors acknowledge the help and support rendered by the research assistants, Mr Ranjith and Mr Santhosha A in the implementation of the module and field work.\n\n\nReferences\n\n(US) NRC, (US) I of M: Children’s Health, The Nation’s Wealth: Assessing and Improving Child Health. Children’s Health, The Nation’s Wealth: Assessing and Improving Child Health Washington (DC): National Academies Press (US): National Academies Press (US); 1st ed.2004.\n\nHasibuan Y, Batubara A, Suryani S: Mother’s Role and Knowledge in Young Children Feeding Practices on the Nutritional Status of Infant and Toddler. Global J. Health Sci. 2019; 11(6): 158. Publisher Full Text\n\nHaycraft E, Blissett J: Predictors of Paternal and Maternal Controlling Feeding Practices with 2- to 5-year-old Children. J. Nutr. Educ. Behav. 2012; 44(5): 390–397. PubMed Abstract | Publisher Full Text\n\nGuerrero AD, Franke T, Kuo AA, et al.: Father Involvement in Feeding Interactions with Their Young Children. Am. J. Health Behav. 2016 Mar; 40(2): 221–230. PubMed Abstract | Publisher Full Text\n\nKansiime N, Atwine D, Nuwamanya S, et al.: Effect of Male Involvement on the Nutritional Status of Children Less Than 5 Years: A Cross Sectional Study in a Rural Southwestern District of Uganda. J. Nutr. Metab. 2017; 2017: 1–9. PubMed Abstract | Publisher Full Text Reference Source\n\nWorld Health Organization-WHO: Global Strategy for Infant and Young Child Feeding.2003.\n\nIto J, Fujiwara T, Barr RG: Is paternal infant care associated with breastfeeding? A population-based study in Japan. J. Hum. Lact. 2013; 29(4): 491–499. PubMed Abstract | Publisher Full Text\n\nYogman M, Garfield CF: Fathers’ roles in the care and development of their children: The role of pediatricians. Vol. 138, Pediatrics. American Academy of Pediatrics; 2016.\n\nKhandpur N, Blaine RE, Fisher JO, et al.: Fathers’ child feeding practices: A review of the evidence. Appetite. 2014; 78: 110–121. PubMed Abstract | Publisher Full Text\n\nMoyo SA, Schaay N: Fathers perceptions and personal experiences of Complementary feeding of children 6 to 23 months in south-western Zimbabwe. World Nutr. 2019 Sep; 10(3): 51–66. Publisher Full Text\n\nPisacane A, Continisio GI, Aldinucci M, et al.: A controlled trial of the father’s role in breastfeeding promotion. Pediatrics. 2005; 116(4): e494–e498. PubMed Abstract\n\nThuita FM, Martin SL, Ndegwa K, et al.: Engaging fathers and grandmothers to improve maternal and child dietary practices: planning a community-based study in western Kenya. Afr. J. Food Agric. Nutr. Dev. 2015; 15(5): 10386–10405.\n\nUSAID-ENGINE: Fathers’ infant and young child feeding practices and their determinants in Amhara, Oromia, SNNP and Tigray regions.2014.\n\nKumar N, Unnikrishnan B, Rekha T, et al.: Infant feeding and rearing practices adapted by mothers in coastal south india. Int. J. Collab. Res. Intern. Med. Public Health. 2012; 4(12): 1988–1999.\n\nSkinner JD, Carruth BR, Bounds W, et al.: Children’s food preferences: A longitudinal analysis. J. Am. Diet. Assoc. 2002 Nov; 102(11): 1638–1647. PubMed Abstract\n\nJoseph N, Kotian S, Mahantshetti N, et al.: Infant rearing practices in south India: A longitudinal study. J. Family Med. Prim. Care. 2013; 2(1): 37–43. PubMed Abstract | Publisher Full Text\n\nShorey S, Ang L, Goh ECL, et al.: Factors influencing paternal involvement during infancy: A prospective longitudinal study. J. Adv. Nurs. 2019 Feb; 75(2): 357–367. PubMed Abstract | Publisher Full Text\n\nMithra P, Unnikrishnan B, Thapar R, et al.: Effectiveness of a module-based intervention on paternal involvement in Infant and young child feeding (IYCF) practices in Coastal South India - A Randomized Controlled Trial. [Dataset].2022, March 29. Publisher Full Text\n\nMithra P, Unnikrishnan B, Thapar R, et al.: Modular intervention to improve paternal involvement and support for better infant and young child feeding in a district of coastal South India: a randomized controlled trial protocol. F1000Res. 2021; 10: 121. PubMed Abstract | Publisher Full Text\n\nHoffmann TC, Glasziou PP, Boutron I, et al.: Better Reporting of Interventions: Template for Intervention Description and Replication (TIDieR) Checklist and Guide. Gesundheitswesen. 2016 Mar 1; 78(3): 175–188. PubMed Abstract | Publisher Full Text\n\nMithra P, Unnikrishnan B, Rekha T, et al.: Paternal Involvement in and Sociodemographic Correlates of Infant and Young Child Feeding in a District in Coastal South India: A Cross-Sectional Study. Front. Public Health. 2021; 9. PubMed Abstract | Publisher Full Text Reference Source\n\nCTRI: [cited 2020 Dec 22]. Reference Source\n\nConsort - The CONSORT Flow Diagram: [cited 2020 Nov 13]. Reference Source\n\nMoher D, Schulz KF, Altman DG: The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. J. Am. Podiatr. Med. Assoc. 2001; 91(8): 437–442. PubMed Abstract | Publisher Full Text\n\nInbaraj LR, Khaja S, George CE, et al.: Paternal involvement in feeding and its association with nutritional status of children in an urban slum in a low-resource setting: A cross-sectional study. Nutrition. 2020; 74: 110735. PubMed Abstract | Publisher Full Text\n\nJordan PL, Wall VR: Breastfeeding and Fathers: Illuminating the Darker Side. Birth. 1990; 17(4): 210–213. PubMed Abstract | Publisher Full Text\n\nBakermans-Kranenburg MJ, Lotz A, Alyousefi-van Dijk K, et al.: Birth of a Father: Fathering in the First 1,000 Days. Child Dev. Perspect. 2019 Dec; 13(4): 247–253. PubMed Abstract | Publisher Full Text\n\nTohotoa J, Maycock B, Hauck Y, et al.: Supporting mothers to breastfeed: The development and process evaluation of a father inclusive perinatal education support program in Perth, Western Australia. Health Promotion International. Oxford Academic; 2011; vol. 26: 351–361.\n\nHan YE, Park S, Kim JE, et al.: Father Engagement in Improving Infant and Young Child Feeding (IYCF) Practices: Evidence from a Clustered Randomized Controlled Trial in Ethiopia (P11-112-19). Curr. Dev. Nutr. 2019 Jun 1; 3(Supplement_1): 1085–1087. [cited 2020 Nov 13].Publisher Full Text Reference Source\n\nSloand E, Gebrian B: Fathers clubs to improve child health in rural Haiti. Public Health Nurs. 2006; 23(1): 46–51. PubMed Abstract | Publisher Full Text\n\nMaycock B, Binns CW, Dhaliwal S, et al.: Education and support for fathers improves breastfeeding rates: A randomized controlled trial. J. Hum. Lact. 2013; 29(4): 484–490. PubMed Abstract | Publisher Full Text\n\nAbdullahi LH, Sheikh A, Elijah M, et al.: Save the Children Somalia Enhancing Infant and Young Child Feeding Practices in Somalia: Effect of Peer Counselling through Mother-to-Mother and Father-to-Father Support Groups.2019.\n\nMoher D, Schulz KF, Altman DG, et al.: The CONSORT statement: Revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet. 2001; 357. : p. 1191–1194. Elsevier Limited."
}
|
[
{
"id": "136589",
"date": "23 May 2022",
"name": "Sathish Thirunavukkarasu",
"expertise": [
"Reviewer Expertise Chronic disease epidemiology",
"particularly diabetes."
],
"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 by Mithra et al. examined the effectiveness of a module intervention in improving the involvement and practices of 120 fathers towards infant and young child feeding in a district in Karnataka state, India. The manuscript addresses an interesting topic, and it is well written. However, as detailed below, I have some significant concerns about the statistical methods used for analyses.\nProvide information on blinding participants and others involved in the trial, including those who conducted the analysis.\n\nThree participants were lost to follow-up, and leaving them out of the analysis is not an intention-to-treat (IIT) analysis. I agree it is a tiny number, but it would be good to impute the missing data using some ideal techniques to satisfy the IIT principle.\n\nThe authors did not use appropriate statistical methods for the analyses. Paired 't' test does not consider the correlation between repeated measurements taken on the same individual over time and does not adjust for any baseline differences in covariates. In this study, occupation and the knowledge score were not balanced between the two arms (please don't rely on the statistical tests for baseline differences), and they were not adjusted for in the analyses. Finally, with 't' test one cannot say that the mean change in one arm was higher or lower than that in the other arm (which the authors claim). I suggest using mixed-effects linear regression models for the analyses.\n\nWas there a possibility of contamination between study arms? If yes, how was it handled?\n\nWhy did the attitude score in the intervention group show lesser improvement than the knowledge and practice scores? Please provide some insights on 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? 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?\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? Yes",
"responses": [
{
"c_id": "8400",
"date": "05 Jul 2022",
"name": "Prasanna Mithra",
"role": "Author Response",
"response": "Reviewer Comments; followed by the response (in bold) by Authors: This article by Mithra et al. examined the effectiveness of a module intervention in improving the involvement and practices of 120 fathers towards infant and young child feeding in a district in Karnataka state, India. The manuscript addresses an interesting topic, and it is well written. However, as detailed below, I have some significant concerns about the statistical methods used for analyses. Provide information on blinding participants and others involved in the trial, including those who conducted the analysis. Thank you for your valuable suggestions and review. It was an open-label intervention. The nature of the intervention was not conducive to blind the participants or investigators. We have now specified the same in methodology. Three participants were lost to follow-up, and leaving them out of the analysis is not an intention-to-treat (IIT) analysis. I agree it is a tiny number, but it would be good to impute the missing data using some ideal techniques to satisfy the IIT principle. We have now used imputation for missing numbers and carried out ITT for all the outcome variables. A sentence is now added in this regard in the data analysis section. Data reanalysis is done and reported in the tables. The authors did not use appropriate statistical methods for the analyses. Paired 't' test does not consider the correlation between repeated measurements taken on the same individual over time and does not adjust for any baseline differences in covariates. In this study, occupation and the knowledge score were not balanced between the two arms (please don't rely on the statistical tests for baseline differences), and they were not adjusted for in the analyses. Finally, with 't' test one cannot say that the mean change in one arm was higher or lower than that in the other arm (which the authors claim). I suggest using mixed-effects linear regression models for the analyses. Thank you for the valuable suggestions and input. We have redone the data analysis using the mixed-effects linear model and reported the findings, to take care of the baseline differences across both arms. Also, we have now reported the adjusted mean scores for all the three outcome variables (adjusted for occupation and baseline knowledge scores). These have been now added to Table 2 to keep up the comprehensive structure and also to make it complete. Was there a possibility of contamination between study arms? If yes, how was it handled? Thank You. We chose the study areas for interventions from different taluks, to avoid contamination. Why did the attitude score in the intervention group show lesser improvement than the knowledge and practice scores? Please provide some insights on this. Both the groups had a higher attitude score in the baseline itself, so it showed the ceiling limit effect. A brief description in this regard has been added in the discussion section with an explanation for the same."
}
]
},
{
"id": "136587",
"date": "24 May 2022",
"name": "Elezebeth Mathews",
"expertise": [
"Reviewer Expertise Behavioural science",
"chronic disease 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\nAuthors have rightly identified the research gap of paternal involvement in child care and nutrition. This was a randomized controlled trial to enhance the involvement of fathers in infant and young child feeding practices among those fathers identified to have poor involvement in child care in Dakshina Kannada District. The authors have described the methodology clearly in this manuscript as deemed necessary and included citations for further details. This is a well-written manuscript.\nThere are no major revisions required, however, the details of the tests for validity and reliability of the outcome measurement tool need to be mentioned. The intervention procedure may be explained further in terms of intervention material and delivery. Though what constitutes the flipchart is mentioned, a table or a figure with the contents of each module in English Language will be useful.\n\nIn the results section, please mention if all participants attended six sessions (once per month for six months). The baseline characteristics were similar for both the groups except for the occupation. Authors may adjust for the inherent occupational differences in the intervention and control arm for the outcome. Consider doing a statistical analysis wherein you estimate the effect size.\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": "8401",
"date": "05 Jul 2022",
"name": "Prasanna Mithra",
"role": "Author Response",
"response": "Reviewer Comments; followed by the response (in bold) by Authors: Authors have rightly identified the research gap of paternal involvement in child care and nutrition. This was a randomized controlled trial to enhance the involvement of fathers in infant and young child feeding practices among those fathers identified to have poor involvement in child care in Dakshina Kannada District. The authors have described the methodology clearly in this manuscript as deemed necessary and included citations for further details. This is a well-written manuscript. There are no major revisions required, however, the details of the tests for validity and reliability of the outcome measurement tool need to be mentioned. The intervention procedure may be explained further in terms of intervention material and delivery. Though what constitutes the flipchart is mentioned, a table or a figure with the contents of each module in English Language will be useful. Thank you for your valuable suggestions and comments. We have now added detail on the test used for the reliability and validity of the data collection tool. We have now added a pictorial component describing the module content briefly. Also we have described the module delivery process for more clarity. In the results section, please mention if all participants attended six sessions (once per month for six months). We have added a sentence mentioning all participants having attended the sessions once a month for 6 months. The baseline characteristics were similar for both the groups except for the occupation. Authors may adjust for the inherent occupational differences in the intervention and control arm for the outcome. Thank you. We have now revised the statistical methods used for analyzing the effect of interventions and adjusted outcomes have been reported. We have used a linear mixed-effects regression model. The baseline differences were included in the model. Consider doing a statistical analysis wherein you estimate the effect size. Thank you for the suggestion. We have now done the analysis and estimated the effect size. The same has been mentioned in the data analysis description."
}
]
},
{
"id": "136588",
"date": "15 Jun 2022",
"name": "Amutha Ramadas",
"expertise": [
"Reviewer Expertise 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\nOverall, the manuscript is clearly written for comprehension of the scientific community. The title and abstract reflected the content of the manuscript.\n\nI believe the article may benefit from the following input:\nIntroduction is brief and should provide more in-depth background info and justification for the research gap.\n\nMethods - The flow is clear, and ethics approval and sample size justification have been provided. However the intervention may need to be described further, perhaps with some examples of the materials used.\n\nResults - I have a concern with the significant difference in occupation status between groups, which could have impacted the results but was not adjusted for when the main outcomes were compared.\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?\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": "8402",
"date": "05 Jul 2022",
"name": "Prasanna Mithra",
"role": "Author Response",
"response": "Reviewer Comments; followed by the response (in bold) by Authors: Overall, the manuscript is clearly written for comprehension of the scientific community. The title and abstract reflected the content of the manuscript. I believe the article may benefit from the following input: Introduction is brief and should provide more in-depth background info and justification for the research gap. Thank you for the valuable input and suggestions. The “Introduction” section is now revised to add relevant points as suggested and background information is made more robust. A stronger justification for the research gap is now added. Methods - The flow is clear, and ethics approval and sample size justification have been provided. However the intervention may need to be described further, perhaps with some examples of the materials used. Thank you. We have now revised the text related to the intervention procedure. Have added more details on the module and added examples at relevant places as per the suggestion. Results - I have a concern with the significant difference in occupation status between groups, which could have impacted the results but was not adjusted for when the main outcomes were compared. Thank you for the suggestion. We have now relooked into the analysis part based on the comments of the reviewers and have adjusted for the baseline differences to report the outcomes. Both the adjusted estimates and effect of interactions have been reported."
}
]
}
] | 1
|
https://f1000research.com/articles/11-486
|
https://f1000research.com/articles/11-745/v1
|
05 Jul 22
|
{
"type": "Research Article",
"title": "Behavioral and psychosocial predictors of depression in Bangladeshi medical students: a cross-sectional study",
"authors": [
"Md Rizwanul Karim",
"Helal Uddin Ahmed",
"Shahnaz Akhter",
"Helal Uddin Ahmed",
"Shahnaz Akhter"
],
"abstract": "Background: Depression, stress, and anxiety were found in a large number of medical undergraduate students, indicating a neglected aspect of their psychology that required immediate attention. The goal of this study was to find out the prevalence of depression among medical students, as well as potential psychosocial and behavioral predictors for depression. Methods:\n\nThis cross-sectional study was conducted from July to November 2021 among 840 randomly selected medical students from four medical colleges using stratified random sampling. Data were collected using a semi-structured, self-administered questionnaire and were analyzed through the SPSS v.23 software. Multiple regression was performed to assess the effect of several behavioral and psychosocial factors on depression.\n\nResults: Among the 840 study participants, 55.7% (n= 468) were female and 44.3% (n= 372) were male. According to the data, the prevalence of depression, anxiety, perceived stress among medical students was found to be 28.8%, 65% and 85% respectively. A strong link was found between depression and anxiety, stress, poor sleep quality, poor academic performance, and a negative social and romantic relationship status.\n\nConclusions: A significant number of medical students are depressed. In order to prevent and treat depression, medical students should be screened for depression and its associated factors.",
"keywords": [
"Depression",
"anxiety",
"Perceived stress",
"sleep quality",
"Facebook addiction"
],
"content": "Introduction\n\nDepression affects about 5.0% of the world’s adult population. There are about 280 million people in the world suffering from depression.1 Recurrent and severe depression can negatively affect a person’s performance at work, at school and life at home. At its worst, depression may lead to suicide. The World Health Organization (WHO) lists suicide as the fourth most common cause of death among 15-29-year-olds. According to the national mental health survey of Bangladesh provisional fact sheet 2018-19, the prevalence of depression was 6.7% (5.8-7.6).2\n\nA medical student’s mental health is generally similar to or better than that of the general population before they enter the medical school.3–7 But among medical students who have begun their course, depression is one of the most common mental health issues due to the intensity of the training.8 Undergraduate medical education requires intense study and training for five to six years. Because of advancing knowledge and evolving therapies, the curricular objectives are constantly evolving. The learning period should prepare medical students to deal independently with lifelong professional challenges by acquiring sufficient professional knowledge, skills, and attitudes. Students’ physical and mental health could be adversely affected by the demands of studying and training. As a consequence, a number of medical students are reported to suffer from depression, anxiety, and stress.9–11\n\nMedical students are subjected to various academic and psychosocial stressors that are thought to be typical of their environment.7,12 As medical students, they deal with workload,12–14 academic pressure,15 the pressure to demonstrate competence as a clinician,16 sleep deprivation,13 peer competition,13 fear of failure,13 the death and suffering of patients,17 student abuse,18 financial problems,13,14 etc. Several systematic reviews and meta-analyses showed that medical students around the world suffer from depression at a rate of 28%, and that suicidal ideation occurs at a rate of 11.1%.19–21 In the world, one in three medical students are depressed,19 a rate much higher than the general population (3.9–6.6%)22,23 and nonmedical students (19% in men, 22% in women).24 In addition, first-year residents reported an increased level of depression.25 Chronic sleep deprivation,25 perceived stress, and anxiety have all been demonstrated to be important predictors of depression.26 Identifying risk factors for depression among medical students should be a priority because depression among this group can lead to low quality of life, dropping out,27 and eventually suicidal ideation.\n\nInternet Addiction (IA) was found to be linked to depression and academic issues in a Thai study and the odds of depression in the possible IA group were 1.58 times higher than in the normal Internet use group (95%CI: 1.04–2.38).28\n\nAround 40% of Bangladeshi students were found to be at danger of Facebook addiction. Being of single status, a lack of physical activity, sleep disruption, Facebook use time, and depression symptoms have all been linked to Facebook addiction.29 Internet Addiction and depression have previously been linked in adults,30 adolescents,31–33 and college students.34 In a systematic review of comorbid psychopathology in pathological Internet use, 75% of the papers examined indicated a substantial link between pathological Internet use and depression.35 When compared to other mental comorbidities, depression exhibited the strongest connection to pathological Internet use.34 The prevalence of depression was consistently higher in the IA group than in the control group, according to a meta-analysis of five trials.36\n\nMedical students have been shown to have a high level of psychological morbidity,37–42 and they experience more psychological distress than the general population.40 Depression, stress, and anxiety were observed in a considerable number of medical undergraduate students, indicating a neglected element of their psychology that needed prompt care.43 Otherwise, students’ distress can have a negative impact on professional development and academic performance, as well as contribute to academic dishonesty, substance abuse, and medical school attrition.40 According to earlier research on medical school graduates, stress has a detrimental impact on patient care quality, patient safety,44 and professionalism.45\n\nBoth physical and mental wellness require adequate and high-quality sleep,46,47 whereas poor sleep quality or insufficient sleep are linked to unhealthy lifestyle habits such as internet use. Excessive internet use is, in fact, a leading predictor of poor sleep quality and workplace negligence.48 Furthermore, during health emergencies, studies show that the general population experiences increased fear, anxiety, and stress, and that these unfavorable emotional and mental health situations negatively affect the public’s sleep quality, particularly university students.49\n\nAlarmingly, many Bangladeshi medical students have recently committed suicide.50,51 Stress, depression, and anxiety among undergraduate students are underdiagnosed in more than half of instances, according to previous studies in other countries. Furthermore, they are frequently undertreated, resulting in increased psychological morbidity, which has a negative impact on their job and personal lives.52\n\nThe purpose of this study was to determine the prevalence of depression among medical students at Public Medical Colleges as well as implicit depression predictors such as anxiety, perceived stress, internet addiction, Facebook addiction, sleep quality, sociodemographic and behavioral factors.\n\nEthical approval was obtained from the Bangladesh Medical Research Council (BMRC) Ethical Review Committee (BMRC/HPNSP-Research IRB 2020-2021 I 320). All ethical issues related to this study were carefully addressed in accordance with the Helsinki Declaration including their privacy, confidentiality and anonymity. There was no invasive procedure or private issue in the study, and no drug was tested. Before starting the data collection process, a brief explanation of the study’s goals and objectives was given to the respondents. Their written informed consent were then obtained in a separate consent form that was attached to the main questionnaire. They were informed of their complete right to participate or decline in the study. A semi-structured self-administered questionnaire was used to collect data. Respondents were assured that the information provided by them e.g., their names or anything which could identify them, would be kept confidential and anonymous and the anonymized data and or results of the study will only be disseminated and published for public interest.\n\n\nMethods\n\nThis cross-sectional study was conducted from July to November 2021, among students from four public medical colleges chosen at random from among 37 public medical colleges in Bangladesh.\n\nThe sample size was determined based on a 95% confidence interval and a 5% sampling error. The required sample size to estimate a true prevalence of depression was computed using Epitools. Assuming the prevalence of depression among medical students of 39.153 and sensitivity 74% and specificity 91% for PHQ9,54 the estimated sample size was 838. Using two-step stratified random sampling we enrolled 840 medical students from a total of 5000 medical students (4*1250) from four selected medical colleges. First, a request letter explaining the study’s objectives was sent to the principal offices of the corresponding medical colleges. The research team then organized a presentation and question-and-answer session on the study protocol for each year’s students in collaboration with the respective medical college administration. In the final step, 42 students were chosen at random from each year, ranging from the first to the fifth year, for a total of 210 students from each medical college.\n\nThe pretested Bengali version of the questionnaire was translated and back-translated by two independent bilingual translators to check the consistencies avoiding response bias. The selected respondents were given the Bengali version of the questionnaire and asked to complete it in their own time within a three-day window. It took them approximately twenty-five minutes to complete the self-reported survey. Before implementing the survey, formal permission from the IRB was obtained as well as written consent from the participants. After checking for inconsistencies and missing values, all 840 participants were found to have completed the entire survey questionnaire and the data were entered into the SPSS v-23 software for further analysis.\n\nThe questionnaire included a total of 122 questions and was divided into eight sections, as follows:\n\n1. Socio-demographic variables\n\nThis section included several questions on socio-demographic variables, including age, gender, permanent residence (city or village area), relationship status (single or in a relationship), Parental education, average monthly income, type and place of residence, religion, etc.\n\n2. Internet use and Facebook use related variables\n\nThe variables in this section were: device used, type of network, time since they started using the internet, primary purpose of internet use, average daily use, average monthly expenditure for internet use, total ID, fake ID, effect of internet on financial status, academic status, effect on relationship with friends and family, effect on romantic relationship, number of friends, followers, average number of posts, average comment and reaction per FB post, self-measures to limit internet use.\n\n3. Chen Internet Addiction Scale CIAS\n\nThe CIAS is a four-point, 26-item self-reported scale that assesses five dimensions of Internet-related behavioral attributes, including compulsive use, withdrawal, tolerance, interpersonal relationship problems, and health/time management issues.55 The Chen Internet Addiction Scale has a total score range of 26 to 84, with higher CIAS scores indicating more severe Internet Addiction. Internal reliability for the scale and its subscales in the initial study ranged from 0.79 to 0.93. A previous literature argued that the diagnostic cut-off point (63/64) gave CIAS the best diagnostic accuracy, Cohen Kappa, and DOR and using this point, more than 80% of cases can be correctly classified.56\n\nWith the exception of the Chen Internet Addiction Scale CIAS, which was used unchanged to measure internet addiction among medical students, all of the scales used in the study had previously been validated in Bengali. For this purpose, a pilot survey was conducted among 260 medical students in two public medical colleges other than the four medical colleges chosen for the study sample; 26 medical students were chosen at random from each session’s attendance registration (first year to fifth year) from two medical colleges. The study purpose was communicated to them prior to any interviews, and their informed consent was obtained. The items and dimensions of the original CIAS scale items used in this study were described and rationalized using factor analysis, which supports the tool’s use in this study.\n\nWe used our study data to conduct principal component analysis (PCA) on the 26 items of the Chen Internet Addiction Scale to support the pilot survey. The suitability of the data for factor analysis was determined prior to performing PCA. The correlation matrix revealed the presence of all coefficients of.36 and higher. The Kaiser-Meyer Olkin value was .94, which exceeded the recommended value of .6,57 and the Bartlett’s Test of Sphericity58 reached statistical significance, indicating that the correlation matrix was factorable. The presence of five components with eigen values greater than one was revealed by principal component analysis. and the five-component solution explained a total of 50.23% of the variance with Component 1 to Component 5 contributing, 12.04%, 11.07%, 10.94%, 10.21 and 5.97% of the variance respectively. An inspection of the scree plot revealed a clear break after the fifth component. Using Cattell’s59 scree test, it was decided to retain five components for further investigation.\n\nTo aid in the interpretation of these five components, varimax rotation was performed. The rotated solution (presented in Table 1) revealed the presence of simple structure (Thurstone, 1947), with components showing several strong loadings, and all variables loading substantially on only one component. The interpretation of the five components was consistent with the type of items; seven items loaded onto Factor 1, which are related to compulsive use. Factor 2 comprised of five items reflect health-time conflict, factor 3 consists of six items related to behavioral and social distraction, factor 4 consists of five items which indicate tolerance and finally factor 5 consists of three items related to withdrawal (Table 1).\n\na Rotation converged in 12 iterations.\n\nThe internal consistency of the whole Chen Internet Addiction Scale (CIAS) is.90 (Chronbach’s alpha). The split half correlation (> .80) and Guttman correlation coefficient (> .80) also support the rationality of use of 26 items Chen Internet Addiction Scale to measure internet addiction among Bangladeshi medical students (see Table 2).\n\n4. Bergen Facebook Addiction Scale (BFAS)\n\nThe Bergen Facebook Addiction Scale60 is 6 items measured with a five-point Likert-type scale (1 = very rarely, 2 = rarely, 3 = sometimes, 4 = often, 5 = very often). This scale is concerned with experiences of six core elements of addiction i.e., salience, tolerance, mood modification, conflict, relapse, and withdrawal during the past year related to Facebook use. The Cronbach’s Alpha of this measure in the original study was 0.83. Item-total correlations ranged from 0.60 to 0.73 and the test-retest reliability was 0.82 as reported by authors.\n\nBangla BFAS had a sufficient level of reliability and validity and this measure could be applicable in Bangladeshi culture for screening out Facebook addiction.61\n\n5. Perceived Stress Scale PSS10 B\n\nThe PSS-10 measures the degree to which one perceives aspects of one’s life as uncontrollable, unpredictable, and overloading.62 Participants are asked to respond to each question on a five-point Likert scale ranging from 0 (never) to 4 (very often), indicating how often they have felt or thought a certain way within the past month. Scores range from 0 to 40, with higher composite scores indicative of greater perceived stress. The PSS10 possesses adequate internal reliability.62\n\nThe original English 10-item version of PSS62 was translated into Bangla by different researchers.63–65 One of the authors observed a significant correlation r = .90, p < .01 between the PSS-10-B (Bengali translated and adapted version of PSS10)64 with the original English version of PSS-10.65 Test-retest reliability of the Bangla adaptation was high over a period of two weeks, r = .94, p < .01, and indicated that the Bangla PSS-10 scale can be used to measure perceived stress of Bangladeshi people.65\n\n6. Patient Health Questionnaire PHQ9\n\nThe Patient Health Questionnaire (PHQ-9) is a nine-item self-administered scale developed to diagnose the presence and severity of depressive symptoms during over two weeks. The PHQ-9 total score ranges from 0 to 27, because each of the 9 items can be scored from 0 (“not at all”) to 3 (“nearly every day”). Easy-to-remember cut-points of 5, 10, 15, and 20 represent the thresholds for mild, moderate, moderately severe, and severe depression, respectively. If only one screening cut-point is used, researchers currently recommend a PHQ-9 score of 10 or higher, which has an 88 percent sensitivity for major depression, an 88 percent specificity, and a positive likelihood ratio of 7.1.66\n\nThe Bengali translated version of PHQ9 showed good reliability; Cronbach’s alpha 0.837, gender-wise 0.839 for males and 0.841 for females; and the Spearman-Brown Coefficient is 0.855, and the Guttman Split-half coefficient is 0.848, which indicate the high Split-half reliability as well.67\n\n7. Generalized Anxiety Disorder GAD7\n\nThe GAD-7 is a self-administered seven-item instrument used as a screening tool for generalized anxiety disorder. Response options for each item range from 0 to 3 on a four-point Likert-scale (0 = not at all, 1 = several days, 2 = more than half the days and 3 = nearly every day). Adding the scores of all seven items provide the GAD-7 total score ranging from 0 to 21. Several validation studies have detected cut-points of ≥5, ≥10 and ≥15 based on receiver operating characteristics analysis for GAD-7, standing for mild, moderate and severe anxiety levels, respectively.68\n\nIn Bangladesh, previous studies revealed good internal consistency of GAD-7 (Cronbach’s α = 0.87)69 and good convergent validity of GAD-7 with two other scales, PHQ-9 and PHQ-ADS.70\n\n8. Pittsburgh Sleep Quality Index (PSQI)\n\nThe PSQI, one of the most widely used tools for evaluating sleep quality, is a parameter-based questionnaire that relies on self-reported responses. It was first developed by Buysse et al. in 1989.71 The PSQI consists of 19 questions that are broken down into seven categories (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, use of sleep medication, and daytime dysfunction), all of which are weighted equally on a 0–3 scale to evaluate the quality of sleep over the previous month.71 The seven component scores are then added together to produce a final PSQI sleep quality score that ranges from 0 to 21, with 0 being the best and 21 being the worst. Poorer sleep quality is indicated by a higher score. The validated Bangla version of the PSQI, also known as the Bengali Pittsburgh sleep quality index, was used in the current study to assess participants’ sleep quality (BPSQI). Poor sleep quality was defined as having a BPSQI score greater than 5.72\n\nData analysis was performed using SPSS statistical software version 23.0 (IBM Corp). Factor analysis and a reliability test were performed to assess the items and dimensions of CIAS in Bangladeshi medical students. Multiple regression was performed to assess the effect of several factors on the likelihood that respondents have depression according to PHQ-9 scale score. Analysis was conducted using depression as the dependent variable and a number of sociodemographic and behavioral factors as the independent variables, including age, sex, income, place of residence, housing status, type of family, physical activity, duration/cost and time of internet use, impact of personal social and academic and romantic life, internet addiction, Facebook addiction, perceived stress, anxiety, sleep quality, etc. The final results were presented with statistical significance, regression coefficients, and 95% confidence intervals for beta-coefficient for each of the predictors.\n\n\nResults\n\nAmong 840 study participants, 55.7% (n = 468) were female and 44.3% (n = 372) were male. The average age of the respondents was 21 years. 84% (n = 702) of the respondents were Muslim and 15% (n = 127) of the students were Hindu. In terms of their parents’ occupations, 31.5% (n = 265) of their fathers were businessmen, while 70% (n = 590) of their mothers stayed at home. One out of every ten respondents live alone, and seven percent of the medical students in the study sample were married. Three quarters of the respondents had personal income and 64%, n = 539 of the medical students resided in medical hostels.\n\nAccording to the data, 65% of respondents experienced mild to severe anxiety, (Figure 1A) and 85% of medical students experienced moderate to high perceived stress (Figure 1B). Alarmingly, 86% (n = 727) of the samples reported having fake Facebook ids and having used Facebook for an average of five years; Mean (SD) = 4.63 (1.88). Facebook Addiction and Internet Addiction were found in 28.8% (Figure 1C) and 30.8% (Figure 1D) of medical students, respectively. Eighty-six percent of the sample population slept poorly (Figure 1E), and 28.8% of respondents suffered from moderate to severe depression (Figure 1F). The full results of the analysis can be found under Underlying data.90\n\nA. Anxiety Levels of the respondents (GAD-7 scale cut-off). B. Perceived Stress Categories of the respondents (PSS10 cut-off). C. Facebook Addiction Categories of the respondents (BFAS cut-off). D. Internet addiction Categories of the respondents (CIAS cut-off). E. Sleep Quality among the respondents (PSQI cut-off). F. Depression categories of the respondents (PHQ-9 cut-off).\n\nTable 3 shows respondents with negative social, familial, and romantic relationships, as well as poor academic performance, were found to be more depressed, and the proportional differences between depression categories were shown to be statistically significant. [(χ2 = 16.31, p = .000), (χ2 = 35.007, p = .000), (χ2 = 22.14, p = .000), (χ2 = 29.54, p = .000)].90\n\nFacebook addiction was present among 28.8% of the study samples and was found to be significantly linked with depression (χ2= 50.59, df 1, p = .000). All six domains of the Bergen Facebook Addiction Scale were also statistically significantly associated with depression (p ≤ .01) (Table 4). Table 4 also shows that the presence of depression is 1.5 to 3 times more likely among the sample population who have features of Facebook addiction.\n\nEach of the Pittsburg Sleep Quality Index’s seven dimensions were statistically significantly associated with depression (p = .001). According to Table 5, 68% (28/41) of the sample population who have “very poor” perceived “overall sleep quality” have depressive symptoms.\n\nTable 6 demonstrates the relationship between depression and other behavioral factors. Internet addiction was measured by the Chen Internet Addiction scale and internet addiction was found to be significantly statistically associated with depression (χ2 = 61.1, df 1, p = .000). Facebook addiction also had a significant relationship with depression among the sample population (χ2 = 50.59, df1, p = .000). According to the data, nearly half of the sample medical students who were addicted to Facebook were also depressed, and this proportion was more than double when compared to those who were not addicted to Facebook. More than three-quarters of medical students who reported severe anxiety and high levels of perceived stress also reported depression, and the link between anxiety and depression, as well as the link between perceived stress and depression, was found to be statistically significant. (χ2 = 273.32, df3, p = .000) and (χ2 = 129.18, df2, p = .000).90\n\nFinally, sleep quality was observed to be statistically related to depression among respondents (2 = 16.94, df1, p = .000), with data revealing that more than a third of poor sleepers experienced depression during the study period.\n\nMultiple regression was used to assess significant predictors (anxiety, perceived sleep, sleep quality, perceived stress, internet addiction, romantic relationship, academic performance, sports and games and period of social media use) for depression score (PHQ9), after controlling for the influence of multiple sociodemographic and behavioral factors in the sample population. Preliminary analyses were performed to ensure that the assumptions of normality, linearity, multicollinearity, and homoscedasticity were not violated.\n\nTotal variance explained by the model as a whole was 59% and F change for the model was (26, 813) = 47.42, p < .001. In the model, anxiety, perceived sleep quality, sleep quality index, perceived stress, internet addiction, romantic relationship, academic performance, sports and games and period of social media use were found to be statistically significant predictors for depression (PHQ9 total score) yielding beta value (beta = .55, p = .000), (beta = .08, p = .001), (beta = .075, p = .007), (beta = .104, p = .001), (beta = .137, p = .000), (beta =.054, p = .028), (beta = -.071, p = .009), (beta = -.057, p = .012), (beta = - .077, p = .001) respectively (see Table 7).\n\n\nDiscussion\n\nThe purpose of this cross-sectional study was to determine the prevalence of depression among medical students, as well as potential depression predictors such as anxiety, perceived stress, internet addiction, Facebook addiction, sleep quality, sociodemographic and behavioral characteristics of medical students.\n\nDepression was observed in 28.8% of medical students in our study, which is five times higher than the national prevalence of depression among adults.2 The exact prevalence had also been observed among medical students in Thailand.28 A meta-analysis of 77 studies that included 62,728 medical students and 1,845 non-medical students revealed a 28.0% global prevalence of depression among medical students.19 Similar findings have been reported among medical students in Nepal,3 Massachusetts4 and Estonia39 though Zaman et al. reported 39.1% depression in a previous study in Bangladesh53 and Iqbal et al. observed 51.3% depression among Indian medical students.43\n\nIn the current study, perceived stress was measured using PSS10B, and 85% of the medical students reported moderate to severe stress; however, in other DASS-based studies, 53% of medical students in India,43 63.7% in Egypt,73 and 47.1% in Brazil74 reported stress. A comparative study of public and private medical students in Bangladesh used GHQ-12 to measure stress, and the overall prevalence of stress was found to be 54%.75 Because it is more about their feelings about lack of control and unpredictability than actual stressors, the prevalence of perceived stress may be higher than actual stress.\n\nAccording to our findings, 65% of respondents experienced mild to severe anxiety, which is nearly double the result of a meta-analysis of 69 studies involving 40,348 medical students, which found that the overall prevalence of anxiety was 33.8%,76 but is consistent with the findings of similar studies conducted in India43 and Egypt.73 However, anxiety was found to be most prevalent among medical students from the Middle East and Asia in a meta-analysis on the global prevalence of anxiety among medical students.76\n\nInternet addiction was found in 30.8% of medical students in our study, which is slightly higher than in two previous studies in Bangladesh.77,78 The current rate (30.8%) was lower than in other Middle Eastern countries such as Jordan (40%)79 and Iran (39.6%),80 but higher than studies conducted among British (18.3%)81 and Taiwanese (17.4%).82 According to a systematic review, the prevalence of Internet overuse/possible Internet addiction among Southeast Asian students ranged from 7.4% to 46.4%.83\n\nFacebook addiction was found to be 28.8% in this study, which is 10% lower than a previous study in Bangladesh.29\n\nA recent study found that 69.5% of Bangladeshi medical college students had poor sleep quality,84 whereas our data revealed that 86% of the study sample had poor sleep quality.\n\nAccording to an editor’s note depression and anxiety are highly comorbid and their symptoms are frequently inseparable.85 Previous research has also found that poor sleep quality,86–88 poor academic performance,28,89 and relationship status89 are strong predictors for depression. Several studies reported a link between perceived stress and the presence of depressive symptoms, particularly severe depression.86,87 Depression was 1.58 times more likely in the possible Internet addiction group than in the normal Internet use group,28 and our data analysis confirmed this significant relationship. In the current study, anxiety, perceived sleep quality, sleep quality index, perceived stress, internet addiction, romantic relationship, academic performance, sports and games, and duration of having a social media account were all found to be statistically significant predictors of depression.\n\nA strength of the study is that it was carried out with validated tools and a random sampling method. Because the current study is cross-sectional, data on the temporality of the relationship between variables is missing. Another flaw is that the mental health outcomes of medical students were not compared to clinician diagnoses.\n\n\nConclusions\n\nAccording to the current study, an alarming proportion of medical students suffer from depression. There is a strong link between depression and anxiety, stress, poor sleep quality, poor academic performance, and a negative social and romantic relationship status. Screening for depression and its associated factors among medical students should be prioritized in order to prevent and treat depression.\n\n\nData availability\n\nMendeley: Behavioral and psychosocial predictors of depression in Bangladeshi medical students: a cross-sectional study. doi: https://doi.org/10.17632/ykmywfnbbf.190\n\nThis project contains the following underlying data:\n\n- Depression among medical students.sav\n\n- Code book for depression among medical students.spv\n\nThis project contains the following extended data:\n\n- Depression among medical students English questionnaire.pdf\n\n- Depression among medical students Bengali Questionnaire.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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PubMed Abstract | Publisher Full Text\n\nHassan T, Alam MM, Wahab A, et al.: Prevalence and associated factors of internet addiction among young adults in Bangladesh. J. Egypt. Public Health Assoc. 2020; 95: 3. PubMed Abstract | Publisher Full Text\n\nIslam MA, Hossin MZ: Prevalence and risk factors of problematic internet use and the associated psychological distress among graduate students of Bangladesh. Asian J. Gambl. Issues Public Health. 2016; 6(1): 11. PubMed Abstract | Publisher Full Text\n\nAl-Gamal E, Alzayyat A, Ahmad MM: Prevalence of internet addiction and its association with psychological distress and coping strategies among university students in Jordan. Perspect. Psychiatr. Care. 2016; 52(1): 49–61. PubMed Abstract | Publisher Full Text\n\nAtaee M, Ahmadi JT, Emdadi SH, et al.: Prevalence of internet addiction and its associated factors in Hamadan University of medical college students. Life Sci. J. 2014; 11(spec. issue 4): 214–217.\n\nNiemz K, Griffiths M, Banyard P: Prevalence of pathological internet use among university students and correlations with self-esteem, the General Health Questionnaire (GHQ), and disinhibition. CyberPsychology Behav. 2005; 8(6): 562–570. PubMed Abstract | Publisher Full Text\n\nHa YM, Hwang WJ: Gender differences in internet addiction associated with psychological health indicators among adolescents using a national web-based survey. Int. J. Ment. Health Addict. 2014; 12(5): 660–669. Publisher Full Text\n\nBalhara YPS, Mahapatra A, Sharma P, et al.: Problematic internet use among students in South-East Asia: Current state of evidence. Indian J. Public Health. 2018 Jul-Sep; 62(3): 197–210. PubMed Abstract | Publisher Full Text\n\nJahan MS, Hossain SR, Sayeed UB, et al.: Association between internet addiction and sleep quality among students: a cross-sectional study in Bangladesh. Sleep Biol. Rhythms. 2019; 17: 323–329. Publisher Full Text Google Scholar\n\nKalin NH: The Critical Relationship Between Anxiety and Depression. Editor’s note. Am. J. Psychiatry. May 2020; 177: 5. Publisher Full Text\n\nMoreira DP, Furegato ARF: Stress and depression among students of the last semester in two nursing courses. Rev. Lat. Am. Enfermagem. 2013; 21(n. spe [Accessed 8 June 2022]): 155–162. Publisher Full Text\n\nLiu Z, Liu R, Zhang Y, et al.: Association between perceived stress and depression among medical students during the outbreak of COVID-19: The mediating role of insomnia. J. Affect. Disord. 2021 Sep 1; 292: 89–94. Epub 2021 May 27. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbdussalam A, Salman MT, Gupta S, et al.: Poor Quality of Sleep and its Relationship with Depression in First Year Medical Students. Adv. Life Sci. Technol. 2013; 12: 17–21.\n\nPaudel K, Adhikari TB, Khanal P, et al.: Sleep quality and its correlates among undergraduate medical students in Nepal: A cross-sectional study. PLOS Global Public Health. February 18, 2022; 2. Publisher Full Text\n\nKarim MR: Behavioral and psychosocial predictors of depression in Bangladeshi medical students: a cross-sectional study. Mendeley Data. 2022; V1. Publisher Full Text"
}
|
[
{
"id": "185702",
"date": "28 Jul 2023",
"name": "Gerasimos N. Konstantinou",
"expertise": [
"Reviewer Expertise Clinical Psychiatry",
"Psychopathology",
"Brain Stimulation",
"Psychoimmunology"
],
"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 review this very well written and interesting (as well as alarming) manuscript. It is indeed well known that medical students frequently have to face or deal with psychological difficulties during Medical School mainly due to the workload, academic pressure, pressure to demonstrate competence as clinicians, sleep deprivation, peer competition. As a result, it is anticipated that this population would experience increased levels of stress, perceived stress, depressive and anxiety symptomatology.\nThe authors conducted a very well structured study and the were able to confirm this hypothesis. The language of the manuscript, as well as the structure of the manuscript and the references are appropriate. The authors may want to elaborate more on their findings in the discussion part, instead of just re-presenting their results, and they could potentially make some recommendations for future research or appropriate interventions that could/should be considered to protect/help this population. It would also be interesting to compare their result with those of countries in Europe, or North and South America, if any. Finally, I think the authors should also comment on the fact that the study was conducted in 2021, during the pandemic, which could be an additional component/stressor.\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": "238190",
"date": "15 Feb 2024",
"name": "Hanaa E bayomy",
"expertise": [
"Reviewer Expertise Public Health and Community Medicine",
"Health Promotion",
"Preventive Medicine",
"and 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\nOverall, this manuscript is technically sound. The components of the research are represented appropriately, as regards the title, introduction, methods, results, discussion, and conclusion. Topic & title: The manuscript introduces an important topic; depression among medical students that warrants careful examination. Medical students are at greater risk of depression due to workload, academic pressure, the pressure to demonstrate competence as a clinician, sleep deprivation, peer competition, fear of failure, the death and suffering of patients, student abuse, financial problems, etc. Depression can negatively impact students’ life quality, academic performance, and social relations. Thus, it is important to investigate this problem to determine predisposing factors and guide prevention and control interventions. The title of the study described the topic well and indicated the study design. Abstract: A structured abstract is there with items of an abstract (background, methods, results, and conclusion). the keywords are suitable for the topic of the study, however, ‘medical students’ should be added to keywords to specify the study population. Introduction: The topic of the study was defined and analyzed leading to the rationale and objectives of the study. Methods: This is a cross-sectional study, suitable to assess the prevalence of depression in medical students. The study population comprised a random sample of medical students from four different medical colleges. Ethical considerations were cleared before implementing the survey and formal permission from the IRB was obtained as well as written consent from the participants. Validated instruments were used for data collection. Data collection instruments were carefully described and validated, as appropriate. Data are available from the given citation. Suitable statistical methods were used to test the validity of data collection tools such as Principal Component Factor Analysis and Cronbach’s Alpha, as well as to evaluate the association between depression and potential risks. Results: Findings were presented in suitable tables and figures. Discussion: Results were explained and discussed. Conclusion: Coincided conclusion based on study results was mentioned. References: Relevant Up-to-date references are presented in a systematic method.\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/11-745
|
https://f1000research.com/articles/11-229/v1
|
24 Feb 22
|
{
"type": "Brief Report",
"title": "Building a database for energy sufficiency policies",
"authors": [
"Benjamin Best",
"Johannes Thema",
"Carina Zell-Ziegler",
"Frauke Wiese",
"Jonathan Barth",
"Stephan Breidenbach",
"Leonardo Nascimento",
"Henry Wilke",
"Johannes Thema",
"Carina Zell-Ziegler",
"Frauke Wiese",
"Jonathan Barth",
"Stephan Breidenbach",
"Leonardo Nascimento",
"Henry Wilke"
],
"abstract": "Sufficiency measures are potentially decisive for the decarbonisation of energy systems but rarely considered in energy policy and modelling. Just as efficiency and renewable energies, the diffusion of demand-side solutions to climate change also relies on policy-making. Our extensive literature review of European and national sufficiency policies fills a gap in existing databases. We present almost 300 policy instruments clustered into relevant categories and publish them as \"Energy Sufficiency Policy Database\". This paper provides a description of the data clustering, the set-up of the database and an analysis of the policy instruments. A key insight is that sufficiency policy includes much more than bans of products or information tools leaving the responsibility to individuals. It is a comprehensive instrument mix of all policy types, not only enabling sufficiency action, but also reducing currently existing barriers. A policy database can serve as a good starting point for policy recommendations and modelling, further research is needed on barriers and demand-reduction potentials of sufficiency policy instruments.",
"keywords": [
"energy demand",
"sufficiency policy",
"behavioural change",
"energy descent",
"socio-ecological transformation",
"policy database"
],
"content": "Introduction\n\nSufficiency is a potentially low-cost, fast and socially just mean of global greenhouse gas (GHG) mitigation. It is linked to multiple benefits for human well-being.1 The understanding of sufficiency varies across disciplines and discursive spheres; in relation to energy, sufficiency is the strategy that aims at achieving absolute reductions in the use of energy-based services.2 Energy sufficiency, renewable energies and energy efficiency are all methods to reduce emissions associated with energy use. Renewables substitute fossil fuels, efficiency means finding ways to reduce losses by improving the input/output relation, and sufficiency equals avoiding/shifting energy services altogether.\n\nJust as renewable energy and efficiency technologies, energy sufficiency is enabled and promoted by policy action. It is a genuine field of policy making, a case for regulatory frameworks and infrastructures, much beyond micro-level individual behaviour changes.1,3–6 We differentiate three sufficiency types to categorise policy instruments by whether they are aimed at a clear avoid strategy, i.e. a reduction of services; at shift, i.e. substituting energy intensive practices by less energy-intensive ones; or in general supporting reductions and substitutions.[1]\n\nThe need for a sufficiency policy database has been formulated by various researchers and ministerial representatives, e.g. Toulouse et al.7 and Zell-Ziegler and Förster.8 Sufficiency is underrepresented in climate change mitigation policy and energy and climate scenarios so far (e.g. Samadi et al.9). A database on energy sufficiency could serve as a starting point for the collection of policy instruments, their assessment in a structured format, as precondition for further research and policy consulting and to complement the discussion on mitigation policy options.\n\nSuch database should provide information on good practices, implementation examples and insights on emission and energy reduction potentials. An openly accessible database can collect findings, ideas and examples and make them better accessible to policy makers than’hidden’ in e.g. a project report.\n\nWhen consulting existing climate end energy policy databases, for example International Energy Agency’s (IEA) Policy Database10 and European Environment Agency’s (EEA) Database on Greenhouse Gas Policies and Measures in Europe,11 it is striking that demand-side solutions to climate change and especially sufficiency options are underrepresented. Many sufficiency-minded bottom-up initiatives are included in the database on Transformative Social Innovations12 hosted by Dutch Research Institute For Transition (DRIFT), but this database does not focus on policy instruments. The NewClimate Institute’s Climate Policy Database13 and the Mesures d’Utilisation Rationnelle de l’Energie (MURE) database on energy efficiency measures14 include sufficiency and/or the reduction of energy service demand in their search masks. However, the scope of these databases is different to our purpose: the Database of NewClimate aims at tracking climate action worldwide and thus focuses on mitigation plans and decarbonisation roadmaps rather than on specific policy instruments. The MURE database explicitly considers sufficiency policies and indicators since spring 2021,15 including detailed descriptions and quantification, but only for policies that are already implemented, which limits the openness for new proposals. Another database is the Policy Ideas Database for Sustainable Prosperity from the Institute for Future-Fit Economies (ZOE).16 The ZOE-database is not a classical database, but a narrative and graphical visualisation, however, it is a valuable source for visionary cross-sectoral policies.\n\n\nMethods\n\nThis section briefly describes the structure of the database, starting with sources for entries. To improve accessibility, and to allow for filtering, clustering and potential further analyses, we propose a number of structuring categorisations including information on sectors, goals, target indicators, policy instruments and sufficiency types. Moreover, we outline our internal review and harmonisation process and the technical setup of the database.\n\nPolicy instruments are mainly extracted from existing literature and databases using the classifying parameters outlined below. Two key sources are first an extensive and detailed report describing policy measures for a “German Zero” emissions scenario until 203517 and second a list of policy measures extracted from all European National Energy and Climate Plans (NECPs) published by Zell-Ziegler et al.2 and condensed to merge instruments described by various NECPs. This is complemented by databases such as the Sustainable Prosperity Database16 and by further literature18–30 as well as exchange with experts. For a full list of references, see the respective tab in the database (please see underlying data).31\n\nTo allow for the analysis of policy instruments, we structured the database along several key categories:\n\nSector includes information on the covered sector: agri-food, buildings, industry/production, transport, LULUCF (land use, land-use change and forestry), energy and cross-sectoral (for overarching policies targeting various sectors).\n\nGoal/policy strategy describes what the respective policy aims at, while\n\nMeasure/action explains the more concrete changes envisaged to achieve the policy goals and the mitigation target.\n\nIndicator lists quantifiable units to be used to estimate the effect of the policy instrument/policy.\n\nSufficiency type categorises instruments according to the strategies avoid, shift or generally supporting.\n\nPolicy instrument lists the specific policy instrument from the respective source that is intended to lead to change and the description gives more details on the specifications of the instrument.\n\nInstrument type categorises the policy instrument types according to UNFCCC categories,32 adding one for \"not specified\", where actions are listed in sources but respective instruments are not specified.\n\nReferences are included with a link and page reference to facilitate retrieval of original sources.\n\nThe latest version of the database is available under https://energysufficiency.de/policy-database/.\n\nAs the database will be further developed, additional categories may be included such as push/pull measures,33 governance levels at which they are implemented in a multi-level governance system,34,35 policy interactions, and whether they constitute a sufficiency promotion or reduction of barriers.\n\nIn order to increase consistency and interrater reliability of the database and to avoid duplicate entries, the data collection and cleaning process was organised with multiple internal review loops:\n\n• Assignation of main sector responsible to each sector (out of the four first authors)\n\n• Initial policy collection by main sector responsible\n\n• Assignation of reviewer to each sector (out of the four first authors), review of all entries including: clarity of entries, correct coding, plausible entries (esp. goal/policy strategy, measure/action, indicator, instrument type)\n\n• Bilateral coder meetings for clearance of divergences where necessary\n\n• Loops of coder-meetings to sort out inconsistencies and establish a common understanding and coding procedure\n\n• Where multiple policy instruments were listed, prioritisation on main instrument or splitting of policy in respective separate instruments (rows)\n\n• Harmonisation of goals and indicators within and across sectors\n\nThe database needs to meet the following requirements in order to be of highest utility and used most efficiently:\n\n• Online availability with open access\n\n• Clear design and easy navigation through the dataset\n\n• Possibility to filter and search for keywords\n\n• Possibility to insert additional information on policies (description as floating text)\n\n• Possibility to include attachments (e.g. sufficiency policy impact chains, planned to be developed)\n\n• Possibility to download the data\n\nFurthermore, the possibility to propose new policies and an integrated feature for a review process is desirable.\n\nIn order to find a software solution that may deliver on these aspects we exchanged with the hosts of comparable policy databases and with persons from our networks and a person from the EnSu project’s advisory board[2].\n\n\nResults\n\nThe database version published with this article contains 281 policies from seven sectors (Figure 1 shows freight transport separately). One third of these are from the transport sector, followed by 62 policies in the building sector and 48 cross-sectoral measures that address more than one sector. Some provide indirect connections with sufficiency measures such as reductions of subsidies for fossil fuels. The sources we analysed contained only very few sufficiency measures for the LULUCF (4) and energy (6) sector. The sufficiency measures in the energy sector concentrate on the overall policy goal ‘reduce energy consumption’ with such instruments as e.g. ‘subsidise energy savings’.28\n\nWe include modal shift measures in the transport sector, labeled as sufficiency type shifting from high-energy to lower-energy modes (shift). Of the 95 transport entries, 56% aim at mode shift from cars to public transport and active modes (walking, cycling) (see Figure 2). In the transport sector, shift policies dominate, indicating that this is a key policy strategy for transport. Somewhat less common is the reduction of necessary trips and thus traffic (avoid), e. g. through support of teleworking or city planning to reduce distances between points of interest. Shift policies also dominate in the industry and agri-food domain.\n\nIn the building sector, sufficiency instruments of the ‘avoid’ type dominate in our database so far, aiming at an efficient use of living space and development of the existing building stock, focusing on quality of living and by that reduce overall living space and required land sealing. In the industry/production sector, avoid measures target at enhancing product lifetimes by increasing reparability and durability.\n\nThe database includes existing and proposed policy instruments of all types as categorised by UNFCCC.32 Most of the policy instruments in the database are of regulatory nature (108), economic (45, e.g. taxation) or fiscal (66, e.g. infrastructural or subsidies) (see Figure 3). The high share of regulatory instruments is in contrast to sufficiency policy instruments that are implemented or planned by EU member states, as listed in NECPs2 where regulatory instruments are underrepresented. The diversity of instrument types shows that sufficiency policies are not only information campaigns leaving the responsibility to the individual, but a comprehensive mix of instruments. Sufficiency policy can thus be regarded as a policy field comparable to energy efficiency or renewable energies.\n\nFigure 4 combines the information on sectors and instrument types. This highlights that the sufficiency policies proposed in the various sectors diverge in focus. In the building sector, fiscal (subsidy) instruments and regulations prevail while for the transport sector, the focus is more on fiscal/infrastructure policies, financial/tax incentives and regulation. For the industry/production sector, mostly regulatory instruments are included while cross-sectoral policy instruments are mostly financial incentives through taxation and subsidies as well as regulation. For the other sectors, fewer instruments of all types are included.\n\nNote: Bubble sizes indicate the number of instruments.\n\nAs a step towards model inclusion of sufficiency policies, we searched for specific target indicators that may eventually be included into models or, vice versa, that models may potentially give as outputs to quantify energy sufficiency. The database includes 79 unique indicators such as e.g. ‘durability of products’, ‘car ownership rate’, ‘kg of exported meat’ and ‘m2 living space/person’ or ‘m2 unused living space’. For a complete list, see underlying data. These are indicators identified from the policy descriptions and may function as linking variables to sector and energy models and climate scenarios.36\n\nBy summarizing the overall goals all identified sufficiency policy instruments, we identify 45 different policy goals (See underlying data).31 While most are quite sector-specific and concrete such as reduce motorized individual transport or efficient use of living space, some goals, especially the ones of cross-sectoral policy instruments, aim at more general goals of human well-being e.g. equal society,alternative welfare indicators and that would involve more fundamental changes of organizing principles of societies e.g. re-distribute and reduce paid work-time or promote commons. This shows that demand-side options are not only a means to mitigate climate change, but can also involve a more general strategy to reach socio-ecological goals and quality of life.\n\n\nDiscussion\n\nPotentially, much like with energy efficiency and renewable energy policy, sufficiency policies are most effective and unfold all advantages, if not reduced to single measures but integrated into a consistent policy framework. We consider it still helpful to depict each policy instrument in detail in such a database on the one and provide the heterogeneity of sufficiency policy on the other side.\n\nThe database published along with this article is a first version and proof of concept. So far, we have a strong focus on European and German sources. We do not claim completeness and since it is a dynamic field, additional policy instruments will be added. We will also invite external persons to propose additional policies and plan to team up with other research stakeholders in the energy sufficiency field at German and EU level to investigate options for a successful continuation of the database including potential future (co-)hosts and possibilities for maintenance. Regarding its format, we plan to implement the sufficiency policy database as an online database.\n\nFurther planned developments of the database are the inclusion of quantitative effects (energy demand & GHG-reduction potentials) of the policies. To this end, policy impact chains need to be investigated and the policy representation in models be expanded to include them in ex-ante assessments and scenario studies.37 Another possible addition is a prioritization regarding maturity, replicability and impact.38 To make more transparent which policies are actually reducing barriers for sufficiency, we will add the categorisation of barrier-reduction and sufficiency-supporting. Furthermore, we will add good practice and implementation examples to the entries of the database.\n\nIn the field of barriers, more research is required to identify current political barriers which might prevent the implementation of sufficiency. Due to the partly fundamental character of the changes some policy instruments of sufficiency represent, further research on economic effects, macroeconomic dynamics and culture is required which is beyond the scope of the database itself but is fundamental for a successful implementation of sufficiency policy.\n\n\nConclusion\n\nOur energy sufficiency policy database of currently 281 policy instruments can serve as a basis to develop policy recommendations in the so far underrepresented field of sufficiency policy. Moreover, it provides a starting point for further research on sufficiency and climate change mitigation policies, especially for modelling and scenario studies. The identification of indicators is a first step to include sufficiency into modelling and be able to assess the effect of the different policy measures.\n\nAs the variety of different instrument types, goals and policy levels shows, sufficiency is a diverse policy field with multiple options of implementation and effect. The database encompasses specific instruments but also fundamental structural changes of societal organisation principles. Our interdisciplinary approach is helpful to cover the heterogeneity of sufficiency. The description on concrete information on sufficiency as policy, with goals, instruments and indicators as an interface to modelling can help to overcome existing barriers on sufficiency policy implementation. Making it more tangible can support its path to becoming a key strategy for energy policy.\n\n\nData availability\n\nUnderlying data Zenodo: Sufficiency Policy Database DOI31: This project contains the following underlying data: Sufficiency Policy Database\n\nSource data https://energysufficiency.de/policy-database/ (latest version of the sufficiency policy database)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0).\n\n\nAuthor contributions\n\nBenjamin Best: Conceptualization, Funding Acquisition, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing; Johannes Thema: Conceptualization, Formal Analysis, Investigation, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Carina Zell-Ziegler: Conceptualization, Formal Analysis, Investigation, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Frauke Wiese: Conceptualization, Funding Acquisition, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing; Jonathan Barth: Resources; Stephan Breidenbach: Resources; Leonardo Nascimento: Resources, Writing – Review & Editing; Henry Wilke: Resources",
"appendix": "Acknowledgements\n\nThe authors would like to thank the members of their advisory boards for policy ideas and feedback. Great thanks to Diana Süsser and Bendix Vogel for technical advice. Thanks to the organizers and the participants of the session “Reaching our Targets - Making Europe fit for 55” of the EMP-E 2021 Conference.\n\n\nReferences\n\nCreutzig F, Niamir L, Bai X, et al.: Demand-side solutions to climate change mitigation consistent with high levels of well-being. Nat. Clim. Chang. 2021; 12: 36–46. Publisher Full Text\n\nZell-Ziegler C, Thema J, Best B, et al.: Enough? The role of sufficiency in European energy and climate plans. Energy Policy. 2021; 157: 112483. Publisher Full Text\n\nGrunwald A: Wider die Privatisierung der Nachhaltigkeit - Warum ökologisch korrekter Konsum die Umwelt nicht retten kann. GAIA-Ecological Perspectives for Science and Society. 2010; 19(3): 178–182. Publisher Full Text\n\nBilharz M, Fricke V, Schrader U: Wider die Bagatellisierung der Konsumentenverantwortung. GAIA - Ecological Perspectives for Science and Society. 2011; 20: 9–13. Publisher Full Text\n\nGrunwald A: Statt Privatisierung: Politisierung der Nachhaltigkeit. GAIA - Ecological Perspectives for Science and Society. 2011; 20: 17–19. Publisher Full Text\n\nHeidbrink L, Schmidt I, Ahaus B: Die Verantwortung des Konsumenten. Sozialwissenschaften 2011. 1st ed.Frankfurt am Main: Campus Verlag GmbH; 2011.\n\nToulouse E, Sahakian M, Lorek S, et al.: Energy sufficiency: how can research better help and inform policy-making?.2019. Reference Source\n\nZell-Ziegler C, Förster H: Mit Suffizienz mehr Klimaschutz modellieren. Number 55/2018 in Texte. Umweltbundesamt, Dessau. 2018. Reference Source\n\nSamadi S, Gröne M-C, Schneidewind U, et al.: Sufficiency in energy scenario studies: Taking the potential benefits of lifestyle changes into account. Technol. Forecast. Soc. Chang. 2017; 124: 126–134. Publisher Full Text\n\nInternational Energy Agency (IEA) and International Renewable Energy Agency (IRENA): IEA Policies database.2022. Reference Source\n\nEuropean Environment Agency (EEA): EEA database on climate change mitigation policies and measures in Europe.2022. Reference Source\n\nDutch Research Institute For Transitions (DRIFT): Critical Turning Points Database.2022. Reference Source\n\nNewClimate Institute: Climate Policy Database.2022. Reference Source\n\nAgence de l’environnement et de la maîtrise de l’énergie (ADEME) and Partners of Odyssee-Mure: MURE database on energy efficiency measures’ of ODYSSEE-MURE.2022. Reference Source\n\nGynther L, Eichhammer W: Energy Sufficiency Indicators and Policies. Technical report. Helsinki: Motiva Oy & Fraunhofer Institute for Systems and Innovation Research ISI; 2021. Reference Source\n\nInstitut für zukunftsfähige Ökonomien e.V: Sustainable Prosperity made in Europe.2021. Reference Source\n\nBreidenbach S, Bußmann-Welsch TM, Fischer L, et al.: Maßnahmen für ein 1,5-Grad- Gesetzespaket. Arbeitsstand: September 2021. Technical report. Hamburg: GermanZero e. V.; 2021. Reference Source\n\nAssociation négaWatt: Scénario négaWatt 2017-2050 - Dossier de synthèse. Technical report. Valence: Fondation Charles Léopold Mayer pour le progrès de l’Homme; 2017. Reference Source\n\nBertoldi P: Are current policies promoting a change in behaviour, conservation and sufficiency? An analysis of existing policies and recommendations for new and effective policies. ECEEE; 2017. Reference Source\n\nBest B, Wagner O: Prepaid-Strom per Smartphone. Energiewirtschaftliche Tagesfragen. 2020; (11): 74–77. Reference Source\n\nBürgerBegehren Klimaschutz e. V: Unsere Empfehlungen für die deutsche Klimapolitik. Technical report, Schöpflin Stiftung, Open Society Foundations, GLS Treuhand, Postcode-Lotterie-Stiftung, Berlin.September 2021. Reference Source\n\nDittrich F, Dünnebeil S, von Köppen A , et al.: Transformationsprozess zum treibhausgasneutralen und ressourcenschonenden Deutschland - GreenSupreme. Number 05/2020 in Climate Change. Umweltbundesamt (UBA), Dessau. 2020. Reference Source\n\nFaber J: Behavioural climate change mitigation options and their appropriate inclusion in quantitative longer term policy scenarios.2012. Reference Source\n\nFuhrhop D: “Bauverbot” und Suffizienz im Stadtwandel. Adler F, Schachtschneider U, editors. Postwachstumspolitiken. oekom; pages 293–304.\n\nGota S, Huizenga C, Peet K, et al.: Decarbonising transport to achieve Paris Agreement targets. Energ. Effic. February 2019; 12(2): 363–386. Publisher Full Text\n\nJackson T: Prosperity without Growth: Foundations for the Economy of Tomorrow. 2nd ed.London/New York: Routledge;2016.\n\nMatthias V, Bieser J, Mocanu T, et al.: Modelling road transport emissions in germany – current day situation and scenarios for 2040.87: 1–17. Publisher Full Text\n\nPotočnik J, Spangenberg J, Alcott B, et al.: Sufficiency. Moving beyond the gospel of eco-efficiency. Technical report, Friends of the Earth Europe, Federal Ministry of the Environment, Nature Conservation, Building and Nuclear Safety and of the Federal Environment Agency of the Federal Republic of Germany, European Commission, Brussels.2018. Reference Source\n\nRepenning J, Emele L, Blanck R, et al.: Klimaschutzszenario 2050-2. Endbericht. Technical report. Öko-Institut; Fraunhofer ISI; 2015. Reference Source\n\nScherhorn G: Die Welt als Allmende – Für ein gemeingütersensitives Wettbewerbsrecht.2012.\n\nBest B, Thema J, Zell-Ziegler C, et al.: Sufficiency policy database [data set]. in f1000research: Vol. energy systems modelling, (v 0.1).Publisher Full Text\n\nUNFCCC: Review of the implementation of commitments and of other provisions of the Convention. UNFCCC guidelines on reporting and review. Bonn: 2000. Reference Source\n\nSteg L, Tertoolen G: Sustainable transport policy: the contribution from behavioural scientists. Public Money Manag. 1999; 19(1): 63–69. Publisher Full Text\n\nMarks G: Structural policy in the European Community. Sbragia A, editor. Europolitics: Institutions and Policy Making in the ‘New’ European Community. Washington D.C.: The Brookings Institution; pages 191–224. 1992.\n\nPier Domenico Tortola: Clarifying multilevel governance. Eur. J. Polit. Res. May 2017; 56(2): 234–250. Publisher Full Text\n\nWiese F, Thema J, Cordroch L: Strategies for climate neutrality. Lessons from a meta-analysis of German energy scenarios. Renewable and Sustainable Energy Transition. December 2021; 2: 100015. Publisher Full Text Reference Source\n\nZell-Ziegler C, Thema J: Impact chains for energy sufficiency policies - a proposal for visualisation and possibilities for integration into energy modelling. TATuP; forthcoming.\n\nMartin B, Pestiaux J, Schobbens Q, et al.: A radical transformation of mobility in Europe: Exploring the decarbonisation of the transport sector by 2040.2020. Reference Source\n\n\nFootnotes\n\n1 For more details and examples see Zell-Ziegler et al. 2\n\n2 EnSu - Research Group on energy sufficiency, https://energysufficiency.de/."
}
|
[
{
"id": "125368",
"date": "24 Mar 2022",
"name": "Gibran Vita",
"expertise": [
"Reviewer Expertise Industrial Ecology"
],
"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 make a very good effort and praiseworthy initiative to try to bring sufficiency into more concrete policy terms and instruments. The database is a living document. As such, it cannot be currently judged as a finished product. It will change shape as it progresses.\nIts current version does seem to over-rely or over-represent few sources and countries (Germany). In that case, I don´t see it as a really comprehensive database. Too many countries and initiatives missing, even in Europe. It is however remarkable that with such a narrow range of sources you still find more than 100 policies. Maybe a full-blown European database would be massive, but highly desirable in my opinion.\nOne of the sources is “expert consultation” but no transparency on this as far as I could read. Maybe this was just meant to get an overview of current databases.\nIn its current form, it seems more like a summarized and user-friendly way to navigate a handful of reports. Which is still useful, especially since you translated German documents into English entries, but not really what the title and abstract seems to sell. I look forward for it to grow and become more diverse and comprehensive.\nConcrete suggestions: The database could benefit from consistency in reporting which countries the policies are present in. In some categories the countries are mentioned, in some others not, even when a given policy seems to only apply to Germany, for example. Would search by country be enabled?\nAnother interesting variable to include would be the broader policy landscape or directive where the particular policy or instrument stems from. EU directive, Paris agreement, SDGs, UN biodiversity, etc. As the purpose of the database is to understand how to promote sufficiency policy, it seems key to understand which kind of broader policy movements facilitated that particular industry.\nThe base year would be relevant to mention.\nYou can abbreviate the Shift, Avoid, to save space and include other things.\nThe title of the database should probably include \"Europe\" in the title. Or even Germany. Whatever you think represents it best. The sector “LULUCF” (and maybe some food and agriculture) doesn’t seem to fit the “energy” exclusive topic.\nIn that sense, I would think that an indication of which resource is mainly spared: energy, carbon, etc. Or if it’s synergistic measure: land, water, energy, etc. I understand this would be much more work at this point as it would have been to consider it since the start.\nPerhaps a more critical point: to make it more useful it would be helpful to have the “implementation challenges” or “complementary policies” to avoid loss of wellbeing or energy backfire. For example, ban of domestic flights might rise car demand if we don’t have a massive train subsidy. Challenges of reducing meat would need more education on plant-based lifestyles or a ban on artificial chemicals of plant-based meat substitutes. We need to think from the policy-maker viewpoint.\nWould have been useful to breakdown the biggest categories: regulation, fiscal and economic into subcategories. For example “regulation: ban”. All these are very broad. For example, if one is interested on looking at bans. The search bar could be used instead but not sure if it’s working properly or if it’s also looking in the reference document? For example, if I write “ban” I get some results but can't find the word “ban” in those entries.\nWhat is the plan to make it grow and have a life of its own? There doesn’t seem to be a way to submit entries. Most importantly, having experience in these kinds of projects I would not rely on the good will of people to submit entries.\nI strongly suggest the authors to consider a massive crowd-sourcing experiment where you extend authorship to many many more researchers and practitioners who are on top of this topic, maybe in exchange for min 5-10 entries. There is no limit to how many authors a database or paper can have. Might be a worthwhile experiment.\nGreat initiative and wish you success,\nGibran Vita\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? 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",
"responses": [
{
"c_id": "8448",
"date": "01 Jul 2022",
"name": "Benjamin Best",
"role": "Author Response",
"response": "Thank you for your valueable feedback. We will update our database and consider your feedback for the next version. Your review provides us with actionable guidance for the next steps."
}
]
},
{
"id": "127903",
"date": "14 Apr 2022",
"name": "Mirko Schäfer",
"expertise": [
"Reviewer Expertise Energy system analysis and modelling"
],
"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 database for sufficiency policies, including and categorising almost 300 policy instruments, with a focus on Germany and Europe.\nSufficiency measures are currently underrepresented in the discussion of transformation pathways towards a climate neutral energy system. In particular, this applies to energy system modelling for scenario development and analysis. Often the focus is on the technological transformation and advancement, without the consideration of demand-side solutions. Although recently an increased interest in such demand-side solutions can be observed, there is still a research gap in identifying, quantifiying and modelling sufficiency strategies and policies. The authors address this issue by presenting a database for energy sufficiency policies.\nIn the current form, the database already represents a valuable source of information about a large number of sufficiency policies, categorised in a very well structured way and linked to references. In this way, already in its present form, it can be seen as an important starting point and gateway for anyone interested in sufficiency policies. The audience already more familiar with such concepts might object to certain categorisation choices or seek additional information, but also for this purpose the database can be helpful as a seed and potential platform for discussion.\nNevertheless, in its current form, the database only represents a starting point for further research. This is clearly acknowledged by the authors in the article and here is not intended as an argument against the publication of this contribution. Very important next steps could be towards more quantification (parameter settings as an input for system modelling), impact chains as a guidance for sector-specific modelling, and the extension beyond Europe.\nTo allow further development, a clearer view on how the community can interact with and through the database should be developed. This should include both the ability for users to contribute to the database (facilitated by clear explanation and examples on the categorisation) and the possibility to provide feedback on the usefulness or shortcomings of the database. For this purpose, it might be an option to link the database to a (moderated) discussion forum.\nWith regard to the analysis of the already represented sufficiency policies, it would be interesting to discuss in more detail why certain types of instruments in certain sectors are dominant in the database. Is this due to limited options for other sectors/instruments, or can this be explained with a bias in the underlying research?\nTo conclude, we are confident that the database serves as a valuable source for the audience seeking a first introduction into sufficiency policies, as well as an important starting point for research towards a broader and deeper integration of sufficiency policies into energy system analysis and modelling.\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? 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",
"responses": [
{
"c_id": "8449",
"date": "01 Jul 2022",
"name": "Benjamin Best",
"role": "Author Response",
"response": "Dear Mirko, thank you for your review! It is very valuable to us for the next versions of our database. We thought about possible explanations why some instrument types are dominant in sectors. A possible reason is that price instruments are easiest to model, so that we need to consider a certain bias due to the methods of the underlying research. This will help to consider limitations when drawing conclusions from analysis of our database."
}
]
}
] | 1
|
https://f1000research.com/articles/11-229
|
https://f1000research.com/articles/11-404/v1
|
08 Apr 22
|
{
"type": "Brief Report",
"title": "Robustness of the aging effect of smiling against vertical facial orientation",
"authors": [
"Naoto Yoshimura",
"Fumiya Yonemitsu",
"Kyoshiro Sasaki",
"Yuki Yamada",
"Fumiya Yonemitsu",
"Kyoshiro Sasaki",
"Yuki Yamada"
],
"abstract": "Background: Previous studies have shown that the association between smiling and youth is a misconception; smiling faces have been estimated to be older than neutral faces. Previous studies have indicated that this aging effect of smiling (AES) is due to eye wrinkles caused by the facial action of smiling. However, whether holistic processing for facial expressions is involved in AES has not been investigated. The present study aimed to clarify these issues. Methods: Participants were recruited to participate in an online experiment that had a 3 (facial expression: smiling/neutral/surprised) × 2 (facial orientation: upright/inverted) mixed design. Participants were presented with an upright or inverted face for each expression (neutral, smiling, and surprised) and were asked to estimate the individual’s age. Results: In total, 104 participants were included in the analysis. The results show that smiling faces were estimated to be older than neutral faces, whereas there was no significant difference between upright and inverted faces. Conclusions: Our findings suggest that direct age estimation is not dependent on holistic processing.",
"keywords": [
"Facial expression",
"Age estimation",
"Face inversion"
],
"content": "Introduction\n\nThe face is a valuable source of information for social communication, and humans have developed specific processing methods for others’ faces. For example, they can perceive the identity, gender, age, ethnicity, attractiveness, and emotions of others from their faces (e.g., Bruce & Young, 1986; Ganel & Goshen-Gottstein, 2002). These multiple abilities for face processing highlights that the face is processed holistically in contrast to other visual stimuli. Therefore, we are unable to identify others’ faces and judge facial expressions when holistic processing is inhibited (e.g., Rakover, 2013). This holistic processing of the face creates complex interactions between multiple factors, such as the interaction between emotion and gender (Atkinson et al., 2005).\n\nAge is among the crucial information obtained from the face. We generally estimate a person’s age from their faces and accordingly change our attitude and manner of speaking (Ryan et al., 1986). Among the many information dimensions that can easily be extracted from a face, age is considered the primary dimension (George & Hole, 1998). Thus, accurate age identification is crucial in determining social roles and facilitating social interaction. However, various factors distort age perception (see Moyse, 2014). Previous studies have specifically focused on the effects of gender and race on perceived age (Dehon & Brédart, 2001; Nkengne et al., 2008).\n\nInterestingly, several studies have reported that humans have a counterintuitive bias regarding age. We associate smiling with youth, that is, it is generally believed that when people see a smiling person, they feel that person is younger. Indeed, previous research has provided evidence that individuals with a smile appear younger than those with other facial expressions (Hass et al., 2016; Voelkle et al., 2012). However, contrary to the commonly held association between smiling and youth, Ganel (2015) showed that a smiling face is estimated to be older than a neutral one. The aging effect of smiling (AES) is attributed to wrinkles around the eyes caused by smiling (Ganel, 2015; Ganel & Goodale, 2021). In contrast, when participants were asked to retrospectively estimate the mean age of several faces (i.e., face group), they estimated that the smiling face group was younger than the neutral face group (Ganel & Goodale, 2018). These studies indicate that the effect of emotional expressions on age estimation depends on the method of estimation (i.e., directly or retrospectively).\n\nRecently, our study showed that AES was consistently confirmed regardless of the stimulus or participants’ race or culture (Yoshimura et al., 2021). Specifically, smiling faces were estimated to be older than neutral faces for both Swedes and the Japanese. In contrast, participants in both countries estimated the smiling faces to be younger when estimating the age retrospectively. These results suggest that AES is robust across cultures, although the direction of this effect changes depending on the task.\n\nThe AES mechanism, however, remains unclear. What can be assumed is that AES is associated with some type of characteristic information of face perception or emotion processing that accompanies changes in facial expressions. Age is considered a relatively primary piece of information extracted from the face (Bruce & Young, 1986), and previous research suggests that age perception may be based on facial surface or shape information (George & Hole, 2000). However, other studies have suggested that facial expression processing relies on holistic processing (Maurer et al., 2002; Tanaka & Sengco, 1997). As shown in previous research, facial expressions interact with other dimensions such as identity and trustworthiness (Engell et al., 2010; Ganel & Goshen-Gottstein, 2002). When the holistic processing of facial expressions is inhibited, observers’ perceptual fields are constricted and facial features are processed sequentially and independently (Rossion, 2009). In such cases, inverted smiling faces could be evaluated as older than upright smiling faces.\n\nTo extend the AES findings, the present study examined how the holistic processing of facial expressions could be involved in AES. Here, we used inverted faces in the experiment because they inhibit the holistic processing of facial expressions while maintaining visual information (e.g., Rakover, 2013). Specifically, we divided the participants into two groups: one observing upright faces, and the other observing inverted faces. They were asked to estimate the ages of the smiling, neutral, and surprised faces. The estimated age for each facial expression obtained was then compared between the groups. Even if AES was boosted with an inverted smiling face, we could not rule out the possibility that inversion itself has the effect of making the facial expression stimulus older. Hence, we set a surprised face (i.e., neutral expression) as the control condition. If the enhancement of AES was due to the prioritization of local information processing for the smiling expression as holistic processing was suppressed, there would not be a significant difference between facial orientations in the surprised face.\n\n\nMethod\n\nThis study employed a mixed factorial design. The participants were recruited through the online survey platform, Yahoo! Crowdsourcing. The target age was 15-35 years old to address potential sources of bias caused by unexpected deviations in the age of the respondents. The survey was published on the platform (survey period: November 24-25, 2021) and participants could select to participate in the survey for a minimal compensation of 10 “PayPay bonus rights” (electronic money). We determined the sample size to be N = 100 because Yahoo! Crowdsourcing has specifications for recruiting participants in units of 50; thus, we recruited 50 participants per facial orientation group. Participants were recruited separately for tasks in which upright or inverted faces were presented, and the study’s purpose was not disclosed to the participants.\n\nThe experiment was conducted in accordance with the principles of the Declaration of Helsinki. The ethics committee of Kyushu University approved the study protocol (approval date: July 27, 2021; approval number: 2021-013). Completion of the experiment was taken as consent to participate from participants. Participants had the right to withdraw from the experiment at any time without providing a reason. It was also explained to them that their responses would not be tied to them personally.\n\nThe Japanese facial stimuli consisted of head-and-shoulder photos of 30 women and 30 men with smiling, neutral, and surprised expressions from the ATR Facial Expression Image Database (DB99) (ATR-Promotions, Kyoto, Japan; 2562 photos; Ogawa & Oda, 1998; Mage = 21.1 years, ranging from 20 to 24 years). The face image database systematically contains the faces of male and female individuals and their three facial expressions. The first 30 images from each list of the faces were used as the facial stimuli for the present study, thus a total of 180 images were selected (2 genders × 3 facial expressions × 30 individuals). Japanese facial photos were adjusted to 7 × 9 cm and divided into three sets for each emotional expression (smiling, neutral, and surprised sets), with each set consisting of 60 photos. Next, we prepared six counterbalanced sets of 60 photos by extracting 20 photos from each emotional expression set. This was done to avoid presenting the same individuals repeatedly with different facial expressions. Therefore, the participants were randomly assigned to one of the six counterbalanced sets.\n\nThe experiments were conducted online, and the procedures were controlled using jsPsych (Version 6.3.1; de Leeuw & Motz, 2016). In addition, the Cognition platform was used for data collection. In each trial, participants were presented with a smiling, neutral, or surprised face. They were then asked to estimate the age of each facial stimulus and enter their estimated age in a text box. To detect satisficers (Maniaci & Rogge, 2014), the directed questions scale (DQS) (answer: “9 years old”) was also set on the 30th trial of the task. In this DQS trial, we also presented a beast-man1 with the same composition as the other stimuli.\n\nAll analyses were conducted using RStudio (Version 1.4.1717; RStudio Team, 2021) and R (Version 4.1.1; R Core Team, 2020). A two-way mixed analysis of variance (ANOVA) was performed to examine the differences in the estimated age of the facial expressions of each face group. Subsequently, a Scheffé multiple comparison test was also performed to compare the difference in each pair. The alpha level of statistical significance was set at 0.05.\n\n\nResults\n\nFrom the internet protocol addresses collected in the experiment, we checked whether any individuals participated in both the upright and inverted face conditions. In total, 104 Japanese people (52 people per group) were recruited to participate in the online experiment (51 males, 51 females, and two non-respondents; Mage = 29.56, SD = 7.04). Duplicate data were excluded from the analysis because we could not confirm whether they were answered by different individuals. We also excluded data from participants who answered the DQS incorrectly. The final number of valid data used in the analysis was 98 (we excluded data from six participants) (Yoshimura, 2022). We also removed trials where the estimated ages were outside ± 2.5 SD from the participants’ mean in each condition.\n\nFigure 1 shows the distribution of the mean estimated age for each expression in the upright and inverted face conditions. We conducted a two-way mixed ANOVA with facial expression (smiling, neutral, or surprised) as the within-subjects factors and facial orientation (upright or inverted) as the between-subjects factors. The results revealed a main effect of facial expression (F(2, 189) = 23.11, p < .001, η2G = .01). However, the main effect of facial orientation (F(1, 96) < 0.000, p = .98, η2G < .001) and the interaction between facial expression and facial orientation (F(2, 189) = 1.33, p = .27, η2G = .01) were not significant. Based on the main effect of facial expression, we also conducted a Scheffé multiple comparison test of the facial expressions. The results showed that participants estimated smiling faces to be significantly older than neutral faces (t(96) = 5.52, p < .001, d = 0.56). In addition, the results also showed that they estimated surprised faces to be significantly older than neutral faces (t(96) = 6.40, p < .001, d = 0.65).\n\np < 0.001 = ***.\n\nWe performed an equivalence test (Lakens et al., 2018) for facial orientation as a post-hoc and exploratory analysis. We set equivalence bounds to ± 0.5, as the medium effect size (i.e., Cohen's d). The results showed that the mean estimated ages in the upright and inverted conditions were significantly equivalent (t(95.34) = 2.453, p < 0.01).\n\n\nDiscussion\n\nThe present study aimed to examine how holistic processing of facial expressions contributes to AES. In the experiment, we asked two groups of participants (given upright or inverted faces) to estimate the age of each facial expression; we then compared the estimated ages. The results showed that smiling faces were estimated to be older than neutral faces, indicating that AES was replicated. However, there was no significant difference in the estimated age between the upright and inverted conditions. More importantly, AES was confirmed even when inverted faces were presented. We predicted that inverted smiling faces would be evaluated as even older than upright faces, because holistic processing was inhibited in favor of local processing. However, the analysis revealed no significant effect on facial orientation. Furthermore, we conducted an equivalence test for facial orientation as an exploratory and post-hoc analysis and found that the mean estimated ages in both upright and inverted conditions were significantly equivalent. Thus, the results suggest that direct age estimation is insensitive to holistic processing.\n\nGiven the results of this experiment, we assume that the holistic processing of emotional expressions is not sufficient to significantly modulate AES. Another unexpected result was an increase in the estimated age of the surprised faces. This suggests that changes in face shape, rather than the association between smiling and youthfulness, affected AES. The results highlight the possibility that AES is processed based on the perceptual analysis of facial features, that is, the structural encoding stage (Calder & Young, 2005). A previous study also reported no decrease in the accuracy of age estimation, even when participants estimated the age of inverted, negation, or blurred face stimuli (George & Hole, 2000). Recent studies have also reported that AES is affected by changes in the skin surface and other facial parts (e.g., wrinkles around the eye region) over the lifespan (Ganel & Goodale, 2021). The results of our study are consistent with these findings. Considering that age is one of the social characteristics critical to encoding the identity of others, the results of this study seem reasonable.\n\nAnother possible factor is that the attractiveness of facial parts may affect age estimation. Some previous studies have reported that masked faces were more attractive or vice versa (Hies & Lewis, 2022; Miyazaki & Kawahara, 2016; Patel et al., 2020). The fact that age could be estimated only for the upper half of the face and that age estimation did not depend on holistic processing leads to speculate the potential involvement of attractiveness. Specifically, the change in shape due to facial expressions may have reduced the attractiveness of the parts, thereby altering the apparent age. Therefore, the attractiveness of facial parts is also worth considering in further studies, such as whether it is indeed involved and, if so, what the causal mechanism entails.\n\nThe findings of the present study indicate that the association between smiling and youth is a misconception, and that direct age estimation is based on more primary and local facial features. However, it remains unclear why smiling faces are rated as younger in memory-based age estimation. Age estimation for memory representations of faces may be processed through different mechanisms than that for perceptual representations of faces in the process of dissociated facial processing (e.g., Weigelt et al., 2014), and such a bias in opposite directions in memory and perception for identical stimuli has been observed in spatial processing (Yamada et al., 2011). Future research should further examine these questions.\n\nThe present study did not address the cross-cultural validity. A previous study compared the differences between Western Caucasians and East Asians in eye movements to inverted faces (Rodger et al., 2010). This study reported cultural differences in the fixation area to the face, even for inverted faces. Given the results, it should be noted that the results of this study are generalizable only to Japanese participants estimating the age of Japanese faces.\n\n\nData availability\n\nOpen Science Framework: Age Estimation and Face Inversion. https://doi.org/10.17605/OSF.IO/7P25C (Yoshimura, 2022).\n\nThis project contains the following underlying data:\n\n- AgeEstimation_dataset.csv (The dataset)\n\n- Description of Dataset.txt\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nCompeting interests\n\nNo competing interests were disclosed.\n\n\nGrant information\n\nThis study was supported by Japan Society for the Promotion of Science KAKENHI Grant Number JP19J21874 to N. Y., 19K14482 to K.S., JP21J01431 to F.Y., JP16H03079, JP17H00875, JP18K12015, JP20H04581 to Y.Y., and JP21H03784 to K.S. and Y.Y.",
"appendix": "Acknowledgements\n\nThe authors would like to thank Editage (www.editage.jp) for the English language review.\n\n\nReferences\n\nAtkinson AP, Tipples J, Burt DM, et al.: Asymmetric interference between sex and emotion in face perception. Percept. Psychophys. 2005; 67(7): 1199–1213. PubMed Abstract | Publisher Full Text\n\nBruce V, Young A: Understanding face recognition. Br. J. Psychol. 1986; 77(Pt 3): 305–327. Publisher Full Text\n\nCalder AJ, Young AW: Understanding the recognition of facial identity and facial expression. Nat. Rev. Neurosci. 2005; 6(8): 641–651. Publisher Full Text\n\nDehon H, Brédart S: An “other-race” effect in age estimation from faces. Perception. 2001; 30(9): 1107–1113. Publisher Full Text\n\nde Leeuw JR , Motz BA: Psychophysics in a Web browser? Comparing response times collected with JavaScript and Psychophysics Toolbox in a visual search task. Behav. Res. Methods. 2016; 48(1): 1–12. PubMed Abstract | Publisher Full Text\n\nEngell AD, Todorov A, Haxby JV: Common neural mechanisms for the evaluation of facial trustworthiness and emotional expressions as revealed by behavioral adaptation. Perception. 2010; 39(7): 931–941. PubMed Abstract | Publisher Full Text\n\nGanel T: Smiling makes you look older. Psychon. Bull. Rev. 2015; 22(6): 1671–1677. PubMed Abstract | Publisher Full Text\n\nGanel T, Goodale MA: The effects of smiling on perceived age defy belief. Psychon. Bull. Rev. 2018; 25(2): 612–616. PubMed Abstract | Publisher Full Text\n\nGanel T, Goodale MA: The effect of smiling on the perceived age of male and female faces across the lifespan. Sci. Rep. 2021; 11(1): 23020. PubMed Abstract | Publisher Full Text\n\nGanel T, Goshen-Gottstein Y: Perceptual integrality of sex and identity of faces: Further evidence for the single-route hypothesis. J. Exp. Psychol. Hum. Percept. Perform. 2002; 28(4): 854–867. PubMed Abstract | Publisher Full Text\n\nGeorge PA, Hole GJ: The influence of feature-based information in the age processing of unfamiliar faces. Perception. 1998; 27(3): 295–312. PubMed Abstract | Publisher Full Text\n\nGeorge PA, Hole GJ: The role of spatial and surface cues in the age-processing of unfamiliar faces. Vis. Cogn. 2000; 7(4): 485–509. Publisher Full Text\n\nHass NC, Weston TD, Lim S-L: Be Happy Not Sad for Your Youth: The Effect of Emotional Expression on Age Perception. PloS One. 2016; 11(3): e0152093. Publisher Full Text\n\nHies O, Lewis MB: Beyond the beauty of occlusion: medical masks increase facial attractiveness more than other face coverings. Cogn. Res.: Princ. Implic. 2022; 7(1): 1. PubMed Abstract | Publisher Full Text\n\nLakens D, Scheel AM, Isager PM: Equivalence Testing for Psychological Research: A Tutorial. Adv. Methods Pract. Psychol. Sci. 2018; 1(2): 259–269. Publisher Full Text\n\nManiaci MR, Rogge RD: Caring about carelessness: Participant inattention and its effects on research. J. Res. Pers. 2014; 48: 61–83. Publisher Full Text\n\nMaurer D, Grand RL, Mondloch CJ: The many faces of configural processing. Trends Cogn. Sci. 2002; 6(6): 255–260. Publisher Full Text\n\nMiyazaki Y, Kawahara J-I: The Sanitary-Mask Effect on Perceived Facial Attractiveness. Jpn. Psychol. Res. 2016; 58(3): 261–272. Publisher Full Text\n\nMoyse E: Age estimation from faces and voices: A review. Psychologica Belgica. 2014; 54(3): 255–265. Publisher Full Text\n\nNkengne A, Bertin C, Stamatas GN, et al.: Influence of facial skin attributes on the perceived age of Caucasian women. Journal of the European Academy of Dermatology and Venereology: JEADV. 2008; 22(8): 982–991. PubMed Abstract | Publisher Full Text\n\nOgawa T, Oda M: Construction and Evaluation of the Facial Expression Database. ATR Technical Report, TR-H-244. 1998. Reference Source\n\nPatel V, Mazzaferro DM, Sarwer DB, et al.: Beauty and the Mask. Plast. Reconstr. Surg. Glob. Open. 2020; (8): e3048. Publish Ahead of Print. PubMed Abstract | Publisher Full Text\n\nRakover SS: Explaining the face-inversion effect: the face-scheme incompatibility (FSI) model. Psychon. Bull. Rev. 2013; 20(4): 665–692. Publisher Full Text\n\nR Core Team: R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; 2021. Reference Source\n\nRStudio Team: RStudio: Integrated Development Environment for R. RStudio, PBC; 2021. Reference Source\n\nRodger H, Kelly DJ, Blais C, et al.: Inverting faces does not abolish cultural diversity in eye movements. Perception. 2010; 39(11): 1491–1503. Publisher Full Text\n\nRossion B: Distinguishing the cause and consequence of face inversion: the perceptual field hypothesis [Review of Distinguishing the cause and consequence of face inversion: the perceptual field hypothesis]. Acta Psychol. 2009; 132(3): 300–312. Publisher Full Text\n\nRyan EB, Giles H, Bartolucci G, et al.: Psycholinguistic and social psychological components of communication by and with the elderly. Lang. Commun. 1986; 6(1): 1–24. Publisher Full Text\n\nTanaka JW, Sengco JA: Features and their configuration in face recognition. Mem. Cogn. 1997; 25(5): 583–592. Publisher Full Text\n\nVoelkle MC, Ebner NC, Lindenberger U, et al.: Let me guess how old you are: effects of age, gender, and facial expression on perceptions of age. Psychol. Aging. 2012; 27(2): 265–277. PubMed Abstract | Publisher Full Text\n\nWeigelt S, Koldewyn K, Dilks DD, et al.: Domain-specific development of face memory but not face perception. Dev. Sci. 2014; 17(1): 47–58. Publisher Full Text\n\nYamada Y, Miura K, Kawabe T: Temporal course of position shift for a peripheral target. J. Vis. 2011; 11(6). PubMed Abstract | Publisher Full Text\n\nYoshimura N: Age Estimation and Face Inversion. [Dataset].2022. Publisher Full Text\n\nYoshimura N, Morimoto K, Murai M, et al.: Age of smile: a cross-cultural replication report of Ganel and Goodale (2018). J. Cogn. Sci. 2021; 5: 1–15. PubMed Abstract | Publisher Full Text\n\n\nFootnotes\n\n1 Image of a cat’s face superimposed on a human face."
}
|
[
{
"id": "134537",
"date": "03 May 2022",
"name": "Tzvi Ganel",
"expertise": [
"Reviewer Expertise Perception and action",
"Visual psychophysics",
"Face perception"
],
"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 is an extension of earlier work that looked at the ageing effect of smiling. This is a nice extension of the effect, which compared it between upright and inverted faces. The AES is maintained in both presentation formats. The authors argue that the results show that age estimations do not rely on holistic processing.\nThe research topic is of interest, the manuscript is generally well written, and the paradigm and analyses are solid. However, there are several theoretical reservations that warrant revisions of some of the arguments put forward in the manuscript.\nI feel that the issue of face inversion and its effects on age judgments is not properly discussed. The facial inversion effect refers to the larger decrement in face recognition accuracy due to inversion compared to other objects that are not faces. This effect probably documents holistic, or configural processing of faces. It is true that similar effects have been found for the processing of expression. It is less clear whether age estimations are affected by holistic processing; George & Hole (2000) showed that biases in age perception are similar for upright and inverted faces.1 Yet, the same authors also provided evidence for holistic processing of age, using the composite paradigm (Hole & George, 2011).2 Now, the AES is proposed to be mediated by smile-related wrinkling in the region of the eyes. This effect is probably not based on holistic processing. The current manuscript provides converging evidence for this idea by using face inversion. Therefore, one important note is that the current results do not speak to whether or not age processing is holistic. They do show that the AES is not based on holistic processing.\n\nTo show that age perception is based on holistic processing, one needs to examine accuracy in age perception and to compare it between upright and inverted faces. To compute accuracy, it is crucial to have data about the real ages of the photographed faces and to compute the average absolute error in each condition (Voelkle et al., 2012).3 What the authors do here is computing biases in age estimations. Bias relates to the AES, but bias and accuracy are partially independent variables. A similar amount (and direction) of bias does not necessarily reflect similar accuracy. In order to make arguments about holistic processing of age, the authors need to use the real ages of the faces and to compute accuracy in each condition. Only if accuracy is not substantially impaired for inverted faces, it is possible to argue that age processing is not holistic. Otherwise, the only inference that could be made is that the AES is not based on holistic processing. Such a conclusion is fine, but the authors need to revise the manuscript accordingly.\n\nIn several places in the text, the authors argue that they study “how the holistic processing of facial expressions could be involved in AES”. This assertion is not correct and should be revised. It is true that expression could be processed in a holistic manner, but this doesn’t mean that the effects of smiling on the AES are holistic; first, it is unclear if smiling is processed before age estimations are made. More importantly, the fact that aspects of the smile (e.g., wrinkling) affect age estimation bias cannot be used to infer that the holistic processing of smiling mediates such an effect. The effect is probably mediated by local aspects of the smile rather than by holistic processing. Such arguments in the text should be revised. It is fine to argue that the AES is mediated by smiling rather than to make the unsupported argument that holistic processing is not involved.\n\nThe authors seem to confuse holistic processing with interactive processing between different facial dimensions (e.g., expression and identity). The two aspects could be related to one another, but they are attributed to different mechanisms. The authors should avoid discussing them as the same concept.\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? 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? Partly",
"responses": [
{
"c_id": "8387",
"date": "17 Jun 2022",
"name": "Naoto Yoshimura",
"role": "Author Response",
"response": "The manuscript is an extension of earlier work that looked at the ageing effect of smiling. This is a nice extension of the effect, which compared it between upright and inverted faces. The AES is maintained in both presentation formats. The authors argue that the results show that age estimations do not rely on holistic processing. The research topic is of interest, the manuscript is generally well written, and the paradigm and analyses are solid. However, there are several theoretical reservations that warrant revisions of some of the arguments put forward in the manuscript. Reply: Thank you for your valuable comment. We are happy to address each comment. I feel that the issue of face inversion and its effects on age judgments is not properly discussed. The facial inversion effect refers to the larger decrement in face recognition accuracy due to inversion compared to other objects that are not faces. This effect probably documents holistic, or configural processing of faces. It is true that similar effects have been found for the processing of expression. It is less clear whether age estimations are affected by holistic processing; George & Hole (2000) showed that biases in age perception are similar for upright and inverted faces.1 Yet, the same authors also provided evidence for holistic processing of age, using the composite paradigm (Hole & George, 2011).2 Now, the AES is proposed to be mediated by smile-related wrinkling in the region of the eyes. This effect is probably not based on holistic processing. The current manuscript provides converging evidence for this idea by using face inversion. Therefore, one important note is that the current results do not speak to whether or not age processing is holistic. They do show that the AES is not based on holistic processing. Reply: As you say, our study does not indicate whether age processing is based on holistic processing, although it could suggest that AES is not based on holistic processing. However, your point is valid, and we are vague in our manuscript regarding this discussion. Therefore, we revised some parts of the manuscript to clarify the argument that the “AES” is not based on holistic processing. To show that age perception is based on holistic processing, one needs to examine accuracy in age perception and to compare it between upright and inverted faces. To compute accuracy, it is crucial to have data about the real ages of the photographed faces and to compute the average absolute error in each condition (Voelkle et al., 2012).3 What the authors do here is computing biases in age estimations. Bias relates to the AES, but bias and accuracy are partially independent variables. A similar amount (and direction) of bias does not necessarily reflect similar accuracy. In order to make arguments about holistic processing of age, the authors need to use the real ages of the faces and to compute accuracy in each condition. Only if accuracy is not substantially impaired for inverted faces, it is possible to argue that age processing is not holistic. Otherwise, the only inference that could be made is that the AES is not based on holistic processing. Such a conclusion is fine, but the authors need to revise the manuscript accordingly. Reply: Thank you for your suggestion. Unfortunately, as you specified, our study did not examine the accuracy of age perception. This is because the dataset of Japanese stimuli used did not include information on the actual age of each individual. However, the mean absolute error for each condition must be calculated and compared to discuss the holistic processing of age perception. Therefore, we revised the Discussion section to reflect our assertion that AES is not based on holistic processing. In several places in the text, the authors argue that they study “how the holistic processing of facial expressions could be involved in AES”. This assertion is not correct and should be revised. It is true that expression could be processed in a holistic manner, but this doesn’t mean that the effects of smiling on the AES are holistic; first, it is unclear if smiling is processed before age estimations are made. More importantly, the fact that aspects of the smile (e.g., wrinkling) affect age estimation bias cannot be used to infer that the holistic processing of smiling mediates such an effect. The effect is probably mediated by local aspects of the smile rather than by holistic processing. Such arguments in the text should be revised. It is fine to argue that the AES is mediated by smiling rather than to make the unsupported argument that holistic processing is not involved. Reply: We appreciate your pointing this out. Following this comment, we revised the sentences that claim “how the holistic processing of facial expressions could be involved in AES” to those that state “whether the AES is mediated by smiling.” The authors seem to confuse holistic processing with interactive processing between different facial dimension (e.g., expression and identity). The two aspects could be related to one another, but they are attributed to different mechanisms. The authors should avoid discussing them as the same concept. Reply: We appreciate your comment and have removed the description of the facial dimensions and added text about holistic processing."
}
]
},
{
"id": "136662",
"date": "13 Jun 2022",
"name": "Michiko Asano",
"expertise": [
"Reviewer Expertise cognitive psychology"
],
"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 investigated the contribution of holistic face processing on the aging effect of smiling (AES) in direct age estimation of faces. The authors conducted an experiment in which participants were presented with either upright or inverted faces and asked to estimate the individuals’ age. There were three conditions involving the expressions of the faces: smiling, surprised, and neutral. The results showed that AES was observed regardless of the face orientations, suggesting that holistic processing of facial processing does not contribute to the occurrence of AES. The results also showed that surprised faces, as well as smiling faces, were estimated to be older than neutral faces.\nThe work is technically sound, and the topic and results would be of interest to a broad audience. However, I have some concerns, both major and minor, which I address below.\n\nMajor concerns:\n(1) The flow of logic regarding the hypothesis is difficult to understand and needs to be improved.\nIn the fifth paragraph of the introduction, the authors write “… and previous research suggests that age perception may be based on facial surface or shape information (George & Hole, 2000). However, other studies have suggested that facial expression processing relies on holistic processing (Maurer et al., 2002; Tanaka & Sengco, 1997). As shown in previous research, facial expressions interact with other dimensions such as identity and trustworthiness (Engell et al., 2010; Ganel & Goshen-Gottstein, 2002). When the holistic processing of facial expressions is inhibited, observers’ perceptual fields are constricted and facial features are processed sequentially and independently (Rossion, 2009). In such cases, inverted smiling faces could be evaluated as older than upright smiling faces”.\nOverall, the text in this paragraph seems to be a bit short on explanations and hard to follow. If I understand correctly, I think the authors are trying to say the following here: (a) Some previous studies suggest that age estimation relies on local features of faces. (b) Some previous studies suggest that facial expression processing relies on the holistic processing of the faces. (c) Holistic processing is inhibited when faces are inverted. (d) Disruption of holistic face processing would lead to a greater impact of the local facial feature processing on age estimation. When holistic processing is inhibited, facial expression processing and the related complex cognitive processing would also be inhibited. It has also been reported that facial features are processed sequentially and independently when holistic processing is inhibited. (e) AES may be caused by a local facial feature, that is, wrinkles around the eyes caused by smiling, not by the facial expression of smiling per se. (f) Collectively, due to the relatively heightened impact of local feature processing in inverted faces, inverted smiling faces may be evaluated as older than upright smiling faces.\nHowever, the explanation about (e) is lacking from the current text, which makes it difficult to understand the logic here.\nI also found it confusing that the authors predict/interpret the results of their experiment in terms of “whether holistic processing is involved in AES” in some parts of the manuscript and “whether the relatively heightened impact of local feature processing in the inverted face condition leads to greater AES” in other parts without a clear and explicit distinction between the two.\n(2) It is not clear to me why the authors set the surprised face condition. The authors write, “Hence, we set a surprised face (i.e., neutral expression) as the control condition.” in the last paragraph of the introduction. I do not understand this sentence because a surprised face cannot be regarded as an emotionally neutral face and, in addition, the authors set the neutral expression condition besides the surprise expression condition.\nI assume that the authors wanted to use a facial stimulus with an expression that was not a smile. If so, the authors should describe the difference between smiling and surprised (and neutral) faces in terms of the local features.\n\nMinor concerns and comments:\n(3) Not only the smiling faces but also the surprised faces were estimated to be older in the current experiment. I suspect that this may be due to the wrinkles on the forehead and nasolabial folds when a surprised expression is generated.\n(4) The last sentence of the third paragraph of the introduction, “These studies indicate that the effect of emotional expressions on age estimation depends on the method of estimation (i.e., directly or retrospectively).”: Does the term “AES” refer only to the phenomenon that smiling faces are estimated to be older than neutral faces in direct age estimations, or does it also refer to the phenomenon that smiling face group is retrospectively estimated to be younger? I got confused to read the sentence above.\n(5) The second to last sentence of the fifth paragraph of the introduction, “perceptual fields”: This term requires a brief explanation.\n(6) Figure 1: The authors should explain what the black dots in this figure are.\n(7) The last sentence of the second paragraph of the discussion, “Considering that age is one of the social characteristics critical to encoding the identity of others, the results of this study seem reasonable.”: I am having difficulty figuring out what they mean here. Specifically to which results are they referring?\n(8) The first sentence of the fourth paragraph of the discussion, “The findings of the present study indicate that the association between smiling and youth is a misconception, …”: Given that the authors, as they state, did not investigate whether smiling faces are rated as younger in memory-based age estimation, the word “misconception” may be too strong and should be toned down.\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? 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? Partly",
"responses": [
{
"c_id": "8388",
"date": "17 Jun 2022",
"name": "Naoto Yoshimura",
"role": "Author Response",
"response": "This study investigated the contribution of holistic face processing on the aging effect of smiling (AES) in direct age estimation of faces. The authors conducted an experiment in which participants were presented with either upright or inverted faces and asked to estimate the individuals’ age. There were three conditions involving the expressions of the faces: smiling, surprised, and neutral. The results showed that AES was observed regardless of the face orientations, suggesting that holistic processing of facial processing does not contribute to the occurrence of AES. The results also showed that surprised faces, as well as smiling faces, were estimated to be older than neutral faces. The work is technically sound, and the topic and results would be of interest to a broad audience. However, I have some concerns, both major and minor, which I address below. Reply: Thank you for taking the time and effort to check our manuscript. We appreciate your helpful comment. Individual replies to your comments are provided below. Major concerns: (1) The flow of logic regarding the hypothesis is difficult to understand and needs to be improved. In the fifth paragraph of the introduction, the authors write “… and previous research suggests that age perception may be based on facial surface or shape information (George & Hole, 2000). However, other studies have suggested that facial expression processing relies on holistic processing (Maurer et al., 2002; Tanaka & Sengco, 1997). As shown in previous research, facial expressions interact with other dimensions such as identity and trustworthiness (Engell et al., 2010; Ganel & Goshen-Gottstein, 2002). When the holistic processing of facial expressions is inhibited, observers’ perceptual fields are constricted and facial features are processed sequentially and independently (Rossion, 2009). In such cases, inverted smiling faces could be evaluated as older than upright smiling faces”. Overall, the text in this paragraph seems to be a bit short on explanations and hard to follow. If I understand correctly, I think the authors are trying to say the following here: (a) Some previous studies suggest that age estimation relies on local features of faces. (b) Some previous studies suggest that facial expression processing relies on the holistic processing of the faces. (c) Holistic processing is inhibited when faces are inverted. (d) Disruption of holistic face processing would lead to a greater impact of the local facial feature processing on age estimation. When holistic processing is inhibited, facial expression processing and the related complex cognitive processing would also be inhibited. It has also been reported that facial features are processed sequentially and independently when holistic processing is inhibited. (e) AES may be caused by a local facial feature, that is, wrinkles around the eyes caused by smiling, not by the facial expression of smiling per se. (f) Collectively, due to the relatively heightened impact of local feature processing in inverted faces, inverted smiling faces may be evaluated as older than upright smiling faces. However, the explanation about (e) is lacking from the current text, which makes it difficult to understand the logic here. I also found it confusing that the authors predict/interpret the results of their experiment in terms of “whether holistic processing is involved in AES” in some parts of the manuscript and “whether the relatively heightened impact of local feature processing in the inverted face condition leads to greater AES” in other parts without a clear and explicit distinction between the two. Reply: The logic of this paragraph is exactly as you have commented. Notably, we have not clarified point (e) in this paragraph. Therefore, we have added a sentence to this paragraph explaining that wrinkles around the eyes drive the AES. We have also revised the paragraphs to enable readers to understand the logic in (a)–(f). Furthermore, based on Reviewer 1's comment, the hypothesis statement has been changed to whether AES is mediated by smiling. (2) It is not clear to me why the authors set the surprised face condition. The authors write, “Hence, we set a surprised face (i.e., neutral expression) as the control condition.” in the last paragraph of the introduction. I do not understand this sentence because a surprised face cannot be regarded as an emotionally neutral face and, in addition, the authors set the neutral expression condition besides the surprise expression condition. I assume that the authors wanted to use a facial stimulus with an expression that was not a smile. If so, the authors should describe the difference between smiling and surprised (and neutral) faces in terms of the local features. Reply: We apologize for this misleading wording. Here the description of “neutral expression” was intended to indicate a neutral emotional valence (neither positive nor negative). The present study used surprised faces because the expression had a change in facial morphology despite neutral emotional valence. Additionally, surprise is a common facial expression used in previous AES studies (Ganel, 2018; Yoshimura et al., 2021). However, we also understand your comment that a surprised face cannot be regarded as emotionally neutral. This is because, for example, in the circumplex affect model, the surprise is neutral in valence but not in arousal (Russell & Barrett, 1999). Moreover, a recent study on facial expressions reported that surprised and neutral faces were mapped separately (Guan, Wei, Hauer, & Liu, 2021). Therefore, we avoided claims about neutral emotions in surprised faces. In our manuscript, we have also explained that surprised faces were selected as facial expression stimuli with facial morphological changes other than smiling. Minor concerns and comments: (3) Not only the smiling faces but also the surprised faces were estimated to be older in the current experiment. I suspect that this may be due to the wrinkles on the forehead and nasolabial folds when a surprised expression is generated. Reply: We also suspect that the older age of the surprised face is due to the wrinkles caused by the change in facial expression. This point is included as an interpretation of the results in the Discussion section. Thus, we have revised the paragraph based on your comment (7). (4) The last sentence of the third paragraph of the introduction, “These studies indicate that the effect of emotional expressions on age estimation depends on the method of estimation (i.e., directly or retrospectively).”: Does the term “AES” refer only to the phenomenon that smiling faces are estimated to be older than neutral faces in direct age estimations, or does it also refer to the phenomenon that smiling face group is retrospectively estimated to be younger? I got confused to read the sentence above. Reply: AES refers only to the effect of smiling faces estimated to be older than neutral ones. To avoid this misunderstanding, we explained this phenomenon in the third paragraph. (5) The second to last sentence of the fifth paragraph of the introduction, “perceptual fields”: This term requires a brief explanation. Reply: The description of “perceptual fields” was intended to refer to the scope of a face that observers can process. Therefore, we revised the relevant description in the manuscript to clarify this point. (6) Figure 1: The authors should explain what the black dots in this figure are. Reply: The black dots represent outliers for each facial expression. We added this explanation to the figure. (7) The last sentence of the second paragraph of the discussion, “Considering that age is one of the social characteristics critical to encoding the identity of others, the results of this study seem reasonable.”: I am having difficulty figuring out what they mean here. Specifically to which results are they referring? Reply: This sentence was intended to refer to the result that the age of each expression was perceptually estimated, regardless of the emotional valence of each expression. However, the relevant descriptions are difficult to understand. We also realized that the logical sentence development of this paragraph itself might not convey the point we are trying to argue. Therefore, we revised this paragraph to convey the intent of our argument. (8) The first sentence of the fourth paragraph of the discussion, “The findings of the present study indicate that the association between smiling and youth is a misconception, …”: Given that the authors, as they state, did not investigate whether smiling faces are rated as younger in memory-based age estimation, the word “misconception” may be too strong and should be toned down. Reply: This study is an extension of our previous research (Yoshimura et al., 2021), and we have already investigated whether the association between smiling and youth is a misconception. Therefore, we apologize for the inadequate explanation of this point in the manuscript. Accordingly, we have removed the relevant sections to avoid confusion. Further, we have added sentences to clarify that this study is an extension of the previous studies. References Ganel T, Goodale MA. The effects of smiling on perceived age defy belief. Psychon Bull Rev. 2018;25(2):612–6. http://dx.doi.org/10.3758/s13423-017-1306-8 Guan H, Wei H, Hauer RJ, Liu P. Facial expressions of Asian people exposed to constructed urban forests: Accuracy validation and variation assessment. PLoS One. 2021;16(6):e0253141. http://dx.doi.org/10.1371/journal.pone.0253141 Russell JA, Barrett LF. Core affect, prototypical emotional episodes, and other things called emotion: Dissecting the elephant. J Pers Soc Psychol. 1999;76(5):805–19. https://psycnet.apa.org/fulltext/1999-13561-009.pdf Yoshimura N, Morimoto K, Murai M, Kihara Y, Marmolejo-Ramos F, Kubik V, et al. Age of smile: a cross-cultural replication report of Ganel and Goodale (2018). J Cult Cogn Sci. 2021;1–15. http://dx.doi.org/10.1007/s41809-020-00072-3"
}
]
}
] | 1
|
https://f1000research.com/articles/11-404
|
https://f1000research.com/articles/11-597/v1
|
01 Jun 22
|
{
"type": "Research Article",
"title": "Association between dermatoglyphic patterns and growth patterns of subjects with skeletal class I relation: A cross sectional study",
"authors": [
"Keerthan Shashidhar",
"Kuttappa M N",
"U S Krishna Nayak",
"Neevan D'Souza",
"Mahabalesh Shetty",
"Sonika Achalli",
"Keerthan Shashidhar",
"Kuttappa M N",
"Neevan D'Souza",
"Mahabalesh Shetty",
"Sonika Achalli"
],
"abstract": "Background: To assess the relationship between dermatoglyphic patterns and various growth patterns of the mandible. Methods: Patients with Class I Skeletal relation were selected after clinical diagnosis followed by digitally tracing the cephalogram. The patients were subdivided into three groups of mandibular divergence patterns ie Average, Horizontal and Vertical. 90 samples ie 30 in each group were selected for the study. The fingerprints of all the selected subjects were then extracted digitally and analysed for the most dominant pattern in each hand. Results: For the left hand, there was a statistically significant (P<0.05) association between fingerprint pattern and growth pattern when Horizontal growers were compared to Average and Vertical Growers. For the right hand, there was a statistically significant (P<0.05) association between fingerprint pattern and growth pattern when Horizontal growers were compared to Average Growers. A significant association (P<0.05) between fingerprint pattern and growth pattern was also found when average growers were compared to vertical growers. Conclusions: Horizontal growers had 80% frequency of appearance of whorls in their left hand and 67% in their right hand. Horizontal growers could easily be differentiated from the average and vertical growers because of the dominance of whorl pattern in their hands. Composite and arch pattern were more frequent in vertical growers when compared to horizontal and average growers.",
"keywords": [
"Dermatoglyphics",
"Orthodontics",
"Mandible",
"Growth",
"Orthodontics",
"Preventive"
],
"content": "Introduction\n\nThe craniofacial growth determines the type of shape of the head, shape of the face and the presence or absence of any anomalies in the head and face region. Many factors influence the craniofacial growth which ultimately maps the face of an individual.\n\nOne of the factors that contributes a large role in determining the final outcome of the face is genetics. The human mandible continues to grow even after the maxilla attains its final position. It is because of this reason that the mandibular growth pattern cannot be easily predicted. Facial growth relative to a cranial base line proceeds along a vector composed of variable amounts of horizontal (forward) growth or vertical (downward) growth.1 These growth patterns of the mandible are each associated with varied treatment modalities in the orthodontic field. The rotations of the mandible can occur for a variety of reasons, but there is undeniably an intrinsically determinant factor ie the genes that play a role in the establishment of the pattern of growth of the lower jaw.2\n\nRecently, a lot of interest has been shown towards dermatoglyphics in the dental fraternity. It has also been reported that dermatoglyphics is associated with a number of medical conditions. The interest of dermatoglyphics in medicine was generated when abnormal dermal patterns were observed in Down’s syndrome.3 Today, dermatoglyphic patterns have been shown to be related to oral clefts,4 dental arch forms,5 dental caries,6 carcinoma of the breast,7 Type 2 diabetes, hypertension8 and head and neck cancer.9\n\nSince dermatoglyphic patterns develop intrauterine (12th–24th week) during the same period as the development of the mandible (14th–29th week) and genetics plays a determining factor in their development, it can be hypothesized that they bear relationship with each other. Since it is said that the dermal configurations remain constant throughout life except for overall size,10,11 fingerprint patterns and other details of dermal ridges could offer distinct advantages wherein, they could be used as a screening tool, which is easily accessible, economical and may serve as non-invasive marker to detect early malocclusion.\n\nIn the field of orthodontics, many studies have been conducted to assess the relationship between dermatoglyphic patterns and sagittal malocclusion. However, currently, only two studies12,13 have focused on the relationship between dermatoglyphic patterns and growth patterns of individuals. Both these studies had low sample sizes and had not clearly defined the parameters of the study.\n\nHence, the objective of this study was to assess the relationship of dermatoglyphic patterns with diverging growth patterns of individuals with Class I Skeletal Relationship with the hypothesis that there was a relationship between dermatoglyphic patterns and diverging growth patterns.\n\n\nMethods\n\nThis cross-sectional study was conducted in A B Shetty Memorial Institute of Dental Sciences, Karnataka, India after obtaining ethical clearance from the institutional ethical committee (Ethical Clearance No. ABSM/ETH/2020-18/092).\n\nSystemically healthy dental patients with no missing teeth (except third molars) between the ages of 20 and 35 years who attended the department of orthodontics and dentofacial orthopaedics at A B Shetty Dental College from December 2020 until December 2021 without any history of previous orthodontic treatment were recruited for the study. Nonprobability convenience sampling was used to select the samples that fit into the inclusion criteria. A detailed case history was taken of each patient to rule out patients with history of habits, or history of any surgical procedures on the digits of the hand and face. Patients with Class I Skeletal relation were selected after clinical diagnosis followed by digitally tracing the cephalogram. Based on the Cephalometric values, the patients were subdivided into three groups of mandibular divergence patterns ie Average, Horizontal and Vertical. 111 samples were selected for this study, of which 21 samples were eliminated due to conflicting cephalometric values. Finally, 90 samples ie 30 in each group were selected for the study. Fingerprints of the subjects were recorded digitally for each finger and then analysed. All subjects signed a written consent form indicating their approval to participate in this study. This human observational study manuscript conforms to STROBE guidelines for cross-sectional studies.\n\nAngles Class I malocclusion was diagnosed by assessing the ANB angle (2±2), the Beta Angle (27-35) and the Wits Analysis (0±1).\n\nThe growth pattern for an individual was diagnosed by assessing the FMA angle, the SNGoGn Angle and the Jarabacks ratio. For the Average group the FMA ranged from 25±5, the SNGoGn ranged from 32±4 and the Jarabacks ratio ranged from 62-65. These values were used as the norms to diagnose the Average group of mandibular divergence. Any values below the range of FMA, SNGoGn and above the Jarabacks ratio would be classified as Horizontal Growth Pattern. Any values above the norms of FMA, SNGoGn and below the Jarabacks ratio would be classified as Vertical Growth Pattern.\n\nEach cephalogram was traced digitally on the One Ceph software twice by the same author to avoid any error in measurements.\n\nThe DG patterns of patients were recorded for all 10 digits of the hands using a digital fingerprint scanner MFS100 (Mantra Tech v54/v54OTG). The subject was asked to wash his/her hand with soap and water, followed by which his/her hand was allowed to be air dried. Once the fingers were dry, the fingers were scanned using the digital scanner. A custom designed application for this study called ‘Fingerprince’ (Designed in Arizona, United States of America) (Figures 1, 2) was used to store and analyse the fingerprint of the subjects. The application also helped store the patient’s case history as well as the cephalometric values. Henry’s classification was used to classify the fingerprints into loops, whorl, arch and composite patterns (Figure 3).\n\nLoops consisted of radial loops and ulnar loops. Whorls consisted of Plain Whorl, Double loop whorl, accidental whorl and central pocket whorl. Arches consisted of plain arches and tented arches. Composite patterns consisted of central pocket loop whorl, lateral pocket loops and accidental loops. In cases where there was no dominant fingerprint pattern, it was classified as a Tie between the 2 patterns.\n\nThe results were evaluated using Version 20 of the Statistical package for social sciences (SPSS INC, Chicago, Illinois, USA). Fisher's Exact test was used to find the association between growth pattern and dermatoglyphic patterns, where P<0.001 was considered significant.\n\n\nResults\n\nThe results of the Left hand are shown in Tables 1-4 and the results of the Right hand are shown in Tables 5-8.\n\nWith respect to the left hand, average growers had the loop pattern as the most dominant pattern with a frequency percentage of 93.3%, followed by composite pattern with a frequency percentage of 3.3% and there were 3.3% of the population that showed a tie between two patterns (Table 1).\n\nHorizontal growers had the whorl pattern as the most dominant pattern with a frequency percentage of 80%, followed by loop pattern with a frequency percentage of 16.7% and there were 3.3% of the population that showed a tie between two patterns (Table 1). The exceptional dominance of the whorl pattern in the horizontal group is striking since the average and vertical groups have only 1/8th the amount of whorls than the horizontal group.\n\nVertical growers had the loop pattern as the most dominant pattern with a frequency percentage of 70%, followed by whorl pattern with a frequency percentage of 10%, followed by the composite pattern with a frequency percentage of 6.7% and lastly the arch pattern with a frequency percentage of 3%. In this group there were 10% of the population that showed a tie between two patterns (Table 1). The higher incidence of presence of composite pattern and arch pattern in the vertical group was an important finding.\n\nUpon intergroup comparison between the average group and the horizontal group (Table 2), there was a statistically significant association between fingerprints and growth patterns (P<0.05).\n\nComparison between average group and vertical group (Table 3) showed no statistically significant association between fingerprints and growth patterns (P>0.05).\n\nComparison between the horizontal group and the vertical group (Table 4) showed a statistically significant association between fingerprints and growth patterns (P<0.05).\n\nWith respect to the right hand, average growers had the loop pattern as the most dominant pattern with a frequency percentage of 93.3%. There were 6.7% of the population that showed a tie between two patterns (Table 5).\n\nHorizontal growers had the whorl pattern as the most dominant pattern with a frequency percentage of 66.6%, followed by loop pattern with a frequency percentage of 26.7% and there were 6.7% of the population that showed a tie between two patterns (Table 5). Although reduced when compared to the left hand, the frequency of the whorl pattern in the horizontal group is still striking since the average and vertical groups have only 1/6th the amount of whorls than the horizontal group.\n\nVertical growers had the loop pattern as the most dominant pattern with a frequency percentage of 66.7%, followed by whorl pattern with a frequency percentage of 10%, followed by the composite pattern with a frequency percentage of 6.7% and lastly the arch pattern with a frequency percentage of 3.3%. In this group there were 20% of the population that showed a tie between two patterns (Table 5). The higher incidence of presence of composite pattern and arch pattern in the vertical group.\n\nUpon intergroup comparison between the average group and the horizontal group (Table 6), there was a statistically significant association between fingerprints and growth patterns (P<0.05).\n\nComparison between average group and vertical group (Table 7) also showed a statistically significant association between finger prints and growth patterns (P<0.05).\n\nComparison between the horizontal group and the vertical group (Table 8) showed a statistically significant association between finger prints and growth patterns (P<0.05).\n\nA point to be remembered is that we only chose the most dominant pattern in each hand (Appearing at least three times in each hand). Therefore, even though none of the growth patterns had a dominant composite pattern in the right hand, it does not mean that the composite pattern did not appear in the right hand.\n\n\nDiscussion\n\nBeing able to predict what one’s facial pattern would be like by assessing their fingerprints may seem far-fetched. But the results of this study prove otherwise. Dermatoglyphics has shown to be positively associated with cleft lip and palate. Some authors also claim that they are able to predict dental malocclusion as well. However, all studies so far seem to have conflicting results. While one may say that the loop pattern is dominant in class I malocclusion,14 another may say that it is the whorl pattern.15 Sagittal skeletal relations have also been studied. The results here also seem to be contrasting. While one author says that Arches16 are the most common pattern in skeletal class I relation, others say it is the loop pattern17,18\n\nOnly two studies have tried to find a relation between growth patterns and dermatoglyphics.\n\nWhile Nivedita Sahoo12 found that there was an increased incidence of whorls in the horizontal group and loops in the vertical group (which is similar to the results found in the present study), the study failed to have a detailed inclusion criteria for the selection of subjects. The skeletal relation of the subjects hadn’t been mentioned and the average group pattern had not been studied. Both of these shortcomings have been addressed in the present study.\n\nA recent study by Harmeet et al.13 showed a higher presence of loops in skeletal class I subjects but concluded saying that there was no statistically significant association between dermatoglyphics and various growth pattern. However, a point to be noted is that their sample size consisted of only 15 subjects in each of the three groups, while the present study had double the sample size of their study.\n\nWhile both the studies mentioned above used the ink method to extract the fingerprints, we used the digital method to extract the fingerprints. We found this method to have an easier mode of operation, better ease of convenience and higher accuracy than the ink method/lipstick method. A recent study by Loveday et al.19 has proven that the digital method of collecting fingerprints was the easiest and the most user friendly methods when compared to the ink/lipstick method. The present study also involved the use of a custom made software called ‘Fingerprince’ which helped store the Case history of the subjects and their fingerprints.\n\nThe present study included subjects with purely class I skeletal relation, with the sole objective of finding out if there was any relation of dermatoglyphics with the normal skeletal relation. However, we did categorize the Skeletal Class I relation into three categories ie the average, horizontal and vertical growth pattern groups. The present study shows that the loop pattern was dominant in both the average and the vertical growth pattern group. But it contradicts other studies in the Class I Horizontal Group. Despite having a Class I skeletal relation, more than 73% of the horizontal growers had the whorl pattern as a dominant pattern making it a very important discovery.\n\nThis shows that horizontal growers could easily be identified by seeing which pattern was dominant in both their hands. The present study showed that horizontal growers had 80% frequency of appearance of whorls in their left hand and 67% in their right hand.\n\nThis could mean that when a child is born, and if he/she has a dominance of whorl pattern on their fingers, we could predict that the child may have a horizontal growth pattern.\n\nAnother important discovery was the increased incidence of finding arches and composite patterns in the vertical growers when compared to the average and horizontal group. Although it was a clinical difference and not a statistically significant difference found while assessing the subjects, it does help in understanding the relationship of dermatoglyphics with growth patterns. We also observed that the average growth pattern had 93% frequency of appearance of loops and a negligible percentage of whorls and composite pattern.\n\nWhile we can confirm and say that horizontal group of patients can easily be differentiated from average and vertical growers, the same cannot be said for average and vertical growers.\n\nA higher sample size will be required to see if the difference between the average and vertical groups are statistically significant.\n\nThe results of this study have drastic implications in treatment planning and diagnosis. For example, if we are able to identify a child with prints that show a dominance of whorl pattern, we can predict that the child may have a horizontal growth pattern. This can be easily intercepted using cervical headgears or anterior bite planes to bring about an average growth pattern. Since orthodontic treatment modalities change according to the growth pattern, even vertical growers can be intercepted to try and achieve an average growth pattern.\n\nA problem we faced was the conflicting cephalometric values that made a subject borderline class I/II, or Average-Horizontal, Average to Vertical. The authors took a decision to eliminate such samples and therefore reduced the samples from 111 to 90. Hence the samples had True Class I Skeletal Relation, true average growth pattern, true horizontal growth pattern and true certical growth pattern (Table 9).\n\nAlthough the sample size was higher than other studies, we do feel that a drawback of the presentstudy was the low sample size. A higher sample size with a target population of a specific area would help us understand the demographic and/or ethnic variation of the dermatoglyphics (if any) and also help validate the findings of the present study. While this study focused on finding the dominant pattern in each hand, it would be interesting to note if there was any particular finger which showed a consistent pattern for each growth pattern. Having found interesting results for this study, the above mentioned drawbacks can increase the scope of research in this field.\n\nWhile all the current methods to predict the growth of the mandible are cumbersome, technique sensitive and manual, predicting the growth pattern by analysing the fingerprints seems to be the most easiest, cost-effective, non-invasive method and can be done anytime and anywhere. The only prerequisite would be to have knowledge of the different types of dermatoglyphic patterns.\n\n\nConclusion\n\nThe following conclusions can be made from this study\n\n1) Horizontal growers had the highest incidence of whorl pattern as the dominant pattern in both the left and right hands when compared to average growers and horizontal growers.\n\n2) Average growers had the highest incidence of loop pattern as the dominant pattern in both the left and right hands when compared to average growers and horizontal growers.\n\n3) The presence of Arch pattern and composite patterns (although not dominant) was more common in vertical growers than the horizontal and average growers.\n\n\nData availability\n\nThe images of the fingerprints cannot be shared because of ethical issues since it can be tied to the identity of a person. However, the interpretation of the data is available in Excel format.\n\nOpen Science Framework: Association between dermatoglyphic patterns and growth patterns of subjects with skeletal class I relation: A Cross Sectional Study, https://doi.org/10.17605/OSF.IO/5VFKJ.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgements\n\nWe would like to thank Dr. Saritha’ D Souza (Head of Department of Criminology and Forensic Science, School of Social Work, Roshni Nilaya, Mangalore) for her timely guidance during the course of this study. We would like to express great gratitude to Mr. Neville Nazerane for helping develop the ‘Fingerprince’ application. We would also like to acknowledge the support of Dr. Tarona Azem Subba in proofreading this manuscript. Lastly, we would like to thank Mangala.S.S, Raju Shashidhar and Nidhi.S.S for their constant support through the course of this study.\n\n\nReferences\n\nIsaacson JR, Isaacson RJ, Speidel TM, et al.: Extreme variation in vertical facial growth and associated variation in skeletal and dental relations. Angle Orthod. 1971 Jul 1; 41(3): 219–219, 229. PubMed Abstract\n\nCakan DG, Ulkur F, Taner TU: The genetic basis of facial skeletal characteristics and its relation with orthodontics. Eur. J. Dent. 2012 Jul; 06(03): 340–345. Publisher Full Text\n\nCummins H: Dermatoglyphic stigmata in mongoloid imbeciles. Anat. Rec. 1939; 73: 407–415. Publisher Full Text\n\nMathew L, Hegde AM, Rai K: Dermatoglyphic peculiarities in children with oral clefts. J. Indian Soc. Pedod. Prev. Dent. 2005 Oct 1; 23(4): 179–182. PubMed Abstract | Publisher Full Text\n\nSachdeva S, Tripathi A, Kapoor P: Dermatoglyphic assessment in subjects with different dental arch forms: an appraisal. J. Indian. Prosthodont. Soc. 2014 Sep; 14(3): 281–288. PubMed Abstract | Publisher Full Text\n\nFathima L, Mohan R, Prashanthy MR: Does Dermatoglyphics An Essential Tool for Predicting Dental Caries?-A Systematic Review. Indian J. Forensic Med. Toxicol. 2021 Jan 1; 15(1).\n\nInggarsih R, Zakyah AD, Hayati L, et al.: Dermatoglyphy in Breast Cancer Patients: A Systematic Review. Bioscientia Medicina: Journal of Biomedicine and Translational Research. 2021 Jun 23; 5(11): 1014–1029. Publisher Full Text\n\nMouneshkumar CD, Anand S, Shilpa RH, et al.: Dermatoglyphics and Cheiloscopy patterns in hypertensive and type 2 Diabetes mellitus patients: An observational study. J. Family Med. Prim. Care 2021 Mar; 10(3): 1177–1182. PubMed Abstract | Publisher Full Text\n\nKaur V, Kaur TP, Sharma M, et al.: Dermatoglyphics, the hidden potential in dentistry-A review. J. Adv. Med. Dent. Sci. Res. 2018 Oct; 6: 110–113.\n\nMulvihill JJ, Smith DW: The genesis of dermatoglyphics. J. Pediatr. 1969; 75: 579–589. PubMed Abstract | Publisher Full Text\n\nWalker NF: Inkless methods of finger, palm and sole printing. J. Pediatr. 1957; 50: 27–29. PubMed Abstract | Publisher Full Text\n\nSahoo N: A comparative study of dermatoglyphics in subjects with hypodivergent and hyperdivergent growth patterns. J. Int. Soc. Prev. Community Dent. 2018 Nov; 8(6): 540–545. PubMed Abstract | Publisher Full Text\n\nKaur H, Tikku T, Khanna R, et al.: Assessment of correlation between dermatoglyphics of individuals with different skeletal growth. Int. J. Orthod. Rehabil. 2020 Apr 1; 11(2): 69. Publisher Full Text\n\nVignesh R, Rekha CV, Annamalai S, et al.: A Comparative Evaluation between Dermatoglyphic Patterns and the Permanent Molar Relationships–An Attempt to Predict the Future Malocclusions. J. Forensic Dent. Sci. 2020 Apr 1: 23–30.\n\nTikare S, Rajesh G, Prasad KV, et al.: Dermatoglyphics—a marker for malocclusion? Int. Dent. J. 2010 Aug; 60(4): 300–304. PubMed Abstract\n\nCharles A, Ramani P, Sherlin HJ, et al.: Evaluation of dermatoglyphic patterns using digital scanner technique in skeletal malocclusion: A descriptive study. Indian J. Dent. Res. 2018 Nov 1; 29(6): 711–715. PubMed Abstract | Publisher Full Text\n\nAchalli S, Patla M, Nayak K, et al.: Assessment of dermatoglyphic patterns in malocclusion. J. Dent. Indones. 2018; 25(2): 104–107. Publisher Full Text\n\nEslami N, Jahanbin A, Ezzati A, et al.: Can dermatoglyphics be used as a marker for predicting future malocclusions? Electron. Physician 2016 Feb; 8(2): 1927–1932. PubMed Abstract | Publisher Full Text\n\nOghenemavwe LE, Gloria O: Analysis of Dermatoglyphic Features: Comparison of the Ink, Lipstick and Improvise Digital Methods. Asian J. Adv. Res. Rep. 2020; 14(3): 6–16."
}
|
[
{
"id": "139572",
"date": "20 Jun 2022",
"name": "Gautham Sivamurthy",
"expertise": [
"Reviewer Expertise Clinical trials in orthodontics assessin growht modification appliances for Class II skeletal patterns",
"arch wire materials and deep bite correction",
"cephalometrics and its clinical use."
],
"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\nInteresting piece of work which would add to the evidence base in this field. Work clearly presented with appropriate study design used and useful to our clinical practice as many a times it is difficult to predict growth pattern of the mandible.\nGood sample size for analysis, which could have been strengthened with a sample size calculation.\n\nRobust Cephalometric evaluation done - possible typo 'Angles Class I malocclusion was diagnosed by assessing the ANB angle (2±2).....', which should have been 'Skeletal Class I....'\n\nGood information regarding methodology to replicate the study, along appropriate use of software to analyse cephalograms and finger prints. Possibly information on intraexaminer reliability on cephalogram tracing could have been included.\n\nAppropriate statistical test employed. - but a very low p value (<0.001) has been used to test significance? - possible typo maybe and meant to be <0.05?\n\nResults well discussed and appropriate data provided in the tables. By 'tie' does the authors mean 'correlation'? If so, authors to consider use of this word instead?\n\nConclusion drawn adequately, but since the population studied is presumably from south India and Class I skeletal, hence the authors should consider including this in the conclusion statement?\n\nAdequate references used - could reference number 9 kindly be checked as article relates to dentistry and reference quoted is to support correlation between dermatoglyphics and cancer?\nOverall a well conducted study and well written article which is appropriate for indexing.\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": "8433",
"date": "29 Jun 2022",
"name": "Keerthan Shashidhar",
"role": "Author Response",
"response": "Dear Dr. Gautham S, We would like to thank you for taking time off your hectic schedule for critically analysing and reviewing our article. We have gone through the points that you have put forth and would like to explain ourselves accordingly. Each of your point has been mentioned below, followed by our comment. Reviewer 1: \"Good sample size for analysis, which could have been strengthened with a sample size calculation.\" Comment from Authors : Yes, we agree. We have now added the Sample Size calculations to the study. Reviewer 1: \"Robust Cephalometric evaluation done - possible typo 'Angles Class I malocclusion was diagnosed by assessing the ANB angle (2±2).....', which should have been 'Skeletal Class I....'\" Comment from Authors : Yes, we apologize for the typo. The same has been corrected in the manuscript. Reviewer 1: \"Good information regarding methodology to replicate the study, along appropriate use of software to analyse cephalograms and finger prints. Possibly information on intraexaminer reliability on cephalogram tracing could have been included.\" Comment from Authors : The tracings were done by an experienced orthodontist. Each cephalogram was traced twice to avoid any intra-operator errors. We have added this point in the manuscript as well. Reviewer 1: \"Appropriate statistical test employed. - but a very low p value (<0.001) has been used to test significance? - possible typo maybe and meant to be <0.05?\" Comment from Authors : Yes, we apologize for the typo. Thank you for pointing it out. Changes have been made in the manuscript. Reviewer 1: \"Results well discussed and appropriate data provided in the tables. By 'tie' does the authors mean 'correlation'? If so, authors to consider use of this word instead?\" Comment from Authors : By 'Tie' we mean, that we could not find a Dominant pattern in the hand. For example, if 2 fingers showed a whorl pattern, 2 showed a loop pattern and 1 showed a composite pattern, then it would be considered a tie between loop and whorl and would come under the 'Tie' Category. Hope it is understood now. Reviewer 1: \"Conclusion drawn adequately, but since the population studied is presumably from south India and Class I skeletal, hence the authors should consider including this in the conclusion statement?\" Comment from Authors : Yes, we understand what you mean. While the majority of the subjects were from south India, we did not prioritize the need to make it a population study. Hence, some subjects were from other parts of India as well. A population study would require a different methodology and we did not intend to make this a population-based study. Reviewer 1: \"Adequate references used - could reference number 9 kindly be checked as article relates to dentistry and the reference quoted is to support correlation between dermatoglyphics and cancer?\" Comment from Authors : Yes, we apologize for the mistake. we quoted the review article instead of quoting the source article. The source article has now been quoted. Thank you for pointing it out."
}
]
},
{
"id": "139573",
"date": "21 Jun 2022",
"name": "Masanobu Abe",
"expertise": [
"Reviewer Expertise Oral Malignancies",
"Malocclusion",
"Periodontal 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\nAuthors assessed the relationship between dermatoglyphic patterns and various growth patterns of the mandible and they found close association between dermatoglyphic patterns and diverging growth patterns of the mandible. The results suggest that mandibular development may be predicted by other physical characteristics. The research is substantial and the manuscript is well written. The results would contribute to the future development of orthodontics.\nThe sample size and statistical tests are appropriate for this analysis.\n\nThe results are well summarized.\n\nThe discussion is well written. However, following issues (#1 and #2 ) need to be discussed.\n#1: The authors found interesting results regarding the relationship between skin pattern and mandibular growth patterns, possibly the scientific mechanisms for the relationship need to be discussed.\n\n#2: The authors state that one of the factors influencing final outcome of the face is genetics in the Introduction. It would be interesting whether facial finish and skin pattern formation are directly related, involving the same genes (e.g., growth-related genes), or whether they are indirect events. I would appreciate discussion on this point.\n\nThe conclusion is appropriate, but authors have to describe the limitations of their study.\n\nThe references are considered to be adequate.\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": "8434",
"date": "29 Jun 2022",
"name": "Keerthan Shashidhar",
"role": "Author Response",
"response": "Dear Dr. Abe. M We would like to thank you for taking time off your hectic schedule to critically analyze and review our study. We have gone through your suggestions and would like to respond to the same. Your comments are labeled as Reviewer 2 and it will be followed by our Comments. Reviewer 2: \"The authors found interesting results regarding the relationship between skin pattern and mandibular growth patterns, possibly the scientific mechanisms for the relationship need to be discussed.\" Comment from Authors : Yes, we understand what you mean and have now included a paragraph in the discussion for the same. However, the only 'scientific' mechanism that we can deduce this to is the fact that the dermatoglyphic prints and the lower jaw form during the same embryologic period. Having found this link, we believe that this opens scope for further research to solidify the claim. Reviewer 2: \"The authors state that one of the factors influencing final outcome of the face is genetics in the Introduction. It would be interesting whether facial finish and skin pattern formation are directly related, involving the same genes (e.g., growth-related genes), or whether they are indirect events. I would appreciate discussion on this point.\" Comment from Authors : Yes, Exactly. Till date, we do not have any study that has focused to find a gene that is responsible for both the fingerprints and the lower jaw growth. We believe that this study forms the base for future genetic studies to find the exact link. Thank you for pointing this out. We have now included a line on the same in our discussion. Reviewer 2: \"The conclusion is appropriate, but authors have to describe the limitations of their study.\" Comment from Authors : We have now included the drawbacks of the study."
}
]
}
] | 1
|
https://f1000research.com/articles/11-597
|
https://f1000research.com/articles/11-33/v1
|
12 Jan 22
|
{
"type": "Correspondence",
"title": "Positional weight matrices have sufficient prediction power for analysis of noncoding variants",
"authors": [
"Alexandr Boytsov",
"Sergey Abramov",
"Vsevolod J. Makeev",
"Ivan V. Kulakovskiy",
"Vsevolod J. Makeev",
"Ivan V. Kulakovskiy"
],
"abstract": "The commonly accepted model to quantify the specificity of transcription factor binding to DNA is the position weight matrix, also called the position-specific scoring matrix. Position weight matrices are used in thousands of projects and computational tools in regulatory genomics, including prediction of the regulatory potential of single-nucleotide variants. Yet, recently Yan et al. presented new experimental method for analysis of regulatory variants and, based on its results, reported that \"the position weight matrices of most transcription factors lack sufficient predictive power\". Here, we re-analyze the rich experimental dataset obtained by Yan et al. and show that appropriately selected position weight matrices in fact can successfully quantify transcription factor binding to alternative alleles.",
"keywords": [
"Transcriptional regulation",
"rSNP",
"TF-DNA binding",
"SNP-SELEX",
"PWM",
"PSSM"
],
"content": "Introduction\n\nGene regulatory regions constitute an important part of non-coding DNA which defines both the global development program of a mammal and individual traits of a particular organism. Specific recognition of DNA sites by transcription factors (TFs) provides the gear system linking individual genomic variants to phenotypes.1 The commonly accepted model to quantify the specificity of transcription factor binding to various DNA sites is the position weight matrix (PWM), which specifies additive contributions of individual nucleotides to the protein-DNA binding energy.2 Recently Yan et al.3 reported that “the position weight matrices of most transcription factors lack sufficient predictive power” for assessment of regulatory variants identified with a new experimental method (SNP-SELEX). This finding could be devastating for a vast array of research projects and software tools which use PWMs for prediction of the regulatory potential of single-nucleotide variants.4–7 Here, we re-analyze the dataset of Yan et al. and argue that the transcription factor binding to alternative alleles detected by SNP-SELEX can be described quantitatively by carefully selected PWMs.\n\nTo rehabilitate PWMs as predictive models of TF-DNA binding, we used the CIS-BP (Catalog of Inferred Sequence Binding Preferences) collection8,9 of pre-made matrices instead of PWMs of Yin et al.10 For each TF, we additionally considered PWMs for related proteins sharing similar DNA binding domains as the benchmarking study of Ambrosini et al.2 demonstrated that PWMs of related TFs often outperform those for the target TF.\n\nWith the 1st batch of SNP-SELEX data of Yan et al., we found that for more than a half (72 of 129) of transcription factors the best PWMs achieve reliable predictions (with the same criterion as in Yan et al. requiring area under the precision-recall curve (AUPRC) > 0.75, see Figure 1a). This is 3 times more transcription factors with reliable PWM predictions than reported in Yan et al. We obtained good predictions in some cases reported as markedly underperforming such as FOXA2 (compare Figure 1b with Fig. 2b of Yan et al.). Furthermore, the achieved performance allows PWMs to compete with and, for 34 transcription factors, outperform advanced models of deltaSVM, recommended by Yan et al. as a substitution for PWMs (Figure 1c). To ensure the reliability of these results, we performed 5-fold cross-validation, which showed that models reaching higher AUPRC simultaneously had a lower variance in prediction quality across individual folds (Figure 1d). Furthermore, we tested the PWMs on the independent 2nd batch data (Figure 1e, compare with Fig. 3d of Yan et al.), and it also showed competitive albeit lower performance, with 36 of 124 transcription factors passing 0.75 AUPRC. Finally, we tested if the PWM predictions agree with the allelic binding ratios and found a small but marginally significant correlation (Figure 1f, r = 0.194, P = 0.052) for 101 SNPs tested in Yan et al. and reaching r = 0.235 (P = 0.047) for a subset of 72 SNPs with significant PWM hits (motif P-value < 0.005), in contrast to almost zero correlation for ΔPWM reported in Yan et al.\n\na. Comparison of performance of Yan et al. ΔPWM (x-axis) and best CIS-BP position weight matrices (PWMs) in predicting preferential binding SNPs in the 1st batch on the SNP-SELEX data. Each point denotes one of 129 TFs, violet and green points denote inferred and direct PWMs, respectively (see the Methods). Both axes show area under the precision-recall curve (AUPRC) values. Transcription factors (TFs) shown in Fig. 2b of Yan et al. are highlighted in orange and labeled. Dashed lines denote AUPRC of 0.75.\n\nb. Examples of the precision-recall curves showing performance of different PWM models in predicting preferential binding SNPs (single-nucleotide polymorphisms) as in Fig. 2b of Yan et al.\n\nc. Comparison of performance of deltaSVM (y-axis) and best CIS-BP PWMs (x-axis) in predicting preferential binding SNPs identified in the 1st batch of SNP-SELEX. Each point denotes one of 129 TFs, violet and green points denote inferred and direct PWMs, respectively. Both axes show mean AUPRC values obtained by 5-fold cross-validation (cv). Dashed lines denote AUPRC of 0.75.\n\nd. Variance of performance of CIS-BP PWMs (x-axis: mean AUPRC, y-axis: s.d.) in 5-fold cross-validation using the complete data of the 1st batch of SNP-SELEX. Each point denotes one of 129 TFs, violet and green points denote inferred and direct PWMs, respectively.\n\ne. Comparison of performance of deltaSVM (y-axis) and best CIS-BP PWMs (x-axis) in predicting preferential binding SNPs identified in the 2nd batch of SNP-SELEX. Each point denotes one of 87 TFs, violet and green points denote inferred and direct PWMs, respectively. Both axes show AUPRC values. Dashed lines denote AUPRC of 0.75.\n\nf. Correlation of allelic biases of DNA binding detected from ChIP-Seq experiments in HepG2 cells by Yan et al. and those predicted by ΔPWM of Yan et al. (blue) and best CIS-BP PWMs (orange). Pearson correlation coefficient (r) and the respective P-value are shown. The allelic binding ratio is computed as in Yan et al.; 101 transcription factor-SNP pairs involving 68 unique SNPs and 6 transcription factors (ATF2, FOXA2, HLF, MAFG, YBX1, and FOXA1) are shown.\n\nSumming up, our results do not compromise the high performance of deltaSVM,11 used by Yan et al. as an advanced substitution of position weight matrices (PWMs). However, properly selected PWMs achieve performance that is very close and in some cases even better than that of deltaSVM. Despite the simplicity of the PWM model, its construction is not trivial and its success depends both on the motif discovery algorithm and reliability of the training data. In our case, almost half of the best PWMs were derived from related TFs, including 8 cases of PWMs based on experimental data from other species. The experiments used to obtain the best PWMs were also of different types, including ChIP-Seq, protein-binding microarrays, and SMiLE-Seq data, see Extended data, Supplementary Table S1.12 Thus, it is important to consider various sources of PWMs and select those the most suitable by proper benchmarking. In the context of applying PWMs to analyze regulatory variants, SNP-SELEX of Yan et al. provides rich, unique, and practically useful data. Advanced multiparametric and alignment-free approaches such as deltaSVM appear very likely to shape the oncoming future of transcription factor binding site models, but today PWMs still deliver a solid standard in representation and bioinformatics analysis of the transcription factor binding sites, including assessment of the functional impact of single nucleotide variants in gene regulatory regions.\n\n\nMethods\n\nThe starting set of position frequency matrices was extracted from TF_Information_all_motifs.txt of CIS-BP 2.0 that includes models derived from direct experimental data for each TF and models that can be inferred given the TF family-specific threshold on DNA-binding domain similarity, see Ref. 10, referred to in Figure 1 caption as ‘direct’ and ‘inferred’ PWMs. All position frequency matrices were converted to log-odds PWMs as in Ref. 13 with an arbitrarily selected word count of 100, a pseudocount of 1, and uniform background nucleotide probabilities. For each TF, the set of PWMs was additionally extended by considering related TFs, i.e. PWMs for all ETV* TFs were added to the ETV1 PWM set, all FOX* (Forkhead box) PWMs were added to the FOXA2 PWM set, etc. (e.g. YY1 and YY2 PWM sets were identical). This procedure was not performed for ZNF* (zinc finger) TFs as these TFs can recognize very dissimilar motifs and thus additional PWMs of other ZNFs would unlikely provide any benefit. The resulting set contained a median of 32 PWMs per TF although the overall distribution was non-uniform e.g. only 2 PWMs for ZNF396 and over a thousand for FOXA2, see Extended data, Supplementary Table S1. Upon assessment with the SNP-SELEX data, there was no correlation between the prediction performance (AUPRC) and the number of tested PWMs per TF (r = −0.07, P = 0.425).\n\nTo assess with a particular PWM whether an SNV affects transcription factor binding, we used PERFECTOS-APE5 that estimates the log-fold change of motif P-values computed for best PWM hits detected among sites overlapping the first and the second of two alternative alleles. To use the prediction as a binary classifier, we treated the cases with P > 0.005 at both alleles as predicted negatives and used the log-fold change as the prediction score in the remaining cases. The auc function of the sklearn.metrics Python package was used to estimate the area under the precision-recall curve (AUPRC).\n\nTo provide a fair assessment, we mimicked the benchmarking protocol of Yan et al. Particularly, true positives and true negatives were selected from the SNP-SELEX data as follows. 1st batch data positives: pbs P-value < 0.01 and obs P-value < 0.05; negatives: pbs P-value > 0.5 and obs P-value < 0.05. 2nd batch data positives: pbs P-value < 0.01, negatives: pbs P-value > 0.5. For each TF, we tested each PWM from its PWM set. For each TF, the PWM reaching the highest AUPRC on the 1st batch data was selected for evaluation against the best ΔPWM on the 1st batch (Figure 1a) and against deltaSVM on the 2nd batch of SNP-SELEX data (Figure 1e). Performance estimates for deltaSVM models (used in Figure 1c,e) were extracted from Supplementary Table S7 of Yan et al. Performance estimates of ΔPWM (used in Figure 1a) were kindly shared on our request by the authors.3\n\nThe data on allelic binding ratios at individual SNPs and respective ΔPWM predictions of Yan et al. (Figure 1f, compare to Fig. 2d of Yan et al.) were kindly shared on our request by the authors. The data included 193 TF-SNP pairs demonstrating allelic imbalance with 101 of 193 pairs annotated with the ΔPWM predictions. For these SNPs, we obtained PWM predictions with the same protocol as for the SNP-SELEX data using the best PWMs selected with the 1st batch of the SNP-SELEX data.\n\n\nData availability\n\nOriginal data on preferential binding SNPs as well as ΔPWM and deltaSVM predictions are provided in the supplementary materials section of the Yan et al. paper.3\n\nCISBP Human PWMs collection was extracted from CIS-BP 2.0.8,9\n\nFigshare: PWM-evaluation-using-SNP-SELEX, https://doi.org/10.6084/m9.figshare.16906789.v1.12\n\nThis project contains the following extended data:\n\n• Supplementary table S1 (Overview of PWMs and their performance in recognizing SNPs affecting transcription factor binding in SNP-SELEX data.)\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\nThis study was supported by Russian Science Foundation grant 20-74-10075 to IVK.",
"appendix": "References\n\nWasserman WW, Sandelin A: Applied bioinformatics for the identification of regulatory elements. Nat. Rev. Genet. 2004; 5: 276–287. Publisher Full Text\n\nAmbrosini G, et al.: Insights gained from a comprehensive all-against-all transcription factor binding motif benchmarking study. Genome Biol. 2020; 21: 114. PubMed Abstract | Publisher Full Text\n\nYan J, et al.: Systematic analysis of binding of transcription factors to noncoding variants. Nature 2021; 591: 147–151. PubMed Abstract | Publisher Full Text\n\nMacintyre G, Bailey J, Haviv I, et al.: is-rSNP: a novel technique for in silico regulatory SNP detection. Bioinformatics 2010; 26: i524–i530. PubMed Abstract | Publisher Full Text\n\nVorontsov IE, Kulakovskiy IV, Khimulya G, et al.: PERFECTOS-APE - Predicting Regulatory Functional Effect of SNPs by Approximate P-value Estimation. Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms 102–108 (SCITEPRESS - Science and and Technology Publications 2015. Publisher Full Text\n\nCoetzee SG, Coetzee GA, Hazelett DJ: motifbreakR: an R/Bioconductor package for predicting variant effects at transcription factor binding sites. Bioinformatics 2015; 31: btv470–bt3849. PubMed Abstract | Publisher Full Text\n\nDeplancke B, Alpern D, Gardeux V: The Genetics of Transcription Factor DNA Binding Variation. Cell 2016; 166: 538–554. Publisher Full Text\n\nLambert SA, et al.: The Human Transcription Factors. Cell 2018; 172: 650–665. Publisher Full Text\n\nWeirauch MT, et al.: Determination and Inference of Eukaryotic Transcription Factor Sequence Specificity. Cell 2014; 158: 1431–1443. PubMed Abstract | Publisher Full Text\n\nYin Y, et al.: Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science 2017; 356: eaaj2239. PubMed Abstract | Publisher Full Text\n\nLee D, et al.: A method to predict the impact of regulatory variants from DNA sequence. Nat. Genet. 2015; 47: 955–961. PubMed Abstract | Publisher Full Text\n\nAbramov S: PWM evaluation using SNP-SELEX. Online resource. 160773 Bytes2021. Publisher Full Text\n\nLifanov AP, Makeev VJ, Nazina AG, et al.: Homotypic Regulatory Clusters in Drosophila. Genome Res. 2003; 13: 579–588. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "123085",
"date": "14 Feb 2022",
"name": "Victor G. Levitsky",
"expertise": [
"Reviewer Expertise bioinformatics",
"massive analysis of genome data"
],
"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\n1. Boytsov et al. in the Abstract of their correspondence cited Yan et al. paper Yet, recently Yan et al. presented new experimental method for analysis of regulatory variants and, based on its results, reported that \"the position weight matrices of most transcription factors lack sufficient predictive power\". Here, we reanalyze the rich experimental dataset obtained by Yan et al. and show that appropriately selected position weight matrices in fact can successfully quantify transcription factor binding to alternative alleles…\nBut actually, Yan et al. in the Abstract wrote: …the position weight matrices of most transcription factors lack sufficient predictive power, whereas the support vector machine combined with the gapped k-mer representation show much improved performance, when assessed on results from independent SNP-SELEX experiments involving a new set of 61,020 sequence variants…. I think that Yan et al. are not wrong Since, in particular, Yan et al. also wrote that …(1) We reasoned that the poor performance of many PWMs was probably because they did not take into account dinucleotide interdependency in transcription factor–DNA interactions and the influence of flanking DNA sequences11,12. Previous studies have shown that dinucleotide interdependency exists for some transcription factor dimers4. For example, according to the PWM model, the SNP rs79124498—located within a binding site of HLF, a bZIP family transcription factor that binds DNA as homodimers—would have little effect on HLF binding. However, SNP-SELEX indicated that the G allele bound more strongly than the T allele to HLF. This could be caused by the dinucleotide interdependency between position 2 (the SNP position) and position 10 in the binding site (Fisher’s exact test P < 2.2 × 10−16, odds ratio = 3.34)… …(2) PWM performed poorly for SNPs located in low-affinity binding sites of transcription factors. However, this limitation could be overcome by using deltaSVM. When we categorized SNPs into five quantiles on the basis of their binding affinities as measured by OBS, and assessed the performance of PWM and deltaSVM in predicting their allelic binding by fivefold cross-validation or using the novel batch of SNP-SELEX experimental results (Extended Data Fig. 7), deltaSVM outperformed PWM in all quantiles, particularly in the lower quantiles corresponding to weak transcription factor binding sites…..\nDoes Boytsov et al. not agree with Yan et al. in these two points?\nAs I know, the alternative model can outperform the standard PWM model (e.g. BaMM, Siebert,M. and Söding,J. 2016 Bayesian Markov models consistently outperform PWMs at predicting motifs in nucleotide sequences. Nucleic Acids Res., 44, 6055–6069). At least this should be if an alternative model incorporates a PWM model (as BaMM does).\nHence, Yan et al. compared PWM (e.g. in BEESEM realization) and deltaSVM, and proved that PWMs are worse than deltaSVM. Boytsov et al. used additional PWMs from public databases such as CIS-BP to select the best performed PWM. This is actually proves that ready PWMs (that respects to the same family, i.e. to other TFs with the same DNA binding domain) may be quite successive, but this does not prove that PWMs are better than deltaSVMs. This also does not imply that PWMs are good or bad. We should develop a special pipeline to compare PWMs and deltaSVMs (this is out of scope of paper). Boytsov et al. did not tried to incorporate the non-traditional model deltaSVMs and data from CIS-BP to potentiate the performance of deltaSVMs. So about what the Boytsov paper? Hence, Boytsov et al. proved that BEESEM realization may be better if we incorporate CIS-BP data or what?\nBoytsov et al. concluded …However, properly selected PWMs achieve performance that is very close and in some cases even better than that of deltaSVM. Despite the simplicity of the PWM model, its construction is not trivial and its success depends both on the motif discovery algorithm and reliability of the training data… Any motif discovery algorithm does not use any motif library on the process of de novo search. Usually, motif libraries are applied to interpret enriched motifs (e.g. STREME and Tomtom in meme suite, https://meme-suite.org/meme/index.html) Hence, application of motifs library is not a step in de novo process. At this step, I again does not understand why Boytsov et al. compared Figure 1b with Fig. 2b of Yan et al.\nOverall, Boytsov et al. should draw attention to the point of disagreement with data or conclusion of Yan et al. paper.\n2. The TF classification by family is wrongly described. …For each TF, the set of PWMs was additionally extended by considering related TFs, i.e. PWMs for all ETV* TFs were added to the ETV1 PWM set, all FOX* (Forkhead box) PWMs were added to the FOXA2 PWM set, etc. (e.g. YY1 and YY2 PWM sets were identical). This procedure was not performed for ZNF* (zinc finger) TFs as these TFs can recognize very dissimilar motifs and thus additional PWMs of other ZNFs would unlikely provide any benefit… This description does not explain several pair from Supplementary Data (Overview of best CIS-BP PWMs), e.g.ETV2 & FLI1 The correct and default approach was described in the previous publication (Ambrosini G , et al. Genome Biol. 2020: Matrices were manually mapped to gene symbols and TF families from TFclass [Wingender E,et al.. Nucleic Acids Res. 2018] and CIS-BP). Moreover, the CIS-BP database contains TF PWMs that were already classified by families.\n3. Currently, links to Figure 1 are contained in the Introduction section. Although the format of correspondence paper is flexible, I propose that authors should either do not user various sections, or apply the standard sections, Introduction, Methods, Results, Conclusions/Discussion.\n\nIs the rationale for commenting on the previous publication clearly described? Partly\n\nAre any opinions stated well-argued, clear and cogent? No\n\nAre arguments sufficiently supported by evidence from the published literature or by new data and results? Partly\n\nIs the conclusion balanced and justified on the basis of the presented arguments? Partly",
"responses": [
{
"c_id": "8403",
"date": "21 Jun 2022",
"name": "Sergey Abramov",
"role": "Author Response",
"response": "… But actually, Yan et al. in the Abstract wrote: …the position weight matrices of most transcription factors lack sufficient predictive power, whereas the support vector machine combined with the gapped k-mer representation show much improved performance, when assessed on results from independent SNP-SELEX experiments involving a new set of 61,020 sequence variants…. I think that Yan et al. are not wrong… In fact, we do not challenge the authors' statement regarding the high performance of deltaSVM in predicting the SNP-SELEX results by sequence analysis. Particularly, we explicitly state that \"... our results do not compromise the high performance of deltaSVM, used by Yan et al. as an advanced substitution of position weight matrices (PWMs)\" (paragraph 4 of Discussion). Yet, we strongly disagree with the authors' conclusion on the PWM performance (\"lack sufficient predictive power\") and believe that their comparison of the performance of the PWM and deltaSVM became one-sided in favor of deltaSVM due to an accidental selection of particular PWMs in their study. We believe that public databases contain PWM which can display much better performance in quantifying allele-specific binding and put it explicitly in the Introduction that “We show that the careful selection of PWMs of many TFs from a public database quantitatively explains the differential TF binding to allelic variants with reliability comparable to that of deltaSVM.” Again, we put into Discussion that “Summing up, our results do not compromise the high performance of deltaSVM, used by Yan et al. as an advanced substitution of position weight matrices (PWMs). However, properly selected PWMs achieve performance that is very close and in some cases even better than that of deltaSVM.” We have also added a detailed discussion on the subject into the Discussion section (see the response to the next question of the reviewer). Since, in particular, Yan et al. also wrote that …(1) We reasoned that the poor performance of many PWMs was probably because they did not take into account dinucleotide interdependency in transcription factor–DNA interactions and the influence of flanking DNA sequences… …(2) PWM performed poorly for SNPs located in low-affinity binding sites of transcription factors. Does Boytsov et al. not agree with Yan et al. in these two points? We agree with the theoretical limitations of position weight matrices regarding their inability to account for non-additive contributions of particular nucleotides into protein affinities. Yet, it is important to distinguish between the general and well-known limitations of the PWM as a model and the low performance of particular matrices. In our opinion the poor performance of PWMs used in the study of Yan et. al. was not due to the intrinsic inability of PWMs to classify TF binding preferences at particular TFBS, but rather due to the way the PWMs used in this study were selected/constructed. We prove it by providing the alternative PWMs that belong to the same class of mononucleotide models but perform better than the PWMs of Yan et al. and comparably to deltaSVM. We have added an explicit statement on this matter in the revised version of the manuscript. “The objective of our study is by no means to undermine the necessity of complex TFBS models with dependent positional contributions. Advanced multiparametric and alignment-free approaches such as deltaSVM appear very likely to shape the oncoming future of transcription factor binding site models. Rather, we want to underline that the prediction performance for transcription factor binding sites in its current stage is more influenced by model training protocols than by model structure restrictions. PWMs still can deliver a solid standard in representation and bioinformatics analysis of the transcription factor binding sites, including assessment of the functional impact of single nucleotide variants in gene regulatory regions. In addition, we underline that better defined 'baseline' PWMs or PWM selection procedures are required for the proper evaluation of advanced models. It is important that such 'baseline' TFBS models, while certainly being handicapped by design, still reach meaningful prediction quality.” … ready PWMs (that respects to the same family, i.e. to other TFs with the same DNA binding domain) may be quite successive, but this does not prove that PWMs are better than deltaSVMs. We used PWMs with the same DNA binding domains to increase the repertoire of candidate PWMs, from which the best PWM for assessing variants identified by SNP-SELEX experiments can be selected. To avoid confusion we have added two subsections to the Methods section: “PWMs used in the study” and “Selection of the best PWM for a TF”. In fact, carefully selected PWMs outperformed deltaSVM models for 34 of 129 TFs (see paragraph 3 of Introduction in the manuscript and Figure 2), and many of these PWMs were initially constructed for different TFs and even different species (see Supplementary Table S1). This does not compromise better deltaSVM performance for other TFs (see Fig. 1e). Hence, Boytsov et al. proved that BEESEM realization may be better if we incorporate CIS-BP data or what? We did not test BEESEM or other types of motif discovery software or alternative PWM-like motif representations, and thus don’t know if they provide even better PWMs than we found in CIS-BP. We only used the existing published PWMs available in the CIS-BP database. SNP-SELEX provides a rich data source to test various types of models in the task of predicting rSNP effects on transcription factor binding, but such testing does not fit the scope of our manuscript. Hence, application of motifs library is not a step in de novo process. At this step, I again does not understand why Boytsov et al. compared Figure 1b with Fig. 2b of Yan et al. We did not discuss de novo motif discovery. The idea of our study was to verify whether the inadequate performance of PWMs reported in Yan et al. was related to the type of the model or if it characterized the particular PWMs they used. In fact, Yan et al. also did not construct PWMs through de novo motif discovery but used the pre-made PWMs of Yin et al. Similarly, we followed the suit and avoided de novo motif discovery in favor of reusing existing PWMs from CIS-BP. Selection of a single PWM from the pool of related PWMs can be considered as \"training\" of the model, and we fully replicated the approach of Yan et al. i.e. the cross-validation on the 1st batch of SNP-SELEX data. Overall, Boytsov et al. should draw attention to the point of disagreement with data or conclusion of Yan et al. paper. We did our best to better highlight the key idea of the study in the revised version of the manuscript and added an extensive Discussion section. 2. The TF classification by family is wrongly described. … This description does not explain several pair from Supplementary Data (Overview of best CIS-BP PWMs), e.g.ETV2 & FLI1 In the pool of possible PWMs for each TF, we included CIS-BP 'inferred' PWMs (as described in Methods) which belonged to TFs with a similar DNA-binding domain, hence there is no contradiction. We revised the Methods section, see the subsection “PWMs used in the study.” The correct and default approach was described in the previous publication (Ambrosini G , et al. Genome Biol. 2020: Matrices were manually mapped to gene symbols and TF families from TFclass [Wingender E,et al.. Nucleic Acids Res. 2018] and CIS-BP). Moreover, the CIS-BP database contains TF PWMs that were already classified by families. CIS-BP classification of DNA-binding domains is very general and leads to very wide sets of PWMs potentially applicable to a particular TF, if all PWMs across the TF family are considered. To reduce computational complexity, we made a compromise of including 'inferred' motifs (see above) but only for related proteins by matching gene names and not relying on the detailed TF family annotation. Even with this simplification in the PWM selection, which greatly reduced the number of available PWMs, the resulting performance of the best PWMs was significantly better than the PWM performance reported by Yan et al. for the same TF. Of note, in Ambrosini et al. (2020) we used all-vs-all testing strategy and reported cross-family applicability of PWMs, although this is computationally ineffective in the practical selection of the best-performing matrices. 3. Currently, links to Figure 1 are contained in the Introduction section. Although the format of correspondence paper is flexible, I propose that authors should either do not user various sections, or apply the standard sections, Introduction, Methods, Results, Conclusions/Discussion. We have revised the manuscript structure according to the reviewer’s suggestion."
}
]
},
{
"id": "128877",
"date": "07 Apr 2022",
"name": "Philip Machanick",
"expertise": [
"Reviewer Expertise Transcription factor binding specificity (computer science perspective)."
],
"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 Yan et al. article is a useful addition to the literature so questioning the validity of their results is also useful. However, this article makes an exaggerated claim of the extent to which Yan et al. reduce the utility of PWMs.\nPWMs are already known to be potentially flawed models, varying from very accurately predicting DNA binding specificity to poorly doing so, with potential confounders like cofactors 1 and indirect binding 3. The extent to which these issues apply can depend on the method used to determine the PWM. For example, using ChIP-seq data can create a composite motif incorporating part of a cofactor. Using PBM may eliminate this effect, but can produce poor binding specificity in some cases, possibly because either the specificity is mediated by cofactor requirements or because binding is indirect 4,5.\nWhile I am specifically mentioning older approaches like PBMs here, any in vitro or in silico method potentially has similar issues.\nFor this reason, I advocate using a range of methods to assess motif quality 2.\nAs regards SNPs and other variability, this sort of issue has to be taken into account, otherwise any variation in specificity may not correspond to in vivo reality.\nSo, back to the approach of this paper: selecting PWMs that match specific criteria for reliability. It is not clear to me that this in any way invalidates the results of Yan et al. as there is variability in the predictive quality of PWMs, given the potential for confounders.\nI would like to see a clearer explanation of the extent to which Yan et al. actually diminish the utility of PWMs (noting this is in a specific context, assessing small genomic variants) and the extent to which this review generalises beyond carefully selected PWMs..\n\nIs the rationale for commenting on the previous publication clearly described? Partly\n\nAre any opinions stated well-argued, clear and cogent? Partly\n\nAre arguments sufficiently supported by evidence from the published literature or by new data and results? Partly\n\nIs the conclusion balanced and justified on the basis of the presented arguments? Partly",
"responses": [
{
"c_id": "8404",
"date": "21 Jun 2022",
"name": "Sergey Abramov",
"role": "Author Response",
"response": "The Yan et al. article is a useful addition to the literature so questioning the validity of their results is also useful. However, this article makes an exaggerated claim of the extent to which Yan et al. reduce the utility of PWMs. We did our best to clarify our claim as it was also questioned by Dr. Levitsky. PWMs are already known to be potentially flawed models, varying from very accurately predicting DNA binding specificity to poorly doing so, with potential confounders like cofactors 1 and indirect binding 3. The extent to which these issues apply can depend on the method used to determine the PWM. For example, using ChIP-seq data can create a composite motif incorporating part of a cofactor. Using PBM may eliminate this effect, but can produce poor binding specificity in some cases, possibly because either the specificity is mediated by cofactor requirements or because binding is indirect 4,5. We fully agree that the data source and the computational procedure used to derive the TFBS model would significantly affect the result in terms of whether it reflects the genuine TF binding specificity or significantly depends on confounding factors. In this paper we restricted ourselves to a more specific context of using PWMs for quantifying the variants identified with the SNP-SELEX, which is an in vitro assay, so indirect binding and cofactors do not influence the outcome. To make it clear, we have revised the Introduction section of our manuscript. For this reason, I advocate using a range of methods to assess motif quality 2. Indeed. A comprehensive assessment of motif models using different types of experimental data was performed e.g. in Ambrosini et al. 2022. In this study, we did not focus on selecting the optimal PWMs for a wide range of practical applications or in terms of representing in vivo binding. Our aim was to demonstrate that PWMs provide the type of a model, which is able to show a reasonable performance in classifying differentially bound oligonucleotides with single-nucleotide substitutions. So, back to the approach of this paper: selecting PWMs that match specific criteria for reliability. It is not clear to me that this in any way invalidates the results of Yan et al. as there is variability in the predictive quality of PWMs, given the potential for confounders. I would like to see a clearer explanation of the extent to which Yan et al. actually diminish the utility of PWMs (noting this is in a specific context, assessing small genomic variants) and the extent to which this review generalises beyond carefully selected PWMs. The same issue was pointed out by Dr. Levistky and we did our best to clarify the aim of the study in the revised version of the manuscript. We believe, that quantifying the effects of single nucleotide variants on TF binding is an important practical problem emerging in the increasingly influential field of personalized genomics, as according to the recent reports up to 80% of causal variants are found in the regulatory regions [see e.g. https://www.medrxiv.org/content/10.1101/2021.06.08.21258515v2]. Even though this is a limited problem, it is worth clarifying the PWM performance for this particular application. We have added the necessary information in the Introduction section."
}
]
}
] | 1
|
https://f1000research.com/articles/11-33
|
https://f1000research.com/articles/11-738/v1
|
04 Jul 22
|
{
"type": "Case Report",
"title": "Case Report: Functioning adrenal adenoma presenting with atypical imaging findings",
"authors": [
"Prakash Dhakal",
"Suraj Sharma",
"Abhishek Sharma",
"Ashik Rajak",
"Prabin Pandey",
"Prakash Dhakal",
"Suraj Sharma",
"Ashik Rajak",
"Prabin Pandey"
],
"abstract": "The most common adrenal lesion is an adrenal adenoma in adults. Adrenal adenomas can have a variety of imaging features due to their widespread prevalence. As a result, distinguishing between typical and atypical imaging features of adrenal adenomas is critical, as is distinguishing atypical adrenal adenomas from potentially malignant lesions. Here, we present a case of adrenal adenoma with atypical imaging findings presenting as Cushing’s syndrome.",
"keywords": [
"Adrenal adenoma",
"Adrenal protocol",
"Atypical",
"Cushing’s syndrome",
"Imaging findings",
"Ultrasonography."
],
"content": "Abbreviations\n\nACTH: Adrenocorticotropic hormone\n\nAPW: Absolute percentage washout\n\nCECT: Contrast-enhanced computed tomography\n\nCT: Computed tomography\n\nDCT: Delayed contrast enhanced CT\n\nDEXA: Dual energy X-ray absorptiometry\n\nHU: Hounsfield Unit\n\nMDCT: Multi-detector computed tomography\n\nMRI: Magnetic resonance imaging\n\nRDW: Red cell distribution width\n\nRPW: Relative percentage washout\n\nUSG: Ultrasonography\n\n\nIntroduction\n\nAdrenal tumors are common in humans, occurring in 9% of autopsy series. The prevalence of adrenal adenoma is reported to be age-related; the frequency of undiagnosed adenoma is 0.14 percent in patients aged 20–29 years and 7% in those older than 70 years.1 Primary adrenal tumors can be hyper-functioning, producing excess hormones and resulting in clinical symptoms, or non-functioning which is more common. However, 10-15% of patients with adrenal adenoma might exhibit clinical features of Cushing's syndrome.2 In the evaluation of adrenal tumors, abdominal ultrasound has a reported sensitivity of 96% for tumors smaller than 2 cm and 100% for tumors larger than 2 cm. Multi-detector computed tomography (MDCT) is the single most useful modality for identification and characterization. Magnetic resonance imaging (MRI) and functional imaging modalities such as nuclear scintigraphy are useful for a thorough evaluation when in doubt.3 Computed tomography (CT) imaging can detect adrenal masses with diameters greater than 5 mm. Adrenal adenomas with typical imaging characteristics account for a vast majority of these benign adrenal masses. However, distinguishing between atypical adrenal adenomas and adrenal malignant lesions is critical, because a small percentage of these are potentially malignant lesions.4 Furthermore, because imaging cannot reliably distinguish between functioning and non-functioning adenomas, the biochemical profile must be used. To identify abnormal adrenal function in an adenoma, NP-59 scintigraphy can supplement biochemical and radiological imaging results.3 This case report highlights atypical findings in a functioning adrenal adenoma as well as possible differential diagnoses that could lead to a misdiagnosis.\n\n\nCase report\n\nWe report a 16-year-old South Asian female who presented at the out-patient service of the Endocrinology department of Bir Hospital, Kathmandu with a chief complaint of increased weight for two years, primary amenorrhea and lethargy. The patient had not sought any prior medical attention or undergone any intervention in the past. She did not have any history of similar illness or genetic conditions in her family. Vitals taken showed blood pressure to be 180/130 mm Hg, pulse rate of 78 beats/minute, respiratory rate of 18 breaths/minute and temperature to be 98°F (36.7°C).\n\nA thorough physical examination was performed: the patient had a moon-shaped face with facial hair, supra-clavicular hump, deepening of voice and purple abdominal striae were noted (Figure 1). However, axillary and pubic hair was present and breast development was normal (Tanner stage 5). A suspicion of Cushing's syndrome was made and further investigations were sent (Table 1). In addition, a bone densitometry scan was performed by dual energy X-ray absorptiometry (DEXA) showing a Z score of -2.8 in the spine along with a Z score of -0.8 and -1.5 in the right and left femur neck, respectively.\n\nUltrasonography (USG): Well-defined hypoechoic lesion measuring 48×43×40 mm in the right suprarenal region. Tiny hyperechoic focus (likely calcification) was noted within the lesion. On color Doppler, the lesion did not show blood flow (Figure 2).\n\nContrast-enhanced computed tomography\n\n(CECT) (adrenal protocol) findings: Well-defined soft tissue density lesion measuring 56×49×45 mm was noted in the right suprarenal gland region, without separate visualization of the right adrenal gland. The lesion showed tiny calcified foci in its posterior aspect. There was no evidence of fat-attenuating foci within the lesion. In non-contrast images, the lesion showed (Hounsfield unit (HU)+41) (Figure 3). On post-contrast images taken 60 seconds after contrast injection, the lesion showed significant homogenous enhancement with (HU+109). On delayed images taken 15 minutes after contrast injection, the lesion showed (HU+56) (Figure 4). The absolute percentage washout of 77.9% (which is >60%) and relative percentage washout of 48.6% (which is >40%) was noted, suggesting lipid-poor adrenal adenoma.\n\nThe patient was counselled about the need for surgery but was non-compliant. She was managed with anti-hypertensive and antidiabetic medications. Her blood pressure and blood glucose has been well under control. She visited the hospital for a follow up one month later in which she had her blood pressure and blood glucose under control. She was again advised of the need for surgery during follow up which is planned for a later date when the patient is compliant.\n\n\nDiscussion\n\nAdrenal tumors that are incidentally found on imaging are known as adrenal incidentalomas, which comprises benign adrenal masses to metastatic tumors. They are found during imaging of areas other than adrenal gland. The prevalence of adrenal incidentalomas is between 0.35% to 1.9% on CT scan. Among them, around 54 percent are found to be adrenal adenomas.5 However, our case was imaged for the proven diagnosis of Cushing's syndrome. In the case of Cushing's syndrome in adults, only 20% of the cases are due to adrenal causes; however, in the first decade of life adrenal causes predominate majority of cases. Among the cases of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome, it was found that 95% of cases were due to adrenal adenomas or carcinomas, among which 65% consisted of hyper-functioning adrenal adenoma, similar to our case, while primary pigmented nodular adrenal dysplasia and ACTH-independent macronodular hyperplasia accounts for the rest of the cases.6 On imaging, adrenal adenomas are usually well-defined ovoid to round nodules measuring 1-5 cm, with homogenous or slight heterogenous attenuation. Imaging cannot differentiate between functional and non-functional adenomas: this needs adrenal venous sampling.7\n\nAn ultrasonography imaging was performed, which found a homogenous and hypoechoic lesion, consistent with the ultrasound imaging criteria for adrenal adenoma. However, in our case we also noted a tiny hyperechoic focus, which was likely a calcification within the mass. The size of the mass on USG was 4.8 cm and comparable to the range of 1.0-6.3 cm seen in an ultrasound study by Fan et al. in China.8\n\nSince MDCT is the imaging of choice in adrenal adenoma, an MDCT was performed and showed well-defined soft tissue density; density evaluation is highly sensitive and specific, as 70% of the cases consist of high lipid density in which <10HU is considered 71% sensitive and 98% specific. However, our case showed a HU of +41 and an adrenal CT washout was performed, showing an absolute percentage washout (APW) and relative percentage washout (RPW) of >60% and >40% respectively, highly suggestive of adenoma.9 Moreover, it was also seen that RPW was more accurate than APW and a 15-minute delayed contrast enhanced CT (DCT) was more accurate than a 10-minute DCT for the diagnosis of adrenal adenoma. Compared to other modalities, washout CT provides the highest accuracy for characterization of adenoma.1 In our case, we calculated RPW and a 15-minute DCT practicing evidence-based medicine at our center. Contrary to the typical findings of adrenal adenoma, this case featured atypical findings which might hinder the accurate identification of the case. Adrenal adenomas with calcifications have been reported in about 14% of cases. This necessitates its differentiation from various other etiologies like adrenocortical carcinomas, myelolipomas and metastases. It was found that calcified adrenal adenomas represent 15% of calcified adrenal masses second only to adrenal cyst.4\n\nIn our patient, bone densitometry scan showed a lowered Z score. The skeletal system's structural and functional impairment is a significant cause of morbidity and disability in Cushing’s syndrome patients, particularly given the high prevalence of vertebral fractures. Glucocorticoids reduce bone collagenous matrix synthesis while increasing its degradation. The reduction in osteoblast number and function appears to be central to the bone loss caused by glucocorticoid excess. Glucocorticoid-induced osteoporosis is reversible, but the recovery of bone loss is slow and takes about ten years. Fractures are common in patients with Cushing’s syndrome who have severe osteoporosis.10\n\n\nConclusions\n\nAdrenal adenomas can present with features of hormonal excess (functioning adenoma). Diagnosis of adrenal adenoma needs a multidisciplinary approach of clinical, biochemical and imaging studies. Cushing's syndrome is one of the presenting clinical feature in functioning adrenal adenoma. Adrenal adenoma presents a diagnostic puzzle when presented with atypical imaging findings in CT. It is essential to have the knowledge of atypical findings and follow an adrenal protocol when dealing with adrenal adenomas to prevent a misdiagnosis.\n\nI reside in a rural area of Nepal due to which I did not seek medical attention for my problems which seemed very minor to me, after visiting the hospital I came to realize that I had a bigger problem than I thought. I am happy that the doctors were able to come to a diagnosis and provided me medications. I will visit the hospital from now onwards without delay if I have any symptoms and will opt for surgery.\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.",
"appendix": "References\n\nPark JJ, Park BK, Kim CK: Adrenal imaging for adenoma characterization: imaging features, diagnostic accuracies and differential diagnoses. Br. J. Radiol. 89(1062): 20151018. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMbouché LO, Epoupa Ngallé FG, Sando Z, et al.: The case series of functional adrenal tumors: Experience of two tertiary hospitals in Yaoundé, Cameroon. Int. J. Surg. Case Rep. 2020 Jan; 72: 577–583. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIlias I, Sahdev A, Reznek RH, et al.: The optimal imaging of adrenal tumours: a comparison of different methods. Endocr. Relat. Cancer. 2007 Sep; 14(3): 587–599. PubMed Abstract | Publisher Full Text\n\nElbanan MG, Javadi S, Ganeshan D, et al.: Adrenal cortical adenoma: current update, imaging features, atypical findings, and mimics. Abdom Radiol. 2020 Apr; 45(4): 905–916. PubMed Abstract | Publisher Full Text\n\nMahmood E, Anastasopoulou C:Adrenal Adenoma. StatPearls. Treasure Island (FL):StatPearls Publishing; 2022 [cited 2022 Jun 1].Reference Source\n\nSahdev A, Reznek RH, Evanson J, et al.: Imaging in Cushing’s syndrome. Arq. Bras. Endocrinol. Metabol. 2007 Nov; 51(8): 1319–1328. PubMed Abstract | Publisher Full Text\n\nWagner-Bartak NA, Baiomy A, Habra MA, et al.: Cushing syndrome: Diagnostic workup and imaging features, with clinical and pathologic correlation. Am. J. Roentgenol. 2017 Jul; 209(1): 19–32. PubMed Abstract | Publisher Full Text\n\nFan J, Tang J, Fang J, et al.: Ultrasound Imaging in the Diagnosis of Benign and Suspicious Adrenal Lesions. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2014 Nov; 20: 2132–2141. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSt-Amant M: Adrenal washout. Radiology Reference Article. Radiopaedia.org. Radiopaedia. [cited 2022 Jun 1].Reference Source\n\nChoi WJ, Jung TS, Paik WY: Cushing's syndrome in pregnancy with a severe maternal complication: a case report. J. Obstet. Gynaecol. Res. 2011 Feb; 37(2): 163–167. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "143227",
"date": "16 Sep 2022",
"name": "Ranjit Kumar Chaudhary, MD",
"expertise": [
"Reviewer Expertise Radiology and 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\nAbbreviations should be used only if the term appears at least 3-5 times in the main text. Abbreviation of MRI has been used only once, CECT and DEXA have been used only twice.\n\nThe Discussion section has repetition of information provided in the Case section. The second paragraph of the discussion, regarding ultrasonography does not add much information. Instead, there is a need to expand the Discussion section about the role of MRI in lipid poor adenomas, advantages of CT vs MRI. Also, a few sentences about the significance of calcification and the pattern of calcification in adrenal lesion would be informative. Also, the role of NP-59 scintigraphy imaging in functional adenomas needs to be added to the Discussion.\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? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-738
|
https://f1000research.com/articles/11-413/v1
|
12 Apr 22
|
{
"type": "Research Article",
"title": "Personal protective equipment used by obstetricians and obstetric nurses during the COVID-19 pandemic in Mansoura, Egypt",
"authors": [
"Eman Khashaba",
"Abdel-Hady El-Gilany",
"Hend Shalaby",
"Rania El-Kurdy",
"Abdel-Hady El-Gilany",
"Hend Shalaby",
"Rania El-Kurdy"
],
"abstract": "Background: This study was done to describe the pattern of personal protective equipment (PPE) use, associated factors, and adverse events among obstetricians and obstetric nurses in obstetrics & gynecology departments. Methods: A cross sectional study was conducted in Obstetrics & Gynecology departments in three hospitals (physician & nurses n=252) using an online Google form including demographic and occupational health data, type of available personal protective equipment during usual care, CS and emergency labor, infection control measures and hazards of full PPE use. Results Full PPE use was 37.7% during CS and 34.9% during emergency labor. The significant predictors of wearing full PPE during CS were daily work hours > 8 hours and receiving formal training about PPE use. During CS & emergency labor most of HCws used sterile gloves and sterile fluid resistant gowns and surgical mask.to less extent used face shields or tight fitting googles and one tenth (11.8%) only used N95. The most common health effects of full PPE use was sense of heat (79.5%). Conclusion: During the COVID-19 pandemic more vigorous respiratory (N95 mask) and eye protection is required during aerosol-generating procedures. Formal training is an evident predictor for full PPE use.",
"keywords": [
"PPE use- Obstetricians",
"Covid 19",
"Emergency labor",
"Intrapartum practice",
"occupational safety"
],
"content": "Introduction\n\nCOVID-19 is a global pandemic affecting all populations, and subsequent worldwide aggressive measures have been taken to mitigate the spread of the infection (World Health Organization (WHO), 2020). According to a study on COVID-19 characteristics and predicting factors among healthcare providers in a developing country, approximately two-thirds of exposure occurred primarily during healthcare provision. Furthermore, one-fifth of the cases were confirmed COVID-19 cases; the majority of them had mild to moderate symptoms, with only 9.1 percent asymptomatic. Almost all became infected while on duty (97.4 percent). Infected patients (39%) were the most common source of infection, followed by colleagues (22.1%), household contacts (5.2%), and unknown sources (33.8 percent) (El-Sokkary et al., 2021).\n\nObstetricians have worked tirelessly for the past three decades to enhance women’s outcomes through the use of evidence-based medicine. The present COVID-19 epidemic has flooded this standardized method with a deluge of contradicting material, causing uncertainty in the birthing ward about recommended practices. As the infection spreads throughout the population, obstetricians are becoming more concerned (Sichitiu & Desseauve, 2020).\n\nAsymptomatic patients are contagious and thus are at a high risk of nosocomial infection (Rothe et al., 2020). Therefore, strict PPE usage for doctors and midwives is necessary at labor if universal screening is not performed (Umazume et al., 2020).\n\nRegulating and adapting all aspects of infection prevention can be difficult in the unfortunate event of a maternal collapse. The delivery room is overloaded when many personnel simultaneously attempt to resuscitate the collapsed patient, perform a perimortem cesarean delivery, and resuscitate the newborn. The resuscitation team should don full PPE. The most common frequent & serious cross-infection to healthcare workers during outbreaks happened when first responders were not wearing the recommended PPE (Schwartz and Graham, 2020).\n\nWearing N95 respirators can reduce clinical respiratory infections by 73 per 1,000 healthcare workers (HCWs). In laboratory-confirmed bacterial colonization, N95 respirators had a protective effect. N95 respirators were found to be more effective in preventing laboratory-confirmed respiratory viral infections and influenza-like illnesses. As regards protection of HCWs, no direct high-quality evidence was found on whether N95 respirators are better than surgical masks for from SARS-CoV-2 (Iannone et al., 2020).\n\nDespite the protective PPE value, one study reported that physicians who work in the intensive care unit (ICU) and deal with such patients are naturally anxious. They would be unable to drink, eat, or go to the toilet for approximately 6 hours after wearing full PPE as required in the ICU. Taking off PPE after duty hours necessitates training and extreme caution to avoid self-infection (Alsubaie et al., 2019).\n\nWorldwide, reports of PPE scarcity and unavailability are emerging. HCWs and the general press use social media to report on the reusing of PPE or the use of household and self-made items in place of PPE. There is limited evidence on the effectiveness of these practices, but they have occasionally been implemented on the advice of their employers or health organizations (England, 2020; CDC, 2020). It is believed that no previous studies discuss the pattern of PPE utilization among obstetricians and obstetric nurses during the COVID-19 pandemic in our country.\n\nThis study aims to describe the pattern of PPE use, associated factors, and adverse events among healthcare workers in obstetrics and gynecology departments.\n\n\nMethods\n\nObservational cross-sectional study with an analytic component.\n\nThe study was conducted in Obstetrics & Gynecology Departments in three hospitals (one is affiliated to Mansoura University and two affiliated to the Ministry of Health & Population) from August 2020 to June 2021.\n\nThe study included on-duty obstetric physicians and nurses during the COVID-19 pandemic. Participation was voluntary and anonymous.\n\nThe sample size was calculated by openepi.com, an online sample size calculator. It was calculated according to the primary outcome of interest which is the anticipated frequency of full PPE use (30%) based on a pilot study of 100 subjects. The current study has a target population (~954 workers), power of the study (80%), and precision degree (5%). The sample size is 242, and 10% was added to cover nonresponse from online surveys. Thus, the final sample was 266 subjects.\n\nThe current study collected, first, personal communication between one of the authors and study subjects in selected hospitals to encourage participation and explain study objectives. Second, an online questionnaire was distributed (n = 266) through posting Google links to WhatsApp personal accounts or WhatsApp groups of their departments. Snowball sampling was used by asking participants to share the link with other healthcare workers in the obstetrics and gynecology departments in their hospitals. Finally, the response rate was 252 (79.2%).\n\nThe questionnaire included demographic data; occupational history; type of available personal protective equipment during usual care, Cesarean section (CS), and emergency labor; infection control measures related to the use and discard of equipment; and hazards of full PPE during COVID-19 pandemic.\n\nOperational case definition of full PPE use was adapted from the national baseline resources and recommendations of the International Society of Ultrasound in Obstetrics and Gynecology, Royal College of Obstetricians and Gynaecologists, Collège National des Gynécologues et Obstétriciens Français (Poon et al., 2020; Royal College of Obstetricians and Gynaecologists, 2021; Peyronnet et al., 2020). The definition of PPE use in the current study included using gown with long sleeves, gloves (sterile gloves for CS and latex gloves for usual care), respiratory protection (N95 mask or FFP or surgical mask), eye protection (face shield or goggle), and foot protection (overshoes or safety boots).\n\nThe study was approved by the Research Ethics Committee of the Faculty of Medicine of Mansoura University (code number: R/20.7.925). Informed verbal consent was obtained from the administration of hospitals affiliated with the Ministry of Health and Population. All study participants were assured of the confidentiality and anonymity of the data at the start of Google form, and participation was voluntary.\n\nData were analyzed using SPSS, version 23. Categorical variables are presented as numbers and percentages, and the chi-squared test was used for comparison between groups. Crude odds ratios and their 95% confidence intervals (CIs) were calculated. Moreover, quantitative variables are presented as means and standard deviations. Binary stepwise logistic regression analysis was used to determine the independent predictors of full PPE use as the dichotomous outcome variable. Variable found to have statistical significance in bivariate analysis were entered into the logistic regression analysis using a forward-Wald model. Adjusted odds ratios and their 95% CIs were calculated. A p value ≤0.05 was statistically significant\n\n\nResults\n\nThe study included 252 healthcare workers in the obstetrics and gynecology departments. Most of the studied workers were females (76.2%), has a mean age of 32.2 (9.9), and nearly half of them are from urban areas (47.2%). About two-thirds (57%) of the studied HCWs were from Mansoura University Hospitals. More than half were nurses (56.7%) and 37.7% were physicians. The median work duration in years and median daily work hours were 7 years and 8 h, respectively. One-fifth of them (20.2%) reported work in hospital isolations. Most of them reported exposure to COVID-19 patients (75.5%). However, the polymerase chain reaction-confirmed COVID-19 infection was about one-third (27.3%) of the studied HCWs. This percentage is exactly half of those were symptomatic workers (50.9%; data are not tabulated).\n\nFull PPE use was 37.7% and 34.9% during CS and emergency labor, respectively. Full PPE use during CS was significantly associated with longer work hours (≥8 h), working in hospital isolation, and receiving formal training about PPE use (p < 0.05). Moreover, it was associated with working in hospital isolations and receiving formal training during emergency labor (p < 0.05; Table 1) (Khashaba, 2022).\n\n# Missing data from type of hospital 11 subjects, row percent is considered, COR: crude odds ratio.\n\nLogistic regression model for predictors of wearing full PPE during CS revealed that >8 h daily work hours (odds ratio [OR], 2.3; 95% CI, 1.3–3.8) and receiving formal training about PPE use (OR, 2.03; 95% CI, 1.16–3.5) were statistically significant among obstetricians during the COVID-19 pandemic. A significant predictor of full PPE use during emergency labor was receiving formal training only (p < 0.05; OR, 2.2; 95% CI, 1.2–3.9; Table 2).\n\nDuring CS, most healthcare workers used sterile gloves (88%), sterile fluid-resistant gowns (75.6%), and surgical masks (79.2%). About half (52.6%) used face shields. About one-third of them used tight-fitting goggles (34.3), and one-tenth (11.8%) only used N95. Moreover, during emergency labor, most healthcare workers used sterile gloves (81.1), sterile fluid-resistant gowns (70.7), and surgical masks (83.7%). Washing gloves and reusing gowns were reported in 26.8% and 14.8% of HCWs, respectively. Most of the study subjects reported changing gloves between patients (87.7%). More than two-thirds of the subjects followed the correct sequence of donning, removing PPE, and receiving formal training on the use of PPE (67.1%, 66.4%, and 63.5%, respectively; Table 3).\n\nThe most common health effect of full PPE use is a sense of health (79.5%) followed by a sense of thirst and pressure areas (64.7% and 64.3%, respectively; Figure 1). More than two-thirds of affected HCWs (68.3%) had more than two symptoms. Adverse events were not associated with age, gender, job description, duration of work in years, work hours, or work in hospital isolations (p > 0.05; data are not tabulated).\n\n\nDiscussion\n\nThis is the first study on PPE use among healthcare workers in the obstetrics and gynecology departments during the COVID-19 pandemic in Egypt. PPE use is influenced by the workload of HCWs as a matter of hours and patients, baseline resources in these hospitals, and stockpiling of personal equipment and safety training for those HCWs (Tabah et al., 2020).\n\nThe present study showed that full PPE use was 37.7% and 34.9% during CS and emergency deliveries, respectively. Full PPE use during CS was significantly associated with longer work hours (≥8 h) and formal training on PPE use. A different description for the pattern of full PPE per facility was noticed by a nationwide survey in Japan including core facilities and affiliated hospitals of obstetrics and gynecology training programs. Authors reported that full PPE was used by doctors and midwives in 7.1% and 6.8% of facilities, respectively, taking into consideration the different definitions of full PPE use in both studies.\n\nThe present study showed that most healthcare workers used sterile gloves, sterile fluid-resistant gowns, and surgical masks during CS and emergency labor. Fewer HCWs used face shields and goggles. Only one-tenth used N95 due to the absence of baseline resources of these hospitals. Of the HCWs, less than one-third reported washing gloves (26.8%) and reusing gowns (14.8%). Surgical masks and N95 respirators are the most consistent and complete support measures used by healthcare personnel, according to a Cochrane-approved systematic review on physical interventions to reduce respiratory virus transmission undertaken in 2011. N95 respirators are noninferior, according to the highest quality cluster-randomized controlled studies included in this systematic review (Jefferson et al., 2011).\n\nAnother web-based survey conducted by Tabah et al. (2020) and distributed worldwide in April 2020 among ICU HCWs found that more than half of the respondents (52%) reported that at least one piece of the standard PPE is not available, and 30% reported that at least a piece of single-use PPE was being reused or washed as a result of shortages. Most of the available PPEs were designed for single-use and brief duration. Hence, the authors reported that urgent design and manufacture of PPE that can be safely worn and remains effective for extended durations are needed.\n\nSimilarly, the first nationwide Japanese survey reported that N95 masks and goggles or face shields were out of stock in 6.5% and 2.7% of facilities, respectively. In addition, disposable N95 masks and goggles or face shields were reused after resterilization in 12% and 14% of facilities, respectively (Umazume et al., 2020).\n\nMasks and respirators play a role in the protection of health workers according to high level of agreement among key agencies. However, there are current differences between these agencies in terms how and when the different products are used. Different recommendations have been made by the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), and other leading health organizations. For example, the WHO recommends using N95, FFP2, FFP3 standards or equivalent in care settings for COVID-19 patients where aerosol-generating procedures are used and medical masks are used in the absence of aerosol-generating procedures (WHO, 2020). In contrast, the US Centers for Disease Control and Prevention (Center for Disease Control and Prevention, 2020) recommend using respirators during both routine care of COVID-19 patients and high-risk situations.\n\nIn this study, more than two-thirds of the subjects followed the correct sequence of donning and removing PPE and receiving formal training on PPE use (67.1%, 66.4%, and 63.5%, respectively). These results came lower than those observed among ICU workers in a worldwide web-based survey who found that most of the respondents (83%) had formal training in PPE use. This included training at the start of the institution (13%) and within the last two months (60%) due to the COVID-19 pandemic (Tabah et al., 2020).\n\nIn addition, current study results revealed that receiving formal training on PPE use among obstetric physicians and nurses was a significant predictor of full PPE use together during CS and emergency labor. These results are in agreement with an Italian study on a cross-section of physicians which reported that access to adequate information on the use of PPE was associated with a better ability to perform donning and doffing procedures as an example for proper PPE use (Savoia et al., 2020).\n\nThe most common health effects of full PPE use in the current study is a sense of heat (79.5%) followed by a sense of thirst and pressure areas (64.7 and 64.3%, respectively). More than two-thirds of affected HCWs (68.3%) had more than two symptoms. These results were different from the results found in ICU workers during the pandemic where 80% had adverse events including heat (51%), thirst (47%), pressure areas (44%), headaches (28%), inability to use the bathroom (27%), and extreme exhaustion (,20%). They were all associated with longer duration of shifts wearing PPE. However, in the current study, adverse events were not associated with age, gender, job description, duration of work in years, work hours, or work in hospital isolation (Tabah et al., 2020).\n\n\nConclusions\n\nMost obstetricians and obstetric nurses used surgical masks, gloves, gowns, foot protection, and, to a lesser extent, N95, goggles, and face shields. Work hours (>8 h) and formal training were significant predictors for full PPE use.\n\nBased on the findings of the current study, adding N95 or FFP mask and eye protection for safety programs in obstetrics and gynecology departments during aerosol-generating procedures is recommended. Also, reducing long shift work hours that may lead to adverse events due to full PPE use is recommended. Providing simple training videos about different types, proper PPE donning and removal, disinfection of reused equipment, and hand hygiene frequently as part of CME hours of physicians and nurses are required to cope with this emerging threat.\n\nThe evaluation of PPE sufficiency during the COVID-19 pandemic was not assessed in this study. Further research is required to address PPE protective value in infected HCWs compared to non-infected controls.\n\n\nData availability\n\nHarvard Dataverse: Personal protective equipment use by obstetricians and obstetric nurses during the COVID-19 pandemic in Mansoura, Egypt, https://doi.org/10.7910/DVN/XQRZB4 (Khashaba, 2022).\n\nThis project contains the following underlying data:\n\n- D.Eman ppe_obestritians.tab\n\nHarvard Dataverse: Personal protective equipment use by obstetricians and obstetric nurses during the COVID-19 pandemic in Mansoura, Egypt, https://doi.org/10.7910/DVN/XQRZB4 (Khashaba, 2022).\n\nThis project contains the following extended data:\n\n- English Questionnaire PPE.pdf\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "References\n\nAlsubaie S, Hani Temsah M, Al-Eyadhy AA, et al.: Middle East Respiratory Syndrome Coronavirus epidemic impact on healthcare workers’ risk perceptions, work and personal lives. J. Infect. Dev. Ctries. 2019; 13(10): 920–926. Publisher Full Text\n\nCenter for Disease Control and Prevention: Recommended guidance for extended use and limited reuse of N95 filtering facepiece respirators in healthcare settings.2020. [Last accessed 31 August 2021]. Reference Source\n\nEl-Sokkary RH, El-Kholy A, Mohy Eldin S, et al.: Characteristics and predicting factors of corona virus disease-2019 (COVID-19) among healthcare providers in a developing country. PLoS One. 2021; 16(1): e0245672. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEngland PH: Considerations for acute personal protective equipment (PPE) shortages 2020.2020. [Last accessed 31 August 2021]. Reference Source\n\nIannone P, Castellini G, Coclite D, et al.: The need of health policy perspective to protect healthcare workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness. PloS One. 2020; 15(6): e0234025. PubMed Abstract | Publisher Full Text\n\nJefferson T, Del Mar CB, Dooley L, et al.: Physical interventions to interrupt or reduce the spread of respiratory viruses. Cochrane Database Syst. Rev. 2011; 6(7): CD006207. Publisher Full Text\n\nKhashaba E: Personal protective equipment use by obstetricians and obstetric nurses during the COVID-19 pandemic in Mansoura, Egypt.2022. Harvard Dataverse, V1 [Dataset]. Publisher Full Text\n\nKhashaba E: Personal protective equipment use by obstetricians and obstetric nurses during the COVID-19 pandemic in Mansoura, Egypt.2022. Harvard Dataverse, V1 [Extended data]. Publisher Full Text\n\nPeyronnet V, Sibiude J, Deruelle P, et al.: Infection with SARS-CoV-2 in pregnancy. Information and proposed care. CNGOF. Gynecol. Obstet. Fertil. Senol. 2020. published online March 18, 2020. PubMed Abstract | Free Full Text Google Scholar\n\nPoon LC, Yang H, Lee JC, et al.: ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals. Ultrasound Obstet. Gynecol. 2020. published online March 11, 2020. PubMed Abstract | Free Full Text Google Scholar\n\nRothe C, Schunk M, Sothmann P, et al.: Transmission of2019-nCoV infection from an asymptomatic contact in Germany. N. Engl. J. Med. 2020; 382(10): 970–971. PubMed Abstract | Publisher Full Text\n\nRoyal College of Obstetricians and Gynaecologists: Coronavirus (COVID-19) infection and pregnancy.2021. [last accessed 25th September 2021]. Reference Source\n\nSavoia E, Argentini G, Gori D, et al.: Factors associated with access and use of PPE during COVID-19: A cross-sectional study of Italian physicians. PloS One. 2020; 15(10): e0239024. PubMed Abstract | Publisher Full Text\n\nSchwartz DA, Graham AL: Potential maternal and infant outcomes from (Wuhan) coronavirus 2019-nCoV infecting pregnant women: lessons from SARS, MERS, and other human coronavirus infections. Viruses. 2020; 12(2): 194. PubMed Abstract | Publisher Full Text\n\nSichitiu J, Desseauve D: Intrapartum care of women with COVID-19: A practical approach. Eur. J. Obstet. Gynecol. Reprod. Biol. 2020; 249: 94–95. PubMed Abstract | Publisher Full Text\n\nTabah A, Ramanan M, Laupland KB, et al.: Personal protective equipment and intensive care unit healthcare worker safety in the COVID-19 era (PPE-SAFE): an international survey. J. Crit. Care. 2020; 59: 70–75. PubMed Abstract | Publisher Full Text\n\nUmazume T, Miyagi E, Haruyama Y, et al.: Survey on the use of personal protective equipment and COVID-19 testing of pregnant women in Japan. J. Obstet. Gynaecol. Res. 2020; 46(10): 1933–1939. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "134790",
"date": "28 Apr 2022",
"name": "Indranil Saha",
"expertise": [
"Reviewer Expertise Non-communicable diseases",
"Mental Health",
"ageing",
"communicable 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 is pertinent in the level of policy implications. The lessons learnt from the field can be implemented to control the infection. Here I have raised some queries, which need to be clarified from the authors.\nThe methodology section needs to be elaborated further. Since three hospitals were studied, what was the representation of the study population in the final sample itself? Moreover, were the original proportion of doctors and nurses in these 3 hospitals maintained in the final sample?\nIdeally, two sampling frames are ideal, or one sampling frame containing both doctors/nurses.\nTable 1: Subheading is absent. Please insert.\n\nWhy was the snowball sampling technique used in this study? It is generally used to reach hard to reach study subjects. That is not the case in this study.\n\nMoreover, which type of snowball sampling technique was used - Linear/Exponential, Non-discriminative/Exponential discriminative?\n\nThe output of the logistic regression was also incomplete. What about the model fitness? The variation of dependent variables explained from independent variables? What proportion can be explained from the model? Please mention as running text in the results section.\n\nThe final model was a multivariable logistic binary regression model. Please mention this.\n\nI would recommend replacing the term 'study subjects' with 'study participants'.\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?\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": "8178",
"date": "03 May 2022",
"name": "Eman Khashaba",
"role": "Author Response",
"response": "Response to reviewer’s comments Thanks a lot for the valuable and informative comments. The methodology section needs to be elaborated further. Since three hospitals were studied, what was the representation of the study population in the final sample itself? Moreover, were the original proportion of doctors and nurses in these 3 hospitals maintained in the final sample? Reply: The actual number of doctors and nurses in each hospital is not of concern as we aimed to complete the sample size calculated. Also the number on duty is not fixed due to frequent sick leaves, and many of them are not regular users of mass media to complete questionnaire in due time. In general, the number of the nurses is more than the doctors in original sample. The proportion of each hospital was not kept in the final sample. This can be added TO STUDY LIMITATIONS. Ideally, two sampling frames are ideal, or one sampling frame containing both doctors/nurses. Reply: For our study, it is one sampling frame containing both doctors/nurses Table 1: Subheading is absent. Please insert. Reply: Yes I agree we can add \"associated factors\". Why was the snowball sampling technique used in this study? It is generally used to reach hard to reach study subjects. That is not the case in this study. Reply: The questionnaire was distributed on line with a Google form through WhatsApp groups of the target population. Direct interview or self-reported questionnaires were not feasible due to being in a lockdown as a result of the COVID-19 pandemic, and strict hospitals policies of minimizing personal contacts with health care workers. Moreover, which type of snowball sampling technique was used - Linear/Exponential, Non-discriminative/Exponential discriminative? Reply: The type of snowball sampling technique is Exponential non discriminative (I agree to add this type in the published manuscript).The first subject recruited to the sample provides multiple referrals for participation in research. The output of the logistic regression was also incomplete. What about the model fitness? The variation of dependent variables explained from independent variables? What proportion can be explained from the model? Please mention as running text in the results section. The final model was a multivariable logistic binary regression model. Please mention this. Reply: Model fitness by Hosmer and Lemeshow test was non-significant ( p value>0.05) which indicates Good fit for model. Nagelkerke R2 was less than 1 for both models. For the comment on multivariable logistic regression, I agree to modify this comment in results section. The necessary changes will be as follows: Multivariable logistic regression model for predictors of wearing full PPE during CS revealed that >8 h daily work hours (odds ratio [OR], 2.3; 95% CI, 1.3–3.8) and receiving formal training about PPE use (OR, 2.03; 95% CI, 1.16–3.5) were statistically significant among obstetricians during the COVID-19 pandemic. A significant predictor of full PPE use during emergency labor was receiving formal training only (p < 0.05; OR, 2.2; 95% CI, 1.2–3.9;). The regression model predicted 64.3% & 65.1% of variation in full PPE use during CS and emergency labor (dependent variable). I would recommend replacing the term 'study subjects' with 'study participants'. Reply: I agree with you it can be replaced in the published manuscript &table headings)."
}
]
},
{
"id": "136541",
"date": "28 Jun 2022",
"name": "Ibrahim Ali Kabbash",
"expertise": [
"Reviewer Expertise epidemiology of infectious diseases",
"HIV/AIDS",
"reproductive 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 articles discusses the issue of protective equipment use among health care workers. The lessons learnt from the field can be implemented to control the infection. Here I would like to raise some queries, which need to be clarified from the authors:\nThe sampling method technique was referred to as snowballing by the authors; however, it is actually a convenient sample as it does not meet the criteria for snowballing.\n\nHow did the authors identify the links of social media they used for recruiting participants to ensure representativeness of their sample to the target population?\n\nHow did the authors motivate the participants to share the data collection, and what was the duration to reach the desired sample size?\nOverall the manuscript is well written. The authors have responded satisfactorily to the comments provided the other reviewer.\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": "8441",
"date": "30 Jun 2022",
"name": "Eman Khashaba",
"role": "Author Response",
"response": "Response to reviewer’s comments Thanks a lot for your valuable and accurate comments The sampling method technique was referred to as snowballing by the authors; however, it is actually a convenient sample as it does not meet the criteria for snowballing. Reply: Thanks for your comment. Actually, snowball sampling technique was used in this study. The questionnaire was distributed as on line Google form through what app groups of target population. Direct interview or self-reported questionnaires were not feasible due to lockdown of COVID-19 and strict hospitals policies of minimizing personal contacts with health care workers. The first subject was recruited to the sample then he provides multiple referrals for research. Further clarification of sampling methods was added based on the comments of the first reviewer. How did the authors identify the links of social media they used for recruiting participants to ensure representativeness of their sample to the target population? Reply: Through WhatsApp groups of related departments whenever available or from one to his colleagues in the same department. How did the authors motivate the participants to share the data collection, and what was the duration to reach the desired sample size? Reply: In general, participation was voluntary and the response rate was 252 (79.2%). The personal protection is crucial part in occupational health & safety of HCws during such pandemic. This research stressed on the value of personal protection among obstetricians & nurses. Duration already present in the manuscript from August 2020 to June 2021 About 1 year."
}
]
}
] | 1
|
https://f1000research.com/articles/11-413
|
https://f1000research.com/articles/10-1276/v1
|
14 Dec 21
|
{
"type": "Research Article",
"title": "“Exclusivity” and quantifier float in bakari",
"authors": [
"Takashi Otsuka",
"Ryo Shirakawa",
"Osamu Hashimoto",
"Yoshiko Numata"
],
"abstract": "This paper presents a descriptive study that analyzes the semantic meaning of Toritate focus particle bakari. Previous studies reported that, although bakari expresses exclusivity, it is characterized by the fact that it permits non-applicable cases, thereby drawing the conclusion that the meaning of bakari is not exclusivity. This paper argues that bakari does indeed denote “exclusivity” as bakari is supported by the phenomenon that non-applicable cases are unacceptable when bakari co-occurs with floating quantifiers. Considering existing research on this subject, the following was observed. Even though the subjective set, as established by the speaker’s past experiences to interpret the meaning of bakari, may not be consistent with the real world, the number of events that form the said set match the number of real-world events when bakari co-occurs with floating quantifiers due to the characteristics of floating quantifiers. In such cases, bakari does not permit non-applicable cases. The interpretation that permits non-applicable cases applies to situations where the set established by the speaker is fixed at a narrower range than the real world, and the non-applicable cases exist outside the set. We thus conclude that bakari denotes “exclusivity” that does not permit non-applicable cases.\n本稿は，とりたて詞「ばかり」の意味を再考する記述的研究である。従来とりたて詞「ばかり」は限定を表す一方で非該当例を許容する特徴を持つことが指摘されてきた。このため「ばかり」の意味を限定ではないと示唆・主張する研究も見られる。これに対し，本稿では，「ばかり」が遊離数量詞と共起する場合に非該当例を許容しない現象の分析から，「ばかり」の意味を「限定」とすべきであると主張する。本稿では，先行研究を踏まえ，以下のことを明らかにする。「ばかり」の意味解釈のために話者が認知的経験記憶により設定する主観的な集合は，必ずしも現実世界と一致しない場合があるが，遊離数量詞の特徴により，これと「ばかり」が共起する場合は，当該の集合を形成する事態の数量が，現実世界の事態の数量と常に一致する解釈となる。この際，「ばかり」は非該当例を許容しない。従来指摘された非該当例が許容される解釈は，話者が設定する集合が現実世界より狭い範囲で設定され，当該集合の外部に非該当例が存在する場合の解釈と考えるべきである。このことから「ばかり」の意味は非該当例を許容しない「限定」と考えるのが妥当である。",
"keywords": [
"とりたて詞",
"ばかり",
"遊離数量詞",
"限定",
"Toritate focus particle",
"bakari",
"exclusivity",
"floating quantifiers"
],
"content": "1. はじめに\n\nとりたて詞「ばかり」は，「だけ」「しか」と同様に限定を表すとされるが，一見するとその位置づけに検討の余地があることを示すような特徴を持つ。それは，非該当例1を許容するという特徴である。例えば，次の文において，白いシャツ以外（例えば赤いシャツ）も購入している，あるいは三毛猫以外（例えば黒猫）も集まっている場合，「だけ」や「しか」を含む (1ab) (2ab) は成立しないのに対し，「ばかり」を含む (1c) (2c) は成立する。\n\n(1) 【白いシャツを 900 枚，赤いシャツを 100 枚購入した場合】\n\na. # 白いシャツだけを購入した。2\n\nb. # 白いシャツしか購入しなかった。\n\nc. 白いシャツばかりを購入した。\n\n(2) 【三毛猫が 40 匹，黒猫が 10 匹集まった場合】\n\na. # 三毛猫だけが集まった。\n\nb. # 三毛猫しか集まらなかった。\n\nc. 三毛猫ばかりが集まった。\n\nこれは，「だけ」「しか」は非該当例を許容しないのに対し，「ばかり」は非該当例を許容するということを示している。「ばかり」がこうした特徴を持つことは既に指摘されており，それを踏まえて「ばかり」は限定を表すものではないと指摘する研究もある。\n\nしかし，「ばかり」は環境を問わず非該当例を許容するわけではない。例えば，(1c) (2c) に遊離数量詞3を加えた次の文は，(1) (2) と同様の場合には成立しない。\n\n(3) 【白いシャツを 900 枚，赤いシャツを 100 枚購入した場合】\n\n# 白いシャツばかりを 1000 枚購入した。\n\n(4) 【三毛猫が 40 匹，黒猫が 10 匹集まった場合】\n\n# 三毛猫ばかりが 50 匹 集まった。\n\n(3) (4) は作例であるが、コーパスにおいても「ばかり」に数量詞が後続した文が存在し、これらについての母語話者の内省判断において (3) (4) と同様に非該当例が許容されないことを確認している4。このことは，「ばかり」は遊離数量詞と共起する場合には非該当例を許容しないということを示している5。本稿は，現代語を対象とした記述言語学的研究の一環で，コーパスのデータと母語話者の内省に基づき，この現象について，先行研究の指摘から導き出される遊離数量詞の特徴と関連づけて考察し，その要因を明らかにするものである。さらに，これが「ばかり」の意味について示唆的な現象であることを指摘し，その意味について考察する。分析にあたっては，注 4 ほかで触れたとおり，「現代日本語書き言葉均衡コーパス」(BCCWJ) において本稿で扱う遊離数量詞と共起する「ばかり」に該当する用例，および作例の意味解釈について，日本語母語話者である筆者らの言語直観で判断する。本稿の主張は次の通りである。\n\n(5) a. 遊離数量詞は，事態の数量を表す（数量を事態の数量として表し直す）。\n\nb. 「ばかり」は，遊離数量詞が共起することで，話者による主観的な集合を形成する事態の数量が，現実世界の事態の数量と一致する解釈となるため，結果的に非該当例が存在する可能性を排除する。\n\n(6) とりたて詞「ばかり」の意味は限定であり，非該当例は「ばかり」が問題にする集合6の外部においてのみその存在が許容され得る。\n\n\n2. 先行研究の指摘と本稿の主眼\n\n「ばかり」が非該当例を許容することは，従来様々な研究において指摘されてきた（菊地 1983； 西村 1994； 定延 2001； 澤田 2007； 日本語記述文法研究会編 2009； 佐藤 2017 など）。以下では，その要因についても言及している定延 (2001) と佐藤 (2017) を取り上げ，それぞれの指摘を概観した上で本稿の主眼とするところを明確にする。\n\nまず，定延 (2001) の指摘を概観する。定延 (2001) は，「探索」という概念を用いて「ばかり」について考察している。「探索」とは「認知領域の拡大行動」（定延 2001: 118）であるが，定延 (2001) は，「ばかり」にはその「探索」が「二重に関わってくる」(定延 2001: 135) と指摘している。例えば，「ばかり」を含む次の (7) の文の場合，初めに (8a) のような，次に (8b) のような「探索」が行われるとされる。\n\n(7) この人物が食べたのはミカンばかりだ （定延 2001: 129，下線は筆者）\n\n(8) a. 【探索①】問題の人物が食べたモノを探索領域とし，[品種は何か]を探索課題とする探索7 （定延 2001: 129，【 】内は筆者）\n\nb. 【探索②】探索の集合を探索領域としてそれらがどういう探索なのか，〔筆者略〕1 探索ずつスキャニング探索 （定延 2001: 129，下線と【 】内は筆者）\n\nその上で，(7) の文はこの「二重」の「探索」のうち，(8b) の「探索」によって次のような結果が得られたことを表現しているとされる。\n\n(9) 【探索②の結果】すべて［ミカン］という情報を得た探索だ （定延 2001: 129，下線と【 】内は筆者）\n\n定延 (2001) の議論において重要となるのは，「ばかり」を含む文が (8b) の「探索」の結果を表現するという点である。(8a)と (8b) の「探索」は，前者が「世界のありさま」を「探索領域」とするのに対し，後者は「世界探索の集合のありさま」を「探索領域」とするという点で異なるが（定延 2001: 134），定延 (2001) によれば，後者の場合は非該当例の有無は大きな問題にならないとされる。定延 (2001)は，次の (10) の例を基に (11) のように述べている。\n\n(10) 先週はうどんばかり食べた （定延 2001: 134，下線は筆者）\n\n(11) 「先週食べたものはうどんがすべてなのか，それともうどんは大部分にすぎず他に何か食べたのか」という問題は，世界のありさまを表現する場合は大きな問題で，仮にうどんが大部分にすぎないにもかかわらず「うどんがすべて」と表現すれば誤りになる。しかし，世界探索の集合がどのような集合であるかを表現する際には，世界じたいについては，多少印象的・感覚的になっても問題ではなく，「うどんをやたら多く見出す世界探索の集合」であることに変わりはないとしてしまえる原注20。 (定延 2001: 134，下線は筆者)\n\nこれに対し，佐藤 (2017) は「探索の領域が〔筆者略〕探索という行動の集合である場合に，多少は印象的・感覚的であってもよいという説明に，妥当性はあるのだろうか」（佐藤 2017: 7）と疑問を呈し，「ばかり」が非該当例を許容する要因について，定延 (2001) とは異なる議論を展開している。\n\n佐藤 (2017) は，「認識的際立ち性」という観点から「ばかり」の振る舞いを説明している。佐藤 (2017) によれば，「認識的際立ち性」とは次のようなものである。\n\n(12) ここ〔筆者注：佐藤 (2017)〕で言う「認識的際立ち性」とは，当該の主体にとって何らかの意味において容易に捉えられるもの，捉えずにはいられない際立ちをもつものである。 （佐藤 2017: 9）\n\n佐藤 (2017) は，集合を問題にする言語形式には，予め確立されている客観的な集合だけでなく，話者の経験に根差して形成された主観的な集合に関与するものがあると述べ（佐藤 2017: 8），その一例として「ばかり」を挙げている。また，後者の集合が形成されるに当たっては様々な動機があり得るとしており（佐藤 2017: 4-5），特に「ばかり」が関与する集合が形成される動機となるのが「認識的際立ち性」であると指摘している（佐藤 2017: 9）。\n\n佐藤 (2017) によれば，「ばかり」が用いられるに当たっては，「認識的際立ち性という動機づけに支えられ，その特徴を有する事態のみを成員とする経験記憶の集合が形成される」（佐藤 2017: 9）とされる。例えば，佐藤 (2017) は次の (13) の文が発話されるに至る過程を (14) のようにまとめている。\n\n(13) あなた，学校に遅刻してばかりでどうするの （佐藤 2017: 3，傍点を下線に改変）\n\n(14) 「ばかり」の集合形成の事例②\n\na. 母親が娘の登校時間を気にしながら日常生活を送る。\n\nb. 週 2 回のペースで娘の学校への遅刻という認識的際立ち性を有する事態を知覚する。\n\nc. 「娘の遅刻」という認識的際立ち性を有する事態のみから成る経験記憶の集合が形成され，「遅刻してばかり」という認識にいたる。（佐藤 2017: 10，下線は筆者）\n\n仮に，週 6 日制の学校に「週 2 回のペース」で遅刻した場合，週 4 回は遅刻していないことになり，(13) の文においてはそれが非該当例となる。しかし，「認識的際立ち性」という特徴を持つもので構成される主観的な集合には「遅刻」のみが含まれる，言い換えれば「非遅刻」は含まれないため8，(13) の文が問題なく成立するとされるのである。\n\n以上，定延 (2001) と佐藤 (2017) の議論を概観した。いずれにおいても「ばかり」が非該当例を許容する要因について興味深い指摘が見られるが，佐藤 (2017) も述べているように，定延 (2001) の指摘には検討の余地がある。これを踏まえ，本稿では「ばかり」が非該当例を許容する要因について，佐藤 (2017) の考えを採る9。\n\n一方で，「ばかり」と非該当例の関係については，従来考察の対象とされていない問題がある。それは，「ばかり」が非該当例を許容しない環境があるということである。例えば，次の文はいずれも「ばかり」を含むため，先行研究に倣えば非該当例（「赤いシャツ」「黒猫」）が存在していても成立することが予測されるが，(15b) (16b) については成立しない。\n\n(15) 【白いシャツを 900 枚，赤いシャツを 100 枚購入した場合】\n\na. 白いシャツばかりを購入した。 (=(1a))\n\nb. # 白いシャツばかりを1000 枚購入した。 (=(3))\n\n(16) 【三毛猫が 40 匹，黒猫が 10 匹集まった場合】\n\na. 三毛猫ばかりが集まった。 (=(2a))\n\nb. # 三毛猫ばかりが 50 匹集まった。 (=(4))\n\n(15a) (16a) と (15b) (16b) の相違点は，後者には数量詞が生起しているという点である。これは，一見すると「ばかり」が数量詞と共起する場合は非該当例が許容されないということを示しているように見える。ただし，「ばかり」と数量詞が共起していても，非該当例が許容される場合もある。例えば，次の文ではいずれも「ばかり」と数量詞が共起しているが，非該当例（「男性」）が存在する場合，(17a) は成立しないのに対し，(17b) は成立する。\n\n(17) 【女性を 400 人，男性を 100 人招待した場合】\n\na. # 女性ばかり 500人招待した。\n\nb. 招待した 500 人は女性ばかりだ。\n\nつまり，「ばかり」と数量詞が共起していても，(15b) (16b) (17a) は非該当例を許容しないのに対し，(17b)はそれを許容するということになるが，これらは数量詞のタイプが異なる。先行研究では，(15b) (16b)(17a) の数量詞は，(17b) の数量詞に対して遊離数量詞と呼ばれて区別されている。この点を踏まえると，(15) (16) (17) は次のことを示していると言える。\n\n(18) 「ばかり」は非該当例を許容し得るが，遊離数量詞と共起する場合はそれを許容しない。\n\n前述の通り，先行研究では「ばかり」が非該当例を許容することやその要因については指摘されてきたが，「ばかり」がそれを許容しない環境があることについて指摘・考察した研究は管見の限り存在しない。従って，本稿ではこの (18) の現象の解明を主眼とし，その要因を明らかにする（3節）。さらに，この現象を踏まえて「ばかり」の意味についても考察する（4節）。\n\n\n3. 「ばかり」と遊離数量詞\n\nまず，(18) の現象の要因について考察する。以下では，この現象を説明するに当たって重要となる「ばかり」の特徴，及び遊離数量詞の特徴について確認し （3.1 節，3.2 節），それらを踏まえてこの現象の要因を明らかにする（3.3 節）。\n\nまず，佐藤 (2017) の議論の中で特に (18) の現象と密接に関わると考えられる指摘を確認する。前述の通り，佐藤 (2017) は「ばかり」と「認識的際立ち性」の関わりを指摘しているが（2.2 節），特に「ばかり」が問題にする集合について次のように述べている。\n\n(19) 認識的際立ち性という動機づけに支えられ，その特徴を有する事態のみを成員とする経験記憶の集合が形成される。 （佐藤 2017: 9，下線は筆者）\n\nまた，佐藤 (2017) は「認識的際立ち性」が生じる要因の 1 つとして次の (20a) を挙げ，これについて (20b) のように述べている。\n\n(20) a. 知覚経験される事態の数が多い。最低でも複数である。 （佐藤 2017: 11，下線は筆者）\n\nb. 一度の失敗しか経験されていない場合，「失敗ばかり」とは言えないだろう。したがって，この要因は「ばかり」が使われるための必要条件である原注6。 （佐藤 2017: 11，下線は筆者）\n\nこのように，佐藤 (2017) は「ばかり」が問題にする集合に含まれるのは「事態」であり，その数が「多い」ことが「ばかり」が用いられる要件であると指摘している。このことは次のようにまとめられる。\n\n(21) a. 「ばかり」は事態を問題にする。10\n\nb. 「ばかり」は事態の数が多いと認識されれば用いられ得る。\n\n次に，この (21) に注目しつつ，「ばかり」が非該当例を許容する背景について改めて検討する。前述の通り，次の (22) の文は (23) の状況において問題なく成立する。\n\n(22) 白いシャツばかりを購入した。\n\n(23) 白いシャツを 900 枚，赤いシャツを 100 枚，計 1000 枚のシャツを購入した。\n\nこのとき，「ばかり」が事態を問題にするということ ((21a)) を踏まえると，(22) の文が成立するに当たり，(23) の状況は次のように捉え直されていると考えられる。\n\n(23’) 「白いシャツを購入する」という事態が 900，「赤いシャツを購入する」という事態が 100，計1000 の「購入する」という事態が生じた。\n\nつまり，(22) の文が成立するということは，事態の総数は 1000 であるものの，「ばかり」はそのうちの 900 の事態 のみを問題にすることが可能ということになる。このとき，(22) では「白いシャツを購入する」という事態の数が多いということは間接的に表現され得るが11，その具体的な数(総数に一致する数なのか，あるいはそれに近い数なのか)には関与していない。つまり，「ばかり」は次のような特徴を持つのであり，これが背景となって非該当例が許容されることになると言える。\n\n(24) 「ばかり」は，（事態の総数が文脈上示されている場合でも）問題にする事態の具体的な数には関与しない。\n\n次に，遊離数量詞に関する先行研究の指摘を見る。矢澤 (1985) は，本稿での遊離数量詞に当たる「NCQ型」の数量詞12について，「何らかの形で動詞の表す動作・作用に関連した数量を表しているのではないか」（矢澤 1985: 104）と述べ13，「NCQ型」の数量詞とそれ以外の数量詞の相違点について次のように指摘している。\n\n(25) NCQ型の数量詞〔筆者注:本稿での遊離数量詞〕は，述部に直接関わり，その述部の表す動作・作用の上で先行名詞句と間接的な意味的関係を結ぶのに対し，NCQ型以外の型の数量詞は，先行名詞句に直接関わり，先行名詞句が述部と関わることによって，数量詞と述部との間接的な関係ができると考えるのである。 （矢澤 1985: 105-106，下線は筆者）\n\nこの指摘は，遊離数量詞が事態と密接に関わることを示している。具体的には，遊離数量詞は次のような特徴を持つと言える。\n\n(26) 遊離数量詞は，事態の数量を表す（数量を事態の数量として表し直す）。 (=(5a))\n\n以上の点を踏まえ，「ばかり」が遊離数量詞と共起する場合に例外を許容しなくなる現象の要因について検討する。次の例を見られたい。\n\n(27) 白いシャツばかりを1000 枚購入した。 (=(3))\n\n前述の通り，「ばかり」はその集合の数量には関与しないが ((24))，遊離数量詞は明示的にその事態の数を表す。(27) の文で言えば，「1000 枚」という遊離数量詞が生起することで，次のようなことが表される。\n\n(28) 問題になる「白いシャツを購入する」という事態の数は 1000 であった。\n\nこれにより，「ばかり」が問題にする「白いシャツを購入する」という事態の数が 1000 にいわば固定され，結果的にその中に他の事態（「赤いシャツを購入する」など）が存在する余地がなくなるのである。つまり，「ばかり」が遊離数量詞と共起する場合に非該当例を許容しない要因は次のようにまとめられる。\n\n(29) 「ばかり」は，遊離数量詞が共起することで，話者による主観的な集合を形成する事態の数量14が，現実世界の事態の数量と一致する解釈となるため，結果的に非該当例が存在する可能性を排除する。 (=(5))\n\n\n4. 「ばかり」の意味について\n\n次に，「ばかり」の意味について考察する。以下では，まず，「ばかり」が非該当例を許容する現象に触れる先行研究のうち，「ばかり」の意味にも言及するものの指摘を概観し，併せてその問題点を明らかにする （4.1 節）。その上で，「ばかり」の意味はあくまで限定と捉えるべきであると主張する （4.2 節）。\n\nとりたて詞「ばかり」の意味については既に様々な先行研究において考察されており，多くの場合，「ばかり」は限定を表すとされる（丹羽 1992； 益岡・田窪 1992； 中西 1995； 沼田 2009 など）。しかし，特に「ばかり」が非該当例を許容する現象に触れる先行研究においては必ずしもそうではない。以下では，「ばかり」が非該当例を許容する現象に触れつつ「ばかり」の意味についても言及している日本語記述文法研究会編 (2009) と澤田 (2007) を取り上げてその指摘を概観し，併せてその問題点を明らかにする。\n\n4.1.1 日本語記述文法研究会編 (2009) の指摘とその問題点\n\nまず，日本語記述文法研究会編 (2009) は次のように述べ，「ばかり」は限定を表すと主張している。\n\n(30) 「ばかり」は，とりたてた要素が唯一のものであることを示し，ほかのものを排除するという限定の意味を表す。（日本語記述文法研究会編 2009: 61，下線は筆者）\n\nまた，日本語記述文法研究会編 (2009) は次の (31) の文について (32) のように述べ，「ばかり」が非該当例を許容することに触れている。\n\n(31) 佐藤さんは来客にコーヒーばかり出した。 （日本語記述文法研究会編 2009: 62）\n\n(32) コーヒー以外のものも出した可能性は完全には否定されない。 （日本語記述文法研究会編 2009: 62）\n\n「ばかり」が限定を表すことと非該当例を許容することには一見すると理論的矛盾がある。しかし，日本語記述文法研究会編 (2009) によれば，「ばかり」が表す限定には次のような2つの下位分類があり，非該当例が許容される (31) の文では，このうち (33b) のような「限定の仕方」が採られているとされる。\n\n(33) a. とりたてた要素が唯一のものであることを示し，ほかのものを排除するという限定の仕方 （日本語記述文法研究会編 2009: 62）\n\nb. とりたてた要素が関わる事態が何度も繰り返されることや，とりたてた要素が重なって多数にのぼることを表すという限定の仕方 （日本語記述文法研究会編 2009: 62，下線は筆者）\n\n日本語記述文法研究会編 (2009) の指摘は，非該当例の許容という現象について限定という意味の下で説明しようと試みている点で注目に値する。しかし，その説明には不十分な点がある。確かに，(31) の文は「コーヒーを出す」という事態が複数回生じていなければ成立せず，その点で (33b) において述べられているように「何度も繰り返されること」「多数にのぼること」を表していると言える。しかし，その (33b) を (30) の下位分類としていることには問題がある。具体的に言えば，「何度も繰り返されること」「多数にのぼること」((33b))と「唯一のものである」「ほかのものを排除する」((30)) ということには隔たりがある。それにもかかわらず，日本語記述文法研究会編 (2009) ではその点について特段の言及がなされていないのである。この点に鑑みれば，日本語記述文法研究会編 (2009) の説明は十分とは言えない15。\n\n4.1.2 澤田 (2007) の指摘とその問題点\n\nこれに対し，澤田 (2007) は「ばかり」の（主たる）意味は限定ではないと主張している。澤田 (2007) は，菊地 (1983) が挙げる次の(34)の文について (35) のように述べている。\n\n(34) この一週間そばバカリ食べたよ。 （菊地 1983: 58，下線は筆者）\n\n(35) 「ばかり」を使用する第一の目的は，「毎日そばを食べた」とカテゴリーを限定するというより，話し手が「この一週間を思い起こせば，よくそばを食べた，それは通常の一週間より多すぎた」ということを伝える方が重要であり，その二次的な効果として明示された要素に対比される要素(明示された要素以外にその現象を成り立たせる可能性のある要素)がその観察された中に少なかった。または，なかったと伝えることになる。派生的に，限定的解釈がでてくるのである。 （澤田 2007: 118-119，下線は筆者）\n\nこのように，澤田 (2007) は，「ばかり」は「通常より多い」ということを表すのであり，限定(的解釈)はそこから「派生」する「二次的な効果」であると捉えている。つまり，限定は「ばかり」の意味ではなく，言わば語用論的効果であるとしているのである。\n\n澤田 (2007) の指摘において注目されるのは，「ばかり」が問題にする集合と非該当例の関係である。(35) では，「ばかり」は場合によっては「明示された要素に対比される要素」が「観察された中に少なかった」ということを伝え得るとされている。これは，「ばかり」が問題にする集合に「明示された要素に対比される要素」が含まれていても構わないということを意味する。澤田 (2007) の言う「明示された要素に対比される要素」が本稿での非該当例に当たると推察されることを踏まえると，澤田 (2007) は次のことを示唆していると言える。\n\n(36) 「ばかり」は，問題にする集合に非該当例が含まれていても用いられ得る。16\n\nしかし，「ばかり」と遊離数量詞が共起した場合の現象を踏まえれば，この (36) は否定せざるを得ない。本稿では，3 節において，非該当例を許容し得る「ばかり」が遊離数量詞と共起した場合にそれを許容しなくなるという現象について考察した。その要因を検討する過程で，遊離数量詞が共起することで，話者による主観的な集合を形成する事態の数量が，現実世界の事態の数量と一致する解釈となるということを指摘したが ((29))，これは次のことを意味する。\n\n(37) 遊離数量詞の共起によって，「ばかり」が問題にする集合（に含まれる事態の数）が遊離数量詞によって示される現実世界の集合と同一の集合に固定される。\n\n仮に，澤田 (2007) が示唆するように，「ばかり」は問題にする集合に非該当例が含まれていても用いられ得るとすれば，遊離数量詞によって「ばかり」が問題にする集合（に含まれる事態の数）が固定された次の文も，場合によっては「1000」の「購入する」という事態の中に非該当例（「赤いシャツを購入する」）が含まれていても成立するということになるが，次の文がそうした状況下では成立しないことは前述の通りである。\n\n(38) 【白いシャツを 900 枚，赤いシャツを 100 枚購入した場合】\n\n# 白いシャツばかりを1000 枚購入した。 (=(3))\n\n以上，「ばかり」が非該当例を許容する現象に触れる先行研究における「ばかり」の意味に関する指摘を確認したが，いずれにおいても問題があると言える。これに対し，本稿では「ばかり」の意味について次のように主張する。\n\n(39) とりたて詞「ばかり」の意味は限定であり，非該当例は「ばかり」が問題にする主観的な集合の外部においてのみその存在が許容され得る。 (=(6))\n\nまず，「ばかり」は限定，即ちとりたてた要素（事態）が唯一存在し，他のものを排除する17ということを表すと主張する。前述の通り，「ばかり」の意味が限定でないとすると，遊離数量詞と共起した場合に非該当例が許容されない現象を説明することができないためである。\n\nただし，その限定は「認識的際立ち性」などに起因して形成される主観的な集合の内部に対してのものである。従って，現実世界において客観的には非該当例が存在していても，それが（「認識的際立ち性」を持たないが故に）「ばかり」が問題にする集合に含まれなければ，「ばかり」は用いられ得るのである。\n\n\n5. おわりに\n\n本稿では，「ばかり」が遊離数量詞と共起する場合に非該当例が許容されない現象を取り上げ，その現象が，「ばかり」が問題にする集合に含まれる事態の数量が遊離数量詞によって現実世界の事態の数量と一致する解釈になることに起因することを明らかにした。また，これを通して，とりたて詞「ばかり」の意味は限定であると主張した。この主張は多くの先行研究に見られるものであるが，「ばかり」が非該当例を許容することを認めた上でそのように主張する研究はほとんど存在せず18，その点で，「ばかり」は限定を表すと考えざるを得ない現象にも触れつつその主張を明示したことに意義があると考える。\n\nところで，本稿では，佐藤 (2017) の指摘を踏まえ，「ばかり」が問題にするのは現実世界を反映する予め確立された客観的な集合ではなく，自己の経験に根差して形成される主観的な集合であると捉えることにより，限定という意味の下で非該当例の許容という現象が説明されると論じた。これは，「ばかり」の意味記述においては，その意味の対象となる集合(以下，対象集合)が重要となることを示しているが，この対象集合という視点の有用性は，「ばかり」の意味記述に限られるものではないと考える。まず挙げられるのは，他のとりたて詞の意味記述に当たっての有用性である。管見の限り，従来のとりたて詞研究で は，とりたて詞各語について対象集合が詳細に議論されることや，それぞれの対象集合の設定のされ方の異同を本格的に取り上げた考察はほとんど行われていない。他のとりたて詞についても対象集合に関する考察を深めることで，個別のとりたて詞の意味やとりたて詞全体の意味体系の記述の精緻化が可能となろう。また，とりたて詞に留まらず，非該当例を許容しないとされる諸形式の意味記述に当たってもこの視点が有用であると考えられる。 例えば，全称量化詞などと呼ばれる「全部」「みんな」，さらに「常に」「いつも」などは，基本的には非該当例を許容しないとされるが，「みんな」や「いつも」など一部の形式については非該当例を許容し得る。このこと自体は既に佐藤 (2017) で指摘されており，意味的な観点からその要因を明らかにしようとする研究も存在する（大塚 2020，2021）。しかし，対象集合に注目して再検討することで，先行研究において未だ解明されていない点について説明を与えることが可能になると考える。これらについては稿を改めて論じることとする。\n\n\nデータ可用性\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。例外として，注4で示したデータ絞り込みの結果，判断を加えた42例の提示は，国立国語研究所による現代日本語書き言葉均衡コーパス(BCCWJ)「中納言」より入手できる。同コーパス利用には登録が必要だが，他の研究者も著者と同じようにデータにアクセスできる。登録方法については https://chunagon.ninjal.ac.jp/auth/login?service=https%3A%2F%2Fchunagon.ninjal.ac.jp%2Fj_spring_cas_security_check を参照されたい。",
"appendix": "謝辞\n\n本稿は，国際研究集会「次世代の日本研究―国際的協働研究と研究交流―」（2021年3月21日，オンライン）における口頭発表の内容に加筆・修正を施したものである。発表に際し，貴重なご意見を賜った方々に感謝申し上げる。\n\n\n参考文献\n\n大塚 貴史: 「「みんな」に関する諸問題の検討と考察」『筑波日本語研究』2020; 24，pp. 67–81，筑波大学大学院博士課程人文社会系日本語学研究室.\n\n大塚 貴史: 「「いつも」と「常に」の意味」『筑波日本語研究』2021; 25，pp. 36–56，筑波大学大学院博士課程人文社会系日本語学研究室.\n\n奥津 敬一郎: 「数量詞移動再論」『人文学報』1983; 160，pp.1–24，東京都立大学人文学部.\n\n加藤 重広: 「日本語の連体数量詞と遊離数量詞の分析」『富山大学人文学部紀要』1997; 26，pp. 31–64，富山大学人文学部.\n\n菊地 康人: 「バカリ・ダケ」国広哲弥編『意味分析』1983; pp.57–59，東京大学文学部.\n\n定延 利之: 「探索と現代日本語の「だけ」「しか」「ばかり」」『日本語文法』2001; 1-1，pp. 111–136.\n\n佐藤 琢三: 「⟨全該当⟩を表す語の主観性―取りたて助詞「ばかり」を中心に―」『国語と国文学』2017; 94–3，pp. 2–16，東京大学国語国文学会.\n\n澤田 美恵子: 『現代日本語における「とりたて助詞」の研究』くろしお出版;2007.\n\n中西 久実子:「シカとダケとバカリ―限定のとりたて助詞―」宮島達夫・仁田義雄編『日本語類義表現の文法(上)単文編』くろしお出版;1995, pp. 317–327.\n\n西村 栄里子: 「「ばかり」の意味変化―八十代から十代まで―」『国文学―解釈と鑑賞―』1994; 59–7，pp. 39–48，至文堂.\n\n日本語記述文法研究会編: 『現代日本語文法5 第9部とりたて 第10部主題』くろしお出版;2009.\n\n丹羽 哲也: 「副助詞における程度と取り立て」『人文研究』1992; 44-13，pp. 93–128，大阪市立大学文学部.\n\n沼田 善子:『現代日本語とりたて詞の研究』ひつじ書房.2009.\n\n益岡 隆志・田窪行則:『基礎日本語文法―改訂版―』くろしお出版.1992.\n\n森田 良行:『基礎日本語2 ―意味と使い方―』角川書店.1980.\n\n矢澤 真人: 「連用修飾成分の位置に出現する数量詞について」『学習院女子短期大学紀要』1985; 23，pp. 96–112，学習院女子短期大学.\n\n矢澤 真人:「数量の表現」金田一春彦・林大・柴田武編(代表)『日本語百科大事典』大修館書店;1988, pp. 209–211.\n\nSperber D, Wilson D: Relevance. Communication and Cognition. 1995;Oxford:Blackwell.\n\nスペルベル・ D, ウイルソン D:『関連性理論―伝達と認知―第2版』内田聖二・中逵俊明・宋南先・田中圭子訳，研究者出版;1999.\n\n\nFootnotes\n\n1 本稿では，「ばかり」がとりたてる要素に該当しない例（いわゆる「例外」）のことを，佐藤 (2017) に倣って「非該当例」と呼称する。なお，2.1 節で触れる定延 (2001) はこれを「夾雑物」と呼称しているが，煩雑化を避けるため，本稿では「非該当例」という用語で統一する。\n\n2 先行研究から引用した例文などの末尾にはその出典を記す。一方，出典のないものは筆者によるものであるが，筆者の作例には「#」を付すことがある。これは，当該の文が文法的ではあるものの，指定の文脈では不自然ということを示す記号である。また，引用した例文には「?」「??」を付すことがあるが，これは引用元の文献に倣ったものであり，いずれも当該の文が（やや）不自然であることを示す記号である。\n\n3 先行研究では，数量詞の捉え方について幾つかの立場があり，遊離数量詞と呼称すべき範囲，あるいは名称そのものについても議論がある（詳細は矢澤 (1988) や加藤 (1997) などを参照されたい）。しかし，本稿ではその点には立ち入らず，副詞位置に生起する数量詞を便宜的に遊離数量詞と呼称する。\n\n4 コーパスは現代日本語書き言葉均衡コーパス (BCCWJ) を使用した。該当文抽出，内省判断の手順は以下の通りである。\n\n・BCCWJをアプリケーション「中納言」で使用\n\n・検索・抽出の手順は，\n\n短単位検索\n\nキー：ばかり\n\n後方共起:キーから1語，品詞の小分類が名詞・数詞\n\n→ヒット数 45 例\n\n→上記 45 例を目視で確認，バグ 3 例を除外\n\n→残った 42 例について母語話者により内省判断抽出された BCCWJ 内の文例を 1 例示す。\n\n(i) 今日は、映画の予告編ばかり二十四本見てきました。（サンプルID:OY15_13680、yahoo 知恵袋））\n\n5 (3) (4) について，非該当例が認められる場合でも成立すると判断する話者の存在も完全には否定できない。ただし，本稿においてこれらが当該の文脈で成立しないと主張するのは意味論のレベルであるのに対し，成立するという判断は語用論のレベルでなされるものであると考える。語用論の1つのモデルである「関連性理論 (Relevance Theory)」を提唱する Sperber and Wilson (1995) は，「思考の最適な解釈的表現は，聞き手にその思考について処理するに値するだけの関連性がある情報を与え，できるだけ処理労力が少なくてすむようにしなくてはなら」(Sperber and Wilson 1995: 284)ず，「厳密に言えば偽とわかっている」(Sperber and Wilson 1995: 284) 内容でも成立する場合があるとしている。非該当例が認められる場合でも (3) (4) が成立するという判断があり得るとすれば，それはこうした語用論のレベルでの判断であり，本稿が目的とする意味論のレベルの議論とは区別されるべきものである。\n\n6 「『ばかり』が問題にする集合」とは，沼田 (2009) 等で述べる，自者とそれに対する同類の他者が構成する集合である。詳しくは沼田 (2009: 43-56) を参照されたい。\n\n7 「探索領域」は「探索が及ぶ領域」（定延 2001: 118）を，「探索課題」は「探索者が探索を通して解決しようとする課題」（定延 2001: 119）を意味する。\n\n8 佐藤 (2017) は，「認識的際立ち性という性質をよりもちやすくする要因」（佐藤 2017: 11） の1つとして次のことを挙げている。\n\n(i) 事態が信念に照らし合わせて有標的である。 （佐藤 2017: 11，下線は筆者）\n\nこの指摘は，次のような文の容認度の差が踏まえられている。\n\n(ii) 太郎は授業をさぼってばかりだ。 （佐藤 2017: 12，下線は筆者）\n\n(iii) ?? 太郎は授業に出席してばかりだ。 （佐藤 2017: 12，下線は筆者）\n\n佐藤 (2017) は，「常識的な信念を有するものにとって，『授業をさぼる』〔筆者略〕といった行為はあるまじきものであり，有標性の高いものといえよう」（佐藤2017: 12）と述べている。そのために「認識的際立ち性」が生じやすく，(ii) は自然な文となる。一方，(iii) が不自然なのは，「授業に出席する」という事態は「有標性」が低く，「認識的際立ち性」を持ちにくいためであると推察される。「非遅刻」という事態が「ばかり」が問題にする集合に含まれないのも，この事態が「授業に出席する」という事態と同様に「有標性」が低いためであると考えられる。\n\n9 なお，佐藤 (2017) は「本稿〔筆者注：佐藤 (2017)〕が論じた集合形成の議論における知覚経験という観点は，定延 (2001) の言うところの『探索』というわれわれの心身の行動を前提とするものであり，その意味で本研究は定延 (2001) の議論の延長線上に位置づけられる」（佐藤 2017: 13）と述べており，定延 (2001) が提唱する「探索」という行動そのものに異議を唱えているわけではない。これについては本稿も同様である。\n\n10 「ばかり」が事態を問題にするということは，佐藤 (2017) 以前にも示唆・指摘されている。例えば，森田 (1980) は次の (iv) のように，菊地 (1983) は (v) のように述べ，「ばかり」と事態の関わりについて言及している。\n\n\n\n(iv) 「ばかり」は，“ある同一同類の主体がある範囲で行う”とか，“同一同類の事柄をある範囲内で行う”とか，“同一同類の対象に対して行われる”とか，また，“ある同一の事物がある範囲の程度内で存在する”とか，あるいは“ある事態に対応するのがいつも同じ人物である”とか，いずれの場合も動詞的叙述(傍点部分(筆者注: 本稿中斜体))を前提としている。 （森田 1980: 402，下線は筆者）\n\n(v) バカリは，<同類として括れる事態が数多くみとめられる>時に使われる。 （菊地 1983: 57，下線は筆者）\n\nなお，定延 (2001) は菊地 (1983) による(v)の指摘に触れた上で，「『ばかり』の探索領域が事物の集合ではなく，事物を探索領域とする探索の集合であると考える点で，本稿〔筆者注：定延 (2001)〕は菊地〔筆者注：菊地 (1983)〕と同じ立場に立つ」（定延 2001: 130）と述べている。その点では，定延 (2001)も「ばかり」は事態に関わると捉えていると言える。\n\n11 事態の数が多いということは「ばかり」が用いられる動機となり得るというだけで，「ばかり」が直接的に表現しようとする内容ではない。ただし，それに起因して「ばかり」が用いられることがある ((21b)) 以上，間接的には「ばかり」は事態の数が多いということを表し得ると言える。\n\n12 奥津 (1983) 以降の数量詞研究では，しばしば「NCQ型」「NQC型」「NノQC型」「QノNC型」といった名称が用いられる。これらの名称は，数量詞をその現れ方によって分類した際に用いられるものであり，Nが名詞を，Cが格助詞を，Qが数量詞を指している。\n\n13 この矢澤 (1985) の指摘は，「NCQ型の数量詞は，述部が動詞句以外のときには，現れにくいという構文上の制約がある」（矢澤 1985: 103）ことに基づいている。矢澤 (1985) は，述部が動詞句以外である次の文において，「NCQ型」の数量詞を含む (vi) (vii) (viii) とそれ以外の数量詞を含む (ix) (x) (xi) では，前者の方が容認度が低いことを示している。\n\n(vi) ? ココニイル女性ハ 五人 高校生ノ先生ダ （矢澤 1985: 103）\n\n(vii) ? アノ会社ノ受付嬢ハ 三人 美シイ （矢澤 1985: 103）\n\n(viii) ? アノ台ノ上ニ並ンダ牛乳ハ 五本 古イ （矢澤 1985: 103）\n\n(ix) ココニイル女性五人ハ 高校生ノ先生ダ （NQC型） （矢澤 1985: 103）\n\n(x) アノ会社ノ受付嬢ノ（中ノ）三人ハ 美シイ （NノQC型） （矢澤 1985: 104）\n\n(xi) アノ台ノ上ニ並ンダ五本ノ牛乳ハ 古イ （QノNC型） （矢澤1985: 104）\n\n14 これまでの議論では事態の「数」が問題となる現象，例をとりあげてきたが，「実験のために，残留塩素濃度が基準値を超える水ばかりを3000cc 集める。」のように「量」が問題となる例もある。これらも含めて扱うため，ここでは事態の「数量」とする。\n\n15 なお，2つ提示されている「ばかり」の「限定の仕方」の 1 つである (33a) の説明は，その上位に当たる限定の意味に関する (30) の説明と完全に一致しているが，これはそもそも下位分類の設定として適切とは言い難い。この点も，日本語記述文法研究会編 (2009) の捉え方に検討の余地があることを示唆している。\n\n16 定延 (2001)も，澤田 (2007) と同じく(36) を示唆しているように読める。定延 (2001) は，「ばかり」は限定を表すという立場を採っており（定延 2001: 113），その点で澤田 (2007) とは異なる。一方で，「ばかり」が問題にする「世界探索の集合」は印象的・感覚的になっても問題ではなく，多少の非該当例の存在は「ばかり」の使用に影響しないとも指摘している（定延 2001: 134）。この点については澤田 (2007)との類似性が認められると言える。\n\n17 この限定についての説明は，「ばかり」に関する先行研究での説明を踏襲したものである。例えば丹羽 (1992) は，「限定とは，当該事態が唯一成立して他の事態は排除されるということ」（丹羽 1992: 109）と述べている。また，沼田 (2009) は「とりたて詞がとりたてる文中の要素」（沼田 2009: 37）を「自者」，それに「端的に対比される『自者』以外の要素」（沼田 2009: 37） を「他者」と呼び，「自者」が肯定され，かつ「他者」が否定されることを限定と呼んでいる（沼田 2009: 196）。\n\n18 そうした研究に当たるものは，管見の限り日本語記述文法研究会編 (2009) のみである。しかし，その分析に問題があることは 4.1.1 節で述べた通りである。"
}
|
[
{
"id": "112371",
"date": "20 Dec 2021",
"name": "Toshiyuki Sadanobu",
"expertise": [
"Reviewer Expertise 言語学、コミュニケーション論、日本語学"
],
"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論文を読ませていただきました。遊離数量詞構文において「ばかり」が「非該当例」を許容しなくなるという観察は意義あるものと判断します。が、この論文が（賛否は別として）一つの論考として成り立つには、クリアしなければならない問題もあると判断し、「条件付き承認」と判定します。以下、問題について説明し、提案を書きます。ご参考になれば幸いです。\n問題１：前提とされている概念「意味」がはっきりしない。 論文では、「「ばかり」の「意味」とは何か？」という論点が設定され、この論点をめぐる形で考察が展開されています。が、その「意味」とは、どういうものを含み、どういうものを含まないのでしょうか？ ある説を対立説（要旨のことばで言えば「「ばかり」の意味を限定ではないと示唆・主張する研究」）と位置付けて反駁したり、自説を主張したりするには、まずこの点が明らかにされる必要があると考えます。 仮にある研究者が「「ばかり」は限定を意味する」あるいは「「ばかり」は限定を意味しない」と明記していても、その研究者の「意味」の概念を、著者の「意味」観と比べ、対応づけを検討しなければ、その研究者の見解を自説の仲間、あるいは対立説に位置付けることはできないでしょう。 論文が挙げている先行研究の中で、対立説と位置付けられているものは唯一、澤田(2007)だけですが、これも、本当に対立説と言えるのか、論文を読んでいて確信できませんでした。というのは、澤田(2007)の考えとして引用されている第4.1.2節の(35)は、「ばかり」を発する話し手の動機（「目的」）について述べられたものであって、「ばかり」の意味について述べられたものではないからです。その末尾の部分には、限定的解釈が「派生的」にせよ「でてくる」とも書かれています。これを本当に、「「ばかり」は限定を意味しない」と述べたものと読み込んでよいのでしょうか。 以上のことを、著者自身自覚されているのではないかと思わせる、記述の弱さが論文には見られます。もし、どうしても澤田(2007)を対立説とみなして「ばかり」の意味論にこだわるのであれば、それらは改めるべきでしょう。具体的に言うと、要旨欄の「示唆・主張」は「示唆・」を削除して「主張」とするべきでしょうし、対立説は第4.1.2節ではなく第1節で真っ先に紹介すべきでしょう。第2節末尾の「ばかりの意味についても考察する」は、これこそがメインのはずですから、「も」は削除すべきでしょう。\n問題２：遊離数量詞を持ち出す意義がはっきりしない。 遊離数量詞を持ち出す意義も、はっきり理解できませんでした。これも、論点として「ばかり」の意味論が設定されている結果ではないでしょうか。というのは、「「ばかり」の意味＝限定」説は、遊離数量詞を持ち出さなくても、他の、ずっと簡単な形でも主張できるからです。以下、それを具体的に２つ述べます。 その１：「厳密に」「厳密な話」などの語句が「～ばかり」にかかるだけで、「非該当例」は許容されにくくなります。例：うどん以外も食べていた場合、「先週はうどんばかり食べてたよ」と比べて「先週は厳密な話、うどんばかり食べてたよ」は自然さが低い。 その２：「非該当例」の存在が会話相手に知られた場合、相手に反駁され得ます。例：うどん以外も食べていたことが聞き手に知られた場合、「先週はうどんばかり食べてたよ」と言えば、「うどんばかりじゃないじゃん。×××も食べてたじゃん」などと反駁される可能性があります。 いずれも、「非該当例」が、いわば「非公式のもの」でしかないことを示すものです。こうした「非該当例」の「非公式性」は、多くの研究者に共有されており、（「意味」の定義はさまざまであれ）「「ばかり」の意味＝限定」説は広く受け入れられているものではないか、というのが評者の認識です。\n問題３：仮説がアドホックに感じられる。 評者の理解によれば、著者は、遊離数量詞の効果で「非該当例」が許容されなくなるという自身の観察を、次の２段階の仮説によって説明することで「ばかり」の意味論につなげようとしています。以下、評者のことばで述べます。（ちなみに「「現実世界の事態の数量」との（不）一致」という表現には、改善の必要を感じます。「もしあの時、白いシャツばかり10枚買っていたなら～」のような、仮定世界や反事実世界の話をも「現実世界」と言わねばならないことになってしまうからです。） 段階１：「ばかり」の話し手が想定する集合は、２種類あり得る。集合は、「当該文脈で想定される候補の集合」（＝とりたて表現一般に想定される集合で、「非該当例」を含む）とは別に、「非該当例を排除した集合」でもよい。 段階２：「ばかり」の文に遊離数量詞が現れ、事態の数が明示される場合は、「非該当例を排除した集合」が想定できず、「当該文脈で想定される候補の集合」しか想定できなくなる。にもかかわらず、この場合、「非該当例」は許容されない。（だから「ばかり」は限定を意味する。） ここでは、以上の２段階のうち、段階１について述べます。 この仮説（段階１）は、「限定を意味するはずの「ばかり」が「非該当例」を許容する」という謎を、「「ばかり」の話し手が想定する集合としては、「非該当例」を排除した集合が許容される」という、別の謎に変換しています。この変換については、佐藤(2017)が参考にされているとはいえ、論拠が出されておらず、アドホックに感じられます。\n提案：諸説の統合 以上の３つの問題を回避あるいは解決し、この論文を一つの論考として成り立たせるための提案をおこないます。（単なる提案ですので、却下していただいても構いません。） それは、「「ばかり」の意味とは限定か、そうでないのか？」という論点の代わりに、「「ばかり」の非該当例が許容される場合と許容されない場合の違いとは？」という別の問題を立て、この問題に、これまでの諸説を統合する形で解答を与える、ということです。 問題３について、論文では、仮説(段階１)の論拠が出されていませんが、これに強く関連する概念「集合」については、菊地(1983)に始まる先行研究の言及があります。これを利用すればどうでしょうか。評者のことばで言えば、それは（(8)に書いていただいているように）「探索の集合」ということです。探索とは体験の中核を占めるもので、探索の集合を語るということは、結局、体験の集合を語るということです。体験談では、その体験を「語るに足る」(つまりreportableな）ものにするために、嘘と思われない程度の誇張や脚色がなされやすいと考えると(Labov 2001)、ある偏り（例：先週の自分の食生活の偏り）を表すのに、知識として語らず、その知識を探る個人的な体験として語る場合、非該当例が許容されやすいということも、自然なこととして理解できるのではないでしょうか。 なお、探索と体験については、たとえば拙著(定延2016)をご覧いただければと思います。そこでは、ある料理について「からいばかりで少しもおいしくない」と言う場合のような、形容詞＋「ばかり」についても取り扱っています。\n要望：非該当例が許容されなくなる根本原因について、さらに論じていただきたい。 上記の段階２について述べます。著者は、遊離数量詞で事態の数が明示されると、「非該当例を排除した集合」が想定できなくなる、と論じています。が、事態の数が明示されると、なぜそのような効果が得られるのでしょうか。つまり、事態の数として、非該当例を含んだ数がなぜ表示できないのでしょうか？ 論文はこの問題について論じておらず、そのため、現象を説明しているのか、説明すべき現象を単に別の形で言い換えているに過ぎないのか、はっきりしないというのが、率直な感想です。この問題について、論じていただきたい、その際、以下２点についても触れていただければというのが、評者の要望です。 その１：上に記したように、「非該当例を排除した集合」を想定不能にするものとしては、いろいろなものがあり得ます。たとえば、「厳密な話」などの語句を挿入することです。またたとえば、相手に反駁され得ないような客観的な描写を話し手が心がけるだけでも、「非該当例を排除した集合」は想定されなくなります。遊離数量詞による事態の数の明示は、「非該当例を排除した集合」を想定不能にする根本的な原因ではなく、さまざまな要因の中の一つとして位置づけられるべきではないでしょうか？ その２：もう少し言えば、遊離数量詞による事態の数の明示が「非該当例を排除した集合」を想定不能にするというのは、傾向であって、例外もある、と考えられないでしょうか？ 著者は、「遊離数量詞」として、数詞から成るものばかりを挙げていますが、遊離数量詞としては、数詞の現れない、より感覚的なものも考えられます。以下の実例をご覧ください。\nまあね、中にはおっさんもいますけど、そうですねぇ、８割ぐらいが若いきれいな女の子なんですわ。もう、絶対顔で客選んでるやろ！っていうぐらい、きれいな子ばっかりの店なんですね。 ［三好康之・ITのプロ46 2020『情報処理教科書 高度試験午後Ⅱ論述 春期・終期 第2版』 p. 63，翔泳社］\nこの例で述べている状況は、「この店には、もう、絶対顔で客選んでるやろ！っていうぐらい、きれいな子ばっかりがいる」という文で表される状況で、この文には「もう、絶対顔で客選んでるやろ！っていうぐらい」という数量詞（と言って悪ければ数量詞句）が現れています。が、著者によればその割合は10割ではなく「８割」で、２割は「おっさん」などのようです。この例は別としても、たとえば「朝からおかしな答案ばっかり、山ほど採点してこっちまでおかしくなる」などと言うことは、「山ほど」採点した答案の中にまともな答案が少しぐらい入っていても自然かもしれません。もしも仮に、遊離数量詞の中に、数詞から成るものと、そうではない、より感覚的なものの違いが見られるのであれば、それもまた、「ばかり」の体験性と関連していると考えられはしないでしょうか。 見知らぬ異国の街をバスで走行中、車外の風景を眺めている観光客が、「この街にはあちこちにレストランがあるね」という意味で同乗者に「この街にはしょっちゅう、レストランがあるね」と言うのは、「この街には30秒に１軒、レストランがあるね」などと言うより自然だとすると（定延 2016）、そうした遊離数量詞の区別も、これと並行しているのかもしれません。このような可能性もご一考いただければ、ご論考がさらに内容豊かなものになると考えました。\n以上、勝手なことを書きましたが、理解の不足や誤りがありましたら失礼します。少しでもご参考になる部分があれば幸いです。\nLabov, William. 2001. “Uncovering the event structure of narrative.” In Deborah Tannen and James E. Alatis (eds.), Georgetown University Round Table on Languages and Linguistics 2001, pp. 63-83, Washington, DC: Georgetown University Press. 定延利之 2016 『煩悩の文法―体験を語りたがる人びとの欲望が日本語の文法システムをゆさぶる話（増補版）』東京：凡人社\n\n本研究は明確かつ正確に提示されたものであり、最新の文献を引用していますか。 はい\n\n研究設計は適切で学術的価値がありますか。 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。 対象外（統計を使っていない\n\n結果の基礎となるソースデータはすべて入手可能で再現性を十全に保証していますか。 はい\n\n結論は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": "8321",
"date": "04 Jul 2022",
"name": "ヨシコ オクツ",
"role": "Author Response",
"response": "定延先生 お忙しい中，拙稿の査読のために貴重なお時間を割いていただき，誠にありがとうございました。早速多くのご意見を頂いたにもかかわらずご回答が遅くなってしまい，大変失礼いたしました。以下，頂いたご意見につきまして，ご回答申し上げます。なお，以下ではご意見を頂いた原稿を「第1稿」，修正した原稿を「第2稿」と呼称しております。 1．「意味」と澤田（2007）について ご指摘の通り，第1稿では「意味」という概念が「どういうものを含み、どういうものを含まない」のかということを明示しておりませんでした。このご指摘は，第1稿において，特に澤田（2007）との差を“「ばかり」の意味を限定とするか否か”という点に求めていることと密接に関係すると思われます。ご指摘いただき誠にありがとうございました。ご指摘については，「意味」一般について十全な定義に及ぶことはできませんでしたが，澤田（2007）と本稿との違いを明確に示すように改稿しました（第2稿4.3節第3段落）。 改めた記述の内容をまとめると次のようになります。澤田（2007）はとりたてる要素が「多い」（あるいは「多すぎる」）ということを伝えるのが「ばかり」にとって重要であり，「限定」はその「二次的な効果」と述べております。この記述につきまして，当該要素が「多い」場合に「ばかり」が用いられるという点は筆者の立場と一致しております。しかしながら，「多い」ということを伝えるのが「重要」であり，「限定」が「二次的」という位置づけについては筆者の立場と異なります。具体的に言えば，筆者は「限定」が「二次的」とは考えず，また，「多い」というのは「ばかり」が集合を形成するに当たっての前提条件であると考えております。 2．要旨欄と第2節の文言について ご指摘を踏まえ，第2節末尾の「ばかりの意味についても考察する」の「も」は削除いたしました（第2稿2.3節最終文）。なお，要旨を全面的に修正した都合上，第1稿の「示唆・主張」はそれ自体を削除いたしました。 3．遊離数量詞を持ち出す意義について 筆者は“「ばかり」は主観的集合の内部に非該当例が存在しないことを表す”ということが遊離数量詞共起下の現象から明らかになると考えており，その点に遊離数量詞を持ち出す意義を見出しております。ご指摘を踏まえ，第2稿ではこの点が（少なくとも第1稿に比べて）明確になるように修正いたしました（第2稿2.3節（17）の直後）。 ところで，ご教示いただいた2つの例のうち，特に「『非該当例』の存在が会話相手に知られた場合、相手に反駁され得」るという例は，ご指摘の通り「『非該当例』が、いわば『非公式のもの』でしかないことを示すもの」であると考えます（同様の例は佐藤（2017: 3-4）でも指摘されていることを確認しております）。しかし，この例では“「非該当例」は「ばかり」によって設定される集合の内部に存在するのか外部に存在するのか”という点までは十分に捉えられないものと思われます。これに対し，筆者は遊離数量詞共起下の現象を観察することで“「非該当例」は「ばかり」によって設定される集合の外部に存在する（内部には存在しない）”ということが明らかになると考えております。 なお，「『厳密に』『厳密な話』などの語句が『～ばかり』にかかるだけで、『非該当例』は許容されにくくな」るというご指摘については検討の余地があると考えます。「厳密に」が介入すれば非該当例を許容しないということであれば，次の例文①②③はいずれも自然に成立することが予測されますが，「ばかり」と共起する③はやや不自然になるように思われます。 ① 先週はうどんをよく食べてました。いや，厳密にはうどんだけ食べてました。 ② 先週はうどんをよく食べてました。いや，厳密にはうどんしか食べませんでした。 ③ ? 先週はうどんをよく食べてました。いや，厳密にはうどんばかり食べてました。 これは，「ばかり」が主観的集合を問題にする（客観的集合ではないことを含意する）のに対し，「厳密に」は客観的集合を問題にする（主観的集合の設定を許さない）ためであると考えます。 4．「現実世界の事態の数量」という表現について ご指摘の通り，「「現実世界の事態の数量」との（不）一致」という表現，特に「現実世界」という表現は不適切でした。ご指摘いただきありがとうございました。第2稿では内容を修正した都合上，この表現自体を削除いたしました。 5．体験談では嘘と思われない程度の誇張や脚色がなされやすいこととの関わりについて 「体験談」では「嘘と思われない程度の誇張や脚色がなされやすい」ため，「個人的な体験として語る場合、非該当例が許容されやすい」という見方については，筆者も関連性理論で言われる「ルース・トーク」（loose talk）に関する記述（Sperber and Wilson 1995※）を参考に検討いたしました。しかし，その場合，「ばかり」が遊離数量詞と共起する際に非該当例が許容されないことを説明できないため，この見方は採りませんでした。また，「ばかり」は「体験」の中から非該当例を排除した集合を設定すると筆者は捉えており，これは少なくとも一般的な「ルース・トーク」とは異なるものと考えております。 ※ Sperber, D. & D. Wilson (1995) Relevance. Communication and Cognition.（内田聖二・中逵俊明・宋南先・田中圭子訳『関連性理論―伝達と認知―第2版』，1999年，研究者出版） 6．遊離数量詞によって非該当例を含んだ数が表示できない理由について 筆者は，遊離数量詞が共起することで主観的な集合を形成する「事態」の数量が計量的に明示され，それによって集合の範囲が明確になると考えております。また，「事態」は「探索」と親和性があり，遊離数量詞が示す「事態」の数は「探索」の数と一致するのではないかと考えております。 以上のご説明で十分なご回答になっているかは確信が持てませんが，現時点での筆者の考えを述べさせていただきました。 7．遊離数量詞による事態の数の明示は非該当例の存在が許容されなくなる根本的な原因ではないというご指摘について ご指摘いただきありがとうございます。確かに，第1稿では遊離数量詞による事態の数の明示が非該当例の存在が許容されなくなる根本的な原因であるかのように述べられております。しかし，これは筆者の述べ方の不備によるものであり，本来の意図はそうではありませんでした。 筆者は，遊離数量詞による事態の数の明示は，非該当例の存在が許容されなくなることの根本的な原因ではなく，“「ばかり」は（主観的）集合の内部に非該当例が無いことを表す”ということを示唆する現象を観察することのできる操作（の1つ）であると考えております。第2稿では述べ方を全面的に修正し，この点が明確になるようにいたしました。 8．「数量詞」の範囲について ご指摘の通り，「朝からおかしな答案ばっかり、山ほど採点してこっちまでおかしくなる」の場合は非該当例（「まともな答案」）の存在が許容されやすい可能性があると思われます。また，先行研究の中には「数詞から成るもの」でない形式も「数量詞」の1つに数える論考があることも確認しております（宇都宮1995※など）。 しかし，「数詞から成るもの」でない形式は一般的な数量詞（「数詞から成るもの」）と異なる性質を有しております。例えば，前者は後者に比べて位置的な制約が強いという点が挙げられます。 ① 答案を山ほど採点する。［NCQ］ cf．答案を30枚採点する。 ② ? 山ほどの答案を採点する。［QノNC］ cf．30枚の答案を採点する。 ③ * 答案山ほどを採点する。［NQC］ cf．答案30枚を採点する。 ご指摘いただいた前述の例は確かに興味深いものですが，今回はこのような相違点が認められることを考慮し，「数詞から成るもの」のみを「数量詞」と捉えることにいたしました。 ※ 宇都宮裕章（1995）「日本語数量詞体系の一考察」『日本語教育』87，pp.1-11．"
}
]
},
{
"id": "112370",
"date": "06 Jan 2022",
"name": "Takuzo Sato",
"expertise": [
"Reviewer Expertise 現代日本語の文法論および意味論"
],
"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「ばかり」の意味解釈に数量詞をからませて分析している着眼に新規性があり、非常に興味深い。また、「ばかり」の、機能をあくまで「限定」として位置づけたうえで、例外的ともみえる現象に対して統一的な説明を与えようとする結論も説得的である。\n唯一、問題点として残るのは、鍵となる例文の解釈が恣意的で説得力に欠ける点である。数量詞の働きにより非該当例解釈が許容されない例文の解釈には再考の必要性があるのではないだろうか。\n例えば、例文（23）の「100枚のシャツを購入した」に関して、（23’）において「計1000の「購入する」という事態が生じた」としている。しかしながら、（23）のデフォルト解釈はむしろ「「1000枚のシャツ購入」という事態が1回生じた」ではないか。（23）において非該当例解釈ができないのは、先行研究のいう「複数制の制約」によるとみるのがより自然である。\nこのような疑問が生じないような説明を与えるか、もしくは上述の線から数量詞による非該当例解釈の阻止という事実に光を与えるべきと思われる。\n\n本研究は明確かつ正確に提示されたものであり、最新の文献を引用していますか。 はい\n\n研究設計は適切で学術的価値がありますか。 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。 一部該当\n\n結果の基礎となるソースデータはすべて入手可能で再現性を十全に保証していますか。 はい\n\n結論は結果により妥当な裏付けを得ていますか。 はい",
"responses": [
{
"c_id": "8322",
"date": "04 Jul 2022",
"name": "ヨシコ オクツ",
"role": "Author Response",
"response": "佐藤先生 お忙しい中，拙稿の査読のために貴重なお時間を割いていただき，誠にありがとうございました。早速多くのご意見を頂いたにもかかわらずご回答が遅くなってしまい，大変失礼いたしました。以下，頂いたご意見につきまして，ご回答申し上げます。なお，以下ではご意見を頂いた原稿を「第1稿」，修正した原稿を「第2稿」と呼称しております。 1．非該当例解釈が許容されない例文の解釈について ご指摘の通り，「シャツばかり1000枚購入した」の一般的な解釈は「“1000枚のシャツ購入”という事態が1回生じた」であると思われます。それにもかかわらず「“購入”という事態が1000回生じた」という解釈を示したのは，いわゆる「探索」が1000回行われた（遊離数量詞の示す数が「探索」の数と一致する）ということを示す意図がございました。 なお，筆者はこのように「探索」の数（「ばかり」が形成する主観的集合の要素の数）に関与するのは遊離数量詞（副詞位置に生起する数量詞）に限られると考えておりました。例えば，女性400人と男性100人を招待した場面では，次のように遊離数量詞が生起する①は不自然であり，そうでない数量詞（以下，非遊離数量詞）が生起する②は自然であると考えておりました。 【女性を400人，男性を100人招待した場合】 ① # 女性ばかり500人招待した。 ② 招待した500人は女性ばかりだ。 しかし，菊地先生に頂いたご意見により，当該の場面では②も不自然と判定する話者も存在することが分かりました。これは，非遊離数量詞も「探索」の数に関与し得ることを示唆しております。 ただし，そうした話者が存在しても，少なくとも①よりは②の方が許容されやすいと考えております。つまり，“数量詞が生起した場合は，それが示す数が「探索」の数と一致し得るが，特に遊離数量詞は（「探索」と親和性がある「事態」と密接に関わるため）その含意が生じやすい”と考えております。 2．非該当例許容解釈の不成立と複数性の制約について 筆者は「複数性の制約」について，概ね“「ばかり」は事態（≒探索）が複数である場合にのみ用いられる”という制約であると理解しております。「シャツばかり1000枚購入した」で言えば，例え1000枚のシャツを一度に購入した（行為の回数＝単数）という場合でも，「シャツである」という結果が得られる「探索」が“複数”行われていれば当該の文が成立するため，その意味では今回の考察課題にも「複数性の制約」が関わっていると捉えられます。 しかし，非該当例許容解釈ができない要因と「複数性の制約」については関係性を見出しておりません。筆者の理解が及んでいない，あるいはそもそも当該の制約に関する理解が不十分であるという可能性がありますが，少なくとも現時点ではそのように考えております。大変恐れ入りますが，修正した第2稿を今一度ご確認いただき，非該当例許容解釈ができない要因についてはやはり「複数性の制約」と関連づけて説明する方が自然という場合には，改めてご指摘いただきたく思います。"
}
]
},
{
"id": "112374",
"date": "06 Jan 2022",
"name": "Mieko Sawada",
"expertise": [
"Reviewer Expertise 認知言語学、日本語学"
],
"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、「ばかり」が非該当例を許容しない現象があることを指摘した点は、学術的新規性が高いと判断する。本論文が主張するように、（27）は非該当例を含まない例として解釈できる。\n（27） 白いシャツばかりを1000 枚購入した。\nしかしながら、「ばかり」が遊離数量詞と共起する場合でも非該当例を含む場合がある。 例えば、Aの例は釣り好きの友人の発話である。\nA：この間、カワハギばかりを10枚釣ったよ。\nAの発話は、「ばかり」が遊離数量詞と共起している例である。筆者がAの発話に対して、「カワハギ以外は釣れなかったのか」と尋ねたところ、「外道（本命以外の魚）も何匹か釣った」という回答だった。つまり、遊離数量詞の場合でも非該当例を含む場合があるということである。 Bはガチャに凝っている友人に聞いたところ、Ｂの発話は自然であるということであった。\nB：10回ガチャやったら、サルばかりが5匹出た。\nBの発話も遊離数量詞の例である。Bは10回ガチャをやって、サルが5回でた場合の発話であった。釣り好きの友人もガチャに凝っている友人も日本語の母語話者である。 では、（27）とA、Bの例の違いについて考えてみたい。（27）を他者の発話として聞き、非該当例を含まないと解釈する場合は、他者が1000枚の白いシャツを買ったと解釈した場合である。また（27）が話し手の自伝的記憶を想起して発話された場合は、話し手は事態をコントロールしており、意図的に1000枚購入している。一方、AとBの共通点は、いずれの話し手も自伝的記憶を想起しており、釣りもガチャも話し手のコントロールが及ばないことを認知しており、複数回行っているという点である。 この現象は、「ばかり」が遊離数量詞と共起する場合の発話でも、話し手が自伝的記憶を想起して、行為が複数回であった場合、非該当例を含む場合があることを示唆している。このように、「ばかり」を使用した文が非該当例を含まない解釈は特別な条件が必要であり、「ばかり」の意味は非該当例を許容しない「限定」と考えるのが妥当であるという主張が理解できない。ゆえに、「ばかり」の意味を「限定」と位置づけることの意義を示してほしい。筆者は、日本語の認知言語学の発展のためにも、「ばかり」のように意味の分化が非常に興味深い不変化詞は、様々な観点から研究をしていくことが有意味であると考える。ゆえに本論文で、今後の方向性と示されている「対象集合についての詳細な議論」は非常に興味深いと考える。\n\n本研究は明確かつ正確に提示されたものであり、最新の文献を引用していますか。 はい\n\n研究設計は適切で学術的価値がありますか。 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結果の基礎となるソースデータはすべて入手可能で再現性を十全に保証していますか。 はい\n\n結論は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": "8323",
"date": "04 Jul 2022",
"name": "ヨシコ オクツ",
"role": "Author Response",
"response": "澤田先生 お忙しい中，拙稿の査読のために貴重なお時間を割いていただき，誠にありがとうございました。早速多くのご意見を頂いたにもかかわらずご回答が遅くなってしまい，大変失礼いたしました。以下，頂いたご意見につきまして，ご回答申し上げます。なお，以下ではご意見を頂いた原稿を「第1稿」，修正した原稿を「第2稿」と呼称しております。 「ばかり」が遊離数量詞と共起しても非該当例を含む場合があるというご指摘について 確かに，ご提示いただいた①②の例はサル以外のキャラクター（非該当例）が出た場合やカワハギ以外（非該当例）が釣れた場合でも成立すると思われます。 ① 10回ガチャやったら，サルばかりが5匹出た。 ② この間，カワハギばかりを10枚釣ったよ。 しかし，“「ばかり」が遊離数量詞と共起した場合は非該当例を許容しない”という筆者の主張は，①の例で言えば，10回出たキャラクターの中にサル以外（非該当例）は含まれないということではなく，“遊離数量詞「5匹」が表す数量の中にサル以外（非該当例）は含まれない”ということを示すものです。同様に，②の例で言えば，“遊離数量詞「10枚」が表す数量の中にカワハギ以外（非該当例）は含まれない”ということを示すものです。特に①の例は「サルが5回でた場合の発話」ということでご紹介いただきましたので，これは筆者の主張を支持する例であると考えております。しかし，第1稿では筆者の主張がやや曖昧になっている箇所がございましたので，第2稿ではその点を修正いたしました（第2稿1節（5）の直後や2.3節（19）などを始めとする複数箇所）。 また，確かに①②の例と次の③の例は「話し手のコントロール」や行為の複数性において差が認められると言えます。 ③ 白いシャツばかりを1000 枚購入した。 しかし，前述の通り，筆者の主張は遊離数量詞が示す数量の中に非該当例が含まれないというものであり，その点では①②と③の間に差は認められません。従って，少なくとも「話し手のコントロール」が及ぶ事態であることと「行為が複数回」でないことを指して「特別な条件」とする場合においては，「『ばかり』を使用した文が非該当例を含まない解釈は特別な条件が必要」ということにはならないと考えます。 一方，ご指摘いただいた内容は，遊離数量詞が表す数量と事態の総数量との関係において，①②の例と③の例で差があるということを示していると理解いたしました。具体的には，①②の場合は「5匹」「10枚」が「出た」「釣った」の総数量と（必ずしも）一致しない（出た数＞5匹，釣った数≧10枚）のに対し，③の場合は「1000枚」が「購入した」の総数量と基本的に一致する（購入した数＝1000枚）ということです。つまり，ご指摘に照らせば，「話し手のコントロール」が及ばない事態，かつ「行為が複数回」である場合（①②）は遊離数量詞が表す数量と事態の総数量が（必ずしも）一致せず，反対に「話し手のコントロール」が及ぶ事態，かつ「行為が複数回」でない場合（③）はそれらが基本的に一致するということになります。これは数量詞研究で言われるところの「全体量」と「部分量」の議論にも関わる可能性があり，大変興味深い現象ですが，今回の議論の範囲を超えていると判断し，第2稿では扱いませんでした。"
}
]
},
{
"id": "112372",
"date": "21 Jan 2022",
"name": "Yasuto Kikuchi",
"expertise": [
"Reviewer Expertise 日本語学、特に日本語文法。日本語教育。"
],
"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\n１ 査読者による要約 先行研究では、バカリは「限定」を表すとしばしば主張されてきたが、その一方で、バカリは「非該当例」を許容するとも指摘されており、この点で「限定」と捉えるのは不適当であるという指摘も行われてきた。この論文は、(1) 遊離数量詞を含む文のバカリは「非該当例」を許容しないという事実を指摘した、(2) (1)の事実について、なぜそうなのかという理由の説明を提示した、(3) (1)の事実をもとに、バカリは「限定」を表すと捉えるべきであると主張した［4.2］、の３点が骨子である。\n２ 評価できる点 (1)の事実の指摘［2.3.後半］は、最も評価してよい点である。 なおまた、取り上げるべき先行研究にほぼ粗漏はなく（ただし，後掲10参照）、先行研究への理解も適正のようである。\n３ 評価できるというほどでもないが、問題ではない点 （2）の理由の説明［3.3］は、内容としては成立はしているように思われる。 ただ、こうした趣旨のことを述べるのに、ここまで難しげに述べなければならないものか、という印象はある。多数の文法研究者に、こうした趣旨で説明文を書いてほしいという課題を課したら、もっとすっきりした答案がありうるように思う。その意味で、内容的には問題はないにせよ、評価できるというほどでもない、というレベルにとどまっている。\n４ 問題点 上記(3)の主張［4.2］は、残念ながら、十分な説得力をもつ論証を伴っていない。この点について、著者に理解してもらうために、以下に詳述する。\n５ 問題点の詳述 (1)により明らかになったのは、 ア．遊離数量詞がない場合は「非該当例」が許容される（「限定」とはいえない）。 イ．遊離数量詞がある場合は「非該当例」が許容されない（「限定」である）。 ということである（アは以前から知られていて、今回この論文が明らかにしたのがイ）。 これは、図式的にいえば、\n\nア． Aの場合はP。\n\nイ． B（Non A）の場合はQ（nonP）。 というケースである。 事実はここまでであり、ここで、もし、ア・イのうちどちらか一方を「普通のケース」と見る、という見方を採らないのであれば、上記ア・イのまま併記して終わりにすることもできる。 だが、ここで、仮にアとイのどちらかが一般的・本来的な在り方（普通のケース）で、他方が例外的な・変則的な在り方だと見ようとするならば、AとBを比べて、いわゆる無標（unmarked）な場合のほうを一般的・本来的な在り方と見、有標（marked）な場合のほうを例外的・変則的と見るのが、普通に採られている見方であろう。遊離数量詞を含む文と含まない文とを比べ、一方を無標、一方を有標とせよと言われたら、大抵の言語研究者は、遊離数量詞を含まないほうを無標、含む文を有標と見るはずである。だとすれば、この場合はアを無標と見る、すなわち、 ［Ⅰ］遊離数量詞を含まない（＝普通の）ケースでは、バカリは非該当例を許容する（「限定」ではない）。 ただし、遊離数量詞を含む場合は、非該当例を許容しない（「限定」的な意になる）。 という見方が順当である。これは、言語研究者の多くがごく普通に採る見方のように思われる。\n\nこれを逆にして、 ［Ⅱ］遊離数量詞を含む場合は、バカリは非該当例を許容しない（「限定」である）。 ただし、遊離数量詞を含まない場合は、非該当例を許容する（「限定」でなくなる）。 という見方を採るとすれば、［Ⅰ］と［Ⅱ］は、どちらを但し書きにするか、つまり、どちらを普通と見るかが逆である、ということになる。 バカリの基本義を「限定」と見るという主張は、［Ⅱ］の見方を採った場合にのみ行える主張である。著者が前掲(3)のように「バカリ」の基本義を「限定」と主張しているということは、つまり、著者は［Ⅱ］の見方を採っているのだ、と見られる。だが、上述のように普通は［Ⅰ］のように見るところなので、［Ⅰ］ではなく［Ⅱ］のように見るためには、相応の根拠が必要なはずであるが、この論文では、それが示されないまま［Ⅱ］が採られているように読めた。 さらにいえば、著者は、 「遊離数量詞を含む文のほうが、遊離数量詞を含まない文よりも、文として「普通」の文である」 という主張をしている（しかも、根拠を示さずにそう主張している）のと、実は、同じことなのではないか、と査読者には見える。この点に大きな違和感を感じる。 一方、著者は、上記要約で査読者が(2)としてあげたように、〈遊離数量詞を含む文で「非該当例」が許容されない理由〉を説明しているが、実は、これは、遊離数量詞を含まない文を「普通のケース」と見た上で、遊離数量詞を含む文ではそのように行かないことの理由を説明した、という発想のものなのではないか。つまり、著者自身、実は［Ⅰ］の見方に拠っているのではないか、とも思われる（だとしたら、「限定」を基本義と見るのは成り立たない）。もし、著者の基本的な主張のとおり［Ⅱ］の見方を採るなら、その場合は、〈遊離数量詞を含まない文で「非該当例」が許容される理由〉のほうを丁寧に説明すべきことになる。その説明が行われていない点も不備であろう。 察するに、著者には、バカリを「限定」と見たいという潜在的な意識があり、それに好都合な遊離数量詞のケースを発見したので（ここまではいいのだが）、その遊離数量詞のケースをスタンダードのように捉えて残りの議論を展開し、望んでいた「結論」に到達させた、というケースなのではなかろうか。だが、後段の議論には、上述のように無理があり、成立していないと言わざるを得ない。上記ア・イのような事実が観察された場合、どちらが一般的・本来的な在り方かを合理的に見極めるべきところ、それを欠いたまま（厳しく言えば、冷静で合理的な「大局観」を欠いたまま）、いわば論点先取的に遊離数量詞を含むほうを本来的な在り方と見てしまった、というケースかと推測される。\n６ 承認ステータスについて 本プラットフォームの承認水準がどのぐらいのものなのか、初めての査読であるため判断できないところがあるが、一応、学内の紀要などではないレベル（学会誌並みのレベル）であるなら、残念ながら、以上のように論証に不十分な点があり、そのままの形での承認には至らない。むしろ、このまま承認し公開を続けることは、著者への評価を下げることになりそうに思われる（→次項）。 しかし、(1）の事実の指摘には意義があるので、不承認とはせず、条件付き承認としておく。相当根本的な修正が必要であり、その方向性を下記に助言しておく。\n７ 改善の方向など 論証に問題がある論文については、普通は論証をしっかり補強するようにという助言を行うところであるが、この論文では、「限定が基本義である」とする議論を成立させることは困難である、と査読者は見る。 そこで、冒頭の要約に示した(1)(2)(3)のうち、(3)は取り下げるべきだと考える。(1)を指摘し、（2）でその理由を説明するだけでも、地味ではあるが、十分立派な論文である。確実に正しいところまでで止めるというのは、研究者として重要な姿勢である。(3)を主張した途端に、少なからぬ読者に、怪しげな論、あるいは強弁だという印象を与えてしまい、著者への評価を下げることになりかねないのではないかと、査読者はその点をおそれるものである。 査読者は、この論文は、次のように仕立て直すのがよいのではないかと考える。： ・(1)を指摘する。 →・「そうはいっても、遊離数量詞がない場合が、基本義が反映されている場合だと見るべきである。」と確認する。（先にア・イなどとして説明した箇所を参考にされたい） →・「では、遊離数量詞がある場合にはなぜ……?」という問を立てて、（2）に相当する議論を展開する。投稿者の(2)の議論は上で批評したようにやや難解であるが、要するに、「バカリは、基本的には〈認識的な際立ち〉に基づいて〈数多く観察される〉ことを表すだけなので、非該当例を許容しうるが、数量詞を伴った場合は、数量情報との合致が求められるため、正確な限定を表す結果となる」という趣旨の説明をすればよいと考える。 →・その上で、遊離数量詞がある場合に「限定」的になることについては、このように説明がつくのだから、バカリの基本義を「限定」でないと見ること自体は問題ない（むしろ支持される）、というふうにまとめる。 これが穏当な道だと査読者は考える（あくまでも査読者の意見であるが）。\n８ 論の補強のための参考 「先行研究では……「ばかり」がそれ（＝非該当例）を許容しない環境があることについて指摘・考察した研究は管見の限り存在しない。」［2節末］とあるが、実は、否定を伴う場合には、「ばかりでなく」は「だけでなく」と事実上同義である、ということは、多くの日本語教授者が承知していて学習者にも教えていることである。研究としての明記はないかもしれないが、これは、「非該当例の許容」のない意味でのバカリを否定している（だから「該当例が他にもある」という意味になる）と見るべきケースであり、こういう難しい言い方はしていなくても、事実としては知られてきたと言いうるものである。 数量詞と否定が「お友達」である、というふうに見える言語現象は、あれこれあるかと思われ、あわせて検討してはどうか。 なお、数量詞や否定絡みで不思議なことが起こる場合（例えば、生成文法の古典期に「変形は意味を変えない」と言っていたときに、manyやsomeが絡む受身文では、能動文とは違う意味になる（スコープ絡み）、ということが指摘された）は、あくまでも、その変わったことが起こる場合が有標なケースである、という理解をすべきことは、念のため付言しておく。\n９ その他の問題点： ■ 例文の適否判断に疑問がある点［2節末］： (17) 【女性を 400 人，男性を 100 人招待した場合】 a. # 女性ばかり 500人招待した。 b. 招待した 500 人は女性ばかりだ。 査読者の語感ではbも#である。［だとすると、この論文の主張（この査読の冒頭で示した要約中の(1)）は、「遊離数量詞」だけについてではなく、「数量詞」全般について成り立つことになる。］ このようなデリケートなケースでは、アンケートの実施が必要であろう。 なお、冒頭に査読者が（２）としてあげた理由の説明について、著者は「事態」ということに依存した説明を考えているが、上記７の中で述べたように、「数量情報との合致が求められる」ということがポイントなのではないかと思われ、「事態」への依存は必ずしも必要ではないように思われる。だとすれば、遊離数量詞でない数量詞について同様の現象が観察されても困らないのではないかと思われ、事実に誠実な論を組み立てることを薦めたい。\n■ 日本語記述文法研究会編 (2009) の紹介と論評の部分［4.1.1］ 著者のこの箇所の骨子に問題はないが、要するに、「同書は、(30)を(33a)と(33b)に分けられるかのように見せているが、この部分を一読するだけで、（33b）が(30)の下位区分になっていないことは、すぐ見て取れる。」というケースなので、もっと簡単に（失礼にならない程度に）、そのような趣旨のことを述べてあっさり片づけてよいのではないか。「注目に値する」と持ち上げるほどのものではないと思う（気を遣ったのかもしれないが、厳然と否定すべきケースだと思う。 なお、(32)の下、「理論的矛盾」とあるのは「論理的矛盾」では ?\n■ 澤田 (2007) の紹介と論評の部分［4.1.2］ 澤田の指摘（の、少なくとも方向）は、ごく全うなものだと査読者には評価できる。 ただ、遊離数量詞の文のバカリについては、その時点で留意されていなかったので、それにかかる補いが必要である、というだけのことであり、この小節のタイトルを「澤田（2007）の指摘とその問題点」とするのは、多少の違和感がある。小さなことではあるが、こう書くと、澤田（2007）の立論自体にすでに不備を抱えていたかのような印象を受けてしまう。遊離数量詞についてはこれまでの先行研究は誰も気づいていなかったのだから、それはやむを得ないであろう。これをカバーできていなかったことを問題点というなら（確かに問題点ともいえるが）、全ての先行研究について「○○（xxxx）の問題点」と言わなければならないことになる。 この節は、遊離数量詞の問題に出会う前から、「限定（のように見える場合があること）」と「非該当例があること」を、どうやって料理するかという問題に取り組んできた研究があるのだ、という話を中核にし（4.1節のタイトルもそのようなものにするのがいいように思う）、日本語記述文法研究会編 (2009) と澤田（2007）を紹介すればよく、両者ともに遊離数量詞については扱っていないということについては、ここでは過大に問題視しなくていいように思う。 また、4, 2の冒頭に、この両研究について「いずれにおいても問題がある」という整理になっているが、澤田は（遊離数量詞の問題に気づいていない点を別にすれば）相応に料理できていたのに対し、日本語記述文法研究会のほうは成功していないので、「問題」とはいっても、だいぶ水準が違うのではないか。このまとめ方はいかがかと思う。 なお、澤田の紹介にあたり、著者は「澤田は……限定(的解釈)はそこから「派生」する「二次的な効果」であると捉えている。つまり、限定は「ばかり」の意味ではなく、言わば語用論的効果であるとしているのである。」と述べているが、細かい点ながら、「派生」「二次的」ということをあっさり「語用論的」と言い換えてよいのかは疑問である。「派生」「二次的」ということは、「意味論」の世界の中でも起こりうることであり、本件に関しては、そう捉えるだけでも、議論が成り立つのではないかと思われる。澤田が、この「派生」「二次的」を意味の問題と考えているのか、語用論の問題と考えているのか、あるいはその点は不問に付しているのかは、わからないというべきであろう。「語用論的」と（勝手に）言い換えることには慎重でありたい。\n10 参考文献 以下を加えてもよいのではないか。 安部 朋世「バカリによる「限定」」『和光大学表現学部紀要』 2000，1，pp.135-144，和光大学表現学部．\n以上\n\n本研究は明確かつ正確に提示されたものであり、最新の文献を引用していますか。 はい\n\n研究設計は適切で学術的価値がありますか。 一部該当\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。 対象外（統計を使っていない\n\n結果の基礎となるソースデータはすべて入手可能で再現性を十全に保証していますか。 ソースデータは不要\n\n結論は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": "8324",
"date": "04 Jul 2022",
"name": "ヨシコ オクツ",
"role": "Author Response",
"response": "菊地先生 お忙しい中，拙稿の査読のために貴重なお時間を割いていただき，誠にありがとうございました。早速多くのご意見を頂いたにもかかわらずご回答が遅くなってしまい，大変失礼いたしました。以下，頂いたご意見につきまして，可能な限りご回答申し上げます（以下ではご意見を頂いた原稿を「第1稿」，修正した原稿を「第2稿」と呼称しております）。なお，すべてのご意見に対して十分なご回答をご用意することはできませんでしたが，第2稿では構成・論じ方を含めて修正を施しました。依然として不十分な点があるかと存じますが，その点につきましては改めてご指摘いただければ幸いです。 1．「5 問題点の詳述」におけるご意見について ご意見をくださりありがとうございます。確かに，第1稿では，「ばかり」は遊離数量詞と共起する場合に「限定」を表し，遊離数量詞と共起しない場合は「限定」を表さないかのように述べられております。しかし，これは筆者の述べ方の不備によるものであり，本来の意図はそうではありませんでした。 筆者は，「ばかり」が遊離数量詞と共起する場合に非該当例が許容されないという現象について，“「ばかり」は（遊離数量詞との共起の有無を問わず）集合の内部に非該当例が無いことを表す（＝「限定」を表す）”ということを示唆していると考えております。つまり，「ばかり」と数量詞の共起については，「ばかり」の「無標」のケース，あるいは「普通」のケースと捉えているのではなく，「ばかり」の意味について示唆的な現象を観察することできるケース（の1つ）と捉えております。第2稿では述べ方を全面的に修正し，この点が明確になるようにいたしました。 2．「9 その他の問題点 例文の適否判断に疑問がある点」におけるご意見について 確かに，第1稿（17b）を（17a）と同様に「#」と判定する話者が存在する可能性は否定できません。そうであれば，ご指摘いただいたように「数量情報との合致」が重要ということになると考えられます。一方で，相対的にはやはり（17b）の方が文脈的自然度は高いとも考えております（第2稿注12）。つまり，「数量情報との合致」が重要ではあるものの，その情報が「事態」の数量である場合にはより強固な「合致」が求められると考えております。 3．「9 その他の問題点 澤田（2007）の紹介と論評の部分」におけるご意見について 確かに，澤田（2007）は「ばかり」の振る舞いについて遊離数量詞と関連付けて議論しているわけではなく，それはご指摘の通り「その時点で留意されていなかった」ためであると思われます。しかし，澤田（2007）について，第1稿では遊離数量詞が生起する場合の現象に触れていない研究として取り上げているわけではなく，“「ばかり」の意味は「限定」ではないと主張する研究”として取り上げております。これは第1稿の主張と対立するものであるため，「澤田（2017）の指摘とその問題点」というタイトルで取り上げた次第です。 ただし，第1稿は筆者の意図が十分に伝わりにくい記述になっておりました。また，第1稿における澤田（2007）の位置づけには不十分な点がございました。これらを踏まえ，第2稿では澤田（2007）との関係性に関わる部分の記述を修正いたしました（第2稿4.2節・4.3節）。 なお，ご指摘の通り，澤田（2007）による「派生」「二次的」という表現を「語用論的」と言い換えていたことは不適切でしたので，第2稿ではこれを削除いたしました（第2稿4.2節（35）の直後）。ご指摘いただきありがとうございました。 4．「10 参考文献」におけるご意見について 安部（2000）を参考文献に加えました（第2稿注17，参考文献欄）。ご指摘いただきありがとうございました。"
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https://f1000research.com/articles/10-1276
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https://f1000research.com/articles/11-733/v1
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01 Jul 22
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{
"type": "Study Protocol",
"title": "Improving symptom assessment and management in the community through capacity building of primary palliative care: A study protocol of exploratory research",
"authors": [
"Malathi G Nayak",
"Radhika R Pai",
"Baby S Nayak",
"Sudhakara Upadya P",
"Naveen Salins",
"Malathi G Nayak",
"Baby S Nayak",
"Sudhakara Upadya P",
"Naveen Salins"
],
"abstract": "Aim: To determine the effectiveness of capacity building program on palliative care (PC) in enhancing the capacity of the primary health care workers in need assessment and symptom management of cancer patients. Background: In India, less than one percent of people living with cancer have access to palliative care since most are from low- and middle-income groups. Accredited social health activist (ASHA) and primary health care workers are grassroots workers who are the first contact with family members and are seldom aware of PC in India. It is essential to train them to give practical and efficient care to needy people. Design: A quasi-experimental design with follow-up will be conducted using an evaluative approach. Methods: The study population consists of 1440 Primary Health Care Workers (staff nurses, ANMs, and ASHA workers) of three taluks of Udupi District, Karnataka State, India. Training on PC will be provided for ASHA workers for one day and ANM/Staff nurses for three days. After their training, they are expected to demonstrate the gain in knowledge & skill in providing PC for cancer patients by identifying and implementing PC services using a mobile app at the primary healthcare level. Discussion: Palliative home care can give comfort and reduce patients' financial burden, and this training may help to improve the quality of life of needy patients. Impact: If this palliative care training program succeeds, it can be integrated into the healthcare continuum, making it an essential component of primary healthcare delivery to achieve universal health coverage. Moreover, home-based PC supports patients who want to die at home even though it reduces hospital stay costs. Trial registration: CTRI/2020/04/024792.",
"keywords": [
"ASHA (Accredited Social Health Activist)",
"Capacity building",
"Field Health Assistants",
"Junior Health worker",
"Palliative Care",
"Symptoms",
"Primary Health Care workers",
"Nurses"
],
"content": "Introduction\n\nThe GLOBOCAN 2020 estimated 19.3 million new cases of cancer and 10 million bereavements due to cancer in 2020 (Sung et al., 2021). Both private and public primary care facilities and public secondary facilities are inadequately prepared to address the burden of non-communicable diseases (NCDs) in India (Krishnan et al., 2021). Inequitable access to palliative care is one of the greatest disparities in global health care and lack of access to palliative care in low- and middle-income countries (LMICs) has led to a huge burden of preventable suffering (Knaul, Bhadelia, Rodriguez, Arreola-Ornelas, & Zimmermann, 2018). Although there are several initiatives towards palliative care development in India, palliative care access is significantly limited to a small population (Rajagopal, 2015). Improving palliative care education and awareness of healthcare professionals in India might be an effective strategy towards facilitating palliative care access (Glass et al., 2020).\n\nAccording to the oncology-based palliative care development project designed for the north-eastern region of India, developing oncology-based palliative care in India could demonstrate the implementation of a local version of the WHO model which emphasizes highlights the strengths of integrating palliative care within the cancer care programs right from its inception. It highlights the supportable public health care services present in comparison with the funded initiatives. This WHO model emphasizes the usefulness of this for LMIC countries with similar health and socio-cultural contexts (Vallath et al., 2021). In this regard, India requires the development of clinical guidelines according to the local needs for palliative home care ensured quality and uniform delivery of clinical services (Jeba et al., 2020).\n\nHelping native populations to institute community-led palliative care programs is the best way to address the lack of accessibility and sustainability of appropriate palliative care services at the end of life to most people in the world which is a complex task. This requires great rigor in both stages of conceptualization and implementation (Kumar, 2020).\n\nCapacity building of community health care workers in Brazil yielded in the successful conduct of the home visits and screening for risk factors in the elderly population (Neto et al., 2021). Nurses play a vital role in the care of patients especially caring for those who are dying, hence it is imperative for them to know the best principles of palliative care (Sadhu, Salins, & Kamath, 2010). The role of the family in the care of chronically ill patients is significant and they should be socially supported and empowered to cope with the situation (Philip, Philip, Tripathy, Manima, & Venables, 2018).\n\nAvailability of the digital health device for the reporting of the symptoms in patients with cancer to attend palliative care needs results in the reduction of the number of emergency department visits and thereby reduced health care costs (Bhargava et al., 2021). There is promising evidence to use mobile health apps to provide expanded and enhanced health care services to individuals and communities, taking advantage of the growing usage of mobile phones among diverse populations (Källander et al., 2013).\n\nAn India-specific document and a supportive quality development program suggested the need for additional training of palliative care providers towards the implementation of palliative care (Salins, Johnson, & Macaden, 2017). Despite having a robust palliative care policy in India, a study carried out through direct fieldwork and interviews with the health care workers reported a lack of public health approach to end-of-life care. This study further suggested the need for increased participation of the local and political readiness to implement palliative care delivery effectively (Jayalakshmi & Suhita, 2017).\n\nNational Health Systems Resource Centre (NHSRC) in India at present is associated with the preparation and training focussing on the Health care workers including ASHA, ANM to Medical Officers at Health and Wellness Centers across India (Centre, 2021b). To build a liaison between the community and public health system in India, under National Rural Health Mission there are Accredited Social Health Activists (ASHA) selected from the village who is planned to gather individuals’ understanding of health rights and empower them to get to their privileges (Centre, 2021a).\n\n\nBackground\n\nThe Global Atlas reveals that over 56.8 million people need Palliative Care (PC) worldwide (Organization). Adults over 50 years’ account for 67.1%, with children accounting for 7.1%. Among the adults, the largest single disease group needing PC is cancer (28.2%). Among children, cancer accounts for 4.1% of PC needs. Across resource settings, 76% of adults and >97% children (0-19 years) are from low and middle-income countries (LMIC). The regional distribution shows that 17.1% of adults and 19.5 of children needing PC are from the South East Asian Region (SEAR). SHS amenable to PC interventions is expected to increase by 87% by 2060 (Connor & Sepulveda Bermedo, 2018).\n\nOne of the key objectives of the National Programme for the prevention and control of cancer is establishing and developing a capacity of health care workers for planning health care activities including home care and palliative care (DIRECTORATE GENERAL OF HEALTH SERVICES & Welfare). One of the aims of the national palliative care program is to improve the capacity among health care workers to provide palliative care service delivery within government health programs (DIRECTORATE GENERAL OF HEALTH SERVICES & Welfare, 2012). Trained ASHA workers in their respective localities were able to identify people with psychiatric disorders and refer them to advanced care settings for further management (Ibrahim et al., 2021). Palliative care intervention that influences the inclusion of community health workers could serve as a feasible model for expanding the reach of palliative care to rural underserved patients (Qanungo et al., 2021). Rethinking of normal hospice services is recommended as they can participate in community capacity building in integrating palliative care (Paul, Cree, & Murray, 2019).\n\nThe process of translating a palliative care plan into action requires strong leadership, competent management, political support, and integration across all levels of care (Kar, Subitha, & Iswarya, 2015). CanSupport a multidisciplinary team approach reported that a home-based care model could be more approachable to the patients in India especially during end-of-life care or among patients with a chronic life-limiting illness. It is even reported in Can Support that the successful implementation could reduce the number of hospital visits, and finally reduce the total cost of the hospital by providing the best possible care by the trained health care people (Yeager et al., 2016).\n\nDeveloping policies concerning inculcating family-centered palliative care and end-of-life care within the nursing curriculum could help in promoting the nurse-led community models to address the palliative and end-of-life service care in India (Ramasamy Venkatasalu et al., 2018).\n\nThere is a disparity between the number of patients who could be benefiting from palliative care and the number of palliative care specialists. It is a vital aspect to improve basic palliative care delivery skills, identification of patients in need, and appropriate referral to palliative care specialists to effectively integrate the same into primary health care (Gorman, 2016).\n\nOrganizing home-based palliative care services as a quality improvement project resulted in a consistent increase in the frequency of home visits, better documentation, coordination, and accountability. Interdisciplinary team coordination helped to develop trust and a better understanding of collaborative research work (Viswanath et al., 2021).\n\nThe implementation of the Neighbourhood Network in Palliative Care (NNPC) in the Indian state of Kerala included the trained volunteers who were encouraged to form groups of 10-15 community volunteers, to identify the problems of the chronically ill people in their area and organize appropriate interventions. This NNPC service was reported as a cost-effective option for most developing countries to develop much-needed sustainable services for chronically ill and dying patients. In 2010, this network saw over 2500 patients per week and attained coverage of over 60% in many areas with NNPC groups that trained doctors and nurses support (Sallnow, Kumar, & Numpeli, 2010). A home-based palliative care program was perceived to improve the lives of patients and their caregivers despite the challenges of maintaining a volunteer-led program (Philip, Venables, Manima, Tripathy, & Philip, 2019).\n\nFamily carers suggested having a minimum number of carers involved in care, increasing or ensuring personal continuity, and maximizing the informational and organizational aspects of care could lead to a more positive experience (Seamark et al., 2014). There was some evidence of increased patient satisfaction with home-based end-of-life care (Shepperd, Wee, & Straus, 2011).\n\nA structured training program on symptom management kit for primary caregivers of cancer patients receiving home care was conducted at CMC, Vellore, India reported that, of the primary caregivers, 96.7% used a symptom management kit and received training resulted in a reduction of hospital visits for acute symptoms reduced by 80%; 90% were satisfied with the training received; 73% stated it was not a burden to treat the patient at home. This study further reported that the program and the kit were reported to be perceived favorably by caregivers from diverse backgrounds. Rural backgrounds and illiteracy were not barriers to acceptance of home-based palliative care (Chellappan, Ezhilarasu, Gnanadurai, George, & Christopher, 2014).\n\nThe mobile phone was chosen because it helps CHWs achieve better results in their daily activities. The five main mobile health functions that support frontline health workers (FHWs) in providing adequate care to their communities are data collection and reporting, decision-making resources and training, emergency referrals, warnings and reminders, and supervision. also, mobile data collection increases data collection promptness, decreases error rates, improves data completeness (Agarwal, Perry, Long, & Labrique, 2015).\n\nStudies have shown that the training programs conducted for primary caregivers help provide palliative care. It also showed that most of them were satisfied with the training provided (Chellappan et al., 2014). A study was carried out to examine the effectiveness of a holistic capacity-building program for volunteers in community-based end-of-life care (EoLC). Following the screening, 88 of the 171 candidates completed core competency training, with 53 continuing to volunteer for the next six months. Their end-of-life care competence, self-care understanding, and death work competence improved significantly following training and remained stable at the 6-month follow-up (Wang, Chan, & Lou, 2020).\n\nA cross-sectional interventional study was conducted in Delhi on the effectiveness of the certificate course on essentials of palliative care program among 29 health care professionals. The study revealed that, in the pretest, about 24.1% of them had good knowledge and which was improved to 82.8% after the training. 62.1% had average knowledge, and only 13.8% had poor knowledge. Since completing the program, participants improved their communication skills, symptom management, negative news breaking, and pain assessment (Bhatnagar & Patel, 2018). Studies also have reported that the scope and coverage of palliative care can be improved by providing training for medical officers and health care professionals and sensitizing the public through an awareness campaign (Kar et al., 2015).\n\nThis current project on improving the symptom assessment and management is intended to help to improve the knowledge and practice of primary health care workers on palliative care for need identification in the community.\n\n\nProtocol\n\nThe objectives of the study are to:\n\n• Assess the knowledge on palliative care pre and post-education among PHCWs by a survey study using a structured knowledge questionnaire.\n\n• Assess the attitude on palliative care pre and post-education among PHCWs by a survey study using a structured attitude questionnaire.\n\n• Assess the interpretive skill on palliative care pre and post-education among PHCWs by a survey study using a structured questionnaire on interpretive skill.\n\n• Identify the challenges and barriers for delivery of palliative care at the community level through qualitative interviews of the focused groups using an interview topic guide.\n\nThe impact of palliative care education on skills, attitude, and interpretive skills will be known through a Quasi-experimental design study having a pre-/post-intervention assessment of PHCWs (staff nurses, ANMs, and ASHA workers). The interventions will be the training of PHCWs on community palliative care and the implementation of a palliative care mobile app in the community. The outcome assessed is improvement in palliative care knowledge and enhancement of identification of palliative care needs in the community.\n\nThe study will be conducted at 59 primary health centers and 316 sub-centers in the rural locations of a district in Southern India. The study participants will be eligible and consenting registered ASHA workers (1011) and Primary Health Care Workers who are working under Primary Health Centers and Sub Centers (staff nurses/ ANMs or Junior health workers/Assistants = 429).\n\nCancer patients often experience financial constraints concerning cancer treatment in India (Oswal et al., 2021). As primary health care centers throughout the country deliver the essential medical assistance and the primary health care workers are the grass root level workers who work with the rural population closely, the national policy on palliative care emphasizes training the health care workers and providing accessible care to the cancer patients at the community level (DIRECTORATE GENERAL OF HEALTH SERVICES & Welfare, 2012). World Health Organization (WHO) emphasizes all countries integrate palliative care at the primary health care level (Organization, 2018).\n\nThus the total population of PHCWs & ASHAs in the selected District is 1440 excluding vacancies (Figure 1).\n\nPHCWs working as Staff nurses, Auxiliary Nurse Midwives or Junior Health Assistants, and ASHA workers who are trained female community health activists who are selected from the same village to be an interface between the community and public health system working under PHC/SCs of Selected District will be the participant in this project. These workers who are willing to participate in the study will be trained to identify the symptoms requiring palliative care for children and adults with cancer and provide palliative care for the same.\n\nTraining\n\nThe palliative care module will be prepared and training will be provided to the PHCWs to sensitize them concerning the concept of palliative care. A series of education will be planned and it will be conducted through workshops.\n\nThe palliative care module for PHCWs will consist of:\n\n• Introduction, definition, principles of palliative care\n\n• The role of a nurse in palliative care\n\n• Symptoms assessment, and management such as pain, dyspnoea, nausea and vomiting, diarrhea, constipation, wounds, edema, skin problems, anorexia, cachexia, fever.\n\n• Practical sessions on colostomy care, nasogastric tube insertion and tube feeding, urinary catheterization and catheter care, oral care, tracheostomy care, wound care, prevention of bedsores, subcutaneous injection procedures, lymphedema care.\n\nTo enable the functioning and tracking, an Android-based Application will be developed for usage by the PHCWs and health service providers. The Android App would contain the following functional modules\n\ni. Knowledge center that includes the information about palliative care needs, symptoms identification management. The content would contain Images, Videos, and links to online resources.\n\nii. Module to register, create and update the patient data\n\niii. Search and generate alerts for patient monitoring by Health workers\n\niv. Option to synchronize the data with the Health center for tracking purpose\n\nThe overall application structure will be as depicted in Figure 2.\n\nThe Public Health Care Worker (PHCW) will have an Android-based application on their mobile devices. The Android App features are as per the details outlined in Figure 2. The App can store the data locally and forward the details to the central data repository for monitoring and reporting purposes. Using the App on their mobile device, health worker refers to the training materials available in the App and also record the patient details of the locality they cover. The patient data collected by the health workers on the Android App will be transferred to the central data store by the health worker using the data synch option of the App.\n\nOn the Health Service Provider section, the application would contain a Web Interface, Web services, and the Central Data-store. The Web services section would help in registering the health worker details and configure the App on the mobile device of the health worker for the intended functioning (Table 1). The web services will also enable data synchronization between the mobile device and central data store. Central Data-store acts as the repository of data collected from all the health workers and acts as the basis from which various findings from the study in the form of different reports can be generated. The Web interface provides the mechanism for the study managers at the Health Service Provider section to monitor the system and generate reports from the system.\n\n\n\n1. Login → User ID for ASHA/ANM/Staff Nurse (ID should begin from 01 for each category) → Password\n\n\n\n1. Patient Id → Name of the patient → Age → Gender → Name of the city/village → Disease condition Symptom\n\n\n\n2. Name of Taluk: Site 1, Site 2, and Site 3\n\n\n\n2. No. of cases identified by the PHCW\n\n\n\n3. Name of ASHA/ANM/Staff Nurse\n\n\n\n3. No. of symptoms identified\n\n\n\n4. Gender\n\n\n\n4. No. of episodes occurred for each patient\n\n\n\n5. Phone number\n\n\n\n5. No. of follow up done\n\n\n\n6. Name of health center: PHC/CHC/SC\n\n\n\n6. Symptoms managed\n\n\n\n7. No. of cases referred\n\n\n\n8. No. of deaths → Case closed (In case of death)\n\n\n\n9. Feedback by patient and family members\n\nThe expected outcome of this study is to identify the impact of palliative care training in improving palliative care knowledge and their ability to assess palliative care needs in the community among PHCWs. To explore views of PHCWs on the facilitators and barriers for palliative care delivery in the community.\n\nAll regulatory and administrative approvals will be sought. After explaining the procedure and objectives of the research project, written informed consent from all the participants will be obtained. The questionnaires are prepared in English and Kannada. The outcome of the project will be measured by using demographic proforma, knowledge questionnaire, attitude scale, skill checklist, and validated set of questions on focus group discussion (Figure 3).\n\nThe questionnaires to be used in this project include demographic proforma, structured knowledge questionnaire on palliative care, attitude scale, and checklist for skill assessment.\n\na) The demographic proforma will be used to assess the demographic characteristics of the PHCWs such as age, gender, marital status, religion, monthly income, designation, place of work, years of experience, and area of working.\n\nb) A structured knowledge questionnaire will be used to assess the existing knowledge on palliative care among PHCWs. The questionnaire includes the areas like essential elements of palliative care, the role of the palliative care team, the role of the nurse in palliative care, nursing ethics, various symptom identification and management, communication skills, end of life care, grief & bereavement care by using an MCQs and dichotomous items and also open-ended items. The knowledge score for staff nurses, ANMs contains 30 MCQs. The scores are categorized as 26 and above (75%), 18 to 25 (50 to 74%), 17 and below (less than 50%), which indicates good knowledge, average knowledge, poor knowledge, respectively. The knowledge score for ASHA workers contains 22 items. The scores are categorized as 17 and above (75%), 11 to 16 (50-74%), ten and below (less than 50%), which indicates good knowledge, average knowledge, and poor knowledge, respectively.\n\nc) Attitude scale: The attitude of PHCWs will be measured by using the Likert scale. The scores are categorized into positive and negative attitude scores. Total 30 items with 5 Likert scores are included. The positive score of attitude scale for staff nurses, ANMs ranges from 91 to 150, and the negative score ranges from 30 to 90. For ASHA workers, the attitude scale contains ten items with five Likert scores. The positive score of the attitude scale for ASHA workers ranges from 31 to 50 and the negative score ranges from 10 to 30.\n\nd) Skill checklist: Various skills will be assessed by using a skill checklist during the training programs like colostomy care, nasogastric tube insertion and tube feeding, urinary catheterization and catheter care, oral care, tracheostomy care, wound care, prevention of bedsores, subcutaneous injection procedures, lymphedema care. The checklist for skill assessment has yes/No questions. The research team will observe the participants using the checklist while performing the procedures to assess their skills.\n\ne) Focus Group Discussion (FGD) among PHCWs from selected PHCs: questions will be asked regarding the facilitators and barriers in providing palliative care at the end of one year after implementing the palliative care training program. Thematic analysis will be used to evaluate the outcome of the focus group discussion.\n\nDescriptive statistics, inferential statistics, and thematical analysis will be used for summarising the data. Using descriptive and inferential analysis, demographic proforma, knowledge questionnaire, skill assessment questionnaire, case, and symptom identification checklist will be summarised by using SPSS 16.0. The Focus group discussion will be analyzed by using thematical analysis.\n\nSample size\n\nThe expected sample size required for the study is given below:\n\nWhere,\n\nZ = 1.96 at = 5% level of significance,\n\np = proportion of Community Health workers who would implement = 65%\n\nq = 1-p\n\nd = precision at 5%\n\nWe propose to include all the PHCWs from the selected district of the southern part of India. As per the sample size calculation, the required sample size is 830, and presently 1440 PHCWs are there in the Udupi district. However, as we aim to cover the whole district PHCs and reach all needy populations, we will take 1440 participants for the capacity enhancement program, including new staff.\n\nAdministrative permission will be obtained from Directorate General Health and Family Welfare, Karnataka state, to relieve ASHA workers and Community Health Workers for training on palliative care. Permission will be obtained from the District Health Officer and Medical Officer of all Primary Health Centres of Udupi District. Approval from Institutional Research Committee (IRC 239/2019) and Institutional Ethical Committee (IEC:164/2020) are obtained. The study is registered in the Clinical Trial Registry of India (CTRI) portal (CTRI/2020/04/024792). Informed written consent will be obtained from all the participants.\n\nThe questionnaire will be tested for its validity and reliability by using split-half reliability. The module is prepared in English and translated into Kannada, which will be sent to five experts for validation. The questionnaires and module will be finalized after making necessary modifications as suggested by the validators.\n\nThe proposed capacity building of primary care workers follows the world health organizations’ recommendation of integration of palliative care into the public health system to achieve universal health coverage. Lack of cooperation from the primary health care workers may hinder the study. PHCWs may find difficulties in approaching the patients due to the varied distribution of cancer patients in a given geographical location. Lack of follow-up of cancer patients admitted and discharged from the different tertiary care hospitals other than research settings will also be the limitation of this study. Participants may face issues related to technology-enhanced learning, like the use of the mobile app.\n\nThe study outcomes will be published through peer-reviewed journals. The results of this study will be communicated to the external funding body through a formal report.\n\nThe study started in November 2020 and will continue until 2023. Capacity building of ASHA workers and ANMs will be initiated by April 2022.\n\n\nConclusion\n\nTo the best of our knowledge, this will be the first study to assess the effectiveness of capacity building of primary care workers on the improvement of their symptom assessment and management in the Indian community setting. This research provides baseline information about palliative care needs in the community as well as possible facilitators and barriers for the implementation of the project. If this capacity enhancement is found to be effective, then the capacity-building program can be extended to state and national levels, so that palliative care services can be integrated at PHCs at affordable/free of cost.\n\nThis research could provide baseline information regarding palliative care needs in the community and even it could be a new community-based initiation taken at the doorstep of cancer patients to promote, restore, and maintain a person’s maximum level of comfort, function, and health, including care toward a dignified death.\n\n\nData availability\n\nNo data are associated with this article.\n\nFigshare: Figshare: Demographic Performa, https://doi.org/10.6084/m9.figshare.19499072 (Pai, 2022a).\n\nFigshare: Participant information sheet and informed consent for ASHA worker, https://doi.org/10.6084/m9.figshare.19499075 (Pai, 2022b).\n\nFigshare: Participant information sheet and informed consent for staff nurses, https://doi.org/10.6084/m9.figshare.19499078 (Pai, 2022c).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgements\n\nWe acknowledge the support received from the India Cancer Research Consortium (ICMR-ICRC), the department of Palliative Medicine and Supportive care, Kasturba Hospital Manipal, and Manipal Academy of Higher Education (MAHE) for their support and guidance.\n\n\nReferences\n\nAgarwal S, Perry HB, Long LA, et al.: Evidence on feasibility and effective use of mH ealth strategies by frontline health workers in developing countries: systematic review. Tropical Med. Int. Health. 2015; 20(8): 1003–1014. PubMed Abstract | Publisher Full Text\n\nBhargava R, Keating B, Isenberg SR, et al.: RELIEF: A digital health tool for the remote self-reporting of symptoms in patients with cancer to address palliative care needs and minimize emergency department visits. Curr. Oncol. 2021; 28(6): 4273–4280. PubMed Abstract | Publisher Full Text\n\nBhatnagar S, Patel A: Effectiveness of the certificate course in essentials of palliative care program on the knowledge in palliative care among the participants: A cross-sectional interventional study. Indian J. Palliat. Care. 2018; 24(1): 86–92. PubMed Abstract | Publisher Full Text\n\nCentre, N. H. S. R: Community Process- ASHA.2021a, 11.03.2021. Reference Source\n\nCentre, N. H. S. R: Training & capacity building.2021b, 25.10.2021. Reference Source\n\nChellappan S, Ezhilarasu P, Gnanadurai A, et al.: Can Symptom Relief Be Provided in the Home to Palliative Care Cancer Patients by the Primary Caregivers?: An Indian Study. Cancer Nurs. 2014; 37(5): E40–E47. PubMed Abstract | Publisher Full Text\n\nConnor SR, Sepulveda Bermedo MC: Global atlas of palliative care at the end of life.2018.\n\nDIRECTORATE GENERAL OF HEALTH SERVICESWelfare, M. o. H. F: National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke.Reference Source\n\nDIRECTORATE GENERAL OF HEALTH SERVICESWelfare, M. o. H. F: 2012. National Program for Palliative Care.Reference Source\n\nGlass M, Rana S, Coghlan R, et al.: Global palliative care education in the time of COVID-19. J. Pain Symptom Manag. 2020; 60(4): e14–e19. PubMed Abstract | Publisher Full Text\n\nGorman RD: Integrating Palliative Care into Primary Care. Nurs. Clin. N. Am. 2016; 51(3): 367–379. Publisher Full Text\n\nIbrahim FA, Nirisha L, Barikar M, et al.: Identification of Psychiatric Disorders by Rural Grass-Root Health Workers: Case Series & Implications for the National Mental Health Program of India. Psychiatry Q. 2021; 92(1): 389–395. PubMed Abstract | Publisher Full Text\n\nJayalakshmi R, Suhita C: Home-based palliative services under two local self-government institutions of Kerala, India: An assessment of compliance with policy and guidelines to local self-government institutions. Indian J. Palliat. Care. 2017; 23(1): 65–70. PubMed Abstract | Publisher Full Text\n\nJeba J, Ponissery J, Ramaswamy A, et al.: Developing Evidence-Based Clinical Guidelines in Palliative Care for Home Care Setting in India. Indian J. Palliat. Care. 2020; 26(3): 319–322. PubMed Abstract | Publisher Full Text\n\nKällander K, Tibenderana JK, Akpogheneta OJ, et al.: Mobile health (mHealth) approaches and lessons for increased performance and retention of community health workers in low-and middle-income countries: a review. J. Med. Internet Res. 2013; 15(1): e17. PubMed Abstract | Publisher Full Text\n\nKar S, Subitha L, Iswarya S: Palliative care in India: Situation assessment and future scope. Indian J. Cancer. 2015; 52(1): 99–101. PubMed Abstract | Publisher Full Text\n\nKnaul FM, Bhadelia A, Rodriguez NM, et al.: The Lancet Commission on Palliative Care and Pain Relief—findings, recommendations, and future directions. Lancet Glob. Health. 2018; 6: S5–S6. Publisher Full Text\n\nKrishnan A, Mathur P, Kulothungan V, et al.: Preparedness of primary and secondary health facilities in India to address major noncommunicable diseases: results of a National Noncommunicable Disease Monitoring Survey (NNMS). BMC Health Serv. Res. 2021; 21(1): 1–12. Publisher Full Text\n\nKumar S: Community participation in palliative care: Reflections from the ground. Prog. Palliat. Care. 2020; 28(2): 83–88. Publisher Full Text\n\nNeto JBF, de Moraes GLA , de Souza Aredes J , et al.: Building the capacity of community health workers to support health and social care for dependent older people in Latin America: a pilot study in Fortaleza, Brazil. BMC Geriatr. 2021; 21(1): 1–9. Publisher Full Text\n\nOrganization, W. H: Global Atlas of Palliative Care. 2nd ed.London: Worldwide Palliative Care Alliance; 2020.\n\nOrganization, W. H: Integrating palliative care and symptom relief into primary health care: a WHO guide for planners, implementers and managers.2018.\n\nOswal K, Kanodia R, Nadkar U, et al.: Cancer patients’ experience of oncology services in Assam, India. J. Cancer Policy. 2021; 27: 100267. Publisher Full Text\n\nPai R: Demographic Performa. figshare. Dataset. 2022a. Publisher Full Text\n\nPai R: Participant information sheet and informed consent for ASHA worker. figshare. Dataset. 2022b. Publisher Full Text\n\nPai R: Participant information sheet and informed consent for staff nurses. figshare. Dataset. 2022c. Publisher Full Text\n\nPaul S, Cree VE, Murray SA: Integrating palliative care into the community: the role of hospices and schools. BMJ Supportive & Palliative Care. 2019; 9(4): bmjspcare-2015-001092–e31. PubMed Abstract | Publisher Full Text\n\nPhilip RR, Philip S, Tripathy JP, et al.: Twenty years of home-based palliative care in Malappuram, Kerala, India: a descriptive study of patients and their care-givers. BMC Palliat. Care. 2018; 17(1): 1–9. Publisher Full Text\n\nPhilip RR, Venables E, Manima A, et al.: “Small small interventions, big big roles”-a qualitative study of patient, care-giver and health-care worker experiences of a palliative care programme in Kerala, India. BMC Palliat. Care. 2019; 18(1): 1–10. Publisher Full Text\n\nQanungo S, Calvo-Schimmel A, McGue S, et al.: Barriers, Facilitators and Recommended Strategies for Implementing a Home-Based Palliative Care Intervention in Kolkata, India. Am. J. Hosp. Palliat. Med. 2021; 38(6): 572–582. PubMed Abstract | Publisher Full Text\n\nRajagopal M: The current status of palliative care in India. Cancer Control. 2015; 22: 57–62.\n\nRamasamy Venkatasalu M, Sirala Jagadeesh N, Elavally S, et al.: Public, patient and carers’ views on palliative and end-of-life care in India. Int. Nurs. Rev. 2018; 65(2): 292–301. PubMed Abstract | Publisher Full Text\n\nSadhu S, Salins NS, Kamath A: Palliative care awareness among Indian undergraduate health care students: A needs-assessment study to determine incorporation of palliative care education in undergraduate medical, nursing and allied health education. Indian J. Palliat. Care. 2010; 16(3): 154–159. PubMed Abstract | Publisher Full Text\n\nSalins N, Johnson J, Macaden S: Feasibility and acceptability of implementing the integrated care plan for the dying in the Indian setting: Survey of perspectives of indian palliative care providers. Indian J. Palliat. Care. 2017; 23(1): 3–12. PubMed Abstract | Publisher Full Text\n\nSallnow L, Kumar S, Numpeli M: Home-based palliative care in Kerala, India: the Neighbourhood Network in Palliative Care. Prog. Palliat. Care. 2010; 18(1): 14–17. Publisher Full Text\n\nSeamark D, Blake S, Brearley SG, et al.: Dying at home: A qualitative study of family carers’ views of support provided by GPs community staff. Br. J. Gen. Pract. 2014; 64(629): e796–e803. PubMed Abstract | Publisher Full Text\n\nShepperd S, Wee B, Straus SE: Hospital at home: home-based end of life care. Cochrane Database Syst. Rev. 2011; 7. PubMed Abstract | 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; 71(3): 209–249. PubMed Abstract | Publisher Full Text\n\nVallath N, Rahul RR, Mahanta T, et al.: Oncology-Based Palliative Care Development: The Approach, Challenges, and Solutions From North-East Region of India, a Model for Low- and Middle-Income Countries. JCO Glob. Oncol. 2021; 7: 223–232. PubMed Abstract | Publisher Full Text\n\nViswanath V, Digumarti L, Raju NS, et al.: Organising home-based palliative care services: A quality improvement project at the homi Bhabha cancer Hospital and Research Centre, Vishakhapatnam. Indian J. Palliat. Care. 2021; 27(2): 197–203. PubMed Abstract | Publisher Full Text\n\nWang Q, Chan IK, Lou VW: Effectiveness of a Holistic Capacity-Building Program for Volunteers in Community-Based End-of-Life Care. Res. Soc. Work. Pract. 2020; 30(4): 408–421. Publisher Full Text\n\nYeager A, Lavigne AW, Rajvanshi A, et al.: Cansupport: A model for home-based palliative care delivery in India. Ann. Palliat. Med. 2016; 5(3): 166–171. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "146042",
"date": "15 Aug 2022",
"name": "Rakesh Garg",
"expertise": [
"Reviewer Expertise Onco-Anaesthesiology and Palliative 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\nImproving symptom assessment and management in the community through capacity building of primary palliative care: A study protocol of exploratory research:\nThe proposed study appears to have translational value in improving palliative care delivery and identifying gaps and role of grass root level workers who are already existing but need to be brought into the streamlining of palliative care.\nPlease elaborate on various tools and instruments - whether there are existing validated tools or new tools will be developed. In this case, elaborate on the process of tool development and its validation. Also emphasize on the compliance assurance of the ASAH cadres with regards to the implementation of various tools and apps.\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? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
},
{
"id": "255915",
"date": "29 Mar 2024",
"name": "Sarah Mollman",
"expertise": [
"Reviewer Expertise Palliative care education",
"palliative care delivery to rural oncology patients."
],
"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 and research objectives are clear. The background and significance (rationale) of the research is difficult to follow, skipping back and forth between points (example, rationale for the study population, use of mobile app, and importance of palliative care).\nThe figures were very helpful in understanding your study and methods. I recommend including information about the security of the app. On page 7, it states it will be added to PHCW's mobile devices. Are these personal devices and what is the security if so? What is the security of the data in local and central storage as well as transferring between the two? How are you protecting the participants' privacy and confidentiality?\nAre the knowledge and attitude questionnaires new? If so, how were they developed? Did the process follow best practices? If not, include information on reliability and validity.\nYour population size is excellent and can lead to a strong study. How realistic is obtaining 58% of this population to participate in your study to reach the expected sample size? Is there literature to support 58% of a population completing a study? What is your goal for sample size of the focus groups?\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": []
},
{
"id": "177647",
"date": "11 Sep 2024",
"name": "Neetha Kamath",
"expertise": [
"Reviewer Expertise Home based care for menopausal women to address the issues of menopause"
],
"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 literature review is extensive and need of the study is explained. The study addresses the current issues related to the problem. The methodology chosen meets the objective of the study. The ethics approval is obtained as per the ICMR guidelines. The sample size and data analysis plan is appropriate to the study protocol.\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": "12420",
"date": "13 Sep 2024",
"name": "Radhika Pai",
"role": "Author Response",
"response": "Dear Madam, Thank you for your approval of this study protocol."
}
]
}
] | 1
|
https://f1000research.com/articles/11-733
|
https://f1000research.com/articles/10-72/v1
|
04 Feb 21
|
{
"type": "Research Article",
"title": "Level of development, foreign direct investment and domestic investment in food manufacturing",
"authors": [
"Justice Gameli Djokoto"
],
"abstract": "Background: Whilst the literature on the complementarity and substitutability of foreign direct investment (FDI) on domestic investment (DI) is not uncommon, the facet of food manufacturing is non-existent. This paper fills this void by investigating the effect of FDI on DI in the food manufacturing sector for developing, economies in transition and developed countries. Methods: Using an unbalanced panel data of 49 countries from 1993 to 2016, from FAOSTAT, estimated by the system generalised method of moments (GMM), the Wald statistics for the short and long-run effects of FDI on DI were computed for the development groups. Results: Developed economies experienced a crowd-out effect of FDI on DI in the short run, whilst the others experienced no significant effect. In the case of the long run, food manufacturing sectors of all three development groups exhibited a crowd-out effect. The effect in the long run for all development groups together is a crowd-in. Analysing all country groups together could mask the results of the various country groups. Conclusions: A review of investment policies to priorities FDI entry mode that favour domestic investment is needed. Improvement of the investment regulatory and administrative efficiency among others are recommended.",
"keywords": [
"Crowding-in",
"crowding-out",
"developing countries",
"developed countries",
"food manufacturing",
"foreign direct investment",
"domestic investment."
],
"content": "Introduction\n\nIn food manufacturing, relatively bulky, perishable and typically inedible raw materials are converted into more useful, shelf-stable and palatable foods or potable beverages with the aid of various unit operations and technologies (FAO, 2010; Stadler et al., 2020). Food processing contributes to food security by minimising waste and loss in the food chain and by increasing food availability and marketability. Food manufacturing also improves food quality and safety (FAO, 2010; Leonard et al., 2020; Phan et al., 2020; Stadler et al., 2020).\n\nGlobal gross domestic product (GDP) of food manufacturing for 2017 is estimated at US$1.68 trillion (FAOSTAT, 2020). The sector appears to be relatively more important to developing and economies in transition as it constitutes 3.03% and 3.11% respectively of GDP than developed countries (2.10%) (FAOSTAT, 2020)1. As the sector needs more investments for growth and development (Hine, 2015; Primanthi, 2015), many countries have pursued policies to attract foreign direct investment (FDI) into the food manufacturing sectors of their respective economies to reap benefits including investment accumulation, technology transfer and job creation (de Mello Jr, 1997; Farla et al., 2016; Kosova, 2010). Aside from these benefits, there is evidence that inflow of FDI compliments domestic investment (DI) (Farla et al., 2016; Mileva, 2008) or substitute DI (Budang & Hakim, 2020; Oualy, 2019) for whole economy cases as well as the agricultural sector (Djokoto et al., 2014). Agosin & Machado (2005) and Gallova (2011) have reported a neutral effect of FDI on DI. A complementary effect of FDI on DI is desirable as an increase in FDI promotes further domestic investment. In the case of the substitution effect, increased FDI decreases DI, which could be detrimental. In the case of the neutral effect, beyond the economic benefits stated earlier, there are no additional benefits related to DI. In light of the foregoing, what is the evidence of FDI on DI for the food manufacturing sector of different country groups?\n\nPagoulatos (1983) studied the effect of FDI in US food and tobacco manufacturing on domestic economic performance. Djokoto et al. (2014) investigated the effect of FDI on DI of agriculture in Ghana. In cross-country studies, Agosin & Machado (2005) studied the effect of FDI on DI for whole economies of developing countries, Budang & Hakim (2020) for Asian countries, Gallova (2011) and Mileva (2008) on transition economies, Pilbeam & Oboleviciute (2012) for EU countries, and Wang (2010) for developed and developing countries. Whilst the cross-country studies focused on whole economies, these were limited to transition, developing, or developed and developing countries. The single-country studies failed to address the effect of FDI on DI for food manufacturing. This paper fills these gaps by investigating the effect of FDI on DI in the food manufacturing sector for developing, economies in transition and developed countries.\n\nThe implications of the effects of FDI inflows on DI are issues that require increased attention by international economists and the facet on food manufacturing concerns agricultural economists as well. Analysing this topic requires linking development and investment theories within the food manufacturing sector. Understanding the issues surrounding the effect of FDI on DI in the food manufacturing sector across countries at varying levels of development is essential in understanding short- and long-term adjustments facing investors and economic managers as food systems become more integrated into the global economy.\n\nIn what follows, the existing theories and empirical evidence regarding the effect of FDI on DI are presented. The section on results and discussions is preceded by the outline of the data, modelling and estimation procedure. The conclusions and recommendations complete the paper.\n\nIn line with the key issues in the paper, the theoretical review is constituted into four parts. The first, theories of development seek to explain the differences in the level of development of countries, one of the foci of the paper. Space is provided for FDI theories as these explain the role of the key variable that influences DI. DI is the dependent variable, thus deserves space, hence the investment theories. To tie-in, the interaction of FDI and DI, the theoretical explanation of the link between FDI and DI is outlined as well.\n\nMany theories have been propounded regarding economic development. These have been classified differently. The classification used here is modernisation, dependency, world systems and globalisation. Modernisation theory uses a systematic process to move underdeveloped countries to a more sophisticated level of development (Reyes, 2001). This theory which stresses the importance of political development in the progress and climactic improvement of a nations’ economic standing, also acknowledges social and cultural reforms. Further, it seeks to explain inequality within or between states by identifying different values, systems and ideas held by different nations (Martinussen, 1997). Also, it gives attention to the shift of modern technology and development institutions and labour habits complementary to industrial production (Chase-Dunn, 1975).\n\nDependency theory that seeks to improve modernisation theory, combines elements from a neo-Marxist theory and adopts a revolution of underdeveloped nations model (Reyes, 2001). This, together with the Marxist position seeks to explain the origin of surpluses, the basis of theoretical evaluation of progress, and inequality. The divide between developed and under-developed countries is well established. The reason for the difference between the divide and what interventions are required to narrow the divide engages the attention of this theory. (Haque, 1999; Muuka, 1997; Shen & Williamson, 2001; Todaro, 2000).\n\nThe \"World System\" is multiple cultural systems with a single division of labour. The basic feature of this system is having a pool of labour in which different divisions and areas are dependent upon each other in exchanging the provisions of those areas (Wallerstein, 1974). In using other levels of quantitative analysis, this theory argues that international trade specialisation and transfer of resources from less developed countries to developed countries prevents development in less developed countries by making them rely on core countries and by encouraging peripheralisation (Szymanskiv, 1982). The theory views the world economy as an international hierarchy of unequal relations. Through the world system, a country can change its position in the global hierarchy (Szymanskiv, 1982).\n\nGlobalisation as a theory of development uses a world mechanism of greater integration with emphasis on the sphere of economic transactions (Reyes, 2001). Whether as an event of interdependence throughout different countries of the world in different aspects of communication, trade, and finance or continuous and widespread unification among different countries, it focuses on communications and international ties directed at cultural and economic factors in communication systems. This theory explains inequality by identifying cultural and economic factors in global connection (Zineldin, 2002). Globalisation endangers global competition. Whilst this could hurt especially developing countries, firms in developing countries can respond by increasing production and efficiency thereby improve their economic situation. Also, rationalisation of production on a global scale and the spread of technology results from globalisation (Intriligator, 2004; Stiglitz, 2004a; Stiglitz, 2004b; Tanzi, 2004).\n\nForeign direct investment theories can be viewed from three perspectives. The first perspective, which is internationalisation theory, explains why firms often prefer FDI to license as a strategy for entering a foreign market (Hymer, 1976). In this theory, FDI is preferred for licensing and exporting. Licensing may result in a firm giving away valuable technological expertise to a potential foreign investor at a fee. This does not give a firm control over manufacturing, marketing, and strategy in a foreign country that may be required to maximise its profitability. Unfortunately, the competitive advantages of management, marketing, and manufacturing capabilities are not amenable to licensing.\n\nThe second perspective relates to the patterns of FDI. In oligopolistic industries, firms invest in other countries as a strategy by following their domestic competitors (Knickerbocker, 1973). Related to this is the product life cycle hypothesis (Vernon, 1966). Firms invest in other advanced countries when local demand in those countries grows large enough to support local production. Production is subsequently shifted to developing countries when product standardisation and market saturation gives rise to price competition and cost pressures.\n\nThe third perspective is Dunnings’ eclectic paradigm. Dunning (1977); Dunning (1988); Dunning (2001) stated that the extent, geography, and industrial composition of foreign production undertaken by the multinational enterprise is determined by the interaction of three sets of interdependent variables which, themselves, comprise the components of three sub-units, namely; ownership, location and internationalisation (OLI). All other factors unchanged, the greater the competitive advantages of the investing firms, relative to those of other firms, the more they are likely to be able to engage in or increase, their foreign production. This is the ownership competitive advantage. For the location, the more the immobile, natural or created endowments, needed by the firms to use jointly with their competitive advantages, favour a presence in a foreign rather than a domestic location, the more firms will choose to supplement or take advantage of their ownership specific advantages by engaging in FDI. The multinational enterprise, thus, would undertake activities to add value to their operations. Internalisation, the final competitive advantage, offers a framework for evaluating alternative ways in which firms may organise the creation and exploitation of their core competencies. These range from buying and selling goods and services in the open market, through a variety of inter-firm non-equity agreements, to the integration of intermediate product markets and outright purchase of a foreign corporation.\n\nThe many theories of investment include accelerator theory, cash flow theory, neoclassical theory, modified neoclassical theory and Q theory. Chenery (1952); Clark (1917) and Koyck (1954) among others, emphasised the accelerator model that sought to explain business cycles. Eisner & Strotz (1963); Eisner & Nadiri (1968) incorporated profits and investment equation into the accelerator theory.\n\nCashflow, the resources left after paying dividends to shareholders determines investment from internal sources. Past profits drive future investment decisions (Kuh, 1963; Meyer & Kuh, 1955; Strong & Meyer, 1990). The decision to invest is informed by the cost of capital which in turn is driven by the profit maximising behaviour of the firm (Jorgenson, 1963; Jorgenson, 1971; Modigliani & Miller, 1965). Biscoff (1971) extended the neoclassical theory to show that it is possible to alter the capital-output ratio so that later, the substitution effect of output goes to zero. Consequently, the investment can be effectively induced by changes in the capital-output ratio.\n\nThe Q theory of investment notes that, if investors seek to maximise the market value of the firm, they will add to their capital stock whenever the marginal addition to the firm’s market value exceeds the replacement cost of the capital stock (Brainard & Tobin, 1968; Tobin, 1969). This theory is driven by the ratio of the market value of capital to its replacement cost, unlike the neoclassical theory that is driven by the cost of capital.\n\nThe fourth theoretical perspective is the interaction between FDI and DI. Markusen & Venables (1999) theorised the relationship between multinational enterprises (MNEs) and domestic firms on the entry of MNEs to be a competition effect and a linkage effect. Regarding the competition effect, the entry of MNEs increases competition in the final product industry and reduces the profitability of domestic firms in the same industry. Consequently, domestic firms do exit the market. For the linkage effect, the entry of multinational corporations (MNCs) could cause the demand for domestic production of intermediate inputs to rise. This tends to create an increased number of domestic firms in the intermediate inputs industry. Barro & Sala-i-Martin (2004) have also acknowledged these effects.\n\nBarrios et al. (2005) posit that as the number of MNEs increases in the host country, the number of domestic firms might drop first and then rise. Assume that MNEs enter the downstream (final product) market, an increase in the total number of firms (both foreign and domestic) in the downstream industry will decrease the price level for the final product. The possibility is the reduction of profit for all firms and thereby forcing some domestic firms to exit. This would happen if the MNEs are more productive than domestic firms. On the other hand, the possible linkage effect can increase the number of upstream domestic firms and then reduce the cost of production in the downstream industry for both MNEs and domestic firms. Therefore, the number of domestic firms in the host country will eventually go up.\n\nThe effect of FDI on DI could be complementary, substitutional or neutral. In the developing country context, Agosin & Machado (2005); Ahmad et al. (2018); Djokoto (2013); Josue et al. (2014); Oualy (2019) and Wang (2010) have reported the neutral effect of FDI on DI in developing countries, in the short run. Kim & Seo (2003) found a significant crowd-in effect of FDI on DI for the whole of Korea. In the long run, whilst Agosin & Machado (2005); Morrissey & Udomkerdmongkol (2012) and Mutenyo & Asmah (2010) reported crowding out effect of FDI on DI for Latin America, developing countries and sub-Saharan Africa respectively, Djokoto et al. (2014) and Farla et al. (2016) found crowding-in effect of FDI on DI for Ghanaian agriculture and developing countries respectively. Djokoto et al. (2014) attributed the positive effect to technology diffusion and spillover of management know-how by MNEs and vertical inter-firm linkages with domestic firms.\n\nMileva (2008) found a crowding-in effect of FDI on DI for economies in transition using data from 1995–2005 in the short run and long run, despite the presence of less developed financial markets and weaker institutions. Cooperation instead of competition can be adduced for the crowd-in effect. Jude (2019) and Kejžar (2016) reported switching effects of FDI on DI for transition economies; short-run crowding-out effect to long run crowding-in effect. The magnitude of the possible linkage and spillover effects over time overcomes the initial competition effect. Also, the period for the long run is such as would allow completed plants to run for some time to generate output and associated benefits. Technology, knowledge transfer, employment and expenditure on social responsibility would come to fruition.\n\nGallova (2011) reported that FDI exerted no effect on DI for Bulgaria and Romania but crowding in effect for Croatia and Slovenia. For the Balkans, for the period 1993–2009, the effect was crowding out. Gallova (2011) explained that foreign companies do employ the services of the same suppliers as their parent companies that are not in the host country. MNEs tend to also bring with them to the host country, foreign producers from which they take the components necessary for their production. Additionally, foreign-owned companies are so strong in individual sectors and effectively functioning. When domestic firms fail to assert themselves effectively and establish cooperation with MNEs they tend to be crowded out of the market. In the long run, however, based on the panel data from 1993–2009, Gallova (2011) found no long-run effect for the Balkans and the individual countries. For the Czech Republic and Hungary, Mišun & Tomšík (2002) concluded on a long run crowding in effect but the crowding out effect for Poland. Other studies on developed countries also concluded on mixed outcomes regarding FDI and DI. Pilbeam & Oboleviciute (2012) found a short and long-run crowd-out effect for EU-15 (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Portugal, Spain, Sweden and United Kingdom) but no effect for EU-12 (Bulgaria, Czech Republic, Estonia, Cyprus, Latvia, Lithuania, Hungary, Malta, Poland, Romania, Slovenia, and Slovakia). In the work of Polat (2017), the effect of FDI on DI was neutral for Organisation for Economic Co-operation and Development (OECD) countries for data covering 2006 to 2013, just as Wang (2010) for developed countries in the long run. In the short run, however, Wang (2010) found crowding out effect for developed countries.\n\nFrom the empirical review, some studies dwelled on whole economies across countries whilst others covered one or single economy. One single economy study addressed agriculture. Food manufacturing, the offtaker of agricultural production and the product supplier for marketing in the agribusiness value chain, has not been given attention. This paper focuses on this.\n\n\nMethods\n\nSome previous studies used time-series data (Chen et al., 2017; Djokoto, 2013; Djokoto et al., 2014; Gallova, 2011; Kim & Seo, 2003) whilst others employed panel data (Agosin & Machado, 2005; Ahmad et al., 2018; Budang & Hakim, 2020). This study used panel data. The data consist of 49 countries for the period 1993 to 2016 (Table 1). The description of the data and measurement are outlined in Table 2. All the data was obtained from FAOSTAT (2020). The panel structure enables pooling the observations for each unit over time resulting in more observations and smaller standard errors. Further, the data structure allows for analysing the dynamic behaviour of units and dynamic models; using lagged outcome variables as explanatory variables (Greene, 2003; Gujarati & Porter, 1999; Wooldridge, 2002).\n\nNote: The development designations are based on United Nations (2020). World Economic Situation and Prospects, Statistical annex\n\nNote: 1. All data from FAOSTAT: http://www.fao.org/faostat/en/#home. The development designations are based on United Nations (2020). 2. * These variables went into Equation 2 as latent variables (reference).\n\nAgosin & Machado (2005) developed a theoretical model based on neo-classical investment model using partial adjustment of capital stock and adaptive expectations of economic growth in which FDI has been included. This model has been applied in the study of the relationship between FDI and DI (See for example, Budang & Hakim, 2020; Oulay, 2019; Pilbeam & Oboleviciute, 2012). The Agosin & Machado (2005) model is adapted and specified in Equation 1.\n\n\n\nWhere εi,t is the error term.\n\nTo account for the levels of development of the countries in the data, for which reason the effects of FDI on DI may differ, Equation 1 is re-specified:\n\n\n\nAll the variables and their sources are described in Table 2. The classification of countries based on the level of development reflects the basic conditions (United Nations, 2020). It does indirectly capture some macroeconomic variables that could otherwise have been included as control variables.\n\nLet βSTk be the short run effects, where k=1,2, 3,4 are developing country, economies in transition, developed countries and all development groups respectively. Then,\n\n\n\nfor developing countries.\n\nIn the case of transition economies,\n\n\n\nWhilst for developed countries,\n\n\n\nFor the three country-groups’ effects, the null hypothesis for the short run is\n\n\n\nFailure to reject these null hypotheses with a chi-square test implies FDI has no short-run or contemporaneous effect on DI. Rejection of the null hypothesis and that βSTk > 0 means a contemporaneous crowd-in effect of FDI on DI. Alternatively, βSTk < 0 means a contemporaneous crowd-out effect of FDI on DI.\n\nThe long-run effect is represented by β^LT1, where k=1,2,3,4 as previously. Then, the null hypotheses for the long-run effects2 are\n\n\n\nfor developing countries. For transition economies\n\n\n\nIn the case of developed countries,\n\n\n\nFor all development groups in the long run,\n\n\n\na. With a chi-squared test, if it is not possible to reject the null hypothesis that β^LT1=1, then, in the long run, an increase in FDI of one currency unit, becomes one currency unit of additional total investment. Stated differently, investment by MNEs simply matches one-to-one to investment by domestic firms, and no macroeconomic externalities are stemming from FDI.\n\nb. If the null hypothesis, β^LTK = 1 is rejected and β^LTK > 1, this is evidence of the long-run crowd-in effect of FDI by DI. Thus, in the long run, one additional currency unit of FDI becomes more than one additional currency unit of total investment.\n\nc. Now, consider the case that the null hypothesis, β^LTK = 1 is rejected and β^LTK < 1, there is then a long-run crowd-out effect. One additional currency unit of FDI leads to less than one currency unit increase in total investment. This means there is a displacement of DI by FDI.\n\nThe pertinent literature used ordinary least squares (OLS) estimator (Chen et al., 2017; Djokoto, 2013; Djokoto et al., 2014; Gallova, 2011; Kim & Seo, 2003). Agosin & Machado (2005); Pilbeam & Oboleviciute (2012) and Polat (2017) used a generalised method of moments (GMM). GMM has some weaknesses. First, in the presence of the lagged dependent variables on the right-hand side of the equation and the time-invariant country-specific factors, the fixed-effects estimator would yield inconsistent estimates because of the correlation between the lagged dependent variable and the error terms. Taking the first differences to remove the time-invariant country-specific factors still results in a correlation between the error term and the DI. Second, FDI inflows are likely to be endogenous and determined jointly with the DI. Impliedly, there is a two-way relationship between DI and FDI (Al-sadiq, 2013; Arellano & Bond, 1991; Arellano & Bover, 1995). The system-GMM estimator enables controlling for the unobserved country-specific factors and solves the correlation problem by using a set of internal instruments based on the assumption of no second-order serial correlation in the first-differenced idiosyncratic errors, and the independent variables are weakly exogenous. In this way, the estimated coefficients would then not be subject to bias from an omitted variable. Using a series of internal instrumental variables based on lagged values of the dependent and independent variables, the system-GMM estimator solves the endogeneity problem as well. All these are accomplished by combining in one system, the regression in differences with the regression in levels under the assumption that there is no correlation between the differences of the right-hand side variables and the unobserved country-specific effects (Al-sadiq, 2013; Arellano & Bond, 1991; Arellano & Bover, 1995; Blundell & Bond, 1998). The assumption of no serial correlation is testable. Whilst first-order autocorrelation (AR(1)) of the errors is permissible, that of the second-order (AR(2)) is inadmissible. As internal instruments are used, the Sargan test tests whether the overidentifying restrictions are valid. Rejection of the null hypothesis would indicate that the instruments are not valid, therefore, the estimates are not reliable.\n\n\nResults and discussion\n\nDue to the unbalanced nature of the panel, the number of observations for the variables is not the same. The observations ranged from 611 to 1,344. The growth rate (GR) for food manufacturing value-added averaged about 3% (Table 3). The means of DI_1 for developing, transition and developed economies were respectively, 0.0369, 0.0079 and 0.1083. These are statistically distinguished (Table 4). Thus, developed countries on average accumulate about 11% of food manufacturing domestic investment as GDP whilst developing countries manage about 4%. Economies in transition posted less than 1%. The positive value of FDI implies that there has been a transfer of FDI from one economy to the other. This is symptomatic of international capital transfer (Dunning, 1977; Dunning, 1988; Dunning, 2001; Reyes, 2001). The means of FDI_1 of the development groups is likewise statistically distinguished. However, the values constitute less than 1% of food manufacturing value-added. As in the case of DI, developed countries post the higher value of 0.99%. Transition economies, however, seem to attract more FDI dollars of food manufacturing GDP than developing economies.\n\nAs the key variables are FDI and DI, linear correlation coefficients were computed (second panel of Table 4). There is a significant positive correlation between FDI and DI for each developing country group. For the country groups together, however, the positive relationship is not statistically distinguishable from zero. Similarly, in the long run, there are positive significant relationships between FDI and DI but no significant relationship for all country groups. Although the linear correlation coefficients could give an early indication of effect between the variables, the influence of other variables during the estimation process could change the effect shown by the linear correlation coefficient.\n\nUp to 15 lags were estimated for the system GMM. This is because lag length is known to influence the size of estimates especially, coefficients and standard errors, that are crucial in the calculation of the short and long-run effects of FDI on DI. Based on the number of significant coefficients and the level of significance lag 4 was selected. The selected system GMM results are reported in Table 5 as model 4.\n\nTo establish the consistency of the estimates of model 4, four other models; 1–3 and 5, were estimated. Model 1 includes only the key variables; the lags of DI and the FDI and its lags. In model 2, GRs are added to model 1. In model 3, the GRs are dropped, and the TIME variables added. Model 5 includes all variables as in model 4, but without some observations. Data of large economies could influence the overall results. Thus, for developed countries, the observations for India and Brazil were dropped. For economies in transition, Russia was dropped whilst the United States of America was dropped from the observations of developed economies (Table 1). The only departures are FDI_TRS1 for model 1, FDI_TRS for model 2, and FDI_2 and FRI_TRS for model 5 (Table 5). For model 1, the coefficient of the variables is weakly significant at 10% whilst those for all other models are statistically insignificant. For model 2, the coefficient of the variable is statistically insignificant together with that of model 5 but the coefficients of the variable for all models are statistically significant at either 1% or 10%. For model 5, the coefficient for FDI_2 is statistically insignificant, whilst one of the lag 2 of FDI is statistically significant at 5% whilst the other three are significant at 10%. It is instructive to note that, despite these minor departures, the size and sign of the magnitudes of the coefficients are comparable. Thus, generally, the estimates are not sensitive to the changes in variables and observations and are consistent and robust.\n\nAs the goal of the estimations is to ascertain the short and long-run effects of FDI on DI, the estimates of model 1 – 5, were used to compute the effects (Table 6). The short and long-run effects are consistent across all five models for developing and developed economies and for the long run for economies in transition. The only departures are for the short run in the case of transition economies; statistically significant effects for model 1 and model 3. This is not surprising. Transition economies in the data are made-up of three countries; Armenia, Kazakhstan and the Russian Federation (Table 1). Thus, the results of the group are more likely to be responsive to the deletion and inclusion of variables and observations than those country groups with larger numbers. Combining all the country groups, the short-run effects for model 1 differ from those of other models. Also, the statistics of the long-run effect of model 5 is statistically insignificant, unlike others that are statistically significant, although the magnitude is like others. Model 5 has two coefficients that were statistically insignificant more than the other models, suggesting high standard errors. This certainly contributed to the statistically insignificant Wald statistic. Overall, however, the results of the short and long-run effects are generally consistent and robust to the estimations of model 4, the standard.\n\n\nDiscussion of estimations\n\nThe AR(1) (Autoregressive 1) and AR(2) (Autoregressive 2) statistics fall within expectations, first-order serial correlation with no second-order serial correlation (Table 7). The Sargan statistics is also statistically insignificant. That is the failure to reject the null hypothesis that the instruments are not valid. Impliedly, the estimates are reliable.\n\nNote: 1. Standard errors in parentheses. 2. *** p<0.01, ** p<0.05, * p<0.1\n\nThe positive and statistically significant TIME coefficient suggests annually, the ratio of DI to GDP in food manufacturing increases by 0.09% (Table 7). Thus, although the countries in the development groups have significantly different levels of DI, collectively, the DI is rising. This is in line with the notion that current years’ investments are explained by previous years’ investments (Hall & Jorgensen, 1967). This contrasts with the negative coefficient for whole economies of developing countries (Agosin & Machado, 2005) and developed countries (Wang, 2010). Both the one- and two-year lags of growth of food manufacturing value-added coefficients suggest for unit increases GR_1 and GR_2, the DI ratio increases by at least 2%. This is expected as increased income from food manufacturing can be channelled into savings. This would then become investable funds for the sector. This result also confirms the theoretical position that the level of output is one of the drivers of the investment function (Jorgenson, 1963).\n\nThe dynamic effects of FDI on DI are presented in Table 8. The null hypothesis that the statistic of 0.0056 is different from zero could not be rejected. Thus, there is no short-run effect of FDI on DI in food manufacturing for developing countries. This result is supported by the evidence from the existing literature on whole economies of individual economies and groups of economies (Agosin & Machado, 2005; Ahmad et al., 2018; Djokoto, 2013; Josue et al., 2014; Oualy, 2019; Wang, 2010). The findings of Kim & Seo (2003) however, disagree with this result.\n\nIn the case of the long run, the null hypothesis that the Wald statistic value of 0.3711 is indistinguishable from 1 was rejected at a chi-square value of 9.16. Since the statistic is less than 1, there is a crowd-out effect in the long run for developing country food manufacturing. For one dollar increase in FDI into food manufacturing, DI in the food manufacturing sector increases by 0.37 (less than one dollar). This is like the findings of Agosin & Machado (2005) for Latin America, Budang & Hakim (2020) for Asia, Morrissey & Udomkerdmongkol (2012) for developing countries, Mutenyo & Asmah (2010) for sub-Saharan Africa countries and Oualy (2019) for Cote d’Ivoire. Josue et al. (2014) and Kim & Seo (2003) however, found a neutral effect whilst Wang (2010) and Farla et al. (2016) reported crowd-in effect.\n\nFor economies in transition, the results are akin to that of the developing countries; no effect in the short run and crowd-out effect in the long run. The exception is that the statistics are larger than those of the developing countries. This suggests the extent of crowding out is less severe for transition economies than for developing economies. In the case of the long run, one dollar increase in FDI will lead to 0.64 dollars (less than one dollar) increase in DI into the food manufacturing sector. Whilst the short-run result agrees with Jude (2019) and Kejžar (2016), it departs from that of Mileva (2008), who found a crowd-in effect for transition economies. However, in the long run, Mileva (2008) found a neutral effect for transition economies.\n\nTurning to developed countries, there is crowd-out for both short-run and long-run effects. For the latter effect, one dollar increases in FDI into food manufacturing results in a decrease of 0.015 dollars in DI. Crowd-out estimates with negative values are more detrimental than those with positive values. In the case of the former, there is an actual decrease in DI whilst for the latter, the magnitude is an increase albeit less than one. The short-run crowd-out found for food manufacturing in developed countries agrees with that found by Wang (2010) for the whole economy for developed countries. Whilst the short-run result departs from those of the developing and transition economies, that for the long run is similar. Further, the coefficient for the long run is slightly higher than that of economies in transition. This result is like that of Mišun & Tomšík (2002) for Poland but departs from the Czechia and Hungary results from Mišun & Tomšík (2002); Pilbeam & Oboleviciute (2012) for EU-12 who reported crowd-in effects and the neutral effect for developed economies by Wang (2010).\n\nSome reasons can be adduced for the long run crowd-out effects. In the case of developed economies, over the study period, they have witnessed significant mergers and acquisitions (M&A). This can be situated within development and FDI theories (Dunning, 1977; Dunning, 1988; Dunning, 2001; Intriligator, 2004; Stiglitz, 2004a; Stiglitz, 2004b; Tanzi, 2004). Transfer of assets from domestic firms to MNEs means loss of the record of DI in food manufacturing particularly in cases where proceeds from acquisitions are not channelled into new food manufacturing facilities. Thus, M&As by foreign firms in host countries could also lead to crowd-out effects although not so much the case for greenfield investments (Ashraf & Herzer, 2014; Punthakey, 2020; UNCTAD, 1998). Secondly, MNEs are known to also set up sister companies within the host country or import inputs from affiliate and non-affiliated companies abroad (Gallova, 2011). This deprives host country firms’ custom of the MNEs in the host country.\n\nFor developing and economies in transition, the above and other reasons account for the long-run effects. First, developing and transition economy countries do engage in food manufacturing using domestic resources and investments. Attracting foreign investment presupposes local investments are inadequate based on the existing policy environment and conditions. Therefore, there will be a need for more attractive conditions to woo foreign investment. As a result, foreign investors tend to enjoy some benefits which may not be available to local investors.\n\nSecond, is the mode of entry; mergers and acquisitions. Through M&As, the original business ceases to exist. In cases where the previous shareholders do not re-invest in food manufacturing, this could result in crowd-out of domestic investment. Third, foreign firms could import inputs from affiliate and non-affiliated companies abroad (Gallova, 2011). Such actions reduce market opportunities for host country firms. Not only do these firms fail to increase output and thereby re-invest, the local firms lose market. This could result in complete shutdowns.\n\nFourth, is the macroeconomic dimension. Domestic currency can depreciate partly due to periodic profit transfers by MNEs and opening of the financial markets. Local firms that do not export would have difficulty remaining in business as re-investments will become more expensive (Desai et al., 2004). The fifth is the weak investment regulation environment in some countries (Ufimtseva, 2020). Whilst these could lead to delays in translating FDI on the balance of payments into investments, the weak investment regulation environment could have other effects. Failure to ensure MNEs comply with domestic investment guidelines would lead to delay in realising the effects of FDI in the host economy; job creation that would lead to increases in income that would transmit to savings and consequently investments. MNEs could flout requirements for joint ownership arrangements.\n\nFinally, lower managerial acumen, consequent lower performance of local firms than foreign firms, and failure of domestic firms to update technology could make it difficult for host country firms to become competitive hence, could be crowded out (Djokoto, 2013; UNCTAD, 2015). This reflects the competition effect (Markusen & Venables, 1999).\n\nCombining all three development groups, the short-run effect coincides with those of developing and transition economies; no significant effect. The effects for the latter two certainly influenced the short-run effect for all three economy-groups more than that of the former, developed economies. Statistical and economic and administrative reasons can be adduced to explain the overall short-run results. The standard errors of the long run statistics are high relative to the coefficients for the short run, in some cases, covering the coefficients almost two times. This accounted for the insignificant effect of FDI on DI in the short run for developing and economies in transition. From the economics and administrative perspective, resource acquisition in the host country could take some time to materialise just like regulatory and administrative processes. In the same vein, the setting up of processing facilities could last more than a year. Therefore, multinational enterprises may fail to transform all FDI into investment in the sense of the national account (Agosin & Machado, 2005). Thus, the economic effects of FDI on DI has a transmission trajectory that can only be transcended over lapsed time. In developing and transition economies where there could be significant regulatory and administrative inefficiencies, these time lags can be pronounced. In the light of these, statistically significant short-run effects of FDI on DI are unlikely.\n\nIn the long run, one dollar increases in FDI into food manufacturing leads to 1.7731 dollars (more than one dollar) increase in DI. It is the crowd-in effect for food manufacturing sector jointly. The long-run result agrees with the findings of Jude (2019) and Kejžar (2016) for transition economies, Pilbeam & Oboleviciute (2012) for EU12 and Wang (2010) for least developed countries. Although the long run crowd-in effect is desirable, the result departs from the long run crowd-out effect for each of the development groups. The departure, from the development groups, is rather interesting yet plausible. As the computation of the long-run effect is not an arithmetic average for which there should be a less than 1.00 value, but a statistical summation of the interaction of the coefficients with the standard errors (the Wald statistic), the more than 1.0 value is an acceptable outcome. Six out of the nine coefficients of FDI were positive. However, a closer examination revealed that the sizes of the positive coefficients were far larger than that of the negative coefficients. The DI coefficients were similar, two coefficients had negative signs but the other four had positive signs. Together, the size of the positive coefficients exceeds that of the negative coefficients. The effects of the DIs result in a small increase in the sum of the DI. Adding these to the coefficients of FDIs in Equation 10, produced a value greater than 1. The departure from the economic grouping results also confirms the approach of the paper to segregate the analysis into levels of development. Indeed, the total sample results would have masked the group results that would have led to a one-size-fits-all recommendation. Thus, different policy propositions will be required for the various development groups.\n\nThe overall crowd-in effect can be explained in the literature. Foreign direct investment is known to promote knowledge, technology transfer, exports expansion, product and process innovation (Djulius, 2017; Jawaid et al., 2016; Jin et al., 2019; Mohanty & Sethi, 2019; Schneider & Wacker, 2020; Viglioni & Calegario, 2020). Whilst employees could share knowledge on the job, labour mobility within the food manufacturing sector (from MNEs to domestic firms), would also lead to knowledge diffusion. Technology transfer through technology transfer agreements and licensing (Hymer, 1976) creates an opportunity to induce investment in the domestic economy. Undoubtedly, the entry of MNEs creates some level of competition. Competition in output markets and observation and imitation of FDI in food manufacturing would lead to expansion of existing businesses, and the establishment of new business ventures (Abebe et al., 2019). Competition could also compel local firms to develop niche markets for their products. The utilisation of products from MNEs could also be sources of new businesses locally (Alfaro, 2015; Santacreu-Vasut & Teshima, 2016). Indeed, linkage effects and the spillover effect of FDI are plausible (Barro & Sala-i-Martin, 2004).\n\n\nConclusion\n\nThis paper fills a void in the literature by investigating the effect of FDI on DI in the food manufacturing sector for developing, economies in transition and developed countries. Using an unbalanced panel data of 47 countries from 1993 to 2016, estimated by the system GMM, and computation of the Wald statistics from key terms including those with interactions, some findings were made.\n\nDeveloped economies experienced a crowd-out effect of FDI on DI in the short run, whilst the others experienced no significant effect. In the case of the long run, whilst food manufacturing sectors of all countries at the three levels of development separately exhibit crowd-out effects, the less than one increase in DI is smaller from the direction of developed-transition-developing countries. Level of development thus, moderates the crowd-out effect in the food manufacturing sector. The effect in the long run for all development groups together is a crowd-in.\n\nDeveloping economies and those in transition need to improve regulatorily and administrate efficiency. Specific attention to improving ease of doing business and reducing time to register new businesses would be helpful. Automation of processes and the use of computer web applications for business transactions would be useful. These would minimise human interface and reduce delays as well as reducing opportunities for rent-seeking.\n\nReview of investment policies and strengthening of the enforcement regimen would ensure improved compliance with the investment regulations, technology transfer, payment of appropriate taxes among others. Investment policies should prioritise partnerships (linkages) and mergers over complete acquisitions. Encouraging MNEs to engage in export through the Free Zones concept would promote exports and increase foreign exchange. This would ease the pressure on the local currency generally and especially during periods of profit repatriation.\n\nFor further research, the role of capital can be considered in the theoretical model as capital markets improve across the globe, leading to the effectiveness of the role of interest rates in determining domestic investment and availability of reliable data.\n\n\nData availability\n\nData have been obtained from the Food and Agriculture Organization of the United Nations: http://www.fao.org/faostat/en/#data\n\nFigshare: Foreign Direct Investment crowding out Domestic Investment in Food Manufacturing, https://doi.org/10.6084/m9.figshare.13591235.v2 (Djokoto, 2021).\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\n1 The estimates include tobacco.\n\n2 Agosin & Machado (2005) proposed β^LT=∑j=35β^j1−∑j=12β^j=1. Multiplying both sides of the equation by 1−∑j=12β^j and adding ∑j=12β^j to both sides yields Equation 7, Equation 8, Equation 9 and Equation 10.",
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Prague Econ Pap. 2002; 11(1): 57–66. Reference Source\n\nModigliani F, Miller MH: The cost of capital, corporation finance and the theory investment. Am Econ Rev. 1965; 55(3): 524–527. Reference Source\n\nMohanty S, Sethi N: Does inward FDI lead to export performance in India? An empirical investigation. Glob Bus Rev. 2019; 20: 1–16. Publisher Full Text\n\nMorrissey O, Udomkerdmongkol M: Governance, private investment and foreign direct investment in developing countries. World Dev. 2012; 40(3): 437–445. Publisher Full Text\n\nMutenyo J, Asmah E: Does foreign direct investment crowd-out domestic private investment in Sub-Saharan Africa? African Finance J. 2010; 12(1): 27–52. Reference Source\n\nMuuka GN: Wrong-footing MNCs and local manufacturing: Zambia's 1992-1994 structural adjustment program. Int Bus Rev. 1997; 6(6): 667–687. 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Publisher Full Text\n\nWooldridge JM: Econometric Analysis of Cross Section and Panel Data. MIT Press. Cambridge, MA. 2002; 108. Reference Source\n\nZineldin M: Globalization, strategic co-operation and economic integration among Islamic/Arabic countries. Management Research News. 2002; 25(4): 35–61. Publisher Full Text"
}
|
[
{
"id": "78909",
"date": "26 Feb 2021",
"name": "Jean Michel Roy Oualy",
"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\nWhich econometric model and economic theory are used?\n\nWhat are the different econometrics and statistical tests used to write the equation (1)?\n\nExplain why you take a linear model with lagged variables and with all countries together.\n\nWhich econometric model and economic theory is used to write the equations (2), (3), (4), (5), (6), (7), (8), (9), and (10)? I suggest you add external instruments.\n\nI suggest you add external instruments.\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": "6399",
"date": "02 Mar 2021",
"name": "Justice Djokoto",
"role": "Author Response",
"response": "AUTHOR RESPONSE TO REVIEWER COMMENTS Comment Which econometric model and economic theory are used? Response The econometric model is the system GMM. The Agosin and Machado (2005) model is based in the neoclassical investment theory. Comment What are the different econometrics and statistical tests used to write the equation (1)? Response Equation 1 was adapted from Agosin and Machado (2005) that theoretically derived the model which has been widely used. The estimation of equation 1 has been subjected to econometric and statistical tests outlined in the section ‘Estimation procedure’. The pieces of evidence of the tests are shown in Table 3 – 7. Comment Explain why you take a linear model with lagged variables and with all countries together. Response Agosin and Machado (2005) who derived the model used linear estimations. Other authors did the same. The lag variables and the possibility of endogeneity of the explanatory variables were recognised by estimating the system GMM. The countries were segregated into development groups, developing, developed, transition. Comment Which econometric model and economic theory is used to write the equations (2), (3), (4), (5), (6), (7), (8), (9), and (10)? I suggest you add external instruments. Response Regarding equation 1, the econometric model is the system GMM. The Agosin and Machado (2005) model is based on the neoclassical investment theory. The nature of the data, comprising developing, developed and the transition was accounted for in equation 2. Equation 3 to 6 presents the Wald computation of the short-run effects of FDI on DI for the respective development groups as well as the combined set of country groups. Equation 7 to 10 presents the Wald computation of the long-run effects of FDI on DI for the respective development groups as well as the combined set of country groups. During the estimation, the appropriate instrument was selected. This was not the same for all the estimated models reported hence the decision to exclude it in the model specification. Comment I suggest you add external instruments. Response The instruments which were various levels of lags differed for each of the model estimations reported. Hence the decision to exclude it in the model specification as the model specification is general."
}
]
}
] | 1
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https://f1000research.com/articles/10-72
|
https://f1000research.com/articles/11-391/v1
|
04 Apr 22
|
{
"type": "Method Article",
"title": "Formal definition of the MARS method for quantifying the unique target class discoveries of selected machine classifiers",
"authors": [
"Felipe Restrepo",
"Namrata Mali",
"Alan Abrahams",
"Peter Ractham",
"Felipe Restrepo",
"Namrata Mali",
"Alan Abrahams"
],
"abstract": "Conventional binary classification performance metrics evaluate either general measures (accuracy, F score) or specific aspects (precision, recall) of a model’s classifying ability. As such, these metrics, derived from the model’s confusion matrix, provide crucial insight regarding classifier-data interactions. However, modern- day computational capabilities have allowed for the creation of increasingly complex models that share nearly identical classification performance. While traditional performance metrics remain as essential indicators of a classifier’s individual capabilities, their ability to differentiate between models is limited. In this paper, we present the methodology for MARS (Method for Assessing Relative Sensitivity/ Specificity) ShineThrough and MARS Occlusion scores, two novel binary classification performance metrics, designed to quantify the distinctiveness of a classifier’s predictive successes and failures, relative to alternative classifiers. Being able to quantitatively express classifier uniqueness adds a novel classifier-classifier layer to the process of model evaluation and could improve ensemble model-selection decision making. By calculating both conventional performance measures, and proposed MARS metrics for a simple classifier prediction dataset, we demonstrate that the proposed metrics’ informational strengths synergize well with those of traditional metrics, delivering insight complementary to that of conventional metrics.",
"keywords": [
"Machine learning",
"Binary classification",
"Classifier performance evaluation",
"Classifier selection optimization",
"Classifier comparative uniqueness"
],
"content": "Introduction\n\nTraditionally, binary classification performance has been assessed using a combination of statistical measures derived from the classifier’s confusion matrix (accuracy, precision, recall/sensitivity, specificity, F score), or the classifier’s various confusion matrices, in the case of classifications at different cut-off thresholds (ROC curve, AUC metric). Accuracy is defined as the percentage of correct predictions out of all predictions. Precision is the percentage of predicted positives that are true. Recall (sensitivity) is the percentage of actual positives that are correctly predicted. Specificity is the percentage of actual negatives that are correctly predicted. F scores (various variants like F1, F2) combine precision and recall, weighting each equally, or unequally, to account for different misclassification costs. Finally, for binary classifiers that assign a probability or score to predictions, ROC curves and AUC metrics account for these ranked predictions, allowing for sensitivity and specificity to be observed at different cut-off thresholds. To plot the ROC curve and assess AUC, sensitivity and specificity are measured @k, where k is the number of top-ranked predictions and increases from 1 to the total number of observations in the dataset. Effective classifiers demonstrate a “bulge” in the ROC curves, and concomitant AUC close to 1, indicating that they discover far more true positives in the top-ranked k items, than would be expected in a random selection of k items. Notably, none of these conventional metrics assess the distinctiveness (uniqueness) of the classifier’s predictions, relative to other classifiers. In other words, conventional metrics are unable to assess what percentage of true positives (‘hits’) are found only by the current algorithm but not by alternatives, nor what percentage of false negatives (‘misses’) were missed by the current algorithm but not by alternatives. The inability of conventional classifier evaluation metrics to quantify how many, and what proportion, of a classifier’s correct (and incorrect) predictions are exclusive to that classifier, is a significant limitation. Two classifiers of equal accuracy (or precision, or recall, or AUC) may each have the unique ability to identify distinct observations from the target class, and this classifier uniqueness ought to be assessable.\n\nSuch assessments about classifier uniqueness have been made possible through the use of novel MARS ShineThrough and MARS Occlusions scores, whose software-level implementation was recently described in Ref. 25. However, since25 focuses solely on the usage and interpretation of the software artifact’s outputs, it does not outline the methodological framework used to generate ShineThrough and Occlusion scores. Hence, in this paper, we present the mathematical foundations behind MARS metrics and their corresponding software artifact. Furthermore, we also provide step-by-step sample calculations that illustrate the inner workings of Shinethrough and Occlusion scores for a simple dataset. Being able to quantitatively assess classifier uniqueness has multiple benefits: better decisions could be made about combining complementary classifiers (vs duplicative classifiers), and improved characterizations could be run of where particular classifiers ‘shine through’ (spot true positives that no other classifiers spot) or ‘occlude’ (hide or miss observations in the target class, by mistakenly classifying those observations as false negatives, when one or more of the other classifiers have been able to spot those observations as true positives).\n\nAs an example of the problematic omission of exclusivity metrics in the evaluation and comparison of classifiers, consider the following cases. Recently,1 evaluated the generalized, binary predictive ability of eight classifiers across ten datasets. ROC curve values for the top-ranked classifiers revealed that Support Vector Machine (SVM), Artificial Neural Network (ANN), and Partial Least Squares Regression (PLS) classifier performances were nearly identical across all datasets.2 compared the performance of several classifiers, namely, Random Forest (RF), Decision Tree (DT), and k-nearest neighbors (kNN), using binary classification schemes for variable stars. Similar to Refs. 1,2’s precision, recall, and F1 scores indicated that all three classifiers performed nearly identically.3–5 reported similar outcomes, with virtually equal performance metric values across the top n-ranked classifiers. In all these cases, while the performance of the classifiers is nearly identical according to conventional classifier evaluation metrics, the classifiers clearly made different false positive and false negative errors, and thus triumphed, or failed, relative to other classifiers on particular observations. Clearly, the scope of traditional statistical performance measures is too narrow to provide the insight required to distinguish between the top n-ranked classifiers based on their respective exclusive hits or misses. Regardless of classifier ranking, traditional performance metrics, such as accuracy and F1 score, may not reliably reflect the classifier’s true performance, particularly on imbalanced datasets.6 Novel classifier exclusivity metrics are needed to illustrate the success or failure of classifiers on particular observations, relative to their competing classifiers. These exclusivity metrics should reflect the extent to which a classifier exclusively finds (“shines through”) observations in the target class (that are not spotted by competing classifiers), or exclusively misses (“occludes”) observations in the target class (that are spotted by competing classifiers).\n\nConsider a classification task where the data scientist is attempting to identify safety concerns expressed by consumers in millions of online product reviews (e.g., see Refs. 7–10), using alternative candidate classifiers C1 and C2. The classification task is critical: missed safety concerns are unaddressed product hazards that could injure current or future product users. Assume the two competing classifiers, C1 and C2, both have precision of 80%, and recall of 80%, superficially (i.e., prima facie) indicating the classifiers have similar performance. However, if we are able to take into consideration the exclusivity of the classifier’s predictions (“shine through” and “occlusion”), we may find that C1 finds a significant proportion of the target class (safety concerns, in this observation) that C2 misses (“occludes”). Assessing classifier exclusivity is thus essential to revealing that two classifiers with 80% precision are by no means identical in their target- observation discovery ability, and may be complementary, rather than simply competing. This realization allows the data scientist to discover more safety concerns, through intelligent classifier combination (e.g., taking true positives from both classifiers), rather than the data scientist simply deciding to eliminate a superficially comparable classifier (when regarding conventional classifier performance metrics only prima facie).\n\nDue to conventional metrics’ vulnerability to class imbalance, researchers have sometimes adopted alternative performance measures that complement traditional classifier evaluation techniques and help provide a more accurate assessment of the classifier’s true performance. Commonly used alternative measures include Cohen’s kappa11 and Matthews Correlation Coefficient (MCC).12 Cohen’s kappa (1960) calculates the agreement between the model’s predicted class labels and the actual class labels. Multiple studies6,13,14 have identified concerns, relating to interpretability and class imbalance, when using Cohen’s kappa for binary classification. Regarding interpretability, the use of a relative metric (Cohen’s kappa) to evaluate model performance may lead to inconsistent results in which superior classifiers receive low kappa scores.14 Additionally, imbalanced class labels generally produce higher kappa scores, generating overoptimistic results that do not reflect true model performance.14 MCC, generally used in imbalanced classification, relies on all four confusion matrix categories (true positives, true negatives, false positives, and false negatives) and is invariant to class label distributions, thus, yielding scores that better assess imbalanced classification performance.6 While the class imbalance problem has received significant attention, the identification and quantification of a classifier’s prediction exclusivity (distinctive predictive successes and failures relative to competing classifiers) has not been studied.\n\nCurrent conventional and alternative classifier performance metrics suggest that the behavior of elite models is generally indistinguishable from that of other elite models. Nevertheless, fundamentally differing mathematical and structural assumptions between different classifier algorithms indicate otherwise, implying that successful classifiers may not be as similar to each other as suggested by current metrics.\n\nIn this paper, we present the methodology for MARS (“Method for Assessing Relative Sensitivity/Specificity”), a novel approach that evaluates the comparative uniqueness of a classifier’s predictions, relative to other classifiers.25 By mathematically defining MARS ‘ShineThrough’ and ‘Occlusion’ scores, we demonstrate how these metrics assess model performance as a function of the model’s ability to exclusively capture unique true positives not found by the other classifiers (‘ShineThrough’) and the model’s inability to capture true positives found by one or more of the other classifiers (‘Occlusion’). These metrics, designed to complement widely used traditional and alternative measures, add another layer to classifier assessment, provide crucial insight that helps better distinguish and explain the behavior of the top n-ranked classifiers, and can be further extended to find optimal complementary classifier combinations (ensembles).\n\n\nRelated work\n\nBinary classification Machine Learning (ML) performance metrics provide quantitative insight pertaining to different facets of a classifier’s true behavior, i.e., its performance on unseen data. For example, while precision is defined as the proportion of predicted positives that are actually positives, recall (sensitivity) is the overall proportion of positives that were correctly labelled as such.15 These metrics, derived from the classifier’s confusion matrix (Figure 1), offer complementary assessments concerning the classifier’s ability to detect and correctly label true positives, as evidenced by their mathematical definitions:\n\nAbbreviations used: TP = True Positives, FP = False Positives.\n\nAbbreviations used: FN = False Negatives.\n\nSimilar to sensitivity, which calculates the model’s true positive rate, specificity evaluates the overall proportion of negatives that were correctly labelled by the classifier (true negative rate).16 Consequently, it follows a similar formulation:\n\nAbbreviations used: TN = True Negatives.\n\nThese metrics (precision, recall, specificity) provide crucial insight relating to classifier-class interactions. Other measures, such as accuracy and F score,17 provide a more generalized interpretation of model behavior. F score, defined as the harmonic mean of precision and recall, evaluates the classifier’s performance across three confusion matrix components: TP, FP, FN, and can be defined as follows:\n\nWhere β is arbitrarily chosen such that recall is β times as important as precision. The two most commonly used implementations are F1 and F2 scores.18–20\n\nAccuracy, unlike the aforementioned metrics, incorporates all four confusion matrix components into its calculations:\n\nUnfortunately, accuracy is poor estimator of overall performance when the dataset labels are imbalanced,6 as the classifier may be correctly labelling the majority class, thus, obtaining a high accuracy score, and misclassifying the minority class, at minimal accuracy cost. Regarding this,21 proposed the use of the MCC12 as a performance metric. MCC utilizes all four confusion matrix components, while also accounting for class imbalance. It does so by only generating a high score if both classes had the majority of their observations correctly predicted, regardless of class distribution. Similar to previous metrics, it is also derived from the classifier’s confusion matrix:\n\nMCC scores range from -1 to 1, representing perfect misclassification and classification, respectively.6 As for visual metrics and evaluation of a classifier over multiple classification cut-off thresholds (ranked predictions), Receiver Operating Characteristics (ROC) curves22,23 and Precision-Recall (PR) curves are generally considered to be the standard. ROC curves display what proportion of the total target class items were found by the classifier (sensitivity) in the x top- ranked target class predictions (x-axis). Comparing the classifier’s ROC curve against the benchmark 45-degree line, defined as the proportion of target class items found in a random sample of size x, allows the reader to rapidly determine whether the specific classifier is performing better than a random sample of size x would have been expected to. While the ROC curve does not provide a single-point estimate of the classifier’s performance, the ROC’s area under the curve (AUC) value does.22 AUC scores, which range from 0 to 1, measure the classifier’s ability to distinguish between classes, and are often reported alongside the ROC curve. AUC values close to 1 indicate the classifier identified all, or almost all, of the available observations in the target class, as true positives, in its top-ranked observations (observations that classifier judged most likely to be in the target class).\n\nPrecision-Recall [PR] curves are sometimes used as an alternative to ROC curves,24 to illustrate fluctuations in hit- and miss-rates, as increasing numbers of top-ranked observations are considered by a classifier. Notably, neither ROC curve nor PR curves indicate how many of the true positives in the top-ranked predictions are exclusive to the current classifier (i.e., were target-class items not found by any other classifier), nor how many of the false negatives are exclusive to the current classifier (i.e., were target-class items correctly found by any other classifier). Regarding this, the use of the MARS software artifact, proposed in Ref. 25, has been suggested as a way to overcome this limitation, which we further validate in this paper by presenting the mathematical foundations behind the software-level implementation of the MARS metrics.\n\n\nMethods\n\nWe assess overall classifier uniqueness across two separate dimensions: MARS ShineThrough and MARS Occlusion scores. These performance measures are briefly defined in Ref. 25 as:\n\n1. MARS ShineThrough Score: The proportion of exclusive true positives discovered only by the classifier under consideration, relative to the total number of unique true positives (i.e., counting each target-class observation once only, if it is found by any classifier) discovered across all classifiers.\n\n2. MARS Occlusion Score: The classifier’s proportion of exclusive false negatives (missed only by the current classifier) that were correctly labelled by at least one other classifier relative to the total number of unique true positives discovered across all classifiers (i.e., counting each target-class observation once only, if it is found by any classifier).\n\nThese performance measures are rigorously analyzed and mathematically anatomized in the subsections MARS Shinethrough scores and MARS Occlusion scores below.\n\nLet n be the number of observations in a given dataset and J the set of classifiers, under consideration. Similarly, let yi be classifier’s predicted class label and ti the true class label (0 or 1) at observation i.\n\nThen, we can define the total number of true positives (TTPall) as the sum, over n observations, of the maximum value of the product between predicted and true class labels across all j classifiers:\n\nTo determine the total number of exclusive true positives (ETPCj) discovered by classifier j, i.e., target class observations found only by the current classifier and not found by the other classifiers, we use:\n\nWhere we sum (over n observations) the difference between the product of predicted and actual class labels and the maximum value of the same product across the remaining j -1 classifiers. Additionally, we multiply the latter by constant Zi, defined as:\n\nConsequently, the sum at observation i will have a non-zero value if and only if the classifier’s predicted and actual labels belong to the target class.\n\nThen, using (1) and (2), we calculate the ShineThrough Score for classifier j as follows:\n\nHence, MARS ShineThrough provides a much-needed numerical interpretation of the classifier’s comparative uniqueness, i.e., what proportion of the total number of true positives were exclusively identified by the classifier under consideration, relative to the competing classifiers. Occlusion scores, on the other hand, provide insight relating to the classifier’s comparative weaknesses.\n\nWe define the total number of false negatives (EFNCj) labelled by classifier j and correctly labelled by any of the remaining\n\nj − 1 classifiers as:\n\nWhere, similar to Eq. (2), we find the maximum value of yi,j·tiacross the remaining j − 1 classifiers and multiply the output by binary constant Zi, defined as:\n\nThus, the summation will have a non-zero value at observation i if and only if the classifier under consideration incorrectly labelled the target class. Using (1) and (4), we then define the MARS Occlusion score for classifier j as:\n\nWhere we divide EFNCj by TTPall to determine what proportion of the classifier’s false negatives are true positives in any of the remaining j – 1 classifiers, therefore, quantitatively assessing the classifier’s comparative weaknesses.\n\nTable 1 provides a quick-reference glossary of the symbols used in our definitions.\n\n\nUse cases\n\nFor the purposes of illustration, in the following subsections, we provide a stylized dataset and step-by-step, worked examples showing the computation of the MARS ShineThrough and MARS Occlusion scores, as well as the plotting of multiple MARS scores visually, in MARS charts.26\n\nWhile we provide an arbitrary, stylized dataset in this paper (to facilitate the understanding of the step-by-step examples), MARS metric performance on a real dataset can be found in Ref. 25. However, the latter does not provide any worked-out examples or rigorous mathematical explanations beyond the software-artifact’s outputs.\n\nWe created a simple, binary classification dataset with ten observations, each assigned an artificially generated “true” class label, for illustrative purposes. We also generated (predicted) labels for arbitrary classifiers: J = {C1, C2, C3, C4}. Actual (true) and classifier (predicted) labels can be seen in Table 2.\n\nIn order to calculate MARS scores, we first determine the total number of true positives discovered across all four classifiers using Eq. (1), that is:\n\nWe illustrate the sum’s inner calculations for the first two observations below:\n\nThus, the sum at i = 10 would be:\n\nSumming over all ten observations yields the value of 6, indicating that every target-class observation was correctly labelled by at least one classifier. This can be double-checked by looking at the classifiers’ target class predictions in Table 2 (i = 2,4,6,7,8,10).\n\nTo calculate individual ShineThrough scores for the classifier under consideration, we divide the total number of exclusive true positives found by Cj by the total number of unique true positives (i.e., correctly classified observations in the target-class) across all classifiers (Eq. (3)). We demonstrate the procedure using C1:\n\nFinally, we use Eq. (3) to obtain C1 ShineThrough scores:\n\nThis reveals that C1 alone accounts for one third of the discovered target class observations, suggesting its behavior is fairly unique amongst its peers. The calculations can be easily verified by looking at observations i = 6 and i = 8 in Table 2. Additionally, we can also calculate combined ShineThrough scores for two or more classifiers by merging their predictions and discarding their individual labels, prioritizing correct labels when possible (Table 4).\n\nFor example, using Table 2 and Table 4, we can obtain the combined ShineThrough score for C1 and C4 using Eq. (1), (2), and (3), as follows:\n\nThis combined-ShineThrough indicates that two-thirds of the total target class observations Eq. (6), were exclusively discovered by classifiers C1 and C4, in combination, indicating that when combined, the classifiers perform extremely well relative to the remaining classifiers. Note that originally (prior to combining classifiers), the observation at i = 7 was not considered to be exclusive for any of the classifiers, however, once C1 and C4 had their predictions combined, it became exclusive for C1,4.\n\nAs for occlusions scores, we can calculate the total number of exclusive false negatives (missed only by the current classifier) that were correctly classified by any of the other classifiers following Eq. (4):\n\nIn the case of C1, the first two iterations of the sum are as follows:\n\nFollowing the same procedure, the final sum at i = 10 would be:\n\nThen, we calculate the Occlusion score for classifier C1 using Eq. (5):\n\nUnlike ShineThrough scores (where higher scores suggest better performance), with Occlusion scores it is the case that lower scores suggest better performance. In the case of C1, its Occlusion score reveals that 50% of the target class observations discovered by any of the other competing classifiers, are being misclassified by C1 and correctly classified by at least one of the remaining classifiers. Similar to ShineThrough scores, we can also merge classifier predictions to calculate combined Occlusion scores. For example, for C3 and C4, whose combined predictions only have false negatives correctly labelled by the other classifiers (C1 or C2) at observations i = 6 and i = 8 (Tables 1 and 3), we can calculate combined Occlusion3,4 as follows:\n\nThen,\n\nOcclusion scores for the combined classifier, C3,4, indicate that one third of the target class labels were misclassified by the combination of classifier C3 and classifier C4, but correctly labelled by at least one of the remaining j − 1 classifiers.\n\nMARS ShineThrough and Occlusion scores can also be visualized, allowing for the rapid depiction of the classifiers’ relative uniqueness. For our example dataset and classifiers above, the MARS metrics can be transformed from proportions (of total true positives) to counts (of unique hits or misses), and visualized, across individual and combined classifiers, as seen in Figure 2 and Figure 3, using a bubble-chart style format. Figure 2 is the MARS ShineThrough chart for classifiers C1-4; the radius of the yellow circle represents the number (count) of exclusive true positives found by the classifier on the y-axis. The radius of the orange circle represents the number of exclusive true positives found by both the classifier on the y-axis and x-axis, i.e., combined ShineThrough. Figure 3 is the MARS Occlusion chart: the radius of the red circle represents the number (count) of exclusive false negatives labelled by the classifier on the y-axis and the radius of the orange circle represents the combined number of exclusive false negatives labelled by the classifiers on both the x and y-axis.\n\nNote that orange circles can only be as small as their respective yellow or red counterparts, which in turn may be as small as zero (indicating that the classifier found no exclusive true positives or false negatives).\n\n\nDiscussion\n\nConventional metrics (Table 5; columns 2-4) all points towards C4 being the unquestionably strongest classifier, due to its high accuracy (column 2), precision (column 3), and recall (column 4) values. However, MARS ShineThrough (ST) and Occlusion (OCC) scores (Table 5; columns 5 and 6, respectively) and MARS charts (Figure 2 and Figure 3) suggest that there is further room for improvement: Table 5 (ST column, row 1), and Figure 2 reveal that C1 is uniquely adept at spotting one third (0.33) of the target class items, and, while C4 performs reasonably well on its own (Table 5; row 4), its combination with C1 results in the creation of a stronger classifier that accounts for two thirds (0.66) of the discovered target class items (Table 5; ST column, row 5). Furthermore (see Table 5; OCC column, row 5; or see Figure 3), the combined classifier C1,4 has an Occlusion score of 0 (indicating that, if any target observations were missed by this classifier-combination, they were also missed by all other classifiers).\n\nWhile some classifier combinations may improve overall performance, the opposite is also possible. For example, Figure 3 shows that the combination of C3 and C4 produces MARS scores identical to those of C4 alone, indicating that it is a weak combination, and should, therefore, be avoided. While traditional performance metrics gauge individual classifier capabilities by quantitively interpreting classifier-data interactions, MARS scores and charts measure classifier capabilities by simultaneously interpreting both classifier-data and classifier-classifier interactions.\n\n\nConclusions\n\nIn this paper, we presented the mathematical background and interpretation for two novel binary classification performance metrics – MARS ShineThrough and MARS Occlusion scores, whose software-level implementation, in the Python language, was recently described in Ref. 25. The formal definition of the MARS method, provided in this paper, will allow the research community to verify the correctness of the MARS method (through peer-review), accurately implement the MARS method in other programming languages (such as JavaScript, PHP, and R), and develop novel alternatives to, and enhancements to, the MARS method (such as visualizations that chart MARS metrics across multiple classifier cut-off thresholds instead of the single classifier cut-off threshold illustrated here). The stylized dataset and worked sample calculations provided in the Use cases section of this paper, above, is usable by the research community as a test case, to validate the correctness of each computational step of future software implementations. MARS metrics and MARS charts add yet another layer to the process of classifier assessment, providing crucial insight about each classifier’s behavior relative to that of its peers. ShineThrough scores evaluate the comparative unique strengths of the classifier, by determining the proportion of total true positives that were exclusively found by the classifier. On the other hand, Occlusion scores measure the proportion of observations that were correctly labelled by the other classifiers but misclassified by the current classifier, i.e., the classifier’s comparative unique weaknesses.\n\nNaturally, the metrics synergize well with conventional measures, as the latter are constrained to the individual classifier’s confusion matrix, severely limiting the breadth of their analysis, while the former make use of the entire observation sample space, thus, evaluating classifier behavior from a previously unseen standpoint: number of target class observations spotted or missed only (i.e., exclusively) by one classifier. This was demonstrated throughout the provided worked-out examples, which calculated ShineThrough and Occlusion scores for our stylized dataset (Tables 2 and 4), and in Ref. 25 with a real dataset, albeit without the comprehensive mathematical explanation and examples presented in this paper. As a result, the MARS methodological framework adds a new classifier-comparison dimension – exclusive hits and misses – not expounded by conventional classifier evaluation methods.\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\nSoftware availability\n\nWebapp: https://mars-classifier-evaluation.herokuapp.com\n\nSource code available from: https://github.com/SoftwareImpacts/SIMPAC-2021-191\n\nArchived source code at time of publication: https://doi.org/10.24433/CO.2485385.v126\n\nLicense: MIT",
"appendix": "References\n\nMendez KM, Reinke SN, Broadhurst DI: A comparative evaluation of the generalised predictive ability of eight machine learnng algorithms across ten clinical metabolomics data sets for binary classification. Metabolomics. 2019; 15: 150–150. PubMed Abstract | Publisher Full Text\n\nHosenie Z, Lyon RJ, Stappers BW, et al.: Comparing multiclass, binary, and hierarchical machine learning classification schemes for variae stars. Mon. Not. R. Astron. Soc. 2019; 488: 4858–4872. Publisher Full Text\n\nMakhtar M, Neagu DC, Ridley MJ: Binary Classification Models Comparison: On the Similarity of Datasets and Confusion Matrix for Predictive Toxicology Applications. Inf. Technol. Bio- Med. Informatics. 2011; 108–122. Publisher Full Text\n\nMostafa FB, Hasan E: Machine Learning Approaches for Binary Classification to Discover Liver Diseases using Clinical Data. MedRxiv. 2021.\n\nNarassiguin A, Bibimoune M, Elghazel H, et al.: An extensive empirical comparison of ensemble learning methods for binary classification. Pattern Anal. Appl. 2016; 19: 1093–1128. Publisher Full Text\n\nChicco D, Jurman G: The advantages of the Matthews correlation coefficient (MCC) over F1 score and accuracy in binary classification evaluation. BMC Genomics. 2020; 21: 1–13. Publisher Full Text\n\nWinkler M, Abrahams AS, Gruss R, et al.: TOY SAFETY SURVEILLANCE FROM ONLINE REVIEWS. Decis. Support. Syst. 2016; 90: 23–32. PubMed Abstract | Publisher Full Text\n\nAbrahams AS, Fan W, Wang GA, et al.: An Integrated Text Analytic Framework for Product Defect Discovery. Prod. Oper. Manag. 2015; 24: 975–990. Publisher Full Text\n\nGoldberg DM, Khan S, Zaman N, et al.: Text Mining Approaches for Postmarket Food Safety Surveillance Using Online Media. Risk Anal. 2020. PubMed Abstract | Publisher Full Text\n\nAdams DZ, Gruss R, Abrahams AS: Automated discovery of safety and efficacy concerns for joint & muscle pain relief treatments from online reviews. Int. J. Med. Inform. 2017; 100: 108–120. PubMed Abstract | Publisher Full Text\n\nCohen J: A Coefficient of Agreement for Nominal Scales. Educ. Psychol. Meas. 1960; 20: 37–46. Publisher Full Text\n\nMatthews BW: Comparison of the predicted and observed secondary structure of T4 phage lysozyme. Biochim. Biophys. Acta - Protein Struct. 1975; 405: 442–451. PubMed Abstract | Publisher Full Text\n\nChicco D, Warrens MJ, Jurman G: The Matthews Correlation Coefficient (MCC) is More Informative Than Cohen’s Kappa and Brier Score in Binary Classification Assessment. IEEE Access. 2021; 9: 78368–78381. Publisher Full Text\n\nDelgado R, Tibau XA: Why Cohen’s Kappa should be avoided as performance measure in classification. PLoS One. 2019; 14: 1–26. Publisher Full Text\n\nDMW Powers: 2020.\n\nAltman DG, Bland JM: Diagnostic tests. 1: Sensitivity and specificity. BMJ. 1994; 308: 1552–1552. Publisher Full Text\n\nChinchor N: MUC-4 Evaluation Metrics. Proc. 4th Conf. Messag. Underst. Association for Computational Linguistics; 1992; pages 22–29.\n\nSasaki Y: 2007.\n\nSokolova M, Japkowicz N, Szpakowicz S: Beyond Accuracy, F-Score and ROC: A Family of Discriminant Measures for Performance Evaluation BT - AI. Sattar A, Kang B, editors. Advances in Artificial Intelligence. Springer; 2006; pages 1015–1021.\n\nVan Rijsbergen C: Information retrieval: theory and practice. Proc. Jt. IBM/University. 1979; pages 1–14.\n\nBaldi P, Brunak S, Chauvin Y, et al.: Assessing the accuracy of prediction algorithms for classification: An overview. Bioinformatics. 2000; 16: 412–424. PubMed Abstract | Publisher Full Text\n\nHanley JA, Mcneil BJ: The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982; 143: 29–36. PubMed Abstract | Publisher Full Text\n\nBradley AP: The use of the area under the ROC curve in the evaluation of machine learning algorithms. Pattern Recogn. 1997; 30: 1145–1159. Publisher Full Text\n\nSaito T, Rehmsmeier M: The precision-recall plot is more informative than the ROC plot when evaluating binary classifiers on imbalanced datasets. PLoS One. 2015; 10: e0118432. PubMed Abstract | Publisher Full Text\n\nMali N, Restrepo F, Abrahams A, et al.: Implementation of mars metrics and Mars charts for evaluating classifier exclusivity: The comparative uniqueness of binary classifier predictions. Software Impacts. 2022; 12: 100259. Publisher Full Text\n\nMali N, Restrepo F, Abrahams A: Implementation of MARS metrics and MARS charts for evaluating classifier exclusivity: the comparative uniqueness of binary classifier predictions [Source Code].2021.Publisher Full Text"
}
|
[
{
"id": "136529",
"date": "17 May 2022",
"name": "Timothy A. Warner",
"expertise": [
"Reviewer Expertise Remote sensing"
],
"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 describes statistics that summarize similarity of the labelling of unknown samples by different classifiers. The method has two levels: (1) individual classifiers vs the rest and (2) groups of two classifiers vs the rest. The method and the visualization of the results were described in an earlier paper; this paper provides a more thorough definition of the statistics and a worked, hypothetical example.\n\nThe fact this paper has the express aim of providing clarification to an earlier paper may constrain how open the authors are to modifying their approach.\nMajor suggestions\nThe two measures of shine through and occlusion are described numerous times as respectively measures of exclusive true positives and exclusive false negatives. However, the definition of exclusive seems to differ in the two cases. For shine through, exclusive means true positives (TP) for *only* the classifier of interest, and no other classifier (i.e. FN for all other classifiers). For occlusion exclusive means false negatives (FN) for the classifier of interest, but a TP for *any* (i.e., at least one) other classifier. Thus for occlusion the word “exclusive” has a more relaxed meaning than for shine through. If the meaning of exclusive for occlusion were the same as for shine through, then the definition of occlusion would be a FN for the classifier of interest, and no other classifier. The paper focuses on “exclusive” TP and FP. However, as Figure 1 from the paper shows, there are two other types of classification outcomes: false positives (FP) and true negatives (TN). A key aspect of classifier behavior is the trade-off between FN and FP. Is there any reason for not developing similar metrics for FP and TN, and thus providing a comprehensive, instead of partial, view of the differences between classifiers? The paper makes a valuable contribution in providing statistical measures that compare decision boundaries between classifiers. However, I think it is potentially confusing to suggest that the MARS statistics are “alternative classification performance metrics” that overcome “limitations” of “traditional performance metrics.” I think that is a bit like saying the problem with the mean as a measure of central tendency is that it doesn’t measure autocorrelation. The MARS statistics don’t seem to be performance metrics, in the sense of quantifying accuracy. I think being clear about the purpose and role of MARS statistics is important in helping readers understand what information the MARS can offer. Based on the above, I suggest removing the extensive discussion of Kappa, F-score, MCC, AUC, ROC, PR curves, and class imbalance, which seems to be a distraction. Furthermore, it seems to me class imbalance will affect MARS metrics as much as any other statistic, so I don’t follow the argument that MARS represents a method to address this limitation in conventional accuracy statistics. I think all you need to say is that two classifiers can have the same summary accuracy statistics (such as overall accuracy, precision and recall), but have different decision boundaries. MARS helps one explore those differences. Similarly, in the discussion, I suggest emphasizing that the power of the MARS measures is not in clarifying the accuracy of the various classifiers, but rather in highlighting differences in their decision boundaries. For the MARS charts, I suggest following the example of a covariance matrix (where the variance is on the diagonal, and covariance on off-diagonal positions), and place the single classifier values on the diagonal, and the classifier combinations on the off-diagonal positions. (However, I suggest keeping the different colors, which I found useful.) I think the use of the diagonal and off-diagonal in this way is conceptually clearer, and also has the benefit that you don’t have the problem of which one to prioritize when the two circles have the same diameter. I don’t understand Table 4. The numbers in table 4 for C1,4 seem to be a duplicate of C1 in Table 2, and C2,3 a duplicate of C2. Crucially, I can’t relate it to the calculation of ETPsub(C1,4), nor does it seem to agree with table 5. In table 5, I don’t understand how the overall accuracy, precision and recall for the combination of classifiers (C1,4 and C3,4) are calculated. For example, I don’t see what objective rule combining C1 and C4 could result in class labels that indicate 100% accuracy for these samples.\n\nMinor suggestions\nPerhaps explain the MARS acronym? I don’t understand the reference to sensitivity and specificity in the context of shine through and occlusion (especially since specificity is the TN as a proportion of the reference Negative class; the current MARS statistics do not seem to include an “exclusive” TN measure). I suggest defining MARS acronym in the main body – currently it seems to be only defined in the abstract. (Unless I missed it. If so, sorry.) Second sentence under the heading “Related work” – I suggest that in defining the recall, add the word “actual” prior to “positives”, so that the definition becomes “the overall proportion of *actual* positives that were correctly labelled as such.” “Accuracy” – defined on p5. I suggest using the term “overall accuracy” rather than just “accuracy” to differentiate this from the generic concept of accuracy. I think the equations would be easier to follow if you moved the reference to Table 1 to the start of the section with the equations. I suggest not using the same symbol for more than one purpose. For example, the constant Z-sub-i has different definitions in 2.1 and 4.1. (When I first read the paper, I incorrectly used the 2.1 definition when I was working through the occlusion example. Using a different letter for the 2 constants would avoid this problem.) Similarly, in eqn 2, it was a bit confusing to me that subscript j on the left side of the equation could (in fact, has to) simultaneously represent a different value on the right hand side of the equation. Using a different symbol on the left side will obviate this confusion. P8 – Second-last paragraph “To calculate individual Shine through scores”….I suggest referring to Table 3 here to clarify how ETP is calculated. P9 –Has variable k been defined? Is it perhaps Z-sub-i? P9. The example of occlusion for C1, @i=1. In the first worked example, is the first 0 and 1 (y11 and t1) switched? I.e, it seems to me that this should read “max (1 x 0, 0 x 0, 0 x 0) x 0 = 0”? Table 3. The value for Z-sub-i for observation 1 is listed in the table as 1. Should it not be 0? End of first paragraph below Table 3. The reference to “Tables 1 and 3” – shouldn’t this be to “Tables 1 and 4”? MARS charts – the discussion and captions simplifies the MARS metrics as “counts” – but they are actually defined as proportions. I think adding a legend that indicates how circle size relates to proportions would be useful.\n\nIs the rationale for developing the new method (or application) clearly explained? Partly\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? 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? Partly",
"responses": [
{
"c_id": "8382",
"date": "20 Jun 2022",
"name": "Peter Ractham",
"role": "Author Response",
"response": "Manuscript Number: 110567 Dear Dr. Warner, Thank you for reviewing our manuscript, Formal definition of the MARS method for quantifying the unique target class discoveries of selected machine classifiers. We greatly appreciate the careful review and valuable feedback you have provided. We have incorporated the suggested changes to the paper and software artifact. Below this letter, we have addressed the comments in a point-by-point manner. Our response, bolded, includes a brief explanation behind the initial reasoning and how and where the paper was modified. Thank you for your time and consideration. Sincerely, Felipe Restrepo Namrata Mali Alan Abrahams Peter Ractham Comments to the Authors: The two measures of shine through and occlusion are described numerous times as respectively measures of exclusive true positives and exclusive false negatives. However, the definition of exclusive seems to differ in the two cases. For shine through, exclusive means true positives (TP) for *only* the classifier of interest, and no other classifier (i.e. FN for all other classifiers). For occlusion exclusive means false negatives (FN) for the classifier of interest, but a TP for *any* (i.e., at least one) other classifier. Thus for occlusion the word “exclusive” has a more relaxed meaning than for shine through. If the meaning of exclusive for occlusion were the same as for shine through, then the definition of occlusion would be a FN for the classifier of interest, and no other classifier. Thank you for pointing this out. We have modified the definition of occlusion so that the definition of exclusive true positives now directly parallels that of exclusive false negatives. The updated mathematical formulation is now: Formula 1: https://f1000researchdata.s3.amazonaws.com/linked/432866.formula1.png Formula 2: https://f1000researchdata.s3.amazonaws.com/linked/432867.formula2.png Following this formulation, Occlusion scores now represent the proportion of the classifier’s unique misses, relative to discovered true positives. A high Occlusion score may suggest that the classifier has a rather specific struggle within the classification task, which the remaining models are capable of handling. Within the manuscript, we updated the MARS Occlusion Scores section (p. 5) with the revised mathematical formulation, the MARS Occlusion Score Metric: Example Computation section (p. 8) with the revised mathematical formulation, and Table 4 (p.10) Occlusion scores. Figure 3 (MARS Occlusion Chart) in the MARS charts section (p. 9) was also updated to reflect the updated definition. The paper focuses on “exclusive” TP and FP. However, as Figure 1 from the paper shows, there are two other types of classification outcomes: false positives (FP) and true negatives (TN). A key aspect of classifier behavior is the trade-off between FN and FP. Is there any reason for not developing similar metrics for FP and TN, and thus providing a comprehensive, instead of partial, view of the differences between classifiers? Thank you for pointing this out. Given that MARS metrics were designed as a tool to optimize big-data, machine-driven discovery efforts in which the value of TPs and the cost of FNs is high, - e.g., flagging potentially hazardous products via online reviews – we focused on defining MARS through TPs and FNs. The approach can easily be adapted to applications in which the value and cost of TNs/FPs is high. Within the manuscript, we have clarified that the approach is easily replicated with TNs and FPs, but we omit detailed calculations (as they would be nearly identical to those of TPs and FNs) for brevity (Methods section, p. 4). The paper makes a valuable contribution in providing statistical measures that compare decision boundaries between classifiers. However, I think it is potentially confusing to suggest that the MARS statistics are “alternative classification performance metrics” that overcome “limitations” of “traditional performance metrics.” I think that is a bit like saying the problem with the mean as a measure of central tendency is that it doesn’t measure autocorrelation. The MARS statistics don’t seem to be performance metrics, in the sense of quantifying accuracy. I think being clear about the purpose and role of MARS statistics is important in helping readers understand what information the MARS can offer. Thank you for your suggestion. We intended for MARS metrics to be used alongside traditional metrics as a tool to optimize big-data, machine-driven discovery efforts. MARS scores were designed to complement traditional ones (e.g., accuracy, recall, precision) in high-volume data applications, where models are likely to have similar conventional summary statistics, even if their decision boundaries are fundamentally different. In these cases, the depth of traditional metric analysis may be significantly limited, as results would simply suggest that all models employed worked well on the data, providing no differentiating power within the set of classifiers. Whereas using MARS metrics, which are far more likely to detect differences in classifier behavior, alongside traditional metrics, would allow for a more complete analysis to be made about the model’s overall (individual and comparative) performance. Within the manuscript, we have modified the Introduction section (p. 2 – 3) so that the purpose and role of MARS statistics is clear for readers. Based on the above, I suggest removing the extensive discussion of Kappa, F-score, MCC, AUC, ROC, PR curves, and class imbalance, which seems to be a distraction. Furthermore, it seems to me class imbalance will affect MARS metrics as much as any other statistic, so I don’t follow the argument that MARS represents a method to address this limitation in conventional accuracy statistics. I think all you need to say is that two classifiers can have the same summary accuracy statistics (such as overall accuracy, precision and recall), but have different decision boundaries. MARS helps one explore those differences. Similarly, in the discussion, I suggest emphasizing that the power of the MARS measures is not in clarifying the accuracy of the various classifiers, but rather in highlighting differences in their decision boundaries. Thank you for your suggestion. The class imbalance discussion was meant to highlight the vulnerabilities of conventional metrics and bring forth the need for novel metrics capable of examining classifiers from a different standpoint. We did not intend to imply that MARS represents a method to address this limitation. Rather, we intended to express that conventional metrics would greatly benefit from the use of MARS alongside, as doing so would allow for a more objective and in-depth analysis of the model’s behavior – which we have now made clear in the Introduction section, rendering the class imbalance discussion unnecessary. Within the manuscript, we have removed the class imbalance discussion in the Introduction section (p. 3) and significantly shortened the Related Works section by doing the same (p. 3-4). Within Related Works (p. 3-4), we also reduced the discussion pertaining to PR and ROC curves. The Discussion section (p. 10) was reworked to better emphasize the power of MARS metrics in spotting differences between classifier behavior and optimizing model combinations. For the MARS charts, I suggest following the example of a covariance matrix (where the variance is on the diagonal, and covariance on off-diagonal positions), and place the single classifier values on the diagonal, and the classifier combinations on the off-diagonal positions. (However, I suggest keeping the different colors, which I found useful.) I think the use of the diagonal and off-diagonal in this way is conceptually clearer, and also has the benefit that you don’t have the problem of which one to prioritize when the two circles have the same diameter. Thank you for your suggestion. We have implemented the suggested changes to the MARS charts and updated Figures 2 and 3 (Mars charts section, p. 9-10). I don’t understand Table 4. The numbers in table 4 for C1,4 seem to be a duplicate of C1 in Table 2, and C2,3 a duplicate of C2. Crucially, I can’t relate it to the calculation of ETPsub(C1,4), nor does it seem to agree with table 5. Thank you for pointing this out. We have removed Table 4 from the manuscript. Upon review, it does not align with the reworked Discussion and Introduction sections, as combined MARS metrics are meant to facilitate the discovery of classifiers with complementary decision boundaries; they are not designed for traditional classifier ensemble creation, as Table 4 suggested. In table 5, I don’t understand how the overall accuracy, precision and recall for the combination of classifiers (C1,4 and C3,4) are calculated. For example, I don’t see what objective rule combining C1 and C4 could result in class labels that indicate 100% accuracy for these samples. Thank you for pointing this out. As per the previous suggestion, we re-evaluated Table 4 and determined it was best eliminated. Consequently, C1,4 and C3,4 have been removed from Table 5. Perhaps explain the MARS acronym? I don’t understand the reference to sensitivity and specificity in the context of shine through and occlusion (especially since specificity is the TN as a proportion of the reference Negative class; the current MARS statistics do not seem to include an “exclusive” TN measure). Thank you for your suggestion. Since sensitivity examines the model’s target-class detection capabilities with respect to the complete TP sample space, we referenced MARS as a tool to determine relative sensitivity, as it examines the model’s target-class detection capabilities with respect to competing classifiers, rather than the “ground truth”. We followed the same logic when referring to relative specificity. However, since we only briefly mention the ease of adaptability to TNs and FPs (refer to revision 2.), we have removed the specificity reference (Abstract, p. 1 & Introduction, last paragraph). I suggest defining MARS acronym in the main body – currently it seems to be only defined in the abstract. (Unless I missed it. If so, sorry.) Thank you for your suggestion. We had previously defined the MARS acronym in the main body (Introduction, last paragraph), and have now added an additional definition when first mentioned (Introduction, p. 2 ¶ 3). Second sentence under the heading “Related work” – I suggest that in defining the recall, add the word “actual” prior to “positives”, so that the definition becomes “the overall proportion of *actual* positives that were correctly labelled as such.” Thank you for your suggestion. We have added “actual” prior to positives (Related work, p. 3, ¶ 1). “Accuracy” – defined on p5. I suggest using the term “overall accuracy” rather than just “accuracy” to differentiate this from the generic concept of accuracy. Thank you for your suggestion. We have added “overall” prior to accuracy (Related Work, p. 4, ¶ 5). I think the equations would be easier to follow if you moved the reference to Table 1 to the start of the section with the equations. Thank you for your suggestion. We have moved Table 1 to the start of the Methods section (p. 5). I suggest not using the same symbol for more than one purpose. For example, the constant Z-sub-i has different definitions in 2.1 and 4.1. (When I first read the paper, I incorrectly used the 2.1 definition when I was working through the occlusion example. Using a different letter for the 2 constants would avoid this problem.) Thank you for your suggestion. We have changed the constant Z-sub-i to R-sub-i for the Occlusion metric. Similarly, in eqn 2, it was a bit confusing to me that subscript j on the left side of the equation could (in fact, has to) simultaneously represent a different value on the right hand side of the equation. Using a different symbol on the left side will obviate this confusion. Thank you for your suggestion. We have added Cw which represents the classifier of interest and resolves the confusion. Within the manuscript, we updated equations 1 – 5 (Methods section, p. 5 – 6) to reflect this change. The new term was also added to Table 1 (p. 5). P8 – Second-last paragraph “To calculate individual Shine through scores”….I suggest referring to Table 3 here to clarify how ETP is calculated. Thank you for pointing this out. We have referenced Table 3 for the worked-out ETP calculation example (MARS ShineThrough score metric: example computation, p. 7). P9 –Has variable k been defined? Is it perhaps Z-sub-i? Thank you for pointing this out. Yes, it was meant to be Z-sub-i (now R-sub-i for Occlusion scores). Within the manuscript we have substituted all mentions of k for R-sub-i (MARS occlusion score metric: example computation, p. 8 -9) P9. The example of occlusion for C1, @i=1. In the first worked example, is the first 0 and 1 (y11 and t1) switched? I.e, it seems to me that this should read “max (1 x 0, 0 x 0, 0 x 0) x 0 = 0”? Thank you for pointing this out. Yes, it should be ‘1 x 0’ instead of ‘0 x 1’. We have corrected the order within the manuscript (MARS occlusion score metric: example computation, p. 8). Table 3. The value for Z-sub-i for observation 1 is listed in the table as 1. Should it not be 0? Thank you for pointing this out. Yes, it should be zero. We have made the change in Table 3 (MARS ShineThrough score metric: example computation, p. 7). End of first paragraph below Table 3. The reference to “Tables 1 and 3” – shouldn’t this be to “Tables 1 and 4”? Thank you for pointing this out. The initial reference should have been Tables 1 and 4. However, since Table 4 was removed, it has been updated to ‘Table 1’ (MARS occlusion score metric: example computation, p. 9). MARS charts – the discussion and captions simplifies the MARS metrics as “counts” – but they are actually defined as proportions. I think adding a legend that indicates how circle size relates to proportions would be useful. Thank you for your suggestion. We have added an additional line to the captions of Figures 2 and 3 (Mars charts section, p. 8 – 9) explaining that bubble size is proportional to ShineThrough/Occlusion score: the larger the bubble, the higher the classifier(s) ShineThrough score."
}
]
},
{
"id": "136525",
"date": "16 Jun 2022",
"name": "Samir Chatterjee",
"expertise": [
"Reviewer Expertise ML in Healthcare"
],
"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 proposes two new binary classifier metrics in addition to existing traditional metrics such as accuracy, precision, recall, F-score. Two classifiers of equal accuracy may each have the unique ability to identify distinct observations from the target class.\nMARS ShineThrough and MARS Occlusion scores are mathematically presented.\nOn page 7, where MARS occlusion scores is first defined, it should read \"total number of expected false negatives (EFNcj).\"\nIn ML, combining algorithms is not too common. While ensemble methods use a similar core algorithms but creates different variations of the classifier (many trees in a Random Forest implementation), it may not be practically feasible to combine classifiers that are inherently built using different algorithms (Logistic regression, SVM, KNN). In those cases, how will this technique apply?\nThe visual bubble graphs are also little hard to understand.\nWhen comparing between different classifiers, while ST and OCC may tell us unique distinguishing capability of the classifiers, it is also important to have a discussion of the consequences of the TP and FN especially when it might be related to disease predictions. What are the trade-offs?\n\nIs the rationale for developing the new method (or application) clearly explained? Partly\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? Partly",
"responses": [
{
"c_id": "8390",
"date": "20 Jun 2022",
"name": "Peter Ractham",
"role": "Author Response",
"response": "Manuscript Number: 110567 Dear Dr. Chatterjee, Thank you for your helpful comments and suggestions regarding our manuscript, Formal definition of the MARS method for quantifying the unique target class discoveries of selected machine classifiers. We have edited the manuscript with the corrections and clarifications prompted by your suggestions. Below this letter, we have addressed the comments in a point-by-point manner. Our response, bolded, includes a brief explanation behind the initial reasoning and how and where the paper was modified. Thank you for your time and consideration. Sincerely, Felipe Restrepo Namrata Mali Alan Abrahams Peter Ractham Comments to the Authors: On page 7, where MARS occlusion scores is first defined, it should read \"total number of expected false negatives (EFNCj) Thank you for noticing this. We have made this fix. In ML, combining algorithms is not too common… it may not be practically feasible to combine classifiers that are inherently built using different algorithms (Logistic regression, SVM, KNN). In those cases, how will this technique apply? We have clarified in the manuscript that we are not proposing that the algorithm procedures be combined, but rather that the predicted positive observations of the algorithms be combined. Specifically, the intersection of the sets of predicted positives of the algorithms is taken, which is a straightforward operation. The combination of predicted positives, from two algorithms that each suggest distinct true positives, allows the data scientist to efficiently boost the number of true positives while constraining total positive predictions, which is highly desirable for applications like our prototypical application: maximizing the volume of safety concerns found in online reviews, while minimizing the close-reading verification effort required to determine if a predicted positive is a true positive. The visual bubble graphs are also little hard to understand. Thank you for your suggestion. To assist readers who find bubble charts difficult to interpret, we have supplemented the visual bubble graphs with MARS bar charts, which show the total distinct true positives, for each algorithm, sorted from algorithm with most distinct true positives down to the algorithm with the least distinct true positives. It is also important to have a discussion of the consequences of the TP and FN especially when it might be related to disease predictions. What are the trade-offs? Thank you for pointing out the importance of adding this discussion. We have added the following: “The MARS evaluation mechanism was developed for a prototypical application of maximizing the volume of safety concerns found in online reviews, while constraining the close-reading verification effort required to determine if predicted positives are true positive. That is, the MARS method assists with elevating binary classifier yield: that is, increasing verified true positives per unit of effort reviewing predicted positives. The MARS evaluation mechanism is best suited to applications where the false positive cost is low, such as our prototypical application of discovering safety concerns in online reviews: a true positive (online review that contains a safety concern) is valuable, while a false positive (online review that does not contain a safety concern) has low cost, as each false positives wastes only a little reading effort, especially when there are few online reviews (predicted positives) shortlisted by the ML algorithm(s) for escalated attention by a human reviewer who is manually reviewing the predicted positive observations. For other applications – such as disease discovery – where the false positives, and false negatives, have differing trade-offs, the MARS evaluation method presented here may not be appropriate, and an inverted MARS evaluation method, aimed at maximizing true negatives, may be preferable. Thank you again for your helpful observations and suggestions, which have helped us improve the clarity of the manuscript."
},
{
"c_id": "8391",
"date": "17 Jun 2022",
"name": "Peter Ractham",
"role": "Author Response",
"response": "Dear Reviewer, It seems that we'll have to wait for the update version of the manuscript from F1000 before we can submit the revised manuscript suggested by you. We'll update it as soon as possible. Thank you."
}
]
}
] | 1
|
https://f1000research.com/articles/11-391
|
https://f1000research.com/articles/11-731/v1
|
01 Jul 22
|
{
"type": "Case Study",
"title": "Towards enhancing indoor environmental quality: a case of smart adaptive building envelopes in a coastal city",
"authors": [
"Sara Abouebeid",
"Nermine Hany",
"Gihan Mosaad",
"Nermine Hany",
"Gihan Mosaad"
],
"abstract": "Background: Earth's temperature has been rising since 1900, and the annual temperature has increased from 20°C to 24°C on the Mediterranean coastline. The external climate directly relates to indoor environmental quality (IEQ) and building performance, particularly in educational buildings. This paper proposes smart adaptive building envelopes (SABEs) as a potential solution for resilient architecture which is prone to unexpected weather patterns posed by climate change. Methods: A multi-dimensional criterion methodology is employed based on Egypt’s local climate, using SABEs to provide thermal comfort and natural daylight using minimum energy. The paper's novelty is in using a comparative methodology that is complemented with a software simulation (OpenStudio 3.0.1) to address the existing educational building design challenges in providing IEQ, and to assess the proposed SABE design’s performance, whilst providing better indoor thermal comfort and daylight. Results: The results show that the application of SABEs has led to significant reduction of the energy consumed, by 7.62% in summer and 5.42% in winter Conclusions: The implications of SABEs on IEQ in terms of thermal comfort and daylight are significant. SABEs also reduce energy consumption.",
"keywords": [
"climate change",
"smart adaptive building envelope",
"indoor environmental quality."
],
"content": "Introduction\n\nBuilding envelopes play an essential role in protecting internal spaces whilst facilitating climate control. These must respond to external forces, whether tangible forces like climate and environmental factors or intangible forces such as social factors and cultural heritage. Solutions to these external forces have been excessively imported to Egypt from western countries due to socio-political changes and swift development. Despite the difference in the environmental and cultural conditions, educational buildings in Egypt have adopted the fully glazed western building design. During the 20th century, heating, ventilation and air conditioning (HVAC) systems and artificial light were used to provide thermal comfort and lighting to buildings,1 which later developed into what is now known as “the international style”. The international style is characterized by its uniform design regardless of the building location, a fully glazed geometric shape without any form of aesthetics or ornamentation.2 This approach diluted the local identity; buildings in Cairo now look similar to those in Moscow or Beijing. The building envelope no longer reflects the identity, context or surrounding climatic conditions.\n\nThe paper evaluates the impact of climate change on coastal cities; in particular, Alexandria, Egypt. It then addresses the relationship between the climate and the built environment, building performance and indoor environmental quality (IEQ); identifying the existing strategies to oppose climate change on different scales, impacts of climate change on building performance and IEQ factors. An overview of smart adaptive building envelopes (SABEs) is then provided as a potential passive solution to overcome the effects of climate change on educational buildings, and an educational building case study is selected, Arab Academy of Science and Technology (AAST), Al-Alamein campus in Alexandria, Egypt. Thermal, light and energy simulations are run to analyze the existing building design challenges and assess SABE performance as a potential solution. Finally, the results are discussed, the challenges and limitations of the paper are addressed, and a set of guidelines on the international and local level are recommended.\n\nBuildings are responsible for 30 to 40% of the global energy demand.3 Disregard for Egypt’s building context, location, and climate is the reason for undesirable building performance in this regard. Occupants’ needs can be often ignored, in terms of well-being and productivity. The primary energy demands of educational buildings are attributed to lighting and ventilation. Since building envelopes are the barrier between the internal and external environment, controlling natural lighting and ventilation would be ideal in order to apply sustainable design strategies to achieve the optimum levels of IEQ, comfort, well-being, health and productivity. With Egypt’s recent development and economic growth, the western aesthetic approach of fully glazed building envelopes has been mimicked in a misplaced environmental context and cultural background. It causes enormous energy demand accompanied by energy shortages.4 This approach has added to the economic crisis. Thus, Egypt has urged stakeholders to use new technologies to reduce energy consumption. This paper aims to address the advantages of using SABEs in educational buildings using simulation-based comparative methodology, to compare between building performance with and without using SABEs. SABEs respond to the local environment and climatic challenges, to provide thermal comfort and natural daylight with the least energy consumption.\n\nClimate change impact on Alexandria\n\nRecently, coastal cities have been vulnerable due to their location; significant events of flooding, sea-level rise or unexpected weather patterns can drastically impact infrastructure, the construction of buildings, transportation networks, drainage systems, and communication networks. These drastic events will affect not only coastal cities but also coastal communities. More than 360 million inhabitants of coastal cities which are 10m above sea level are prone to natural catastrophes that threaten their lives, like storm surges and floods, due to climate change.5\n\nAlexandria is already facing the impacts of climate change and is expected to face serious challenges in the future. It is the second-largest city in Egypt. The population is in continuous increase; currently it is 5,449,817 and growing by 1.9% every year. The city of Alexandria has the largest harbor in Egypt. Alexandria has a moderate climate as a result of its location. The climate in Alexandria is classified as BWh by the Köppen-Geiger system,6 with subtropical deserts, moderate winters with light rainfall and dry summers.7 During the past few years, Alexandria has witnessed a decrease in temperature accompanied by rain during winter, and significant heat waves with a high percentage of humidity during summer.8 The average annual temperature of Alexandria is 20.8 °C, a continuous increase as it was 14 °C in 2018.7 The average yearly precipitation is 181 mm.\n\nExternal climate and built environment\n\nSince it is quite challenging to withhold climate change phenomena,9 global efforts are now focused on developing sustainable methods and strategies to anticipate, assess, and control buildings’ performance under the foreseen consequences of climate change.10 Buildings act as a climate modifier since they separate the indoor spaces from the external climate change events. Buildings and climate influence each other; they have a direct interrelationship.11 Buildings contribute to climate change due to their heavy energy consumption, which also affects the functionality of buildings.12,13 Thus, the sustainable design of buildings is key in overcoming the consequences of climate change by responding to different climatic patterns.\n\nDesigning sustainable and resilient buildings has significant potential for greenhouse gases reduction.14 Several factors, however, must be considered to achieve sustainability in the built environment, such as energy efficiency and thermal comfort.15 Strategies for designing sustainable and resilient buildings can broadly be categorized as mitigation strategies and adaptation strategies16 as shown in Figure 1. Mitigation strategies focus on preventing or reducing greenhouse gases to make the impact of climate change less severe. Adaptation strategies, on the other hand, focus on responding and adjusting to the current or the future impacts of climate change. Table 1 shows the difference between mitigation and adaptation strategies in terms of spatial scale, time and sector. Adaptation strategies are further classified into two categories: active and passive.17 Active strategies encompass the efficiency of ventilation technologies and strategies like HVAC. On the other hand, passive responses focus on bio-climatic concepts, for example building orientation, insulation methods and natural ventilation. Passive strategies are used to attain thermal comfort within the interior environment by reducing thermal exchange between the interior and exterior environment. This paper focuses on the passive strategies of sustainable educational buildings to provide the optimum comfort for building users and reduce energy consumption.\n\nBuilding performance: IEQ\n\nHistorically, IEQ did not receive much attention from designers or users than other building-related topics.18 But recently, IEQ has been gaining more attention than ever; it is involved in building design, policymaking, and building regulations. However, IEQ itself is a contested topic due to the multidisciplinary interest in it. As a result, there are several competing definitions, further leading to misinterpretations of what is considered good IEQ for building users.\n\nThe objective concept of energy efficiency in combination with subjective ideas of well-being is vital to achieving sustainable buildings. Well-being, health and comfort are defined as perceptual and physical qualities that play a vital role in the everyday experience of architecture and in connecting indoor to outdoor spaces.19 Users’ perception of indoor thermal comfort or discomfort depends on physiological and psychological reactions to the thermal characteristics of a space.20 Therefore, thermal characteristics are interweaved between tangible characteristics and the immaterial dimensions of the built environment.21\n\nThe quality of life inside buildings is defined by the IEQ.22 IEQ influences occupants’ comfort, health and productivity.23 However, IEQ is influenced by climatic conditions, occupants’ factors24 and different building-related factors.25 There are four main factors that tackle IEQ: indoor air quality (IAQ), thermal comfort, visual comfort, and acoustic comfort.26 This paper focuses on thermal comfort and visual comfort as follows:\n\nThermal comfort\n\nThermal comfort is one of the main parameters that control IEQ. Building occupants have to be thermally comfortable to be optimally productive. Thermal comfort depends on the occupant’s thermal adaptation, influenced by personal factors such as metabolic rate and clothing, and environmental parameters such as solar radiation, humidity, air velocity, and temperature.27 In the case of occupants’ exposure to a sense of thermal discomfort, this leads to increased energy consumption to achieve thermal comfort. Factors that influence thermal characteristics need to be considered during the design phase to achieve optimum thermal comfort. Making early decisions and considering these factors in the early design stage reduce energy consumption save money and time.\n\nVisual comfort\n\nVisual comfort plays a vital role in well-being and productivity, especially in educational buildings.28 Work productivity, performance and satisfaction are affected by visual comfort within workspaces.29 Lighting is a key factor affecting visual comfort, and physical and psychological health is affected by visual discomfort. For instance, insufficient light decreases the ability to see small details clearly.30,31\n\nVisual comfort is an essential quality in educational buildings. Thus, a building’s sources of light (daylight and artificial light) should be considered during the architectural design phase to get a more holistic image32 since it directly impacts well-being, productivity, and satisfaction. Window dimensions, geometry, and glazing control the amount of natural light inside spaces. Artificial light is as crucial as natural light to ensure visual comfort throughout the day. Natural light is important for creating better IEQ. However, glare can occur due to big windows that allow excessive light. Glare can cause significant visual and health problems.33 The acceptable range of glare is between 500-1500 cd/m2.\n\n“Adaptivity/adaptation” is to understand, interpret, and interact due to alterations in the surrounding context and environment. The contextual and environmental changes are described by dynamism. Meanwhile, contemporary designs are often based on a set of static factors that hardly can adapt to dynamic changes, such as opening size and building structure. Environmental and climatic changes directly impact people’s daily lives and needs. Thus, the paradigm of designing a performance system has to change to attain a higher level of climatic response. Responding to dynamic environmental variables like solar patterns and wind variation in the static structure of conventional buildings creates disengagement between the building’s structure and its surrounding environment. High-performance dynamic adaptive systems must respond to climatic conditions; these systems offer better efficiency and IEQ than static systems.34 Table 2 shows the advantages and disadvantages of SABEs.\n\nFor instance, in educational buildings that depend on mechanical air conditioning, there is a gap between the building envelope and its role as an environmental moderator. It also causes insensitivity to the surrounding environment. Sustainable buildings can adapt to the surrounding environment and its changes and take advantage of it. A building envelope is a key component in making the building sustainable, and its material, geometry, thermo-physical and optical properties.35 The majority of existing envelopes are used for heating or cooling purposes, depending on the climate. Adaptive building envelopes improve building energy efficiency by actively changing their thermal and optical properties, using kinetic energy to respond to climatic changes.36\n\nThe high-performance adaptive design approach adopts a passive design strategy for building envelope, impacting a building’s energy performance and consumption.37 The application of smart materials in building envelopes plays an important role in creating a sustainable passive design that can cope with environmental changes and offer building users different forms of comfort. The hybrid of adaptive and smart building envelopes achieves the goal of creating a comfortable indoor environment, regardless of the unexpected patterns of weather, with the minimum energy consumption.\n\nSABEs can respond to climatic changes and integrate daylighting, shading and natural ventilation as mentioned in Table 2, which decreases the energy consumed by building operations.34 The building envelope is a significant aesthetic element. It can motivate architects and designers to settle for high-performance envelopes that will attract stakeholders and clients due to the design flexibility in using different technologies and materials to create varied visual features. SABEs are described as envelopes that can change their properties as a response to the surrounding environment and climatic changes, as they control the different parameters of the building envelope.38 The changes can occur in various forms, such as introducing airflow or chemical change in a material—the SABE helps create a better indoor environment to boost well-being and achieve the optimum IEQ for building occupants.\n\n\nMaterials and methods\n\nThe paper focuses on educational buildings in coastal cities, choosing the AAST Al Alamein campus’s main building in Al-Alamein, Alexandria, Egypt. The methodology is simulation-based; it is divided into two steps, as shown in Figure 2. Step one is pre-study, for problem identification (result 1A) and solution identification (result 1B); step two is assessing the proposed outcomes of step one and simulation of the proposed SABE design. Comparing the existing results to the proposed results concludes a set of guidelines and decision support tools for designing SABEs for educational buildings in coastal cities (result 1C).\n\nThe pre-study step of the methodology aims to identify the problems facing the existing design of the studied building (AAST Al-Alamein campus) due to climatic changes. This step is divided into three parts as follows.\n\nProblem identification: existing building simulation\n\nThis part analyzes the building performance to identify the problems encountered by the building.\n\nThe energy simulations for this project are conducted using an energy simulation engine called OpenStudio 3.0.1 by NREL.39 The 3d modelling software Rhino 7.0 educational version40 is used along with the Grasshopper 1.0.0 tool41 to perform a parametric analysis of the existing and proposed SABE solutions. Blender is a free software that can work with Grasshopper the same way as Rhino using the same Grasshopper script. Honeybee 1.142 is a wrapper for OpenStudio that enables parametric energy simulation within Rhino as a plug-in. As shown in Figure 3, all the simulation results in the following section are produced via Honeybee. The simulation is a 3-step process to generate the results.\n\n1. Zoning and 3D modelling: a thermal model is created based on auto computer-aided design (CAD) drawings provided by the AAST to represent the existing building accurately. Zoning is an important step in the energy modelling process. It captures the real use cases of each room in the building; the energy consumption and comfort requirements in classrooms are different from those in a mechanical room. In addition to the zoning, details about the existing building envelope are also considered using the auto CAD drawing; the windows and atrium’s location, type and size are extracted.\n\n2. Material: existing materials of the building, construction type and weather conditions. The construction type assigned for the building is an ‘American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) zone 2 hot climate concrete construction’.\n\n3. Loads and schedule: loads are assigned used occupancy schedules. The purpose of the building is set as ‘school’, specific functions are categorized, like classrooms, corridors and offices. Assigning the occupancy serves multiple purposes:\n\n• Defines the functioning energy requirement of each space.\n\n• Defines the schedule (time, dates and holidays) of occupancy of the building.\n\n• Makes appropriate assumptions for the number of people present inside the rooms.\n\n• Regulates and controls windows (open/closed), the lighting (on/off), the HVAC (on/off/and temperature control) and equipment loads such as computers and lights.\n\n• Regulates the body heat given up by each person and the ventilation requirements for each person considering their zone.\n\n4-Results: building simulations are used in the AAST Al-Alamein campus with a focus on three aspects as follows:\n\n(2) Material selection. (3) Loads and schedule. (4) Results.\n\nIndoor thermal comfort\n\n• This component requires input like outdoor temperature, wind speed and mean radiant temperature.\n\n• Model: a Honeybee Model for which adaptive comfort is mapped. The environmental parameters are set based on the location of the AAST campus in Al-Alamein.\n\n• Weather data: the path to an EPW weather file is used for the comfort map simulation. Weather data (.EPW file) for the Al-Dabaa area was the closest identified weather data to the building’s location.\n\n• Airspeed: a single number for airspeed in m/s or an hourly data collection of airspeeds that align with the input run period. Airspeed is used for all indoor comfort evaluations.\n\n• Comfort parameters: optional comfort parameters from the “LB Adaptive Comfort Parameters” component specify the criteria under which conditions are considered acceptable/comfortable. The default will use ASHRAE-55 adaptive comfort criteria.\n\n• Solar body parameters: optional solar body parameters from the “LB Solar Body Parameters”. The default assumed average skin/clothing absorptivity, and a human subject always has their back to the sun at a 45-degree angle.\n\nThe output of this component is thermal comfort percentage, operative temperature –summer and operative temperature- winter, and predicted mean value (PMV).\n\nDaylight\n\nThis component requires input such as:\n\n• Annual radiance: a list of annual radiance configuration files from the “Honeybee (HB) Annual Daylight” which includes predefined components such as weather file, test points for measuring daylight and the sun-up hours, while setting the complicated components as default.\n\n• Occupancy Schedule: an annual occupancy schedule. It can be the identifier of the energy schedule in schools and universities; a schedule from 9 AM to 5 PM on weekdays is used. It identifies weekends and vacations.\n\n• Threshold: threshold for daylight autonomy in lux, set to 300.\n\n• Minimum and maximum: the minimum and maximum values for useful daylight illuminance are set to 100-3000.\n\nThe output of this component is useful daylight illuminance (UDI) and glare analysis; amongst other outputs, daylight autonomy (DA) and continuous daylight autonomy (cDA). DA and cDA are the previous version of the UDI method and provide no additional data. Hence, they are not considered in this study.\n\nEnergy usage\n\n• Holidays: all holidays, including the weekends, summer and winter holidays, are identified.\n\n• Start day of the week: assigned as Sunday.\n\n• Start hour: when users start occupying the building.\n\n• End hour: the time when occupants leave the building.\n\n• Terrain: identifying the surroundings of the building (two buildings on the east and west sides of the building) to determine the wind speed around the studied building.\n\n• Monthly ground temperature: a list of 12 monthly ground temperatures. The temperature data is imported via the EPW file.\n\nThe outputs of this component are a data tree with all of the building-wide energy balance terms; normalized energy balance is the one chosen as the normalized values make the energy consumption results comparable.\n\nSolution identification: material selection\n\nSABEs are claimed to be a solution for achieving optimum IEQ and reducing energy consumption. However, a SABE is a hybrid, incorporating smart materials in adaptive envelopes. There are different types of smart materials, each has a unique set of factors which are:\n\n• Physical properties (response factors).\n\n• Morphology.\n\n• Cost of manufacturing.\n\n• Location of production.\n\nThe factors of adaptation, location of the building and cost budget are the decision support tool for choosing the right smart material for the building envelope.\n\nSolution identification: movement selection\n\nThe movement of the building envelope is another variable that is selected based on a set of factors as follows:\n\n• Environmental factors (adaptation factors)\n\n• Suitable type of movement\n\n• View allowance\n\nThese factors are also part of the decision support tool to select the right movement of the building envelope.\n\nThe purpose of step two is to apply the identified solution (material and movement of SABEs) to assess the building performance by simulating indoor thermal comfort, daylight and energy usage. Comparing the existing building results and the proposed design serves to confirm or disprove the hypothesis that SABEs can enhance IEQ for occupants and reduce energy consumption. This step is divided into three parts as follows:\n\nProposed SABE design\n\nThe two results from the previous step, identifying the problems and solutions, are used to inform the design of the hypothetical SABE. Identifying the problem allows the proposed design to be specific to the site and its context, whereas identifying the solutions ensures that the SABE is suitable for the building theoretically and feasible practically.\n\nProposed building simulation\n\nSimulations analyze the indoor thermal comfort, daylight and energy usage of the building with the proposed SABE design; to evaluate the performance of SABEs.\n\nComparison: existing vs proposed\n\nComparing the existing design results to the proposed building performance in terms of indoor thermal comfort, daylight and energy usage gives an idea of how effective the SABE is in addressing the problems identified in result 1A. Hence, ensuring that the decision support tool functions as intended.\n\n\nResults\n\nIndoor thermal comfort\n\nThe indoor thermal comfort component analyzes the adaptive comfort for building users. Building occupants adapt themselves to the monthly mean temperature; occupants would feel comfortable if the building temperature is close to the monthly mean temperature, above 10 °C and below 33.5 °C.\n\nThermal comfort percentage\n\nThermal comfort percentage is the annual percentage of time during the building’s active occupancy that occupants feel thermal comfort. The comfort percentage is determined using ASHRAE-55, the adaptive comfort criteria and the metabolic rate for the occupants performing daily activities according to a schedule. The results of the simulation for the existing AAST Al-Alamein building indicate the following44:\n\n• The atrium of the building has the worst performance,\n\n• This is followed by zones closer to the windows in the southern, eastern and western sides of the building.\n\n• The low percentage of thermal comfort along the windows is due to heat gain into zones via the glass windows, which must be addressed.\n\n• The internal zones (zones with no external windows) are reasonably comfortable, whereas the corridors with few windows are the most comfortable.\n\nThe atrium serves as a transitional space for circulation and special events; in comparison, students and teachers spend most of their active hours in classrooms and internal zones.\n\nOperative temperature\n\nOperative temperature is the calculated temperature of each grid point in the simulation model. The analysis period selected is for two key hours: the summer solstice (21st of June from 13:00 to 14:00) and the winter solstice (21st of December from 13:00 to 14:00). These hours are selected to present the shortest and longest days representing the highest and lowest operative temperature, respectively.\n\n• The zones along the west and south of the buildings experience heat.\n\n• The southern rooms are exposed to more intense heat.\n\n• The rooms adjacent to the north and south of the atrium are affected by heat.\n\nPredicted mean value (PMV)\n\nPMV is the prediction index value of a group of occupants on their thermal sensation scale; the scale has seven points. Thermal equilibrium is achieved when the heat loss is equivalent to internal heat production. The heat balance is influenced by personal factors and environmental parameters, such as metabolic rate, clothing and airspeed, temperature. Personal factors are identified based on the material selection, load and schedule steps. Simulation runs calculating PMV during the summer solstice (21st of June from 13:00 to 14:00) and winter solstice (21st of December from 13:00 to 14:00). The result of the simulation shows the following:\n\n• Building occupants feel slightly warm on the eastern side and feel hot closer to the southern and western windows of the building during the summer.\n\n• Occupants feel neutral in the inner rooms of the building, slightly cool in the south room and cool in the rest of the building during winter.\n\n• In contrast to the summer, the heat by the windows in the south is more noticeable in the winter and has more spread.\n\n• No neutral PMV is achieved, which means that none of the occupants are thermally comfortable during these seasons of the year, other than the inner rooms in winter.\n\nDaylight\n\nDaylight analysis calculates the quantity and quality of daylight within indoor spaces. It analyzes the daylight factor- the ratio between the interior and exterior natural lighting illuminance level.\n\nUseful daylight illuminance (UDI)\n\nUDI is a metric of available daylight in a space, which corresponds to the percentage of occupied time when a target range of illuminances at a point is met by sunlight. Daylight illuminances are set to be desirable between the ranges of 300 to 3000 lux.43\n\nThe UDI low-value analysis shows the areas that need artificial lighting, approximately 70% of the whole building, as shown in Figure 4(a). On the other hand, The UDI high-value analysis shows the spaces that have natural daylight-as shown in Figure 4(b). However, some of them have a high intensity of natural sunlight that may cause discomfort to the building occupants.\n\n(a) Existing design; (b) Proposed smart adaptive building envelope (SABE) design.\n\nThe UDI simulation of the existing building design shows the following:\n\n• The rooms facing the west, south and north sides of the buildings require no artificial lighting.\n\n• The rooms on the west side of the building require minimum lighting.\n\n• The corridors and interior rooms show the UDI value 0, which fully requires artificial lighting.\n\nGlare analysis\n\nGlare is visual discomfort caused by excessive and uncontrolled light. When direct light shines into the eyes, it is hard for the eyes to adjust to the sudden level change of illumination. Glare problems in educational buildings are significant and can cause occupants health problems. The glare analysis aims to visualize indoor spaces with glare problems. Four classrooms are analyzed to examine the glare situation to measure the glare occurrence in an internal space; the rooms were selected based on the location as shown in Figure 5 and Figure 6; to show the effect of glare on each side of the building; north, south, east and west. The acceptable glare is up to 1500 cd/m2.\n\nAs shown in Table 3, the maximum glare exposure to the four rooms is below 1500 cd/m2, within the acceptable range. Thus, glare is not one of the issues affecting the existing building performance and IEQ.\n\nEnergy usage\n\nEnergy usage analysis calculates the energy consumption of the building. The cooling demand is generated based on standard equipment load for the zone, and occupancy load is generated from the users occupying the zones. The major areas of energy consumption of buildings are heating, cooling, lighting.\n\nNormalised energy balance\n\nThe energy demanded for heating and cooling is directly related to the external temperature. The energy needed for cooling begins consumption in March and increases gradually to reach the peak during July, which has the highest temperature, and stops by October. The energy required for heating begins consuming in November, gradually increasing until reaching the peak in January, which has the lowest temperature, and gradually decreases till April.\n\n• Peak energy consumption comprises heating, cooling, lighting, and equipment demands.\n\n• During summer, the cooling demand is the highest contributor, as it reaches up to 209.86 kWh/m2.\n\n• During winter, the heating demand is the highest contributor, as it reaches up to 188.88 kWh/m2.\n\n• Heating demands during summer and cooling demands during winter are unnoticeable.\n\nThe results show unusually high results for the atrium; therefore, the atrium results are not included. Upon further investigation into the results, it is determined that the tools used in this simulation are not appropriate to analyze complex building physics, such as convection in the atrium. To sum up, Table 4 shows the highlights of the existing building design challenges.\n\nMaterial selection\n\nThe selection of smart materials used in building envelopes located in coastal cities is based on criteria of identifying material properties (as shown in Table 5), environmental conditions of the building context, cost and accessibility (as shown in Figure 7).\n\nThis paper focuses on SABEs in coastal cities and, in particular, Alexandria. Successful material selection is based on choosing a material which is produced within Egypt or proximity countries and which has the properties that can adapt to the local climate. This has the added advantage of reducing carbon dioxide emissions in procuring the materials, stimulating the local economy of the region and incentivizes designers and decision-makers to choose the specified materials.\n\nFigure 7 shows that the clustering of smart materials manufactured within Egypt is shape memory polymer (SMP), shape memory alloy (SMA), and electro active polymer (EAP). However, color-changing materials and phase change material (PCM) may also be available due to Alexandria’s ease of access and proximity to these. Regarding cost, PCM, thermos bimetals and EAP are considered the cheapest, while SMA is regarded as the most expensive. Therefore, SMP, SMA, EAP are focused on. Their properties, advantages, disadvantage and morphology are identified as follows:\n\nBy considering different types of smart materials in terms of advantages, disadvantages, morphology and factors of adaptation as shown in Table 5, and cost of manufacturing and location of production as shown in Figure 7, the SMA nickel titanium is selected to be applied as the “smart” material in SABEs (see Table 6).\n\nMovement selection\n\nA decision support tool is created to select the right SABE design for the building based on factors of adaptation, as shown in Figure 8. Based on result 1A, sunlight and temperature are the main adaptation factors for the selected case study; rotational panels have been selected. There are different typologies of panels (as shown in Figure 9); vertical panels are preferred if the north, east and west elevations are exposed to the sun since they can block the sun relatively well. Egg-crate shading devices are usually used for non-south facing, high-rise buildings. However, horizontal panels are selected since results-1A show the thermal comfort and light issues are mainly concentrated on the south, east and west sides of the building. It also allows a field for the external view (as shown in Figure 9) which is important for occupants of educational buildings.\n\nThere are two types of external shading devices: fixed and movable. Movable shadings can adapt to variable environmental factors like sun path (solar radiation) and external air temperature. It can be mechanically dependent or made from smart materials. Horizontal, vertical or egg-crate are the basic designs of shading devices as shown in Figure 9. It is necessary during the design phase to measure the preferable solar penetration during summer. Horizontal shading is suitable for southern exposure to the sun. For low rise buildings, south elevations can be shaded using roof overhangs. Horizontal panels and horizontal louvres are considered the most aesthetically pleasing solution for buildings that require good view access for outdoor spaces, like hospitals, residential and educational buildings.\n\nSABE design\n\nAs a result of identifying the problems facing the existing building design (result 1A) and identifying potential solutions (result 1B), the SABE is proposed (Figure 10).\n\nThe SABE consists of horizontal panels, static ones covering external walls (to add additional insulation to the western and southern sides of the building and aesthetically blend the window panels to the rest of the envelope) and dynamic ones covering windows. The panels are made of SMA (nickel titanium) supported by structure frames. The panels respond to solar radiation and temperature; they can respond automatically in two movements, primary and secondary, as shown in Figure 11. The horizontal panels vertically divided with the dimensions x*y are 0.30*0.20 m, to get better articulation of the panels. The actuators and sensors control the primary movements of the dynamic panels on the building envelope (open/closed movement). At the same time, the finer movement among individual panels is the properties of SABEs responding to environmental changes, as shown in Figure 12.\n\nA SABE has two movements, primary and secondary, as shown in Figure 11. The primary movement is controlled by actuators and sensors on the building envelope that react at a larger time interval. The secondary movement controls the fine adjustments between the larger time intervals through a SABE’s smart properties. The actuators and sensors can also supplement the secondary movement during times with low solar radiation due to low thermal conductivity of SMA.\n\nProposed building simulation: results comparison\n\nBuilding simulation runs again after applying SABEs to compare the difference between the existing building performance and the proposed SABE design in terms of indoor thermal comfort, daylight and energy usage as follows:\n\nThermal comfort percentage\n\nThe results vary from 0-100% and are colored from red to blue. Red regions imply that occupants in these zones are least comfortable, and the blue zones imply most comfort. It must be noted that the comfort percentage includes both heat and cold sensation. Hence, extreme hot and cold zones are both colored in red.\n\nThermal comfort percentage has significantly increased with the proposed SABE design to 40% of comfortability in rooms with external windows on the north, west, south and east sides, as shown in Figure 13. The percentage of time when the atrium is comfortable has also increased from 0 to 20%. The number of rooms that are 30% thermally comfortable and more has increased from 13 rooms to 57 rooms, as shown in Figure 14.\n\n(a) Thermal comfort percentage of existing building design. (b) Thermal comfort percentage of proposed smart adaptive building envelope (SABE) design.\n\nOperative temperature\n\nThe analysis grid is colored with its operative temperature in Celsius using a blue-yellow-red gradient color scheme. Blue is the lowest temperature, and red is the highest temperature. It must be noted that the range of values is different. The atrium is excluded from the analysis as previously mentioned, as it is a transitional space for circulation.\n\nThere is an extreme variation between the minimum and maximum temperature (24 °C). This intense heat is focused on the western window, and it is essential to address it. Though the hot spots are more prominent, the minimum and maximum temperature variations are not extreme (16 °C).\n\nThe operative temperature of the building during the winter solstice (21st of December between 1-2 pm), as shown in Figure 15, has a slight increase on the north and east sides by 1 degree. However, the temperature of the rooms on the south and west side of the building has dropped to 20-21 °C. The rooms overlooking the atrium have decreased by 2 degrees, reaching a range of 23.9 to 25.8 °C.\n\n(a) Operative temperature of existing design during winter. (b) Operative temperature of proposed smart adaptive building envelope (SABE) design during winter.\n\nDuring the summer solstice in the proposed SABE design, the operative temperature, as shown in Figure 16, has decreased (on the 21st of June between 1-2 pm). In rooms on the west side, the operative temperature dropped close to the window from a range of 45-50 °C to 26 °C. The operative temperature of rooms on the east side had reduced from 28.5 °C to 26.5 °C. Rooms on the north and south sides’ temperature decreased from a range of 28.5 °C and 30.9 °C to 26.1 °C and 26.5 °C.\n\nBy comparing the existing building design and the SABE design, the number of rooms with an operative temperature of 26 °C has increased from 35 rooms to 48 rooms, as shown in Figure 17a, and the amount with temperatures of 28 °C have decreased from eight to three rooms. During winter, the operative temperature dropped in most rooms, as most rooms’ (20 rooms) temperature is 20 °C, as shown in Figure 17b.\n\nThe charts compare the operative temperature of the existing building design to the proposed smart adaptive building envelope (SABE) design: (a) During summer. (b) During winter.\n\nPMV\n\nPMV has improved in the proposed SABE design, as shown in Figure 18. PMV has changed from hot to slightly warm during summer on the west and south sides of the building (close to windows) and rooms that overlook the north of the atrium.\n\nThe scale has seven points to predict the thermal sensation of building occupants; predicted mean value (PMV) analysis results of building occupants during summer for: (a) Existing building design. (b) Proposed smart adaptive building envelope (SABE) design.\n\nOn the other hand, PMV during winter, as shown in Figure 19, for rooms on the four sides of the buildings have degraded from slightly cool to cool. However, the south of the building and the atrium (close to windows openings) have improved, from hot to slightly cool and slightly warm, respectively.\n\nPredicted mean value (PMV) analysis results of building occupants during winter for: (a) Existing building design. (b) Proposed smart adaptive building envelope (SABE) building.\n\nOccupants feel slightly warm in all rooms during summer in the case of the SABE design. However, occupants feel a range of slightly warm, warm and hot in the existing building rooms, as shown in Figure 20a. During winter (as shown in Figure 20b) the majority of building occupants feel slightly cool in the proposed SABE design (46 rooms), and 38 rooms in the existing design, whereas occupants feel neutral in 15 rooms in the SABE design and 20 rooms in the existing design.\n\n(a) During summer. (b) During winter.\n\nDaylight: UDI\n\nSABEs have a minor impact on the UDI of the rooms located on the north, east and north side of the building, as shown in Figure 21. However, UDI degraded in rooms located on the west side of the building, requiring more artificial light increasing electrical energy usage.\n\n(a) Existing design; (b) Proposed smart adaptive building envelope (SABE) design.\n\nThe number of rooms with UDI values of zero and 80 has increased from 25 to 28 rooms and from 7 to 11 rooms, respectively, as shown in Figure 22. The number of rooms with a UDI value of 60 has significantly decreased from 14 to 9 rooms.\n\nEnergy usage: normalized energy balance\n\nEnergy usage has significantly decreased, as shown in Table 7. The total peak energy consumed has reduced by 7.62% during summer and 5.42% in winter. Heating demand during winter has decreased by 5.52%, and cooling demand during summer reduced by 5.84%. Lighting demand has reduced during summer and winter by 7.04% and 4.67%, respectively. A fraction of energy is used for other mechanical purposes throughout the year.\n\nIndoor thermal comfort, daylight and energy consumption is improved by using SABEs. The peak end-use energy for heating, cooling and lighting is calculated as follows:\n\nEnd-use energy = energy-use intensity (see Table 8)/coefficient of performance (CoP).\n\nCoP of heating ranges between 2.0-4.0, CoP of cooling ranges between 2.3-3.5.\n\nCoP of heating is assumed as 4 and cooling as 3.5.\n\n\nDiscussion\n\nSABEs can improve the IEQ, thermal comfort, levels of daylight and energy use. The results demonstrate that when a SABE is designed according to the local context, weather and building use, they can significantly improve thermal comfort, PMV and daylight. The results also show that while the occupants’ comfort is improved, it does not necessarily come at the cost of increased energy consumption; rather, SABEs reduced the heating and cooling demand. While SABEs are dynamic in their movement, it must be noted that they are permanent envelope fixtures and may pose a problem while optimizing for both summer and winter. The improvement can only be optimized for a particular season; the summer scenario was considered to cause a significant negative impact in the case study discussed. Hence, it was chosen as the optimization goal; this slightly decreased the winter comfort levels in some zones.\n\nIt is imperative to acknowledge the technical limitations of software and the limited time and resources available for the case study. Energy simulation is an extremely complex process requiring detailed input on various parameters such as wall composition glazing (gap, air, thickness and so on). Appropriate assumptions were made to the best ability of the author with the available data, but detailed material information may change the results. Large areas with complex geometries and mechanical systems must be simulated at a high resolution (spatially and in time). That requires extremely high computational power, often scaling exponentially. For instance, the area of a room of 5*5 m is 25 m2, but the area of a room of 10*10m is 100 m2 (i.e., doubling the size scales the area by four times), which is not possible with common personal computers.\n\nHoneybee and lb tools are built around the EnergyPlus energy simulation engine. The primary purpose of this energy modelling tool is to calculate radiative heat transfer between the different zones in the building and the outside. However, the study building consists of an atrium that spans multiple floors. The building physics in such a space involve radiative and convective heat transfer. It is determined that EnergyPlus alone is not sufficient to accurately calculate the energy demand for the zone. Hence, results for the atrium are not included. In future studies, it is recommended to use a combination of EnergyPlus and computational fluid dynamics (CFD).\n\nThe scope of this paper is limited to the envelope design, while respecting the existing design decisions. Hence, the scope for influencing the building’s performance is extremely limited. Important components of the design that influence the performance, such as the atrium and the window to wall ratio, are already decided prior to the design intervention.\n\n\nConclusion\n\nClimate change is a global issue that is inevitable. The effects of climate change manifest across the economic, environmental and social dimensions. It is impossible to ‘beat nature’ and stop climate change events from happening entirely. New courses of action must be taken on different scales; the built environment must be adaptively designed to respond to unpredictable climatic changes. Building envelopes are physical layers that separate the unconditioned exterior from the interior environment where people live, work, study and perform everyday activities.\n\nEnvironmental and climatic changes directly impact people’s daily lives, needs, and performance. Internal environments must be designed to offer the optimum IEQ; this cannot be achieved using static building envelopes. This paper demonstrates that SABEs can respond to climatic changes and offer efficient IEQ for occupants. Smart materials have high performance, responsive and changeable properties. The usage of SABEs creates a better IEQ by providing thermal comfort and daylight availability, and by reducing energy consumption. Climatic changes have to be addressed based on the location and the context of the building; to identify the suitable smart material, adaptive structure and movement design. Different smart materials have various properties and adapt to certain climatic changes; each can be selected based on the required adaptation.\n\nThe guidelines are sorted into two scales, internationally and locally, to improve educational buildings located in coastal cities. The following guidelines are for the international scale:\n\n• Analyze climatic zone and understanding climatic challenges.\n\n• Identify suitable smart materials based on adaptation factors, material properties, availability in terms of access and cost.\n\n• Analyze the dynamic pattern of the envelope that can adapt to the addressed climatic changes.\n\n• In the case of improving an existing building, it is important to identify the factors negatively affecting IEQ.\n\n• Analyze the improvement rate, with and without SABEs.\n\n• Priorities thermal, acoustic and visual comfort in classrooms, study areas and offices, respectively.\n\n• Zones which are not regularly populated for long periods of time are important and must be comfortable. However, this should not be at the cost of comfort in more frequently used zones such as classrooms, study rooms and offices.\n\nA set of recommendations are given for educational buildings located in Alexandria, Egypt, the local scale:\n\n• Three types of smart materials that are recommended to be used, which are SMP, SMA and EAP.\n\n• Horizontal shading panels are recommended due to the sun’s path in the southern hemisphere and higher sun angles at the equator.\n\n• Windows must be adequately sized in the south and west façade in case trees, buildings, etc. provide no external shading to prevent thermal discomfort caused by solar heat gain.\n\n• While prioritizing the trade-off between thermal comfort and daylight, thermal comfort must be given higher priority as the environmental impact is significantly higher than correcting for daylight.\n\n\nData availability\n\nMendeley data: SABE Simulation. http://doi.org/10.17632/b9db42k7pm.144\n\nThis project contains the following underlying data:\n\n• annual_daylight_inputs.json (The required inputs for the Honeybee annual daylight simulation).\n\n• Base_Model.hbjson (The Honeybee base repetitive floor model of Al-Alamein simulations).\n\n• Dabaa.wea (EPW weather data file of Al Dabaa, Egypt -the closest available weather data to Al-Alamein- available at https://www.ladybug.tools/epwmap/).\n\nMendeley data: SABE Simulation. http://doi.org/10.17632/b9db42k7pm.144\n\nThis project contains the following extended data:\n\n• iso_01.jpg (Exploded diagram of SABE design).\n\n• SampleRoom_FacadePanel.jpg (A figure shows the SABE adapting to the sun path).\n\n• SampleRoom_NoFacadePanel.jpg (A figure showing the SABE adapting to the sun path -static envelope is hidden).\n\n• summer_01.gif (A gif showing primary movement of proposed SABE movement during summer).\n\n• summer_02.gif (A gif showing primary movement of proposed SABE movement adapting to the sun path during summer - static envelope is hidden).\n\n• winter_03.gif (A gif showing primary and secondary movement of proposed SABE movement during winter).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgments\n\nThe authors would like to acknowledge the support received from the AAST administration and staff for providing full access to Al-Alamein campus construction drawings. We would also like to thank Sanjay Somanath for providing technical support.\n\n\nReferences\n\nHeiselberg P: Integrated building design.2007.\n\nMcMullin PW, Price JS, Seelos RT: Steel Design. Routledge;2017.\n\nPark JY, Nagy Z: Comprehensive analysis of the relationship between thermal comfort and building control research-A data-driven literature review. Renew. Sust. Energ. Rev. 2018; 82: 2664–2679. Publisher Full Text\n\nGhiasvand J, Akhtarkavan M, Akhtarkavan H:Adaptive re-use of Islamic and Iranian architecture’s elements. WSEAS International Conference. Proceedings. Mathematics and Computers in Science and Engineering. WSEAS;2008.\n\nHoornweg D, Bhada P, Freire M, et al.: Cities and Climate Change: an Urgent Agenda (World Bank). Urban Development Series. 2010; 10: 17. 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Proceedings of the 13th international IBPSA conference held in Lyon, France Aug. 2013; pp. 3128–3135.\n\nMardaljevic J, Andersen M, Roy N, et al.: Daylighting metrics: is there a relation between useful daylight illuminance and daylight glare probabilty?. Proceedings of the building simulation and optimization conference BSO12, no. CONF. 2012.\n\nAbouebeid S: SABE Simulation. Mendeley Data. 2022; V1. Publisher Full Text"
}
|
[
{
"id": "175407",
"date": "13 Jun 2023",
"name": "Waqas Ahmed Mahar",
"expertise": [
"Reviewer Expertise Thermal Comfort",
"Indoor Environmental Quality",
"Sustainable Architecture",
"Design-Decision Support",
"Building Performance Simulation",
"Passive and Bioclimatic Design"
],
"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 focuses on the improvement of indoor environmental quality using small adaptive building envelopes in Alexandria, Egypt. The study is based on the simulation of an educational building using simulation tools and programs.\nThe paper presents a significant discussion on climate change, disasters and energy. However, the focus is very limited. The authors must limit themselves to the subject matter rather than stating long paragraphs on an issue that is barely solved by this study. Moreover, acoustic comfort and air quality were also not focused on in this paper. So the title does not match the methods and findings.\n\nPlease find my comments below:\nGeneral comment: Too many details are missing. The authors claim they have done a lot, yet the scope is not clearly defined. Many vague statements are included. I will only highlight a few. Several irrelevant details are given and essential details are missing.\n\nIntroduction: \"The paper evaluates the impact of climate change on coastal cities\". It is a wrong statement. You can not evaluate the impacts just by analyzing the limited parameters of a building.\n\n\"It then addresses the relationship between the climate and the built environment, building performance and indoor environmental quality (IEQ); identifying the existing strategies to oppose climate change on different scales, impacts of climate change on building performance and IEQ factors.\" Also, a wrong statement. Must be rewritten and corrected.\n\nThere is too much discussion on IEQ, the focus however remains on Thermal and visual comfort.\n\nA building envelope doesn't only contain windows and openings. The study only focuses on smart shading devices and openings.\n\nFig 1 and Table 1. Irrelevant. The study doesn't focus on climate change adaptation or mitigation.\n\n\"This paper focuses on the passive strategies of sustainable educational buildings to provide the optimum comfort for building users and reduce energy consumption.\" Only one strategy is focused. The authors need to understand passive design principles and strategies.\n\n\"A building envelope is a key component in making the building sustainable, and its material, geometry, thermo-physical and optical properties.\" Most of these details are not provided in the manuscript. Details of input datasets are missing. Building plans, models, geometry, details of materials, construction techniques, and thermophysical properties of materials are missing.\n\nDefine: how zoning was done for this building? Is it s a single-storey or multi-storey building?\n\n\"Material: existing materials of the building, construction type and weather conditions.\" The reader can not get the info on the existing situation unless given in the paper. One can not just assume and know the materials and building type in Alexandria.\n\nLoads and schedule: loads are assigned using occupancy schedules: Since it is an existing building. Where is the validation? Existing Loads and schedules? I assume this data was collected.\n\n\"Makes appropriate assumptions for the number of people present inside the rooms.\" Based on what data?\n\nWhat is LB adaptive comfort?\n\nASHRAE-55 adaptive comfort model shows comfort for 80% and 90% of the occupants. Which criteria are used for this study?\n\nWhy questionnaire was not used for the comfort survey?\n\nWhat is the actual energy consumption of the base case?\n\nWhat is the validation and reliability of the simulation model?\n\nThe performance analysis of the base case is missing.\n\nLocation of production: what do you mean by this? Building's location?\n\nWhat do you mean by movement selection? and view allowance?\n\n\"Right movement of the building envelope\". Do you mean the whole building envelope would move or just the shading devices?\n\nThermal comfort: no figures/ tables are given in support of the results.\n\nAdd a table of the analysed scenarios for improvement of thermal, and visual comfort and the reason behind the selection of these scenarios.\n\nThe paper is vaguely written and confuses the readers. All of the sections must be rewritten. The results show no significant results that help to reduce climate change impacts. The IEQ is not fully analysed. However, the introduction, methods, discussion and conclusion focus on climate change and IEQ.\n\nClearly add the aim, objectives, research questions, limitations, input variables, building geometry and plans. Focus on methods, results, discussion and conclusion.\n\nIs the background of the case’s history and progression described in sufficient detail? No\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? Partly\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\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? No",
"responses": []
},
{
"id": "175401",
"date": "05 Jul 2023",
"name": "Hanan Alkhatri",
"expertise": [
"Reviewer Expertise Thermal comfort",
"Climate responsive design"
],
"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 research reports the findings of integrating smart adaptive building envelope techniques into an educational building using software simulations. The paper in its current state looks more like a report more than a journal article. The introduction section lacks focus and integrity. The importance of the research is not clear nor is the justification for the selection of educational buildings as a case study. Additionally, the discussion of previous similar studies is missing, which is not acceptable. Also, the selection of the particular building is not clear. In what ways does the building represent the educational buildings in Egypt? Here are additional comments:\nAbstract >> Methods>> [The paper’s novelty is in using a comparative methodology that is complemented with a software simulation (OpenStudio 3.0.1) to address the existing educational building design challenges in providing IEQ, and to assess the proposed SABE design’s performance, whilst providing better indoor thermal comfort and daylight.]: what is novel in applying the methodology? Please explain in what ways this is authentic. I suggest approaching the novelty of the paper from a different direction.\n\nIntroduction: [The international style is characterized by its uniform design regardless of the building location, a fully glazed geometric shape without any form of aesthetics or ornamentation.] Please consider rewriting this sentence.\n\nIntroduction: [This approach diluted the local identity; buildings in Cairo now look similar to those in Moscow or Beijing. The building envelope no longer reflects the identity, context or surrounding climatic conditions.] These two sentences can be considered as claims. Please provide appropriate references to support your idea. You can also compare examples of buildings from the mentioned cities to support the idea. There are other sentences that can be considered as claims like:\n[Occupants’ needs can be often ignored, in terms of well-being and productivity.]\n\n[This approach has added to the economic crisis.]\n\n[Alexandria is already facing the impacts of climate change and is expected to face serious challenges in the future.]\n\n[The acceptable range of glare is between 500-1500 cd/m2.]\n\n[Building occupants adapt themselves to the monthly mean temperature; occupants would feel comfortable if the building temperature is close to the monthly mean temperature, above 10 °C and below 33.5 °C.]\n\nIntroduction: [The paper evaluates the impact …. and a set of guidelines on the international and local level are recommended.]: please replace this paragraph with another one discussing the importance of the reported research and its relevance to Egypt's current situation regarding climate change, built environment, and IEQ. I also suggest moving the paragraph to another part of the introduction to maintaining the coherence between the discussed ideas.\n\nPlease explain what is SABEs in one paragraph for the reader.\n\nPlease rewrite this paragraph, so the sentences are more connected: [Alexandria is already facing the impacts of climate change …]\n\n[A building envelope is a key component in making the building sustainable, and its material, geometry, thermos-physical and optical properties.] This is an incomplete sentence. Please rewrite it.\n\n[The majority of existing envelopes are used for heating or cooling purposes, depending on the climate.] Please elaborate more. This sentence is not clear.\n\nThe methodology section is noticeably long. Please consider shortening it to enhance the paper's readability. Despite this, it lacks a section about the validation of the constructed model, which is not acceptable. The architectural description of the selected case study is missing as well, which is again not acceptable.\n\nPlease consider presenting the indoor thermal comfort results in figures or tabulation formats instead of descriptive paragraphs. This will enhance the readability of the paper.\n\n[Building occupants fell slightly warm on the eastern side and feel hot closer to the southern and western windows ….] Please provide the architectural description of the investigated case study, so the reader can understand your results better.\n\nPlease improve the quality of figures 4, 5, 13, 15, 16, 18, 19, and 21.\n\nThe discussion of the results should explain clearly how the suggested modifications helped in solving the issues that the case study suffers from in terms of energy consumption and IEQ.\n\nMovement selection >> [A decision support tool is created to select the right SABE design for the building based on factors of adaptation, as shown in Figure 8.] Please explain the details of this tool, the rationale behind it, how was it created, how was it validated, etc.\n\n[It is imperative to acknowledge the technical limitations of software and the limited time and resources available for the case study.] Does this mean that the results are not reliable? Please be careful when discussing the limitation of the research. The limited time is not acceptable; you can take the time you need to finish your simulations and investigations and then report your results.\n\nThe findings of the study were not presented in context by comparing them with the results of similar previous studies.\n\nThe conclusion section should be rewritten to reflect the reported research.\n\nA few of the listed references were published recently.\n\nIs the background of the case’s history and progression described in sufficient detail? No\n\nIs the work clearly and accurately presented and does it cite the current literature? No\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? No\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-731
|
https://f1000research.com/articles/11-495/v1
|
05 May 22
|
{
"type": "Research Article",
"title": "Association of leukocyte nadir with complete remission in Indonesian acute myeloid leukemia patients undergoing 7+3 remission induction chemotherapy",
"authors": [
"Dwi Wahyunianto Hadisantoso",
"Dody Ranuhardy",
"Wulyo Rajabto",
"Aulia Rizka",
"Lyana Setiawan",
"Ikhwan Rinaldi",
"Arif Mansjoer",
"Erni Juwita Nelwan",
"Hamzah Shatri",
"Dody Ranuhardy",
"Wulyo Rajabto",
"Aulia Rizka",
"Lyana Setiawan",
"Ikhwan Rinaldi",
"Arif Mansjoer",
"Erni Juwita Nelwan",
"Hamzah Shatri"
],
"abstract": "Background: The 7+3 regimen is still the main choice of remission induction chemotherapy in acute myeloid leukemia (AML). Successfully achieving complete remission (CR) and the time required to achieve it determine patient’s survival. Hence, bone marrow examination on 14th day of chemotherapy is recommended to predict CR. However, the examination is invasive and still inaccurate. Methods: A prognostic study with retrospective cohort design was conducted at two central hospitals in Indonesia based on medical record data of AML patients who underwent 7+3 induction chemotherapy from January 1st, 2015, to December 31st, 2019. The association of nadir leukocyte level and the time required to achieve it with CR occurrence was assessed. Results: One hundred and one subjects were recruited with median age 39 years and 55% men. A total of 55.4% subjects achieved CR. Nadir leukocyte level below 200/mcl was the most optimal cut-off point and independently associated with CR (OR 2.45; 95% CI 1.01–5.94) while time required to achieve it was not. Conclusions: The nadir leukocyte level is associated with an increase probability of CR but not for the time required to achieve it in AML patients undergoing 7+3 induction chemotherapy.",
"keywords": [
"acute myeloid leukemia",
"leukocyte nadir",
"induction chemotherapy",
"complete remission",
"association"
],
"content": "Introduction\n\nAcute myeloid leukemia (AML) is the most common form of acute leukemia in the adult population.1,2 AML is not a single disease entity, but rather a heterogeneous group of diseases, at least from the clinical picture of blast cell morphology and also at the genetic level which turns out to have a more pronounced prognostic impact.3–7 This heterogeneity has implications for treatment response and prognosis.8,9 However, the treatment principles for AML have not changed much. The first goal of curative treatment of AML is always to achieve complete remission through induction chemotherapy whose backbone regimen has not changed since it was first introduced 40 years ago.10,11\n\nFor the purpose of curative treatment in AML, achieving complete remission (CR) as soon as possible after induction chemotherapy is very important because it determines the patient's survival.12 Patients with a treatment response less than CR have lower survival rate than the group of patients who achieve CR.4,13 The time required to reach CR also carries prognostic significance. Ciftciler reported that patients who achieved CR within 30 days of the start of remission-induced chemotherapy had a better prognosis than patients who required a longer time.14\n\nTherefore, both National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) recommend bone marrow examination on the 14th day of chemotherapy to predict the occurrence of CR so that reinduction chemotherapy can be carried out earlier if the patient is predicted not to achieve CR. If the bone marrow does not reach a hypoplastic condition, defined as bone marrow cellularity <20% and residual blast cells <5%, it is recommended that the patient be given reinduction chemotherapy immediately.9,15 However, this examination is invasive and the general condition of the patient during this period is usually very weak with severe pancytopenia which means the procedure still carries some risk for the patient.16 Some reports also show that bone marrow examination is still less accurate in predicting CR because there are some patients who still achieve CR even when their bone marrow examination on day 14 does not show hypoplastic conditions.15–19\n\nOn the other hand, induction chemotherapy also causes cells in the peripheral blood to undergo a nadir and recovery cycle similar to conditions in the bone marrow, especially the leukocyte series. The understanding that the sensitivity of tumor cells to chemotherapy drugs is influenced by the genetic predisposition of the host also supports the idea that this chemotherapy sensitivity is shared by other cells in the individual's body, including leukocytes.20 Pharmacokinetic tests of drugs used for induction chemotherapy has also shown that the level of the drug in leukocytes was directly proportional to its concentration in nucleated cells in the bone marrow.21 This has sparked the idea of the potential use of the leukocyte nadir pattern as a predictor of CR in AML patients undergoing 7+3 remission induction chemotherapy. Examination of peripheral blood leukocyte levels also has several advantages. First, peripheral blood sampling does not have to be done by a trained specialist doctor but can also be done by nurses or laboratory personnel. Second, the examination is also widely available, and the cost is much cheaper than bone marrow examination. Third, from the patient's perspective, peripheral blood examination is more comfortable and causes less anxiety than bone marrow examination.\n\nThe aim of this study was to examine the associations of nadir leukocyte level and the time to reach it with the occurrence of CR in AML patients who underwent “7+3” remission induction chemotherapy. The hypothesis of this study was that the nadir leukocyte level and the time to reach it were associated with the occurrence of complete remission in AML patients undergoing 7+3 remission induction chemotherapy.\n\n\nMethods\n\nThis was a prognostic study with a retrospective cohort design. The research sample was taken by total sampling from the medical record data of patients with a diagnosis of AML who were not acute promyelocytic leukemia (APL) or AML M3 FAB classification who underwent 7+3 induction chemotherapy at Dharmais Hospital National Cancer Center and Dr. Cipto Mangunkusumo National Central Public Hospital during the period from January 1st, 2015, to December 31st, 2019. The acceptance criteria for this study were patients aged ≥18 years, diagnosed with AML according to WHO diagnostic criteria (based on at least a bone marrow smear or biopsy and myeloid lineage confirmation from bone marrow aspirate or peripheral blood immunophenotyping), who underwent a first-line remission induction chemotherapy 7+3 regimen, and had never undergone any remission induction chemotherapy before. The criteria for rejection were AML M3 (FAB criteria) or acute promyelocytic leukemia (APL), a myeloblastic crisis phase of chronic myeloid leukemia (CML) or when the required data were not found in the patient's medical record. By estimating the proportion of achieving CR of 60% with margin of error of 5%, a total of 103 subjects were needed for this study. The study was approved by the Universitas Indonesia Ethics Board, approval number KET-603/UN2.F1/ETIK/PPM.00.02/2021. Data were collected from June 15th to August 31st, 2021.\n\nThe nadir leukocyte level and the time required to reach it were assessed for their associations to the occurrence of CR during the evaluation of 7+3 remission induction chemotherapy treatment. Treatment evaluations were done when the peripheral blood cells had recovered. The criteria used to define the occurrence of CR during treatment evaluation were in accordance with those established by European LeukemiaNet 2017.22 Factors considered as potential confounders were age, gender, AML subtype, Charlson Comorbidity Index (CCI), history of myelodysplasia syndrome (MDS), history of chemotherapy/radiotherapy, prechemotherapy leukocyte level, bone marrow myeloblast cell level at diagnosis, occurrence of febrile neutropenia and administration of granulocyte colony-stimulating factor (GCSF).\n\nData processing was carried out using IBM SPSS Statistics version 28 (IBM SPSS Statistics, RRID:SCR_016479). Numerical data were presented as a mean with a standard deviation if the distribution was normal or as a median with a range if the distribution was not normal. Statistical significance testing was carried out according to the characteristics of the data and their objectives. Bivariate testing on nominal data was carried out by using the chi-square test or by using Fisher's exact test as an alternative if the requirements were not met. To see the difference in the mean in two groups with numerical data that had a normal distribution, an unpaired t-test was used, or the alternative Mann-Whitney U test was used instead if the distribution was not normal. The limit of significance (α) was set at 5% in the conclusion of statistical significance.\n\nFor data on nadir leukocyte levels and the time required to achieve it in the form of numerical data, the most optimal threshold was sought through the ROC (receiver operating characteristic) curve by assessing sensitivity and specificity values. The power of discrimination of the two variables was measured by the AUC (area under the curve) value. The strength of the association was expressed in terms of relative risk (RR) or odds ratio (OR) with a 95% confidence interval (CI). Variables that had the potential to become confounders were assessed for their relationship with CR occurrence through the bivariate test. When there was a variable that had p-value <0.25 in the bivariate test, this variable would be further analyzed through a multivariate logistic regression test to determine whether the variables acted as a confounder or not by looking at the changes in the OR it caused. A variable was defined as a confounder when it changed the OR (ΔOR) >10%.\n\n\nResults\n\nWe found 125 patients with newly diagnosed AML non-APL who underwent 7+3 remission induction chemotherapy in the period from January 1st, 2015, to December 31st, 2019. Twenty-four patients were excluded because they died while undergoing the chemotherapy hence, they did not have treatment outcome data. In the end, there were 101 subjects whose data could be analyzed. The recruitment process of research subjects is shown in Figure 1.\n\nThe median age of the research subjects was 39 years (range 18–66 years). Male subjects were slightly more common than females with a ratio of 1.2, while the most common subtype was AML M2 (48.5%). The majority of patients had no comorbidities, no history of MDS, and none had a history of chemotherapy/radiotherapy. No patient had cytogenetics nor day-14 bone marrow examination data. Median doses of chemotherapy agents used, daunorubicin and cytarabine, in the 7+3 protocol were 50 and 102 mg/m2/day, respectively, as shown in Table 1.\n\nA total of 56 subjects (55.4%) achieved CR. There was a difference in the median nadir leukocyte level between the group of subjects who managed to achieve CR (190/mcl; range 40–940/mcl) and the group of subjects who did not (250/mcl; range 70–2,020/mcl; p = 0.02). However, the median number of days required to reach the leukocyte nadir did not differ between the groups that achieved CR (13.5 days; range 4–35 days) and those who failed (14 days; range 5–24 days; p = 0.50). Therefore, in the next analysis, only nadir leukocyte level as the independent variable was examined and its relation to CR occurrence as the dependent variable.\n\nTo find the optimal threshold of the nadir leukocyte level that has a prognostic value to CR occurrence, the specificity and sensitivity of each value of nadir leukocyte level in the occurrence of CR during treatment evaluation were analyzed using the ROC (receiver operating characteristic) curve as shown in Figure 2.\n\nDiagonal segments are produced by ties.\n\nFrom this curve, the AUC value was 0.63 (95% CI 0.52–0.74) and the most optimal cut-off point for the nadir leukocyte level was 200/mcl (73% specificity, 50% sensitivity). Based on this cut-off point, there were 40 subjects (39.6%) whose nadir leukocyte level was <200/mcl with the RR achieving complete remission of 1.52 (95% CI 1.09–2.14) compared to the group whose nadir leukocyte level was higher. In the subgroup analysis, the subject groups that reached nadir leukocytes level of <200/mcl had a higher CR proportion compared to the groups that had higher nadir leukocyte level even though not all of them reached statistical significance (see Underlying data).23 In addition, along with the lower cut-off value of the nadir leukocyte level, the proportion of subjects with CR became higher (see Underlying data).23\n\nAfter dividing subjects into two groups based on the 200/mcl leukocyte level threshold, bivariate analysis was performed along with the other variables that had the potential to be confounders to the occurrence of CR as the dependent variable as shown in Table 2. For the GCSF administration variable, only GCSF given to subjects before the leukocyte nadir was reached was considered to be a potential confounder for the relationship between the nadir leukocyte level and the occurrence of CR. A total of 41 subjects (40.6%) received GCSF before the nadir leukocyte level was reached.\n\n* variable with p < 0.25.\n\nFrom the results of the bivariate test, there were three variables that had p < 0.25 other than the nadir leukocyte level (p = 0.02), those were administration of GCSF before the leukocyte nadir (p = 0.08), cytarabine dose (p = 0.08) and myeloblast level at diagnosis (p = 0.17). To see the magnitude of the effect of nadir leukocyte level on the achievement of CR and to determine whether the other variables would act as confounders, a multivariate test was carried out using the logistic regression method. The crude OR was 2.75 (95% CI 1.12–6.39) while fully adjusted OR 2.45 (95% CI 1.01–5.94). None of the variables presumed as confounders changed OR more than 10% as shown in Table 3.\n\n\nDiscussion\n\nOut of 125 patients who underwent “7+3” remission induction chemotherapy, 24 subjects (19.2%) did not have treatment outcome data because they died before treatment evaluation and had to be excluded. Deaths in this period were grouped into treatment related mortality (TRM). This figure is not much different from that obtained by Kayal in India (16.9%) but definitely higher than that obtained by Gbadamosi in the US (6.9%).24,25 The results of this study indicate that there is still a gap in the quality of AML treatment between developing and developed countries.2,5,26,27\n\nThe median age of this study (39 years) differs from the median age of AML cases in the general population (68 years) because the subjects taken were only AML patients who underwent intensive treatment and successfully completed it. Of all subjects whose treatment results could be evaluated, 55.4% managed to achieve CR. Again, this figure is not much different from that obtained by Kayal in India (52.8%) but lower than Gbadamosi in the US (62%).24,25 Gbadamosi’s higher CR figure was probably due to the fact that the US treatment facilities are better than Indonesia and India.2,10,28 Another factor that might play a role in this low rate was the low dose of chemotherapy drugs used in this study. Infection control barriers and TRM rates in developing countries might encourage clinicians to use lower limits of the recommended dose.\n\nThere was a difference in median nadir leukocyte levels in the group that managed to achieve CR compared to the group that did not, but the same could not be said on the number of days required to reach the leukocyte nadir. The data that showed a uniform median number of days needed to reach the leukocyte nadir between the two groups (i.e. 14 days) was in accordance with the day recommended by ESMO and NCCN guidelines to perform a bone marrow examination.9 This result is similar to that reported by Marras where the time required for nadir leukocyte level to be reached was also 12 days for both responder and non-responder groups.29 This reinforces the premise that the nadir pattern of leukocytes in the peripheral blood is similar to the pattern of hypoplasia in the bone marrow.\n\nHowever, this result is different from that obtained by Han who reported that there was a difference in the proportion of subjects who achieved CR between the groups who needed more than 10 days to reach the leukocyte nadir and those who needed less.17 These different results are probably due to differences in the characteristics of the subjects in that Han's study only recruited subjects over 55 years of age as well as differences in the AML treatment technique used. Old age is associated with a decrease in the activity of hematopoietic stem cells in the bone marrow and the mobilization of PMN cells from the bone marrow to the peripheral blood.30,31 The most striking difference in treatment technique was that Han allowed his subjects to undergo reinduction chemotherapy if the results of the bone marrow examination on day 14 still contained blast cell residues >5% while none of our subjects received reinduction chemotherapy before treatment evaluation.\n\nThis study found that the threshold for the most optimal nadir leukocyte level that had a prognostic value on the occurrence of CR during treatment evaluation was 200/mcl with an acceptable discriminant power (AUC 0.63) in identifying subjects who would achieve CR and those who would not (p = 0.02).32 From the RR calculation, the number of subjects whose nadir leukocyte levels was <200/mcl managed to achieve CR 1.52 times more than subjects with higher nadir leukocyte levels. This association was independent based on the results of the multivariate analysis using the logistic regression method with fully adjusted OR 2.45 (95% CI 1.01–5.94). By looking at the OR changes from each step of the logistic regression analysis, none of them made OR changes >10%. Hence, it could be concluded that there were no variables acting as confounders in this study.\n\nThe association between nadir leukocyte level to the achievement of CR was then analyzed to see if it met the principles of causality by Sir Austin Bradford Hill.33 The first principle is the temporal relationship, in which the independent variable in terms of time must precede the dependent variable. In this case, the nadir leukocyte level as an independent variable always preceded the occurrence of CR.\n\nThe second principle is an association that emphasizes the strength of the relationship between the independent variable and the dependent variable where the stronger the relationship between the variables, the more probable the concept of causality. From this study, the strength of the association was represented by a fully adjusted OR of 2.45 which is statistically significant.\n\nThe third principle is dose-dependent, if the size of the dependent variable changes along with the change in size of the independent variable, then a causal relationship becomes more likely. For the group of subjects with nadir leukocyte levels below 300/mcl, 200/mcl, and 100/mcl, the proportions of achieving CR were 58.1%, 70%, and 81.8% respectively (see Underlying data).23 The proportion of the occurrence of CR was getting higher as the threshold for the nadir leukocyte level lower.\n\nThe fourth principle is consistency, the relationship between the independent variable and the dependent variable remains consistent when applied to different subjects or observations. In the group of male and female subjects or the elderly and non-elderly, the group of subjects with a nadir leukocyte level <200/mcl consistently achieved more CR than the group of subjects with a higher nadir leukocyte level, although the differences were not always statistically significant (see Underlying data).23\n\nThe fifth principle is coherence in which research results do not conflict with existing knowledge about the disease. Kinetics of leukocyte has long been used as an indicator of bone marrow recovery, which is characterized by absolute neutrophil count (ANC) levels reaching above 500/mcl after nadir.29 This shows that the concept of low nadir leukocyte levels as a surrogate marker of the degree of bone marrow hypoplasia associated with CR does not conflict with existing knowledge about AML.\n\nThe sixth principle is biological plausibility where research results can be explained by existing theories. The degree of decrease in peripheral blood leukocyte levels due to chemotherapy exposure is considered to be comparable to what happened in blast leukemia cells, and it has been demonstrated, at least in breast cancer and lung cancer, that the degree of leukopenia is associated with response to chemotherapy.34,35\n\nThe seventh principle is the suitability of the results with other studies. To our knowledge, there have been no other studies reporting similar results, thus the nadir leukocyte nadir level of 200/mcl is the novelty of this study. Therefore, this principle cannot be determined at this time, and further research is needed to confirm the results found in this study. Thus, it has been shown that the results of this study are in accordance with most of the causality principles introduced by Sir Austin Bradford Hill but still require further research to confirm this relationship.\n\nThis study showed that lower nadir leukocyte levels (<200/mcl) were associated with higher proportion of subjects achieving CR than the group with higher nadir leukocyte levels. A lower level of leukocyte nadir has long been associated with the higher exposure level of chemotherapy drugs in the bone marrow and blood cells and is expected to describe drug exposure to tumor cells.20 It is expected that the lower level of leukocyte nadir is related to the higher amount of eradicated leukemic blast cells in the patient's bone marrow. However, the role of nadir leukocyte level on CR occurrence during treatment evaluation in this study was only as strong as 63% which was symbolized by the AUC value of the ROC curve thus opening up the possibility that other variables might play roles in AML patients who achieved CR. Hence, the cut-off point for the nadir leukocyte levels reported in this study still cannot be directly applied to daily clinical practice. A predictive model that involves other variables is needed to improve the performance of predicting CR occurrence.\n\nThe main limitation of this study as in other studies with retrospective design is the impossibility in controlling the variables studied. Although regimens and protocols of chemotherapy for remission induction 7+3 are standard, other treatments given to patients might vary widely between clinicians and might have prognostic impacts on patients that were not possible to include in the analysis. The sample of this study also involved only a few elderly subjects, subjects with comorbidities, or subjects with secondary AML so that the influence of these variables might be less visible in this study. In addition, the absence of cytogenetic profile data in the study sample made it impossible to assess the role of leukemia blast cell characteristics, especially in terms of the sensitivity of AML to treatment. Yet, the limited facilities for cytogenetics and molecular examinations in developing countries, including Indonesia, make simpler alternative tests (e.g., peripheral blood leukocyte levels) in providing information about disease behavior even more necessary to determine the best treatment strategy in AML patients. However, the results of this study still need to be confirmed in the patient group based on the risk of AML through cytogenetics in follow-up studies.\n\n\nConclusions\n\nAML patients undergoing “7+3” remission induction chemotherapy who managed to achieve nadir leukocyte level <200/mcl is associated with an increased probability of CR. Time to reach the nadir leukocyte level does not have an association with the occurrence of CR.\n\n\nData availability\n\nMendeley Data: Underlying data for ‘Association of leukocyte nadir with complete remission in Indonesian acute myeloid leukemia patients undergoing 7+3 remission induction chemotherapy’. https://doi.org/10.17632/xfx39znwzp.223\n\nThis project contains the following underlying data:\n\n• Data file 1: Dataset file.sav\n\n• Data file 2: Supplementary Data – Changes in Proportion of CR Occurrence Along with Changes in the Nadir Leukocyte Level Threshold.docx\n\n• Data file 3: Supplementary Data – Association of Nadir Leukocyte Level Less Than 200mcl with CR Occurrence in Several Subjects Groups.docx\n\n\nReporting guidelines\n\nMendeley Data: STROBE checklist for ‘Association of leukocyte nadir with complete remission in Indonesian acute myeloid leukemia patients undergoing 7+3 remission induction chemotherapy’. https://doi.org/10.17632/xfx39znwzp.223\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nConsent\n\nWritten informed consent for publication of the patients’ details was obtained from the patients.",
"appendix": "Acknowledgements\n\nThe authors wish to thank Dr. Lies Dina Liastuti as director of Dr. Cipto Mangunkusumo National Central Public Hospital and Dr. R Soeko Werdi Nindito D. as director of Dharmais Hospital National Cancer Center for their valuable support. Special thanks should be given to Prof. DR. Dr. Dadang Makmun as the head of Internal Medicine Department, Universitas Indonesia and DR. Dr. Cosphiadi Irawan as the head of Hematology-Medical Oncology Division, Internal Medicine Department, Universitas Indonesia for valuable technical support on this project. The authors also thank Dr. Sanjung Pamarta for his help in the writing of this article.\n\n\nReferences\n\nBray F, Ferlay J, Soerjomataram I, et al.: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018; 68: 394–424. Publisher Full Text\n\nShort NJ, Rytting ME, Cortes JE: Acute myeloid leukaemia. Lancet. 2018; 392: 593–606. Publisher Full Text\n\nBennett JM, Begg CB: Eastern cooperative oncology group study of the cytochemistry of adult acute myeloid leukemia by correlation of subtypes with response and survival. Cancer Res. 1981; 41: 4833–4837. PubMed Abstract\n\nCheson BD, Bennett JM, Kopecky KJ, et al.: Revised Recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J. Clin. Oncol. 2003; 21: 4642–4649.\n\nEstey EH: Acute myeloid leukemia: 2019 update on risk-stratification and management. Am. J. Hematol. 2018; 93: 1267–1291. PubMed Abstract | Publisher Full Text\n\nDöhner H, Estey EH, Amadori S, et al.: Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010; 115: 453–474. PubMed Abstract | Publisher Full Text\n\nArber DA, Orazi A, Hasserjian R, et al.: The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127: 2391–2405. PubMed Abstract | Publisher Full Text\n\nLichtenegger FS, Krupka C, Haubner S, et al.: Recent developments in immunotherapy of acute myeloid leukemia. J. Hematol. Oncol. 2017; 10: 1–20.\n\nHeuser M, Ofran Y, Boissel N, et al.: Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2020; 31: 697–712. PubMed Abstract | Publisher Full Text\n\nMurphy T, Yee KWL: Cytarabine and daunorubicin for the treatment of acute myeloid leukemia. Expert. Opin. Pharmacother. 2017; 18: 1765–1780. Publisher Full Text\n\nPophali P, Litzow M: What is the best daunorubicin dose and schedule for acute myeloid leukemia induction?. Curr. Treat. Options in Oncol. 2017 18:1 2017; 18: 1–14.\n\nEstey EH, Shen Y, Thall PF: Effect of time to complete remission on subsequent survival and disease-free survival time in AML, RAEB-t, and RAEB. Blood. 2000; 95: 72–77. PubMed Abstract | Publisher Full Text\n\nWalter RB, Kantarjian HM, Huang X, et al.: Effect of complete remission and responses less than complete remission on survival in acute myeloid leukemia: a combined Eastern Cooperative Oncology Group, Southwest Oncology Group, and M. D. Anderson Cancer Center study. J. Clin. Oncol. 2010; 28: 1766–1771. PubMed Abstract | Publisher Full Text\n\nCiftciler R, Demiroglu H, Haznedaroglu IC, et al.: Impact of time between induction chemotherapy and complete remission on survival outcomes in patients with acute myeloid leukemia. Clin. Lymphoma Myeloma Leuk. 2019; 19: 729–734. PubMed Abstract | Publisher Full Text\n\nVainstein V, Buckley SA, Shukron O, et al.: Rapid rate of peripheral blood blast clearance accurately predicts complete remission in acute myeloid leukemia. Leukemia. 2014; 28: 713–716. PubMed Abstract | Publisher Full Text\n\nHan EJ, Lee B, Hee KJA, et al.: Early assessment of response to induction therapy in acute myeloid leukemia using 18F-FLT PET/CT. EJNMMI Res. 2017; 7: 1–9. Publisher Full Text\n\nHan HS, Rybicki LA, Thiel K, et al.: White blood cell count nadir following remission induction chemotherapy is predictive of outcome in older adults with acute myeloid leukemia. Leuk. Lymphoma. 2009; 48: 1561–1568. Publisher Full Text\n\nAlsaleh K, Aleem A, Almomen A, et al.: Impact of day 14 bone marrow biopsy on re-induction decisions and prediction of a complete response in acute myeloid leukemia cases. Asian Pac. J. Cancer Prev. 2018; 19: 421–425. PubMed Abstract\n\nNachar VR, Perissinotti AJ, Scappaticci GB, et al.: Predictors for requiring re-induction chemotherapy in acute myeloid leukemia patients with residual disease on day 14 bone marrow assessment. Leuk. Res. 2017; 63: 56–61. PubMed Abstract | Publisher Full Text\n\nKvinnsland S: The leucocyte nadir, a predictor of chemotherapy efficacy?. Br. J. Cancer. 1999 80:11 1999; 80: 1681–1681. PubMed Abstract | Publisher Full Text\n\nKokenberg E, Sonneveld P, Sizoo W, et al.: Cellular pharmacokinetics of daunorubicin: relationships with the response to treatment in patients with acute myeloid leukemia. J. Clin. Oncol. 2016; 6: 802–812.\n\nDöhner H, Estey E, Grimwade D, et al.: Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017; 129: 424–447. PubMed Abstract | Publisher Full Text\n\nHadisantoso DW, Ranuhardy D, Rajabto W, et al.: Underlying data for ‘Association of leukocyte nadir with complete remission in Indonesian acute myeloid leukemia patients undergoing 7+3 remission induction chemotherapy.’. Mendeley Data. 2022; v2.\n\nKayal S, Sengar M, Jain H, et al.: Induction related mortality in acute myeloid leukemia: multivariate model of predictive score from the Indian Acute Leukemia Research Database (INwARD) of the Hematology Cancer Consortium (HCC). Blood. 2019; 134: 2615–2615. Publisher Full Text\n\nGbadamosi B, Ezekwudo D, Bastola S, et al.: Predictive and prognostic markers in adults with acute myeloid leukemia: a single-institution experience. Clin. Lymphoma Myeloma Leuk. 2018; 18: e287–e294. PubMed Abstract | Publisher Full Text\n\nPercival MEM, Tao L, Medeiros BC, et al.: Improvements in the early death rate among 9380 patients with acute myeloid leukemia after initial therapy: A SEER database analysis. Cancer. 2015; 121: 2004–2012. PubMed Abstract | Publisher Full Text\n\nOthus M, Kantarjian H, Petersdorf S, et al.: Declining rates of treatment-related mortality in patients with newly diagnosed AML given “intense” induction regimens: a report from SWOG and MD Anderson. Leukemia. 2014; 28: 289–292. PubMed Abstract | Publisher Full Text\n\nFaderl S, Kantarjian HM: Clinical manifestations and treatment of acute myeloid leukemia. Hoffman R, Benz E, Silbertain L, et al., editors. Hematology: Basic Principles and Practice. 7th ed.Philadelphia: Elsevier Inc.; 2018; p. 924–943.\n\nMarras T, Dettori M, Caocci G, et al.: White blood cell count nadir and duration of aplasia do not associate with treatment outcome in adult patients with acute myeloid leukemia undergoing intensive chemotherapy. Chemotherapy. 2020; 65: 110–114. Publisher Full Text\n\nGazit R, Weissman IL, Rossi DJ: Hematopoietic stem cells and the aging hematopoietic system. Semin. Hematol. 2008; 45: 218–224. Publisher Full Text\n\nChatta GS, Price TH, Stratton JR, et al.: Aging and marrow neutrophil reserves. J. Am. Geriatr. Soc. 1994; 42: 77–81. PubMed Abstract | Publisher Full Text\n\nMandrekar JN: Receiver operating characteristic curve in diagnostic test assessment. J. Thorac. Oncol. 2010; 5: 1315–1316. Publisher Full Text\n\nSastroasmoro S, Aminullah A, Rukman Y, et al.: Variabel dan hubungan antar-variabel. Sastroasmoro S, Ismael S, editors. Dasar-Dasar Metodologi Penelitian Klinis. 3rd ed.Jakarta: Sagung Seto; 2008; p. 255–277.\n\nPoikonen-Saksela P, Lindman H, Sverrisdottir A, et al.: Leukocyte nadir as a predictive factor for efficacy of adjuvant chemotherapy in breast cancer. Results from the prospective trial SBG 2000-1. Acta Oncol. 2020; 59: 825–832. PubMed Abstract | Publisher Full Text\n\nLiu W, Zhang C-C, Li K: Prognostic value of chemotherapy-induced leukopenia in small-cell lung cancer. Cancer Biol. Med. 2013; 10: 92–98. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "137006",
"date": "27 May 2022",
"name": "Shinta Wardani",
"expertise": [
"Reviewer Expertise Hematology and medical oncologist"
],
"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 idea is very original and applicable, especially in countries with limited resources. The golden standard for assessing hypoplasia in AML (acute myeloid leukemia) patients after induction therapies bone marrow aspiration, with criteria for bone marrow cellularity <20% and residual blast <5%, which are also a criteria for complete remission. If the author wants to replace the bone marrow aspiration with the nadir leucocyte count, then my question is, has this nadir leucocyte count been compared with the hypoplastic condition through the golden standard bone marrow aspiration?\nOn page 8 of the last paragraph, how do the authors show that a low nadir leucocyte count is a surrogate marker of the degree of bone marrow hypoplasia?\nI need your comment, the number of blast cells in the periphery is not needed in assessing bone marrow hypoplasia? Why is it only the nadir leucocyte that is used as a surrogate marker?\nI want to confirm the number of subjects who took part in this study, because the abstract mentioned 101 subjects, but in the method on the full paper 103 patients.\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?\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? Yes",
"responses": [
{
"c_id": "8340",
"date": "17 Jun 2022",
"name": "Dwi Wahyunianto Hadisantoso",
"role": "Author Response",
"response": "Dear Dr. Shinta Wardani, we would like to thank you for your valuable comments and questions. Here is our response: We need to clarify that the goal of this research is to elucidate the association between leukocyte nadir and complete remission (CR) occurrence in acute myeloid leukemia (AML) patients undergoing 7+3 remission induction based on some evidence that day-14 bone marrow examination (BME), as the gold standard for predicting CR, still has some limitations and inaccuracy. Hence, the result of this research is not meant to replace the BME with leukocyte nadir count, yet the latter might give some information for the treating clinicians in predicting CR occurrence irrespective of whether the day-14 BME was done or not to the patient. In this retrospective research we have stated in the article that none of our subjects underwent day-14 BME. Since none of our subjects underwent day-14 BME, we could not directly analyze leukocyte nadir as a surrogate marker of bone marrow hypoplasia. Yet, the study results do not contradict the concept of the pattern of leukocyte nadir in the peripheral blood is similar to the hypoplasia pattern of nucleated cells in the bone marrow. The median time needed to achieve the nadir leukocyte level was equal for both groups (CR group and non-CR group) that were 14 days. This result is in-line with Marras et al (citation no. 29) who also found 12 days as uniform median time needed to achieve nadir leukocyte level for both responder and non-responder groups. These numbers of days are so similar to the bone marrow hypoplasia period, as the ultimate reason why the BME is recommended to be done on day-14 of induction chemotherapy. The study result that showed subjects who succeeded in achieving nadir leukocyte level less than 200/mcl had higher probability in achieving CR than who did not (RR 1.52; CI 95% 1.09 – 2.14) is analogous to the well-accepted paradigm that subjects who succeed achieving bone marrow hypoplasia in day-14 BME are predicted to achieve CR on treatment evaluation. Another concept based on association between leukocyte in peripheral blood and hematopoietic cells in bone marrow has also been used for long, as level of absolute neutrophile count (ANC), one of the leukocyte components, rising above 500/mcl from previously nadir level marks the recovery of the bone marrow. Although we are aware some previous studies have showed correlation between peripheral blast clearance with treatment response, yet we decided to not include it in analysis. Not all AML patients have peripheral blast when they are diagnosed. In this study, there were 8 subjects (7.9%) whose peripheral blast level was 0% and up to 21% of the sample had very few peripheral blast count (less than 5%) before treatment. This condition would make analysis of peripheral blast clearance to treatment response for this group of subjects become impossible and they were always excluded in such studies. Thus, we choose leukocyte nadir as independent variable since it is a universal event that can be analyzed in all AML patients undergoing 7+3 induction chemotherapy. From statistic sample size calculation 103 subjects were needed (as we wrote in Method section), yet the study found 101 subjects eligible for analysis (as we wrote in Results section), thus this study sample comprised of 101 subjects."
}
]
},
{
"id": "137004",
"date": "07 Jun 2022",
"name": "Hyewon Lee",
"expertise": [
"Reviewer Expertise Hematooncology"
],
"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 the study is to investigate the correlation between nadir leukopenia and complete remission in patients treated with conventional induction therapy for AML (acute myeloid leukemia). It was a retrospective study, which included 101 patients who could recover from nadir and underwent response evaluation.\nThe binominal analyses and ROC (receiver operating characteristic) curve were adopted to explore any association between the two variables in this study. For this, the outcome should be defined as two groups, such as ’CR achieved’ or ‘CR not achieved’. The authors excluded 24 patients from initial cohort (n=125), because they died early before response evaluation. However, this may be a bias underestimating the proportion of CR (complete remission) group, because early death might be associated with treatment toxicity, low WBC count and prolonged nadir. This may be one of the reason why CR rate is relatively low in developing countries compared to developed countries.\nIn addition, nadir leukopenia is a result of intensive chemotherapy. However, the median dose of daunorubicin in this study was 50mg/m2/day, which is lower than standard dose. It should be considered when the authors analyze nadir leukocyte count and the outcome of chemotherapy. Furthermore, dose intensity should be described median cumulative dose of entire induction therapy. Because lower dose intensity is supposed to correlate to relatively higher nadir leukocyte count and subsequent induction failure, it might mislead the authors to conclude that nadir leukocyte count itself has an impact on complete remission. To avoid this misinterpretation, multivariate analysis for achieving CR should be performed with more variables such as age, cumulative dose intensity and cytogenetic risk group of AML, in addition to variables which were included in the presented study. Then comprehensive discussion on the results should be done, focusing on possible reasons why it was shown like that. If there is no available data of AML biology, it should be described as a limitation of this study in discussion session.\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? Partly",
"responses": [
{
"c_id": "8428",
"date": "29 Jun 2022",
"name": "Dwi Wahyunianto Hadisantoso",
"role": "Author Response",
"response": "Dear Dr. Hyewon Lee, we are so delighted to have your valuable response and comments. Here is our response: We agree that subjects who underwent treatment related mortality (TRM) can be a bias for the reported proportion of complete remission (CR). On the same reason, we also agree that higher rate of TRM in developing countries can be the reason why the rate of CR is lower compared to developed countries. Nevertheless, we had to exclude this group of subjects from analysis since the treatment response could not be determined. Follow up study to elucidate the characteristics of subjects who underwent TRM after induction chemotherapy might give valuable information of these premises and help to reduce its rate. We agree that lower dose of chemotherapy used in this study could have an impact in the outcome of induction chemotherapy, as we wrote in the last two sentences of the second paragraph in “Discussion” section. As this study had retrospective design that recruited subjects from January 2015 to December 2019 we think another reason that could explain the lower dose of daunorubicin is the possibility that clinicians need time to move on from the previous guidelines that recommended daunorubicin dose range between 45 – 60 mg/m2/day to the current 60 – 90 mg/m2/day as there is significant difference of median daily dose of daunorubicin for subject who were diagnosed before 2018 and 2018 afterward (47 vs 58 mg/m2/day, respectively; p=0,004). More and more clinicians were implementing higher dose of daunorubicin with increasing year to the dose range recommended by current guidelines. We agree to use “median cumulative dose” as it seems more appropriate to describe the chemotherapy dose intensity (and consequently used in analysis) rather than the median of daily dose, yet we still report the median daily dose of each drug in the article as it is easier to compare them to the recommended daily doses provided by the AML guidelines. Nevertheless, these changes did not change the conclusion of the analysis, there was still no significant association between the median cumulative dose of daunorubicin nor cytarabine with the occurrence of CR (p=0.88 for daunorubicin and p=0.10 for cytarabine). There was indeed a significant association between the subjects who had higher cumulative dose of daunorubicin (≥150 mg/m2) with lower leucocyte nadir level (<200/mcl) (RR=2.11; CI 95% 1.22 – 3.67, p<0.01) but not for cytarabine cumulative dose with leukocyte nadir level (p=0.80). This interesting result may warrant follow-up study to further explore the relationship between chemotherapy dose intensity and nadir of leukocyte. This study aimed to explore the relationship between leukocyte nadir with CR occurrence and some variables that were thought to potentially act as confounders were also analyzed in two steps manner of analysis as we wrote in the “Methods” section and “Statistical analysis” subsection. Those variables were age, gender, AML subtype, Charlson Comorbidity Index (CCI), history of myelodysplasia syndrome (MDS), history of chemotherapy/radiotherapy, prechemotherapy leukocyte level, bone marrow myeloblast cell level at diagnosis, dose intensity of chemotherapy agents, occurrence of febrile neutropenia and administration of granulocyte colony-stimulating factor (GCSF). For each of these variables we initially did bivariate analysis to identify the significancy of its relationship to the CR occurrence as the dependent variable. Only variables with p<0.25 from bivariate analysis (GCSF administration, cytarabine cumulative dose, and myeloblast level at diagnosis, as shown in Table 2) were considered “significant” then further analyzed in multivariate analysis to be determined whether they act as confounders in the relationship of leukocyte nadir level (as independent variable) and CR occurrence (as dependent variable) or not. This is to explain that the study already considered variables suggested by the reviewer as potential confounders other than cytogenetic risk group, which the latter had been written at the “Research limitations” section."
}
]
},
{
"id": "137008",
"date": "13 Jun 2022",
"name": "Smita Kayal",
"expertise": [
"Reviewer Expertise hemato-oncology",
"transplant",
"supportive care"
],
"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 retrospective study on role of leucocyte nadir in predicting remission outcomes of intensive induction therapy in AML (acute myeloid leukemia) is an important work, especially in resource limited limited settings. It is well written with lucid discussion.\n\nLimitations of absence of cytogenetic data, and other aspects are mentioned. However, a comment should be added on lower average dose of daunorubicin used in the study and reason for it.\n\nIn table 2, n to be added in column headings.\n\nWhether other cell components (neutrophil or lymphocyte) were also analyzed for their predictive value?\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": [
{
"c_id": "8429",
"date": "29 Jun 2022",
"name": "Dwi Wahyunianto Hadisantoso",
"role": "Author Response",
"response": "Dear Dr. Smita Kayal, we are so delighted for your valuable response and comments. Here is our response: We have added some conditions that might explain the lower median daily dose of daunorubicin in this study in the last two sentences of second paragraph in “Discussion” section. We think of the higher TRM (treatment related mortality) rates in developing countries and time needed by treating clinicians to absorb newer guidelines might have significant contributions. We have added “n” as total subjects in column headings of Table 2. We did not analyze the counts of leukocyte differential because as the lower the level of leukocyte, the more unreliable the differential count result would become as the CV (coefficient of variance) would increase dramatically. Thus, we were afraid this could lead to a significant bias, especially for a retrospective study using secondary data. This effect also happens on leukocyte (as total white blood cells) count but far less than on its differential. The other reason is not all subjects had daily leukocyte differential count data."
}
]
}
] | 1
|
https://f1000research.com/articles/11-495
|
https://f1000research.com/articles/11-727/v1
|
01 Jul 22
|
{
"type": "Research Article",
"title": "Factor puzzles from definition to applications",
"authors": [
"Raghib Abusaris",
"KIFAH ALHAMI",
"Raghib Abusaris"
],
"abstract": "Background: Factor puzzles are a salient tool that has been consigned to oblivion. Methods: In this paper, we introduce factor puzzles and study the existence and uniqueness of solutions along with their connections to other areas of mathematics and real-world applications. Results: Using concepts from elementary number theory, we prove several theorems pertinent to the existence and uniqueness of a solvable factor puzzle, and the number of solutions. Furthermore, we established connections between factor puzzles and polynomial as well as matrix factorizations. In addition, we demonstrate the importance of factor puzzles in the real world was evidenced by an application in cryptography. Conclusion: Factor puzzles are a prominent tool with many remarkable connections and real-world applications.",
"keywords": [
"Factor puzzles",
"prime numbers",
"relatively prime numbers",
"common factors",
"greatest common devisor",
"polynomials",
"matrices",
"crypography"
],
"content": "1. Introduction\n\nPuzzles, due to their playful nature, have the potential to engage students.1 Furthermore, if they are well-designed, they can be used to engage students and introduce important concepts in any subject, particularly in mathematics.1,5,6,11 On the other hand, they can be used to give a practical exposition of the mathematical habits of mind3 and the five strands of mathematical proficiency.6 The mathematical habits of mind include pattern sniffing, experimenting, describing, tinkering, inventing, visualizing, conjecturing, and guessing.3 On the other hand, mathematical proficiency encompasses five intertwined strands, namely conceptual understanding, procedural fluency, strategic competence, adaptive reasoning, and productive disposition.7 Indeed, the main aim of this paper is to demonstrate how mathematicians think and approach problem solving through investigating factor puzzles.\n\nIn an m×n factor puzzle, you are given an array A=aij of natural numbers (or integers) arranged in m rows and in n columns, and you are expected to find a solution which consists of vectors B=bi,1≤i≤m and C=cj,1≤j≤n of natural numbers such that aij=bicj for 1≤i≤m and 1≤j≤n. For clarity, consider the following depiction (factor puzzle A).\n\nAs an example, a 2 × 2 factor puzzle looks like the following (factor puzzle B):\n\nTo the best of our knowledge, there is no systematic study of factor puzzles. As such, to mathematically study factor puzzles, the following questions were crystallized:\n\n1. Under what condition(s) does a factor puzzle possess a solution?\n\n2. How to solve a factor puzzle if it has a solution?\n\n3. If a factor puzzle is solvable, how many solutions does it have?\n\n4. When does a factor puzzle has a unique solution?\n\n5. Given a number of solutions, can we construct a factor puzzle that has this number of solutions?\n\n6. Do factor puzzles have connections to other mathematical concepts?\n\n7. Do factor puzzles have real-world applications?\n\nIn this paper, we shall provide answers to the forgoing questions. Moreover, while our work will be focused on 2 × 2 factor puzzles, the extension to larger puzzles should be clear from the context. To be precise, in Section 2.1, we address the important question of existence. In Section 2.2, we explain how to solve a factor puzzle, and establish criterion for the existence of a unique solution and develop an upper bound for the number of solutions of a factor puzzle. Connections to polynomial and matrix factorizations are demonstrated in Sections 2 and 3.\n\nThe overarching goal of cryptography is to securely communicate information.2 However, communicating securely, particularly sensitive information, requires encoding messages using a certain scheme. To decode a received message, the intended receiver needs the key used in encryption. It is possible, to add an extra layer of security, to mask the key by sending a factor puzzle whose solution is the key needed for decoding. This is the main purpose of Section 4.\n\nFinally, we conclude in Section 5 by suggesting future directions.\n\n\n2. Methods\n\nIn the following sections we will discuss the solvability of a factor puzzle, i.e., the existence of a solution and conditions for uniqueness, and its connection to factoring polynomials.\n\nTo avoid wasting time, efforts, and resources, it is important to examine if a factor puzzle is solvable, i.e., has a solution, before attempting to solve it. To establish necessary and sufficient conditions for the solvability of a factor puzzle, we begin by considering a 2 × 2 factor puzzle. Furthermore, for ease for notation, we shall write it as follows:\n\n\n\nA 2 × 2 factor puzzle has a solution if and only if ac=bd, or equivalently, detadbc=0.\n\nAssume solvability. Then a=pr,b=ps,c=qs, and d=qr, and therefore ac=prqs=psqr=bd.\n\nConversely, suppose ac=bd. Then a divides bd. This means that a=αβ such that α divides b and β divides d. Therefore, c=bαdβ, and so bα and dβ both divide c. Hence, p=α,q=dβ,r=β, and s=bα define a solution of the given factor puzzle.◽\n\n\n\nFor the sake of illustration, consider the following examples.\n\n1. Factor puzzle D\n\n2. The following factor puzzle (E), on the other hand, has a unique solution. Namely, p = 2, q = 3, r = 1, s = 2, which can be obtained using the method outlined in the following section.\n\nAs a consequence of Theorem 2.1, we have the following general result.\n\nAn m × n factor puzzle has a solution if and only if aijakl=akjail for all 1≤i<k≤m and 1≤j<l≤n.\n\nNote that there are m2n2 2×2 sub-arrays. However, there will be some redundancy. For example, if m=2 and n=3, then it suffices to check the condition for\n\nAlthough it may be simple to prove that a factor puzzle is solvable, this does not provide an incite in how to actually solve these puzzles. In this section, we will attempt to put forward different methods that can be used for solving various puzzles.\n\n2.2.1 Common factors\n\nAlthough not efficient, one way to solve a satisfiable factor puzzle is to map it on a multiplication table.4 In contrast, a more proficient approach is investigating the common factors. To demonstrate, consider the following factor puzzle (G).\n\nUsing the times table (Table 1), one solution is p=6,q=4,r=2,ands=6.\n\nTo discover other solutions, if there is any, one may need a bigger table. On the other hand, with Theorem 2.1 in mind, the common factors of 12 and 36 are 1, 2, 3, 4, 6, and 12. Furthermore, 36 divided by these common factors gives 36, 18, 12, 9, 6, and 3. Of these, only 12, 6, and 3 also divide 24. Hence, as shown below, the given factor puzzle affords three solutions (H):\n\nNote that the aforementioned proficient approach can be utilized to estimate the number of solutions a factor puzzle has. In fact, we have the following result.\n\nLet NFx denote the number of factors of x and k=minNFgcdabNFgcdadNFgcdbcNFgcdcd.\n\nIf a 2×2 factor puzzle is solvable, then there are at most k solutions. Here, gcd stands for greatest common divisor.\n\nFirst, we verify that number of common factors of a andb equals number of factors of gcd(a,b). This follows from the fact that a common divisor of a and b divides any linear combination of a and b and, by Bézout’s theorem, gcdab can be written as a linear combination of a and b.9,p. 85\n\nNow, since p is a common factor of a and b, q is a common factor of c and d, r is a common factor of a and d, and s is a common factor of b and c, the result follows.◽\n\nTo illustrate Theorem 2.3, consider the following factor puzzle (I):\n\nObserve that the above factor puzzle is solvable (63 × 54 = 27 × 126). Furthermore,\n\nHence, the above factor puzzle has at most 3 solutions. In fact, as shown below, it has 3 solutions (J).\n\nAs a corollary of Theorem 2.3, we have the following result, which follows from the fact that 1 is the greatest common divisor between two relatively primes numbers.\n\nIf one of the pairs ab,bc,cd,orda is relatively prime, then a solvable factor puzzle has a unique solution.\n\nMoreover, utilizing Theorem 3.1, we can construct a factor puzzle with a desired number of solutions. This exemplifies an inverse problem. The following factor puzzle has k solutions for any positive integer k. Additionally, there is nothing special about the number 2 in this context. In fact, any prime number can be used instead.\n\n2.2.2 Factoring polynomials\n\nIf we think of the numbers bi’s and cj’s as the coefficients of a polynomial of degrees m−1 and n−1, respectively, then the aij’s can be thought of as the coefficients of a polynomial of degree m+n−2; see the depiction below (L):\n\nThe 2×2 factor puzzle corresponds to factoring a quadratic equation into linear factors, the 2×3 or 3×2 corresponds to factoring a cubic equation into quadratic and linear factors, etc. Therefore, solving factor puzzles corresponds to factoring polynomials. For example, consider the polynomial fx=3x2+11x+6. The corresponding factor puzzle is\n\nUsing Theorem 2.1, this factor puzzle is solvable if t(11 − t) = 18, or t = 2,9. Hence, we have two solutions depicted in (N):\n\nIn other words, fx=3x2+11x+6=3x+2x+3.\n\nSimilarly, if fx=2x3+9x2+10x+3, then the corresponding factor puzzle is\n\nBy Theorem 2.2, this factor puzzle is solvable if s9–s=2t and s10–t=6, or st=14, (2,7), (6,9). Hence, we have the following three solutions depicted in (P):\n\nIn other words, fx=2x3+9x2+10x+3=2x+1x2+4x+3=x+12x2+7x+3=x+32x2+3x+1.\n\n\n3. Factor puzzles and matrix factorization\n\nAnother perspective of factor puzzles is matrix factorization (Q):\n\n.\n\nNote that matrices B and C constitute a factorization of the matrix A.\n\nThat being said, an interesting observation is that if a square matrix A is factorizable in the fashion depicted above (Q), then the matrix is singular, i.e., det(A) = 0.8 This fact follows from the definition of determinant and Theorem 2.2. In particular, a 2×2 matrix A is factorizable in the fashion depicted above (Q) if and only if the matrix is singular, i.e., det(A) = 0.\n\n\n4. Use case\n\nTo secure communicating information, a sender encrypts the original message using a scheme (key), unknown except for the intended parties, and the intended receiver decrypts using the key inverse.2 One approach for encryption is to replace a text message by a sequence of numbers using a linear transformation. Table 2 demonstrates a correspondence between English alphabets and the numbers 1−26. The space corresponds to number 27. Alternative correspondences are possible.\n\nFor example, consider the message “TOP SECURITY CLEARANCE”.10,p. 146 Using the above tabulated correspondence (Table 2), this message can be written as follows:\n\nTo encode the message, one can use, for example, the solution vectors of the following factor puzzle (R):\n\ni.e., 2312.Consequently, the encrypted message, which will be sent along with the factor puzzle, will be as follows\n\nThe calculations are explained below (S).\n\nTo decode the received message, the receiver can solve the factor puzzle and then use the inverse matrix for decryption. Note that the solution is unique in this.\n\n\n5. Conclusion\n\nIn this paper, we defined factor puzzles and their solutions. Furthermore, we addressed the important questions of existence and uniqueness of solutions, number of solutions, and its connections to polynomial and matrix factorizations. In addition, application to cryptography was discussed.\n\nWhile the factor puzzles might be elementary, the combination of ideas presented in this manuscript are far from being elementary. Furthermore, while this line of research is still in its infancy, there is ample room for extension.\n\n\nData availability\n\nThere is no data associated with this article.",
"appendix": "References\n\nAtabekovna RF: Puzzles as a factor in the formation of elementary mathematical concepts in preschool education. International Journal on Integrated Education. 2021; 2(2): 133–137.\n\nAumasson J: Serious cryptography: A practical introduction to modern encryption. No Scratch Press; 2018.\n\nCuoco A, Goldenberg EP, Mark J: Habits of mind: An organizing principle for mathematics curricula. Journal of Mathematics Behavior. 1996; 15: 375–402.\n\nFuson K, Beckmann S: Multiplication to ratio, proportion, and fractions within the common core. NCTM Annual Meeting. 2012. 2012. Reference Source\n\nGorev PM, Telegina NV, Karavanova LZ, et al.: Puzzles as a didactic tool for development of mathematical abilities of junior school children in basic and additional mathematical education. EURASIA Journal of Mathematics, Science and Technology Education. 2018; 14(10): 12. Publisher Full Text\n\nKlymchuk K: Puzzle-based learning in engineering mathematics: Students’ attitudes. International Journal of Mathematical Education in Science and Technology. 2017; 48(7): 1106–1119. Publisher Full Text\n\nNational Research Council: Adding it up: Helping children learn mathematics. National Academy Press; 2001.\n\nPoole D: Linear algebra: A modern approach. (4th ed.).Cengage Learning; 2015.\n\nRosen K: Discrete mathematics and its applications. (8th ed.).McGraw-Hill; 2019.\n\nSullivan M: Finite mathematics: An applied approach. (11th ed.).Wiley; 2011.\n\nThomas C, Badger M, Ventura-Medina E, et al.: Puzzle-based learning of mathematics in engineering. Engineering Education. 2013; 8(1): 122–134. Publisher Full Text"
}
|
[
{
"id": "232328",
"date": "22 Jan 2024",
"name": "Otobong Gabriel Udoaka",
"expertise": [
"Reviewer Expertise Pure Mathematics (Algebra: Semigroup theory",
"Group theory",
"Representation theory",
"Combinatories"
],
"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 is well written, is well organized and followed the manuscript guidelines of the journal to a large extent. The introduction section is good and shows the importance of the study. Literature review is adequate. Outcomes of the study are consistent with the findings. The approach used is praiseworthy. All the questions raised has been answered judiciously.\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? No source data required\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "237908",
"date": "14 Feb 2024",
"name": "Ammar Ali Neamah",
"expertise": [
"Reviewer Expertise My areas of expertise are Number Theory and Cryptography."
],
"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 work, the authors provide Factor puzzles from definition to applications. The paper is well-written and nice to read, however I have the following concerns that I would like to ask authors to address them to improve the quality of their work:\n[Comment 1] The introduction of the manuscript needs improvement by extending the related works.\n[Comment 2] In P.2 L. 9-10, avoid the word “you” since it is not academic writing.\n[Comment 3] In section 4, the application of factor puzzles in cryptography must improve and address the following questions:\nHow can one encrypt the original message if the key is not a square matrix? Can one find the inverse of the key to decrypt the ciphertext if the key is not a square matrix? If not, how can one address the issue in the paper? How can one decrypt the ciphertext if the key is a square matrix and its determinant is not ±1? Usually, the encryption process gives ciphertexts instead of numbers. How can one transfer the numbers in Equation (S) to letters? Can one apply the proposed approach to encrypt videos, voices, and images? What are your suggestions?\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?\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
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https://f1000research.com/articles/11-727
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https://f1000research.com/articles/11-726/v1
|
01 Jul 22
|
{
"type": "Research Article",
"title": "Resilience and entrepreneurial intentions of people with disabilities: in search of the Sustainable Development Goals (SDGs)",
"authors": [
"Noemí Pérez-Macías",
"José L. Fernández-Fernández",
"Antonio Rúa Vieites",
"José L. Fernández-Fernández",
"Antonio Rúa Vieites"
],
"abstract": "Background: There is a significant gap in employment between people with and without disabilities, despite the importance of work in achieving their independence, autonomy, and integration into society. There are several reasons that cause this gap to exist, such as: people with disabilities feel less prepared, there is a stigma or discrimination to hire people with disabilities and the incompatibility of schedules due to medical issues, among others. That is why entrepreneurship emerges as a good option for the integration of people with disabilities in our society, improves their confidence and promotes some of the Sustainable Development Goals set out in the 2030 Agenda. According to existing literature, people with disabilities have certain virtues such as resilience and motivation that favor entrepreneurship. Thus, the purpose of this study is to provide new insights into the variables that determine the entrepreneurial intention of people with disabilities. Methods: In order to respond to this objective, an online questionnaire was given to people with disabilities between the ages of 16 and 65 years, residing in diverse regions of Spain. To analyze the results, this study uses Partial Least Squares-Structural Equation Modeling (PLS-SEM) in a sample of 235 people with disabilities in Spain using as a framework Krueger´s improved model, adding resilience as a new variable. Results: The results reflect the importance of resilience, the subjective norm, and perceived collective efficacy in the entrepreneurial processes of people with disabilities. Conclusions: This study contributes to the underdeveloped literature on entrepreneurship in people with disabilities; it provides insights that can have a practical effect on the reduction of the inequality gap between people with and without disabilities making recommendations to clinicians, vocational psychologists, and policymakers; also, this study would advance the achievement of Sustainable Development Goals 8 and 10.",
"keywords": [
"People with Disabilities",
"Resilience",
"Entrepreneurial Intentions",
"Entrepreneurship",
"Personal Factors",
"Perceived Collective Efficacy Sustainable Development Goals",
"Partial Least Squares-Structural Equation Modeling."
],
"content": "Introduction\n\nAccording to the UK Equality Act 2010 “Persons with disabilities include those who have long-term physical, mental, intellectual or sensory impairments which in interaction with various barriers may hinder their full and effective participation in society on an equal basis with others”. In Spain, in fact, for personal income tax purposes and according to the ODISMET,1 people with disabilities are considered disabled if they show a degree of disability (ranked from 0 to 100%) equal to or greater than 33%. For people with disabilities, work is a fundamental tool that increases social welfare and savings on social costs in addition to supporting autonomy, freedom, and independence for people with disabilities.2–4 However, there is an important employment gap between people with and without disabilities,5,6 and people with disabilities are less likely to find jobs.1,7,8 On the one hand, this could be because people with disabilities may think they are not prepared for employment9 and may depend on social assistance9,10; on the other hand, they face certain social barriers to employment, such as prejudice, discrimination or marginalization.5–7,11–13 This employment gap not only increases inequalities and social exclusion, but also undermines the Sustainable Development Goals (SDG) and Spain’s own national legislation.\n\nGiven the increasing number of unemployed people with disabilities,1 it is worthwhile considering entrepreneurship14 as an alternative means of income and development. This approach could increase the gross domestic product (GDP),3,5,7,8,12,13,15–18 and improve economic development.6 On an individual level, self-employment could improve their social integration and increase self-esteem for people with disabilities. Advancing the economic inclusion of people with disabilities would show progress toward the 2030 Agenda and some of the Sustainable Development Goals (SDGs), which expressly advocate for reduced inequality and peaceful societies that achieve sustainable development.\n\nEntrepreneurship is a feasible option for people with disabilities, as it offers the possibility of accommodating their needs and establishing independence.19 However, in Spain, compared with other countries such as USA, UK, or Australia, only 11.2% of people with disabilities are entrepreneurs,20–22 which indicates under participation among this population.23 In fact, the Inclusive Entrepreneurship Policies: Country Assessment Notes24 report indicates that there is no specific legislation or specific action plan to promote entrepreneurship among people with disabilities. This statement is not surprising, since the General Law on the Rights of People with Disabilities and Social Inclusion (Real Decree 1/2013 from November 29th) clearly discusses the need to promote entrepreneurship in Spain.\n\nIt is important to identify the specific variables that foster entrepreneurship among people with disabilities, who, according to existing literature, have certain virtues such as resilience and motivation that favor entrepreneurship.2,7,13,18,25,26\n\nThis article aims to deepen the knowledge about the variables that determine the EI-Entrepreneurial_Intention of people with disabilities. Since existing literature associates RES-Resilience with entrepreneurship, we adopt Krueger’s27 improved model, as model framework including several modifications following Esfandiar et al.28 and add the RES-Resilience construct.29\n\nAs a practical contribution, we aim to achieve three objectives: improve social integration of people with disabilities,5,30,31 reduce costs of public social services,4 and propose ideal and efficient policies regarding social integration and entrepreneurship.\n\nFurthermore, the immediate justification of this work stems from the fact that research on this subject is scarce,32 especially in Spain.33 Prior research suggests continued investigation, similar to the study presented in this article.6,7,13,16,25,30,31,34\n\n\nTheoretical foundations\n\nKrueger27 proposes a new model (see Figure 1) that improves the predictive capability of the frameworks of understanding entrepreneurial intention (EI) by integrating the theory of planned behaviour (TPB) and the entrepreneurial event model (EEM). This improvement to the model responds to the fact that, although TPB35 is the most used theory in the entrepreneurship literature and one of the standards to predict entrepreneurial intentions (EI), it does not consider external influences.27 According to TPB, there are three attitudes that precede EI, namely, the attitudes towards the act itself, in this case A_Attitudes_Towards_the_Behaviour –the individual’s assessment of their desire to create a new project; the SN_Subjective_Norm –or the perception one has about what the people around him/her think about becoming an entrepreneur; and the PBC_Perceived_Behavioural_Control –or the perception the individual has about the absence or presence of the resources and opportunities to develop a certain behaviour.35\n\nThis figure has been adapted from Krueger27 with permission from Springer Nature, by including the specifications about the models that were included in this figure.\n\nKrueger's Entrepreneurial Intention Model27 is described. This model consists of attitude, perceived social norms that influence the perception of desirability. Perceived self-efficacy and perceived collective efficacy influence perceived feasibility. Both, perceived desirability and perceived feasibility influence perceived opportunity, which in turn influences entrepreneurial intention and is moderated by the propensity to act. Finally, entrepreneurial intention influences action.\n\nKruger27 states that the EEM36 considers external factors but does not consider social norms. When this is considered, social norms add a predictive value to the entrepreneurial intentions (EI) model. This model establishes that the EI predictors are PD-Perceived_Desirability –the individual’s will to become an entrepreneur-,36,37 PF_Perceived_Feasibility - the individual’s belief that he or she possesses the skills to be an entrepreneur-,36 and the propensity to act –how an event can trigger a specific action-. Even though both models are similar, they are not identical. Each has its own specificities.38,39\n\nThe resulting model proposed by Krueger27 adds PCE_Perceived_Collective_Efficacy as an additional variable. In our case, this variable can be significant because many of these individuals depend on (or at least frequently request the participation of) others to perform some activities.6,40\n\nAccording to Abbas and Khair,23 people with disabilities consider entrepreneurship feasible. This is partly because of the barriers they face in terms of employment.7,8,12,26 In addition, they may have some personality traits that favor entrepreneurship, such as resilience, tolerance to uncertainty, and persistence.2,7,13,25,26 Academic studies on EI analysis among people with disabilities are still scarce, especially in Spain.2,33,41–43 This is despite the fact the advantages that entrepreneurship presents and the important social benefits it can bring.2,5,13,16,17,25,26,30,31,43,44 Therefore, it is of interest to conduct studies that contribute to increasing the number of entrepreneurs among people with disabilities.\n\nIn this regard, Pérez-Macías and Fernández-Fernández2 qualitatively approximate the factors that influence the EI of people with disabilities. They point out the following: First, they identify the cognitive, personal, and psychological factors, as well as motivators and personal barriers. They then consider factors related to entrepreneurship training. In the same way, they point out contextual factors (e.g., role models and social capital) and institutional factors, as well as barriers or environmental support. Even so, we must specify that the influence of the factors detailed on EI will depend on the context, as well as on possible bias among the sample.\n\nAlong with institutional and environmental factors, EIs are influenced by personal dynamics.45,46 For example, there is evidence that people who face important challenges in life, such as an acquired disability, tend to develop greater RES_Resilience, as well as motivational, cognitive, and social resources that help them successfully adapt to the situation.47 For some authors, this psychological mechanism boosts entrepreneurship among people with disabilities.7 Given this context, we focus on these personal factors.\n\n\nDevelopment of hypothesis\n\nWe start with Krueger’s improved model27 (see Figure 1), which has been validated in studies conducted on people who do not have disabilities.28,48 In this study, we use an enriched version that incorporates resilience (see Figure 2), which other authors have identified as relevant in studies with people with disabilities.2 The objective is to establish mechanisms that aid the rise of entrepreneurship among this group while reducing their vulnerabilities in the job market. The proposed model is illustrated in Figure 2.\n\nThis figure shows our proposed model.\n\nWe are establishing resilience direct influence on attitude, subjective_norms and perceived_behavioral_control (H5a;H5b;H5c). It is also indicated that it indirectly affects EI (yellow_dashed_line_H5d). It is established that attitude directly influences perceived_desirability (H1b) and indirectly influences EI (red_dashed_line_H1c). Subjective_norms directly affects perceived_desirability and EI (H2b;H2a). Perceived_behavioral_control directly affects perceived_feasibility (H3b) and indirectly affects EI (green_dashed_line_H2e). Perceived collective efficacy directly affects perceived_behavioral_control (H3d) and indirectly affects EI (blue_dashed_line_H3f). Perceived_desirability directly affects EI and perceived_opportunities (H1a; H4b). Perceived_factibility_perceived directly affects EI and perceived_opportunities (H3a;H4a). Finally, it is established that perceived_ opportunities directly influences EI (H4c).\n\nShapero and Sokol36 prove that individuals that have a high PD-Perceived_Desirability had a greater probability of becoming entrepreneurs. This is corroborated by others who say that, when an individual perceives becoming an entrepreneur as desirable, it increases their EI.28,39,49 At the same time, Shapero and Sokol36 mention how cultural aspects, as well as family, can increase the PD-Perceived_Desirability to become an entrepreneur; in turn, they affect EI positively.\n\nTherefore, people with disabilities who decide to become entrepreneurs must have previously built a favorable A-Attitude6 when they identified entrepreneurship as a possible way to reach the levels of freedom and independence they desire.3,5,16 Furthermore, they may believe that financial self-reliance will remove some of the barriers that restrict their full integration into the community.17,22,48 Together, these factors contribute to increased EI whenever entrepreneurship is considered a desirable option. Shook and Bratinau49 concur and articulate that the more favorable the individual’s efforts towards becoming an entrepreneur, the higher their PD-Perceived_Desirability. Consequently, we developed the following hypotheses:\n\nH1a: PD-Perceived_Desirability has a direct effect on EI.\n\nH1b: A-Attitude_towards_Entrepreneurship has a direct effect on PD-Perceived_Desirability\n\nH1c: A-Attitude_towards_Entrepreneurship has a direct effect on EI.\n\nThe SN-Subjective_Norm, which, in general terms, can influence certain behaviors and opinions that, in turn, affect EI,35 refers to the way individuals interpret the opinions of their significant others and how they can affect their own likelihood of becoming entrepreneurs.50 In fact, in the case of people with disabilities, family members and friends have a strong influence on their decision making,6 extending to EI itself. However, existing studies are not conclusive regarding the degree to which this is true. In fact, the influence of close relations is one of the variables that generates controversy in entrepreneurship studies of people without disabilities. Some studies state that it has a direct influence on EI,51 whereas others say it is indirect, through PBC-Perceived_Behavioural_Control and A-Attitude_Towards_Entrepreneurship,52 or through PF-Perceived_Feasibility and PD-Perceived_Desirability.48 Other studies have concluded that there is no influence at all.28,53\n\nFor our part, we developed the hypothesis that the SN-Subjective_Norm exerts a direct influence, either over the EI of people with disabilities or their PD-Perceived_Desirability. This is in line with other authors39 that show how parental support, because of their economic and emotional dependence, has a strong influence on the PD-Perceived_Desirability of college students. Similarly, Solesvik et al.54 state that family bonds and other cultural aspects can influence individuals’ PD-Perceived_Desirability towards entrepreneurship and EI. Therefore, we consider the opinions of family members, friends, and classmates about PD-Perceived_Desirability and EI to be significant among people with disabilities, who are influenced either at an emotional or economic level.6,13 In this sense, explicit support will make entrepreneurship desirable.55 Consequently, we propose the following hypotheses:\n\nH2a: SN-Subjective_Norm has a direct effect on EI.\n\nH2b: SN-Subjective_Norm has a direct effect on PD-Perceived_Desirability.\n\nPeople that normalize adapting to change, as many people with disabilities,13 must develop certain psychological resources that allow them to spot business opportunities, better confront uncertainty, mobilize resources that improve their ability to succeed in new circumstances, and focus on a specific career goal.56 Such resources tend to favor PF-Perceived_Feasibility because of the development of capabilities, such as persistence, resilience, independent problem-solving, creativity, and innovation.13,57 These characteristics are related to successful entrepreneurship.58\n\nPBC-Perceived_Behavioural_Control plays an important role in entrepreneurship,59 even in the face of adversity.58 Thus, it has been said that people who struggle and survive the difficulties that a disability brings can develop a higher level of optimism and higher risk tolerance. These two traits could, likewise, increase the ability to overcome challenges60 and their PBC-Perceived_Behavioural_Control. Ultimately, this could increase the PF-Perceived_Feasibility and reinforce EI.\n\nBy contrast, given the challenge that people with disabilities have in finding employment, they often develop a higher level of persistence and improve creative problem-solving skills.13 These skills increase PBC-Perceived_Behavioural_Control by supporting the development of a greater PF-Perceived_Feasibility, which can be translated into higher EI.7 In fact, there is evidence that people with disabilities who develop strong self-efficacy or PBC-Perceived_Behavioural_Control and a higher level of PF-Perceived_Feasibility manage to influence their EI significantly.16\n\nOverall, although the support of family members and friends is a required condition,2,13 it is not enough to become an entrepreneur.6,61 Hence, those who become entrepreneurs may need the support of others to help develop new networks13 and access new funding and resources. This support will result in a reinforcement of the PCE-Perceived_Collective_Efficacy,6 which could increase individual PBC-Perceived_Behavioural_Control regarding a particular action, such as entrepreneurship.62 Additionally, it can also increase PF-Perceived_Feasibility which in turn could increase EI.28 This appears to be because when an individual thinks that their support system (e.g., friends or co-workers) can help them successfully address any problems that could arise, then it is more likely that they will decide to become an entrepreneur.62 Given all the above-mentioned considerations, we propose the following hypotheses:\n\nH3a: PF-Perceived_Feasibility has a direct effect on EI.\n\nH3b: PBC-Perceived_Behavioural_Control has a direct effect on PF-Perceived_Feasibility.\n\nH3c: PCE-Perceived_Collective_Efficacy has a direct effect on PF-Perceived_Feasibility.\n\nH3d: PCE-Perceived_Collective_Efficacy has a direct effect on PBC.\n\nH3e: PBC-Perceived_Behavioural_Control has an indirect effect on EI.\n\nH3f: PCE-Perceived_Collective_Efficacy has an indirect effect on EI.\n\nIt has been confirmed that knowledge and experience are decisive in identifying and exploiting business opportunities”.63,p.108 Nevertheless, people with disabilities generally have lower levels of education and experience.31,48,64 Consequently, this could affect the perception of opportunities and, therefore, EI.65 Even so, because of the limited number of opportunities they have and the myriad barriers they must overcome,13 people with disabilities are forced to tap into all their potential3 and develop skills, personality traits, and creativity to seize opportunities to conduct new businesses in an innovative way.12,13,41\n\nSome studies confirm that certain types of disabilities allow a greater level of creativity, thus facilitating the identification of entrepreneurship opportunities.66 Similarly, Wiklund et al.25 state that people who suffer from attention deficit disorder tend to develop certain capabilities that allow them to identify market opportunities, which would ordinarily go unnoticed by others. This may also benefit the development of EI. Caldwell et al.12 show how people with disabilities attempt to overcome and confront challenges and develop new ideas that seek to find answers and solutions to the problems they face. These circumstances favor social entrepreneurship.\n\nThere is also evidence that individuals who tend to adapt easily to new circumstances and barriers often have psychological resources, such as resilience, which is a trait associated with a successful entrepreneur.58 RES-Resilience allows them to recognize business opportunities and mobilize resources to overcome the uncertainty of every business. In any case, the PO-Perception_of_Opportunities must be framed in terms of how desirable and feasible entrepreneurship is on a personal level.28\n\nEntrepreneurship is likely desirable for people with disabilities because of their limited employment options8 and the stigmas and discrimination they face.12,22,26 Considering what we have stated, we developed the following list of complementary hypotheses:\n\nH4a: PF-Perceived_Feasibility has a direct effect on PO-Perceived_Opportunities.\n\nH4b: PD-Perceived_Desirability has a direct effect on PO.\n\nH4c: PO has a direct effect on EI.\n\nRES-Resilience is the ability to remain relatively stable and healthy, either at a psychological or physical level, against the consequences of complex and painful events.67 In the face of traumatic situations, RES-Resilience can cause emotions that can counteract the objective negativity that such circumstances could represent and produce positive experiences.68\n\nAlthough the concept of RES-Resilience has been systematically ignored in the literature that focuses on entrepreneurship, it resonates strongly, particularly when resilience is associated with EI.29,58,68 Those who have studied the correlation often highlight the presence of a significant influence between RES-Resilience and EI.58,68,69\n\nIt is almost a cliché to claim that people with disabilities tend to be resilient and persevere.13 In fact, authors such as Wiklund et al.25 confirm the above when they state that people with disabilities develop skills and resources that improve RES-Resilience, and that this circumstance in turn allows them to develop certain capabilities typical of entrepreneurial activity, such as self-confidence and a higher risk tolerance.7,13 In short, this would reinforce a proactive A-Attitude_toward_Entrepreneurship, and a higher level of PBC-Perceived_Behavioural_Control. In addition, experience in overcoming obstacles can be successfully translated into a stronger work ethic and tenacity.25 This will benefit both A-Attitude_toward_Entrepreneurship and PBC-Perceived_Behavioural_Control, resulting in an increased EI.58,70 Similarly, resilient individuals are characterized as more optimistic and generate positive feelings, which foster adaptation and openness to social support.71 Social support is important in adverse, threatening, and risky moments.72 However, these circumstances are present when resilient people tend to succeed,13 which only reinforces positive perceptions of support from family and friends (again increasing EI).\n\nThe literature reflects studies on the influence of RES-Resilience on EI in people without disabilities.29,69 In the same way, we have compared studies that also focus on analysing the influence of RES-Resilience on situations of war or conflict.58 However, we did not find any specific analysis that explicitly covers the relationship between RES-Resilience and EI in people with disabilities. Furthermore, this gap is interesting in the entrepreneurship space.25\n\nWe developed the corresponding working hypotheses, under the following terms:\n\nH5a: RES-Resilience has a direct effect on A-Attitude_toward_Entrepreneurship.\n\nH5b: RES has a direct effect on SN-Subjective_Norm.\n\nH5c: RES has a direct effect on PBC-Perceived_Behavioural_Control.\n\nH5d: RES has an indirect effect on EI.\n\n\nMethods\n\nThis study received ethical approval from the Committee of Ethics of Universidad Pontificia Comillas of Madrid on 11th May 2022. No formal written consent was recorded; however, all the people who responded to the questionnaire were informed about the purpose of the study and how the data would be used. Answering or not answering the questionnaire was optional.\n\nIn April and May 2020, empirical analysis was carried out through an online questionnaire (written in Spanish) given to people with disabilities between the ages of 16 and 65 years, residing in diverse regions of Spain. As requested by our funder the questionnaire was distributed to people with all types of disabilities without any restrictions. The configuration settings ensured that none of the participants answered the questionnaire twice. The study determined the minimum sample size by multiplying the number of highest arrows pointing to a particular endogenous construct by 10, as recommended by Barclay, Higgins and Thompson (1995H).73 We have 9 constructs of which 8 are endogenous. The total number of arrows pointing to them directly is 13. This implies that a minimum sample size of 130 would be sufficient for our analysis. Also, Hair et al.74 mentioned that, if G*power analysis is employed, 52 observations are needed to reach a statistical power (G*power) of 80% to detect R2 values of at least 0.25 (with a 5% probability of error). After waiting two months to obtain responses from people with disabilities and after the organizations that collaborated with us made several reminders to them, the total number of people who answered the online questionnaire was 240. Of these 5 were incomplete data, so they were eliminated from the database. Thus, taking into account that our sample is 235 people, it is believed that the size is adequate to apply the PLS tool and thus be able to test the hypotheses raised.\n\nTo collect the data, we were assisted by workers from the Once Foundation, through the Inserta program, a worker from the Ilunion Organization, and 16 other organizations. In the data collection process, an attempt was made to obtain a sample whose structure was adjusted to the profile of the population under study. For this reason, different collaborating organizations were chosen for data collection, in order to try to bias the sample as little as possible. The organizations that collaborated with us contacted potential participants by sending them an informative email. This email explained the purpose of the study, how the data would be treated and the importance of their participation. In the same way, the email sent by the organizations included the link to access the online questionnaire. To ensure anonymity in the questionnaire, we established the restriction of not being able to collect the e-mail addresses of the participants. Likewise, the data published were shown in aggregate form to avoid singling out attacks. People with intellectual disabilities, as well as people with visual impairments, had support staff provided by some of these organizations. This means, for example, that in the case of people with visual disabilities who did not have the means to read the questionnaire, a person from the organization was in charge of reading the questionnaire and writing down their answers. On the other hand, in the case of people with intellectual disabilities, if they did not understand any of the questions, the organizations were there to provide support and explain the concepts they did not understand.\n\nThe items included in the questionnaire were taken from validated scales using a 7-point Likert scale (1 = strongly disagree; 7 = strongly agree). The questions employed are shown in the Underlying data.75\n\nThe dependent variable was EI-Entrepreneurial_Intention. This was measured using the six-item scale developed by Liñán et al.52\n\nIndependent variables: PD-Perceived_Desirability was measured by Shapero and Sokol’s36 and Shook and Bratinau’s49 scales; PF-Perceived_Feasibility was measured using Shook and Bratinau’s49 and Krueger et al.38 scales; A-Attitude_Towards_Entrepreneurship, PBC-Perceived_Behavioural_Control, and SN-Subjective_Norm were measured by Liñán et al.52 scale. PCE-Perceived_Collective_Efficacy was measured using Chen’s76 and Esfandiar et al.’s28 scales. PO-Perceived_Opportunities were measured using the scale employed in the GEM77 study. Finally, RES-Resilience was measured using Sinclair and Wallston’s78 scale.\n\nControl variables: To avoid possible biases, we used the following control variables.28,34,53 Age was coded as a categorical variable (16-29 years old = 1; 30-44 years = 2; 45-65 years = 3). Gender: coded as a dichotomous variable (Men = 1; Women = 2). EDU-Level_of_Education: is coded as a categorical variable (primary education = 1, secondary education = 2, higher level specific vocational training cycles = 3, university = 4, doctorate = 5, and others = 6). EE-Entrepreneurial_Experience: is coded as a dichotomous variable, where 1 = has entrepreneurial experience and 2 = does not have entrepreneurial experience.\n\n\nAnalysis\n\nDescriptive statistics were performed with SPSS 24 (IBM SPSS Statistics, RRID:SCR_016479). The proposed model was tested using Partial Least Squares-Structural Equation Modeling (PLS-SEM) with the SmartPLS 3.2.7 version, which has been widely used in entrepreneurship research.28,79 In addition, it is considered appropriate for complex structural models.80 The analysis is developed in two stages.\n\n1. Assessment of the measurement model: a) This includes a reliability analysis of the indicators. As shown in Table 1, several indicators must be removed. (ACT=0.429; ACT5=0.611; PBC5=0.641; PBC6=0.500; EI5=0.256; EI6=0.560; PO1=0.641; RES=0.660). The remaining variables have a loading greater than 0.707 for their corresponding constructs (Table 1); b) for internal consistency, all the constructs meet the strict criteria for Cronbach’s alpha (0.8/0.9), as well as the Dijkstra-Henseler (rho_A) indicator and composite reliability (0.7). Additionally, the constructs reach convergent validity as they exceed the threshold required for AVE (0.5) (Table 1).\n\nc) To analyze discriminant validity, we employ a Heterotrait-Monotrait ratio of correlations (HTMT), where values above 0.90 indicate multicollinearity problems.81 We observe that the correlation between PD-Perceived_Desirability and A-Attitude_Towards_Entrepreneurship is 0.929 and the correlation between PD-Perceived_Desirability and PF-Perceived_Feasibility is 0.918. Then, to relax multicollinearity problems80 we remove the most correlated indicators PD3, PF2, and ACT3 (Table 2). After this process, this criterion is established including the confidence intervals (Table 2).\n\nA = Attitude_Towards_Entrepreneurship, PBC = Perceived_Behavioural_Control, PD = Perceived_Desirability, EE = Entrepreneurial_Experience, Edu = Level_of_Education, EI = Entrepreneurial_Intention, PO = Perceived_Opportunities, PCE = Perceived_Collective_Efficacy, RES = Resilience, SN = Subjective_Norms, PF = Perceived_Feasibility.\n\nA = Attitude_Towards_Entrepreneurship, PBC = Perceived_Behavioural_Control, PD = Perceived_Desirability, EE = Entrepreneurial_Experience, Edu = Level_of_Education, EI = Entrepreneurial_Intention, PO = Perceived_Opportunities, PCE = Perceived_Collective_Efficacy, RES = Resilience, SN = Subjective_Norms, PF = Perceived_Feasibility.\n\nFirst, the possible collinearity of the models is rejected based on the Variance Inflaction Factor (VIF) value,74 except for the relationship between PD-Perceived_Desirability and EI, which is 0.508 when the limit is 0.500 (Table 3).\n\n2. In the study of the structural relationships among the constructs (once the first stage is accomplished) we have used: a) The coefficient of determination (R2), where R2 exceeds the required values (ACT=0.179; PBC=0.531; PF=0.530; EI=0.791; SN=0.345; PO=0.486; PD=0.693) in all cases; b) The Stone-Geisser’s Q282,83 to check the model’s capability to predict. We use the cross-validity redundancy to estimate the predictive relevance of our model84 obtaining a Q2 of 0.596 (See Figure 2) which is an indication of a highly predictive model;74 and c) the model fit, using the standardized root mean square residual (SRMR) and the normed fit index (NFI). SRMR fit values of 0 would indicate perfect fit and less than 0.05, acceptable fit. NFI values above 0.90 are considered acceptable.85 Our SRMR value is 0.030, and the NFI value is 0.918, indicating that our model is well specified. Consistent bootstrapping (5,000 samples) is used to generate standard errors and t-statistics, which allow us to verify our hypothesis.84 Figure 3 shows the results of the model.\n\nA = Attitude_Towards_Entrepreneurship, PBC = Perceived_Behavioural_Control, PD = Perceived_Desirability, EE = Entrepreneurial_Experience, Edu = Level_of_Education, EI = Entrepreneurial_Intention, PO = Perceived_Opportunities, PCE = Perceived_Collective_Efficacy, RES = Resilience, SN = Subjective_Norms, PF = Perceived_Feasibility.\n\nThis figure shows the results obtained in each of the hypotheses raised. Resilience does have a direct and significant influence on attitude, subjective_norm, and perceived_behavioral_control (H5a; H5b; H5c_Accepted), and indirectly on EI (H5d_Accepted). Attitude directly and significantly influences perceived_desirability (H1b_Accepted) and indirectly EI (H1c_Accepted). Subjective_norm directly affects perceived_desirability and EI significantly (H2b;H2a_Accepted). Also, perceived_behavioral_control affects significantly and directly perceived_feasibility (H3b_Accepted) and indirectly EI (H2e_Accepted). Perceived_collective_efficacy affects directly and significantly perceived_behavioral_control (H3d_Accepted) and indirectly EI (H3f_Accepted). Perceived_desirability directly and significantly affects EI (H1a_Accepted) and perceived opportunities (H4b_Accepted). Perceived_feasibility significantly affects EI and perceived_opportunities (H3a:H4a_Accepted). Perceived_ opportunities directly and significantly influences EI (H4c_Accepted).\n\n\nResults and discussion\n\nThe total number of people who answered the online questionnaire was 240. Of these 5 were incomplete data, so they were eliminated from the database. The final sample comprised 235 respondents (descriptive statistics in Table 4 performed with SPSS 24).75\n\nWe assert that the PD-Perceived_Desirability has a direct influence over EI (path: 0.284, t-value: 2.466); A_Attitude_Toward_Entrepreneurship increases PD-Perceived_Desirability (path: 0.690, t-value: 10.323), and A_Attitude towards the fact that becoming an entrepreneur has an influence on EI through the mediation of PD-Perceived_Desirability (path 0.272, t-value: 3.378). Thus, we accept hypotheses H1a, H1b, and H1c.\n\nThese results have been obtained by other authors in prior studies of people without disabilities28,49,54; however, these are considered novel in the study of entrepreneurship among people with disabilities. The importance of shaping positive A_Attitude_Toward_Entrepreneurship can be observed, because they are led to perceive entrepreneurship as a more desirable career choice.49 This has already been established by others,36 who show that people with a high level of PD-Perceived_Desirability would have a greater probability of developing EI. Governments and public administrations, as well as educational institutions, non-profit organizations and vocational rehabilitation centers, specialist and educators, could attempt to stimulate entrepreneurship in people with disabilities, so that they might perceive it as a feasible employment option. Doing so requires a process of cultural change, because Spanish culture does not favor entrepreneurship.63 However, culture has a strong influence on the PD-Perceived_Desirability of entrepreneurship.36\n\nSimilarly, it is necessary to create positive A_Attitude_Toward_Entrepreneurship among people with disabilities by showing them and their influential loved-ones the possible results on a personal or professional level.42 Therefore, the key is to send a clear message to loved ones, who could break down barriers and significantly influence a person with disabilities’ interest and success in entrepreneurship.22,48 Such positive encouragement could lead to the freedom and economic independence they seek.5,16 In this regards the vocational rehabilitation centers and specialist play a key role.\n\nSN-Subjective_Norm has a direct and significant influence on the EI of people with disabilities (path: 0.156; t-value: 2.676) as does PD-Perceived_Desirability (path: 0.229; t-value: 3.506). This leads us to accept H2a and H2b. We tested the importance of the opinions of family members, friends, and colleagues for people with disabilities when deciding to become an entrepreneur.6 This finding concurs with Martínez-León et al.,42 who showed that for people with disabilities who wanted to become entrepreneurs, moral support from one’s immediate circle was even more important than having start-up funding. Therefore, the opinions of family members, friends, and other close relatives had great relevance in decision-making. In fact, Shen et al.39 showed that college students who depended on their parents, emotionally and economically, tended to develop a higher EI.\n\nRegarding the positive and significant relationship found between the SN-Subjective_Norm and PD-Perceived_Desirability, this relationship has been supported by other studies on people without disabilities.54 However, this did not seem to be a trend in people without disabilities, especially in cultures that have a strong sense of individualism.28,53 Nonetheless, it makes sense in our study. Thus, it is advisable that rehabilitation centers, educators and specialist focus on family members and friends who can provide critical encouragement.\n\nPF-Perceived_Feasibility has a significant influence on EI (path: 0.321; t-value: 3.108), leading us to accept H3a. People with disabilities who perceive that they are capable of becoming entrepreneurs develop a higher level of EI. This is in line with other studies on people without disabilities.28,39,59 Similarly, observations show that PBC-Perceived_Behavioural_Control has an influence on PF-Perceived_Feasibility, with the acceptance of H3b (Path: 0.622; t-value: 8.196), which goes hand in hand with studies on people without disabilities.27,28,49 Therefore, showing that those individuals who perceive that they have more control over their own skills feel that it is more feasible to become an entrepreneur. Thus, it becomes evident that the relationship between PBC-Perceived_Behavioural_Control and PF-Perceived_Feasibility is direct, positive, and significant.27,49\n\nBy contrast, we observed that the PCE-Perceived_Collective_Efficacy has a direct and significant influence on PF-Perceived_Feasibility, which leads us to accept H3c (Path: 0.159; t-value: 2.069), consistent with other studies about people without disabilities.28 Therefore, it seems evident that for people with disabilities, starting a business with other partners or in a collective setting is critical, because social support from their environment is very important.42 Support can come from close relatives or people who Granovetter61 refers to as having weak relationships, but who may provide the most current resources and knowledge. This support increases the feeling that they can become entrepreneurs, which reflects PF-Perceived_Feasibility.28\n\nIn addition, the PCE-Perceived_Collective_Efficacy increases PBC-Perceived_Behavioural_Control on behalf of the individual considering the entrepreneur, who can rely on support and help provided by others.62 Therefore, we accept H3d (path: 0.283; t-value:3.764). In fact, when a person with disabilities increases their PBC-Perceived_Behavioural_Control, they increase their PF-Perceived_Feasibility, which results in a higher EI. Finally, these considerations allow us to accept both hypothesis H3e (Path: 0.237; t-value: 3.165) and hypothesis H3f (Path: 0,128; t-value: 3.053) as true.\n\nThus, in our context, we confirm how important it is for people with disabilities to start a business in cooperation with others and not individually.28 Some support can benefit the process of overcoming existing barriers, as well as the growth and development of new networks, which increases the individuals’ levels of PBC-Perceived_Behavioural_Control. Additionally, access to capital, resources, and high-quality information increases with collaboration, without disregarding the importance of moral support in collaborative relationships.13,42 This ultimately results in an increase in the PF-Perceived_Feasibility and EI. Hence, we confirm what is stated in Pérez-Macías and Fernández-Fernández,2 where many participants talked about the need for partnership in entrepreneurship, which could make them feel safer and more supported.\n\nWhereas it seems that when someone considers themselves capable of performing an entrepreneurial action (perceived feasibility), the PO-Perception_of_Opportunities increases. This leads us to accept H4a (path: 0.256; t-value: 2.052), which aligns with the findings of other studies.28 When people with disabilities have knowledge, they often consider themselves capable of becoming entrepreneurs and have high EI. To fill any gaps in education and experience, providing specialized training is important,86 and an influential mentor could help with certain processes and perceptions.50\n\nIn the same way, considering entrepreneurship desirable helps increase the PO-Perception_of_Opportunities leading to the acceptance of H4b (path: 0.462; t-value: 3.635), which aligns with Esfandiar et al.28 Additionally, the PO-Perception_of_Opportunities increases the EI of people with disabilities (path: 0.238; t-value: 3.478). This leads to accept H4c.28,65\n\nTaking into consideration the above, specialized training and mentors or role models are essential to help people with disabilities feel safer about becoming entrepreneurs. These support systems could help people with disabilities feel a greater desire to become entrepreneurs and allow them to detect a greater number of entrepreneurial opportunities and to develop a higher EI. This could be either because of the confidence derived from the ad hoc training received, or from the positive life examples of other entrepreneurs. This could help alleviate negative experiences and discrimination.12,22\n\nLikewise, we proved that when an individual is more resilient, it allows them to have more favourable A-Attitudes_Toward_Entrepreneurship (path: 0.423; t-value: 4.983). Thus, we confirm what other authors stated previously: resilient individuals tend to develop more favorable A-Attitudes_Toward_Entrepreneurship and, therefore, have a higher EI.29,58,68,69 Renko, Bullough, and Saeed68 point out the key role of RES-Resilience in entrepreneurship, leading us to accept H5a and H5d, where RES-Resilience has an indirect influence on EI (path: 0.385; t-value: 7.207).\n\nWe also confirm that RES-Resilience has a positive influence on the SN-Subjective_Norm (path: 0.587; t-value: 7.730), which leads us to accept H5b, meaning that the more resilient an individual is, the more positive their A-Attitudes_Toward_Entrepreneurship.71 This positive A-Attitudes_Toward_Entrepreneurship and coping ability are perceived positively by close-loved ones, who promote even greater support.71\n\nFinally, we confirm that RES-Resilience has a direct and significant influence on PBC-Perceived_Behavioural_Control, which leads us to accept H5c (path: 0.526; t-value: 7.641). This makes sense because challenging environments trigger RES-Resilience; in the case of people with disabilities, RES-Resilience enables a more determined will to become an entrepreneur because individuals feel better prepared and more likely to succeed.7,13 Among the distinguishing traits developed in challenging environments, it is worth highlighting the different barriers faced by people with disabilities,7,13,22 fewer work opportunities,8 and the stigmatization and discrimination they.12,22,26 RES-Resilience improves positive attitudes and self-confidence.58\n\nIt is important to emphasize that RES-Resilience plays a critical role that must be considered, especially in adverse environments in which people with disabilities live. Consequently, it would be advisable to carry out training activities that work on said skill in the form of a simulation, which may be a practical methodology (see Table 5 for a summary).\n\nA = Attitude_Towards_Entrepreneurship, PBC = Perceived_Behavioural_Control, PD = Perceived_Desirability, EE = Entrepreneurial_Experience, Edu = Level_of_Education, EI = Entrepreneurial_Intention, PO = Perceived_Opportunities, PCE = Perceived_Collective_Efficacy, RES = Resilience, SN = Subjective_Norms, PF= Perceived_Feasibility.\n\nNote: *p < 0.05; **p < 0.01; ***p < 0.001; based on a one-tailed Student’s t-distribution (499): t(0.05; 499) = 1.6479, t(0.01; 499) = 2.3338, t(0.001; 499) = 3.1066.\n\n\nConclusions\n\nAmong the 17 Sustainable Development Goals (SDGs), the 2030 Schedule defines (among others) to “reduce inequalities within and among countries” and to “promote peaceful and inclusive societies for sustainable development, provide access to justice for all and building effective, accountable and inclusive institutions at all levels.”[1]\n\nAs part of making progress towards achieving these goals, this work aims to deepen the knowledge of the variables that determine the EI of people with disabilities, based on the theory-based contributions of Krueger27 and Esfandiar et al.,28 and including the RES-Resilience construct.2\n\nTherefore, the aim is to provide an understanding of the subject of EI among people with disabilities to help reduce the gap in employment between people with disabilities and those without and to improve the regional development of Spain. We aim to promote a form of occupational activity based more on creating employment and self-employment, rather than on the search for salaried work. The ultimate goal of this study is to leverage systematic academic research to achieve a more inclusive society, which also reduces the social costs of unemployment benefits and subsistence subsidies for people with disabilities. Ultimately, this study aims to contribute to improving the self-esteem and quality of life of people with disabilities through its contribution to society.\n\nThe results attest to the importance of personalized factors in the entrepreneurial process. The model we use shows the importance of positive A-Attitudes_Toward_Entrepreneurship, PD-Perceived_Desirability, and PF-Perceived_Feasibility. In other words, the people surveyed believe that they are capable of entrepreneurship. PBC-Perceived_Behavioural_Control, PO-Perception_of_Opportunities, and PCE-Perceived_Collective_Efficacy should also be presented as relevant aspects in the entrepreneurial process. This is something that had already been found in other studies carried out among people without disabilities, but which, so far, we have not seen corroborated in analyses of people with disabilities. Given the importance of support and companionship for people with disabilities, both at the beginning and in the process of the entrepreneurial journey, it is advisable to create a technological platform for entrepreneurs, with and without disabilities, to establish mutual interconnection and to share mutual motivations, concerns, ideas, experiences, best practices, objectives, and so on. The reason for creating an App is that people with disabilities face many barriers, such as mobility.2 Therefore, the App would greatly facilitate interaction between people with disabilities and people without disabilities without the need to move from home. However, it is necessary that the people who work with them in rehabilitation centers, for example, have knowledge of the advantages of entrepreneurship and know the existing tools (for example, the App), in order to be able to inform people with disabilities.\n\nSimilarly, and unlike studies carried out with people without disabilities, where the variable SN - Subjective_Norm creates controversy, in the specific case of people with disabilities, we observe the importance of other people's opinions and the way in which this perception can influence the EI of differently abled people directly and significantly. Then, it is necessary to educate family members, friends, and relatives of such people, to make them aware of the importance of their opinions in terms of decision-making about entrepreneurship and employment. In these sense, rehabilitation centers, rehabilitation specialist and educators play a key role.\n\nSimilarly, the RES-Resilience variable, which is beginning to emerge frequently among studies on entrepreneurship, is seen to be important to the EI of people with disabilities. We know that persistence, perseverance, strength, and a future-focused orientation are crucial aspects in any entrepreneurial process; they are even more significant in the specific case of people with disabilities. Then, considering the importance of personal attitudes, the fact that the person feels capable of carrying out certain actions and resilience, we recommend the establishment of coaching groups aimed at strengthening the personality traits and character resources that we know can help and encourage entrepreneurship. For this purpose, it would be convenient to alert not only educational centers and rehabilitation centers, but also the abundant list of organizations dedicated to the design and implementation of tools that facilitate social inclusion through entrepreneurship.\n\nFinally, entrepreneurial culture in Spain is not very popular. However, well-thought-out messages, elaborated with art and communicated effectively, could contribute to more people taking entrepreneurship seriously, as an alternative to traditional employment. Consequently, we encourage that entrepreneurship be branded as a lever of social progress and personal development for all people. We believe that well-designed and deployed campaigns could emphasize the value –in quantitative terms–that entrepreneurship brings to owners and to various stakeholders, interest groups, and agents, as well as society.\n\nThis study has several limitations. First, it was conducted in Spain. It would be interesting to develop this study in other countries to determine if cultural factors change the prediction capacity of this model. Additionally, generalizations should be made with care. This is because it may be applicable to countries such as Spain with a low entrepreneurial culture, but the same results may not be obtained in more entrepreneurial countries. In addition, in the VIF matrix, the correlation between PD and EI was 0.5080, above the limit (0.5).\n\nConsidering that we live in the information age, when information provides power and competitive advantage, it would be useful to develop an unsupervised machine learning model. Considering that machine learning models learn from the data provided, such a model can create segmented groups by disabilities. This would allow us to classify people with similar disabilities in the same dataset and differentiate between different characteristics in different sets. This would help researchers distinguish between people with entrepreneurial tendencies and those with no entrepreneurial spirit. Finally, it would be interesting to add other personal variables that can help us better understand this population and decipher what drives their entrepreneurial intentions. Likewise, it will be interesting to consider self-efficacy as a multidimensional construct considering its importance is several contexts.59\n\n\nData availability\n\nFigshare: People with disabilities Dataset in spanish. https://doi.org/10.6084/m9.figshare.19615710.v2.75\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nODISMET: General report of the situation of people with disabilities in the job market. Madrid:ODISMET;2019.Reference Source\n\nPérez-Macías N, Fernández-Fernández JL: Personal and contextual factors influencing the entrepreneurial intentions of people with disabilities in Spain. Disability & Society. 1–23. Publisher Full Text\n\nSchur LA: Barriers or opportunities? the causes of contingent and part time work among people with disabilities. Industrial Relations: A Journal of Economy and Society. 2003; 42(4): 589–622. Publisher Full Text\n\nTussy-Flores MC, Bonino-Covas V, Carcedo-Illera M, et al.: Impacto de la inserción laboral de personas con discapacidad del Programa INSERTA. Informe de resultados octubre 2019.2019.Reference Source\n\nParker HS, Renko M, Caldwell K: Social entrepreneurship as an employment pathway for people with disabilities: Exploring political–economic and socio-cultural factors. Disability & Society. 2014; 29(8): 1275–1290. Publisher Full Text\n\nRenko MS, Parker H, Caldwell K: Entrepreneurial entry by people with disabilities. International Small Business Journal: Researching Entrepreneurship. 2016; 34(5): 555–578. Publisher Full Text\n\nMiller D, Le Breton-Miller I: Underdog entrepreneurs: A model of challenge-based entrepreneurship. Entrepreneurship Theory and Practice. 2017; 41(1): 7–17. Publisher Full Text\n\nYamamoto S, Unruh D, Bullis M: The viability of self-employment for individuals with disabilities in the United States: A synthesis of the empirical-research literature. Journal of Vocational Rehabilitation. 2011; 35(2): 117–127. Publisher Full Text\n\nFiroz F, Alam M: Sustainability of self-efficacy among nascent disable entrepreneurs: A case study on disable’s home. Asian Business Review. 2015; 5(2): 43–49. Publisher Full Text\n\nIpsen C, Arnold N, Colling K: Small business development center experiences and perceptions: Providing service to people with disabilities. Journal of Developmental Entrepreneurship. 2003; 8(2): 113–132.\n\nBalcazar FE, Kuchak J, Dimpfl S, et al.: An empowerment model of entrepreneurship for people with disabilities in the United States. Psychosocial Intervention. 2014; 23(2): 145–150. Publisher Full Text\n\nCaldwell K, Parker HS, Renko M: Social entrepreneurs with disabilities: Exploring motivational and attitudinal factors. Canadian Journal of Disability Studies. 2016; 5(1): 211–244. Publisher Full Text\n\nSaxena SS, Pandya RSK: Gauging underdog entrepreneurship for disabled entrepreneurs. Journal of Enterprising Communities: People and Places in the Global Economy. 2018; 12(1): 3–18. Publisher Full Text\n\nPagán-Rodríguez R: Transitions to and from self- employment among older people with disabilities in Europe. Journal of Disability Policy Studies. 2012; 23(2): 82–93. Publisher Full Text\n\nONTSI: Barómetro de emprendimiento en España conceptos e indicadores. Colección Economía Digital.2019.Reference Source\n\nCastillo YA: Fischer JM Self-Employment as Career Choice for People with Disabilities: Personal Factors that Predict Entrepreneurial Intentions. Journal of Rehabilitation. 2019; 85(1): 35–43.\n\nJones MK, Latreille PL: Disability and self-employment: Evidence for the UK. Applied Economics. 2011; 43(27): 4161–4178. Publisher Full Text\n\nKitching J: Entrepreneurship and self-employment by people with disabilities. Background Paper for the OECD Project on Inclusive Entrepreneurship.2014.Reference Source\n\nCasado ABF, Casaú PM: Personal Self-Knowledge, a Key Factor for Entrepreneurship in People with Disabilities. Journal of Entrepreneurship Education. 2019; 22: 1–6.\n\nDarcy S, Collins J, Stronach M: Australia’s Disability Entrepreneurial Ecosystem: Experiences of People with Disability with Microenterprises, Self-Employment and Entrepreneurship. Sydney:University of Technology Sydney;2020. [Google Scholar].\n\nINE: El Empleo de las Personas con Discapacidad (EPD) Year 2018.2019.Reference Source\n\nMaritz A, Laferriere R: Entrepreneurship and self-employment for people with disabilities. Australian Journal of Career Development. 2016; 25(2): 45–54. Publisher Full Text\n\nAbbas LN, Khair SN: Entrepreneurial intention among special needs students. Social Sciences and Humanities. 2017; 25(S): 57–66.\n\nOECD: Inclusive entrepreneurship policies country assessment notes.2018.Reference Source\n\nWiklund J, Hatak I, Patzelt H, et al.: Mental disorders in the entrepreneurship context: When being different can be an advantage. Academy of Management Perspectives. 2018; 32(2): 182–206. Publisher Full Text\n\nOstrow L, Nemec PB, Smith C: Self-employment for people with psychiatric disabilities: Advantages and strategies. The Journal of Behavioral Health Services & Research. 2019; 46(4): 686–696. PubMed Abstract | Publisher Full Text\n\nKrueger NF:Entrepreneurial intentions are dead: Long live entrepreneurial intentions. The Entrepreneurial Mind. Carsrud A, Brännback M, editors.New York:Springer;2009; 97–140.\n\nEsfandiar K, Sharifi-Tehrani M, Pratt S, et al.: Understanding entrepreneurial intentions: A developed integrated structural model approach. Journal of Business Research. 2017; 94: 172–182. Publisher Full Text\n\nRenko M, Bullough A, Saeed S: How do resilience and self-efficacy relate to entrepreneurial intentions in countries with varying degrees of fragility? A six-country study. International Small Business Journal. 2020; 39: 130–156. Publisher Full Text\n\nDe Clerq D, Honing B: Entrepreneurship as an integrating mechanism for disadvantage persons. Entrepreneurship and Regional Development. 2011; 23(5-6): 353–372. Publisher Full Text\n\nPavey B: Human capital, social capital, entrepreneurship and disability: An examination of some current educational trends in the UK. Disability & Society. 2006; 21(3): 217–229. Publisher Full Text\n\nMuñoz RM, Salinero Y, Fernández MV: Sustainability, entrepreneurship, and disability: A new challenge for universities. Sustainability. 2020; 12(6): 2494. Publisher Full Text\n\nOlaz-Capitán A, Ortiz-García P: A prospective approach to the moderating elements of entrepreneurial intention in people with disabilities. Journal of Entrepreneurship Education. 2019; 22(S2).\n\nMartin BC, Honig B: Inclusive management research: Persons with disabilities and self-employment activity as an exemplar. Journal of Business Ethics. 2019; 166(3): 553–575.\n\nAjzen I: The theory of planned behavior. Organizational Behavior and Human Decision Processes. 1991; 50(2): 179–211. Publisher Full Text\n\nShapero A, Sokol L:The social dimensions of entrepreneurship.Kent C, Sexton D, Vesper KN, editors. The encyclopedia of entrepreneurship. Englewood Cliffs, NJ:Prentice-Hall; 1982; p. 72–90.\n\nSchlaegel C, Koenig M: Determinants of entrepreneurial intent: A Meta-Analytic test and integration of competing models. Entrepreneurship Theory and Practice. 2014; 38(2): 291–332. Publisher Full Text\n\nKrueger NF, Reilly MD, Carsrud AL: Competing models of entrepreneurial intentions. Journal of Business Venturing. 2000; 15(5-6): 411–432. Publisher Full Text\n\nShen T, Osorio AE, Settles A: Does family support matter? the influence of support factors on entrepreneurial attitudes and intentions of college students. Academy of Entrepreneurship Journal. 2017; 23(1): 24–43.\n\nJasniak M, Ermakova T, Baierl R, et al.: What drives social entrepreneurial appraisal among hearing-impaired individuals?. International Journal of Entrepreneurial Venturing. 2018; 10(2): 236–255. Publisher Full Text\n\nAnderson M, Galloway L: The value of enterprise for disabled people. International Journal of Entrepreneurship and Innovation. 2012; 13(2): 93–101. Publisher Full Text\n\nMartínez-León I, Olmedo-Cifuentes I, Nicolás-Martínez C: Entrepreneurship of people with disabilities in Spain: Socioeconomic aspects. Business Addition. 2019; 10(22): 42–50. Publisher Full Text\n\nYamamoto S, Alverson CY: Individuals with disabilities in self-employment through vocational rehabilitation: Predictors of successful case closure from 2008 to 2012. Journal of Career Assessment. 2017; 25(3): 450–466. Publisher Full Text\n\nPagán R: Self-employment among people with disabilities: Evidence for Europe. Disability & Society. 2009; 24(2): 217–229. Publisher Full Text\n\nKurczewska A, Białek J: Is the interplay between self-efficacy and entrepreneurial intention gender-dependent?. Argumenta Oeconomica. 2014; 2(33): 23–38. Publisher Full Text\n\nGough V: Relationships between entrepreneurial attitudes and intentions in an experiential education. The Journal of Business Inquiry. 2018; 18(2): 100–119.\n\nCarsrud A, Brännback M, Elfving J, et al.:Motivations: The entrepreneurial mind and behavior.Brännback M, Carsrud A, editors. Revisiting the entrepreneurial mind: Inside the black box: An expended edition. New York:Springer; 2017; p. 185–210.\n\nAhdanisa DS: Where are we now? The State of Self-employment and Entrepreneurship for People with Disabilities in Indonesia. Indonesian Journal of Disability Studies. 2019; 6(2): 239–249. Publisher Full Text\n\nShook CL, Bratianu C: Entrepreneurial intent in a transitional economy: An application of the theory of planned behavior to Romanian students. International Entrepreneurship and Management Journal. 2010; 6(3): 231–247. Publisher Full Text\n\nBosma N, Hessels J, Schutjens V, et al.: Entrepreneurship and role models. Journal of Economic Psychology. 2012; 33(2): 410–424. Publisher Full Text\n\nKautonen T, Gelderen M, Fink M: Robustness of the theory of planned behavior in predicting entrepreneurial intentions and actions. Entrepreneurship Theory and Practice. 2015; 39(3): 655–674. Publisher Full Text\n\nLiñán F, Urbano D, Guerreo M: Regional variations in entrepreneurial cognitions: Start-up intentions of university students in Spain. Entrepreneurship & Regional Development. 2011; 23(3-4): 187–215. Publisher Full Text\n\nSebjan U, Tominc P, Borsic D: Cross-country entrepreneurial intentions study: The Danube region perspective. Croatian Economic Survey. 2016; 18(2): 38–76. Publisher Full Text\n\nSolesvik MZ, Westhead P, Kolvereid L, et al.: Student intentions to become self-employed: The Ukrainian context. Journal of Small Business and Enterprise Development. 2012. 2012; 19(3): 441–460. Publisher Full Text\n\nBrüderl J, Preisendörfer P: Network support and the success of newly founded businesses. Small Business Economics. 1998; 10: 213–225. Publisher Full Text\n\nTolentino LR, Sedoglavich V, Lu VN, et al.: The role of career adaptability in predicting entrepreneurial intentions: A moderated mediation model. Journal of Vocational Behavior. 2014; 85(3): 403–412. Publisher Full Text\n\nDakung RJ, Orobia L, Munene JC, et al.: The role of entrepreneurship education in shaping entrepreneurial action of disabled students in Nigeria. Journal of Small Business and Entrepreneurship. 2017; 29(4): 293–311. Publisher Full Text\n\nBullough A, Renko M, Myatt T: Danger zone entrepreneurs: the importance of resilience and self–efficacy for entrepreneurial intentions. Entrepreneurship Theory and Practice. 2014; 38(3): 473–499. Publisher Full Text\n\nFuller B, Liu Y, Bajaba S, et al.: Examining how the personality, self-efficacy, and anticipatory cognitions of potential entrepreneurs shape their entrepreneurial intentions. Personality and Individual Differences. 2018; 125: 120–125. Publisher Full Text\n\nKendall E, Buys N, Charker J, et al.: Self-employment: An under-utilized vocational rehabilitation strategy. Journal of Vocational Rehabilitation. 2006; 25(3): 197–205.\n\nGranovetter M: The strength of weak ties. American Journal of Sociology. 1973; 78(6): 1360–1380. Publisher Full Text\n\nPradhananga AK, Davenport MA: Community attachment, beliefs and residents’ civic engagement in storm water management. Landscape and Urban Planning. 2017; 168: 1–8. Publisher Full Text\n\nGEM: Global Entrepreneurship Monitor. GEM Report, Spain 2019-2020. RED Association GEM España.2019.Reference Source\n\nMaziriri ET, Madinga W, Lose T: Entrepreneurial barriers that are confronted by entrepreneurs living with physical disabilities: A thematic analysis. Journal of Economics and Behavioral Studies. 2017; 9(1): 27–45. Publisher Full Text\n\nCanavati S, Libaers D, Sarooghi H, et al.:The impact of prior knowledge on the identification: A cross-country meta-analysis of institutional factors. United States Association for Small Business and Entrepreneurship Conference Proceeding. San Diego, CA:USASBE; 2016; p. IT1–IT34.\n\nLogan J, Martin N: Unusual talent: A study of successful leadership and delegation in entrepreneurs who have dyslexia. Inclusive Practice. 2012; 4: 57–76.\n\nAbebe MA, Welbourne JL: Blessing in disguise? coping strategies and entrepreneurial intentions following involuntary job loss. Journal of Developmental Entrepreneurship. 2015; 20(4): 1–22.\n\nRenko M, Bullough A, Saeed S:Entrepreneurship under adverse conditions: Global study of individual resilience and self-efficacy. Academy of Management Proceedings. Briarcliff Manor, NY 10510:Academy of Management; 2016; p. 18103.\n\nMuslim R, Habidin NF, Latip NAM: The Influences between the Planned Behavior, the Resilience and the Student Entrepreneurship Intention. International Journal of Academic Research in Business and Social Sciences. 2019; 9(5): 1030–1043.\n\nBird BJ: The operation of intentions in time: The emergence of the new venture. Entrepreneurship Theory and Practice. 1992; 17(1): 11–20. Publisher Full Text\n\nOng AD, Bergeman CS, Bisconti TL, et al.: Psychological resilience, positive emotions, and successful adaptation to stress in later life. Journal of Personality and Social Psychology. 2006; 91(4): 730–749. PubMed Abstract | Publisher Full Text\n\nHsu SH, Wang YC, Chen YF, et al.: Building business excellence through psychological capital. Total Quality Management and Business Excellence. 2014; 25(1): 1210–1223. Publisher Full Text\n\nBarclay DW, Higgins CA, Thompson R: The partial least squares approach to causal modeling: Personal computer adoption and use as illustration. Technology Studies. 1995; 2: 285–309.4.\n\nHair JF, Hult GTM, Ringle CM, et al.: A primer on partial least squares structural equation modeling (PLS-SEM). Thousand Oaks:Sage;2014.\n\nPerez-Macias N, Fernández-Fernández JL, Rua-Vieites A: People with disabilities Dataset in spanish. figshare. Dataset. 2022. Publisher Full Text\n\nChen M-F: Self-efficacy or collective efficacy within the cognitive theory of stress model: Which more effectively explains people's self-reported pro-environmental behavior?. Journal of Environmental Psychology. 2015; 42: 66–75. Publisher Full Text\n\nGEM:2016. Global Entrepreneurship Monitor. GEM Report, Spain 2016.Reference Source\n\nSinclair VG, Wallston KA: The development and psychometric evaluation of the brief resilient coping scale. Assessment. 2004; 11(1): 94–101. PubMed Abstract | Publisher Full Text\n\nGarcía-Rodríguez FJ, Gil-Soto E, Ruiz-Rosa I, et al.: Entrepreneurial process in peripheral regions: the role of motivation and culture. European Planning Studies. 2017; 25(11): 2037–2056. Publisher Full Text\n\nHair JF, Ringle CM, Sarstedt M: PLS-SEM: Indeed, a silver bullet. Journal of Marketing Theory and Practice 2011; 19(2): 139–152. Publisher Full Text\n\nHenseler J, Ringle CM, Sarstedt M: A new criterion for assessing discriminant validity in variance-based structural equation modeling. Journal of the Academy of Marketing Science. 2015; 43(1): 115–135. Publisher Full Text\n\nGeisser S: A predictive approach to the random effect model. Biometrika. 1974; 61(1): 101–107. Publisher Full Text\n\nStone M: Cross-validatory choice and assessment of statistical predictions. Journal of the Royal Statistical Society. 1974; 36(2): 111–147.\n\nChin WW:The partial least squares approach for structural equation modelling.Marcoulides GA, editor. Modern methods for business research. Mahwah, NJ:Erlbaum Lawrence Associates;1998; p.295–336.\n\nByrne BM: Structural equation modeling with LISREL, PRELIS, and SIMPLIS: Basic concepts, applications, and programming. Stanford, CA:Psychology Press;2013.\n\nViriri P, Makurumidze S: Engagement of disabled people in entrepreneurship programmes in Zimbabwe. Journal of Small Business and Enterprise Development. 2014; 2(1): 1–30.\n\n\nFootnotes\n\n1 https://sdgs.un.org/goals"
}
|
[
{
"id": "146532",
"date": "31 Aug 2022",
"name": "Virginia Barba-Sanchez",
"expertise": [
"Reviewer Expertise Entrepreneurship",
"Entrepreneur with Disabilities",
"Social value",
"ICT"
],
"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 appreciate the authors for concentrating on such a relevant issue. I enjoyed reading the manuscript and found it to be an informative and intriguing study on the variables that determine the entrepreneurial intention of people with disabilities. The general quality of the manuscript is so good. Nevertheless, certain issues are inherent in this manuscript, and I propose a minor revision although the article might be accepted for indexing as is. Therefore, I've made the following observations and suggestions to improve the quality of the current work:\nThe manuscript's title should be catchy and reader-friendly. I suggest that the authors reconsider it.\n\nThe 2030 Agenda for Sustainable Development of the United Nations (UN) includes in its Sustainable Development Goal (SDG) 8.5 “to achieve full and productive employment and decent work for all women and men, including for young people and persons with disabilities (PWD), and equal pay for work of equal value” (p. 22). For their part, the Entities of the Social and Solidarity Economy (SSE), by their very nature, are presumed to be more sensitive in the labour insertion of groups in danger of social exclusion than are the Capitalist companies (CC) such as people with disabilities (PwD). Nevertheless, Calderón et al. (2021) provide empirical evidence of the difficult integration of PwD even in SSE. Therefore, I suggest using this reference to enrich the justification for your manuscript:\nCalderón, M.J., Calderón, B, Barba-Sánchez, V. (2020). Labour Inclusion of People with Disabilities: What Role Do the Social and Solidarity Economy Entities Play? 1\n\nYou stated: “The study determined the minimum sample size by multiplying the number of highest arrows pointing to a particular endogenous construct by 10, as recommended by Barclay, Higgins, and Thompson (1995H).” I agree that the sample size depends on the complexity of the model, but the use of G*power is correct and appropriate for the assessed sample size. Why use too the rule of Barclay, Higgins, and Thompson (1995)? Please remove this last one.\nGood luck with your future work.\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": "147748",
"date": "14 Sep 2022",
"name": "Yuleinys A Castillo",
"expertise": [
"Reviewer Expertise disability studies",
"vocational services",
"mental 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\nThis novel topic will be of interest to the readers of the journal especially considering the importance of resilience and entrepreneurial intentions of people with disabilities.\n\nAbstract: This is a good attempt to summarize the manuscript. You can provide context to this study since the SDG can be confusing for some readers. Revise your organization to better connect ideas.\n\nGeneral\nProperly cite your statements.\n\nThere are numerous minor editorial errors throughout the manuscript (e.g., plurals, hyphens, possessive punctuation)\n\nProperly format references list\n\nRevise for the flow of ideas, including sentence structure and proper tense used in writing.\n\nBody\nOverall, the introduction is well organized. However, consider enhancing transitions between major sections and reorganizing paragraphs.\n\nWhat’s ODISMET?\n\nIf possible, add or modify information to understand the context of this study\n\nExpand your section on your framework or aim to explain it in a simple manner.\n\nCombine your paragraphs. Some of your paragraphs are one sentence only.\n\nMethod\nRevisit to improve readability\n\nAny analysis for demographics?\n\nDiscussion\nReorganize information to support your arguments\n\nAny other implications\n\nMake sure that you organize information together to improve readability\n\nRevise some of your sentences, as they seem like incomplete ideas.\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/11-726
|
https://f1000research.com/articles/11-97/v1
|
26 Jan 22
|
{
"type": "Research Article",
"title": "Dry textile electrode for ambulatory monitoring after catheter ablation of atrial fibrillation: A pilot study of simultaneous comparison to the Holter electrocardiogram",
"authors": [
"Takeshi Machino",
"Kazutaka Aonuma",
"Yuki Komatsu",
"Hiro Yamasaki",
"Miyako Igarashi",
"Akihiko Nogami",
"Masaki Ieda",
"Kazutaka Aonuma",
"Yuki Komatsu",
"Hiro Yamasaki",
"Miyako Igarashi",
"Akihiko Nogami",
"Masaki Ieda"
],
"abstract": "Background: Holter electrocardiogram (ECG) is the gold standard for ambulatory monitoring of atrial fibrillation (AF) but it is insufficient because of its limited recording time. A wearable ECG with a medical-grade dry textile electrode is a promising technology to remedy this limitation. This pilot study aimed to simultaneously compare the wearable and Holter ECGs for ambulatory monitoring in a clinical setting. Methods: This prospective observational study enrolled 18 patients who underwent AF ablation. One day after AF ablation, ambulatory ECG was obtained for three hours simultaneously using both the wearable and Holter ECG devices. Automatic ECG interpretations between devices were compared with correlation and agreement analyses. Results: Simultaneous ECG monitoring demonstrated a comparable analysis time and total heart beats between the two devices. Almost complete correlation and agreement were also demonstrated in all clinically relevant testing aspects except in R-wave amplitude (r = 0.743, p < .001). AF was detected in three patients. AF duration was the same in both ECG devices in two patients with continuous AF. In the remaining patient with intermittent AF, AF duration was shortened by 0.6% with the wearable ECG as compared to that with the Holter ECG. Conclusions: Simultaneous ECG comparison revealed a high consistency between the wearable and Holter ECG devices. The results of this study warrant further clinical studies for long-term monitoring of ambulatory ECG after AF ablation.",
"keywords": [
"atrial fibrillation",
"textile electrode",
"wearable electrocardiogram",
"ambulatory monitoring",
"catheter ablation"
],
"content": "Introduction\n\nAtrial fibrillation (AF) is the most prevalent form of arrhythmia with an increasing incident worldwide; it is associated with an increased lifetime risk of stroke, heart failure, myocardial infarction, dementia, and mortality.1,2 Whether AF presents or not is crucial for making a clinical decision regarding treatment strategy. Accordingly, long-term monitoring with an electrocardiogram (ECG) is essential for the management of AF, which can present with short and silent forms, especially those treated with catheter ablation.3,4\n\nConventional ECG monitoring for medical examination is limited to 24 h. Although long-term monitoring devices have revealed under-detection of AF via Holter ECG,5,6 they also have shortcomings. A cardiac event recorder cannot provide continuous monitoring, while an implanted loop recorder is too invasive for mere AF monitoring. Although several consumer devices have been marketed recently, their ECG results are sometimes not precise and are very noisy.7 Furthermore, those devices generally do not undergo the regulatory process for medical use. Therefore, AF patients are still in need of a medical-grade device for long-term non-invasive and continuous ECG monitoring.\n\nRecently, a novel dry textile electrode “hitoe®” (Toray Industries Inc., Tokyo, Japan) has been registered as a medical device for wearable ECG in Japan (13B1X0001500034). The hitoe® is highly conductive for recording ECG in a non-invasive and continuous manner.8 Wearable ECG with hitoe® demonstrated its usefulness for a few minutes in healthy volunteers.9 However, consistency between the wearable and Holter ECG has not been evaluated simultaneously in clinical settings. Therefore, this pilot study aimed to simultaneously compare both devices for ambulatory ECG monitoring after AF ablation.\n\n\nMethods\n\nThis prospective observational study enrolled patients with AF who were admitted for catheter ablation to the University of Tsukuba Hospital from August 2017 to March 2018. Eligible patients were aged 20 years or older (legal adult in Japan) with an under-bust size between 84 and 100 cm (suitable circumference for the wearable ECG). To avoid the potential risk of skin-related issues associated with ECG monitoring, we excluded patients with known skin allergy and skin sensitivity to adhesive tape as denoted by a history of redness, erosion, and scarring post exposure.\n\nAll participants provided written informed consent before enrollment. This study complied with the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects as well as the Declaration of Helsinki. The study protocol was approved by the Review Committee of University of Tsukuba Hospital (H29-88).\n\nAmbulatory ECG was simultaneously obtained from both wearable and Holter ECGs for 3 h on the day after AF ablation, which mainly consisted of electrical isolation of the pulmonary veins from the left atrium.10 The ECG was recorded via a bipolar CC5 lead from dry textile electrodes (wearable ECG) as well as via wet gel electrodes (Holter ECG). Both ECG recordings were interpreted by the same automatic analyzer to avoid a reporting bias. The simultaneous ECG comparison eliminated length and lead-time biases between the two devices. In addition, a dropout bias was reduced by an in-hospital ECG recording on the day after AF ablation. All electrodes were carefully positioned to avoid interference from each other.\n\nThe wearable ECG was a smart wear device equipped with the dry textile electrode (hitoe®). The electrode consisted of woven nanofibers coated with a highly conductive polymer (PEDOT-PSS). An insulated electro-conductive lead ribbon was connected between the electrodes, and a connector terminal was utilized for signal transmission.9\n\nHolter ECG recording was obtained using a conventional Ag/AgCl electrode (Cardyrode-P®, SUZUKEN Co., Ltd., Nagoya, Japan). An electroconductive gel surrounded the electrode for skin adhesion. The conventional electrodes were equipped with connecting cables between them and utilized a connector terminal for signal transmission.\n\nBecause both devices were not waterproof, bathing and showering were prohibited during the three-hour study period. MRI was also prohibited to avoid thermal skin injury secondary to an induced electromotive force evoked by time-varying magnetic fields in the presence of electrical monitoring devices.11\n\nThe ECG signal was transmitted to a Holter ECG recorder (Kenz Cardy 303 Pico+®, SUZUKEN Co., Ltd.). Recordings obtained from the wearable and Holter ECG devices were interpreted using the same automatic analyzer (Kenz Cardy Analyzer 05®, SUZUKEN Co., Ltd.).\n\nAnalysis time was defined as the signal recording time after artifact removal. Tiny spikes, notches, large baseline swings, widened isoelectric line, loss of ECG signal, and electromagnetic interference were defined as artifacts.9 Based on template matching, the automatic analyzer categorized QRS morphologies into a normal QRS complex, atrial premature complex (APC), ventricular premature complex (VPC), and noise signal. Noise signals were excluded from the calculation of total QRS complexes.\n\nThe R-wave amplitude was measured from the PQ segment to the top of the R wave and was averaged over 10 consecutive beats of normal QRS complexes, which were obtained simultaneously from both devices for comparison. AF was detected based on any RR interval irregularity lasting over 30 s.12 Noise signals and VPCs were excluded from the RR interval analysis for AF detection. The number of AF episodes and the total AF duration were compared between the wearable and Holter ECG.\n\nCategorical variables were summarized as numerical counts (percentages) and were compared using McNemer’s test. Continuous variables were expressed as mean ± standard deviation (SD) or as median (interquartile range [IQR]) and were compared using the paired t-test or Wilcoxon signed-rank test. Normality was assessed using the Shapiro-Wilk test. Agreement of measurements between the wearable and Holter ECG was assessed with the Bland-Altman analysis for normally distributed variables. Alternatively, the Passing-Bablok analysis was used for non-normally distributed variables. Correlations between the wearable and Holter ECG were evaluated using Pearson’s or Spearman’s analysis. The minimum sample size to detect a correlation coefficient (≥ 0.70) differing from zero (power 0.8; alpha 0.05) was 13 for Pearson’s and 15 for Spearman’s analysis.13 A two-tailed P-value < .05 was considered significant. Statistical analyses were performed using IBM SPSS Statistics for Macintosh, Version 26 (IBM Corp., Armonk, N.Y., USA) (RRID:SCR_019096) and SciStat Version 2.9 (MedCalc Software Ltd., Ostend, Belgium) (RRID:SCR_021918).\n\n\nResults\n\nA total of 18 patients with AF were included in this study (Table 1). The majority of patients were men with non-paroxysmal AF. Two-thirds of AF ablation cases were completed within the first session. The most frequent CHADS2 score was 1. All patients completed the three-hour ambulatory ECG recording, which was simultaneously obtained from the wearable and Holter ECG. None of the patients demonstrated skin issues associated with the electrodes. Representative examples of simultaneous ECG are shown in Figure 1.\n\nElectrodes were positioned to compose a bipolar lead CC5 in both ECG devices. ECG, electrocardiogram; HR, heart rate.\n\nThere was no difference in analysis time, the number of QRS complexes, heart rate, and R-wave amplitude between the devices (Table 2), and almost complete correlation was demonstrated in those parameters (Figure 2A–C), with the exception of R-wave amplitude (Figure 2D). The Bland-Altman analysis revealed a small bias with narrow 95% limits of agreement in analysis time, the number of total QRS complexes, and heart rate between devices (Figure 2E–G). R-wave amplitude, however, demonstrated poor agreement (Figure 2H).\n\nThe scatterplot diagrams (A–D) illustrate correlation analysis with Pearson’s coefficient (r) and P values. The Bland-Altman plots (E–H) show a bias (solid line) with 95% limits of agreement (dotted line). Each dot represents paired values derived from all patients. An open circle indicates a patient with skin-electrode contact failure. ECG, electrocardiogram.\n\nThe number of APCs and VPCs did not differ between the two devices (Table 2). A very strong correlation in the number of APCs (ρ = 0.98; P < .001) and VPCs (ρ = 0.87; P < .001) was also demonstrated. The Passing-Bablok analysis demonstrated the absence of systemic and proportional bias in the number of APCs and VPCs (Table 3). Noise signals, however, were more frequent in the wearable ECG than in the Holter ECG (Table 2). There was no correlation between the two devices with regard to noise count (ρ = –0.16; P = .54). The agreement in noise count was not demonstrated (Table 3). Furthermore, a difference in noise count was negatively correlated with the difference in R-wave amplitude (ρ = –0.52; P = .03).\n\nAn episode of skin contact failure of the textile electrode occurred in the fifth case (open circle in Figure 2). Accordingly, the wearable ECG demonstrated a shorter analysis time (164 vs. 190 min, Figure 2A, E) and a smaller number of QRS complexes (10,352 vs. 12,259 counts, Figure 2B, F) than the Holter ECG in this case. The patient was a non-obese (body mass index, 23.8 kg/m2) 72-year-old man who underwent a second ablation for paroxysmal AF with a CHADS2 score of 1 for comorbid hypertension. A Velcro adjuster was then applied to the wearable ECG for all cases thereafter. This action prevented skin-electrode contact failure in the remaining 13 cases.\n\nAF was detected in three patients. Two of these patients had a continuous AF episode. AF duration was completely equal between the two devices in both patients (196 and 225 min, respectively). In the remaining patient, the Holter ECG demonstrated seven AF episodes (99 min in total), whereas the wearable ECG detected nine AF episodes (96 min in total). AF episodes were fragmented by increased noise signals on the wearable ECG as compared to the Holter ECG (888 vs. 515 counts). Most of the increased noise signals on the wearable ECG were counted as normal QRS complexes on the Holter ECG (Figure 3).\n\nTime in atrial fibrillation was indicated by the blue line. Most noise signals on wearable ECG were labeled as normal QRS complexes on Holter ECG. The gray signal with asterisk indicates noise; black signal, normal QRS complex; blue signal, atrial premature complex; pink signal, ventricular premature complex. ECG, electrocardiogram\n\n\nDiscussion\n\nThis pilot study evaluated whether wearable ECG using the hitoe® electrode would demonstrate simultaneous consistency with Holter ECG in a typical clinical setting. Ambulatory ECG monitoring after AF ablation was found to have generally consistent findings between the two devices (Figure 2), although a slight discrepancy was found as follows. The wearable ECG demonstrated a 0.6% increase in noise signals on counting, which was related to a negative difference in R-wave amplitude as compared to the Holter ECG. The increased amount of noise signal caused a total 3-min (0.6%) interruption in recorded AF episodes. This is the first study demonstrating that the wearable ECG using the hitoe® electrode is a promising medical device for ambulatory AF monitoring without remarkable discrepancy against Holter ECG.\n\nThis study evaluated the use of dry textile electrodes (hitoe®) in ambulatory ECG monitoring for the first time in patients with AF. Wearable ECG devices are usually evaluated in healthy subjects for a very short monitoring period.14,15 Use of a hitoe® textile ECG was previously reported to demonstrate consistency with Holter ECG in healthy volunteers for 3.5 min of sequential comparison.9 Our study extended the feasibility of this ambulatory ECG monitoring period with hitoe® for up to three hours and expanded it into clinical settings, showing simultaneous consistency with Holter ECG (Table 2, Figure 2). These results of inpatient ambulatory ECG monitoring after AF ablation warrant further study for outpatient applications.\n\nOur simultaneous comparison revealed a slight increase in noise signals from hitoe® as compared to Holter ECG (Table 2). Wearable ECG sensors were regarded previously as having 5–10% higher noise signals than Holter ECG during ambulatory monitoring.14 Functional twisting movements were also reported to introduce up to 35% higher noise signals from a shirt-type ECG sensor with hitoe® as compared to Holter ECG.9 Recently, a bra-type ECG sensor was reported to have better skin contact and signal quality versus a shirt-type sensor.15 Our bra-type ECG sensor using hitoe® equipped with a Velcro adjuster (Figure 1) demonstrated only 0.6% higher noise signals against Holter ECG when measuring around 17 thousand beats during a three-hour simultaneous ambulatory monitoring period.\n\nBra-type equipment is widely used to improve ECG acquisition through textile electrodes because the electrodes are highly sensitive to motion artifacts.16 Similar to our results, the R-wave amplitude has been reported to decrease with textile electrodes.16,17 Better skin-electrode contact can result in a smaller R-wave amplitude; however, that change has been reported to be small.18 Furthermore, ECG signals become clear with better skin-electrode contact.19 Therefore, the skin-electrode contact should be maintained as much as possible. The potential risk of noise signal count increase owing to skin contact failure when using textile electrodes can be reduced by using a bra-type ECG with a Velcro adjuster.\n\nAn automatic analyzer revealed that increased noise signal counts were associated with decreased R-wave amplitude (ρ = –0.52; P = .03). Although hitoe® is both hydrophilic and flexible to enhance adequate skin contact,8 textile electrodes remain vulnerable to motion artifacts that subsequently interfere with R wave detection.20 In addition, an amplitude of R wave against noise signal from hitoe® was reported to decrease during movement.9 Despite the absence of a significant difference in the R-wave amplitude (Table 2), a signal intensity that can fluctuate during ambulatory monitoring remains an issue of hitoe® (Figure 2H).\n\nOur simultaneous comparison revealed a fragmented interpretation of AF episodes in one patient (Figure 3). On the wearable ECG, some R waves during AF episodes were interpreted as noise signals, which were excluded from the AF analysis. As discussed above, the under-detection of R waves resulted in increased noise signals in wearable ECG versus Holter ECG during ambulatory monitoring.21 The increased noise signals fragmented AF episodes, which appeared continuous on the Holter ECG. However, the discrepancy in AF duration between the two devices was only 0.6% (3/520 min), owing to the hydrophilic and flexible nature of hitoe® and the bra-type ECG design with Velcro adjuster for skin-electrode contact. The 0.6% discrepancy in AF duration is clinically negligible for AF detection in long-term monitoring. Consequently, an ECG system using the hitoe® electrode seems quite amenable to long-term AF monitoring in clinical settings.\n\nOne limitation of this pilot study was the small sample size. However, this is the first patient study demonstrating AF detection with the hitoe® electrode. Although the monitoring duration was limited to three hours, the continuous recording of ambulatory ECG for both devices was compared in a simultaneous fashion. Another limitation of this study was that it entailed an in-hospital ECG recording on the day after AF ablation. Although there was no restriction on physical activity, in-hospital ECG monitoring at this early time point might have reduced patient activity level and subsequently reinforced our highly consistent results. These issues should be addressed in future clinical trials.\n\n\nConclusions\n\nMonitoring of patients using a wearable ECG device that utilizes a medical-grade dry textile electrode (hitoe®) provided simultaneous consistency with Holter ECG after AF ablation. The wearable ECG demonstrated a slight increase in noise signal episodes with associated deterioration in R-wave amplitude. This increased noise signal count caused a negligible interruption in a continuous AF episode in a patient with intermittent AF. Long-term monitoring of AF with wearable ECG warrants further clinical investigation.\n\n\nData availability\n\nThe datasets generated and/or analyzed during the current study are not publicly available due to the limited permission from the participants but are available from the corresponding author if they have ethical approval for using the data according to the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects. The ethical committee’s name and the approval number of the study are also required.\n\n\nConsent\n\nWritten informed consent for publication of the participants’ details and their images was obtained from the participants.",
"appendix": "Acknowledgements\n\nWe thank all the participants in this study and our hospital staff at the physiological laboratory.\n\n\nReferences\n\nBenjamin EJ, Wolf PA, D'Agostino RB, et al.: Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998; 98: 946–952. Publisher Full Text\n\nKornej J, Börschel CS, Benjamin EJ, et al.: Epidemiology of atrial fibrillation in the 21st century: novel methods and new insights. Circ. Res. 2020; 127: 4–20. PubMed Abstract | Publisher Full Text\n\nVerma A, Champagne J, Sapp J, et al.: Discerning the incidence of symptomatic and asymptomatic episodes of atrial fibrillation before and after catheter ablation (DISCERN AF): a prospective, multicenter study. JAMA Intern. Med. 2013; 173: 149–156. PubMed Abstract | Publisher Full Text\n\nTondo C, Tritto M, Landolina M, et al.: Rhythm-symptom correlation in patients on continuous monitoring after catheter ablation of atrial fibrillation. J. Cardiovasc. Electrophysiol. 2014; 25: 154–160. PubMed Abstract | Publisher Full Text\n\nGladstone DJ, Spring M, Dorian P, et al.: Atrial fibrillation in patients with cryptogenic stroke. N. Engl. J. Med. 2014; 370: 2467–2477. Publisher Full Text\n\nSanna T, Diener H-C, Passman RS, et al.: Cryptogenic stroke and underlying atrial fibrillation. N. Engl. J. Med. 2014; 370: 2478–2486. Publisher Full Text\n\nIkeda T: Current use and future needs of noninvasive ambulatory electrocardiogram monitoring. Intern. Med. 2021; 60: 9–14. PubMed Abstract | Publisher Full Text\n\nTsukada S, Nakashima H, Torimitsu K: Conductive polymer combined silk fiber bundle for bioelectrical signal recording. PLoS One. 2012; 7: e33689. PubMed Abstract | Publisher Full Text\n\nTsukada YT, Tokita M, Murata H, et al.: Validation of wearable textile electrodes for ECG monitoring. Heart Vessel. 2019; 34: 1203–1211. PubMed Abstract | Publisher Full Text\n\nKuck K-H, Brugada J, Fürnkranz A, et al.: Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N. Engl. J. Med. 2016; 374: 2235–2245. Publisher Full Text\n\nDempsey MF, Condon B: Thermal injuries associated with MRI. Clin. Radiol. 2001; 56: 457–465. Publisher Full Text\n\nKirchhof P, Benussi S, Kotecha D, et al.: 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart J. 2016; 37: 2893–2962. PubMed Abstract | Publisher Full Text\n\nMay JO, Looney SW: Sample size charts for Spearman and Kendall coefficients. J Biom Biostat. 2020; 11: 1–7. Publisher Full Text\n\nAkintola AA, van de Pol V , Bimmel D, et al.: Comparative analysis of the Equivital EQ 02 Lifemonitor with Holter ambulatory ECG device for continuous measurement of ECG, heart rate, and heart rate variability: a validation study for precision and accuracy. Front. Physiol. 2016; 7: 391. PubMed Abstract | Publisher Full Text\n\nSteinberg C, Philippon F, Sanchez M, et al.: A novel wearable device for continuous ambulatory ECG recording: proof of concept and assessment of signal quality. Biosensors (Basel). 2019; 9: 17. PubMed Abstract | Publisher Full Text\n\nAlizadeh Meghrazi M, Tian Y, Mahnam A, et al.: Multichannel ECG recording from waist using textile sensors. Biomed. Eng. Online. 2020; 19: 48. PubMed Abstract | Publisher Full Text\n\nArquilla K, Webb AK, Anderson AP: Textile electrocardiogram (ECG) electrodes for wearable health monitoring. Sensors (Basel). 2020; 20: 1013. PubMed Abstract | Publisher Full Text\n\nSong J, Zhang Y, Yang Y, et al.: Electrochemical modeling and evaluation for textile electrodes to skin. Biomed. Eng. Online. 2020; 19: 30. PubMed Abstract | Publisher Full Text\n\nPeng S, Xu K, Chen W: Comparison of active electrode materials for non-contact ECG measurement. Sensors (Basel). 2019; 19: 3585. PubMed Abstract | Publisher Full Text\n\nNangalia V, Prytherch DR, Smith GB: Health technology assessment review: remote monitoring of vital signs – current status and future challenges. Crit. Care. 2010; 14: 233. PubMed Abstract | Publisher Full Text\n\nBrage S, Brage N, Franks PW, et al.: Reliability and validity of the combined heart rate and movement sensor Actiheart. Eur. J. Clin. Nutr. 2005; 59: 561–570. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "121135",
"date": "23 Feb 2022",
"name": "Takanori Arimoto",
"expertise": [
"Reviewer Expertise Clinical electrophysiology",
"catheter ablation",
"device implantation."
],
"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\nMonitoring of atrial fibrillation (AF) is important for the management of AF after catheter ablation. Machino et al. demonstrated the clinical usefulness of novel wearable ECG with a medical-grade dry textile electrode. There was almost complete correlation in the number of QRS complexes and heart rate. Importantly, the frequency of atrial premature complex (APC) count, APC burden, and AF recorded on the wearable device was highly consistent with the result of Holter ECG. On the other hand, some QRS complexes on the Holter ECG were sometimes shown as different QRS morphologies on the wearable ECG, as shown in Figure 3. The result of out-hospital ECG during daily physical activity may increase the credibility of this study. Wearable ECG monitoring may become a one of promising device in the near future.\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": "121137",
"date": "30 Mar 2022",
"name": "Katya Arquilla",
"expertise": [
"Reviewer Expertise Bioastronautics",
"wearable sensor 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\nThis study compares a wearable ECG monitoring system with the gold-standard Holter monitor system in the detection of atrial fibrillation during a 3-4 minute monitoring session. The article is clear and the study is sound, but a few small changes would help readers understand the work and implications:\nAbstract, Background: \"Limited recording time\" really means lack of comfort for long-duration recordings, right? Should be clearer with that distinction, because existing systems are capable of longer recording times, they're just not ideal for comfort.\n\nIntroduction, paragraph 2, line 4: Should be more specific here about what threshold is required to deem something \"very noisy\".\n\nMethods, Recruitment: Should state here how many males/females were tested, in addition to where it is shown in the table.\n\nStudy design: It would be helpful to show an image of the simultaneous placement of the two systems in this section.\n\nMeasurements, paragraph 2, line 1: What was the approach to artifact removal?\n\nStatistical analysis, paragraph 1, line 1: What are the categorical variables here? Can you include an example in this sentence of which metrics are treated in this way?\n\nResults, paragraph 1, line 2: \"CHADS2\" is not defined anywhere, so the reader will not necessarily know what this metric means.\n\nResults, paragraph 2: Was signal-to-noise ratio not included in this analysis?\n\nFigure 2: Were the instances of skin-electrode contact failure quantified and compared between the systems?\n\nDiscussion, paragraph 1, line 4-6: A signal-to-noise ratio measurement would be helpful here.\n\nDiscussion, paragraph 2, line 4: Is there a plan for testing at the 24-hour scale in addition to this 3-minute test?\n\nDiscussion, paragraph 3, line 5-7: Until this point, it wasn't clear that the bra-type wearable system was developed by this group and not the company that produces the electrodes. It would be good to make this distinction earlier on.\n\nDiscussion, paragraph 4: Given the bra-type wearable, it's important to test this system on both male and female participants, due to the added challenges during motion created by the presence of breast tissue. Is there any plan to test the system with more participants that have breast tissue?\n\nDiscussion, paragraph 5, line 1: Include specifications of this analyzer.\n\nDiscussion, paragraph 5, line 2: Does this hydrophilic characteristic impact the signal over time? I imagine it would, given the changes in electrical conductivity caused by sweat.\n\nDiscussion, paragraph 6, line 7-8: Would this discrepancy scale linearly or would it become more of a problem in longer-duration tests?\n\nDiscussion, paragraph 7: It's mentioned earlier in the paper that some sort of power analysis was conducted to justify the sample size. It would be helpful to include that here.\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? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "8320",
"date": "12 Apr 2023",
"name": "Takeshi Machino",
"role": "Author Response",
"response": "We wish to express our appreciation for the Reviewer's insightful comments, which have helped us significantly improve the manuscript. Comment 1: Abstract, Background: \"Limited recording time\" really means lack of comfort for long-duration recordings, right? Should be clearer with that distinction, because existing systems are capable of longer recording times, they're just not ideal for comfort. Response: Although several consumer ECG devices provide longer recording time, they generally do not undergo the regulatory process for medical use. Furthermore, current medical-grade devices for longer ECG monitoring are not continuous or too invasive for AF monitoring. We have clarified this point in the revised manuscript. Comment 2: Introduction, paragraph 2, line 4: Should be more specific here about what threshold is required to deem something \"very noisy\". Response: This is a quotation from reference #7 that describes clinical impressions. Comment 3: Methods, Recruitment: Should state here how many males/females were tested, in addition to where it is shown in the table. Response: We have added this information in the Recruitment section of Methods. Comment 4: Study design: It would be helpful to show an image of the simultaneous placement of the two systems in this section. Response: A new figure showing simultaneous electrode placement of the two systems has been added as Figure 1. According to this change, previous figures have been renumbered. Comment 5: Measurements, paragraph 2, line 1: What was the approach to artifact removal? Response: The artifact was manually removed. We have added this point in the revised manuscript. Comment 6: Statistical analysis, paragraph 1, line 1: What are the categorical variables here? Can you include an example in this sentence of which metrics are treated in this way? Response: Thank you for pointing it out. Categorical variables are included in the patient characteristics, and no need for comparison between the two devices because the patients were identical. We have deleted the description of McNemar’s test. Comment 7: Results, paragraph 1, line 2: \"CHADS2\" is not defined anywhere, so the reader will not necessarily know what this metric means. Response: The CHADS2 score estimates stroke risk in AF, which includes chronic heart failure, hypertension, diabetes, and age ≥75 years for one point each, and history of stroke or transient ischemic attack as two points. We have added an explanation of the CHADS2 score in the revised manuscript. This information has been added to the revised manuscript. Comment 8: Results, paragraph 2: Was signal-to-noise ratio not included in this analysis? Response: It wasn’t included in the analysis because artifacts were removed before analysis. Comment 9: Figure 2: Were the instances of skin-electrode contact failure quantified and compared between the systems? Response: The skin-electrode contact failure occurred only in one case during wearable ECG monitoring. That event was removed as an artifact before analysis. The Holter ECG did not demonstrate the skin-electrode contact failure. Therefore, the comparison between the two systems was not performed. Comment 10: Discussion, paragraph 1, line 4-6: A signal-to-noise ratio measurement would be helpful here. Response: Artifacts were removed before analysis. Therefore, the analysis including artifacts was not performed. Comment 11: Discussion, paragraph 2, line 4: Is there a plan for testing at the 24-hour scale in addition to this 3-minute test? Response: There isn’t a plan for 24-hour simultaneous comparison. The present study extended the scale to 3 hours as described in the manuscript. Comment 12: Discussion, paragraph 3, line 5-7: Until this point, it wasn't clear that the bra-type wearable system was developed by this group and not the company that produces the electrodes. It would be good to make this distinction earlier on. Response: The wearable ECG system including bra-type equipment was developed by the company that produces the hitoe® electrode. The sentence pointed out has been revised in line with the above context. This point also has been clarified in the second paragraph of the Study design. Comment 13: Discussion, paragraph 4: Given the bra-type wearable, it's important to test this system on both male and female participants, due to the added challenges during motion created by the presence of breast tissue. Is there any plan to test the system with more participants that have breast tissue? Response: A shirt-type ECG monitoring with hitoe® electrode demonstrated poorly recorded data in a few females during a marathon in a previous study (New Reference #20). In contrast to the shirt-type ECG, the bra-type ECG does not cover the female breast tissue. This merit warrants further investigation to test a comparable ambulatory recording between females and males using the bra-type ECG. This point has been included in the revised manuscript. According to this change, previous references #20 and # 21 have been renumbered. Comment 14: Discussion, paragraph 5, line 1: Include specifications of this analyzer. Response: We have specified the automatic analyzer (Kenz Cardy Analyzer 05 ®, SUZUKEN Co., Ltd.) in addition to the Methods section. Comment 15: Discussion, paragraph 5, line 2: Does this hydrophilic characteristic impact the signal over time? I imagine it would, given the changes in electrical conductivity caused by sweat. Response: Ousaka et al. reported that ECG acquisition by hitoe® electrode was better in the mid-phase of running than in the early phase. (New Reference #20) They speculated that sweat production by running diminished friction between the hydrophilic electrode and skin. Accordingly, the textile electrode was wetted with 30% glycerol aqueous solution before use to improve ECG acquisition. This point has been added to the revised manuscript. Comment 16: Discussion, paragraph 6, line 7-8: Would this discrepancy scale linearly or would it become more of a problem in longer-duration tests? Response: The discrepancy would be linearly, and the longer-duration test would minimize the problem because the longer monitoring period will more than compensate for this slight discrepancy. This point has been added to the revised manuscript. Comment 17: Discussion, paragraph 7: It's mentioned earlier in the paper that some sort of power analysis was conducted to justify the sample size. It would be helpful to include that here. Response: Thank you for your comment. The power analysis has been included in the Study limitations of the revised manuscript. We wish to thank the Reviewer again for her valuable comments."
}
]
}
] | 1
|
https://f1000research.com/articles/11-97
|
https://f1000research.com/articles/11-723/v1
|
30 Jun 22
|
{
"type": "Research Article",
"title": "Expressive writing in a Saudi university English foreign language (EFL) classroom: Evaluating gains in syntactic complexity",
"authors": [
"Shatha Ahmed Abdulaziz Alkhalaf"
],
"abstract": "Background: This study determines if the English foreign language (EFL) Saudi students achieve greater syntactic complexity when they engage in expressive writing than when they write about a general topic. Methods: This study employs an ex post facto research design to compare the writing output of EFL learners. The sample comprised of 24 college students enrolled in an English writing course, at Department of English and Translation, College of Sciences and Arts, Qassim University, Saudi Arabia for the academic year 2021-2022. The participants were assigned randomly, and their writing was analyzed using the computer software named Web-based L2 Syntactic Complexity Analyzer. Lu’s (2010) four board element of syntactic complexity and 14 units is employed to analyze the data. Results: Results show that students achieve higher syntactic complexity when engaging in writing on emotional topics (expressive writing) than when writing on general topics. Further, analysis shows that students' emotional writings are significant on three syntactic complexity measures, i.e., length of production units; amount of subordination; and phrase sophistication. The fourth measure, i.e., coordination, does not reflect significant differences between their expressive writing and general writing. Conclusions: The study's implications are expected to aid EFL instructors and curriculum designers in successfully implementing language education, particularly in writing, in the Saudi context. In line with the input hypothesis, this research suggests that writing about personal emotional events may enhance the quality of language two (L2) writing by increasing syntactic complexity. In this dimension, this study could be additional evidence of the Krashen hypothesis.",
"keywords": [
": Expressive writing",
"EFL",
"general writing",
"Saudi learners",
"syntactic complexity in English."
],
"content": "Editorial note\n\nEditorial Note (4th August 2023): The authors of this article have provided the information requested to the F1000 Editorial Team to confirm that this research was presented at an IIARP conference. Therefore, this article will remain in the IIARP gateway.\n\n\nIntroduction\n\nCreative writing skills enhance one’s capacity to retain knowledge, link concepts, and synthesize information in new ways. In academic settings, its importance cannot be understated not only as a language enhancement exercise, but also, in relieving academic stress. Expressive writing is part of the writing curriculum in English foreign language (EFL) courses in Saudi Arabia but its role in enhancing learners’ ability in forming complex syntactic structures in English has so far not been researched.\n\nThe input hypothesis of Krashen suggests that acquiring a language is a natural process in which adults and children can subconsciously obtain written or spoken proficiency. Krashen (1985) asserts that language learners should focus on the meaning rather than the form, hence, acquiring a language depends upon meaningful interaction in the target language. Furthermore, as a huge corpus of research has shown, language two (L2) writing quality (Al-Ahdal and Abduh, 2021; Taguchi et al., 2013) and grammatical complexity (Lu, 2011) are linked with L2 proficiency studies (Ortega, 2000, 2003; Wolfe-Quintero et al., 1998). Syntactic complexity may be used to distinguish between levels of skill and to predict the quality of writing in a second language. Syntactic complexity in L2 writing may be impacted by a range of learner, task, and context-related factors such as subject matter (genre), preparation time, and instructional setting among others (Ellis and Yuan, 2004; Sotillo, 2000; Yang et al., 2015). As a result of these studies, we have gained a better understanding of how L2 writing research and instruction may best utilize the concept of syntactic complexity. In line with the input hypothesis, this research suggests that writing about personal emotional events may enhance L2 wiring by increasing syntactic complexity. Thus, this paper could be additional evidence of the Krashen hypothesis.\n\nStudies on the effect of learners’ first language (L1) and other learner-related factors on the difficulty of L2 writing show that, in order to make informed judgments, it is vital to pay particular attention to any L1-related variations. Until now, few studies have examined these sorts of differences in depth. In most research comparing the complexity of writing by non-native speakers (NNS) and native speakers (NS), learners’ L1 background has not been included as an independent variable; rather, the studies have either looked at a homogenous L1 group or regarded all NNS learners as one group (e.g., Ai and Lu, 2013). Crossley and McNamara’s (2012) pioneering study revealed that there were statistically significant differences in the complexity of L2 English writing by four L1 groups. Syntactic complexity was measured just by the average number of words preceding the principal verb in the phrase. Thus, our current understanding of the grammatical complexity variations in L2 writing that are produced by variances in L1 writing has been severely limited.\n\nThere has been a lot of research on how difficult it is to write in a second language, but one thing that has not been looked at very carefully is how difficult it is for people to write in their first language (L1). There is already a lot of research on how people who speak more than one language write in their second language (e.g., Al-Ahdal and Alqasham, 2020; Edelsky, 1982; Lally, 2000; Lefrançois, 2001; Paquot, 2013; Uysal, 2008; van Weijen et al., 2009). Some of the characteristics that have been looked at are as follows: idea generation (Lally, 2000); information structure (van Vuuren, 2013); rhetorical patterns (Uysal, 2008); syntactic structures (Rankin, 2012) and; lexical bundles (Paquot, 2013; Rankin, 2012). Further, Lefrançois (2001) said that in addition to knowing how to write and read, the way grammar and syntax work, how general techniques work, and how cultural schemas work in the first language could all have an effect on writing in the second language. With written data from the International Corpus of Learner English (ICLE) Version 2.0, the research in a recent book edited by Jarvis and Crossley (2012) looked at linguistic patterns that are unique and different for people who speak a different language than their first language (ICLE 2.0; Granger et al., 2009). Specifically, they said that patterns of coherence, lexical style, n-grams, mistakes, conceptual understanding, and syntactic complexity, might all be used to identify people who speak a different language than their first language.\n\nA thorough grasp of these distinctions, on the other hand, would have significant consequences for L2 writing research and teaching in general. Research on L1-related differences in L2 writing will benefit from this understanding if it is applied, and researchers will be able to determine whether and how learners’ L1 should be controlled or taken into account when collecting, analyzing, and interpreting data, among other things, in syntactic complexity research. We may now re-examine previous claims about the link between syntactic complexity in L2 writing and L2 competency that were made without considering the potential of an L1 influence. This is a good thing! L2 writing pedagogy can benefit from an appreciation of these differences, which can help teachers see that the same patterns of syntactic complexity aren’t always indicative of L2 proficiency in the same way for learners from varied L1 backgrounds. As a result of this knowledge, they will be able to better address the difficulties associated with syntactic complexity for students from a range of L1 backgrounds. An in-depth look at how changes in L1-related syntactic complexity affect L2 writing will also be helpful in the current study on learner texts’ automatic native language identifiability (Tetreault et al., 2013).\n\nEmotions also have a crucial effect in the grammatical complexity of second language writing, as several studies have demonstrated. Studying 2,600 Chinese college students’ essays, Wang and Curdt-Christiansen (2016) found that emotions and grammatical complexity in second language writing are linked. They concluded that emotional writing affects EFL students and leads them to write simpler syntactic clauses and sentences.\n\nWriting prompts have been shown to have a significant impact on the emotional and grammatical complexity of second language writing. Tabari and Wang (2022) recruited 53 advanced-mid ESL students by inviting them to write essays on the COVID-19 pandemic and non-pandemic topics alike. The second language writers’ emotionality and vocabulary complexity were found to be affected by writing prompts. The study also shows that emotions play an important role in second language writing which may be taken into consideration in teaching and learning a second language.\n\nSince there no studies that examine Saudi EFL college students’ performance in expressive writing as a factor in their ability to compose complex syntactical structures in English, the current study aims to fill this gap by examining L2 writing of EFL Saudi students in order to discover if there is a substantial link between writing on emotional topics and syntactic complexity. The length of the production unit, the degree of subordination, the degree of coordination, the degree of phrasal sophistication, and the overall complexity of the phrase are all employed by the researcher to gauge syntactic complexity (see Table 1).\n\nThus, the hypothesis of this study proposes that the emotionality of the writing topics positively affect the writers’ productions by increasing the syntactic complexity in L2 writing overall. It can be hypothesized that, ‘Saudi EFL learners achieve better syntactic complexity on emotional subject that other general subject’.\n\nConsequently, the current study attempted to answer the following research question:\n\n• Do EFL Saudi students achieve better syntactic complexity when they engage in expressive writing (write about an emotional subject) than when they write about a general topic?\n\n\nMethods\n\nEthical approval for this study was given by the Scientific and Ethical Committee of the Department of English and Translation, College of Sciences and Arts, Qassim University, Saudi Arabia. Verbal informed consent was obtained from all participants prior to participation in the study to the effect that their data will be published. The reason behind getting only verbal consent from the participants as notified in the consent letter is for the global interest of research.\n\nThis study employed an ex post facto research design. Ex post facto research design is also referred to as correlational research (Griffee, 2012). On the other hand, Tavakoli (2012) stated that in ex post facto research, the researcher sets hypotheses as recommendations at the end of the study. Furthermore, Cohen et al. (2007) affirmed that ex post facto is used instead of experimental research whenever it is impossible to control variables. In this study, a two-paragraph essay was required from the participants to be produced, one of which discussed their feelings on keeping a pet and the other of which told the tale of an emotionally charged incident that had occurred in their lives. Using Web-based L2 Syntactic Complexity Analyzer, 2010, a comparison was done between those two paragraphs in order to identify in which case syntactic complexity was higher.\n\nThe exercise was completed by all the 50 students taking the English writing course, and 33 were randomly taken as sample participants. However, when the data were analyzed it was found that nine of these samples were not viable as they were either incomplete or fell short of the requisite length. Hence, these were removed. The respondents for this survey were all females selected through the use of a random sampling procedure because in Saudi Arabia, females study in segregated classrooms, with no male students around. The class for this study was a female only class due to this. The randomness was achieved using an application called Raosoft (Raosoft, 2004), in which all the 50 students wrote the two paragraph essays and only the written essays of 24 of them were chosen for analysis. It was actually very difficult to include all the 50 students written paragraphs for analysis. The participants were all studying at the second language level (L2) and they shared the same or comparable cultural backgrounds and ability level in English. They were all between the ages of 19-21 studying in their third year, semester six, which is referred to as level six in Saudi Arabia. Before participation, the students were explained the aims of the research and their consent to participate in the study was sought. The rationale behind using random sampling was that this way everyone in the population was guaranteed a fair chance at being selected. The technique is simple to follow and is considered fair because any individual can be chosen (Berndt, 2020). It was determined using Raosoft that the respondents’ sampling representation would be the most accurate.\n\nAmongst free writing tasks, short compositions are most favored in Saudi EFL classrooms given the fact that they can be finished in one sitting by the students without break in the train of thoughts and are also more feasible for the teachers to provide early and detailed feedback on. For the purpose of this study, the students were asked to submit a short composition in two paragraphs at the start of the summer semester on 15 June 2021 as part of the writing class, and the second in the following week, on 22 June. In the first paragraph, they were asked to write on their experience to have a pet at home and in the second, they were instructed to narrate a story/situation that they experienced in life. All the students in this course, studying in their third year of the English department, wrote the two required paragraphs in the first class of the semester, but only the responses of 24 of them were added to the Web-based L2 Syntactic Complexity Analyzer (L2SCA) after random selection, as shown in Table 1. Further information about the data processing was included in the analysis section. The setting for data collection was Qassim University and the activity was in-class. Thus, in all, there were 24 emotional and an equal number of narrative manuscripts. All data were initially in the form of paper submissions, these were later converted to word documents in the computer by the researcher herself to rule out the possibility of inadvertent error corrections or any other changes in the original manuscripts. These were then analyzed as discussed in the following sections.\n\nA computer tool called the L2SCA by Lu (2010), which is built to assess English writing samples for syntactic complexity using the 14 metrics (Table 1), was utilized to analyze all of the datasets in this study. L2SCA was seen as the most suitable software due to its free availability, its ability to process files in batches, and its high degree of dependability when it comes to processing files.\n\nThere are 14 syntactic difficulty indices that are derived based on the frequency counts supplied by L2SCA for each writing sample in this study. According to the frequency counts, these are: verb phrases, sentences (which include dependent clauses), tenses (T units), complex tenses, coordinate phrases (complex nomen), and complex nominatives. L2SCA’s correlations with human annotators’ syntactic difficulty scores ranged from .834 to 1.000, while the accuracy of structural unit recognition varied from .830 to 1.000. The level of significance that has been determined is 0.05.\n\n\nResults\n\nThere was a total of 33 participants randomly selected, however, only the paragraphs of 24 participants were analyzed in this study as nine were removed from the analysis due to being incomplete or not to the required level. Participants were between the ages of 19-21 studying at level 6 at Qassim University in the female only English writing course. As two essays were submitted from each student, the total number of essays included in this study was 48 (Alkhalaf, 2022b).\n\nIn order to compare the level of syntactic complexity, we looked at both emotional and broad topics. All 14 indices of syntactic complexity were shown to be statistically significant by the t-test. Syntactic complexity may be broken down into five distinct categories: length, subordination, coordination, and phrasal sophistication. These variations (or sentence structures) are analyzed in the next section.\n\nLength of production unit\n\nFor the three-length metrics, as shown in Table 2, the emotional and wide themes had considerably different means and standard deviations than the narrow and emotional topics. When it comes to MLS, in the emotional topic students achieved a general mean score of 22.309 and standard deviation of 5.584 whereas in the general subject they scored a mean of 14.672, and standard deviations 3.574. As can be seen, there is a range difference between students’ emotional and general writing, at 7.637. Furthermore, there is a significance level of.001 between the two types of writing. When it comes to MLC, students scored a mean of 10.624 in the emotional topic and standard deviation of 1.217. The mean score and standard deviation were 8.307,1.984, respectively.\n\nThe difference between the two scores is 2.317, which seems less than the difference in the MLS. However, the difference is not huge, it still significant as the p value showed a significance level of .001.\n\nThe third area checked was students’ production in MLT, in the emotional topic, the students got a mean score and standard deviation of 18.982 and 4.612, respectively; they scored in the general subject a mean score of 13.115, and standard deviation of 2.574. The range difference between students’ scores in the two types of writing is 5.867 which is considered as significant as the p value is .001. This means that the values for the two topics have significant differences. These results are summarized in Table 2 below.\n\nAmount of subordination\n\nTable 3, shows the amount of subordination in students’ writing. The emotional and general themes had significantly different means and standard deviations for all the four subordination assessments when compared to the emotional and broad subjects. The mean for the emotional subject for C/T is 2.108, whereas that for the general topic is 1.583, with a p value of .001 for both. When it comes to CT/T, the mean value for the emotional topic is .576 and that for the general subject is .436. The p value for both of these measures is .0001. In the DC/C sample, the mean for the emotional topic is .456 and that for the general subject is .345; both have p values less than .0001. With a p value of .001, the mean for the emotional topic is 1.019 and that for the general subject is .567 for DC/T, respectively. This indicates that there are considerable discrepancies in the values for the two themes.\n\nAmount of coordination\n\nAs demonstrated in Table 4, the emotional and wide themes did not have significantly different means and standard deviations from the narrow and emotional topics when it came to the three coordination measures. For CP/C, the mean for the emotional topic is .301, and that for the general subject is .168; both of these mean values are statistically significant at a threshold of .121. With regard to the correlation coefficient (CP/T), the mean for the emotional topic is .528 and that for the general subject is .263, with a significance level of .064 for both. When it comes to T/S, the mean for the emotional topic is 1.186, and that for the general subject is 1.092, with a significance level of .729. This indicates that the numbers for the two topics do not differ statistically significantly.\n\nPhrasal and overall sentence complexity\n\nTable 5 shows that the averages and standard deviations for the four subordination evaluations differ significantly between emotional and wide-base themes. The mean for the emotional subject for CN/C is 1.281, while that for the general subject is .913, with both having a p value of .001. The mean for the emotional topic for CN/T is 2.140, whereas that for the general subject is 1.499. Both of these measurements have a p value of .001. The mean for the emotional topic in the VP/T sample is 2.862, whereas that for the general subject is 2.075; both have p values less than .001. For C/S, the mean for the emotional topic is 2.496 and that for the general subject is 1.748, both with a p value of .001. This demonstrates that there are significant disparities in the values assigned to the two topics.\n\n\nDiscussion\n\nThe current study compared the level of syntactic complexity between students’ writing on emotional and general topics. The comparisons in students’ writing were made in five sub elements. The study found that students achieved higher scores in the emotional essays than they achieved in general topic, however, the differences were significant in only four elements out of five. Students’ expressive writings were more developed than their writings on general topics with reference to length of production unit, amount of coordination, and phrase complexity. Nevertheless, the differences in students’ writing regarding amount of coordination were not significant. These findings indicate that interest and motivation in topics chosen for writing urge students to write well when compared with writing on topics they do not prefer. The findings of this study are in line to some extent with Lu and Ai (2013). According to their findings, when the L1 backgrounds of the EFL learners were taken into consideration, just three of the 14 measures indicated statistically significant variations between the groups. Nonetheless, when learners were divided into groups according to their L1 backgrounds, statistically significant differences in all 14 measures were discovered, and the other groups had significantly different patterns from the other group. L2 writing and L2 proficiency have been explored in a number of research (Ai and Lu, 2013; Norrby and Håkansson, 2007; Stockwell and Harirington, 2003; Wolfe-Quintero et al., 1998). It is feasible to consistently utilize some measures of syntactic complexity to distinguish levels of L2 proficiency and some to predict the quality of L2 writing, according to these studies. There are newer studies that show L2 writing difficulties can be impacted by several factors, including learner and task-related ones like the subject matter of the assignment, preparation time and instructional context. Writing in L2 requires a highly evolved understanding of grammatical complexity, and the analysis in this study corroborates this.\n\nSeveral studies, like Badenhorst (2018), which used the reflections of 19 Masters and PhD students engaged in a course called graduate research writing to represent student experiences across a semester, showed results similar to this study. Emotional awareness and decision making were aided by the use of instructional tactics that encouraged students to take control of their own emotional responses to critical feedback. Emotional or expressive writing encourages students to be more creative, innovative, and imaginative.\n\nAdditionally, student emotions were managed differently in the Driscoll and Powell’s (2016) study, with some students approaching their learning less emotionally (rational interpreters), others more emotionally (emotional interpreters), and a final group employing metacognitive practices to manage their emotions (metacognitive interpreters or emotional managers). Students’ ability to navigate the complicated emotional terrain of writing in higher education appears to be facilitated by metacognitive ideas of monitoring and control, according to the findings.\n\nThis study generally determined that the EFL Saudi students achieve better syntactic complexity when they write about an emotional subject than when they write about a general topic. According to all three indicators, the duration of the production unit has statistically significant differences between the two variables. All four variables point to statistically significant differences in the levels of subordination across the various categories. There were no statistically significant variations in the level of coordination measured by the three metrics. Finally, it was discovered that there are statistically significant variations in phrasal and total phrase complexity for all of the measures. The study’s implications will aid EFL instructors and curriculum implementers in successfully implementing language education, particularly in writing, in the Saudi context, according to the findings.\n\nEmotional intelligence and the capacity to express one’s feelings in writing go hand in hand, according to Castillo et al., (2019). This study lends credence to prior studies that shown how expressive writing may promote positive emotional well-being and how an expressive writing program can improve emotional processing abilities, both of which are important components of emotional intelligence. As a result, the study recommends that expressive or emotional writing be pursued more rigorously in EFL classrooms to enhance the ability of the students to compose syntactically complex structures that will bring their writing closer to that of native users of the language. Additionally, this research recommends to teachers to give more space to expressive writing as writing about one’s feelings might help their students better regulate their own emotions. Individuals appear to be affected in a similar way by writing, whether it is about joyful or sad events. The study also recommends further research that links with past research to help us understand how expressive writing is related to emotional intelligence, which has been established in earlier studies as well.\n\nThe study faced the limitation of being focused on an exclusively female sample given the practices prevalent in the Saudi society. The other limitation was the small group of participants. Both of these factors somewhat limit the applicability of the findings of this study.\n\n\nConclusion\n\nThe study compared Saudi EFL students’ writing of narrative/general and opinion/emotional essays. It used five elements of analyses and found that students scored higher in the latter category than they scored in the former type of essays, in respect to their use of syntactic complexity. Out of the five sub-elements of syntactic complexity, the differences between students’ writing were found in three elements, i.e., length of production unit, amount of coordination, and phrase complexity. Nevertheless, the students’ use to the amount of coordination was compared in their emotional and general writings; no significant difference was found, though. It is thus recommended that English instructors and curriculum designers make use of topics which are of interest to the students and are part of their life experiences to enhance their writing abilities—topics that are of relevance and significance to them.\n\n\nData availability\n\nFigshare. Expressive Writing in a Saudi university EFL classroom: Evaluating gains in syntactic complexity. https://doi.org/10.6084/m9.figshare.19632732.v1 (Alkhalaf, 2022a).\n\nThis project contains the following underlying data:\n\n• Shatha –Underlying Data.pdf (Data analysis of narrative and opinion paragraphs).\n\nFigshare. Expressive Writing in a Saudi university EFL classroom: Evaluating gains in syntactic complexity. https://doi.org/10.6084/m9.figshare.20041250.v1 (Alkhalaf, 2022b).\n\nThis project contains the following underlying data:\n\n• Narrative details.rar. (File with the 24 anonymized narrative paragraphs used in this study).\n\n• Opinion paragraphs.rar. (File with the 24 anonymized opinion paragraphs used in this study).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nAi H, Lu X: A corpus-based comparison of syntactic complexity in NNS and NS university students writing.Díaz-Negrillo A, Ballier N, Thompson P, editors. Automatic treatment and analysis of learner corpus data. Amsterdam: John Benjamins; 2013; pp. 249–264.\n\nAl-Ahdal AAMH, Alqasham FH: EFL writing tasks and the application of the concept of situatedness: Evaluating the theoretical and practical aspects of the Saudi EFL context. TESOL Int. J. 2020; 15(4): 167–190.\n\nAl-Ahdal AAMH, Abduh MYM: English writing proficiency and apprehensions among Saudi College students: Facts and remedies. TESOL Int. J. 2021; 16(1): 34–56.\n\nAlkhalaf S: Expressive writing in a Saudi university EFL classroom: Evaluating gains in syntactic complexity. Figshare. Dataset.2022a. Publisher Full Text\n\nAlkhalaf S: Expressive writing in a Saudi university English foreign language (EFL) classroom: Evaluating gains in syntactic complexity. Figshare. Dataset.2022b. Publisher Full Text\n\nBadenhorst C: Emotions, play and graduate student writing. Discourse and Writing/Rédactologie. 2018; 28: 103–126. Publisher Full Text\n\nBerndt AE: Sampling methods. J. Hum. Lact. 2020; 36(2): 224–226. Publisher Full Text\n\nBisquerra R: Metodología de la investigacióneducativa. Madrid: Plaza; 2004.\n\nCastillo YA, Fischer J, Davila S: Managing emotions: relationships among expressive writing and emotional intelligence. Integrated Research Advances. 2019; 6(1): 1–8.\n\nCohen L, Manion L, Morrison K: Research methods in education. 6th ed.London: Routledge; 2007.\n\nCrossley SA, McNamara DS: Detecting the first language of second language writers using automated indices of cohesion, lexical sophistication, syntactic complexity and conceptual knowledge. Jarvis S, Crossley S, editors. Approaching language transfer through text classification: Explorations in the detection-based approach. Bristol: Multilingual Matters; 2012; pp. 106–126.\n\nDriscoll DL, Powell R: States, traits, and dispositions: The impact of emotion on writing development and writing transfer across college courses and beyond. In Composition Forum (Vol. 34). Association of Teachers of Advanced Composition. 2016.\n\nEdelsky C: Writing in a bilingual program: The relation of L1 and L2 texts. TESOL Q. 1982; 16: 211–228. Publisher Full Text\n\nEllis R, Yuan F: The effects of planning on fluency, complexity, and accuracy in second language narrative writing. Stud. Second. Lang. Acquis. 2004; 26: 59–84. Publisher Full Text\n\nGriffee T: An introduction to second language research methods: Design and data. 1st ed.Berkeley, California: TESL-EJ Publications; 2012.\n\nGranger S, Dagneaux E, Meunier F, et al.: International corpus of learner English. Louvain-la-Neuve: Presses universitaires de Louvain; 2009; vol. 2.\n\nKrashen SD: The input hypothesis: Issues and implications. Addison-Wesley Longman Limited; 1985.\n\nLally CG: First language influences in second language composition: The effect of pre-writing. Foreign Lang. Ann. 2000; 33: 428–432. Publisher Full Text\n\nLefrançois P: Le Point sur les transferts dans l’ecritureen langue seconde [Transfer in second-language writing]. Can. Mod. Lang. Rev. 2001; 58: 223–245. Publisher Full Text\n\nLu X: Automatic analysis of syntactic complexity in second language writing. International Journal of Corpus Linguistics. 2010; 15: 474–496. Publisher Full Text\n\nLu X: A corpus-based evaluation of syntactic complexity measures as indices of college-level ESL writers’ language development. TESOL Q. 2011; 45: 36–62. Publisher Full Text\n\nLu X, Ai H: Syntactic complexity in college-level English writing: Differences among writers with diverse L1 backgrounds. J. Second. Lang. Writ. 2015; 29: 16–27. Publisher Full Text\n\nNorrby C, Håkansson G: The interaction of complexity and grammatical processability: The case of Swedish as a foreign language. IRAL— International Review of Applied Linguistics. Lang. Teach. 2007; 45: 45–68.\n\nOrtega L; Understanding syntactic complexity: The measurement of change in the syntax of instructed L2 Spanish learners. (Unpublished PhD dissertation). Honolulu: University of Hawaii.2000.\n\nOrtega L: Syntactic complexity measures and their relationship to L2 proficiency: A research synthesis of college-level L2 writing. Appl. Linguis. 2003; 24: 492–518. Publisher Full Text\n\nPaquot M: Lexical bundles and L1 transfer effects. Int. J. Corpus Linguist. 2013; 18: 391–417. Publisher Full Text\n\nRankin T: The transfer of V2: Inversion and negation in German and Dutch learners of English. Int. J. Biling. 2012; 16: 139–158. Publisher Full Text\n\nRaosoft I: Sample size calculator.2004. Reference Source\n\nSotillo SM: Discourse functions and syntactic complexity in synchronous and asynchronous communication. Lang. Learn. Technol. 2000; 4: 82–119.\n\nStockwell G, Harrington M: The incidental development of L2 proficiency in NS-NNS email interactions. CALICO J. 2003; 20: 337–359. Publisher Full Text\n\nTaguchi N, Crawford B, Wetzel DZ: What linguistic features are indicative of writing quality? A case of argumentative essays in a college composition program. TESOL Q. 2013; 47: 420–430. Publisher Full Text\n\nTabari MA, Wang Y: The effects of prompt types on L2 learners’ textual emotionality and lexical complexity. J. Second Lang. Stud. 2022; 5(1): 34–57. Publisher Full Text\n\nTavakoli H: A dictionary of research methodology and statistics in applied linguistics. Rahnama Press; 2012.\n\nTetreault J, Blanchard D, Cahill A: A report on the first native language identification shared task. Proceedings of the eighth workshop on innovative use of NLP for building educational applications. 2013: 48–57.\n\nUysal HH: Tracing the culture behind writing: Rhetorical patterns and bidirectional transfer in L1 and L2 essays of Turkish writers in relation to educational context. J. Second. Lang. Writ. 2008; 17: 183–207. Publisher Full Text\n\nvan Vuuren S : Information structural transfer in advanced Dutch EFL writing: A cross-linguistic longitudinal study. Linguist. Neth. 2013; 30: 173–187. Publisher Full Text\n\nvan Weijen D , van den Bergh H , Rijlaarsdam G, et al.: L1 use during L2 writing: An empirical study of a complex phenomenon. J. Second. Lang. Writ. 2009; 18: 235–250. Publisher Full Text\n\nWang W, Curdt-Christiansen XL: Teaching Chinese to international students in China: Political rhetoric and ground realities. Asia Pac. Educ. Res. 2016; 25(5): 723–734. Publisher Full Text\n\nWolfe-Quintero K, Inagaki S, Kim HY: Second language development in writing: Measures of fluency, accuracy, & complexity (No. 17).University of Hawaii Press; 1998.\n\nYang W, Lu X, Weigle SA: Different topics, different discourse: Relationships among writing topic, measures of syntactic complexity, and judgments of writing quality. J. Second. Lang. Writ. 2015; 28: 53–67. Publisher Full Text"
}
|
[
{
"id": "144438",
"date": "01 Aug 2022",
"name": "Mohammed Shormani",
"expertise": [
"Reviewer Expertise My research interests include language acquisition",
"syntax",
"phonology",
"morphology",
"e-learning",
"psycholinguistics",
"etc."
],
"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\nEvaluation report\nThis research article tackles an interesting aspect of EFL students' writing skills. It highlights the connection between syntactic complexity and the sort of topic students write about, and how this affects students’ L2 syntactic achievement. It is also a valuable addition to the existing knowledge on this particular aspect, and in the field in general.\nPedagogically, the study provides syllabus makers and curriculum designers with important findings to be considered during the syllabus designing of Writing Courses.\nSome observations to be paid attention to:\nthe repetition of abbreviations.\nplease state the phrase and its abbreviation only once: you keep repeating Second language (L2) and First language (L1). Some of these reparations include:\n“…..it is for people to write in their first language (L1).\nTable (1) 14 indices for language two (L2) syntactic complexity\n\nthe abbreviation should be given in the first use:\nExample: “Web-based L2 Syntactic Complexity Analyzer (L2SCA)”.. you gave the abbreviation in the second use.\n\nit is better to write the full forms of “MLS”, “MLC”, “MLT” (in the text not in the tables) vis-à-vis their abbreviations/acronyms.\n\n\"These results are summarized in Table 2 below\" replace the word “below” with “above”.\n\nLanguage mistakes: The article should be carefully revised for language mistakes. Some examples of these mistakes are provided as follows (including the section):\nAbstract\ncomprised of 24 college students enrolled delete the preposition “of”\n\nResearch gap\nSince there no studies that examine insert the verb “are”\n\nResearch question\n“‘Saudi EFL learners achieve better syntactic complexity on emotional subject that other general subject” replace the word “that” with “than”\n\nConclusion\n\n“the students’ use to the amount of coordination” replace the word “to” with “of”\n\nRecommendations\n“…to prior studies that shown how expressive writing” insert the Aux. “have”\n\nThe conclusion should be a little bit elaborated, stating the five elements of analysis examined … “It used five elements of analyses”, please write these elements in the conclusion for ease of reference.\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": []
},
{
"id": "150844",
"date": "28 Mar 2023",
"name": "Jamal Kaid Mohammed Ali",
"expertise": [
"Reviewer Expertise Motivation",
"Online Learning",
"Language Skills"
],
"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 compares Saudi EFL students' syntactic complexity in writing production due to their contribution in two writing types: expressive writing and writing on general topics. The study revealed that students' syntactic complexity in expressive wring was ameliorated significantly in three of the four tested areas, i.e., length of production units; the amount of subordination; and phrase sophistication. On the contrary, the fourth area, i.e., coordination, had no significant difference between students' production in expressive and general topic writing.\n\nThe article is well-written and has a good structure. It is well-planned and executed. It demonstrates the field's originality. The goal and results of the current research have been briefly and succinctly summarized in the conclusion; suggestions and implications have been presented at the end of the paper. This manuscript is written in an engaging manner. It addressed one of the most significant ideas. Elements of the articles are well presented and written academically. However, there are some minor suggestions for the improvement of the paper:\nThe abstract seems intriguing. It does an excellent job at establishing the topic and transitioning from one part to the next. However, it is advised to consistently combine the single and plural forms of key phrases (expressive writing, emotional writing, and writing on general topics). It is probably not advisable to use possessive pronoun as used in \"study's implications\", instead preferably use \"Implication of the study\".\n\nThe issue has been introduced in the introduction, which also demonstrates the gap and the significance of this study. In the introduction, there are a few minor errors that need fixing:\n- There are \"run on\" sentences:\n\"its importance cannot be understated not only as a language.... Expressive writing is part of the writing curriculum in English foreign language (EFL) courses in Saudi Arabia, but its role in enhancing learners' ability to form complex syntactic structures in English has so far not been researched.\"\nThe better version would be, \"its value as a language cannot be overstated,\" \"In Saudi Arabia, expressive writing is a component of the writing curriculum for English as a foreign language (EFL) classes, although its impact in boosting students' capacity to build complex syntactic structures in English has not yet been investigated.\"\n\nThe methodology section is adequate and provides detailed information on the steps taken in the procedure.\n\nThe results are shown and discussed. The research question is well-addressed. It is recommended that recent references are used to support the findings. It is recommended that the author discuss the previous research results with the current findings.\n\nSeveral pieces of research are discussed in the literature review. They contain important references and some recent studies. However, the second paragraph needs more citations, if possible. It is also recommended that more recent citations should be used. The Research questions can also be shifted into the introduction section. Furthermore, Table 1 should be moved from the literature review to the methods section (data analysis).\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/11-723
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https://f1000research.com/articles/11-659/v1
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15 Jun 22
|
{
"type": "Research Article",
"title": "Knowledge and practice of community pharmacists towards SGLT2 inhibitors",
"authors": [
"Abdelrahim Alqudah",
"Muna Oqal",
"Ahmad Al-Samdi",
"Esam Qnais",
"Mohammed Wedyan",
"Majd Abu Gneam",
"Roaa Alnajjar",
"Manar Alajarmeh",
"Elaf Yousef",
"Omar Gammoh",
"Muna Oqal",
"Ahmad Al-Samdi",
"Esam Qnais",
"Mohammed Wedyan",
"Majd Abu Gneam",
"Roaa Alnajjar",
"Manar Alajarmeh",
"Elaf Yousef",
"Omar Gammoh"
],
"abstract": "Background: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs which improve glycaemic control in type 2 diabetes mellitus (T2DM) by preventing the kidney from reabsorbing glucose back to blood. Community pharmacists have long-term relationships with most of their chronic patients, so they play a key role in care for people with diabetes. Therefore, the objective of this study was to assess pharmacists’ knowledge and practice towards SGLT2 inhibitors. Methods: A cross-sectional study was conducted to meet the study objectives. A convenience sample of 348 community pharmacists in Jordan was recruited. knowledge and practice were assessed using a self-administered questionnaire created for the purpose of this study. Results: A total of 400 community pharmacists were reached, of whom 348 answered the survey (response rate 87%). The results indicated that SGLT2 inhibitors knowledge score among community pharmacists in Jordan was 6.61 (out of 12). Factors like age, gender, location of the pharmacy, years of pharmacists’ experience had no effect on knowledge score; however, pharmacists who attended training courses on diabetes had higher knowledge scores. Additionally, pharmacists’ dispensing practice toward SGLT2 inhibitors had insufficient knowledge, such as lack of knowledge about the superiority of SGLT2 inhibitors over other anti-diabetics and inability to give the best advice to patients. Conclusions: Our findings reflect a moderate knowledge among community pharmacists about SGLT2 inhibitors which may negatively affect the patients’ outcome; thus, continuous education for the pharmacists is essential.",
"keywords": [
"Diabetes",
"SGLT2 inhibitors",
"Pharmacists",
"Jordan"
],
"content": "Introduction\n\nType 2 diabetes mellitus (T2DM) is a metabolic disorder affecting carbohydrate, fat, and protein metabolism.1 This condition results from inadequate insulin secretion, insulin resistance, or both, often at later stages in life.2,3 T2DM is characterised by chronic hyperglycaemia and dyslipidaemia which results in the development of renal disease, cardiovascular disease and microvascular complications.4 T2DM management should begin in most patients with lifestyle changes which is often followed up by metformin monotherapy. If target blood glucose is not achieved within 3 months, another hypoglycaemic agents can be added.5\n\nThe expression of sodium-glucose cotransporter-2 (SGLT2) proteins selectively occurs in the kidney specifically in the proximal convoluted tubule. Roughly 90% of the absorption of the filtered glucose is under the responsibility of these transporters. Therefore, SGLT2 represents an ideal target and effective options for the treatment of diabetes.6,7 In patients with T2DM, the renal threshold for reabsorption of glucose is increased above 180 mg/dL (serum glucose concentration), which corresponds to the normal renal threshold reabsorption level of glucose. In addition, it has been reported that the expression of these transporters could be up-regulated in T2DM patients which has the potential to cause a maladaptive response that in turn deteriorates hyperglycaemia.8 Accordingly, the selective SGLT2 inhibitors can cause a reduction to the respective threshold to as low as 40 to 120 mg/dL.9 In fact, the combination of metformin and a SGLT2 inhibitor may be beneficial for patients who are at a high risk of experiencing hypogylcemia, because the hypoglycaemic effect of SGLT2 inhibitors is small in comparison to insulin and sulfonylureas.10 Currently, the Food and Drug Administration (FDA) has approved three SGLT2 selective inhibitors for use in mono, dual, and triple therapy: Canagliflozin, Dapagliflozin and Empagliflozin, and they recently were introduced to the Jordan market.7,11\n\nThe prevalence of T2DM is high in the Middle East because of the development, diet patterns, and the rapid expansion in economy.12 Jordan has a high prevalence of T2DM and has been higher than the global average, as the prevalence rate for diabetes among Jordanian population aged between 25 and 70, was increased from 17.1% in 2004 to 23.7% in 2017.13 Therefore, one treatment approach for improving glycaemic control in T2DM is enhancing the quality of pharmaceutical interventions, increasing patients’ compliance, and using the most recently approved anti-diabetic classes SGLT2 inhibitors.14,15 In fact, community pharmacists have long-term relationships with most of their chronic patients, because patients obtain their chronic medications and diabetes supplies from community pharmacies; therefore, they play a key role in the care of people with diabetes. A large body of evidence revealed that community pharmacists education about diabetes and its medications has improved patients’ glucose and lipid profile in addition to improving cardiovascular outcomes and other complications.16–18 Thus, the lack of professional pharmaceutical knowledge might have a negative impact on patients with diabetes’ outcomes. Accordingly, assessing the current related basic pharmacological knowledge and dispensing practice of community pharmacists of SLGT2 inhibitors, as well as uncovering the weakest areas related to this new anti-diabetic class, has the potential to improve the pharmaceutical outcomes of these medications. Therefore, the objectives of this study were to assess pharmacists’ knowledge and dispensing practice toward SGLT2 inhibitors and explore their perception and dispensing practice.\n\n\nMethods\n\nA cross-sectional design was conducted to meet the study objectives. Data collection was performed between March and September 2020 using a self-administrated questionnaire. The participant pharmacists in our study were visited by the researchers to establish a relationship with them and explain the goals of this research prior to study commencement. Participants were recruited from community pharmacies located among different cities in Jordan including: Amman, Zarqa, Ajloun, Irbid, and Salt, and countryside and city were both targeted based on socio-economic status among each city. The questionnaire was distributed face-to-face with participants at their workplace by four male and female pharmacy students well-trained on data collection and study methods from the Hashemite University. A signed informed consent was obtained from the participants as a pre-requisite to proceed with participation. Participants were interviewed alone for 20-30 minutes to answer the survey questions without anybody beside them and no audio or video recordings were used.\n\nThe sample size was calculated based on a 95% confidence level, and 5% confidence interval. The total community pharmacies pool in Jordan is 2,864; the sample size calculation revealed the need for at least 346 community pharmacies pharmacists.\n\nThe study was approved by the Institutional Review Board at the Hashemite University in Jordan (Reference number: 8/5/2019/2020). Participants’ involvement in the study was voluntary, and they were informed that they had the right to withdraw from the study at any time.\n\nA self-administered questionnaire was created especially for the purpose of this study, and was validated by a group of experts constituted of two pharmacologists, one endocrinologist, and two pharmacists. This questionnaire was composed of 28 questions which were divided into three sections. The first section consisted of eight questions about demographics data including gender, age, pharmacy location, working time, years of experience, holding a postgraduate degree, attending training courses on diabetes, and the bachelor degree (BSc) of the pharmacists; BSc in Pharmacy or BSc in Pharmacy doctor (Pharm D). The second section was composed of 12 questions regarding the knowledge of community pharmacists about SGLT2 inhibitors as shown in Table 2. The third section was composed of nine question in relation to practice of community pharmacists toward SGLT2 inhibitors including their impression about this group of medications, the frequency at which they received prescriptions for these agents, the best advice for the patients while using these agents, the obstacles they faced while dispensing these agents, how they evaluated their knowledge about SGLT2 inhibitors, how they assessed their need for training courses about SGLT2 inhibitors, how they assessed their need to attend training courses about SGLT2 inhibitors, and what was the source of information they used to improve their knowledge about SGLT2 inhibitors. The questionnaire was pretested for reliability through the pilot study. The views scale was calculated and showed an excellent reliability with a Cronbach’s alpha of 0.885. Piloting of the questionnaire was performed to assess the comprehension and accuracy of the questions in relation to the research topic, identify possible redundancy among the 28 questions, and ensure the usability of the data collection method.\n\nData were coded and incorporated into Statistical Package for Social Sciences (SPSS) version 24.0 (SPSS Inc., Chicago, IL, USA) software after extracting it from Google forms. Demographics numerical variables were described using mean and standard deviation. Knowledge difference in demographics with two categories was tested using independent t-tests; however, knowledge difference in demographics with more than two categories was examined using a one-way analysis of variance (ANOVA) followed by a Scheffe posthoc test. Significance was considered when p<0.05.\n\nThe knowledge scale was assessed for validity by examining the content validity index (CVI). Five experts were consulted for their opinion for each scale item including relevancy, clarity, and simplicity and scores from 1 (not all) to 4 (strongly agreed). Questions were tested/re-tested for their clarity and simplicity by interviewing 20 participants. The CVI were ranged from 0.8-0.9 and it was deemed that the scale was valid. SGLT2 inhibitors knowledge score was 6.61 (SD=2.22, range 1-12).\n\n\nResults\n\nA total of 400 community pharmacists were reached (response rate 87%), and 348 completed this survey. Most of the participant pharmacists were less than 30 years old (n=225, 64.7%). Female participants were slightly predominant (n=203, 58.3%) compared to male participants (n=145, 41.7%). The vast majority of the participants were working in city areas (n=331, 95.1%), their working experience was 0-4 years (n=191, 54.9%), and had no postgraduate degree (n=304, 87.4%). Most participants had not attended training courses on diabetes (n=255, 73.3%) and they had a bachelor’s degree in pharmacy (n=307, 88.2%). More details about the sociodemographic characteristics are presented in Table 1.\n\nCommunity pharmacists’ knowledge score was 6.61 (SD=2.22, range 1-12) which is around the knowledge scale average. The results of this study showed that only 32.5% of the pharmacists provided an adequate answer that SGLT2 inhibitors decrease blood pressure. In addition, 34.5% of the pharmacists knew the best consultation to the patients using SGLT2 inhibitors is to keep genital area clean to avoid infection. Moreover, only 38.5% of them knew that patients with diabetes and hypertension are the best candidates for SGLT2 inhibitor agents. On the other hand, pharmacists provided a good knowledge that SGLT inhibitors are contraindicated in patients with renal failure, and they have a better protective effect in patients with diabetes and hypertension compared to sulfonylurea (63.5% and 63.8%; respectively). The highest knowledge of the pharmacists was for their response to the question related to the dosage form of SGLT2 inhibitors, which is tablets (92.5%). Further details about the pharmacists’ knowledge are provided in Table 2.\n\nMore than half of the respondent pharmacists thought that SGLT2 inhibitors have a better effect when they are prescribed to a particular group of patients (n=195, 56%). However, more than 20% of them thought that they are slightly better than the available anti-diabetic medications (n=76, 21.8%). Moreover, 49.1% of the pharmacists reported that they received one to five SGLT2 inhibitor prescriptions per month, and only 8.3% reported that they received more than ten prescriptions per month. Around half of the pharmacists said that the patient’s feedback about SGLT2 inhibitors was very good (n=168, 48.3%). However, very few pharmacists said that the patients had a bad impression of these medications (n=5, 1.4%). A total of 54.9% of the pharmacists revealed that the most common feedback from the patients about these agents is their high price compared to the other anti-diabetic medications. Furthermore, half of the pharmacists thought that their knowledge about SGLT2 inhibitors was good (n=174, 50%), however, 21.6% thought they had a weak knowledge. The vast majority of the pharmacists had not attended a training course about SGLT2 inhibitors before (n=269, 77.3%). In addition, the vast majority of respondents demonstrated that they were in high (n=150,43.1%) to moderate (n=161, 46.3%) need of training courses about SGLT2 inhibitors.\n\nAn independent sample t-test was performed to examine the differences in knowledge levels based on the demographics of the pharmacists and other factors with two categories that might affect their knowledge level which are shown in Table 3. The test demonstrated that age and gender of the pharmacists had no significant effect on their knowledge level. In addition, there was no significant difference in pharmacist’s knowledge based on pharmacy location, pharmacist’s working time (either morning or afternoon or night) and their bachelor’s degree major (either pharmacy or pharmacy Doctor). The t-test indicated that holding a postgraduate degree did not affect the pharmacist’s knowledge. Interestingly, the test showed that the pharmacists who had attended training courses on diabetes before had a higher knowledge score compared to those who had not attended training courses (p=0.02).\n\nA one-way ANOVA test was used to examine the differences in knowledge level in relation to variables which had more than two categories, and results are shown in Table 4. The results showed that the years of experience of the pharmacists has no significant effect on their knowledge about SGLT2 inhibitors. Similarly, the number of prescriptions received by the pharmacist per month, the feedback of the patients who were using SGLT2 inhibitors, and the source of information that the pharmacists used to gain knowledge about SGLT2 inhibitors, had no significant effect on pharmacist’s knowledge. However, pharmacists who thought that SGLT2 inhibitors had no superiority over the other available anti-diabetic medications had lower knowledge scores compared to those who thought the opposite (Scheffe posthoc, p=0.018). In addition, results showed that pharmacists who thought that SGLT2 inhibitors have a better effect when they are administered to a particular group of patients had a higher knowledge score (Scheffe posthoc, 0.0001). Moreover, pharmacists who thought that the best advice they could give for patients who use SGLT2 inhibitors is to keep genital area clean to avoid infection had a higher knowledge score compared to those who thought the best advice was monitoring blood glucose to avoid hypoglycaemia events or monitor body weight to avoid weight gain, or compared to those who had no specific advice to give to the patients (Scheffe posthoc, p=0.0001). Surprisingly, pharmacists who thought they did not face any obstacles while prescribing SGLT2 inhibitors had significantly lower knowledge scores compared to those who thought that the price of these medications is the main obstacle they encounter (Scheffe posthoc, p=0.05). Expectedly, pharmacists who considered their knowledge is excellent had higher knowledge scores compared to those who considered their knowledge was weak (Scheffe posthoc, p=0.04). Furthermore, pharmacists who assessed their need for training courses about SGLT2 inhibitors as moderate had higher knowledge scores compared to those who thought their need for this kind of courses was high or thought there was no need for these courses (Scheffe posthoc, p=0.003, 0.004; respectively).\n\n\nDiscussion\n\nThe present study has assessed pharmacists’ knowledge level, views, and practice about a new anti-diabetic group of medications, SGLT2 inhibitors, in Jordan. In addition, the study explored the factors which could influence their knowledge level. No surveys have been conducted to assess pharmacists’ knowledge and views toward SGLT2 inhibitors in Middle East countries, and to our knowledge this is the first questionnaire survey that was conducted in Jordan.\n\nThis study revealed a fair knowledge and understanding about SGLT2 inhibitors pharmacotherapy among the study sample. Our results indicate that there was no significant impact of gender and age of the pharmacists on their knowledge level. This finding is consistent with a previous study which showed that the knowledge of pharmacists was not affected by their age and gender.19,20 Notably, the findings showed that there was no significant difference in knowledge level between respondents based on their pharmacy location (cities or countryside) or their postgraduate degree. These results are inconsistent with previous reports which showed that pharmacists’ knowledge in rural areas was poor compared to pharmacists’ knowledge in urban areas.21,22 This finding could be partly explained by the fact that the majority of the participants in our study were working in urban areas, and they did not hold postgraduate degrees. Additionally, SGLT2 inhibitors were introduced recently to the market in Jordan, which was many years after their graduation (more than 45% of respondents had more than five years of experience). Moreover, possibly due to high price of these agents,23 they have been introduced selectively to certain pharmacies, so many pharmacists were unexposed to these medications. Consistent with the literature, this research found that community pharmacists who attended training courses on diabetes had a higher knowledge about SGLT2 inhibitors.24,25 In fact, previous studies have shown that continuous training for pharmacists and engaging them in diabetes self-management training programmes is essential to improve their skills and role in assisting the patients they serve.24,25 However, the majority of the participants indicated that they were in high or moderate need for training courses about SGLT2 inhibitors.8 This response was reflected in their average score of knowledge about SGLT2 inhibitors. Moreover, the present study found non-significant differences in the knowledge score of the pharmacists regarding SGLT2 inhibitors based on their demographics data and in association with their different factors. The low score of knowledge about SGLT2 inhibitors can be explained by various factors including the insufficient courses about diabetes in pharmacy schools,26,27 and the inadequate continuous pharmaceutical education for the community pharmacists after graduation,28,29 particularly, a training program on the newly registered pharmaceutical products such as SGLT2 inhibitors.30 Taken together, the lack of knowledge about SGLT2 inhibitors might affect community pharmacists’ practice, which may lead to negative impact on patients’ outcomes.31,32\n\nFurthermore, this study highlights the views and dispensing practice of community pharmacists in Jordan towards SGLT2 inhibitors. More than half of the respondent pharmacists supported that SGLT2 inhibitors have a better effect when they are prescribed to a particular group of patients. This view concords with the fact that SGLT2 inhibitors are useful for a particular group of patients such as obese or hypertensive patients with diabetes, or patients who are at higher risk of hypoglycaemia.33,34 Importantly, SGLT2 inhibitors provide greater HbA1c reduction when compared with sulphonylureas or other oral anti-diabetic agents.35,36 Our results demonstrated that most pharmacists think that these agents have no superiority over the other available anti-diabetic medications; however, many studies show the superiority of SGLT2 inhibitors and different classes of new anti-diabetic agents in reducing the HbA1c,37–39 which could be explained by their lack of knowledge about these anti-diabetic agents. Around half of the patients provided positive feedback about these agents. This finding is consistent with that of previous studies which indicated that SGLT2 inhibitors improved clinical treatment satisfaction in people with diabetes.40,41 However, positive and negative feedback from patients about these agents have been reported.42 Note that the last American Diabetes Association (ADA) guideline in 2018 has recommended to combine SGLT2 inhibitors with metformin for their benefits in decreasing the risk of cardiovascular events.43 Therefore, with this recommendation, more physicians are expected to prescribe these medications,44 which supports the need for increasing pharmacists’ knowledge about SGLT2 inhibitors.\n\nFurthermore, only about one third of the pharmacists in this study could give the proper advice for patients with diabetes who are using SGLT2 inhibitors, which is to keep genital area clean to avoid infection.35 This is an important advice that should be given to the patients who use SGLT2 inhibitors, because these agents increase the glucose excretion in the urinary tract, which pre-dispose patients to genital tract infections. These infections are usually fungal in nature, and can present as vulvitis in women, and balanaposthitis or balanitis in men.45–47\n\n\nConclusions\n\nThe findings of this study demonstrated that pharmacist’s knowledge about SGLT2 inhibitors is moderate, which may negatively affect the outcomes of this medication on patients. In addition, it shed light on the importance of continuous education for the community pharmacists on these new anti-diabetic agents, because pharmacists have essential roles in the healthcare system due to their accessibility to patients. The findings of this study encourage to conduct further research on the awareness of pharmacists of these medications in all healthcare settings.\n\n\nData availability\n\nOpen Science Framework. Knowledge and Practice of Community Pharmacists towards SGLT2 Inhibitors, https://doi.org/10.17605/OSF.IO/W928T.\n\nThis project contains the following underlying data:\n\n‐ SGLT2 inhibitors data.sav\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
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PubMed Abstract | Publisher Full Text\n\nLam D, Shaikh A: Real-Life Prescribing of SGLT2 Inhibitors: How to Handle the Other Medications, Including Glucose-Lowering Drugs and Diuretics. Kidney360. 2021; 2: 742–746. PubMed Abstract | Publisher Full Text\n\nWatson LL, Bluml BM: Integrating pharmacists into diverse diabetes care teams: Implementation tactics from Project IMPACT: Diabetes. J. Am. Pharm. Assoc. 2014; 54: 538–541. PubMed Abstract | Publisher Full Text\n\nCranor CW, Christensen DB: The Asheville Project: Short-term outcomes of a community pharmacy diabetes care program. J. Am. Pharm. Assoc. 2003; 43: 160–172. Publisher Full Text\n\nMasson W, Lavalle-Cobo A, Nogueira JP: Effect of SGLT2-Inhibitors on Epicardial Adipose Tissue: A Meta-Analysis. Cells. 2021; 10. PubMed Abstract | Publisher Full Text\n\nSørensen AMS, Christensen MB: Cardiovascular effects of antidiabetic drugs. Drugs Today (Barc). 2018; 54: 547. Publisher Full Text\n\nOpie LH: Sodium glucose co-transporter 2 (SGLT2) inhibitors: new among antidiabetic drugs. Cardiovasc. Drugs Ther. 2014; 28: 331–334. Publisher Full Text\n\nSipos Á, et al.: Dual-Target Compounds against Type 2 Diabetes Mellitus: Proof of Concept for Sodium Dependent Glucose Transporter (SGLT) and Glycogen Phosphorylase (GP) Inhibitors. Pharmaceuticals (Basel). 2021; 14. PubMed Abstract | Publisher Full Text\n\nJia S, et al.: Incretin mimetics and sodium-glucose co-transporter 2 inhibitors as monotherapy or add-on to metformin for treatment of type 2 diabetes: a systematic review and network meta-analysis. Acta Diabetol. 2021; 58: 5–18. PubMed Abstract | Publisher Full Text\n\nWang Z, et al.: Efficacy and safety of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as monotherapy or add-on to metformin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes. Obes. Metab. 2018; 20: 113–120. PubMed Abstract | Publisher Full Text\n\nSundström J, et al.: A registry-based randomised trial comparing an SGLT2 inhibitor and metformin as standard treatment of early stage type 2 diabetes (SMARTEST): Rationale, design and protocol. J. Diabetes Complicat. 2021; 35: 107996. PubMed Abstract | Publisher Full Text\n\nIshibashi R, et al.: Assessing Patient Satisfaction Following Sodium Glucose Co-Transporter 2 Inhibitor Treatment for Type 1 Diabetes Mellitus: A Prospective Study in Japan. Diabetes Ther. 2021; 12: 453–460. PubMed Abstract | Publisher Full Text\n\nSuzuki D, et al.: Sodium-glucose cotransporter 2 inhibitors improved time-in-range without increasing hypoglycemia in Japanese patients with type 1 diabetes: A retrospective, single-center, pilot study. J. Diabetes Investig. 2020; 11: 1230–1237. PubMed Abstract | Publisher Full Text\n\nNakajima H, et al.: Dapagliflozin improves treatment satisfaction in overweight patients with type 2 diabetes mellitus: a patient reported outcome study (PRO study). Diabetol. Metab. Syndr. 2018; 10: 11. PubMed Abstract | Publisher Full Text\n\nLopaschuk GD, Verma S: Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: A State-of-the-Art Review. JACC. Basic Transl. Sci. 2020; 5: 632–644. PubMed Abstract | Publisher Full Text\n\nAlzarah HA: Evaluation of pharmacists’ knowledge of sodium-glucose cotransporter 2 inhibitors in the eastern province, Saudi Arabia. Int. J. Med. Dev. Ctries. 1046–1050. Publisher Full Text\n\nBrown E, Rajeev SP, Cuthbertson DJ, et al.: A review of the mechanism of action, metabolic profile and haemodynamic effects of sodium-glucose co-transporter-2 inhibitors. Diabetes. Obes. Metab. 2019; 21 Suppl 2: 9–18. PubMed Abstract | Publisher Full Text\n\nJohnsson KM, et al.: Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J. Diabetes Complicat. 2013; 27: 479–484. PubMed Abstract | Publisher Full Text\n\nMcGovern AP, et al.: Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation. BMJ Open Diabetes Res. Care. 2020; 8: e001238. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "140908",
"date": "23 Jun 2022",
"name": "Ayman G. Mustafa",
"expertise": [
"Reviewer Expertise Free radicals in biology and 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\nThis paper discusses community pharmacists’ knowledge and practices toward a group of a new anti-diabetic group, SGLT2 inhibitors, in Jordan which is an important topic that gives new insight into this group of medications.\nThe paper is well-written and of high quality, however, I have some minor comments that would improve the paper:\nIn the abstract, Add the expected impact of this study, for example; Improving pharmacists’ knowledge about this group of medications could improve the treatment outcome of people with diabetes.\n\nIn the introduction, in the first paragraph, line 5, insert reference after ‘’metformin monotherapy’’\n\nAlso in the second paragraph of the introduction, line 5, insert reference after ‘’glucose level’’\n\nIn methods, the section entitled ‘Knowledge scale validity and score’’ is best be moved up before the statistical analysis section.\n\nThe results of this study are quite novel which could help the pharmacists to improve their knowledge about this group of medications that will improve the quality of life for people with diabetes. I think the study is of good value and I recommend it for indexing.\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": "8438",
"date": "30 Jun 2022",
"name": "Abdelrahim qudhah",
"role": "Author Response",
"response": "The authors would like to thank you for your valuable feedback on the manuscript which will improve the quality of it. C1: In the abstract, Add the expected impact of this study, for example; Improving pharmacists’ knowledge about this group of medications could improve the treatment outcome of people with diabetes. R1: The expected impact of this study was added to the abstract. C2: In the introduction, in the first paragraph, line 5, insert reference after ‘’metformin monotherapy’’ R2: A reference is now added. C3: Also in the second paragraph of the introduction, line 5, insert reference after ‘’glucose level’’ R3: A reference is now added. C4: In methods, the section entitled ‘Knowledge scale validity and score’’ is best be moved up before the statistical analysis section. R4: The title of this section is amended as recommended."
}
]
},
{
"id": "140911",
"date": "27 Jun 2022",
"name": "Hala Jehad Mahdi Al-Obaidi",
"expertise": [
"Reviewer Expertise Diabetic patient’s knowledge",
"attitude and Practice using questionnaire in a cross sectional method."
],
"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 very well designed and well written. I enjoyed reading it. Decision made: Approved with only minor changes are required as follows:\nMethod:\nIn the data analysis section, it is stated that the \"Data were analysed by using SPSS software after extracting it from Google forms\", this means that the questionnaire was computer-based, i.e. iPads/PCs were used, however, in the design and data collection section, you’ve mentioned that the questionnaire was distributed face-to-face with participants at their workplace, which made me think that the questionnaire was a paper-based survey. Please clarify this point.\nDevelopment of the survey questionnaire:\nIt is mentioned that the questionnaire was composed of 28 questions which were divided into three sections: The first section consisted of eight questions; the second section was composed of 12 questions and the third section was composed of nine questions. The total number of 8, 12, and 9 is 29, not 28. Please check the accurate number of the questions under each section accordingly.\nData Analysis:\nIt is mentioned (in data analysis section) that ‘Demographics numerical variables were described using mean and standard deviation’. This was used in Table 3 and Table 4 (Knowledge difference in demographics with two categories) i.e. the mean (±SD). While in other Tables, i.e. Table 1 (demographic details) and Table 2 (Community pharmacists’ knowledge about SGLT2 inhibitors) the total number and percentages (no.; %) were used not Mean and SD. You can specify those separately. Also, it is recommended to mention the name of the statistical test used either under each Table or in the data analysis section.\nKnowledge scale validity and score:\nIn this section, full details of the scores are needed, i.e. not only from 1 (not all) to 4 (strongly agreed). It is well explained how the knowledge scale is validated but it is not clear how the SGLT2 inhibitor's knowledge was calculated to 6.61 (SD=2.22, range 1-12). You may explain here more about it and state the range of the high, moderate, or low/poor knowledge scores to compare your findings with the knowledge scale average. And explain how the pharmacist’s knowledge is considered a low or moderate level.\nDiscussion:\nAcross the discussion part, it is recommended to add the P-value for each significant/not significant finding. Also, in the discussion section, it is stated that “Around half of the patients provided positive feedback about these agents”. It is better to write the exact percentage and reference to support this statement.\nConclusion: In the conclusion, it is stated that the findings of this study demonstrated that pharmacists’ knowledge about SGLT2 inhibitors is Moderate. It is recommended to add the score for this evaluation.\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?\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": "8440",
"date": "30 Jun 2022",
"name": "Abdelrahim qudhah",
"role": "Author Response",
"response": "The authors would like to thank you for your positive valuable feedback on the manuscript which will improve the quality of it. The study is very well designed and well written. I enjoyed reading it. Decision made: Approved with only minor changes are required as follows: Method: C1: In the data analysis section, it is stated that the \"Data were analysed by using SPSS software after extracting it from Google forms\", this means that the questionnaire was computer-based, i.e. iPads/PCs were used, however, in the design and data collection section, you’ve mentioned that the questionnaire was distributed face-to-face with participants at their workplace, which made me think that the questionnaire was a paper-based survey. Please clarify this point. R1: Thank you for your comment. The questionnaire was computer-based, however, it was distributed to the participants face-to-face, not over social media platforms. C2: Development of the survey questionnaire: It is mentioned that the questionnaire was composed of 28 questions which were divided into three sections: The first section consisted of eight questions; the second section was composed of 12 questions and the third section was composed of nine questions. The total number of 8, 12, and 9 is 29, not 28. Please check the accurate number of the questions under each section accordingly. R2: Thank you for your comment. The third section was composed of eight questions. It is now corrected. C3: Data Analysis: It is mentioned (in data analysis section) that ‘Demographics numerical variables were described using mean and standard deviation’. This was used in Table 3 and Table 4 (Knowledge difference in demographics with two categories) i.e. the mean (±SD). While in other Tables, i.e. Table 1 (demographic details) and Table 2 (Community pharmacists’ knowledge about SGLT2 inhibitors) the total number and percentages (no.; %) were used not Mean and SD. You can specify those separately. Also, it is recommended to mention the name of the statistical test used either under each Table or in the data analysis section. R3: Thank you for your comment. The ‘’mean and standard deviation is amended to ‘’frequencies’’. The test used is now added beside the title of each table. C4: Knowledge scale validity and score: In this section, full details of the scores are needed, i.e. not only from 1 (not all) to 4 (strongly agreed). It is well explained how the knowledge scale is validated but it is not clear how the SGLT2 inhibitor's knowledge was calculated to 6.61 (SD=2.22, range 1-12). You may explain here more about it and state the range of the high, moderate, or low/poor knowledge scores to compare your findings with the knowledge scale average. And explain how the pharmacist’s knowledge is considered a low or moderate level. R4: Thank you for your comment. This section is now amended. Full details of the scores were added. The knowledge score was calculated as an average for the adequate answers of the participants. Knowledge score was classified as poor (1-4), moderate (4-8), and high (8-12). C5: Discussion: Across the discussion part, it is recommended to add the P-value for each significant/not significant finding. Also, in the discussion section, it is stated that “Around half of the patients provided positive feedback about these agents”. It is better to write the exact percentage and reference to support this statement. R5: Thank you for your comment. P value and percentage are now added. C6: Conclusion: In the conclusion, it is stated that the findings of this study demonstrated that pharmacists’ knowledge about SGLT2 inhibitors is Moderate. It is recommended to add the score for this evaluation. R6: The score is added now."
}
]
},
{
"id": "140909",
"date": "27 Jun 2022",
"name": "Belal Azab",
"expertise": [
"Reviewer Expertise Molecualar biology",
"pharmacogenetics",
"human genetics"
],
"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 well-written manuscript that assessed the knowledge practice of community pharmacists about SGLT2 inhibitors in Jordan. This manuscript gets to a great conclusion that is well supported by extensively analyzed data. I have some minor comments below that won’t affect the robustness of the manuscript, but they are just opportunities for improvement.\nIn paragraph 3 in the introduction, add a reference after ‘’people with diabetes’’ line number 9.\n\nAt the end of the introduction, it would be better to elaborate more on the impact of this study which explains the aims of this study.\n\nThe section entitled ‘’Development of the survey questionnaire’’ in the methods should be amended to ‘’Development of study instrument’’\n\nI think the first paragraph in the discussion is a repetition, so, should be deleted.\n\nOverall, this is an interesting study and the authors have collected and analyzed a good dataset using appropriate methodology. The paper is generally well written and structured, and I recommend it for indexing.\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": "8439",
"date": "30 Jun 2022",
"name": "Abdelrahim qudhah",
"role": "Author Response",
"response": "The authors would like to thank you for your positive valuable feedback on the manuscript which will improve the quality of it. C1: In paragraph 3 in the introduction, add a reference after ‘’people with diabetes’’ line number 9. R1: A reference is now added. C2: At the end of the introduction, it would be better to elaborate more on the impact of this study which explains the aims of this study. R2: The impact of this study is added now. C3:The section entitled ‘’Development of the survey questionnaire’’ in the methods should be amended to ‘’Development of study instrument’’ R3: The title of this section is amended as recommended. C4: I think the first paragraph in the discussion is a repetition, so, should be deleted. R4: This paragraph is now deleted."
}
]
}
] | 1
|
https://f1000research.com/articles/11-659
|
https://f1000research.com/articles/11-341/v1
|
21 Mar 22
|
{
"type": "Research Article",
"title": "Scientific literacy and preferred resources used by Latin American medical students during the COVID-19 pandemic: A multinational survey",
"authors": [
"Bryan Nicolalde",
"Diego Añazco",
"Maria Jose Jaramillo-Cartwright",
"Ivonne Salinas",
"Aldo Pacheco-Carrillo",
"Saliha Hernández-Chávez",
"Gimena Moyano",
"Enrique Teran",
"Bryan Nicolalde",
"Diego Añazco",
"Maria Jose Jaramillo-Cartwright",
"Ivonne Salinas",
"Aldo Pacheco-Carrillo",
"Saliha Hernández-Chávez",
"Gimena Moyano"
],
"abstract": "Background: This study aims to identify the preferred sources for acquiring knowledge about COVID-19 and to evaluate basic knowledge on critical scientific literature appraisal in students from medical schools located in Spanish speaking countries in Latin America. Methods: We designed an online survey of 15 closed-ended questions related to demographics, preferred resources for COVID-19 training, and items to assess critical appraisal skills. A snowball method was used for sampling. We conducted a descriptive analysis and Chi-squared tests to compare the proportion of correct identification of the concept of a preprint and a predatory journal when considering a) self-perceived level of knowledge, b) public vs private school, c) inclusion of a scientific literature appraisal subject in the curriculum, and d) progress in medical school. Results: Our sample included 770 valid responses, out of which most of the participants included were from Mexico (n=283, 36.8%) and Ecuador (n=229, 29.7%). Participants preferred using evidence-based clinical resources (EBCRs) to learn more about COVID-19 (n=182, 23.6%). The preferred study design was case report/series (n=218, 28.1%). We found that only 265 participants correctly identified the concept of a preprint (34.4%), while 243 students (31.6%) correctly identified the characteristics of a predatory journal. We found no significant differences in the proportion of correct answers regardless of the self-perceived level of knowledge, progress in medical school, or scientific literature critical appraisal classes. Conclusion: This study is novel in its approach of identifying sources of knowledge used by Latin American medical students and provides insights into the need to reinforce training in critical appraisal of scientific literature during medical school.",
"keywords": [
"COVID-19",
"medical students",
"Latin America",
"critical scientific literature appraisal"
],
"content": "Introduction\n\nIn December 2019, a cluster of cases of pneumonia of unknown origin was reported in Wuhan, China and since then, the virus has spread globally. On March 11, 2020, the World Health Organization (WHO) declared coronavirus disease 19 (COVID-19) as a pandemic.1 Researchers throughout the globe have worked arduously to rapidly fill in the gaps of knowledge on this novel disease and this has resulted in an unprecedented surge in scientific production.2 However, the pressure of produce science quickly can cause an overproduction of low-quality research. Notably, before the pandemic, it was estimated that approximately 85% of research was wasted due to flaws in design, methodology or interpretation of the data, and these challenges have been augmented due to the time constraints and poor research infrastructure during the COVID-19 pandemic.3,4\n\nThe role of medical students has been diverse throughout history, from being participatory agents in the evolution of medical curricula to being agents of promotion, prevention and treatment of diseases.5,6 Medical students have helped during previous disasters and emergencies such as the Spanish flu outbreak of 1918 and the 1952 polio epidemic in Denmark; and they might have an important role during the COVID-19 pandemic through essential tasks such as assistance in clinical care, telemedicine, and fighting against misinformation.7,8\n\nTo provide high-quality healthcare services, future physicians should develop abilities to critically assess research to inform evidence-based decisions during their career, including critical appraisal of scientific literature within the curriculum of medical schools and promoting involvement in research opportunities could help students develop these skills.9–12 Notably, the percentage of student authorship in published articles has increased importantly throughout the years.13\n\nDue to their role, and the unprecedent low quality scientific information, it is indispensable that medical students have enough skills to analyse scientific data. In this study, we intend to identify preferred resources used by medical students in Spanish speaking countries in Latin America to obtain information about COVID-19 and evaluate basic critical appraisal skills through a self-report online survey.\n\n\nMethods\n\nThis study was approved by the Independent Review Board at Universidad San Francisco de Quito (2020-033M). Although data was anonymous and did not include identifying information, electronic informed consent was requested before the survey was collected. Participation was voluntary, and medical students were informed that data from the survey would be used for analysis and scientific publication. Participants did not receive any compensation from participating in the study.\n\nThis was a multinational cross-sectional study based on a self-report online survey. Participants were medical students currently enrolled in a medical school in a Spanish-speaking country in Latin America. The inclusion criteria required for participation were that they were aged 18 or older, with active student status in a medical school based in a Spanish-speaking country in Latin America, and with Spanish language fluency. Exclusion criteria were non-active student status, medical students from a country where Spanish is not the primary language, and previous participation in the survey.\n\nAs we intended to include participants from multiple countries and achieve significant variation in characteristics within our purposive sample, a link to the survey and an accompanying standardized text explaining the purpose of the survey was sent via e-mail from the authors to the initial “point of contact” in each country for further distribution following a snowballing approach. The link to the survey was then shared through different social networks by authors to medical students from their own and other medical schools, and authors instructed participants to share the link with their peers. The survey was distributed to students from different academic years to gather a diverse sample in terms of progress in medical school. We also actively tried to contact students from as many countries in Latin America as possible through e-mails sent to the medical students’ organizations publicly available to ask them to distribute the survey to their members. Data collection took place from October 22 to November 6, 2020. During the first week after the survey was released we obtained a huge amount of the answers, but then there was a very low number of new responses daily, therefore we decided to shorten the period for data gathering.\n\nWe designed an electronic survey using the Google Forms web application. The survey consisted of fifteen closed-ended questions to gather basic demographic information and evaluate resources used to obtain information on the COVID-19 and explore knowledge and attitudes that medical students had in terms of scientific information appraisal. The survey was designed specifically for this study by the authors; they included active students, alumni, and faculty with vast experience in medical education and research.\n\nThe survey was developed in Spanish and reviewed in a telematic session by all authors to provide feedback about the questionnaire and also to ensure that was appropriate despite regional language variations. In addition, two independent academic advisors reviewed the survey for clarity. At this stage, no changes were required. Then, the survey was piloted in medical students from Ecuador (n=5), Mexico (n=3), and Argentina (n=2), who were mainly friends of the authors, to get their input. Those surveys were not included in the analysis. The pilot suggested very few changes, most related to grammar and punctuation After incorporating the feedback, we deployed the survey. As the survey was originally in Spanish, for readers to understand it, a translation to English was performed by an author (BN) with certified proficiency and then by a native speaker who did not participate in the study (The original version in Spanish and a translated version to English are available as extended data).14\n\nData captured through the Google Forms web application was exported directly to Microsoft Excel (v. 16.58). An initial descriptive analysis of the responses to the survey to determine demographic characteristics and preferred resources used to gather COVID-19 related information was performed. All variables obtained in the results of the survey were analyzed. There was no missing data as the setting in the online survey did not allow for the submission of incomplete forms. We analyzed the difference in the proportion of correct identification of the concept of a preprint and predatory journals when comparing students based on their self-reported level of knowledge, progress in medical school, public vs. private status of medical school, and inclusion of a scientific literature critical appraisal subject during their curriculum. For data analysis, we decided to group low-medium and advanced-experts’ responses in the self-reported level of knowledge and first-second quarter and third-fourth quarter in progress in medical school responses to create dichotomized variables. Due to the categorical nature of our data, we decided to use Chi-squared tests. A one-tailed alpha value of 0.05 was set. All our statistical analyses were conducted on IBM SPSS version 25 (IBM. Corp., Armonk, N.Y., USA).\n\nBy incorporating different stakeholders in medical education (active junior and senior students, alumni, and faculty), and researchers from different countries, we could design a study that contained different valuable perspectives on critical appraisal of scientific information.\n\nAlthough ET is a professor in one of the medical schools where the survey was conducted, participants were not aware of his role in the research. No economic or academic incentive was offered by any of the authors to the participants.\n\nAfter data gathering, BN and DA performed an initial statistical analysis and shared the results with the other authors. A researcher not involved in this study was invited to validate the statistical analysis. Additionally, all authors had access to the database and agreed with the final data analysis and processing.\n\n\nResults\n\nThere were 770 valid responses to the survey (Underlying data: Survey results-Scientific literacy and preferred resources used by Latin American medical students during COVID-19 pandemic).14 Almost two-thirds of the participants were females (n=487, 63.2%). Most of the participants were from Mexico (n=283, 36.8%) and Ecuador (n=229, 29.7%). Students equally attended private (n=388, 50.4%) or public universities (n=382, 49.6%). We also found a similar distribution in terms of completed progress in medical school: 24.0% (n=185) in the first quarter, 24.3% (n=187) in the second quarter, 24.9% (n=192) in the third quarter, and the remaining 26.8% (n=206) in the final quarter of medical school. Distribution by gender and country is shown in Table 1.\n\nMost medical students considered that they had a low or medium level of knowledge about COVID-19 (n=539, 70.0%), while 231 participants reported an advanced or expert level (30.0%).\n\nOverall, medical students preferred using evidence-based clinical resources (EBCRs), such as UpToDate or Medscape, to learn more about COVID-19 (n=182, 23.6%), followed by academic journals (n=171, 22.2%), and open access courses provided by entities such as the World Health Organisation (WHO) (n=141, 18.3%). Our survey responses were grouped according to the different sub-regions of Latin America (Table 2).\n\nRegarding the type of article, medical students preferred using case reports or case series (n=218, 28.1%) to learn more about COVID-19, followed by review articles (n=168, 21.8%) (Figure 1).\n\nThe critical factor that medical students considered when reading a scientific article was most frequently the affiliation of the authors (n=366, 47.5%), followed by the journal of publication (n=176, 22.85%), the type of study (n=138, 17.92%), and the publication status (preprint vs. published) (n=44, 5.71%).\n\nIn terms of receiving news related to the COVID-19 pandemic, medical students preferred official websites of organizations such as the WHO (n=221, 28.7%), followed by scientific journals (n=185, 24.0%), and medical platforms (n=128, 16.6%) (Table 3).\n\nWe found that approximately a third of the participants correctly identified the concept of a preprint (n=265, 34.4%), while 243 students (31.6%) correctly identified the characteristic of a predatory journal. On the other hand, 553 students (71.8%) correctly identified the concept of an open-access journal.\n\nTwo-thirds of the participants (n=526, 68.3%) had a subject focused on scientific literature critical appraisal as a part of their curriculum during medical school.\n\nWe conducted chi-squared tests to identify factors that were associated with a significant difference in the proportion of students that correctly identified the concept of a preprint or predatory journals (Extended data: Frequencies of answers and results of Chi-squares performed).14 We did not find a significant difference when comparing participants in terms of self-reported level of knowledge (low/medium vs advanced/expert) in the chance of correctly identifying the concept of a preprint (df=1, χ2=0.632, P=0.456) or a predatory journal (df=1, χ2=0.435, P=0.554).\n\nParticipants from public schools correctly identified the concept of predatory journals (n=142, 37.1%) more frequently than students that attended a private medical school (n=101, 26.0%) (df=1, χ2=11.063, P<0.01); however, there was not a significant difference while identifying the concept of a preprint (df=1, χ2=2.805, P=0.094).\n\nAdditionally, we did not find significant differences in the correct identification of preprint (df=1, χ2=0.502, P=0.514) or predatory journal (df=1, χ2=0.694, P=0.406) concepts regardless of the inclusion of a scientific literature critical appraisal subject during medical school. Finally, the proportion of participants that answered correctly was not significantly different for preprints (df=3, χ2=7.124, P=0.068) and predatory journals (df=3, χ2=5.741, P=0.125) despite the progress in medical school (first-second quarter vs third-four quarter).\n\n\nDiscussion\n\nOverall, most medical students perceived that their knowledge about COVID-19 was either low or medium independently of the current academic year they belonged. This differs from what could be expected in previous studies in which students from superior years were more knowledgeable on COVID-19.15 Medical students preferred using evidence-based clinical resources as their main source for learning about COVID-19. This result is consistent with previous research that shows the popularity of these resources within the medical community.16,17 The use of evidence-based electronic resources has been associated with reduced lengths of stay and mortality rates, and it has resulted in improved performances in standardized examinations.18,19\n\nMost of participants preferred getting news related to the pandemic on official websites by entities such as the WHO and the Centre for Disease Control (CDC), which could be a way to combat the current misinformation outbreak (infodemic). Social media platforms provide users with immediate access to massive amounts of content and are the perfect medium to spread questionable information easily.20 A study showed that fake news is easily spread through Latin American countries through social media platforms, and fact-checking could be a potential solution to fight back against the infodemic.21\n\nNotably, participants mentioned a preference for case series/reports to learn more about COVID-19, followed by narrative reviews and case-control studies. Only 112 participants (15%) preferred systematic literature reviews (SLRs) or metanalyses. The importance of addressing this trend relies on the level of evidence that well-conducted SLRs and metanalysis have compared to case series/reports, which has traditionally been portrayed on the top and the bottom of the evidence pyramid, respectively.22,23 It would be expected that medical students who had exposure to a subject focused on critical appraisal skills during their formation would choose study designs higher among the evidence pyramid, however, our results did not show a significant difference. These could be partially attributed to the fact that during the start of the pandemic most of the articles published were retrospective studies or case reports focusing on patients’ characteristics.2 Remarkably, we found that regardless of the progress in medical school, self-perceived level of knowledge about COVID-19, and the inclusion of a critical appraisal subject in the curriculum, most of the participants could not correctly identify the concept of a preprint or a predatory journal, in spite of the enormous surge in preprint production during this pandemic.24 As well, in our study, only 44 participants (5.71%) chose the publication status (preprint vs published article) as a critical factor when reading an article. This is concerning as medical students might fail to recognize that preprints are preliminary reports that have not been peer-reviewed and might contain faulty or low-quality information.25\n\nAdditionally, as medical students are more frequently involved in research, they could be potential targets for predatory journals that promise easy and rapid pathways to publish, through unethical practices, which could further contribute to the infodemic.13 As expected, predatory journals have exploited the uncertainty and prolonged reviewing and editing processes by multiple scholarly journals due to the pandemic to increase their profits.26–28 A previous study conducted in the Kingdom of Saudi Arabia and New Zealand also revealed a poor understanding of medical students regarding predatory journals.29\n\nThe main limitation to our study is the sample size, particularly in some of the Spanish-speaking countries in Latin America, which could be related to the short time that the survey was available or ineffective sampling strategies for some specific countries. The chain-referral sampling method employed, despite its pragmatism, is a significant limitation, as the sampling is non-random due to the referral process, in which the sample is dependent on the researchers’ contacts, which is reflected by the significantly higher proportion of participants from Mexico and Ecuador. As well, there is uncertainty of whether the sample is representative of the target population. Furthermore, participants could be susceptible to subject bias and might have elected responses that seemed more appropriate for a medical student.\n\nThis study is novel in its approach to identify sources used by Latin American medical students to learn about COVID-19 and to evaluate critical appraisal skills used to interpret new scientific information. Additionally, even though we had difficulties in sampling medical students from certain nationalities, we did recruit an equative number of medical students representing different stages of medical degree completion. Our results support the need to reinforce training in critical appraisal of scientific literature during medical school.30,31\n\n\nConclusions\n\nThroughout history medical students have an important role, and the COVID-19 crisis is not an exception. Our study found that most of medical students have good behaviours regarding acquire new information related to COVID-19 such as using evidence-based clinical resources to learn about COVID-19 and official websites of recognised organizations to receive news. However, they have problems in terms of correctly identifying predatory journals or preprint articles independently of the region, self-perceived level of knowledge, progress in medical school, or literature critical appraisal classes. Besides, these students prefer a study design that is not at the top of the evidence pyramid. Our findings could provide insights into the need to reinforce training in critical appraisal of scientific literature during medical school in Latin America.\n\n\nData availability\n\nOpen Science Framework (OSF). Scientific literacy and preferred resources used by Latin American medical students during COVID-19 pandemic. https://doi.org/10.17605/OSF.IO/7MS64.14\n\nThis project contains the following underlying data:\n\n• Survey results-Scientific literacy and preferred resources used by Latin American medical students during COVID-19 pandemic. (These data contain the answers obtained from the surveys that were applied in medical students about scientific literacy and preferred resources).\n\n• Frequencies of answers and results of Chi-squares performed. (These data include how data was analysed)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nOpen Science Framework (OSF). Scientific literacy and preferred resources used by Latin American medical students during COVID-19 pandemic. https://doi.org/10.17605/OSF.IO/7MS64.14\n\nThis project contains the following extended data:\n\n• Infodemic survey English version. (These data include the English version of the survey that was applied to medical students from Latin American Countries)\n\n• Infodemic survey Spanish version. (These data include the original Spanish version of the study that was used in medical students from Latin American Countries)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "References\n\nWHO: Coronavirus (COVID-19) events as they happen.[cited 2021 Sep 11]. Reference Source\n\nFidahic M, Nujic D, Runjic R, et al.: Research methodology and characteristics of journal articles with original data, preprint articles and registered clinical trial protocols about COVID-19. BMC Med. Res. Methodol. 2020 Jun 22; 20(1): 161. PubMed Abstract | Publisher Full Text\n\nChalmers I, Glasziou P: Avoidable waste in the production and reporting of research evidence. Lancet Lond. Engl. 2009 Jul 4; 374(9683): 86–89. PubMed Abstract | Publisher Full Text\n\nGlasziou PP, Sanders S, Hoffmann T: Waste in covid-19 research. BMJ. 2020 May 12; 369: m1847.\n\nMcLean S, Charlesworth L, May S, et al.: Healthcare students’ perceptions about their role, confidence and competence to deliver brief public health interventions and advice. BMC Med. Educ. 2018 May 24; 18(1): 114. PubMed Abstract | Publisher Full Text\n\nEstrella Porter PD, Ayala Mullo JF, Barba Carrera DA, et al.: Medical education from the point of view of medical students: Results from four participatory Delphi panels in Quito, Ecuador. Med. Teach. 2020 Sep 1; 42(9): 1051–1057. Publisher Full Text\n\nPatrinely JR, Zakria D, Berkowitz ST, et al.: COVID-19: the Emerging Role of Medical Student Involvement. Med. Sci. Educ. 2020 Aug 12; 30(4): 1641–1643. PubMed Abstract | Publisher Full Text\n\nMiller DG, Pierson L, Doernberg S: The Role of Medical Students During the COVID-19 Pandemic. Ann. Intern. Med. 2020 Jul 21; 173(2): 145–146. PubMed Abstract | Publisher Full Text\n\nNikkar-Esfahani A, Jamjoom AAB, Fitzgerald JEF: Extracurricular participation in research and audit by medical students: Opportunities, obstacles, motivation and outcomes. Med. Teach. 2012 May 1; 34(5): e317–e324. PubMed Abstract | Publisher Full Text\n\nInam SB: Experience of Teaching Critical Appraisal of Scientific Literature to Undergraduate and Postgraduate Students at the Ziauddin Medical University, Karachi, Pakistan. Int. J. Health Sci. 2007 Jan; 1(1): 119–124. PubMed Abstract\n\nMabvuure NT: Twelve tips for introducing students to research and publishing: A medical student’s perspective. Med. Teach. 2012 Sep 1; 34(9): 705–709. PubMed Abstract | Publisher Full Text\n\nMurdoch-Eaton D, Drewery S, Elton S, et al.: What Do Medical Students Understand By Research And Research Skills? Identifying Research Opportunities Within Undergraduate Projects. Med. Teach. 2010 Jan 1; 32(3): e152–e160. PubMed Abstract | Publisher Full Text\n\nKan CK, Qureshi MM, Paracha M, et al.: Effect of Medical Student Contributions on Academic Productivity: Analysis of Student Authorship Over Time. Adv. Med. Educ. Pract. 2021 May 12; 12: 481–489. PubMed Abstract | Publisher Full Text\n\nNicolalde B, Añazco D, Jaramillo MJ, et al.: Scientific literacy and preferred resources used by Latin American medical students during COVID-19 pandemic.2022 Feb 27 [cited 2022 Feb 27]. Reference Source\n\nNguyen HT, Do BN, Pham KM, et al.: Fear of COVID-19 Scale—Associations of Its Scores with Health Literacy and Health-Related Behaviors among Medical Students. Int. J. Environ. Res. Public Health. 2020 Jan; 17(11): 4164. PubMed Abstract | Publisher Full Text\n\nValtis YK, Rosenberg J, Bhandari S, et al.: Evidence-based medicine for all: what we can learn from a programme providing free access to an online clinical resource to health workers in resource-limited settings. BMJ Glob. Health. 2016 May 23; 1(1): e000041. PubMed Abstract | Publisher Full Text\n\nEgle JP, Smeenge DM, Kassem KM, et al.: The Internet School of Medicine: use of electronic resources by medical trainees and the reliability of those resources. J. Surg. Educ. 2015 Apr; 72(2): 316–320. PubMed Abstract | Publisher Full Text\n\nIsaac T, Zheng J, Jha A: Use of UpToDate and outcomes in US hospitals. J. Hosp. Med. 2012 Feb; 7(2): 85–90. PubMed Abstract | Publisher Full Text\n\nReed DA, West CP, Holmboe ES, et al.: Relationship of electronic medical knowledge resource use and practice characteristics with Internal Medicine Maintenance of Certification Examination scores. J. Gen. Intern. Med. 2012 Aug; 27(8): 917–923. PubMed Abstract | Publisher Full Text\n\nCinelli M, Quattrociocchi W, Galeazzi A, et al.: The COVID-19 social media infodemic. Sci. Rep. 2020 Oct 6; 10(1): 16598. PubMed Abstract | Publisher Full Text\n\nCeron W, Gruszynski Sanseverino G, de-Lima-Santos M-F, et al.: COVID-19 fake news diffusion across Latin America. Soc. Netw. Anal. Min. 2021; 11(1): 47. PubMed Abstract | Publisher Full Text\n\nMurad MH, Asi N, Alsawas M, et al.: New evidence pyramid. BMJ Evid-Based Med. 2016 Aug 1; 21(4): 125–127. PubMed Abstract | Publisher Full Text\n\nMurad MH, Montori VM, Ioannidis JPA, et al.: How to Read a Systematic Review and Meta-analysis and Apply the Results to Patient Care: Users’ Guides to the Medical Literature. JAMA. 2014 Jul 9; 312(2): 171–179. PubMed Abstract | Publisher Full Text\n\nElse H: How a torrent of COVID science changed research publishing — in seven charts. Nature. 2020 Dec 16; 588(7839): 553–553. PubMed Abstract | Publisher Full Text\n\nAñazco D, Nicolalde B, Espinosa I, et al.: Publication rate and citation counts for preprints released during the COVID-19 pandemic: the good, the bad and the ugly. PeerJ. 2021 Mar 3; 9: e10927. PubMed Abstract | Publisher Full Text\n\nSingh-Chawla D: Warning over coronavirus and predatory journals.[cited 2021 Sep 11]. Reference Source\n\nAllen RM: When peril responds to plague: predatory journal engagement with COVID-19. Libr. Hi Tech. 2021 Jan 1; 39(3): 746–760. Publisher Full Text\n\nVervoort D, Ma X, Shrime MG: Money down the drain: predatory publishing in the COVID-19 era. Can. J. Public Health Rev. Can. Santé Publique. 2020 Sep 4; 111(5): 665–666. PubMed Abstract | Publisher Full Text\n\nAlamri Y, Al-Busaidi IS, Bintalib MG, et al.: Understanding of medical students about predatory journals: A comparative study from KSA and New Zealand. J. Taibah Univ. Med. Sci. 2020 Oct; 15(5): 339–343. PubMed Abstract | Publisher Full Text\n\nKling J, Larsen S, Thomsen SF: The Need for Focused Literacy Training in the Medical School Curriculum: A Cross-Sectional Study of Undergraduate Students. Educ. Res. Int. 2017 Dec 19; 2017: 1–6. Publisher Full Text\n\nJones R: Critical reading for primary care: a new resource for readers, authors, and reviewers. Br. J. Gen. Pract. 2013 Jan; 63(606): 9. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "137265",
"date": "12 May 2022",
"name": "Chung-Ying Lin",
"expertise": [
"Reviewer Expertise psychosocial"
],
"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 can be improved with the following considerations:\nPlease elaborate on how the 15 closed-ended questions were generated. It is unclear where the 15 questions come from. Did the authors conduct a literature review to identify potential items and then reduce the items via expert panels? It is also unclear what the following procedure is: \"The survey was designed specifically for this study by the authors; they included active students, alumni, and faculty with vast experience in medical education and research.\" Is this an expert panel that discusses the survey questions? Or, is this an informal chat between the authors and all the other stakeholders? Accordingly, it is unclear what the purpose of pilot testing on the medical students is. The authors mentioned that they wanted to get \"input\" from the piloted medical students. However, it is unclear what \"input\" the authors wanted to get. I suspect that the authors did not provide proper instructions to these students and thus they only obtained some minor comments. Also, it is unclear what the background of these students was (e.g., their gender, their studying progress).\n\nThe authors only used chi-squared tests for all the inferential statistics. Only using chi-squared tests has the problem of not controlling potential confounders. Given that the sample size was large, the authors should be able to apply multivariable statistics that control potential confounders (e.g., multivariable logistic regression).\n\nI wonder how representative the sample was. Specifically, does the demographic distribution of the present sample similar to these surveyed countries? I found that it is interesting to have a higher proportion of females.\n\nFollowing the previous comment, I wonder how the authors ensure if the participants were the target participants. For example, maybe a student who was not a medical student received the email and completed the survey. Can the authors catch these invalid responses?\n\nGiven that health literacy on COVID-19 is the key information in the present study, I think that the authors should examine other potential factors on the COVID-19 literacy. Specifically, why don't the authors examine if the resources obtaining COVID-19 knowledge is a factor explaining the student's COVID-19 knowledge? Similarly, it would be interesting to examine if different types of articles the students read play a role in their COVID-19 knowledge.\n\nI disagree with the statement \"The main limitation to our study is the sample size\". Specifically, the entire sample size is good, and the problem is that the authors had an imbalanced sample size. After all, the authors did not separate the participants into different countries for the data analysis. Therefore, the authors did not have the problem of a small sample size in statistics.\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?\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": "8413",
"date": "30 Jun 2022",
"name": "Enrique Teran",
"role": "Author Response",
"response": "Please elaborate on how the 15 closed-ended questions were generated. It is unclear where the 15 questions come from. Did the authors conduct a literature review to identify potential items and then reduce the items via expert panels? It is also unclear what the following procedure is: \"The survey was designed specifically for this study by the authors; they included active students, alumni, and faculty with vast experience in medical education and research.\" Is this an expert panel that discusses the survey questions? Or, is this an informal chat between the authors and all the other stakeholders? Accordingly, it is unclear what the purpose of pilot testing on the medical students is. The authors mentioned that they wanted to get \"input\" from the piloted medical students. However, it is unclear what \"input\" the authors wanted to get. I suspect that the authors did not provide proper instructions to these students and thus they only obtained some minor comments. Also, it is unclear what the background of these students was (e.g., their gender, their studying progress). Thank you for your comment. This has been improved in v2 of our manuscript. Briefly, potential item were obtained either from literature or previous experience. As most of the authors were not experts in the field, the survey questions were defined through informal chat between the authors and other stakeholders. The pilot testing was a strategy to ensure the questions were fully understood or to get feedback to improve it. In fact, they were very well instructed about their role, not only in the answer as potential participants. The authors only used chi-squared tests for all the inferential statistics. Only using chi-squared tests has the problem of not controlling potential confounders. Given that the sample size was large, the authors should be able to apply multivariable statistics that control potential confounders (e.g., multivariable logistic regression). We thank you Professor Chung-Ying Li for his suggestion. However, as all our data is qualitative, after consulting with our advisor in statistics, could not find any added value to applying multivariable analysis. I wonder how representative the sample was. Specifically, does the demographic distribution of the present sample similar to these surveyed countries? I found that it is interesting to have a higher proportion of females. As was described in the Results section, according to our knowledge, the distribution of the data is consistent with other Cross-Sectional studies performed in Latin America Region. Therefore, yes, our sample was representative. In the same sense, we initially had the same concern that reviewer 1 regarding the gender distribution. However, once again, in most of these kinds of studies, females are more active in response. Following the previous comment, I wonder how the authors ensure if the participants were the target participants. For example, maybe a student who was not a medical student received the email and completed the survey. Can the authors catch these invalid responses? It is important to mention that although the collection of data was performed through an online survey, and the risk of someone outside the target population might answer the survey, we consider that this risk was reduced by employing a chain-referral method with other medical students. Given that health literacy on COVID-19 is the key information in the present study, I think that the authors should examine other potential factors on COVID-19 literacy. Specifically, why don't the authors examine if the resources obtaining COVID-19 knowledge is a factor explaining the student's COVID-19 knowledge? Similarly, it would be interesting to examine if different types of articles the students read play a role in their COVID-19 knowledge. To explore other factors that could contribute to Covid-19 literary among medical students, we perform an additional descriptive analysis where we make a relationship between the percentage of undergraduate studies completed, self-perceived knowledge on COVID-19, and source of preference for COVID-19 information that is summarized in Table 4 and discussion section. This analysis was performed to study if the behavior among medical students changes along with the progress of their career or the level of auto perception in knowledge choosing better sources to acquire medical knowledge. I disagree with the statement \"The main limitation to our study is the sample size\". Specifically, the entire sample size is good, and the problem is that the authors had an imbalanced sample size. After all, the authors did not separate the participants into different countries for the data analysis. Therefore, the authors did not have the problem of a small sample size in statistics. We agree with Professor Chung-Ying Li that the correct term is not a sample size, instead, we change the term to imbalanced sample size."
}
]
},
{
"id": "137749",
"date": "18 May 2022",
"name": "Fernando Spilki",
"expertise": [
"Reviewer Expertise Virology",
"infectious 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 issue of information quality proved to be extremely relevant in the context of the COVID-19 pandemic, especially during the first year. An infinity of obscure sources of information, including from social networks to a profusion of material published without any type of quality review, gave the opportunity for untruths to be raised to the level of scientific knowledge, greatly harming the fight against the pandemic in many scenarios.\nIn this sense, the study becomes relevant and very interesting to assess the levels of understanding of medical students at different levels of training, about what they consider reliable sources of information, and how they judge dubious sources.\nFrom the point of view of minor points that require further investigation, it would be interesting to clarify and discriminate more clearly how students have judged the diverse types of information sources, depending on their level of completion of the medical curriculum, from the beginning to the end of graduation, and how this does evolves or not throughout.\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": "8414",
"date": "30 Jun 2022",
"name": "Enrique Teran",
"role": "Author Response",
"response": "- From the point of view of minor points that require further investigation, it would be interesting to clarify and discriminate more clearly how students have judged the diverse types of information sources, depending on their level of completion of the medical curriculum, from the beginning to the end of graduation, and how this does evolves or not throughout. We thank you Professor Spilki for his comments and regarding his suggestion, in the new version, this information has been added to new table 4."
}
]
}
] | 1
|
https://f1000research.com/articles/11-341
|
https://f1000research.com/articles/11-548/v1
|
19 May 22
|
{
"type": "Review",
"title": "Emerging threat and vaccination strategies of H9N2 viruses in poultry in Indonesia: A review",
"authors": [
"Saifur Rehman",
"Fedik Abdul Rantam",
"Khadija Batool",
"Aamir Shehzad",
"Mustofa Helmi Effendi",
"Adiana Mutamsari Witaningrum",
"Muhammad Bilal",
"Muhammad Thohawi Elziyad Purnama",
"Saifur Rehman",
"Fedik Abdul Rantam",
"Khadija Batool",
"Aamir Shehzad",
"Adiana Mutamsari Witaningrum",
"Muhammad Bilal",
"Muhammad Thohawi Elziyad Purnama"
],
"abstract": "Avian influenza virus subtype H9N2 was first documented in Indonesia in 2017. It has become prevalent in chickens in many provinces of Indonesia as a result of reassortment in live bird markets. Low pathogenic avian influenza subtype H9N2 virus-infected poultry provides a new direction for influenza virus. According to the latest research, the Indonesian H9N2 viruses may have developed through antigenic drift into new genotype, posing a significant hazard to poultry and public health. The latest proof of interspecies transmission proposes that, the next human pandemic variant will be avian influenza virus subtype H9N2. Manipulation and elimination of H9N2 viruses in Indonesia, constant surveillance of viral mutation, and vaccines updates are required to achieve effectiveness. The current review examines should be investigates/assesses/report on the development and evolution of newly identified H9N2 viruses in Indonesia and their vaccination strategy.",
"keywords": [
"avian influenza",
"public health",
"emergence",
"vaccination",
"Indonesia"
],
"content": "Introduction\n\nThe avian influenza virus subtype H9N2 is a LPAIV widely circulated in Asian poultry.1 In the future, the LPAI H9N2 virus like H5N1 could pose a serious zoonotic threat2 because they have been isolated from backyard and wild bird species. It was discovered in a variety of avian species throughout Eurasia, the poultry industry has suffered significant financial losses as a result of this.3 The H9N2 virus has gained much attention due to its rapid dispersion between native birds.4 This low pathogenic virus survive in chicks and transmits to unaffected birds via the fecal-oral route despite causing extreme clinical signs.5 The avian influenza virus subtype H9N2 causes severe respiratory illness in immunocompromised chickens. It causes an increase in early chick mortality as well as a considerable decline in egg production in laying chickens, resulting in financial loss.6 When this virus is co-infected with other pathogens, the intensity of clinical symptoms, death rates, and viral replication can increase.7,8 Based on their genetic and antigenic properties H9N2 viruses prevalent in Asia have been classified into three genotypes: A/Quail/Hong Kong/G1/97-like (G1-like); the Y280 lineage, represented by A/Chicken/Hong Kong/Y280/97-like (Y280-like); and the Korean lineage, represented by A/Chicken/Korea/38349-p96323/96 (Korean-like).9 The G1 prototype virus (A/Quail/Hong Kong/G1/97) is common in southern Chinese quail. It may have been the source of internal genes for the highly pathogenic avian influenza (HPAI) subtype H5N1 that hit Hong Kong in 1997. H9N2 viruses with G1 lineages have been found in field epidemics of influenza in poultry in the Middle East and the Indian subcontinent since 1997. Since the early 1990s, H9N2 has evolved to create a more diversified genotype in grassland poultry birds by acquiring gene fragments from other viruses. The genomes of newly isolated avian influenza (H9N2) viruses showed significant genetic recombination in HPAI viruses.10–12\n\nA novel H9N2 genotype, expressed by A/chicken/West Java/BBLitvet-RI/2017, A/chicken/East Java/Spg147/2018, A/chicken/East Java/BLi25Ut/2018 and A/chicken/Central Java/SLO.105/2018 was isolated from Indonesian poultry birds, and these replaced by Y280 or G1 Lineage.13,14 Inter- and Intra-subtype genotype genomic recombination between LPAIV subtype H9N2 (G1-like), HPAIV subtype H5N1 (clade 2.2), and H7N9 viruses resulted in these novel reassortants (Figure 1). A novel H9N2 genotype in Indonesia represented 98% sequence identity with that of (A/Muscovy duck/Vietnam/LBM719/2014(H9N2) was isolated from chicken in a study conducted by Melina Jonas.15 Co-circulation of the LPAI virus subtype H9N2 has been reported in Egypt with H5N1 since 2011 infecting the same hosts. Subsequently, H9N2 has established an endemic status in the poultry sector. Human infections with both H7N9 and H10N8 viruses highlighted that H9N2 has an emerging state of new human infecting virus.16\n\nIn Indonesia, the circulation of the H9N2 and H5N1 viruses and the possibility of reassortment between the two viruses have resulted in various virus control situations.17 The LP avian influenza subtype H9N2 virus raises a public health risk. It has human-like receptor specificity2,18,19 that might surpass the species barrier.20,21\n\nIn 1999, LPAIV subtype H9N2 was first discovered from a human patient in Hong Kong.22,23 This discovery raises concerns about the H9N2 pandemic potential alongside the H5N1 virus.24,25 The recent isolation of AI H9N2 from a patient in Bangladesh and poultry workers in China has heightened public health concerns about LP avian influenza.26–28 Bangladesh, Pakistan, and Egypt have all reported further cases.29–31 Even though low pathogenic avian influenza H9N2 viruses could harm humans, the significance of low pathogenic H9N2 viruses has been surpassed by HPAI H5N1 viruses.32 A further indication of the significance of the H9N2 subtype of the low pathogenic avian influenza virus is discovering of two other subtypes (H10N8 and H7N9) with internal genomes comparable to those of H9N2.33 In the Western Pacific Region, 72 cases of avian influenza A(H9N2) infection have been reported to WHO since December 2015, including two deaths (both due to underlying diseases).34\n\nOil-based inactivated H9N2 LPAI vaccines were used in the poultry sector in many countries to avoid H9N2 infection owing to the extensive essence of H9N2 viruses and their zoonotic potential.7,35–37 However, because the nature of HA antigenic epitopes is constantly changing, influenza vaccines must be updated each year to make sure strain-specific immunity, posing a significant challenging task to vaccine manufacturers. As a result, a global flu vaccine with broad protection against conserved influenza protein regions is required.\n\nIn the Indonesian poultry industry, this review addresses critical issues concerning to the evolution of AI viruses and vaccination strategy. Vaccination against the LPAI H9N2 virus is also discussed, including recent advances and challenges.\n\n\nThe emergence and evolution of the LPAI H9N2 virus\n\nTill to date, poultry industry in Indonesia has faced a serious threat from highly pathogenic avian influenza (HPAI). The H5N1 virus has rapidly spread across most provinces since its initial report in 2003–2004, eventually subsiding by the end of 2007 after killing over 16 million chickens.38,39 A second epidemic was recorded in Gorontalo in April 2011, leaving only one province disease-free.40 A phylogenetic assessment of the Indonesian 2.1. clade virus revealed a direct relationship to viruses of genotype Z discovered in Hunan Province, China, in 2002, indicating that they were likely introduced together. However, the propagation and transmission of the virus from Hunan to Indonesia remained unknown.41,42 All Indonesian H5N1 viruses were categorized as clade 2.1 up until 2008, with three virus sub-lineages: 2.1.1, 2.1.2, and 2.1.3. During the outbreaks between 2003 and 2005, the viruses of clade 2.1.1 were mostly isolated from HPAI-infected poultry. Clade 2.1.2 viruses with avian and human origins were primarily detected in Sumatra between 2004 and 2007, whereas clade 2.1.3 viruses were detected in 2004 and isolated from either birds or humans. Surprisingly, when clade 2.1.3 viruses became more prevalent, the number of clade 2.1.1 and 2.1.2 isolates began to fall. Despite the fact that 2.1.3 viruses have expanded throughout Indonesia and grown endemic in several areas, a new sub-lineage virus has arisen since 2004. In September 2012, AIV H5 subtype mortality was detected at several duck farms in Central Java. The HA genes of the duck isolates did not match those of long-established Indonesian clade 2.1 isolates, but they were surprisingly comparable to clade 2.3.2.1 viruses found lately in Vietnam, China, and Hong Kong.43 Although Bali is thought to be an excellent environment for influenza re-assortment because of its world-renowned tourism destination, suckling pigs, and fighting cocks’ history, until 2017, the island had reported only one human death from avian influenza. Between 2009 and 2011, surveillance of AI (H5N1) viruses in Bali revealed that the circulating A(H5N1) viruses belonged to clade 2.1.44–46\n\nIn early 2017, I Ketut Diarmita, Director General of Livestock and Animal Health at the Ministry of Agriculture, Indonesia announced that newly emerging AIV subtype H9N2 was discovered during surveillance by the Ministry of Agriculture’s Veterinary Center in South Sulawesi, West Java, Bali, Central Java, and Yogyakarta. As a result of these incidents, egg supply has decreased by the end of 2017.47\n\nAccording to Drh. Ni Made Ria Isriyanti, Ph.D., Head of Sub-Supervision of Veterinary Medicine, Directorate General of Livestock and Animal Health, Indonesia, the current state of the H9 virus is its proliferation in several provinces in Indonesia, including Java, Sumatera, Kalimantan, Sulawesi, and Bali. The number of H9N2 positive samples amounted to 49. Infected chickens are typically 30–60 weeks old. Although mortality is normally modest, one indication of the H9 virus is a decrease in egg production of up to 40–60% of normal, resulting in significant economic losses for farmers.48 The LPAI virus subtype H9N2 has been circulating in poultry and ducks in Indonesia, causing significant financial losses. It was also happening because of higher mortality and decreased production, particularly in broiler and layer chickens.15 Since 2003, the HPAIV subtype H5N1 highly pathogenic avian influenza (HPAI) virus has been found in Indonesia,49 with human cases resulting from H5N1 viruses being transmitted cross-species.\n\nA study conducted by Muflihanah et al. (2017) in Sidrap Regency, South Sulawesi found that the occurrence of AIV disease occurs within a period of 3–14 days, with an average mortality rate of less than 5% and a 50–80 percent decline in egg production. The genetic similarity of three isolates A/Chicken/Sidrap/07161511-1/2016, A/Chicken/Sidrap/07161511-61/2016, and A/Chicken/Sidrap/07170094-44OA/2017 is 98 percent H9N2. The phylogenetic tree results suggest that the tested sample appears to be from the Asian group or lineage Y280-H9N2.50\n\nAnother study conducted by Nugroho et al. (2018) in layer chicken in Java Island, 13 of the 33 virus isolates were VAI subtype H9N2 and belonged to the Y280 lineage, clade h9.4.2.5, and had genetic closeness with Chinese isolates in 2013 and Vietnam in 2014, with a nucleotide homology percentage of 96.9 percent–98.8 percent.51\n\nAccording to a study conducted by Wibawa H, et al. (2020) phylogenetic analysis of H9N2 virus HA9 gene (Bt/1291-OP/16) was found to be part of the China-Vietnam-Indonesia linage (CVI lineage).52\n\nIt indicated a close relationship with H9N2 viruses prevalent in China and Vietnam. That is why it was classified with the H9N2 viruses of the China Vietnam-Indonesia (CVI) lineage. Vietnam H9N2 viruses (H7F-LC4-51/14, H7F-LC4-26/14, and H7F 14 BN4 423/14) had already been recognized as members of the Y280-like group.53 The probable transmission paths of the AIV subtype H9N2 from Hong Kong to Indonesia (Figure 2).\n\nLive and Wet bird markets play an essential role in the ecology of HPAI subtype H5N1 and LPAI subtype H9N2 in Indonesia (Figure 3) and are a critical factor in the disease’s prevalence and endemicity.54 The co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets have raised the danger of human infection, complicating the epidemiological picture and heightening fears of a new influenza A virus pandemic.55\n\nIn Indonesia, primarily poultry (layer, backyard, and broiler) and duck are raised in conventional methods on small outdoor farms with poor management, and are primarily sold through Wet and LBMs. Ducks, commercial and domestic poultry, pigeons, starlings, quails, and other species of fancy birds are among the avian species found in Wet and LBMs.56,57\n\nSome farmers have begun to grow chickens and ducks in semi-intensive or intense ways. In Indonesia, conventional farming involves herding ducks and poultry onto open rice fields after harvest to consume leftover rice, other grains, and insects.58 H9N2 and high pathogenic avian influenza focused on continuing avian influenza surveillance. The subtype H5N1 was found in chicken farms and backyard chickens traded in LBMs.15 This previously confirmed findings that the trade of poultry, ducks and other birds in live bird markets (LBMs) played a crucial role in discovering a new AIV.59,60 According to a research, H9N2 viruses may operate as “new ventures” or “implementers” for human-infecting wild-bird influenza viruses (H7N9, H10N8).61,62\n\nMoreover, any reassortment of LPAI H9N2 viruses with highly pathogenic avian viruses may result in a more remarkable ability to cause human infection.63 Together with the tropical temperature in this region, these features allow long-term survival, multiplication, and spread among various chicken species, as well as transfer from chicken to humans. These variables also provide enough possibilities for existing influenza viruses, such as H9N2 and H5N1, to rejoin and form newer viruses with different host specificity. In Indonesia’s wet and live bird markets, the broad co-circulation of H9N2, H7N9, and high pathogenic H5N1 acts as a perfect mixing vessel for forming novel influenza subtypes. It is making the country a hotspot for the AI epidemic. Comprehensive vaccination programs have been implemented to mitigate the effects of H5, particularly newly emerging H9 subtype viruses spreading in Indonesia.14\n\n\nProspects for AI vaccination in the future\n\nIn Indonesia, vaccination is one of the most effective ways to combat the spread of avian influenza (AI) viruses. The vaccine master seed used in the field must be updated to keep up with the variety of circulating viruses and their potential to change. A vaccination strain (LPAI H9N2) virus isolated in 2017 (A/chicken/West Java/BBLitvet-RI/2017) vaccine (Patent IDP000056903)64 and BLi25Ut/18 virus were chosen in Indonesia based on their pathogenic, antigenic, and genetic features. Inactivated bivalent and monovalent H9N2 influenza vaccinations can induce an antibody response. It can lower mortality and virus shedding caused by reassortant H9N2 virus infection.17 With the help of FAO/OFFLU, the Indonesian government has built an effective vaccination strategy against H5N1 and H9N2 strains. Influenza Virus Monitoring (IVM online) is a web-based animal health laboratory system. This system manages antigenic and genomic data of circulating HPAI and LPAI viruses in Indonesia.65 Animal Disease Investigation Centers (DICs), private companies, and universities collaborate to monitor, collect isolates. The data is then submitted to IVM Online, which provides an up-to-date map of circulating HPAI and LPAI virus throughout Indonesia, allowing the optimal AI vaccine to be prescribed. In backyard farms, HPAI vaccines are commonly used to prevent LPAI using homologous (H5N1) or mixed with H9N2 strains.\n\nIn Indonesia, oil-based inactivated bivalents and monovalent vaccinations produce detectable antibody titers for all structural proteins, especially nucleoprotein and matrix protein. Antigens for antibody testing can be one or both of these proteins. As a result, using this method vaccinated birds cannot be discriminated from naturally sick birds. The inability to conduct surveillance has been a critical impediment to vaccination to combat avian influenza. There has been a lot of effort put towards matching the vaccination to the field variations. This is partly because immunization with any H9 virus appears to protect against clinical illness from a low pathogenic avian influenza exposure of the same subtype, irrespective of genetic variations. Oil-based inactivated bivalent and monovalent vaccinations produce many serum antibodies. The heterogeneity between vaccine and field strain can be estimated by comparing genomic information in the HA gene. However, when the vaccine is utilized as a control tool, both clinical safety and virus replication are concerns. According to experimental research, the closer the vaccine is to the field strain, the less virus is released in exposed birds.37 Genetic variation is a significant issue with avian influenza vaccines, as it reduces immunization effectiveness. Antigenic drift is considered to unfold when the field virus changes in response to the host’s antibodies. This method could be owing to vaccination or natural infection. However, in any scenario, the virus is under evolutionary changes to elude the body immunity, allowing multiplication at more significant titers in the host. There is a higher probability that a strain of the virus will spread to new hosts if the proliferative phase is better managed.\n\nVirus detection has decreased in Indonesia following vaccination programs against HPAI H5N1, showing that HPAI H5N1 is now under control. While the LPAI H9N2 virus is a new subtype, recent research has shown that monovalent and bivalent vaccines can protect chickens against reassortants H9N2 virus infections. It could lower mortality and virus shedding in chickens.17 Active surveillance of chicken farms and live bird markets is essential for further identifying new variants of the LPAI H9N2 virus in Indonesia. In order to prevent future epidemics, suitable vaccine seed viruses should be evaluated. Differentiation Infection in Vaccinated Animals (DIVA), a vaccine strategy, could be useful in assuring trading partners of the safety of poultry and poultry products. It has enhanced surveillance to detect virus infections.66 West Java has tested a proposed DIVA technique involving sentinel chickens.67,68 In Indonesia, the DIVA approach has not been widely accepted. Several different ways for employing viral protein as a marker in chickens, such as HA2,69 NS170 and M2e71 have been developed. New prospects for developing novel concept vaccines arise due to better molecular virology and the accessibility of genetic data on avian influenza. VLPs (Virus-like particles) have been proposed as a new generation of non-egg-based vaccinations with potential safety profiles for some viral illnesses.72–74 VLP is structurally and morphologically similar to infectious virus particles. Various antigenic epitopes have been shown to be particularly effective, owing to their ability to induce a wide spectrum of immune responses in the host.75,76 Insect or mammalian cells can easily create virus-like particles (VLP) vaccines incorporating influenza hemagglutinin (HA) and neuraminidase (NA) antigens by expressing HA and NA proteins together with a viral core protein, such as influenza M1.\n\nThe majority of influenza VLPs were created using viral nucleic acid expression methods. Their safety and immunogenicity were tested in various animal models.76,77 The H5N3 avian influenza virus-like particles (VLP) vaccine was studied in ducks. This study has demonstrated that the VLP vaccination may be administered safely in poultry.78 In a specified pathogen-free (SPF) chicken model, a VLP vaccination including the HA and M1 proteins was designed and tested against H9N2 LPAI.32,35 The pure VLP protein solution can be emulsified with Montanide ISA70 oil adjuvant (Seppic, Paris, France) to make a VLP vaccine. A single dose of H9 VLP vaccination resulted in significant antibody titers and reduced expulsion and release of virus progeny from the respiratory and gastrointestinal tracts in chickens. Furthermore, it enabled ELISA-based discrimination of avian influenza-infected poultry from vaccinated poultry utilizing a nucleocapsid antigen, availed DIVA approach.79 On the other hand, vaccination cost is regarded to be a major factor influencing the efficacy of synthetic subunit vaccines, such as VLP for poultry. Two subunits make up the influenza virus’s haemagglutinin (HA). The current influenza vaccine largely produces antibodies against the HA1 component, which is continually developing unexpectedly. The other component, HA2, is more stable, but the HA head region protects it. As a result, increasing the immunological response to HA2 may elicit broadly inhibiting antibodies.80,81 For the activation of protecting immune responses against infectious diseases, DNA vaccination has emerged as a viable alternative for standard protein-based vaccines. DNA vaccines have many advantages over traditional vaccinations, including greater stability, quick and low-cost manufacture, and the capacity to create vaccines for a broad range of infectious diseases. After being inoculated directly into mouse muscle for the first time in 1990, it was discovered that plasmid DNA vaccines could be made for the first time.81–83 These DNA vaccines are capable of encoding a chimeric DNA molecule of numerous antigenic sequences, which decreases production time and costs when compared to the traditional vaccinations we now use, without carrying the illnesses related with live attenuated vaccines. These vaccines based on plasmids can trigger both immune responses (humoral and cellular) while expressing high amounts of proteins of interest in cells. They can also neutralize antibodies produced by the mother.84,85\n\n\nConclusion\n\nIn Indonesia, the avian influenza subtype H5N1 is still endemic. In 2017, the newly developing subtype LPAI H9N2 was reported for the first time in Indonesia, on the island of Java. According to a previous study, H9N2 viruses have experienced substantial genetic reassortment in recent years, resulting in novel genotypes of H9N2 viruses in Indonesia. H9N2 virus genotypes that have recently emerged could play a vital role in the disease’s transmission in poultry and ducks. In order to detect future evolution and potential adaption of the LPAI H9N2 virus to humans and other mammalian species, active surveillance of these viruses is required in Indonesia. The widespread use of AI vaccinations in populations of animals may raise immunological selection pressure and mutation rates, which can lead to fast antigenic drift at antigenic locations. Better vaccination procedures and regular updating of vaccine seed variants are needed to boost immunogenicity and protective efficacy on poultry and duck farms. These techniques might be involved in selecting highly immunogenic vaccine seed strains, using efficient adjuvants for chickens and ducks, and utilizing innovative technology. In Indonesia, the co-circulation of H9N2 and H5N1 viruses in the field and live bird markets will increase the chances of gene reassortment between the viruses. Continued intensive monitoring of chicken farms and live bird markets for new variant low pathogenic H9N2 viruses and investigation of relevant vaccine seed viruses should be explored for future prevention. In Indonesia, inactivated bivalent and monovalent vaccinations have been utilized, and numerous new technology vaccines have been proposed to create low-cost, high-immunogenic vaccines. Together with efficient adjuvants, these novel vaccinations will undoubtedly lead to improved immunity against low pathogenic avian influenza subtype H9N2. In Indonesia, vaccination must be included in a complete, integrated disease-control strategy. National monitoring must be maintained at all times, as well as agricultural biosecurity and the DIVA strategy. In Indonesia, the eradication of these viruses could only be accomplished if all components of the control implemented.\n\n\nData availability\n\nNo data are associated with this article.",
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Virus Research. 2009; 143(2): 140–146. Publisher Full Text\n\nSwayne DE, Kapczynski DJI: Strategies and challenges for eliciting immunity against avian influenza virus in birds. Immunological Reviews. 2008; 225(1): 314–331. Publisher Full Text\n\nPrel A, Le Gall-Recule G, Jestin VJAP: Achievement of avian influenza virus-like particles that could be used as a subunit vaccine against low-pathogenic avian influenza strains in ducks. Avian Pathology. 2008; 37(5): 513–520. Publisher Full Text\n\nLee D-H, Park J-K, Lee Y-N, et al.: H9N2 avian influenza virus-like particle vaccine provides protective immunity and a strategy for the differentiation of infected from vaccinated animals. Vaccine. 2011; 29(23): 4003–4007. Publisher Full Text\n\nFan X, Hashem A, Chen Z, et al.: Targeting the HA2 subunit of influenza A virus hemagglutinin via CD40L provides universal protection against diverse subtypes. Mucosal Immunology. 2015; 8(1): 211–220. Publisher Full Text\n\nKhanna M, Saxena L, Gupta A, et al.: Influenza pandemics of 1918 and 2009: a comparative account. Future Virology. 2013; 8(4): 335–342. Publisher Full Text\n\nFarris E, Brown DM, Ramer-Tait AE, et al.: medicine. Micro-and nanoparticulates for DNA vaccine delivery. Experimental Biology Medicine. 2016; 241(9): 919–929. Publisher Full Text\n\nWolff JA, Malone RW, Williams P, et al.: Direct gene transfer into mouse muscle in vivo. Science. 1990; 247(4949): 1465–1468. Publisher Full Text\n\nDhama K, Mahendran M, Gupta PK, et al.: DNA vaccines and their applications in veterinary practice: current perspectives. Veterinary Research Communications. 2008; 32(5): 341–356. Publisher Full Text\n\nKhanna M, Sharma S, Kumar B, et al.: Protective immunity based on the conserved hemagglutinin stalk domain and its prospects for universal influenza vaccine development. BioMed Research International. 2014; 2014: 1–7. Publisher Full Text\n\nHafez MHYAA: Challenges to the poultry industry: Current perspectives and strategic future after the COVID-19 outbreak. Frontiers in Veterinary Science. 2020; 7. Publisher Full Text\n\nUmar S, Sarfraz S, Mushtaq A, et al.: Emerging threat of H9N2 viruses in poultry of Pakistan and vaccination strategy. World’s Poultry Science Journal. 2016 Jun; 72(2): 343–352."
}
|
[
{
"id": "138444",
"date": "08 Jun 2022",
"name": "Asghar Abbas",
"expertise": [
"Reviewer Expertise Pathobiology 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\nDear Editor/Authors,\nI have review of the manuscript \"Emerging threat and vaccination strategies of H9N2 viruses in poultry in Indonesia: A review\". The Article is well written and contains valuable information on Vaccination against Avian influenza Disease. However the manuscript needs minor revisions and improvement as per following comments\nEnglish Language of whole manuscript should be revised and improved. Justification (4-5 lines) of study should be added in introduction with proper latest references. Kindly add Associated risk factors of Avian influenza disease in Indonesia.\nI recommend manuscript be accept after minor revision.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Yes",
"responses": [
{
"c_id": "8422",
"date": "28 Jun 2022",
"name": "Saifur Rehman",
"role": "Author Response",
"response": "Dear Reviewer, Thanks for your valuable comments and suggestions on the manuscript entitled: “Emerging threats and vaccination strategies of H9N2 viruses in poultry in Indonesia: A review” We welcome feedback. We have made modifications to the study on the following points: English Language of the whole manuscript should be revised and improved Response: We have revised the English language of the whole manuscript. Justification (4-5 lines) of study should be added in the introduction with proper latest references. Response: We have added the Justification of the study in the Introduction section. Kindly add the Associated risk factors of Avian influenza disease in Indonesia. Response: We have added the associated risk factors of AIVs which showed association with AIV in Indonesia"
}
]
},
{
"id": "138445",
"date": "16 Jun 2022",
"name": "Agumah Nnabuife Bernard",
"expertise": [
"Reviewer Expertise I am a medical Microbiologist with specialties in Fungi of both medical and veterinary importance. I am also a certified Medical Laboratory Scientist with specialties in Medical Parasitology and entomology"
],
"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 have gone through the review article. The author did wonderfully well as the facts and figures were aptly captured with most categorical statements backed up with appropriate citations.\nThe author did well in:\nCapturing the history and the first documentation of the H9N2 Avian Influenza in Indonesia. Noting the fact that the contemporary low pathogenic nature exhibited by the ethiologic agent and its prospects of becoming highly pathogenic in the nearest future. This is also a good headway. It is worthy of note that the author threw good light to the prospects of antigenic drift and zoonotic transmission. Though only the Hongkong and the Korean genotypes were explained by way of history; the author was able to fully highlight how Indonesia currently has a very high distribution of H9N2 in Indonesian poultry Industry. It is also worthy of note that the author highlighted how the conventional methods used in raising birds has contributed in the endemicity of the H9N2 Avian Influenza in Indonesia. Poor management and sales in wet and live birds market are well cited as contributing factors in the spread of Avian influenza. The author was able to highlight various subtypes especially the H5N1 which caused the Bird flu pandemic that lasted from 2003-2007. The most novel information from the authors review is that it is highly likely that the next form of Influenza to be contracted by humans in Indonesia is the H9N2 Avian influenza. Hence adequate surveillance and analysis of the genetic flexibility of the virus opens up a huge prospect for vaccine development should the H9N2 virus infect humans.\nA little correction I may suggest is with the topic. It should read Emerging threats and not threat. . . . as there may be many variables with respect to the medical importance of the H9N2 virus in Poultry in Indonesia.\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Yes",
"responses": [
{
"c_id": "8423",
"date": "28 Jun 2022",
"name": "Saifur Rehman",
"role": "Author Response",
"response": "2nd Reviewer comments A minor correction I may suggest is with the topic. It should read Emerging threats and not threat. as there may be many variables with respect to the medical importance of the H9N2 virus in Poultry in Indonesia. Response: We have changed the Title according to your suggestions as “Emerging threats and vaccination strategies of H9N2 viruses in poultry in Indonesia: A review\"."
}
]
}
] | 1
|
https://f1000research.com/articles/11-548
|
https://f1000research.com/articles/10-1015/v1
|
06 Oct 21
|
{
"type": "Research Article",
"title": "COVID19 vaccination choice among Iraqi students at Al-Zahraa University for women",
"authors": [
"Hassan Hadi Al Kazzaz"
],
"abstract": "Background: COVID19 vaccine rejection is a global issue that most developing countries face. A study of COVID-19 vaccine preference among Al-Zahraa University female students will pave the way to resolving the issue of vaccine rejection among students. Students' preferences and refusals of the COVID19 vaccine were evaluated to determine the reasons for their decisions. Methods: This study involved 198 students from Al-Zahraa University for women. An observational cross-sectional study was conducted at Al-Zahraa University in Karbala, Iraq, to find out which Health and Medical Technology students preferred the COVID19 vaccine. Tests based on statistics made use of frequency and rate data. Results: Most students (95%) were over the age of 19. The COVID-19 vaccine was rejected by 138 people (70.4%). A total of 43 students (28.5%) believed that the COVID19 vaccine may not be completely safe. 49.3% of students were not aware of the differences between the various types of vaccines. Pfizer was the most preferred by 64 (34.8%), AstraZeneca by 17 (9.2%), and Chinse-Sinovac by only 11 (6%). 20 students (16.4%) believed that with the vaccine they could return to life as it was before the COVID-19 pandemic. Covid-19 vaccine acceptance among Al-Zahara University students may be low in part because of myths, and partly because of the fear of side-effects associated with the vaccine. Conclusion: Information about COVID-19 vaccines should be transparently communicated to the media by health authorities to help the public make informed decisions.",
"keywords": [
"COVID-19",
"vaccine",
"preference",
"Iraqi students",
"refusal."
],
"content": "Introduction\n\nScientists are searching for vaccines and medicines to combat the current global COVID-19 pandemic. COVID-19's origins and relationship to bats still needs to be uncovered, but according to current scientific thinking, it's origin was not the result of genetic experimentation, but rather of natural selection.1 This disease has become a major source of concern for medical professionals all over the world due to its rapid spread. It is imperative that all health care providers are up to date with COVID-19 information.2 COVID-19 affects the respiratory system and other internal organs in both animals and humans.3\n\nA thoughtful understanding of vaccine hesitation must be established in the specific historical, political, and socio-cultural context in which vaccination takes place, in addition to an understanding of the factors affecting vaccine acceptance at the individual level. Wider variables effecting vaccination hesitation, such as the function of public health and vaccines, should also be considered.4 In developing nations, parents' failure to bring their children to a vaccination session is frequently linked to vaccination service deficiencies, mirroring the common low-quality immunization pattern in many of those countries. The collective non-adherence form of resistance appears to be mostly driven by religious convictions in poor countries.5 Medical students are among the group of frontline healthcare providers most likely to be exposed to COVID-19 patients. In a recent study on American medical students, concern for serious side effects from the vaccine was independently predictive of lower odds of intent to participate in a COVID-19 vaccine trial (AOR = 0.41, P = 0.01).6 Attitudes towards the vaccine do appear to be mostly positive amongst health care worker however, in a recent study on French healthcare workers intention to get vaccinated against COVID-19 reached 75%.7 Many countries have researched to develop the coronavirus SARS-COV-2 vaccine.8 Fear, stress, and worry are normal responses to real threats, especially in times of uncertainty and thus some vaccine hesitancy is to be expected.9\n\nThis potential hesitancy and lack of acceptance of COVID vaccines is likely to affect vaccination uptake. A lack of trust in the media amongst college students in the digital era could affect the uptake and acceptance of the COVID-19 vaccine. When the world was faced with a new and terrifying epidemic, television played a crucial role in connecting the government with its citizens. This hesitancy is a serious concern as the vaccine becomes effective only when it is accepted and used by the majority of the global population.10\n\n\nMethods\n\n198 first-year students in the Department of Anesthesia at the University of Al-Zahra participated in this cross-sectional questionnaire-based study. A Google Classroom event was attended by 198 students resulting in a response rate of (100%). This research study was analytical in nature. The questionnaire was created by the researcher, and a few questions were adapted from another study13 and incorporated into the questionnaire. The period of research and data collection was between Feb. 2021 and August 2021. Questionnaires were distributed among the students using Google Classroom and were returned by the students after completion via the same method. The responses were retrieved as an excel file from google form a questionnaire and imported into the SPSS version.23 (IBM SPSS Statistics, RRID:SCR_019096) to be analyzed and frequencies and percentages determined. An alternative open-access software would be R (R Project for Statistical Computing, RRID:SCR_001905). The multiple-choice questionnaire is related to COVID19 vaccination preference. The questionnaire is comprised of four tables with eight questions. Statistical tests used frequency and rates.\n\nEthical approval was granted by the independent ethics committee of Al-Zahra University in Karbala-Iraq prior to the research, approval number (HREC 35). The requirement for written consent was waived by the ethics committee. To all those who received a questionnaire, consent messages were sent out, outlining the importance of the study, as well as the researcher's right to privacy. Following a brief explanation of the study's objectives, time commitment, confidentiality, and future benefits to their community to each female participant's consent, they verbally agreed to participate in the study.\n\n\nResults\n\nThe Al-Zahra University for Women's Anesthesia Department has 198 students in its first year. Table 1 shows the participants' demographic and health-related characteristics. Most students were above 19 years (95%). Out of 170 students, 132 (86.2%) were not married. Most of the students were from Karbala (152, 77.9%). 110 people reported that a close family member had been previously diagnosed with COVID-19 (56.1%), Those with a history of other vaccines rejection were (79%). After being offered the COVID19 vaccine, 188 (70.4%) said that they would decline the vaccine if offered. The type of COVID19 vaccine that students prefer is shown in Table 2. Approximately (49.3%) of students didn't know the difference between types of vaccines. In comparison, 64 (34.8%) preferred the Pfizer vaccine, while 17 (9.2%) preferred the AstraZeneca vaccine, and only 11 (6%) favored the Chinse-Sinovac vaccine. Reasons for wanting to be vaccinated against COVID-19 are shown in Table 3. Among the students, 20 (16.4 %t) reported believing that it would enable them to return to a normal life as a reason for wanting to be vaccinated, and 45 (36.7%) had other reasons to accept the vaccine besides those mentioned in this study. A list of reasons for rejecting COVID-19 vaccination is provided in Table 4. 42.5% of students believed that the COVID19 vaccines may not be completely safe, whilst 33 (21.9%) expressed concern over the vaccine's possible side effects.\n\n\nDiscussion\n\nRecently, the COVID-19 pandemic has resulted in a rise in mortality and morbidity and affected the lives of people around the world.11 In the AL-Snaafi study,12 COVID19 experience in individuals or their families was 523 (48.7%), which was the same in our study. This could occur because of frequent visits between the two neighboring countries. 154 (79%) of the participants had a history of vaccine rejection. 138 people (70.4%) of our participants said that they would reject the COVID19 vaccine. In a recent study of Egyptian medical students,13 90.5% perceived the importance of vaccination against COVID-19 while in an Italian study of vaccine hesitancy13 only 51.2% reported that they planned to get the COVID-19 vaccine. This might reflect a difference in the degree of vaccine importance concept (Table 1). The availability of the COVID-19 vaccine has proven critical in containing the COVID-19 pandemic. Acceptance of the COVID-19 vaccination by the general public will result in the success of this program.14\n\nAl-Zahraa medical students prefer Pfizer vaccine 46 (34.8%), Oxford-AstraZeneca vaccine 17 (9.2%), Chinse-Sinovac vaccine 11 (6%), and 92 (50%) were not aware of the differences between the vaccines. In the aforementioned Italian study13 amongst health workers asked about taking the COVID-19 vaccine, only 20% and 24% preferred to take the Oxford-AstraZeneca or Pfizer vaccine, respectively. Participants in a Saudi Arabian study15 preferred the Pfizer-BioNTech vaccine (20.9%), which was lower than the result in our study. Most Iraqis in this study thought Pfizer's vaccination was the best because it had fewer side effects, and this perception may have been influenced by social media promotion.\n\nIn Saied's study16 among Egyptian health workers (46.2%) reported preferring Pfizer-BioNTech and in AL-Snaafi's study12 preferred the Pfizer-BioNTech vaccine which is much higher than Al-Zahraa university students' preference for the same vaccine. The difference might be due to the unfamiliarity of Al-Zahraa university students with the vaccine mechanism and other details in addition to the rumors accompanied with the release of the COVID19 vaccine (Table 2).\n\nIn this study, 20 students (16.4%) wanted to be vaccinated against COVID-19 so that they could resume their normal lives. 45 (36.9%) had other reasons not mentioned. In the Yoda study on a Japanese sample 86.4% of survey respondents thought that vaccination was effective and preventive, and 21.3% thought they would be able to resume their normal lives.17 The disparity between the results of the studies could be attributed to higher living standards and distinctive health promotion activity in Japan as compared to Iraq (Table 3). Furthermore, in our study on the reasons for refusing to be vaccinated against COVID-19, we discovered that 43(28.5%) of the participants were concerned about potential side effects, while 33 (21.5) believed that the COVID-19 vaccine is not safe. In a survey of the Pakistani general public 28.4% felt the COVID-19 vaccination was developed in a relatively short time, while 19.0% thought that the vaccine was not safe and could kill people.18 This indicates that both participants in Iraq and Pakistan have similar myths about the COVID-19 vaccine.\n\nIn Yoda's study about 66.5% were concerned about side effects. Nearly 20% did not trust vaccine efficiency. Comparing with this study, the Japanese study shows more hesitation about side effects than in our Iraqi sample (Table 4).\n\n\nConclusion\n\nAs a result of this research, Al-Zahraa university students' low acceptance of the COVID-19 vaccine has been attributed to myths and fear of side effects. This may be due to the belief that Oxford-AstraZeneca vaccines have more side effects than Pfizer vaccines, and the fact that most of them do not know the difference between COVID19 vaccines at Al-Zahraa University. Vaccine refusal in underdeveloped nations should be addressed with public precautions and emergency measures.\n\n\nRecommendation\n\nInformation provided to the media about COVID-19 vaccines should be transparent, especially in terms of side effects and safety. Government must also build public trust so that people believe in the government's health advice.\n\n\nConsent\n\nIt was agreed upon by participants that a message would be sent to the entire recipient list of the questionnaire, mentioning the study's significance as well as their freedom to share their information with the researcher while maintaining their privacy. They were given the option of declining to participate, and they were informed that they might withdraw at any point during the research without giving a reason.\n\nThis study was approved by the Human Research Ethics committee at Al-Zahraa university, Approval number (HREC 35).\n\n\nData availability\n\nZenodo: COVID19 vaccination choice among Iraqi students at Al-Zahraa University for women. https://doi.org/10.5281/zenodo.5457852.19\n\nThis project contains the following underlying data:\n\n• Blank Quiz (Responses).xlsx (Spreadsheet of questionnaire responses).\n\n• COVID19 vaccination choice among Iraqi students at Q.pdf (a blank copy of the questionnaire used in the research).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgment\n\nI thank all student participants who contributed to this study.\n\n\nReferences\n\nA.A. D: Using Remdesivir and Dexamethasone for Treatment of SARS-CoV-2 Shortens the patient's stay in the Hospital. researchgate.net. 2021 [cited 2021 Aug 31]; 11(2): 138–140. Reference Source\n\nFernandes M, Thakur JR, Gavanje M: A Study to assess knowledge regarding covid-19 among Nursing students. Asian J. Nurs. Educ. Res. 2021 [cited 2021 Jan 14]; 11: 65–67. Reference SourcePublisher Full Text\n\nPatil V: Research AS-AJ of P, 2020 U: Corona (Covid-19). asianjpr.com. 2020 [cited 2021 Aug 31]; 10(4): 275–285. Reference Source\n\nDubé E, Laberge C, Guay M:Vaccine hesitancy: an overview. Taylor Fr; 2013 Aug [cited 2021 Sep 4]; 9(8): 1763–1773. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPH Streefland d: Public doubts about vaccination safety and resistance against vaccination. Elsevier; 2001 [cited 2021 Sep 4]; 55(3): 159–172. Reference SourcePublisher Full Text\n\nLucia V, Kelekar A: Oxford NA-J of PH, 2020 U: COVID-19 vaccine hesitancy among medical students. J Public Heal (Oxford, England). 2020 [cited 2021 Sep 4]; 43: 445–449. Reference SourcePubMed Abstract | Publisher Full Text | Free Full Text\n\nGagneux-Brunon A, Detoc M, Bruel S, et al.: Intention to get vaccinations against COVID-19 in French healthcare workers during the first pandemic wave: a cross-sectional survey. J Hosp Infect. 2021 [cited 2021 Sep 4]; 108: 168–173. Reference SourcePubMed Abstract | Publisher Full Text | Free Full Text\n\nIngole R, et al.: Is Prevaccination the reason for less morbidity and mortality for COVID-19 in India: An Epidemiological study. Res J Sci Technol. 2020 [cited 2021 Sep 6]; 12(4): 285–288. Reference SourcePublisher Full Text\n\nBiradar V: And PD-IJ of NE, 2020 U: Impact of COVID19 on Child Health: Parents Perspective. Int J Nurs Educ Res. 2020 [cited 2021 Sep 6]; 8(4): 463–467. Reference SourcePublisher Full Text\n\nQiao S, Friedman D, Tam C, Zeng C: Vaccine acceptance among college students in South Carolina: Do information sources and trust in information make a difference?. medrxiv.org. [cited 2021 Sep 21]. Publisher Full Text\n\nKhasawneh A, Humeidan A: JA-F in public, 2020 U: Medical students and COVID-19: knowledge, attitudes, and precautionary measures. A descriptive study from Jordan. frontiersin.org. 2020 [cited 2021 Aug 31]; 8: 253. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAl-Sanafi M, Sallam M: Psychological determinants of covid-19 vaccine acceptance among healthcare workers in kuwait. Vaccines. 2021 [cited 2021 Aug 31]; 9: p. 701. Reference SourcePubMed Abstract | Publisher Full Text | Free Full Text\n\nReno C, Maietti E, Fantini MP, et al.: SavEnhancing COVID-19 Vaccines Acceptance: Results from a Survey on Vaccine Hesitancy in Northern Italyoia, E.,… - Google Scholar. Vaccines. 2021 [cited 2021 Aug 31]; 9: 378. Reference SourcePubMed Abstract | Publisher Full Text | Free Full Text\n\nBell S, Clarke R, Mounier-Jack S: Parents’ and guardians’ views on the acceptability of a future COVID-19 vaccine: A multi-methods study in England. Elsevier; 2020 [cited 2021 Aug 31]; 38(49): 7789–7798. Reference SourcePublisher Full Text\n\nTemsah M, Barry M, Aljamaan F, et al.: Adenovirus and RNA-based COVID-19 vaccines’ perceptions and acceptance among healthcare workers in Saudi Arabia: a national survey. bmjopen.bmj.com. 2021 [cited 2021 Aug 31]; 11(6): e048586. Reference Source\n\nSaied S, Saied E: IK-J of medical, 2021 U: Vaccine hesitancy: Beliefs and barriers associated with COVID-19 vaccination among Egyptian medical students. Wiley Online Libr; 2021 [cited 2021 Aug 31]; 93(7): 4280–4291. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYoda T, Katsuyama H: Willingness to receive COVID-19 vaccination in Japan. Vaccines. 2021 [cited 2021 Aug 31]; 9: 48. Reference SourcePubMed Abstract | Publisher Full Text | Free Full Text\n\nArshad MS, Hussain I, Mahmood T, et al.: National Survey to Assess the COVID-19 Vaccine-Related Conspiracy Beliefs, Acceptability, Preference, and Willingness to Pay among the General Population of Pakistan. Vaccines. 2021 [cited 2021 Aug 31]; 9: 720. Reference SourcePubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "121595",
"date": "22 Mar 2022",
"name": "Mohammad Yasir Essar",
"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 study “COVID19 vaccination choice among Iraqi students at Al-Zahraa University for women” by Hassan Hadi Al Kazzaz has investigated the COVID-19 vaccination choice In Al-Zahraa university. I appreciate the author for conducting this important study. However, I would suggest some comments.\nFirst, please talk about COVID-19 statistics in Iraq and particularly in city where this university is located.\nSecond, talk about what is Vaccine Hesitancy in your introduction. Provide a short description. Use these articles for reference if needed. 12\nThird, in your discussion, try to compare more studies with your findings. One study I would like you to compare could be Nehmat et al.3\nFourth, it would be great if you could add more to the recommendations. For instance, how your findings could help address the problem. How health policymakers can benefit from 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? 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": "8047",
"date": "06 Apr 2022",
"name": "HASSAN al-kazzaz",
"role": "Author Response",
"response": "Dear Dr Mohamad, Thank you so much for your very fruitful notes. I will work on these notes and let you know. Wishing you all the best, Hassan Al-Kazzaz"
}
]
},
{
"id": "125307",
"date": "01 Apr 2022",
"name": "Bijaya Kumar Padhi",
"expertise": [
"Reviewer Expertise Public 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 authors used an online-based cross-sectional study among students (n=198) to understand students' preferences and refusals of the COVID19 vaccine in Iraq. Though low sample size is a concern, the study demonstrated a high rate of vaccine refusal. The manuscript is well written, data presentations are clear and adequate. My specific comments are as under:\nIntroduction – How this research fills the gap in the literature? Hypothesis is not mentioned.\n\nMethod section – How were the study samples obtained? Does the study sample reflect the appropriate and representative population? Inclusion and exclusion criteria not mentioned. Data collection procedure not clearly written.\n\nDevelopment of study tools should be described in the method section.\n\nPsychometrics of the survey instruments should be provided.\n\nDiscussion section – more details are needed with regard to implications of the findings for clinical audiences.\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? Partly",
"responses": [
{
"c_id": "8046",
"date": "06 Apr 2022",
"name": "HASSAN al-kazzaz",
"role": "Author Response",
"response": "Dear Sir, Thank you so much for your very fruitful notes. In regard to: No.1 - The hypothesis was most of Alzahraa university students refuse COVID-19 vaccine. The results in this study approved this hypothesis. No. 2- the study include all students in the university which represent the university and also represent the inclusion criteria. The inclusion criteria will be all students outside Al Zahrraa university. Also the study used google class room in collection of the data because of the event of COVID-19 pandemic and the students were taking their lessons via intermate. No.3 - About study tools I had used google classroom and statistics that mention in methodology and will be more than happy if you need any other information of interest. No.4- Most of the students refuse to do psychometric test because they think it have some discriminatory against gender. The study respects the privacy of the students. No.5 - Rejection of Covid19 vaccine is a global problem. The study pointed out that alzahraa students were on the same floor. Governmental and nongovernmental agencies have to take their roles in convincing their communities to accept COVID-19 vaccination through out media and other steps. this will be done through building trust bridges between the people and health authorities. Its my pleasure and great honor to have you as reviewer to my research and hope my answer will be convenient to you. Please do not hesitate to ask any questions which will add to my knowledge new information. Waiting for your reply, wishing you all the best, Hassan Al Kazzaz"
}
]
}
] | 1
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https://f1000research.com/articles/10-1015
|
https://f1000research.com/articles/10-765/v1
|
06 Aug 21
|
{
"type": "Study Protocol",
"title": "Protocol for a systematic review and meta-analysis: to investigate the association of adherence to plant-based diets with cardiovascular disease risk",
"authors": [
"Tatum Lopes",
"Annalise E. Zemlin",
"Mieke Faber",
"Solange Durao",
"Rajiv T. Erasmus",
"Andre P. Kengne",
"Annalise E. Zemlin",
"Mieke Faber",
"Solange Durao",
"Rajiv T. Erasmus",
"Andre P. Kengne"
],
"abstract": "Background: Plant-based diets (PBDs) are characterised as healthy dietary patterns that emphasise the intake of plant foods and limit the intake of animal foods. The Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets are common examples of healthy dietary patterns that are mainly plant based. There are different dietary pattern analysis approaches and scoring systems available to construct indices that measure adherence to a dietary pattern. Nutritional epidemiology studies necessitate the use of appropriate dietary indices when investigating diet-disease associations. Methods: This systematic review protocol was developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols (PRISMA-P) guidelines. PubMed–Medline, Scopus and relevant biomedical databases within EBSCOhost will be searched up to August 2021 using relevant key words. Two reviewers will independently screen the identified records and review the eligible full texts for inclusion. Discrepancies will be resolved by consensus or through discussion with a third reviewer. Appropriate meta-analysis will be performed where possible and consistency of the findings checked through subgroup analysis. Heterogeneity across studies will be assessed and quantified, and publication bias investigated. Relevant sensitivity analyses will be performed to substantiate the robustness of the study findings. Conclusion: Currently, there is some inconsistency in defining and measuring adherence to a PBD across study populations. In addition to this, a lack of global data on the association between adherence to a PBD and CVD risk. This systematic review could aid in promoting the worldwide uptake of these findings for policy and practice purposes. This research will use previously published studies; and therefore, will not require ethical approval.",
"keywords": [
"Plant-based diet",
"dietary methods",
"diet-disease associations",
"cardiovascular disease risk"
],
"content": "List of abbreviations\n\nCVD: Cardiovascular disease\n\nDASH: Dietary Approaches to Stop Hypertension\n\nHR: Hazard ratio\n\nISI: Institute for Scientific Information\n\nNHLBI: National Heart, Lung, and Blood Institute\n\nOR: Odds ratio\n\nPBD(s): Plant-based diet(s)\n\nPEO: Population, Exposure, and Outcome\n\nPRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analysis\n\nPRISMA-P: Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols\n\nRCTs: Randomized controlled trials\n\nRR: Relative risk\n\nWHO: World Health Organization\n\n95% CIs: 95% Confidence intervals\n\n\nIntroduction\n\nIn the literature, there are widespread inconsistencies with regards to how plant-based diets (PBDs) have been described. This is due to the scarcity of data on how to define a PBD. PBDs are known for emphasising the consumption of foods derived from plants, such as fruits, vegetables, whole grains, legumes, nuts, and seeds. Ostfeld defined a PBD as a diet solely made up of naturally derived plant foods, which does not include any animal foods (e.g. resembling a vegan diet), not exempting eggs or dairy products.1 Other well-known healthy dietary patterns that predominantly contain plant foods are the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets. The Mediterranean diet encourages the consumption of healthy plant foods namely vegetables, fruits, whole grains, and nuts, with olive oil as primary source of added fat. Moreover, the Mediterranean diet limits the intake of red and processed meat, poultry, and dairy products and is low in sugar.2 The DASH diet also promotes the consumption of plant foods that are primarily characteristic of a PBD, such as fruits, vegetables, whole grains, nuts, and seeds. Additionally, animal foods are also included in the DASH diet in minimal amounts of red meat, fish, poultry and low-fat dairy products.2\n\nA dietary pattern is the amount, variety, combination of foods and beverages in a diet and the frequency with which they are usually consumed.3,4 Dietary pattern analysis can be predefined (a priori) or data driven (a posteriori); these are two different approaches used to assess dietary patterns. An a posteriori analysis identifies similarities and assesses the variance (i.e. variables or the foods consumed) within a group (i.e. the observations in a data set or rather the study population). Principal component analysis, cluster analysis and factor analysis are among the multivariable statistical techniques utilised to obtain a posteriori scores. In comparison, a priori analysis assigns a score to each nutrient or food, based on existing nutrition knowledge that has a strong health-related focus, and the recommendations relative to a specific population’s dietary guidelines.5–7 Different scoring systems can be used to construct a priori indices, which can subsequently measure adherence to a dietary pattern.8\n\nDietary indices are based on an individual’s reported intake of either nutrients, foods or the combination of them. Certain foods and nutrients are beneficial for health and consumption thereof should be encouraged to achieve nutritional adequacy, while others are detrimental for health and should be limited and consumed in moderation.9 Dietary indices may include only certain nutrients, foods or food groups in their construction and therefore often do not reflect total dietary intake. Nutrient intake data should preferably be based on country-specific food composition tables, if available. Often energy-adjusted intakes of nutrients or foods are used when constructing dietary indices. Each of the dietary components (e.g. nutrients or foods) included in the dietary index are scored either as absolute using predefined cut-off values or relative based on the distribution of intake (e.g. quintiles).\n\nPredefined cut-off values10 are based on dietary recommendations and are indicative of healthy intakes. Relative scoring depends on the distribution of intake within a specific population; whereby higher intakes are scored higher for the adequacy components and lower for the moderation components. However, relative scoring may not necessarily reflect optimum intakes. The scores of the individual components are summed to obtain the final dietary index score, which can be used as either a continuous variable11 or to group individuals in absolute or relative categories. The total score of a dietary index may range depending on the number of food items, grouping of dietary components, and type of scoring system that is used.6,7 An example of relative scoring is illustrated in the approach by Satjia et al. In their study they created different versions of a PBD index. Food groups were classified as healthy plant foods, less healthy plant foods, and animal foods. These food groups were ranked by quintiles of consumption and graded with positive or reverse scores, depending on which PBD index was calculated.12\n\nDifferent dietary indices might rank an individual’s PBD adherence differently and create inconsistences, which may consequently influence the diet–disease associations across published studies.13 Evidence-based literature has shown that there are diverse associations reported between PBDs and cardiovascular disease (CVD) and CVD risk. A PBD1 has been encouraged as a lifestyle intervention in two case reports on CVD.14,15 These patients with angina refused surgery, but opted to join a Cardiac Wellness Program that recommended adopting a PBD for the reversal of CVD and/or the prevention of CVD risk.1,14,15 Another study by Lara and colleagues16 reported on the association between a plant-based dietary pattern amongst other dietary patterns and the incidence of CVD hospitalisation due to heart failure. A high adherence to the plant-based dietary pattern was statistically significantly associated with a decreased likelihood of incident heart failure. However, several studies have focussed on the association of PBDs with CVD risk, specifically the reduced risk of developing hypertension and type 2 diabetes.13,17–19\n\n\nRationale\n\nNutrition-based epidemiological studies are crucial to generate findings on the association between a PBD and health outcomes. Evidence of these associations may be inconsistent amongst studies that are conducted across different regions and countries. The latter may be due to studies utilising different dietary pattern analysis and scoring systems to construct plant-based diet indices for measuring adherence to a PBD. Furthermore, the extent of such discrepancies between the definitions of a PBD and measures of adherence as they apply globally; to the study of the associations between adherence to a PBD and CVD risk, warrants further investigation. Thus, considering these variations, it could prove valuable to investigate to what extent different methods may influence study findings. This is important prior to conducting studies in under-researched populations such as Africa, where there is a scarcity of resources and paucity of data on the association of PBDs with CVD risk. Therefore, this review aims to address this gap in the literature on PBD studies.\n\n\nObjectives\n\nThis protocol is for a systematic review of studies on the association of PBD with CVD risk in order to:\n\n• Assess how PBDs have been defined across those studies;\n\n• Examine which methods are used to measure adherence to a PBD; and\n\n• Examine the effect of differences in the definition and measures of adherence on the association of PBD with CVD risk\n\n\nReview questions\n\nAcross studies of the association of PBD with CVD risk, the review will seek to address the following questions:\n\n\n\n1. How has a PBD been defined across published studies globally?\n\n2. Which methods have been used to measure adherence to a PBD?\n\n\n\n3. Does the association of PBD with CVD risk differ by definition of PBD and methods for measuring adherence to a PBD?\n\n\nProtocol\n\nInclusion criteria\n\nObservational (i.e. cohort, cross-sectional and case–control) studies reporting on the association between PBDs and CVD risk will be included in the review. The population, exposure, and outcome (PEO) strategy will be applied to identify relevant studies. Study populations will consist of men and/or women (aged 18 years and above), irrespective of their ethnicity. Studies published in English and French will be eligible. We will include studies that assessed adherence to a PBD, using any definition to investigate its association with CVD risk. However, only studies with a clear description of a PBD as a dietary exposure will be included. These studies should also report which dietary methods they used to measure adherence to a PBD. We will focus on assessing the association between adherence to a PBD and CVD risk as a health outcome. Studies will be eligible if: measurements for hypertension and/or overweight/obesity, and/or biomarkers measurements for assessing dysglycaemia and/or diabetes mellitus and/or dyslipidaemia were reported. Studies will also be included if they assessed CVD risk factors in combination as metabolic syndrome and/or reported an absolute CVD risk score. In addition to this, studies reporting on major cardiovascular outcomes, such as myocardial infarction and/or coronary heart disease, stroke and/or cerebrovascular disease and/or sudden cardiac death will be included in the review.\n\nExclusion criteria\n\nThe exclusion criteria will pertain to studies that were conducted in children, female participants that are pregnant or breastfeeding or animals. Studies that have reported on the Mediterranean or DASH diets, which are predominantly plant-based will be included in the secondary analysis; if the authors did not state that they were using it to define a PBD. Published studies without primary data such as reviews, letters to the editor, commentaries and/or editorials will not be eligible. After full-text assessment, studies that have investigated the associations of PBD with CVD risk, but have not reported the risk estimates, measures of correlation and regression analyses will be excluded. Studies will also be excluded if they do not have the necessary supplementary materials or have insufficient information for estimating adherence to a PBD, and such information cannot be obtained from the authors of the study.\n\nThe literature search will be performed in PubMed–Medline and Scopus databases amongst other biomedical databases within the EBSCOhost platform, i.e. Global Health. The databases will be searched for population and/or hospital-based observational studies that were published up to August 2021. Manual searches will be conducted by screening the reference lists of the eligible studies to identify other articles of interest. The ISI Web of Science will be utilised to trace the citations.\n\nGrey literature\n\nThe World Health Organization (WHO) website will be browsed according to themes, i.e. nutrition and non-communicable diseases for any pertinent information or reports available from the Global Health Observatory data repository. The Institute for Scientific Information (ISI) Web of Science will be searched for conference proceedings that are relevant to the review questions. Conference abstracts will be retrieved from the conference websites. If necessary, authors or experts in the field will be contacted for any unpublished studies with relevant data.\n\n\nSearch strategy\n\nA comprehensive literature search will be conducted to identify eligible studies without any restriction to country. A search strategy will be applied in all electronic databases and adapted accordingly. The search terms will utilise the following key words as free texts and/or medical subject headings to find relevant studies: plant-based diet OR plant-based OR adherence to a plant-based diet OR healthy dietary pattern AND dietary pattern analysis OR a priori OR a posteriori OR dietary indices AND cardiovascular disease OR heart disease OR ischaemic/ischemic chest pain OR myocardial infarction OR heart attack OR coronary artery disease OR congestive heart failure OR cardiac arrest OR stroke OR cerebrovascular disease OR sudden death OR sudden cardiac death OR hypertension OR high blood pressure OR diabetes OR dysglycaemia OR dysglycemia OR dyslipidaemia OR dyslipidemia OR hyperglycaemia OR hyperglycemia OR prediabetes OR impaired glucose tolerance OR impaired fasting glycaemia/glycemia OR obesity OR overweight OR metabolic syndrome OR cardiovascular risk score OR cardiovascular risk model.\n\n\nStudy records\n\nEndNote X8 citation management software (RRID:SCR_014001) will be used to identify any duplicates; Zotero (RRID:SCR_013784) is an open-access alternative. Duplicate records will be removed prior to screening. If multiple publications from the same study are found the most comprehensive publication will be included. The Rayyan application for systematic reviews (RRID:SCR_017584)20 will be used to manage and screen the identified records.\n\n\nSelection process\n\nThe titles and abstracts of identified records will be screened independently by two reviewers. The full text of all eligible studies will be reviewed independently by the two reviewers and checked by a third reviewer for consensus. The Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) flow diagram will be utilised to summarise the study selection process. Exclusion reasons will be provided and documented for all the full-text reviewed studies, which do not meet the criteria of the review.\n\n\nData extraction\n\nTwo reviewers will independently extract data from all eligible studies, using the data collection form for RCTs and non-RCTs from the Cochrane Collaboration21 that will be adapted if necessary. Disagreements will be discussed with a third reviewer and resolved by consensus. Data items will be captured in Microsoft Excel (RRID:SCR_016137) spreadsheets; Google Sheets (RRID:SCR_017679) is an open-access alternative. The following general data items will be extracted from each study: the first author’s name, year of publication, geographical region, country, and study design and sample size. The PEO strategy will also be utilised to extract study-specific data. It will include the demographics of study participants such as age, sex and ethnicity, the dietary exposure and how it was defined and how adherence was measured including the dietary assessment method and reference period that was used, how the food intake was quantified, which dietary pattern analysis approach was applied to construct the dietary index, also which health outcome was assessed.\n\n\nRisk of bias assessment\n\nThe risk of bias will be assessed independently by two reviewers. Each study will be appraised using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational studies to rate the methodological quality. The quality scores of the included studies will be calculated based on 14 criteria and classified as good, fair or poor.22\n\nSynthesis, analysis, and assessment of heterogeneity\n\nDescriptive data will be presented by the major study characteristics of the eligible studies such as the mean or median age with the estimates of variance, sex proportions and ethnicity of the study participants. A list of all the PBD definitions identified across the eligible studies will be compiled and presented in a table depicting the differences and similarities. We will quantitatively synthesise prevalence data to evaluate the level of adherence to a PBD across studies. The prevalence of adherence to a PBD will be summarised by geographical region and countries, and which method was used to construct the dietary index. Association data of adherence to a PBD with CVD risk and/or CVD will be analysed according to study design, showing the reported measures of association by major CVD risk such as the odds ratio (OR), CVD risk score and/or CVD such as hazard ratio (HR) or risk ratio (RR).\n\nMeta-analytic techniques will be applied to combine the data from studies investigating the association between adherence to a PBD and CVD risk: with sufficient data depending on the study design, assessing the same dietary exposure and health outcome, and with comparable measures of association. Separate forest plots will be generated to present the summary statistics for cross-sectional and/or case–control studies (e.g. ORs) and cohort studies (e.g. RRs) with their 95% confidence intervals (95% CIs). A random-effects model will be used to calculate the pooled estimated measure of association of study populations with adherence to a PBD and at risk of developing or having CVD. Subgroup analyses will be performed by geographical regions and country, sample size, the type of dietary pattern analysis approach and scoring system. Meta-analyses will be stratified according to study population, the type of PBD definition, if the same criteria were used to assess dietary exposure, and by CVD risk for studies that have assessed the same health outcome. Thus, grouping all the studies that investigated association in study participants with similar demographics, using an identical dietary exposure and assessing the same CVD risk and/or CVD.\n\nHeterogeneity across studies included in the meta-analysis will be assessed using the Cochrane Q statistic. The degree of heterogeneity will be determined will be assessed using the inconsistency index (I2): 25%, 50% and 75%, suggesting low, medium, and high heterogeneity, respectively.23 Publication bias will be evaluated graphically with the funnel plot asymmetry test and statistically using Egger’s test.24,25 Sensitivity analysis will be applied to evaluate and confirm the robustness of the findings. The Tweedie and Duval trim and fill methods will be used to impute missing studies and examine the plausibility of the imputed studies.26 The data analysis will be conducted using the ‘meta’ package of the statistical software R (RRID:SCR_019055; The R Foundation for statistical computing, Vienna, Austria). A narrative summary of the findings will be provided for studies with significant differences in their study designs and methodologies.\n\nThis study has a systematic review and meta-analysis design, which will assess published data and does not require ethical approval. This review will form part of a PhD thesis by publication that will be submitted at Stellenbosch University for degree purposes. The PhD study proposal has obtained ethics approval from Stellenbosch University Health Research Ethics Committee (SU HREC number: S19/03/056). The results will be published in peer-reviewed journals. Study findings will be presented at relevant research meetings and conferences.\n\nThis systematic review and meta-analysis will investigate the association of PBD adherence with CVD risk profile from a global perspective. Published studies have applied various dietary methods to assess adherence to a PBD, therefore, this study aims to evaluate which PBD definitions are utilised and assess the accuracy of PBD indices across high and low-to-middle income countries. A considerable degree of heterogeneity may be present due to the different dietary methods and including studies with small sample sizes may be a limitation when performing the meta-analysis. Statistical techniques will be applied to collate and report robust findings in this systematic review.\n\nAmendments to the study protocol, if any, will be published in accordance with the 2015 PRISMA-P guidelines.27\n\n\nConclusion\n\nThis systematic review will aim to highlight the inconsistencies in defining a PBD and the need for a universal definition. It will summarise which methods are commonly used to construct dietary indices that measure adherence to a PBD. Furthermore, it will investigate the association of adherence to a PBD with CVD risk from a global perspective. This may be important to improve the global acceptance of these study findings to inform policymakers and practitioners.\n\n\nData availability\n\nFigshare: PRISMA-P checklist for “Protocol for a systematic review and meta-analysis: to investigate the association of adherence to plant-based diets with cardiovascular disease risk” https://doi.org/10.6084/m9.figshare.14988249.v1.28\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAuthor contributions\n\nTL and APK conceived and designed the protocol. TL drafted the manuscript. APK, AEZ, MF, SD and RTE critically revised the manuscript for methodological and clinical content. All authors approved the final version of the manuscript.",
"appendix": "References\n\nOstfeld RJ: Definition of a plant-based diet and overview of this special issue. J Geriatr Cardiol. 2017; 14(5): 315. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKerley CP: A Review of Plant-based Diets to Prevent and Treat Heart Failure. Card Fail Rev. 2018; 4(1): 54–61. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCespedes E, Hu FB: Dietary patterns: from nutritional epidemiologic analysis to national guidelines. Am J Clin Nutr. 2015; 101(5): 899–900. PubMed Abstract | Publisher Full Text | Free Full Text\n\nReal H, Queiroz J, Graça P: Mediterranean food pattern vs. Mediterranean diet: a necessary approach? Int J Food Sci Nutr. 2020; 71(1): 1–12. PubMed Abstract | Publisher Full Text\n\nPanagiotakos D: α-Priori versus α-posterior methods in dietary pattern analysis: a review in nutrition epidemiology. Nutr Bull . 2008; 33(4): 311–315. Publisher Full Text\n\nBurggraf C, Teuber R, Brosig S, et al.: Review of a priori dietary quality indices in relation to their construction criteria. Nutr Rev. 2018; 76(10): 747–764. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTrijsburg L, Talsma EF, de Vries JHM, et al.: Diet quality indices for research in low- and middle-income countries: a systematic review. Nutr Rev. 2019; 77(8): 515–540. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAljuraiban GS, Gibson R, Oude Griep LM, et al.: Perspective: The Application of A Priori Diet Quality Scores to Cardiovascular Disease Risk-A Critical Evaluation of Current Scoring Systems. Adv Nutr. 2020; 11(1): 10–24. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHemler EC, Hu FB: Plant-Based Diets for Cardiovascular Disease Prevention: All Plant Foods Are Not Created Equal. Curr Atheroscler Rep. 2019; 21(5): 18. PubMed Abstract | Publisher Full Text\n\nWillett W, Rockström J, Loken B, et al.: Food in the Anthropocene: the EAT-Lancet Commission on healthy diets from sustainable food systems. Lancet. 2019; 393(10170): 447–492. PubMed Abstract | Publisher Full Text\n\nPanagiotakos DB, Pitsavos C, Stefanadis C: Dietary patterns: a Mediterranean diet score and its relation to clinical and biological markers of cardiovascular disease risk. Nutr Metab Cardiovasc Dis. 2006; 16(8): 559–568. PubMed Abstract | Publisher Full Text\n\nSatija A, Bhupathiraju SN, Spiegelman D, et al.: Healthful and Unhealthful Plant-Based Diets and the Risk of Coronary Heart Disease in U.S. Adults. J Am Coll Cardiol. 2017; 70(4): 411–422. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKim H, Rebholz CM, Garcia-Larsen V, et al.: Operational Differences in Plant-Based Diet Indices Affect the Ability to Detect Associations with Incident Hypertension in Middle-Aged US Adults. J Nutr. 2020; 150(4): 842–850. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMassera D, Zaman T, Farren GE, et al.: A Whole-Food Plant-Based Diet Reversed Angina without Medications or Procedures. Case Rep Cardiol. 2015; 2015: 978906. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMassera D, Graf L, Barba S, et al.: Angina rapidly improved with a plant-based diet and returned after resuming a Western diet. J Geriatr Cardiol. 2016; 13(4): 364–366. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLara KM, Levitan EB, Gutierrez OM, et al.: Dietary patterns and incident heart failure in U.S. adults without known coronary disease. J Am Coll Cardiol. 2019; 73(16): 2036–2045. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKahleova H, Levin S, Barnard N: Cardio-metabolic benefits of plant-based diets. Nutrients. 2017; 9(8). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcMacken M, Shah S: A plant-based diet for the prevention and treatment of type 2 diabetes. J Geriatr Cardiol. 2017; 14(5): 342–354. PubMed Abstract | Publisher Full Text | Free Full Text\n\nQian F, Liu G, Hu FB, et al.: Association between plant-based dietary patterns and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA Intern Med. 2019; 179(10): 1335–1344. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOuzzani M, Hammady H, Fedorowicz Z, et al.: Rayyan—a web and mobile app for systematic reviews. Syst Rev . 2016; 5: 210. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThe Cochrane Collaboration - Data collection form [S.a.] [Online]. Accessed 02 October 2020. Reference Source\n\nMéndez-Bustos P, Calati R, Rubio-Ramírez F, et al.: Effectiveness of Psychotherapy on Suicidal Risk: A Systematic Review of Observational Studies. Front Psychol. 2019; 10: 277. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHiggins JP, Thompson SG: Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11): 1539–1558. PubMed Abstract | Publisher Full Text\n\nSterne JA, Sutton AJ, Ioannidis JP, et al.: Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011; 343: d4002. PubMed Abstract | Publisher Full Text\n\nEgger M, Davey Smith G, Schneider M, et al.: Bias in meta-analysis detected by a simple, graphical test. BMJ . 1997; 315: 629–634. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDuval S, Tweedie R: Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000; 56(2): 455–463. PubMed Abstract | Publisher Full Text\n\nShamseer L, Moher D, Clarke M, et al.: PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; g7647: 350. PubMed Abstract | Publisher Full Text\n\nLopes T: PRISMA-P Checklist. figshare. Dataset. 2021. Publisher Full Text"
}
|
[
{
"id": "100345",
"date": "26 Nov 2021",
"name": "Amanda Sainsbury",
"expertise": [
"Reviewer Expertise Obesity and methodology used to assess treatments (e.g.",
"fundamental studies in animals",
"clinical trials",
"epidemiological studies",
"systematic reviews and meta-analyses)."
],
"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 a thorough protocol for a systematic review and potential meta-analysis. The rationale for the study is clear and compelling. I have some specific comments to help clarify parts of the text:\nIt seems a shame to limit the review to articles in English and French only when free translators for non-English non-French articles would be readily available. For example, associates known to the research team that speak other languages besides English or French could translate the small proportion of articles that are not in one of these two languages. Then there are free internet translators.\n\nUnder the heading of exclusion criteria, The second sentence in the paragraph is not clear. This could benefit from expansion for clarification.\n\nThe first two sentences under the heading of the selection process are not very clear to me and could benefit from clarification.\n\nMore information about the risk of bias assessment tool to be used could be of benefit. Will this proposed risk of bias assessment tool be applicable to all types of studies that are eligible for inclusion in the current review? What other risk of bias assessment tools have been considered, and why was this tool selected as the most appropriate?\n\nThe last sentence before the heading of ethical approval and dissemination is not clear to me, can you say it another way?\n\nIn the paragraph on heterogeneity, it is mistakenly written that I2 provides an indication of the heterogeneity of the studies in the meta-analysis. It does not. It is the proportion of the observed variation in effect sizes between studies that is due to variability in the true effect size1.\n\nReference number 272 seems old, given that revised Prisma guidelines were released in 2020. It would be better to report and undertake the study in accordance with Prisma 2020 guidelines.\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": "8397",
"date": "28 Jun 2022",
"name": "Tatum Lopes",
"role": "Author Response",
"response": "Thank you for reviewing this protocol paper. Your comments and suggestions have been discussed and addressed to improve the manuscript. Herewith the response to each of the comments/suggestions. In response to comment 1: Thank you for this suggestion. We acknowledge that language bias is a study limitation. Please see amendment below and in the revised manuscript. “Studies published will be included without language restriction.” In response to comment 2: Thank you for your comment. Please see the amendment below and in the revised manuscript. “Studies that have reported on the Mediterranean and/or DASH diet/dietary patterns, which are predominantly plant-based will be excluded from the primary analysis. However, such studies will be included in our secondary analysis; if the authors did not state that they were assessing a PBD as their exposure variable.” In response to comment 3: Please see the amendment below and on page 7 of the revised manuscript. “The Rayyan application will be utilised during the selection process. Two reviewers will independently screen the identified titles and abstracts of identified records will be screened independently by two reviewers. The inclusion and exclusion criteria will serve as guide for the reviewers to select eligible records and studies. After completing the titles and abstracts screening, the two reviewers will discuss any discrepancies and reach a consensus to include or exclude the record. Subsequently, the full text of all eligible records will be retrieved. Full text will be reviewed independently by the two reviewers and checked by a third reviewer for consensus.” In response to comment 4: Thank you for your comment. Yes, the NHLBI risk of bias assessment tools will be used to assess the quality of all study types. Please see the amendment below. “The NHLBI tools will be utilised to assess the risk of bias for all observational study types namely cross-sectional, cohort and case-control studies. The quality scores of the included studies will be calculated based on 14 criteria for cross-sectional and cohort studies and 12 criteria for case-control studies. This risk of bias assessment tool was selected because it was developed by a working group assessing cardiovascular risk which is the outcome of interest for our systematic review. Moreover, the NHLBI tools are accompanied by a user-friendly guide that assists the reviewer(s) to answer/interpret the questions/criteria that are included in each tool.” In response to comment 5: Please see the amendment below and on page 8 of the revised manuscript. “A narrative summary will be provided for studies with significant differences to allow pooling of the estimates via meta-analysis.” In response to comment 6: Thank you for this comment. We have consulted the reference by Borenstein et al., 2017 and amended the sentence regarding the use of I2. Please see the correction below. “The degree of heterogeneity will be determined using the I2, which indicates the proportion of variation in the observed effects as a result of sampling error and variation in the true effects.” In response to comment 7: Thank you for the recommendation. Please see the amendment below and on page 11, the reference has been updated. “Amendments to the study protocol, if any, will be published in accordance with the 2020 PRISMA-P guidelines.” Page MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ . 2021 Mar 29;372:n71. doi: 10.1136/bmj.n71"
}
]
},
{
"id": "121313",
"date": "14 Feb 2022",
"name": "Vanessa Bullón-Vela",
"expertise": [
"Reviewer Expertise Nutrition 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 presented research is quite interesting. Suggestions are below:\nAbstract: It has to include the objective.\n\nIn the secondary outcome, specify the cardiovascular disease risk factors.\n\nIn the selection process, there is a new version (2020) of the flow diagram and checklist. Also, investigators have to clarify this section.\n\nIn data extraction, you can also include the level of intake category (tertile, quantile, others), follow-up duration, baseline participant status, outcome ascertainment, covariates that were adjusted in the final models. Moreover, it would be interesting to include other variables (vegan, vegetarian diets).\n\nRisk of bias assessment, clarify the threshold for the bias classification, and include relevant information about that. Also, why did you use this tool?\n\nData: In the statistical analyses, authors can also include: Subgroup analysis for study quality, by sex (men, women, or both), participant status. Also, a leave-one-out sensitivity 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": "8398",
"date": "28 Jun 2022",
"name": "Tatum Lopes",
"role": "Author Response",
"response": "Thank you for reviewing this protocol paper. Your comments and suggestions have been discussed and addressed to improve the manuscript. Herewith is the response to each of the comments/suggestions. In response to comment 1: Please see the amendment below and on page 2 of the revised manuscript. “This protocol is for a review that will: 1) evaluate how a PBD has been defined in studies published globally; and 2) assess the methods used to construct dietary indices that measure adherence to a PBD; with a focus on studies that have assessed the association between adherence to a PBD and CVD risk.” In response to comment 2: Thank you for your comment. Please see below and stated in the inclusion criteria section on page 5 of the revised manuscript. CVD risk outcomes - hypertension - overweight/obesity - diabetes mellitus - metabolic syndrome - CVD risk score CV outcomes - myocardial infarction/coronary heart disease - stroke/cerebrovascular disease - cardiac death In response to comment 3: Thank you for your comment regarding the new flow diagram and checklist. We have consulted the updated guideline by Page and colleagues. Page MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ . 2021 Mar 29;372:n71. doi: 10.1136/bmj.n71 In response to comment 4: Thank you for this recommendation. We have amended the data extraction section and added the suggested data items. “The PEO strategy will also be utilised to extract study-specific data. For example, data related to the baseline characteristics of cohort study participants, and the duration of follow-up will be extracted. Study-specific data will include the demographics of study participants such as age, sex and ethnicity, the dietary exposure and how it was defined, how adherence was measured including the dietary assessment method and reference period that was used, how the food intake was quantified such as the level of intake (e.g., tertiles of consumption), which dietary pattern analysis approach was applied to construct the dietary index, also which health outcome was assessed and how the outcomes were ascertained. Moreover, we will extract data on which covariates were adjusted for in the regression models of the included studies, and report on the measurement of potential confounders.” We have also specified that vegan and vegetarian diets will be included as exposure variables for our analysis on plant-based diet adherence. “We will include studies that assessed adherence to a PBD, using any definition including, vegan and/or vegetarian diets to investigate its association with CVD risk.” In response to comment 5: Thank you for your comment. Please see clarification below and on page 8 of the revised manuscript. “The NHLBI tools will be utilised to assess the risk of bias for all observational study types namely cross-sectional, cohort and case-control studies. The quality scores of the included studies will be calculated based on 14 criteria for cross-sectional and cohort studies and 12 criteria for case-control studies. This risk of bias assessment tool was selected because it was developed by a working group assessing cardiovascular risk which is the outcome of interest for our systematic review. Moreover, the NHLBI tools were developed using a rigorous approach and are accompanied by a user-friendly guide that assists the reviewer(s) to answer/interpret the questions/criteria that are included in each tool. All the included studies will be categorised as having a methodological quality that is good (score > 11), fair (score 6-9), or poor (score < 6).” . In response to comment 6: Thank you for this suggestion. Please see the amendment below and in the revised manuscript. “The leave-one-out sensitivity analyses will also be conducted to assess the likely influence of studies on the pooled estimates in meta-analyses. Subgroup analyses will be performed by geographical regions and country, sample size, sex, participant status, the type of dietary pattern analysis approach, scoring system, and study quality.”"
}
]
}
] | 1
|
https://f1000research.com/articles/10-765
|
https://f1000research.com/articles/11-710/v1
|
28 Jun 22
|
{
"type": "Research Article",
"title": "Intrapartum care intervention fidelity and factors associated with it in South Wollo Administrative Zone, Northeast Ethiopia.",
"authors": [
"Asressie Molla",
"Dr Abebaw Gebeyehu",
"Professor Solomon Mekonnen",
"Professor Kassahun ALemu",
"Dr Zemene Tigabu",
"Dr Abebaw Gebeyehu",
"Professor Solomon Mekonnen",
"Professor Kassahun ALemu",
"Dr Zemene Tigabu"
],
"abstract": "Abstract\nBackground: Implementation of recommended intrapartum care intervention varies across places due to contextual socio-cultural and behavioral determinants. Previous research has utilized several operationalizations to measure intrapartum intervention content and has failed to analyze provider and facility-related factors that influence intrapartum intervention content. So yet, no study has used intervention fidelity metrics to assess intrapartum care. Therefore, this study aimed at assessing institutional intrapartum care intervention fidelity & factors associated with it. Methods: On randomly selected keabeles (study sites), a cross-sectional study design was used. All health posts and health extension workers within the specified area were included, as were 898 postnatal mothers within six months of delivery. Data was collected via an interview, self-administered questionnaires, and an observation checklist. To calculate the institutional delivery coverage and intrapartum care intervention fidelity, descriptive statistics were used. The weighted sum of all intrapartum care components and institutional delivery coverage were used to calculate intrapartum care intervention fidelity. The researchers utilized a multilevel linear regression analysis model to find characteristics linked to intrapartum care intervention fidelity. Results: In this study, institutional delivery coverage was 60.9% (95% CI: 57.7 – 64.1) with intrapartum care intervention fidelity of 35.6% (95% CI: 31.3-35.9). Moreover, only 21 (2.3%) of mothers received all of the contents of intrapartum care intervention. Health posts’ distance from mothers’ home, unskilled birth attendant, poor relationship between HEWs and HC staffs and low HEWs knowledge of danger signs were statistically significant barriers while HEWs as birth attendant were facilitators for Intrapartum care intervention fidelity. Conclusion: This study investigated that intrapartum care intervention fidelity was low. This finding indicated that distance from health institution inhibit mothers to receive skilled intrapartum care interventions as recommended.",
"keywords": [
"Intrapartum care",
"fidelity",
"institutional delivery"
],
"content": "Introduction\n\nIntrapartum period is critical for the life of mothers and newborns as well as human capital for future generation which is associated with 904,000 (23%) of the global total of 4 million neonatal deaths.1,2 Maternal and newborn deaths during intrapartum period can be averted if quality intervention is applied. An intervention during intrapartum period is essential for the healthy start of life. Health facility delivery, cord care, thermal care, eye care, providers’ clean hand, clean surface and newborn feeding are some of the safe, effective and feasible evidence-based interventions recommended during intrapartum period.3 There has been a lot of issues researched on the effects of intrapartum care interventions on neonatal mortality reduction. According to synthesis result, births attended by skilled attendant (25%), basic emergency obstetric care (40%) and comprehensive emergency obstetric care (85%) can significantly reduce intrapartum neonatal mortality.4 Other study that pooled three cluster randomized community trial results from Bangladesh, India and Nepal found that appropriate use of delivery kit was associated with 48% neonatal mortality reduction: this study also indicated that clean delivery surface (31%) and clean cord cut (27%) were associated with significant neonatal mortality reduction.5 A systematic review indicated that attendants’ hand washing alone can reduce 19% of neonatal mortality, 30% of cord infection and 49% of neonatal tetanus. This study’s Delphi expert estimated that clean birth practice at home can significantly reduce 15% of neonatal sepsis and 30% of neonatal tetanus. Clean birth practice at facility would result in a significant reduction of 27% and 38% of neonatal sepsis and tetanus respectively.6 Other sub-Saharan study estimated that clean delivery practice at home, clinic or hospital resulted in a 61.2% neonatal mortality reduction. The combination of clean delivery practice, chlorhexidane application to cord and antibiotic administration at hospital reduced neonatal mortality by 88.4%.7 Delayed bathing (72 hours) significantly reduces 84% of neonatal mortality based on Bangladesh cross-sectional study.8\n\nAll studies reviewed here clearly indicate that intrapartum care interventions are evidenced to be effective in reducing neonatal mortality.\n\nHowever, implementation of these recommended interventions varied spatially. This varying level of implementation is associated with contextual, socio-cultural and behavioral determinants.9–17 Previous research has utilized several operationalization to measure intrapartum intervention content and has failed to analyze provider and facility-related factors that influence intrapartum intervention content. So yet, no study has used intervention fidelity metrics to assess intrapartum care. Therefore, this study aimed at assessing intrapartum care intervention fidelity & factors associated with it. Intrapartum care intervention fidelity is defined as the degree to which an intrapartum intervention is implemented as recommended by EMOH.18\n\n\nMethods\n\nThe method was published in a prior work elsewhere.19 To make things apparent for readers, the next section describes the methods used in this paper.\n\nCommunity-based cross-sectional study was conducted to evaluate the implementation of intrapartum care intervention.\n\nThis research was carried out in South Wollo Zone, 400 kilometers north of Addis Ababa. North Shewa and Oromia Region border South Wollo on the south, East Gojjam on the west, South Gondar on the northwest, North Wollo on the north, and Afar Region on the northeast. There were 900 rural and 150 urban HEWs in the zone, with 499 HPs, 126 health centers, and 9 hospitals (including one referral). It has been suggested that clean delivery care be implemented throughout the spatial continuum of care (household - health post - health center to hospital levels). Mothers in labor are intended to be notified and linked to a primary health care facility by HDAs. HEWs are required to refer laboring mothers to primary health care facilities. They are also expected to provide safe and clean intrapartum care in the event of an unavoidable home birth. Skilled practitioners (nurses, midwives, health officers or physicians) at the HC and hospital level are expected to arrange ambulance services, accept delivery referrals, support HEWs and provide basic emergency obstetric care. To reduce neonatal mortality, family members, HDAs, HEWs, and skilled practitioners should all play a complementary role.20\n\nAll postnatal mothers who have been expected to receive, all health posts and HEWs that have been providing intrapartum care intervention in South Wollo Zone were illegible for this study. Kebele’s (one health post each) was chosen using computer generated random numbers. Then all postnatal mothers who had given birth within six months of the survey and lived in those selected kebeles were included.\n\nThe outcome of this study was intrapartum care intervention fidelity while the considered predictors include customer level (maternal age, educational status, occupation, paternal education, parity, gravidity, number of abortions and stillbirths) and provider level (supervision, feedback, technical assistance, HDAs support, distance between HP and farthest maternal home, relationship between HEWs and health center staffs, place of delivery, type of attendant, HEWs age, experience, and knowledge of danger sign).\n\nThis study utilized multiple data sources which includes postnatal mothers, HEWs and HPS. Intrapartum care intervention fidelity was measured by the composite index of institutional delivery coverage and intrapartum care intervention content. Data were collected by using interview and self-administered questionnaires and facility audit checklist. Postnatal mothers were interviewed at their home. Health facility audit was undertaken by principal investigator while self-administered questionnaire was responded by HEWs in their HP at working hours.\n\nDifferent strategies were employed to reduce biases at different stages of the study. Accordingly, data collection tool was developed by reviewing the implementation guideline, HEWs training manual, lancet review, every newborn lancet series-2 & 3 and other relevant literatures.20–24 Facility audit checklist and HEWs questionnaire was mainly developed by reviewing the implementation guideline. The questionnaire was first developed in English then translated to Amharic for maternal interview. Mothers were interviewed at their home by 12th grade completed students who have been living in the same kebeles to reduce social desirability bias. Multiple multilevel linear regression model was used to control the possible confounding biases.\n\nUsing single population proportion formula in Epidemiological information (Epi info) version 7 statistical software and by considering 95% confidence level, 5% margin of error, 19% of births attended by trained professionals in Ethiopian study,14 design effect of 2 and 10% non-response rate, the calculated sample size was 521 mothers. However, because of the cluster nature of sampling, the study included all 898 mothers who could be serviced by the chosen health posts. Ten Kebeles and 16 HEWs working in those kebeles were included in this study.\n\nIntrapartum care intervention contents include all practices of clean care (clean hands, clean genitalia, clean cord cut, clean cord tie, utilizing clean cloths/towel), thermal care, eye care, vitamin K supplementation and breast feeding. Therefore, content of intrapartum care that each mother received were weighted by dividing each received service by the recommended quantity of care. Accordingly, 14 recommended intrapartum contents were considered and weighted as 114content received. Intrapartum care intervention fidelity was calculated as 1898Institutional delivery coverage∗Intrapartum care content recieved.Thus the values of intrapartum care intervention fidelity ranges from 0 to1 or 0 to100%. Danger sign knowledge of HEWs was categorized as knowledgeable for those scored above the mean and non-knowledgeable for those scored below the mean score out of 21 questions.25,26\n\nDescriptive statistics was employed to compute proportion and mean. Mean of intrapartum care intervention fidelity was computed to estimate the average amount of intrapartum care intervention that a mother received. Multilevel linear regression analysis with p value of ≤ 0.05 and 95% confidence interval were used to identify factors influencing for intrapartum care intervention fidelity.\n\n\nResults\n\nThe mean age of study participants were 31 ± 7 years. 768 (85.91%) mothers were married, while 96 (10.94%) were separated. Concerning educational status, 638 (71.44%) of mothers did not attend formal education with 817 (92%) farmer in occupation. 617 (70.03%) study participants’ partner did not attend formal education but 202 (22.93%) attended elementary (1–8 grade) school. Concerning partners occupation, 704 (80.09%) of them were farmers while 143 (16.27%) merchants. Only 180 (20.04%) of women walked less than 15 minutes from their home to the nearest HP while 333 (37.08%) of them walked more than 45 minutes.\n\nCoverage: 547 (60.9%, 95% CI: 57.7 – 64.1) of eligible mothers gave birth at health institutions. 53% of antenatal care attended women, 24.2% FANC attended women (≥ 4 visits), 49.2% women attended ANC at health center, 45.9% of referred and 59.2% of counseled for institutional delivery women were attended institutional delivery (Table 1).\n\nContents: Concerning the contents of intrapartum care intervention, only 21 (2.3%, 95% CI: 1.3 – 3.3%) of mothers received all the recommended contents. Using clean cord cut (92.8%) and cord tie (89.7%), cleaning the women genitalia and wrapping the newborn with clean towel (84.5% each) were the commonly practiced intrapartum care intervention contents by HEWs. On average an intrapartum mother received 34.8% (95% CI: 31.96 – 37.66), 70.69% (95% CI: 67.39 – 73.99), 54.53% (95% CI: 52.06 – 56.99) and 62.24% (95% CI: 52.26 – 72.23) of the recommended intrapartum intervention contents when gave birth at home, health post, health center and hospitals respectively (Table 2).\n\nIntrapartum care intervention fidelity: An average intrapartum care intervention fidelity is 33.57% (95% CI: 31.29 – 35.86) meaning that on average a mother receives only 33.6% of the recommended intrapartum care intervention. Only 16 (1.8%) of mothers received intrapartum care interventions with full fidelity. The weighted average intrapartum intervention fidelity was 54.53% (95% CI: 52.06 – 56.99) in health center and 62.24% (95% CI: 52.26 – 72.23) in hospital deliveries.\n\nIn multilevel linear regression model, random intercept variance of 3.1% and ICC of 38.4% indicates that intrapartum care intervention fidelity varies across study sites. In this model, an average of one minute increase in walking distance from HP to farthest home resulted in a 5% decrease in intrapartum care intervention fidelity. Intrapartum care intervention fidelity was reduced by 21% and 27% when attended by TBA and family members than skilled attendants respectively. Intrapartum care intervention fidelity was increased by 14% when attended by HEWs than skilled attendants. Poor relationship between HEWs and HC staffs reduced intrapartum care intervention fidelity by 27% than good relationship. HEWs low knowledge of maternal and newborn danger signs reduced intrapartum care intervention fidelity by 40% (Table 3).\n\n\nDiscussion\n\nThis study was aimed at assessing intrapartum care intervention fidelity and its associated factors. Accordingly, average intrapartum care intervention fidelity was 33.6% with about 40% of mother gave birth outside the health facilities. Only 2.3% of mothers received all the recommended intervention contents. Distance between health post and furthest maternal home, delivery attended by traditional birth attendant and family member, poor relation between HEWs and health staffs and low level of HEWs knowledge of danger signs were statistically significant barriers whereas, delivery attended by HEWs was facilitator for intrapartum care fidelity in this study.\n\nReception of all the recommended intrapartum care intervention in this study is consistent with Pakistan’s (2.9%)13 but lower than Ethiopian study (62%).9 The reason for the difference might be due to the difference in study setting (institution and community based). In this study, on average a woman receives 33.6% of the recommended intrapartum care interventions which is too low to result in an anticipated neonatal mortality reduction.\n\nThe weighted average intrapartum care intervention fidelity in non-institutionally delivered mother in this study (44.7%) is greater than other studies in Ethiopian (2.9 – 40.7%), Nepal’s (0.9%) and Ghana’s (15.8%).27–34 In contrast, this finding is lower than other Ethiopian Awi (62.7%) study.35 The difference might be due to measurement difference in that other studies used only three domains (cord care, thermal care, and neonatal feeding) while this study uses wider intrapartum care intervention contents as mentioned in method above. The other reason for the difference might be the recall period in that this study used six-months while others used one-year postnatal recall period.\n\nIn this study, increased average distance between HP and farthest mothers’ home decreased intrapartum care intervention fidelity which is consistent with other Ethiopian study.36 This could be justified by those mothers who are far distant from health facility may not attend and get the recommended intrapartum care.37–40\n\nIntrapartum care intervention fidelity is lower when births are attended by unskilled attendants which might be justified by home deliveries attended by unskilled attendants is challenged by inappropriate delivery environment, insufficient supplies, inadequate training thereby dearth with the desired knowledge and skill about delivery care.41\n\nIntrapartum care intervention fidelity is higher when attended by HEWs than skilled attendants. This might be due to low work load in the curative service at health post and more time allocation to clinical activities by HEWs.42–44\n\nPoor relationship between HEWs and HC staffs (midwifes and nurses) reduced intrapartum care intervention fidelity. HEWs and HC staffs are the immediate health care cadres in the client referral pathways. So, their respectful, open, effective and collaborative relationship across the service provision platform is integral to providing safe and high quality care.45–47\n\nHEWs’ knowledge to diagnose danger sign was another barrier for intrapartum care intervention fidelity. This finding implies that HEWs competency is directly related with the implementation of an intervention as planned. Considering provider level factors and multilevel nature of the analysis is the strength of this study while recall bias might be inevitable to the finding.\n\n\nConclusion\n\nIn summary, this study investigated that intrapartum care intervention fidelity is low. Moreover, far distance of HP from maternal home, births attended by unskilled attendants, poor relationship between HEWs & HC staffs and HEWs competency were found to be statistically significant barriers while HEWs birth attendant is facilitator for intrapartum care intervention fidelity. This finding implies that distance from health institution inhibit mothers to attend and receive skilled intrapartum care interventions as recommended.\n\n\nEthics approval\n\nThis study has granted an ethical clearance from institutional review board of University of Gondar numbered O/V/P/RCS/05/810/2018 and Amhara public health research institute numbered -@¼M¼t&¼>¼Ä 03/938/10. Moreover, support letter was received from South Wollo administrative zone. Besides, written informed consent was secured from study participants (mothers and health extension workers).\n\n\nData availability\n\nThis study's data is accessible from the corresponding author. It can be provided upon request because this is a PhD big data research containing sensitive personal information and more subsequent activities are continued.\n\n\nAuthor contributions\n\nAM, the corresponding author, contributes to conceptualization, designing and conducting the study, data curation and analysis, validation, visualization and writing this paper. AG, SM, KA and ZT contributes to supervising the overall research process,",
"appendix": "Acknowledgments\n\nAuthors would like to acknowledge the study participants, data collectors, South Wollo administrative zone and district health office officials. Finally, the authors’ gratitude goes to UoG and German academic exchange services for their financial assistance for data collection.\n\n\nReferences\n\nLawn J, Shibuya K, Stein C: No cry at birth: Global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths. Bull. World Health Organ. 2005; 83(6): 409–417. PubMed Abstract Reference Source\n\nLawn JE, Lee ACC, Kinney M, et al.: Two million intrapartum-related stillbirths and neonatal deaths: Where, why, and what can be done?. Int. J. Gynecol. Obstet. 2009; 107(SUPPL): S5–S19. PubMed Abstract | Publisher Full Text\n\nWHO: Essential delivery care practices for maternal and newborn health and nutrition. 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PubMed Abstract | Publisher Full Text\n\nEthiopian Federal ministry of health: Community Based Newborn Care Implementation plan.2013.\n\nBhutta ZA, Das JK, Bahl R, et al.: Can available interventions end preventable deaths in mothers, newborn babies, and stillbirths, and at what cost? Lancet. 2014 Jul 26 [cited 2017 Oct 26]; 384(9940): 347–370. PubMed Abstract | Publisher Full Text Reference Source\n\nKerber KJ: Continuum of care for maternal, newborn, and child health: from slogan to service delivery. Lancet. 2007; 370: 1358–1369. PubMed Abstract | Publisher Full Text\n\nFederal Minster of Health (FMOH): COMMUNITY BASED NEWBORN CARE TRANING FOR HEALTH EXTENSION WORKERS: FACILITATORS GUIDE.2013.\n\nDarmstadt GL, Bhutta ZA, Cousens S, et al.: Evidence-based, cost-effective interventions: How many newborn babies can we save? Lancet. 2005 Mar 12 [cited 2019 Mar 14]; 365(9463): 977–88. PubMed Abstract | Publisher Full Text\n\nJemberia MM, Berhe ET, Mirkena HB, et al.: Low level of knowledge about neonatal danger signs and its associated factors among postnatal mothers attending at Woldia general hospital, Ethiopia. Matern Heal Neonatol Perinatol. 2018; 4(1): 1–8. Publisher Full Text\n\nArba A: Knowledge of Essential Newborn Care and Associated Factors among Nurses and Midwives: A Cross-Sectional Study at Public Health Facilities in Wolaita Zone, Southern Ethiopia, 2019. Hindawi-International J Pediatr. 2020; 2020: 1–8. Publisher Full Text\n\nKasaye HK, Yilma MT, Bobo FT, et al.: Poor Universal Coverage of Immediate Essential Newborn Care at Hospitals of Wollega Zones, The Case of Western Ethiopia. Res Reports Neonatol. 2020; Volume 10: 37–46. Publisher Full Text\n\nBryce E, Mullany LC, Khatry SK, et al.: Coverage of the WHO’s four essential elements of newborn care and their association with neonatal survival in southern Nepal. BMC Pregnancy Childbirth. 2020; 20(1): 1–9. Publisher Full Text\n\nAmsalu ET, Kefale B, Muche A, et al.: The effects of ANC follow up on essential newborn care practices in east Africa: a systematic review and meta - analysis. Sci Rep. 2021; 11: 1–10. PubMed Abstract | Publisher Full Text\n\nSaaka M, Ali F, Vuu F: Prevalence and determinants of essential newborn care practices in the Lawra District of Ghana. BMC Pediatr. 2018; 18(1): 1–12. Publisher Full Text\n\nHealth P: Essential Newborn Care and Associated Factors Among Obstetrical Care Providers in Awi Zone Health Facilities. Northwest Ethiopia:An Institutional-Based Cross-Sectional Study;2020.\n\nAgonafir M, Shimbre MS, Hussen S, et al.: Community Based Essential Newborn Care Practices and Associated Factors among Women Who Gave Birth at Home in Last 12 Months in Amaro.2021.\n\nGebremariam Y, Tekola KB: Community-Based Essential Newborn Care Practices and Associated Factors among Women of Enderta, Tigray, Hindawi.2020; 2020: 1–8.\n\nMersha A, Assefa N, Teji K, et al.: Essential newborn care practice and its predictors among mother who delivered within the past six months in Chencha District, Southern Ethiopia, 2017. PLoS One. 2018; 13: 1–17. Publisher Full Text\n\nAyenew A, Abebe M, Ewnetu M: Essential Newborn Care and Associated Factors Among Obstetrical Care Providers in Awi Zone Health Facilities, Northwest Ethiopia: An Institutional-Based Cross-Sectional Study. Pediatr Heal Med Ther. 2020; Volume 11: 449–458. Publisher Full Text\n\nKebede ZT: Determinants of Health Facility Delivery in Northwest Ethiopia: A Community-Based Case-Control Study. Int J Gen Med. 2021; 14: 993–1001. Publisher Full Text\n\nKyei-nimakoh M, Carolan-olah M, Mccann TV: Access barriers to obstetric care at health facilities in sub-Saharan Africa — a systematic review.2017; 1–16.\n\nTesfahun Melese AG: The Role of Geographical Access in the Utilization of Institutional Delivery Service in Rural Jimma Horro District, Southwest Ethiopia. Prim Heal Care Open Access. 2014; 04(01): 1–6. Publisher Full Text\n\nAyenew AA, Nigussie AA, Zewdu BF: Childbirth at home and associated factors in Ethiopia: a systematic review and meta-analysis. Arch Public Heal. 2021; 79(1): 1–18. Publisher Full Text\n\nTegegne TK, Chojenta C, Loxton D, et al.: The impact of geographic access on institutional delivery care use in low and middle-income countries: Systematic review and meta-analysis. PLoS One. 2018; 13(8): 1–16. Publisher Full Text\n\nBlum LS, Sharmin T, Ronsmans C: Attending home vs. clinic-based deliveries: perspectives of skilled birth attendants in Matlab, Bangladesh. Reprod Health Matters. 2006 May [cited 2017 Sep 4]; 14(27): 51–60. PubMed Abstract | Publisher Full Text\n\nAssefa Y, Gelaw YA, Hill PS, et al.: Community health extension program of Ethiopia, 2003 – 2018: successes and challenges toward universal coverage for primary healthcare services. Glob Health. 2019; 15(21): 1–11.\n\nMangham-Jefferies L, Mathewos B, Russell J, et al.: How do health extension workers in Ethiopia allocate their time? Hum. Resour. Health. 2014 Oct 14 [cited 2017 Sep 2]; 12(1): 61. PubMed Abstract | Publisher Full Text\n\nTilahun H, Fekadu B, Abdisa H, et al.: Ethiopia’ s health extension workers use of work time on duty: time and motion study.2017; (September 2016): 320–328.\n\nOldland E, Botti M, Hutchinson AM, et al.: A framework of nurses’ responsibilities for quality healthcare — Exploration of content validity. Collegian. 2020; 27(2): 150–163. Publisher Full Text\n\nGeerligs L, Rankin NM, Shepherd HL, et al.: Hospital-based interventions: a systematic review of staff-reported barriers and facilitators to implementation processes.2018; 1–17.\n\nFetene N, Linnander E, Fekadu B, et al.: The Ethiopian Health Extension Program and Variation in Health Systems Performance: What Matters? PLoS One. 2016; 11(5): 1–19. Publisher Full Text"
}
|
[
{
"id": "206296",
"date": "27 Sep 2023",
"name": "Abrham Debeb Sendekie",
"expertise": [
"Reviewer Expertise Obstetrics and gynecological related practices."
],
"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 provided valuable data and it is important to help governments, communities and healthcare providers in decreasing fetal mortality and related diseases. However, some questions and suggestions need to be made to further improvement of the manuscript.\n\nThe title of your manuscript is ‘’ Intrapartum care intervention fidelity and factors associated with it’’\nAccording to the WHO definition, \"intrapartum\" is the time surrounding labor and delivery. Regular contractions signal the start of labor, which lasts until the baby and placenta are delivered. The main goals of intrapartum care are to keep an eye on the health of both the mother and the neonate and to handle any issues that might develop at this period. Although the title of your manuscript is wide, the methods, results, and discussion sections of the paper exclusively evaluate neonatal care and say nothing about the intrapartum care of mothers or the procedures. As a result, there needs to be major revisions and justifications because the title and manuscript details do not match.\n\nAlthough your study was community-based and its participants were 898 postnatal moms who had given birth within the previous six months, the abstract section of the technique section of your study indicated that data was acquired via an interview, self-administered questionnaires, and an observation checklist. Please explain when and where the observational checklist was used.\n\nIntrapartum care intervention fidelity was low in the study area what is your reference to say low?\n\nPoor relationships between HEWs and HC personnel were statistically significant impediments to the integrity of the intrapartum care intervention in your results section, although HEWs' role as birth attendants was a facilitator. Justify it with what kinds of relationships, please.\n\nPlease include the entire population size, paying specific attention to the total number of women who are of reproductive age, and provide references in your study setting.\n\nAlthough the majority of the mothers (768, 85.91%) were married and had ANC follow-ups, your study's conclusion that more than 97% of current pregnancies were unwanted doesn't convince me.\n\nWhen attended by HEWs rather than skilled attendants, intrapartum care intervention fidelity increased by 14%, according to your study's findings, which were included in your results section. Could you kindly explain this outcome to someone who is a skilled birth attendant?\n\nWhen attended by HEWs rather than skilled attendants, intrapartum care intervention fidelity increased by 14%, according to your study's findings, which were included in your results section. Could you kindly explain this outcome to someone who is a skilled birth attendant?\n\nThe same justification for the different countries?\n\nRecommendation should be based on your findings?\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "203919",
"date": "27 Sep 2023",
"name": "Jenny Jung",
"expertise": [
"Reviewer Expertise Maternal and perinatal health",
"epidemiology",
"health inequity",
"global health",
"low- and middle-income countries",
"guideline development",
"evidence synthesis"
],
"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 presented on the intrapartum intervention fidelity and associated factors in Northeast Ethiopia. The authors did a great job in designing the study and presenting the findings which is relatively novel and will contribute to advancing findings in the field. There are several comments related to the method and the interpretation which were raised.\n\nMethod:\nThis work was conducted in one setting and published elsewhere focusing on the antenatal care interventions. Although this paper focuses on the intrapartum care, there is query about why this part of the findings were published separately. To prevent multiple articles from the same study, this has to be raised and ask whether the authors also assessed postpartum interventions and if so, what are the authors planning to do with these findings?\n\nWas there any training received, or any attempt by the investigators to validate the self-administered questionnaire by HEWs?\n\nMy main concern is about the data extraction tool. There is insufficient information within the manuscript to assess the data extracted therefore reducing the replicability of this research. Additionally, authors mention the data extraction tool was derived from a combination of guidelines, manuals, peer-reviewed papers, and 'other relevant literatures'. The authors would need to specify on what grounds the data extracted were selected, what the search strategy to develop the data extraction tool were, and present the data extraction questions (at minimum for intrapartum interventions studied) in supplement to this paper.\n\nI have to clarify if the sample size was for the entire study (including antenatal intervention paper published previously), or whether these figures reflect only women who underwent intrapartum care?\n\nIf the study assessed from antenatal care, how were the sample size and recruitment for this study different?\n\nQuantitative variables:\nThe authors specified which intervention contents were included however does not justify why these were selected. This is important when assessing the overall coverage and quality of intrapartum services provided. In the above section, the authors mentioned they used a variety of sources to identify the interventions to be studied, therefore the intervention contents - whether in this section or data source and measurement section - need to be justified.\nInterpretation:\nThe authors presented an absolute value to assess fidelity and associated factors. However, using these findings, it would be valuable to add deeper interpretation related to what these findings would mean for intrapartum care in Ethiopia.\nIf certain interventions were demonstrated with low or high fidelity, why do the authors suggest this occurs? Also, how do these findings support progress towards comprehensive and quality intrapartum care as set by National or International standards?\nMinor:\nSlight edits towards grammar and presentation of results are required. Minor errors in Ethics approval section which need to be addressed.\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": []
}
] | 1
|
https://f1000research.com/articles/11-710
|
https://f1000research.com/articles/10-317/v1
|
23 Apr 21
|
{
"type": "Clinical Practice Article",
"title": "Atypical odontalgia and trigeminal neuralgia: psychological, behavioural and psychopharmacologic approach – an overview of the pathologies related to the challenging differential diagnosis in orofacial pain",
"authors": [
"Riccardo Tizzoni",
"Marta Tizzoni",
"Carlo Alfredo Clerici",
"Marta Tizzoni",
"Carlo Alfredo Clerici"
],
"abstract": "Orofacial pain represents a challenge for dentists, especially if with a non-odontogenic basis. Orofacial neuropathic pain is chronic, arduous to localize and develops without obvious pathology. Comorbid psychiatric disorders, such as anxiety and depression, coexist and negatively affect the condition. This article presents one case of atypical odontalgia and one of trigeminal neuralgia treated with psychological and psychopharmacologic tailored and adapted therapies, after conventional medications had failed. In addition, an overview of the pathologies related to the challenging differential diagnosis in orofacial pain is given, since current data are insufficient.\n\nA 68-year-old male complained of chronic throbbing, burning pain in a maxillary tooth, worsening upon digital pressure. Symptoms did not abate after conventional amitriptyline therapy; psychological intervention and antianxiety drug were supplemented and antidepressant agent dosage incremented; the patient revealed improvement and satisfaction with the multidisciplinary approach to his pathology. A 72-year-old male lamented chronic stabbing, intermittent, sharp, shooting and electric shock-like pain in an upper tooth, radiating and following the distribution of the trigeminal nerve. Pain did not recur after psychological intervention and a prescription of antidepressant and antianxiety agents, while conventional carbamazepine therapy had not been sufficient to control pain. Due to concern with comorbid psychiatric disorders, we adopted a patient-centered, tailored and balanced therapy, favourably changing the clinical outcome. Comorbid psychiatric disorders have a negative impact on orofacial pain and dentists should consider adopting tailored therapies, such as psychological counselling and behavioural and psychopharmacologic strategies, besides conventional treatments. They also need to be familiar with the signs and symptoms of orofacial pain, recollecting a comprehensive view of the pathologies concerning the differential diagnosis. A prompt diagnosis prevents pain chronicity, avoiding an increase in complexity and a shift to orofacial neuropathic pain and legal claims.",
"keywords": [
"atypical odontalgia",
"trigeminal neuralgia",
"case report",
"psychiatric disorders",
"orofacial pain"
],
"content": "Introduction\n\nIn clinical dental practice there are difficult situations to be managed by the practitioner, but the most challenging and gratifying are those related to the diagnosis and treatment of pain, especially if with a non-odontogenic basis.1\n\nIn the orofacial region, aesthetic, biological, emotional and relational importance and psychological sphere prominence have to be considered.2\n\nPre-existing pre-treatment, especially long-lasting, inflammatory pain seems to have paramount importance and might represent a key factor to evolve into orofacial neuropathic pain in the same area.3 Therefore, it is advisable to avoid an increase in complexity and a shift to chronic pain, conditions which may dispose to psychological distress2 and may magnify the degree of pain and its characteristics.\n\nThe patient may become deprived of confidence and hope due to diagnostic procrastination, irreversible dental treatments and lack of knowledge and may experience frustration up to clinical depression.4,5\n\nPrevention, early diagnosis, and treatment of inflammatory pain may thus have utility in avoiding the development of neuropathic pain3 and consequent anxiety.2,6\n\nDepression is a mood disorder characterized by persistent sadness associated with other symptoms. The four most common types of depression are major depression (a bad temper associated with reduction in psychological vitality, or even inability to experience pleasure, and a decrease of other physiological functions, such as sleep), persistent depressive disorder (a form of depression which has lasted for at least two years without reaching the magnitude of major depression), bipolar disorder (a form characterized by episodes of depression, alternating with intervals of unusually high energy or vitality) and seasonal affective disorder (a mental condition which characteristically arises in autumn and winter as a consequence of alterations in the body’s natural daily rhythms, in the eyes’ sensitivity to light, or in changes in serotonin and melatonin chemical messages).\n\nTwo other depression types, unique to women, are those influenced by reproductive hormones: perinatal depression and premenstrual dysphoric disorder.7\n\nAnxiety is a mental state that arises spontaneously rather than through conscious effort and is characterized and often accompanied by stress, worried thoughts and physical changes.8\n\nBased on available psychometric evidence, the Beck depression inventory – version two (BDI-II) can be viewed as a cost-effective, reliable tool to measure depression intensity of a patient, with broad applicability for research and clinical practice. It can easily discriminate between depressed and non-depressed subjects.9\n\nIt is also of paramount importance to understand the intensity of patient anxiety since this allows appropriate management. However, anxiety level is not easily measured. There are different methods accessible to dentists to measure patient dental anxiety; for example, the modified dental anxiety scale (MDAS).10\n\nThere are also many strategies available to the dental team to safely provide comprehensive care to quell patient anxiety and depression.\n\nWhen patients afflicted with orofacial pain and associated comorbid psychiatric disorders cannot be treated by conventional therapies, reassuring them by providing an explanation and comforting professional empathy, counselling and psychological therapy should be considered, and well-tolerated and effective antidepressants and antianxiety drugs should be prescribed.\n\nIn many cases of orofacial pain, due to the absence of radiographic signs and clinical symptoms of endodontic or restorative dentistry related pathologies, or other identifiable causes,11,12 the dental practitioner should be very well trained and also aware of the difficult differential diagnostic process (a mental activity and computing, following logical methods, which utilizes the combination of knowledge and reasoning about current symptoms, medical history, results from physical and possibly laboratory or other examinations and discriminates amongst different diseases which partially share signs or symptoms, specific signs or symptoms of the pathology intended to be diagnosed).\n\nThe differential diagnostic process and treatment are extremely important while dealing with these pathologies, to avoid diagnostic delays, useless and superfluous dental treatments4 and risks of legal claims.\n\nAmongst other orofacial pain, atypical odontalgia (AO), also termed persistent dentoalveolar pain disorder,4 and trigeminal neuralgia (TN) are the main diagnosed neuropathic pains.2\n\nAO can affect up to 6% of patients after they have undergone endodontic therapies4,13 and usually leads to tooth extraction without recovery of the pain.11\n\nThere is heterogeneity in the classification proposed in the literature but, in accordance with the third edition of the international classification of headache disorders (ICHD-3), this condition is now classified as a subtype of persistent idiopathic facial pain or, due to occasional presence of traumatic trigger, may also be considered a subdivision of post-traumatic painful trigeminal neuropathy.14\n\nPatients affected by AO describe the pain as localized to the tooth, or to the tooth surrounding bone, generally continuous, with periods of relief, aching, dull, throbbing, sometimes sharp, with a mild to moderate intensity. Paraesthesia or dysesthesia may be detected during examination.1 Sometimes touching of the area may represent an aggravating factor.\n\nThe pathophysiological mechanisms to justify the onset and persistence of the condition are not fully elucidated,4 but the most endorsed hypothesis is that of a neuropathic origin, assuming that injuries to teeth and/or periodontal tissues may modify health status, leading to alteration in the periodontal nerve plexus and resulting in peripheral sensitization.15\n\nIn the pathophysiological mechanisms of AO, comorbid psychiatric disorders should also be taken into account. In a recent study,16 46.2% of patients with AO showed comorbid psychiatric disorders. Of those patients, 15.4% showed depressive disorders and 10.1% showed anxiety disorders. Serious mental disorders like bipolar disorder and schizophrenia were present only in 3.0% and 1.8% of the cases, respectively. Thus, pain might have a significant emotional basis, besides the previously discussed sensory one.16\n\nTN is reportedly the most frequent condition (82.1%) amongst patients with neuropathic pain.2\n\nTN is characterized by paroxysmal, sharp, severe unilateral pain in the distribution of the trigeminal nerve, although patients may experience a variety of symptoms that simulate pain of odontogenic origin.1\n\nTrigger areas around the nose and the mouth characterize the condition, provoking the sudden onset of the pain which can lasts seconds to minutes, giving relief to patients with pain free intervals.17\n\nFrom a pathophysiological standpoint, as the most supported theory, it is assumed that tumour or vascular compression may lead to partial and focal nerve demyelination and consequent abnormal transmission and processing of impulses along the trigeminal nerve.1,18,19\n\nChronic irritation or trauma have also been thought to be involved in the origin of TN1.\n\nIn the development of TN, magnetic resonance imaging (MRI) supported the most recent evidence of superior cerebellar artery aneurysms20 and venous compression,21 but also revealed benign or malignant lesions and plaques of multiple sclerosis.20\n\nPain characteristics of TN often have unfavourable effects on the daily life of patients. Patients are affected by disruptive pain with a consequent poor quality of life and significantly reduced working performance.22 For these reasons, it is also important to evaluate the psychological aspects of patients affected by TN.\n\nIn this article, due to the above mentioned comorbid psychiatric disorders, one case of AO and one case of TN are presented and discussed taking into consideration patient-centered, tailored and adapted therapies, compared to conventional treatment: strategies for psychological suffering managing were introduced, combining psychological counselling and cognitive behavioural therapies with antidepressants and antianxiety drugs while managing patients affected with these diseases, after conventional therapy had exhibited limited efficacy.\n\nThere are several available data on single form of orofacial pain but there is still a lack of knowledge and a lack of up to date available data summarizing, or fully describing, different pain arising from the regions of the face and mouth, which would enable dental practitioners to become familiar with the signs and symptoms of orofacial pain, especially if related to non-odontogenic pain.4,23\n\nOn the bases of these reasons the two case reports acted as stimuli to accomplish also an overview of the pathologies concerning the difficult and challenging differential diagnosis in orofacial pain, which might be a helpful tool for the dental practitioner to broaden the clinical view and bear in mind more information during practice: in fact, a prompt diagnosis prevents pain chronicity, avoiding an increase in complexity and a shift to orofacial neuropathic pain and legal claims.\n\n\nCase presentation\n\nClinical presentation and history\n\nA Caucasian 68-year-old Italian attorney male was referred to our private practice with the chief complaint of moderate pain in the site of the second maxillary left premolar. The patient complained of a perpetuated period of throbbing or burning pain in the tooth or in the alveolar process, also characterized by a tingling sensation upon digital pressure with a troublesome feeling on his prosthetic zirconia crown. The pain was described as chronic but was absent during sleep, with pain-free intervals during the day. The pain had not been susceptible to non-steroidal anti-inflammatory drugs for six months.\n\nPatient clinical history did not present relevant findings, nor familiar pathologies were referred by the patient. In an addition, an anamnestic psychiatric consultation was scheduled: the patient reported a marked lack of concentration during working hours and considerable impact on his personal and social life. Additionally, the patient displayed anxiety and irritability, especially relating to the difficulties of the diagnostic process. As a consequence of the condition, significant symptoms of depression were referred by the patient.\n\nThe tooth had undergone uneventful root canal therapy many years before, a big cast post had been inserted and a gold alloy crown manufactured. The pain had been persisting for about six months, since a dentist had insisted on removing the old gold alloy crown from the tooth to make a new aesthetic zirconia crown.\n\nPatient assessment\n\nA comprehensive analysis of the mucosae and gingivae was carried out in quadrants two and three: the neighbouring teeth showed normal responses as a result of testing for vitality with cold; the occlusion was checked and normal and balanced occlusal points were found, and the contact points of the crowns in the area were checked too, to exclude food impaction coexistence. Percussion of the teeth or intra-oral palpation of the above-mentioned quadrant did not provoke pain, with the exception of the second maxillary left premolar.\n\nWe also evaluated the function and possible symptoms of the temporomandibular joints; results were within the normal range of motion and without pain. A periapical X-ray of the second maxillary left premolar, and of the neighbouring teeth, was also taken and showed normal tooth and surrounding bone structure, with no signs of pathology.\n\nWe based our diagnostic method on the anamnesis, on the comprehensive physical examination, on the X-ray examination, and on the specific anamnestic psychiatric consultation.\n\nPain intensity was investigated using the short-form McGill pain questionnaire (SF_MPQ).24\n\nDiagnosis and therapeutic intervention\n\nSince the patient had been experiencing symptoms for several months, he insisted on having an appointment for tooth extraction, despite our clinical advice. After the patient had signed a specific informed consent form for tooth extraction, and even though painful micro-fractures of the root were thought to be possible due to a big post inserted within the root canal of the tooth for restorative purposes, we reluctantly extracted the tooth and inserted an immediate loaded implant. After topical analgesia had been applied on the vestibular and palatal aspects of the gingivae (Lidocaine 15% spray), local analgesia injection was administered in the vestibular and palatal aspects of the gingivae in the area of the tooth (Mepicain 2%, 1,8 ml, 1:100.000 adrenaline).\n\nAfter a five-minute period, to allow analgesia onset, a periosteal elevator was used to cut the gingival periodontal fibers and subsequently a forceps was used to gently luxate and ultimately extract the tooth. Since an immediate loaded implant was planned to replace the extracted tooth and for the purpose to obtain primary implant stability, particular attention was paid not to damage the alveolar bone during the extraction. Successively, an osteotomy for implant placement was performed according to the manufacturer’s instruction. The implant (Biomet 3i, 15 mm length x 4mm diameter) got a primary implant stability of 25 Ncm (Newton-centimeter).\n\nAfter implant insertion, it was not necessary to suture the wound.\n\nAfter the insertion of the implant, a temporary titanium abutment was selected and a temporary resin crown manufactured. The interpoximal contact points were checked and the temporary crown was cemented on the abutment out of the occlusion to allow proper osseointegration processes.25\n\nPost-operatively, amoxicillin and clavulanic acid (875+125 mg) was prescribed twice a day for 8 days. Chlorhexidine mouth wash 0,20% was recommended three times a day for 15 days. Non-steroidal anti-inflammatory drugs were also prescribed, twice a day on a full stomach (Sodic diclofenac 25 mg) for three days.\n\nFor the final prosthetic phases, after a conventional six-month period of healing to allow osseointegration to occur, a superior impression with an open tray and a polyvinyl siloxane material was taken for the replication of the precise position of the implant (rotation, depth in the soft and hard tissues and angulation) relatively to the other oral structures (neighbouring teeth and gingiva).\n\nAn alginate impression of the inferior arch was also taken and the bite registered with a polyvinyl siloxane material. The color of the tooth was assessed and a clear lab prescription written. In the lab an upper and lower stone models were obtained and a proper titanium abutment was selected and parallelized for proper crown insertion.\n\nThe stone models were then scanned to acquire 3D models to mill a CAD/CAM metal framework of the crown. Afterwards, the abutment and the metal framework were directly checked in the mouth of the patient to evaluate the marginal and internal fit and were sent back to the lab for the final phase of ceramic shaping. During the next dental chair appointment, 8 months after implant insertion, it was possible to screw the titanium abutment and cement the metal-ceramic crown to prosthetically rehabilitate the dental implant of the upper jaw.26\n\nAfter tooth extraction and implant placement, the patient was strictly followed-up with weekly visits for four weeks and the pain did not remit. Tooth extraction was an unfortunate but an important and discriminating fact, ascertaining that the tooth was not the cause of the pain. In addition, due to the absence of any noticeable odontogenic aetiology and based on the psychological suffering reported by the patient and on the clinical and radiographical findings, the pain was deemed to be neuropathic in origin and specifically AO was diagnosed.\n\nThe prognostic characteristic of this pathology is generally thought to be a treatment-resistant condition,27 but a multi-disciplinary approach to treatment can lead to a positive outcome. Since the pain (SF-MPQ: score 2) had not remitted after a six-month-period of non-steroidal anti-inflammatory drugs, nor after tooth extraction, we settled for a more patient-centered approach and a combination therapy consisting of psychological counselling, behavioural and pharmacological intervention was prescribed. According to the literature and according to the previous hypothesis of neurogenic pain and specifically of AO, tricyclic antidepressant amitriptyline was prescribed. Nevertheless, symptoms did not abate (SF-MPQ: score 2) after three weeks of increasing doses of amitriptyline (starting dose: 25 mg in the evening for one week; 25 mg in the morning and in the evening during the second week; 25 mg in the morning and 50 mg in the evening during the third week) up to 75 mg per day. Thus, psychological intervention was added (i.e. psychological counselling and cognitive behavioural therapies, based on one session per week with a psychotherapist); also an increment of 25 mg of amitriptyline per week, up to 150 mg per day for six months (then gradually reducing 50 mg per week, until suspension was achieved within three weeks) was prescribed and five drops of clonazepam in the evening for one month (then gradually reducing to three drops for one week and then suspended) were added.\n\nThe rationale for the changes in our professional intervention were based on the medical and psychological history, from which we assumed we were facing a case of AO associated with comorbid psychiatric disorders.\n\nFollow-up and outcomes\n\nThe patient’s psychological sphere difficulties had been revealed by his medical history and upon this basis we decided on psychological counselling and behavioural support and tailored antidepressant and anxiolytic therapy, besides conventional therapy.\n\nThe patient reported satisfaction at each follow-up visit with the previously prescribed treatment, which also resulted in a rewarding and gratifying result for the dental team.\n\nFortunately, dental extraction was not a precipitating event and the clinical case was resolved, from a prosthetic standpoint, with the aid of an implant-supported rehabilitation.\n\nThe rehabilitation phases lasted eight months, from first-stage implant insertion surgery to the delivery of the implant-supported ceramic crown. The patient was followed up every 15 days by the dentist and the psychiatrist and was asked about pain intensity (SF-MPQ: score from 1 to 0) and characteristics and psychological conditions. After six months, since he reported decisive improvements in symptoms (SF-MPQ: score 0) and psychological suffering, we prescribed the patient a gradually reduced regimen of antidepressant therapy until suspension. The patient has been pain-free since then. The patient is now in a two-month follow-up programme with the psychiatrist and in a six-month recall programme for dental hygiene.\n\nPsychiatrist and dentist visits were interspersed with phone calls, or with e-mails, or with phone text messages to accomplish a comprehensive check of pharmacotherapy adherence and tolerability. As a consequence, pain, symptoms and psychological conditions were also assessed.\n\nWe report no adverse or unanticipated event with regards to the described clinical case.\n\nThe diagnosis and treatment of this clinical case was challenging and difficult, even though gratifying, from a differential diagnostic process point of view, especially because the pain had a non-odontogenic basis.\n\nPsychiatric counselling and cognitive behavioural therapies, along with a specific psychopharmacologic approach, are effective treatments for patients suffering acute anxiety, distress and depression while experiencing neuropathic pain. It offers several advantages: the patient may become more compliant and even major pain can be kept under control, with a reduced duration of the symptomatology. The dental office should have a good professional relationship with a specialist psychiatrist.\n\nClinical presentation and history\n\nA Caucasian 72-year-old Italian engineer male came to our private practice with a six-month history of pain of variable amplitude from moderate to severe, in the molar region of the right maxillary quadrant, radiating distant from the tooth area to the ipsilateral region and following the distribution of the branches of the trigeminal nerve. He reported a variety of symptoms and pain characteristics similar to odontogenic pain, which he insisted as originating from the second upper right molar, then radiating to the ipsilateral region.\n\nThe patient was eventually able to define his suffering as a stabbing, intermittent pain and sharp, shooting, and electric shock-like.\n\nFamily history revealed relevant depressive syndrome in the father with repeated hospitalizations.\n\nSince he revealed his psychological discomfort, which reflected on his private and professional life, sometimes affecting his concentration abilities while working, a psychiatric consultation was also scheduled.\n\nThe patient confided to the psychiatrist his uneasiness and reported that he was unsettled and tense: he experienced discomfort and anxiety due to worries about recurrence of pain. He also revealed his state of depression, especially originating from rumination about the condition.\n\nAs part of the current episode of care, after a combination of systemic medications had failed to ameliorate an assumption of maxillary sinusitis, the patient underwent an endodontic procedure, reportedly to reduce patient's suffering and complaints. A root canal therapy was carried out on his second maxillary right molar, the tooth considered by the patient as the cause of his pain. Since the pain had not alleviated during the four months following the procedure, the patient eventually decided to refer to our dental office for consultation.\n\nPatient assessment\n\nWe visited the patient and we did not detect signs of gingival inflammation, or radiographic signs of other pathologies, on the bases of a orthopantogram and of a periapical X-Ray of the second upper right molar. The first upper right molar had undergone endodontic treatment. Percussion of quadrant one and four was negative. Intra-oral palpation did not elicit pain. In quadrant one, the second premolar was an implant that had been in situ for four years; the first premolar, canine and incisors all responded within normal limits when tested with cold for pulpal vitality. Occlusion was also checked and was well balanced with no pain during masticatory muscle palpation. Temporomandibular joints were pain-free during palpation or function and had a normal range of motion.\n\nPain intensity was investigated using the short-form McGill pain questionnaire (SF-MPQ).24\n\nIt was immediately realized that we were dealing with an enigmatic pain, probably neuropathic in origin, and a complex and delicate situation, where quick and correct diagnosis seemed to be the principal goal.\n\nDiagnosis and therapeutic intervention.\n\nAs pain was radiating distant from the tooth area to the ipsilateral region and following the distribution of the branches of the trigeminal nerve, a regimen of an increasing doses of carbamazepine (starting dose: 100 mg. twice a day for one week; then 200 mg three times a day for another week), up to 200 mg three times daily, was prescribed to the patient for two weeks. Unfortunately, this only led to slight pain reduction (SF-MPQ: score: from 3 to 2) and more psychological suffering and concerns of the patient about the condition. We then immediately discussed the psychological aspects of the patient and decided to prescribe a more tailored and patient-centered therapy: psychological, behavioural and psychopharmacologic approaches were modulated based on the patient’s psychological profile.\n\nIn addition, carbamazepine therapy was maintained, following the same regimen. We based our diagnostic method on the anamnesis, on the comprehensive physical examination, on the X-ray examination and on the specific psychiatric consultation. In addition to this and despite low efficacy, carbamazepine was also a useful diagnostic tool, because it was able to somewhat reduce pain intensity (SF-MPQ: score 2) and characteristics.\n\nBased on the physical examination; the account of pain magnitude and distinctive features of the pathology; the report of the state of anxiety and depression; the absence of any noticeable radiographic signs of pathology; and the slight improvement of pain intensity (SF-MPQ: score 2) and characteristics after carbamazepine had been prescribed, we concluded that we were dealing with a neuropathic pain and specifically with a case of TN.\n\nTN is one of the most disabling orofacial pain conditions and the prognosis widely depends on the aetiology of the problem.28\n\nAfter a regimen of an increasing dose of carbamazepine up to 200 mg three times daily for two months had failed to completely quell the pain (SF-MPQ: score 2), psychological intervention was added (one session per week with a psychotherapist for three months, then reduced to one session every fifteen days up to now) and a regimen of three drops per day of citalopram, up to seven drops in the next ten days (starting dose: three drops per day for two days, then one more drop per day every two days) , and five drops of clonazepam in the evening for two months (then gradually reduced until suspension: reduced to three drops in the evening for one week and then suspended) were prescribed.\n\nAccording to the diagnosis of TN, we recommended the patient to adhere to his carbamazepine prescription too (200 mg three times daily).\n\nThe rationale behind the decision to change our intervention was primarily based upon medical and psychological history; however, carbamazepine was maintained during treatment since it was deemed to be consistent in a clinical case of TN.\n\nFollow-up and outcomes\n\nThe patient experienced relief of pain (SF-MPQ: score 1) and mood symptoms with a subjective perception of a satisfactory quality of life, which pleased the dental team.\n\nAfter drug prescription, the patient was followed up every 15 days and was asked about pain intensity (SF-MPQ: score from 1 to 0) and characteristics and psychological suffering.\n\nAfter two months, since he reported decisive improvements in symptoms (SF-MPQ: score 1-0) and psychological suffering, he was required to gradually reduce the therapy of antianxiety drugs until suspension.\n\nThree months later, after he had confirmed decisive ameliorations in pain intensity (SF-MPQ: score 1-0) and features and psychological suffering, he was prescribed to reduce the dosage of antidepressant drug (citalopram drug) from seven to five drops per day. The same regimen of carbamazepine was maintained (200 mg three times daily).\n\nThe patient has reported mild symptomatology since then, but his uneasiness during pain attacks has manifested as fear of pain recurrence: due to these reasons the patient is now in a 15-day follow-up programme with the psychiatrist and is also currently under a regimen of five drops of citalopram per day and he is still adherent to a reduced dosage of 200 mg of carbamazepine twice a day. Subsequently, we also included the patient in a six month-recall programme to accomplish dental hygiene.\n\nPhone calls, e-mails, and phone text messages, besides visits, were extremely efficient tools to assess patient prescription adherence and tolerability.\n\nWe report no adverse or unanticipated event in regard to the described clinical case.\n\nWhen facing a patient with comorbid psychiatric disorders associated with a neuropathic pain, the dental team should preserve patient confidence, reduce anxiety and depression and obtain compliance. In addition to conventional therapies, the dentist should be prepared to supplement a behavioural approach, a psychiatric consultation and a pharmacologic treatment to adopt appropriate patient-centered, modulated and balanced medical care. Thus, a psychiatrist should be available as part of the dental team.\n\n\nDiscussion\n\nOrofacial pain always represents a demanding and stimulating situation for the practitioner. Treatment can be troublesome.2 Long lasting pre-existing pre-treatment pain can represent a risk factor for the pain to become chronic.3\n\nPersistent pain tends to magnify the degree of pain and pain characteristics2 and can cause stress in both the patient and the clinician.\n\nEventually, lack of knowledge, diagnostic procrastination and possible useless irreversible dental treatment can lead to frustration4 up to real psychological distress, becoming a more complex condition to be managed.\n\nDealing with a wide range of patients, from the relaxed and collaborative to the anxious and depressed, the dental team should have a patient-centered approach and optimize and tailor the treatment, considering patients’ psychological profiles, pathology and pain characteristics. Therefore, a comprehensive anamnesis, including psychological assessment, and history listening is necessary and has been advocated.3,29 Drug history also has to be included29. According to patient’s characteristics and needs, a combination of reassurance, psychological counselling and psychopharmacologic treatment should be considered in cases of psychological distress. The proposed psychological, behavioural and psychopharmacologic approach has demonstrated advantages to control pain magnitude and peculiarities in AO and TN case reports, drastically reducing pain duration over time, ameliorating the clinical scenario and improving the patient’s psychological profile with patient satisfaction.\n\nThe limitation in our approach to these cases is that the evaluation and treatment of the comorbid psychiatric disorders were made by scheduled psychiatric consultation, clinical observation and patient self-report, but were not based on a standardized evaluation scale or a questionnaire, since these are not habitually available in a dental office.\n\nIn TN clinical case, the diagnosis and treatment was challenging and demanding: the pain was neuropathic in origin and therefore uncommonly managed in a dental clinic. Despite correct diagnosis and initial treatment, the severity and distinctive features of the pain did not significantly ameliorate after carbamazepine had been prescribed, which is considered an effective drug. Associated comorbid psychiatric disorders made a shift to a more complex condition to be managed.\n\nSome patients find relief in the treatment provided, others experience a chronic, severe pain, affecting the psychological sphere28. In this case report of TN, a multi-disciplinary approach to treatment radically improved the symptoms of the condition and enhanced the psychological state of the patient. After we had prescribed a psychiatric consultation and after we had also explained to the patient the planned treatment, we adopted a more patient-centered approach and we used all the appropriate behavioural techniques, psychiatric counselling and antidepressant and antianxiety drugs for the patient to remain emotionally balanced in his daily life and confident with the professional team.\n\nFor these reasons, dentists who frequently deal with orofacial pain should be well trained in recognising and interpreting the signs and symptoms of a specific pathology for an early diagnosis to avoid unnecessary psychological suffering and possible unwanted legal claims.\n\nThe diagnostic process might be particularly difficult, especially in cases of neuropathic pain with a non-odontogenic basis.1,2\n\nMoreover, the medical diagnosis can vary tremendously if a patient with pain below the imaginary line drawn between the eyes is assessed by a dentist or another medical specialist: in fact, orofacial pain in a dental environment is probably attributed to dental pathology, in contrast to orofacial pain patients in another medical environment likely being referred to a neurologist or to a maxillo-facial surgeon.29\n\nIn regard to the diagnostic process, a comprehensive record of pain history and extraoral and intraoral examination of the head and neck region is mandatory. Laboratory investigations and imaging can sometimes be helpful.29\n\nEventually, for an overview of the pathologies related to the challenging differential diagnosis in orofacial pain, several factors have to be taken into account.\n\nAs a general summary, comorbid psychiatric disorders are more frequent clinical findings in patients whose pathologies have shifted from an acute form to a chronic condition16 and all types of diagnosed orofacial pain are more prevalent in females than males,2 with myofascial pain remarkably more frequent. The peak age of prevalence is 50-67. Manual palpation of the muscles thought to be the origin of the pain must be carried out and must be bilateral. The pain is generally acute and can be unilateral or bilateral. Careful investigation of potential myofascial trigger points seems to be of paramount importance in migraine-associated neck and shoulder muscle pain.30 Mental health comorbidity has been recently investigated.31\n\nMyofascial pain usually positively responds to benzodiazepines and muscle relaxants2 and this may help in the diagnostic process.\n\nTemporomandibular disorders are also predominant in females32 and are very frequent, affecting 5% to 12% of the population. The peak age of prevalence is 20-40.29 Pain is related to the muscles used for mastication and of the neck. Being the only double joint of the human body, the pain is usually bilateral and all clinical investigations must be performed bilaterally. For the diagnostic process it is of primary importance that pain onset, during bilateral palpation, matches pain characteristics previously experienced by the patient. Clicking, locking, crepitus and limited opening (<40 mm) may be present and can lead to correct diagnosis.29 Imaging of both joints can be helpful. Generally, with an acute onset, comorbid psychiatric disorders can increase the risk of chronicity. Hard full arch splints are advantageous. Non-steroidal anti-inflammatory drugs, benzodiazepines29 and muscles relaxants have been considered controversial as medications to treat these patients, although in a more recent study the above-mentioned medications and opioids, corticosteroids, anticonvulsants, anxiolytics and antidepressants were considered efficacious in alleviating pain.33\n\nTemporal tendinosis is an underestimated musculoskeletal pathology inadequately studied, reported and comprehended.34 It is a chronic condition and causes orofacial pain.\n\nEmphasis has been placed on the diagnostic and differential diagnostic process, as well as on proper treatment and clinical care. Nevertheless, there is still a lack of agreement on the most effective therapeutic management. Clinically, it can appear as unilateral facial pain accompanied, or not, by temporal headache; the second, most frequent clinical presentation is orofacial pain radiating from the distal temporalis tendon to the temporalis muscle.\n\nDespite symptom similarity with temporomandibular disorders and giant cell arteritis, temporal tendinosis should be identified by means of anamnesis, proper related history, physical examination and dedicated imaging, such as ultrasound or MRI.34\n\nDental causes evoke acute pain and they are in all probability unilateral. Dental caries and periodontal diseases affect approximately 20-50% of the world’s population, with childhood prevalence but no gender prevalence for caries, and with no gender prevalence for periodontal diseases, which can affect patients from childhood to adulthood. Both pathologies represent the main reason for tooth loss.35\n\nIn most cases, the involved tooth is identifiable by the patient. Other times, e.g. in cases of pulpal involvement, the pain is more radiating and difficult to pinpoint to a specific tooth. Nevertheless, these conditions and the others related to dental problems are generally easily diagnosed and managed by dentists.\n\nA simple initial screening by periapical X-ray is very effective in the diagnostic process in the case of a decayed tooth, or to evaluate the alveolar bone and to recognize a periodontal disease. A comprehensive periodontal evaluation by gingival sulcular probing depth should always be undertaken.\n\nFor therapeutic or prophylactic reasons antibiotics are still largely prescribed to these patients, despite the known increasingly critical situation of antimicrobial resistance.35\n\nNon-steroidal anti-inflammatory drugs are also widely used for pain relief.\n\nAn accurate intraoral inspection to detect lesions related to diseases of the oral mucosa is also mandatory.36 A histological examination of the oral mucosae can be supportive to more specifically identify a suspected pathology. After the diagnostic process is completed, the patient undergoes appropriate therapy29 or is referred to the oral pathologist.\n\nMaxillary sinusitis can be acute or chronic. Generally unilateral, it can also be bilateral. There is not age nor gender prevalence. There is an odontogenic and a non-odontogenic form.37 The acute form is usually accompanied by pain and slight to moderate swelling of the cheek. Extraoral palpation of the skin, or intraoral palpation of the mucosa of the maxillary sinus area may provoke slight pain. Acute sinusitis is usually due to bacteria37 and viruses. If a bacterial infection is suspected, it is advisable to prescribe antibiotics, decongestants, and nasal saline solution rinses. In cases of acute sinusitis related to pathologies affecting the premolars or molars, proper dental care therapy solves signs and symptoms. Acute sinusitis can also follow dental extractions. In these cases, possible oral antral fistula must be identified and all surgical efforts need to be done to close the fistula.29\n\nChronic sinusitis can be unexpectedly detected by 3D X-ray imaging, for example when a better anatomical study of the surgical area is needed to detect possible septa, as in implantology, when an associated sinus lift procedure is planned.38 Chronic sinusitis is not usually associated with pain. Transnasal endoscopy done by an otolaryngologist is likely to be a useful and quick method for the diagnostic process.\n\nIn implantology, in case of a surgical complication during a sinus lift procedure due to dental implant displacement into the maxillary sinus, psychological distress can possibly be displayed by patients. This emotional condition is primarily due to the increasing length of the treatment planning for the diagnostic process to detect the foreign body position and for transnasal endoscopy removal. Proper treatment of distress needs to be accomplished.\n\nIn salivary gland disorders, a reduced volume of secretion or a change in the chemical composition of the saliva may be caused by salivary gland disfunction and can affect 5% to 46% of the population.39 This is usually a chronic condition, difficult to treat, known as xerostomia and may negatively affect patients’ quality of life, thus causing psychological suffering. Acute pain in the region of the salivary glands can be elicited by salivary stones, characteristically at the sight of food or immediately before eating. In the case of tumours or duct obstruction of a salivary gland, pain in the trigeminal nerve can follow. Bimanual palpation can allow the clinician to recognize the stone. More frequently, it is a unilateral condition and can be non-invasively diagnosed by ultrasounds and possibly with associated sialendoscopy40 or imaging.\n\nMany new cases of AO following relatively common dental procedures have been reported in industrialized countries. It is an increasingly recognized condition affecting up to 6% of patients after they have undergone endodontic therapies13 that has as an endpoint therapy the extraction of the involved tooth, without recovery of the pain.11\n\nIt can be diagnosed in both sexes in adulthood, although women around mid-40s are singularly more affected by the condition.41 It is a chronic condition, sleep can be undisturbed and pain can remit, with pain-free intervals, during the day.1 It is a neuropathic pain,29 characterized by continuous toothache following root canal therapy, apicoectomy, tooth extraction, implantology and even local analgesia administration.11,42–44 AO can also follow facial trauma and inferior alveolar nerve block.45 Poor analgesia at the time of the dental procedure has been regarded as an etiologic factor.29\n\nPrior long history of pain seems to have paramount importance since may represent a risk factor, and thus may increase the possibility of progression and origination of orofacial neuropathic pain in the same area.3\n\nCharacteristically, patients with AO describe the pain as continuous, non-paroxysmal, throbbing, sometimes burning or stabbing,11,15 which may make the differential diagnosis with trigeminal neuralgia difficult. The pain is referred to teeth or to the alveolar process, in the absence of any identifiable dental cause on clinical or radiographic examination.11\n\nMaxillary molars and premolars are more frequently affected.41\n\nPain can spread and be diffused unilaterally or bilaterally42 and thus difficult to localize for the patient.45 As already mentioned above, chronicity is at the base of demoralization, but it is unclear if this is the cause or the effect of the condition.42\n\nAO now seems to have various psychiatric comorbidities, having a great impact on treatments.16\n\nAmitriptylina has been reported to be helpful in treating AO,1,11,16 but an association with cognitive-behavioural therapy is highly recommended,2 especially for those patients experiencing impaired social and occupational function and relationships with others.\n\nTN is the most frequent cause of orofacial neuralgia, affecting four to five people per 100,000 population with the highest prevalence in women, with a reported proportion in women and men of three to one, aged between 37 and 67. Pain follows the distribution of one or more branches of the trigeminal nerve with a predilection for the maxillary and mandibular branches.1\n\nIt is a chronic condition. The pain is described as sudden, usually unilateral, brief, severe and stabbing. It can also be presented as a shooting, burning or paraesthesia sensation.12\n\nThese paroxysmal attacks can last seconds to minutes. Other variants report pain for hours. Patients may experience as many as 10 to 30 attacks daily, although attacks may remit for weeks or months.29 Pain rarely occurs during sleep.12\n\nTrigger points are characteristics of TN and attacks are provoked by light touch, washing, cold wind, eating, brushing teeth, talking, chewing.12\n\nFrom a pathophysiological stand point, tumour or vascular compression, leading to partial and focal nerve demyelination and consequent abnormal transmission and processing of impulses along the trigeminal nerve, or chronic irritation or trauma, have been thought to be involved in the origin of TN.1,18,19 More specifically, superior cerebellar artery aneurysms20 and venous compression21 have been taken into account in the development of TN. Moreover, TN affects 1% of patients with multiple sclerosis and 2% to 8% of patients with TN are affected by multiple sclerosis.18\n\nMRI can be used to reveal juxtaposition of vessels to the trigeminal nerve,12 benign or malignant lesions and plaques of multiple sclerosis.20\n\nAs a result of the fact that carbamazepine is very often able to alleviate the pain, the logical conclusion in the diagnostic process of these clinical cases might be that the pathology faced and tackled by the practitioner might match the criteria of TN.\n\nAlthough carbamazepine remains the most commonly used drug and is sometimes used as a diagnostic tool, many others have therapeutic coherence.18\n\nIn cases of unbearable drug side-effects or uncontrolled pain, surgical management should be considered,1 even if possibly followed by complications. TN has a profound impact on quality of life of affected patients.1\n\nThe act of concentrating during working hours can become very difficult and social relationships can be impaired too.\n\nFor these reasons a multidisciplinary approach can be helpful for the management of the neuropsychologic aspect of chronic pain, such as in TN46.\n\nA branch of the trigeminal nerve can also be involved in a neuro cutaneous viral infection, known as herpes zoster, which can sometimes lead to trigeminal post-herpetic neuralgia. It is a fairly frequent event in the elderly and immunocompromised patients, and is less frequently observed amongst children.47\n\nThe distribution of vesicles along nerves represents a diagnostic aid. Differential diagnosis can involve herpes simplex virus infection, recurrent aphthae, lichen planus, pemphigoid, pemphigus and immune defect consequent to drugs.47\n\nAlthough glossopharyngeal neuralgia may mimic TN due to paroxysmal pain attacks of two seconds to minutes, recurrent throughout the day, characteristically remitting for weeks or months, a difference in pain location is advantageous for the differential diagnosis: in fact, the pain is usually unilateral deep in the ear and/or back of the tongue, tonsils or neck.48\n\nIt may be confused at the beginning with a temporomandibular disorder because pain is referred in the auditory meatus,29 but a description of the pain as sharp, shooting electric shock, moderate to very severe, and the presence of evoking factors such as swallowing, coughing and touch of an ear, are likely to lead to the diagnosis of glossopharyngeal neuralgia.\n\nSyncope is a rare complication due to anatomical propinquity with the vagus.29\n\nMRI may be indicated to identify areas of vascular compression and surgery may be used to treat the condition.49\n\nPercutaneous radiofrequency thermocoagulation is another option to treat glossopharyngeal neuralgia.50\n\nThe trigeminal autonomic cephalalgias are a group of unilateral episodic pains29 characterized by prominent headache and ipsilateral cranial signs controlled by the autonomic nervous system, like conjunctival injection, lacrimation, tearing and rhinorrhoea. Some trigeminal autonomic cephalalgias share their short-lasting painful characteristics with TN and thus they must be distinguished and eventually treated differently.51\n\nAffecting the oral cavity, burning mouth syndrome is a ubiquitous oral rare chronic condition with a burning sensation of the oral mucosa and tongue, without relation to clinical causes; a unique and elucidating symptom for a prompt diagnosis.52 The syndrome usually affects peri- and post-menopausal women29 often wearing removable prosthesis.\n\nThis condition is often chronic and, due to unexplained oral symptoms, the patient usually experiences psychological distress and frustration, as it happens in neuropathic pain patients. Reassurance of no worsening of the symptoms can act as a helpful factor.\n\nGiant cell arteritis is the most frequent primary vasculitis of the elderly.\n\nPatients complain about pain in the temporal region and this fact can be confusing, leading to a misdiagnosed temporomandibular disorder or vice versa.\n\nIf not rapidly treated, giant cell arteritis can result in blindness and sometimes in stroke with associated extreme pain of part or of the whole face.\n\nTemporal artery biopsy as a diagnostic test is recommended, as well as other laboratory examinations. Steroids are the most credited therapy for patient management, but other efficacious therapies are now available.29\n\nPersistent idiopathic facial pain (PFIP), previously termed atypical facial pain, is a chronic condition and a rare disorder with an incidence rate of 4.4 per 100.000 persons per year.53 Females are more affected by the condition compared to males and the mean age of onset is in the mid 40s54.\n\nThe International Classification of Headache Disorders, 3rd edition, published by the Headache Classification Committee of the International Headache Society (IHS)14 presents PIFP as a continuous daily pain, lasting for more than two hours per day over a period of more than three months, but in the absence of clinical neurological deficit. Rarely, some patients report hours or days without pain. The pain is described as dull, aching, burning, throbbing and often stabbing and sharp. The pain is difficult to localize; most of the time it is radiating and unilateral, but sometimes bilateral.54\n\nComorbid psychiatric disorders and psychosocial impairments have frequently been associated with PIFP, jeopardizing personal relationships of the patient.29\n\nPIFP patients affected by higher pain intensity frequently experience anxiety and depression.\n\nDue to the complexity of the pathophysiology of the condition and comorbid psychiatric disorders, it has been concluded that an interdisciplinary approach is mandatory for the diagnostic process and management.55 Treatment may include tricyclic antidepressants; more recent antidepressants such as duloxetine56 and venlafaxine;57 anticonvulsants;58 low-level laser treatment;59 and high-frequency repetitive transcranial magnetic stimulation.60 From a psychological standpoint, it is important for the patient that the pain is acknowledged by the clinician as real.29\n\nSince comorbid psychiatric disorders may be frequently associated with orofacial pain, due to the effect of emotional states on pain perception and modulation, psychiatric and/or psychological counselling and proper drug management, together with an empathic attitude, might be determinant in patient compliance and an improvement in the clinical condition.\n\nMoreover, the diagnosis and treatment of orofacial pain, especially if with a non-odontogenic basis, is difficult and challenging for the dental practitioner and, thus, they must be familiar with the signs and symptoms related to these conditions.\n\nDentists need to be well trained in this specific field to avoid diagnostic delays and multiple, irreversible and ineffective dental treatments.\n\nIt is imperative that dentists have a patient comprehensive, health-centered approach during the differential diagnostic process, refraining from focusing on ordinary, common sources of tooth pain, thus aggravating the clinical condition of the patient and exposing themselves to the risk of legal claims.\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 was obtained from the patients.",
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PubMed Abstract | Publisher Full Text\n\nDavidowitz G, Kotick PG: The use of CAD/CAM in dentistry. Dent Clin North Am. 2011 Jul; 55(3): 559–70. PubMed Abstract | Publisher Full Text\n\nPigg M, Svensson P, Drangsholt M, et al.: Seven-year follow-up of patients diagnosed with atypical odontalgia: a prospective study. J Orofac Pain. 2013 Spring; 27(2): 151–64. PubMed Abstract | Publisher Full Text\n\nJones MR, Urits I, Ehrhardt KP, et al.: A Comprehensive Review of Trigeminal Neuralgia. Curr Pain Headache Rep. 2019 Aug 6; 23(10): 74. PubMed Abstract | Publisher Full Text\n\nZakrzewska JM: Differential diagnosis of facial pain and guidelines for management. Br J Anaesth. 2013; 111(1): 95–104. PubMed Abstract | Publisher Full Text\n\nSollmann N, Mathonia N, Weidlich D, et al.: Quantitative magnetic resonance imaging of the upper trapezius muscles – assessment of myofascial trigger points in patients with migraine. J Headache Pain. 2019 Jan 18; 20(1): 8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLorenc A, Feder G, MacPherson H, et al.: Scoping review of systematic reviews of complementary medicine for musculoskeletal and mental health conditions. BMJ Open. 2018 Oct 15; 8(10): e020222. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMontero J, Llodra JC, Bravo M: Prevalence of the signs and symptoms of temporomandibular disorders among Spanish adult and seniors according to five national surveys performed between 1993 and 2015. J Oral Facial Pain Headache. 2018 Fall; 32(4): 349–57. PubMed Abstract | Publisher Full Text\n\nOuanounou A, Goldberg M, Haas DA: Pharmacotherapy in temporomandibular disorders; a review. J Can Dent Assoc. 2017 Jul; 83: h7. PubMed Abstract\n\nBressler HB, Markus M, Bressler RP, et al.: Temporalis tendinosis: A cause of chronic orofacial pain. Curr Pain Headache Rep. 2020; 24(5): 18. PubMed Abstract | Publisher Full Text\n\nHaque M, Sartelli M, Haque SZ: Dental infection and resistance-global health consequences. Dent J (Basel). 2019 Mar 1; 7(1). Pii:E22. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlasser GD, Balasubramaniam R, Epstein J: Topical review-connective tissue diseases: orofacial manifestations including pain. J Orofac Pain. 2007; 21: 171–84. PubMed Abstract\n\nPuglisi S, Privitera S, Maiolino L, et al.: Bacteriological findings and antimicrobial resistence in odontogenic and non-odontogenic chronic maxillary sinusitis. J Med Microbiol. 2011 Sep; 60(Pt): 1353–9. PubMed Abstract | Publisher Full Text\n\nTkachenko PI, Pankevych AI, Kolisnyk IA, et al.: Diagnostic information of computed tomography of the upper jaw in patients required implant rehabilitation. Wiad Lek. 2018; 71(9): 1645–52. PubMed Abstract\n\nDonaldson M, Goodchild JH: A systematic approach to xerostomia diagnosis and management. Compend Contin Educ Dent. 2018 Nov/Dec; 39(suppl5): 1–9; quiz 10. PubMed Abstract\n\nGoncalves M, Mantsopoulos K, Schapher M, et al.: Ultrasound supplemented by sialendoscopy: diagnostic value in sialolithiasis. Otolaryngol Head Neck Surg. 2018 Sept; 159(3): 449–55. PubMed Abstract | Publisher Full Text\n\nGraff-Radford SB(1), Solberg WK: Atypical odontalgia. J Craniomandib Disord. 1992 Fall; 6(4): 260–5. PubMed Abstract\n\nMarbach JJ: Orofacial phantom pain: theory and phenomenology. J Am Dent Assoc. 1996 Feb; 127(2): 221–9. PubMed Abstract | Publisher Full Text\n\nBenoliel R, Kahn J, Eliav E: Peripheral painful traumatic trigeminal neuropathies. Oral Dis. 2012 May; 18(4): 317–32. PubMed Abstract | Publisher Full Text\n\nMarbach JJ, Hulbrock J, Hohn C, et al.: Incidence of phantom tooth pain: an atypical facial neuralgia. Oral Surg Oral Med Oral Pathol. 1982 Feb; 53(2): 190–3. PubMed Abstract | Publisher Full Text\n\nMarbach JJ: Is phantom tooth pain a deafferentation (neuropathic) syndrome? Part II: Psychosocial considerations. Oral Surg Oral Med Oral Pathol. 1993 Feb; 75(2): 225–32. PubMed Abstract | Publisher Full Text\n\nSpina A, Mortini P, Alemanno F, et al.: Trigeminal Neuralgia: Toward a Multimodal Approach. World Neurosurg. 2017 Jul; 103: 220–30. PubMed Abstract | Publisher Full Text\n\nFrancis M, Subramanian K, Sankari SL, et al.: Herpes Zoster with Post Herpetic Neuralgia Involving the Right Maxillary Branch of Trigeminal Nerve: A Case Report and Review of Literature. J Clin Diagn Res. 2017 Jan; 11(1): ZD40–ZD42. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBlumenfeld A, Nikolskaya G: Glossopharyngeal neuralgia. Curr Pain Headache Rep. 2013 Jul; 17(7): 343. PubMed Abstract\n\nNapenas JJ, Zakrzewska JM: Diagnosis and management of trigeminal neuropathic pains. Pain Manag. 2011; 1: 353–65. PubMed Abstract | Publisher Full Text\n\nSong L, He L, Pei Q, et al.: CT-guided percutaneous radiofrequency thermocoagulation for glossopharyngeal neuralgia: A retrospective clinical study of 117 cases. Clin Neurol Neurosurg. 2019 Mar; 178: 42–45. PubMed Abstract | Publisher Full Text\n\nEller M, Goadsby PJ: Trigeminal autonomic cephalalgias. Oral Dis. 2016 Jan; 22(1): 1–8. PubMed Abstract | Publisher Full Text\n\nTu TTH, Takenoshita M, Matsuoka H, et al.: Current management strategies for the pain of elderly patients with burning mouth syndrome: a critical review. Biopsychosoc Med. 2019 Jan 31; 13(1). ECollection 2019. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKoopman JS, Dieleman JP, Huygen FJ, et al.: Incidence of facial pain in the general population. Pain. 2009 Dec 15; 147(1-3): 122–7. Epub 2009 Sep 26. PubMed Abstract | Publisher Full Text\n\nMaarbjerg S, Wolfram F, Heinskou TB, et al.: Persistent idiopathic facial pain - a prospective systematic study of clinical characteristics and neuroanatomical findings at 3.0 Tesla MRI. Cephalalgia. 2017 Nov; 37(13): 1231–40. Epub 2016 Oct 27. PubMed Abstract | Publisher Full Text\n\nHals EKB, Stubhaug A: Mental and somatic co-morbidities in chronic orofacial pain conditions: Pain patients in need of multiprofessional team approach. Scand J Pain. 2011 Oct 1; 2(4): 153–54. PubMed Abstract | Publisher Full Text\n\nNagashima W, Kimura H, Ito M, et al.: Effectiveness of duloxetine for the treatment of chronic nonorganic orofacial pain. Clin Neuropharmacol. 2012 Nov-Dec; 35(6): 273–7. PubMed Abstract | Publisher Full Text\n\nForssell H, Tasmuth T, Tenovuo O, et al.: Kalso E Venlafaxine in the treatment of atypical facial pain: a randomized controlled trial. J Orofac Pain. 2004 Spring; 18(2): 131–7. PubMed Abstract\n\nVolcy M, Rapoport AM, Tepper SJ, et al.: Persistent idiopathic facial pain responsive to topiramate. Cephalalgia. 2006 Apr; 26(4): 489–91. PubMed Abstract | Publisher Full Text\n\nYang HW, Huang YF: Treatment of persistent idiopathic facial pain (PIFP) with a low-level energy diode laser. Photomed Laser Surg. 2011 Oct; 29(10): 707–10. Epub 2011 Sep 9. PubMed Abstract | Publisher Full Text\n\nLindholm P, Lamusuo S, Taiminen T, et al.: Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation. Pain. 2015 Jul; 156(7): 1276–83. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "83851",
"date": "14 May 2021",
"name": "Joanna M. Zakrzewska",
"expertise": [
"Reviewer Expertise Expert in facial pain and report to be the world expert in trigeminal neuralgia by expertscape"
],
"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 a case report article highlighting two cases of non dental facial pain which had psychiatric co-morbidity.\nIt is now well established that all chronic conditions and especially chronic pain results in mental health co-morbidities. These should always be explored and seeing these patients in a multidisciplinary team setting is advantageous.\nThe introduction should provide the criteria of depression and anxiety as provided by the DSM classification. The IMMPACT1 group have suggested the outcome measures that should be used to ascertain various aspects of pain including mood and quality of life.\nThe diagnostic criteria for the two conditions could be summarized in a table using the ICHD2 classification which would then highlight the similarities and differences between the two conditions.\nThe two cases should provide more detailed history rather then very detailed treatment plans. For the trigeminal neuralgia (TN) case the reader should be provided with details of onset of the condition e.g memorable, timing of each attack, severity, frequency of attacks, provoking factors, possible remission periods. According to guidelines for TN an MRI should have been done and its result reported. How was the impact on mood and quality of life measured? SF-MPQ is insufficient and we have shown the considerable impact this condition has on life3 and how this can be improved over time4. If the pain does not respond to carbamazepine initially then the diagnosis needs to be re-visited and potentially other anti-epileptics used as per guidelines5. Why use clonazepam, potentially addictive drug when addressing the TN pain which often resolves the depression as we have shown?3.\nThese patients certainly benefit from a cognitive behaviour programme6. A liaison psychiatrist is a useful addition to the team but one needs clinical psychologists and clinical nurse specialists as we have shown in our pathway7.\nDiscussion is very long winded and makes an attempt to provide differential diagnosis. This could best be summarised through a table as has been done in other publications. I do not think this article provides any new information. There is an excellent series of articles on facial pain in a special issue of Cephalalgia 2017 Vol 37 No 7.\n\nIs the background of the cases’ history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No\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? Partly",
"responses": [
{
"c_id": "7206",
"date": "18 Oct 2021",
"name": "Riccardo Tizzoni",
"role": "Author Response",
"response": "Dear Prof. Joanna M. Zakrzewska, we thank you very much for the reviewing process. Your review stimulated us to amend and ameliorate the article, creating a second version. We hope that our responses and revisions may now satisfy you. Again, thank you very much I send my Best Regards, Riccardo Tizzoni"
}
]
},
{
"id": "90507",
"date": "12 Aug 2021",
"name": "Giulia Di Stefano",
"expertise": [
"Reviewer Expertise Facial Pain",
"Neuropathic pain mechanisms",
"treatment of trigeminal neuralgia"
],
"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 paper, the Authors described two cases of orofacial pain, focusing on the psychiatric comorbidity and the need of a multidisciplinary treatment approach.\nI have the following suggestions to improve the quality of the report.\nDiagnostic criteria should be reported more clearly in a table.\n\nIn patients with odontalgia, the neuropathic origin of pain should be excluded through neurophysiological tests (trigeminal reflexes) evaluating trigeminal afferents integrity. I suggest mentioning this point in the text.\n\nI suggest citing the etiological classification of trigeminal neuralgia. Recent diagnostic criteria distinguish trigeminal neuralgia as “classical”, related to neurovascular compression producing morphological changes on the trigeminal root, ‘‘secondary’’ to a major neurological disease or ‘‘idiopathic’’ with unknown etiology. Genetic factors may play a role in the pathophysiology of idiopathic trigeminal neuralgia. These points should be addressed in the text\n\nPathophysiology of paroxysmal pain should be expanded. Vascular compression is the usual cause of demyelination at the site just before the nerve enters the pons, and multiple sclerosis is the typical cause at the site just after entry into the pons.\n\nThe possibility of concomitant continuous in a significant portion of patients with trigeminal neuralgia should be cited.\n\nIn the description of patients with trigeminal neuralgia, the term “pain amplitude” should be replaced with “pain intensity”\n\nWere trigger zones or maneuvers reported by the patient? What about remission periods? Were MRI data available?\n\nIn the discussion, I suggest a more concise description of the alternative orofacial pain diagnosis. Some sections seem redundant.\n\nOxcarbazepine should be cited with carbamazepine as first line drugs. Second line drugs should be mentioned.\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? 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 conclusion balanced and justified on the basis of the findings? Partly",
"responses": [
{
"c_id": "7205",
"date": "18 Oct 2021",
"name": "Riccardo Tizzoni",
"role": "Author Response",
"response": "Dear Prof. Giulia Di Stefano we thank you very much for the entire, precious process of reviewing our article. The comments and suggestions indicated by you have been considered and we hope satisfactorily addressed. We amended the whole manuscript accordingly. Thank you very much. I send you my Best Regards Riccardo Tizzoni"
}
]
}
] | 1
|
https://f1000research.com/articles/10-317
|
https://f1000research.com/articles/10-581/v1
|
16 Jul 21
|
{
"type": "Data Note",
"title": "A large-scale image dataset of wood surface defects for automated vision-based quality control processes",
"authors": [
"Pavel Kodytek",
"Alexandra Bodzas",
"Petr Bilik",
"Pavel Kodytek",
"Petr Bilik"
],
"abstract": "The wood industry is facing many challenges. The high variability of raw material and the complexity of manufacturing processes results in a wide range of visible structure defects, which have to be controlled by trained specialists. These manual processes are not only tedious and biased, but also less effective. To overcome the drawbacks of the manual quality control processes, several automated vision-based systems have been proposed. Even though some conducted studies achieved a higher recognition rate than trained experts, researchers have to deal with a lack of large-scale databases and authentic data in this field. To address this issue, we performed a data acquisition experiment set in the industrial environment, where we were able to acquire an extensive set of authentic data from a production line. For this purpose, we designed and implemented a complex technical solution suitable for high-speed acquisition during harsh manufacturing conditions. In this data note, we present a large-scale dataset of high-resolution sawn timber surface images containing more than 43 000 labelled surface defects and covering 10 types of the most common wood defects. Moreover, with each image record, we provide two types of labels allowing researchers to perform semantic segmentation, as well as defect classification, and localization.",
"keywords": [
"wood surface defects",
"high resolution dataset",
"wood industry",
"wood processing",
"wood quality control process",
"wood defects dataset"
],
"content": "Introduction\n\nIn the wood industry, each step of the manufacturing process affects material utilization and cost efficiency.1 The heterogeneity of wood material with the complexity of these manufacturing processes may result in various defects, which not only degrade the mechanical properties of the wood such as the strength and stiffness but also reduce its aesthetic value.2 These mechanical and aesthetical defects have furthermore a large impact on the commercial value of the wood and can diminish the utilization of such materials for further processing. There are many various types of defects arising from many different causes. The major wood defects include knots, fungal damage, cracks, warping, slanting, wormholes, and pitch defects. The seriousness of a defect, and therefore the grade and the cost of the material, is primarily determined by four criteria, including the size, location, type of the defect, and the purpose for which the wooden product will be used.3,4\n\nEven though the automation in this industrial sector is growing, many market leader companies still utilize trained domain experts to detect undesirable features and to perform quality grading.5 Besides the fact that the manual examination is tedious and biased, it was found that domain experts are not able to check large production volumes. Moreover, the study conducted by Urbonas et al.6 stated that due to factors such as eye fatigue or distraction, manual inspection rarely achieves 70 % reliability. To overcome the drawbacks of the manual examination, researchers try to develop automated systems, which are accurate and won't slow down the manufacturing process. According to the repeatability and quality of the inspection, the study performed by Lycken7 has already proved that automatic systems slightly outperformed human graders. Most of these systems were based on conventional image processing techniques in combination with supervised learning algorithms, however, over the last decade deep learning has achieved remarkable success in the forestry and wood products industry.8 Although researchers in the field were able to achieve satisfying results with the average recognition rate above 90 %,9 most of the authors worked with small-scale image datasets obtained in laboratory conditions by using self-developed vision system setups. Performing experiments in such conditions usually entails the disadvantage of a limited number of available products. In most of the studies,2,6,10,11 researchers compensate for the lack of real products by using data augmentation techniques, which can expand the dataset up to 10 times its original size. From one point of view, data augmentation is considered to be an excellent tool to generalize the classification model and therefore prevent overfitting.12 Nonetheless, it cannot ensure that the variability of the observed phenomenon will be sufficiently captured, especially in cases where the variability might be limitless.\n\nIn order to address the lack of extensive databases in the field, we performed an experiment with the goal to acquire a large-scale dataset of timber surface defects. Unlike other conducted studies, our experiment was placed in an industrial environment during real production, which allowed us to acquire a large amount of authentic data from the production line. To face the challenges arising from the manufacturing process, such as the high speed of the conveyor belt and heavy vibrations, we designed hardware as well as a software solution, which enabled acquisition of high-resolution images at the acquisition rate of 66 kHz. In this experiment, we acquire 20 276 original data samples of sawn timber surface, from which 1 992 images were without any surface defects, and 18 284 images captured one or more defects covering overall 10 types of common wood surface defects. The most frequent defects include live knots and dead knots, with an overall occurrence in the dataset of 58.8 % and 41.2 %, respectively. Furthermore, to provide more valuable information in this data descriptor, all dataset samples were complemented with two types of labels: a semantic label map for the semantic segmentation and a bounding box label.\n\n\nMethods\n\nDue to the industrial environment where the experiment was set, the most challenging part of this work was the dataset acquisition. Performing data acquisition in such an environment entailed several negative factors. One of those factors was that the sawmill production line utilized for this experiment is used for more than 300 days per year, with minimal pauses, which maximizes the manufacturer's profits. Also, we had to deal with the high speed of the sawmill conveyor belt, which reached a value of 9.6 m s−1 at the place of the acquisition. This high speed of the conveyor causes constant heavy vibrations that in some peaks may result in fluctuations that are even centimetres in length. The main goal of the technical solution was therefore to create a robust and at the same time portable construction, which can be easily implemented in the sawmill environment.\n\nTo overcome the limitation of this environment, we developed a mechanical construction for carrying the camera and the light source. The final construction assembled from ITEM aluminium profiles was at the place of the acquisition fixed to the production line construction and the floor, which helped to avoid the acquisition of blurry images. Although this solution didn’t deal directly with heavy vibrations, it ensured the harmonization of the conveyor vibrations with the mounted camera. The final mechanical solution implemented in the sawmill environment is demonstrated in Figure 1.\n\nThe distance between the line scan camera and the light source from the conveyor belt is 40 and 15 centimetres, respectively.\n\nIn order to obtain high-quality images at a speed of 9.6 m s−1, a trilinear line scan camera SW-4000TL-PMCL manufactured by JAI was chosen. This camera was able to acquire 3 × 4096 pixels per line at the speed of 66 kHz. The required speed of the image acquisition was achieved by connecting the camera interface to a high-performance Camera Link frame grabber with the transfer speed parameter set to 10 tap mode. For this application, we selected the Silicon Software microEnable five marathon VCLx frame grabber with a PCIe interface that allows on-board high-speed data processing and high data throughput up to 1800 MB s−1. The required field of view, which obtains a part of the sawn timber piece, with a width of 15 cm and the full length of 500 cm was achieved by using the Kowa LM50LF line scan camera lens. The selected camera, together with a 50 mm focal length lens placed at a distance of 40 cm from the measured object, led to a horizontal resolution of 16.66 pixels per millimetre. The vertical resolution Rv of the image was computed before the experiment by the following formula.\n\nwhere vw is the velocity of the conveyor, L is the number of lines per image, and vc is the line rate of the camera. The resulting vertical resolution of 6.67 pixels per millimeter was afterward experimentally verified during the acquisition process.\n\nSince the shutter of the camera was set to 3 μs to ensure the high-speed image acquisition, we had to use a powerful light source, which would sufficiently illuminate the desired field of view. For this purpose, we selected one of the most powerful light sources on the market, a linear LED light Corona II by Chromasens with the ability to provide a light intensity of 3.5 million lux. To achieve the best possible images, a white spectrum of the light was utilized.\n\nInstead of saving every single line during the acquisition process, we captured a block of 1024 lines, which resulted in an image resolution of 1024×4096. Such a high-resolution color image takes up approximately 12 MB of disk space. The used sampling frequency of 66 kHz with the total number of captured pixels resulted in a data transfer speed of 773 MB s−1, which means that we were able to capture 66.4 images per second. Even though we used a very powerful computer, we found the process of saving this amount of data at such a high speed quite challenging. To overcome this challenging task, we had to separate image acquisition and image saving into two separate processes. While the acquisition process consisted of capturing a set of 84 images with a subsequent saving into the PC's RAM, the only task of the saving process was the transfer of the images from the computer RAM to the local hard disk drive. For this experiment, we employed two external 1 TB hard drives. To save CPU time during the acquisition and saving process, no online processing was performed.\n\nBecause transferring such a large amount of data between different software have a negative impact on CPU utilization and would decrease the frame rate, we used optimized frame grabber software, microDisplay X (runtime version 5.7) from Silicon Software.13 To use this software in an automated way, we developed an automatic clicker with a feedback loop based on the captured computer screen. In simple terms, the software reads the desired information from the screen and based on the information decides whether the acquisition or saving process is already completed. Additionally, it automatically assigns an incrementing filename to each captured image. This was mainly realized by using Windows library user32.dll, which allows the control of various aspects of mouse motion and button clicking. Since the saving process (loop) is almost 10 times slower than the acquisition process, the acquisition loop had to be temporarily stopped in each cycle. Despite the fact that this causes loss of the data continuity, it does not affect the study validity and reliability. We assumed that the acquisition process with the other support subroutines takes approximately 1.4 s while the saving process lasts 7.5 s. To maintain a predictable acquisition speed, including software delays, we introduced synchronization, which started a new cycle every 9 s.\n\nDuring four hours of acquisition, 60 480 images were acquired overall. Due to the limited third-party software functionality, the acquisition process had to be performed in a continuous mode, without any triggering option. This resulted in a large number of images of an empty conveyor or partly captured wood surface. To filter these meaningless data from the dataset, an offline histogram-based algorithm was created. The basic idea behind this algorithm is the sum calculation of the image green color space histogram. This sum value of the histogram can be in the next step divided by any number from the range of 5 to 10 (values in the range were deduced from the size of the images). The last step of the algorithm is based on a simple threshold, where all images with a resulting value of less than 10 were removed. Using this value of threshold ensured that only images that contained in the horizontal direction at least 40 % of the wood surface were kept. Since this filtration approach proved 100 % reliable in successfully filtering images with no wooden surface on 1500 randomly selected and manually sorted samples, we applied this filtering algorithm on the whole dataset. The filtering process reduced the dataset to a final number of 20 275 images.\n\nAdditionally, besides the filtration, we performed image cropping to remove the undesirable background from the images. This operation not only reduced the file size but also decreased the potential computation time for future use. To automatically crop each image in the dataset without any relevant data loss, we employed a simple straight-line edge detection technique in a vertical direction. Basically, the main principle of the algorithm is finding as many raising edge points in the desired direction as are needed to construct a line. The cropping operation was then performed on the image bounding box derived from the following formula.\n\nwhere BBx1y1x2y2 is the cropped bounding box, and Lx1y2x1y2 stands for the image coordinates of the detected straight edge. Cropping the image, changed the image resolution to 2800 × 1024, and reduced the overall dataset size by almost 80 GB. An example of the image after the image crop operation is demonstrated in Figure 2.\n\nThe dataset annotation in this study was performed manually by a trained person. To accelerate this time-consuming process, we developed a customizable annotation tool. In comparison with other annotation tools available on the market, which didn’t fulfil our requirements, we created a universal application with the ability to manage bounding box labels, as well as labels for the semantic segmentation at the same time.14\n\nFor every single image, we created a BMP file representing a semantic map of the labeled defects. During the labeling process, the user manually painted zones in a displayed image, where each zone drawn with a selected color represents a specific defect. Each drawn zone was then automatically bounded with a zone of the particular label and a bounding rectangle. From the created zones, the tool automatically generated coordinates (left, top, right, bottom respectively) in the form of percent divided by 100, where a certain defect is located. For each processed image from the dataset, the annotation tool therefore created a text file including labels and bounding box coordinates and a semantic segmentation map with the configured color labels.\n\n\nData records\n\nThe dataset containing the data acquired in this experiment is publicly available.15 The dataset includes 1 992 images of sawn timbers without any defects and 18 283 timber images with one or more surface defects. On average, there are 2.2 defects per image, while only 6.7 % of images contain more than three defects. The highest occurrence of defects, which was captured during the experiment, was 16 defects per image. In this dataset, we present altogether 10 types of wood surface defects, including several types of knots, cracks, blue stains, resins, or marrows. An overall overview of all available wood surface defects with a number of occurrences is summarized in Table 1.\n\nEach colour image with a resolution of 2800×1024 is provided in a BMP format in 10 separated zip folders labelled as Images.15 Additionally, we provide two types of annotations, semantic label maps, and bounding box labels. Both labels are provided in separate zip folders. The bounding box labels are located in a folder Bounding_Boxes and named as imagenumber_anno.txt, where the image number corresponds to the name of the original image in the dataset. Each original image has therefore one assigned text file, which can have multiple label records for each defect in the image. All bounding box labels have the following structure, where the first record represents the object label, and the subsequent values correspond to left, top, bottom, and right absolute positions of the defect in the image divided by 100.\n\nSemantic label maps, used for semantic segmentation, are located in a folder, Semantic Maps. For each image in the dataset there exists just one semantic map in a BMP format with the label name in the form of imagenumber_segm.bmp, where the image number represents the corresponding name of the original image. In comparison to bounding box labels, each pixel of the semantic map image has its label, which is determined by a specified colour (see Figure 3).\n\nThe red label represents dead knots, the green label stands for live knots, and the dark yellow represents knots with cracks.\n\nTo see the exact label specification for the provided wood surface defect dataset, refer to Semantic Map Specification text file,15 or Table 2.\n\n\nTechnical validation\n\nThe technical validation of the dataset was conducted by assessing the quality of the assigned labels by employing deep learning-based classification. For this purpose, we utilized a standard state-of-the-art Convolution neural network detector based on the ResNet-50 model.16 The selected neural network architecture was modified by adding Batch Normalization and ReLu layers after each convolution layer. The input layer of the network, and therefore all dataset images were downsampled to 1024×357. To train the neural network, we employed a transfer learning paradigm using pre-trained weights from the COCO dataset.17 Moreover, we performed data augmentation, including horizontal, vertical flip, translation and scaling, and divided the dataset into training and testing set in a conventional ratio of 40/60. To increase the detection of the labelled defects by the ResNet-50 model, several parameters were additionally modified on the basis of the trial-and-error process. These included sizes, strides, ratios and scales (see Table 3).\n\nAt the beginning of the training, the first four layers of the network were frozen. After freezing the layers, the neural network was tuned by unfreezing the layers in a reverse order except for the Batch Normalization layer. The whole neural network was then finally fine-tuned at a low training speed. The overall number of epochs during the training was 30, while the training speed ranged between 10-4 at the beginning and 10-6 at the end of the training.\n\nThe trained ResNet-50 model resulted in an accuracy of 81 %. Since the neural network output a large number of false positives, the dataset was re-evaluated by a trained person who didn’t participate in the primary dataset labelling process.\n\n\nData availability\n\nZenodo: Underlying data for A large-scale image dataset of wood surface defects for automated vision-based quality control processes. ‘Deep Learning and Machine Vision based approaches for automated wood defect detection and quality control’. http://doi.org/10.5281/zenodo.4694695.15\n\nThis project contains the following underlying data:\n\n• Bounding boxes\n\n• Images 1–10\n\n• Semantic map specification\n\n• Semantic maps\n\nData are available under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0).\n\n\nSoftware availability\n\nZenodo: Software for labeling wood surface defects and managing images. ‘Supporting tools for managing and labeling raw wood defect images’. http://doi.org/10.5281/zenodo.4904736.14\n\nThis project contains the following underlying data:\n\nLabeler tool:\n\nSubVI\n\n\n\n• Labeler_software.vi\n\n• Readme.txt\n\n• Labeler.ini\n\nSupport Utils:\n\n• Cutter.vi\n\n• Sorter.vi\n\nData are available under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0).",
"appendix": "References\n\nBroman O, Fredriksson M: Wood material features and technical defects that affect yield in a finger joint production process. Wood Mater. Sci. Eng. 2012. Publisher Full Text\n\nDing F, Zhuang Z, Liu Y, et al.: Detecting defects on solid wood panels based on an improved SSD algorithm. Sensors. 2020. PubMed Abstract | Publisher Full Text | Free Full Text\n\nProkhorov M: Great Soviet Encyclopedia: A Translation of the Third Edition . New York: Collier Macmillan Publishers; 1973.\n\nÇetiner I, Var AA, Çetiner H: Wood surface analysis with image processing technique. 22nd Signal Processing and Communications Applications Conference (SIU). 2014. Publisher Full Text\n\nGu IYH, Andersson H, Vicen R: Automatic classification of wood defects using support vector machines. In: Bolc L, Kulikowski JL, Wojciechowski K, editors. Lecture Notes in Computer Science. Berlin: Springer Science+Business Media; 2009. p. 356–367.\n\nUrbonas A, Raudonis V, Maskeliūnas R, et al.: Automated identification of wood veneer surface defects using faster region-based convolutional neural network with data augmentation and transfer learning. Appl. Sci. 2019. Publisher Full Text\n\nLycken A: Comparison between automatic and manual quality grading of sawn softwood. Forest Prod. J. 2006; 56: 13–18.\n\nLiu Z, Peng C, Work T, et al.: Application of machine-learning methods in forest ecology: Recent progress and future challenges. Environmental Reviews. 2018; 26. Publisher Full Text\n\nKryl M, Danys L, Jaros R, et al.: Wood recognition and quality imaging inspection systems. J. Sens. 2020; 2020. Publisher Full Text\n\nHe T, Liu Y, Xu C, et al.: A Fully Convolutional Neural Network for Wood Defect Location and Identification. IEEE Access. 2019. Publisher Full Text\n\nGao M, Chen J, Mu H, et al.: A Transfer Residual Neural Network Based on ResNet-34 for Detection of Wood Knot Defects. Forests. 2021; 12. Publisher Full Text\n\nJackson PTG, Amir A-A, Bonner S: Style augmentation: data augmentation via style randomization. Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition. 2019.\n\nBasler AG: microDisplay X – The Reliable Path to Your First Image: Basler. Basler AG. 2021, May 28. Reference Source\n\nKodytek P, Bodzas A: Supporting tools for managing and labeling raw wood defect images. Zenodo. 2021. Publisher Full Text\n\nKodytek P, Bodzas A, Bilik P: Supporting data for Deep Learning and Machine Vision based approaches for automated wood defect detection and quality control. Zenodo. Dataset. 2021. Publisher Full Text\n\nHe K, Zhang X, Ren S, et al.: Deep Residual Learning for Image Recognition. 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR). 2016. Publisher Full Text\n\nLin T, Maire M, Belongie S, et al.: Microsoft COCO: Common objects in context. ECCV. 2014."
}
|
[
{
"id": "100946",
"date": "25 Nov 2021",
"name": "Mariusz Pelc",
"expertise": [
"Reviewer Expertise Computer science",
"data / signal processing",
"automation and robotics",
"bio-medical engineering",
"expert sytsems."
],
"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 deals with a relevant problem which is detection of wood surface defects.\nFor the purpose of the research, the authors have come up with a coherent methodology allowing them to acquire all required data, then mapping and detecting defects. From an algorithmic viewpoint it all makes sense, besides, the whole methodology/algorithm validation has also been performed.\nSo, the paper ticks pretty much all the boxes (relevance, novelty, etc.) and as such it qualifies for publication.\nHowever, the paper requires some substantial changes in the following areas:\nThere is no related work section which makes it really difficult to understand the authors' contribution to the field. I would recommend adding such a section (even if it is brief) where similar solutions would be discussed and confronted with what the authors are proposing in this paper.\n\nEvery single paper should include a conclusion section allowing all readers to understand key findings of the research. This paper is lacking a conclusion section which is quite an omission.\n\nSome tables (e.g. Table 1) should be re-done as their versions included in the paper are hardly readable. Usually one look at a table provides a lot of information about the results whilst in this paper this is not the case. I would suggest the authors re-format all tables to make all the dates gathered in the table easy to see and understand.\n\nThe \"Software availability\" section should be rewritten. I would suggest the authors make this section easily comprehensible via adding some more description of the software tools used and maybe outline some key feature(s) of the software. Also, based on the section contents, the section title better reflecting this would be e.g. \"Supporting software tools\" where first paragraph should say that in this research the following software was used (then outline the software and how it was used).\n\nReferencing - I only want to make sure that the authors have used the proper referencing style since the most frequently used are either Harvard or IEEE, whilst the authors have used a foot-note like referencing style.\n\nThe whole paper is written in maybe not error-free but still quite coherent and comprehensible English. But I would still recommend at least one more proof reading to make sure that there are no obvious mistakes left in the text.\n\nBased on the above consideration I would recommend accepting the paper for indexing after revision.\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": "8411",
"date": "27 Jun 2022",
"name": "Alexandra Bodzas",
"role": "Author Response",
"response": "The point-by-point responses to comments: 1. Our paper was written in accordance with the journal guidelines for a Data Note article, which slightly differs from an original research article. Concerning the Data Note article, there is no related work section included in the article structure. However, to fulfill your requirements, we complemented the introduction section with a paragraph where we discussed similar solutions. The importance of this research is then explained in subsequent paragraphs. 2. The conclusion section is omitted intentionally again since we followed the data note article guidelines. 3. The tables in the article cannot be re-formatted since the article had been formatted by the editorial team before the publication. Table formatting is within the scope of an editorial team that formats the table according to the journal standards. Since the article is an online article, the tables are accessible and visible in full size after clicking on them. 4. The original Software availability section was rewritten before the publication to fulfill the editorial team's requirements. However, we complemented this section by adding some descriptions of the software. The title of this section cannot be changed since it follows the guidelines for a data note article and journal standards. 5. We unified the reference styles within the references. All references in a reference list are according to the Harvard referencing style. The in-text citation on the other hand are according to the journal standards, and the footnotes were added by the editorial team during the typesetting process 6. The paper was proofread and edited. The obvious mistakes were corrected."
}
]
},
{
"id": "136809",
"date": "26 May 2022",
"name": "Sri Rahayu",
"expertise": [
"Reviewer Expertise Single-cell technologies"
],
"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\nWood defect datasets are still rare, so this research is very helpful for the wood industry and researchers interested in this field. The authors explain in detail the reasons for building this database with clear data acquisition and collection techniques.\nSome of the methods used to construct semantic images and image testing may be replicated in others. The image acquisition technique used will be of great value if you mention the acquisition technique in other similar studies.\nIt would be even better if the authors provide examples of images for each image class and also presents the stages of the research in the form of a chart\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? Partly",
"responses": [
{
"c_id": "8412",
"date": "27 Jun 2022",
"name": "Alexandra Bodzas",
"role": "Author Response",
"response": "The point-by-point responses to comments: 1. We complemented the Introduction section with a paragraph describing wood defects acquisition techniques used in other studies (Paragraph 3). 2. We complemented the paper with a diagram presenting the particular stages of the dataset acquisition (Figure 1) and a figure containing image examples for each class (Figure 4)."
}
]
}
] | 1
|
https://f1000research.com/articles/10-581
|
https://f1000research.com/articles/11-706/v1
|
27 Jun 22
|
{
"type": "Research Article",
"title": "Stakeholders’ readiness in the development of an Islamic smart city",
"authors": [
"Raja Faisal Raja Haron",
"Junainah Mahdee",
"Normazalila Abu Bakar",
"Raja Faisal Raja Haron",
"Normazalila Abu Bakar"
],
"abstract": "Background - Smart City integrates systems with the latest technologies to enable fast track of information and decision making by individuals, government, businesses, and public. Smart City connects people and information to manage public amenities, control crime rates, enhance services effectiveness, create vibrant, competitive, and innovative cities, and improve quality of life. Islamic Smart City can be defined as a smart city that incorporates the Islamic Syariah from Al-Quran and Hadith as a way of life; and impart the main component of Islamic Syariah compliance in individual and organisational behaviour aspects such as ethics, cleanliness, trust, security, and others. This research aims to explore the stakeholders’ readiness in four aspects of technology, human, institutional and Islamic factors, which are important in the development and implementation of the Islamic Smart City. Methods – This qualitative research design collected data through interviews with 20 selected stakeholders. Results– The findings provide the state government with insights into stakeholders’ readiness, which is crucial to the development of Islamic Smart City. The findings also show that the stakeholders’ readiness in the technology is high; but it is lacking in the Institutional and Islamic factors. Conclusion: This research provides insights that the development of Islamic Smart City requires major concern such as ensuring the stakeholders’ readiness for technology, human factors, the institutional and the Islamic factors are met.",
"keywords": [
"Islamic",
"Smart City",
"Development",
"Stakeholders",
"Readiness"
],
"content": "Introduction\n\nThe existing Smart City integrates systems with the latest technologies to enable fast track of information and decision making by individuals, government, businesses, and public. It connects people and information to manage public amenities, control crime rates, enhance services effectiveness, create vibrant, competitive, and innovative cities, as well as to improve quality of life. The new concept of Islamic Smart City introduced in this paper can be defined as a smart city that incorporates the Islamic Syariah from Al-Quran and Hadith as a way of life; and impart the main components of Islamic Syariah compliance in individual and organisational behaviour aspects such as ethics, trust, security, etc. Scholars agreed that the concept and the success factors of Smart City had never been discussed within a comprehensive understanding or solid conceptualisation.1 Thus, this research is the first to understanding the vital components of an Islamic Smart City.\n\nThe main objective of an Islamic Smart City development is to address urban issues efficiently, in particular to improve the city’s sustainability and quality of life via integration of smart technologies; with the main focus of imparting Islamic values in its development. However, the main question in this research is about the governments’ readiness for its development. This research will explore the issues of government readiness in implementing the development of an Islamic Smart City. Stakeholders are the ones who are directly or indirectly involved in the development of the fundamental components that contribute to the success or failure of an Islamic Smart City, thus their opinions should be taken into consideration when deciding on various strategies, planning and implementations. The aim of this research is mainly to explore the stakeholders’ readiness in four aspects: technology, human, institutional and Islamic factors, which are important in the development and implementation of an Islamic Smart City.\n\n\nLiterature review\n\nA city is considered smart “when investments in human and social capital and modern transport and communication infrastructure fuel sustainable economic growth and a high quality of life, with a wise management of natural resources”.2 In addition to these fundamental factors, an Islamic Smart City incorporates all the Islamic religious values of lives of people living in the smart city.\n\nFigure 1 shows three fundamental components of a Smart City that includes the Technology Factors, Institutional Factors and Human Factors.1\n\n(Source: Taewoo and Pardo, 2010).1\n\nIslamic Smart City uses the latest technologies to connect people and information to create vibrant, green, competitive, and innovative cities whilst improving quality of life.3 Various initiatives in relation to technology development or availability of digital workers may influence development of Islamic Smart City.4 Government must invest in upgrading knowledge and skills of digital workers to support fast growth technologies, via formal education at schools, vocational centres, colleges or universities. New generation must be equipped with digital capabilities to support development of technology infrastructure of Islamic Smart City. Future digital workers must also be capable in designing new technologies, systems, platforms, gadgets, or equipment to avoid importing from other countries.\n\nThe latest collective understanding about an Islamic Smart City is that it relates to a city development that used different types of Internets of Things (IoT) sensors to gather data and information, which later can be used to integrate or manage internal assets, manpower, resources, and other services that have been received or delivered to the public. Information that is collected from the public, any devices or assets that are used in managing traffic system, hospital administration, universities, power plants and others, are solely for the benefits of societies.5,6\n\nThe institutional factors are other contributors to the success of an Islamic Smart City, with substantial focus on de-regulations of the existing legal aspects inclusive codes, rules and regulations and the law of different states in this country.7 This is to ensure that the utilisation of new technologies is not harmful, lead to more crimes or against the Islamic values. Government support and governance policy are key to designing and implementing an Islamic Smart City, that include variety of organisational factors derived from the clever community discussions or smart development initiatives: not only to support government policies, but also the connection between government agencies and nongovernmental groups, and its governance.8\n\nThe administrative ecosystem (initiatives, framework, and interaction) promotes an Islamic Smart City to be developed in such ways of integrating an efficient governance, strategic and promotional tasks, networking, and collaborations in order to enable an Islamic Smart City development. The government must focus on the real-time utilisation of online data and information systems to reduce problems with silo management in delivering quality services especially by the public sectors to the communities.9 This is to ensure the effectiveness of public services and reduce the problems faced by the companies in delivering the services in the right manners.\n\nA smart government in an Islamic Smart City initiative must put efforts via partnering with departments, agencies, subsidiaries and other stakeholders in utilising available technologies and resources. Smarter governance on the most fundamental level requires more citizen-centred activities and services. It is important to prepare organisations to thoroughly understand the legal and regulatory barriers.10 A citizen-centred approach is the central spirit of governance. Stakeholder’s consideration (i.e., end-user groups, end-users, IT experts, legislation or service domain specialists, and public directors) is crucial for the Islamic Smart City architecture and technologies implemented to be accepted by all parties.\n\nAn Islamic Smart City re-conceptualised its emphasis on human infrastructure, to create balance with development of digital technologies infrastructure. The government must allocate huge investment in developing human capital in technical and management aspects of the Islamic Smart City; such as tolerance, technology, and talent to attract creative workers with the two components of tolerance and talent in human infrastructure.11 “Smart people” with advanced education, mastering specific expertise, open-mindedness, creative, innovative, high connectivity in communication can support development of an Islamic Smart City that provides intelligent solution to the public and business communities that transforms work, leisure, community and everyday lifestyles.12\n\nEffective smart cities could integrate the government of the Islamic Smart City with the entire communities via the top-down and bottom-up integrative technologies’ platforms with all the sectors and publics.13 Government and communities must work together in ensuring the success of an Islamic Smart City development. The communities must unite to utilise the new information and communication technology (ICT) in their daily lives with business platforms for its online business transactions under citizen-centred integrative operational and services delivery system. Transforming a conventional city to an Islamic Smart City requires an integration of technologies within the communities, with engagement in Islamic life values to harmonise the differences in a homogeneous technology platform, appropriately design within the communities’ capabilities, regardless of their ideologies, religions, culture, and other elements.14\n\nThe evolution of an Islamic Smart City begins with the municipality of Islam Smart City process that emphasises the implementation of Syariah laws and standards, while integration of technologies being the focus of the overall city development. There are three main elements that make up the driving line in the formation of Islamic Smart City: the formation of Ukhuwwah and social integration, the city carries a warning message, and a balanced development between human values and nature environment.15 The communities of public, government and businesses must have good relationships and understanding between each other to ensure that they have consensus in the technologies to be implemented in the public services and business transactions.\n\nIslamic municipality was born since the reign of the Prophet Muhammad P.B.U.H., and the first Islamic municipality was the city of Medina which is the ‘Role Model’ of global Islamic countries especially in the Middle East. Islamic municipalities aim to maintain the interests of the Ummah fairly without being individualistic.16 Development of an Islamic Smart City is part of civilisation’s development, and many Islamic scholars believe that Muslim communities should not build a civilisation by liberating themselves of Islamic bonds. The Islamic rules must not be forgoing even though there are non-Muslim communities living in the Islamic Smart City. Based on the deliberations of the new concept of Islamic Smart City, the theoretical framework for this research is shown in Figure 2.\n\n\nMethods\n\nIn this qualitative research 20 stakeholders were interviewed in their workplace from April – May 2020 (Figure 3). Both written and oral consent were obtained from each stakeholder. They were contacted via phone and were willing to contribute information during the interview session.\n\nAll interview scripts were transcribed and themed on the readiness of the technology, institutional, human, and Islamic factors. The triangulation of data (using multiple sites) was also carried out to ensure the validity and reliability of this research.\n\n\nResults\n\nThe results of this research found that the stakeholders’ readiness in technology and human factors are high; but lacks the institutional, and the Islamic factors. These findings provide the state government with insight into stakeholders’ readiness, which is crucial to the development of Islamic Smart City.\n\n\nDiscussion\n\nThe stakeholders have appropriate knowledge about the concept of Islamic Smart City and the applied technologies that can improve their daily life and work activities. Only a few groups including the non-government organisations and businesses with elder generation have difficulties in transforming into the latest technological changes.\n\nThe budget for technology advancement has become another issue for all the stakeholders since technology is fast changing. While it is costly to buy the latest equipment, software or system, all organisations have to face this challenge when upgrading their facilities with latest technologies in Islamic Smart City.\n\nIn the aspect of human factor, owners, and traders in industries such as batik, keris, tembaga and craft, are expected to face difficulties in coping with the development of new technologies. The vast majority of these business owners are elder generations, and this industry is inherited from one generation to another. The elderly crafters prefer to sustain with the manual and traditional production in promoting and selling their products. Moreover, the originality values of such hand-made products are much higher in the market.\n\nThe stakeholders’ knowledge about how Islamic values would be incorporated in the Islamic Smart City are lacking despite years of religious education system. Fortunately, there are many implementations of advanced technologies in religious activities at mosques and public religious events. But somehow, the promotional activities, or dissemination of information about religious activities are not fully linked with the use of technology devices. Another reason may be due to the elder generations’ preference on the traditional or conventional conducts when it comes to religious activities. Conversely, younger generations are more receptive to the incorporation of technologies with Islamic values.\n\nAs for the institutional factor, there is no specific legal framework available for an Islamic Smart City. One major issue in a multinational country like Malaysia is that the Islamic Syariah Law for Muslims is different than the Civil Law for non-Muslims. Nevertheless, the strong bond between the Muslims and non-Muslims will make it possible for them to accept the concept of Islamic Smart City. The Non-Muslims understand that the Islamic Syariah Law will positively affect prosperous living in a smart city.\n\n\nConclusions\n\nThis research contributes to a new knowledge for the establishment of Islamic Smart Cities globally, by imparting the Islamic values as a way of life in the era of new technologies. In order to become a smarter city, there is a need to ensure sustainable urban development as well as its connection with the rural areas being supported by the latest technologies.\n\nThere is also a need to redesign the conventional city with a top down and bottom-up strategic planning that focuses on the community building with ICTs and digital infrastructure. A holistic Islamic Smart City strategic framework must be based on integration of the ideological services applications.17\n\nThe integration process in constructing the strategic development framework requires the state government to consider all stakeholders that have connections with the planning of Islamic Smart City; since they will be the ones to engage with the ICTs and digital infrastructure design, planning, implementation, and continuous monitoring to ensure the success of an Islamic Smart City.18\n\nThe limitation of this research is that it only included main stakeholders in the interviews. Future research can be conducted using quantitative method with larger sample size, especially from professionals and public to enable the state government to design a long-term strategic framework that take into considerations all factors in ensuring the success of the Islamic Smart City project.\n\nDANS: Stakeholders’ readiness in the development of an Islamic smart city. DOI: 10.17026/dans-2zk-eqz4\n\nThis project contains the following underlying data:\n\n‐ Data set information Islamic_Smart_City_Paper: This dataset includes information on data collection, study population, and the interview transcript used in this study.\n\n‐ The results of the respondents\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\nEthical approval\n\nEthical Approval Number: EA1182021 (Multimedia University).\n\n\nAuthor contributions\n\nRFRH as the main author contributed to the whole process of this research especially in meetings with the relevant person for the interviews. NAB assisted in the processing of the interview scripts. While JM monitored the production of this article.",
"appendix": "Acknowledgements\n\nWe acknowledge the support from the State Government of Terengganu and all the agencies, companies, and non-governmental organisations; for the success of this research. Also, the Multimedia University (MMU) for providing opportunity to publish this article.\n\n\nReferences\n\nTaewoo N, Pardo TA: Conceptualizing Smart City with Dimensions of Technology, People, and Institutions. The Proceedings of the 12th Annual International Conference on Digital Government Research. 2010; 282–291.\n\nAxelsson K, Granath M: Government Stakeholders’ Stake and Relation to Smartness in Smart City Development: Insights from a Swedish City Planning Project. Information Quarterly. 2018; 35: 693–702. Publisher Full Text\n\nBakici TY, Almirall E, Wareham J: A Smart City Initiative: The Case of Barcelona. J. Knowl. Econ. 2012; 4: 30–41.\n\nAlbino V, Berardi U, Dangelico R: Smart Cities: Definitions, Dimensions, Performance, and Initiatives. J. Urban Technol. 2015; 22: 3–21. Publisher Full Text\n\nBerg JC: Sharing Cities: A Case for Truly Smart and Sustainable Cities. New Polit. Sci. 2017; 39(3): 17–419.\n\nRezaul Karim SM, Sabbir Ahamed FA, Shadman S, et al.: Smart City Architecture and Applications based on IoT: A Theoretical Overview. Int. J. Sci. Eng. Res. 2019; 10(1): 1815–1820.\n\nWeber M, Zarko PI: A Regulatory View on Smart City Services. Sensors. 2019; 19(2): 1–18. Publisher Full Text\n\nMyeong S, Jung Y, Lee Y: A Study on Determinant Factors in Smart City Development: An Analytic Hierarchy Process Analysis. Sustainability. 2018; 10: 1–17.\n\nWeber M, Zarko PI: A Regulatory View on Smart City Services. Sensors. 2019; 19(2): 1–18. Publisher Full Text\n\nMutiara D, Yuniarti S, Pratama B: Smart Governance for Smart City. IOP Conf. Ser.: Earth Environ. 2018; 126: 012073–9. Publisher Full Text\n\nFlorida R: The Rise of the Creative Class and How It’s Transforming Work, Leisure, Community and Everyday Life. 1st ed.New York:Basic Books;2002; 416.\n\nSujata J, Saksham S, Tanvi G, et al.: Developing Smart Cities: An Integrated Framework. Procedia Comput. Sci. 2016; 93: 902–909. Publisher Full Text\n\nAnthopoulos L, Reddick CG: Smart City and Smart Government: Synonymous or Complementary? The International World Wide Web Conference, April 11–15, 2016, Montréal, Quebec, Canada. 351–355.\n\nBernd W, Wirtz BW, Weyerer JC, et al.: An Integrative Public IoT Framework for Smart Government. Gov. Inf. Q. 2019; 36(2): 333–345. Publisher Full Text\n\nFredy Purnomo MHP: Smart City Indicators: A Systematic Literature Review. J. Telecommun. Electron. Comput. Eng. 2016; 8(3): 161–164.\n\nAli MA: A Knowledge Smart City in the Middle of the Desert: Al-Madinah Al-Munawarah Saudi Arabia as an Example. paper submitted to IGU Urban Commission Annual Meeting Held at Dortmund-Germany. August 21-26, 2012.\n\nMora L, Deakin M, Reid A: Strategic Principles for Smart City Development: A Multiple Case Study Analysis of European Best Practices. Technol. Forecast. Soc. Chang. 2018; 1–34.\n\nMayangsaria L, Novani S: Multi-stakeholder Co-Creation Analysis in Smart City Management: An Experience from Bandung, Indonesia. Procedia Manufacturing: Industrial Engineering and Service Science. 2015; 4: 315–321. Publisher Full Text"
}
|
[
{
"id": "152916",
"date": "31 Oct 2022",
"name": "Marco Tregua",
"expertise": [
"Reviewer Expertise Business management",
"innovation management"
],
"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 several shortcomings in the manuscript. Please consider the suggestions below:\nThe introduction is way too short; it should set the ground for the research, clarify the theoretical perspective, describe the goal, anticipate the structure of the manuscript.\nThe problem statement is weakly related to the research gap you identified. This is also due to the fact the review comes later. I would make the opposite.\n\nReview:\nplease expand the considerations on the 3 factors. I would suggest you to embed conceptualizations from:\nBibri, S. E., & Krogstie, J. (2020). The emerging data–driven Smart City and its innovative applied solutions for sustainability: The cases of London and Barcelona. Energy Informatics, 3(1), 1-42. [on technology] Anthopoulos, L. G. (2017). Understanding smart cities: A tool for smart government or an industrial trick? (Vol. 22, p. 293). Chap: Springer International Publishing. [on institutions] Angelidou, M. (2015). Smart cities: A conjuncture of four forces. Cities, 47, 95-106. [on human beings]\n\nthe debate on what a smart city is offered various advances to describe the interplay among multiple factors. I would expand your view by considering:\nBifulco, F., Tregua, M., Amitrano, C. C., & D'Auria, A. (2016). ICT and sustainability in smart cities management. International Journal of Public Sector Management.\n\nHow can you state that 'The institutional factors are other contributors to the success of an Islamic Smart City' before performing the analysis?\nPlease expand the considerations on the Islamic factors. This is an under-researched topic, but it is interesting and needs to be properly presented to scholars.\nMethods:\nSeveral information are missing.\n\nHow did you select respondents? How long did the interviews last? What is the research context? How did you set questions? What were the questions about? How did you analyse results?\n\nThe section on results is almost non-existing.\nThe Islamic feature of a city are properly presented in the discussion only with reference to the human factor.\nIn the conclusion there are very limited theoretical implications.\n\nIn the limitations you should have considered also the research context.\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?\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": []
},
{
"id": "160098",
"date": "03 Feb 2023",
"name": "Hasniyati Hamzah",
"expertise": [
"Reviewer Expertise Urban studies and real estate."
],
"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\nOverall, the study involves an interesting topic and is potentially valuable for urban study literature.\nHowever, there are several issues that somewhat limit its usefulness and replicability.\nLiterature review: What constitutes an Islamic Smart City is missing from the discussion. There needs to be some kind of benchmarking on the parameters of Islamic City before a Smart City is proposed to be Islamised. The article fails to discuss the dimensions of Smart City e.g. Giffinger's Six Dimensions of Smart City that could have provided a more systematic exploration on the aspects that could have been imbued with Islamic \"flavour\". The suggestion of \"imparting Islamic values in its development\" is quite vague. How are the \"Islamic values\" different from, for instance, Sustainable Development principles? There are some overlaps between Islamic values and existing city development principles readily available and implemented in most Malaysian cities. Therefore, the article needs to clearly posit what exactly is the Islamic model of Smart City and not let the respondents decide.\n\nMethodology: Being a qualitative study, there needs to be a brief discussion on biases. Terengganu is a state located in the east coast of Malaysia which is regarded as the Malay hinterland whereby an overwhelming majority of its population is Malay. Malays are Muslims, and thus the readiness of the state government in adopting the Islamic Smart City is obvious. Additionally, the state is not known for its technological advancement, as compared to west coast cities or states. Therefore, using Terengganu as a case to showcase the readiness of adopting Islamic Smart City may not be justified. There needs to be more description on the methods used for data collection and analysis. Was semi-structured/structured interview used? Focus group or individual interviews? These will have a direct bearing on the findings.\n\nResults: There is no report of findings, more on discussion of findings. Findings from qualitative data could have been presented in diagrams, tables or verbatim quotations. Therefore, in my opinion, the \"Results\" section is weak. Regular articles do provide the findings in the main text, which would have helped the reader to understand the Discussion section.\nTherefore, I would not recommend indexing the article in its present form.\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? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-706
|
https://f1000research.com/articles/10-988/v1
|
30 Sep 21
|
{
"type": "Research Article",
"title": "Utilizing data sampling techniques on algorithmic fairness for customer churn prediction with data imbalance problems",
"authors": [
"Maw Maw",
"Su-Cheng Haw",
"Chin-Kuan Ho",
"Maw Maw",
"Chin-Kuan Ho"
],
"abstract": "Background: Customer churn prediction (CCP) refers to detecting which customers are likely to cancel the services provided by a service provider, for example, internet services. The class imbalance problem (CIP) in machine learning occurs when there is a huge difference in the samples of positive class compared to the negative class. It is one of the major obstacles in CCP as it deteriorates performance in the classification process. Utilizing data sampling techniques (DSTs) helps to resolve the CIP to some extent. Methods: In this paper, we review the effect of using DSTs on algorithmic fairness, i.e., to investigate whether the results pose any discrimination between male and female groups and compare the results before and after using DSTs. Three real-world datasets with unequal balancing rates were prepared and four ubiquitous DSTs were applied to them. Six popular classification techniques were utilized in the classification process. Both classifier’s performance and algorithmic fairness are evaluated with notable metrics. Results: The results indicated that Random Forest classifier outperforms other classifiers in all three datasets and, using SMOTE and ADASYN techniques cause more discrimination in the female group. The rate of unintentional discrimination seems to be higher in the original data of extremely unbalanced datasets under the following classifiers: Logistics Regression, LightGBM, and XGBoost. Conclusions: Algorithmic fairness has become a broadly studied area in recent years, yet there is a very little systematic study on the effect of using DSTs on algorithmic fairness. This study presents important findings to further the use of algorithmic fairness in CCP research.",
"keywords": [
"Customer churn prediction",
"Data sampling techniques",
"Algorithmic fairness",
"Class imbalance problem"
],
"content": "Introduction\n\nCustomer churn, the phenomenon in which customers are shifting to rival companies due to dissatisfaction with the existing services or to other inevitable reasons,1 is one of the common issues usually encountered in every customer-oriented sector, including telecommunication. Customer churn prediction (CCP) is a supervised binary classification procedure that detects the potential churners before they are churned. Since there are no standardized principles for collecting data for CCP tasks, data distribution between classes will be varied from one data set to another. Therefore, one class might have extremely underrepresented compared to another class. In CCP, the target class is those being churned or not. To be exact, churn is always a minority class when the non-churn class usually comes in large numbers. Therefore, churn is used to consider a rare object2 in service-based domains including telecom. Thus, telecom datasets always suffer from a class imbalance problem (CIP) and lead to a situation in which minority instances remain unlearned.\n\nAdvanced machine learning techniques can be applied to predict potential churners. Let us consider a dataset with 10,000 data instances with 10% of churn samples i.e., 1000 churners and 9,000 non-churners. Even if a carefully built model could predict 90% correctly on the minority class, it means 100 customers are misclassified to the wrong class. Suppose 60 churners are misclassified as non-churners, i.e., false negatives, the company will lose a huge amount of revenue since recruiting new customers is more expensive than keeping the existing ones.3 Thus, the ultimate goal in the telecom sector is to increase profit by decreasing customer churn. Hence, CIP is a block when trying to achieve the major goal of CCP, since it degrades classification accuracy. Algorithmic fairness has become a very active research topic since ProPublica observed that the algorithms could yield discriminative outcomes, which impacted a minority group in real life.4\n\nAlgorithmic fairness is monitored in line with the protected features or sensitive variables in the dataset. Sensitive data could generally be, but not limited to gender, race, age group or religion. Algorithmic fairness is achieved if the decisions generated by a model do not favor more or less any individual or a group.5 The lesser the bias in the training data, the bigger the chance of achieving algorithmic fairness. However, it is almost not possible to train a zero-bias model since the historical data could have contained bias for many reasons.6 The common reasons for bias in the training data involve the compounding of initial bias over time, using proxy variables, and unbalancing of sample size between minority and majority group.7\n\nIn the CCP process, customers’ behavior is analyzed within specific time windows, for example within one month.8 Once the prediction is done, the outcomes are reused as training data for the next prediction. Therefore, there are high chances to have repeated bias in the historical data without even noticing. One solution for CIP is to apply data sampling techniques (DSTs) to the training data. Since the major function of DSTs is to increase or decrease the sample instances to balance between majority and minority classes, there are changes in the number of samples in the different groups in the dataset. The main goal of this study is to explore and identify the impact of using DSTs on training data on algorithmic fairness in the CCP process. To the best of our knowledge, there is very little research concerning algorithmic fairness in the CCP process. We believe the findings of this study would provide valuable insights to future CCP research.\n\n\nMethods\n\nEthical Approval Number: EA1742021\n\nEthical Approval Body: Research Ethics Committee 2021, Multimedia University\n\nIn this study, the original data set is prepared to make three versions of unbalanced datasets, with rates of 5%, 15% and 30%. Each version is applied with four DSTs and compared the results with the unsampled original dataset to evaluate the classification performance and impacts on algorithmic fairness. The step-by-step methods to conduct the study are presented in Figure 1.\n\nA real-world telecom dataset was provided by one of Malaysia’s leading telecom companies (see Underlying data for details on access to this dataset). The original dataset contains 1,265,535 customer records, which were collected from January 2011 to December 2011. Since the original data set is huge in volume, we randomly selected 100,000 records and utilized them for this study. We included demographics, call information, network usage, billing information, and customer satisfactory data in our dataset since they are considered as influential factors in the CCP process.9,10 A total of 22 features were extracted after careful aggregation, i.e., new features were created based on the original data and some unnecessary features were deleted from it, and features are listed in Table 1.\n\nThe final dataset was prepared with three different rates of unbalancing: 5%, 15%, and 30%. We created a Python script (see Extended data) which used the Pandas tool of Scikit-learn machine learning library to prepare three versions of datasets. We set up these specific rates because we wanted to experiment with extremely unbalanced cases up to intermediate levels.\n\nIn the data preprocessing stage, we excluded any null values. Since we found only a few outliers in the selected dataset, we manually removed them without using any specific procedure. We applied four DSTs to the data: Random Over Sampler (ROS), Random Under Sampler (RUS),11 Synthetic Minority Oversampling Technique (SMOTE),12 and Adaptive Synthetic Oversampling Technique (ADASYN).13 The selection of DSTs was based on their popularity and to know the impact of each of them on the algorithmic fairness in the CCP process.\n\nWe applied six popular classifiers: Random Forest (RF), Decision Tree (DT), LightGBM (LGBM), Gradient Boosting (GB), Logistics Regression (LR), and XGBoost.14 We created our own Python script (see Extended data) using Scikit-learn machine learning library to perform this step. After a careful exploratory data analysis, we dropped Customer ID, Avrg local amt, Avrg std amt, Avrg idd amt, Avrg dialup amt from the predictor variable list since they were weakly correlated to the target variable.\n\nWe performed two evaluations: performance measures15 and algorithmic fairness metrics.16\n\nPerformance measures\n\nIn measuring the classifier's performance, we applied standard measures which are commonly used in most of machine learning classification tasks, including precision, recall and accuracy. We applied F-1 and AUC-ROC scores since accuracy alone is not enough to evaluate the actual performance of the classifiers. We created an own script (see Extended data) using Scikit-learn, a free machine learning software library for Python programming language. The performance of each classification was done as follows:\n\nwhere\n\nAlgorithmic fairness metrics\n\nWe emphasized the assessment of whether the classifier is discriminated between women, a protected group, and men, a non-protected group. We applied two well-known fairness definitions in measuring algorithmic fairness, and utilized the popular AI-fairness 360 tool to calculate algorithmic fairness.16\n\nStatistical parity (SP): Also known as an equal acceptance rate. SP is achieved if women have an equal probability to be predicted in the positive, i.e., churn class, as the men.17\n\nSP difference measures the difference of a specific outcome between the protected (female group) and non-protected (male group). The smaller the SP difference between the two groups, we can say that the model treats the unprotected group statistically similar to the protected group.\n\nSP is calculated as follows:\n\nDisparate Impact (DI): Also known as indirect discrimination where no protected variables are directly applied, but biased outcomes are still produced relying on the variables correlated with protected variables.18 The standardized threshold in calculation of DI is 0.8, which means the group whose DI values are under 0.8 are discriminated by the classifier.\n\nThe threshold value 80% is advised by the US Equal Employment Opportunity Commission.19 The model could be DI-free when the value is larger than 80% but it should be lower than 125% according to.20\n\nDI is calculated as follows:\n\n\nResults\n\nThe preliminary classification results for the datasets with different data unbalanced rates using four DSTs are shown in Tables 2–4. Table 2 shows the specific results of classification performance gotten when testing on 5% of unbalanced rate with respect to the chosen classifiers and four DSTs.\n\nTable 3 shows the details results of classification performance obtained when testing on 15% of unbalanced dataset with respect to the chosen classifiers and four DSTs.\n\nTable 4 shows the details results of classification performance obtained when testing on 30% of unbalanced dataset with respect to the chosen classifiers and four DSTs.\n\nIn our study, we have observed that a variable, is-senior remained unbalanced even after applying the DSTs. The algorithmic fairness scores for each group with different unbalanced rates are described in Tables 5–7. Table 5 shows the comparative results of SP difference and DI scores calculated on 5% unbalanced dataset and original dataset.\n\nTable 6 displays the comparative results of SP difference and DI scores calculated on 15% unbalanced dataset and original dataset.\n\nTable 7 describes the comparative results of SP difference and DI scores calculated on 30% unbalanced dataset and original dataset.\n\n\nDiscussion\n\nRecent works of algorithmic fairness research in machine learning applications is broadly organized into three main trends. Some studies emphasize enhancing or proposing better fairness notions and evaluation metrics in line with the domains concerned,17,21 some focus on the ways to mitigate the bias in the classification process (which can further be divided into three main groups: pre-, in-, and post-processing techniques),22-25 while the last trend proposes how to maintain the ethical AI standards and policies in practicing machine learning applications in different sectors.26,27\n\nDespite some previous empirical studies on the impact of using preprocessing techniques on algorithmic fairness, the findings of previous works could not pinpoint the direct impact of using DSTs on algorithmic fairness. Lourenc and Antunes,28 which is the closest work to our research, distinguish the effect of data preparation on algorithmic fairness. However, their work has been tested with two small datasets and provides general results of using random under- and over- DSTs. Importantly, their work fails to be tested on the widely-applied DSTs, SMOTE and ADASYN. In contrast, we apply real-world business data and show how different DSTs influence dissimilar levels of imbalance rate.\n\nIn the classification task, RF seems to be the best classifier since it yielded the best results over the other five models, while LR provided the worst scores for almost all metrics. It was observed that RUS worked better for the extremely unbalanced situation compared with 15% and 30% imbalanced rates. The best outcomes were found via ROS, SMOTE, and ADASYN in all different unbalanced rates, thus, could be concluded that oversampling techniques seem to provide more promising prediction results over undersampling techniques. This might be because the undersampling technique modifies the data by decreasing the majority of instances, which makes the dataset lack useful information for learning.\n\nFor all three unbalanced rates, the original dataset always gave less statistical parity differences (SPD) comparing to sampled datasets created using four DSTs, while datasets with RUS and ROS yield a slightly larger SPD but the statistics showed there is no disparate impact. However, we can hypothetically consider there might still be a bias as both RUS and ROS have their limitations. With RUS, important and essential data could have been removed and the classifier could provide a biased result since there was less information to learn from. On the other hand, with ROS, the prediction performance could also be biased due to the overfitting problem. In this sense, it is suggestible to apply different fairness measures and to compare the fairness scores. For the DI scores, if there is DI less than 0.8, there is indirect discrimination towards the unprotected group. The mathematical equivalence of DI suggests equalizing the outcomes between protected and unprotected groups. However, in reality, the conditions in the context of interest drive us to allow DI to a specific group up to some percentage. For example, in telecom CCP, the number of female customers could be very less than the dataset, since most males usually apply for a network plan representing the whole household. Therefore, we assume considering DI with 80% rule is reasonable.\n\nIn the 5% unbalanced original dataset, LGBM, LR and XG-Boost imposed with DI values of 0.79, 0.64, and 0.78 respectively. But there is no DI in the other two original datasets for 10% and 30%. This reveals that more discrimination could occur on a more unbalanced dataset. The analysis on all datasets with SMOTE and ADASYN provides alarming information on the classifier’s discrimination on the unprotected group. The 30% unbalanced dataset yields the worst unfair results since this is the highest SPD between female and males’ group with LR as 0.38 and 0.43, respectively. Overall, among all DSTs, ADASYN, and SMOTE tend to provide more unfair outcomes compared to other DSTs. In contradiction, they both provide a better classification performance in comparison to RUS and ROS. There is not a huge difference among the three different data unbalanced levels. However, in this study, we experimented with the gender attribute as a sensitive variable.\n\nDue to the nature of the CCP process and the rarity issue, training datasets have high chances to have compounded bias and suffer from unbalanced problems not only for the target class but also in the other attributes including sensitive variables. We have noticed that one variable remained unbalanced even after applying the DSTs; in such a case, a careful selection of data attributes should be done to avoid selection bias.\n\nAs the quality of training data is important, we would suggest enhanced mechanisms of data repairing techniques to prevent bias in the training data. Furthermore, the algorithmic fairness problem is mostly concerns societal discrimination. For example, in the scholarship selection process, if classifiers give more favors to males than females who have the same qualifications as males but are not selected, this will decrease their chances of scholarship. In a profit-centered industry like telecom, one could think there will be no loss for the customers though any group is less or more favored. It is important to consider the impact of biased decisions for the sake of the company’s reputation, the importance of equal treatment to customers, and to practice ethical AI policies.\n\n\nConclusions\n\nIn this paper, we experimented on three versions of unbalanced real-world telecom datasets to assess the impact of using four types of DSTs on the algorithmic fairness in the CCP process and compared the results with the unsampled original dataset. Classification performance and algorithmic fairness were evaluated with well-known metrics. The outcomes imply that RF provides the best classification results. Using SMOTE and ADASYN yields larger SPD between male and female groups as well as a disparate impact on the female over the male group. Previous work emphasizes the use of this method in choosing a scholarship candidate, releasing prisoners on parole, and choosing a credit candidate. Since machine learning applications would be applied to almost every sector in the near future, the practice of using fairer or unbiased systems is essential. Our study highlights the importance of paying attention to algorithmic fairness in the machine-driven decision-making process of the profit-centered and customer-oriented sectors on which very little research work has been done. Particularly, our finding highlights the fact that a careful choice of DSTs must be done to achieve unbiased prediction results. In future work, we would like to test the same procedure on a larger dataset and would like to measure more algorithmic fairness metrics to investigate the best suitable algorithmic measures for the CCP task. Moreover, we would like to test more sensitive variables rather than just gender.\n\n\nData availability\n\nThe real-world telecom dataset was obtained from the Business Intelligence and Analytics department of Telekom Malaysia Bhd. The authors were required to go through a strict approval process following established data governance framework. Interested readers/reviewers may contact the Business Intelligence and Analytics department to request the data (technicalsuport@tm.com.my). The decision as to whether or not to grant access to the data is at the discretion of Telekom Malaysia Bhd.\n\nAs most telco companies own similar customer data, other customer churn datasets that are representative of the data being used in this research can be found as follows:\n\n1. https://www.ibm.com/docs/en/cognos-analytics/11.1.0?topic=samples-telco-customer-churn.\n\n2. https://datasetsearch.research.google.com/search?query=Telco%20Customer%20Churn%20dataset%20site%3Akaggle.com&docid=L2cvMTFsbDF0dzJ5NA%3D%3D.\n\nAnalysis code available from: https://github.com/mawmaw/fairness_churn.\n\nArchived analysis code as at time of publication: https://doi.org/10.5281/zenodo.5516218.29\n\nLicense: MIT License.",
"appendix": "References\n\nEria K, Marikannan BP: Systematic Review of Customer Churn Prediction in the Telecom Sector.2018; vol. 2(no. 1).\n\nAmin S, Anwar, et al.: Comparing Oversampling Techniques to Handle the Class Imbalance Problem: A Customer Churn Prediction Case Study. IEEE Access. 2016; 4(Ml): 7940–7957. Publisher Full Text\n\nGui C: Analysis of imbalanced data set problem: The case of churn prediction for telecommunication.2017; vol. 6(no. 2): pp. 93–99.\n\nDieterich W, Mendoza C, Brennan T: COMPAS Risk Scales: Demonstrating Accuracy Equity and Predictive Parity.2016.\n\nNtoutsi E, et al.: Bias in Data-driven AI Systems -- An Introductory Survey.2020; pp. 1–19.\n\nKamiran F, Žliobaitė I: Explainable and non-explainable discrimination in classification. Stud. Appl. Philos. Epistemol. Ration. Ethics. 2013; 3(January 2012): 155–170. Publisher Full Text\n\nBarocas S, Selbst AD: Big Data’ s Disparate Impact.2016; vol. 671: pp. 671–732.\n\nBallings M, Van Den Poel D, Verhagen E: Improving customer churn prediction by data augmentation using pictorial stimulus-choice data. Adv. Intell. Syst. Comput. 2012; 171(1): 217–226. Publisher Full Text\n\nColumelli L, Nunez-Del-Prado M, Zarate-Gamarra L: Measuring churner influence on pre-paid subscribers using fuzzy logic. Proc. 2016 42nd Lat. Am. Comput. Conf. CLEI 2016. 2017.\n\nAhmed U, Khan A, Khan SH, et al.: Transfer Learning and Meta Classification Based Deep Churn Prediction System for Telecom Industry.2019; pp. 1–9.\n\nMohammed R, Rawashdeh J, Abdullah M: Machine Learning with Oversampling and Undersampling Techniques: Overview Study and Experimental Results. 2020 11th Int. Conf. Inf. Commun. Syst. ICICS 2020. 2020; 243–248.\n\nChawla NV, Bowyer KW, Hall LO: SMOTE: Synthetic Minority Over-sampling Technique.2002; 16: 321–357.\n\nGosain A, Sardana S: Handling class imbalance problem using oversampling techniques: A review. 2017 Int. Conf. Adv. Comput. Commun. Informatics, ICACCI 2017. 2017; 2017-January: 79–85.\n\nKotsiantis SB: Supervised Machine Leanring: A Review of Classification Techniques. Informatica. 2007; 31(2007): 249–268.\n\nKotu V, Deshpande B: Model Evaluation. Predict. Anal. Data Min. 2015; 257–273. Publisher Full Text\n\nBellamy RKE, et al.: AI Fairness 360: An Extensible Toolkit for Detecting, Understanding, and Mitigating Unwanted Algorithmic Bias.2018.\n\nDwork C, Hardt M, Pitassi T, et al.: Fairness through awareness. ITCS 2012 - Innov. Theor. Comput. Sci. Conf. 2012; 214–226.\n\nCalmon FP, Wei D, Ramamurthy KN, et al.: Optimized Data Pre-Processing for Discrimination Prevention.2017; 1–18.\n\nFeldman M, Friedler SA, Moeller J, et al.: Certifying and removing disparate impact. Proc. ACM SIGKDD Int. Conf. Knowl. Discov. Data Min. 2015; 2015-Augus: 259–268.\n\nZafar MB, Valera I, Rodriguez MG, et al.: Fairness Constraints: Mechanisms for Fair Classification.2017; 54.\n\nHardt M, Price E, Srebro N: Equality of opportunity in supervised learning. Adv. Neural Inf. Proces. Syst. 2016; 3323–3331.\n\nZemel R, Wu Y, Swersky K, et al.: Learning fair representations. 30th Int. Conf. Mach. Learn. ICML 2013. 2013; 28(PART 2): 1362–1370.\n\nCalmon FP, Wei D, Vinzamuri B, et al.: Optimized pre-processing for discrimination prevention. Adv. Neural Inf. Proces. Syst. 2017; 2017-Decem(Nips): 3993–4002.\n\nZhang BH, Lemoine B, Mitchell M: Mitigating Unwanted Biases with Adversarial Learning. AIES 2018 - Proc. 2018 AAAI/ACM Conf. AI, Ethics, Soc. 2018; 335–340.\n\nPleiss G, Raghavan M, Wu F, et al.: On fairness and calibration. Adv. Neural Inf. Proces. Syst. 2017; 2017-Decem(Nips): 5681–5690.\n\nGursoy ME, Tamersoy A, Truex S, et al.: Secure and Utility-Aware Data Collection with Condensed Local Differential Privacy. IEEE Trans. Dependable Secur. Comput. 2019; X: 1–1.\n\nHube C, Fetahu B, Gadiraju U: Understanding and mitigating worker biases in the crowdsourced collection of subjective judgments. Conf. Hum. Factors Comput. Syst. - Proc. 2019.\n\nLourenc N, Antunes N: The Impact of Data Preparation on the Fairness of Software Systems.\n\nmawmaw: mawmaw/fairness_churn: Initial (v1.0). Zenodo. 2021. Publisher Full Text"
}
|
[
{
"id": "96164",
"date": "11 Jan 2022",
"name": "Chu Kiong Loo",
"expertise": [
"Reviewer Expertise 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\nThis paper addresses an important issue of algorithmic fairness, i.e. to investigate whether the results pose any discrimination between male and female groups and compare the results before and after using DSTs.\n\nI suggest to add some discussions on confusion matrix, learning curve and the improvement of fairness index before and after implementing the DSTs.\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": "8343",
"date": "30 Jun 2022",
"name": "Haw Su Cheng .",
"role": "Author Response",
"response": "Learning curves for Random Forest before and after applying DSTs (for three versions of datasets) are provided. We discussed briefly in the discussion section as well."
}
]
},
{
"id": "120732",
"date": "24 Feb 2022",
"name": "Prabu P",
"expertise": [
"Reviewer Expertise Machine Learning",
"Cloud Computing ad Mathematical Modeling"
],
"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 work mainly focus on data imbalance problems in customer churn prediction. The author has to incorporate the following suggestion in his/her article in-order to improve the quality of the work\nThe author need to clearly defined performance metrics for comparing random forest classifier with other classifiers.\n\nMore experimental studies required for unequal balancing datasets and author expected to try the experiment with large datasets.\n\nAuthor need to identify some proper technique to manage outliers in the datasets instead of removing manually.\n\nResults and Algorithms fairness need to be explain properly.\n\nIntroduction section are too short and the section is not continuous. Correct it. The introduction section is not clearly explaining the basics and also lack of some details of about \"issues in existing work, scope of work, goal of work and organization of work\" can be included.\n\nNo significant limitations are discussed. A number of limitations and learning points are also be considered after the conclusion.\n\nAuthor could take more recent research papers for the literature review and most of the literature review papers are not suitable to the proposed work. Author is expected to include few existing recommender system suggested for e-commerce platform. So I would suggest the author should identify few more recent papers based on his proposed research work and also include the objective and limitations of each work in table format.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "8344",
"date": "30 Jun 2022",
"name": "Haw Su Cheng .",
"role": "Author Response",
"response": "AUC-ROC score was applied to compare the performance of the respective classifiers and this information is added for clarification in the discussion section/ performance measure section Due to the dataset availability on propriety company, the focus on this paper is on 100,000 records only. Testing with large dataset is put as future work. In future work, we would like to test the same procedure on a larger dataset and would like to measure more algorithmic fairness metrics to investigate the best suitable algorithmic measures for the CCP task. Since there were not a lot of outliers in the original dataset, they were manually removed and we added this fact in the data pre-processing section. In our study, we do not go further process of mitigating algorithmic unfairness yet. If so, we will need to apply and discuss. But here, we only evaluate and compare the bias in the training dataset before and after applying the data sampling techniques. Introduction section is updated with related works, scope of work and organization work. Since my background is the combination of three different topics, algorithmic fairness, customer churn prediction and data sampling techniques, Due to the page limitation, could not put a lot of materials in the introduction section but most important and relevant background study was provided in the introduction section in a compact way. Goal of work is provided in the last paragraph of the introduction section, “The main goal of this study is to explore and identify the impact of using DSTs on training data on algorithmic fairness in the CCP process.” We updated with the limitations in the conclusion section as per suggestion. Although there is very limited work which are related to my work, we organize some of the articles of fairness in recommender system in the table format as per your suggestion"
}
]
}
] | 1
|
https://f1000research.com/articles/10-988
|
https://f1000research.com/articles/11-703/v1
|
27 Jun 22
|
{
"type": "Research Article",
"title": "Bayesian subjectivism and psychosocial attitude toward COVID-19 vaccines",
"authors": [
"Alberto Zatti",
"Nicoletta Riva",
"Nicoletta Riva"
],
"abstract": "Background: People resistant to vaccination against the coronavirus disease 2019 (COVID-19) pandemic have been counted in almost all countries worldwide. This anti-scientific subjectivity attitude could be explained by assuming as background the individual probability theory originally elaborated by the statistical school of de Finetti. Methods: This research method is based on a sample of 613 subjects from European countries who completed a questionnaire on attitudes towards COVID-19 vaccinations. On a six-value scale, a questionnaire investigated knowledge, assessments, degree of confidence, level of fear, anguish, and anger. Some items proposed an imaginary bet on the probability of not getting sick to deepen the possible presence of subjectivist assumptions about pandemics. Results: 50.4% were against vaccines and 52.5% against the so-called \"Green Pass\". Results of t-tests and correlations and stepwise regressions indicate that the sample’s reasons for opposing vaccination are related to an ego centred vision of the values that assign minor, if any, confidence to authority. Conclusions: This result supports the conclusion that No Vax decisions are more based on subjectivist probabilistic assumptions, thus in line with the significant social trend called \"individualism\".",
"keywords": [
"COVID-19 pandemic",
"decision-making psychological",
"subjectivism orientation",
"attitude towards vaccines",
"attitude change or persuasion",
"attitude-behavior relations",
"authoritarianism",
"Bayesian estimation",
"citizenship behavior",
"decision making"
],
"content": "Introduction\n\nIn September 2021, one year after the arrival of the first vaccines against coronavirus disease 2019 (COVID-19) infection, a part of the Italian and European population manifested a solid opposition to vaccination. Surveys on the propensity to vaccinate carried out in different countries (Barello et al. 2020; Dratva et al. 2021; Mylan & Hardman 2021; Hossain et al. 2021) reported significant percentages of individuals wary of vaccination. The health authorities of many countries launched incentive policies for COVID-19 vaccination (see Green Pass in Italy and Europe, but also a lottery in the USA, see Mallow et al. 2021). Still, they failed to involve a relatively large percentage of people resistant to vaccination. In Italy, as of October 20, 2021, 9,829,232 citizens of the eligible population group (12 – 99 years old and more) had not yet been vaccinated against the COVID-19 virus (on contrary, at that time, 44,180,669 Italians were partially or completely vaccinated, AA.VV. 2021). Still, in Italy in March 2022, 10% of people who should compulsorily be vaccinated are not.\n\nMore recently, some researchers have tried to identify the psychological factors that could explain the anti-vaccine attitude of a part of the population present in each country (Barello, Palamenghi, Graffigna 2021; Salerno et al. 2021; Simione et al. 2021; Hughes et al. 2021). Research on correlations with personality traits or forms of intellectualism (Huynh & Senger 2021) and the propensity to populism have made it possible to grasp some psychological variables related to vaccine resistance. However, the results are not entirely evident. With the Big Five test, Murphy and collaborators (Murphy et al. 2021) found that individuals hesitant to vaccinate score lower on personality traits such as agreeableness and conscientiousness. Roccato and Russo (2021) record in a vaccine-hesitant sample little trust in institutions, strong religious beliefs, and a tendency of thought prone to conspiratorial beliefs.\n\nOpposition to COVID-19 vaccination was exacerbated after the request to certify one’s condition with the so-called Green Pass. The legal “pass” called Green Pass was issued following the COVID-19 vaccination. Those in possession of it can go to all public places for all those months declared a pandemic by authorities (full 2021 and early 2022). Subjects not yet vaccinated (from now on indicated for reasons simplification “No/Yes Vax”) and in favour or against the so-call Green Pass is the target of the research. This study aims to prove that the implicit reasoning of the No Vax is better understood within the theoretical framework of subjective probability.\n\nThe subjectivist theory of probability (de Finetti 1959, see also Galavotti 2009 and Savage (1954)) highlights how the prediction on which an individual bases his choices of action depends not only on the probabilities theoretically assignable to an event based on a frequency collected from observation, as evidenced by the theory of causal attribution (see Heider 1958) or on a theoretical probability that can be assumed a priori (Neyman & Pearson 1933), but on a “calculation” in which the focus is placed on: 1) the intentionality of the subject; 2) his assumptions of value; and 3) his knowledge of the expected probabilities. For example, deciding whether to take the umbrella to leave the house depends on how one sees the weather and if an individual considers getting wet more or less important, his assessment of the “annoyance” of carrying an umbrella, and his desire to show a particular self-image.\n\nSubjective probability theory is a decision theory in a world where uncertainty and degrees of freedom are questionable, primarily because of the specific intentionality of the individual making the prediction. In this regard, Savage (1959) prefers to speak of “personal probability” rather than “subjective probability” to emphasise that the entire complex construct that psychology calls “personality” falls into the evaluations of an individual.\n\nSo far, the present research aims to identify the presence of possible individualistic assumptions, let us say structurally ego-centred and anti-authority, in those who are against COVID-19 vaccination and more in those against the Green Pass.\n\nIn a previous study (called ‘Anguish and Fears About Attitude Towards Covid-19 Vaccines: Contrasts between Yes and No Vax’), the researchers examined differences in responses on items about fear and anguish about vaccination in the subsample against vaccination vs the subsample in favour of vaccination against COVID-19. In this publication (Zatti & Riva 2022) authors assumed the hypothesis that No Vax will evidence a kind of anguish (not just a generic “anxiety”) that in psychoanalysis is called “anguish to be invaded” (Anzieu, 1989). Statistical analysis with Student T-test revealed that the Yes Vax sample has more fear about the COVID-19 pandemic and anguished about social relations and esteem, but the No Vax subsample effectively results in more anguished about the “invasion” of a pharmaceutical substance into their body. In this paper, and using the same dataset, authors focus on another set of item-questions referring to the semantic field simplifying with “how much a person is willing to bet about falling ill by covid”. The formulation of such questions tends to approximate the individualistic probability theory by de Finetti and Savage (1958), which is, this theory, an alternative interpretation of Thomas Bayes’s assumptions. “The role of probability theory in setting inductive logic consists in indicating how the probability assessment relating to future events should change as a result of the result of observed events. From this point of view, inductive logic is substantially reduced to the compound probability theorem or to its slightly more elaborate variant called Bayes’ theorem.” (de Finetti, 1959, p. 8).\n\nThe hypothesis that will therefore be put to the test by this research is that the sample that declares itself No Vax and No Green Pass will have higher values in the questionnaire specifically elaborated on the basis of information collected in the Telegram Chat focused group, here called “ad hoc questionnaire” statements that express the inviolability of individual choices vs the choices of the community, as well as at those statements asking a judgment of public authorities’ decisions.\n\n\nMethod\n\nInformed consent was obtained from all individual participants included in the study. This, according to art. 13 of EU Regulation 2016/679 and the single country applicable legislation, with particular reference to the Italian Legislative Decree 196/2004 integrated with Decree 101/2018, data collected for the present research guarantees respect for personal privacy sample rights in all senses.\n\nA total of 613 individuals from Italy (56.4 %) and other European countries (11.7 % from Poland, 8.5 % from Britain, and a minor percentage from other 15 EU countries, such as Greece, 4.2 %, France, 2.1 %, etc.) undertook this study. Table 1 presents the sample’s characteristics. Respondents were collected online via Prolific services because it provided a special descriptive section on value respondent position in which it is possible to select those people not favourable to vaccinating against COVID-19. With this specific respondent categorization by Prolific, it was possible to recruit a sample enough balanced between Yes and No Vax respondents.\n\nData were collected online in September 2021. A survey was created and is composed of an ad hoc 92 items (see extended data (Zatti 2022)). Research questions are original and come from Telegram Chat communication exchange between the researchers and No Vax activists. For this reason, it is not possible to apply reliability criteria, because it is a one-time shot search.\n\nThe individuals who responded to the entire questionnaire, including questions on the willingness to bet on the risk of getting sick with COVID-19, were 400. Table 1 shows the distribution of the final research sample (213 subjects did not respond to this last section).\n\nData were collected using an ad hoc questionnaire. An original questionnaire was prepared based on the results of an online (via Telegram) focus group with No Vax declared activists. The focus group was conducted in a private chat of no vax activists to which researchers were presented by another activist. An a-synchronal dialectic exchange was conducted with the chat group (it is not possible to count how many people participated). This atypical focus group was conducted during the first two weeks of September 2021. On a six-value scale, the questionnaire proposed statements which the subject had to choose their point of agreement (1 not at all agreed, 6 very much agreed). The questionnaire aimed to collect the subject’s opinions on their social positioning regarding vaccination (Harré et al. 2009).\n\nA series of questions investigated the level of agreement on claims regarding the obligation to vaccinate and the so-called Green Pass (Opinion Index); how much the subject trusts administrative, health, pharmaceutical, and information institutions (Trust Index); and questions on individual choices versus public choices (section \"Index of Egoic Values vs Society Values\" simplified to “Egoic Values Index”). A large section of items required participants to choose, always on a six-level scale, how much they felt fear and how much they felt anger regarding relevant phenomena or events of the COVID-19 vaccination campaign (section \"COVID-19 Fear Index\" and section \"COVID-19 Anger Index\"). Another series of questions asked them to choose on the six-level scale how anguished he would feel and how angry he was in general (Section \"Anguish Index\" and Section \"Anger Index in General\").\n\nAnother section of questions consisted of items in which subjects were asked to choose the probability that they would fall ill with COVID-19 in the future and the “bet” that they would be willing to “gamble” by betting on the fact that they would not get sick in the next six months (section \"Subjective Probability Index of getting sick with COVID-19\" also called “Subjective Probability Index”). The final index, called “Index pro vs against authority” (summarised in “Authority Index”), asked questions about agreement on the authorities’ policies regarding the pandemic.\n\nNote that tables of correspondences between indexes and items used to build them are reported in the extended data (Zatti 2022).\n\nResponses were analysed by indexes constituted with the average of single items of the same section. Indexes’ statistical elaboration will be presented on the following pages. The other statistical analysis results can be consulted in the extended data (Zatti 2022), where it is also possible to read which item follows in each Index.\n\nTo evaluate the hypothesis that subjectivist orientation in assessing the attitude towards health policies on the COVID-19 epidemic also involves a position substantially resistant to the decisions coming from authorities, an “Authority Index” was built with the items that asked how much the individuals agreed on the impositions of the institutions.\n\nAs reported in the Introduction, the subjectivist theory of probabilities considers that the subjectivist attribution to the occurrence of an event involves the articulation between personal values and knowledge that an individual has of a specific event. To further analyse the subjectivist hypothesis, four new other indexes have been constructed. These “Subjective Indexes” are (comparable items are reported in extended data (Zatti 2022)): A) Objective Knowledge Index; B) Subjective Knowledge Index; C) Subjectivism-values Index; and D) Authority Index. A strong positive correlation between the “Authority Index” with the indexes “Subjective knowledge subjectivism” (r 0.451, N 530, p 0.00) and “values subjectivism” (r 0.844, N 530, p 0.00) and, also, a strong negative correlation with the “Objective knowledge Index” (r -0.633, N 530, p 0.00) have been reported.\n\nData were initially analysed through simple descriptive statistics, including means, standard deviations, frequencies and percentages. We then tested for the presence of significant differences between those favourable to COVID-19 vaccination (i.e., the Yes Vax) and those opposed to it (i.e., the No Vax) on all items of the survey through independent samples t-tests, and a p-value ≤ .05 was deemed significant. All analyses were performed with SPSS version 26. Regression analysis and Analysis of Variance were also performed.\n\n\nResults\n\nTable 2 shows how the two samples record statistically significant different averages at the t-test only for the items related to the “Egoic Values Index”. Student’s test results are: t = 20.88, df = 611, p < .01 = 99%, confidence interval (Conf. Int.) [1.47, 1.77], in the No Vax sample (M = 4.58, SD = 0.89) compared to the Yes Vax sample (M = 2.96, SD = 1.03).\n\nTo test the research hypothesis according to which the two Yes Vax and No Vax samples differ in a propensity to assign causal probabilities, such as getting sick with COVID-19, based on different probability attributions (the former in line with the frequentist probability, the latter in line with the subjective or personal probability – Savage, in de Finetti 1959 –) an analysis between items forming the Egoic Values Index was done. Tables 3 and 4 show the correlations recorded by the Yes Vax sample and the No Vax sample between the indexes and the three items that specifically asked for an assessment of the self-attributed probability of getting COVID-19. Statistically significant Pearson correlations are reported at 99% (marked with two asterisks) or 95% (one asterisk).\n\n* Statistically significant Pearson correlations are reported at 95%.\n\n** Statistically significant Pearson correlations are reported at 99%.\n\n* Statistically significant Pearson correlations are reported at 95%.\n\n** Statistically significant Pearson correlations are reported at 99%.\n\nFor the Yes Vax sample, there were only three statistically significant correlations of the item “I bet I will not contract the virus in the next six months”: a positive correlation with “Egoic Values Index” r (N 135) = .227, p .008; a negative correlation with the “Trust Index” r (N 135) = -.217, p .011; and a positive correlation with the “COVID-19 Fear Index” r (N 135) = .173, p. 045.\n\nThese correlation results were put under a stepwise multiple regression analysis to ascertain the best predictors of the item “I bet not to contract the virus in the future” (v. Table 5). The study indicated a two-variable model, finding that the item “Trust in large pharmaceutical companies” has a Beta weight of .271. This item was inserted first and explained 29% of the variance of the item “I bet not to contract the virus in the future” F = 12.244, p = .001. The item “Fear that the majority of the population determines my behaviours” has a Beta weight of.175. It was inserted second and explained a further 4.8%, F = 4.498, p = .036.\n\na Dependent variable: I bet I don't want to translate the virus in future.\n\nThe linear regression shows that the item “Trust towards large pharmaceutical companies” constitutes the primary variable to influence, according to a negative trend, the probability of the Yes Vax sample betting not to contract the COVID-19 virus. This could mean two things: the higher the trust in pharmaceutical companies, the lower the bet of not getting sick, and (or) vice versa.\n\nIn the No Vax sample, we find more positive correlations between the index and the items related to risk-taking in a possible bet with the COVID-19 disease. It is relevant that in the No Vax sample, the Egoic Values Index correlates with all three items linked to detecting a tendency to subjective evaluation of future events probability: item “Percentage of the probability of contracting the virus”; item “I bet not to contract the virus in the future”; and item “Betting odds vs opponent”. Finally, in the No Vax sample, for this last item, which evokes a confrontation with an opponent, significant correlations emerge with the indexes of Anger to COVID-19 and Anger in general.\n\nLinear regression was performed to identify which items related to anger can be associated with the item “Bet towards an opponent”, which gave the following results (see Table 6).\n\nTargeting the item “Odds bet vs opponent” (full text provided as extended data (Zatti 2022)) and by inserting in the regression all the items that make up the “Egoic Values Index”, the “COVID-19 Anger Index”, and the “Anger Index in general”, the data were subjected to the gradual multiple regression analysis to ascertain which were the best predictors of the item itself. The result was a three-variable model in which, as the first variable, the item “In general I can say that I get angry when limits are imposed on me” had a Beta of .117, which explained 20% of the variance of the target item (F = 11.070, p = 0.001). For the second, the item “I want myself to determine the values to follow”, which has a Beta weight of .143 which explained a further 4% of the variance (F = 5.861, p = 0.016); third, the item “In general I can say that I get angry when someone takes away something I care about” with a Beta of.138 which again explained a 2.1% of the variance of the target item (F = 4.696, p = 0.031).\n\nTargeting now the “Subjectivism Index” and inserting in the regression all the items that create the “Egoic Values Index”, the “COVID-19 Anger Index”, and the “Anger Index in general”, the stepwise multiple regression analysis has been identified as the best predictors of the index itself, a two-variable model. The item “I want to be myself to determine the values to follow” has a Beta weight of .194 which explains the 23.9% the variance of the target index (F = 15.930, p = 0.000) and the item “In general, I can say that I get angry when limits are imposed on me” has a Beta weight of.180 which explained a further 5.7% of the variance of the index (F = 8.7, p = 0.003 – see Table 7).\n\nWe thus proceeded to extract two categories of individuals with the analysis of the clusters (SPSS Quick Cluster procedure). This statistical analysis highlights two groups (see extended data (Zatti 2022) and the relative Tables of correspondences between indexes and items used to build them): Subjectivists Against Authority, containing 308 individuals, and Subjectivists in favour of Authority, 222 individuals (see Table 8).\n\na Exact statistics.\n\nCrossing cluster membership with the position for or against vaccination, 59 subjects out of 244 in favour of vaccines (24%) fall within the Subjectivists cluster opposed to the Authority (see table in extended data (Zatti 2022)). This means that the anti-authority subjectivist position characterises the sample against vaccines and is also present in subjects favouring the vaccine. Vice versa, 37 individuals out of the 286 opposed to the vaccine (13%) are categorised as Subjectivists in favour of Authority. Compared with multivariate analysis, these four sub-samples significantly differ for some significant profiles (see Figures 1-4). Pillai’s trace (see Table 8) records a significance of 0.000 for all these comparisons. Considering the many differences for each variable found with the MANOVA test between the four samples together, reduced in number (1. Yes Vax No Authority – 55 sub-sample subjects; 2. Yes Vax Yes Authority – 80 SS; 3. No Vax No Authority – 234 SS; and 4. No Vax Yes Authority – 31 SS), only some results of the most relevant differences for this part of the research will be presented. The aim is to indicate potential overlaps between the sub-sample No Vax Yes Authority and the subjects favouring vaccination. For synthesis, only the distributions of the four sub-samples with the four main indexes are presented: Egoic Index, Green Pass Opinion Index, Subjectivism Index, and COVID-19 Anger Index. It seems particularly important to observe the sample which, despite declaring themselves No Vax, turns out to have an attitude accepting Authority.\n\nAt the “Egoic Values Index”, the sample under observation (No Vax but Yes Authority) presents an average close to the Yes Vax, thus indicating that the availability of the injunctions of authority lowers the probability of having a self-centred value orientation (Figure 1). This conclusion is also confirmed by the sample’s position placed under attention records in the “Opinion Index”, below the averages of the two sub-samples against the Authority (Figure 2).\n\nFrom Figure 3, it is then noted that the No Vax Yes Authority sample is the one that appears to be much less willing to bet on the probability of not contracting the COVID-19 virus. Finally, it can be seen from Figure 4 how the index of anger towards the limits set by the pandemic is lower precisely for the two sub-samples Yes Vax and favourable toward Authority, as well as in the group that declares themselves No Vax and favourable attitude towards vaccination.\n\n\nDiscussion\n\nThe research highlights how the subjectivist position is associated with evaluating the facts in which individual values filter the personal interpretation of the data of reality. Subjective knowledge, egoic values, and anti-authority are the three factors that support an individualistic approach, in line with what is stated by the theory of personal probability of the Savage and de Finetti school (1959).\n\nThe hypothesis of accentuation of subjectivist value assumptions in the No Vax population has been confirmed. The Egoic Values Index and all the items that compose it (see Table 2) are significantly different in the t-test in the means between the sample against the vaccine (No Vax) and the sample in favour of the vaccine (Yes Vax).\n\nThe Yes Vax sample records a positive correlation between one of the three items dedicated to the “measurement” of subjectivist probabilistic assumptions. The linear regression analysis shows that it is above all towards pharmaceutical companies that an ambiguous “game” is played because the correlation with the Confidence Index follows a negative trend. As if to say that the less one has confidence in Big Pharma and the more one expects not to get sick in the future, even if, as is known, the correlation could also mean that the more one trusts pharmaceutical companies, the less likely one is prone to bet not to get sick in the future.\n\nOn the other hand, the No Vax sample records positive correlations between three indexes (Egoic Values Index, COVID-19 Anger Index, and Anger Index in general) and all the items intended to detect the subjectivist orientation, including the Subjective probability index itself (Table 4). In the No Vax sample, the analysis of the stepwise multiple regression shows that the “push” to bet not to get sick correlates significantly with some items of the section dedicated to anger in general, such as “I get angry when limits are imposed on me” and “I get angry when something is taken away from me”.\n\nTherefore, the anger emotion seems to be the critical factor of the subjectivist orientation in assessing the probability of not getting sick. The linear regression analysis also adds that the anger of the No Vax individuals seems to increase just when they are confronted with a supporter of the opposite position, a Yes Vax. According to these statistical analysis results, the No Vax subjects’ anger arises from the impositions and the feeling of being defrauded, all accentuated by the opposition, even if only imagined, with an opponent. From the stepwise linear regression analysis, the two main variables related to a subjectivist attitude towards the COVID-19 pandemic are the association between value self-centeredness and anger reaction when limits are set.\n\nThe evocation of a subject placed in the out-group (Tajfel, 1982) seems to induce a growing sense of anger in such individuals. The oppositional relationship particularly emphasises the anger of the No Vax sample: when an antagonist appears (which for the No Vax are the Yes Vax), anger increases.\n\nIn our research sample, a certain number of unvaccinated individuals (309 were vaccine contrary but 322 were “against the so-called Green Pass) have also signed they are No Green Pass. A result of the present research shows that some of those favouring vaccination stated they are against the Green Pass itself. This third sub-sample (10.9% of the total) gives a response profile to compare with those of the other two, let’s say, “coherent” samples: the one of Yes Vax and Yes Green Pass and the other of No Vax and No Green Pass. This sample of individuals opposed to vaccinating but sensitive to messages coming from institutions results in being less egoic values-oriented and less reactive to the impositions resulting from the obligation of the Green Pass (Figures 1 and 2). Moreover, this sub-sample is even the one that, among the four that cross the dimensions Yes/No Vax and Yes/No authority, results in less risk in betting that in the future they will not get sick (Figure 3). The level of anger resulting from the events of this period of the COVID-19 pandemic is lower than that of the “cousins” No Vax No Authority, even that of the Yes Vax No Authority subjects.\n\nThe small number of subjects of the sub-sample No Vax Yes Authority extracted from the analysis of the clusters does not allow a detailed profile of the characteristics of these individuals, even if it does not seem that the gender variables and the level of education are distinctive. A thesis, that for now is only hypothetical, is derived from another set of data referring on a projective tool aiming to describe subjects’ body mental representation (Body Image and Schema Test, Zatti Riva in press) and offers partial indications according to which an idealised body image primarily characterises the sub-sample No Vax Yes Authority. In addition, they, like the other sample, Yes Authority Yes Vax, record a higher level of sensitivity to social anguish (i.e. “not being estimated”, “staying alone”) than the two sub samples No Authority. In other words, the No Vax sample who are inclined to authority could be positively influenced by objective communications about the harm of COVID-19 infection due to a potential openness towards the indications coming from the authority.\n\nThe fact that a No Vax sample percentage may join the vaccination prevention campaign launched in all countries asks the question of which kind of communication campaign could convince them to vaccinate. It may be that focusing on an idealisation of the vaccine, for instance, on the pioneering, almost heroic, role of the inventors of the M-RNA technology and putting in the background the references to the pharmaceutical industries, would seem to be an applicable indication that the present research can offer to those responsible for the COVID-19 vaccination campaign.\n\nRecalling the classic psychosocial parallelism of Thibaut and Kelley (1959), according to whom the ordinary person evaluates social events implicitly using the laws of statistics (such as covariation), the hypothesis advanced in this study that No Vax individuals do not follow post hoc inferences, but they tend to be “subjectivists” from the point of view of the statistical assumptions with which they interpret reality (de Finetti 1931; Savage 1954) is substantially confirmed. Therefore, the central question on how the No Vax population could be better understood for better communication with them points to turning the theoretical framework to Bayesian statistics, just as the Subjectivist School interpreted Thomas Bayes’ theorems (de Finetti 1959). The answer to this question is, in fact, the central argument for how public communication can orient social behaviour. To assume that people use ante hoc evaluation of social reality, as Serge Moscovici affirm (1988), will implicate that social speech should adopt the scientific language and the symbolic one.\n\n\nData availability\n\nOpen Science Framework: Bayesian subjectivism and psychosocial attitude toward COVID. https://doi.org/10.17605/OSF.IO/FPA3U (Zatti 2022).\n\nThis project contains the following underlying data:\n\n- SpssDataBaseCovidSS613ESSENTIAL2.sav (raw data file, SPSS format)\n\n- BayesianSubjectYesNoVax613SS2 (1).xlsx (raw data file, Excel format)\n\nOpen Science Framework: Bayesian subjectivism and psychosocial attitude toward COVID. https://doi.org/10.17605/OSF.IO/FPA3U (Zatti 2022).\n\nThis project contains the following extended data:\n\n- Items related to Indexes calculation.pdf\n\n- Data Key of Questionnaire Items and relative Values.pdf\n\n- Objective and Subjective Knowledge et al Indexes Cluster raw data.pdf\n\n- Subjectivism Article Items Text.pdf\n\n- Tables & Figures.pdf\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "References\n\nAnzieu D: The Skin Ego: A Psychoanalytic Approach to the Self. New Haven:Yale University Press;1989.\n\nArmitage R: Online ‘Anti-Vax’ Campaigns and Covid-19: Censorship is not the solution. Public Health. 2021; 190: e29–e30. Publisher Full Text\n\nAw J, Seng JJB, Ying Seah S, et al.: COVID-19 Vaccine Hesitancy—A Scoping Review of Literature in High-Income Countries. Vaccines. 2021; 9(8): 900. PubMed Abstract | Publisher Full Text\n\nBarello S, Nania T, Dellafiore F, et al.: Vaccine Hesitancy Among University Students in Italy During the Covid-19 Pandemic. Eur. J. Epidemiol. 2020; 35: 781–783. PubMed Abstract | Publisher Full Text\n\nBarello S, Palamenghi L, Graffigna G: Looking Inside the ‘Black Box’ of Vaccine Hesitancy: Unlocking the Effect of Psychological Attitudes and Beliefs on COVID-19 Vaccine Acceptance and Implications for Public Health Communication. Psychol. Med. 2021; 1-2: 1–2. Publisher Full Text\n\nBreckler SJ: Empirical Validation of Affect, Behavior, and Cognition as Distinct Components of Attitude. J. Pers. Soc. Psychol. 1984; 47(6): 1191–1205. PubMed Abstract | Publisher Full Text\n\nCaserotti M, Girardi P, Rubaltelli E, et al.: Associations of COVID-19 Risk Perception with Vaccine Hesitancy over Time for Italian Residents. Soc. Sci. Med. 2021; 272: 113688. PubMed Abstract | Publisher Full Text\n\nde Finetti B : Probabilismo: saggio critico sulla teoria delle probabilità e sul valore della scienza. Napoli:Perrella;1931.\n\nde Finetti B : Induzione e statistica. Milano:Springer;1959.\n\nDe Zwart O, Veldhuijzen IK, Elam G, et al.: Perceived Threat, Risk Perception, and Efficacy Beliefs Related to SARS and Other (Emerging) Infectious Diseases: Results of an International Survey. Int. J. Behav. Med. 2009; 16(1): 30–40. PubMed Abstract | Publisher Full Text\n\nDratva J, Wagner A, Zysset A, et al.: To Vaccinate or Not to Vaccinate—This is the Question Among Swiss University Students. Int. J. Environ. Res. Public Health. 2021; 18: 9210. PubMed Abstract | Publisher Full Text\n\nGalavotti MC: Bruno de Finetti, Radical Probabilist. London:College Publications;2009.\n\nGiuliani M, Ichino A, Bonomi A, et al.: Who Is Willing to Get Vaccinated? A Study into the Psychological, Socio-Demographic, and Cultural Determinants of COVID-19 Vaccination Intentions. Vaccines. 2021; 9(8): 810. PubMed Abstract | Publisher Full Text\n\nGratz K l, Roemer L: Multidimensional Assessment of Emotion Regulation and Dysregulation: Development, Factor Structure, and Initial Validation of the Difficulties in Emotion Regulation Scale. J. Psychopathol. Behav. Assess. 2004; 26: 41–54. Publisher Full Text\n\nHarré R, Moghaddam F, Cairnie T, et al.: Recent Advances in Positioning Theory. Theory Psychol. 2009; 19(1): 5–31.\n\nHeider F: The psychology of interpersonal relations. New York:J. Wiley;1958.\n\nHornsey MJ, Harris EA, Fielding KS: The Psychological Roots of Anti-Vaccination Attitudes: A 24-Nation Investigation. Health Psychol. 2018; 37(4): 307–315. PubMed Abstract | Publisher Full Text\n\nHossain MB, Alam Z, Islam S, et al.: Health Belief Model, Theory of Planned Behavior, or Psychological Antecedents: What Predicts Covid-19 Vaccine Hesitancy Better Among the Bangladeshi Adults. Front. Public Health. 2021; 9: 1172.\n\nHudson A, Montelpare W: Predictors of Vaccine Hesitancy: Implications for COVID-19 Public Health Messaging. Int. J. Environ. Res. Public Health. 2021; 18(15): 8054. PubMed Abstract | Publisher Full Text\n\nHughes B, Miller-Idriss C, Piltch-Loeb R, et al.: Development of a Codebook of Online Anti-vaccination Rhetoric to Manage Covid-19 Vaccine Misinformation. Int. J. Environ. Res. Public Health. 2021; 18(14): 7556. PubMed Abstract | Publisher Full Text\n\nHuynh H, Senger A: A Little Shot of Humility: Intellectual Humility Predicts Vaccination Attitudes and Intention to Vaccinate Against Covid-19. J. Appl. Soc. Psychol. 2021; 51(4): 449–460. PubMed Abstract | Publisher Full Text\n\nIstituto Superiore di Sanità: Report Vaccini Anti COVID-19. 2021.Reference Source\n\nKhubchandani J, Sharma S, Price JH, et al.: COVID-19 Vaccination Hesitancy in the United States: a Rapid National Assessment. J. Community Health. 2021 Apr; 46 (2): 270–277. PubMed Abstract | Publisher Full Text\n\nLazarus JV, Ratzan S, Palayew A, et al.: A Global Survey of Potential Acceptance of a COVID-19 Vaccine. Nat. Med. 2021; 27(2): 225–228. PubMed Abstract | Publisher Full Text\n\nMacDonald NE: Vaccine Hesitancy: Definition, Scope and Determinants. Vaccine. 2015; 33(34): 4161–4164. PubMed Abstract | Publisher Full Text\n\nMallow P, Alec E, Wackler M, et al.: Covid-19 Financial Lottery effect on Vaccine Hesitant Areas: Results from Ohio’s Vax-a-million Program. Am. J. Emerg. Med. 2021; 08.\n\nMoscovici S: La Machine a faire des dieux. Librairie Artheme Fayard;1988.\n\nMurphy J, Vallières F, Bentall R, et al.: Psychological Characteristics Associated with Covid-19 Vaccine Hesitancy and Resistance in Ireland and the United Kingdom. Nat. Commun. 2021; 12: 29. PubMed Abstract | Publisher Full Text\n\nMylan S, Hardman C: Covid-19, Cults, and the Anti-Vax Movement. The Lancet (British Edition). 2021; 397: 1181. Publisher Full Text\n\nNeyman J: First course in probability and statistics. New York:Holt;1950.\n\nNeyman J, Pearson ES: On the Problem of the Most Efficient Tests of Statistical Hypotheses. London:The Royal Society by Harrison and Sons;1933.\n\nReno C, Maietti E, Fantini MP, et al.: Enhancing COVID-19 Vaccines Acceptance: Results from a Survey on Vaccine Hesitancy in Northern Italy. Vaccines. 2021; 9(4): 378. PubMed Abstract | Publisher Full Text\n\nRoccato M, Russo S: A New Look on Politicized Reticence to Vaccination: Populism and COVID-19 Vaccine Refusal. Psychol. Med. 2021; 1–2. Web. PubMed Abstract | Publisher Full Text\n\nSalerno L, Craxì L, Amodio E, et al.: Factors Affecting Hesitancy to m-RNA and Viral Vector Covid-19 Vaccines Among College Students in Italy. Vaccines. 2021; 9: 927. PubMed Abstract | Publisher Full Text\n\nSallam M: COVID-19 Vaccine Hesitancy Worldwide: A Concise Systematic Review of Vaccine Acceptance Rates. Vaccines. 2021; 9(2): 160. PubMed Abstract | Publisher Full Text\n\nSavage L: The foundations of statistics. New York:John Wiley & Sons;1954.\n\nSavage L:La probabilità soggettiva nei problemi pratici della statistica. de Finetti, Induzione e statistica. Milano:Springer;1959; pp. 123–200.\n\nSimione L, Vagni M, Gnagnarella C, et al.: Mistrust and Beliefs in Conspiracy Theories Differently Mediate the Effects of Psychological Factors on Propensity for Covid-19 Vaccine. Front. Psychol. 2021; 12: article 683684. Publisher Full Text\n\nSoares P, Rocha J, Moniz M, et al.: Factors Associated with COVID-19 Vaccine Hesitancy. Vaccines. 2021; 9(3): 300. PubMed Abstract | Publisher Full Text\n\nTagini S, Brugnera A, Ferrucci R, et al.: It Won’t Happen to Me! Psychosocial Factors Influencing Risk Perception for Respiratory Infectious Diseases: A Scoping Review. Appl. Psychol. Health Well Being. 2021; 13: 835–852. aphw.12274. PubMed Abstract | Publisher Full Text\n\nTajfel H: Social identity and intergroup relations. New York:Cambridge University Press;1982.\n\nThibaut JW, Kelley HH: Social psychology of groups. New York:Wiley;1959.\n\nZatti A: Bayesian subjectivism and psychosocial attitude toward COVID-19.2022, June 14. Publisher Full Text\n\nZatti A, Riva N: Anguish and Fears about Attitude towards Covid-19 Vaccines: Contrasts between Yes and No Vax. Discov. Psychol. 2022; 2: 1–8. Publisher Full Text\n\nZellner A: An Introduction to Bayesian Inference in Econometrics. New York:John Wiley & Sons;1971."
}
|
[
{
"id": "158411",
"date": "07 Feb 2023",
"name": "Hamid Allahverdipour",
"expertise": [
"Reviewer Expertise Health psychology and behavioral 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\nIn the abstract, the method section is unclear.\n\nIntroduction is too long.\n\nWhat was the conceptual framework for using \"individual probability theory\"?\n\nIn addition, why authors used the bayesian method for analyzing data? For unprofessional who are not familiar with statisticians would be confusing.\n\nI suggest that this paper is suited for review by statisticians.\n\nIn the method section, more details should be brought about participants and procedures and recruiting of samples.\n\nThe following papers may be useful in the introduction and discussion as well:\nPeoples’ attitude toward COVID-19 vaccine, acceptance, and social trust among African and Middle East countries1 Prioritizing ‘equity’ in COVID-19 vaccine distribution through Global Health Diplomacy2\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? Partly",
"responses": [
{
"c_id": "9318",
"date": "08 Feb 2023",
"name": "Alberto ZATTI",
"role": "Author Response",
"response": "Dear reviewer, I here answer you in italic at your points: In the abstract, the method section is unclear. The research has been based on a questionnaire you can visit on the OSF page linked in the article. It is a psycho-social instrument that asks directly what is a subject's position about a social topic. Introduction is too long. I needed to make a longer introduction because the theoretical approach is not so confident. What was the conceptual framework for using \"individual probability theory\"? De Finetti and Savage are two eminent representatives of the statistical school called \"subjective probability\". This statistical school was, at the same time, a theoretical and a technical school. In my article, I assumed the theoretical approach to probability, that is, that people use their own subjective judges to attribute a certain probability to an event and/or to a behaviour. In addition, why did the authors use the bayesian method for analyzing data? For unprofessional who are not familiar with statisticians would be confusing. The article statistical elaboration are not realized with the bayesian statistic method. The De Finetti and Savage approach interpret Thomas Bayes theorem's in the subjective manner. This is because the bayesian statistic is based on the effective frequencies ov an event, not on the theoretical probability of it. But, in the article, the statistic used is traditional. Bayesian subjectivity, as you read in the title, is the way we used to stress the subjectivity approach of the study. I suggest that this paper is suited for review by statisticians. I hope to have made clearer with the above answer that statistic used in the article is very classic, let's say. In the method section, more details should be brought about participants and procedures and recruiting of samples. As reported in the article, the standard recruiting of a psycho-social sample is via the professional services of private societies as Prolific. It was just a random recruiting onto the specific database of a panel of subjects prone or not to vaccination."
}
]
},
{
"id": "179424",
"date": "03 Jul 2023",
"name": "Igor Sotgiu",
"expertise": [
"Reviewer Expertise General psychology."
],
"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 collected very interesting data about the attitudes towards vaccinations and Green Pass of a large sample of European citizens. My specific comments on the article are reported in the following:\nI think the article would benefit from expanding the description of the Bayesian theoretical framework. In fact, a reader not trained in statistics might not be familiar with this approach. Otherwise, the authors might also consider to eliminate the word “Bayesian” from the title.\n\nIn my opinion, the authors could provide further details on the various regression models they estimated to find the best predictors of participants’ belief that they will not contract the virus in the future. Were the potential predictors selected according to any psychological theory? I think that explaining this could significantly improve the readability of the article.\n\nCluster analysis should be mentioned in the Statistical Analysis section of the article. Similar to what I said about the regression analyses, I think that the article would greatly benefit from better explaining the aims of the cluster analysis computed by the authors. In fact, it seems to me that this analysis allowed the authors to test hypotheses which were much more complex than the one they reported in the Introduction (see p. 4, 1st paragraph).\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/11-703
|
https://f1000research.com/articles/11-701/v1
|
24 Jun 22
|
{
"type": "Research Article",
"title": "Knowledge and attitudes regarding HIV/AIDS and its prevention among Ghanaian women",
"authors": [
"Jacob Loonin Laari",
"Abdul Rauf Alhassan",
"Jacob Loonin Laari"
],
"abstract": "Background: HIV/AIDS is still a major public health issue around the world, especially in Sub-Saharan Africa (SSA), where this has resulted in unquantifiable human suffering, social and cultural disruption, and enormous economic losses. Methods: This study aims to assess women’s knowledge and attitude toward HIV/AIDS and its prevention in Ghana. To perform an analytic cross-sectional study, this study used data (the women in reproductive age 15-49 years dataset) from the Ghana Multiple Indicator Cluster Survey (MICS) 2017/18. Bivariate analysis was done using chi-square and predictor variables were identified using binary logistics regression. Results: This study recorded good HIV knowledge and attitude levels of 81.9% and 10.5%. Factors that predicted only good HIV knowledge levels were ethnicity, and disability status. Also, predictors of only good attitude level were type of residence and marital status. Factors implicated in the prediction of both good knowledge and attitude levels were age, educational status, region of orientation, health insurance status, economic status, and media exposure. Conclusions: This study recorded a good HIV knowledge level among the majority of the women, but recorded most respondents having a poor attitude toward HIV.",
"keywords": [
"HIV/AIDS",
"Knowledge",
"Attitudes",
"Women",
"Ghana"
],
"content": "Introduction\n\nHIV/AIDS is still a major public health issue around the world, especially in Sub-Saharan Africa (SSA), where this has resulted in unquantifiable human suffering, social and cultural disruption, and enormous economic losses, according to UNAIDS, which estimates that there are 36.7 million people are living with HIV (PLHIV) worldwide, with 25.6 million in SSA (UNAIDS, 2016). According to UNAIDS, 274,600 people are living with HIV in Ghana, with 9,200 deaths attributable to AIDS and an HIV prevalence of 2.4 percent (UNAIDS, 2016).\n\nPatients with HIV infection may be ignorant of their infection and transfer it to others because they are asymptomatic for years (Ataei, Shirani, Alavian, & Ataie, 2013). HIV can be spread by the use of unsterilized tools in therapeutic injections, blood transfusions, mother-to-child transmission (MTCT), unsafe sexual behaviors, and several aesthetic procedures such as tattooing, piercing, pedicure, and barbershop shaving (Patel et al., 2015).\n\nHIV prevention in Ghana has mostly focused on sexual contact, blood transfusion, and MTCT. The reality that far more than 90% of HIV transmission happens via a mix of these channels must have influenced their decision (UNFPA, 2014). Women in various places have been disproportionately impacted by HIV since the outbreak of the global epidemic. Women now account for over half of all HIV-positive people, and AIDS-related illnesses represent the top cause of mortality among women aged 15 to 49 (USAIDS, 2019).\n\nAdolescent girls (ages 10-19) and young females (ages 15-24) make up a significant number of new HIV infections. In 2017, 7,000 adolescent girls and young women tested positive for HIV (USAIDS, 2017). This is considerably greater than the incidence of new HIV infections among young males, with young women being twice as likely as their male counterparts to contract the virus (USAIDS, 2017).\n\nAbout 80% of new HIV infections in Sub-Saharan Africa are accounted for by young adolescents, although they form only 10% of the population. In the worst-affected nations, girls account for 80% of HIV infections among teenagers, and they are significantly more likely than adolescent boys to be infected (USAIDS, 2019).\n\nThe transmission of HIV is hampered by a lack of HIV preventive knowledge and a poor attitude toward prevention (Obidoa, M’Lan, & Schensul, 2012; Fagbamigbe, Lawal, & Idemudia, 2017; Bamise, Bamise, & Adedigba, 2011). According to a study conducted in Nigeria, women's understanding and attitudes about HIV/AIDS in Nigeria require more attention to meet the worldwide goal of eradicating epidemics and other infectious diseases by 2030 (Yaya et al., 2018). While gender differences in HIV awareness are linked to education, household wealth, and geographic position (rural vs. urban), other factors such as education, household wealth, and geographic location (rural vs. urban) also play a role (Yaya et al., 2018). In SSA, Asia, and Latin America, the positive association between lower socioeconomic studies and HIV progression is proven (Ramjee & Daniels, 2013; Idele et al., 2014). Women in low-income households are frequently unaware of the dangers of HIV/AIDS. While poor socioeconomic status has been associated with risky sexual behavior and increased HIV sensitivity, new research suggests that economic inequality, is a factor in HIV transmission (Piot, Greener, & Russell, 2007).\n\nPromoting women's HIV/AIDS knowledge and attitudes is critical for avoiding and controlling the epidemic. However, there is little research in Ghana that links HIV/AIDS awareness among adult women to their attitudes toward those living with the disease. Using nationally representative Multiple Indicator Cluster Survey data, this study aims to assess women’s knowledge and attitude toward HIV/AIDS and its prevention in Ghana.\n\n\nMethods\n\nTo perform an analytic cross-sectional study, this study used data (Women in reproductive age 15-49 years dataset) from the Ghana Multiple Indicator Cluster Survey (MICS) 2017/18. From October 2017 to January 2018, the Ghana Statistical Service gathered data with the assistance of collaborators including the Ministries of Health, Education, Sanitation and Water Resources, Gender, Children and Social Protection, Ghana Health Service, and Ghana Education Service. Under the Statistics for Results Facility – Catalytic Fund, UNICEF provided technical help, while UNICEF, KOICA, UNDP, USAID, and the World Bank provided financial assistance (SRF-CF).\n\nThe sample frame was the 2010 Ghanaian Population and Housing Census (PHC). All women between the ages of 15 and 49 years who were either inhabitants or guests who slept in selected residences the night before the survey (14,374) were included.\n\nThe studies were conducted using MICS data that was made publicly available. Institutions that ordered, funded, or oversaw the surveys were responsible for ethical procedures. Each participant's verbal consent was gained, and minors aged 15-17 years were individually interviewed after adult approval was secured in advance from their parents or caretakers. All participants were made aware of the voluntary nature of their involvement, as well as the confidentiality and anonymity of their data. Respondents were also advised of their right to refuse to answer any or all of the questions, as well as their freedom to end the interview at any moment.\n\nThe data was analyzed using SPSS version 20. (IBM Corp., 2011, and NY). Tables with frequencies and percentages were used to present the results of categorical variables including sample characteristics. The link between the dependent and independent variables was determined using the chi-square test. A binary logistic regression model was used to identify the predictive determinants of HIV knowledge and attitude levels. And results were given as exponentiated B coefficients or adjusted odds ratios (AOR) with matching confident intervals (CI). A p-value of 0.05 was used to determine the research's statistical significance.\n\n\nResults\n\nTable 1 describes the women included in this study, most (40.6%) of them were within the youth age group (15-24 years), and the majority (78.5%) had history of attending school. In terms of the type of residence more than half of them (51.2%) were from rural areas, most (13.8%) from the Ashanti region, and the majority (38.2%) were of the Akan tribe. About 43.5% of them were married and the majority (91.1%) were without functional difficulties. In terms of media exposure most (88.0%) were not at all into new paper reading, and only 28.6% of them were listening to the radio every day, majority of them never used computers or tablets and never used the internet (Table 2).\n\nTable 3 reports the HIV prevention knowledge variables that respondents were assessed on. Their responses to these questions were recorded as 1 for correct answer and 0 for incorrect answer and composite scored. Those with composite scores of 5 and below were categorized as having a poor knowledge level regarding HIV prevention and those composite scores of 6 and above were classified as having a good knowledge level regarding HIV prevention. At the end of the categorization the majority (81.9%) had a good knowledge level regarding HIV prevention and the remaining (18.1%) had a poor knowledge level. Further analysis revealed that all under-studied independents variables of the respondents were significantly associated with the dependent variable (HIV knowledge level) (P < 0.001) as presented in Table 5.\n\nTable 4 reports the HIV attitude variables that women were assessed on. Their responses to these questions were recorded as 1 for correct answer and 0 for incorrect answer and composite scored. Those with composite scores of 3 and below were categorized as having poor attitude levels towards HIV and those composite scores of 4 and above were classified as having good attitude levels towards HIV. At the end of the categorization the majority (89.5%) had a poor attitude level towards HIV and the remaining (10.5%) had a good attitude level towards HIV. Further analysis revealed that all under-studied independents variables of the respondents were significantly associated with the dependent variable (attitude level towards HIV) (P < 0.05) as presented in Table 5.\n\nAll understudied independent variables (demographic characteristics and media exposure) of the respondents were significantly associated with the dependent variable (HIV knowledge level) and were therefore included in the binary logistics model. The model revealed the following factors as predictors of good knowledge on HIV prevention: age, history of education, region of orientation, ethnicity, health insurance status, wealth index, radio use, computer or tablet use, and internet use (Table 6).\n\nRelative to the respondents’ age group of 15-24 years, the likelihood of a good HIV knowledge level was 17% more for women of the age group of 25–34 years (AOR = 1.17, 95%, C.I. = 1.02–1.36). Those with no educational history were 54% less likely to have good HIV prevention knowledge when compared to those with educational attendance history (AOR = 0.46, 95%, C.I. = 0.40–0.52).\n\nIn terms of regional prediction, a good HIV knowledge level occurred 76% more for women from the Upper East region relative to women from the Western region (AOR = 1.76, 95%, C.I. = 1.31–2.35). Meanwhile, women from the Ashanti region, Brong Ahafo Region, and Northern region were less likely to have good HIV prevention knowledge when compared to those from the Western region. Women from Ashanti region were 27% less likely (AOR = 0.73, 95%, C.I. = 0.58–0.93), women from Brong Ahafo region were 35% less likely (AOR = 0.65, 95%, C.I. = 0.51–0.82), and women from Northern region were 28% less likely (AOR = 0.72, 95%, C.I. = 0.56–0.93).\n\nAlso, respondents’ ethnicity predicted their good HIV knowledge level. Relative to women from the Akan tribe, women from the Mole Dagbani tribe were 23% less likely to have a good HIV knowledge level (AOR = 0.77, 95%, C.I. = 0.64–0.94), women from the Grusi tribe were 32% less likely to have good HIV knowledge (AOR = 0.68, 95%, C.I. = 0.52–0.89), women from the Mande tribe were 48% less likely to have good HIV knowledge (AOR = 0.52, 95%, C.I. = 0.28–0.97) and lastly women from other tribes not specified in this current study were 27% less likely to have a good HIV knowledge level (AOR = 0.73, 95%, C.I. = 0.59–0.89).\n\nThose without health insurance were 10% less likely to have good HIV knowledge as compared to those with health insurance (AOR = 0.90, 95%, C.I. = 0.81–0.99). Also, those with no disability were 22% more likely to have good HIV knowledge as compared to those with a disability (AOR = 1.22, 95%, C.I. = 1.04–1.44).\n\nThe increased wealth index status of the women positively predicted HIV good knowledge, women of the second wealth index were 29% more likely to have good HIV knowledge when compared to those of the poorest wealth index (AOR =1.29, 95%, C.I. = 1.11–1.48). Also, women of the middle wealth index were 53% more likely to have good HIV knowledge when compared to those of the poorest wealth index (AOR = 1.53, 95%, C.I. = 1.30–1.80). Again, women of the fourth wealth index were 96% more likely to have good HIV knowledge when compared to those of the poorest wealth index (AOR = 1.96, 95%, C.I. = 1.62–2.37). Finally, women of the richest wealth index were 130% more likely to have good HIV knowledge when compared to those of the poorest wealth index (AOR =2.30, 95%, C.I. = 1.83–2.89).\n\nFinally, women's exposure to media predicted their HIV knowledge. Women who spent less than a week listening to the radio were 25% more likely to have good HIV knowledge when compared to those who did not listen to the radio at all (AOR = 1.25, 95, C.I. = 1.08–1.45). Also, women with at least once a week listening to the radio were 62% more likely to have good HIV knowledge when compared to those who did not listen to the radio at all (AOR = 1.62, 95, C.I. = 1.40–1.89). Women who spent almost every day listening to the radio were 46% more likely to have good HIV knowledge as compared to those who did not listen to the radio at all (AOR = 1.46, 95, C.I. = 1.28–1.67). With computer and internet use, those who did not ever use of computer or tablet were 34% less likely to have good HIV knowledge when compared to those who had used computers or tablets (AOR = 0.64, 95%, C.I. = 0.49–0.83). Those who had never used the internet were 45% less likely to have good HIV knowledge as compared to those who had ever used computers or tablets (AOR = 0.55, 95%, C.I. = 0.43–0.71).\n\nAll of the respondents’ understudied independent variables (demographic characteristics and media exposure) were significantly associated with the dependent variable (attitude level towards HIV) and were therefore included in the binary logistics model. The model revealed the following factors as predictors of a good attitude level towards HIV: age, ever attended school, residence type, region of orientation, health insurance status, wealth index, media exposure, and marital status.\n\nWomen aged 35 years and above were 30% more likely to have a good attitude toward HIV as compared to women of the age group 15-24 years (AOR = 1.30, C.I. = 1.08–1.57). A good attitude toward HIV was 20% less likely among those without a history of education attendance as compare to those with a history of attending education (AOR = 0.80, 95, C.I. = 0.66–0.98). Rural women were 36% less likely to have a good attitude towards HIV when compared to those from urban residences (AOR = 74, 95%, C.I. = 0.63–0.88). Those with the ‘single’ marital status were 31% more likely to have a good attitude toward HIV as compared to those married (AOR = 1.31, 95%, C.I. = 1.11–1.55). With regard to regional prediction, all the studied regions positively predicted good attitudes toward HIV relative to the Western region.\n\nRegarding health, women with no health insurance were 24% less likely to have a good attitude towards HIV as compared to those with health insurance (AOR = 0.76, 95%, C.I. = 0.66–0.87). Considering the wealth index, women of the middle wealth index were 34% more likely to have a good attitude towards HIV as compared to those of the poorest wealth index (AOR = 1.34, 95%, C.I. = 1.03–1.72). Women of the fourth wealth index were 44% more likely to have a good attitude towards HIV as compared to those of the poorest wealth index (AOR = 1.44, 95%, C.I. = 1.11–1.87). Lastly, women of the richest wealth index were 110% more likely to have a good attitude towards HIV as compared to those of the poorest wealth index (AOR = 2.10, 95%, C.I. = 1.60–2.77).\n\nFinally, media exposure predicted a good attitude towards HIV, those who read newspapers or magazines almost every day were 138% more likely to have a good attitude toward HIV as compared to those who don’t read at all (AOR = 2.38, 95%, C.I. = 1.41–4.03). Those who did not ever use computers or tablets were 33% less likely to have a good attitude toward HIV as compare to those with ever use (AOR = 0.77, 95%, C.I. = 0.63–0.95).\n\n\nDiscussion\n\nThe United Nations (UN) has recognized good HIV/AIDS education as a requirement for people to undertake preventive sexual behaviors. One of its goals for avoiding HIV transmission was to have ‘95% aged 15–24 years old properly identify measures to prevent HIV transmission and reject main misconceptions' by 2010 (UNAIDS, 2002). In this current analytic cross-sectional study focused on knowledge, and attitudes regarding HIV/AIDS prevention among Ghanaian women, the majority (81.9%) of the women had a good knowledge level on HIV prevention. In terms of knowledge level, this study is consistent with earlier studies but inconsistent when it comes to attitude (Iqbal et al., 2019; Bhagavathula AS, 2015; Quarm, Mthembu, Zuma, & Tarkang, 2021). These studies all recorded good knowledge levels, though lower as compare to the current study and positive attitude towards HIV higher compare to this present study. The current study's greater knowledge level compared to prior studies could be attributed to the long-term health education that has been taking place in ANCs in Ghana (Nyarko, Pencille, Akoku, & Tarkang, 2021). Despite having a high degree of adequate information about higher prevention, the current investigation found a low level of a positive attitude toward HIV. In this present study, all understudied independents variables of the respondents were significantly associated with HIV knowledge and attitude level with chi-square analysis.\n\nRelative to respondents’ age group of 15-24 years, the likelihood of a good HIV knowledge level was 17% more for women of the 25-34 years age group. Also in the Nigerian study, a higher HIV knowledge score was predicted by increased respondent age (Yaya et al., 2018). In an earlier study the educational level of respondents had an influence on their HIV knowledge level and this is reported similarly in the current study, as those with no educational history were less likely to have good knowledge when compared to those with educational attendance history (Nyarko, Pencille, Akoku, & Tarkang, 2021). Adding up some studies also revealed that women with higher education (tertiary) were more likely to have a thorough knowledge of HIV/AIDS than women with no education (Yaya, Bishwajit, Danhoundo, & Seydou, 2016a; Yaya, Bishwajit, Danhoundo, Shah, & Ekholuenetale, 2016b).\n\nIndeed, according to Gillespie et al., those who are wealthier and more educated will have better access to reproductive healthcare and, as a result, better information on health-related issues like HIV/AIDS (Gillespie, Kadiyala, & Greener, 2007). Wealth and better education, which indicate a higher socio-economic standing, have been proven to play a role in influencing the decision to engage in safer sexual behavior (De Walque, Jessica, June, & Jimmy, 2005; Glynn JR, 2004). Also, in this present study, an increase in the wealth index status of the women positively predicted HIV good knowledge, women of second, middle, fourth, and richest wealth index were more likely have good HIV knowledge as compared to those of poorest wealth index. Also in this current study, those with health insurance and no disability were likely to have good HIV knowledge.\n\nA study in Nigeria revealed that good HIV knowledge was more likely in the north when compared to the south (Yaya et al., 2018). Also, in the present study in Ghana, good HIV knowledge was more likely for women from the north (Upper East region) relative to women from the south (Western region). In this current study, women with exposure to radio, computer, and internet use were likely to have good HIV knowledge. The impacts of mass media campaigns against HIV transmission were demonstrated to be effective in 13 Sub-Saharan Africa (SSA) countries by regulating safe sex behavior (Yaya et al., 2018).\n\nAdolescent girls (ages 10–19) and young females (ages 15–24) make up a significant number of new HIV infections. In 2017 7,000 adolescent girls and young women tested positive for HIV (USAIDS, 2017). The transmission of HIV is encouraged by poor attitudes toward prevention (Obidoa, M’Lan, & Schensul, 2012; Fagbamigbe, Lawal, & Idemudia, 2017; Bamise, Bamise, & Adedigba, 2011). This present study confirms that poor attitude towards HIV could be one of the reasons for the high prevalence of HIV among younger individuals. In this study, women aged 35 years and above were likely to have a good attitude toward HIV when compared to women of the age group 15–24 years. This was equally reported in a similar study in Nigeria (Yaya et al., 2018).\n\nAnalysis of the attitude survey for the influence of higher education on attitude revealed an association between the two, and this present study confirmed that (Brennan et al., 2015). Also, this present study result is not different from an earlier similar study in Nigeria (Yaya et al., 2018). Urbanization in Ghana influences the availability of higher quality education, media exposure, healthcare, and economic opportunities (Crookes, 2015). This explains the reason for more likelihood of good attitude among those from urban areas, health insurance availability, media exposure, and better economic status in this current study and that of what was done earlier in Nigeria (Yaya et al., 2018). In Ghana, more urbanization is associated with the south as compared to the north, but this study result rather indicated more likelihood of good HIV attitude among those from the north (Upper East, Upper West, and Northern regions) as compared to those from the south (Western region). In a Nigerian study, a similar result was revealed (Yaya et al., 2018).\n\nFinally, those who were single in terms of marital status were more likely to have a good attitude toward HIV as compared to those who were married, and the same was reported in a similar study in Tajikistan (Zainiddinov, 2019). However, as reported in an earlier study, married women in Nigeria were more likely to have a good attitude towards HIV (Gebremedhin, Youjie, & Tesfamariam, 2017).\n\nThe use of cross-sectional data, which is insufficient to demonstrate causality, is a disadvantage of this study. Furthermore, because the study relied on secondary data, it was impossible to quantify key characteristics such as exposure to behavior change communication via HIV/AIDS-related treatments across different groups and across time.\n\n\nConclusion\n\nThis study recorded a good HIV knowledge level among the majority of the women but recorded most respondents as having a poor attitude toward HIV. Factors implicated in the prediction of both good knowledge and attitude levels were: age, educational status, region of orientation, health insurance status, economic status, and media exposure.\n\n\nRecommendation\n\nThese findings can be used by health knowledge and awareness programs to better define target populations and plan intervention programs. Future research can employ a broader range of context-specific variables to better show the factors of HIV awareness and attitude in Ghana.\n\n\nData availability\n\nAll data relating to the findings of this study are available from the Multiple Indicator Cluster Survey (MICS) website (https://mics.unicef.org) upon request. The MICS 2017/18 dataset is available for download from the website after free registration.",
"appendix": "References\n\nAtaei B, Shirani K, Alavian SM, et al.: Evaluation of knowledge and practice of hairdressers in women’s beauty salons in Isfahan about hepatitis B, hepatitis C, and AIDS in 2010 and 2011. Hepat. Mon. 2013; 13(13): 1–6. Publisher Full Text\n\nBamise O, Bamise C, Adedigba M: Knowledge of HIV/AIDS among secondary school adolescents in Osun state, Nigeria. Niger. J. Clin. Pract. 2011; 14: 338–344. PubMed Abstract | Publisher Full Text\n\nBhagavathula AS, Bandari DK, Elnour AA, et al.: A cross sectional study: the knowledge, attitude, perception, misconception and views (KAPMV) of adult family members of people living with human immune virus-HIV acquired immune deficiency syndrome-AIDS (PLWHA). Springerplus. 2015; 4(769): 769. PubMed Abstract | Publisher Full Text\n\nBrennan J, Chanfreau J, Finnegan J, et al.: The effect of Higher Education on graduates’ attitudes: Secondary Analysis of the British Social Attitudes Survey. London: Department for Business Innovation & Skills; 2015.\n\nCrookes YB: Rising through Cities in Ghana: The time for action is now to fully benefit from the gains of urbanization. NW Washington: The World Bank; 2015.\n\nDe Walque D, Jessica SN-M, June B, et al.: Changing Association between Schooling Levels and HIV-1 Infection over 11 Years in a Rural Population Cohort in South-West Uganda. Trop. Med. Int. Health. 2005; 10(10): 993–1001. PubMed Abstract | Publisher Full Text\n\nFagbamigbe A, Lawal A, Idemudia E: Modelling self-assessed vulnerability to HIV and its associated factors in a HIV-burdened country. SAHARA-J J Soc. Asp. 2017; 14: 140–152. PubMed Abstract | Publisher Full Text\n\nGebremedhin S, Youjie W, Tesfamariam E: Predictors of HIV/AIDS Knowledge and Attitude among Young Women of Nigeria and Democratic Republic of Congo: Cross-Sectional Study. J. AIDS Clin. Res. 2017; 08(3): 1–8. Publisher Full Text\n\nGillespie S, Kadiyala S, Greener R: Is Poverty or Wealth Driving HIV Transmission?. AIDS. 2007; 21(7): S5–S16. Publisher Full Text\n\nGlynn JR, Carael M, Buve A, et al.: Does increased general schoolinprotect against HIV infection? A study in four cities. Trop. Med. Int. Health. 2004; 9(1): 4–14. PubMed Abstract | Publisher Full Text\n\nIdele P, Gillespie A, Porth T, et al.: Epidemiology of HIV and AIDS among adolescents:current status, inequities, and data gaps. J. Acquir. Immune Defic. Syndr. 2014; 66: S144–S153. Publisher Full Text\n\nIqbal S, Maqsood S, Zafar A, et al.: Determinants of overall knowledge of and attitudes towards HIV/AIDS transmission among ever-married women in Pakistan: evidence from the Demographic and Health Survey 2012–13. BMC Public Health volume. 2019; 19: 714–793. PubMed Abstract | Publisher Full Text\n\nNyarko V, Pencille L, Akoku DA, et al.: Knowledge, attitudes and practices regarding the prevention of mother-to-child transmission of HIV among pregnant women in the Bosome Freho district in the Ashanti region of Ghana: a descriptive cross-sectional design. PAMJ-ClinicalMedicine. 2021; 1. Publisher Full Text\n\nObidoa C, M’Lan C, Schensul S: Factors associated with HIV/AIDS sexual risk among young women aged 15–24 years in Nigeria. J Public Health Africa. 2012; 3: 15–64. PubMed Abstract | Publisher Full Text\n\nPatel R, Choudhary N, Bhat N, et al.: Knowledge, attitudes and practice of barbers regarding HIV/HBV/HCV infections of Udaipur City, Rajasthan, India. International Journal Oral Health Med Res. 2015; 2(1): 221–227.\n\nPiot P, Greener R, Russell S: Squaring the circle: AIDS, poverty, and human development. PLoS Med. 2007; 4: 1571–1575. PubMed Abstract | Publisher Full Text\n\nQuarm MD, Mthembu J, Zuma K, et al.: Knowledge, attitudes and prevention practices regarding HIV/AIDS amongbarbers in Ho municipality, Ghana. Journal of Social Aspects of HIV/AIDS. 2021; 18: 42–51. PubMed Abstract | Publisher Full Text\n\nRamjee G, Daniels B: Women and HIV in Sub-Saharan Africa. AIDS Res. Ther. 2013; 10(30): 30. PubMed Abstract | Publisher Full Text\n\nUNAIDS: Monitoring the Declaration of Commitment on HIV/AIDS: Guidelines. UNAIDS; 2002. Publisher Full Text\n\nUNAIDS: Global-AIDS-Update.2016. Retrieved from March 19, 2022. Reference Source\n\nUNFPA: HIV/AIDS epidemic in Ghana. State of Ghanaian Population 2014. Accra: UNFPA; 2014. Retrieved from UNFPA.\n\nUSAIDS: When women lead change happens. USAIDS; 2017; pp. 1–36. Retrieved August 11, 2021. Reference Source\n\nUSAIDS: Women and HIV — A spotlight on adolescent girls and young women. USAIDS; 2019. Retrieved August 11, 2021. Reference Source\n\nYaya S, Bishwajit G, Danhoundo G, et al.: Extent of Knowledge about HIV and Its Determinants among Men in Bangladesh. Front. Public Health. 2016a; 4. PubMed Abstract | Publisher Full Text\n\nYaya S, Bishwajit G, Danhoundo G, et al.: Trends and determinants of HIV/AIDS knowledge among women in Bangladesh. BMC Public Health. 2016b; 16(812): 812. PubMed Abstract | Publisher Full Text\n\nYaya S, Ghose B, Udenigwe O, et al.: Knowledge and attitude of HIV/AIDS among women in Nigeria: a cross-sectional study. Eur. J. Public Health. 2018; 29(1): 111–117. Publisher Full Text\n\nZainiddinov H: Trends and Determinants of Attitudes Towards People Living with HIV/AIDS Among Women of Reproductive Age in Tajikistan. Cent. Asian J. Glob. Health. 2019; 8(1). PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "294363",
"date": "26 Jun 2024",
"name": "Sonila Dubare",
"expertise": [
"Reviewer Expertise Maternal and child health",
"AI",
"ML",
"substance use",
"Mental health",
"child Development",
"Women's health",
"Community-Based Participatory Research Program (CBPR)",
"Coping mechanisms",
"epidemiology",
"study design",
"policy 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\nPeer Review Report Title: Knowledge and attitudes regarding HIV/AIDS and its prevention among Ghanaian women Authors: Jacob Loonin Laari, Abdul Rauf Alhassan Summary This study investigates the knowledge and attitudes regarding HIV/AIDS and its prevention among Ghanaian women using data from the Ghana Multiple Indicator Cluster Survey (MICS) 2017/18. The study highlights the levels of knowledge and attitudes and identifies predictors for both. Abstract The abstract succinctly presents the background, methods, results, and conclusions. The key findings are summarized well, providing a clear snapshot of the study's outcomes. Strengths:\nClear articulation of study goals and methodology. Summary of key results is straightforward and informative.\nAreas for Improvement:\nThe paper could benefit from a brief mention of the specific recommendations of the findings. Detailed composite scores calculations, questions included etc might be beneficial in the methods section and maybe some supplementary tables. A discussion of the limitations of the data or analysis (e.g., potential biases or unmeasured confounders) is necessary.\nIntroduction The introduction provides a comprehensive background on the significance of HIV/AIDS in Sub-Saharan Africa and the specific context of Ghana. It outlines the public health challenges, modes of transmission, and the need for improved knowledge and attitudes toward HIV/AIDS. Strengths:\nDetailed background with relevant statistics and references. Clearly establishes the importance of the study.\nAreas for Improvement:\nThe introduction could be more concise. Maybe it could be organized a bit differently because some sections feel a bit repetitive and could be condensed to maintain reader engagement.\nMethods The methods section describes the analytic cross-sectional study design, data sources, sampling, ethical considerations, and data analysis procedures. Strengths:\nDetailed description of data sources and sampling design. Ethical considerations are well addressed. Clear explanation of data analysis techniques.\nAreas for Improvement:\nMore detail on the specific survey questions used to assess knowledge and attitudes would enhance reproducibility. Clarification on how composite scores were calculated and categorized.\nResults The results section provides a comprehensive analysis of the demographic characteristics, knowledge, and attitudes of the respondents. It identifies significant predictors of good knowledge and attitudes. Strengths:\nExtensive use of tables to present detailed findings. Clear reporting of statistical significance and odds ratios.\nAreas for Improvement:\nThe results section is dense with data; summarizing key findings in a few sentences at the beginning of each subsection could improve readability.\nDiscussion The discussion contextualizes the findings within the broader literature, comparing results with previous studies and exploring the implications for public health interventions. Strengths:\nThoughtful comparison with prior research. Clear articulation of the implications for HIV/AIDS prevention efforts in Ghana.\nAreas for Improvement:\nThe discussion could benefit from a more structured format, explicitly separating key findings, comparisons with other studies, and implications. A discussion of the limitations of the data or analysis (e.g., potential biases or unmeasured confounders) is necessary. Specific recommendations for policy or future research are somewhat scattered and could be consolidated for greater impact.\nConclusion The conclusion summarizes the key findings and emphasizes the need for targeted interventions to improve attitudes toward HIV/AIDS prevention among Ghanaian women. Strengths:\nClear and concise summary of the study's main outcomes.\nAreas for Improvement:\nMore concrete recommendations for policymakers and health practitioners would strengthen the conclusion.\nOverall Assessment This study provides valuable insights into the knowledge and attitudes regarding HIV/AIDS among Ghanaian women, with robust analysis and clear implications for public health policy. The manuscript would benefit from some structural and editorial refinements to enhance clarity and impact. Recommendations\nAbstract: Include specific recommendations or implications of the findings. Introduction: Condense repetitive sections for greater conciseness. Methods: Provide more detail on survey questions and composite score calculations. Results: Summarize key findings at the beginning of each subsection; Discussion: Structure the discussion more clearly, discuss potential limitations. and consolidate recommendations. Conclusion: Include more concrete policy and practice recommendations.\nWith these improvements, the manuscript will be well-positioned to contribute significantly to the literature on HIV/AIDS prevention in Ghana.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-701
|
https://f1000research.com/articles/9-1178/v1
|
28 Sep 20
|
{
"type": "Systematic Review",
"title": "The effect of non-pharmacologic strategies on prevention or management of intensive care unit delirium: a systematic review",
"authors": [
"Julie S Cupka",
"Haleh Hashemighouchani",
"Jessica Lipori",
"Matthew M. Ruppert",
"Ria Bhaskar",
"Tezcan Ozrazgat-Baslanti",
"Parisa Rashidi",
"Azra Bihorac",
"Julie S Cupka",
"Haleh Hashemighouchani",
"Jessica Lipori",
"Matthew M. Ruppert",
"Ria Bhaskar",
"Tezcan Ozrazgat-Baslanti",
"Parisa Rashidi"
],
"abstract": "Background: Post-operative delirium is a common complication among adult patients in the intensive care unit. Current literature does not support the use of pharmacologic measures to manage this condition, and several studies explore the potential for the use of non-pharmacologic methods such as early mobility plans or environmental modifications. The aim of this systematic review is to examine and report on recently available literature evaluating the relationship between non-pharmacologic management strategies and the reduction of delirium in the intensive care unit. Methods: Six major research databases were systematically searched for articles analyzing the efficacy of non-pharmacologic delirium interventions in the past five years. Search results were restricted to adult human patients aged 18 years or older in the intensive care unit setting, excluding terminally ill subjects and withdrawal-related delirium. Following title, abstract, and full text review, 27 articles fulfilled the inclusion criteria and are included in this report. Results: The 27 reviewed articles consist of 12 interventions with a single-component investigational approach, and 15 with multi-component bundled protocols. Delirium incidence was the most commonly assessed outcome followed by duration. Family visitation was the most effective individual intervention while mobility interventions were the least effective. Two of the three family studies significantly reduced delirium incidence, while one in five mobility studies did the same. Multi-component bundle approaches were the most effective of all; of the reviewed studies, eight of 11 bundles significantly improved delirium incidence and seven of eight bundles decreased the duration of delirium. Conclusions: Multi-component, bundled interventions were more effective at managing intensive care unit delirium than those utilizing an approach with a single interventional element. Although better management of this condition suggests a decrease in resource burden and improvement in patient outcomes, comparative research should be performed to identify the importance of specific bundle elements.",
"keywords": [
"critical care",
"delirium",
"intensive care",
"non-pharmacologic",
"systematic review"
],
"content": "Introduction\n\nDelirium is a multifactorial, acute, confusional state characterized by the disturbance of consciousness and cognition; it is particularly common in the intensive care unit (ICU) with incidence ranging from 19 to 87% with especially high rates in mechanically ventilated patients1–3. ICU delirium is associated with adverse outcomes including increased mortality, prolonged mechanical ventilation and hospitalization, increased risk of cognitive dysfunction after discharge, and increased cost of care4–7.\n\nWhile the pathophysiology of delirium is not well understood, there are multiple factors associated with an increased risk for developing delirium including age, neurologic or psychological disorders, polypharmacy, medications, and sensory impairment8–11. Modifiable environmental risk factors including immobilization, use of restraints, isolation, and levels of environmental light and sound are also considered risk factors for the development of delirium in the ICU8,12.\n\nThe morbidity associated with delirium as well as the multitude of delirium risk factors present in the ICU make delirium prevention and management strategies essential. These strategies have included pharmacological, non-pharmacological, and multicomponent interventions with the aim of decreasing the incidence and duration of delirium. Research into pharmacological interventions has focused on haloperidol and dexmedetomidine, though there has also been limited research into the effects of ramelteon, melatonin, and ziprasidone13–16. Despite continued research, current literature does not support the use of anti-psychotic agents, benzodiazepines, or melatonin in the management of delirium13,17.\n\nGiven the lack of evidence supporting pharmacological measures, further research into the efficacy of non-pharmacologic interventions such as early mobilization, environmental modifications, or management bundles is crucial. The implementation of effective delirium management shows promise in decreasing morbidity, mortality, length of stay, and resource burden in the ICU setting. In terms of the PICOS framework (Population, Interventions, Comparisons, Outcomes, Study Design)18, our systematic review aims to address the effects of any non-pharmacologic prevention or management strategy on the incidence, prevalence, duration, or severity of delirium in critically ill adult patients compared to control patients, with no restrictions on study design.\n\n\nMethods\n\nThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in this review and included as Reporting guidelines19,20. The electronic databases of PubMed, Embase, Cochrane Central, Web of Science, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov were systematically searched on May 15, 2019 for articles concerning non-pharmacologic treatments for delirium in the ICU. Search terms were tailored to each database in order to best utilize the individual subject headings, keywords, and medical subject headings (MeSH) terms included in the individual databases. A full list of search terms is shown in the Extended data20.\n\nIn addition to our search terms, search results were restricted to articles published in English within five years of the date of the search (Jan 1, 2014 to May 15, 2019). This date range was chosen in order to provide a review of the most recent developments in this field of research. After search results were compiled and duplicates were removed, a total of 5234 articles were selected for title and abstract review. The authors screened the titles and abstracts and retrieved articles for eligibility resulting in 113 articles selected for full text review. The authors then independently reviewed the full text of eligible articles, completed data extraction worksheets adapted from the Cochrane Review Group’s Data Extraction Form, and assessed the articles for risk of bias using the Cochrane risk of bias tool21. Elements of the data extraction worksheet included study design and setting, participant characteristics, details of the intervention and control groups, diagnostic tools, and patient outcomes (Extended data, Supplementary Table 1)20. Any disagreements were resolved by thoroughly discussing any points of concern. During the full text review 86 articles were removed because they failed to meet our inclusion criteria resulting in a total of 27 included articles (Figure 1).\n\nOur review addresses non-pharmacological management strategies for delirium in the ICU. Included articles were those investigating non-pharmacologic interventions and their impact on delirium incidence, prevalence, duration, or severity in an adult (≥ 18 years) intensive care unit setting. Articles were excluded if they focused on non-human subjects, pediatrics, terminally ill subjects, withdrawal related delirium, case reports, or where no full-text article was available (abstract only). There were no restrictions on study design. Studies solely investigating delirium-free-coma-free days were excluded since it is not possible to review as a delirium-specific result. One multi-center study was excluded as both the frequency and method of assessment for delirium were not specified for all study centers, making it difficult to reliably compare the results with other trials22. Another study was excluded because neither the screening process nor the cohort were described other than total number of patients enrolled, and there were no exclusion criteria noted to infer any characteristics of the selected population23.\n\nIn addition to data extraction using the Cochrane Review Group’s Data Extraction Form, a risk of bias assessment was performed by all authors on all included randomized controlled trials (RCTs) and randomized pilot studies. A risk of bias worksheet was developed by modifying Cochrane’s Risk of Bias Tool and articles were ranked as having a low, high, or unclear risk of bias21. Disagreements were settled by discussion between the authors. A total of eleven included studies underwent this assessment. Details of the risk of bias assessment categories can be found in the Extended data, Supplementary Table 220.\n\n\nResults\n\nAfter searching the literature, 27 articles are included in our systematic review24–50 (Figure 1). Study details of each reviewed trial are located in Table 1. The 27 included studies provide results on many distinct outcomes; however, only the delirium-related outcomes of incidence, prevalence, duration, and severity were reviewed (Table 2–Table 5). Outcomes combining delirium and coma into the same statistic were excluded, as no delirium-specific results could be assessed outright. An overall summary of delirium outcomes can be found in Table 2.\n\nAbbreviations: BADLs: basic activities of daily living; CABG: coronary artery bypass graft; CAM: Confusion Assessment Method; CNS: central nervous system; CVA: cerebrovascular accident; DI: Delirium Index; DOS scale: Delirium Observation Screening scale; DRS/DRS-R-98: Delirium Rating Scale-Revised-98; DSM-V: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition; FAQ: Functional Activity Questionnaire; GCS: Glasgow Coma Score; ICDSC: Intensive Care Delirium Screening Checklist; ICU: intensive care unit; IQCODE: Informant Questionnaire on Cognitive Decline in the Elderly; LOS: length of stay; MMSE: Mini-Mental State Examination; OT: occupational therapy; QI: quality improvement; RASS: Richmond Agitation-Sedation Scale; RCT: randomized controlled trial; SICU: surgical ICU.\n\n* exclusion criteria of 'family history for surgery': cannot confirm whether for elective open heart surgery, or surgery in general.\n\nLegend: x, p>0.05; y, p<0.05; o, not analyzed for significance; --, not measured in this study; y/x, some measured time-points are significant.\n\nAbbreviations: AOR: adjusted odds ratio; CABG: coronary artery bypass graft; CG: control group; FES: functional electrical stimulation; IG: intervention group; FES: functional electrical stimulation; NA: not analyzed; OR: odds ratio; OT: occupational therapy; ROM: range of motion; RR: relative risk.\n\nLegend: a = Percent of patients with at least one positive CAM-ICU screening; b = Number of recorded delirium events; c = Number of patients with at least one positive CAM-ICU screening; d = Number of patients with at least one positive CAM-ICU screening, patients with RASS -4 or -5 counted as ‘not delirious’; e = Number or percent of patients with at least one positive ICDSC screening; f = Number of patients with at least one NEECHAM score of < 25; g = Number of patients with a positive CAM-ICU after an initial negative result; h = Number of patients with any CAM-ICU positive result; i = not reported; * = significant difference, p<0.05; † = 95% confidence interval; ‡ = contradictory numbers reported, see referenced text.\n\nAbbreviations: CG: control group; FES: functional electrical stimulation; FG: family voice group; IG: intervention group; IQR: interquartile range; IRR: incidence risk ratio; OT: occupational therapy; ROM: range of motion; RR: relative risk; SD: standard deviation; UG: unknown voice group.\n\nLegend: * = significant, p<0.05; † = 95% confidence interval.\n\nAbbreviations: DI: Delirium Index; DRS: Delirium Rating Scale; DRS-R-98: Delirium Rating Scale-Revised-98; NA: not analyzed; OT: occupational therapy.\n\nLegend: * = significant difference, p<0.05; † = confidence interval not specified.\n\nOf these 27 articles, 24 assessed incidence and/or prevalence within their cohorts24–43,45–48,50, 16 assessed for duration24–28,34,35,38,42,44–46,48–50, and four for severity24,36,42,50. Additionally, 12 focused on the effect of single interventions24,29,31,32,34,38,41,42,44,45,47,48 while 15 considered bundled, multicomponent interventions25–28,30,33,35–37,39,40,43,46,49,50. Individual interventions included mobility protocols, distinct family visiting policies, dynamic lighting, music therapy, automated reorientation messages, mindfulness exercises, and the structured use of mirrors in recovery. These individual interventions also comprised multiple components of the bundled interventions. A summary of study details can be found in Table 1.\n\nMeasurements for incidence, prevalence, and duration were based upon multiple methods of delirium screening, including the Confusion Assessment Method (CAM), CAM-ICU, Intensive Care Delirium Screening Checklist (ICDSC), and Neelon and Champagne (NEECHAM) scales. Incidence and prevalence were similarly defined in all studies except for one, and are recorded separately in Table 3; only one study looked at both incidence and prevalence39. Severity was assessed by using the Delirium Index (DI), the Delirium Rating Scale (DRS), the Revised Delirium Rating Scale (DRS-R-98), and NEECHAM scale (Table 5).\n\nOf the 27 included studies, 11 were RCTs or randomized pilot studies24,31,32,34–36,38,42–44,48, eight were pre-post prospective studies26,28,39,40,46,47,49,50, and two were quasi-experimental25,30. The remaining six were a case-matched control study, an evidence based protocol, a mixed-methods pilot study, a prospective multicenter cohort study, a retrospective cohort study, and an action research study27,29,33,37,41,45.\n\n\nRisk of bias assessment\n\nThe ten RCTs and the randomized pilot study underwent a risk of bias assessment performed by all authors. Risks of bias fell into five major groups (selection bias, performance bias, detection bias, attrition bias, and reporting bias), and based on a study’s scores in each of these groups it was labeled as having an overall high, low, or unclear risk of bias. Four were considered low risk of bias24,34,42,48, two had a high risk of bias32,44, and five had an unclear risk of bias31,35,36,38,43. The most common source of bias was performance bias due to the impossibility of blinding participants or personnel to certain treatments. Common sources of unclear and high risk of bias included the methods of randomization and allocation concealment, as well as how missing data was handled.\n\nEarly mobility. The effect of early mobility protocols on delirium was the most commonly studied individual intervention. Four of the studies included in our review individually assessed the efficacy of early mobility24,29,38,45 in treating and preventing delirium; of these, two were RCTs24,38, one was an evidence-based project29, and one was a case-matched control study45. They assessed delirium through CAM24 and CAM-ICU29,38,45.\n\nThe pilot RCT performed by Álvarez et al. investigated the effect of early mobilization through early and intensive occupational therapy (OT), including polysensory stimulation, body positioning, cognitive stimulation exercises, basic activities of daily living, upper extremity motor exercises, and family involvement, on non-intubated, elderly patients (≥ 60) in addition to the study center’s standard, non-pharmacological delirium prevention care24. Delirium associated outcomes included incidence, duration, and severity; they found significant differences in incidence and duration of delirium, with both p-values ≤ 0.001, but no significant difference in severity (Table 3–Table 5).\n\nAnother RCT by Karadas and Ozdemir assessed the effect of range of motion (ROM) exercises on delirium in elderly ICU patients (≥ 65 years)38. Interventional care included ROM exercises for 30 minutes daily after establishing the patient’s ability to complete 10 repetitions on each of the four extremities while lying in bed. They reported no statistically significant differences between cohorts for delirium associated outcomes (Table 3 & Table 4).\n\nCampbell addressed early mobilization in mechanically ventilated ICU patients with an evidence-based project29. They measured the effect of a tiered protocol of ROM exercises, bed mobility exercises, seated balance activities, transfer activities (such as bed to chair), standing exercises, and ambulation on delirium incidence and duration but found neither to be significant (Table 3 & Table 4).\n\nThe effectiveness of functional electrical stimulation (FES) to promote mobility and recovery in mechanically ventilated patients with sepsis was evaluated by Parry et al. in a case-matched control study45. The intervention included use of a motorized cycle ergometer to directly stimulate four major lower limb muscles (quadriceps, hamstrings, gluteals, and calves) five times weekly for 20–60 minutes a session dependent on the individual patient’s tolerance. While delirium incidence was not significantly affected (Table 3), the median days of delirium differed between arms (6.0 in control and 0.0 in intervention) (Table 4).\n\nFamily involvement. Of the 12 studies in our review which focused on individual interventions, three studied the effect of family involvement on delirium in adult ICU patients. One was a randomized pilot study42, one an RCT32, and one was a pre-post study47. All three studies utilized CAM-ICU in their assessment of delirium.\n\nMailhot et al. constructed a randomized pilot study to explore the effect of a family caregiver (FC) assisting with delirium management after being ‘mentored’ by nurses in the ‘MENTOR_D’ intervention42. They assessed the efficacy of this intervention on all delirious, adult coronary artery bypass graft (CABG) patients admitted to the surgical ICU by measuring the outcomes of duration, occurrence, and severity of delirium over three days42. This intervention enrolled 14 patient-nurse (control) care dyads and 16 patient-FC care dyads, which had the FC apply bedside strategies to aid the patient in reorientation. In addition to reorientation, the FC was asked to observe and communicate signs of delirium with nursing staff, present family memories, and speak clearly and simply. Delirium duration and occurrence on post-operative Day 2 improved clinically between groups (duration, mean days from 4.14 to 1.94; occurrence, from 71.40% to 43.80%); however, this result was not assessed for statistical significance and the severity result was not found to be significant (Table 3–Table 5).\n\nThe RCT performed by Eghbali-Babadi et al. investigated a modified family visitation policy, implementing an additional 30–40 minute special visit by an approved family member, and its effect on delirium incidence in non-intubated adults aged 18–70 after elective open heart surgery32. They found a statistically significant reduction in delirium incidence in the intervention group with a p-values of 0.04, <0.05, and 0.03 at three different time points (Table 3).\n\nRosa et al. also measured the effect of a modified family visitation policy on delirium incidence, although their population was less restrictive and included any adult ICU patient47. Their pre-post study included the extension of visitation hours from 4.5 hours per day over three visitation blocks to 12 hours per day between 09:00–21:00. This resulted in a statistically significant difference in delirium incidence, improving from 20.5% to 9.6% (Table 3).\n\nEnvironmental approaches (lighting, music therapy, automated reorientation). Three RCTs assessed the impact of environmental factors on delirium in the ICU, assessed by CAM-ICU, through manipulation of light48, music therapy31, or automated reorientation44.\n\nIn Simons et al.’s dynamic lighting application RCT, adult ICU patients were exposed to variations in high intensity, blueish-white lighting while delirium incidence and duration were measured48. The intervention group was exposed to a peak of 1700 lux (brightness)/4300 K (color temperature) from 09:00–11:30 and 13:30–16:00, and a daytime minimum of 300 lux/3000 K from 11:30–13:30; the control group was exposed solely to 300 lux/3000 K (Table 1). Neither the cumulative incidence of ICU-acquired delirium nor the duration were significantly affected, and the trial was ended early after the intervention was deemed futile (Table 3 & Table 4).\n\nIn another RCT, Damshens et al. introduced therapeutic music selected by a music expert, twice a day for 45 minutes to assess the effect on delirium incidence in adults admitted to ICU trauma service31. Patients in the control group received conventional care for the duration of their admission. There was no resultant change to delirium incidence between the two groups (Table 3).\n\nMunro et al. developed a novel patient reorientation strategy in an RCT, which utilized bilingual (Spanish or English) messages pre-recorded by either family members or females unknown to the adult ICU subjects44. The recordings included an introduction with the patient’s name and location, with several additional randomly ordered statements in order to reorient the patient to their unfamiliar surroundings and reason for hospitalization. All three arms (two intervention groups and one control group) were compared and it was found that the family voice group had a significant improvement in delirium free days (p= 0.0437) but not mean days of delirium (Table 4).\n\nSelf-involvement approaches (mirror usage, mindfulness exercises). The remaining two studies on the effect of individual interventions assessed the impact of self-involvement approaches, including mirror usage34 and mindfulness exercises41, on ICU delirium measured by CAM-ICU. One study was a pilot RCT34, while the other was a mixed-methods pilot study41.\n\nIn a pilot time-cluster RCT, Giraud et al. tested the effect of introducing structured mirror usage into post-operative recovery in elderly ICU patients (≥70 years) after cardiac surgery34. Mirror usage was standardized by developing a protocol for nurses and physiotherapists, aiming to use both small, personal mirrors as well as larger posture mirrors in order to help the patient with reorientation and self-awareness, enhance multisensory feedback on minor procedures, and augment passive and active physical therapies. The control cohort received usual care, including allowing control patients who brought a mirror from home to use it per their normal habits. After comparing the usual care group with the mirrors group, no significant improvement was found in delirium incidence, ICU days with delirium, or the proportion of the total ICU length of stay that the patient spent delirious (Table 3 & Table 4).\n\nThe mixed-methods study by Lisann-Goldman et al. had subjects who were 40 years of age or older participate in Langerian mindfulness discussion exercises both prior to and after elective cardiac surgery with cardiopulmonary bypass41. In addition to discussion exercises, patients listened to an audio file before surgery. This audio file walked them through techniques on how to re-assess one’s situation and improve their outlook by taking emotional control of the situation, encouraging the patients to focus on the process of change and allowing oneself to accept new ideas and remain confident about the unknown. The discussion exercises continued post-operatively twice daily. In contrast, the ‘informational control’ group went through normal pre-operative discussions followed by an audio file describing the process of cardiac surgery. They found that no subject developed delirium in either the interventional or the ‘informational control’ group so the effectiveness of the treatment could not be assessed.\n\n‘Wake Up and Breathe’ protocol. Khan et al. designed a ‘Wake Up and Breathe’ protocol in a pre-post interventional study to assess for any change in delirium and sedation in mechanically ventilated, adult ICU patients39. They modified elements of the Awakening and Breathing Controlled trial (ABC) to implement a spontaneous awakening trial and daily sedation vacation followed by a spontaneous breathing trial, depending on the patient’s response51. Delirium was assessed by CAM-ICU, and both the incidence and prevalence of delirium were analyzed, with the study finding no significant change in either measured outcome (Table 3).\n\nABCDE(F) bundles. Five of the 15 studies which examined delirium bundles studied the effectiveness of ABCDE(F) bundle protocols on reducing delirium. ABCDE(F) bundles have multiple components including: spontaneous awakening (A) and breathing (B) trials, interdisciplinary coordination of sedatives and medications (C), delirium screening and management (D), early mobilization (E), and family engagement and involvement (F)52. Of these five studies, two were pre-post studies26,40, one was a prospective multicenter cohort study37, one was a quasi-experimental quality improvement project30, and one was a retrospective cohort study27. Three measured delirium outcomes using CAM-ICU26,30,40, one utilized ICDSC27, and one multicenter study used either CAM-ICU or ICDSC37.\n\nBalas et al. assessed the impact of an ABCDE bundle on adult ICU patients, evaluating the prevalence and duration of delirium in both total days and percent of ICU days spent delirious, with a pre-post study26. The prevalence and percent of ICU days spent delirious were improved in the post period with p-values of 0.03 and 0.003 respectively (Table 3 & Table 4). However, the overall duration of delirium was not significantly different (Table 4).\n\nThe retrospective assessment of an ABCDE bundle by Bounds et al. evaluated its effect on delirium prevalence and duration in an adult ICU population27. Both the prevalence and duration were significantly decreased in the ABCDE bundle group (p= 0.01 and 0.001 respectively; (Table 3 & Table 4).\n\nKram et al. also looked at a similar patient cohort, all adult patients 18 or older admitted to the ICU, in a pre-post ABCDE bundle study with a smaller subject population (Kram, n=83; Balas, n=296; Bounds, n=159)40. They assessed the effectiveness of the ABCDE bundle on delirium by measuring delirium prevalence and comparing it to a control based on literature values. The measured delirium prevalence of 19% (Table 3) fell outside their cited literature values of 20–80%.\n\nChai initiated an ABCDEF bundle in a mixed ICU setting and analyzed delirium incidence in the adult patients in a pre-post, quasi-experimental quality improvement project30. Delirium incidence was compared between morning and night occurrences (morning 08:00–11:00; night 20:00–23:00); both showed significant improvement in the intervention group with a p-value <0.001 for both morning and evening measurements (Table 3).\n\nA prospective cohort study performed by Pun et al. through a national quality improvement initiative compared complete ABCDEF bundle performance with proportional ABCDEF bundle performance in adult ICU patients with an ICU stay of at least 48 consecutive hours37. Complete bundle performance was defined as a patient-day where 100% of the eligible bundle elements were performed, whereas proportional performance was anything less37. Their study was comprehensive, including 10,840 patients for delirium outcome analysis across 68 ICUs in the United States and Puerto Rico37. When comparing the incidence of delirium between patients with complete and proportional ABCDEF bundle performance, they found that patients with complete performance were significantly less likely to develop delirium (Table 3)37. In an additional analysis, Pun et al. found a dose-dependent reduction of delirium incidence when the more eligible ABCDEF bundle elements were performed (p < 0.0001)37. It is worth noting that this study had a high rate of ‘missingness’ for delirium data and the analysis team chose not to perform multiple imputations37.\n\nOther bundled protocols. The remaining nine bundle studies developed new, unique bundles. They included four pre-post studies28,46,49,50, three RCTs35,36,43, one quasi-experimental study25, and one action research study33. Seven assessed delirium incidence and duration using CAM-ICU25,28,33,35,43,49,50, one used NEECHAM36, and one used ICDSC46.\n\nA quasi-experimental study designed by Arbabi et al. developed a multi-component delirium management bundle comprised of staff education and environmental and non-pharmacologic care changes25. They measured the effectiveness of their bundle by assessing delirium incidence and duration in all adult patients admitted to the general ICU, finding a significant difference in both outcomes (p = 0.01 and 0.001 respectively; Table 3 & Table 4).\n\nBryczkowski et al. assessed the effectiveness of their bundle, which included a staff-patient-family education program, medication management strategies, and non-pharmacological sleep enhancement protocols, on delirium incidence and delirium free days in patients over the age of 50 years28. The research team found no significant improvement in delirium incidence (Table 3), although the average total number of delirium-free days out of 30 changed significantly from 24 to 27 between groups (p=0.002; Table 4).\n\nAnother bundle study developed by Fallahpoor et al. focused specifically on adults admitted to the ICU after elective CABG in an action research study. Their post-CABG delirium management bundle was assessed in an action research study and had three elements focusing on pre-, intra-, and post-operative methods to identify delirium risk factors, optimize time spent in surgery, and introduce staff education and post-operative environmental changes33. Delirium related outcomes included the incidence ratio and total number of recorded delirium events, with significant differences found in both (p=0.001 and 0.008 respectively; Table 3).\n\nIn the RCT conducted by Guo et al., the effect of a bundle consisting of cognitive prehabilitation, post-operative cognitive stimulation activities, environmental changes, music therapy, and non-pharmacologic care changes on delirium incidence and duration after oral tumor resection in patients aged 65–80 years was studied35. The incidence of delirium improved significantly overall, but was only significantly different on post-operative day one compared to days two and three (p=0.035, p=0.374, p=0.364 respectively; Table 3); the duration of delirium also differed significantly (p< 0.001; Table 4).\n\nHamzehpour et al. designed an RCT and implemented the Roy adaptation nursing model for all adult ICU patients, which focuses on balance of nutrition, electrolytes, and fluids while promoting activity, sleep hygiene, and monitoring of circulation and endocrine function36. Their primary delirium-specific outcomes were incidence and severity, and they analyzed both outcomes for two time points (morning & night) for seven days. Their research only showed significant improvements to incidence on day seven, both morning and night (p<0.008 and p<0.05; Table 3), but delirium severity, assessed with NEECHAM, improved through the morning of day four to the night of day seven at all measured time points (every time point, p≤0.028; Table 5).\n\nMoon and Lee implemented a bundle which included early cognitive assessments and reorientation, sensory aids, environmental changes, consistent care staff and location, familiar items from home, nursing care changes, and early mobility as part of an RCT aimed at assessing delirium incidence in adult ICU patients with at least a 48 hour stay43. Their study did not show a significant difference between the intervention and the control group who received usual care (Table 3).\n\nIn a pre-post, observational quality improvement project, Rivosecchi et al. combined staff education with a non-pharmacologic bundle to look at incidence and duration of delirium in any adult patient aged 18 or older admitted to the medical ICU46. Their M.O.R.E. bundle included (M)usic, (O)pening blinds, (R)eorientation and cognitive stimulation, and (E)ye and ear care. Both delirium incidence and duration were significantly impacted, with incidence decreasing from 15.7% to 9.4% and a reduction in duration from 16.1% of the ICU stay to 9.6% (p = 0.04 and <0.001 respectively; Table 3, Table 4).\n\nSullinger et al. enrolled adult surgical-trauma ICU patients with acute delirium in a pre-post retrospective study, tailoring their bundle to incorporate staff education with sensory aids, healing arts techniques, mobility, environmental changes, and family presence49. Their bundle also included the initiation of anti-psychotic medications if non-pharmacologic tactics failed. The only specifically delirium related outcome was the number of days spent delirious, resulting in a significant decrease from 8.2 to 4.5 median days (Table 4).\n\nAny patient 18 years or older admitted to a cardiothoracic ICU after CABG surgery was analyzed for incidence, duration, and severity of delirium by Zhang et al. in a prospective pre-post study50. Their delirium bundle targeted risk factor screening and modifications, including increased family visits, reorientation, and changes to nursing care. The only significant improvement was to incidence of delirium which dropped from 29.93% to 13.48% (Table 3), while the intervention had no impact on duration or severity (Table 4 & Table 5).\n\n\nDiscussion\n\nOur review included 27 trials that evaluated the effect of various non-pharmacological treatment and management protocols on delirium in an ICU setting. Assessment of the efficacy of these protocols in the last five years was most commonly done by considering incidence and/or prevalence. A total of 25 studies assessed for the effects of these protocols on incidence and/or prevalence, with 11 studying individual approaches and 14 studying bundles. Of these 25 trials, 11 reported significant improvements overall24–27,30,32,33,37,46,47,50, nine found no significant improvement28,29,31,34,38,39,43,45,48, and two only found significant change at certain time points35,36; the remaining three did not analyze for statistical significance of their results40–42. The 11 effective interventions for incidence and/or prevalence were primarily bundled protocols (eight trials)25–27,30,33,37,46,50, followed by family approaches (two trials)32,47, and early and intensive OT (one trial)24. The two studies with time point dependent changes were both bundles, one non-pharmacologic35 and the other introduced the Roy adaptation nursing model36. The multicomponent non-pharmacologic bundle found improvements in incidence both overall and on day one, while the Roy adaptation trial only saw a change in incidence on day seven in both the morning and the evening. Three studies did not analyze for statistical significance40–42; however, the family caregiver intervention saw an overall reduction in the percent of subjects who developed delirium from 71.40% to 43.80%42. The study on mindfulness exercises had no subjects in either investigational group develop delirium41, and an ABCDE bundle reported a post-bundle incidence of 19% but stated there was no pre-bundle data with which to compare40. No other studies that looked at delirium incidence were effective.\n\nIn addition to incidence and prevalence, another common outcome was a change in the duration of delirium. Sixteen of the reviewed studies evaluated the duration of delirium, eight focusing on individual interventions and eight introducing bundled protocols. Of these 16 studies, eight found significant changes overall24,25,27,28,35,45,46,49, two had significant improvements at select time points26,44, and five did not have significant results29,34,38,48,50; the one remaining study did not assess for statistical significance42. Six of the eight successful trials were bundles and both of the two effective individual therapies were mobility-focused (early and intensive OT, and FES)24,45. Only four studies looked at delirium severity24,36,42,50 with only one finding any significant results, and only finding them at select time-points (Roy Adaptation Model)36.\n\nThe pilot RCT performed by Alvarez et al. utilized a unique method for assessing the performance of their intervention. In addition to assessing delirium incidence, they measured the ratio of delirium duration to the amount of time exposed to the treatment (IRR)24. They found that IRR decreased as the time exposed to treatment increased to a significant degree (p= 0.000). This ratio could be explained in three ways. Either the duration of delirium stayed the same as the time exposed to treatment increased, the duration of delirium increased slower than the time exposed increased, or the duration of delirium decreased while the time of exposure increased. However, the last explanation is impossible, due to the duration of delirium being a sum overtime which could not decrease, such that the result must be explained by either a small increase or no increase in the duration of delirium. If the decrease in the IRR is explained by smaller and smaller increases to delirium duration it is likely that the IRR results from either the trend of patients slowly becoming healthier over time, or the conjunction of that with the intervention. However, if the IRR is explained by the delirium duration ceasing to increase, then once it stops the treatment may still be effective, but it is not becoming more effective over time and plateaus in effectiveness.\n\nThe reviewed studies focused on individual interventions that had a wide range of limitations and were, on the whole, less effective than bundled protocols in the treatment and management of delirium. Many of these studies had limited reliability due to small or extremely small sample sizes29,41,44,45. Additionally, even when results were significant, they often had limited applications to practice due to the prevalence of restricted populations. Three of the individual intervention studies limited their study cohort to elderly adults15,24,38, a population which is at an increased risk of delirium. It is unclear whether these results would apply to younger patients. Studied populations were also commonly narrowed to either exclusively intubated patients45, non-intubated patients24,32 or patients with a particular illness34,42,45. Another possible limitation was in the questionable reliability of delirium assessment criteria. This is mentioned by Campbell who stated that 35% of CAM-ICU were incorrectly labeled as ‘unable to assess’29. The question of reliability was also raised in Lisann-Goldman et al.. This study could not assess the effectiveness of their intervention as no patients developed delirium41. However, this could be explained by the fact that fully sedated patients were considered ‘not delirious’ since CAM-ICU could not be performed. The authors also noted that since it often takes weeks or months to fully integrate new behavioral thought techniques, a study focused on changing thought patterns in days would not entirely reflect the full benefit if any were present41.\n\nEight of the individual intervention studies were RCTs. This type of study introduces the possibility of additional limitations due to the nature of its design. Two of these RCTs had a high risk of bias32,44 due to a failure to blind patients and personnel, as well as blinding of the outcome assessment and improper allocation concealment. The question of blinding raises another possible limitation of many of these studies, namely the possibility of the Hawthorne effect in patients who knew that they were being observed and receiving an intervention for the treatment/prevention of delirium.\n\nThe 15 studies which investigated bundled protocols had, overall, larger sample sizes, fewer cohorts with limited populations, and indicated better reliability in their delirium assessment than the studies which focused on individual interventions. The smallest sample size was 83 patients40; however, this study did not split the sample into multiple cohorts and all patients received the intervention. One study had a sample size of 8949, and all other studies had a sample size of at least 100 patients. A total of five studies restricted their studied population beyond adult ICU patients28,33,35,39,50. Two of these limited their population by age28,35; however, Bryczkowski et al., despite limiting their population by age, included any patients greater than 50 years old, younger than the age when delirium risk is noted to increase53,54. One study limited its population to mechanically ventilated patients39, two considered only patients undergoing CABG33,50, and one studied patients after oral tumor resection35. These population restrictions could limit the generalizability and applicability of the interventions; however, this risk is reduced since bundles were often investigated in multiple studies with similar results.\n\nOnly three of the bundle studies were RCTs35,36,43. Each of these RCTs had an unclear risk of bias with the most common risk being the inability to blind participants and personnel. The impossibility of blinding in delirium intervention studies makes RCTs a questionable approach. Eight of the bundle studies, recognizing blinding as an impossibility, chose to conduct pre-post prospective studies rather than RCTs26,28,30,39,40,46,49,50. These studies carried a lower risk of introducing bias to their studies and avoided crossover between arms. The pre-post study performed by Kram et al. had the major limitation of not including a pre cohort and only comparing the results of their intervention with literature values40. Additionally, while they found their measured delirium prevalence to fall outside their included literature values (19%), this prevalence falls within the values provided by the current literature (19- 87%) (2). Chai’s pre-post study had a delirium assessment with questionable reliability. While all other studies assessed delirium whenever the Richmond Agitation-Sedation Scale (RASS) was ≥ -3, they reported that patients were unable to be assessed whenever RASS was < -2, resulting in a greater proportion of patients not assessed for delirium30.\n\nGiven the findings of this systematic review, further research is warranted in order to confirm these results and apply them to other patient populations. Multicomponent, bundled approaches were more successful at improving delirium outcomes compared to individual techniques; however, the effective individual tactic of family engagement was included as a component in the effective bundles. Although a majority of the reviewed bundles were effective, it is difficult to compare results as the trials had large differences in study design, enrollment numbers, and delirium assessment measures.\n\nThe strengths of our systematic review include thorough search terms and the methodology to assess a vast majority of recent literature in this field.\n\nOne limitation of this systematic review is that we only focused on trials within the past five years which excluded some well-cited early studies on delirium. We also did not evaluate other listed outcomes which could provide additional insight into any change in delirium status. Since the condition can be transient and delirium screenings are not performed as frequently throughout the ICU day as other measurements, outcomes such as restraint use or amount of prescribed sedatives or anti-psychotic medications would be beneficial to assess in this setting. While the decision to omit exclusion criteria on study design allowed for assessment of a broader range of trials, it was difficult to compare outcomes when multiple differing designs and measurement tools were used. Although the CAM-ICU was widely used, some studies used alternative tools and there was no standardized way of defining or measuring delirium duration or severity. A different measurement tool was used to evaluate severity in each of the four studies reviewing this outcome, and duration was defined in a multitude of fashions. Combining this realization with the fact that some studies focused on highly specific subpopulations suggests that some trials may need to be replicated in a standardized fashion to account for any differences in methodology or subjective assessments.\n\n\nConclusions\n\nMany ICU delirium treatment and management protocols were developed and tested within the last five years in a variety of study designs. Few trials on individual interventions had positive effects on delirium incidence and duration, but multicomponent bundles were found to be more effective overall while incorporating the effective individual intervention of family engagement. Based on the results of bundle studies, the implementation of multi-component protocols in ICUs can reduce ICU delirium, thereby reducing cost of care, improving overall outcomes, and limiting time spent mechanically ventilated, medicated, or admitted. Despite these results, further research is needed on individual interventions in order to improve specific elements of multicomponent bundles by adding or removing ineffective therapies. Additional research is also warranted to evaluate for any positive effects in more generalized hospital populations.\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\nOSF: The Effect of Non-Pharmacologic Strategies on Prevention or Management of Intensive Care Unit Delirium: A Systematic Review. https://doi.org/10.17605/OSF.IO/C3RHF20.\n\nThis project contains the following extended data:\n\nSupplementary Appendix 2 – Database search terms\n\nSupplementary Table 1 – Data extraction form\n\nSupplementary Table 2 – Risk of bias assessment\n\nData are available under the terms of the ‘Creative Commons Zero \"No rights reserved\" data waiver’ (CC0 1.0 Public domain dedication).\n\nOSF: PRISMA checklist for ‘The Effect of Non-Pharmacologic Strategies on Prevention or Management of Intensive Care Unit Delirium: A Systematic Review’. https://doi.org/10.17605/OSF.IO/C3RHF20\n\nData are available under the terms of the ‘Creative Commons Zero \"No rights reserved\" data waiver’ (CC0 1.0 Public domain dedication).",
"appendix": "Acknowledgements\n\nA previous version of this article is available from medRxiv: https://doi.org/10.1101/2020.05.20.20100552.\n\n\nReferences\n\nLin WL, Chen YF, Wang J: Factors Associated With the Development of Delirium in Elderly Patients in Intensive Care Units. J Nurs Res. 2015; 23(4): 322–9. PubMed Abstract | Publisher Full Text\n\nKalabalik J, Brunetti L, El-Srougy R: Intensive care unit delirium: a review of the literature. J Pharm Pract. 2014; 27(2): 195–207. PubMed Abstract | Publisher Full Text\n\nPage VJ, Ely EW, Gates S, et al.: Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2013; 1(7): 515–23. PubMed Abstract | Publisher Full Text | Free Full Text\n\nParker AM, Sricharoenchai T, Raparla S, et al.: Posttraumatic stress disorder in critical illness survivors: a metaanalysis. Crit Care Med. 2015; 43(5): 1121–9. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nThom RP, Bui MP, Rosner B, et al.: A Comparison of Early, Late, and No Treatment of Intensive Care Unit Delirium With Antipsychotics: A Retrospective Cohort Study. Prim Care Companion CNS Disord. 2018; 20(6): 18m02320. PubMed Abstract | Publisher Full Text\n\nKnauert MP, Pisani MA: Dexmedetomidine for hyperactive delirium: worth further study. J Thorac Dis. 2016; 8(9): E999–e1002. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGirard TD, Exline MC, Carson SS, et al.: Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness. N Engl J Med. 2018; 379(26): 2506–16. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen S, Shi L, Liang F, et al.: Exogenous Melatonin for Delirium Prevention: a Meta-analysis of Randomized Controlled Trials. Mol Neurobiol. 2016; 53(6): 4046–53. PubMed Abstract | Publisher Full Text\n\nBarbateskovic M, Krauss SR, Collet MO, et al.: Pharmacological interventions for prevention and management of delirium in intensive care patients: a systematic overview of reviews and meta-analyses. BMJ open. 2019; 9(2): e024562. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuang X, Lin J, Demner-Fushman D: Evaluation of PICO as a knowledge representation for clinical questions. AMIA Annu Symp Proc. 2006; 2006: 359–63. PubMed Abstract | Free Full Text\n\nMoher D, Liberati A, Tetzlaff J, et al.: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009; 151(4): 264–9, w64. PubMed Abstract | Publisher Full Text\n\nBihorac A: The Effect of Non-Pharmacologic Strategies on Prevention or Management of Intensive Care Unit Delirium: A Systematic Review. OSF. 2020. http://www.doi.org/10.17605/OSF.IO/C3RHF\n\nHiggins JP, Sterne JA, Savovic J, et al.: A revised tool for assessing risk of bias in randomized trials. Cochrane database of systematic reviews. 2016; 10(Suppl 1): 29–31. Reference Source\n\nSchaller SJ, Anstey M, Blobner M, et al.: Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet. 2016; 388(10052): 1377–88. PubMed Abstract | Publisher Full Text\n\nPatel J, Baldwin J, Bunting P, et al.: The effect of a multicomponent multidisciplinary bundle of interventions on sleep and delirium in medical and surgical intensive care patients. Anaesthesia. 2014; 69(6): 540–9. PubMed Abstract | Publisher Full Text\n\nÁlvarez EA, Garrido MA, Tobar EA, et al.: Occupational therapy for delirium management in elderly patients without mechanical ventilation in an intensive care unit: A pilot randomized clinical trial. J Crit Care. 2017; 37: 85–90. PubMed Abstract | Publisher Full Text\n\nArbabi M, Zebardast J, Noorbala AA, et al.: Efficacy of Liaison Education and Environmental Changes on Delirium Incidence in ICU. Arch Neurosci. 2018; 5(2): e56019. Publisher Full Text\n\nBalas MC, Vasilevskis EE, Olsen KM, et al.: Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle. Crit Care Med. 2014; 42(5): 1024–36. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBounds M, Kram S, Speroni KG, et al.: Effect of ABCDE Bundle Implementation on Prevalence of Delirium in Intensive Care Unit Patients. Am J Crit Care. 2016; 25(6): 535–44. PubMed Abstract | Publisher Full Text\n\nBryczkowski SB, Lopreiato MC, Yonclas PP, et al.: Delirium prevention program in the surgical intensive care unit improved the outcomes of older adults. J Surg Res. 2014; 190(1): 280–8. PubMed Abstract | Publisher Full Text\n\nCampbell MR: The Effect of an Early Mobility Protocol in Critically Ill Mechanically Ventilated Patients on Incidence and Duration of Delirium and Length of Stay. 2014. Reference Source\n\nChai J: The effect of the ABCDEF bundle on incidence of delirium in critically ill patients. Brandman University. 2017. Reference Source\n\nDamshens MH, Sanie MS, Javadpour S, et al.: The Role of Music on the Delirium in Traumatic Patients: A Case Study in the ICU of Peymanieh Hospital of Jahrom, Fars Province, Iran. Ambient Science. 2018; 5: 97–101. Reference Source\n\nEghbali-Babadi M, Shokrollahi N, Mehrabi T: Effect of Family-Patient Communication on the Incidence of Delirium in Hospitalized Patients in Cardiovascular Surgery ICU. Iran J Nurs Midwifery Res. 2017; 22(4): 327–31. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFallahpoor S, Abedi H, Mansouri M: Development and Evaluation of Care Programs for the Delirium Management in Patients after Coronary Artery Bypass Graft Surgery (CABG). International Journal of Medical Research Health Sciences. 2016; 5(7): 547–53. Reference Source\n\nGiraud K, Pontin M, Sharples LD, et al.: Use of a Structured Mirrors Intervention Does Not Reduce Delirium Incidence But May Improve Factual Memory Encoding in Cardiac Surgical ICU Patients Aged Over 70 Years: A Pilot Time-Cluster Randomized Controlled Trial. Front Aging Neurosci. 2016; 8: 228. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGuo Y, Sun L, Li L, et al.: Impact of multicomponent, nonpharmacologic interventions on perioperative cortisol and melatonin levels and postoperative delirium in elderly oral cancer patients. Arch Gerontol Geriatr. 2016; 62: 112–7. PubMed Abstract | Publisher Full Text\n\nHamzehpour H, Valiee S, Majedi MA, et al.: The Effect of Care Plan Based on Roy Adaptation Model on the Incidence and Severity of Delirium in Intensive Care Unit Patients: A Randomised Controlled Trial. Journal of Clinical Diagnostic Research. 2018; 12(11): LC21–LC25. Publisher Full Text\n\nPun BT, Balas MC, Barnes-Daly MA, et al.: Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults. Crit Care Med. 2019; 47(1): 3–14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaradas C, Ozdemir L: The effect of range of motion exercises on delirium prevention among patients aged 65 and over in intensive care units. Geriatr Nurs 2016; 37(3): 180–5. PubMed Abstract | Publisher Full Text\n\nKhan BA, Fadel WF, Tricker JL, et al.: Effectiveness of implementing a wake up and breathe program on sedation and delirium in the ICU. Crit Care Med. 2014; 42(12): e791–5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKram SL, DiBartolo MC, Hinderer K, et al.: Implementation of the ABCDE Bundle to Improve Patient Outcomes in the Intensive Care Unit in a Rural Community Hospital. Dimens Crit Care Nurs 2015; 34(5): 250–8. PubMed Abstract | Publisher Full Text\n\nLisann-Goldman LR, Pagnini F, Deiner SG, et al.: Reducing Delirium and Improving Patient Satisfaction With a Perioperative Mindfulness Intervention: A Mixed-Methods Pilot Study. Holist Nurs Pract. 2019; 33(3): 163–76. PubMed Abstract | Publisher Full Text\n\nMailhot T, Cossette S, Côté J, et al.: A post cardiac surgery intervention to manage delirium involving families: a randomized pilot study. Nurs Crit Care. 2017; 22(4): 221–8. PubMed Abstract | Publisher Full Text\n\nMoon KJ, Lee SM: The effects of a tailored intensive care unit delirium prevention protocol: A randomized controlled trial. Int J Nurs Stud. 2015; 52(9): 1423–32. PubMed Abstract | Publisher Full Text\n\nMunro CL, Cairns P, Ji M, et al.: Delirium prevention in critically ill adults through an automated reorientation intervention - A pilot randomized controlled trial. Heart Lung. 2017; 46(4): 234–8. PubMed Abstract | Publisher Full Text\n\nParry SM, Berney S, Warrillow S, et al.: Functional electrical stimulation with cycling in the critically ill: a pilot case-matched control study. J Crit Care. 2014; 29(4): 695.e1–7. PubMed Abstract | Publisher Full Text\n\nRivosecchi RM, Kane-Gill SL, Svec S, et al.: The implementation of a nonpharmacologic protocol to prevent intensive care delirium. J Crit Care. 2016; 31(1): 206–11. PubMed Abstract | Publisher Full Text\n\nRosa RG, Tonietto TF, da Silva DB, et al.: Effectiveness and Safety of an Extended ICU Visitation Model for Delirium Prevention: A Before and After Study. Crit Care Med. 2017; 45(10): 1660–7. PubMed Abstract | Publisher Full Text\n\nSimons KS, Laheij RJ, van den Boogaard M, et al.: Dynamic light application therapy to reduce the incidence and duration of delirium in intensive-care patients: a randomised controlled trial. Lancet Respir Med. 2016; 4(3): 194–202. PubMed Abstract | Publisher Full Text\n\nSullinger D, Gilmer A, Jurado L, et al.: Development, Implementation, and Outcomes of a Delirium Protocol in the Surgical Trauma Intensive Care Unit. Ann Pharmacother. 2017; 51(1): 5–12. PubMed Abstract | Publisher Full Text\n\nZhang W, Sun Y, Liu Y, et al.: A nursing protocol targeting risk factors for reducing postoperative delirium in patients following coronary artery bypass grafting: Results of a prospective before-after study. Int J Nurs Sci. 2017; 4(2): 81–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGirard TD, Kress JP, Fuchs BD, et al.: Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008; 371(9607): 126–34. PubMed Abstract | Publisher Full Text\n\nMorandi A, Brummel NE, Ely EW: Sedation, delirium and mechanical ventilation: the 'ABCDE' approach. Curr Opin Crit Care. 2011; 17(1): 43–9. PubMed Abstract | Publisher Full Text\n\nKim MY, Park UJ, Kim HT, et al.: DELirium Prediction Based on Hospital Information (Delphi) in General Surgery Patients . Medicine (Baltimore). 2016; 95(12): e3072. PubMed Abstract | Publisher Full Text | Free Full Text\n\nvan den Boogaard M, Pickkers P, Slooter AJ, et al.: Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study. BMJ. 2012; 344: e420. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "73595",
"date": "05 Nov 2020",
"name": "Elizabeth Mahanna-Gabrielli",
"expertise": [
"Reviewer Expertise perioperative brain health",
"delirium - ICU and postoperative",
"sleep"
],
"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 is a systematic review of the effect of non-pharmacologic strategies on prevention or management of delirium in the ICU. The manuscript is comprehensive, well written, and follows appropriate PICOS framework and PRISMA guidelines for a systematic review.\nThe introduction is well written, succinct and appropriately gives background information on the importance of ICU delirium prevention and management.\nThe methods clearly state how the authors followed the PRISMA guidelines. The authors searched Pubmed, Embase, Cochrane Central, Web of Science, CINAHL, and Clinciattrials.gov. MeSH terms appropriately included delirium and other terms that are often used to describe the delirium syndrome such as “acute brain dysfunction” and “psychosis”. A full list of the search terms for each database is included in supplementary appendix 2 to allow for reproducibility.\nCould the authors clarify if the date range was 5 years from the date of search (Jan 1, 2014 to May 15, 2019) as stated in the manuscript? Or was it 10 years, as is listed in the search terms of the supplementary appendix 2?\n\nDid all the authors screen the titles and abstracts? And did all the authors independently review the full text of the 113 eligible articles, or only some of the authors?\nBias was appropriately assessed by the Cochrane risk of bias tool. Disagreements between authors were adjudicated as a group through discussion.\nThe results are clearly written and concise.\n\nFor Table 2, I found it confusing using x’s, y’s and o’s. It may be better to title the Table “Summary of delirium outcomes by statistical significance (p<0.05),” and then spell out “yes” instead of y, and either “no” or “not significant” instead of x. For the outcomes that were measured but not analyzed, it may be clearer to write “not analyzed” or “NA” rather than “o.”\n\nThe other tables were clear and appropriately organized.\n\nThe discussion is well written and discusses the limitations of the included studies and of this systematic review. I have no suggestions for improvement.\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": [
{
"c_id": "6808",
"date": "24 Sep 2021",
"name": "Azra Bihorac",
"role": "Author Response F1000Research Advisory Board Member",
"response": "Could the authors clarify if the date range was 5 years from the date of search (Jan 1, 2014 to May 15, 2019) as stated in the manuscript? Or was it 10 years, as is listed in the search terms of the supplementary appendix 2? Thank you so much for this comment so that we can clarify. The searches for each database listed in Supplementary Appendix 2 were initially performed for 10 years from the date of the search. During the title and abstract screening process, we ultimately decided to narrow the results further to within 5 years of the dated search. This step can be seen in Fig 1 PRISMA Record Screening Flow Chart, where we removed 3039 records prior to 2014. We added a statement to our methods section to further clarify this aspect. Did all the authors screen the titles and abstracts? And did all the authors independently review the full text of the 113 eligible articles, or only some of the authors? Thank you for informing us of this insufficiency. Four authors (JSC, HH, MMR, RB) screened the titles and abstracts, and three authors independently reviewed the full text (JSC, HH, JL). We added a statement to our methods section clarifying this point. For Table 2, I found it confusing using x’s, y’s and o’s. It may be better to title the Table “Summary of delirium outcomes by statistical significance (p<0.05),” and then spell out “yes” instead of y, and either “no” or “not significant” instead of x. For the outcomes that were measured but not analyzed, it may be clearer to write “not analyzed” or “NA” rather than “o.” Thank you for the feedback about this table. This change will definitely make our table more clear to the reader, and Table 2 has been updated to reflect this amendment."
}
]
}
] | 1
|
https://f1000research.com/articles/9-1178
|
https://f1000research.com/articles/11-700/v1
|
24 Jun 22
|
{
"type": "Research Article",
"title": "The level of community behaviour towards hearing loss in Indonesia",
"authors": [
"Nyilo Purnami",
"Indra Zachreini",
"Jenny Bashiruddin",
"Susyana Tamin",
"Harim Priyono",
"Ika Dewi Mayangsari",
"Sagung Rai Indrasari",
"Tengku Siti Hajar Haryuna",
"Tjandra Manukbua",
"Respati Ranakusuma",
"Ronny Suwento",
"Yanuar Iman Santosa",
"Eka Savitri",
"Indra Zachreini",
"Jenny Bashiruddin",
"Susyana Tamin",
"Harim Priyono",
"Ika Dewi Mayangsari",
"Sagung Rai Indrasari",
"Tengku Siti Hajar Haryuna",
"Tjandra Manukbua",
"Respati Ranakusuma",
"Ronny Suwento",
"Yanuar Iman Santosa",
"Eka Savitri"
],
"abstract": "Background: Hearing loss is the most common disability in the world, with a prevalence of 5% of the world's population of 466 million people. Knowledge about noise exposure and hearing protection equipment is related to hearing loss. Health is associated with a person's healthy lifestyle behaviour. This study aimed to determine the level of community behaviour towards hearing loss. Methods: This study used a descriptive analytical approach with a cross-sectional study design. The population in this study was Indonesian people who were not healthcare workers aged 17 years and over. The sample inclusion criteria included individuals who were not healthcare workers (such as doctors, nurses and midwives etc.), aged 17 years and over, and willing to participate in the study. The sampling method in this study was consecutive sampling. Results: Based on the distribution of patients, there were more female participants (1484, 61.6%) than male participants. Diploma-3 (D3) was the most common education type, with as many as 1095 people (45.4%), while the least common education type was not in school (eight, 0.3%). Most participants were in the ‘employee’ profession, namely 509 people (21.1%), while the lowest number of participants was in the Police profession (20, 0.8%). There were significant relationships between the respondent's knowledge and action about hearing loss, and the respondent’s knowledge and attitudes regarding hearing loss (p=0.000). Conclusions: There were significant relationships between the respondent's knowledge and actions about hearing loss and the respondent's knowledge and attitude, while there was no significant relationship between the respondent's attitude and actions regarding hearing loss.",
"keywords": [
"Human health",
"Behaviour",
"Knowledge",
"Attitude",
"Hearing loss",
"Public health"
],
"content": "Introduction\n\nThe behaviour of a person's life, including health, is influenced by many factors. These factors can come from the individual themself, the influence of others who encourage good or bad behaviour, or environmental conditions supporting behaviour change. For example, a psychologist, Skinner (1938), formulated that behaviour is a person's response or reaction to a stimulus (external stimulus), because this behaviour occurs through the process of a stimulus to someone, and then that person responds. Behaviour that is carried out continuously will become a person's attitude, namely actions, which are based on convictions and beliefs1–3.\n\nThe World Health Organization (WHO) estimates that 1.1 billion young people worldwide could be at risk of hearing loss due to unsafe listening practices, which is nearly half of all teenagers and young adults (12–35 years old). About 40% of people are exposed to potentially hearing-damaging noises from clubs, discotheques and bars. Exposure to unsafe high levels of sound from personal audio devices is common in middle and high-income countries4.\n\nNoise-induced hearing loss (NIHL) has been gaining significant attention in recent years and worldwide it contributes to approximately 16% of hearing loss occurring in adults (based on four million disability-adjusted life years (DALYs)). Noise exposure can lead to auditory and non-auditory effects5.\n\nBased on the above, behaviour can affect a person's action against hearing loss, which is influenced by their knowledge of hearing loss. For example, their attitude when there is a recommendation or prohibition against hearing loss and ends by action.\n\nWHO states that there are five causes of preventable hearing loss: Impacted cerumen, presbycusis, congenital deafness, noise-induced deafness, and chronic suppurative otitis media. Starting from public knowledge about hearing loss, public attitudes towards recommendations or prohibitions on hearing loss and ending with actions taken against hearing loss, it is hoped that the five hearing disorders can be prevented so that the number of hearing loss cases in Indonesia decreases.\n\n\nMethods\n\nThis study used a descriptive analytical approach by collecting respondent’s data and then analysing the respondent's behaviour towards hearing loss. The research design was a cross-sectional study. The research was conducted in all places/locations of residents in the territory of Republic Indonesia within three months (January-March 2021). Respondent's research data comes from Rs. Zainul Abidin Aceh, RS. H Adam Malik Medan, RS Sardjito, Jogjakarta, RSUPN. Cipto Mangunkusumo Jakarta, RS. dr. Wahidin Sudirohusodo Makasar.\n\nThe population in this study was Indonesian people who were not healthcare workers aged 17 years and over. The sample inclusion criteria included individuals who were not healthcare workers (such as doctors, nurses, and midwives etc.), aged 17 years and over, and willing to participate in the study. The sampling method in this study was consecutive sampling.\n\nThe independent variable was the community's action on hearing loss. The dependent variable in this study was people's knowledge about hearing loss and people's attitudes towards recommendations or prohibitions against hearing loss in respondents. Data collection in this study used the interview method using a questionnaire based on the google form link provided6.\n\nThe data processing process included checking data (editing), coding (coding) and compiling data (tabulating) and data entry. The analysis for descriptive data with a categorical scale (nominal and ordinal) was carried out by presenting it in the form of a percentage (proportion).\n\nThis research received ethical approval from the Health Research Ethics Committee, Faculty of Medicine, University of Indonesia-RSUPN Dr Cipto Mangunkusumo with Ethical Eligibility Number: KET-884/UN2.F1/ETIK/PPM.00.02/2021. Data collection was based on a google form. At the beginning of the questionnaire, it was asked whether the respondent was willing to participate in the study\n\nThe collected data was processed and analyzed using IBM SPSS computer statistical program version 22 (IBM SPSS Statistics, RRID:SCR_016479). The data processing process examined data (editing), coding and compiling data (tabulating) and data entry. The analysis for descriptive data with a categorical scale (nominal and ordinal) was carried out by presenting it in the form of percentages (proportions).\n\n\nResults\n\nA total of 2410 respondents took part in this study following the research inclusion criteria.\n\nBased on the distribution of patients, there were more female participants than male, namely 1484 people (61.6%). The most common type of education was Diploma-3 (D3), with as many as 1095 people (45.4%), while the least common type of education was not in school, which included eight people (0.3%). Most participants were employees, namely 509 people (21.1%), while the lowest number of participants were in the Police profession, namely 20 people (0.8%) (Table 1;7).\n\nFindings were based on the frequency distribution of knowledge, attitudes, actions, and behaviour based on a scale of ‘good’, ‘moderate’, and ‘not good’ about hearing loss. For the knowledge variable, the highest distribution was 1603 people (66.5%) on the ’not good’ scale, the highest distribution for the attitude variable was 1175 people (48.8%) on the ‘moderate’ scale, the highest distribution for the action variable was 1449 people (60.1%) on the ‘moderate’ scale. For the behaviour variable, the highest distribution was 1778 people (73.8%) on the ‘moderate’ scale (Table 2).\n\nBased on Table 3, there was a significant relationship between the respondent's knowledge and the respondent's action regarding hearing loss (p=0.000). Based on Table 4, there was no significant relationship between the respondent's attitude and the respondent's action regarding hearing loss (p=0.224). Based on Table 5, there was a significant relationship between the respondent’s knowledge and respondent’s attitudes about hearing loss (p=0.000).\n\n\nDiscussion\n\nThe lack of healthy living behaviour and protecting the environment invites unhealthy habits in society. These habits tend to ignore the safety of oneself and the environment to facilitate disease transmission. The behaviour of an individual, including health, is influenced by many factors. These factors can come from the person themself, the influence of others who encourage good or bad behaviour, and environmental conditions that can support behaviour change1.\n\nKnowledge is the result of knowing, and this occurs after the person senses a particular object. Sensing occurs through the five human senses, namely sight, hearing, smell, taste, and touch - most of the human knowledge is obtained through the eyes and ears. Knowledge of cognition is a fundamental domain in shaping one's actions (overt behaviour)1,2,8.\n\nAttitude is a reaction or response that is closed from a person to a stimulus or object, stimuli can affect behaviour. Attitudes clearly show the connotation of appropriate reactions to certain stimuli, which are emotional reactions to social stimuli in everyday life. For example, Newcomb, one of the experts in social psychology, stated that attitude is a readiness or willingness to act and not an implementation of certain motives. Attitude is not yet an action or activity but is a predisposition to the action of behaviour. That attitude is still a closed reaction, not an open reaction or open behaviour. Attitude is a readiness to react to objects in a particular environment to appreciate the thing1,2.\n\nFactors that influence the formation and change of a person's attitude can be internal or external. Internal factors come from the individual themself, while external factors come from outside the individual in a stimulus to change and shape attitudes. Meanwhile, according to other literature, factors that influence the formation of attitudes are personal experience, the influence of other people who are considered important, and culture1,4.\n\nFuture research should focus on gender similarities and differences to better indicate differences in attitudes and perceptions of NIHL across various demographic characteristics9.\n\nPrevious research on hearing loss knowledge conducted in India found that most respondents were aware that hearing loss could be congenital (63%), noise exposure (62%), or discharge from the ear (61%)10. The present study investigated adults' knowledge, behaviours, and attitudes concerning the factors that contribute to NIHL and the use of hearing protection11. Signs that indicate NIHL include difficulty understanding spoken words in a noisy environment, the individual needs to be near or look at the person speaking to help understand terms; familiar sounds, complaints that people do not speak clearly and a ringing noise in the ears12.\n\n\nConclusions\n\nThere was a significant relationship between the respondent's knowledge and the respondent's actions about hearing loss, and there was also a significant relationship between the respondent's knowledge and the respondent's attitude about hearing loss. At the same time, there was no significant relationship between the respondent's attitude and the respondent's actions regarding hearing loss.\n\n\nData availability\n\nFigshare: Underlying data for ‘The level of community behaviour towards hearing loss in Indonesia’ https://doi.org/10.6084/m9.figshare.190762557.\n\nFigshare: Questionnaire for ‘The level of community behaviour towards hearing loss in Indonesia’, https://doi.org/10.6084/m9.figshare.191853386.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nNotoatmodjo S: Health Promotion and Health Behavior. Jakarta, PT. Rineka Cipta, hal, 2020; 131–144.\n\nNotoatmodjo S: The science and art of public health. Jakarta PT Rineka Cipta, 2007.\n\nAzwar S: Human Attitudes and Their Measurement. 2nd edition. Pustaka Pelajar, Yogyakarta, 2016.\n\nWorld Health Organization: Hearing loss due to recreational exposure to loud sounds: a review. World Health Organization. 2015. Reference Source\n\nNational Institute for Occupational Safety and Health: Criteria for a recommended standard: occupational noise exposure: revised criteria 1998. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, 1998. Reference Source\n\nPurnami N: Questionnaire THE LEVEL OF COMMUNITY BEHAVIOUR TOWARDS HEARING LOSS IN INDONESIA. figshare. Dataset. 2022. http://www.doi.org/10.6084/m9.figshare.19185338.v1\n\nPurnami N: The Level Of Community Behaviour Towards Hearing Loss In Indonesia. figshare. Dataset. 2022. http://www.doi.org/10.6084/m9.figshare.19076255.v1\n\nCrandell C, Mills TL, Gauthier R: Gauthier.Ricardo. Knowledge, Behaviour, and Attitudes about Hearing loss and hearing protection among racial/ethnically diverse young adults. J Natl Med Assoc. 2004; 96(2): 176–86. PubMed Abstract | Free Full Text\n\nRavi R, Yerraguntla K, Gunjawate DR, et al.: Knowledge and attitude (KA) survey regarding infant hearing loss in Karnataka, India. Int J Pediatr Otorhinolaryngol. 2016; 85: 1–4. PubMed Abstract | Publisher Full Text\n\nRajagopalan R, Selvarajan HG, Rajendran A, et al.: Grandmothers' perspective on hearing loss in children and newborn hearing screening. Indian J Otol. 2014; 20(1): 20–23.Publisher Full Text\n\nAlzahrani RAM, Alzahrani AOS, Alghamdi AAM, et al.: Knowledge, Behaviors, and Attitudes about Noise-induced Hearing Loss among Adults in Albaha Region: A Cross-sectional Study. Egypt J Hosp Med. 2018; 70(5): 824–827. Publisher Full Text\n\nDobie RA: Cost-Effective Hearing Conservation: Regulatory and Research Priorities. Ear Hear. 2018; 39(4): 621–630. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "166643",
"date": "04 Apr 2023",
"name": "Maurizio Barbara",
"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 manuscript is related to behavioral aspects of a local population in regard to an impairment such as hearing loss due to acoustic trauma. The authors have included in their study some variables (gender, age, scholarity) that could be of some interest.\nHowever, since the issue regards the awareness of a healthy problem, one may expect to have some considerations when comparing the attitude of the population towards other diffused health issues, such as blood glucose level and/or hypertension, for instance. A similar comparison would increase the robustness of the conclusions that, if limited to the exposed data, appear weak for being drawn.\nOverall, a control group for this report is highly recommended for finalizing its acceptance for indexing.\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?\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": "9579",
"date": "18 Apr 2023",
"name": "Nyilo Purnami",
"role": "Author Response",
"response": "Thank you for your response, Thank you for your comments and suggestions; please allow me to answer the following: We apologise in advance that our research was not that deep, so we need the data you are referring to. Thanks for your advice; I will include it in the limitations of my research."
}
]
},
{
"id": "164226",
"date": "26 Apr 2023",
"name": "Herman Jenkins",
"expertise": [
"Reviewer Expertise Long career in otology/neurotology and written on hearing loss remediation with various devices",
"middle and inner ear mechanics and the results of various procedures for remediation on the outcomes on improved hearing."
],
"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 manuscript of Dr. Purnami and colleagues addresses a common problem in all developed and developing countries alike. It is investigating psychosocial relationships of understanding of problem, educational levels, gender and patient attitude in obtaining help in communication difficulties. These issues have to be addressed in how we counsel patients with hearing loss. At all ages, the psychosocial aspects must be addressed. In developed countries in Europe, Asia and the USA, the acceptance of hearing aids to remediate a hearing loss leading to communication difficulties remain relatively low. Attitude as feeling it makes one look old have tremendous impact on success. This study has demonstrated a similar attitudinal effect is very strong in relation to hearing loss and its management, This is a universal problem and one that has been difficult to remedy throughout the world. I answered partly to the reviewer question Are all the source data underlying the results available to ensure full reproducibility? as I did not see a lot of the source code presented in depth. It is primarily a summary of data, which I think works well 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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "9610",
"date": "17 Nov 2023",
"name": "Nyilo Purnami",
"role": "Author Response",
"response": "Thank you for agreeing to be our manuscript reviewer, and thank you for accepting our manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/11-700
|
https://f1000research.com/articles/11-695/v1
|
23 Jun 22
|
{
"type": "Case Report",
"title": "Case Report: Detailed Clinical Course and Management Plan for Status Epilepticus Pediatric Patient with Resected Choroid Plexus Papilloma: A Case Report and a Single Center Experience",
"authors": [
"Osama Muthaffar",
"Anas Alyazidi",
"Fahad Alotibi",
"Osama Muthaffar",
"Anas Alyazidi"
],
"abstract": "Choroid plexus papilloma (CPP) is a benign but rare central nervous system (CNS) neoplasm of the choroid plexus. The onset of symptoms is usually in the first decade and may occur at birth (i.e., congenital). It accounts for 0.4–0.6% of all brain tumors. Usually seen in patients who are young children. The object of this clinical case to highlight early surgical intervention, intensive and multidisciplinary care, and pharmaceutical prescriptions can enhance the patient's condition and quality of life. We herein report a rare presentation of CPP in a 6-year-old Sudanese female child with seizures. Who suffered from obstructive hydrocephalus with lateral ventricular choroid plexus papilloma. The patient underwent resection at the age of 6 months in our center's neurosurgery department. Intensive and multidisciplinary follow-up managed to maintain positive outcome and better quality of life in a relatively benign neoplasm. In spite of a wide range of therapeutic options for the management of CPP described in the literature, studies demonstrated that patients with CPP alone and underwent a surgical procedure can live independently as adults and work full-time with uncommon recurrences.",
"keywords": [
"Pediatrics",
"Female",
"Choroid plexus papilloma",
"Epilepsy",
"Seizures",
"Ventricle"
],
"content": "Introduction\n\nChoroid plexus papilloma (CPP) is a rare benign neoplasm of the choroid plexus that accounts for 0.4–0.6% of all brain tumors.1 It is a vascular neuroepithelial tumor The choroid plexus is a structure made from tufts of villi within the ventricular system that produces cerebrospinal fluid (CSF).2 CPP most commonly presents in the lateral ventricles in the pediatric population.3 Nonetheless, extra-ventricular sites have been described in the literature.4 CPP can be detected in all age groups, however, there is a particular preponderance among infants and extremely young children with a median age of 3.5 years at diagnosis.5 Compressive activity on the certain horns of the lateral ventricles could subsequently lead to developing seizures.6 Moreover, current treatment of choroid plexus tumors (CPT) is based on little evidence7 and the clinical management of CPT cases could be complicated if the presented patient is in the pediatric population and simultaneously experiencing epileptic seizures. On this note, we presented a detailed clinical management experience of a single patient with resected CPP in her early life and currently diagnosed with status epilepticus. To the extent of our knowledge, this is the first detailed clinical management report by a tertiary care center in Saudi Arabia.\n\n\nCase report\n\nEthical approval is not required at our institution to publish an anonymous case report. Written informed consent for publication of their clinical details was obtained from the patient.\n\nFollowing the CARE Guidelines, a six-year-old Sudanese female child presented to the emergency department (ED) with a history of an uprolling eye for two minutes. The mother is a 45 year old housewife, and the father is a 55 year old. She has one sister and four brothers, and all are healthy. Negative history of parents’ consanguinity. The mother was following up during her pregnancy with no history of either passive or active smoking, no history of diabetes mellitus (DM) or hypertension, and no history of using any medications. Prenatal, natal, and post-natal care was given. The child is a product of full-term, spontaneous vaginal delivery (SVD) with a birth weight of 4.5 kg, discharged with the mother in good conditions. At five months, the mother noticed head enlargement and sought medical advice. She was diagnosed with obstructive hydrocephalus with lateral ventricular choroid plexus papilloma underwent resection at the age of six months in our center’s neurosurgery department. Postoperative computed tomography (CT) included frontal craniotomy and large extra-axial pneumocephalus with large frontal air-fluid levels causing a mass effect on the brain more dominant in the left hemisphere. A previously noted large cauliflower-like mass in the left ventricle has been resected with multiple small hyperdense masses that could represent residual. Hyperdense area anteriorly within the fluid on the left extra-axial space and another adjacent to the left parietal-temporal lobe most likely representing postoperative hemorrhage. No Acute intra-axial hemorrhage. No acute ischemic insult. Less dilatation of ventricular system as compared to the previous imaging. Periventricular hypodensity likely related to spontaneous fracture (SF) permeation was noted again. A small intraventricular hemorrhage is noted with air in both temporal horns. Cystic area in the posterior fossa communicating with the fourth ventricle with no mass effect consistent with mega cisterna magna. External ventricular drain (EVD) tip was noted in the anterior left lateral ventricle with a right frontal approach. Left frontoparietal-temporal subcutaneous swelling and air are associated with two fractures of the left parietal bone. The patient underwent her first magnetic resonance imaging (MRI) postoperatively. Multiple axial, sagittal, and coronal sequences of the brain with and without IV contrast were used. With no previous MRI examinations available for comparison, a comparison was made with the last examination, a CT study that revealed marked irregular supratentorial ventricular dilatation, which is increased. No MRI evidence of residual or recurrent neoplastic tissue. Diffuse pachymeningeal enhancement is most likely related to meningeal irritation and not due to leptomeningeal metastasis. Left parietal brain gliosis related to previous operative interference. It is still seen as bilateral subdural fluid; however, it is less than seen in the previous examination. No midline shift, no mass effect, no intraventricular hemorrhage and no other significant abnormality was identified. Moreover, at the age of four-year-old, she developed a seizure in the form of focal eye movement. She started on Keppra, requiring pediatric intensive care unit (PICU) admission once last year as a case of status epilepticus. Regarding her current ED visit, the patient was in her usual state of health until 9:30 AM, when she started to have abnormal uprolling eye movements while being fully awake during the episode with normal limb movement and communicating with her mother. The first episode aborted by itself. Furthermore, according to her legal guardian, the patient experienced multiple attacks of vomiting with food content, not projectile. Upon arrival in the ED, she developed another attack with desatting to 70% in room air. However, the second episode aborted after administering diazepam (20 mg/kg). The patient was vitally stable, drowsy, and communicating with her legal guardian. CT did not reveal significant or acute changes or other interval changes besides the previously resected brain tumor, which resulted in dilated lateral ventricles compared to her right ventricles. On physical examination, her pupils were equally reactive to light, she was hypotonic in the right upper limb with normal tone in other limbs, and had hyperreflexia and negative clonus and a negative Babinski sign (plantar reflex). The requested tests included complete blood count (CBC), urea and electrolytes (U&E), and bone function, where they were all within normal range. The case was discussed with a pediatric neurology consultant, and she started on Keppra 30 mg/kg/day divided twice a day (BID) with follow-up in the clinic. The patient was discharged once fully awake. A week later, the patient followed up on her seizure, where she only had four attacks in a previous couple of years in the form of a complex partial seizure. She remained on Keppra with the same dosage and was discharged. Ten days later, she presented to the ED complaining of a seizure lasting for ten minutes with eyes deviating to the left side, according to her legal guardian. The patient presented in post-ictal status in the ED with no significant systematic findings. She was vitally stable with a triage category three until she suddenly deteriorated to 80% in room air, respiratory rate (RR) 12 breaths per minute (BPM), heart rate (HR) 114 with on and off eye deviation to the right side. However, her pupils were three mm reactive to light. The patient, however, was shifted to the resuscitation room and connected to oxygen, and given intravenous (IV) diazepam of six mg (0.2 mg/kg). The patient was well hydrated, with shallow breathing with no added sounds or heart murmurs, and the abdomen was soft and lax with no tenderness or organomegaly. Ambu bagging was initiated, and PICU was contacted for further profound care. During the time, the patient’s pupils were bilaterally equal and reactive to light and maintaining oxygen saturation at 100%. Upon PICU team arrival, the patient developed generalized clonic status epilepticus, code announced, and then the patient was intubated for one day only. Phenytoin and Keppra were given in a loading dose, then started on midazolam infusion of 1 mg/kg/hr and fentanyl as sedation until she was extubated 24 hours later. The patient was stabilized and transferred to the PICU. She did not experience any epileptic seizures and was sleepy. On the next morning (7 AM), the patient entered a state of metabolic acidosis resulting in intervening with four plus 10/kg of Lasix (furosemide) in addition to vancomycin for two doses before discontinuing it. On the next day, the patient was transferred to the medical ward. On the fourth day of the recent admission, the patient’s vitals were as follows: body temperature (Temp.) 36.5, heart rate (HR) 86, oxygen saturation (SaO2) 99% at room air, and blood pressure (BP) 99/50. Body weight (BW) was 30 kg and height (Ht.) 138 cm. No distress or complaints, according to her legal guardian. Upon central nervous examination, she was Keppra 40 mg/kg/day BID, conscious and alert, right-sided weakness with hyperreflexia, normal tone and power on the left side, pupil bilaterally equal and reactive to light, and no meningeal signs. She was hemodynamically stable with no systemic manifestations. On her follow-up with the infectious disease (ID) department, she started to receive ceftriaxone-D3 and vancomycin. C-reactive protein (CRP) was initially three mg/L, then repeated where it was 17.4 mg/L. She was discharged with culture pending, and neurological stabilization was achieved. Nine months later, the patient became seven-year-old, and she returned to the neurological clinic after her legal guardian noticed a developmental delay in the child. The last seizure episode was two months earlier after she had another episode nine months earlier. During this visit, she was conscious of the normal motor exam. However, she was diagnosed with hydrocephalus and developmental delay. A plan to increase Keppra dosage to seven ml BID was made and titrated to eight ml if seizures are not controlled. She was discharged and returned six months later to conduct a developmental assessment as she became an eight-year-old. Her developmental history started with expressive language assessment: At an early age, around two-to four, she requested things by using the other hand with no eye contact and no joint attention. She started to talk at the age of four years with few words MAMA and BABA were unspecific, then she started to improve at the age of six years after enrolment in speech session in a specialized center, at that time till now she can say three words sentences mainly order with no eye contact and no joint attention, and she still cannot run conversions. She cannot answer only specific simple questions and only her mother when she repeats them many times. Receptive assessment: The patient only obeys simple commands. She can sometimes obey two steps for specific things that she likes (go to bring an orange, clean it, and cut it Into pieces). Sometimes she repeats other words (Echolalia). Socially, she initiates playing with younger children. She likes no specific toys, only she likes to run, scream, and produce unspecific voices, and sometimes she expresses playing by hitting the younger children. Routine and sensory: According to the mother, she used to flap with her hand at the age of one-two years which disappeared at the age of four years, and currently no specific repetitive pattern. She likes specific clothes, and when she does not find them, she cries. Other sensory fields, including visual, hearing, and taste, were unremarkable. Emotionally: She does not understand others’ emotions. When she sees others crying, she usually laughs. Cognitively: She does not understand the concept of danger. She usually runs in the street with no sense of fear of cars or being cautious. Sleep: She sleeps for roughly eight hours from 1:00 AM till 10:00 AM, with no interruption and no nap. Media: She likes mobile most of the time. She likes to watch and listen to music. School: She started rehabilitation and mainly physiotherapy for the motor aspect as early as two years. Then at the age of four, she started speech and behavior modification sessions in a specialized center. She quit the rehabilitation center for more than one year because the family had traveled to Sudan. On physical examination, her weight was 37 kg, height 138.6 cm, all in the 95th percentile, and head circumference 57 cm above the 95th percentile. Her vitals were Temp. 37, HR 85, RR 22, BP 90/53, SaO2 100% at room air. Her laboratory work was as follow: white blood cell (WBC) count 8.02 k/μl (reference range: 4-11 k/μl), red blood cell (RBC) count 3.99 M/μl (reference range: 4.8-6.4 M/μl), hemoglobin (Hb) 10.6 g/dl (reference range: 13-17 g/dl), hematocrit (HCT) 31.8% (reference range: 41%-50%), mean cell volume (MCV) 79.7 fl (reference range: 76-92 fl), platelet (PLT) count 235 k/μl (reference range: 150-450 k/μl), prothrombin time (PT) 12.4 seconds (reference range: 11.7-15.3 seconds), activated partial thromboplastin time (APTT) 28.1 seconds (reference range: 28.9-38.1 seconds), and international normalized ratio (INR) 1.11 seconds (reference range: 0.89-1.18 seconds). On clinical observations, she looked well, with no dysmorphic features, no eye contact, and sat at the clinic’s beginning, calm, watching online videos. However, after 30 minutes, she started to clean her hand around five times, then after 45 minutes, she started to scream and produce nonspecific sounds. She does not like to draw or use any toys in the clinic. She is only interested in mobile phones, and when her sister took them from her, she cried and hit her sister. No systematic findings. However, her current presentation was consistent with Autism Spectrum Disorder (ASD). Her 8th and most recent CT scan redemonstrated a dilatation of the supratentorial ventricular system, with stable porencephalic cystic changes adjacent to the left lateral ventricle. Preserved gray-white matter differentiation. No extra/intra-axial hemorrhage or herniation. The posterior fossa structures are unremarkable. The visualized osseous and orbital structures are unremarkable. The paranasal sinuses and mastoid air cells are well aerated. In conclusion, her imaging work-up displayed a stable appearance, without acute findings or other interval changes. Her second MRI imaging, which used a non-enhanced sagittal T1W, axial T2W, FLAIR, DW, GE, SW, and coronal T2W images of the brain, were obtained with axial, sagittal, and coronal T1W after IV contrast administration. A comparison was made based on her previous MRI. Findings included ventricular enlargement and irregularity of the left lateral ventricle are stable in appearance. Cystic structure communicating with the left lateral ventricle is also unchanged. A small amount of periventricular increased signal in the left dorsal thalamus is unchanged. No new enhancing ventricular or parenchymal lesions. Near complete resolution of the left frontal subdural hematoma with a small residual right frontal subdural collection remaining, measuring a maximum of three mm on the axial plane. She was on keppra (levetiracetam) 100 mg/mL, oral solution 300 mt, phenytoin Na 250 mg/5 mL ampule, and carbamazepine 200 mg tablets. Her management plan included extensive speech and behavior modification sessions through enrollment into rehabilitation centers and encouraging the family to be part of behavior modifications and follow-up after six months.\n\n\nDiscussion\n\nWe reported a case of a resected lateral ventricle CPP presenting with seizures, to the extent of our knowledge, it is the first case to be reported from Saudi Arabia. The brain tumor which accounts for 0.4–0.6% of all brain tumors.8 Demonstrated to create a puzzling clinical course which requires multidisciplinary intervention. Having this condition in a pediatric patient demands caregivers to develop detailed management plans that takes into consideration physical and psychological aspects of the child for a better quality of life. The median age for diagnosing CPP is 3.5 years,5 however, our patient was diagnosed very earlier. Although there was no indication of CPP on our patient’s MRI at the corrected age of 34 weeks’ gestation, because no contrast scan was performed, it is difficult to rule out the presence of a minor lesion at the time. As a result, the majority of tumor growth occurred within the five-month period between the two MRI tests, confirming that certain CPP grow rapidly throughout early childhood. Such observation is indirectly supported by the finding that in the literature prenatal detection of CPP is relatively infrequent compared to the presentation of a substantial CPP in the first year of life.9 The motives behind certain CPP growing rapidly during childhood is still unknown. CPP can also grow because to tumor hemorrhage and malignant progression. Furthermore, CPP can develop to a big size regardless of its ventricular position, it appears logical to believe that tumor location and ventricular size may affect the rate of growth.9,10 Moreover, MRI testing is an essential part when investigating hydrocephlus which was presented in our case. Intractable epilepsy etiologies must be closely monitored to maintain the patient’s health, literature findings suggests that intracranial hypotension could cause intractable epilepsy in pediatric patients with resected CPP.11 Continuous treatment, dose adjustment according to the patient’s condition and repeated clinic visit proved to be a successful approach in advancing the patients’ outcome. Finally, the diagnosis of pediatric brain tumors has long been regarded as a serious threat to children and their families, due to poor prognosis in certain tumors. however, according to our experience, intensive and multidisciplinary follow-up for our patient managed to maintain positive outcome and better quality of life in a relatively benign neoplasm. According to studies with broader subjects, the short-term survival rates for CPP are optimistic after a surgical intervention alone, nonetheless, clinical results were disappointing.12 It is wise to say that when the patient experiences a chronic condition such as epilepsy could complicate the management plan. Long-term survival and quality of life for CPP patients with epilepsy remains an area of research, however, studies demonstrated that patients with CPP alone and underwent a surgical procedure can live independently as adults and work full-time with uncommon recurrences.8\n\n\nConclusion\n\nWe presented one of the most detailed clinical reports of a CPP patient with epilepsy. It is important to highlight daily practices for managing this condition. We reported a positive outcome for a patient diagnosed very early in her life and today lives in her 10th years of age in her usual state of health. Our report confirms that early surgical intervention, intensive and multidisciplinary care, and pharmaceutical prescriptions can enhance the patient’s condition and quality of life. Repeated and justified use of MRI and CT showed to be of great interest in detecting other comorbidities. This case demonstrated great challenges in terms of follow-up, management, and caregiving. In the future, we recommend more inclusive guidelines that take into consideration epilepsy during the management of CPP.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and/or clinical images was obtained from the patient/parent/guardian/relative of the patient.\n\n\nData availability\n\nFigshare: CARE checklist from the case report entitled “detailed clinical course and management plan for status epilepticus pediatric patient with resected choroid plexus papilloma: a case report and a single center experience.” DOI: https://doi.org/10.6084/m9.figshare.20029580.v1.13\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgment\n\nAuthors would like to express their special thanks of gratitude to the patient and her family for giving us the opportunity to conduct this research. Outcomes from such research can potentially increase scientific knowledge and can improve patient care. Therefore, the patient and her family deserve our highest gratitude. We are also grateful to every healthcare worker and staff working on the patient’s condition and contributing to recording her findings. Finally, the completion of this undertaking could not have been possible without the facilitation of the Faculty of Medicine at King Abdulaziz University and its staff.\n\n\nReferences\n\nLenders JW, Eisenhofer G, Mannelli M, et al.: Phaeochromocytoma. Lancet. 2005 Aug 20-26; 366(9486): 665–675. PubMed Abstract | Publisher Full Text\n\nLun M, Monuki E, Lehtinen M: Development and functions of the choroid plexus–cerebrospinal fluid system. Nat. Rev. Neurosci. 2015; 16: 445–457. PubMed Abstract | Publisher Full Text\n\nHien NX, Duc NM, My TT, et al.: A case report of atypical choroid plexus papilloma in the cervicothoracic spinal cord. Radiol. Case Rep. 2021 Dec 15; 17(3): 502–504. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNakano I, Kondo A, Iwasaki K: Choroid plexus papilloma in the posterior third ventricle: case report. Neurosurgery. 1997 Jun; 40(6): 1279–1282. PubMed Abstract | Publisher Full Text\n\nGupta N: Choroid plexus tumors in children. Neurosurg. Clin. N. Am. 2003 Oct; 14(4): 621–631. PubMed Abstract | Publisher Full Text\n\nIannelli A, Pieracci N: Tumors in the temporal horn of the lateral ventricle as a cause of epilepsy. J. Child Neurol. 2008 Mar; 23(3): 315–320. PubMed Abstract | Publisher Full Text\n\nWolff JE, Sajedi M, Brant R, et al.: Choroid plexus tumours. Br. J. Cancer. 2002 Nov 4; 87(10): 1086–1091. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLundar T, Due-Tønnessen BJ, Frič R, et al.: Choroid Plexus Tumors in Children: Long-Term Follow-Up of Consecutive Single-Institutional Series of 59 Patients Treated over a Period of 8 Decades (1939-2020). World Neurosurg. 2021 Nov 22; 150: e228–e235. S1878-8750(21)01771-X. Epub ahead of print. PubMed Abstract | Publisher Full Text\n\nPicht T, Jansons J, avn Baalen A, et al.: Infants with unusually large choroids plexus papilloma undergoing emergency surgery. Pediatr. Neurosurg. 2006; 42: 116–121. Publisher Full Text\n\nGafner M, Lerman-Sagie T, Constantini S, et al.: Refractory epilepsy associated with ventriculoperitoneal shunt over-drainage: case report. Childs Nerv. Syst. 2019 Dec; 35(12): 2411–2416. PubMed Abstract | Publisher Full Text\n\nSchuto T, Sekido K, Ohtsubo Y, et al.: Choroid plexus papilloma of the III ventricle in an infant. Childs Nerv. Syst. 1995; 11: 664–666. PubMed Abstract | Publisher Full Text\n\nSiegfried A, Morin S, Munzer C, et al.: A French retrospective study on clinical outcome in 102 choroid plexus tumors in children. J. Neuro-Oncol. 2017 Oct; 135(1): 151–160. PubMed Abstract | Publisher Full Text\n\nAlyazidi A: CARE Checklist for a detailed clinical course and management plan for status epilepticus pediatric patient with resected choroid plexus papilloma: a case report and a single center experience. figshare. Online resource.2022. Publisher Full Text"
}
|
[
{
"id": "141966",
"date": "27 Jun 2022",
"name": "Ayman Zaky Elsamanoudy",
"expertise": [
"Reviewer Expertise Medical Biochemistry and Molecular biology",
"Molecular aspect of metabolic syndrome and its related genetic metabolic disorders.The genetic and molecular aspects of 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\nThe authors provided a full description of the case and its management. They provided a full explanation in the discussion section. Moreover, they provided a satisfactory conclusion and recommendation.\nThese comments to be addressed:\nAbstract: includes only the background of the disease. I recommend adding the aim of the study and the conclusion to give concise information about the context of the case report.\n\n2- They mentioned that(To the extent of our knowledge, this is the first detailed clinical management report by a tertiary care centre in Saudi Arabia.).They have to mention that the patient is not a Saudi but she is Sudanese but by chance, the management was in Saudi Arabia.\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": "201416",
"date": "02 Nov 2023",
"name": "Aaron Mohanty",
"expertise": [
"Reviewer Expertise Pediatric Neurosurgery",
"minmallly invasive endoscopci neurosurgery"
],
"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 have reported a case of left lateral ventricular choroid plexus papilloma (CPP) in a 6-year-old girl which was resected initially at 6 months of age and presented subsequently with multiple seizures at 4 years of age requiring anticonvulsants. At follow-up, she was noted to have a developmental delay.\nAs the authors mention, CPP is a childhood tumor but can be also seen in adults. It is one of the few tumors which is accompanied by increased CSF production with hydrocephalus. The large ventricles aid in the surgical approach with the dissection easier than an intraparenchymal tumor. The large ventricles also permit an endoscopic approach to the tumors and there are several reports where these tumors have been resected by a pure endoscopic approach. Asymptomatic subdural collections and intraventricular bleeds are common in the postoperative period and often a ventricular drain is required. Persistent postoperative ventriculomegaly may require a CSF shunting procedure. Though total excision is possible, it is not uncommon to leave a small amount of tumor in close proximity to the periventricular vital venous structures. Children may develop seizures in the postoperative period which often can occur late. Close follow-up will be required to detect any recurrences. The overall morbidity is associated with the surgical approach in the young developing brain and associated blood loss, degree of hydrocephalus, residual tumor, and any chronic anticonvulsant usage. In recent years, some choroid plexus papillomas are resected by a minimally invasive endoscopic burr hole approach which significantly reduces postoperative morbidity. The vascularity of the tumor often can be a concern1.\nRecent genetic studies have reported an association of CPP with Aicardi syndrome; von Hippel–Lindau syndrome; and infrequently with Li–Li-Fraumeni and rhabdoid predisposition syndrome.\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/11-695
|
https://f1000research.com/articles/10-870/v1
|
31 Aug 21
|
{
"type": "Opinion Article",
"title": "Python for gene expression",
"authors": [
"Leonid Bystrykh"
],
"abstract": "Genome biology shows substantial progress in its analytical and computational part in the last decades. Differential gene expression is one of many computationally intense areas; it is largely developed under R programming language. Here we explain possible reasons for such dominance of R in gene expression data. Next, we discuss the prospects for Python to become competitive in this area of research in coming years. We indicate that Python can be used already in a field of a single cell differential gene expression. We pinpoint still missing parts in Python and possibilities for improvement.",
"keywords": [
"differential gene expression",
"single cell expression",
"python",
"R",
"limma"
],
"content": "Introduction\n\nFundamental breakthrough in sequencing technologies in late 1990 promoted explosive growth of the data accumulated in biology in the last two decades. First, the introduction of expression microarrays has initiated accumulation of genome-wide gene expression data from different organisms, which stimulated creation of dedicated databases and development of computational tools for its analysis. Second, a more substantial wave of expression data arrived along with progress in high-throughput DNA sequencing,1(p),2 which demanded even bigger data storage and more sophisticated means of maintenance, programming support and analysis.3-5 This coincided with improved performance of our computers accompanied by the development of programming languages, especially those that paid attention to the biology-specific demands in data analysis, such as R and Python.6-8 Although the current list of known programming languages is approaching 400 (compiled by Wikipedia), there are only a handful of languages supporting dedicated biology-oriented packages (Table 1). Thus, the theoretical choices for languages with specialized support of biological applications is still very limited.\n\n1 Snakemake9 is python based workflow managing system, in other words pipelines organizing software, which is more than a regular package (compared to others mentioned in this table).\n\n\nR and Perl\n\nPython, as a fully functional and ready for tasks of general programming, arrived with as version 2.0 in 2000. By that time R was already a well-established language in bioinformatics, especially for statistical applications, see for instance.11 At that time Perl was probably the most used programming language in genome biology (especially suited for string operations on DNA, RNA and protein sequences), due to its better computational performance,12 and it stays strong in a field of genome sequence analysis even now, although it’s difficult syntax and accumulating problems with maintenance of the packages has caused a gradual decline in popularity (as for instance recorded in codementor.io site for the worst programming languages). Nevertheless, Perl scripts can be seen on the back pages of Ensembl BioMart and also Unigene pages.\n\nSince the introduction of the Affymetrix expression microarrays in the 2000s, it immediately required means of programming development; and the R language with its strong statistical component was ready for the immediate use in the field of expression data analysis. The key elements in e establishing R as a standard language in the field was resolving a problem of (microarray) data normalization13,14 and subsequent implementation as an R package (for instance Bioconductor preprocessCore15). Publishing the Limma package16,17 was absolutely crucial for success of R in that area; it resolved a problem of a small sample size for microarray expression data systematically provided by biologists at that time. Since 2003-2005 clear separation of tasks became visible: Perl was focused on tasks of sequencing analysis, while R covered statistics and differential analysis, including expression microarrays.\n\n\nLimma package\n\nSince the first publication of the Limma package by the group of Gordon Smith,16,18 it became a central and indispensable element of major differential expression protocols in R for at least a decade since its introduction. In the early 2000s, microarrays were expensive and many labs could afford only a limited number of samples to analyze. The core issue resolved by this package was how to bypass a dilemma of a small number of samples in groups and still obtain credible and statistically validated results. Suppose you try to apply a t-test to a set of data with only 2 or 3 replicates per group and a total number of tests up to 20000 times. This is equivalent to analyzing expression microarray data containing 20000 gene expression in a series of 2 controls and 2 experimental samples. Regular t-test with correction for multiple testing has little chance for success. Limma has two essential steps circumventing this problem. One is using a linear model for a data fit for the entire table of data, followed by using empirical Bayesian statistics to recalculate probabilities based on the entire distribution of the expression data for all genes across the expression array.\n\nThis concept was directly inherited in later protocols for the bulk RNAseq analysis with edgeR package.19 Namely, the Voom function in edgeR implements very similar steps of data conversion compared to the original Limma package. Another popular protocol in R, namely deseq220(p2) (as well as deseq) used a similar approach, although not directly copying the Limma algorithms. Details can be found in corresponding tutorials to the packages in Bioconductor.\n\nNo packages were designed in other programming languages. This lack of diversity of choices created a monopoly of R protocols for the “classic” gene-expression analysis based on microarray data or bulk-RNAseq with limited number of samples per group.\n\nTechnically Python allows to “wrap” or quote other programming languages within its own scripts. Python can currently “quote” some lines from JavaScript, especially when ipynb file format is used. For R language there is a special wrapper, rpy2,21 which can incorporate parts of the R functions within Python. Potentially, there is a possibility to wrap R-functions from any R package into Python. However, there is not a genuine alternative in another language, and besides, it is not a popular approach in current publications, which could be recommended to biologists as a standard protocol. Note, that by standard protocol we imply a script suggested by package developers, which can be followed by the user with “average” skills in programming.\n\nConsequently, for quite a while the Python language had no usable application for the differential gene expression analysis, especially in times when expression microarrays and bulk RNAseq data with small sample numbers dominated the literature. Sporadically, one can find some reports with peculiar options available in Python. For instance, a “geometrical approach” was suggested a while ago for finding differentially expressed genes,22 for which the implementation in jupyter notebook is also available.23 A similar “geometric approach” is discussed in another publication24 (although the later analysis was performed in R). Inspection of some of those scripts22,23 reveals that the “geometric” approach rehearses a fold change statistics rather than eBayes probability approach and thus is not recommended.\n\n\nWhy Python?\n\nIndeed, if R and Perl performed so well, each in its own niche, why do we need Python after all? In fact, with further evolution of biological sciences more biologists realized the necessity of some elementary data analysis by themselves. Whereas R is still strong and powerful for professional statisticians, it is also recognized as a difficult language to learn and to comprehend (see for instance introduction in Quick-R, https://www.statmethods.net/). The same in part is true for Perl. Python, on the contrary was originally designed to be more human-friendly, more transparent, and a clearer computer language compared to Perl and R. More details of languages in comparison can be found on the Python official site (https://www.Python.org/doc/essays/comparisons/). This gradually became recognized by the broad community of interested people, including all kinds of scientists and non-scientists in Universities, secondary education and other businesses. This made Python the most popular computer language in recent years (according to https://pypl.github.io/PYPL.html for instance).\n\nThe second useful feature of Python is how functions are organized and stored. Unlike R, where each individual contributor writes their own package, and gradually it becomes a collection of millions of functions, often redundant. Python has a policy of bigger consortia and bigger collections of functions within libraries with less redundancy in its content (although small packages also exist). The core packages like SciPy and Numpy collect long lists of useful functions for elementary math and statistics. They are universally used as a source of scientific and numeric functions. On top of these, other more dedicated libraries are developed, like Scikit-learn (a.k.a. Sklearn) package for machine learning applications, Pandas for file and table management, Statsmodels for various kinds of a model fitting. Regarding visualisations, most core options are in Matplotlib library, beyond that more specific illustrations could be found in Seaborn, others in Bokeh and so on. Noteworthy, Pandas, Statsmodels and Seaborn are stylistically similar and resemble R-style to some degree in their exterior. Unfortunately, Sklearn package currently does not support Pandas data frame data structures, although it can be worked around via Numpy array conversions.\n\n\nWhat is missing in Python for expression microarrays analysis?\n\nSaying that the entire Limma package is missing in Python is a bit vague statement. It is important to specify what is exactly missing, what part of it cannot be replaced by existing alternatives. Typically, a microarray protocol is built in steps, many of which are already available in Python. Expression microarray data are deposited in public databases, the most known is GEO site, which also has a built-in tool GEO2R with an R script attached25; the script would begin with package enabling fetching the data from the site. Next, data are converted to the table. Values and their distribution are inspected by checking the histogram, boxplots, and maybe MDS plot. It enables us to find out whether data are already log2-transformed and normalized (high or low scale of intensities, also whether data look reasonably normally-distributed or not) or has to be log2 transformed and normalized (equalized) to one another. If required, we add a step of log2-transform (available as core function in R) and quantile normalization (available in Limma and preprocessCore). All those mentioned steps are also available in Python (see Table 2 for details). Next, we define groups, then the model for our lmFit function. This is a sort of lm function available in Python statsmodels and core R, but lmFit works for entire table of data and it collects the results for an entire table as well. It is accompanied by another contrasts.fit step which is more of the same for specified groups of data. Further we have a function eBayes, which recalculates statistics obtained from the fit steps above and finally generates Bayes corrected values for significance. This is essentially the heart of Limma, which is not available in Python in any form. At last, topTable function organizes a final table of differential expressions, what we well know from our own work and publications. Further, it can be decorated by more illustrations, like volcano plot or another PCA plot, etc. All those decorative functions can be done in Python as well. To summarize, the lmFit and eBayes are the only critical elements missing in Python precluding its use for microarray gene expression analysis.\n\nNote: packages for functions are in brackets behind the function.\n\n\nWhat is missing in Python for bulk RNAseq analysis?\n\nMajor packages in RNAseq differential gene expression analysis in R utilize the concepts/functionalities implemented in Limma package directly or indirectly. For instance, edgeR package designed for bulk RNAseq differential expression imports Limma as a dependent package and uses elements of it. The basic steps are slightly different, but the outline is very much the same. The first step is usually either trivial read file function or read raw mapped data as series of separate files, and makes a table out of it. The data can be either raw read counts, coming directly from the step of sequencing reads counts per transcript, or corrected by transcript length (in RNA seq it is essential for comparison expression levels across different genes). Unlike to microarray data, which are the smallest expression data among all others, RNAseq primary data are much bigger in size, and they contain lots of low-level or not expressing genes. Consequently, there is a step removing genes with low read values. Those genes are useless in terms of differential analysis and only overload the memory. Since different samples in RNAseq can have different read coverage, and also a different number of detected genes (above zero), the whole philosophy of normalization is rather complicated. However, the resulting procedure of normalization is reduced to familiar log2-transform step followed by dividing all gene-expression values by so-called normalizing factors. Fortunately, algorithms of finding normalizing factors are mostly well described, especially for deseq2 (an outline can be found in Maza, 201626). Therefore, it is possible to write a custom script in any available language including Python, which would recapture this sort of the normalization step. When normalization is done, the next important step is estimation of data dispersion. This step is rather complicated in details not suitable for this type of article. In edgeR there are many alternative options for this step available. After that the step of statistical estimation of significance comes to a play. The resulting differential expression table follows the steps of a topTable from Limma. If we inspect options for Python, we will find out that similar to microarrays Python largely misses a step of dispersion analysis, estimation of fold change statistics, and statistical significance. Other steps can be replaced by known functions or custom scripts (Table 3).\n\nNote: deseq2 protocol makes steps from normalization to differential expression table in one function.\n\n\nSingle cell RNAseq in R\n\nSince R set a good trend for making all previous protocols for differential gene expression, it also pioneered a single cell gene expression protocol. Out of many protocols generated so far, the most frequently used are Scater,27 Scran,28 Seurat29,30 and Monocle. Scater and Scran packages are built on a common data type, SingleCellExperiment,31 and thus can be combined in one script using the same data type (which is often the case). In contrast, Seurat is built on its own data type and aims to be a self-sufficient package. It is currently a popular choice; it is especially appreciated for good tutorials and colorful illustrations, although integration of Seurat with other tools or packages is limited.\n\nSingle cell protocol for differential gene expression likely originated from bulk-RNAseq, but it diverged from its ancestor in subsequent years. Some steps in both protocols are still common, some are different. For instance, SC-RNAseq acquired a step to check sample quality and removal of bad quality samples (which are gene expressions per cell in this case). Normalization and log2-transform are carried out in a similar fashion as in bulk RNAseq, although normalization became even more simple: samples are usually adjusted to the median read counts across entire sets of data and proportional to the detected genes per sample. Next, there is tedious step of identifying groups of cells for differential expression analysis and other characterization. Unlike other differential expression protocols, SC-RNAseq is aimed on characterization of cells, not genes, and possible discovery and/or classification of existing cell types. This is a unique and specific chapter for SC-RNAseq only. The differential gene expression is performed using regular statistical tests (there is no particular preference to those). Close to the end of the SC-RNAseq protocols, we observe increasing diversity of options and specific interests.\n\nIt is important to emphasize that while R scripts in general often serve as standard protocols (or claimed to be a standard protocols), it is not really the case for bulk RNAseq and SC-RNAseq protocols. Currently used packages are known to differ substantially in detail, as well as the results of those data analysis. Therefore, we cannot pinpoint any particular protocol as standard in the field of differential gene expression analysis in R. This and availability of alternative commercial protocols for differential gene expression might be an extra source of the data irreproducibility problem in this particular field of research.\n\n\nSingle cell RNAseq in Python\n\nUnlike expression microarrays or a bulkRNAseq experiment, a single cell expression experiments contains lots of samples (and samples in each group if groups are defined). Therefore, the major constraint, which existed in early years, namely circumventing a dilemma of small sample numbers does not apply here. With hundreds of samples per group we can apply regular statistics, which is available in Python and other languages. Therefore, with the introduction and development of a single cell differential gene expression analysis it became possible to assemble the entire protocol from available Python functions. Surely, the development of a dedicated package might facilitate the use and popularity of Python for such analysis. In this regard, it is worth mentioning the release of the very first dedicated package of this sort, namely Scanpy.32 Scanpy basically follows the sequence of data transformation and analysis from Seurat. They both provide tutorials on the same data sources, which makes them especially attractive for use and open for cross analysis and cross validation. Hopefully Scanpy will stimulate program developers for more interesting projects in a field of single cell analysis.\n\nThere is also an alternative to this, namely create specific functions, which can be recruited with regular tools and functions already available in different packages in Python. Table 4 shows a sketchy comparison of how minimal protocol is organized in Seurat, Scanpy and reassembled from scratch.\n\n* read.csv() in Seurat used for regular table read. Read10X() is for reading matrix data format.\n\nCurrently this field is wide open for more examples of Python-base analysis for differential expression in single cells. Some simple examples can be found on GitHub as Extended data (which should not be taken as a standard protocol for the differential expression). Researchers should not be confused by the fact that different protocols result in different lists of the differentially expressed genes. This is already described for different RNAseq protocols in R, caused for instance by differences in normalization26,33 or other steps.34 The differences between those protocols are acceptable since we use not identical, but only comparable, steps and functions. The major and most prominent differentially expressed genes are usually consistent and not prone to variation upon changing options within protocols or between those. In addition, the researcher can also try artificial data to check details of the protocols on reproducibility and consistency.35\n\n\nConcluding remarks\n\nEven though R remains the major language for differential gene expression analysis, further rise of Python popularity in biological applications is expected in the coming years. Regarding single cell expression data, Python has broad possibilities for data analysis. Moreover, the rise and diversification of the single cell protocols will require more programming flexibility, where Python might offer more options with respect to R. This is also dependent of community efforts within Python developers. We might expect some restructuring of existing packages and emergence of specialized dedicated packages in the direction of the single cell analysis. The time is right for more efforts in Python applications. Regarding flexibility, it is essential to keep all options open for integrating functions from different existing and future packages.\n\nMore active use of Python in biological studies will certainly improve transparency and reproducibility of currently used protocols for differential gene expression and beyond. It is also a satisfying feeling that biological science makes a substantial shift from descriptive empirical style into a more exact and analytical mode.\n\n\nData availability\n\nNo data is associated with this article.\n\nExtra information and example scripts are available: https://github.com/LeonidBystrykh/PY4DE/tree/main.\n\nArchived scripts as at time of publication: http://doi.org/10.5281/zenodo.5044809.36\n\nLicense: GPL-2",
"appendix": "Acknowledgments\n\nMany thanks to David Porubsky for thorough reading and detailed comments.\n\n\nReferences\n\nXuan J, Yu Y, Qing T, et al.: Next-generation sequencing in the clinic: promises and challenges. Cancer Lett. 2013; 340(2): 284–295. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCarrasco-Ramiro F, Peiró-Pastor R, Aguado B: Human genomics projects and precision medicine. Gene Ther. 2017; 24(9): 551–561. PubMed Abstract | Publisher Full Text\n\nChing T, Himmelstein DS, Beaulieu-Jones BK, et al.: Opportunities and obstacles for deep learning in biology and medicine. J R Soc Interface. 2018; 15(141). PubMed Abstract | Publisher Full Text | Free Full Text\n\nBolouri H: Modeling genomic regulatory networks with big data. Trends Genet. 2014; 30(5): 182–191. PubMed Abstract | Publisher Full Text\n\nRoy SS, Mukherjee AK, Chowdhury S: Insights about genome function from spatial organization of the genome. Hum Genomics. 2018; 12(1): 8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuber W, Carey VJ, Gentleman R, et al.: Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods. 2015; 12(2): 115–121. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSadowski MI, Grant C, Fell TS: Harnessing QbD, Programming Languages, and Automation for Reproducible Biology. Trends Biotechnol. 2016; 34(3): 214–227. PubMed Abstract | Publisher Full Text\n\nMadsen C, Goni Moreno A, Palchick Z, et al.: Synthetic Biology Open Language Visual (SBOL Visual) Version 2. J Integr Bioinform. 2019; 16(2). PubMed Abstract | Publisher Full Text | Free Full Text\n\nKöster J, Rahmann S: Snakemake–a scalable bioinformatics workflow engine. Bioinformatics. 2012; 28(19): 2520–2522. PubMed Abstract | Publisher Full Text\n\nGrüning B, Dale R, Sjödin A, et al.: Bioconda: sustainable and comprehensive software distribution for the life sciences. Nat Methods. 2018; 15(7): 475–476. PubMed Abstract | Publisher Full Text\n\nZhang Y, Szustakowski J, Schinke M: Bioinformatics analysis of microarray data. Methods Mol Biol. 2009; 573: 259–284. PubMed Abstract | Publisher Full Text\n\nFourment M, Gillings MR: A comparison of common programming languages used in bioinformatics. BMC Bioinformatics. 2008; 9: 82. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBolstad BM, Irizarry RA, Astrand M, et al.: A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003; 19(2): 185–193. PubMed Abstract | Publisher Full Text\n\nIrizarry RA, Hobbs B, Collin F, et al.: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003; 4(2): 249–264. PubMed Abstract | Publisher Full Text\n\nBolstad B: Bmbolstad/PreprocessCore. 2021; 19: 2021. Accessed April 2021. Reference Source\n\nSmyth GK: Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004; 3: Article3. PubMed Abstract | Publisher Full Text\n\nWettenhall JM, Smyth GK: limmaGUI: A graphical user interface for linear modeling of microarray data. Bioinformatics. 2004; 20(18): 3705–3706. PubMed Abstract | Publisher Full Text\n\nRitchie ME, Phipson B, Wu D, et al.: limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7): e47. PubMed Abstract | Publisher Full Text\n\nRobinson MD, McCarthy DJ, Smyth GK: edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010; 26(1): 139–140. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLove MI, Huber W, Anders S: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12): 550. Publisher Full Text\n\nGautier L: An intuitive Python interface for Bioconductor libraries demonstrates the utility of language translators. BMC Bioinformatics. 2010; 11(12): S11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nClark NR, Hu KS, Feldmann AS, et al.: The characteristic direction: a geometrical approach to identify differentially expressed genes. BMC Bioinformatics. 2014; 15(1): 79. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang Z, Ma’ayan A: An open RNA-Seq data analysis pipeline tutorial with an example of reprocessing data from a recent Zika virus study. F1000Res. 2016; 5: 1574. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTambonis T, Boareto M, Leite VBP: Differential Expression Analysis in RNA-seq Data Using a Geometric Approach. J Comput Biol. 2018; 25(11): 1257–1265. PubMed Abstract | Publisher Full Text\n\nBarrett T, Wilhite SE, Ledoux P, et al.: NCBI GEO: archive for functional genomics data sets–update. Nucleic Acids Res. 2013; 41(Database issue): D991–D995. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaza E: In Papyro Comparison of TMM (edgeR), RLE (DESeq2), and MRN Normalization Methods for a Simple Two-Conditions-Without-Replicates RNA-Seq Experimental Design. Front Genet. 2016; 7: 164. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcCarthy DJ, Campbell KR, Lun ATL, et al.: Scater: pre-processing, quality control, normalization and visualization of single-cell RNA-seq data in R. Bioinformatics. 2017; 33(8): 1179–1186. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLun ATL, McCarthy DJ, Marioni JC: A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor. F1000Res. 2016; 5: 2122. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSatija R, Farrell JA, Gennert D, et al.: Spatial reconstruction of single-cell gene expression data. Nat Biotechnol. 2015; 33(5): 495–502. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHao Y, Hao S, Andersen-Nissen E, et al.: Integrated analysis of multimodal single-cell data. bioRxiv. October 12, 2020: 2020.10.12.335331. Publisher Full Text\n\nAmezquita RA, Lun ATL, Becht E, et al.: Orchestrating single-cell analysis with Bioconductor. Nat Methods. 2020; 17(2): 137–145. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWolf FA, Angerer P, Theis FJ: SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 2018; 19(1): 15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZyprych-Walczak J, Szabelska A, Handschuh L, et al.: The Impact of Normalization Methods on RNA-Seq Data Analysis. Biomed Res Int. 2015; 2015: 621690. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchurch NJ, Schofield P, Gierliński M, et al.: How many biological replicates are needed in an RNA-seq experiment and which differential expression tool should you use? RNA. 2016; 22(6): 839–851. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRigaill G, Balzergue S, Brunaud V, et al.: Synthetic data sets for the identification of key ingredients for RNA-seq differential analysis. Brief Bioinform. 2018; 19(1): 65–76. PubMed Abstract | Publisher Full Text\n\nBystrykh L: LeonidBystrykh/PY4GE: Python for gene expression (Version v0.0.1). Zenodo. 2021, June 30. Publisher Full Text"
}
|
[
{
"id": "136995",
"date": "17 May 2022",
"name": "Sergio Peignier",
"expertise": [
"Reviewer Expertise Gene regulatory networks inference",
"gene expression analysis",
"hyperspectral image analysis",
"Subspace clustering"
],
"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\nDear Leonid Bystrykh,\nThe opinion article \"Python for gene expression\" is well written, and clear, it provides an interesting historical and contextual description and explanation for the dominance of R in differential gene expression analysis, and it also clearly points the interest and benefits of developing python projects dedicated to differential gene expression analysis.\nI hope the following remarks will be useful to improve this interesting paper.\nKind regards,\nSergio Peignier\nMaybe you can show from the title that the paper is mostly oriented towards differential gene expression analysis (e.g., \"Python for differential gene expression\").\n\nIn Table 1 you can replace the column \"Name\" by \"Main library\" or something like this to be more explicit.\n\n\"such as R and Python.6-8\" <- maybe keeping citations for R and Python separated will give a better insight to the reader.\n\n\"approaching 400 (compiled by Wikipedia)\" <- consider adding a citation.\n\n\"decline in popularity (as for instance recorded in codementor.io site for the worst programming languages)\" <- consider adding a citation.\n\n\"in e establishing\" <- \"in establishing\".\n\n\"One is using a linear model [...] the expression array.\" <- consider adding a citation to the paper.\n\n\"Potentially, there is a possibility to wrap R-functions from any R package into Python.\" <- there are some DEseq2 wrapped versions available e.g., GReNaDIne: Data-Driven Approaches to Infer Gene Regulatory Networks in Python (gitlab link).\n\n\"peculiar options available in Python\" <- Maybe \"specific\" instead of \" \"peculiar\"?\n\n\"rehearses a fold change statistics \" <- \"rehearses fold change statistics\".\n\nThe following sentence could be clarified and a justification or citation to support it could be incorporated: \"approach rehearses a fold change statistics rather than eBayes probability approach and thus is not recommended.\"\n\nRegarding the comparison between Python and other languages,\n\"This essay was written sometime in 1997. It shows its age. It is retained here merely as a historical artifact. (https://www.Python.org/doc/essays/comparisons/)\" the website that was cited by the author states: \"Disclaimer: This essay was written sometime in 1997. It shows its age. It is retained here merely as a historical artifact.\", so a more recent citation could be included instead. Moreover, I think that the comparison between python and R could be extended, in order to better support the idea that developing such a research field in Python would be valuable.\n\nInclude citations for SciPy, Numpy, Scikit-learn, Pandas, statmodels, Matplotlib, bokeh and seaborn.\n\n\"does not support Pandas\" <- I would replace by \"does not fully support Pandas\" since some operations can be executed on pandas DataFrames, but the output is always a numpy array.\n\nThere are also classical methods for RNAseq normalization such as TPM, RPKM, that are not mentioned in the article, what is the place of such techniques in this context?.\n\n\"Unlike other differential expression protocols, SC-RNAseq is aimed on characterization of cells, not genes, and possible discovery and/or classification of existing cell types\" <- these datasets can also be used to study genes, and specially to infer Gene Regulatory Networks1.\n\nSC-RNAseq also incurs in a missing values problem, that should be addressed by some pre-processing techniques, it could be interesting to discuss this problem.\n\nMaybe you can try to include a few citations to new python programs dedicated to the analysis of gene expression, to support the idea that there is a community in computational biology and bioinformatics that is working in python.\n\nThe test scripts that are associated to the paper could be transformed into small tutorials, and could be very beneficial for the community.\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": "136994",
"date": "24 May 2022",
"name": "Yasha Hasija",
"expertise": [
"Reviewer Expertise Bioinformatics",
"Machine Learning",
"Polymorphisms"
],
"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 \"Python for gene expression\" discusses the applicability of Python and R for gene expression data analysis. Beginning with a brief history of several programming languages and their compatibility with biological problems/data, the article then discusses their compatibility with biological problems/data. The authors then describe the advantages of R packages for the processing and statistical analysis of big expression data, as well as their replacement in Python. The article concludes that the Python programming language has wide use in biological data processing processes and that the scientific community should consider adopting it.\nThe piece is well-written and effectively conveys its intended message. A few of my recommendations are:\nThe sections on microarray data, RNAseq data, and SC-RNAseq data analysis describe the application of R packages and the limitations of Python due to the absence of a few libraries. It would be interesting to list a few advantages of using Python for bulk data processing.\n\nAlso, advantages of Python over R in terms of automation, integration, and application development can be included.\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/10-870
|
https://f1000research.com/articles/10-873/v1
|
01 Sep 21
|
{
"type": "Research Article",
"title": "The acceptability and side effects of COVID-19 vaccine among health care workers in Nigeria: a cross-sectional study",
"authors": [
"Oluwatosin Ruth Ilori",
"Oluwatosin Stephen Ilori",
"Phillip Oluwatobi Awodutire",
"Olabisi Roseline Ige",
"Adesanmi B Idowu",
"Oluwafemi Samson Balogun",
"Olamide Idris Lawal",
"Oluwatosin Ruth Ilori",
"Oluwatosin Stephen Ilori",
"Phillip Oluwatobi Awodutire",
"Olabisi Roseline Ige",
"Adesanmi B Idowu",
"Olamide Idris Lawal"
],
"abstract": "Background: The COVID-19 pandemic is global public health crisis. Mass vaccination, until herd immunity is achieved, is one of the most effective ways of combating the deadly infectious virus. The disposition of health workers towards the AstraZeneca vaccine will most likely determine if other members of the community will be willing to get vaccinated or not. Thus, the purpose of this study is to determine the attitudes of healthcare workers to the COVID-19 vaccine, as well as determine the various side effects experienced by those who have already been vaccinated.\nMethod: Frequency tables were created, and Chi-square was used to determine the relationship between respondents' socio-demographic characteristics, as well as their acceptance or rejection of the COVID-19 vaccine and attitude towards it. Using IBM SPSS Statistics for Windows, version 22.0, multinominal logistic regression was used to determine the key factors which influenced respondents’ decision to have the vaccine.\nResult: There was a statistically significant relationship between the cadre of health care workers, their tribe, and their involvement in the care of COVID-19 patients and their attitude towards the vaccine.\nConclusion: Previous involvement in the care of COVID-19 patients is one of the most important determinants of health care workers' acceptance of the COVID-19 vaccine. Most respondents were positive about the vaccine; however, the fear of side effects was the primary reason why those who were yet to be vaccinated, do not plan to do so. The most common side effect reported by those who had already been vaccinated, was pain at the injection site. Public awareness of the vaccine and its benefits should be increased, and the vaccine should be made available in all health care facilities.",
"keywords": [
"COVID-19",
"vaccine",
"acceptance rate",
"health care workers"
],
"content": "Introduction\n\nFollowing its emergence in Wuhan, China, in November 2019, the coronavirus disease (COVID-19) was declared a global pandemic in March 2020.1 Globally, there were 126,359,540 confirmed COVID-19 cases and 2,769,473 deaths as of 28th March 2021. On the 30th January 2020, COVID-19 was declared as Public Health of International concern (PHEIC) by the World Health Organization (WHO). The disease has ravaged more than 200 countries worldwide, which necessitated its declaration as a global pandemic in March 2020.\n\nCOVID-19 was first detected in Nigeria on 24th March 2020. Since then, the pandemic has spread rapidly throughout the country, with over 146,000 cases and 2402 deaths as of 16th March 2021. The Nigerian healthcare system was unprepared for the pandemic; facing issues such as a lack of training and retraining of health workers on disease preparedness, lack of personal protective equipment, lack of testing centres in many cities, and unwillingness to be tested.2\n\nDifferent national governments have imposed a number of measures and protocols to help halt the spread of COVID-19, including the mandatory wearing of face masks, lockdowns, social distancing, and frequent hand washing with soap and water, among other measures. Following the introduction of the non-pharmaceutical interventions, vaccines have been developed to curb the spread of COVID-19 infection.2 Herd immunity is defined as the indirect protection from an infectious disease that happens when a population is immune either through vaccination or immunity developed through previous infection. To curb COVID-19, experts estimate that herd immunity would require around 80-90% of the population to have COVID-19 immunity. Hence there is a need to get the populace immunized.3\n\nVaccination is an effective method of combating infectious diseases by training the immune system to recognize and combat pathogens, either viruses or bacteria.4 Pharmaceutical companies and researchers around the world have collaborated to develop safe and effective vaccines. Pfizer, Sinovac, Janssen, Oxford/AstraZeneca, Moderna, Sputnik V, and Sinopharm are among the companies that have produced COVID-19 vaccines to combat the virus’s spread.5 The AstraZeneca vaccine was the only vaccine available for use in Nigeria as at the time of this study and it is the vaccine still currently being given. AstraZeneca was rolled out in Nigeria on the 18th of February 2021, however at the time of study, vaccinations had not commenced in some states. The vaccine is available free of charge to all, at government health facilities throughout Nigeria. The availability of a vaccine does of course not guarantee its uptake, and the acceptance of the COVID-19 vaccination is entirely voluntary in Nigeria. In a study done among healthcare providers in Nigeria on COVID-19 vaccine acceptability, 53.5% of respondents were willing to get vaccinated against the disease and the reason why 69.4% of respondents will not receive the COVID-19 vaccine was because of fear of side effects.6\n\nHealth care workers are an important group to consider, as they are in a pivotal position to determine if other members of the populace will be willing to get vaccinated or not.7 Health care workers are a reliable source of vaccination information to the general public and thus their acceptance or rejection of the COVID-19 vaccine may be critical to its uptake among the general population.7 Identifying the reasons why healthcare workers may be hesitant to take the COVID-19 vaccine could be used to inform policy makers, in modifying such factors to ensure better attitudes towards vaccination, and thus increased herd immunity.8 The purpose of this study is to determine the acceptability of the COVID-19 vaccine among healthcare workers, as well as the various side effects experienced by those who have already been vaccinated. Knowledge of the side effect will help pharmaceutical companies modify the production of the vaccines in order to limit the side effects.\n\n\nMethods\n\nThe research team obtained approval from the Ethical Review Committee of LAUTECH Teaching Hospital, Ogbomoso.\n\nRespondents took part in a cross-sectional study by filling out an online survey through Google forms; all participants were health workers from Nigeria’s six geopolitical zones. Health care workers in different health institutions across the six geopolitical zones in Nigeria who were colleagues and former colleagues of the authors were randomly selected and contacted through their already known phone numbers. They helped to circulate the link on their various hospital health workers’ WhatsApp groups. Respondents’ WhatsApp details were obtained from their colleagues. Some participants also shared the link via e-mails to colleagues who were not active on WhatsApp. The respondents did not undergo any form of screening before they were recruited. The introductory part of the Google form contained a statement on the aim and details of the study and it also contained a request for the patient’s consent to be part of the study. The Google form was designed to learn about the participants’ attitudes towards the vaccine, side effects experienced by those already vaccinated, and willingness to get vaccinated (Extended data (Ilori et al., 2021)). The survey was available to participants from the 23rd March 2021 to the 3rd May 2021. Only responses that were completed were counted and recorded. Surveys completed by respondents with the same email address were disqualified because they were deemed to be overlapping responses. Ethical approval was obtained from the Ethical Review Committee of LAUTECH Teaching Hospital, Ogbomoso.\n\nA total of 309 responses were collected and analysed using SPSS version 22 [16]. Questions 1-6 were on sociodemographic characteristics of respondents, questions 7-19 handled the willingness to get vaccinated and questions 20-27 answered the attitudinal questions. After data collection, numbers were assigned to answers for the purpose of computing. Respondents’ attitudes were graded by assigning scores to the likert scale responses. All the likert scale questions were negative except the penultimate and the last questions which were neutral and positive respectively. For the negative statements, strongly agreed, agree, indifferent, disagree and strongly disagree corresponds to scores of 1,2,3,4,5 respectively. For the positive statement, strongly agreed, agree, indifferent, disagree and strongly disagree corresponds to 5,4,3,2,1 respectively. The mean was calculated by adding the sum of all the scores for all respondents. Respondents who scored higher than the calculated mean were considered to have a positive attitude towards the AstraZeneca vaccine, while those who scored lower than the calculated mean were considered to have a negative attitude toward the vaccine. The questions on the respondents’ willingness to accept the vaccine and the readiness to recommend same for others were scored 1 for a ‘yes’ answer and 0 for a ‘no’ answer. Vaccine acceptability was determined by adding the scores for willingness to be vaccinated and readiness to recommend the vaccine to patients. The mean was calculated after adding up all the scores. Respondents with scores lower than the mean were considered to have poor acceptability, while those with scores higher than the mean were considered to have good acceptability. Data was analysed using SPSS version 22, after sorting. Frequency tables were created, and the Chi square test was used to determine the relationship between respondents’ socio-demographic characteristics, as well as their attitude and acceptability of the AstraZeneca COVID-19 vaccine. The factors influencing COVID-19 acceptability were identified using multinominal logistic regression. Tribe of respondents, cadre as well as past involvement in management of COVID-19, were tested for their association with vaccine acceptability at the multivariate level.\n\n\nResults\n\nTable 1 shows that 195 respondents were female, while 114 (36.9 %) were male. The majority (82.2%) were Yorubas, and 237 (76.7%) were Christians. The majority of the respondents came from the geopolitical zone of the South West. 121 respondents (39.2%) were Doctors, 89 (28.8%) were Community Health Extension Workers (CHEWs) and 57 (18.4%) were Nurses. Physiotherapists, Pharmacists, and Porters were among the 17% (5.4 percent).\n\nTable 2: At the time of this research, 238 respondents (80.3%) were willing to be vaccinated, and 117 (37.9%) were already vaccinated; the majority of whom were only one week away from the day of vaccination. The reason given by 127 (66.2%) of those who had not been vaccinated was that the vaccine was not yet available in their facility. Even if the vaccine was made available, 41 (60.3%) of respondents would not get vaccinated because they are not just at peace with the vaccine.\n\nTable 3 shows that 250 (80.9%), 250 (80.9%), and 111 (35.9%) of respondents can recommend COVID-19 vaccine to their patients, have attended COVID-19 seminars, and have been involved in the care of COVID-19 patients.\n\nTable 4 shows that 85 respondents (72.6%) experienced side effects after receiving the COVID-19 vaccine, while 32 (27.4%) did not. 73 participants (85.9%) reported pain at the injection site, while 36 (42.3%) and 34 (40.0%) reported fever and headache, respectively.\n\nTable 5 shows that 168 (54.4%) of respondents had a positive attitude toward COVID-19 vaccination, while 141 (45.6%) had a negative attitude.\n\nTable 6 shows that 237 (76.7%) of respondents thought the COVID-19 vaccine was acceptable, while 72 (23.3%) had a poor acceptability of the vaccine.\n\nTable 7 shows a statistically significant relationship between respondent’s tribe and cadre, and their attitude toward COVID-19 vaccination. More males and respondents of Christian religion had good attitude towards COVID-19 vaccination\n\nTable 8: When compared to their acceptability of COVID-19 vaccination, there is a statistically significant association between tribe and cadre of respondents; more laboratory scientists had poor acceptability of the COVID-19 vaccination, while a high proportion of CHEWs had good acceptability of the COVID-19 vaccination.\n\nTable 9 lists the predictors of COVID-19 vaccine acceptability among health workers, which include Tribe, Cadre, and involvement in the care of a COVID-19 patient. The Igbo and other tribes are 3.962 and 3.631 times more likely, respectively, to accept the COVID-19 vaccine, than the Yoruba tribe. When compared to Doctors, CHEWS are 0.048 times less likely to accept COVID-19 vaccination. Participants who have been involved in the care of a COVID-19 patient are 1.824 times more likely than those who have not to accept the vaccine.\n\n\nDiscussion\n\nThis study aims to determine the willingness and acceptability of COVID-19 vaccination among Nigerian health care workers, as well as the potential side effects among those who have already been vaccinated. A higher proportion of health workers were willing to get vaccinated with AstraZeneca vaccine available in Nigeria than a similar study done among health workers in France and the French-speaking part of Belgium, which had a 46.8 % acceptance rate of the same AstraZeneca vaccine.7 Our findings could be attributed to increased vaccine awareness. Despite the widespread misconception about vaccination, health care worker’s acceptance of the COVID-19 vaccine will go a long way toward informing patients about the importance of getting vaccinated.\n\nOur findings are quite different from another study conducted in Ghana, where there was a self-reported, low intention of health workers to accept the AstraZeneca vaccine.4 The reason for this similarity may because of several myths about the vaccine as well as the rapidity in the development of the vaccine. Some of the myths and misconception about the vaccine are that there was inadequate clinical trials to support its usage, mutation of gene etc..9 Many respondents may have been sceptical about the Nigerian government’s ability to intervene by providing a liable vaccine within a year of the commencement of the pandemic in such a short period of time. Continuous public sensitization about the benefits of getting vaccinated against this infectious disease will go a long way toward convincing health workers and the general population in this category to reconsider accepting the vaccine. In study conducted in Saudi Arabia between 8th December to 14th December 2020, out of 673 health workers sampled, half were willing to receive the COVID-19 vaccine, and 49.71% planned to do so as soon as it became available.10 Their findings are comparable to those in this study, in which more than three-quarters of respondents said they would get vaccinated as soon as they could. This is very encouraging because a high vaccination rate is essential to achieving herd immunity within the global population and working towards managing the spread of the virus.\n\nThe AstraZeneca COVID-19 vaccine’s side effects have been widely documented within research. In a study conducted in the United Kingdom, among Pfizer-BioNTech vaccine recipients, two-thirds of those polled reported one or more side effects, with fatigue and headache being the most common.11 This is in contrast to the findings of the current study, which found that pain at the injection site was the most common side effect experienced. The likely reason for this is due to the different types of vaccines used in both study areas. There is an urgent need for the manufacturers to ensure that the side effects of these vaccines, regardless of type, are kept to a minimum to encourage greater acceptance.\n\nIn a similar study conducted among health care workers in New York, USA, gender, age, and place of residence were statistically significant with the willingness to get vaccinated with BioNTech Pfizer COVID-19 vaccine.9 However, in this study, the statistically significant factors were cadre of health care workers and their tribe. The probable reason why tribe is statistically significant may be because tribal values are held in high esteem in African communities. Thus, people of the same tribe tend to share similar views about general health issues including vaccination. Furthermore, when compared to CHEWs, doctors were more willing to accept the vaccination. The reason for this among the various cadres of health workers may be that doctors are more likely have had the opportunity to treat as well as witness complications associated with COVID-related illnesses, than the other cadres of health care workers. This could explain why those who had previously been involved in the care and management of COVID-19 patients were significantly more likely to accept COVID-19 vaccination than those who have never treated COVID-19 patients.\n\nIn terms of the limitations of the study, considering the fact that the study was conducted online, only respondents who got the link through WhatsApp or e-mail alone were able to respond to the questions. Thus, it is not every health worker that is active on WhatsApp and there is no common data base where email of all health workers could be assessed.\n\n\nConclusion\n\nIn this study, the rate of acceptance of COVID-19 vaccination among health workers was quite high, especially among doctors when compared with other cadres. The acceptability of COVID-19 vaccination was statistically significant by tribe and cadre of respondents, and health workers who had been involved in COVID-19 management were more likely to accept the vaccine. The main reason respondents would not get vaccinated was the fear of side effects which was closely linked to various myths accrued to AstraZeneca vaccines available in Nigeria, such as getting infected with the virus through the vaccine, alteration of recipient’s gene etc. To encourage vaccine acceptability by the general population, side effects from COVID-19 vaccine, regardless of the brand, should be kept to a minimum.\n\n\nData availability\n\nFigshare: Ilori et al., 2021 The acceptability and side effects of COVID-19 vaccine among health care workers in Nigeria: a cross sectional study. https://figshare.com/articles/dataset/The_Acceptability_and_side_effects_of_COVID_19_vaccine_among_health_care_workers_in_Nigeria_a_cross_sectional_study/15078498/1 (Ilori et al., 2021).11\n\nThis project contains the following underlying data:\n\n- Data file 1. (Complete survey responses, CSV format).\n\nFigshare: Ilori et al., 2021 Copy of online survey. https://figshare.com/articles/figure/Copy_of_online_survey_used_in_Health_Care_Worker_survey_2021/15078588/1 (Ilori et al., 2021).12\n\nThis project contains the following underlying data:\n\n- Copy of online survey used in Health Care Worker survey 2021.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0).\n\n\nGrant information\n\nThis work was supported by Digiteknologian TKI-ymparisto project A74338 (ERDF, Regional Council of Pohjois-Savo).\n\n\nCompeting interests\n\nNo competing interests were disclosed.",
"appendix": "References\n\nZhong B-L, 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): 1745–1752.\n\nMadubike UA, Ishmael JF, Obichukwu CN, et al.: A perspective on Nigeria’s preparedness, response and challenges to mitigating the spread of COVID-19. Challenges . 2020; 11(2): 22. Publisher Full Text\n\nAgyekum MW, Afrifa-Anane GF, Kyei-Arthur F, et al.: Acceptability of COVID-19 Vaccination among Health Care Workers in Ghana. Adv Public Heal. 2021; 3(4): 31–40. Publisher Full Text\n\nCohen J: Dosing debates, transparency issues roil vaccine rollout. Science (80-). 2021; 371(6525): 109–10. PubMed Abstract | Publisher Full Text\n\nWong MCS, Wong ELY, Huang J, et al.: Acceptance of the COVID-19 vaccine based on the health belief model: a population-based survey in Hong Kong. Vaccine. 2021; 39(7): 1148–1156. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPierre V, Dimitri S, Nicolas D, 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. 2021; 26(3). PubMed Abstract | Publisher Full Text | Free Full Text\n\nFrares S: COVID-19 Vaccination Perception and Attitude among Healthcare Workers in Egypt. SAGE. 2021; 32(2). Publisher Full Text\n\nAmeerah MN, Qattan NA, Omar A, et al.: Acceptability of a COVID-19 Vaccine Among Healthcare Workers in the Kingdom of Saudi Arabia. Front Med. 2021; 8: 644300. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMenni C, Klaser K, Anna May M, et al.: Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. Lancet. 2021; 3099(21): 0024. Publisher Full Text\n\nMenon V: Knowledge, Attitudes and Perceptions of COVID-19 Vaccination among Healthcare Workers of an Inner-City Hospital in New York. Vaccine. 2021; 9: 516. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIlori OR, Ilori OS, Awodutire OP, et al.: The Acceptability and side effects of COVID 19 vaccine among health care workers in Nigeria: a cross sectional study. figshare. 2021. Publisher Full Text\n\nIlori OR, Ilori OS, Awodutire OP, et al.: Copy of online survey used in Health Care Worker survey 2021. igshare. 2021. Publisher Full Text"
}
|
[
{
"id": "98181",
"date": "17 Nov 2021",
"name": "Ozayr H. Mahomed",
"expertise": [
"Reviewer Expertise Health system strengthening"
],
"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' work is commendable. The strength of the study is in clear explanation. However, I have the following points:\nThe abstract is weak and needs to be more focused on the objectives.\n\nThe methodology is not provided - needs to be clearly articulated using sub-headings.\n\nThe conclusion is not linked to the findings.\n\nIntroduction: lines 14 to 17 should be after the explanation of vaccines.\n\nThe results section should be represented in line with explaining findings from the table.\n\nThe odds ratio adjusted and unadjusted have not been provided. What were the confounding variables?\n\nLimitation of the study not discussed.\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?\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": "99629",
"date": "14 Dec 2021",
"name": "Malina Osman",
"expertise": [
"Reviewer Expertise Infectious disease",
"epidemiology",
"socio-behavioural 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\nDefinition of acceptability based on the mean of the scores in my opinion is not suitable in this kind of situation. As we have to deal with a pandemic and all matters related to its management, stricter rules should be imposed.\n\nContents/items for acceptability have not been explained clearly, I recommend if the authors can present the descriptive data on each question that has been asked to the respondents.\n\nI am not sure how the tool for the study was developed, and the authors did not mention at all the reliability and validity of the instrument used.\n\nThe number of sample size was not calculated, I'm not sure whether the samples were representative or not. But obviously, this study adopted a non-probability sampling technique.\n\nFinally, the statistical analysis in my opinion needs further analysis, particularly when the contingency table is more than 2x2. Difficult to conclude when there was no posthoc test being performed.\n\nThe table for regression was too simple, and based on my understanding it needs further detailed explanation.\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?\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/10-873
|
https://f1000research.com/articles/10-761/v1
|
05 Aug 21
|
{
"type": "Case Report",
"title": "Case Report: Retinal vein occlusion as the first clinical manifestation of systemic lupus erythematosus in a male patient",
"authors": [
"Marwa Ben Brahim",
"Sondes Arfa",
"Fadia Boubaker",
"Jihen Chelly",
"Wafa Ammari",
"Sonia Hammami",
"Fatma Arbi",
"Olfa Berriche",
"Sondes Arfa",
"Fadia Boubaker",
"Jihen Chelly",
"Wafa Ammari",
"Sonia Hammami",
"Fatma Arbi",
"Olfa Berriche"
],
"abstract": "Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease characterized by widespread clinical manifestations and immunological disorders. A myriad of ocular manifestations can be seen in patients with SLE. The most vision-threatening complication is vaso-occlusive retinopathy including retinal vein occlusion (RVO). RVO associated with SLE is well described in the literature and its association with antiphospholipid antibodies is recognized. However, RVO as the initial manifestation of SLE is scarcely reported. Herein, we report the first case of recurrent RVO as the primary manifestation of SLE in a 40-year-old male patient. He had two consecutive episodes of decreased vision. Ophthalmologic examination disclosed a branch retinal vein occlusion the first time and a central retinal vein occlusion the second time. The diagnosis of SLE was established based on clinical and immunological criteria. He was prescribed antiplatelet therapy, hydroxychloroquine at 5.5 mg/kg/day, and intravitreal anti-vascular endothelial growth factor (VEGF) antibodies regimen. He slowly improved under treatment.",
"keywords": [
"Retinal vein occlusion",
"Systemic Lupus Erythematosus",
"Male patient",
"Intra-vitreal anti-vascular endothelial growth factor antibodies treatment",
"case report"
],
"content": "Introduction\n\nRetinal vein occlusion (RVO) is a common retinal vascular disorder that, if left untreated, can lead to vision loss.1 Classic risk factors are hypertension, hyperlipidemia and diabetes mellitus.2 Systemic and inflammatory diseases such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome were found to be associated with the development of RVO.2 RVO associated with SLE is well described in the literature and its association with antiphospholipid antibodies is recognized.1,2 However, RVO as the initial manifestation of SLE is very uncommon. Herein we report a unique case of recurrent RVO as the initial presentation of SLE in a male patient.\n\n\nCase report\n\nA 40-year-old Caucasian man, with no family history of autoimmune diseases and a personal medical history of hypertension, was admitted to the Ophthalmology Department of Taher Sfar University Hospital with blurred vision in the right eye. On detailed physical examination, he had no fever, arthritis, or chest complaints. On ophthalmologic examination, the best corrected visual acuity was 20/20, and a retinal branch vein occlusion in the right eye was disclosed. He was treated with aspirin (100 mg/day) associated with equilibration of his hypertension.\n\nOne year later, he experienced another episode of blurred and decreased vision in the same eye. Physical examination was unremarkable. A skin exam revealed he had an erythema over the malar area. His blood pressure was normal. Fundus examination disclosed central retinal vein occlusion, superficial flame-shaped retinal hemorrhages, and macular oedema (Figure 1). Fluorescein angiography (FA) demonstrated vascular tortuosity, retinal hemorrhage, and cotton wool spots on the right eye (Figure 2). Spectral-domain optical coherence tomography demonstrated cystoid macular oedema (Figure 3). The left eye examination showed normal sizes of the retinal vessels and retina. A refraction study showed a best corrected visual acuity at 20/70 in the right eye and 20/20 in the left eye. On laboratory investigations, a blood test showed platelets: 229 * 109/l, leukocytes: 9 * 109/l, and hemoglobin level: 13.5 g/dl. Erythrocyte sedimentation rate was 30.\n\nAutoantibodies tests revealed positive antinuclear antibodies (1: 800), anti-DNA antibodies, anti-nucleosomes antibodies, and slightly positive anti-citrullinated protein antibodies and rheumatoid factors. Antiphospholipid antibodies screening displayed high titer (> 40 UI) of IgG anticardiolipines and IgG antiβ2 glycoprotein antibodies. Total blood complement, C3, C4, protein S, protein C and antithrombin III levels were normal. The diagnosis of SLE was established based on clinical and immunological criteria including malar rash, positive anti-nuclear antibodies, anti-DNA antibodies, and antiphospholipid antibodies.\n\nThe patient was started with hydroxychloroquine at 5.5 mg/kg/day and intra-vitreal anti-vascular endothelial growth factor (VEGF) antibodies regimen, in combination with aspirin (100 mg/day). The patient is still regularly taking his treatment without significant side effects. His vision has slowly improved under treatment. The patient remained under close observation. After two years of follow up, a refraction study showed a stable visual acuity.\n\n\nDiscussion\n\nThe atypical clinical presentation of SLE, in a male patient with a medical history of hypertension, and without any clinical objective criteria, led to the delay of the diagnosis of this autoimmune disease. The diagnosis was made after a second retinal vein occlusion. The patient had cutaneous involvement concomitantly with ocular complication. He had immunological criteria including positive antinuclear antibodies, anti-DNA antibodies and antiphospholipid antibodies which made the diagnosis clearer.\n\nSLE is a chronic and autoimmune disease characterized by widespread clinical manifestations and immunological disorders. It occurs in both genders but it is much more common in females than males, with female:male sex-ratio of 8:1 to 15:1.3 Male patients have a higher prevalence of life threatening manifestations including lupus nephritis, central neurological system involvement and hemolytic anemia.3,4 Regarding immunological features, anti-phospholipid antibodies were found to be more frequent in male SLE patients.5 Thus, it would be expected that they present an increased risk of thromboembolic manifestations and antiphospholipid syndrome, which could worsen the course of the illness and increase the mortality rates. We report a case of SLE associated with antiphospholipid antibodies in a male patient. He presented a recurrent RVO as the first manifestation of the disease making this case unique.\n\nA myriad of ocular manifestations can be seen in patients with SLE including keratoconjunctivitis, scleritis, episcleritis, retinopathy, choroidopathy, orbital and lachrymal system disorders.6 The most common ocular manifestation is keratoconjunctivitis but the most visually-threatening is retinopathy. The prevalence of lupus retinopathy varies from 3% to 28%.6,7 The most common manifestations of lupus retinopathy are cotton wool spots, retinal hemorrhage and optic disk oedema.7 Vaso-occlusive retinopathies is a subset of retinal vasculopathy, including retinal artery or vein occlusions which are a rare but severe complication. The vascular retinopathy in SLE results from immune complex mediated vascular injuries and micro-vascular thrombosis.8 Patients with retinal vessel occlusion seem to have a poorer visual prognosis.\n\nPatients with SLE have a higher prevalence of developing RVO than the general population. A higher incidence of antiphospholipid antibodies in SLE patients with RVO has been reported.7,9,10 Typically, RVO occurs in the first four years follow-up of SLE. Retinal vasculitis was scarcely reported as the first manifestation of SLE.11–13 As far as we know, this would be the first case of a recurrent RVO as the primary presentation of SLE to be reported in literature.\n\nRegarding the treatment of RVO in patients with SLE, anticoagulation and anti-platelet therapies have contributed to the stabilization of the retinal occlusion and the prevention of recurrent thrombosis either used separately or combined. The use of an immunosuppressant is still controversial due to the lack of evidence about its effects in improving the visual acuity and the retinal vascular occlusion recurring.7 Intravitreally administrated anti-VEGF antibodies were introduced in the treatment regimen of RVO. Its main desired effect is to reduce the macular edema, which is the major cause of decreased visual acuity in patients with RVO.14 Our patient received a combination of anti-platelet therapy and anti-VEGF antibodies. Clinical improvement was achieved under this treatment.\n\n\nConclusion\n\nSLE in males may have an atypical presentation. This often leads to a delay in making the diagnosis and starting treatment. In this article, we have reported a unique case of SLE in a male patient presenting with a severe and sight- threatening ocular complication. The diagnosis was overlooked, as the patient did not have any clinical criteria of SLE initially. Our case report’s core contribution is to raise awareness about the possible typical and severe presentation of SLE in men.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and clinical images was obtained from the patient.\n\n\nData availability statement\n\nAll data underlying the results are available as part of the article and no additional source data are required.",
"appendix": "References\n\nJaulim A, Ahmed B, Khanam T, et al.: Branch retinal vein occlusion: epidemiology, pathogenesis, risk factors, clinical features, diagnosis, and complications. An update of the literature. Retina Phila Pa. 2013; 33(5): 901–10. PubMed Abstract | Publisher Full Text\n\nHernández JL, Sanlés I, Pérez-Montes R, et al.: Antiphospholipid syndrome and antiphospholipid antibody profile in patients with retinal vein occlusion. Thromb Res. 2020; 190: 63–8. PubMed Abstract | Publisher Full Text\n\nPons-Estel GJ, Ugarte-Gil MF, Alarcón GS: Epidemiology of systemic lupus erythematosus. Expert Rev Clin Immunol. 2017; 13(8): 799–14. PubMed Abstract | Publisher Full Text\n\ndo Socorro Teixeira Moreira Almeida M, da Costa Arcoverde J, Barros Jacobino MN, et al.: Male systemic lupus erythematosus, an overlooked diagnosis. Clin Pract. 2011; e103: 1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDey D, Ofori E, Hutton-Mensah KA, et al.: Clinical characteristics of males with systemic lupus erythematosus (SLE) in an inception cohort of patients in Ghana. Ghana Med J. 2019; 53(1): 2–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSilpa-archa S, Lee JJ, Foster CS: Ocular manifestations in systemic lupus erythematosus. Br J Ophthalmol. 2016; 100(1): 135–41. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAu A, O’Day J: Review of severe vaso-occlusive retinopathy in systemic lupus erythematosus and the antiphospholipid syndrome: associations, visual outcomes, complications and treatment. Clin Experiment Ophthalmol. 2004; 32(1): 87–100. PubMed Abstract | Publisher Full Text\n\nYen Y-C, Weng S-F, Chen H-A, et al.: Risk of retinal vein occlusion in patients with systemic lupus erythematosus: a population-based cohort study. Br J Ophthalmol. 2013; 97(9): 1192–6. PubMed Abstract | Publisher Full Text\n\nMontehermoso A, Cervera R, Font J, et al.: Association of antiphospholipid antibodies with retinal vascular disease in systemic lupus erythematosus. Semin Arthritis Rheum. 1999; 28(5): 326–32. PubMed Abstract | Publisher Full Text\n\nNangia PV, Viswanathan L, Kharel R, et al.: Retinal Involvement in Systemic Lupus Erythematosus. Lupus Open Access. 2017; 2: 1000129. Publisher Full Text\n\nAlhassan E, Gendelman HK, Sabha M, et al.: Bilateral Retinal Vasculitis as the First Presentation of Systemic Lupus Erythematosus. Am J Case Rep. 2021; 22: e930650. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBandyopadhyay SK, Moulick A, Dutta A: Retinal vasculitis--an initial presentation of systemic lupus erythematosus. J Indian Med Assoc. 2006; 104(9): 526–7. PubMed Abstract\n\nKremer I, Gilad E, Cohen S, et al.: Combined arterial and venous retinal occlusion as a presenting sign of systemic lupus erythematosus. Ophthalmol J Int Ophtalmol Int J Ophthalmol Z Augenheilkd. 1985; 191(2): 114–8. PubMed Abstract | Publisher Full Text\n\nStahl A, Agostini H, Hansen LL, et al.: Bevacizumab in retinal vein occlusion-results of a prospective case series. Graefes Arch Clin Exp Ophthalmol. 2007; 245(10): 1429–36. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "91272",
"date": "17 Aug 2021",
"name": "Bouomrani Salem",
"expertise": [
"Reviewer Expertise Connective tissue disease",
"autoimmunity",
"immunogenic."
],
"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 provide an interesting and original Case Report of retinal venous occlusion revealing systemic lupus erythematosus in a man. This observation is distinguished by the initial atypical clinical manifestation, male sex, and recurrence of retinal occlusion. This case is therefore the first to report recurrent retinal venous occlusion as an initial manifestation of lupus.\nSome comments are however useful to improve the quality of this manuscript:\n1. Title:\nReplace the proposed title with \"recurrent retinal vein occlusion as...\" to highlight the recurrent character which is the originality of this observation.\n2. Abstract:\nReplace “primary” by initial or revealing.\n3. Keywords:\nAdapt the list of keywords to international standards: remove “patient” from “male patient”, remove “case report”, remove “intra- vitreal and treatment” from “Intra-vitreal anti-vascular endothelial growth factor antibodies treatment”.\n4. Case Report:\nSpecify the anti-hypertensive treatment received by the patient (possibility of induced lupus)?.\n\nReplace \"caucasian\" by \"Tunisian\".\n\nRemove \"s\" from \"rheumatoid factors\",\n\nAdd, if possible, a photo of the patient's malar erythema.\n\nIf possible, give the results of the explorations made to support the diagnosis of systemic lupus erythematosus: cardiac ultrasound (lupus pericarditis? which is asymptomatic in 30% of cases), cerebral MRI (infra-clinical neurolupus? Especially the association with retinal vasculitis is noted in more than 70% of cases1), and urinalysis?.\n\nSpecify, if they were carried out, the results of the following tests: factor V mutation? (main thrombophilia causing venous thrombosis in Tunisia), and homocysteinemia? (hyperhomocysteinemia may be an added risk factor for retinal vein occlusions during SLE (1 patient/3 in Kumar K et al series2).\n5. Discussion:\nReplace \"primary\" by initial or revealing.\n\nDiscuss the significance of anti-CCP antibodies in this observation: associated rheumatoid arthritis? (positive anti-CCP antibodies and positive RF: Rhupus syndrome?) Or a simple positivity of anti-CCP which can be seen in 10-15% of patients with SLE3?\n6. Conclusion:\nRephrase “delay in making the diagnosis…” by “diagnostic and therapeutic delay”.\n\nReplace \"article\" by \"paper\".\n\nCorrect \"typical\" by \"atypical\".\n\nEmphasize the recurrent and revealing nature of the retinal venous occlusion which is the originality of this case.\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? Yes",
"responses": [
{
"c_id": "7214",
"date": "13 Oct 2021",
"name": "Marwa Ben Brahim",
"role": "Author Response",
"response": "1. Done 2. Done 3. Done, the keyword \"case report\" was kept because it has to be mentioned. 4. We, unfortunately, do not have any pictures of the patient's malar rash. Since the patient had not had any neurological symptoms, we did not demand a Brain-MRI. We have assed further details about the laboratory investigation. 5. Done. The patient had slightly positive anti-citrullinated protein antibodies and rheumatoid factor without bone erosion or joint stiffness or deformity evoking the diagnosis of rhupus. In fact, the positivity of anti-CCP can be seen in 10-15% of patients with SLE without an association to rheumatoid arthritis. 6. We rephrased \"delay in making the....\" as you suggested. We corrected typical by atypical as you suggested. We have emphasized the recurrent and revealing character of the retinal vein occlusion in all parts of the paper."
}
]
},
{
"id": "91273",
"date": "23 Sep 2021",
"name": "Matias Iglicki",
"expertise": [
"Reviewer Expertise DME",
"RVO",
"NAMD and retina surgical cases"
],
"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\nMarwa Ben Brahim et al. present an interesting study about Retinal vein occlusion (RVO) as the first clinical manifestation of systemic lupus erythematosus (SLE) in a male patient. The study results certainly suggest to some degree that the RVO as the initial manifestation of SLE is scarcely reported.\nBesides how the magnitude of these data add new findings compare to the current standard can not be determined only based on this study. The results are encouraging and further study is warranted.\nHere some relevant points:\nPlease add on keywords - these do not match with the manuscript.\n\nThe authors should express why it is relevant for an RVO patient to link Retinal vein occlusion as the first clinical manifestation of systemic lupus erythematosus in a male patient? What does it change for the current standard of care?\n\nThe authors should explain why their findings make a difference for ophthalmologists around the world and for the readers of F1000Research.\n\nThe authors should explain the source of the information and what criteria they used for adding it to the paper. Were the assessors masked? What was the ICC (Inter class Correlation) between them in order to analyze the data? Was the randomization digitalized?\n\nPlease add in the introduction that papers have been published showing how the Optical Coherence Tomography (OCT) and new devices lead us to proper diagnoses in Retinal diseases - add one line in the introduction of this and also in the discussion section. These papers should be described in the general considerations. See references1,2,3.\n\nPlease add how and how long takes for a retina specialist to link and ask the patient about SLE and other Rheumatology and Rheumatic Diseases.\n\nResults could be misinterpreted - add a short summary of the similarities in different devices and also add different OCT modalities, etc., and what can be improved in the process of detecting RVO is mandatory in the discussion section i.e wide-field angiography, different types of OCT modalities OCT angiography (OCTa).\n\nPlease apply correction for misspelling and English grammar.\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? 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 case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": [
{
"c_id": "8375",
"date": "22 Jun 2022",
"name": "Marwa Ben Brahim",
"role": "Author Response",
"response": "Keywords: they match the manuscript Since systemic lupus erythematosus is a chronic inflammatory disease with a periodic evolution it may require anti-inflammatory and/or immunosuppressant treatments in addition to symptomatic treatments of visceral manifestation such as the case of RVO how required Hydroxychloroquine, aspirin, and antiangiogenic treatment as well as long term follow-up in order to reduce relapses. In fact, publishing this case report may raise awareness about this severe sight-threatening manifestation of SLE in men patients. Dear reviewer, I do not think that interclass correlation could be applied in a case report. Optical coherence tomography (OCT) allows the visualization of retinal layers and early diagnosis of the small retinal lesions. Although the scarcity of ophthalmological manifestations as the primary manifestation of SLE, retina specialists should keep this diagnosis in mind and carefully look for other signs of an autoimmune systemic disease. Done."
}
]
}
] | 1
|
https://f1000research.com/articles/10-761
|
https://f1000research.com/articles/10-1066/v1
|
20 Oct 21
|
{
"type": "Systematic Review",
"title": "Sustainable business model for local council’s smart city initiatives: a systematic literature review",
"authors": [
"Ezatul Faizura Mustaffa Kamal Effendee",
"Magiswary Dorasamy",
"Abdul Aziz Bin Ahmad",
"Azrin Aris",
"Saida Harguem",
"Maniam Kaliannan",
"Ezatul Faizura Mustaffa Kamal Effendee",
"Abdul Aziz Bin Ahmad",
"Azrin Aris",
"Saida Harguem",
"Maniam Kaliannan"
],
"abstract": "Background: Malaysia is embarking on sustainable, resilient, and prosperous living conditions initiatives. Malaysian cities are embracing the smart city aspiration through their respective local authorities. However, they face challenges regarding funding allocation for smart city implementation. Local authorities primarily operate on a conventional business model. Based on their current business model, they are unlikely to sustain their smart city initiatives. A more financially sustainable business model is required by these local authorities to embark on smart city initiatives. This study presents a systematic review concerning the business models adopted by local authorities to implement smart cities. This paper also explores the applicability of frugal innovation towards developing a smart city business model. Methods: This article undertakes a systematic review based on combination sets of eight main keywords: smart city, business model, frugal innovation, local authorities, performance, inclusivity, technology and success factor. The search strategy includes journal articles and conference proceedings from five major online databases: Emerald, ProQuest, Scopus, IEEE Xplore, ScienceDirect, and Springer Link between 2001-2021. The data is tabulated for clear expression of knowledge gaps. Results: A total of 17 articles from 300 articles on smart city business models matched the search on smart city business models for local authorities . The study revealed that hardly any in-depth research providing the crucial elements for a successful smart city business model for local authorities has been conducted. No research has linked frugal innovation to smart city business models. Conclusions: The study calls upon the research community to explore further, the possible linkage between frugal innovation and smart cities for local authorities.",
"keywords": [
"smart city",
"local authority",
"business model",
"frugal innovation",
"financial sustainability",
"municipality",
"resilience"
],
"content": "Introduction\n\nIn Malaysia, many goals have been adopted as compasses for smart city initiatives at the national and global level, such as the United Nation’s Sustainable Development Goals, the New Urban Agenda, the Twelfth Malaysia Plan, the National Physical Plan 3 and the National Urbanisation Policy 2. Malaysia currently has 150 local councils or ‘Pihak Berkuasa Tempatan’ (PBT), comprising 19 city councils, 37 municipal councils and 94 district councils.1 Through their respective PBTs, cities around Malaysia are beginning to embrace digital city services, in line with the global movement to achieve smart and sustainable cities. However, they do not have enough funding allocated for that purpose. If they continue to operate on their conventional operations model, how can cities even hope to start embarking on the smart city aspiration when they do not have the financial means to do so? With the many challenges surrounding the financing of smart cities, practitioners and academics are exploring alternative methods. Traditional business models mainly consider how much value can contribute to the equation. However, with the increasing complexity of the smart city ecosystem, new business models must also be considered. This study contributes toward one of the 10 priority areas of the 10-10 MySTIE framework and provides insight and ways forward for smart city knowledge community.\n\nThe year 2007 marked a significant milestone in modern urban living, when the number of city dwellers across the world, tipped the number of those living in rural areas.2 This number is not expected to slow down anytime soon, with almost two-thirds of the world’s population expected to live in urban areas by 2050.2 This mass migration to the cities has inevitably strained city resources and given rise to social issues. City authorities, developers, town planners, and all those tasked with providing a better standard of living have been forced to find better, cheaper, and more efficient solutions. Fortunately, the advancement of information and communication technology (ICT) supporting these services is quite advanced. The stakeholders can leverage these technologies to ensure a better quality of life for city inhabitants. Thus, the term ‘smart cities’ has been coined; whereby cities embark on initiatives that leverage ICT and technology to provide a better quality of life.\n\nOne significant challenge with smart city projects is the investments needed. In a conference held in 2018,3 the Iskandar Regional Development Authority of Malaysia (“IRDA”) presented the Malaysian government’s aspiration for the Iskandar Malaysia smart city. One of the items mentioned was on the matter of funding, in regards that more smart city developments need private organizations’ support to fund and sustain the cities. Traditionally, cities are funded by government, for example, through tax collections. However, with funds getting more depleted, cities pursuing smart city initiatives need to find alternative sources of income; thus, the need for private investments.4 However, one significant challenge with private corporations’ involvement in smart cities is the business model, where traditional government-funded projects are predominately driven by altruistic motivation. Private corporations’ obligation is ultimate to their shareholders, where expectations are simple: a healthy bottom line.\n\nStrategic smart city initiatives often come with non-financial benefits, for example, data. Smart cities collect a lot of data from many data points. The Selangor Smart City initiative for example, involves implementation of many digital services to facilitate city dwellers’ everyday living, including CCTV, intelligent traffic management systems, smart parking, cashless payments, air quality indicators and water quality indicators. If analysed and synthesised correctly, these data can be transformed into other meaningful information that can be useful to many parties. However, the question of how these data can be properly and effectively monetised is still in its infancy. Until these issues can be resolved, the data collected, though valuable, would be difficult to be valued and quantified for financial analysis. Investment in smart cities is fraught with challenges; returns are uncertain, business models are still in infancy, and investments take a long time to recover.5 Thus, perhaps many smart cities would not have been realised if decision-makers had relied solely on financial motivations. With the many challenges surrounding the financing of smart cities, practitioners and academics are exploring alternative approaches for sustainable smart city funding. With the increasing complexity of the smart city ecosystem, new business models need to be explored; ideally where the city can financially sustain its smart services. The frugal innovation concept is about doing more with less, by reducing complexity and focusing on delivering the actual needs.6 This approach has been used mainly in engineering and industrial design, but how the same concept can also be applied to smart city business models is worth investigating.\n\nGiven that backdrop, the research questions for this study are as follows:\n\n1. How extensive is the literature coverage for smart city business models, specifically concerning local authorities?\n\n2. For the literature that covers the above, what are the business models proposed, if any?\n\n3. Can frugal innovation theory be applied to develop a smart city business model?\n\nThe objectives of this research are as follows:\n\n1. To investigate the extent to which business models for local authorities’ smart city initiatives are covered by literature.\n\n2. To identify any business models that have been proposed for local authorities to deploy smart city initiatives successfully.\n\n3. To investigate whether frugal innovation theory can be applied to the smart city business model.\n\n\nMethods\n\nThis study was conducted according to the guidelines and approved by the Research Ethical Committee of Multimedia University, Malaysia (EA1402021).\n\nThis study was designed to present a literature review, research gap analysis, and insights on the extent to which business models for local authorities’ smart city initiatives are covered by literature. This literature review was based on the Tranfield’s five stages of systemic review7 as shown in Figure 1.\n\nThe main goal of this review is to ascertain the nature and form of research about business models adopted by local authorities to deploy smart city initiatives. The paper aims to offer researchers a comprehensive review of previous works related to smart city business models. The outcome is to offer the smart city community a series of research ideas to move the field forward.\n\nOne of the issues identified that hindered the identification of all papers that analysed business models adopted by local authorities is that other terms are also used to refer to ‘local authority’, such as local councils and municipalities. Therefore, for this study, all three terms were used and cross-referenced with other terms, including smart city, business model and frugal innovation. The study then reviewed all the available literature and excluded those that were irrelevant.\n\nInclusion and exclusion criteria\n\nTo perform the literature review and ensure only quality studies were included, it was decided to include journal/conference papers and research articles from 2001 to 2021. The keywords that were used to select the studies are further explained in the section below.\n\nRegarding the exclusion factors, the study excluded books, book chapters and dissertations from the sampling frame to keep the studies’ quality high, with only peer-reviewed content. Non-English content was also excluded because most recognized academic contributions are usually published in English.\n\nFigure 2 summarizes the analysis’ inclusion/exclusion criteria.\n\nKeywords\n\nThis study focuses on business models for local authorities to implement smart city initiatives and the applicability of the frugal innovation theory. Thus, the keywords used were as follows:\n\n(1) ‘Smart city’ AND ‘business model’ AND ‘frugal innovation’ and\n\n(2) ‘Local authorities’ OR ‘local councils’ OR ‘municipalities’, which many authors use interchangeably.\n\nOther keywords, such as ‘performance’, ‘inclusivity’, ‘technology’ and ‘success factor’ were also introduced to paint a comparative landscape on the breadth of literature available covering smart cities.\n\nSearch strategy\n\nThe main strategy adopted was to comb through the vast online database to discover literature that discussed smart city business models for local authorities. The covered online databases were Emerald, ProQuest, Scopus, IEEE Xplore, ScienceDirect, and Springer Link. The identified keywords are then looked up in all the databases above to indicate the number of literature available related to the specific topics.\n\nThe findings of the above exercise are indicated in Table 1.8\n\nFrom the above exercise, the narrowed search results related to the smart city business model for local authorities were reviewed to exclude any further irrelevant research. The PRISMA methodology was adopted to facilitate further the inclusion and exclusion process illustrated in Figure 3. Nevertheless, the Tranfield method remains the primary methodology adopted for this systematic literature review. Stages four and five of the Tranfield method will be discussed in the following sections.\n\n\nResults\n\nWith more than 33,273 papers, the topic of smart cities is well-covered. Specific topics within smart cities are also well-covered, including smart city technology, with 12,542 papers representing 38% from the total smart city research, smart city performance (6,489/19%) and smart city sustainability (2,224/7%). However, only 300 papers on smart city business models were found, representing only 0.9% of the research. When further analysed, a further gap regarding smart city business models for local authorities was observed, with only 17 papers found, out of which 13 were excluded because the discussions were not specifically related to business models. Further investigation revealed no papers linking the smart city business model in local authorities to frugal innovation theory. The summary of the papers reviewed are presented in Table 2.\n\nTable 2 mentions several business models. However, discussion on the business models’ theory to allow a generic application to local authority smart city initiatives, has been insufficient.\n\nThe exercise in Table 2 revealed that no papers linked the smart city business model in local authorities to frugal innovation theory, thus presenting a potential research gap.\n\n\nDiscussion\n\nFrom the many engagements with the Malaysian local authorities relating to smart cities, five common ingredients of a smart city regularly emerge: the people, the needs, financial sustainability, inclusivity and technology. Technology plays a key role in enabling a smart city, but it is important not to fall into technological determinism; whereby a smart city’s function is blindly dictated by technology.26 Any smart city is about the citizens’ needs. A smart city merely uses technology to address those specific needs. Thus, a smart city should intuitively adapt and respond to the needs of its citizens.\n\nA good business model would increase a smart city’s chances of success. Firstly, a good business model would ensure financial sustainability for the city’s smart services and reduce the chances of those services being abandoned. Secondly, a good business model would also include existing players from within the city’s ecosystem. By having these elements, there would be less resistance, a lower entry barrier and a greater sense of ownership, encouraging the services’ longevity. With this in mind, the findings of this study are as follows:\n\n1. Table 1 reveals that the topic of the smart city is well-covered by research and specific sub-topics within smart cities, including technology, performance, and sustainability. However, a research gap is found in the smart city business model for local authorities, with only 17 papers found, out of which only four were somewhat relevant. Thus, the study posits that gaps exist between the problems faced in the industry itself and available research on the subject, and that the business models that are researched are still insufficient to address the problems faced by the local authorities.\n\n2. Table 2 shows that the following business models were mentioned concerning local authorities’ smart city initiatives:\n\n• PPP\n\n• Prosumer\n\n• Outright purchase\n\n• Subscription\n\n• Freemium\n\n• Ad-supported\n\n• City-sponsored\n\n• Ownership\n\n• Open model\n\n• Municipal-owned development\n\nHowever, the papers did not extensively cover the elements that are needed for a smart city business model. Thus, it would be challenging to apply the business models mentioned to a generic local authority smart city initiative.\n\n3. Based on the findings, there are no papers related to frugal innovation theory. However, literature and evidence in frugal innovation prove that it can be a game-changer for a sustainable business model.27 The framework applying the concept of frugal innovation to the elements of smart city mentioned above is submitted to depict frugal innovation applicability in the smart city business model. In this model, it is submitted that frugal innovation can be applied to the three elements that make up a successful smart city business model: the user element, the commercial elements and the technological elements. When considering each of these three, the question that must consistently be asked is how they all can be successfully achieved with the least resources, as depicted in Figure 3 below.\n\nA limitation of this study is the number of keywords selected. Keyword selections are based on research focus. However, there is possibility of obtaining more articles if the keywords are expanded to field of study that are not specific in nature such as municipality. This could possibly be publication bias.\n\n\nConclusions\n\nBased on our findings, future research can study frugal innovation initiatives in smart cities. Future research can also study alternative smart city business models for local authorities. Finally, future research could also assess the impact of frugal innovation on smart cities operations efficiency. This can potentially address how government agencies can convince private corporations to participate in smart city initiatives by convincing them that capital investment made into smart city initiatives are financially beneficial.\n\nFinancial sustainability is crucial for implementing smart cities, and a good business model would support this sustainability. Unfortunately, there are not a lot of studies dedicated to this topic. Frugal innovation has been applied to many other areas and industries; no literature supports the notion that it has been applied to the smart city business model. Further research on this concept would be beneficial because frugal innovation theory is a proven model for success,6 and thus would potentially benefit an initiative that ultimately aims to provide a better life for all.\n\n\nData availability\n\nFigshare: Summary of papers reviewed for business models for local authority smart city https://doi.org/10.6084/m9.figshare.14877123.8\n\nThis project contains the following underlying data:\n\n• Data file 1. (summary of papers, xlsx format).\n\nFigshare: PRISMA checklist and flow diagram https://doi.org/10.6084/m9.figshare.16722991\n\nData are available under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0)",
"appendix": "Acknowledgements\n\nWe thank the Multimedia University, Malaysia, for sponsoring the publication fee of this paper.\n\n\nReferences\n\nStatistic of Local Authorities According to State: Official Portal Local Government Department:2021, June 14.Reference Source\n\nITU, Technical Report on Smart Sustainable cities: An analysis of definitions:2014.\n\n“Smart Cities: Re-Imagining Smart Solution In Today’s Digital Age Conference”, 28th – 29th March 2018, Kuala Lumpur.\n\nFishman TD, Flynn M: Using public-private partnerships to advance smart cities. Deloitte. 2018. Retrieved September 20, 2021. Reference Source\n\nGalati SR: Funding a Smart City: From Concept to Actuality. Smart Cities. 2017; 17–39. Publisher Full Text\n\nRadjou N, Prabhu JC: Frugal Innovation: How to Do Better with Less. London:Economist;2016.\n\nTranfield D, Denyer D, Smart P: Towards a methodology for developing evidence-informed management knowledge by means of systematic review. Br. J. Manag. 2003; 14: 207–222. Publisher Full Text\n\nMustaffa Kamal Effendee EF: Summary of Papers Reviewed for Business Models for Local Authority Smart City.xlsx (Version 1). figshare. 2021. Publisher Full Text\n\nMcLean L, Roggema R: Planning for a prosumer future: The case of central park, sydney. Urban Plan. 2019; 4(1): 172–186. Publisher Full Text\n\nPapageorgiou G, Balamou E, Maimaris A:Developing a Business Model for a Smart Pedestrian Network Application.Yang XS, Sherratt S, Dey N, et al., editors. Fourth International Congress on Information and Communication Technology. Advances in Intelligent Systems and Computing. Singapore:Springer;2020; vol 1027. . Publisher Full Text\n\nAnthopoulos L, Fitsilis P, Ziozias C: What is the source of smart city value? A business model analysis. Int. J. Elect. Govern. Res. 2016; 12(2): 56–76. Publisher Full Text\n\nLiu T, Mostafa S, Mohamed S, et al.: Emerging themes of public-private partnership application in developing smart city projects: a conceptual framework. Built Environment Project and Asset Management. 2021; 11(1): 138–156. Publisher Full Text\n\nSchrotter G, Hürzeler C: The Digital Twin of the City of Zurich for Urban Planning. PFG – Journal of Photogrammetry, Remote Sensing and Geoinformation Science. 2020; 88(1): 99–112. Publisher Full Text\n\nSpruytte J, Benhamiche A, Chardy M, et al.: Modeling the relationship between network operators and venue owners in public Wi-Fi deployment using non-cooperative game theory. EURASIP J. Wirel. Commun. Netw. 2019; 2019(1). Publisher Full Text\n\nLiu W, Li F, Li Y:Development and Future Trends of Internet of Things.Xu Z, Choo KK, Dehghantanha A, et al., editors. Cyber Security Intelligence and Analytics. CSIA 2019. Advances in Intelligent Systems and Computing. Cham:Springer;2020; vol 928. . Publisher Full Text\n\nRamos CD, Clamor WL, Aligaya CD, et al.:A Disaster Management System on Mapping Health Risks from Agents of Disasters and Extreme Events.Arai K, Kapoor S, Bhatia R, editors. Proceedings of the Future Technologies Conference (FTC) 2020, Volume 2. FTC 2020. Advances in Intelligent Systems and Computing. Cham:Springer;2021; vol 1289. . Publisher Full Text\n\nKumar N, Liu X, Narayanasamydamodaran S, et al.: A systematic review comparing urban flood management practices in India to China’s sponge city program. Sustainability. 2021; 13(11): 6346. Publisher Full Text\n\nNg R: Cloud computing in Singapore: Key drivers and recommendations for a smart nation. Politics and Governance. 2018; 6(4): 39–47. Publisher Full Text\n\nCohen T: Being ready for the next uber: Can local government reinvent itself?. Eur. Transp. Res. Rev. 2018; 10(2): 1–11. Publisher Full Text\n\nJi Z, Ganchev I, O’Droma M, et al.: A cloud-based car parking middleware for IoT-based smart cities: Design and implementation. Sensors. 2014; 14(12):, 22372–22393. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSpiliotopoulou M, Roseland M: Urban sustainability: From theory influences to practical agendas. Sustainability. 2020; 12(18): 7245. Publisher Full Text\n\nFord R, Maidment C, Vigurs C, et al.: Smart local energy systems (SLES): A framework for exploring transition, context, and impacts. Technol. Forecast. Soc. Chang. 2021; 166: 120612. Publisher Full Text\n\nGallico D: Design point. an integrated E-learning & industry 4.0 fashion platform from Italy to Zambia. Paper presented at the Proceedings of the 13th IADIS International Conference ICT, Society and Human Beings 2020, ICT 2020 and Proceedings of the 6th IADIS International Conference Connected Smart Cities 2020, CSC 2020 and Proceedings of the 17th IADIS International Conference Web Based Communities and Social Media 2020, WBC 2020 - Part of the 14th Multi Conference on Computer Science and Information Systems, MCCSIS 2020. 2020; 231–235.\n\nMcShane I, Grechyn V: Public wi-fi provision by Australian local government authorities. Aust. J. Public Adm. 2019; 78(4): 613–630. Publisher Full Text\n\nOctavianthy D, Purwanto WW: Designing smart energy system for smart city through municipal solid waste to electricity: Techno-economic analysis. Paper presented at the E3S Web of Conferences. 2018; 67. Publisher Full Text\n\nSmith M, Marx L: Does Technology Drive History?: The Dilemma of Technological Determinism. Cambridge:MIT Press;1994; 70.978-0262193474.\n\nHossain M: Frugal innovation and sustainable business models. Technol. Soc. 2021; 64: 101508. Publisher Full Text"
}
|
[
{
"id": "120222",
"date": "09 Feb 2022",
"name": "Marco Tregua",
"expertise": [
"Reviewer Expertise Innovation management",
"international management"
],
"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,\nThere are some interesting proposals in your manuscript as well as some relevant shortcomings, please take a look at my comments below and - first and foremost - take care of proposing implications.\nIntroduction:\nIn the very first lines you refer to smart (and sustainable) city initiatives but you recall digital city services, please be aware of the difference and note it it at the beginning. I would suggest you to see what scholars mention about the comparison of these topics. You can refer to several publications, I can mention few as examples: Hollands, R. G (2008) 1, Tregua, M., D’Auria, A., & Bifulco, F. (2014)2, and Ishida, T. (2017).3\nYou recalled the notion of smart city, I'd do that with a definition and a quote from one of the most important works in this domain, e.g., Giffinger, R. (2015),4 or Fernandez-Anez, V., Fernández-Güell, J. M., & Giffinger, R. (2018).5\nFinally, I agree with your justification of the reason to perform this study, but since you deal with business models and several big firms have proposed their solutions for smart cities, I would wrap up the introduction by recalling a model or two proposed by big companies such as IBM, Microsoft, Cisco, and so on.\nPlease complete the introduction with a description of the structure of the chapter.\nMethod\nThis section is well written and reliable; anyway, there are two missing elements:\na) I would start from previous reviews, if any, to justify the reason for your study. b) I would describe how you avoided subjectivity in your selection of extant literature.\nResults:\nReferring to table 2 is not enough to justify/describe your two research gaps. Please debate it some more. Table 2 simply reports the evidence you picked up, while it is needed to clearly state why what you reported led you to highlight a research gap.\nMoreover, I wonder why this section is called results, since there are no 'real' results. This section is not actually hosting results, but it is a description of the process you carried out.\nDiscussion:\nI agree with your consideration on smart cities, as per the text in the first 5 lines. This consideration would have worked even better with a definition of smart city in the first section of this manuscript.\nSub-section 2 of the Discussion:\nThis view is limited, since big companies have their business model for smart cities. Thus, either you should explicitly consider them too, or highlight if these models are recalled by scholars in the contributions you analysed. Considering big companies would lead you to observe how business models for smart cities were set. Moreover, local agencies very often involve big companies in running smart cities projects and they cooperate in defining a business model suitable for a specific area. This is also relevant in considering 'how' and 'why' a big company gets involved in such projects.\nConclusions:\nI am very surprised by the lack of implications. I agree with some of your considerations, but such a manuscript would have a very limited usefulness with nor theoretical neither practical implications and appears as an opinion paper instead of being a research paper.\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? No",
"responses": []
}
] | 1
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https://f1000research.com/articles/10-1066
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https://f1000research.com/articles/11-368/v1
|
30 Mar 22
|
{
"type": "Research Article",
"title": "Burnout and work satisfaction are differentially associated in gastroenterologists in Germany",
"authors": [
"Charles Christian Adarkwah",
"Joachim Labenz",
"Oliver Hirsch",
"Charles Christian Adarkwah",
"Joachim Labenz"
],
"abstract": "Background: Burnout in the field of gastroenterology is an under-researched phenomenon. So far, only a few studies have dealt with this topic. There are large geographical variations in burnout rates with 16–20% of gastroenterologists in Mexico and Germany being at risk or having burnout, 30–40% in the United Kingdom, and 50–55% in South Korea, Canada, and the USA. The investigation of differential associations of burnout with important factors in gastroenterologists leading to tailored therapy recommendations is lacking. Therefore, we investigated the associations between work satisfaction and burnout in this specialization.\nMethods: We distributed an electronic survey to gastroenterologists organized mainly in the Federal Organization of Gastroenterology in Germany (the BVGD - Bundesverband Gastroenterologie Deutschland). The Maslach Burnout Inventory (MBI) and the Work Satisfaction Questionnaire (WSQ) were examined regarding their postulated internal structure in our sample of gastroenterologists. Canonical correlations were performed to examine the association between work satisfaction and burnout in endoscopy physicians.\nResults:\nAn acceptable model fit was shown for both the MBI and the Work Satisfaction Questionnaire. The canonical correlation analysis resulted in two statistically significant canonical functions with correlations of .62 (p<.001) and .27 (p<.001). The full model across all functions was significant (χ2 (18) = 386.26, p<.001). Burden, personal rewards, and global item regarding the job situation were good predictors for less exhaustion, while patient care and professional relations were good predictors for personal accomplishment. This supports the recognition of burnout as being a multidimensional construct which has to be thoroughly diagnosed.\nConclusions: Specific interventions should be designed to improve symptoms of burnout in endoscopy physicians according to their individual complaints as burnout is a multidimensional construct. Differential interventions should be offered on the basis of our study results in order to alleviate the issue of work satisfaction and burnout in endoscopy physicians.",
"keywords": [
"work satisfaction",
"risk of professional burnout",
"endoscopy",
"correlation of data",
"factor analysis"
],
"content": "Introduction\n\nGastroenterology is a part of internal medicine. Unlike many other parts of internal medicine, it combines both cognitive aspects of medicine and medical interventions, i.e. endoscopy. The vast majority of gastroenterologists perform procedures, e.g. colonoscopy, endoscopic retrograde cholangiopancreatography or liver biopsy. These procedures have a potential risk of complications. They imply the risks of adverse events, missed diagnoses or misdiagnoses. In essence, this field can be compared to surgery regarding procedural stresses, in contrast to non-procedure based internal medicine subspecialties.1 Important insights regarding burnout in gastroenterology can be concluded from examining both interventional and non-interventional gastroenterology.1 Poor job satisfaction is an increasing issue in physicians in Germany. It is well known that low work satisfaction as well as high levels of stress can lead to symptoms of burnout2 that have been noticed in up to 45% of physicians.3 High levels of burnout can have negative effects on physicians’ health status, job performance, and patient satisfaction.4 Burnout in the field of gastroenterology is an under-researched phenomenon. So far, only a few studies have dealt with this topic.\n\nEndoscopy personnel should receive more recognition, their work environment should be improved, and they should have better job promotion.5 In their systematic review regarding the prevalence of burnout in gastroenterologists, Ong et al. found work volume, heterogeneous age groups, and female gender to be the most frequently reported risk factors for higher levels of stress and burnout.6 Gleeson et al. found significant stress levels in 20% of UK gastroenterologists which was associated with impaired health and suboptimal patient care.7 Excessive work was found to be the main cause of high stress, also working conditions beyond control and conflict. Women were more susceptible to stress. Happiness with work was an important protective factor, relief from some duties and mentoring were perceived as possible solutions. Overall burnout prevalence in UK gastroenterology trainees measured by the MBI was 35.3% with more than half of the participants experiencing emotional exhaustion.8 High workload, inadequate staffing levels, and interpersonal problems with colleagues were the most prominent stressors. In a sample of 411 Mexican gastroenterologists, an overall burnout prevalence of 26.3% was observed. Lack of support in case of complications, frequent reprimands from superiors, nonmedical duties during work, harassment/workplace violence were important factors associated with burnout.4 Half of gastroenterologists in a survey in the USA reported burnout measured by the Maslach Burnout Inventory (MBI). Important factors associated with burnout were female gender, younger age, childless or younger children.9 An international survey amongst 770 endoscopy trainees from 63 countries revealed a burnout rate of 18.8% which was measured with a single-item burnout scale. There was a positive correlation between burnout and anxiety severity.10 Gastroenterologists, Surgeons, Radiologists, and Oncologists working as hospital consultants took part in a survey regarding burnout and psychiatric morbidity.11 Radiologists had lower personal accomplishment scores, on all other scales of the MBI there were no significant differences. Feeling overloaded, and its effect on home life, feeling poorly managed and resourced, and dealing with patients’ suffering were associated with burnout. Problematic relationships with patients, relatives, and staff, low satisfaction with professional status/esteem, and low intellectual stimulation, younger than 55 years of age, and being single were all associated with burnout. Furthermore, those consultants who considered themselves to be not adequately trained in communication and management skills were also associated with burnout. Autonomy and self-management skills could be approaches for improvement. The development of standards assessing the performance of physicians judged without their participation undermines professional morale and may further increase the risk of burnout.11This is further emphasized by Barnes et al. who cite results which show that young gastroenterologists are at higher risk of developing burnout.12 Stress and burnout levels were moderately elevated in gastroenterologists, and it was demonstrated that younger interventional gastroenterologists with fewer years of experience showed higher stress and burnout levels. This might be caused by the complexity of procedures and by the fear of misinterpreting important findings.1 In a previous publication of our representative sample of German gastroenterologists we were able to demonstrate relevant differences regarding burnout risk and job satisfaction. Younger physicians had significantly higher depersonalization and exhaustion scores with almost medium and small effect sizes. Those having a higher position in the clinic had higher accomplishment scores in the Maslach Burnout Inventory (MBI).\n\nPhysicians with more years of work were more satisfied in terms of patient care. Nevertheless, 17 % had high exhaustion scores, about 30% of our sample showed high depersonalization scores, and approximately half revealed low personal accomplishment scores. This altogether results in a higher general burden among German gastroenterologists.13\n\nTo the best of our knowledge, no studies for the German setting are available to date examining differential associations between burnout and work satisfaction in physicians working in endoscopy units. With this study, we aim to investigate these differential associations and to extract predictors for burnout in the area of work satisfaction which can inform the design of future interventions.\n\n\nMethods\n\nThe design and sample recruitment are already described in a previous publication.14 The description is presented again here. We performed an online survey using the platform Limesurvey Version 3 for research institutions, universities and other educational institutions. Written informed consent was obtained from all individual participants included in the study. Physicians were queried about their baseline demographic variables, work satisfaction and their risk of burnout.\n\nThis survey was performed among gastroenterologists in Germany between January and April 2019. All members of the Federal Association of Gastroenterology in Germany (BVGD – Bundesverband Gastroenterologie Deutschland e.V.) were invited to take part in the study. The vast majority of physicians working in the field of gastroenterology, i.e. from residents to department heads in clinics, as well as physicians in private practice, hold a membership in this organization (n=3142). Participation in the survey was voluntary, anonymized and not incentivized.\n\nThe survey was comprised of an invitation with a detailed study description, an informed consent form and the study questionnaire. The German versions of the Work Satisfaction Questionnaire (WSQ-D) and the Maslach Burnout Inventory (MBI-D) were used in the study. Members of the BVGD received an email invitation to participate and a link to the study was also published on the BVGD website. After eight weeks a reminder to participate in the study was sent to all members. The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the data protection commissioner of the University of Siegen and the Ethics Committee of the University of Essen Medical School (16-7125-BO). Informed written consent was given by all participants.\n\nThe Work Satisfaction Questionnaire is comprised of 17 items to be scored on a seven-point scale from “1 – very dissatisfied” to “7 – very satisfied”15,16 and was also described in a previous publication.14 The questionnaire was constructed based on the main components of work satisfaction which were identified by qualitative research conducted by the Society of General Internal Medicine Career Satisfaction Study Group.17 The items of the questionnaire address satisfaction with overall quality of care, current income, type of payment mechanism, respect and prestige, enjoyment of work, continuing medical education opportunities, intellectual stimulation at work, autonomy to refer patients to a specialist, autonomy in treating patients, administrative burden, workload and work stress, time for family, friends or leisure, relationships with patients, peers, nurses and other non-medical staff, and job satisfaction in general. It has a five-factor structure, comprised of patient care (four items, Cronbach’s-α = .76), burden (four items, α = .79), income-prestige (three items, α = .83), personal rewards (three items, α = .71), and professional relations (two items, α = .66). Furthermore, a global item asks for the respondent’s satisfaction with their current job situation. This item correlates with the subscale scores from .39 – .71.15 The instrument was shown to be sensitive to structural changes in healthcare systems.18 The five-factor structure was supported in our study of GPs in a rural area of Germany by a confirmatory analysis.19\n\nWe used the German version of the Maslach Burnout Inventory (MBI) to assess occupational burnout which was also described in another previous publication.20 The MBI is designed in order to measure an enduring state of experiencing burnout, an assumption that is borne out by the stability of its scores over time.21 The MBI is comprised of 22 items, each scored on a seven-point scale from “0 – never” to “7 – every day”. It consists of three subscales, namely “emotional exhaustion” (nine items) which measures exhaustion at work, “depersonalization” (five items), which measures emotional distance to others and loss of empathy, and “personal accomplishment” (eight items), which measures competence and a positive attitude towards work. The three-factor structure was confirmed: the Cronbach’s-α of the emotional exhaustion scale was .85, of the personal accomplishment subscale .71, and of the depersonalization subscale just .48.22 Other studies found higher internal consistencies for this subscale with Cronbach’s-alphas of .69 and .86, respectively.23,24 Convergent and discriminant validity of the MBI could be demonstrated. The three-factor structure was also supported by our study of German GPs.19\n\nThe following statistical measures were also applied in a previous publication.20 We used chi-square tests with effect size Cramér’s V for comparing categorical variables and the Welch test with effect size Cohen’s d for comparing independent groups.25,26\n\nWe conducted confirmatory factor analysis with the R package lavaan 0.6-727 to examine the hypothesized factorial structures of the MBI and the Work Satisfaction Questionnaire in our sample of gastroenterologists. We used the robust Unweighted Least Squares Estimator (ULSMV), as this estimation method makes no distributional assumptions.27,28 Different model-fit statistics were calculated. The χ2/df ratio is a badness-of-fit-index as smaller values indicate a better fit.29 Values between 2 and 5 signal an acceptable model fit.30,31 The Root Mean Square Error of Approximation (RMSEA) is a population-based index that relies on the noncentral χ2 distribution. It can be regarded as an “error of approximation” index because it assesses the extent to which a model fits reasonably well in the population.32 Values ≤ .08 are considered to indicate an adequate model fit.33 The standardized root mean square residual (SRMR) was calculated to measure the mean absolute value of covariance residuals.34 Values below .10 indicate a good model fit.35 The Comparative Fit Index (CFI) and the Tucker Lewis Index (TLI) were not considered as it was observed that they were sensitive to models with more variables than ours.36 The resulting items and scales were examined by parameters based on classical test theory like Cronbach’s-α, discriminatory power, and average intercorrelations. Omega coefficients for the applied scales were also computed using R packages psych 2.0.7 (RRID:SCR_021744) and GPArotation 2014.11-1 as they have known advantages over Cronbach’s-α.37\n\nWe used canonical correlation analysis to examine the association between work satisfaction and burnout in gastroenterologists.38 According to previous findings we labelled the five scales and the overall item of the Work Satisfaction Questionnaire as independent variables and the three scales of the Maslach Burnout Inventory as dependent variables. The subject to variable ratio was 76 to 1 and therefore much higher than the recommended 10 to 1 ratio.39 R packages yacca 1.4 (RRID:SCR_021746) and yhat 2.0-3 were used for calculations. All calculations were performed using R version 4.0.2 (R Project for Statistical Computing, RRID:SCR_001905). The underlying data can be found at Figshare.40\n\n\nResults\n\nReferring to the whole population of BVGD members, 22% of them took part in our study, resulting in a sample of 683 gastroenterologists. Of those, 508 were male (74.4%). The sample characteristics were compared to membership characteristics of the Federal Association of Gastroenterology in Germany as these members are considered to be a representative sample for the population of gastroenterologists in Germany. The single-sample chi-square test shows a significant result (χ2 (1) = 18.67, p = .0000155), but the effect size Cramér’s V signals a small effect with .06. In conclusion, our sample should still be representative regarding gender. The mean age of the participants was 48.3 years (SD 9.1), with a median of 48 years, a minimum age of 27 and a maximum age of 75 years. Our sample was significantly older than the population (mean 44.4, SD 9.4; Welch-Test (df = 1006), t = -10.09, p < .001). Cohen’s d signals almost a medium effect with 0.42. This might be explained by an age effect. Members young in age and residents who are early in their training in this field have not yet gained endoscopy experience and do not fulfil inclusion criteria, because we focus explicitly on physicians working in endoscopy units.\n\nParticipants were working in the field of endoscopy on average for 16.5 years (SD 9.5). Most of the physicians were specialists in internal medicine and gastroenterology (n = 547, 80.1%). Exactly 500 (73.2%) were working in a hospital while 183 (26.8%) were working in practice. In the population, 94.3% are working in a hospital while 5.7% are working in practice. In comparison with the population, significantly more physicians in our sample work in practice (χ2 (1) = 294.58, p < .0001). The effect size of Cramér’s V signals a medium effect with .27.\n\nWe tested the hypothesized three-factor structure in our sample of gastroenterologists. The confirmatory factor analysis with the robust ULSMV estimation method showed an acceptable model fit: χ2/df = 4.45, RMSEA = .071, SRMR = .072.\n\nOne item has a factor loading under the recommended cut-off value of .30.32 It is item four (“I can easily understand how my colleagues feel about things”) of the factor personal accomplishment with a loading of .07. All other items have loadings between .35 and .88.\n\nIntercorrelations of factors are satisfactory with emotional exhaustion correlating with depersonalization/loss of empathy by r = .73 and with personal accomplishment by r = -.48 while depersonalization/loss of empathy correlates with personal accomplishment by r = -.41.\n\nThe Cronbach’s-α coefficient of the emotional exhaustion subscale was .88, the omega coefficient was .88, and the average inter-item correlation was .45. The discriminatory power of the items ranged from .46 – .79. The Cronbach’s-α coefficient of the depersonalization/loss of empathy subscale was .75, the omega coefficient was .77, and the average inter-item correlation was .38. Discriminatory power of the items ranged from .27 – .67. The Cronbach’s-α coefficient of the personal accomplishment subscale was .77, the omega coefficient was .78, and the average inter-item correlation was .30. Discriminatory power of the items ranged from.23 (item four) – .59. All values can be classified as satisfactory to high except for the low discriminatory power of item four.\n\nThe mean of the scale emotional exhaustion was 16.5 (SD 10.1) with a median of 14, a minimum of 0, and a maximum of 48. In the main its distribution deviated significantly from a normal distribution: Shapiro-Wilk test, p < .0001; Skewness, p = .0001 (right-skewed); Kurtosis, p = .48. According to normative values published in Soler et al.,41 311 physicians (45.5%) had a low level of emotional exhaustion, 259 (37.9%) an average level, and 113 (16.6%) reported a high level of emotional exhaustion.\n\nThe mean of the scale depersonalization/loss of empathy was 6.8 (SD 5.7); Huber’s M estimator was 6.2 with a median of 5, a minimum of 0, and a maximum of 28. Its distribution mainly deviated significantly from a normal distribution: Shapiro-Wilk test, p < .0001; Skewness, p < .0001 (right-skewed); Kurtosis, p = .002. According to normative values published by Soler et al.,41 349 physicians (51.1%) had a low level of depersonalization/loss of empathy, 145 (21.2%) an average level, and 189 (27.7%) reported a high level of depersonalization/loss of empathy.\n\nThe mean of the scale for personal accomplishment was 32.5 (SD 8.3), with a median of 33, a minimum of 0, and a maximum of 48. Its distribution mainly deviated from a normal distribution: Shapiro-Wilk test, p < .0001; Skewness, p < .0001 (left-skewed); Kurtosis, p = .07. According to normative values published by Soler et al.,41 154 physicians (22.5%) had a high sense of personal accomplishment, 161 (23.6%) an average level, and 361 (53.9%) reported a low level of personal accomplishment. This result might underestimate the sense of personal accomplishment of gastroenterologists as 100 (14.6%) physicians were just below the cut-off in the range of 31–33 points.\n\nWe tested the hypothesized five-factor structure in our GP sample. The confirmatory factor analysis with the robust ULSMV estimation method showed an acceptable model fit: χ2/df = 4.97, RMSEA = .076, SRMR = .055.\n\nAll items had factor loadings over the recommended cut-off value of .30.32 The range was between .38 and .89.\n\nIntercorrelations of factors were heterogenous. The majority were in the moderate range while the intercorrelations between factors personal rewards, patient care, and professional relations were high (.83 – .94) (Table 1).\n\nThe Cronbach’s-α coefficient of the patient care subscale was .86; the omega coefficient was .86, and the average inter-item correlation was .60. Discriminatory power of the items ranged from .65 – .76. The Cronbach’s-α coefficient of the burden subscale was .86; the omega coefficient was .87, and the average inter-item correlation was .61. Discriminatory power of the items ranged from .57 – .79. The Cronbach’s-α coefficient of the income-prestige subscale was .69; the omega coefficient was .73, and the average inter-item correlation was .43. Discriminatory power of the items ranged from .44 – .63. The Cronbach’s-α coefficient of the personal rewards subscale was .81; the omega coefficient was .81, and the average inter-item correlation was .59. Discriminatory power of the items ranged from .62 – .69. The Cronbach’s-α coefficient of the professional relations subscale was .75, and the omega coefficient was .75; both items correlated by r = .60.\n\nThe mean of the scale for patient care was 21.8 (SD 4.7) with a median of 23, a minimum of 4, and a maximum of 28. Its distribution deviated from a normal distribution: Shapiro-Wilk test, p < .0001; Skewness, p < .0001 (left-skewed); Kurtosis, p < .0001 (leptokurtic). There were no significant differences in comparison with our GP sample (Welch-Test, t(120) = 0.18, p = .86, Cohen’s d = 0.02).19\n\nThe mean of the scale for burden was 15.4 (SD 2.7) with a median of 16, a minimum of 9, and a maximum of 21. In the main its distribution corresponded to a normal distribution: Shapiro-Wilk test, p = .08; Skewness, p = .006 (right-skewed); Kurtosis, p = .0005 (platykurtic). Our GP sample reported a significantly higher satisfaction in this area with a medium effect size (Welch-Test, t(115) = -5.54, p < .001, Cohen’s d = 0.56).19\n\nThe mean of the scale for income-prestige was 13.4 (SD 3.7) with a median of 14, a minimum of 3, and a maximum of 21. In the main its distribution deviated from a normal distribution: Shapiro-Wilk test, p < .0001; Skewness, p = .0001 (left-skewed); Kurtosis, p = .08. Our GP sample reported significantly higher satisfaction in this area with a medium effect size (Welch-Test, t(126) = -6.10, p < .001, Cohen’s d = 0.56).19\n\nThe mean of the scale for personal rewards was 15.3 (SD 4.0) with a median of 16, a minimum of 3, and a maximum of 21. Its distribution deviated from a normal distribution: Shapiro-Wilk test, p < .0001; Skewness, p < .0001 (left-skewed); Kurtosis, p < .0001 (leptokurtic). Our GP sample reported significantly higher satisfaction in this area with almost a medium effect size (Welch-Test, t(138) = -5.38, p < .001, Cohen’s d = 0.45).19\n\nThe mean of the scale for professional relations was 10.7 (SD 2.5) with a median of 11, a minimum of 2, and a maximum of 14. Its distribution deviated from a normal distribution: Shapiro-Wilk test, p < .0001; Skewness, p < .0001 (left-skewed); Kurtosis, p < .0001 (leptokurtic). Our GP sample reported significantly higher satisfaction in this area with a small effect size (Welch-Test, t(122)= -2.56, p = .01, Cohen’s d = 0.24).19\n\nThe canonical correlation analysis resulted in three canonical functions with canonical correlations of .62 (p < .001), .27 (p < .001), and .10 (p = .12). The full model across all functions was significant (χ2 (18) = 386.26, p < .001).42 The first two functions are statistically significant and the first function accounts for a considerable amount of variance (38% versus 7.5%, respectively). It is debated if squared multiple correlations are representing the amount of shared variance between two variable sets.43 Cramer and Nicewander44 proposed the average squared multiple correlation as the measure of variance accounted for which in our case would result in a shared variance of 15.5% and is according to standards in the behavioural and life sciences still in the acceptable range.45\n\nFunction 1 The first criterion canonical variate is mainly characterized by exhaustion (r=-.96) which explains 92% of the variance of this variate (Table 2). There is also a higher cross-loading of depersonalisation/lack of empathy which has its highest value in function 3, which did not reach significance. Burden, personal rewards, and the global item regarding the job situation seem to be particularly good predictors for less exhaustion, as exhaustion has a negative correlation with the first criterion canonical variate (Table 2). This means that the more satisfied the gastroenterologists were with burden, personal rewards, and with their job situation in general, the less exhausted they felt. The low standardized function coefficients of income-prestige and professional relations and their relatively high correlations with the first canonical variate indicates that the variance of this variable is explained by the other variables. The predictor canonical variate is characterized by burden, personal rewards, and the global item regarding the job situation in general (Table 3). Prestige displays a pattern of cross-loadings with similar correlations with functions 1 and 2 but a slightly higher value in function 1 (Tables 3 and 4). Figure 1 displays the structure correlations (loadings) of the WSQ scales on the first predictor canonical variate and of the structure correlations (loadings) of the MBI scales on the first criterion canonical variate and visualizes the differential loading patterns and associations between job satisfaction and burnout variables in function 1.\n\nBlack bars correspond to positive correlations; white bars correspond to negative correlations.\n\nFunction 2 Patient care and professional relations seem to be good predictors for personal accomplishment. The predictor canonical variate is characterized by patient care and professional relations and the above-mentioned cross-loading of income/prestige (Table 4). The second criterion canonical variate is characterized mainly by personal accomplishment (r = .76), which explains 57% of the variance of this variate (Table 5). Figure 2 displays the structure correlations (loadings) of the WSQ scales on the second predictor canonical variate and of the structure correlations (loadings) of the MBI scales on the second criterion canonical variate. It visualizes the differential loading patterns and associations between job satisfaction and burnout variables in function 2. In relation to the other variables there is also a higher loading of personal relations, but this WSQ scale has a higher loading on the first predictor canonical variate.\n\nThe third canonical correlation was low not significant, with .10 (p = .12). Therefore, the third function should not be interpreted.\n\n\nDiscussion\n\nWe could demonstrate acceptable model fits in confirmatory factory analyses regarding the measurement of work satisfaction and burnout in gastroenterologists. These results are of importance, as the theoretical structure of questionnaires has to be confirmed in special subpopulations before respective subscores can be calculated.32\n\nWe were able to confirm the three-factor structure of the Maslach Burnout Inventory in our sample. Item four (“I can easily understand how my colleagues feel about things”) of the personal accomplishment subscale had a factor loading < .30 and might be eliminated in this special subgroup. The internal consistency of the exhaustion subscale was high, while the internal consistencies of the depersonalization/loss of empathy and personal accomplishment subscales were satisfactory. According to norms published by Soler et al.,41 16.6% of gastroenterologists could be classified as showing high emotional exhaustion, 27.7% high depersonalization/loss of empathy, and 53.9% were showing low personal accomplishment, although the last result might be misleading due to 15% being close to the cut-off value. Nevertheless, qualitative studies should evaluate the reasons for these numbers. Our results contradict1,46 but also corroborate earlier studies.12 In the systematic review of Ong et al. median values for emotional exhaustion, depersonalization, and low personal accomplishment were 25.7%, 25.6%, and 45.1%, respectively. They observed geographical variations in burnout rates with 16–20% of gastroenterologists in Mexico and Germany being at risk or having burnout, 30–40% in the United Kingdom, and 50–55% in South Korea, Canada, and the USA. The definition for burnout, its operationalisation, and cut-off values within the same instruments varied across studies; standardisations should be implemented at each level for better comparability of study results.47 A three-fold definition of burnout based on a subscale algorithm within the MBI is proposed by Ong et al.6 However, it should be critically noted that it is unclear to what extent the cut-off values mentioned there are valid for the special population of gastroenterologists.\n\nAmong the most important measures for improving their situation were taking care of themselves and delegating administrative tasks. Higher burnout scores were associated with long working hours, especially in surgeons, and in physicians early in their career.48\n\nThe five-factor structure of the Work Satisfaction Questionnaire was also confirmed. Internal consistencies were satisfactory and comparable with those of the original publications,15,18 except for the subscale “income-prestige” which has a Cronbach’s-α coefficient of .69 and an omega coefficient of .73. The Spearman intercorrelations between the subscale scores were between .24 and .65 and are close to those listed in the original publications. In our confirmatory analyses, factor intercorrelations between the factors, personal rewards, patient care, and professional relations, were high, which shows a possible overlap between these subconstructs in our sample. Work satisfaction should be regarded as a multi-dimensional construct which contains different aspects with different internal structures in special subsamples.14\n\nWe applied canonical correlation analysis to examine the association between work satisfaction and burnout in gastroenterologists. The first canonical function revealed that burden, personal rewards, and the global item regarding the job situation were good predictors for less exhaustion. The second canonical function showed that patient care and professional relations were good predictors for personal accomplishment. Our results corroborate several other findings. Feeling of support from colleagues had a protective effect.4 Job satisfaction in health care had a relevant association to interprofessional teamwork.49 In a previous study with primary care physicians, burden and the global item in the WSQ were good predictors of emotional exhaustion, while patient care, personal rewards and professional relations were good predictors of depersonalization/lack of empathy.14 These different results in different physician groups suggest differential associations within physician subgroups which have consequences for interventions.\n\nOur results have important implications for the clinical management of burnout in gastroenterologists. Burnout is a multidimensional construct, which should be examined in a differentiated way with all its facets. Depending on the severity of the manifestations on the different factors, differentiated interventions should be designed and individually planned. As our results reveal, a gastroenterologist scoring high on emotional exhaustion would need a different intervention, as there are different associations with work satisfaction than for an gastroenterologists scoring low on personal accomplishment. Therefore, the results of our study could be used to design specific interventions to improve circumscribed symptoms of burnout. To date, several global interventions have been developed to reduce job stress and the risk of burnout in gastroenterologists. A psychoeducational intervention reduced burnout and anxiety symptoms in physicians in comparison with a control group, but other health and habit-related outcomes were unaffected, as they were measured just seven days after the end of the intervention.50 The effects of problem-focused coping become evident as one engages in strategies to change the stressful situation. This was associated with lower levels of burnout, distress, and higher levels of job-related self-efficacy. Problem-focused coping strategies were more likely to be used by female gastroenterologists. Higher burnout scores were associated with emotion-focused coping.51 The new specific interventions to be developed must first undergo an evidence-based evaluation process before they can be applied in individual cases. Long-term studies must then additionally show whether any effects remain stable. Quality in endoscopy is a complex construct. Accordingly, evaluation of such a complex construct is difficult, as interactions between endoscopy personnel, patients, cultural, and societal perspectives must all be considered. One can imagine that work satisfaction and burnout symptoms in endoscopy personnel can have a decisive influence on these subtle processes and consequently both can impact quality in endoscopy.52 Increased job stress and burnout might result in suboptimal care, a higher rate of medical errors, and earlier retirement.1 Distress negatively affects cognitive functioning and clinical decision-making53 and puts patients at risk.54 By addressing these areas, a contribution is made to improving care in the field of gastroenterology.\n\nOur study has limitations that should be considered. Our response rate was 22% and could therefore have been higher, to gain a more complete understanding of the associations between work satisfaction and burnout. Nevertheless, this response rate is almost identical4,7 or is considerably higher than in other studies in this area.1,9,51 The survey was sent to members of a professional society which may not fully represent the population of gastroenterologists. We collected cross-sectional data based on self-reports which always have to be interpreted with caution. We had to refer to reference numbers from other specialties, mainly primary care, as German norms in work satisfaction and burnout are lacking in gastroenterology, but as these were European data, we think that they are more comparable than existing American norm data.\n\n\nConclusions\n\nSpecific interventions should be designed to improve symptoms of burnout in gastroenterologists according to their individual complaints as burnout is a multidimensional construct. For example, gastroenterologists scoring high in emotional exhaustion need a different intervention than gastroenterologists scoring low in personal accomplishment, as each group of respondents has different associations regarding work satisfaction. Consequently, differential interventions should be offered on the basis of our study results in order to alleviate the issue of work satisfaction and burnout in endoscopy physicians.\n\n\nData availability\n\nFigshare: Underlying data for ‘Burnout and work satisfaction are differentially associated in gastroenterologists in Germany’. https://doi.org/10.6084/m9.figshare.12144738.v6.40\n\nFigshare: STROBE checklist for ‘Burnout and work satisfaction are differentially associated in gastroenterologists in Germany’. https://doi.org/10.6084/m9.figshare.12144738.v6.40\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nConsent\n\nWritten informed consent for publication of the participants’ details was obtained from the participants.",
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Publisher Full Text\n\nPanagioti M, Geraghty K, Johnson J, et al.: Association Between Physician Burnout and Patient Safety, Professionalism, and Patient Satisfaction: A Systematic Review and Meta-analysis. JAMA Intern. Med. 2018; 178(10): 1317–1331. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "135853",
"date": "11 May 2022",
"name": "Amritpal Pali Hungin",
"expertise": [
"Reviewer Expertise Primary/Secondary interface care",
"medical professionalism",
"gastroenterology",
"barriers to evidence based clinical care"
],
"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 an important piece of research in an increasingly important topic. Burnout and a lack of work satisfaction amongst clinicians is an international issue and is compromising patient care as well has causing health harm to clinicians themselves. In an area of ever increasing technological advances, increased patient and public expectations and the limited availability of health resource the situation is likely to worsen unless clearly recognised and accepted by the medical profession and the health authorities. Timely solutions need to be suggested.\nThis manuscript captures the situation well, highlighting the relevant international literature and researching the situation in Germany amongst gastroenterologists using appropriate and accepted assessment tools. The authors suggest strategies for responding to the different, individual dimensions contributing to burnout as based on assessment tools and analysed data.\nThe study design is appropriate for the research question, which is clearly set out: a study of the burnout and work satisfaction amongst gastroenterologists in Germany. The sampling frame is appropriate - the official professional group of gastroenterologists in Germany. Whilst the conventionally measured response rate might be considered low by some (22%) this is reasonable for such surveys and the overall numbers of respondents was high (683 gastroenterologists). The electronic survey method used is appropriate for a large, widely dispersed population. The responders were reasonably representative of the target population even though the authors recognise that the respondents’ age was somewhat skewed upwards.\nThere is sufficient detail of methods and analysis to allow replication by others wishing to conduct similar studies and the statistical analysis appears comprehensive, even if somewhat complex to me personally. The interpretation of the data is appropriate although it is likely to be better understood by someone familiar with the questionnaires and their sub-domains. The source data and the results match up well.\nThe conclusions are thoughtfully drawn. In addition to providing data on burnout and work satisfaction amongst this group in Germany, there are suggestions about the need to delineate and to tailor remedial actions based on specific subset findings from the survey. This is an important point in guiding interventions to help gastroenterologists who are struggling – the need to use problem focussed solutions to enhance coping strategies.\nThis research represents an important step in better understanding the field of burnout and work satisfaction amongst gastroenterologists and I hope it will be more widely disseminated. It adds to the literature from other fields.\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": [
{
"c_id": "8315",
"date": "06 Jun 2022",
"name": "Oliver Hirsch",
"role": "Author Response",
"response": "Thank you very much for the kind consideration of our work. We really appreciate this."
}
]
},
{
"id": "129523",
"date": "30 May 2022",
"name": "Klaus Weckbecker",
"expertise": [
"Reviewer Expertise Family doctor",
"General practitioner"
],
"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\nWhether physicians are satisfied with their work and feel comfortable in their working environment is an important aspect. Dissatisfaction with the working conditions and even symptoms of burnout reduce the quality of the physician's performance. Thus, dissatisfaction with working conditions and the presence of a burnout syndrome endanger not only the health of the physicians concerned, but also the health of the patients entrusted to their care.\nThe authors address this very interesting topic using the example of the specialist group of gastroenterologists in Germany. These doctors work in their own practices and are thus active both as business owners and as physicians. Another special feature of outpatient gastroenterologists in Germany is that they are active both interventively with endoscopies and in the long-term care of patients with gastrointestinal diseases.\nThus, this work addresses a particularly interesting issue with high relevance for the health of practicing physicians as well as for the patients entrusted to their care.\nThe authors provide an excellent summary of the current state of knowledge, taking into account the international literature.\nThe chosen study design is appropriate to the research question. The chosen methodology of a cross-sectional survey by an online questionnaire is appropriate, the response rate and number of participants is good. Nevertheless, with this methodology there is always the risk that certain subgroups participated in the survey in excess. Here, for example, it would be conceivable that gastroenterologists in particular, who feel overwhelmed, frequently participate in the study. This is a weakness of the study that cannot be avoided due to the methodology, but which the authors also clearly state. Nevertheless, the results are highly relevant and should give rise to further research activities in this field. It would be particularly interesting to examine whether satisfaction with working conditions in other countries and / or under other economic conditions differs significantly from the data collected here.\nThis interesting work can thus be the basis for further research projects, but also the trigger for discussions and reflections on our working conditions as physicians.\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": "8318",
"date": "06 Jun 2022",
"name": "Oliver Hirsch",
"role": "Author Response",
"response": "Thank you very much for the kind consideration of our work. We really appreciate this. We have extended our evaluations of burnout to include the tri-criteria approach recommended by Ong et al (2021): (1) EE≥27 together with DP≥13, (2) EE≥27 together with PA≤31, and (3) EE>27 together with DP>10 and PA<33."
}
]
}
] | 1
|
https://f1000research.com/articles/11-368
|
https://f1000research.com/articles/10-1038/v1
|
12 Oct 21
|
{
"type": "Method Article",
"title": "Deep supervised hashing for gait retrieval",
"authors": [
"Shohel Sayeed",
"Pa Pa Min",
"Thian Song Ong",
"Pa Pa Min",
"Thian Song Ong"
],
"abstract": "Background: Gait recognition is perceived as the most promising biometric approach for future decades especially because of its efficient applicability in surveillance systems. Due to recent growth in the use of gait biometrics across surveillance systems, the ability to rapidly search for the required data has become an emerging need. Therefore, we addressed the gait retrieval problem, which retrieves people with gaits similar to a query subject from a large-scale dataset. Methods: This paper presents the deep gait retrieval hashing (DGRH) model to address the gait retrieval problem for large-scale datasets. Our proposed method is based on a supervised hashing method with a deep convolutional network. We use the ability of the convolutional neural network (CNN) to capture the semantic gait features for feature representation and learn the compact hash codes with the compatible hash function. Therefore, our DGRH model combines gait feature learning with binary hash codes. In addition, the learning loss is designed with a classification loss function that learns to preserve similarity and a quantization loss function that controls the quality of the hash codes Results: The proposed method was evaluated against the CASIA-B, OUISIR-LP, and OUISIR-MVLP benchmark datasets and received the promising result for gait retrieval tasks. Conclusions: The end-to-end deep supervised hashing model is able to learn discriminative gait features and is efficient in terms of the storage memory and speed for gait retrieval.",
"keywords": [
"Gait Retrieval",
"Deep Supervised Hashing",
"Convolutional Neural Network",
"Binary codes"
],
"content": "Introduction\n\nGait recognition is perceived as the most promising biometric approach1-3 among behavioural biometric approaches, especially because of its efficient applicability in surveillance systems. However, gait recognition and identification tasks are becoming increasingly difficult due to the large-scale images and videos generated from surveillance systems. To ease the burden of real-world large dataset problems, researchers have applied person re-identification and retrieval approaches for surveillance video analysis or identify the person of interest. The re-identification approach finds the targeted person given by a query image from different cameras and a different time.4 Similar to re-identification, gait retrieval is also used to retrieve people with similar gait from a large-scale dataset given by the query subject. In contrast, gait re-identification considers the one-to-one problem with the top-ranked item within the dataset and from the dataset, and the retrieval normally considers all the top items from the ranked list (from one to many). The retrieval problem is addressed in many biometric applications, such as face retrieval and other large-scale content searches, because of the efficiency in tracking and locating similar content.5\n\nTo retrieve visually or semantically similar content, the traditional approach is to search for similar contents by ranking the contents from the database based on the similarity with the query features, and the nearest contents are returned. Nevertheless, this approach affects the computation time and memory of large-scale databases. To address these speed and storage issues, hashing methods have been proposed for use in different text, video, and image retrieval tasks.6\n\nThis paper presents the deep gait retrieval hashing (DGRH) model to address the gait retrieval problem for large-scale datasets. Due to the recent growth in gait data across surveillance systems, the ability to rapidly search for the required data has become an emerging need. Linearly searching for real-value features may affect the computation time and memory storage, so the approximate nearest neighbour (ANN) search approach via hashing has attracted increasing attention. The goal of the hashing approach is to represent the input images as hash codes and learn the similarity of the learned binary codes. Similarity searching can be efficiently implemented when the high-dimensional data are transformed into compact binary codes with hashing functions. Our proposed method used the supervised hashing method with a deep convolutional network. The supervised hashing approach takes label information of each gait to generate binary codes. To extract the discriminant features from the input gait, we use a deep convolutional neural network instead of manually extracting the features. We use the convolutional neural network (CNN) to capture the semantic gait features for feature representation and learn the compact hash codes with the compatible hash function. Therefore, our DGRH model is a supervised hashing model that combines gait feature extraction and binary hash code learning. The pipeline for our proposed (DGRH) model includes:\n\n• The sub-network of convolutional layers and pooling layers is used to extract the gait features\n\n• The binary hash codes are generated from the last fully connected layer\n\n• The classification and quantization loss are used to optimize the network and learn the hash function\n\nSimilarity searching can be efficiently implemented with compact binary codes generated with hashing methods. The current hashing methods can be divided into unsupervised and supervised hashing. Unsupervised hashing methods use unlabelled data and only training data to learn the hash function and perform neighbourhood relation clustering in a Hamming space. For example, kernelized locality-sensitive hashing7 uses the random projection of the hash function and constructs the kernel function to perform the similarity search. Liu et al.8 proposed anchor graph hashing to build a neighbourhood graph that learns binary hash codes to map similarities in a Hamming space. Neighbourhood discriminant hashing (NDH)9 utilizes the local discriminant information from the neighbourhood structure so that the data labels can be predicted in a Hamming space.\n\nTo reduce the complexity and perform efficient semantic similarity searching, supervised hashing approaches are practised. Supervised hashing takes advantage of label information, pairwise similarity information, or data point similarity. Liu et al.10 proposed supervised hashing with kernels by using image pairs and converted them into binary code to map the data in Hamming distance. The kernel formulation minimizes the distance between similar pairs and maximizes the distance on dissimilar pairs. Shen et al.11 also introduced supervised discrete hashing, which combines linear classification with the generation of hash codes into a model and addresses supervised hashing problems. Then, Lin et al.12 proposed supervised hashing with a two-step model: binary code learning in the first step and hash function learning in the second step.\n\nThe above papers used manual feature learning, which has limitations on the diversity of the dataset and the performance. Therefore, current researchers utilize the advantages of deep networks, which can extract visual features from raw data with minimal pre-processing. Xia et al.13 introduced a two-step paradigm for supervised hash learning with a convolutional neural network. They pre-processed the input images with a pairwise similarity matrix to give the approximated hash codes for training images and then used a convolutional neural network (AlexNet) for the feature learning of input images as well as for learning the hash codes. However, a CNN has limitations for improving hash code learning, and the one-stage method became the norm of later deep supervised hashing methods. Other researchers proposed deep supervised hashing techniques for different kinds of inputs, such as single data, paired data, and triplet pairs of data. Lai et al.14 proposed a deep hashing architecture with triplet pair images as the input and convolutional layers to extract effective image features. They used the divide and encode module to extract the image features into branches that correspond to each hash code, and then the triplet ranking loss function was used to perceive the similarities. Thereafter, Zhang et al.15 were inspired to use this approach for their person re-identification problem because the optimization of triplet ranking is able to capture the variation differences between the intra-class and inter-class rankings. The supervised hashing of semantic similarity based on data pairs has also received attention because of improvements in the quality of hash coding. The deep hashing network (DNH) proposed by16 uses paired data for image representation and a convolutional neural network for feature extraction. The last layer of the deep network, a fully connected layer, is used to generate binary hash codes. To preserve the similarity between the pairs of images, the pairwise cross-entropy loss is adopted, and the pairwise quantization loss is adopted to control the quality of the hash code. The improved version of pairwise deep hashing is presented in DCH (deep Cauchy hashing), which uses the Cauchy distribution to design the pairwise cross-entropy loss.17 The Cauchy cross-entropy loss is adapted from the Bayesian framework and well designed for the Hamming space retrieval.\n\nTo address the gait retrieval problem, Zhou et al.5 presented the kernel-based semantic hashing method and used the Gaussian kernel function to map the gait data into the hashing function. The learned hashing function is later optimized by the triplet ranking loss, and the binary codes of gait data are stored in a database. To retrieve the given query data, the semantic ranking list is obtained based on the Hamming distance between the query data and the gait database. Rauf et al.18 also proposed deep supervised hashing for gait retrieval using triplet pair gait data. They designed the hash model with a three-channel convolutional neural network sharing the same parameter. The hash layer is added after fully connected layers to generate the hash code. The triplet ranking loss is used for optimization, and the associated ranking list is based on labels. Their method outperformed other traditional methods because of the robustness of the CNN in visual feature learning.\n\nGait representation\n\nAs shown in Figure 1, we use the gait energy image (GEI). The gait energy image is a spatiotemporal gait representation that represents gait features in a single image. GEIs convert a sequence of gait silhouettes into a two-dimensional image that preserves the human motion. GEIs were first introduced by19 to reduce the burden of limited gait training templates. Since the GEI can capture both temporal and spatial information, it has become the most popular gait representation. In addition, GEIs also include information on both the silhouette shape and the dynamic walking motion. GEIs can be obtained by extracting the silhouette of the human and averaging the sequence of silhouettes. The details of computing the gait energy image can be found in.19\n\nProposed deep gait retrieval hashing (DGRH) model\n\nThe idea of similarity preservation in a hashing method is that similar codes are generated from semantically similar data. Therefore, mathematically, the goal of the hash function is to learn the image space X to the mapping with H→:X−11K into the Hamming space. Here, K is the k-bit binary hash code generated from the input image X.\n\nSuppose N training GEI images are given, denoted by xii=iN, and each xi is represented by the dimension feature vector D so that xi ∈ℝD. Therefore, X = [x1,x2,x3,…,xN] ∈ℝD×N. The label matrix Y in N training GEIs is denoted as Y=[y1,y2,y3,…,yN] ∈ℝC×N, and the number of classes is denoted as C. If the ith GEI belongs to the jth class, yij = 1, and if not, yij = 0. Therefore, our proposed hashing method will learn the hash codes hi∈−11K from each input GEI, where K is the length of the binary codes.\n\nAs shown in Figure 2, our proposed model takes the gait energy image (GEI) as the input gait data and extracts the features using the deep convolutional neural network (CNN) presented by.20 The architecture of the CNN is composed of convolutional and pooling layers, a fully connected layer, and a hashing layer; the last layer of the CNN network generates the binary hash code. There are four convolutional layers with different numbers of filters for each layer (16, 32, 64, 128), and the filter size for all layers is 3*3. After each convolutional layer, there is a max-pooling layer with a stride of 2. The first fully connected layer also takes the number of hidden neurons (1024) as the parameter, and the last fully connected layer serves as the fully connected hash (FCH) layer for hash function learning. The detailed architecture of the CNN proposed by20 is shown in Table 1. We used the leaky rectified linear unit (LeakyReLU) activation function for all the layers except the hash layer. To learn the hash function, we used a hyperbolic tangent (tanh) activation function to compress the output of the last fully connected layers to the range of [−1,1]. The tanh function is defined as:\n\nThe tanh activation function maps the data into the range of [−1,1], and the number of neurons (K) for the fully connected layer is the desired length of binary hash codes (such as 16 bits, 32 bits, 64 bits, and so on). The learned hash function from the deep convolutional network is hi∈−11K×N with N GEI images. To calculate the binary hash code (bi) from the output of the hash layer, we utilize the sign(.) function; bi=signhi. Here, the sign(.) function on a vector and a matrix is expressed as\n\nSupervised loss function and optimization\n\nWe introduced the loss function to learn the ability of the hash codes. The designed loss functions measure the similarity-preserving ability of the hash codes. Since the well-learned hash codes have a solid classification ability, we expected that the supervised hash function can generate similar hash codes for the gait inputs with the same label. To preserve the similarity of the hash codes, we used the softmax function, which is a multinomial logistic regression function and suitable for predicting the class labels. The formulation for the softmax function is\n\nHere, we denote Wh as the linear weight vectors that connect the output from the last hash layers, so Wh∈ℝk×N. The softmax linear function for the learned representation hi can be rewritten as\n\nTo minimize the loss across the training sample to further reduce the classification error, we used the cross-entropy loss function. The function of the cross-entropy loss measures the dissimilarity of the predicted label distribution with the true label probability distribution. Therefore, Ŷij is the vector of the predicted label that sample i belongs to class j. The ground truth vector Yij is 1 if i belongs to class j and 0 otherwise. Therefore, the cross-entropy loss for Ŷij and Yij is\n\nTo reduce overfitting and the variance of the network, we introduced L2 regularization terms to generalize the training of the deep network. Here, the regularization term is\n\nwhere λ is the regularization parameter and .F2 indicates the Forbenious norm defined as WlF2=∑i∑iWijL2=WTW. Therefore, the final classification loss for our proposed model is as follows:\n\nQuantization loss\n\nThe real-value features (hi) from the hash layer need to be converted into binary codes to perform the retrieval in the Hamming space. To control the learned hash codes’ quality, we introduced the quantization loss. Discrete optimization of the classification loss function LC is very challenging because of the binary constraints hi∈−11K×N. To reduce the quantization errors, existing hashing methods apply discrete optimization to the similarity-preserving loss (classification loss) and continuous optimization to the quantization loss. The quantization error (Q=hi−sgnhi2) is optimized by applying continuous relaxation to the binary constraint. The optimization of the quantization error is very difficult due to the computation intensity and lack of compatibility with the training of the deep network with back-propagation because of the non-differentiable sgn function. Therefore, we employed the quantization loss function proposed by,21 which is suitable to control the quantization error. The quantization loss is defined as follows:\n\n. is an elementwise vector, and we applied the smooth surrogate function to the L1 norm.\n\n.1≈logcosh. to ease the differentiation during back-propagation. The optimized quantization loss can be derived as\n\nTherefore, by taking equations (7) and (9), we achieve the DGRH optimization loss:\n\nBy optimizing the classification loss (LC), we can learn similarity-preserving quality hash codes and control the learned hash codes with the joint optimization function quantization loss (LQ). The k-bit binary codes are achieved using the sgn function, and the final DGRH optimization loss function is able to reduce the quantization error and increase the retrieval performance. Our proposed DGRH model is trained using adaptive moment estimation (Adam) via back-propagation. In the testing stage, the new query image is converted into hash codes by the trained network. The k-bit binary codes can be obtained using the sgn function. Once we obtain the k-bit binary codes from the gallery and query sets, we can compute the Hamming distance between them to obtain the result.\n\n\nMethods\n\nThe proposed model is developed using the Python programming language. For the data-pre-processing, the Pandas library was used to create and analyse the training and testing gait dataset, and Pickle library was used to import and load the data. The proposed model uses the deep learning approach i.e. the convolutional neural network. To build the convolutional neural network, the deep learning framework known as Keras library with the TensorFlow backend was used. The Keras library allows to construct the neural network easily, and can perform the training and testing of the proposed model. The other important libraries that were used in the development of the model are Numpy and Math libraries for array data manipulation and mathematical formula construction. Finally, the Matpoltlib and Seaborn libraries were used for the data visualization of the performance. The source code used for the analysis can be found at Zenodo.25\n\nWe evaluated our proposed deep gait retrieval with public benchmark datasets (CASIA-B, OUISIR-LP, and OUISIR-MVLP). Since we are dealing with the retrieval problem, we considered both short-term and long-term retrieval. For short-term retrieval, we divided the datasets into the same conditions (being in view, wearing clothes, carrying a bag) since gait is captured from the camera in a short amount of time. In real-world gait applications, people are captured at different times and views from different cameras. Therefore, we considered the prepared dataset for both same and mixed conditions to further evaluate our proposed gait retrieval framework.\n\nCASIA-B dataset\n\nThe CASIA-B gait dataset contains 124 subjects with 11 views and three walking conditions (normal walking, wearing a coat and carrying a bag).22 We evaluated only the same view (90°) with the same walking condition for this setting. For the normal walking condition, four walking sequences (nm1- nm4) are used for the training set, and the remaining sequences (nm5 and nm6) are used for the testing set. There are only two walking sequences for both wearing a coat (cl1, cl2) and carrying the bag (bg1, bg). Therefore, we prepared cl1 as the training set and cl2 as the testing set. Likewise, bg1 was used for training and bg2 was used for testing in the condition of carrying a bag. To evaluate the long-term retrieval problem, we mixed three conditions (NM, CL, BG) and prepared the datasets. The training sets (nm1, nm2, nm3, nm4, cl1, bg1) are included, and for the testing set, we used nm5, nm6, cl2, and bg2.\n\nOUISIR Large Population (LP) dataset\n\nTo evaluate the proposed framework, we used a subset of the OULP datasets with 1912 subjects and 4 different views (55°,65°,75°,and85°) following the protocol in.23 The training and testing dataset is divided equally with 956 subjects each. Therefore, each subject also has eight GEIs with 4 views and 2 sequences. For the evaluation under the same condition, we prepared the datasets with only the same views (55°−55°,65°−65°,75°−75°,and85°−85°). Under mixed conditions, each subject with 4 different views is combined for evaluation. Therefore, each subject has eight GEIs (2 walking sequences * 4 views) to perform long-term gait retrieval.\n\nOUISIR-Multiview Large Population (MVLP) dataset\n\nOUISIR-MVLP includes 10307 subjects; 5114 subjects are males, and 5193 are females. For the experiments in the OU-MVLP dataset, we followed the protocol setting of24 which divided the dataset into nearly equal groups with 5153 subjects for the training set and 5154 subjects for the testing set. As we pre-processed the gait sequences into gait energy images with normalized dimensions (128×88), we obtained 28 GEIs with 14 different views and 2 walking sequences for each. To evaluate our proposed method, we used only four views (0°, 30°, 60°, and 90°) for both the same-condition and mixed-condition settings since the GEIs with 180° view differences are flipped versions of the images and are considered same-view pairs based on the perspective of the projection. Only the same view was used to perform the short-term gait retrieval. Under mixed conditions, we created datasets with all four views for each subject. Therefore, the number of subjects was still the same, and each subject had eight sequences (2 walking sequences * 4 views).\n\nWe adopted the Hamming space retrieval approach to evaluate the performance of our proposed model. In hashing, similarity-preserving hash codes are represented instead of data points to increase the speed of retrieval and reduce the storage space. The common methods for searching hash-based codes are the Hash lookup table and the Hamming ranking. The Hamming ranking uses the Hamming distance between the query image and the images from the database. The Hamming distance is computed using a bitwise operation, and the ranked list is generated according to the distance. The returned ranked list is in ascending order with the nearest neighbour in the database with the query. For the hash lookup table approach, lookup tables are constructed with the data points in the database within the Hamming radius (r) of the query. Hash lookup, also known as bucket searching, tries to retrieve all r-neighbours for each query.\n\nThe k-bit hash code lengths for the proposed model are 16 bits, 32 bits, 48 bits and 64 bits. The retrieval results are evaluated in three different matrices: precision curves with respect to the Hamming radius, precision curves based on different returned images and the mean average precision (MAP). The precision of r (P@r) is calculated, and the accuracy of the returned images based on the Hamming distance of the query and database images is less than or equal to r (≤r). Here, we set r=2for the hash lookup and constructed the precision curves within the Hamming radius (P@r=2)with respect to different bit lengths. In Hamming ranking, the precision is calculated by the given top returned image. Therefore, we analysed the precision curves with different numbers of top returned images (P@N).\n\nThe MAP (mean average precision) is the most important metric to evaluate the hashing algorithms. The ranked list achieved by the Hamming distance between the database and each query is evaluated against the given top returned images. First, we compute the average precision for each query with\n\nwhere N represents the top returned images in Hamming ranking and Pn is the precision of the top-N retrieved results. Then,δn is 1 if the n-th retrieved result is in the list and δn = 0 otherwise. Then, we can calculate the mean AP for all the testing queries to obtain the mean average precision (MAP). The larger the number of MAPs is, the better the quality of retrieval performance.\n\n\nResults and discussion\n\nThe mean average precision (MAP) of different datasets with the code length (16,32,48,64) for the same condition are described in Table 2, Table 3 and Table 4. In these tables, the MAP is calculated from the top-100 returned images from the given queries. The precision curves within the Hamming radius (P@r=2) are also illustrated for different code lengths in Figures 3 to 5. Additionally, based on the top-N returned images, precision curves are also shown for further evaluation of the proposed model.\n\nComparison of the (a) precision curves at a Hamming radius of 2 (P@r = 2) with different bit lengths and the (b) precision curves of the top-N returned images on the CASIA-B dataset.\n\nComparison of the (a) precision curves at a Hamming radius of 2 (P@r = 2) with different bit lengths and the (b) precision curves of the top-N returned images on the OUISIR-LP dataset.\n\nComparison of the (a) precision curves at a Hamming radius of 2 (P@r = 2) with different bit lengths and the (b) precision curves of the top-N returned images on the OUISIR-MVLP dataset.\n\nAccording to the results, the CASIA-B dataset has the lowest MAP values for the carrying condition (bg-bg) since the motion features of the gait are affected by human walking motion. In addition, normal walking (nm-nm) achieves the highest MAP because of its uncorrupted gait features, and the clothing condition (cl-cl) achieves the second-best result. The MAP for the OUISIR-LP dataset is quite similar for all of the views since the motion features of the different views are observable in the side view. The highest MAP values are achieved at (85°) and a 64-bit code length. Compared to the other datasets, the MAP of the OUISIR-MVLP datasets is the lowest overall for the training and testing pairs since this dataset has the largest number of subjects. The highest MAP is in the lateral view pair (90°–90°), and the lowest is in the frontal view pair (0°−0°). For the bitwise comparison, the hashing performance is better for 48 bits and 64 bits. As the bit length increases, the MAP also increases for the proposed model. Therefore, the precision curves @ top-N are constructed based on the precision values at 64 bits with different returned images (10, 50, 100), as shown in Figure 5.\n\nThe evaluation result for the mixed condition is shown in Table 5. The purpose of the mixed condition is to address long-term gait retrieval. The CASIA-B dataset explores different walking conditions, such as carrying bags and wearing conditions, in the same view. According to the results, the MAP of the mixed condition in the CASIA-B dataset is able to achieve a higher performance than the same condition. Hamming distance is able to overcome the covariate factors in the retrieval task. To analyse the retrieval performance in view changes, the OUISIR-LP dataset and OUISIR-MVLP datasets are subjected to experiments with four different views. The angular difference for the OUISIR-LP is 10°, and the largest difference is only 30°. Therefore, the MAP for the OUISIR dataset is the highest among other datasets, and the results of the precision curves for a Hamming radius of 2 and top-returned images are also desirable. The MAP for the OUISIR-MVLP dataset is the lowest among the datasets, which is probably due to the large angular difference in the view changes. The gait is captured from both frontal and lateral views ranging from 0° to 90°. The motion and gait features might not be observed well in the frontal view compared to the lateral view. However, the retrieval performances are quite desirable given the large population dataset with larger view changes. In terms of the bit comparison, the 64-bit scheme also achieves better precision results than the other bit lengths. Therefore, the precision curves for the top-returned images are illustrated based on the precision of 64 bits, and the results are shown in Figure 6. According to the result, the highest precision value based on the different number of bits is from the OUISIR-LP dataset with 4 different views and small angular differences. The CASIA-B dataset is also able to achieve the desired result, and the lowest value is for the OUISIR-MVLP dataset. In Figure 6, we compare the precision values based on the number of top-returned images in 64 bits. The OUISIR-LP dataset is also able to achieve a high precision value, while the OUISIR-MVLP dataset has the lowest precision with a large number of angular views.\n\nComparison of the (a) precision curves at a Hamming radius of 2 (P@r = 2) with different bit lengths and the (b) precision curves of the top-N returned images on the different datasets.\n\nThe performance of the DGRH (deep gait retrieval hashing) method is compared against the current gait retrieval works with the same datasets. There are only two papers that address the gait retrieval problem.5,18 Therefore, the first method to be evaluated is the kernel-based semantic hashing method (KSH) proposed by Zhou et al.5 The KSH uses the handcrafted feature learning approach with the Gaussian kernel function to generate the hashing function, and a semantic ranking list is used to retrieve the gait data. Another gait retrieval method that is compared is the deep hashing method presented by Rauf et al.,18 who used deep supervised hashing methods with triplet deep learning channels. This method takes the triplet pairs of gait data into the shared triplet channel to calculate the hash function, and the triplet ranking loss is used to retrieve the query from the ranking list.\n\nThe proposed framework is compared with the existing methods in Figure 7. The mean average precision (MAP) of the top-100 returned images is used as the evaluation criterion for the retrieval performance.\n\nThe mixed condition in different datasets is analysed since gait retrieval is mostly a long-term retrieval problem. According to the results, our proposed method outperforms the other two methods. The retrieval performance of our proposed method is better because of the deep representation of the gait features, and the strength of the CNN can learn better information about the gait motion. The pairwise-based or triplet-based loss in hashing might cause a data imbalance problem because of its complex data preparation for suitable data pairs. In addition, this approach can also suffer from optimization problems. The combination of the classification loss and quantization loss in the proposed method can effectively predict gait labels and control the quality of the hash codes.\n\n\nConclusion\n\nThis paper proposed the deep gait retrieval hashing (DGRH) model to address gait retrieval. The DGRH uses supervised deep hashing to retrieve the individual gait from the given query. The deep convolutional neural network is used to extract the gait features and generate the hash codes from the last layer of the network. The hash function is learned by optimization of the classification loss and quantization loss, and then gait retrieval is performed in the Hamming Space. The end-end-end hashing model is able to learn discriminative gait features and is efficient in terms of the storage memory and speed. The proposed method is evaluated on three different public datasets and outperforms other methods.\n\n\nData availability\n\nCASIB-B Dataset: The dataset is provided by The Institute of Automation, Chinese Academy of Sciences (CASIA) for the research purposes. We used the dataset B from the CASIA Gait Dataset which available on http://www.cbsr.ia.ac.cn/english/Gait%20Databases.asp by signing the release agreement.\n\nOU-ISIR LP Dataset: The OU-ISIR Gait Database, Large Population Dataset is provided by The Institute of Scientific and Industrial Research (ISIR), Osaka University (OU). We used that dataset from http://www.am.sanken.osaka-u.ac.jp/BiometricDB/GaitLP.html by signing the release agreement for research purposes.\n\nOU-ISIR MVLP Dataset: The OU-ISIR Gait Database, Multi-View Large Population Dataset (OU-MVLP) is provided by The Institute of Scientific and Industrial Research (ISIR), Osaka University (OU). We used the dataset from http://www.am.sanken.osaka-u.ac.jp/BiometricDB/GaitMVLP.html by signing the release agreement for research purpose.\n\nAll the datasets can be obtained by signing the release agreement under research purpose.\n\n\nSoftware availability\n\nSource code available from: https://github.com/papamin/Deep-Supervised-Hashing-for-Gait-Retrieval/tree/v1.0.1.\n\nArchived source code at the time of publication: https://doi.org/10.5281/zenodo.5256521.25\n\nLicense: GPL 3.0.",
"appendix": "References\n\nChao H, He Y, Zhang J, et al.: GaitSet: Regarding Gait as a set For CROSS-VIEW gait recognition. Proc AAAI Conf Artificial Intelligence. 2019; 33: 8126–8133. Publisher Full Text\n\nRida I, Almaadeed N, Almaadeed S: Robust gait recognition: A comprehensive survey. IET Biometrics. 2018; 8(1): 14–28. Publisher Full Text\n\nWang X, Yan WQ: Human gait recognition based On Frame-by-frame Gait Energy images and Convolutional Long short-term memory. Int J Neural Syst. 2019; 30(1): 1950027. PubMed Abstract | Publisher Full Text\n\nXiao T, Li S, Wang B, et al.: Joint Detection and Identification Feature Learning for Person Search. 2017 IEEE Conf Computer Vision Pattern Recognition (CVPR). 2017. Publisher Full Text\n\nZhou Y, Huang Y, Hu Q, et al.: Kernel-Based Semantic Hashing for Gait Retrieval. IEEE Transactions on Circuits and Systems for Video Technology. 2018; 28(10): 2742–2752.\n\nWang J, Shen HT, Song J, et al.: Hashing for similarity search: A survey. CoRR. 2014.\n\nKulis B, Grauman K: Kernelized locality-sensitive hashing for scalable image search. 2009 IEEE 12th Int Conf Computer Vision. 2009. Publisher Full Text\n\nLiu W, Wang J, Kumar S, et al.: Hashing with graphs. In Proc. ICML; 2011.\n\nTang J, Li Z, Wang M, et al.: Neighborhood Discriminant Hashing for Large-Scale Image Retrieval. IEEE Transactions Image Processing. 2015; 24(9): 2827–2840. Publisher Full Text\n\nLiu W, Wang J, Ji R, et al.: Supervised hashing with kernels. 2012 IEEE Conf Computer Vision Pattern Recognition. 2012. Publisher Full Text\n\nShen F, Shen C, Liu W, et al.: Supervised Discrete Hashing. 2015 IEEE Conf Computer Vision Pattern Recognition (CVPR). 2015.\n\nLin K, Yang H-F, Hsiao J-H, et al.: Deep learning of binary hash codes for fast image retrieval. 2015 IEEE Conf Computer Vision Pattern Recognition Workshops (CVPRW). 2015. Publisher Full Text\n\nXia R, Pan Y, Lai H, et al.: Supervised hashing for image retrieval via image representation learning. Proc AAAI Conf Artificial Intelligence. 2014; pages. 2156–2162.\n\nLai H, Pan Y, Liu Y, et al.: Simultaneous feature learning and hash coding with deep neural networks. 2015 IEEE Conf Computer Vision Pattern Recognition (CVPR). 2015. Publisher Full Text\n\nZhang R, Lin L, Zhang R, et al.: Bit-Scalable Deep Hashing With Regularized Similarity Learning for Image Retrieval and Person Re-Identification. IEEE Transactions on Image Processing. 2015; 24(12): 4766–4779. Publisher Full Text\n\nZhu H, Long M, Wang J, et al.: Deep hashing network for efficient similarity retrieval. In Thirtieth AAAI Conference on Artificial Intelligence. 2016.\n\nCao Y, Long M, Liu B, et al.: Deep Cauchy Hashing for Hamming Space Retrieval. 2018 IEEE/CVF Conference Computer Vision Pattern Recognition. 2018. Publisher Full Text\n\nRauf M, Huang Y, Wang L: Gait Retrieval: A Deep Hashing Method for People Retrieval in Video. Communications in Computer and Information Science Pattern Recognition. 2016: 383–391. Publisher Full Text\n\nHan J, Bhanu B: Individual recognition using gait energy image. IEEE Transactions Pattern Analysis Machine Intelligence. 2006; 28(2): 316–322. Publisher Full Text\n\nMin PP, Sayeed S, Ong TS: Gait Recognition Using Deep Convolutional Features. 2019 7th Int Conf Information Communication Technology (ICoICT). 2019. Publisher Full Text\n\nGong Y, Lazebnik S: Iterative quantization: A procrustean approach to learning binary codes. Cvpr. 2011; 2011. Publisher Full Text\n\nYu S, Tan D, Tan T: A Framework for Evaluating the Effect of View Angle, Clothing and Carrying Condition on Gait Recognition. 18th Int Conf Pattern Recognition (ICPR'06). 2006. Publisher Full Text\n\nMuramatsu D, Makihara Y, Yagi Y: Cross-view gait recognition by fusion of multiple transformation consistency measures. IET Biometrics. June 2015; 4: 62–73(11). Publisher Full Text\n\nTakemura N, Makihara Y, Muramatsu D, et al.: Multi-view large population gait dataset and its performance evaluation for cross-view gait recognition. IPSJ transactions on Computer Vision and Applications. 2018; vol. 10, no. 1.\n\nSayeed S, Min PP, Ong TS: Deep Supervised Hashing for Gait Retrieval (v1.0.1). Zenodo. 2021. Publisher Full Text"
}
|
[
{
"id": "96767",
"date": "28 Oct 2021",
"name": "D. I. George Amalarethinam",
"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\nThe salient features of gait are analysed using three different benchmark dataset in connection with storage memory and speed.\n\nThe data Tables 3 , 4, and 5 need to be spelled out so as to provide more clarity towards further proceedings by others.\n\nThough the paper is technically sound, the limitations or negative aspects of the proposed methodology need to be included.\n\nThe recent year (2020) references may be provided towards strengthening of the paper.\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? Partly\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? Partly",
"responses": []
},
{
"id": "96765",
"date": "15 Dec 2021",
"name": "Md. Rajibul Islam",
"expertise": [
"Reviewer Expertise Machine learning",
"Artificial intelligence",
"Data mining."
],
"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 demonstrates the deep gait retrieval hashing (DGRH) model to address the gait retrieval problem using public benchmark datasets (CASIA-B, OUISIR-LP, and OUISIR-MVLP). This method is based on a supervised hashing method with a deep convolutional network. I think this paper proposes an interesting scheme of gait retrieval. The analysis process and results presented in this paper are technically sound. I do have a few comments for the authors. I would recommend it being indexed if these were addressed.\nSupervised hashing methods with a well-designed deep convolutional neural network have been used by various researchers in the literature. However, the authors have compared their results with only two papers that demonstrated hashing method to address the gait retrieval problem. What about the other techniques that had been used to solve the gait retrieval problem? Does the proposed method outperform those techniques too?\n\n“Comparison with other existing methods” section requires improvement. The comparison statements in this section should be supported by analytical outcomes. For instance, it should be mentioned that which outcome of this article demonstrates that data imbalance and optimization problems can be solved by the proposed method and how.\n\nThe statement, “The hashing method is efficient in terms of the storage memory and speed” has been written at the beginning and end of the article but no results/theoretical explanation has been presented to support it.\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": []
}
] | 1
|
https://f1000research.com/articles/10-1038
|
https://f1000research.com/articles/10-503/v1
|
25 Jun 21
|
{
"type": "Research Article",
"title": "Discrimination of the SARS–CoV-2 strains using of coloured s-LASCA-imaging of GB-speckles, developed for the gene “S” nucleotide sequences",
"authors": [
"Onega Ulianova",
"Yury Saltykov",
"Sergey Ulyanov",
"Sergey Zaytsev",
"Alexander Ulyanov",
"Valentina Feodorova",
"Onega Ulianova",
"Yury Saltykov",
"Sergey Zaytsev",
"Alexander Ulyanov"
],
"abstract": "Background: A recent bioinformatics technique involves changing nucleotide sequences into 2D speckles. This technique produces speckles called GB-speckles (Gene Based speckles). All classical strategies of speckle-optics, namely speckle-interferometry, subtraction of speckle-images as well as speckle-correlometry have been inferred for processing of GB-speckles. This indicates the considerable improvement in the present tools of bioinformatics.\n\nMethods: Colour s-LASCA imaging of virtual laser GB-speckles, a new method of high discrimination and typing of pathogenic viruses, has been developed. This method has been adapted to the detecting of natural mutations in nucleotide sequences, related to the spike glycoprotein (coding the gene «S») of SARS–CoV-2 gene as the molecular target.\n\nResults: The rate of the colouring images of virtual laser GB-speckles generated by s-LASCA can be described by the specific value of R. If the nucleotide sequences compared utilizing this approach the relevant images are completely identical, then the three components of the resulting colour image will be identical, and therefore the value of R will be equal to zero. However, if there are at least minimal differences in the matched nucleotide sequences, then the value of R will be positive.\n\nConclusion: The high effectiveness of an application of the colour images of GB-speckles that were generated by s-LASCA- has been demonstrated for discrimination between different variants of the SARS–CoV-2 spike glycoprotein gene.",
"keywords": [
"LASCA",
"SARS–CoV-2",
"GB-speckles",
"gene"
],
"content": "Introduction\n\nAs it is well known, if laser light diffracts on random objects, then laser speckles are formed.1-3 Recently, the possibility of transforming a nucleotide sequence into a pattern of 2D speckles had been demonstrated.4-9 This new type of speckle pattern has been called “GB-speckles” (gene-based speckles).5,7,9 Changes within in the structure of the GB-speckles can reflect even negligible changes in the nucleotide sequence, caused by inartificial mutations. This allows detection of single-nucleotide polymorphisms (SNP) using virtual GB-speckles with outstanding precision. In addition, it offers unlimited potential of improving the diagnosis’ accuracy by increasing the Fourier transform area.10\n\nEssential advancement in the area of GB-speckles has been reported in previous years. According to previously published reports,4-9,11 implementation of speckle-optics methods, like speckle-interferometry and subtraction of speckle-images as well as speckle-correlometry for processing of GB-speckles, provides considerable progress in the current bioinformatics toolbox. This can become crucial to significantly improve existing routine methods of laboratory diagnostics of infectious diseases. GB-speckles as a technique opens the door to the new horizons in digital biology.12,13\n\nRecently, model GB-speckle patterns of nucleotide sequences of the omp1 genes for two different of Chlamydia spp., such as Chlamydia trachomatis and Chlamydia psittaci of at least six genovars (D, E, F, G, J and K) have been composed.4,5 Probability density functions and correlation properties of spatial intensity fluctuations for the relevant GB-speckle patterns have been studied.5-7 As it has been shown in previous studies,4-7,9 the presence of inartificial mutations in analysed strains, including single SNP cases, can be easily defined using methods of speckle-optics.4-7,9 More recently, the encoding algorithm’s optimization for nucleotide sequences of C. trachomatis into two-dimensional GB-speckle pattern had been carried out;4,6 and speckle-interferometric technique may give rise the ultra-fast optical processors of DNA sequences.4 This is ensured by the development of the exclusive system of interferential fringes which are generated by the model interference pattern led by the existence of any type of mutations. Additionally, the method of virtual phase-shifting speckle-interferometry was reported to be efficacious11 to investigate of polymorphism of the C. trachomatis omp1 gene. This approach allowed the detection of the C. trachomatis omp1 gene with SNPs, including both a single SNP and a combination of several SNPs in the bacterial strains with genetic mutations (11 known subtypes in total) had been developed.6\n\nThe format of GB-speckles had been successfully applied to transform the nucleotide sequences of the genes expressing the serine proteases, the well-known Omptin family proteins within the Enterobacteriaceae. These proteins have been found on the surface of several bacterial agents causing different enteric infections, such as salmonellosis, shigelosis, yersiniosis, and escherichiosis.7 Further, the phase and the relevant two-dimensional distributions of the intensity of GB-speckles in various strains of viral pathogens, namely of lumpy skin disease virus of cattle, LSDV, and also for sheep-pox virus, SPPV have been obtained.8 Additionally, interference patterns for generated the specific superposition in the relevant fields of GB-speckle and the certain difference in their images have been successfully investigated to reveal a minimal discrimination between the initial viral nucleotide sequences.\n\nA new bioinformatics approach has been proposed very recently:14 GB-speckles processing via an s-LASCA technique (from the spatial Laser Speckle Contrast Analysis) application. As it had been demonstrated, it is possible to extend affectability of the proposed approach comparing to current bioinformatics strategies15 using s-LASCA imaging in the GB-speckles’ processing. It had been shown in Ref. 16, that the GB-speckles’ generation combined with s-LASCA imaging method are very effective to analyze nucleotide polymorphism in several genes of C. trachomatis.\n\nThis paper is devoted to development of advantageously new technique: the coloured s-LASCA imaging of GB-speckles. Such a technique is an improved version of previously suggested “greyscale” s-LASCA imaging that was recently developed especially for GB-speckles. Nucleotide sequences for some target genes SARS–CoV-2 have been successfully processed using coloured s-LASCA-imaging. Natural mutations in the comparing genes have been reliably and accurately detected.\n\n\nMethods\n\nSeven nucleotide sequences of spike glycoprotein of SARS-CoV-2, namely:\n\nthe gene#1. hCoV-19/cat/USA/TX-TAMU-078/2020 (Accession ID: EPI ISL 699509),\n\nthe gene#2. hCoV-19/cat/Russia/RII-LEN-22246S/2021 (Accession ID: EPI ISL 811147),\n\nthe gene#3. hCoV-19/cat/Greece/2K/2020 (Accession ID: EPI ISL 717979),\n\nthe gene#4. hCoV-19/Wuhan/WIV04/2019 (Accession ID: EPI ISL 402124),\n\nthe gene#5. hCoV-19/England/QEUH-B11766/2020 (Accession ID: EPI ISL 642476),\n\nthe gene#6. hCoV19/South Africa/KRISP-EC-K005299/2020 (Accession ID: EPI ISL 678597),\n\nthe gene#7. hCoV-19/Russia/MOS-CRIE-13604226/2020 (Accession ID: EPI ISL 754198).\n\nhave been compared on the base of analysis of GB-speckles. The official reference sequences were taken from the GISAID database.\n\nAlgorithm for the total conversion of a nucleotide sequence to a colour GB speckle structure, processed by s-LASCA imaging technique\n\nFirst, the sequence of the letters derived from the original one-dimensional nucleotide sequence was converted into the sequence of numbers in accordance with the following rule:4\n\nIt is critical to emphasize that the specific relationship between the letters and numbers in this case is not critical as used earlier;6 thus, other rules could have been applied to the encoding, for instance:\n\nNext, all possible triad combination are generated. As a result, a complete set of all triads is formed:\n\nThe number of all possible combinations of four numbers combined in triads is 64.\n\nThen, a discrete magnitude, h, is allotted to each triad in accordance with the simple algorithm described previously.4 This algorithm was implemented in Matlab R2015a (RRID:SCR_001622); an open access alternative is Julia. The value of h is a positive integer, varying in the range from 1 to 64. In this case, each triad from the original nucleotide sequence is associated with only one h value. So, for example, the combination (1 1 1) conforms to the value h = 1, (1 1 2) corresponds to h = 2, (1 1 3) conforms to h = 3, (1 1 4) conforms to h = 4, (1 2 1) conforms to h = 5, (1 2 2) conforms to h = 6, and so on. Finally, the latest combination (4 4 4) conforms to the value h = 64. Finally, a square matrix Hn,m was formed by a one-dimensional array h. The physical significance of the shaped matrix Hn,m is that each of its elements represents the local height of some virtual rough surface corresponding to the local content of the analyzed genetic construction. The resulting virtual rough surfaces could be used to model original speckle structures corresponding to diverse particular nucleotide sequences.\n\nThe two-dimensional speckle patterns that corresponded to each specific sequence was generated with the use the diffraction of a coherent beam with a square cross-section profile on a virtual scattering surface with a microrelief described by the matrix Hn,m. At each point of the virtual diffuser (in the beam scattering plane), some phase modulation Un,m = exp(−2πj Hn,m/64) is introduced (j is an imaginary unit). The surface is illuminated at the normal incidence of the beam; the phase in the illuminating beam was a constant value.\n\nThe procedure for transcoding the original nucleotide sequence into a GB-speckle structure using the example of the hCoV-19/cat/USA/TX-TAMU-078/2020|2020-07-29 gene (the gene #1) is shown below.\n\nThe original nucleotide sequence is as follows:\n\nATGTTTGTTTTTCTTGTTTTATTGCCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACCCCCTGCATACACTAATTCTTTCACACGTGGTGTTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAGGACTTGTTCTTACCTTTCTTTTCCAATGTTACTTGGTTCCATGCTATACATGTCTCTGGGACCAATGGTACTAAGAGGTTTGATAACCCTGTCCTACCATTTAATGATGGTGTTTATTTTGCTTCCACTGAGAAGTCTAACATAATAAGAGGCTGGATTTTTGGTACTACTTTAGATTCGAAGACCCAGTCCCTACTTATTGTTAATAACGCTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATGATCCATTTTTGGGTGTTTATTACCACAAAAACAACAAAAGTTGGATGGAAAGTGAGTTCAGAGTTTATTCTAGTGCGAATAATTGCACTTTTGAATATGTCTCTCAGCCTTTTCTTATGGACCTTGAAGGAAAACAGGGTAATTTCAAAAATCTTAGGGAATTTGTGTTTAAGAATATTGATGGTTATTTTAAAATATATTCTAAGCACACGCCTATTAATTTAGTGCGTGATCTCCCTCAGGGTTTTTCGGCTTTAGAACCATTGGTAGATTTGCCAATAGGTATTAACATCACTAGGTTTCAAACTTTACTTGCTTTACATAGAAGTTATTTGACTCCTGGTGATTCTTCTTCAGGTTGGACAGCTGGTGCTGCAGCTTATTATGTGGGTTATCTTCAACCTAGGACTTTTCTATTAAAATATAATGAAAATGGAACCATTACAGATGCTGTAGACTGTGCACTTGACCCTCTCTCAGAAGCAAAGTGTACGTTGAAATCCTTCACTGTAGAAAAAGGAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTGCCCTTTTGGTGAAGTTTTTAACGCCACCAGATTTGCATCTGTTTATGCTTGGAACAGGAAGAGAATCAGCAACTGTGTTGCTGATTATTCTGTCCTATATAATTCCGCATCATTTTCCACTTTTAAGTGTTATGGAGTGTCTCCTACTAAATTAAATGATCTCTGCTTTACTAATGTCTATGCAGATTCATTTGTAATTAGAGGTGATGAAGTCAGACAAATCGCTCCAGGGCAAACTGGAAAGATTGCTGATTATAATTATAAATTACCAGATGATTTTACAGGCTGCGTTATAGCTTGGAATTCTAACAATCTTGATTCTAAGGTTGGTGGTAATTATAATTACCTGTATAGATTGTTTAGGAAGTCTAATCTCAAACCTTTTGAGAGAGATATTTCAACTGAAATCTATCAGGCCGGTAGCACACCTTGTAATGGTGTTGAAGGTTTTAATTGTTACTTTCCTTTACAATCATATGGTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAGAGTAGTAGTACTTTCTTTTGAACTTCTACATGCACCAGCAACTGTTTGTGGACCTAAAAAGTCTACTAATTTGGTTAAAAACAAATGTGTCAATTTCAACTTCAATGGTTTAACAGGCACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTGCCTTTCCAACAATTTGGCAGAGACATTGCTGACACTACTGATGCTGTCCGTGATCCACAGACACTTGAGATTCTTGACATTACACCATGTTCTTTTGGTGGTGTCAGTGTTATAACACCAGGAACAAATACTTCTAACCAGGTTGCTGTTCTTTATCAGGGTGTTAACTGCACAGAAGTCCCTGTTGCTATTCATGCAGATCAACTTACTCCTACTTGGCGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTGCAGGCTGTTTAATAGGGGCTGAACATGTCAACAACTCATATGAGTGTGACATACCCATTGGTGCAGGTATATGCGCTAGTTATCAGACTCAGACTAATTCTCCTCGGCGGGCACGTAGTGTAGCTAGTCAATCCATCATTGCCTACACTATGTCACTTGGTGCAGAAAATTCAGTTGCTTACTCTAATAACTCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAGAAATTCTACCAGTGTCTATGACCAAGACATCAGTAGATTGTACAATGTACATTTGTGGTGATTCAACTGAATGCAGCAATCTTTTGTTGCAATATGGCAGTTTTTGTACACAATTAAACCGTGCTTTAACTGGAATAGCTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTGCACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTGGTGGTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAGCAAGAGGTCATTTATTGAAGATCTACTTTTCAACAAAGTGACACTTGCAGATGCTGGCTTCATCAAACAATATGGTGATTGCCTTGGTGATATTGCTGCTAGAGACCTCATTTGTGCACAAAAGTTTAACGGCCTTACTGTTTTGCCACCTTTGCTCACAGATGAAATGATTGCTCAATACACTTCTGCACTGTTAGCGGGTACAATCACTTCTGGTTGGACCTTTGGTGCAGGTGCTGCATTACAAATACCATTTGCTATGCAAATGGCTTATAGGTTTAATGGTATTGGAGTTACACAGAATGTTCTCTATGAGAACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTGGCAAAATTCAAGACTCACTTTCTTCCACAGCAAGTGCACTTGGAAAACTTCAAGATGTGGTCAACCAAAATGCACAAGCTTTAAACACGCTTGTTAAACAACTTAGCTCCAATTTTGGTGCAATTTCAAGTGTTTTAAATGATATCCTTTCACGTCTTGACAAAGTTGAGGCTGAAGTGCAAATTGATAGGTTGATCACAGGCAGACTTCAAAGTTTGCAGACATATGTGACTCAACAATTAATTAGAGCTGCAGAAATCAGAGCTTCTGCTAATCTTGCTGCTACTAAAATGTCAGAGTGTGTACTTGGACAATCAAAAAGAGTTGATTTTTGTGGAAAGGGCTATCATCTTATGTCCTTCCCTCAGTCAGCACCTCATGGTGTAGTCTTCTTGCATGTGACTTATGTCCCTGCACAAGAAAAGAACTTCACAACTGCTCCTGCCATTTGTCATGATGGAAAAGCACACTTTCCTCGTGAAGGTGTCTTTGTTTCAAATGGCACACACTGGTTTGTAACACAAAGGAATTTTTATGAACCACAAATCATTACTACAGACAACACATTTGTGTCTGGTAACTGTGATGTTGTAATAGGAATTGTCAACAACACAGTTTATGATCCTTTGCAACCTGAATTAGACTCATTCAAGGAGGAGTTAGATAAATATTTTAAGAATCATACATCACCAGATGTTGATTTAGGTGACATCTCTGGCATTAATGCTTCAGTTGTAAACATTCAAAAAGAAATTGACCGCCTCAATGAGGTTGCCAAGAATTTAAATGAATCTCTCATCGATCTCCAAGAACTTGGAAAGTATGAGCAGTATATAAAATGGCCATGGTACATTTGGCTAGGTTTTATAGCTGGCTTGATTGCCATAGTAATGGTGACAATTATGCTTTGCTGTATGACCAGTTGCTGTAGTTGTCTCAAGGGCTGTTGTTCTTGTGGATCCTGCTGCAAATTTGATGAAGACGACTCTGAGCCAGTGCTCAAAGGAGTCAAATTACATTACACATAA (5)\n\nAfter converting a sequence of letters into a sequence of numbers in accordance with the algorithm described by rule (1) described previously, the nucleotide sequence takes the following form:\n\n143444344444244344441443221241342424134213434344114244121122131124211441222224321412124114424442121234334344414412224312111344442131422421344441214421124213312443442441224442444422114344124433442214324141214342424333122114334124113133444314112224342241221444114314334344414444324422124313113424112141141131332433144444334124124441314423113122213422241244144344114112324124114344344144111342434311444211444434114314221444443334344414412212111112112111134433143311134313442131344414424134323114114432124444311414342424213224444244143312244311331111213334114442111114244133311444343444113114144314334414444111141414424113212123224144114441343234314242224213334444423324441311221443341314443221141334144112142124133444211124441244324441214131134414443124224334314424424421334433121324334324321324414414343334414244211224133124444241441111414114311114331122144121314324341312434321244312224242421311321113434123443111422442124341311111331142414211124424112444131342211221121311424144344131444224114144121112443432224444334311344444112322122131444321424344414324433112133113131142132112434344324314414424342241414114422321421444422124444113434414331343424224124111441114314242432444124114342414321314421444341144131334314311342131211142324221333211124331113144324314414114414111441221314314444121332432344141324433114424112114244314424113344334334114414114412243414131443444133113424114242111224444313131314144421124311142414213322334132121224434114334344311334444114434412444224441211421414334442211222124114334344334412211221412131341341341244424444311244241214321221321124344434331224111113424124114443344111112111434342114442112442114334441121332121334344244124313424112111113444243224442211211444332131312144324312124124314324342234314221213121244313144244312144121221434424444334334342134344141121221331121114124424112213344324344244414213334344112432121311342224344324144214321314211244124224124433234344414424121334424114344444211121234321332434441141333324311214342112112421414313434312141222144334321334141432324134414213124213124114424224233233321234134341324134211422142144322412124143421244334321311114421344324412424114112424144322141222121114444124144134344122121311144241221343424143122113121421341314434121143412144434334314421124311432132114244443443211414332134444434121211441112234324441124331141324344311211312111112122211311344444321211342111211144412111121221221144111314444334334444114444421211141441221314221421111221132113133421444144311314241244442112111343121244321314324332442142111211414334314432244334314144324324131312242144434321211113444112332244124344443221224443242121314311143144324211412124424321243441323334121142124424334433122444334321334324321441211141221444324143211143324414133444114334144331344121213114344242414313112211111443144322112211444114134324144332111144211312421244424422121321134321244331111244211314343342112211114321211324441112123244344111211244132422114444334321144421134344441114314142244421234244312111344313324311343211144314133443142121332131244211134443213121414343124211211441144131324321311142131324424324114244324324124111143421313434341244331211421111131344314444434331113332414214244143422442224213421321224214334341342442443214343124414342224321211311113112442121124324224322144434214314331111321212444224234311334342444344421114332121212433444341121211133114444414311221211142144124121312112121444343424334112434314344341141331144342112112121344414314224443211224311441312421442113313313441314111414444113114214121421221314344314441334312142424332144114324421344341112144211111311144312232242114313344322113114441114311424242142314242211311244331113414313213414141111433221433412144433241334444141324332443144322141341143343121144143244432434143122134432434134434242113332434434424434331422432432111444314311312312424313221343242111331342111441214412121411 (6)\n\nAs a result of diffraction of coherent beam on the phase screen (the virtual heights of the irregularities presented in the table (6)) with a square cross-section is formed GB-speckle-structure of two-dimensional intensity distribution, see Figure 1a. Two-dimensional phase distribution GB, the speckle structure is shown in Figure 1b.\n\ns-LASCA strategy has been connected for handling of GB-speckles. The strategy of s-LASCA is based on the examination of an individual realization of static speckles.3 In this case, the whole realization of the speckle field is divided into square zones; typically, each counting 5×5 or 7×7 pixels.\n\nFor each zone, the contrast of GB-speckles was calculated using the simplest formula:\n\nwhere I was the varying intensity of GB-speckles, changing from point to point; σI was the standard deviation of the intensity of fluctuations. After the contrast C is calculated in each point, LASCA image is developed. Here, the size of subarea for the local contrast calculating was 2×2 pixels. As it has been demonstrated14 this size of subarea is close to optimal.\n\nTo generate three two-dimensional implementations of GB speckles built for different genetic sequences, it is necessary to construct a colour image, where each colour component (red, green, and blue) has its own GB speckle structure. When all three speckle structures were totally indistinguishable, the colour images look grey-scale. If the colour components differ from each other, then, as a result, colouring will appear in the image.\n\nIn Figure 2a, the coloured speckle-pattern for intensity distribution is presented (the red component obtained for the nucleotide sequence derived from gene #1, the green component corresponded to the nucleotide sequence of gene #2, and blue component was the relevant to gene #3 nucleotide sequence, respectively).\n\nFigure 2a, demonstrates the differences in the initial nucleotide sequences, a slight staining appears in the colour speckle-pattern structure for a two-dimensional intensity distribution.\n\nIn Figure 2b, the coloured speckle-pattern for phase distribution is shown for such nucleotide sequences as: (i) the red component for gene #1, greenfor gene #2, blue for gene #3.\n\nIt is quite obvious that in the case under consideration, there is a pronounced colouring over the whole image for the field of GB-speckle.\n\nThus, the obtained colour image for the intensity and phase of GB speckles is a reliable diagnostic sign of the presence of polymorphism.\n\nOnce an s-LASCA image is obtained for each of the three components of the matched genetic sequence, the final colour image can be constructed. An example of such an image is shown in Figure 3a.\n\n\nResults and discussion\n\nIt is obvious that the image shown in Figure 3a in comparison with the image in Figure 2a has a more pronounced colouring over the entire field of view, but is characterized by a higher contrast. From a quantitative point of view, the degree of colouring can be described by the value\n\nwhere Iri, Igi and Ibi are values of intensity for the red, green, and blue components in each pixel,\n\nis the average intensity value in each pixel, i is the pixel number, M and N are the number of rows and columns of the analyzed image, N × M is the total number of pixels in the image.\n\nObviously, if the nucleotide sequences compared using s-LASCA imaging of GB-speckles are completely identical, then the three components of the resulting colour image will be identical, and therefore the value of R will be equal to zero. However, if there are at least minimal differences in the compared nucleotide sequences, then the value of R will take a positive value. Thus, the value of R calculated for the Figure 3a is 0.1 (gene#1, gene#2 and gene#3 are compared).\n\nIn Figure 3b, comparison of new SARS–CoV-2 genes: hCoV-19/Wuhan/WIV04/2019|2019-12-30 (gene#4), hCoV-19/England/QEUH-B11766/2020|2020-11-02 (gene#5) and hCoV19/South Africa/KRISP-EC-K005299/2020|2020-11-19 (gene#6) is presented. R calculated for Figure 3b equals to 0.596.\n\nFinally, three SARS–CoV-2 genes are reflected in Figure 3c (hCoV-19/England/QEUH-B11766/2020|2020-11-02 (gene#5), hCoV19/South Africa/KRISP-EC-K005299/2020|2020-11-19 (gene#6) and hCoV-19/Russia/MOS-CRIE-13604226/2020|2020-11-09 (gene#7). Again, R equals to 0.596 for this case.\n\nIt is important to note that the value of R calculated for Figure 2a and Figure 2b (coloured bare GB-speckle) equals to 0.049 and 0.026, respectively. This means that the value of R at least in two times higher for GB speckles, processed by s-LASCA imaging technique.\n\nEvidently, R is positive for all images in Figures 3; so, R is an important diagnostic feature when detecting the presence of SNPs in SARS–CoV-2 genes. This is the main result.\n\n\nConclusion\n\nA fundamentally new bioinformatics technique for reliable detection of single SNPs is proposed. The new method is based on the applying of the s-LASCA ‘imaging technique’ generating original GB-speckles. It is established that even one SNP can be reliably detected. It has been demonstrated that suggested technique is very effective tool for discrimination between different variants of the SARS–CoV-2 spike glycoprotein gene.\n\n\nData availability\n\nGISAID Gene: hCoV-19/cat/USA/TX-TAMU-078/2020. Accession number EPI ISL 699509;\n\nGISAID Gene: hCoV-19/cat/Russia/RII-LEN-22246S/2021. Accession number EPI ISL 811147;\n\nGISAID Gene: hCoV-19/cat/Greece/2K/2020. Accession number EPI ISL 717979;\n\nGISAID Gene: hCoV-19/Wuhan/WIV04/2019. Accession number EPI ISL 402124;\n\nGISAID Gene: hCoV-19/England/QEUH-B11766/2020. Accession number EPI ISL 642476;\n\nGISAID Gene: hCoV19/South Africa/KRISP-EC-K005299/2020. Accession number EPI ISL 678597;\n\nGISAID Gene: hCoV-19/Russia/MOS-CRIE-13604226/2020. Accession number EPI ISL 754198.\n\nSequences are available after registration at the GISAID public database.",
"appendix": "References\n\nDainty C: Laser speckle and related phenomena. Topics in Applied Physics . 1984; 9. PubMed Abstract\n\nAizu Y, et al.: Biospeckle method for retinal blood flow analysis: flexible correlation measurements. Optical Diagnostics of Biological Fluids and Advanced Techniques in Analytical Cytology. SPIE Press; 1997; 91–102.\n\nBriers JD: Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. Physiol Meas. 2001; 22:R35–R66. PubMed Abstract | Publisher Full Text\n\nUlyanov SS, et al.: Using of methods of speckle optics for Chlamydia trachomatis typing. Proc. SPIE. 2017; 10336: 103360D.\n\nUlyanov SS, et al.: Statistics on gene-based laser speckles with a small number of scatterers: implications for the detection of polymorphism in the Chlamydia trachomatis omp1 gene. Laser Physics Letters . 2018; 15. Publisher Full Text\n\nFeodorova VA, et al.: Optimization of algorithm of coding of genetic information of Chlamydia. Proc. SPIE. 2018; 10716: 107160Q. Publisher Full Text\n\nUlyanov SS, et al.: Study of statistical characteristics of GB-speckles, forming at scattering of light on virtual structures of nucleotide gene sequences of Enterobacteria. Izv. Saratov Univ. (N. S.), Ser. Physics . 2018; 18:123–137. Publisher Full Text\n\nSaltykov YV, et al.: Analysis of nucleotide sequences of the gene GPCR of the genus Capripoxvirus representatives using speckle interferometry of GB speckles and subtracting their images. Math. mod., comp. and natural exp. in natural sci. 2020: 2.\n\nUlianova OV, et al.: Speckle-interferometry and speckle-correlometry of GB-speckles. Front Biosci (Landmark Ed). 2019; 24: 700–711. PubMed Abstract\n\nGoodman JW: Introduction to fourier optics . New York: McGraw Hill Companies; 1988.\n\nFeodorova VA, et al.: Application of virtual phase-shifting speckle-interferometry for detection of polymorphism in the Chlamydia trachomatis omp1 gene. Proc. SPIE. 2018; 10716: 107160M. Publisher Full Text\n\nSleator RD: Digital biology. A new era has begun. Bioengineered . 2012; 3: 311–312. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFreddolino PL, Tavazoie S: The Dawn of Virtual Cell Biology. Cell . 2012; 150: 248–250. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUlianova OV, et al.: LASCA-imaging of gene-based speckles: application to detection of the gene polymorphism in a bacterial model. Laser Physics Letters . 2020; 17. Publisher Full Text\n\nLesk AM: Introduction to Bioinformatics Oxford University Press; 2002.\n\nUlianova OV, et al.: Could LASCA-imaging of GB-speckles be applied for a high discrimination and typing of pathogenic bacteria? PloS one . 2021; 16."
}
|
[
{
"id": "88324",
"date": "16 Jul 2021",
"name": "Oleg Angelsky",
"expertise": [
"Reviewer Expertise Singular and Correlation Optics"
],
"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 devoted to the investigations of virtual Gene Based speckles for the determination the difference between SARS-Cov-2 spike glycoprotein genes. As it was noted by the authors the given method can use the classical approaches of speckle-optics. But there are some questions:\n\nAny optical speckle is the result of the interference of waves scattered by inhomogeneities, and to obtain a speckle pattern, the wavelength is decisive. Thus, the question arises about the concrete wavelengths used in the study and their relationships with pseudo inhomogeneities. It would be interesting to know about the coherence of the sources used the modelling.\n\nPlease present an experiment setup, and the results of experimental modelling.\n\nIt would be interesting to conduct a complete analysis of the entered parameter R, to represent its physical, biochemical meaning. The virus is constantly mutating, how is it possible to estimate the degree of virus mutation using this parameter.\nThe paper can be indexed after reworking.\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": [
{
"c_id": "6974",
"date": "06 Sep 2021",
"name": "Valentina Feodorova",
"role": "Author Response",
"response": "Reply to the comments of reviewer Prof. Oleg Angelsky: Any optical speckle is the result of the interference of waves scattered by inhomogeneities, and to obtain a speckle pattern, the wavelength is decisive. Thus, the question arises about the concrete wavelengths used in the study and their relationships with pseudo inhomogeneities. It would be interesting to know about the coherence of the sources used the modelling. Response: This is really reasonable and very important question. Fragment below is added to the new version of the text: It is assumed that speckles are formed in the far diffraction zone and described in the Fraunhofer approximation. In this case, the expression for the amplitude of the scattered field is the Fourier transform of the field in the diffraction plane, evaluated at frequencies spaces Fx=Xo/( z* λ), Fy=Yo/( z* λ), (*) where Xo and Yo are the coordinates in the observation plane, z is the distance between the scattering plane and the observation plane, λ is the wavelength. The illuminating radiation is completely monochromatic, thus, λ =const. Reference to Goodman, J. W. Introduction to fourier optics. McGraw Hill Companies, New York (1988). In this situation, the structure of speckles does not depend on the wavelength and z. Only the sizes of GB-speckles depend on these values, the average size of which is determined by the ratio: d~3*z* λ /a (**) where a is the size of the illuminated fragment of virtual surface. It is important to emphasize that the ratio λ/a characterizes the diffraction angular divergence of a laser beam in the far field, and the product of this divergence angle by the light traveled distance z is equal to the lateral size of the beam. New reference: M. Francon. La granularite laser (speckle) et ses applications en optique. Masson, Paris, New York, Barcelone, Milan 1978. Thus, it can be seen that the diameter of the undisturbed laser beam (namely, this value is on the right side of the expression (**)) and the average speckle size are approximately equal to each other in any observation plane. In other words, when the parameters z and λ change, a proportional change in the size of all speckles occurs synchronously. At the same time, the structure of speckle-patterns in all observation planes are completely similar, only their scale changes from plane to plane, but not the shape of the speckles or their location in the speckle pattern. Please present an experiment setup, and the results of experimental modelling. Response: Experimental studies were not carried out in this work, only computer modeling. The scheme for calculating GB speckles during radiation diffraction on a virtual scattering surface is described in detail in the work: Ulianova OV, et al.: Speckle-interferometry and speckle-correlometry of GB-speckles. Frontiers in Bioscience-Landmark 2019; 24, 700-711. This fact is mentioned in the new version of this article. It would be interesting to conduct a complete analysis of the entered parameter R, to represent its physical, biochemical meaning. The virus is constantly mutating, how is it possible to estimate the degree of virus mutation using this parameter. Response: The physical meaning of the introduced parameter R is that this parameter characterizes the degree of coloring of the picture (GB-speckle- pattern). The bioinformatic (molecular biology) value of R is that it takes positive values, even in the case of the appearance of a one SNP in the analyzed nucleotide sequences. Thus, the minimum natural mutations of the virus can be determined using the parameter R. This circumstance is also noted in the Conclusions of new version of this article. The authors are extremely grateful to the respected reviewer, whose critical comments have significantly improved the quality of this article."
}
]
}
] | 1
|
https://f1000research.com/articles/10-503
|
https://f1000research.com/articles/11-691/v1
|
22 Jun 22
|
{
"type": "Study Protocol",
"title": "A mixed-methods study on the design of Artificial Intelligence and data science-based strategies to inform public health responses to COVID-19 in different local health ecosystems: A study protocol for COLEV",
"authors": [
"Catalina González-Uribe",
"Nicolás Yañez",
"Alf Onshuus Niño",
"Nubia Velasco",
"Juan Manuel Cordovez",
"Mauricio Santos-Vega",
"Natalia Niño-Machado",
"Andres Burbano",
"Angus Forbes",
"Ciro Alberto Amaya Guio",
"Simon Turner",
"Diana Higuera-Mendieta",
"Sandra Martínez-Cabezas",
"Nicolás Yañez",
"Alf Onshuus Niño",
"Nubia Velasco",
"Juan Manuel Cordovez",
"Mauricio Santos-Vega",
"Natalia Niño-Machado",
"Andres Burbano",
"Angus Forbes",
"Ciro Alberto Amaya Guio",
"Simon Turner",
"Diana Higuera-Mendieta",
"Sandra Martínez-Cabezas"
],
"abstract": "Background: Artificial Intelligence (AI) and data science research are promising tools to better inform public policy and public health responses, promoting automation and affordability. During the COVID-19 pandemic, AI has been an aid to forecast outbreak spread globally. The overall aim of the study is to contribute to the ongoing public health, socioeconomic, and communication challenges caused by COVID-19. Protocol: COLEV is a five-pronged interdisciplinary mixed methods project based on AI and data science from an inclusive perspective of age and gender to develop, implement, and communicate useful evidence for COVID-19-related response and recovery in Colombia. The first objective is identification of stakeholders’ preferences, needs, and their use of AI and data science relative to other forms of evidence. The second objective will develop locally relevant mathematical models that will shed light on the possible impact, trajectories, geographical spread, and uncertainties of disease progression as well as risk assessment. The third objective focuses on estimating the effect of COVID-19 on other diseases, gender disparities and health system saturation. The fourth objective aims to analyze popular social networks to identify health-related trending interest and users that act as ‘super spreaders’ for information and misinformation. Finally, the fifth objective, aims at designing disruptive cross-media communication strategies to confront mis- and dis-information around COVID-19. To understand stakeholders’ perspectives, we will use semi-structured interviews and ethnographic work. Daily cases and deaths of COVID-19 reported from the National Surveillance System (INS) of Colombia will be used for quantitative analysis, and data regarding the online conversation will be obtained from Facebook and Twitter. Conclusions: COLEV intends to facilitate the dialogue between academia and health policymakers. The results of COLEV will inform on the responsible, safe and ethical use of AI and data science for decision-making in the context of sanitary emergencies in deeply unequal settings.",
"keywords": [
"COVID-19",
"artificial intelligence",
"decision-making",
"data science"
],
"content": "Introduction\n\nThe coronavirus disease of 2019 (COVID-19) has been responsible for more than three million deaths worldwide up to July 2021.1 Latin America is home to approximately 30% of such deaths according to the World Health Organization (WHO). Global vaccine research and development against COVID-19 was unprecedented in terms of scale and speed1; in May 2020, there were 73 candidates in the pre-clinical stages. On December 2020, 13 of the vaccine candidates were on phase 3, and by February 2021, four vaccines were already licensed for emergency use in several countries.1 Likewise, academic cooperation and production increased at rates never seen before,2 evidenced by an increase of 92% in submissions of health and medicine manuscripts during 2020 compared to 2019.3\n\nArtificial Intelligence (AI) and data science research are promising tools to better inform public policy and public health responses, promoting automation and affordability.4 During the COVID-19 pandemic, AI aids to forecast outbreak spread globally.5–7 Other AI applications have been documented on clinical applications aiding diagnosis and prognosis about COVID-19,8 and contact tracing and strict enforcement of quarantines.9 However, with the recent advances and applications in the field of AI to tackle COVID-19, ethical tensions have risen.10 The implementation of AI solutions might reinforce bias and discrimination, thus exacerbating social inequalities.11,12 For instance, when discriminatory structures are ingrained in datasets used to train algorithms, the AI systems will be biased and will reproduce, and even reinforce, the already discriminatory practices.12 In this context, diverse stakeholders and developer groups are essential to avoid unintended harmful consequences of building AI systems from a dominant, “one fits all” point of view.\n\nWith the pandemic, pre-existing social inequalities became more evident worldwide. The effect of the pandemic with regards to deepening social disparities are expected to be the highest in Latin America, where income inequality is the highest in the world; the top 1% wealthiest individuals owned 24.9% of the total income for 2019, while in the world, the same proportion of individuals owned the 19.1% of the income.13 Colombia, is no exception since it is one of the countries with the highest income inequality in the region and this situation is exacerbated by having also one of the highest labor market informality in Latin America, according to The World Bank In Colombia. Particularly, during 2020, 3.4 million people became unemployed, but women were disproportionally affected; while there was an 18% reduction in male employment, there was a 27.2% reduction for women.14 Additionally, there was an increase of 123% in emergency calls for domestic violence evidencing how gender disparities intensified.15\n\nSocial networks and mass media have played a fundamental role in disseminating public health content in recent years.16 The COVID-19 pandemic increased the public exposure to information regarding the prevention and management of the diseases.16 With massive amounts of information online, there is increased exposure to hoaxes and misinformation as well.17 Research has shown that misinformation is correlated with engaging in erroneous health practices that increase the spread of COVID-19 and leave room for several conspiracy theories and mistrust in health authorities and professionals.17,18\n\nThis protocol describes a five-pronged interdisciplinary research endeavor based on AI methods and data science from an inclusive perspective of age and gender to develop, implement, and communicate useful evidence for COVID-19-related response and recovery in Colombia, South America. The overall aim of the COLEV study is to contribute to the ongoing public health, socioeconomic, and communication challenges caused by the COVID-19 pandemic, as part of an initiative of the International Development Research Centre (IDRC) of Canada and the Swedish International Development Cooperation Agency (Sida) aiming to understand the response to the COVID-19 pandemic and support research based on AI in low and middle-income countries.\n\n\nProtocol\n\nCOLEV is a mixed-methods study on the design of AI and data science-based solutions to inform public health responses to COVID-19 in different local health ecosystems. Our purpose is to produce and communicate evidence for differential public health measures to address COVID-19-related challenges in Colombia tailored to regional contexts and vulnerable populations, through the interdisciplinary rigorous ethical use of AI and data science.19\n\nWe have five principal aims: 1) To identify health ecosystem stakeholders’ preferences and perceived needs regarding AI and data science, and their use in decision-making relative to other forms of evidence in response to COVID-19. 2) To develop a long-term and real-time model that allows forecasting of COVID-19 cases, hospital and intensive care unit (ICU) occupancy, and COVID-19 fatalities, based on estimated epidemiological parameters that account for age, socioeconomic, gender, and comorbidity variation and tailored input for decision making allowing to compare the impact of possible interventions and targeting resources. 3) To evaluate the impact of COVID-19 on health and health-related outcomes and their effect on the resource management policies for the health ecosystems. 4) To characterize the online public conversation about COVID-19 analyzing popular social networks with AI methods. And 5) to design a disruptive communication strategy tailored to different societal groups to confront mis- and dis-information around COVID-19 and reinforce our local and national public health measures and policies. Table 1 summarizes the research questions that we seek to answer.\n\nEthical approval has been obtained by Ethics Committee at the Universidad de Los Andes (Acta: No.1394 – 2021). The participants will provide written informed consent to participate in this study.\n\nColombia is located in South America, with a population of 50,372,424 with about two million indigenous and three million Afro-Colombians,20 and has profound social inequalities as evidenced by its income Gini coefficient (0.51 in 2019),21 and deep urban/rural disparities. For example, the multidimensional poverty index was 17.5% at national level in 2019, while in rural areas was 34.5%.22\n\nThe Colombian health system is an insurance-based model with 98% of the population affiliated. Amid social inequalities, the healthcare system is based on the solidarity principle in which employees and self-employed workers with capacity to pay, along with taxes, cover the affiliation of those of lower income and unemployed who account for 47% of the population.23\n\nDuring 2020, Colombia implemented different measures to mitigate and control the COVID-19 pandemic, land and river borders were closed, schools and universities were closed, and a mandatory lockdown was declared on March 24/2020, which lasted until August 31/2020. In September, a selective lockdown phase began to mitigate the economic impact of the virus locally and to allow productive life.24\n\nThis study employs a mixed-methods design. The quantitative and qualitative data will be obtained from several sources, mentioned below:\n\nQualitative data collection\n\nTo understand stakeholders’ perspectives on the development and use of AI and data science for public health and COVID-19 responses in the country, we will use semi-structured interviews and ethnographic work. Interviews will be conducted with stakeholders of relevance in decision-making about the COVID-19 response, and ethnography will be conducted with scientists or engineers developing technologies based on AI and data science. We will observe the processes of developing technological tools and their efforts to transfer them to the field of policy. Stakeholders include national and local government representatives, health policy planners, health providers, research centers, and AI and data science developers and experts. We will develop a map of actors to select potential interviewees. We will leverage our current, close and longstanding relationships with such stakeholders to recruit our participants. Then, we will follow a snowball sampling until we reach theoretical saturation. In addition to the stakeholders’ interviews, we will select relevant case studies, up to three, of AI development or use targeting COVID-19 that we can analyze using ethnography. All interviews will be audio-recorded and transcribed. The interviews, fieldwork diaries, and relevant documents will be coded and analyzed using NVivo (NVivo, RRID:SCR_014802).\n\nAdditionally, data from curated pieces of mis- and dis-information associated with COVID-19 in Colombia should be collected from the national network of factcheckers, Colombiacheck. The number of pieces of mis- and dis-information will depend on the criteria that Colombiacheck uses to publish and check including virality, and engagement.\n\nQuantitative data collection\n\nQuantitative data will rely on secondary sources. We will use daily cases and deaths of COVID-19 reported from the National Surveillance System ‘Instituto Nacional de Salud’ (INS) of Colombia. The data from other morbidities, such as mental health disorders, will be extracted from the National Record of Services reported by the Ministry of Health.25 Mortality due to other causes different from COVID-19, live-births by ages and sex at the municipal level will be taken from the Vital Statistics generated by the Department of National Statistics of Colombia (DANE). The population data will be extracted from the population projections calculated by DANE. And, the information of daily doses of vaccines is available from the official records and reports of the Ministry of Health.\n\nData regarding the online conversation will be obtained from Facebook, and Twitter COVID-19 data streams. These data sources will be complemented with The Americas Barometer survey, conducted by ‘Observatorio de la Democracia’ (Democracy Observatory). Table 1 summarizes the pool of secondary sources according to aims and research questions.\n\nThe interview guides that will be used to collect data can be found as Extended data.38\n\nTo answer the research questions for each objective, an interdisciplinary team will be formed including researchers from several disciplines such as data scientists, social scientists, and health professionals. An advisory committee with national and international experts in public health and governance was created to guide the project’s priorities, analyze, and validate the results. To establish a common language and to deliver aligned products, the team is going to work around four cross cutting topics: return to schools, vaccination, mental health, and vulnerable groups such as migrant populations.\n\nCOLEV was envisioned as a means to co-construct AI and data science-based solutions to inform public health responses to COVID-19 in different local health ecosystems. It builds upon the experience of several research groups from Universidad de los Andes, University of California–Santa Cruz (UCSC) and Non-Governmental Organizations (NGOs) like the health observatory ‘Así Vamos en Salud’ and ‘ASI ES SALUD’. These two organizations are articulated and plan to use COLEV results to guide actions in the context of the pandemic leveraging on long standing relationship with stakeholders in Colombia (i.e., decision makers, other academic groups, the civil society, and health care providers and ensures). We recognize the need for collaboration between different institutions and research projects, interacting with different sectors such as education, health, city planning, amongst others (Figure 1).\n\nCOVID-19, coronavirus disease of 2019.\n\nThe analysis plan for each objective is described below:\n\nObjective 1. To identify health ecosystem stakeholders’ preferences and perceived needs regarding AI and data science, and their use in decision-making, relative to other forms of evidence in response to COVID-19. Upon recording and transcription of the interviews, we will conduct a thematic analysis26 that will be centered in comparing processes of development, communication, and use of data to inform decision-making on COVID-19. The ethnography will involve tracing how AI and data science are used for different applications in relation to COVID-19 so that comparisons can be drawn between data use in different geographical localities and a variety of applications in public health. We will conduct joint mapping of stakeholder arrangements, informing the topics discussed in interviews, and joint observations of decision-making processes.\n\nObjective 2. To develop a long-term and real-time model that allows for forecasting of COVID-19 cases, hospital and ICU occupancy, and COVID-19 fatalities, based on estimated epidemiological parameters that account for age, socioeconomic, gender, and comorbidity variation and tailored input for decision-making allowing to compare the impact of possible interventions and targeting resources. We will start by developing and providing a forecasting system for the country that combines space-time AI approaches, statistical inference methods, and data assimilation algorithms. We will combine different forecasting approaches to create a standardized set of data on forecasts making projections of COVID-19 cases, hospital and ICU occupancy, and COVID-19-fatalities in Colombia. Multiple outputs from the model will be collected, standardized, visualized, and synthesized in a dashboard with accuracy measures and description of the methods. Every week, we will update our COVID-19 Forecast ensemble and interactive visualization using the most recent forecast from each approach.\n\nObjective 3. To evaluate the impact of COVID-19 on health and health-related outcomes and their effect on the resource management policies for the health ecosystems. We will gather secondary data regarding non-communicable diseases (e.g., cardiovascular diseases), mental illnesses (e.g., depression and anxiety); adolescent pregnancies, domestic violence, and other infectious diseases (e.g., Dengue, Malaria). We will develop descriptive and predictive models using data mining,27 identifying trends and behaviors before and after the arrival of COVID-19.\n\nTo characterize the process services, we will describe the pathway followed by a patient in the system and the resources consumed. To do that, we will use time-motion studies and process and network analysis. The time-motion studies are useful for identifying the stages, times, physical and technical resources, and staff required to provide a specific health service.28,29\n\nObjective 4. To characterize the public online conversation about COVID-19 analyzing popular social networks with AI methods. This study will use the Twitter data stream starting from March 1, 2020, based on the keywords “COVID-19”, “coronavirus”, and “Colombia”. Foundational information (i.e., raw text, user IDs, timestamps, unique tweet ID, among others), sub dictionaries (i.e., user, place, extended tweets, retweeted status), as well as any other available metadata (e.g., language, retweets, favorites, replies), will be retrieved.\n\nWe will organize the information as Pandas DataFrame, and any hierarchical structures will be flattened. The Twitter data stream will be analyzed in two ways: 1) as snapshots of periods of time based on the occurrence of key events of national importance and peaks in Twitter usage and content creation, and 2) as a time series with the intent of capturing content variation over time. Sentiment analysis is a useful technique to indicate the prevailing emotion attached to a specific 28/59 keyword, cluster, or network employing several machine learning algorithms of the natural language processing (NLP) family. To this end, the VADER toolkit of the NLKT python package will be used for tweets and replies. This toolkit allows for the interpretation of capital letters, exclamation marks, and emojis as well as raw text. A pilot analysis of a 1% sample of the retrieved tweets will be assessed manually in order to confirm the face validity of the algorithm. The same procedure will be repeated using Facebook data.\n\nObjective 5. To design a disruptive communication strategy tailored for different societal groups to confront mis- and dis-information around COVID-19 and our local and national public health measures and policies. We will follow a three-step routine:\n\nFirst, we will develop custom-made solutions to organize, systematize, and visually display the data acquired to identify and represent patterns and insights regarding the narrative components of COVID-19 mis- and dis-information in the Colombian context.30,31 Several of the tools that will be used are based on JavaScript and Python integration with AI and ML methods, such as Text Mining, Statistical Natural Language Process (NLP), and NLP topic modeling, which are previously applied to translate into rich visual experiences of high accuracy that help with information understanding in the decision-making process.32\n\nSecond, after having a visual representation of the data, we will share this visualizations with the public sector media, traditional media leaders, and digital media key practitioners interested in the problem of mis- and dis-information around COVID-19 using User-Centered Design and Service Design methodologies.33,34 We will conduct workshops with these media outlets to discuss the insights about the use of Data-Driven Journalism and Data Visualization Storytelling to communicate them.35,36\n\nThird, upon identification of the narrative components we will then design and prototype the disruptive communication strategy. We will use Speculative Design and Co-Design methods to break and subvert the narratives created by mis- and dis-information going back to the media stream with concrete interventions.37\n\nThis study was approved by the Ethics Committee at Universidad de Los Andes (Acta No.1394 – 2017). All subjects will sign an informed consent form during the qualitative data collection. Findings will be disseminated through open access publications, academic events, newspaper outlets, and presentations with stakeholders.\n\nFor the quantitative components, we are currently in the data collection stage. Interviews are being conducted, and snowball sampling is still in place. The researchers have not yet reached theoretical saturation. Researchers are currently cleaning and depurating the datasets provided by official sources in the quantitative component. Additionally, the team is currently designing Application Programming Interfaces that facilitate automatic acquisition and cleaning of the datasets to be ready for analysis.\n\n\nDiscussion\n\nThe COLEV study aims to generate evidence for decision-makers at the local level. The interdisciplinary nature of our working group will allow a greater understanding of the complexity of the pandemic in a country in which inequalities have increased. We hope to facilitate the dialogue between the academia and health policymakers by first exploring their needs, priorities and concerns regarding AI and data science solutions for COVID-19 control; and then co-construct such strategies. Additionally, we expect to identify the main super-spreaders of misinformation in social networks and build disruptive communication strategies to combat misinformation with an emphasis on COVID-19 vaccination and the emergent main topics of the online conversation in Colombia.\n\nThe results of COLEV will inform local and regional researchers and stakeholders on the responsible, safe and ethical use of AI and data science for decision-making in the context of sanitary emergencies in deeply unequal settings.\n\n\nData availability\n\nNo data are associated with this article.\n\nOpen Science Framework: Decisions and Data. https://doi.org/10.17605/OSF.IO/AYU9W.38\n\nThis project contains the following extended data:\n\n- Interview guide - Stakeholders.pdf\n\n- Interview guide - Stakeholders involved in COVID-19 decision making processes.pdf\n\n- Participant informed consent.pdf\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "References\n\nThanh Le T, Andreadakis Z, Kumar A, et al.: The COVID-19 vaccine development landscape. Nat. Rev. Drug Discov. 2020; 19(5): 305–306. Publisher Full Text\n\nMaher B, Van Noorden R: How the COVID pandemic is changing global science collaborations. Nature 2021; 594(7863): 316–319. PubMed Abstract | Publisher Full Text\n\nElse H: How a torrent of COVID science changed research publishing - in seven charts. Nature 2020; 588(7839): 553. Publisher Full Text\n\nMellado B, Wu J, Kong JD, et al.: Leveraging Artificial Intelligence and Big Data to Optimize COVID-19 Clinical Public Health and Vaccination Roll-Out Strategies in Africa. J. Environ. Res. Public Heal. 2021; 18: 7890. PubMed Abstract | Publisher Full Text\n\nAlbahri OS, Zaidan AA, Albahri AS, et al.: Systematic review of artificial intelligence techniques in the detection and classification of COVID-19 medical images in terms of evaluation and benchmarking: Taxonomy analysis, challenges, future solutions and methodological aspects. J. Infect. Public Health 2020 Oct 1 [cited 2021 Dec 14]; 13(10): 1381–1396. Publisher Full Text Reference Source\n\nShinde GR, Kalamkar AB, Mahalle PN, et al.: Forecasting Models for Coronavirus Disease (COVID-19): A Survey of the State-of-the-Art. SN Comput. Sci. 2020 [cited 2021 Aug 31]; 1: 197. PubMed Abstract | Publisher Full Text\n\nAlimadadi A, Aryal S, Manandhar I, et al.: AI and Machine Learning for Understanding Biological Processes: Artificial intelligence and machine learning to fight COVID-19. Physiol. Genomics 2020 Apr 1 [cited 2021 Dec 17]; 52(4): 200–202. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWilliams CM, Chaturvedi R, Urman RD, et al.: Artificial Intelligence and a Pandemic: an Analysis of the Potential Uses and Drawbacks. J. Med. Syst. 2021; 45(3): 5–7.\n\nLin L, Hou Z: Combat COVID-19 with artificial intelligence and big data. J. Travel Med. 2020; 27(5): 1–25.\n\nCave S, Whittlestone J, Nyrup R, et al.: Using AI ethically to tackle covid-19. BMJ 2021 Mar 16 [cited 2021 Aug 31]; 372(364). Publisher Full Text Reference Source\n\nKorinek A, Stiglitz JE: Covid-19 driven advances in automation and artificial intelligence risk exacerbating economic inequality. BMJ 2021; 372(367): 1–3. Publisher Full Text\n\nLeslie D, Mazumder A, Peppin A, et al.: Does “AI” stand for augmenting inequality in the era of covid-19 healthcare? BMJ 2021 Mar 16 [cited 2021 Aug 31]: 372.Reference Source\n\nWID.world: World Inequality Data - 2020 Update. World Inequality Database.2020 [cited 2021 Aug 31].Reference Source\n\nDepartamento Administrativo Nacional de Estadística. Mujeres y Hombres: Brechas de Género en Colombia. Mujeres y Hombres. Brechas de Género en Colombia 2020; 246.Reference Source\n\nVicepresidencia de Colombia: Aumentan en 142% llamadas a Línea 155, por violencia intrafamiliar durante Aislamiento. Noticias 2020 [cited 2022 Jan 19].Reference Source\n\nTagliabue F, Galassi L, Mariani P: The “Pandemic” of Disinformation in COVID-19. SN Compr. Clin. Med. 2020; 2(9): 1287–1289. PubMed Abstract | Publisher Full Text\n\nTasnim S, Hossain M, Mazumder H: Impact of rumors and misinformation on COVID-19 in social media. J. Prev. Med. Public Heal. 2020 [cited 2021 Aug 31]; 53(3): 171–174. PubMed Abstract | Publisher Full Text\n\nIslam MS, Sarkar T, Khan SH, et al.: COVID-19-Related Infodemic and Its Impact on Public Health: A Global Social Media Analysis. Am. J. Trop. Med. Hyg. 2020 Oct 1 [cited 2021 Aug 31]; 103(4): 1621–1629. PubMed Abstract | Publisher Full Text\n\nUNESCO: Preliminary study on the ethics of artificial intelligence. París2019.\n\nDepartamento Nacional de Estadística: Resultados Censo Nacional de Población y Vivienda: tercera entrega. Reports.2019.Reference Source\n\nThe World Bank: Income GINI. Indicators.2020.Reference Source\n\nDepartamento Administrativo Nacional de Estadística: Pobreza multidimensional. Bogotá2020.Reference Source\n\nde Salud M ; Protección Social: Reportes Aseguramiento: Afiliados a Salud, Noviembre de 2021. Bodega de datos de SISPRO.2021 [cited 2021 Dec 17].Reference Source\n\nInstituto Nacional de Salud: COVID-19 en Colombia, consecuencias de una pandemia en desarrollo. Bogota2020.Reference Source\n\nMinisterio de Salud y Protección Social: Preguntas frecuentes RIPS ¿Qué son los RIPS?. Bogotá, Colombia2015 [cited 2022 Jan 11].Reference Source\n\nVaismoradi M, Turunen H, Bondas T: Content analysis and thematic analysis: Implications for conducting a qualitative descriptive study. Nurs. Health Sci. 2013 Sep; 15(3): 398–405. Epub 2013 Mar 11. Publisher Full Text PubMed Abstract |\n\nJothi N, Aini N’, Rashid A, et al.: ScienceDirect The Third Information Systems International Conference Data Mining in Healthcare-A Review. Procedia Comput. Sci. 2015 [cited 2022 Jan 14]; 72: 306–313. Publisher Full Text Reference Source\n\nStarmer AJ, Destino L, Yoon CS, et al.: Intern and Resident Workflow Patterns on Pediatric Inpatient Units: A Multicenter Time-Motion Study. JAMA Pediatr. 2015 Dec 1 [cited 2022 Jan 14]; 169(12): 1175–1177. PubMed Abstract | Publisher Full Text Reference Source\n\nWagenaar BH, Gimbel S, Hoek R, et al.: Wait and consult times for primary healthcare services in central Mozambique: a time-motion study.2016 [cited 2022 Jan 14]. Publisher Full Text\n\nKirk A: Data Visualisation: A Handbook for Data Driven Design. Second ed.London:Sage Publishing;2019; 15–30.\n\nLima M: Visual complexity: mapping patterns of information. New York:Princeton Architectural Press;2011; 272.\n\nMeirelles I: Design for Information. An introduction of the histoires, theories, and best practices behind effective information visualization. Illustrated. Rockport Publishers;2013 [cited 2022 Jan 14]; 224.Reference Source\n\nCreswell JW, Creswell JD: Research design: Qualitative, quantitative, and mixed methods approaches. Fifth ed.Los Angeles:Sage Publications;2017.\n\nMartin B, Hanington B: Universal Methods of Design: 100 Ways to Research Complex Problems, Develop Innovative Ideas, and Design Effective Solutions. Berkeley; 2012; 12–13 p.\n\nMarconi F: Newsmakers: artificial intelligence and the future of journalism. Columbia University Press;2020.\n\nNussbaumer C:2015; Storytelling with data. First ed.Hoboken, New Jersey:Wiley.Reference Source\n\nDunne A: Consuming monsters: big, perfect, infectious. First ed.Cambridge, Massachusetts; London:The MIT Press;2013; 2013 [cited 2022 Jan 14]; 47–58.Reference Source\n\nGonzález-Uribe C, Niño-Machado N, Turner S: Decisions and Data. [Dataset]. 2022, May 30. Publisher Full Text"
}
|
[
{
"id": "163597",
"date": "07 Mar 2023",
"name": "Natali Valdez",
"expertise": [
"Reviewer Expertise clinical trial design",
"evidenced-based medicine",
"public health",
"epigenetics",
"maternal 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 aim of this project and paper are to co-create data science-based solutions to inform public health responses to pandemics. The research was rigorously and thoughtfully designed to include both qualitative and quantitative approaches that critically inform processes of Big Data. This type of methodological approach is vital to the advancement of precise technological innovations at local and global scales. The strengths of this study protocol are that the objectives are clearly outlined and feasible, and that the broader impacts of this study are clearly connected to methodological design.\nMy understanding is that COLEV is a mixed methods project composed of interdisciplinary scholars that aim to tackle the urgent issue of developing and communicating transparent, trustworthy data for the creation of effective public health interventions on COVID-19. It aims to address this large issue through 5 objectives.\nThese objectives center around\n\n1) Understanding the ways in which AI and data science are used to communicate topics related to COVID-19, which draws on ethnographic data from people who are using data science to inform decisions about public health interventions.\n2) To develop a forecasting system based on a variety of public health data in relation to COVID-19.\n3) To understand the impact of COVID-19 on related health outcomes and resource management systems, which draws uniquely on a patient-centered perspective.\n4) To analyze public conversations of COVID-19 drawing on available twitter data in order to illustrate the understanding or comprehension among people in Colombia.\n5) To disrupt avenues of disinformation, this objective is closely connected to objective #4 and work together to address the impacts of effective medical/scientific communication.\nAll of these objectives are valuable and important in narrating a complex and nuanced understanding of the role of data science in relation to pandemics. The report outlines clear strategies for addressing these objectives with strong methodological research design.\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": "173708",
"date": "14 Sep 2023",
"name": "Arriel Benis",
"expertise": [
"Reviewer Expertise Health Data Science",
"Healthcare Informatics",
"Digital Health",
"Public Health",
"Epidemiology",
"Health Communication",
"One Health",
"One Digital 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\nThis manuscript is a research protocol dealing with a project entitled COLEV. COLEV's main and final aim is to deliver disruptive cross-media communication strategies to confront mis- and disinformation around COVID-19 and pandemics. COLEV will be based on AI approaches and data science processes developed with standard tools.\nThe protocol is clear and exhaustive.\nHowever,\nThe authors could more clearly point out (1a) the start and end dates of the qualitative and quantitative data collection, (1b) the expected date of the publication of the results.\n\nThe authors are not providing clear information about the Machine Learning algorithms they will use and why.\n\nIt will be interesting to add a short \"Discussion\" dealing with the\n(3a) \"Strengths and Limitations\" and\n\n(3b) the expected results for operational perspectives (i.e., policies) of this protocol.\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? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": [
{
"c_id": "11393",
"date": "21 Jun 2024",
"name": "Catalina González-Uribe",
"role": "Author Response",
"response": "Response to reviewers: Thanks you for your comments, below you can find our responses. The authors could more clearly point out: (1a) the start and end dates of the qualitative and quantitative data collection Quantitative data was collected between January 2019 and September 2021, and qualitative data was collected between March 2021 and July 2022. (1b) the expected date of the publication of the results. As the aim of our project is to support and inform decision-making amid the COVID-19 pandemic, results will be shared with stakeholders and decision-makers as they are being produced. The authors are not providing clear information about the Machine Learning algorithms they will use and why. Data processing and analysis will be done using Python, R, and Spark. We will organize the queried information in data frames, and any hierarchical structures resulting from the original JSON formatting will be flattened. It will be interesting to add a short \"Discussion\" dealing with the: (3a) \"Strengths and Limitations\" The strengths of this study are its comprehensive coverage of a wide range of topics related to the use of AI and data science in addressing the COVID-19 pandemic in Colombia. The study is interdisciplinary, involving researchers from various fields, including public health, epidemiology, computer science, and social science. Additionally, the study employs mixed-methods, incorporating both qualitative and quantitative data collection methods. Furthermore, the study is specifically tailored to the unique social, economic, and political challenges of Colombia, making it highly relevant to the country's context. It's essential to acknowledge that the tools used in this study are still in their initial stages. Therefore, it may be too soon to determine the impact of the AI and data science interventions being developed. Furthermore, it's worth noting that the study focuses specifically on Colombia, and the findings may not apply to other countries. (3b) the expected results for operational perspectives (i.e., policies) of this protocol. The results of the study will be used to shape public policy and address the needs of decision-makers and stakeholders. The study is expected to have specific applications, such as predicting the number of COVID-19 cases, estimating the effectiveness of interventions like social distancing and quarantine, and supporting policies and decision-making related to the reopening of schools and the logistics of vaccination."
}
]
},
{
"id": "161479",
"date": "19 Sep 2024",
"name": "Leonardo Arregoces",
"expertise": [
"Reviewer Expertise Health policy",
"health economy",
"health financing",
"pharmaceutical and medical devices policy",
"regulatory affaris",
"health technology assessment"
],
"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\nMany thanks for considering me for reviewing this manuscript. It is a well thought, very ambitious research protocol that aims to provide relevant information for decision-making at different levels. The researchers do a great job in discussing with decision-makers their information needs and using their answers to develop models and dashboards suitable for informing the complicated decisions that the Covid-19 pandemic brought. Building an interdisciplinary team with skills in qualitative and quantitative skills makes the study robust. It is a quite ambitious project, so I hope the objectives were achieved.\nThat being said, it is complicated to review a research protocol after almost three years of pandemic. Because there are no dates on the manuscript, it is hard to tell if the protocol was originally written or planned as stated, or if it had amendments over time. All research suffers changes overtime. It is almost impossible to assess a priori changing circumstances that require adjustments to the protocol. Given that this protocol is being submitted for publication after the work was done, I suggest dates are added and a description of the changes that were needed overtime. This could be at the end of the paper after the analysis plan is described. Probably it could inform better future planning to have a thorough reflection on what was planned at the beginning and what changes were needed over time. It could be called lessons learned or something that capture the flexibility of the team in adjusting to the fast-changing situation that the Covid-19 pandemic showed.\nAlthough the product of this research is offered to be mostly graphical, such as dashboards and visual results of modelling, the protocol does not use a graphic method to describe how the objectives work together, how the information flows to meet them. For example, objective 1 aims at understanding preferences and information needs in the decision-making process, while objective 4 aims at characterising online conversations and sentiments. It is not clear if that feeds into objectives 2 or 5. A visual aid of how objectives work together to attain a higher purpose of better health would be appreciated. Theory of change might be interesting here.\nFinally, the paper is very well written, easy to read and understand what the research team is aiming for. I believe taking into consideration my two suggestions might be useful for this team and other researchers when planning future endeavors of the magnitude of this work.\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
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https://f1000research.com/articles/11-691
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https://f1000research.com/articles/11-689/v1
|
21 Jun 22
|
{
"type": "Research Article",
"title": "Single blind, randomized study comparing clinical equivalence of Trusilk® and Mersilk® silk sutures for mucosal closure following surgical removal of mesioangular impacted mandibular third molar",
"authors": [
"Ramdas Balakrishna",
"Dharnappa Poojary",
"Arvind R",
"Shrikanth Sali",
"Ashok Kumar Moharana",
"Deepak TS",
"Ramdas Balakrishna",
"Arvind R",
"Shrikanth Sali",
"Ashok Kumar Moharana",
"Deepak TS"
],
"abstract": "Background: Mesioangular impacted mandibular third molar is a common dental anomaly, for which surgical extraction is required. Post-surgery closure of mucosa reduces the prevalence of pain and other surgery-associated complications. We compared tissue reaction/inflammation after 3 and 7 days of mucosal closure with Trusilk® and Mersilk® silk sutures, following impacted mandibular third molar removal. Methods: This multicenter, prospective, two-arm, parallel-group, randomized (1:1), single-blind study (July 2020-November 2021) included subjects (Trusilk®, n=65 and Mersilk®, n=64), requiring mucosal suturing following impacted mandibular third molar removal. The primary endpoint, incidence of pain, swelling and trismus at the extraction area on post-surgery day 3 and 7 was evaluated. The secondary endpoints, incidence of tissue reaction, wound infection, suture loosening, other complications, operative time, amount of anesthesia, intraoperative suture handling, time needed for complete wound healing and suture removal, and adverse events were also recorded. Results: Socio-demographic and intra-oral characteristics were comparable between the groups. In Trusilk® and Mersilk® groups, a gradually decreasing pain score, starting from day 0 post-surgery (42.17±22.38 vs. 45.97±22.20) to day 7 (8.40±11.93 vs. 8.28±12.13) to day 30 (1.98±0.89 vs. 1.75±0.76) was witnessed. After the surgery, 21.54% and 17.19% subjects in Trusilk® and Mersilk® groups, respectively, had no post-operative swelling, while at the last two visits none of the subjects had swelling. Non-significant difference in wound infection, suture loosening, wound healing, bleeding, taste changes, operative time, amount of anesthesia, intraoperative suture handling, and time needed for complete wound healing and suture removal was noted among the groups. No suture-related adverse events were recorded. Conclusions: The results indicated that the Trusilk® and Mersilk® silk sutures are clinically equivalent and can be used for mucosal closure after removal of an impacted mandibular third molar with a minimal rate of pain, swelling and trismus. Clinical Trial Registry of India Registration: CTRI/2020/03/024100 (20/03/2020)",
"keywords": [
"Impacted third molar",
"Mucosal suturing",
"Silk suture",
"Pain",
"Swelling",
"Trismus"
],
"content": "Introduction\n\nImpacted tooth is a common dental anomaly that usually occurs in the mandibular third molars, maxillary canines, and maxillary second premolars.1 Mandibular third molar is commonly impacted (72%), in comparison to maxillary third molars (37.9%), reason for which can either be the lack of space and physical barrier posed by the permanent second molar, or malalignment due to delayed mineralization and early physical maturation.2 In addition, genetic characteristics and food habits also contribute to the occurrence of tooth impaction.3 The prevalence of third molar impaction has already been reported in various countries, such as India, Pakistan, Iran, Saudi Arabia, Oman, Turkey and Sweden.4\n\nDental surgeons prefer third molar extraction based on pain, recurrent infection, local and/or regional swelling, dental caries or cysts, etc.5,6 In the oral surgical field, surgical removal of third molar is considered as a common dental operative procedure,4 which involves accessibility of the tooth by removing the overlying bone and exposing the tooth. After sectioning, the sectioned tooth is delivered following closure of the wound.7 The associated complications of impacted tooth surgery are pain, paresthesia (i.e., damage to sensory nerve), dry socket, infection, and hemorrhage. Several factors such as patient’s age, health status, and position of the tooth further influence the rate of complications.8\n\nFollowing the surgery, primary tissue closure or mucosal closure using a braided silk suture has been found to reduce pain, edema, and trismus, and improve wound healing.9 In comparison to other non-absorbable suture materials, silk suture is mostly used for dental procedures due to its cost-effectiveness.10 The present study was designed to evaluate clinical equivalence of two common silk suture brands, Trusilk® and Mersilk® for mucosal closure in subjects undergoing planned surgical removal of mesioangular impacted mandibular third molar.\n\n\nMethods\n\nThis was a multicentric, prospective, two-arm, parallel-group, randomized (1:1), single-blind study, conducted in two different centers between July 2020 and November 2021. The primary objective of the study was to compare tissue reaction/inflammation with Trusilk® and Mersilk® silk sutures post primary closure of mucosa in subjects undergoing planned surgical removal of impacted mandibular third molar at 3 and 7 days. The secondary objectives were to compare the incidence of tissue reaction and infection, the effect of suture material on wound healing and other surgical outcomes, overall intraoperative handling, and the common post-surgical complications between the two groups, Trusilk® and Mersilk®.\n\nThis clinical study was registered on 20th March 2020 with Clinical Trial Registry of India (CTRI Registration No- CTRI/2020/03/024100). The institutional ethics committee of both participating sites approved this study protocol (K.L.E Society’s Institute of Dental Sciences Ethics Committee approved the study on 21st November 2019 with approval number KIDS/IEC/NOV-19/3; and Manipal Academy of Higher Education Ethics Committee approved the study on 8th February 2020). The study was designed, conducted, recorded, and reported in compliance with the principles of International Conference on Harmonization of Technical Requirements-Good Clinical Practice (ICH-GCP E6 R2) guidelines, EN ISO 14155:2020 guidelines, Indian MDR rules 2017, MDR (EU) 2017/745, Indian New Drugs and CT rules 2019, and Consolidated Standards of Reporting Trials (CONSORT).19\n\nWritten informed consent was obtained from all participants for participation in the study as well as for publication of their clinical data.\n\nMale and female subjects, aged 20-40 years with mesioangular impacted mandibular third molar, requiring mucosal suturing after removal, who visited Department of Oral & Maxillofacial Surgery of both the centers were invited to participate in this research. They were included after obtaining informed consent. Subjects only with American Society of Anesthesiology classification of grade I or II were included.\n\nSubjects with infected molar or complicated impacted third molar, pregnant or lactating women and subjects, who were unlikely to comply with surgical procedure or complete the scheduled visits in the opinion of the Investigators were excluded. Subjects with a history of allergy to silk or similar products, and a history of systemic diseases (diabetes mellitus, tuberculosis, bleeding disorders, osteoporosis, unstable or life-threatening conditions), or undergoing radiation therapies were also excluded. Subjects receiving any type of local and systemic drugs, or drugs like aspirin, blood thinners and anticoagulant therapy, or an experimental drug or used an experimental medical device within 30 days prior to surgery, or who had the habit of drug abuse were excluded. Subjects who were already participating in another trial or had direct involvement in the proposed study or other studies under the direction of that Investigator or study center were excluded.\n\nThe study was conducted at two sites: (i) The Department of Oral & Maxillofacial Surgery, KLE Society’s Institute of Dental Sciences & Research Center, Bangalore, India, and (ii) The Department of Oral & Maxillofacial Surgery, Manipal College of Dental Sciences, Mangalore, India.\n\nBoth Trusilk® (Healthium Medtech Limited) and Mersilk® (Ethicon, Johnson & Johnson) are natural non-absorbable black braided sterile silk suture. Both sutures are indicated for use in soft tissue approximation and or ligation. Both the sutures are composed of an organic protein called fibroin (derived from the domesticated species Bombyx mori) and are coated with wax to reduce friction.\n\nDemographics and other relevant characteristics\n\nAge, gender, ethnicity, weight, height, body mass index, history of smoking, gutkha chewing (tobacco use), education and employment status were recorded at screening visit. The vital signs like pulse rate, respiration rate, and systolic and diastolic blood pressure (measured after the subjects were in supine position for 5 minutes) were recorded. A general medical or surgical history was also noted. Intraoral examination for present teeth, missing teeth, interincisal mouth opening, tongue size (macroglossia/normal/microglossia), dental scaling, dental caries, tooth deposits, and oral/dental cyst was done. Diagnosis of impacted third molar was done by dental X-rays.\n\nPrimary endpoints\n\nThe primary endpoint was incidence of clinical inflammation/tissue reaction in the extraction area at 72 hours (3 days) and 7 days post-surgery. It was identified with assessment of pain, swelling and trismus. Visual analogue scale (VAS) score for pain was recorded at screening, post-surgery (Day 0), and on all follow-up days. 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. Swelling and trismus were also assessed using a VAS scale ranging from 0 to 5, where 0 is no swelling, 1 is slight swelling, 2 is mild swelling, 3 is severe swelling, 4 is very severe swelling, and 5 is extremely severe swelling.\n\nSecondary endpoints\n\nThe secondary endpoints, included incidence of tissue reaction, wound infection, suture loosening, other complications (delayed wound healing, bleeding, and taste changes), operative time (time from oral incision to the end of wound closure), amount of anesthesia used, intraoperative suture handling, time needed for complete wound healing and suture removal. Other postoperative complications, including dry socket, paresthesia, taste changes, suture sent for culture (in case of microbial deposits on sutures), and adverse events were also assessed. Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs, which were already reported as study endpoints, were not labelled and reported as adverse events. All the medications prescribed to the subjects during the study period were also registered.\n\nThe handling characteristics viz. ease of passage through tissue; first-throw knot holding; knot tie-down smoothness; knot security; surgical handling; memory; suture fraying of both sutures were rated on a five-point scale as follows: 1 poor, 2 fair, 3 good, 4 very good, and 5 excellent. Wound healing was measured by using a healing index proposed by Landry, Turnbull and Howley11 to describe the extent of clinical healing after surgery. The scale evaluated tissue color, suppuration, granulation tissue, bleeding on palpation and incision margins on a five-point scale: 1 is very poor, 2 is poor, 3 is good, 4 is very good, and 5 is excellent. Bleeding assessment was done on a modified VAS scale, on which 0 corresponds to no bleeding, 1 to oozing, 2 to accidental low bleeding, 3 to continuous low bleeding and 4 to massive bleeding.\n\nAssumptions for sample size calculations were based on clinical data reported by Chaudhary et al., 2012.12 Mean VAS score for swelling on Day 1 and Day 3 was reported as 2.58 and 2.08 respectively with a SD of 0.79. Assuming type I error as 5% (α=0.05) and power as 80% (1-β=0.8) and non-inferiority margin as 10%, the minimum sample size requirement was calculated to be 50 in each arm. Mean VAS score for pain on Day 1 and Day 3 was reported as 2.25 and 1.58 respectively with a SD of 0.67. Assuming type I error as 5% and power as 80% and non-inferiority margin as 10% of the difference (δ), the minimum sample size requirement was calculated to be 20 in each arm. The sample size was found to be maximum when the Day 3 rather Day 7 VAS scores were considered vis-a-vis Day 1 scores. So, a sample size of 50 in each arm could safely be adopted to address both pain and swelling (primary endpoint). Further, considering a drop out of 20% and post-randomization exclusion of 10% the required sample size was increased to 66 in each arm. So, a total of 132 subjects participated in this trial, with 66 subjects randomized to Trusilk® arm and 66 to Mersilk® arm.\n\nSample size calculation formula:\n\nni: Sample size required in each group, Zα: Conventional multiplier for alpha, Zβ: Conventional multiplier for power, μ1: Mean score of swelling and pain in the standard Mersilk® arm, μ2: Mean score of swelling and pain in Trusilk® arm, δ: Margin of non-inferiority difference, σ: Standard deviation.\n\nTwo random lists of the size n=66 (33 vs. 33) were generated by using version 1.0 of Random Allocation Software, using block sizes of 4, 6 or 8. Subjects were randomized using block randomization to ensure an unbiased treatment assignment in a 1:1 ratio to receive either the Trusilk® or Mersilk® suture. The randomization concealment was done by SNOSE (Sequentially Numbered Opaque Sealed Envelopes) technique and codes were issued to the sites in sealed envelopes.\n\nThis was a single-blind study and the subjects were kept blinded to the device allocation status. Due to the nature of the intervention, the operating staff could not be blinded to allocation but they were instructed not to disclose the allocation status of the participant at any time.\n\nPost-screening (screening visit), the study participants underwent surgical procedures (baseline visit, Day 0). All routine aseptic precautions according to the existing standards were followed before, during and after the surgery. The subjects were treated as per the standard of care, after transferring to the observation room. An inflammation recording card was given to subjects after surgery to manually mark the level of pain, swelling and trismus, after onset of symptoms at the home. The subjects were followed-up on Day 3 (In-person visit), Day 7 (In-person visit), Day 12 (In-person visit), Day 30 (Telephonic visit) and Month 3 post-surgery (Telephonic visit) to record the primary and secondary endpoints.\n\nThe subjects were analyzed using the per-protocol or PP analysis set, which consist of all subjects who had complete data on the primary effectiveness parameter at 3 months of follow-up. All continuous variables were expressed as mean±SD (standard deviation). The normally distributed data were compared using t-test and distribution-free data was compared using Kruskal–Wallis test. All qualitative variables were expressed as proportions or percentages and were compared using Chi-square test or Fisher's Exact test. A p-value of < 0.05 was considered statistically significant. The primary endpoint was summarized as mean±SD (pain VAS score) and proportion/ percentage of subjects with no pain, swelling and trismus. Mean values were compared using Kruskal–Wallis test and proportion was compared using Chi-square test. The secondary endpoints were expressed as mean±SD or as proportions/percentages based on quantitative or qualitative nature of the variable. All analyses were carried out with SPSS version 28.0 (SPSS, Chicago, Illinois, USA, RRID:SCR_016479).\n\n\nResults\n\nBetween July 2020 and August 2021, a total of 132 subjects were screened. One participant from each group was excluded and reported as a protocol violation (age <20 years). One participant from Mersilk® group was also excluded because of consent withdrawal. Data was analyzed for a total of 129 subjects (Trusilk®, n=65; Mersilk®, n=64), who completed the study (Figure 1).18 The follow-up of the last subject was completed in November 2021.\n\nAll the subjects who participated in the trial were Indian. Out of all participants, 84 (65.12%) were women and 45 (34.88%) were men (Table 1). The education level of the participants was comparable between the groups, with 57 (87.69%) in Trusilk® group, and 59 (92.19%) subjects in Mersilk® group who attended college and above. Overall, 35 (53.85%) and 32 (50.00%) subjects in Trusilk® and Mersilk® groups, respectively, were employed. In total, four (6.15%) subjects in Trusilk® group, and one (1.56%) subject in Mersilk® group had smoking history, while one subject in each Trusilk® (1.54%) and Mersilk® (1.56%) group had a habit of gutkha chewing. Baseline demographics and vital signs were comparable between the treatment groups (Table 1). The participants had no medical or surgical history.\n\nIntra oral examination\n\nThe tongue size of all the study participants appeared normal. Full set of adult teeth was evident in majority of subjects of both groups, followed by 31 and 30 teeth. Average number of present and missing teeth along with findings of other intra oral examination is summarized in Table 1. Oral/dental cyst was absent in all the study participants. Before the surgery, mild swelling was recorded in 1 (1.54%) subject of Trusilk® group and 3 (4.69%) subjects of Mersilk® group, while mild trismus was noted in 2 (3.08% in Trusilk® group and 3.13% in Mersilk® group) subjects of both groups. Pain in the subjects prior to surgery is presented in Table 1.\n\nThe pain was assessed using VAS scale on day 1 after recovery from anesthesia (post-surgery), on day 3 and 7, as well as on all follow-up visits. The pain score was highest on the day of the surgery (42.17±22.38 vs. 45.97±22.20) in both Trusilk® and Mersilk® group and declined steadily with each passing visit (Figure 2a and 2b). In Trusilk® and Mersilk® groups, at day 3 and day 7 the mean pain VAS score was recorded as 26.22±20.64 vs. 23.05±19.09, and 8.40±11.93 vs. 8.28±12.13, respectively. At day 0, 3 and 7 visits, 4 (6.15%), 15 (23.08) and 42 (64.62) subjects of Trusilk® group, and 3 (4.69%), 16 (25.00) and 39 (60.94%) subjects of Mersilk® group had no pain. Similarly, the rate of swelling and trismus was also improved across the follow-up visits (Figure 2c). At day 0 visit, the incidence of no swelling was recorded in 14 (21.54%) and 11 (17.18%) subjects of Trusilk® and Mersilk® groups, respectively. At day 3 and 7 visits, 31 (47.69%) and 58 (89.23%) subjects respectively in Trusilk® group, and 25 (39.06%) and 52 (81.25%) subjects, respectively, in Mersilk® group had no swelling. Results of pain, swelling and trismus showed non-significant differences between the groups.\n\nVAS: Visual Analogue Scale.\n\nIntraoperative profile\n\nLignocaine+Adrenaline was used for local anesthesia during the surgery in all subjects. The amount of anesthesia and active pharmaceutical ingredients strength of the anesthesia is given in Table 2. One suture was used in all subjects of the Trusilk® as well as Mersilk® group. In all subjects, 3/8 circle reverse cutting needle was used. Total operative time, and time of onset of pain, swelling and trismus after tooth extraction are comparable between the studied groups (Table 2). The intraoperative suture handling characteristics in Trusilk® and Mersilk® groups are shown in Figure 3. The result of suture handling characteristics viz., ease of passage, knot holding, knot security, knot tie-down, stretch capacity, memory and suture fraying were marked as “excellent” or “very good” or “good” or “fair” and were comparable between the groups. None of the suture handling characteristics was graded as “poor” (Table 3).\n\nPost-operative profile\n\nSimilar to the results of primary endpoint, pain score, swelling and trismus were improved in the next post-operative visits (day 12, day 30 and month 3). In Trusilk® and Mersilk® group, the mean pain VAS score on day 12, 30 and month 3 was recorded as 3.34±6.11 vs. 2.08±1.47, 1.98±0.89 vs. 1.75±0.76, and 1.82±0.85 vs. 1.94±0.94, respectively. On last two visits, i.e., on day 30 and month 3, all the subjects of both arms had no pain, swelling or trismus (Figure 2a, b and c). Scores of both pain and swelling showed no significant difference between the groups. A decreasing rate of dental bleeding was recorded in subjects of both treatment arms with each follow-up visit (Figure 4a). Incidence of accidental bleeding or massive bleeding was noted in none of the study participants. Emergency care was not required for any subject after the surgery. A good outcome of surgery was registered for all the subjects. Inferior alveolar nerve paresthesia was reported in one (1.56%) subject randomized to Mersilk® group during day 7 visit. After the surgery, each subject was followed for signs and symptoms of dry socket. In total, one (1.54%) subject in the Trusilk® group had dislodged clot on day 7 visit. The subject recovered after treatment, and none of other subjects in both the groups showed further symptoms of dry socket at follow-up visits. Findings of suture loosening and taste change are shown in Table 2. In Mersilk® group, suture was loosened in one (1.56%) subject on day 3, and in three (4.69%) subjects on day 7 visit. On the other hand, in Trusilk® group, suture was loosened in four (6.15%) subjects only on day 7 visit. Due to food impaction, a total of three subjects in Trusilk® group reported to have incidence of wound infection on day 12, day 30 and month 3 visits respectively. Both first and second incidents took place after 8 days of suture removal, while the third incident occurred after 28 days of suture removal. As the suture was removed prior to infection, the incidents were not considered as device-related. The subjects recovered after treatment and reported no further incidence of infection. None of the sutures removed were sent for culture. Time required for wound healing was comparable between the groups (Table 2). Wound healing scores at three consecutive visits (day 3, 7 and 12) are presented in Figure 4b.\n\nAdverse events\n\nDuring the study period, a total of four (0.78%) mild, non-serious adverse events were noted, and they were not related to the study device. Out of these, two (3.08%) subjects were from Trusilk® group and two (3.13%) subjects were from Mersilk® group. In Trusilk® group, both subjects had upper respiratory tract infection. In Mersilk® group, one subject had fever and one subject had diarrhea. Any incidence of unexpected serious adverse events, adverse device effect, serious adverse device effect, or unanticipated serious adverse device effect were not recorded during the entire study period.\n\nDuring the study period, analgesics and antibiotics were prescribed to almost all of the subjects (Table 4).\n\n\nDiscussion\n\nImpacted third molar removal is essential to minimize the discomfort and complications caused by an unerupted tooth. Pain is one of the most common complications related to impacted third molar tooth. Its prevalence varies between 5 and 53%. On the other hand, the post-operative complication includes incidence of paresthesia, dry socket, infection, hemorrhage along with pain, severity of which depends on the patient’s age, health, and position of the tooth.8 Post-extraction suturing aids in controlling hemorrhage and promoting wound healing. A previous study reported decreased pain, edema, and trismus, and improved wound healing, after using braided silk suture for mucosal closure.9 To our knowledge, no randomized controlled trial has been conducted comparing clinical equivalence of two common silk suture brands for primary mucosa closure after surgical removal of impacted mandibular third molar. The present study compared tissue reaction/inflammation with Trusilk® and Mersilk® silk sutures post primary closure of mucosa in subjects undergoing planned surgical removal of impacted mandibular third molar after 3 and 7 days.\n\nInflammation or swelling, dental caries, oral/dental cysts, and trismus that ultimately result in pain are the usual symptoms associated with impacted mandibular third molars.8 In this study, all the study participants had normal tongue size, and majority of them had full set of teeth (32). Though oral/dental cyst was absent in all the subjects but dental caries, dental scaling and dental deposits, as well as mild swelling and trismus, were recorded in some of the subjects of both study groups. In addition, pre-operative pain was noted in most of the subjects (109/129). Pain, swelling, and trismus, also take place after tooth extraction.13 Incidence of clinical inflammation/tissue reaction such as, pain, swelling and trismus was recorded at all post-operative visits in the subjects of present study. The pain score was highest on the day of the surgery which declined steadily with each passing visit and became nil on the last two follow-up visits. An improvement in rate of swelling and trismus were noted in both treatment arms, Trusilk® and Mersilk®. Post-operative dental pains are usually not severe and will last for 1-2 days after tooth extraction.14 Likewise, the subjects of the present study received analgesics mostly after the surgery for 72 hours. A marked decrease in prescribed number of analgesics was noted in the next consecutive visits, suggesting a reduction in dental pain.\n\nSilk suture is universally used for dental surgery, as it is easy to handle and also to place knots.15 The intraoperative suture handling parameters were comparable between Trusilk® and Mersilk® treatment arms. In both groups, excellent, very good, good and fair scores were recorded, but none of the suture handling characteristics was graded as poor. Mean duration of the surgery was comparable between the groups. At the end of the surgery, good outcome of surgery was marked by both Investigators for all subjects. The rate of paresthesia and dry socket varies from 0.5-20% and 0-35% in patients after removal of impacted teeth.8 Another study on impacted third molar removal complications reported an incidence of 9.2% post-surgical emergency appointments. The majority of them were due to severe pain, swelling and bleeding with a prevalence of 4.8%, 2.6%, and 2.4% respectively. Alveolar osteitis, paresthesia, and trismus with a prevalence of less than 1% were the other reasons for post-surgical emergency appointments.16 Similar to these findings, the present study also recorded incidence of paresthesia in Mersilk® group (1/64) and dry socket in Trusilk® group (1/65), 7 days after the tooth extraction. Change in taste was observed in total of two subjects in Trusilk® group and one subject in Mersilk® group. However, the changes were temporary, and no further incidence of these complications was noted on the next follow-up visits. Furthermore, post-surgery emergency care was not required for any of the study participants.\n\nWound infection following impacted third molar extractions is a frequently occurring complication and is considered a risk factor for the healing of the wound. A previous study also reported wound infection in one patient with silk suture.17 The incidence of infection at the site of extraction was observed in three subjects of Trusilk® group (3/65) on day 12, day 30 and month 3 visits, respectively. As the suture was removed prior to infection, the incidents were not considered as device-related. The suture was loosened in four subjects each of Trusilk® and Mersilk® group. However, time required for complete wound healing was comparable between the groups. Additionally, incidence of dental bleeding was observed in majority of subjects of both groups on the day of surgery that declined with each passing visit, reflecting healing in those subjects. The types of adverse events noted in both arms during the study period (4/129) were of low risk, and not related to the suture material.\n\nThe limitations of the present study are: (i) potential bias may have occurred in reporting or favoring one suture or another by the staff or surgeons, as they were not blinded, and (ii) all surgical interventions in this trial were clean or clean contaminated elective surgeries, in which risk of infection is minimal and can originate only from contaminants in the operating room environment, or from the surgical team, or oral mucosal colonists present in plaque, cavity or any other soft and hard tissue inflammation.\n\nThe findings of this study can be generalized to the wider population since the study is methodologically robust and appropriately powered to detect a difference in the primary and secondary outcomes. Though the two sutures have been compared in one indication but looking into the clinical equivalence (comparable efficacy and safety) achieved in this study, it’s imperative to state that Trusilk® suture can be used in all surgeries indicated for Mersilk® suture.\n\n\nConclusion\n\nTrusilk® silk suture is clinically equivalent to the Mersilk® silk suture, as a non-significant difference was observed in clinical inflammation and tissue reaction with respect to swelling, pain and trismus in the extraction area (at 72 hours and 7 days post-surgery and all follow-up visits), incidence of wound infection, and suture loosening, total operative time and amount of anesthesia, intraoperative suture handling parameters, time needed for complete wound healing and suture removal, incidence of other complications such as bleeding and taste changes, and other adverse events among the groups. Both the sutures can be used for mucosal closure after removal of an impacted mandibular third molar with a minimal rate of pain, swelling and trismus.\n\n\nData availability\n\nFigshare. Trusilk Study Complete PP Data. https://doi.org/10.6084/m9.figshare.20059679.v1.18\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\n\nReporting guidelines\n\nFigshare: CONSORT check list for ‘Single blind, randomized study comparing clinical equivalence of Trusilk® and Mersilk® silk sutures for mucosal closure following surgical removal of mesioangular impacted mandibular third molar’. https://doi.org/10.6084/m9.figshare.20055599.v2.19\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 Contract Research Organization support towards designing, conducting, recording, and reporting of this clinical study. The authors are also thankful to WorkSure® India for providing medical writing assistance for this manuscript.\n\n\nReferences\n\nKashmoola MA, Mustafa NS, Qader OAJA, et al.: Retrospective demographic study on tooth impaction in a Malaysian sample. J. Int. Dent. Med. Res. 2019; 12(2): 548–552.\n\nHashemipour MA, Tahmasbi-Arashlow M, Fahimi-Hanzaei F: Incidence of impacted mandibular and maxillary third molars: A radiographic study in a southeast iran population. Med. Oral Patol. Oral Cir. Bucal. 2013; 18(1): e140–e145. PubMed Abstract | Publisher Full Text\n\nPillai AK, Thomas S, Paul G, et al.: Incidence of impacted third molars: A radiographic study in People’s Hospital, Bhopal, India. J. Oral Biol. Craniofacial Res. 2014; 4(2): 76–81. PubMed Abstract | Publisher Full Text\n\nAlfadil L, Almajed E: Prevalence of impacted third molars and the reason for extraction in Saudi Arabia. Saudi Dent. J. 2020; 32(5): 262–268. PubMed Abstract | Publisher Full Text\n\nWehr C, Cruz G, Young S, et al.: An insight into acute pericoronitis and the n1. Wehr C, Cruz G, Young S, Fakhouri WD. An insight into acute pericoronitis and the need for an evidence-based standard of care. D. Dent. J. 2019; 7(3): 1–10.\n\nPeñarrocha-Diago M, Camps-Font O, Sánchez-Torres A, et al.: Indications of the Extraction of Symptomatic Impacted Third Molars. A Systematic Review. J. Clin. Exp. Dent. 2021; 13(3): e278–e286. PubMed Abstract | Publisher Full Text\n\nFarish SE, Bouloux GF: General Technique of Third Molar Removal. Oral Maxillofac. Surg. Clin. North Am. 2007; 19(1): 23–43. Publisher Full Text\n\nSantosh P: Impacted mandibular third molars: Review of literature and a proposal of a combined clinical and radiological classification. Ann. Med. Health Sci. Res. 2015; 5(4): 229–234. PubMed Abstract | Publisher Full Text\n\nBalamurugan R, Zachariah T: Comparison of primary and secondary closure with a buccal mucosal-advancement flap on postoperative course after mandibular impacted third molar surgery. Oral Maxillofac. Surg. 2020; 24(1): 37–43. Publisher Full Text\n\nFaris A, Khalid L, Hashim M, et al.: Characteristics of Suture Materials Used in Oral Surgery: Systematic Review. Int. Dent. J. 2022; 72(3): 278–287. PubMed Abstract | Publisher Full Text\n\nLandry R, Turnbull R, Howley T: Effectiveness of benzydamyne HCl in the treatment of periodontal post-surgical patients. Res. Clin. Forums. 1988; 10: 105–118.\n\nChaudhary M, Singh M, Singh S, et al.: Primary and secondary closure technique following removal of impacted mandibular third molars: A comparative study. Natl. J. Maxillofac. Surg. 2012; 3(1): 10–14. PubMed Abstract | Publisher Full Text\n\nCho YD, Kim KH, Lee YM, et al.: Periodontal wound healing and tissue regeneration: A narrative review. Pharmaceuticals. 2021; 14(5): 1–17. PubMed Abstract | Publisher Full Text\n\nOsunde O, Adebola R, Omeje U: Management of inflammatory complications in third molar surgery: A review of the literature. Afr. Health Sci. 2011; 11(3): 530–537. PubMed Abstract\n\nSilverstein LH, Kurtzman GM, Shatz PC: Suturing for optimal soft-tissue management. J. Oral Implantol. 2009; 35(2): 82–90. PubMed Abstract | Publisher Full Text\n\nLee CTY, Zhang S, Leung YY, et al.: Patients’ satisfaction and prevalence of complications on surgical extraction of third molar. Patient Prefer. Adherence. 2015; 9: 257–263. PubMed Abstract | Publisher Full Text\n\nSala-Pérez S, López-Ramírez M, Quinteros-Borgarello M, et al.: Antibacterial suture vs silk for the surgical removal of impacted lower third molars. A randomized clinical study. Med. Oral Patol. Oral Cir. Bucal. 2016; 21(1): e95–e102. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBalakrishna R, Poojary D, Arvind R, et al.: Trusilk Study Complete PP Data. figshare. [Dataset].2022. Publisher Full Text\n\nBalakrishna R, Poojary D; R A et al.: CONSORT check list. figshare.2022 [cited 2022 Jun 11]. Publisher Full Text Reference Source"
}
|
[
{
"id": "143057",
"date": "25 Jul 2022",
"name": "Abhay Taranath Kamath",
"expertise": [
"Reviewer Expertise My areas of expertise and interest are distraction osteogenesis",
"temporomandibular joint dysfunction and management",
"maxillofacial trauamatology"
],
"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\n3rd August 2022: A COI statement was added detailing a collaboration between author and reviewer which was not declared at the time of publishing of this report.\nThis study by Balakrishna et al., is a meticulously planned and systematically executed study as reflected from the methodology of this study. Addressing a common condition (i.e., mesioangular impaction of third molars and the common post operative complication following its removal), the authors have evaluated equivocal influence between use of two suture materials for mucosal closure. While secondary outcome of the intervention are more practically related, the primary outcome like trismus may be not directly correlated to the suture material used instead may be relative to the impaction procedure employed.\nIn terms of sample size selection and standardisation of subjects recruited for the study, this study is quite scientific. However the assessment criteria for pain, swelling and trismus used in this study was VAS. VAS is an excellent tool to assess pain subjectively. The validity of assessing swelling using VAS is moderate and its validity in assessing trismus is lower. The authors could have used objective tools routinely used clinical for assessing swelling and degree of trismus. However from use of suture point of view these may not influence its selection, hence I classified it as minor issue.\nThe secondary endpoints as addressed in this study are more relevant for clinicians for the selection of type of suture material, these parameters were assessed scientifically. The study design does not reflect any major flaws. The result analysis clearly redefines the aim of the study. The authors declare equivalence towards the performance of both the materials. However such an outcome was expected as both the materials do not vary in their composition. Probably by establishing the equivalence the authors intend to allow the clinicians to choose between the providers of this suture material.\nThe discussion section of this article describe clinical findings in terms of post operative outcomes with use of both the suture materials. The article describes the limitations and generalizability of the study well.\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": "145906",
"date": "12 Sep 2022",
"name": "Jingade Krishnojirao Dayashankara Rao",
"expertise": [
"Reviewer Expertise Orthognathic surgery",
"cleft lip & palate",
"Dental implants",
"maxillofacial trauma",
"Minor oral surgeries"
],
"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 good clinical work highlighting the benefits of Trusilk® on comparison to Mersilk®.\nAs both sutures are natural non-absorbable black braided sterile silk in nature-Ideally there should not be any significant difference in the outcome of this clinical trial which is in agreement with this study conclusion. The study is well structured and executed.\nFollowing are some of the minor points which could have been considered to make it more standardised:\nAs per the literature, it is very well known that tissue handling, difficulty of surgery, and duration of surgery play major roles for the development of the study variables which include pain, swelling, and Trismus rather than sutures alone. It might be the sutures per se will play a very minor role here - that too comparing 2 similar sutures.\n\nThe tissue reaction varies from patient to patient. There is no mention in this study if the comparison is made on the same patients going for bilateral surgical impaction.\n\nDouble blind study would have been ideal for this study to avoid any operator bias.\n\nThe Bone cutting technique (burs/tooth section/ combination) should be mentioned so that comparison is standardized. Little info about type of impaction/incision methods should be added as its affects the variables mentioned in this trial.\n\nThis is multicenter study-which again affects the variables because the tissue reaction is varies among different surgeons for the similar procedure.\nThe author can clarify the above minor points which would help to strengthen this clinical trial.\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": []
}
] | 1
|
https://f1000research.com/articles/11-689
|
https://f1000research.com/articles/11-688/v1
|
21 Jun 22
|
{
"type": "Research Article",
"title": "Factors associated with the presence of cataracts in the Peruvian population older than 50 years: a cross-sectional study",
"authors": [
"Guido Bendezu-Quispe",
"Daniel Fernandez-Guzman",
"Brenda Caira-Chuquineyra",
"Lisbeth Evelyn Lazo",
"Rodrigo Vargas-Fernández",
"Guido Bendezu-Quispe",
"Daniel Fernandez-Guzman",
"Brenda Caira-Chuquineyra",
"Lisbeth Evelyn Lazo"
],
"abstract": "Background: Cataracts are a public health problem, especially in low- and middle-income countries, where the greatest limitations of health care systems are observed, making access to treatment difficult. This study aimed to determine the factors associated with the presence of cataracts in adults over 50 years of age in Peru. Methods: A cross-sectional analytical observational study was performed of data from the 2019 Demographic and Family Health Survey (ENDES – acronym in Spanish). The dependent variable was the self-reported diagnosis of cataracts (yes or no). Crude and adjusted prevalence ratios (aPR) were calculated using a generalized linear model of the Poisson family with a log link function to estimate factors associated with self-reported cataract diagnosis. Results: We analyzed the data of 8775 Peruvian adults older than 50 years; 1322 (16.68%) self-reported a diagnosis of cataract. A higher prevalence of having cataracts was associated with being aged 60-69 years (aPR: 1.40; 95% confidence interval (CI): 1.21-1.61) and 70 years and older (aPR: 2.78; 95% CI: 2.44-3.18), identifying as being of native ethnicity (aPR: 1.30; 95% CI: 1.16-1.47), having undergone ophthalmologic evaluation in the last 12 months (aPR: 2.29; 95% CI: 2.07-2.53) and having diabetes mellitus (aPR: 1.30; 95% CI: 1.13-1.51). The prevalence of cataracts was lower in subjects belonging to the poorest wealth quintile (aPR: 0.55; 95% CI: 0.43-0.70) and those with a higher level of education (aPR: 0.74; 95% CI: 0.62-0.88). Conclusions: In Peru, one out of six adults older than 50 years self-reported a diagnosis of cataracts. People older than 60 years, being of native ethnicity, having had a visual acuity evaluation in the last 12 months and having diabetes were associated with a higher prevalence of cataracts. These factors should be considered when implementing strategies for health education, promotion and prevention to ensure access to early ophthalmologic care.",
"keywords": [
"Cataract",
"Risk Factors",
"Elderly",
"Cross-Sectional Studies",
"Peru"
],
"content": "Introduction\n\nCataracts continue to be a global public health problem because they are one of the most prevalent eye diseases.1,2 This disease has a multifactorial cause that generates the opacity of the crystalline lens of the eye, subsequently causing progressive and painless loss of vision.3 Globally, by 2015, cataracts were the leading cause of blindness (about 12.6 million people; 35.0% of all cases of blindness) and the second leading cause of moderate or severe visual impairment in all age and ethnic groups (about 52.6 million people; 24.3% of all causes).4 In 2020, it was estimated that at least 13.4 million cases of blindness were due to cataracts, and about 127.7 million cases of low vision were related to this disease,4 generating more than 6 million disability-adjusted life years in 2019.5 Due to this increase in the prevalence and burden of cataract disease, the need for timely diagnosis is essential to provide accessibility to surgical treatment of this disease.1\n\nBiomedical literature has described an increase in the number of cases of cataracts. This increase translates into a greater burden for health care systems, since untimely diagnosis and treatment can have immediate and long-term consequences such as the development of ocular complications,6 causing increased dependence on others due to visual impairment,5 increased risk of fractures,7 decreased quality of life,8 increased risk of mortality,9,10 and economic losses for the individual, family and society.11 Despite vision impairment and blindness being most common in people over the age of 5012 and cataracts being a disease that can be treated by surgery.13 The prevalence of avoidable visual impairment and cataracts in the adult population aged 50 years or older has not improved, in fact the number of cases has continued to rise since 2010.2 Similarly, lack of population health awareness and literacy, shortage of trained eye health personnel in all urban and rural areas, limited accessibility to an ophthalmologist, the high cost of access to corrective surgery, and insufficient outcomes to correct the visual defect with surgery remain an obstacle for reducing blindness by cataracts, particularly in low-income countries.3,14\n\nIn low- and middle-income countries, it is necessary to know the factors associated with an increased risk of cataracts in order to design screening strategies and public health intervention measures. Although different factors have been associated with the development of cataracts, including marital status, age, educational level, smoking, diabetes mellitus, as well as exposure to sunlight, and body mass index (BMI), most of these factors have been evaluated in specific populations with ophthalmologic problems.15–17 In the countries that make up the Andean region of Latin America (Bolivia, Ecuador, and Peru), cataracts account for 27.5% of cases of blindness and 44.6% of cases of moderate to severe visual impairment.4 However, there is little scientific research in these countries on the factors related to cataract diagnosis in the general population.\n\nIn Peru, cataracts account for 58.0%, 59.3%, and 21.8% of the cases of blindness, severe visual impairment and moderate visual impairment, respectively.18 In addition, about one in three patients diagnosed with a cataract do not undergo surgical treatment.18 Although cataracts are the main cause of blindness and severe visual impairment in Peru and prevalence significantly increases with age (being most common in people over the age of 50 years),19 no previous study has evaluated the magnitude and factors associated with cataract diagnosis in this population. Therefore, the objective of this study was to determine the factors associated with cataracts among adults over 50 years of age in Peru.\n\n\nMethods\n\nA cross-sectional analytical observational study was conducted using data from the Demographic and Family Health Survey (ENDES – acronym in Spanish) 2019. This survey is prepared by the National Institute of Statistics and Informatics of Peru (INEI – acronym in Spanish) and consists of three questionnaires: household and its members, individual health of women, and health (persons over 15 years of age). The ENDES used a two-stage, probabilistic, balanced, stratified, and independent sampling. The unit of analysis is the usual residents of the dwellings selected through complex sampling. The ENDES allows obtaining representative results at the national level, by urban and rural areas, in each of the country's 24 departments and the constitutional province of Callao, as well as for the natural regions of Peru (Coast, Highlands, and Jungle). Geographically, Peru is divided into three natural regions: the Coast, which borders the Pacific Ocean, includes Lima (the capital of Peru) and is one of the regions with the highest population density and access to health services in the country; the Highlands, which includes the areas with the highest altitude in the country and the lowest wealth index; and the Jungle, the region with the greatest biodiversity, the largest geographic territory and the greatest barriers to access to health services. Further details of the methodology used in the ENDES are reported in the technical sheet of the survey.\n\nIn this study, the ENDES 2019 Health Questionnaire data were used, which collected information from 36,760 households. From these households, only participants with complete information on self-reported cataract diagnosis and who were 50 years of age or older were included. Finally, a total of 8775 individuals were included for analysis.\n\nDependent variable\n\nCataract diagnosis, defined by the respondent's self-report, indicated that the respondent had previously been diagnosed with cataracts by an eye doctor (ENDES question: Have you ever been diagnosed with cataracts by an eye doctor?). For the analysis, two categories were considered for this variable: “Yes”, when the respondent gave a positive answer to the survey question, and “No”, when the answer was negative.\n\nCovariates\n\nThe covariates for this study were considered to be characteristics that have previously been described in the scientific literature as associated with the presence of cataracts, including20–22: sex (male/female), age (50-59/60-69/70 or older), ethnic self-identification (native/non-native), educational level (no level/primary/secondary/higher), area of residence (urban/rural), natural region (Coast/Highlands/Jungle), altitude of residence (0-499, 500-1499, 1500-2999, 3000 or more), wealth quintile (richest/richer/middle/poorer/poorest), health insurance (yes/no), diabetes (yes/no), hypertension (yes/no), visual acuity assessment in the last 12 months (yes/no), and cigarette smoking within the last 12 months (yes/no).\n\nThe analyses were performed with the statistical program R (R Project for statistical computing, RRID:SCR_001905). The loading of the databases in.sav. format and their union were performed using the haven function, tidyverse (RRID:SCR_019186), and survey using different relational and hierarchical structures depending on the database needed to perform our analysis. All analyses considered the weighting and sample specifications of the ENDES 2019 using the svydesign function. A value of p<0.05 was considered statistically significant.\n\nThe characteristics of the participants included were described using absolute frequencies and weighted proportions. Then, to compare the proportions of the dependent variable (self-reported cataract diagnosis) among the categories of the independent variables, the chi-square test with Rao-Scott correction was used. Finally, crude (PR) and adjusted (aPR) prevalence ratios and their respective 95% confidence intervals (95% CI) were reported using generalized linear models of the Poisson family with logarithmic link function to estimate the factors associated with self-reported cataract diagnosis. In the fitted model, all independent variables with a p<0.05 in the crude model were included. To evaluate the collinearity of the independent variables included in the adjusted model, the variance inflation factor was used, where a value >10 determined multicollinearity among the variables; however, all values obtained were less than 10.\n\nApproval by an ethics committee was not requested because this is an analysis of secondary data that are in the public domain and do not allow the identification of the participants. The ENDES databases are freely accessible and can be freely obtained on the web platform of the INEI. This institution requested the consent of participants to obtain the information required in the survey. All participant data were anonymized prior to access.\n\n\nResults\n\nThe data of 8775 Peruvian adults over 50 years of age were analyzed. Of these, 52.29% were women, 43.91% were in the 50-59 age group, 24.50% were of native ethnicity, 45.22% had no or only primary education, 78.62% had health insurance, 28.85% of the respondents had not had a visual acuity examination in the last 12 months, 6.18% had high blood pressure, 9.22% had diabetes, and 28.23% had obesity. Regarding wealth quintiles, most households were in richer (20.67%) and richest quintile (24.00%). In relation to the area of residence, 21.38% lived in rural areas. In terms of geographic area, most of the participants resided in the Coastal region (63.26%) and at an altitude of 0 to 499 meters (65.42%) (Table 1).\n\n* The weighting factor and the complex sampling of ENDES 2019 were included.\n\nRegarding the presence of cataracts, 1322 (16.68%) people self-reported the diagnosis of this disease. The proportion of cataracts was higher in the age group of 70 years and older (34.02%; p<0.001), natives (19.18%; p=0.021), those living in an urban area of residence (18.71%; p<0.001), wealth quintiles 4 (19.88%; p<0.001) and 5 (18. 83%; p<0.001), from the natural Coast region (18.39%; p<0.001), living at an altitude of 500 to 1499 meters (18.64%; p=0.005), having primary or no education (19.14%; p=0.005), health insurance (18.20%; p<0.001), and having undergone a visual acuity examination in the last 12 months (29.15%; p<0.001). Likewise, higher proportions of cataracts were present in respondents with arterial hypertension (20.28%; p<0.001), diabetes mellitus (23.53%; p<0.001), and in non-smokers (17.23%; p=0.034) (Table 2).\n\n* p values were calculated using the chi-square test.\n\nIn the multivariate model to evaluate the association of factors with the presence of cataracts, it was found that being between 60 to 69 years old (aPR: 1.40; 95% CI: 1.21-1.61; p<0.001) and 70 or older (aPR: 2.78; 95% CI: 2.44-3.18; p<0.001) increased the prevalence of presenting this disease compared to being between 50 to 59 years old. Likewise, being of native ethnicity (aPR: 1.30; 95% CI: 1.16-1.47; p<0.001), having had an ophthalmologic evaluation in the last 12 months (aPR: 2.29; 95% CI: 2.07-2.53; p<0.001) and having diabetes mellitus (aPR: 1.30; 95% CI: 1.13-1.51; p<0.001) increased the prevalence of presenting cataract. On the other hand, belonging to the lowest wealth quintile (aPR: 0.55; 95% CI: 0.43-0.70, p<0.001) and having a higher educational level (aPR: 0.74; 95% CI: 0.62-0.88; p=0.001) were associated with a lower prevalence of cataracts (Table 3).\n\n* Variables with a p-value <0.05 in the crude model were included.\n\n\nDiscussion\n\nThis study sought to estimate the factors associated with cataract diagnosis in Peruvian adults over 50 years of age. The factors associated with a higher prevalence of presenting cataracts were older age groups, higher education level, belonging to the highest wealth quintiles, self-identification of native ethnicity, presenting diabetes mellitus as a comorbidity, and having had a visual acuity evaluation in the last 12 months. Conversely, having a higher level of education was associated with a lower prevalence of having cataracts.\n\nOne out of six adults over 50 years of age self-reported a diagnosis of a cataract. This finding coincides with that reported previously in a systematic review of population-based studies in which the global prevalence of cataracts of 15.2% was reported.2 In addition, previous studies in China, India, Taiwan, and Singapore reported cataract prevalence ranging from 14% to 59%.15,23–25 On the other hand, a previous nationwide study, in Peru, found a prevalence of cataracts of 16.7%26 and in another study, this disease was identified as the leading cause of blindness (47 to 87%)27 and severe visual impairment (59.3%) in Latin America.18 The presence of cataracts can be related to multiple long-term negative outcomes, including blindness and visual impairment, especially in the older adult population,28–30 and therefore, we suggest promoting national strategies to ensure the screening and diagnosis of this health problem, as well as access to an ophthalmologic evaluation in primary care facilities. In this regard, the American Academy of Ophthalmology recommends that adults should undergo a complete ophthalmologic evaluation at the age of 40 since the first signs of diseases or changes in vision, including cataracts, begin to appear at this age.31 In addition, it is important to increase cataract surgery coverage since Peru has one of the lowest rates in Latin America (20 to 24%).27,32\n\nA higher probability of cataracts was associated with being an older adult (60 years and older). In general, increasing age is described as the main factor for the presence of any type of cataract.22 The results of the present study are consistent with previous population-based studies in Australia and Asia, which reported that the prevalence of cataracts increases with age, from 3.9% between the ages of 55 and 64 years to 92.6% after the age of 80 years.16,17 The lens opacity that occurs in age-related cataracts may be directly caused by oxidative stress that increases with aging, which causes normal lens proteins to begin to disintegrate, resulting in opacity.1,33 Therefore, older adults are more susceptible to cataracts, thereby requiring greater efforts in the prevention of this disease.\n\nA higher education level was associated with a lower prevalence of cataracts. The difference in the prevalence of cataracts with respect to the educational level found in this study coincides with what has previously been reported in the literature.34,35 It should be considered that a higher level of schooling is related to a higher level of knowledge of this disease and, therefore, to a greater understanding of prevention and treatment.14 In this regard, it has been reported that a low educational level could be related to a higher rate of rejection of surgical cataract treatment.18 Therefore, increasing access to information about this disease, with emphasis on lower educational level groups, would help to prevent its progression, as well as to detect and treat the disease early, giving this approach the chance of being a useful strategy for the control of this disease.\n\nConcerning the wealth quintile, we found that belonging to the poorest quintile was associated with a lower prevalence of cataracts. This finding differs from other literature since it has been suggested that the poorest socioeconomic levels have a higher frequency of cataracts36,37 and that poverty represents a barrier to early diagnosis of cataracts.38 This finding could be explained by the fact that the diagnosis of cataracts was obtained by self-reporting. It is possible that people with a higher socioeconomic level have greater access to medical specialists and that in the event of a possible decrease in visual acuity, they can go to an ophthalmologist early for evaluation of a possible diagnosis of cataracts. On the other hand, the respondents who belonged to the poorest quintiles possibly face difficulties in going to a medical specialist for a timely diagnosis of cataracts, even though, according to scientific evidence, these groups have a higher incidence and prevalence of cataracts. Therefore, the lack of access to diagnosis in this group of people could be related to the lower prevalence of cataracts observed in comparison to the groups in the higher welfare quintile. Taking this into account, the promotion of greater vision care and ophthalmologic evaluations for early detection of the disease in the less socioeconomically favored groups should be considered.\n\nSelf-identification as native ethnicity was found to be associated with a higher prevalence of cataracts. In this regard, a previous study in a geographically isolated Guatemalan native population reported a high prevalence of cataracts (54.8%).39 It has been reported that the native population (including Quechua, Aimara, and native or indigenous ethnic groups of the Amazon), which is part of ethnic minorities, tends to experience limitations in access to health services, including ophthalmologic care, with a lack of effective strategies to achieve better communication and distribution of medical care among the native population.39 In Peru, there are barriers such as the shortage of ophthalmologists, surgeons, and equipment for the definitive treatment of cataracts, thereby generating great inequity mainly affecting socially and economically disadvantaged populations such as the native population.40 Therefore, it is necessary to improve the epidemiological surveillance of cataracts to identify vulnerable populations in need of intervention and promote cataract surgery campaigns in populations with a higher prevalence of the disease.\n\nHaving diabetes mellitus was associated with a higher prevalence of cataracts. This risk factor has been identified in several population-based studies suggesting a causal association between diabetes and nuclear, cortical, posterior subcapsular, and age-related cataracts.23,35,41,42 This relationship is explained by changes in the cortical and nuclear lenses resulting from increased glycosylation of lens proteins.35 Since diabetes is a major public health problem in Peru affecting between 5.1 and 7.0% of the adult population,43,44 reflecting the aging and unhealthy lifestyles of the population, primary prevention programs against diabetes should be strengthened and implemented in order to reduce the prevalence of eye problems such as cataracts, glaucoma, or diabetic retinopathy that may result in an increased risk of severe ocular disability or blindness.\n\nFinally, among the associated factors, having had a visual acuity evaluation within the last 12 months was also associated with a higher prevalence of cataracts. This finding is likely because people who visited the ophthalmologist within the previous 12 months may have had a previous diagnosis of cataracts or problems related to visual acuity and therefore had control or appointment for evaluation by the ophthalmologist with possible confirmation of a diagnosis of a cataract.26 In our study, about seven out of ten adults aged 50 years and older had never had an ophthalmologic evaluation, which implies and highlights a lack of coverage in the detection of ophthalmologic problems (including cataracts) within the Peruvian health system. Therefore, it is necessary to provide a free and timely ophthalmologic evaluation from the first level of care in order to intervene early in a greater number of patients.\n\nThere are some limitations in the present study that should be considered. First, the use of a secondary database implies the unavailability of other variables of interest in relation to the outcome studied, including environmental and respondent characteristics, which could not be considered in the analyses. Second, the possible introduction of bias regarding the condition of having or not having cataracts should be kept in mind because the responses to questionnaire questions were self-reported. Third, due to the absence of temporality according to the study design employed, it is not possible to study causality between the factors included in the analysis and the presence of cataracts. Despite these limitations, we consider that the findings of this study can provide a macro view of the factors associated with cataracts in the Peruvian population over 50 years of age. Likewise, the use of the ENDES, a nationally representative survey conducted annually using methodological quality control processes, allows the adequate study of the problem of interest.\n\nIn Peru, one out of six adults over 50 years of age have been diagnosed with cataracts. We identified that those older than 60 years, of native ethnicity, higher wealth quintiles, having diabetes mellitus, and having had a visual acuity evaluation in the last 12 months were associated with a higher prevalence of cataracts, while having a higher educational level was associated with a lower prevalence of cataracts. These factors should be used to improve and implement strategies or programs for health education, promotion, and prevention that ensure access to early ophthalmologic care, prioritizing the oldest age groups, native ethnic groups, and the poorest population, in order to detect and treat this disease early, leading to lower costs for both individuals and the health system.\n\n\nData availability\n\nThe ENDES 2019 dataset used in this study is freely available at Microdatos INEI: http://iinei.inei.gob.pe/microdatos/. A login or registration to access the database is not required.",
"appendix": "Acknowledgments\n\nThe authors would like to thank the Instituto Nacional de Estadística e Informática of Peru for making the database available. The authors are grateful to Donna Pringle for reviewing the language and style.\n\n\nReferences\n\nLiu YC, Wilkins M, Kim T, et al.: Cataracts. Lancet. 2017; 390: 600–612. Publisher Full Text\n\nBourne RRA, Steinmetz JD, Saylan M, et al.: Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: The Right to Sight: An analysis for the Global Burden of Disease Study. Lancet Glob. Health. 2021; 9(2).\n\nWHO: World report on vision. World health Organization;2019; 214(14).\n\nFlaxman SR, Bourne RRA, Resnikoff S, et al.: Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. Lancet Glob. Health. 2017; 5(12): e1221–e1234. PubMed Abstract | Publisher Full Text\n\nYang X, Chen H, Zhang T, et al.: Global, regional, and national burden of blindness and vision loss due to common eye diseases along with its attributable risk factors from 1990 to 2019: a systematic analysis from the global burden of disease study 2019. Aging. 2021; 13(15): 19614–19642. PubMed Abstract | Publisher Full Text\n\nAstbury N, Nyamai LA: Detecting and managing complications in cataract patients. Community Eye Health J. 2016; 29(94): 27–29. PubMed Abstract\n\nLim JY, Yoo JI, Kim RB, et al.: Comparison of the incidence rates of hip and vertebral fragility fractures according to cataract surgery in elderly population: a nationwide cohort study. Arch. Osteoporos. 2022 Feb; 17(1): 30. PubMed Abstract | Publisher Full Text\n\nLim ME, Minotti SC, D’Silva C, et al.: Predicting changes in cataract surgery health outcomes using a cataract surgery appropriateness and prioritization instrument. PLoS One. 2021; 16(1 January). Publisher Full Text\n\nWang L, Zhu Z, Scheetz J, et al.: Visual impairment and ten-year mortality: the Liwan Eye Study. Eye (Basingstoke). 2021; 35(8): 2173–2179. Publisher Full Text\n\nZhu Z, Wang L, Scheetz J, et al.: Age-related cataract and 10-year mortality: the Liwan Eye Study. Acta Ophthalmol. 2020; 98(3): e328–e332. PubMed Abstract | Publisher Full Text\n\nNICE: Cataracts in adults: management Guidance. NICE Guidelines 77.2017;(October 2017).\n\nWorld Health Organization: Vision impairment and blindness.2021 [cited 2022 May 13].Reference Source\n\nDyrda A, Martínez-Palmer A, Martín-Moral D, et al.: Clinical results of diffractive, refractive, hybrid multifocal, and monofocal intraocular lenses. J. Ophthalmol. 2018; 2018: 1–12. PubMed Abstract | Publisher Full Text\n\nAlimaw YA, Hussen MS, Tefera TK, et al.: Knowledge about cataract and associated factors among adults in Gondar town, northwest Ethiopia. PLoS One. 2019; 14(4): e0215809. PubMed Abstract | Publisher Full Text\n\nDuan XR, Liang YB, Wang NL, et al.: Prevalence and associations of cataract in a rural Chinese adult population: The Handan Eye Study. Graefes Arch. Clin. Exp. Ophthalmol. 2013; 251(1): 203–212. Publisher Full Text\n\nChua J, Koh JY, Tan AG, et al.: Ancestry, Socioeconomic Status, and Age-Related Cataract in Asians: The Singapore Epidemiology of Eye Diseases Study. Ophthalmology. 2015; 122(11): 2169–2178. PubMed Abstract | Publisher Full Text\n\nMitchell P, Cumming RG, Attebo K, et al.: Prevalence of cataract in Australia: The Blue Mountains Eye Study. Ophthalmology. 1997; 104(4): 581–588. Publisher Full Text\n\nCampos B, Cerrate A, Montjoy E, et al.: Prevalencia y causas de ceguera en Perú: encuesta nacional. Revista Panamericana de Salud Pública = Pan American Journal of Public Health. 2014; 36(3).\n\nInstituto Nacional de Estadística e Informática: Perú: Enfermedades no transmisibles y transmisibles, 2019.2020.Reference Source\n\nRim THT, Kim MH, Kim WC, et al.: Cataract subtype risk factors identified from the Korea National Health and Nutrition Examination survey 2008-2010. BMC Ophthalmol. 2014 Jan; 14: 4. PubMed Abstract | Publisher Full Text\n\nChang JR, Koo E, Agrón E, et al.: Risk factors associated with incident cataracts and cataract surgery in the Age-related Eye Disease Study (AREDS): AREDS report number 32. Ophthalmology. 2011 Nov; 118(11): 2113–2119. PubMed Abstract | Publisher Full Text\n\nMukesh BN, Le A, Dimitrov PN, et al.: Development of cataract and associated risk factors: The Visual Impairment Project. Arch. Ophthalmol. 2006; 124(1): 79. Publisher Full Text\n\nTsai SY, Hsu WM, Cheng CY, et al.: Epidemiologic study of age-related cataracts among an elderly Chinese population in Shih-Pai, Taiwan. Ophthalmology. 2003; 110(6): 1089–1095. PubMed Abstract | Publisher Full Text\n\nSeah SKL, Wong TY, Foster PJ, et al.: Prevalence of lens opacity in Chinese residents of Singapore: The Tanjong Pagar survey. Ophthalmology. 2002; 109(11): 2058–2064. PubMed Abstract | Publisher Full Text\n\nVashist P, Talwar B, Gogoi M, et al.: Prevalence of cataract in an older population in India: The india study of age-related eye disease. Ophthalmology. 2011; 118(2): 272–278.e2. PubMed Abstract | Publisher Full Text\n\nBarrenechea-Pulache A, Portocarrero-Bonifaz A, Hernández-Vásquez A, et al.: Determinants of Eye Care Service Utilization among Peruvian Adults: Evidence from a Nationwide Household Survey. Ophthalmic Epidemiol. 2021; 1–10. PubMed Abstract | Publisher Full Text\n\nUmburg H, Silva JC, Foster A: Cataract in Latin America: Findings from nine recent surveys. Revista Panamericana de Salud Publica/Pan American Journal of Public Health. 2009; 25(5). Publisher Full Text\n\nNanayakkara SD: Vision-Related Quality of Life Among Elders With Cataract in Sri Lanka: Findings From a Study in Gampaha District. Asia Pac. J. Public Health. 2009 Jul 1; 21(3): 303–311. PubMed Abstract | Publisher Full Text\n\nLi Y, Crews JE, Elam-Evans LD, et al.: Visual impairment and health-related quality of life among elderly adults with age-related eye diseases. Qual. Life Res. 2011 Aug 1; 20(6): 845–852. Publisher Full Text\n\nMenezes C, Vilaça KHC, de Menezes RL : Falls and quality of life of people with cataracts. Rev bras.oftalmol. 2016 Feb; 75: 40–44. Publisher Full Text\n\nCaltrider D, Gupta A, Tripathy K: Evaluation Of Visual Acuity. StatPearls. 2021.\n\nSilva JC, Bateman JB, Contreras F: Eye disease and care in Latin America and the Caribbean. Surv. Ophthalmol. 2002; 47: 267–274. PubMed Abstract | Publisher Full Text\n\nVinson JA: Oxidative stress in cataracts. Pathophysiology. 2006; 13: 151–162. PubMed Abstract | Publisher Full Text\n\nNavarro Esteban JJ, Gutiérrez Leiva JA, Valero Caracena N, et al.: Prevalence and risk factors of lens opacities in the elderly in Cuenca, Spain. Eur. J. Ophthalmol. 2007; 17(1): 29–37. Publisher Full Text\n\nKlein R, Klein BEK, Jensen SC, et al.: The Relation of Socioeconomic Factors to Age-related Cataract, Maculopathy, and Impaired Vision: The Beaver Dam Eye Study. Ophthalmology. 1994; 101(12): 1969–1979. PubMed Abstract | Publisher Full Text\n\nSingh S, Pardhan S, Kulothungan V, et al.: The prevalence and risk factors for cataract in rural and urban India. Indian J. Ophthalmol. 2019; 67(4): 477. Publisher Full Text\n\nDas G, Boriwal K, Chhabra P, et al.: Presenile cataract and its risk factors: A case control study. J. Family Med. Prim. Care. 2019; 8(6): 2120. Publisher Full Text\n\nPimprikar S, Karve S: Factors associated with late presentation of cataract in rural and urban patients: A cross-sectional study in Maharashtra. Indian J. Clin. Exp. Ophthalmol. 2020; 6(2): 208–212. Publisher Full Text\n\nHicks PM, Au E, Self W, et al.: Article pseudoexfoliation and cataract syndrome associated with genetic and epidemiological factors in a mayan cohort of guatemala. Int. J. Environ. Res. Public Health. 2021; 18(14). PubMed Abstract | Publisher Full Text\n\nSilva JC, Mújica OJ, Vega E, et al.: A comparative assessment of avoidable blindness and visual impairment in seven Latin American countries: prevalence, coverage, and inequality. Revista Panamericana de Salud Publica = Pan American Journal of Public Health. 2015 Jan; 37(1): 13–20. PubMed Abstract\n\nRowe N, Mitchell P, Cumming RG, et al.: Diabetes, fasting blood glucose and age-related cataract: The Blue Mountains Eye Study. Ophthalmic Epidemiol. 2000; 7(2): 103–114. PubMed Abstract | Publisher Full Text\n\nFoster A, Resnikoff S: The impact of Vision 2020 on global blindness. Eye. 2005; 19(10): 1133–1135. Publisher Full Text\n\nVillena JE: Diabetes Mellitus in Peru. Ann. Glob. Health. 2015; 81: 765–775. Publisher Full Text\n\nCarrillo-Larco RM, Bernabé-Ortiz A: Diabetes mellitus tipo 2 en Perú: una revisión sistemática sobre la prevalencia e incidencia en población general. Revista Peruana de Medicina Experimental y Salud Publica. 2019 Jan; 36(1): 26–36. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "180600",
"date": "26 Jul 2023",
"name": "John C Buchan",
"expertise": [
"Reviewer Expertise Cataract"
],
"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 study is not surprising or novel in its findings but is nonetheless robust and publishable. Telling us that you are more likely to get a diagnosis of cataract if you have been to an eye doctor is not surprising. Similarly, higher prevalence of cataract in people who are older and diabetic is expected.\nThe authors describe the cases as \"self-identifying as having cataract\" - however they were asked the question, \"Have you ever been diagnosed with cataracts by an eye doctor?\".\nI think they should be described as \"self-identifying as having been diagnosed with cataract by an eye doctor\" - which is a different thing from being self-diagnosed.\n\nWith cataract being the main cause of blindness in Peru - identifying risk factors to drive public health inititatives is a good idea. The main thing that might inform their public health efforts is around ethnicity perhaps.\n\nOverall it is a worthwhile and carefully written up paper - even though the results could have been predicted without doing 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? 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/11-688
|
https://f1000research.com/articles/11-687/v1
|
21 Jun 22
|
{
"type": "Research Article",
"title": "E-Wallet: A Study on Cashless Transactions Among University Students",
"authors": [
"Anushia Chelvarayan",
"Sook Fern Yeo",
"Han Hui Yi",
"Hazlaili Hashim",
"Sook Fern Yeo",
"Han Hui Yi",
"Hazlaili Hashim"
],
"abstract": "E-wallet is an application that enable users to download payment cards using a mobile device. It is a new trend for consumers to use an e-wallet application to replace the traditional payment method. With E-wallet, a user does not need to bring cash or a credit card along with them. It enables users to make purchases in a more convenient way. Hence, this research analyses the factors that affect university students’ intention to use e-wallet. The Technology Acceptance Model (TAM) serves as the theory underpinning this research A total of 140 respondents from a Malaysian private institution participated in this study. Convenience sampling was used to select samples, and respondents completed the questionnaire using a Google form and a paper and pencil approach. The questionnaire was created using a nominal scale and a five-point Likert scale. Descriptive analysis, reliability analysis, and multiple regression analyses were utilised to analyse the data in this study. Students, supervisors, academics, researchers, learning institutions, commercial organisations, and the government will all benefit immensely from the data and information gathered from this study as we will be able to examine and understand the factors that influence students' decision to use an e-Wallet for their daily financial operations. This study, however, has certain limitations as it does not reflect the complete student population in Malaysian tertiary education and only examines four variables: perceived usefulness, perceived ease of use, perceived risk, and trust. Future studies could focus on other impacting elements such as risk, complexity, pervasive technology use and tech-savvy future generations.",
"keywords": [
"E-Wallet",
"Intention",
"University Students",
"Perceived usefulness",
"Perceived ease of use",
"perceived risk",
"trust"
],
"content": "Introduction\n\nAn e-wallet is a mobile application that allows users to download payment cards. The usage of an e-wallet application to substitute a traditional payment method is a new trend among customers. A user does not need to bring cash or a credit card while using an e-wallet. It allows people to acquire items that meet their requirements and desires in a more convenient manner. Due to the advancement of technology, there are many e-wallet platforms that exist in the market such as Touch n Go, Boost and Grabpay. Hence, this research will analyse the factors that affect university students’ intention to use an e-wallet by adopting the Technology Acceptance Model (TAM).\n\nPrevious research carried out by Yap & Ng (2019), claimed that convenience, confidentiality and social influence are the contributing factors for people to use an e-wallet1 application. Users believe that an e-wallet brings a lot of convenience in their life as technology helps users to complete their tasks in a faster and convenient way. This study will use perceived usefulness (PU), perceived ease of use (PEOU), perceived risk (PR) and trust (T) to measure the acceptance of e-wallet among university students in Malaysia.\n\n\nLiterature review\n\nE-wallet is an application that enables user to use it when making purchases. According to Qasim, Siddiqui & Rehman (2012), e-wallet is a mobile application that enables the consumers to make financial transactions.2\n\nTechnology Acceptance Model (TAM) is partly adopted in this research to determine the intention of consumers using e-wallet. Besides TAM, there are another two variables that will be used in identifying the intention for consumers to use e-wallet, which are perceived risk (PR) and trust (T). This is to ensure that readers can clearly observe the relationship with all the independent variables on the intention of university students to use e-wallet. TAM was developed by Davis in 1989 and it was developed based on a previous theoretical model called Theory of Reasoned Action (TRA).3\n\nE-wallet is a new market trend which has been widely used by everyone. It brings many benefits to users as it offers quite a number of services. Therefore, it is important for researchers to know users’ intention in using e-wallet so that e-wallet platform developers can improve to serve users better. According to Zhao et al. (2010), intention is a person’s willingness and eagerness to obtain something desirable.4 Additionally, Venkatesh et al. (2003) stated that intention to use can be defined as the consumer’s interest and desire to try the new product and services.5 In this context, Tan et al. (2020) stated that the key variables of TAM which are perceived usefulness (PU), and perceived ease of use (PEOU) are the key determinants of using a new technology intentionally.6\n\nIn this study, there are four independent variables that will be adopted in determining the intention to use e-wallet. The independent variables are perceived usefulness (PU), perceived ease of use (PEOU), perceived risk (PR) and trust (T).\n\nIn the technology acceptance model (TAM), perceived usefulness (PU) is one of the most commonly used variables and the most important component to examine the impact towards the adoption of e-wallet. Perceived usefulness (PU) refers to the level of belief perceived by the consumers when they are using the new tools to do their tasks.7 Perceived usefulness can be said to be a strong indicator to determine the user acceptance towards technology.7\n\nAnother significant component in the technology acceptance model (TAM) is the perceived ease of use (PEOU), where it measures the convenience and how easy for users to use e-wallet in their daily life. Davis (1989) defined perceived ease of use (PEOU) as a person’s thought on how easy to use a new technology or system.3 According to Davis, Bagozzi & Warshaw (1989), the degree of easiness in terms of physical and mental on using a new technology perceived by a person is the perceived ease of use (PEOU).7 From here, the contributing factor of PEOU is significant enough to affect user’s intention to use a new technology, in this study, the e-wallet. Based on previous research done by Guriting & Ndubisi (2006), there is a significant positive relationship between perceived ease of use (PEOU) and consumer intention to use e-wallet.8\n\nPerceived risk (PR) on the other hand is the customer feelings of predictability of an unfavourable outcome.9 According to Widodo, Irawan & Sukmono (2019), perceived risk (PR) is the possible losses assumed by the consumers when they are purchasing goods.10 The examples of potential losses are monetary losses, privacy breach, safety issues, bad user experience and waste of time.10 According to Razif, Misiran, Sapiri & Yusof (2020), consumers will hesitate when they want to purchase a good, especially expensive goods.11 Consumers might worry that the goods purchased does not meet their expectation. By using e-wallet, there are certain risks faced by the users such as leaking of personal information to unauthorized parties. Therefore, this might cause worry among users.\n\nTrust can be defined as the level of consumer belief on the value and usefulness of e-wallet services.12 According to Malik & Annuar (2019), trust is described as a person’s feelings toward another person in completing a task, and it is a critical aspect for electronic monetary services.13 Trust would result in better achievement while doubt results in failure that will stop people from further using online payment systems.14,15 Trust is an important independent variable to investigate the adoption of technology. Based on previous research done by Ajmera & Bhatt (2020), trust is a significant aspect to decide the consumer’s intention towards a particular technology.16\n\n\nMethods\n\nThe research adopted two variables from the Technology Acceptance Model (TAM) and another two variables: perceived risk (PR) and trust (T). The following research framework is developed for this study:\n\nThe link between the dependent and independent variables is depicted in Figure 1. The research framework was built around the links between intention to use e-wallet as the dependent variable and perceived usefulness (PU), perceived ease of use (PEOU), perceived risk (PR) and trust (T), as the independent variables. In this research especially during the COVID – 19 pandemic, the independent variables are employed as intermediary variables to examine factors affecting e-wallet use among university students (as shown in the Underlying Data).20 Consumers were spending more via online transactions as they were not able to visit physical stores due to the Movement Control Order in Malaysia This research uses the descriptive research design whereby a descriptive research design is a type of research design that aims to obtain information to systematically describe a phenomenon, situation, or population. More specifically, it helps answer the what, when, where, and how questions regarding the research problem. As of 31 March 2021, a total of 1.32 million students pursued their tertiary education in Malaysia, whereby 52.1% registered in public universities and 47.9% were in PHEIs.17 Hence, a total of 140 students from a Malaysian private institution participated in this study as part of the sample population. In this research G-Power 3.1.9.7 has been used to find out the sample size. The sample size recommended by G-Power is 129. However, the sample size of this research was 140 students. Convenience sampling was used to pick samples, and respondents completed the questionnaire using a Google form and a paper and pencil approach. The questionnaire (shown in the Extended data)21 which was adopted from G. M. M. Dewi et al. (2021)18 and A,M,A Nashren et al. (2019),19 were then distributed to the respondents and included a written statement requesting their consent before proceeding to fill in. The respondents who proceeded to answer the questionnaire automatically consented to participate as research respondents. The questionnaire was created using a nominal scale and a five-point Likert scale. Descriptive analysis, reliability analysis, and multiple regression analysis were utilised to analyse the data in this study. The demographic data, the ideas included in this study, and their interactions were all analysed using the Statistical Package for the Social Sciences (SPSS (Statistical Package for the Social Sciences) is a software program used by researchers in various disciplines for quantitative analysis of complex data. It is a software package created for the management and statistical analysis of social science data.). The processed data was double checked by team members. It went through a thorough screening process.\n\nThe study was reviewed and approved by research ethic committee, Multimedia University Malaysia. The responses of each respondent were kept confidentially. The data were collected and analyzed anonymously. Ethical approval number: EA2342021.\n\n\nResults and discussion\n\nTo provide a clear understanding, the findings are reported in the tables below. The theories that were created were also tested and summarised as follows:\n\nTable 1 summarises the demographic information collected for this research, with a total of 140 respondents who are students from a private University in Malaysia.\n\nTable 2 shows the Cronbach’s Alpha for each variable. All of the variables in this study had Cronbach’s Alpha values over 0.7, indicating that they were all acceptable. The independent factors with the greatest Cronbach’s Alpha are perceived risk (0.912), trust (0.878), perceived ease of use (0.844), and perceived usefulness (0.819). At the same time, Cronbach’s Alpha for the dependent variable of intention to use E-Wallet is 0.814. Cronbach’s Alpha is used to measure the reliability of all the variables. Hence, the results in Table 2 shows that all independent variables are reliable and acceptable.\n\nTable 3 shows the result of coefficients analysed by SPSS. It demonstrates the relationship between dependent and independent variables through multiple linear regression analysis. The hypotheses are supported if the p-value (significance level) does not exceed 0.05. Thus, Table 3 shows that three of the independent variables of the study i.e., perceived usefulness, perceived risk and trust have a significant positive relationship towards intention to use e-wallet among students, whereby the variables of p-value of perceived usefulness, perceived risk and trust is 0.000, 0.002 and 0.018 respectively. However, perceived ease of use does not have a significant relationship toward the intention to use e-wallet among students. This is due to the p-value is more than 0.05 as the p-value is 0.068.\n\nBased on the above summary in Table 4, H1, H3 and H4 are accepted as the p-value is less than 0.05. This shows that perceived usefulness, perceived risk and trust have a significant relationship with the intention to use e-wallet among students. However, H2 is rejected because the p-value is more than 0.05. Hence, there is no significant relationship between perceived ease of use and intention to use e-wallet among students.\n\n\nDiscussion\n\nThe purpose of this research is to study the e-wallet acceptance among university students. The four independent variables of this research are perceived usefulness, perceived ease of use, perceived risk and trust while the dependent variable of this research is intention to use e-wallet. In order to determine the sample size, G-Power has been used to determine the accurate sample size. 140 questionnaires were distributed to the target respondents. Furthermore, the SPSS software has been used to analyze the validity of the data collected. Moreover, the relationship between the independent variables and dependent variable has been determined.\n\nIn conclusion, three independent variables of this research were found to have significant relationship with intention to use e-wallet. These three independent variables are perceived usefulness, perceived risk and trust. On the other hand, perceived ease of use does not have significant relationship with intention to use e-wallet. Hence, this research will benefit the consumers. The consumers can know more about e-wallet and realize that there are more people to using e-wallet nowadays. For those consumers who are still not using e-wallet, they will be more confident towards e-wallet after reading this research because they will realize that many people are using e-wallet these days especially during pandemic and e-wallet actually brings a lot of benefits to the consumers. In near future, the number of e-wallet users in Malaysia will increase.\n\n\nConclusion\n\nThe research was conducted to investigate the factors affecting the intention to use e-wallet among university students especially during the COVID-19 pandemic in Malaysia. This research will influence future studies for e-wallet adoption among students in Malaysia, especially during the current global pandemic. The findings from this research could contribute to the development of e-wallet platforms especially for student market. The findings are useful for online platform or application developers whereby they can use the findings from this research to enhance their existing platforms or develop new platforms specially dedicated for students.\n\nHowever, when conducting this study, there were some constraints that should be noted. To begin with, the sample size in this study was modest, with only 140 participants. As a result, the findings may not be able to provide an accurate picture of e-wallet adoption among Malaysian students.\n\nSecondly, the data could not be collected easily in a short period of time as there were many challenges faced by the researcher. This is due to the fact that the majority of responders were unwilling or unable to complete the questionnaire as they feel it was too much effort for them and a waste of time his makes the data collection difficult for researchers.\n\nFurther research should be conducted to gather a larger sample size from students from other parts of Malaysia. To improve the accuracy of the data collected, the questionnaires should be sent to multiple locations.\n\nFinally, this study clearly demonstrates students’ perceptions on the intentions to use e-wallet. As a result, mobile learning developers can attract more users by making mobile learning systems that are more user-friendly and publicising their benefits to students.\n\n\nData availability\n\nChelvarayan, AC (Multimedia University) (2021): E-Wallet: A Study on Cashless Transactions Among University Students. DANS [Dataset] https://doi.org/10.17026/dans-z3u-j7c8.20\n\nThis project contains the following underlying data:\n\n• E-WALLET ACCEPTANCE AMONG UNIVERSITY STUDENTS.csv. Responses from participants.\n\nChelvarayan, AC (Multimedia University) (2022): E-Wallet: A Study on Cashless Transactions Among University Students. DANS. [Dataset] https://doi.org/10.17026/dans-xzh-qzjc.21\n\nThis project contains the following extended data:\n\n• Questionnaire administered to 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\nAuthor contributions\n\nAll authors contributed equally for this research including the overall direction, the development of the framework, the collection of data, the analysis of the data and manuscript writing.",
"appendix": "Acknowledgements\n\nFirstly, the researchers would like to express deepest appreciation to fellow researchers for their continuous support and encouragement to ensure the completion of this project. The researchers also want to express gratitude to all participants and Multimedia University for the support in making this study possible.\n\n\nReferences\n\nYap CM, Ng BA: Factors Influencing Consumers’ Perceived Usefulness of M-Wallet in Klang Valley, Malaysia. Review of Integrative Business and Economics Research. 2019; 8(4): 1–23.\n\nQasim T, Siddiqui S, Rehman S: Interactive shopping with mobile wallet. IEEE. 2012; 32–36.\n\nDavis FD: Perceived Usefulness, Perceived Ease Of Use, And User Acceptance Of Information Technology. MIS Q. 1989; 13(3): 319–340. Publisher Full Text\n\nZhao W, Othman MN: Predicting and Explaining Complaint Intention and Behavior of Malaysian Consumers: An Application of The Planned Behavior Theory. Adv. Int. Mark. 2010; 9(1): 229–252.\n\nVenkatesh V, Morris MG, Davis GB, et al.: User acceptance of information technology: Toward a unified view. MIS Q. 2003; 27: 425–478. Publisher Full Text\n\nTan OK, Aziz FA, Ong CH, et al.: E-Wallet Acceptance among Undergraduates in Malaysia. TEST Engineering & Managemet. 2020; 83: 12990–12998.\n\nDavis FD, Bagozzi RP, Warshaw PR: User acceptance of computer technology: A comparison of two. Manag. Sci. 1989; 35(8): 982–1003. Publisher Full Text\n\nGuriting P, Oly Ndubisi N: Borneo online banking: evaluating customer perceptions and behavioural intention. Manag. Res. News. 2006; 29(1/2): 6–15. Publisher Full Text\n\nBauer RA: Consumer behavior as risk taking. Critical Perspectives on Business and Management. 1960; 13–21.\n\nWidodo M, Irawan MI, Sukmono RA: Extending UTAUT2 to Explore Digital Wallet Adoption in Indonesia. International Conference on Information and Communications Technology. 2019; 878–883.\n\nRazif NNM, Misiran M, Sapiri H, et al.: Perceived Risk for Acceptance of E-Wallet Platform in Malaysia among Youth: Sem Approach. Manag. Res. J. 2020; 9: 1–24.\n\nVerkijika SF: Factors influencing the adoption of mobile commerce applications in Cameroon. J. Telemat. Inform. 2018; 35(6): 1665–1674. Publisher Full Text\n\nMalik ANA, Annuar SNS: The effect of perceived usefulness, perceived ease of use, trust and perceived risk toward E-wallet usage. Insight J. 2019; 5: 183–191.\n\nLinck K, Pousttchi K, Wiedemann DG: Security Issues in Mobile Payment from the Customer Viewpoint. ECIS. 2006; 2006: 1–11.\n\nKousaridas A, Parissis G, Apostolopoulos T: An open financial services architecture based on the use of intelligent mobile devices. Electron. Commer. Res. Appl. 2008; 7(2): 232–246. Publisher Full Text\n\nAjmera H, Bhatt V: Factors affecting the consumer’s adoption of E-wallets in India: An empirical study. Alochana Chakra J. 2020; 9(6): 1081–1093.\n\nMalaysian Investment Development Authority (MIDA): 2021. Reference Source\n\nMeyta Dewi GM, Joshua L, Ikhsan RB, et al.: Perceived Risk and Trust in Adoption E-Wallet: The Role of Perceived Usefulness and Ease of Use. 2021 International Conference on Information Management and Technology (ICIMTech). 2021; pp. 120–124. Publisher Full Text\n\nMalik A, Nashren A, Annuar S, et al.: The effect of perceived usefulness, perceived ease of use, trust and perceived risk toward E-wallet usage/Akmal Nashren Abd Malik and Sharifah Nurafizah Syed Annuar. Insight Journal (IJ). 2019; 5 (21). pp. 183–191. 2600-8564\n\nChelvarayan AC: E-Wallet: A Study on Cashless Transactions Among University Students. DANS [Dataset]. 2021. (Multimedia University). Publisher Full Text\n\nChelvarayan AC: E-Wallet: A Study on Cashless Transactions Among University Students. DANS. [Dataset]. 2022. (Multimedia University). Publisher Full Text"
}
|
[
{
"id": "141632",
"date": "07 Jul 2022",
"name": "Fararishah Abdul Khalid",
"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\nThe paper reads well as a whole, bringing out a good topic and valuable data. There are just some minor issues that I noticed at the beginning, with regards to references. In the Introduction, the authors used Harvard style and then had a mix of numbered style and Harvard style in Literature Review.\nIn the Methods section, the authors could provide a description of the sample (on what basis were they considered as a respondent for the study, how were they identified and invited to participate). Maybe talk more about the convenient sampling method that they used. The last sentence in the second paragraph of Methods section mentioned about a screening process. It may be good to expand on the screening process.\nThe second paragraph of the Methods section seems more appropriate for a Theoretical Framework section. The discussion section needs to provide more interpretation of the results, for example, how does perceived usefulness influence the intention to use e-wallet, and analyse why perceived ease of use if not significant in impacting intention to use e-wallet. This could give the paper more depth in terms of its findings.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "143478",
"date": "01 Aug 2022",
"name": "Fathey Mohammed",
"expertise": [
"Reviewer Expertise Technology innovation adoption",
"information system and e-business"
],
"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 paper analyses the factors that affect university students’ intention to use e-wallets. E-wallet application use is an interesting area of research. However, this study has many major issues and it's not publishable in current format. The authors need to consider the following comments:\nGeneral comments: -A lot of studies investigated the factors influencing the use of e-wallet applications. However, this study failed to report what has been done in the literature, so the gap is not clear and accordingly the contribution is questionable. Please, refer to some of the most relevant studies as follows1,2,3,4,5,6,7,8\n-What is the research problem? What is special in the use of e-wallet applications in the private educational institution targeted in this study?\n-Why is the TAM model selected to be the underpinning model? Why were “behaviour intention” and “actual use” omitted? Why were only perceived risk and trust included? Why were, for example, complexity, pervasive technology use and tech-savvy future generations not including in the current study model?\n-Integrating perceived risk and trust with TAM has been done in the literature (refer to the above references), so what is the theoretical contribution of this study?\n-The main independent variable measured in this study is “intention to use” and based on the definition “intention is a person’s willingness and eagerness to obtain something desirable”, however based on the survey only 6 respondents haven’t used any e-wallet application, while 134 respondents use e-wallet applications frequently. So, how to measure the intention to use among those who already use the application?\n-The sample size is limited. “As of 31 March 2021, a total of 1.32 million students pursued their tertiary education in Malaysia”, and the sample size is only 140, so the results cannot be generalized.\n-Poor academic writing. To me, the following are unsound statements/arguments:\n“An e-wallet is a mobile application that allows users to download payment cards.” “It allows people to acquire items that meet their requirements and desires in a more convenient manner”. “Students, supervisors, academics, researchers, learning institutions, commercial organisations, and the government will all benefit immensely from the data and information gathered from this study” “This is to ensure that readers can clearly observe the relationship with all the independent variables on the intention of university students to use e-wallet” “Therefore, it is important for researchers to know users’ intention in using e-wallet so that e-wallet platform developers can improve to serve users better.” “Consumers might worry that the goods purchased does not meet their expectation.” “This research uses the descriptive research design whereby a descriptive research design is a … ” “The demographic data, the ideas included in this study, and their interactions were all analysed using the Statistical Package for the Social Sciences (SPSS)” “The theories that were created were also tested and …” “This research will influence future studies for e-wallet adoption among students in Malaysia, especially during the current global pandemic.” “The findings are useful for online platform or application developers whereby they can use the findings from this research to enhance their existing platforms or develop new platforms specially dedicated for students.”\n\n-The paper structure is misleading:\nThe model’s constructs were introduced in the Literature Review section, while the model was presented in Methods section. Also, the hypotheses are missed. I suggest having a section “proposed model and the hypotheses” to include everything about the proposed model. “Results and discussion” and “Discussion” are two subsections.\n\nSpecific Comments:\n-Abstract: It lacks the problem statement and the main results. Remove the limitations from the abstract.\n\n-Introduction: In the introduction you should provide a background of the problem by introducing the research area then narrowing down to the specific problem of the current study. The problem should be supported by most recent and related literatures and reports. The motivation and significance of the study should be highlighted. Then the main aim of the study should be stated. The paper structure then may be presented (recommended).\n-Literature review: This section mainly presented a theoretical background related to TAM and the factors investigated in the current study, however this section should report and analyse the most related studies.\n-Method: The methodology is not well organized and justified. The research design should be clearly presented.\n-Results and discussion: Remove “discussion” from the title, you can use “Analysis and results”. In this section, all measurements and criteria should be clear and justified. Reliability was tested using Cronbach’s Alpha, but the validity of the constructs was not measured. It is not clear how was SPSS used to test the hypotheses?\n-Discussion: What is presented in this section is a conclusion. In this section, the results should be discussed to show how the aim was achieved and how this study contributed to the area of research in compared with similar studies’ results.\n\nRegards\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": []
},
{
"id": "202820",
"date": "13 Dec 2023",
"name": "Femmy Effendy",
"expertise": [
"Reviewer Expertise Bussines",
"Digital marketing",
"adoption technology",
"marketing management",
"strategic management",
"supply chain management",
"system information management"
],
"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 articles reviewed clearly and accurately cite the latest literature examining the acceptance and use of e-wallets as well as literature references from the TAM theory proposed by Davis. An appropriate research design uses quantitative descriptive and inferential methods. The details of the methods and analysis provided are sufficient to allow other parties to imitate them because they are based on clear models and theories and use measurable methods. Statistical analysis and interpretation are correct, but the gradual stages of analysis such as validity, reliability, normality and regression tests must be further explained to obtain the results of the relationship between variables. The conclusions drawn are sufficiently supported by the results, but need to be linked to previous research, whether the research carried out is in accordance with the reference of the referenced article or rejects the reference. so that the research results strengthen previous theories or weaken previous theories and do not matter about the sample size taken\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/11-687
|
https://f1000research.com/articles/10-10/v1
|
08 Jan 21
|
{
"type": "Systematic Review",
"title": "A systematic review on the effects of high frequency chest wall compression and intrapulmonary percussive ventilation in patients with neuromuscular disease",
"authors": [
"Katia Giacomino",
"Roger Hilfiker",
"Tina Magnin",
"Lara Allet",
"Roger Hilfiker",
"Tina Magnin",
"Lara Allet"
],
"abstract": "Background: Respiratory insufficiency is the most common cause of mortality among patients with a neuromuscular disease. Methods: We explored the effects of high frequency wall compression and intrapulmonary percussive ventilation, compared with standard care or no treatment, on the lung volume and capacity, and quality of life in patients with neuromuscular disease during respiratory infections or in stable periods. We further assessed the effects of these two interventions on clinical value, complications, and survival. The literature search was performed on Embase, MEDLINE, CINAHL, CENTRAL and PEDro. Randomised controlled trials and cross-over studies were eligible. Results: Five studies were included, and results were presented narratively. High frequency wall compression was not shown to be superior to standard care in terms of lung volume and capacity, quality of life, complications, and survival rate. Compared with standard care, intrapulmonary percussive ventilation showed non-significant differences in terms of lung volume and capacity, and the risk of respiratory infection. Standard care was nevertheless associated with a significantly higher risk of days of hospitalisation (Incidence Rate Ratio 8.5 [1.1-67]) and of antibiotic use than intrapulmonary percussive ventilation (Incidence Rate Ratio 43 [6-333]). Conclusions: Due to large variety of reported outcomes, missing data and limited number of studies, no meta-analysis could be conducted. The results should be interpreted with caution as the results have a very low certainty of evidence and reported outcomes have a high risk of bias. The evidence for high frequency wall compression and intrapulmonary percussive ventilation is still insufficient to draw final conclusions. Protocol registration: PROSPERO ID: CRD42017064703.",
"keywords": [
"Neuromuscular diseases",
"chest wall oscillation",
"intra-pulmonary percussive ventilation",
"lung function measurements",
"quality of life"
],
"content": "Abbreviations\n\n95% CI, Confidence interval; cmH2O, Centimetre of water; FEV1, Forced expiratory volume in 1 second; FVC, Forced vital capacity; GRADE, Grading of recommendations assessment development and evaluation; HFCWC, High frequency chest wall compression; IPV, Intrapulmonary percussive ventilation; IRR, Incidence rate ratio; MD, Mean difference; NMD, Neuromuscular disease; PRISMA, Preferred reporting items for systematic reviews and meta-analyses; QoL, Quality of life; RCT, Randomised controlled trial; RXO, Randomised cross-over study\n\n\nIntroduction\n\nIneffective cough mechanisms can occur in patients with neuromuscular disease (NMD) as a result of inspiratory and expiratory muscle weakness, as well as impaired glottic function1,2. In the long term, secretion retention leads to airway obstruction, inflammation, breathing difficulty, repeated acute respiratory tract infection, and consequently chronic lung disease and a predisposition to ventilatory failure3–6. Maintaining clear airways is crucial in patients with NMD, because respiratory insufficiency is one of the main causes of death4.\n\nFor secretion clearance, secretion mobilisation techniques and assisted coughing techniques are recommended7. However, the standard secretion mobilisation techniques, such as postural drainage techniques, chest wall strapping, positive expiratory pressure and oscillatory positive expiratory pressure, are ineffective in very weak patients because they are effort-dependent2,8, and these patients are generally unable to generate sufficient expiratory flow3. These techniques are also difficult to apply in cases of chest wall or spinal deformities, as well as osteoporotic ribs9. In these specific cases, other techniques are favoured, such as high frequency chest wall oscillations (HFCWO), high frequency chest wall compression (HFCWC) or intrapulmonary percussive ventilation (IPV)9. These methods have the benefit of working without the patient’s active participation, especially in patients with tracheostomy and/or bulbar failure, and/or intellectual impairment3.\n\nArcuri et al. conducted a systematic review of airway clearance and analysed patients with NMD. They reported that HFCWC does not improve the survival rate or the loss of FVC. In addition, HFCWC does not decrease the frequency of respiratory infections, and IPV is unsuccessful in enhancing peak expiratory flow10.\n\nEven if there is a growing interest in the use of IPV and HFCWC, Arcuri et al. did not include every existing publication in their recent review10, probably because they included studies with a majority of adults and the severity of the chronic disease had to be identified with the National Hospice Organisation Criteria11. It is thus of clinical relevance to make an up to date synthesis of the available evidence regarding the use of IPV and HFCWC12.\n\nWe hypothesised that IPV and HFCWC might mobilise secretions, recruit obstructed areas of the lungs and prevent the negative consequences of muscle weakness related to neuromuscular disease. Hence, our main objective was to explore the effects of HFCWC and IPV, as compared with standard care or no treatment, on lung volume and capacity (as a result of secretions mobilisation), as well as quality of life (QoL) in patients with neuromuscular disease in acute or stable condition. We further assessed the effects of IPV and HFCWC on clinical value (arterial blood gases and the patient’s subjective respiratory perception of dyspnoea), complications and survival.\n\n\nMethods\n\nThis systematic review followed the recommendations of the Cochrane Guidelines for systematic review of interventions as well as the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement13. The registration number of PROSPERO is CRD42017064703.\n\nOn 30 June 2020, reviewer KG performed the search on the following databases: Embase, MEDLINE (through PubMed), CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PEDro. No language restriction was set. We used the filter for RCTs in PubMed and Embase recommended by Cochrane. We also searched the grey literature in the reference lists of articles, Google Scholar and registered trials in the US National Institutes for Health Clinical Trials Registry14. The research strategy was composed of two parts that were combined with “AND” (see Extended data: File 1 for full search strategies). The first part was composed of relevant terms to identify the population. The second part included terms related to the studied interventions. In both parts, MeSH terms were used when available.\n\nStudy type. Randomised controlled trials (RCTs) and randomised cross-over studies (RXOs) were eligible.\n\nParticipants. We included adults and children with NMD with or without tracheotomy.\n\nInterventions. The interventions of interest were HFCWC or HFCWO and IPV.\n\nComparator. The intervention was compared to either standard care or no treatment. We considered as standard care to comprise active cycles of breathing techniques and chest physiotherapy, such as postural drainage therapy.\n\nOutcomes. The primary outcomes were lung volume and capacity, as measured with lung function tests, including forced vital capacity (FVC), total lung capacity, functional capacity, vital capacity, predicted FVC%, forced expiratory volume in the first second (FEV1), peak expiratory flow, peak cough expiratory flow and the Tiffeneau-Pinelli index (FEV1/FVC). The respiratory muscle strength was assessed with the maximal inspiratory pressure and maximal expiratory pressure. The additional outcomes were a) clinical values comprising arterial blood gases and the patient’s subjective respiratory perception of dyspnoea, b) complications (e.g., the number of days of hospitalisation, respiratory tract infection rate, death rate and antibiotic use), c) survival rate, and d) patient QoL.\n\nThree reviewers (TC, KG, and RH) independently screened the titles and the abstracts and read the full texts. At each step, the results were compared, and disagreements were discussed until a consensus was reached. If disagreement persisted, a third person (LA) made the final decision. Articles in languages other than English, French, German and Italian were excluded if no translator could be found and if articles did not report separate results for patients with NMD. Reviewers KG and TC extracted the data regarding the study characteristics (country, diagnosis, inclusion and exclusion criteria, age, sex and number randomised patients), the interventions (type of interventions, frequency, duration and intensity), and the outcome measures (lung function, blood gas analysis, hospitalisations or antibiotic use, survival rate, mortality rate, respiratory tract infection rate and QoL). Disagreements were discussed, and a consensus was reached. Then, reviewer KG integrated the data into Review Manager 5.3.\n\nReviewers KG and TC independently evaluated the risk of bias of the RCTs and the RXO with the Cochrane revised risk of bias tool (RoB 2.0 tool; 9 October 2018 version)15. The results were compared, and differences in the evaluation were discussed until a consensus was reached. If the two reviewers still disagreed, the third reviewer, LA, was contacted to make the final decision. Risk of bias plots are available in the appendix (Extended data: File 2, Figures 2–8).\n\nWe extracted or calculated the treatment effects of the RCTs with the between-group differences of the mean change values and calculated the 95% confidence intervals (95% CIs) if data were available. The relative risk (risk ratio, RR) with a 95% CI was extracted or calculated for dichotomous data. We extracted the incidence rate ratio (IRR) for person-time data. The outcomes were collected after the end of the intervention. We used the Review Manager 5.3 for the analysis.\n\nOne reviewer (KG) assessed the certainty of evidence by using the Grade of Recommendation, Assessment, Development and Evaluation Working Group (GRADE Working Group) guidelines16.\n\n\nResults\n\nThe electronic search identified 1588 records. After removing 406 duplicates, we screened 1182 titles and abstracts and 1058 records were excluded. In total, 124 full texts were screened, and 119 were excluded for the following reasons: wrong design 13, wrong intervention 4, wrong population 101, study in Hebrew 1. (PRISMA flow diagram in Figure 1). Five studies were included according to the eligibility criteria17–21.\n\nThe characteristics of the included studies are described in Table 1. We could not perform a meta-analysis due to the diversity of the reported outcomes, the small number of studies, missing data and heterogeneity among studies.\n\n*Statistically significant differences; **randomisation included cerebral palsy and NMD patients; in the table only the results of the sub-group of NMD are reported; ***median (25th-75th percentile); NIV = non-invasive ventilation; CG = control group; EG = experimental group; HFCWC = high frequency chest wall compression; HFCWO = high frequency chest wall oscillation; hr = hour; Hz = hertz; IPV = intrapulmonary percussive ventilation; ml = millilitre; min = minutes; mo. (plural mos) = month-s; NA = not available; NMD = neuromuscular disease; No. = number; RCR = retrospective chart review; RCT = randomised controlled trial; RXO = randomised cross-over study; USA = United States of America.\n\nThe results of the studies are displayed in Table 2 and Table 3.\n\nItalics stand for calculated value; *Result expressed in median (25th-75th percentile); 95% CI = 95% confidence interval; CG = control group; EG = experimental group; GRADE = grading of recommendations assessment development and evaluation; IQR = interquartile range; L = litre; min = minutes; ml = millilitre; NA = not available; NM = not measurable; No. = number; NS = not significant; P = P-value; Post = post-intervention; Pre = pre-intervention; QoL = quality of life; RCR = retrospective chart review; RCT = randomised controlled trial; RR = relative risk; RXO = randomised cross-over study; SD = standard deviation;1 = Studies are retrospective and do not have a control group, so no randomisation and no concealment; 2 = Randomisation was not or probably not concealed; 3 = The study did not analyse the results in the intention-to-treat; 4 = Assessors, care givers or patients were not blinded; 5 = An important proportion of patients were lost to follow up; 6 = Difference in the effect size can be due to inconsistency in the method; 7 = Difference in the effect size can be due to inconsistency in age between groups; 8 = Difference in the effect size can be due to inconsistency in the difference of treatment intensity; 9 = Indirect because of inadequate comparison or no comparison group; 10 = Indirectness in the intervention, short duration of the treatment; 11 = Indirectness due to indirect outcome of interest for the quality of life; 12 = The studies are composed of small sample size (between 9 and 46 participants) or small number of events; 13 = The confidence interval is wide; 14 = Results are not fully reported; 15 = Conflict of interest exists due to material donation from an industry, sponsoring by an industry or the fact that an author is employed by an industry.\n\nGRADE level of certainty of the evidence: ⊕⊕⊕⊕ = high certainty of the evidence, ⊕⊕⊕◯ = moderate certainty of the evidence; ⊕⊕◯◯ = low certainty of the evidence, ⊕◯◯◯ = very low certainty of the evidence.\n\nItalics stand for calculated value; *Result expressed in median (25th-75th percentile); 95% CI = 95% confidence interval; CG = control group; EG = experimental group; GRADE = grading of recommendations assessment development and evaluation; IQR = interquartile range; L = litre; NA = not available; NM = not measurable; NS = not significant; P = P-value; Post = post-intervention; Pre = pre-intervention; RCT = randomised controlled trial; RXO = randomised cross-over study; SD = standard deviation; 1 = Studies are retrospective and do not have a control group, so no randomisation and no concealment; 2 = Randomisation was not or probably not concealed; 3 = The study did not analyse the results in the intention-to-treat; 4 = Assessors, care givers or patients were not blinded; 5 = An important proposition of patients were lost to follow up; 6 = Difference in the effect size can be due to inconsistency in the method; 7 = Difference in the effect size can be due to inconsistency in age between groups; 8 = Difference in the effect size can be due to inconsistency in the difference of treatment intensity; 9 = Indirect because of inadequate comparison or no comparison group; 10 = Indirectness in the intervention; short duration of the treatment; 11 = Indirectness due to indirect outcome of interest for the quality of life; 12 = The studies are composed of small sample size (between 9 and 46 participants) or small number of events; 13 = The confidence interval is wide; 14 = Results are not fully reported; 15 = Conflict of interest exists due to material donation from an industry, sponsoring by an industry or the fact that an author is employed by an industry.GRADE level of certainty of the evidence: ⊕⊕⊕⊕ = high certainty of the evidence, ⊕⊕⊕◯ = moderate certainty of the evidence; ⊕⊕◯◯ = low certainty of the evidence, ⊕◯◯◯ = very low certainty of the evidence.\n\nLung volume, capacity and HFCWC. For the FVC (1 RCT), we were unable to find evidence against the Null-Hypothesis that HFCWC is equal to the standard care in the rate of decline (mean difference (MD) of 0.8 ml/day in favour of standard care with a 95% CI [-2.56, 4.16])17.\n\nOne RCT18 assessed the predicted FVC (%) and we failed to find evidence against the Null-Hypothesis that HFCWC is equal to the untreated group in the rate of decline (MD: -1.2% in favour of HFCWC with a 95% CI [-9.70, 7.30]; P = .78).\n\nThe peak expiratory flow rate, evaluated in one RCT18, showed no statistically significant difference between the HFCWC group and the untreated group (MD: 40 L/min in favour of HFCWC with a 95% CI [-16.93, 96.93], P = .18).\n\nLung volume, capacity and IPV. One RCT19 assessed the total lung capacity and the difference between IPV and incentive spirometry post-intervention (0.5L in favour of IPV) was not statistically significant.\n\nIn the predicted FVC (%), they were unable to find evidence against the Null-Hypothesis that IPV is equal to incentive spirometry post-intervention (1% in favour of standard care)19.\n\nThe difference between IPV and standard care post-intervention for the predicted FEV1(%) (0%) was not statistically significant19.\n\nThe peak expiratory flow rate was examined in one RXO study20. We were unable to find evidence against the Null-Hypothesis that the treatment sequence with IPV is equal to without IPV (5.8L/min with a 95% CI [-4.45, 16.05], P= .27).\n\nThe difference between IPV and standard care in the maximum expiratory pressure post-intervention (8 cmH2O in favour of standard care), and the maximum inspiratory pressure (-1 cmH2O in favour of standard care) were not statistically significant19.\n\nClinical value and HFCWC. The data on arterial blood gases and mortality rate were not available.\n\nDyspnoea and HFCWC. One study18 assessed dyspnoea, and we found evidence against the Null-Hypothesis that HFCWC is not equal to the untreated groups (MD: -2.12 in favour of HFCWC with a with a 95% CI [-3.83, -0.41]; P= .02).\n\nComplications and HFCWC. There was no difference in the number of hospitalisation days between the HFCWC and the usual care groups (0 events in both groups) in one study17. The difference in the relative risk of requiring hospitalisation and intravenous antibiotics was 80% lower in the HFCWC group than the standard care group, but statistically not significant (RR: 0.20 with a 95% CI [0.01, 3.54])21. The relative risk of requiring oral antibiotics was 33% lower in the HFCWC group than in the standard care group (RR: 0.67 with a 95% [0.16, 2.84]), but statistically not significant21.\n\nComplications and IPV. One RCT19 assessed hospitalisation and observed more days of hospitalisation for respiratory reasons in the standard care group than the IPV group, although the lower limit of the CI was close to 1 (IRR: 8.5 with a 95% CI [1.1-67]).\n\nThree events of pulmonary infection (pneumonias or bacterial bronchitis) were observed in the standard care group, whereas the IPV group had no events (IRR: 3.9 with a 95% CI [0.43-35], P= NS). The number of days of using antibiotics was significantly higher in the standard care groups than the IPV group (IRR: 43 with a 95% CI [6-333])19.\n\nSurvival and HFCWC. One RCT with nine patients17 found 340±247 days of survival for the HFCWC group and 470±241 days of survival for the standard care. This difference was not statistically significant (P = .26) and there were only five patients in the HFCWC group and four in the standard care group.\n\nQuality of life and HFCWC. Lange et al. (2006) studied the proportion of worsened QoL18. The five sub-categories of QoL assessment showed inconsistent results in terms of relative risk, but none were statistically significant (Table 2).\n\n\nDiscussion\n\nBased on this systematic review, 104 patients in five randomised studies, including the diagnoses amyotrophic lateral sclerosis (two studies) or Duchenne muscular dystrophy (three studies, two of them with a mix of other neuromuscular diagnoses), we can report the following main findings: there is very low certainty of evidence that A) HFCWC is not superior to standard care for lung capacity, lung volume, antibiotic use, quality of life, and survival rate, B) HFCWC is superior to standard care for perception of dyspnoea, C) IPV is not superior to standard care for lung capacity, lung volume, and the risk of respiratory infection, and D) IPV is superior to standard care for the reduction of hospitalisation rate and number of days of antibiotic use.\n\nThis review has some limitations. First, it is possible that we missed unpublished studies, or studies that were only published in languages other than English and in journals not listed in the searched databases or the clinical trial registries. Because of the low number of studies, we were not able to evaluate the risk of a small study effect or a publication bias. Second, it is known that the reliability of the risk of bias tool is not very high and other authors might come to different conclusions regarding risk of bias of the include studies.\n\nThere are limitations regarding the included studies. First, the included studies were very small, had a high risk of bias, and it was not possible to perform a meta-analysis. Therefore, we only have very low confidence in our results, given the downgrading in the GRADE rating because of very serious risk of bias, serious inconsistency and very serious statistical imprecision22. Second, our research question was the effects of HFCWC and IPV on lung volume and capacity as a result of secretions mobilisation. Airway clearance measurement trough sputum weight is inappropriate due to day-to day variability, as well as variability during the day and the fact that secretions can be swallowed23. Therefore, our primary outcomes were lung volume and capacity as it is often used in the literature as an outcome for airway clearance and to assess the progression of the disease in patient with NMD. Many trials have reported that the use of lung function parameters is questionable because of the lack of observed changes8. Jones et al. (2006) suggest that lung function parameters are insensitive in assessing the acute effects of airway clearance techniques24. In addition, van der Schans (2002) reports that lung function measurement does not appear to reflect differences in mucus transport or mucus expectoration25. Thus, the ineffectiveness of the two interventions might be influenced by the inefficacy of lung function to assess airway clearance. The lack of significant results could be influenced by the inefficiency of lung function to assess airway clearance.\n\nThe results of studies using IPV and HFCWC for other pathologies show similarities and differences as compared with our results. Reychler et al. (2018) have performed a systematic review and compared IPV with other airway clearance techniques. They found a reduction in the duration of hospitalisation and have observed an improvement in gas exchange only during the exacerbation phase in patients with chronic obstructive airway disease. In patients with cystic fibrosis, no difference was observed in the static and dynamic lung volume26. Cough is usually not impaired in patients with chronic obstructive airway disease and cystic fibrosis, thus potentially explaining the contrasting results.\n\nIn a recent publication, Chatwin et al. (2018)3 highlight that airway clearance such as IPV and HFCWC depend on a normal cough to clear proximal airway. In patients with NMD, these interventions may be ineffective if not combined with cough augmentation technique or device. To our knowledge, no studies investigated the combination of a secretion mobilisation device such as IPV and HFCWC with cough augmentation technique or device.\n\nOur review differs from previous ones in that we included only patients with NMD treated either with HFCWC or IPV. We could include additional studies18,19,21, but we still can only report very low certainty of evidence for or against the use of HFCWC or IPV for airway clearance. In one study, patients in the HFCWC groups showed substantial but statistically not significant fewer survival days compared to the standard care, which was in this case bilevel positive airway pressure. There are no other studies in any type of patients, to our knowledge, that reported increased mortality for patients treated with HFCWC. Therefore, we strongly believe that this decreased survival time in the mentioned study should not be overrated, but future studies should monitor mortality under HFCWC.\n\nFuture studies should include larger sample sizes in multi-centre trials involving international collaborations and should avoid risk of bias. The comparison treatment should avoid using a ‘no treatment’ group, and the intervention should be described precisely to facilitate comparison with other studies. We invite researchers to focus on the effects of combined treatments, such as secretion mobilisation interventions with cough augmentation technique, manual cough techniques or mechanical insufflation-exsufflation. We further encourage researchers to investigate more reliable, sensitive and patient-relevant outcome measures to assess the effects of airway clearance techniques.\n\n\nConclusions\n\nIn this systematic review we explored the effects of IPV and HFCWC, compared with standard care, and found no effects on lung volume and capacity, and QoL. HFCWC might decrease the perception of dyspnoea but shows no difference in the development of complications and survival. Treatment with IPV, compared with control treatment, appears to reduce the number of hospitalisation days and to lessen the need for antibiotics, but no difference was observed regarding the respiratory infection rate.\n\nThe certainty of evidence of these results is very low, and all studies presented high risk of bias. The implementation of these interventions in clinical practice should be further evaluated in clinical trials. We invite future studies to improve on these aspects, to explore the effects of combined treatments and to investigate more reliable, sensitive, and patient-relevant outcome measure.\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\nDryad: A systematic review on the effects of high frequency chest wall compression and intrapulmonary percussive ventilation in patients with neuromuscular disease, https://doi.org/10.5061/dryad.n8pk0p2tj27\n\nThis project contains the following extended data:\n\n- File 1: Search strategy for all databases used\n\n- File 2: Risk of bias analysis\n\nDryad: PRISMA checklist for ‘A systematic review on the effects of high frequency chest wall compression and intrapulmonary percussive ventilation in patients with neuromuscular disease’, https://doi.org/10.5061/dryad.n8pk0p2tj27\n\nData are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).",
"appendix": "Acknowledgements\n\nWe would like to thank Elodie Glerum for proofreading the article and Martin Sattelmayer for designing the graphs.\n\n\nReferences\n\nBenditt JO: Respiratory Care of Patients With Neuromuscular Disease. Respir Care. 2019; 64(6): 679–88. PubMed Abstract | Publisher Full Text\n\nFinder JD: Airway clearance modalities in neuromuscular disease. Paediatr Respir Rev. 2010; 11(1): 31–4. PubMed Abstract | Publisher Full Text\n\nChatwin M, Toussaint M, Goncalves MR, et al.: Airway clearance techniques in neuromuscular disorders: A state of the art review. Respir Med. 2018; 136: 98–110. PubMed Abstract | Publisher Full Text\n\nGozal D: Pulmonary manifestations of neuromuscular disease with special reference to Duchenne muscular dystrophy and spinal muscular atrophy. Pediatr Pulmonol. 2000; 29(2): 141–50. PubMed Abstract | Publisher Full Text\n\nHomnick DN: Mechanical insufflation-exsufflation for airway mucus clearance. Respir Care. 2007; 52(10): 1296–305. PubMed Abstract\n\nMorrow B, Zampoli M, van AH, et al.: Mechanical insufflation-exsufflation for people with neuromuscular disorders. Cochrane Database Syst Rev. 2013; (12): CD010044. PubMed Abstract | Publisher Full Text\n\nAmbrosino N, Carpene N, Gherardi M: Chronic respiratory care for neuromuscular diseases in adults. Eur Respir J. 2009; 34(2): 444–51. PubMed Abstract | Publisher Full Text\n\nLauwers E, Ides K, Van Hoorenbeeck K, et al.: The effect of intrapulmonary percussive ventilation in pediatric patients: A systematic review. Pediatr pulmonol. 2018; 53(11): 1463–1474. PubMed Abstract | Publisher Full Text\n\nHaas CF, Loik PS, Gay SE: Airway clearance applications in the elderly and in patients with neurologic or neuromuscular compromise. Respir Care. 2007; 52(10): 1362–81. PubMed Abstract\n\nArcuri JF, Abarshi E, Preston NJ, et al.: Benefits of interventions for respiratory secretion management in adult palliative care patients-a systematic review. BMC Palliat Care. 2016; 15: 74. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStuart B: The NHO Medical Guidelines for Non-Cancer Disease and local medical review policy: hospice access for patients with diseases other than cancer. Hosp J. 1999; 14(3–4): 139–54. PubMed Abstract | Publisher Full Text\n\nAuger C, Hernando V, Galmiche H: Use of Mechanical Insufflation-Exsufflation Devices for Airway Clearance in Subjects With Neuromuscular Disease. Respir Care. 2017; 62(2): 236–245. PubMed Abstract | Publisher Full Text\n\nMoher D, Liberati A, Tetzlaff J, et al.: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010; 8(5): 336–41. PubMed Abstract | Publisher Full Text\n\nMedicine USNLo. ClinicalTrials. 2017. Reference Source\n\nJorgensen L, Paludan-Muller AS, Laursen DR, et al.: Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews. Syst rev. 2016; 5: 80. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchünemann H, Brożek J, Guyatt G, et al.: GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group. 2013. Reference Source\n\nChaisson KM, Walsh S, Simmons Z, et al.: A clinical pilot study: high frequency chest wall oscillation airway clearance in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2006; 7(2): 107–11. PubMed Abstract | Publisher Full Text\n\nLange DJ, Lechtzin N, Davey C, et al.: High-frequency chest wall oscillation in ALS: an exploratory randomized, controlled trial. Neurology. 2006; 67(6): 991–7. PubMed Abstract | Publisher Full Text\n\nReardon CC, Christiansen D, Barnett ED, et al.: Intrapulmonary percussive ventilation vs incentive spirometry for children with neuromuscular disease. Arch Pediatr Adolesc Med. 2005; 159(6): 526–31. PubMed Abstract | Publisher Full Text\n\nToussaint M, Win H, Steens M, et al.: Effect of intrapulmonary percussive ventilation on mucus clearance in duchenne muscular dystrophy patients: a preliminary report. Respir Care. 2003; 48(10): 940–7. PubMed Abstract\n\nYuan N, Kane P, Shelton K, et al.: Safety, tolerability, and efficacy of high-frequency chest wall oscillation in pediatric patients with cerebral palsy and neuromuscular diseases: an exploratory randomized controlled trial. J Child Neurol. 2010; 25(7): 815–21. PubMed Abstract | Publisher Full Text\n\nBalshem H, Helfand M, Schünemann HJ, et al.: GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011; 64(4): 401–6. PubMed Abstract | Publisher Full Text\n\nSilva YR, Greer TA, Morgan LC, et al.: A Comparison of 2 Respiratory Devices for Sputum Clearance in Adults With Non-Cystic Fibrosis Bronchiectasis. Respir Care. 2017; 62(10): 1291–7. PubMed Abstract | Publisher Full Text\n\nJones PW, Agusti AG: Outcomes and markers in the assessment of chronic obstructive pulmonary disease. Eur Respir J. 2006; 27(4): 822–32. PubMed Abstract | Publisher Full Text\n\nvan der Schans CP: Airway clearance: assessment of techniques. Paediatr Respir Rev. 2002; 3(2): 110–4. PubMed Abstract | Publisher Full Text\n\nReychler G, Debier E, Contal O, et al.: Intrapulmonary Percussive Ventilation as an Airway Clearance Technique in Subjects With Chronic Obstructive Airway Diseases. Respir care. 2018; 63(5): 620–31. PubMed Abstract | Publisher Full Text\n\nGiacomino K, Hilfiker R, Magnin T, et al.: A systematic review on the effects of high frequency chest wall compression and intrapulmonary percussive ventilation in patients with neuromuscular disease. Dataset. Dryad. 2020. http://www.doi.org/10.5061/dryad.n8pk0p2tj"
}
|
[
{
"id": "127677",
"date": "05 Apr 2022",
"name": "Ivanizia S. Silva",
"expertise": [
"Reviewer Expertise Systematic review and Respiratory physiotherapy"
],
"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 review is well done overall but I would ask the authors to make some revisions.\n\nMethods:\nIn the 'Study selection and data extraction' section: if disagreement persisted, a fourth person (LA) made the final decision.\n\nHow were missing data and heterogeneity handled?\n\nDescribe the methods of analysis for crossover trials.\n\nResults:\nInclude the results of risk of bias.\n\nThe results needs some revision. It is important not to rely on statistical significance. If the minimal important difference for an instrument is known, describing the probability of individuals achieving this difference may be more intuitive. Review authors should always seriously consider this option.\n\nI suggest that the authors integrate GRADE assessments into the review so that there is a consistent message between results and summaries (conclusions, abstract and plain language summary) on the size of any effect and the quality of the evidence.\n\nDiscussion:\nAs with any study, if the methods proposed in the protocol are changed during the course of conducting the review, these changes should be documented and reported.\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? Yes",
"responses": [
{
"c_id": "8311",
"date": "30 May 2022",
"name": "Katia Giacomino",
"role": "Author Response",
"response": "Dear Doctor Ivanizia S. Silva, we would like to thank you for your comments and suggestions for improvement. We have responded to each of your comments below. Your comment in the method: In the 'Study selection and data extraction' section: if disagreement persisted, a fourth person (LA) made the final decision. Our response: We thank for noticing this typing mistake, the corrections were done. Your comment in the method: How were missing data and heterogeneity handled? Our response: We now specified the section “Study selection and data extraction”. We also specified the paragraph about “heterogeneity” in the results section. Your comment in the method: Describe the methods of analysis for crossover trials. Our response: In the chapter “Data synthesis and analysis”, we specified how we performed the analysis of the cross-sectional study. Your comment in the results : Include the results of risk of bias. Our response: Thank you for this comment. We now added a section with results of the risk of bias in the chapter of the results. Your comment in the results : The results needs some revision. It is important not to rely on statistical significance. If the minimal important difference for an instrument is known, describing the probability of individuals achieving this difference may be more intuitive. Review authors should always seriously consider this option. Our response: Thank you for this relevant remark. We now added in the result section the minimal clinically important difference when this value was known. Your comment in the results : I suggest that the authors integrate GRADE assessments into the review so that there is a consistent message between results and summaries (conclusions, abstract and plain language summary) on the size of any effect and the quality of the evidence. Our response: Thanks for this relevant suggestion. We added in every outcome category the rating of the quality of evidence in the result section. Your comment in the discussion: As with any study, if the methods proposed in the protocol are changed during the course of conducting the review, these changes should be documented and reported. Our response: We now specified this change in the discussion section and added a paragraph reporting the changes between the protocol and our study."
}
]
},
{
"id": "134658",
"date": "19 Apr 2022",
"name": "Masahiro Banno",
"expertise": [
"Reviewer Expertise clinical 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 study aimed to provide an overview of the effects of HFCWC and IPV, as compared with standard care or no treatment, on lung volume and capacity. The strength of this study was to conduct analysis using a rigorous method of systematic reviews. However, there were some concerns in this study.\nFirst, the authors had better describe the inclusion criteria and exclusion criteria of the included studies, the search date for each database, the Cochrane revised risk of bias tool, GRADE, and the summary of the risk of bias in the abstract.\nSecond, they had better follow the recommendations of the PRISMA 2020, not the previous version they cited.\nThird, it would be better to add the PRISMA 2020 checklist, not the PRISMA 2009 checklist they clarified, as a supplemental file with the page numbers of the manuscript for each item in the PRISMA 2020 checklist.\nFourth, they had better revise the manuscript, or add new limitations in the discussion if any important items in the PRISMA 2020 checklist were not met.\nFifth, they had better clarify PRISMA 2020 flow diagram in Figure 1. The present Figure 1 was the PRISMA flow diagram in the previous version, not PRISMA 2020 flow diagram.\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? Yes",
"responses": [
{
"c_id": "8312",
"date": "30 May 2022",
"name": "Katia Giacomino",
"role": "Author Response",
"response": "Dear Doctor Masahiro Banno, we would like to thank you for your comments and suggestions for improvement. We have responded to each of your comments below. Your first comment: First, the authors had better describe the inclusion criteria and exclusion criteria of the included studies, the search date for each database, the Cochrane revised risk of bias tool, GRADE, and the summary of the risk of bias in the abstract. Our response: Thank you for your relevant suggestion. We now specified the in and exclusion criteria, the search date, the risk of bias and the GRADE in the abstract. Your second comment: Second, they had better follow the recommendations of the PRISMA 2020, not the previous version they cited. Our response: Thank you for having noticed that we used the old version of the PRISMA guideline, we now corrected with the last version. Your third comment: Third, it would be better to add the PRISMA 2020 checklist, not the PRISMA 2009 checklist they clarified, as a supplemental file with the page numbers of the manuscript for each item in the PRISMA 2020 checklist. Our response: We thank you for your remark, we now used the new version of the checklist of the PRISMA guideline and made the necessary changes. We will also precise the page number of each item. Your fourth comment: Fourth, they had better revise the manuscript, or add new limitations in the discussion if any important items in the PRISMA 2020 checklist were not met. Our response: Thank you for this important remark, we changed the checklist for the new version and made the necessary changes in the manuscript. Your fifth comment: Fifth, they had better clarify PRISMA 2020 flow diagram in Figure 1. The present Figure 1 was the PRISMA flow diagram in the previous version, not PRISMA 2020 flow diagram. Our response: The last version of the flow diagram is now available."
}
]
}
] | 1
|
https://f1000research.com/articles/10-10
|
https://f1000research.com/articles/11-685/v1
|
21 Jun 22
|
{
"type": "Case Report",
"title": "Case Report: Long QT syndrome in the setting of post COVID depression",
"authors": [
"Aymen Noamen",
"Houssem Ben Ayed",
"Youssef Ebn Ebrahim",
"Sarra Chenik",
"Nadhem Hajlaoui",
"Wafa Fehri",
"Houssem Ben Ayed",
"Youssef Ebn Ebrahim",
"Sarra Chenik",
"Nadhem Hajlaoui",
"Wafa Fehri"
],
"abstract": "Long QT syndrome is a genetically inherited heart disease caused by mutations in genes coding for the ion channels expressed in the heart cells. Like any other hereditary pathology Long QT Syndrome manifestations often start at a young age. We report the case of a 65-year-old woman who presented a syncope after taking antidepressants, revealing a congenital long QT syndrome. The onset of cardiovascular symptoms in elderly subjects with such an unrecognized entity is very rare and is most often due to transient biological disturbances or to the use of certain drugs, which prolong the QT interval.",
"keywords": [
"Long QT syndrome",
"COVID-19",
"depression",
"antidepressants",
"syncope"
],
"content": "Introduction\n\nThe Coronavirus Disease (COVID-19) Pandemic has caused over five million deaths at the time of this publication worldwide.1 In addition to the direct pathological impact of the virus and its social and economic repercussions, there has been a significant increase in the incidence of depressive and anxiety disorders, especially with lockdown and sanitary curfew taking effect in different countries. Simultaneously, there has been a rise in the prescription of different classes of anti-depressants with numerous side effects often forgotten, sometimes neglected, that may have serious cardiovascular consequences. For instance, these medications may be an occasion to reveal rare latent hereditary conditions, such as long QT syndrome (LQTS). It is a genetically transmitted cardiac condition due to mutations in cardiac ion channels genes, usually revealed by syncope, palpitations, seizures, and sudden cardiac death, in patients with structurally normal heart, with different degrees of QT prolongation and repolarization abnormalities on the surface EKG. Clinical manifestations usually begin in young age with recurrent cardiovascular events.\n\n\nAim\n\nWe aim through this case report to raise the awareness of practitioners on the importance of pretreatment screening of possible signs and symptoms of latent LQTS as well as EKG abnormalities, even in the elderly, in addition to the importance of continuous surveillance under certain types of treatment that could prolong the QT interval.\n\n\nCase report\n\nA 65 year old woman with a personal past medical history of diabetes mellitus, arterial hypertension and dyslipidemia, and with family history of sudden unexplained death, was admitted in Cardiology department with repetitive syncope following the use of Escitalopram, a selective serotonin reuptake inhibitor (SSRI) prescribed for a major depressive disorder, developed in the middle of the first sanitary lockdown announced in the country during the first vague of COVID-19, a few weeks after getting infected with mild symptoms. No chest pain was reported, nor palpitations, nor dyspnea. An EKG was not performed prior to the prescription of this treatment.\n\nClinical examination was normal. EKG findings revealed multiple torsades de pointe with a long QT Interval of 480 ms and negative T waves in inferior and anterior leads. No biological abnormalities were found particularly no electrolyte disorders and normal troponin levels. Trans-thoracic echocardiography showed a preserved ejection fraction with mild mitral regurgitation. Coronary angiography was normal. The initial diagnosis was acquired Long QT syndrome following exposure to Escitalopram and the patient was discharged.\n\nEight months later, she was readmitted with the same symptoms. EKG findings revealed the same abnormalities with long QT interval of 490 ms. All first investigations were normal. No iatrogenic factor was found. Cardiac magnetic resonance imaging was performed in search of signs of arrhythmogenic dysplasia of the right ventricle, showing only one minor criterion: regional right ventricle dyskinesia with an ejection fraction of 43%. Congenital Long QT syndrome was thus suspected, and the patient was put under Nadolol 80 mg per day with regression of symptoms. She also received a list of contraindicated drugs.\n\nEight months later, the patient, still under Nadolol, was readmitted with recurrence of syncope and upper abdominal pain following emotional stress (death of her sister), where multiple torsades de pointe were recorded in the EKG realized in the Emergency department, treated with 2 g intravenous magnesium sulfate followed by continuous intravenous infusion of 6 g/24 h.\n\nAfter the tachycardia was stopped, EKG revealed multiple multiform premature ventricular contractions, sometimes in form of non-sustained ventricular tachycardia, with long QT interval of 638 ms (Figure 1). Biological tests were normal and no iatrogenic factor was found. The patient was admitted in our cardiology department for Dual chamber implantable Cardioverter Defibrillator (ICD) implantation.\n\n\nDiscussion\n\nAnxiety, memory or concentration difficulties, and depressed mood, have increasingly been reported since the outbreak of The virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) - the causative pathogen of the coronavirus disease 2019 (COVID-19) - in Wuhan city, Hubei Province, China on December 8, 2019. These symptoms have long been attributed to the isolation conditions with lockdown and sanitary curfew being more and more indicated, as well as the increase in hospitalization especially among relatives and the fear of death.2 However, since many systemic effects of the virus are progressively being discovered and understood each day, scientists have been conducting various studies in search for a molecular mechanism that may explain the relationship between COVID-19 and the development of depressive conditions. Current findings suggest that the production of high concentrations of pro-inflammatory mediators may alter the permeability of the Blood-brain barrier, activating Toll-like receptors of the microglia and astrocytes, exacerbating neuro-inflammation and altering the homeostasis of the central nervous system, which causes cognitive and mood changes.3\n\nTreatments of depression aim to increase the concentration of certain central neuromodulators incriminated in its emergence, mainly serotonin, noradrenalin, and dopamine. Simultaneously, as the arrhythmogenicity of certain Psychotropic medications, especially neuroleptics, continue to raise concern with more restrictive pretreatment screening recommended with time, studies are continuously examining rates of sudden death among various antidepressants with varying conclusions.4 For instance, in august 2011, the Food and drug administration (FDA) issued a Drug Safety Communication to health care professionals and the public warning them of QT prolongation with citalopram use.5 However, no other guidelines or reviews that state this adverse effect among SSRIs other than citalopram have been issued yet and the risks associated with paroxetine, fluvoxamine, fluoxetine, and sertraline are only limited to case reports. Whereas the FDA alert regarding citalopram specifies that the risk of QT prolongation does not apply to Escitalopram; the S-isomer of citalopram; regardless the dose administrated, the British Medicines and Healthcare Products Regulatory Agency (MHRA), the Arizona Center for Education and Research on Therapeutics (ArizonaCERT), as well as the product package insert itself, approve of the risk of this side effect with Escitalopram, despite controversial studies on the matter.4\n\nConcerning tricyclic antidepressants, the impact on QT interval is well documented. Charlotte van Noord et al. study the impact of psychotropic drugs on QT interval among more than 8000 patients as part of the Rotterdam study, a prospective cohort study ongoing since 1990 in the city of Rotterdam in the Netherlands, found a statistically significant QTc prolongation with maprolitine, amitriptyline, nortriptyline and imipramine. However, this statistical significance was found when calculating the QTc using the Bazett and Fridericia formula, and appears to be lost when adjusting the QT interval to the heart rate.6\n\nLong QT syndromes represent a large variety of conditions with similar manifestations, EKG findings and consequences. They may be due to several acquired causes like electrolyte disturbances and certain drugs/medications, or hereditary, due to mutations in cardiac ion channels genes, mainly K+ channels, sometimes sodium channels, resulting in abnormal myocardial repolarization with prolongation of the action potential.7 Congenital LQTS affects approximately 1:2500 individuals of the general population, with symptoms varying from syncope, palpitations, seizures, to sudden cardiac death, representing a major cause of sudden unexplained death accounting for 20–25% of the cases.7,8 Therapeutic measures have considerably changed the course of the condition, and include mainly Lifestyle modifications, beta- blockers and implantable cardioverter defibrillator (ICD) implantation.\n\nβ-Adrenergic blocking agents, specifically propranolol and nadolol, represent the first-choice therapy in symptomatic or asymptomatic LQTS patients. They have shown excellent results in preventing stress-triggered arrhythmias, reducing the risk by 80% or more, all types of LQTS included, but have low to no effect on sleep-triggered cardiac events. ICD implantation is an important treatment, indicated for patients suffering from LQTS who survived a cardiac arrest, patients who remain symptomatic despite a well-conducted treatment using beta-blockers, or for whom they are contra-indicated. In all cases, precautions including avoiding competitive and exertional sports, exposure to loud noises, the use of medicines that prolong the QT interval and treatment of electrolyte abnormalities that may occur during diarrhea, vomiting or some diets, should be done as much as possible regardless to the symptoms or the type of LQTS.7–10\n\n\nConclusion\n\nPatients undergoing antidepressant treatment should be screened for long QT syndrome regardless to their age, based on family history, search for neglected or forgotten cardiac events and EKG characteristics. Furthermore, even with an initial normal QT interval, Surveillance should remain active during treatment to detect QT prolongation that may be the only expression of the disease. This raises the problem on the modalities of treatment of depressive patients suffering from LQTS and should benefit of standardized guidelines.\n\n\nConsent\n\nWe confirm that we have obtained written consent to use data from the patient included in this study.\n\n\nData availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.",
"appendix": "References\n\nRitchie H, Mathieu E, Rodés-Guirao L, et al.: Coronavirus Pandemic (COVID-19). Our World in Data. 2020 Mar 5 [cited 2022 Apr 4]; 5: 947–953. Publisher Full Text Reference Source\n\nArmitage R, Nellums LB: COVID-19 and the consequences of isolating the elderly. Lancet Public Health. 2020; 5(5): e256. Publisher Full Text\n\nda Silva LL , Silva RO, de Sousa LG , et al.: Is there a common pathophysiological mechanism between COVID-19 and depression?. Acta Neurol. Belg. 2021; 121(5): 1117–1122.\n\nFunk KA, Bostwick JR: A Comparison of the Risk of QT Prolongation Among SSRIs. Ann. Pharmacother. 2013; 47(10): 1330–1341. PubMed Abstract | Publisher Full Text\n\nResearch C for DE and: FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. FDA;2019 Jun 26 [cited 2022 Apr 4].Reference Source\n\nvan Noord C , Straus SMJM, Sturkenboom MCJM, et al.: Psychotropic Drugs Associated With Corrected QT Interval Prolongation. J. Clin. Psychopharmacol. 2009; 29(1): 9–15. Publisher Full Text\n\nSteinberg C: Diagnosis and clinical management of long-QT syndrome. Curr. Opin. Cardiol. 2018; 33(1): 31–41. Publisher Full Text\n\nShah SR, Park K, Alweis R: Long QT Syndrome: A Comprehensive Review of the Literature and Current Evidence. Curr. Probl. Cardiol. 2019; 44(3): 92–106. PubMed Abstract | Publisher Full Text\n\nSchwartz PJ, Crotti L, Insolia R: Long-QT Syndrome: From Genetics to Management. Circ. Arrhythm. Electrophysiol. 2012; 5(4): 868–877. PubMed Abstract | Publisher Full Text\n\nCarter C, Shah M: Long QT syndrome: A therapeutic challenge. Ann. Pediatr. Card. 2008; 1(1): 18–26. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "141646",
"date": "03 Oct 2022",
"name": "Rania Hammami",
"expertise": [
"Reviewer Expertise cardiology"
],
"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 the current manuscript, the authors reported a misdiagnosed latent Long QT syndrome in the setting of COVID 19 infection related depression.\nThey raise the awareness on antidepressant pre-treatment screening in all patient regardless to their age and importance of continuous monitoring under treatments that could prolong the QT interval.\nDiscussion is sufficient with a good review of literature.\nGenerally, the manuscript is well written and the topic is quite interesting for the reader. The paper seems suitable for indexing in its actual version.\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/11-685
|
https://f1000research.com/articles/11-684/v1
|
21 Jun 22
|
{
"type": "Research Article",
"title": "Clinical characteristics and outcomes of hospitalized COVID-19 patients with diabetes mellitus in East Java, Indonesia: A cross-sectional study",
"authors": [
"Erwin Astha Triyono",
"Joni Wahyuhadi",
"Jongky Hendro Prajitno",
"Hermina Novida",
"Nenci Siagian",
"Cupuwatie Cahyani",
"Arinditia Triasti Putri",
"Michael Austin Pradipta Lusida",
"Amal Arifi Hidayat",
"Karisma Septari Idamusaga",
"Nastiti Imana Intansari",
"Jose Asmara",
"Agrasenfani Hadi",
"I Ketut Mega Purnayasa Bandem",
"Joni Wahyuhadi",
"Jongky Hendro Prajitno",
"Hermina Novida",
"Nenci Siagian",
"Cupuwatie Cahyani",
"Arinditia Triasti Putri",
"Michael Austin Pradipta Lusida",
"Amal Arifi Hidayat",
"Karisma Septari Idamusaga",
"Nastiti Imana Intansari",
"Jose Asmara",
"Agrasenfani Hadi",
"I Ketut Mega Purnayasa Bandem"
],
"abstract": "Introduction: Diabetes mellitus has been perceived as the worsening factor for coronavirus disease 2019 (COVID-19), where diabetes mellitus patients with pre-existing inflammatory condition could develop acute respiratory disease syndrome as well as multi-organ dysfunction. Managing diabetes mellitus amidst severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is also a matter of concern as several antidiabetic therapies could affect the progression of COVID-19. This study aimed to provide the clinical characteristics and outcomes of patients with both COVID-19 and diabetes mellitus receiving blood glucose lowering therapies and COVID-19 symptomatic treatments. Methods: This retrospective study was performed on 260 medical records of patients hospitalized between May 2020 to February 2021 in East Java, Indonesia. Patients were confirmed COVID-19 positive based on the results from real time polymerase chain reaction (RT-PCR) using nasal swab samples collected on hospital admission. Data included were demographic characteristics, COVID-19 symptoms, severity of COVID-19, comorbidities (other than diabetes mellitus), fasting blood glucose (FBG), and 2-hours post-prandial blood glucose (2hPBG), and outcomes. Results: Most of the patients had age range of 41–60 years old (76.1%) with more than a half of the subjects (60%) were obese. Patients with uncontrolled diabetes were distributed evenly among the COVID-19 severities (74.3% in asymptomatic group, 73.6% in mild group, and 74.1% in moderate group). There were reductions in FBG and 2hPBG levels measured before (210.75±81.38 and 271.19±100.7 mg/dL, respectively) and after the treatment (181.03±68.9 and 222.01±86.96 mg/dL, respectively). All patients received multivitamin and symptomatic treatment for COVID-19. Oral antidiabetic drug (57.6%) and insulin (28.8%) were administered to lower the blood glucose level of the patients. As many as 96.9% patients survived, while 3.1% died. Conclusion: COVID-19 could affect the blood glucose level, suggesting the importance of antihyperglycemic therapies among patients with both COVID-19 and diabetes mellitus.",
"keywords": [
"ACE2",
"blood glucose",
"diabetes mellitus",
"hyperglycemia",
"SARS-CoV-2"
],
"content": "Introduction\n\nA novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has been responsible to almost 153,000 mortalities in Indonesia as of March 2022 based on Indonesian Government database and has caused many disruptions in the communities.1,2 SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor, in which the enzyme is available in various organs (such as lungs, heart, kidneys, intestines, and so on).3 Diabetes mellitus is a condition responsible for high number of global morbidities, especially due to vascular diseases it induces through chronic inflammation. As any other underlying diseases, diabetes mellitus could contribute to the poor prognosis of COVID-19.4–6 This is ascribed to the role of inflammation in the pathogenesis of severe COVID-19, where chronic inflammation is a common condition in individuals with diabetes mellitus.4 Common comorbidities found in diabetes mellitus, such as obesity and hypertension, have been evidenced to be responsible for acute respiratory disease syndrome (ARDS) as well as multi-organ dysfunction.5\n\nUnderstanding clinical characteristics of diabetes mellitus of patients who are infected with SARS-CoV-2 is important to provide proper management. For example, those with poor glycemic control could have worse viral infections, as proven by SARS and influenza H1N1 cases.4 Respiratory distress induced by the viral infection could lead to the apoptosis of pancreatic beta cells that consequently causes insulin insufficiency.7 Therefore, glucose-lowering therapies should be continued or performed during the COVID-19 management. Nonetheless, clinicians should also consider the pro-inflammatory effect of some antidiabetic drugs which could contribute to the progression of severe COVID-19. Thiazolidinediones (TZDs) is one of the antidiabetic therapies that has been found to induce inflammation by elevating ACE2 and angiotensin 1-7 expressions.8 Moreover, in a meta-analysis of 13 trials, increased risk of developing pneumonia was found in TZD group.9 These explanations suggest that there are strong associations between COVID-19 and both diabetes mellitus and its management.\n\nIn the case of COVID-19, based on a meta-analysis, the number of patients with diabetes mellitus could reach 8% of the total patients.10 However, the prevalence was dramatically higher (36%) in Italian population, where 34% of which died during the treatment.11 In Indonesia itself, the data from Jakarta province (n=20,481) revealed that the prevalence was only 3.4%, but the mortality rate was higher in diabetes mellitus group (21.28%) than that in non-diabetes mellitus group (2.77%).12 By using a larger data set from the Indonesian COVID-19 Task Force, a study revealed that diabetes mellitus as the second most common comorbidity (33.6%) after hypertension (52.1%).13 Taken altogether, it is still uncertain whether the prevalence of diabetes mellitus among COVID-19 patients, especially in Indonesia, is high. Herein, we reported the data from East Java Province, Indonesia, regarding the clinical characteristics of the COVID-19 and diabetes mellitus patients and the treatment they received during the hospitalization. Moreover, we also reported the outcomes from symptomatic management for COVID-19 in combination with diabetes mellitus therapies which could be recommended for hospitals in developing countries with limited medical and financial resources.\n\n\nMethods\n\nThis study was a retrospective study using the medical records of COVID-19 patients with diabetes mellitus who underwent a hospitalization from May 2020 to February 2021 in Indrapura Forefront Hospital Surabaya, East Java Province – Indonesia (n=260). Patients were confirmed COVID-19 positive by real time polymerase chain reaction (RT-PCR) through nasal swab admission. Diabetes mellitus was confirmed by the officially recorded medical history. The obtained data were collected from electronic medical records including demographic, treatments, laboratory results as well as clinical outcomes. All patients with COVID-19 enrolled in this study were diagnosed and managed according to the national guidelines. This study had received ethical approval from the Ethics Committee of the Faculty of Medicine, Airlangga University, Surabaya, Indonesia (registration number: 37/EC/KEPK/FKUA/2021). Since this study collected the data from the available medical records, the Ethics Committee waived of consent from the patients and this allows by the Indonesian law.\n\nData used in this study were collected from electronic medical records. Demographic characteristics of the patients included age, sex, and occupation. Clinical characteristics extracted from the medical records were body mass index (BMI), comorbidities, and COVID-19 symptoms. Comorbidities included hypertension, cardiovascular diseases, chronic kidney diseases, and asthma. As for the COVID-19 symptoms, they were cough, fever, rhinorrhea, anosmia, dyspnea, nausea, and headache. Severity of the COVID-19 was classified following the national guideline; asymptomatic, mild, moderate, and severe. Patients showing no COVID-19 symptoms were assigned to asymptomatic groups. Mild COVID-19 was labeled to those who were presenting mild symptoms (such as fever, cough, and nausea) without dyspnea. Patients having manifestation of pneumonia and oxygen saturation ≥93% fell under moderate category. The patients with severe COVID-19 presented with pneumonia accompanied by one of the followings: respiratory rate > 30 times/minute, severe respiratory distress, or oxygen saturation <93%. Fasting blood glucose (FBG) and 2-hours post-prandial blood glucose level (2hPBG) of the patients were measured during the 24 hours of the admission (first measurement) and the last day prior to hospital discharge (second measurement). Changed values of FBG (∆FBG) and 2hPBG (∆2hPBG) were determined by subtracting the value obtained from the first measurement with that from the second measurement. Herein, we also collected the data pertaining to the previous treatment and antihyperglycemic agents received by the patients including their changes during the hospitalization. Length of stay was assigned as the outcome of the treatment, in addition with the COVID-19 positivity. Patients were grouped based on the RT-PCR results on the hospital discharge; patients recovered with COVID-19 negative result and patients discharged with COVID-19 positive results and required additional self-quarantine or referred to another healthcare facility.\n\nResults of this study were processed on SPSS software version 24 (SPSS Inc., Chicago, IL, USA) (SPSS, RRID:SCR_019096) and expressed as descriptive data. All continuous data were presented in mean ± standard deviation (SD). Meanwhile, categorical data were presented in numbers and percentages.\n\n\nResults\n\nDemographic characteristics of the COVID-19 patients with diabetes mellitus (n=260) have been presented in Table 1. The average patients’ age was 51.33 ± 8.85 years old, predominated by those who were 41–60 years old (76.1%) and followed by 61–80 years old group (13.1%) and 21–40 years old group (10.8%). The numbers of female and male patients were almost similar with percentages of 46.2% and 53.8%, respectively. Most of the patients were self-employed (45%), civil servants (19.2%), and housewives (13.8%).\n\nAs many as 156 (60%) of the total patients were categorized as obese, whereas 55 (21.2%), 36 (13.8%), and 11 (4.2%) others fell into overweight, normal, and underweight categories, respectively (Table 2). Hypertension was observed as the most common comorbidity (47.7%) recorded upon the hospital admission. There were close numbers of patients between those who were having 1 comorbidity (46.2%) and those who were having 2-3 comorbidities (53.8%). From the highest to the lowest frequency, the COVID-19 symptoms presented included cough (47.7%), fever (23.8%), rhinorrhea (15.4%), dyspnea (13.1%), anosmia (11.5%), nausea (10.0%), and headache (9.6%). As many as 65 (25.0%) patients had COVID-19 symptoms other than those aforementioned (Table 2).\n\nAccording to the severity, most of the patients suffered mild COVID-19 (55.4%), followed by asymptomatic (26.9%), and moderate (10.4%). There were only 19 (7.3%) patients who were diagnosed with severe COVID-19. Individuals with asymptomatic, mild, and moderate levels of COVID-19 had similar proportion of patients with uncontrolled diabetes (74.3%, 73.6%, and 74.1%, respectively). Meanwhile, the proportion of patients with uncontrolled diabetes was fewer in severe COVID-19 group (57.9%). There was reduction of FBG and 2hPBG levels observed before (210.75 ± 81.38 and 271.19 ± 100.7 mg/dL, respectively) and after the treatment (181.03 ± 68.9 and 222.01 ± 86.96 mg/dL, respectively). Higher mean reduction value was obtained in ∆2hPBG (49.5 ± 89.6 mg/dL) as compared with that in ∆FBG (33.14 ± 66.0 mg/dL).\n\nTherapies performed on the patients during the hospitalization to manage the COVID-19 symptoms as well as comorbidities have been presented (Figure 1). All patients herein were prescribed with multivitamin. Most of the patients were treated for their COVID-19 symptoms with antitussive/mucolytic agents (47.3%) and antipyretic agents (24.5%), where 31 of the patients (11.9%) received oxygen support. Frequencies of diabetes mellitus treatments received by the patients before and during the hospitalization have been presented (Figure 2). There were 150 (57.6%) and 75 (28.8%) patients who were given oral antidiabetic drug and insulin, respectively, where 22 (8.4%) others received both therapies. None of the patients included in this study were given antivirals.\n\nDPP4 = dipeptidyl peptidase-4; OAD = oral antidiabetic drug; SGLT = sodium-glucose linked transporter; TZD = thiazolidinedione.\n\nClinical outcomes of the COVID-19 patients with diabetes mellitus have been presented in Table 3. A total of 202 (77.7%) patients were treated in the hospital for more than 10 days. There were 22 (8.5%) patients who underwent the hospital treatment within 10 days. Meanwhile, 36 (13.8%) patients had the total hospital stay shorter than 10 days. As for the outcome, most of the patients were discharged from the hospital with COVID-19 negative results (88.1%). Only 2 (0.8%) patients who were discharged from the hospital and required for self-quarantine following the COVID-19 positive results. There were few individuals referred to the other healthcare facility who then survived (8.1%) and died (3.1%).\n\n\nDiscussion\n\nHerein, patients presented with cough and fever as the most common symptoms during the onset of COVID-19.14 These results were similar to that of a previous report investigating 904 patients with COVID-19 and diabetes mellitus in China.15 According to multiple reports, combination of COVID-19 and diabetes is fatal because the diseases could complement one another.5 Most patients in this present study were in age group of 41–60 years old (76.1%) with an average of 51.33 ± 8.85 years old. In combination with pre-existing health conditions, such as obesity (60%) and hypertension (47.7%), COVID-19 patients with diabetes mellitus were at higher risk of poor prognosis.16 Obesity could cause poor outcomes in COVID-19 patients with diabetes mellitus because of its association with chronic inflammation.4 Hypertension could downregulate the expression of ACE2, which subsequently increases levels of angiotensin-2 and decreases angiotensin 1-7, leading to the worsening of ARDS.17 Upon the SARS-CoV-2 infection, ACE2 was also found to have decreased,18 becoming an interplay between COVID-19 and hypertension in causing multiple organ failures.19\n\nDespite the fact that individuals with diabetes mellitus could have higher risk to develop severe COVID-19,5 our current findings suggest that only a small percentage of patients reported developing severe COVID-19 (7.3%). Most of the patients had mild (55.4%) and asymptomatic COVID-19 (26.9%). When glycemic control was observed, the majority of patients in asymptomatic, mild, and moderate COVID-19 groups were predominated by individuals with poor blood glucose control (>70%). It is worth mentioning that hyperglycemia could induce the glycation of ACE2, contributing to increased entry of SARS-COV-2 into the host cells.20 Our obtained data suggest that there is no association between diabetes mellitus or hyperglycemic condition with the severity of COVID-19. During the time frame of this study, people have been already aware of COVID-19 and massive testing was carried out.21 We argue that early detection of SARS-CoV-2 infection could prevent the development and the progression of the disease.\n\nPrior to the hospital admission, more than 80% of the patients have received glucose-lowering agents. However, the FBG and 2hPBG were found to be in high levels during the admission. A study found that COVID-19 could cause a dysregulation of lipid metabolism which eventually contributes to insulin resistance.22 Another study reported that as a result of ACE2 downregulation following the SARS-CoV-2 infection, insulin resistance could be developed owing to the exaggeration of angiotensin II.23 During the treatment in the hospital, there was a significant increase of patients receiving sodium-glucose linked transporter (SGLT) inhibitors and insulin therapies. Following the recovery from COVID-19 symptoms, patients showed a reduction of FBG and 2hPBG levels, though they were still far higher than the normal ranges (80–130 mg/dL and <180 mg/dL for FBG and 2hPBG, respectively).24 Here, we could conclude that it is important to control the blood glucose level and maintain diabetes mellitus treatments during the course of COVID-19, as advised by the international panel of diabetes experts.4 Secondly, our data suggests that COVID-19 could influence the level of the blood glucose in diabetic patients.\n\nIn this study, there was no specific treatment for COVID-19, only vitamins and symptomatic treatment. None of the patients were given antivirals as there is currently no antiviral specified to treat SARS-CoV-2 infection. The majority of patients (97%) survived after the hospital treatment. As the limitation, with a small number of patients included in this study, it is impossible to draw conclusions that have clinical implications. Within the time frame of the observation, COVID-19 variants have emerged,25 which could contribute to the biased results.\n\n\nConclusions\n\nMost of the patients with both COVID-19 and diabetes mellitus were over 50 years old, and hypertension and obesity were commonly found preexisting conditions in them. Blood glucose level could be increased by the COVID-19, suggesting the importance of blood glucose lowering therapies in diabetic patients with COVID-19. Symptomatic management without antiviral and antibiotic therapy followed by blood glucose lowering therapies contribute to the survivability of the patients.\n\n\nData availability\n\nFigshare: ‘Clinical characteristics and outcomes of hospitalized COVID-19 patients with diabetes mellitus in East Java, Indonesia: A cross-sectional study.’ DOI: https://doi.org/10.6084/m9.figshare.19388771.26\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nThis project contains the following underlying data:\n\n- Master Data.xls [Table containing the raw data of the study].\n\n- Master Data.sav [Table containing the raw data of the study and the code book].\n\nFigshare: STROBE checklist for “Clinical characteristics and outcomes of hospitalized COVID-19 patients with diabetes mellitus in East Java, Indonesia: A cross-sectional study” - https://doi.org/10.6084/m9.figshare.19388975.\n\nAll data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgement\n\nThe authors wish to thank the chairman of Indrapura Forefront Hospital, I.D.G. Nalendra Djaya Iswara and Djanuar Firtriadi for their supports throughout the making of this paper.\n\n\nReferences\n\nFahriani M, Anwar S, Yufika A, et al.: Disruption of childhood vaccination during the COVID-19 pandemic in Indonesia. Narra. J. 2021; 1(1): e7. Publisher Full Text\n\nBintari DC, Sudibyo DA, Karimah A: Correlation between depression level and headache severity: A study among medical students during the COVID-19 pandemic. Narra. J. 2021; 1(3): e64. Publisher Full Text\n\nHamming I, Timens W, Bulthuis ML, et al.: Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol. 2004 Jun; 203(2): 631–637. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLim S, Bae JH, Kwon HS, et al.: COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat. Rev. Endocrinol. 2021 Jan; 17(1): 11–30. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLandstra CP, de Koning EJP : COVID-19 and Diabetes: Understanding the Interrelationship and Risks for a Severe Course. Front. Endocrinol. (Lausanne). 2021; 12: 649525. Epub 2021/07/06. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZahra Z, Ramadhani C, Mamfaluti T, et al.: Association between depression and HbA1c levels in the elderly population with type 2 diabetes mellitus during COVID-19 pandemic. Narra. J. 2022; 2(3): e51. Publisher Full Text\n\nWu CT, Lidsky PV, Xiao Y, et al.: SARS-CoV-2 infects human pancreatic beta cells and elicits beta cell impairment. Cell Metab. 2021 Aug 3; 33(8): 1565–1576.e5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nConsoli A, Devangelio E: Thiazolidinediones and inflammation. Lupus. 2005; 14(9): 794–797. PubMed Abstract | Publisher Full Text\n\nSingh S, Loke YK, Furberg CD: Long-term use of thiazolidinediones and the associated risk of pneumonia or lower respiratory tract infection: systematic review and meta-analysis. Thorax. 2011 May; 66(5): 383–388. PubMed Abstract | Publisher Full Text\n\nYang J, Zheng Y, Gou X, et al.: Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int. J. Infect. Dis. 2020 May; 94: 91–95. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOnder G, Rezza G, Brusaferro S: Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020 May 12; 323(18): 1775–1776. PubMed Abstract | Publisher Full Text\n\nHarbuwono DS, Handayani DOTL, Wahyuningsih ES, et al.: Impact of diabetes mellitus on COVID-19 clinical symptoms and mortality: Jakarta’s COVID-19 epidemiological registry. Prim. Care Diabetes. 2022; 16(1): 65–68. PubMed Abstract | Publisher Full Text\n\nKaryono DR, Wicaksana AL: Current prevalence, characteristics, and comorbidities of patients with COVID-19 in Indonesia. J. Community Empowerment Health. 2020; 3(2): 82–89.\n\nLarsen JR, Martin MR, Martin JD, et al.: Modeling the onset of symptoms of COVID-19. Front. Public Health. 2020; 8: 473. Epub 2020/09/10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen Y, Yang D, Cheng B, et al.: Clinical characteristics and outcomes of patients with diabetes and COVID-19 in association with glucose-lowering medication. Diabetes Care. 2020 Jul; 43(7): 1399–1407. PubMed Abstract | Publisher Full Text\n\nZhang W, Du RH, Li B, et al.: Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg. Microbes. Infect. 2020; 9(1): 386–389. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRevercomb L, Hanmandlu A, Wareing N, et al.: Mechanisms of Pulmonary Hypertension in Acute Respiratory Distress Syndrome (ARDS). Front. Mol. Biosci. 2020; 7: 624093. Epub 2021/02/05. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNi W, Yang X, Yang D, et al.: Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit. Care. 2020 Jul 13; 24(1): 422. Epub 2020/07/15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTsioufis C, Dimitriadis K, Tousoulis D: The interplay of hypertension, ACE-2 and SARS-CoV-2: Emerging data as the “Ariadne’s thread” for the “labyrinth” of COVID-19. Hell. J. Cardiol. 2020 Jan - Feb; 61(1): 31–33. PubMed Abstract | Publisher Full Text | Free Full Text\n\nD’Onofrio N, Scisciola L, Sardu C, et al.: Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte. Cardiovasc. Diabetol. 2021 May 7; 20(1): 99. Epub 2021/05/09. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHarapan H, Anwar S, Nainu F, et al.: Perceived Risk of Being Infected With SARS-CoV-2: A Perspective From Indonesia. Disaster Med. Public Health Prep. 2020 Sep; 10: 1–5. Epub 2020/09/11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHe X, Liu C, Peng J, et al.: COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors. Signal Transduct. Target. Ther. 2021 Dec 16; 6(1): 427. Epub 2021/12/18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGovender N, Khaliq OP, Moodley J, et al.: Insulin resistance in COVID-19 and diabetes. Prim. Care Diabetes. 2021 Aug; 15(4): 629–634. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTanaka M: Relationship between fasting and 2-hour postprandial plasma glucose levels and vascular complications in patients with type 2 diabetes mellitus. J. Int. Med. Res. 2012; 40(4): 1295–1303. PubMed Abstract | Publisher Full Text\n\nKorber B, Fischer WM, Gnanakaran S, et al.: Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell. 2020 Aug 20; 182(4): 812–827.e19. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTriyono E: Clinical characteristics and outcomes of hospitalized COVID-19 patients with diabetes mellitus in East Java, Indonesia: A cross-sectional study. Figshare. Journal Contribution. 2022. Publisher Full Text"
}
|
[
{
"id": "141584",
"date": "07 Jul 2022",
"name": "Kurnia Fitri Jamil",
"expertise": [
"Reviewer Expertise Internist",
"Tropical Diseases and Infectious Consultant",
"Professor in Internal 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 suggestions that I can give to the manuscript with the title \"Clinical characteristics and outcomes of hospitalized COVID-19 patients with diabetes mellitus in East Java, Indonesia: A cross-sectional study\", are:\nThere are some grammatical errors in the text. Authors need to re-examine the manuscript.\n\nIn my opinion, some of the information provided in the Introduction section are more suitable to be included in the Discussion instead. A lengthy introduction compared to the Discussion might give the impression that available studies in the literature on this matter is more than adequate in contributing the information without the need of the current study.\n\nI suggest displaying the figures (figures 1 and 2), in a more attractive form.\n\nIn my opinion, data or comparison groups are needed for users of single oral anti-diabetic drugs only, and users of antidiabetic drugs with insulin, especially in obese patients.\n\nIt is better if the authors can provide more updates or additional facts that can be obtained from this study compared to what already been published in the literature, and also presents data from others Asian countries, especially Southeast Asia, as comparison data.\n\nI would advise you in the future to use a prospective research design.\n\nReference: correct or cite in full reference numbers 14, 17, 26.\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": []
},
{
"id": "144898",
"date": "09 Aug 2022",
"name": "Kuldeep Dhama",
"expertise": [
"Reviewer Expertise Infectious diseases",
"emerging pathogens."
],
"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 study “Clinical characteristics and outcomes of hospitalized COVID-19 patients with diabetes mellitus in East Java, Indonesia: A cross-sectional study” described the clinical characteristics and determined the outcomes of 260 COVID-19 patients with comorbid diabetes mellitus who received the blood glucose lowering therapies. The study used the medical reports between May 2020 and February 2021 in Indonesia.\n\nThere are some suggestions / recommendations to improve the quality of the article:\nThe diabetes mellitus diagnosis should be provided in more detail. In the article written: \"Diabetes mellitus was confirmed by the officially recorded medical history.\" This criteria used should be explained.\n\n\"All patients with COVID-19 enrolled in this study were diagnosed and managed according to the national guidelines.\" Please explain the guidelines. Provide the references here.\n\nIt is not clear the outcome groups. It is written: \"Patients were grouped based on the RT-PCR results on the hospital discharge; patients recovered with COVID-19 negative result and patients discharged with COVID-19 positive results and required additional self-quarantine or referred to another healthcare facility\". Please revise this sentence.\n\nPlease provide the reference of how the BMI was classified into obese, overweight, normal, and underweight.\n\nIt is not clear the criteria of \"uncontrolled diabetes\". Please explain in Method and provide the references.\n\nPlease explain how previous treatment of diabetes was assessed in this study.\n\nMinor: Please define \"SARS\" in the second paragraph of Introduction.\n\nSummary Diabetes mellitus is an important comorbidity with COVID-19, and COVID-19 also affects blood glucose levels, hence antihyperglycemic therapies for lowering blood glucose levels and COVID-19 symptomatic treatments are of importance for treating such patients.\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/11-684
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https://f1000research.com/articles/11-683/v1
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21 Jun 22
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{
"type": "Research Article",
"title": "A cross-sectional study of Malaysian low-income drug addict wives: Relationship between family impact, coping and mental wellbeing",
"authors": [
"Haikal Anuar Adnan",
"Zarinah Arshat",
"Nurul Saidatus Shaja’ah Ahmad Shahril",
"Haikal Anuar Adnan",
"Nurul Saidatus Shaja’ah Ahmad Shahril"
],
"abstract": "Background: The involvement of the husbands in the issue of drug addiction has impacted the wives’ livelihoods. Due to drug addiction amongst husbands, the wives experience stress and strain. The Stress Strain Coping Support Model (SSCS) was established to better comprehend how coping influences stress and strain. Thus, the purpose of this study was to determine the relationship between the stress which refers to family impact experienced by the wives of drug addicts, in terms of economic difficulties and marital conflict, and mental wellbeing. Furthermore, this study examines the role of coping as a mediating factor between family impact and mental wellbeing. Methods: This study involved 132 wives of low-income drug addicts in Malaysia, who were selected using a purposive sampling method. Economic Strain Scale (ESS) and Braiker-Kelly Marital Conflict Scale (BKMCS) were used to measure family impact. Coping and Adaptation Processing Scale Short Form (CAPS-SF) and Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS) were used to measure coping and mental wellbeing of the respective respondents. Results: Path analysis using SmartPLS software version 3.3.7 showed that there is a direct association between family impact and coping, and between coping and mental wellbeing. The results also showed that family impact was associated indirectly with mental wellbeing through coping. Conclusions: The findings benefited drug addict wives and practitioners related to this field in terms of enhancing the use of coping mechanisms in managing family impact and improving mental wellbeing, specifically amongst low-income drug addict wives.",
"keywords": [
"marital conflict",
"economic strain",
"stress",
"family impact",
"coping",
"mental wellbeing",
"drug addict wives",
"low income"
],
"content": "Introduction\n\nDrug addiction is a global issue that affects every country, including Malaysia. According to,1 around 275 million people worldwide have engaged in drug misuse, with up to 36 million of those people suffering from substance abuse disorders. Meanwhile the statistics from Ref. 2 shown there were 142,199 drug misuse cases in Malaysia in 2019, compared to a population of approximately 32.4 million to 32.6 million Malaysians. These figures indicate that around one person in every 229 people in Malaysia is a drug user. At least 95.5 percent of drug addicts are men, while women make up only 4.5 percent.\n\nDrug abuse has a harmful impact not only on the addicted person, but also on their family members. A previous study found that people who live with drug abusers are stressed out a lot3 and women who are drug addicts’ wives or mothers face more severe negative consequences than other family members.4–7 For the wives of drug addicts, mental health is a major issue.8–16 Wives of drug addicts also often have problems with their social networks, like not being able to get help from others and not being able to keep in touch with family and friends,10,13,16–18 experiencing violence and persecution,10,12,17,19–21 experiencing issues related to marital conflict8,10,18,22 and experiencing economic strain.12,14–17,22–25 It is predicted that the wives of drug users will have a negative impact on their overall wellbeing as a result of having to deal with a large number of negative situations. However, although the wives of drug addicts face a variety of difficulties in their lives, not everyone wishes for the marriage to end in a dissolution. One of the reasons wives want to stay with their husbands is a sense of obligation to help their husbands deal with addiction and worry about life after separation because they have strong physical and emotional ties with their partners.18 Thus, a study should be conducted to see how they deal with them. This is because living with drug addicts without the right coping skills will have a negative effect on their wellbeing.\n\nThe Stress Strain Coping Support Model is one of the models that focuses on the stress and strain experienced by the wife of a drug addict.26 The main idea behind this model is that people who are stressed because family members have addiction problems can respond to that stress and reduce the amount of strain they experience. The stress that families feel because of their loved one’s addiction problems can come in many different forms, including family problems, life management issues, and concerns about money and resources.27 The concept of stress was measured in this study using the concept of family impact, which includes marital conflict and economic strain. The strain felt by family members of addicts is a direct result of the environment in which they live. According to this model, family member strain refers to the health of family members. These health problems arise as a result of the addict’s immediate family members experiencing behavioural disorders, distinctive changes, and serious challenges. Health issues that affect direct family members can range from physical to psychological. The concept of strain was measured in this study using mental wellbeing. It is assumed that the stress that drug users’ wives suffer contributes to their poor mental wellbeing. The existence of symptoms of either happy feelings or positive functioning in life can be regarded as mental wellbeing.28 The concept of mental wellbeing, according to Ref. 29, encompasses two perspectives: a subjective experience perspective on happiness (affect) and life satisfaction (hedonic perspective); and a positive psychological functioning perspective on good relationships with others and self-realization (eudaimonia perspective).\n\nCoping is an important concept in the SSCS model, which means that family members who face problems in their lives because of the involvement of immediate family members with addiction problems must figure out how to understand and respond to family problems. The way a family understands and responds to the problems they face is a sign of how well they are coping. Coping is a broad term that refers to an effort that entails cognitive and behavioural processes in order to deal with an unpleasant event in life30 while31 define coping as the variety of ways in which individuals think and behave in response to problems and stress. Coping is a fundamental premise of the SSCS model because it assumes that family members are not helpless but capable of improving their own health.32 describe three coping strategies used by family members to deal with their family members’ addictions: putting up, withdrawing, and engaging in active coping, or standing up. Even though the SSCS model is often used to look at the relationships between these variables, some of the model’s flaws have been found. To begin with, it is ineffective at examining how stress affects strain because it uses data from European countries such as Mexico, England, and Italy. However, it excludes data from Asian and Muslim countries.27 Second, the SSCS model focuses on interpersonal coping, and an examination of intrapersonal coping is necessary.11 Third, the role of coping as a moderating or mediating factor in the relationship between stress and strain remains unclear and requires additional research.33\n\nAs a result, this study was conducted to close the gap that currently exists: 1) the respondents in this study are Muslim wives of drug addicts in Malaysia. 2) recognise the scope of coping specifically through concept of coping process introduced by Ref. 32. According to Ref. 32 coping is a behaviour in which the process of adaptation occurs during a stressful situation and is classified into four adaptive modes: physiology, self-concept, role function and interdependence. 3) this study determined the role of coping as a mediating factor in the relationship between family impact and mental wellbeing.\n\nBased on the preceding discussion, the purpose of this study was to identify the association between the family impact experienced by wives of drug addicts in terms of economic strain and marital conflict, as well as their ability to cope and their mental wellbeing. In addition, this study looks into the role of coping as a mediator between family impact and mental wellbeing relationship. The conceptual framework of this study is as shown in Figure 1.\n\n\nLiterature review\n\nMarriage is a natural part of practically everyone’s life. According to a prior study, married individuals had a higher sense of wellbeing than unmarried, divorced, or widowed individuals.34–37 However, the problems that married couples have because their husbands are addicted to drugs have a negative effect on the quality of their marriage.38–40 Numerous previous studies have examined the relationship between family impact such as marital conflict and various aspects of wellbeing. The majority of previous research has established a direct link between marital conflict and aspects of life quality, such as mental health,41–44 subjective wellbeing,45 life satisfaction46 and suicide ideation.44,47 However,48 study contradicts the findings of other researchers, as he discovered that marital conflict has no significant relationship with psychological wellbeing.\n\nAdditionally, previous researchers examined the relationship between the variables in this study. A study conducted by Refs. 3, 49 discovered a significant relationship between family impact, coping, and strain among addicts’ family members. In a study of infertile couples,50 found that marital satisfaction, marital communication, conflict resolution style, and coping were all linked to each other.33 conducted a study to examine the association between family impact and involvement coping, tolerance coping, depression, anxiety, stress, and quality of life, and discovered a strong relationship between these variables. Withdrawal coping, on the other hand, has not been linked to stress. The study by Ref. 51 found that higher levels of burden showed significant associations with greater psychological distress and more use of coping, whereas greater acceptance of the situation showed an association with less psychological distress.\n\nNumerous researchers have examined the capacity for coping as a mediator between the relationship between family impact and strain. However, the methods used by previous researchers to assess family impact and strain are clearly different. Study conducted by5 examined stress and strain using the Family Member Impact Scale and the Symptom Rating Scale. This study discovered that involvement and tolerant coping both function as partial mediators of family stress and strain.49 Horváth and Urbán used the Zarit burden interview - short version to assess stress, while Beck hopelessness scale - short version was used to assess strain. The study’s findings indicate that tolerant inactive is a significant mediator of the stress-strain relationship. Coping’s ability to act as a mediator is also supported by Ref. 3 findings that coping acts as a significant mediator between stress and strain. However, the findings of33 study differ from those of other researchers. Significant mediators for stress-strain relationships were not found to be coping.\n\nAccording to the literature review above, the following gaps were discovered during the analysis of this previous study; First, the findings regarding the relationship between the variables are varied. Second, this previous study did not include wives of drug addicts in its sample selection; rather, it included a variety of samples, including wives of alcohol addicts,52 married couples in general,46 working wives,43,47 and patients diagnosed with depression.42 Third, studies involving Malaysian participants are still lacking. Fourth,49 suggest that the measurement tools used to measure variables should also be different. Thus, a study focusing on the wives of low-income drug addicts in Malaysia is necessary to examine the relationship between family impact, coping, and mental wellbeing in the Malaysian context.\n\n\nMethods\n\nThe quantitative approach was chosen because the primary goal of this study was to determine the relationship between the study variables, which were family impact, coping, and mental wellbeing. Using SMART-PLS software, this study also aimed to test the role of coping factors in mediating the relationship between family impact and mental wellbeing. This study employs a cross-sectional design and a questionnaire-based survey method. Furthermore, this is a correlation-shaped study. A correlation-shaped study, according to Refs. 53, 54, is a study that involves data collection to determine whether there is a relationship between the variables measured and to investigate the extent to which the impact of various variables is independent of the dependent variable. The independent variable in this study is family impact, and the dependent variable is mental wellbeing. While coping is a mediator variable between the family impact and mental wellbeing relationship. Because the cross-sectional study is prone to common method bias, common method variance analysis was conducted using Harman’s Single Component approach to address this issue.\n\nPurposive sampling method was used to select the study sample, which included 132 wives of drug addicts. The subject criteria for this study were low-income wives, i.e., household income less than RM4,849 (USD1,103.56); wife of a drug addict who is in a drug rehabilitation centre; not involved in drugs; Malay; and has at least one child between the ages of 17 and under living together. Wives who do not meet all of the criteria will be left out of the study sampling process. The total amount of wives’ information received from drug addicts in NARC was 296. However, after screening, a total of 45 wives did not meet the following criteria, and a total of 85 individuals could not be reached through the use of phone calls or questionnaire posting. In addition, 32 wives declined to participate in the study, bringing the total number of respondents to 132. The GPower software was used to figure out the sample size for the study. The minimal sample size necessary for this investigation is 107 respondents at the 95 percent confidence level (α=0.05) due to the inclusion of two independent variables. The participants in the study ranged in age from 18 to 53 years old, with an average age of 37.92. This study also considered the following socio-demographic characteristics for wives of drug addicts: education level; marriage duration; and number of children younger than 17 years old.\n\nPermission was granted to use a questionnaire created by the original author. All the measurement instruments used in the study were created in English. Due to the fact that one of the selection criteria for study respondents is Malay, all measurement tools have been translated into Malay using back-to-back translation by professional translators from the Centre for the Advancement of Language Competence (CALC), Universiti Putra Malaysia. The instruments used in this study were checked for content validity by two experts in developmental psychology and human development before they were used in the study.\n\nThe Economic Strain Scale (ESS)55 and the Braiker-Kelly Marital Conflict Scale (BKMCS)56 were used to assess family impact in this study. The ESS has four items and is scored on four Likert scales that range from “strongly disagree” to “strongly agree.” The ESS is made up of four items. Cronbach’s alpha ESS values for looking at internal consistency by earlier researchers were 0.8657 and 0.81.55 In this study, the internal consistency coefficient for ESS was 0.83 for the pilot study and 0.89 for the actual study. The BKMCS has five items and is measured on a type 5 Likert scale, with items 1 to 3 ranging from “not very much” to “very much,” and items 4 and 5 ranging from “not very often” to “very often”. The value of Cronbach’s alpha BKMC to see the reliability by previous researchers is in the range of 0.69 to 0.89.58–67 In this study, the internal consistency coefficient for ESS was 0.84 for the pilot study and 0.90 for the actual study.\n\nThe Coping and Adaptation Processing Scale Short Form (CAPS-SF)68 was used to assess coping in this study. CAPS-SF has 15 items and is scored on a four-point Likert scale ranging from “never” to “always”. In this measurement tool, each item is a short statement about how people react to things that are stressful or hard in their lives. Cronbach’s alpha CAPS-SF values used by earlier researchers to figure out how consistent they were ranged from 0.74 to 0.87.68–72 In the current study, the internal consistency coefficient for CAPS-SF was 0.75 for the pilot study and 0.79 for the actual study.\n\nMental wellbeing in this study was measured using the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), developed by a group of researchers from the Universities of Warwick and Edinburgh.29 SWEMWBS contains 7 items and uses a 5-likert scale that ranges from “none of the time” to “all of the time”. The study conducted by73 found that SWEMWBS has a good reliability of 0.83. In the current study, the internal consistency coefficient for SWEMWBS is 0.68 for the pilot study and 0.83 for the actual study.\n\nThe study protocol was approved by the Ethics Committee for Research Involving Human Subjects, Universiti Putra Malaysia (Reference No.: JKEUPM-2020-406). A set of questionnaires was used to collect the data in this study. Prior to the study, permission was granted to the Malaysian National Anti-Drug Agency (AADK) to gather information about the wife from drug addicts (clients) at the Narcotics Addiction Rehabilitation Centre (PUSPEN) involved. Their wives were called by phone to ask for their permission to take part in the study after the drug addicts’ wives’ information was found. Next, the questionnaire was then distributed through WhatsApp in the form of a “Google form”. Written informed consent was also given to the respondents along with the distributed questionnaires. A pilot study, including 30 women of drug addicts whose husbands were seeking treatment at PUSPEN Batu Kurau and PUSPEN Perlop, Perak, was conducted prior to the main study.\n\n\nAnalysis and findings\n\nPrior to the other analytic tests, a Common Method Variance analysis was performed. According to Harman’s Single Component approach,74 the first factor explained the greatest proportion of the overall variance, at 20.203% (i.e., less than 50%). The findings of the factor analysis revealed that no general factors appeared, indicating that common technique bias was not significant in this data set.75\n\nThe demographic features listed in the present study include age, education level, marriage duration, and the number of children younger than 17 years old as depicted in Table 1. Referring to Table 1, majority of the respondents fell under the age group of 31 to 40 years old (i.e., 44.7%); 28.0% of the respondents were 21 to 30 years old; 24.2% of the respondents were 41 to 50 years old; 2.3% were more than 51 years old; and only 0.8% were younger than 20 years old. In terms of education level, the majority of respondents (48.5%) complete upper secondary school; 26.5% complete junior secondary school; 9.8% complete a diploma; 7.6% complete a certificate; and 4.5 percent complete a bachelor’s degree; 2.3% have completed primary school; and only 0.8 % have completed a master’s degree. For the duration of marriage, the majority of the respondents fell under the duration group of 6 to 10 years (i.e., 27.3%); 22.7% of the respondents were in the group of less than five years and the 11 to 15 years group; 12.9% were in the 16 to 20 years group; 7.6% 21 to 25 years; 6.1% 26 to 30 years; and only 0.8% fell under the group of more than 31 years.\n\nThe partial least squares (PLS) technique, a variance-based structural equation modelling (SEM) was used in this investigation through the SmartPLS programme.76 The higher-order construct using disjoint two-stage approach was analysed.77 PLS–SEM was chosen due to the fact that it imposes fewer constraints on population size, scale measurement, and dispersion.78 The model’s constructs were all measured reflectively.\n\nSince this study used a disjoint two-stage approach, the steps that were proposed by Ref. 77 were implemented. The first step is to see if the lower order components fulfil the criteria that have been outlined, such as internal consistency, convergent validity, and discriminant validity. Then, the latent variable scores of the lower order components will be incorporated into the model in the second stage. After that, higher-order components that met the requirements (internal consistency, convergent validity, and discriminant validity) were determined.\n\nTable 2 shows the outcomes of the measurement model evaluation. Numerous items discovered in the coping construct (i.e., CAPS_1, CAPS_5, CAPS_8, CAPS_9, CAPS_12, CAPS_13, CAPS_14) were discarded due to their extremely low loading values as suggested by Ref. 79. After removing several coping items, all constructs in this study met the standards, with the exception of several coping constructs. The accepted values suggested by Ref. 79 is the loading values exceeding 0.708, composite reliability (CR) values exceeding 0.7, and AVEs (Average Variance Exact) values over 0.5. For coping constructs, several items were retained even though the loading value fell below the 0.708 requirement. The reason for this is that indicators that have loadings between 0.40 and 0.708 should only be removed if they make internal consistency, reliability, or convergent validity better above the threshold value.79 As a result, all constructs fulfilled the criterion for reliability and convergent validity. Discriminant validity in this study was analysed using HTMT technique.80 As shown in Table 3, all discriminant values exceeded the HTMT threshold value. 90. As a result, discriminant validity was proven.\n\nFor the higher-order components as shown in Table 4 and Table 5, all the values of loadings, CR, AVE and HTMT accomplish the recommended value suggested by.79 Therefore, structural model measurements can be carried out.\n\nThe structural model assessment was conducted after the construct validity and reliability were verified by the measurement model assessment. The R-Square, or coefficient of determination, structure path co-efficient (B value), T-statistic value, and P-values are critical Smart PLS indicators used for determining results with a 95 percent confidence interval for the purpose of analysis interpretation. The R-square might be high (>0.75), moderate (>0.50), or low (>0.25). The Inner VIF is used to investigate the issue of collinearity. VIF readings are significantly lower than the 3.33 criterion,82 as shown in Table 6. As a result, there is no issue with multicollinearity in this model.\n\nPath-coefficient for structural model was assessed to examine the objective of this study using the bootstrap re-sampling technique (5000 re-sample). The R2 value was 0.138, which suggested that 13.8% of the variance mental wellbeing may be explained by coping and family impact. As shown in Table 7, family impact was found to be positively related (β=0.247, p<0.05) to coping. Coping was also found to be positively related (β=0.380, p<0.05) to mental wellbeing. However, results show that family impact not related (β=0.380, p>0.05) to mental wellbeing.\n\n* t>1.96.\n\n** p<0.05.\n\nThe mediation effect was further investigated using bootstrapping approaches. Table 8 shows the results of the study on the influence of family impact on mental wellbeing through coping, which showed that the impact of mediation was statistically significant (β=0.094, p<0.05).\n\n** p<0.05.\n\n\nDiscussion\n\nThe purpose of this study was to see if there was an association between family impact, coping, and mental wellbeing. The goal of the study is also to figure out what role coping plays in the relationship between family impact and mental wellbeing for low-income drug addicts’ wives. The findings of the study indicate that family impact has a significant association with coping. Coping was also discovered to have a substantial association with mental wellbeing. The family impact, on the other hand, was found to have an indirect association with mental wellbeing through coping rather than a direct relationship. This means that coping plays a big part in the way that family impact and mental wellbeing are linked.\n\nThe findings of this study are consistent with those of52 who discovered that there is no direct association between family impact (marital conflict) and mental wellbeing. Furthermore, the findings of this study contradict those of41–47 who discovered a direct association between these two factors. This study’s findings are also in line with those of,3,33,49,50 who found that family impact on coping and coping with strain are linked. The ability of coping as a significant mediator in the relationship between family impact and mental wellbeing is also in line with the findings of,3,5,49 while contradicting the findings of.33 It is critical to highlight, however, that prior research employed a different concept to measure stress and strain. The current study measured the impact on families in terms of marital conflict and economic strain. Current research also uses a variety of different tools to assess coping and strain, making it impossible to duplicate previous findings.\n\nThe dimensions found in the coping construct developed by83 must be examined to explain how coping acts as a mediator factor in the relationship between family impact and mental well-being. The primary dimensions found in the coping and adaptation processing construct are resourceful and focused. When dealing with stress, being resourceful and focused reflects behaviours that make use of oneself and one’s resources. It focuses on increasing input, being creative, and achieving results. The second dimension, physical and fixed, emphasises physical reactions as well as the input phase of dealing with situations. Alert processing is a coping and adaptation dimension that employs behaviours that represent both the personal and physical self. It focuses on all three processing levels: input, central, and output. As a coping dimension, systematic processing describes personal and physical strategies used to take in situations and methodically handle them. Finally, knowing and relating is a dimension in which strategies reflect the use of oneself and others, memory, and imagination. It can be shown that, despite the fact that people are exposed to numerous sorts of stress, they can achieve mental well-being by improving their coping processes in these four aspects.\n\n\nLimitations and future research directions\n\nThere are some limitations to this study. For starters, the study’s cross-sectional design made it difficult for researchers to make causal findings. Second, the study’s sample size was tiny, and it was chosen using a nonprobability sampling method. As a result, generalisations are impossible. Third, one crucial feature of the SSCS model, namely social support, was not included in this study. As a result, there was no way to determine the role of social support in examining the relationship between familial impact and mental wellbeing. However, there are some positive aspects to this research. First, the findings of this study can give drug users’ wives an early sense of the necessity of building coping and mental wellbeing when dealing with family stress. Second, the findings of this study can be used by professionals in this field to help the wives of drug addicts improve their mental health. Therefore, there are some recommendations for future studies. First, a longitudinal study can be done to look at the causal relationship. Second, sample selection should be done using a probability sampling method to enable the results of the study to be generalized. Third, using the same concepts and measurements as in this study, the role of social support in the relationship between family impact and mental wellbeing needs to be explored.\n\n\nData availability\n\nFigshare. Malaysian Low Income Drug Addict Wives: Family Impact, Coping and Mental Wellbeing. DOI: https://doi.org/10.6084/m9.figshare.19865176.v3.84\n\nThis project contains the following underlying data:\n\n‐ This data was used for an article published titled “A cross-sectional study of Malaysian low-income drug addict wives: Relationship between family impact, coping and mental wellbeing”\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nCredit authorship contribution statement\n\nHaikal Anuar Adnan: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Resources, Software, Writing – Original Draft Preparation, Writing – Review & Editing. Zarinah Arshat: Funding acquisition, Supervision, Methodology, Conceptualization, Writing – review & editing. Nurul Saidatus Shaja’ah Ahmad Shahril: Data Curation, Project Administration, Writing – review & editing.",
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}
|
[
{
"id": "184781",
"date": "03 Aug 2023",
"name": "Marek A. Motyka",
"expertise": [
"Reviewer Expertise drug addiction",
"youth",
"sociology",
"harm reduction",
"psychoactive substances",
"social work"
],
"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 manuscript.\nThe topics are clearly presented and the paper cites current literature. One of the items cited is from the late 1970s, but it relates to a research tool, so in my opinion this citation is entirely appropriate.\nI find the study design adequate. The topics taken up by the Authors are definitely relevant, especially since the use of psychoactive drugs in the world is becoming more and more popular, and already the topics concerning the coping of wives (but also husbands) of people suffering from addiction is a research area that requires research or additions to existing studies.\nI consider the reviewed manuscript to be a solid scientific work. In my opinion, the methodology and sampling methodologies were clearly described, and I have nothing to complain about here. I also have no objections to the results, however, in my opinion, the \"Discussion\" section should be expanded to subject the results obtained to comparisons with studies conducted in other countries and with people of a different religion. In my opinion, the comparisons could prove interesting.\nSufficient details of the methods and analyses used in the study are presented. The study can be replicated by other authors. The statistical analysis and its interpretation are appropriate.\nSource data are available. The study can be fully replicated.\nYes, as I indicated above I would expand the \"Discussion\" section, which is why I indicated that the conclusions are partially supported by the results. What I pay attention to with purposive sampling is the need to point out that the results obtained occur in this particular study population. It should be emphasized that the results cannot be generalized because repetition by others of such studies can lead to falsification of the science. Fortunately, the Authors did so in the section \"limitations and future research directions.\" This section confirms that the Authors are aware of the limitations of the research. I found it to be very well written, including directions for future research initiatives.\nAlso:\nI suggest instead of the term \"drug addicts\" to use the term \"people suffering from addiction\" because it is a stigma-free term. It is also important to be aware that stigma affects not only drug users but also their loved ones. Addiction has long been recognized as a disease, and the way it is written can affect how we think and how we view this not insignificant part of society (both those who use drugs and their families). I believe that, if only for this reason, some of the terms in this manuscript should be changed, especially \"wives of drug addicts.\"\nRecommended research articles to develop the discussion section:\nHomish, G. G., Leonard, K. E., & Cornelius, J. R. (2008). Illicit drug use and marital satisfaction. Addictive behaviors, 33(2), 279–291. Joolaee, S., Fereidooni, Z., Seyed Fatemi, N., Meshkibaf, M. H., & Mirlashari, J. (2014). Exploring needs and expectations of spouses of addicted men in Iran: a qualitative study. Global journal of health science, 6(5), 132–141. Maghsoudi, J., Alavi, M., Sabzi, Z., & Mancheri, H. (2019). Experienced Psychosocial Problems of Women with Spouses of Substance Abusers: A Qualitative Study. Open access Macedonian journal of medical sciences, 7(21), 3584–3591. Panaghi, L., Ahmadabadi, Z., Khosravi, N., Sadeghi, M. S., & Madanipour, A. (2016). Living with Addicted Men and Codependency: The Moderating Effect of Personality Traits. Addiction & health, 8(2), 98–106.\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": []
},
{
"id": "284913",
"date": "08 Jun 2024",
"name": "Mohd Radzi Tarmizi A Halim",
"expertise": [
"Reviewer Expertise suicide",
"adolescent mental 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\nIntroduction:\nCultural Context:\nGap: Existing research primarily uses data from European countries, lacking insights from Asian and Muslim contexts. Recommendation: Emphasize how studying Muslim wives of drug addicts in Malaysia will provide unique cultural insights and contribute to a more diverse understanding of the issue. Interpersonal vs. Intrapersonal Coping:\nGap: The SSCS model focuses on interpersonal coping, whereas intrapersonal coping needs more exploration. Recommendation: Clearly state the importance of exploring intrapersonal coping mechanisms and how this study aims to fill that gap by examining specific coping processes. Role of Coping as a Mediator:\nGap: The role of coping as a mediating factor between stress (family impact) and strain (mental wellbeing) remains unclear. Recommendation: Highlight how this study will investigate the mediating role of coping, adding a new dimension to existing literature.\nRecommendations for Improvement:\nClarification of Research Gap:\nMake the research gap more explicit at the beginning of the introduction. Clearly state what is missing in the current literature and how this study aims to address those gaps. Literature Citations:\nEnsure all statistics and claims are properly cited. For instance, the first statistic about global drug misuse needs a reference.\nModel Explanation:\nWhile the SSCS model is introduced and explained, ensure that the connection between the model and the specific objectives of this study is clearly articulated. This will help readers understand why this model is relevant and how it will be used in the study.\nIssue: While back-to-back translation was used, cultural adaptation of the instruments should be ensured.\nRecommendation: Report any steps taken to culturally adapt the instruments to the Malaysian context, beyond mere translation, to ensure that the questions are culturally relevant and comprehensible to the participants.\nIssue: The procedure for contacting participants and obtaining consent is described, but it could be clearer. Recommendation: Provide more details on how confidentiality and anonymity were maintained, and how participants were supported throughout the study to ensure their comfort and safety.\nResult:\nReporting of Non-Significant Relationships:\nIssue: The finding that family impact is not directly related to mental wellbeing (β=0.380, p>0.05) should be discussed in more detail. Recommendation: Provide a thorough interpretation of why this relationship might be non-significant and how it aligns or contrasts with existing literature.\nMeasurement Model for Lower-Order Components:\nIssue: Several coping items were retained despite low loading values. Recommendation: Explain the rationale for retaining these items in more detail, including any theoretical justification or impact on the overall model.\nDiscriminant Validity:\nIssue: While the HTMT criterion was met, it’s important to discuss the practical implications of these findings. Recommendation: Briefly explain the importance of discriminant validity in the context of this study and how it supports the reliability of the constructs.\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": []
}
] | 1
|
https://f1000research.com/articles/11-683
|
https://f1000research.com/articles/11-682/v1
|
21 Jun 22
|
{
"type": "Research Article",
"title": "Remote sensing and machine learning for yield prediction of lowland paddy crops",
"authors": [
"Lala Septem Riza",
"Afina Hadaina Yudianita",
"Eki Nugraha",
"Lili Somantri",
"Imas Sukaesih Sitanggang",
"Khyrina Airin Fariza Abu Samah",
"Shah Nazir",
"Afina Hadaina Yudianita",
"Eki Nugraha",
"Lili Somantri",
"Imas Sukaesih Sitanggang",
"Khyrina Airin Fariza Abu Samah",
"Shah Nazir"
],
"abstract": "Background: Paddy is one of the crops with the largest production worldwide, after corn and wheat. In Indonesia, paddy crops play a role as one of the main boosters of national economic growth based on their contribution to Indonesia's gross domestic product (GDP). Therefore, it is imperative to do research aimed at predicting the yield of paddy crops. Methods: This research exploits the technology of remote sensing and machine learning methods (i.e. Gradient Boosting Regressor) to predict the yield of lowland paddy crops. Remote sensing with a Landsat 8 satellite was used to obtain the input data in the form of the vegetation index (i.e. NDVI) value, surface temperature, and total pixels of the observed area. Afterward, the input data was arranged into training data by combining paddy yield data and the paddy harvest period. Results: The obtained training data was modelled to predict the yield of paddy crops using a Gradient Boosting Regressor. The results obtained from experiments conducted in Bandung, Indonesia, showed the scenario with the best parameter combination is an estimator of 2000, a learning rate of 0.001, minimum samples split of 2, and a maximum depth of 4, which has RMSE of 9766.72. Conclusions: This research succeeded in designing a computational model to predict the yield of lowland paddy crops by involving remote sensing and Gradient Boosting Regressor.",
"keywords": [
"remote sensing",
"NDVI",
"Landsat 8 satellite",
"Gradient Boosting Regressor",
"machine learning",
"agriculture",
"crop yield",
"Geographic information systems (GIS)"
],
"content": "Introduction\n\nAgriculture is a term that is used broadly to describe the various aspects and origin of plant and animal foodstuffs and plant growth. This term exists in a framework consisting of three environments, i.e. the biophysical environment, socio-political environment, and economic and technological environment (Yunlong and Smit, 1994). Agriculture plays an important role in a country, both developed and developing countries. However, not all countries have the same agricultural technology, and the differences are seen in developed and developing countries. For example, according to the United States Department of Agriculture, corn yields in the US in 2020 were around 4.3 t/ha. Meanwhile, corn yields in Ethiopia have only increased from 0.9 to 3.5 t/ha since 1960 (Petersen, 2018). In Indonesia, corn yields increased by about 4.52% from 2014 to 2015 (BPS-Statistics Indonesia, 2015). Farmers in developing countries don’t have financial and educational resources available compared to farmers in developed countries, in general. Therefore, yield prediction in developing countries is imperative as the crop yields are more susceptible to droughts and other dangerous issues (Petersen, 2018).\n\nThere are a few agriculture-related research methods that have been used to predict crop yields. Petersen (2018) predicted the yield of corn, soybean, and sorghum –two to four months before its harvest time. He utilized remote sensing technology from MODIS satellite imagery to obtain the relationship between a few vegetation indices and crop yields using a machine learning method (i.e. multivariate regression). Shiu and Chuang (2019) predicted the yield of rice paddy using SPOT-7 satellite imagery to obtain the vegetation index of rice paddy. They used a machine learning method (i.e. support vector regression) to predict the yield of rice paddy. Pantazi et al. (2016) also used a machine learning method (i.e. artificial neural network) and satellite imagery to predict the yield of wheat. Ahmad et al. (2010) estimated soil moisture using TRRM satellite imagery using machine learning methods (i.e. support vector machine and artificial neural network). Maas (1988), utilized Landsat satellite imagery to estimate the yield of sorghum grain.\n\nThe following research shows that crop vegetation indices have a linear relationship with yield. These researchers used machine learning methods called linear regression. Bartlett et al. (1989) utilized satellite imagery to estimate solar radiation and carbon dioxide exchange of a grass canopy. Du Plessis (1999) obtained a linear relationship between a vegetation index and rainfall using NOAA AVHRR satellite imagery. Irsan et al. (2019) predicted corn yield from a few types of vegetation indices extracted from Sentinel 2A satellite imagery. Zhang et al. (2019) predicted rice paddy productivity from a vegetation index extracted from Landsat 8 satellite imagery and Sari et al. (2013) utilized Landsat 8 satellite imagery to estimate rice paddy yield.\n\nCurrently, remote sensing technology can be used to detect the phenomenon of food plant vegetation because satellite imagery is easily accessible to anyone (Maas, 1988). Useful data such as vegetation indices and the earth’s surface temperature can be generated from satellite imagery. Vegetation indices describe how healthy the crop is (Zhang et al., 2019), and surface temperature is one of the external factors that affect crop growth (Bartlett et al., 1989). This research utilized Landsat 8 satellite imagery to obtain a vegetation index (i.e. NDVI) and surface temperature. The relationship between remote sensing data and crop yields was obtained using Gradient Boosting Regressor machine learning methods as Gradient Boosting Regressor is a linear method that uses boosting techniques to produce a powerful and robust model in predicting crop yields (Friedman, 2001).\n\n\nMethods\n\nIn this research, we built a computational model in several stages to predict the yield of lowland paddy crops, which is illustrated in Figure 1. This workflow diagram is described in detail in the following section.\n\nThe first stage in the workflow diagram was remote sensing data gathering and processing using ENVI remote sensing software version 5.3 or other software that has the ability to process Landsat 8 satellite data, such as the open-access alternatives: QGIS (RRID:SCR_018507), Orfeo ToolBox, and GRASS GIS, which can provide equivalent functions. Landsat 8 (L8) satellite imagery were downloaded from the EarthExplorer website with the following criteria: 1) dataset using satellite Landsat 8 OLI/TIRS C1 Level-1; 2) coordinate on Bandung (Lat: -6.9455, Lon: 107.6138); 3) date from May 21, 2013 to December 5, 2015. The specific location that was studied included four different sub-districts in Bandung, which were Cikancung, Ciparay, Majalaya, and Paseh. Landsat 8 (L8) satellite imagery data was processed to obtain the Normalized Difference Vegetation Index (NDVI) and the earth’s surface temperature value. Lowland rice yield data was obtained from reports published by BPS-Statistics Indonesia of Bandung (see Data availability).\n\nAn Indonesian topographical map was used to determine the boundaries of the paddy field area in Bandung. This can be downloaded through the Indonesia Geospatial Portal. All relevant data can be found in Riza et al. (2022a).\n\nBefore the satellite imagery data was processed, the data was resized and divided into subsets so that the data size was not too large. Large data sizes caused slow processing and consumed a lot of storage on the computer. Resizing and sub setting of data were performed using Region of Interest (ROI) files created based on the topographical map. Satellite imagery data was cleaned if pixels were considered as clouds and shadows using the Quality channel in L8 imagery. The pixels that were considered disrupting were greater than 2800 on the Quality L8 band (Landsat Missions | U.S. Geological Survey (usgs.gov)). The pixels that were processed were pixels with a value below 2800. Satellite imagery data needed to be calibrated and corrected so that the image was free from disturbances caused by the atmosphere. An example of this is the absorption of red light by ozone gas in the atmosphere that distorts the reflectance value in the imagery so that it cannot represent the phenomenon of vegetation (Tanre et al., 1992).\n\nNot every pixel in the imagery could be involved in the process of obtaining NDVI and the earth’s surface temperature value due to the disturbances of the clouds and shadows. Clouds and shadows cause variations in the number of pixels in various locations every day. Therefore, sampling techniques were required. The number of samples can be obtained by the Cochran formula (Cochran, 2007) as follows:\n\nWhere:\n\nn0= number of samples\n\nZ= Z value depends on confidence level\n\np= percentage picking a choice (0.5 used for sample size needed)\n\ne= confidence interval\n\nFor a finite population number, there are adjustments to the formula as follows:\n\nWhere:\n\nn= number of samples\n\nN= number of populations\n\nThe sampling technique used was stratified random sampling that is already available in the ENVI software. ENVI will automatically stratum the total pixels and determine which pixels will be sampled.\n\nThe NDVI vegetation index is a transformation of the combination of the red and near-infrared band (Ikasari et al., 2016) that is formulated as follows:\n\nWhere:\n\nNIR = reflectance of near infrared\n\nRed = reflectance of red\n\nNear infrared contributes to light reflected by leaf structures, while the red band contributes to light absorbed by leaf structures (Jensen, 1996). In ENVI, NDVI calculations can be obtained automatically based on the type of satellite imagery using the NDVI tool.\n\nThe temperature of the earth’s surface is one of the external factors that can affect the growth of paddy crops. Cold temperatures will cause rice seedlings to grow slower than warmer temperatures (Vergara, 1992). In the L8 imagery, the temperature of the earth’s surface can be obtained by performing a brightness temperature calibration on the thermal band of the satellite imagery.\n\nThe second stage in the workflow is the data pre-processing stage. This stage consists of three stages, which are the one-hot encoding process, adjusting the array of input data, and data standardization. One-hot encoding is an approach to convert categorical features into a more suitable format as input in a machine learning model (Zheng and Casari, 2018). Gradient Boosting Regressor model as a regression model requires input data in numerical form. The categorical features of remote sensing data used in this study were the harvest period or harvest sub round features.\n\nAdjusting the input data array converts the data from Pandas DataFrame into a NumPy array. This conversion is intended so that the data can be processed using various mathematical operation functions available in the NumPy library version 1.19.1 (RRID:SCR_008633) in Python (Python Programming Language, RRID:SCR_008394).\n\nData standardization aims to change each feature in the input data so it has the same value range, which is between 0 and 1. With standardization, each feature has the same opportunity to influence the computational model. Standardization was done using Z-score standardization (Zill et al., 2011) which is formulated as follows:\n\nWhere:\n\nz= standardized samples\n\nx= samples\n\nμ= mean of samples\n\nThe Gradient Boosting algorithm uses the boosting technique to the Gradient Descent method, both for classification and regression problems (Bishop, 2006). The model built with the Gradient Boosting Regressor algorithm (Friedman, 2001) can be seen in Table 1.\n\nThe training process begins with an input consisting of input data and loss function derivatives. The loss function that can be used in this model is the square loss function (Friedman, 2001) which is formulated as follows:\n\nConstant value initialization is done by calculating the optimal value that can minimize the loss function. After the constant value has been initialized, calculate the rim (pseudo residual) for each row of data. Once rim is obtained, create a Regression Tree that predicts rim. Calculate γjm (output value) for each leaf in the Regression Tree. Update the output function Fmx every time the Regression Tree is built.\n\nThe Regression Tree (James et al., 2013) model as a weak learner in Gradient Boosting Regression can be seen from the algorithm in Table 2.\n\nThe metric used for the data splitting process in the Regression Tree used in this study is variance reduction (Loh, 2011), which involves the variance value for the total data and two splitting results based on the threshold. Model testing is done by tracing each Regression Tree that has been created. The learning rate is involved in the leaf value obtained in each tree to obtain the prediction result. The prediction results at the testing stage are the output of this research workflow. The source code of this computational model can be found in Riza et al. (2022b).\n\n\nExperimental study\n\nWe conducted experiments based on the workflow diagram that was built. This section describes the experimental study in constructing a computational model to predict the yield of lowland paddy crops.\n\nFigure 2 is a map of Bandung as a research area and the zone of interest is in white. Pixels that interfered with image data (clouds and shadows) were removed using the Quality channel on the Landsat 8 (L8) image data. The Region of Interest (ROI) was created based on disrupting pixels. Figure 3 shows the ROI file of the cloud pixels and its shadow in green.\n\nAfter the imagery data was clean of disturbing pixels, the next step was to perform radiometric calibration and atmospheric correction. The differences in the image before and after being calibrated and corrected are not visible to the human eye. Nevertheless, the difference can be seen in the reflectance value that changes at each stage as in Table 3. After the data was calibrated and corrected, the pixel value was adjusted to obtain the accurate reflectance value by dividing 10,000 by all pixels.\n\nThe sampling process on ENVI was done using the Generate Random Sample Tool Using Ground Truth ROIs by creating an ROI file specifically for the paddy crop area to be sampled. ROI files can be created in the Band Threshold to ROI tool by marking all pixels. After the ROI file was available, the next step was to determine the required sample size using the Cochran formula (Cochran, 2007). The sampling technique used in ENVI was stratified random sampling. Figure 4 shows the appearance of the sample pixel dots on the L8 imagery data.\n\nNDVI vegetation index was calculated after the imagery data was calibrated and corrected. Calculations were done by the NDVI tool in ENVI by selecting the type of OLI sensor (Landsat 8) with the red channel band (number four) and the near-infrared channel band (number five). Figure 5 is the difference in the appearance of the image before and after being transformed into NDVI. The image on the right is the result of adding a colour slice so that the difference between high NDVI values and low NDVI values can be seen properly.\n\nAfter the NDVI was obtained within a predetermined period, the next step was to plot the NDVI value into a parabolic graph. It represents one harvest season for the paddy crop. The NDVI value taken from one harvest season is the biggest.\n\nThe temperature of the earth’s surface can be obtained by performing the Brightness Temperature radiometric calibration on the thermal band of the L8 satellite imagery. After calibration, the pixel values in the image represent Kelvin units. To convert Kelvin to Celsius, we can use the Band Math tool and enter the formula below:\n\nAfter the satellite imagery data was processed using ENVI, the next step was to combine the remote sensing data with the yield of lowland paddy crop reported by BPS-Statistics Indonesia. The report from BPS-Statistics Indonesia is a report for each district per year in one file. The data available in each report file is the yield of lowland paddy crop and the area of planted paddy crop for each village. Data downloaded from BPS-Statistics Indonesia is required to obtain the percentage of paddy crop yield in each period.\n\nTable 4 is the input data as a result of combining remote sensing data with lowland paddy yield reported for several different harvest seasons. The NDVI column, total pixels, and temperature are data obtained from remote sensing data collection, while the period column, planted area, and paddy crop yield are data obtained from the BPS-Statistics Indonesia.\n\nThe total pixels (population) are included in Table 4, but the sample size is not. This is because the total pixels already represent the sample value itself. In Table 4 there is also a period column that indicates the period or sub round for taking NDVI values. P1 indicates January – April, P2 indicates May – August, and P3 indicates September – October. This period column represents the date of the image data used to obtain the NDVI value. The column for the planted area is in hectares and the column for production is in quintal units, obtained from reports on food crop yield in Bandung.\n\nRemote sensing and loss function data were required to build the computational model. In doing so, the model also required several parameters, e.g. the number of Regression Trees to be created (estimators), learning rate, the maximum value of the Regression Tree depth (maximum depth), and the minimum amount of data obtained by a node in the Regression Tree for data splitting.\n\nScenarios were performed to compare the accuracy and speed of computations. In the scenario of comparing the accuracy, the root mean squared error (RMSE) was used to evaluate the experimental results. RMSE is the standard deviation for the residual or the resulting predictive error. RMSE shows how much residual dispersion occurs (Barnston, 1992). RMSE is formulated as follows:\n\nWhere:\n\nf= index of predicted data\n\no= index of observed data\n\nzfi= predicted data\n\nzfo= observed data\n\nN= number of samples\n\nAll parameters may influence the RMSE value in the scenario of comparing the accuracy. The larger the size and number of regression trees built, the greater the opportunity for the model to study the data. The greater the learning rate value used, the shrinkage of the predicted results for each Regression Tree will also be greater. Therefore, all of the parameters in the RMSE value testing scenario were involved.\n\nThe computation speed of the Gradient Boosting Regressor algorithm depends on the number and size of the Regression Tree being built. Therefore, the computation speed can be influenced by several parameters, e.g. estimators, minimum samples split, and maximum depth.\n\n\nResults and discussion\n\nThe output of the program is a file in the comma-separated value (CSV) format which contains data on the prediction of lowland paddy crop yield based on the data input at the beginning of the program. Table 5 is the output of the program displayed in the CSV file with an estimator parameter of 2000, a learning rate of 0,001, a maximum depth tree of 4, and minimum samples split of 2. The scatter plot and RMSE value are shown in Figure 6.\n\nTo test the effect of parameters on the RMSE value, a model was built based on several scenarios. The scenario in Table 6 is a combination of various parameters. The parameter estimator was tested at the values of 200, 500, 1000, 1500, and 2000. The learning rate parameters were tested at values of 0.1, 0.01, and 0.001. The minimum parameters of samples split were tested at values 2 and 10. The maximum depth parameters were tested at values 4, 6, and 8.\n\nFrom Table 6, we could see that the value of scenario number 75 produces the best RMSE value. From this experiment, the scenario with the best parameter combination is an estimator of 2000, a learning rate of 0.001, minimum samples split of 2, and a maximum depth of 4.\n\nFigure 7 contains graphs showing the average RMSE value for each estimator, learning rate, minimum samples split, and maximum depth. The RMSE value tends to be constant in the estimator with a value of 1000 to 2000. The value of the estimator with the best RMSE was 1500. The value of the learning rate with the best RMSE was 0.01. The minimum value of samples split with the best RMSE was 2. The maximum depth value with the best RMSE was 4.\n\nAccording to the experiments, it can be seen that the developed application was able to predict crop yields with reasonable accuracy. This result can be compared with research conducted by Petersen (2018). This study predicts production 2-4 months before harvest time based on MODIS satellite imagery. The model was created and validated using satellite imagery of Illinois, United States of America by calculating the linear fit between production and vegetation index. The model is made by looking for a linear regression relationship between the average vegetation index and the vegetation index anomaly with production. The model made is able to predict the production of corn, soybeans, and sorghum, respectively, the median error is 5.7%, 5.8%, and 22%. The next model is applied in several countries on the African continent by making predictions for 2-4 months before harvest time. The result is that the prediction has an error of less than 5%.\n\n\nConclusions\n\nAfter performing some experiments, we came to several conclusions that were in line with the research objectives as follows: (i) This research succeeded in conducting a regression analysis between the NDVI vegetation index and rice production using the Gradient Boosting Regressor algorithm with five main stages. The stages are remote sensing data collecting, data preprocessing, data standardization, model training, and model testing; (ii) This research succeeded in designing a computational model to identify the yield of lowland paddy crops based on the regression relationship in the Gradient Boosting Regressor algorithm between the vegetation index and its yield; and (iii) This study conducted 90 experiments divided into two main scenarios. From the results and discussions, the authors conclude that the estimator parameters, learning rate, minimum samples split, and maximum depth used have different contributions to the accuracy and speed of computation in the computational model to predict the yield of lowland paddy crops.\n\n\nData availability\n\nOpen Science Framework: Underlying data for ‘Remote sensing and machine learning for yield prediction of lowland paddy crops’, https://doi.org/10.17605/OSF.IO/P9CY3 (Riza et al., 2022a).\n\nThis project contains the following underlying data:\n\n• Data NDVI with ENVI.zip: Data containing vegetation index (i.e., NDVI)\n\n• Data Portal Geospasial Indonesia.zip: The Indonesian topographical map was used to determine the boundaries of the paddy field area in Bandung.\n\n• Dataset Final.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\nLandsat 8 (L8) satellite imagery were downloaded from the EarthExplorer website. An Indonesian topographical map was used to determine the boundaries of the paddy field area in Bandung and is available from the Indonesia Geospatial Portal). Lowland rice yield data was obtained from reports published by BPS-Statistics Indonesia of Bandung:\n\n• Ciparay City: Ciparay, 2013; Ciparay, 2014; Ciparay, 2015.\n\n• Cikancung City:: Cikancung, 2013; Cikancung, 2014; Cikancung, 2015.\n\n• Paseh City: Paseh, 2013; Paseh, 2014; Paseh, 2015.\n\n• Majalaya City: Majalaya, 2013; Majalaya, 2014.\n\n\nSoftware availability\n\nSource code available from: https://github.com/lala-s-riza/Remote-sensing-and-machine-learning-for-yield-prediction-of-lowland-paddy-crops.git\n\nArchived source code at time of publication: https://doi.org/10.5281/zenodo.6459715 (Riza et al., 2022b).\n\nLicense: GNU General Public License (GPL-2.0)",
"appendix": "References\n\nAhmad S, Kalra A, Stephen H: Estimating soil moisture using remote sensing data: A machine learning approach. Adv. Water Resour. 2010; 33(1): 69–80. Publisher Full Text\n\nAriza AA: Machine Learning and Big Data Techniques for Satellite-Based Rice Phenology Monitoring. The University of Manchester;2019.\n\nBarnston AG: Correspondence among the correlation, RMSE, and Heidke forecast verification measures; refinement of the Heidke score. Weather Forecast. 1992; 7(4): 699–709. Publisher Full Text\n\nBartlett DS, Whiting GJ, Hartman JM: Use of vegetation indices to estimate indices to estimate intercepted solar radiation and net carbon dioxide exchange of a grass canopy. Remote Sens. Environ. 1989; 30(2): 115–128. Publisher Full Text\n\nBishop CM: Pattern recognition and machine learning. Springer;2006.\n\nBPS-Statistics Indonesia: Production of Food Crops. Jakarta:CV. Tapasuma Ratu Agung;2015.\n\nCochran WG: Sampling techniques. John Wiley & Sons;2007.\n\nDu Plessis WP: Linear regression relationships between NDVI, vegetation and rainfall in Etosha National Park, Namibia. J. Arid Environ. 1999; 42(4): 235–260. Publisher Full Text\n\nFriedman JH: Greedy function approximation: a gradient boosting machine. Ann. Stat. 2001; 29: 1189–1232.\n\nIkasari IH, Ayumi V, Fanany MI, et al.: Multiple regularizations deep learning for paddy growth stages classification from LANDSAT-8. International Conference on Advanced Computer Science and Information Systems (ICACSIS). 2016; 2016: 512–517.\n\nIrsan LM, Murti SH, Widayani P: Estimasi Produksi Jagung (Zea Mays L.) dengan Menggunakan Citra Sentinel 2A Di Sebagian Wilayah Kabupaten Jeneponto Provinsi Sulawesi Selatan. Jurnal Teknosains. 2019; 8(2): 93–104. Publisher Full Text\n\nJames G, Witten D, Hastie T, et al.: An introduction to statistical learning. New York:springer;2013.\n\nJensen JR: Introductory digital image processing: a remote sensing perspective. Prentice-Hall Inc.;1996.\n\nLoh WY: Classification and regression trees. Wiley Interdisciplinary Reviews: Data Mining and Knowledge Discovery;2011.\n\nMaas SJ: Using satellite data to improve model estimates of crop yield. Agron. J. 1988; 80(4): 655–662. Publisher Full Text\n\nPantazi XE, Moshou D, Alexandridis T, et al.: Wheat yield prediction using machine learning and advanced sensing techniques. Comput. Electron. Agric. 2016; 121: 57–65. Publisher Full Text\n\nPetersen LK: Real-time prediction of crop yields from MODIS relative vegetation health: A continent-wide analysis of Africa. Remote Sens. 2018; 10(11): 1–31.\n\nRiza LS, Yudianita AH, Nugraha E, et al.: Remote sensing and machine learning for yield prediction of lowland paddy crops. Dataset. 2022a. Publisher Full Text\n\nRiza LS, Yudianita AH, Nugraha E, et al.: Remote sensing and machine learning for yield prediction of lowland paddy crops. Source Code.2022b. Publisher Full Text\n\nSari DK, Ismullah IH, Sulasdi WN, et al.: Estimation of water consumption of lowland rice in tropical area based on heterogeneous cropping calendar using remote sensing technology. Procedia Environ. Sci. 2013; 17: 298–307. Publisher Full Text\n\nShiu YS, Chuang YC: Yield Estimation of Paddy Rice Based on Satellite Imagery: Comparison of Global and Local Regression Models. Remote Sens. 2019; 11(2): 1–18.\n\nTanre D, Holben BN, Kaufman YJ: Atmospheric correction algorithm for NOAA-AVHRR products: theory and application. IEEE Trans. Geosci. Remote Sens. 1992; 30(2): 231–248. Publisher Full Text\n\nVergara BS: A farmer’s primer on growing rice. Int. Rice Res. Inst.;1992.\n\nYunlong C, Smit B: Sustainability in agriculture: a general review. Agric. Ecosyst. Environ. 1994; 49(3): 299–307. Publisher Full Text\n\nZhang K, Ge X, Shen P, et al.: Predicting rice grain yield based on dynamic changes in vegetation indexes during early to mid-growth stages. Remote Sens. 2019; 11(4): 1–24.\n\nZheng A, Casari A: Feature engineering for machine learning: principles and techniques for data scientists. O’Reilly Media, Inc.;2018.\n\nZill D, Wright WS, Cullen MR: Advanced engineering mathematics. Jones & Bartlett Learning;2011."
}
|
[
{
"id": "143635",
"date": "01 Aug 2022",
"name": "Daniel Peralta",
"expertise": [
"Reviewer Expertise Machine learning"
],
"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 analyzes a dataset of satellite images to predict the yield of crop production. This research is valuable and sound. Furthermore, the dataset used has been published by the authors, which adds a lot of value to this research . Therefore, I recommend to Approve this article.\nI have a few comments about aspects that could be further clarified:\nI miss a paragraph in the introduction that would summarize the contribution of this paper.\n\nFurther details about data pre-processing e.g. the data was resized and divided into subsets, but what size? How many subsets?\n\nInclude a table with the input features that were used.\n\nHow was the data split into training/test?\n\nInclude a table comparing the results of this paper with those in the literature.\n\nThere is one point in Figure 6 that appears to be badly predicted, while the rest of the dataset has very good predictions. I wonder if it would be possible to explain why?\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": []
},
{
"id": "253183",
"date": "02 Apr 2024",
"name": "Attila Nagy",
"expertise": [
"Reviewer Expertise remote sensing",
"GIS",
"yield prediction",
"water 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\nThe manuscript describes the use of one type of ML for paddy crop yield prediction using Landsat 8. The topic has broad importance, but due to several issues and discrepancies I recommend to reject this manuscript. My detailed reasons: Overall, it looks more a thesis than a scientific paper, sounds like a student book in some parts, especially in the introduction (e.g. first rows of the introduction. Linear regression itself is no ML method. English has to be improved significantly, it is hard to read the text fluently Lack of references throughout the text, and not using the original references (e.g. in the case of NDVI). There is not a word about the aim, motivation of the study in the introduction. There is no explanation why Landsat 8 (out of several potentials) was used. There is no explanation why only one ML model (out of several potentials) was used, and why that specific one. The method requires restructuring and rewriting in general. Study site should be the first chapter, then data, data collection, followed by method. Listed several softwares, but not stating (or stating later) which one is used in data processing. But the used algorithms, GIS solutions are not adequately explained. Figure 2 is not informative. Interpretation of the data is not acceptable. Authors should discuss about the results (it is totally missing and inadequate) There are only set of tables, with no proper assessments. It is not enough to state “shown in figure x”.\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? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-682
|
https://f1000research.com/articles/11-681/v1
|
21 Jun 22
|
{
"type": "Case Report",
"title": "Case Report: Adrenocortical carcinoma in an adult male with hypokalemic hypertensive: Report of a rare case in Nepal",
"authors": [
"Indu K.C.",
"Md Zafar Alam",
"Nabin Simkhada",
"Rabindra Jang Rayamajhi",
"Rizwan Alam",
"Indu K.C.",
"Md Zafar Alam",
"Rabindra Jang Rayamajhi",
"Rizwan Alam"
],
"abstract": "Adrenocortical carcinoma (ACC), with an incidence of 2-5 percent, is an uncommon source of unilateral adrenal mass and hyperaldosteronism. In Nepal, there is no literature on this uncommon adrenocortical cancer. A forty-year-old Nepalese army regular with resistant hypertension on various antihypertensive medicines presenting with a background of considerable weight loss decreased appetite, and repeated episodes of vomiting were described. His blood tests revealed hypokalemia and a high aldosterone/renin ratio. A tumor in the left adrenal gland was discovered during an abdominal CECT scan. He was operated on for left adrenal incidentaloma and the procedure was uneventful. We recommend clinicians suspect hyperaldosteronism in an adult with refractory hypertension and hypokalemia.",
"keywords": [
"Adrenocortical carcinoma",
"Hypokalemia",
"Hypertension",
"Aldosterone/Renin ratio"
],
"content": "Introduction\n\nAdrenocortical Carcinoma is a cancerous tumor. In 25% of seemingly spontaneous ACC, somatic mutations in the tumor-suppressor gene TP53 are detected. The Li-Fraumeni syndrome is linked to a variety of solid organ malignancies, including ACC, and is caused by TP53 mutations in the sperm. Variations in the Wnt/-catenin system and the insulin-like growth factor 2 (IGF2) clusters are also evident in ACC; IGF2 amplification is reported in 90% of the cases.1\n\nAround 60% of ACCs seem to be adequately secretive in character to manifest as a clinical condition of hormone overabundance.2 Cushing's syndrome (45 percent) or a combination Cushing's and virilization syndrome (oversaturation of both glucocorticoids and androgens) are the most common symptoms in adults with hormone-secreting ACCs (25 percent).3 Cushing's syndrome, virilization, hypertension, hypokalemia, abdominal discomfort, and vomiting are examples of clinical symptoms linked with hormone imbalances. Diagnosis is done by radio-imaging (CECT abdomen and pelvis) or MRI abdomen and pelvis for the size of tumor and local invasion as well as metastasis. The size of the adrenal tumor at its widest point indicates if it is cancerous. Adenomas of the adrenal glands typically have a dimension smaller than 4 cm. When an ACC is detected, it usually has a diameter of larger than 4cm. FNAC cannot differentiate benign from malignant.\n\nWe should always rule out pheochromocytoma by using serum and urinary catecholamines before surgery and biopsy. For adrenocortical cancer (ACC) stages I-III, total surgical removal is the only possible therapeutic strategy.4\n\n\nCase presentation\n\nA 40-year-old serving soldier who has history of hypertension presented initially with decrease in appetite and loss of weight of around two to three kg over 30 days. He had been vomiting for two days about 3-4 episodes, non-projectile, and non-bloody. He also complained of generalized weakness which started after vomiting, however, he could walk and perform daily activities. He had a past history of hypertensive urgency with multiple hospital admissions. Fundoscopy revealed grade III hypertensive retinopathy changes.\n\nHis blood pressure was 170/100 mmHg and pulse rate was 56 beats per minute and it was regular, respiratory rate was 18/min, saturation was 96% at room air. His systemic examinations were unremarkable. His initial hematological, renal, and liver function parameters were in the normal range but serum sodium was 146mmol/l and potassium was 2.0 mmol/l. His USG imaging and X-ray chest were unremarkable.\n\nHe was admitted for evaluation of hypokalemia. His antihypertensive medications were optimized and started on Losartan, amlodipine, Beta-blocker, alpha-blocker, and diuretics (spironolactone). An extensive evaluation was done to find the cause of hypokalemia. His 24 hours urine analysis revealed potassium 18 meq/dl, osmolality 300 mosm/l, and sodium 54 mmol/dl. His serum calcium was 8.4 mg/dl and Phosphate 4.1mg/dl. The transtubular potassium gradient (TTKG) was 15 (which was 3.5 times normal levels). His aldosterone renin ratio was increased and urinary catecholamines levels were normal as shown in Table 1 and Table 2.\n\nThe contrast-enhanced CT abdomen showed well defined, smooth marinated, heterogeneously enhancing mass lesion in the left adrenal gland measuring 5.1 cm × 5.9 cm × 5.7 cm with few tiny calcifications in the lesion. The coronal section of the contrast-enhanced CT abdomen is shown in Figure 1 and the transverse section is shown in Figure 2. An overnight dexamethasone suppression test was done, and serum cortisol at 8 AM was 10.61 nmol/l. Color Doppler of bilateral renal arteries showed normal flow. The thyroid function test was normal. ABG showed metabolic alkalosis. Potassium was supplemented from the IV route as well as the oral route and six times hourly potassium was monitored but even after continuous supplement, there was no rise in serum potassium level. Intravenous fluid was given as ½ NS to avoid hypernatremia and serum sodium was monitored along with potassium.\n\nArrow showing heterogeneously enhancing mass lesion of 5.1 cm × 5.9 cm × 5.7 cm with few tiny calcification in the lesion.\n\nArrow showing well defined, smooth marinated, heterogeneously enhancing mass lesion.\n\nAfter confirming our diagnosis of left adrenal incidentaloma with hyperaldosteronism, He underwent laparoscopic unilateral adrenalectomy (left) and intraoperative and postoperative periods were uneventful. The Operated left adrenal mass is shown in Figure 3. Histopathological examination showed atypical cells showing marked pleomorphism exhibiting small cells to giant bizarre-shaped cells indicating adrenocortical carcinoma. The capsular invasion was seen. The immunohistochemistry report is shown in Table 3.\n\nShowing operated left adrenal mass with capsulated, smooth surface, prominent surface vascular marking with maximum diameter of 7 cm and weight of 195 g.\n\nHe was discharged with antihypertensive medications (calcium channel blocker and alpha-blocker), analgesics, oral antibiotics planned to tapper off antihypertensive every 2-3 weekly as there is a high chance of normalization of blood pressure.\n\n\nDiscussion\n\nAdrenocortical carcinoma (ACC) is an uncommon adrenal neoplasm that is regarded as a highly malignant tumor. There are two variants of tumor functional and nonfunctional, functional variants are more common than nonfunctional. Females are generally more affected than males (3:1).5 There are Bimodal peaks, appearing first in the forties and fifties and a second one appearing in their first decade. The prognosis for elderly men is poorer, although younger people with ACC have a better prognosis than adults. The majority of tumors are sporadic in nature.6\n\nACC can be functional with a sole endocrine condition like Cushing's, or it can be a mixed syndrome with virilization. Virilization is common in youngsters and is associated with a 70% likelihood of cancer. The majority of patients with ACC, particularly those with the non-functional form, have advanced illness with several abdominal or extra-abdominal metastatic masses.7 As a result, tumor diagnosis at an early clinical stage is critical for curative excision.\n\nAdrenal adenoma, Pheochromocytoma, and renal cell cancer are our differential diagnoses. The weight of the tumor distinguishes adenoma from carcinoma; if it weighs more than 95 g, it is typically malignant. Radio-imaging also distinguishes adenoma and carcinoma by the size, carcinoma is usually greater than 4 cm. The tumor in contrast-enhanced CT appeared heterogeneously enhanced mass lesion in the left adrenal gland measuring 5.1 cm × 5.9 cm × 5.7 cm with few tiny calcifications in the lesion. We have Weiss criteria for assessing the prognosis in ACC. If the mitotic figures are less than 20 per HPF, the tumor is low grade; if the mitotic figures are more than 20 per HPF, the tumor is high grade. The tumor is malignant if three of the nine criteria are met.8 We have calculated Weiss criteria which were 4 points out of a total of 9 points (Capsular infiltration, Necrosis, Clear cells <25%, and Mitosis 10/50 HPF).\n\nENSAT (European Network for the Study of Adrenal Tumors) and the TNM staging system are used for the tumor staging as shown in Table 4. We classified this tumor as stage II (T1N0M0).\n\nThe most important differential diagnosis is Pheochromocytoma. A classic zellballen pattern characterized by elevated catecholamine levels in serum and urine, as well as positive for immunohistochemical markers such as chromogranin, will suggest a Pheochromocytoma. Whereas, inhibin, calretinin, and Melan-A, are positive in ACC. Cushing syndrome was ruled by a dexamethasone suppression test. Normal serum cortisol and high aldosterone level ruled out Liddle syndrome, a Syndrome of apparent mineralocorticoid excess (SAME). High serum level of renin is seen in renal artery stenosis (RAS), renin secreting tumor (RST), and malignant hypertension.\n\n\nConclusion\n\nWe reported a very rare case of adrenocortical carcinoma in an adult who presented with hypokalemia and hypertension and he is living a disease-free postoperative period. Because their prognoses are distinct, it's critical to distinguish it from an adrenocortical adenoma with biochemical, imaging, and histological markers. The most common therapy is surgical resection.\n\n\nData availability\n\nNo extra source data is necessary because all of the data that underpins the results is included in the article.\n\n\nConsent\n\nThe patient's written informed consent for publishing the clinical details and/or clinical photos was acquired.",
"appendix": "References\n\nKasper DL, Fauci AS, Hauser SL, et al.: Harrison's principles of internal medicine. New York:McGraw Hill Education;19th edition.2015.\n\nNg L, Libertino JM: Adrenocortical carcinoma: diagnosis, evaluation and treatment. J. Urol. 2003 Jan; 169(1): 5–11. PubMed Abstract | Publisher Full Text\n\nWajchenberg BL, Albergaria Pereira MA, Medonca BB, et al.: Adrenocortical carcinoma: clinical and laboratory observations. Cancer. 2000 Feb 15; 88(4): 711–736. PubMed Abstract | Publisher Full Text\n\nAllolio B, Hahner S, Weismann D, et al.: Management of adrenocortical carcinoma. Clin. Endocrinol. 2004 Mar; 60(3): 273–287. PubMed Abstract | Publisher Full Text\n\nBellantone R, Ferrante A, Boscherini M, et al.: Role of reoperation in recurrence of adrenal cortical carcinoma: Results from 188 cases collected in the Italian National Registry for Adrenal Cortical Carcinoma. Surgery. 1997; 122: 1212–1218. PubMed Abstract | Publisher Full Text PubMedGoogle Scholar\n\nKock CA, Paka K, Chrousos GP: Molecular pathogenesis of hereditary and sporadic adrenocortical and adrenomedullary tumors. J. Clin. Endocrinol. Metab. 2002; 87: 5367–5384. Publisher Full Text PubMedGoogle Scholar\n\nLatronico AC, Pinto EM, Domenice S, et al.: An inherited mutation outside the highly DNA-binding domain of the P53 tumor suppressor protein in children and adults with sporadic adrenocortical tumors. J. Clin. Endocrinol. Metab. 2001; 86: 4970–4973. PubMed Abstract | Publisher Full Text PubMedGoogle Scholar\n\nJain M, Kapoor S, Mishra A, et al.: Weiss criteria in large adrenocortical tumors: A validation study. Indian J. Pathol. Microbiol. 2010; 53: 222–226. PubMed Abstract | Publisher Full Text PubMedGoogle Scholar"
}
|
[
{
"id": "164069",
"date": "06 Mar 2023",
"name": "Apar Kishor Ganti",
"expertise": [
"Reviewer Expertise Medical oncology"
],
"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 well written case report of a case of adrenal cortical carcinoma.\n\nComments:\n\nTable 4 does not add much to the article and may be omitted.\n\nIt would be helpful if the authors presented the histopathology of the resected specimen as a figure.\n\nThe discussion can be enhanced by a discussion of the management of adrenocortical carcinoma.\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/11-681
|
https://f1000research.com/articles/10-859/v1
|
26 Aug 21
|
{
"type": "Opinion Article",
"title": "Introducing R as a smart version of calculators enables beginners to explore it on their own",
"authors": [
"Krishna Choudhary",
"Alexander R. Pico"
],
"abstract": "Rapid technological advances in the past decades have enabled molecular biologists to generate large-scale and complex data with affordable resource investments, or obtain such data from public repositories. Yet, many graduate students, postdoctoral scholars, and senior researchers in the biosciences find themselves ill-equipped to analyze large-scale data. Global surveys have revealed that active researchers prefer short training workshops to fill their skill gaps. In this article, we focus on the challenge of delivering a short data analysis workshop to absolute beginners in computer programming. We propose that introducing R or other programming languages for data analysis as smart versions of calculators can help lower the communication barrier with absolute beginners. We describe this comparison with a few analogies and hope that other instructors will find them useful. We utilized these in our four-hour long training workshops involving participatory live coding, which we delivered in person and via videoconferencing. Anecdotal evidence suggests that our exposition made R programming seem easy and enabled beginners to explore it on their own.",
"keywords": [
"students",
"data science training",
"learn programming",
"R"
],
"content": "Introduction\n\n\n\n“The stepwise introduction into R from the simple explanation of the system as a calculator was very approachable and I felt that I was able to move into the system with a lot less trepidation and more curiosity to explore on my own.”— Anonymous feedback from an attendee of our R workshop in March, 2019\n\nThe surveys that we referred to above have identified challenges in delivering high-value content in short workshops.9 They revealed that most postgraduate learners seek training when they have already collected data for their ongoing projects. Attwood et al. noted that the retention of skills acquired to perform specific analyses at a particular time tends to be poor. Hence, trainees often need to attend the same workshops again. Furthermore, if the trainees cannot apply their newly acquired skills to performing research in their own time in the weeks and months since training, their confidence may be diminished. Yet, we found that most introductory workshops for absolute beginners in, say, R or Python programming often focus on basic operations such as reading data, basic arithmetic, subsetting tables, basic plots, etc. In our assessment, these operations are essential to analysis and should be a part of an introductory workshop, but they alone do not generate a feeling of confidence that one could derive practical utility from one short workshop. Given that some of the trainees may not have time nor motivation for a second workshop, it is important that the very first workshop yield real value for the trainees, and more importantly, equip them with a mental framework to explore computational analysis on their own. Additionally, postgraduate learners may possess higher levels of experience in research and teaching than undergraduates, which makes them harder to persuade. For example, if undergraduates are told in a class that they need to work with a programming language to analyze data instead of Excel spreadsheets, they may commit to learning without asking why. In our experience, postgraduate learners may not vocally demand a justification, but at the same time, they may not be sold on programming without one. Even for undergraduates, this seems to be an unreasonable expectation. Effective workshop designs are required to train the postgraduate learners and can enhance the quality and quantity of biological research.9,13\n\nIn this article, we propose that introducing programming languages for data analysis as smart versions of calculators can enhance the effectiveness of introductory workshops. Given the popularity of R language for statistical analysis of biological data, we use R programming as a means to elucidate our proposition. Our view is that for data analysis, R is an evolved form of traditional calculators in the same way that smartphones are an evolved form of earlier-generation mobile phones. The evolution in both cases has been made possible by adoption of a new and intuitive way to interface with technology—touch interface over buttons in the case of smartphones, and programmable functions over push-button functions of calculators in the case of R programming. In training someone on how to use a smartphone, even if the instructor were to show how to use a specific application on a smartphone, the transferable learning for independent smartphone use by the trainee would be an implicit understanding of the interface itself and not the knowledge of options in menus of the application that they might have been shown. Similarly, in an introductory R workshop, if absolute beginners are given an understanding of design elements of R using a set of commands as a means but not the primary intended deliverable, it might enable them to independently explore R in the weeks after the workshops. In our workshops, this design philosophy has helped us dispel prior beliefs of absolute beginners that they need to memorize a large number of R commands before deriving practical use from R. Instead, with a knowledge of how to interface with the “smart” version of calculators that we view R to be, intuition underlying its design, and hands-on analysis experience that we were able to integrate in one 4-hour-long workshop, we found that our trainees felt equipped to explore R for their practical research purposes. Further, we could provide trainees with specific use cases that they could make a part of their research process. Our approach helped us shift the focus to statistical concepts in later hands-on analysis workshops while the code took a backseat. Here, we utilize analogies with commonly known objects to explain the intuition underlying key elements of the R system and present it as a “smart” version of calculators. Additionally, we propose how trainees could begin to integrate R in their research after an introductory workshop. Volunteered comments in anonymous feedback forms (collected online) and direct feedback from researchers in our local community indicated that for at least some of the trainees, our workshops achieved the desired outcome of enabling beginners to explore R on their own. Borrowing ideas from our work might yield beneficial outcomes in other introductory workshops on programmatic data analysis.\n\n\nHighlighting the analogy between calculators and R can enhance the effectiveness of training\n\nSince the dawn of civilization, humanity has needed to perform quantitative analyses for a variety of purposes, e.g. commerce and taxation. To serve this need, quantitative notation systems, tools and devices have been under development throughout our history.16 Calculators for basic arithmetic operations and R for statistical analyses are examples of such devices. Most postgraduate learners almost certainly have prior experience with calculators. This makes them a useful analogous prior knowledge that can serve as a bridge to the world of programming that is unknown to absolute beginners (see17-20 for discussion on the use of analogies in teaching). We have leveraged this analogy to make the following points in our workshops.\n\n\n\n1. R uses programmable functions, which are like the push-button functions on a calculator, only much more customizable and dynamic. This supports the myriad quantitative operations required for modern biosciences that far outnumber the basic arithmetic operations supported by calculators. An illustration such as in Figure 1 makes programming appear as a logical and more practical way to do statistical analyses.\n\n2. An absolute beginner may feel that they need to be good at statistics to derive any use out of R. This can result in loss of motivation and prevent them from exploring R on their own. We used the analogy with calculators to convey that this is not the case. For example, the square root function on a calculator can be used effectively, even if one is not skilled at performing the operation mentally or manually on paper. Similarly, postgraduate learners may already have a high-level understanding of the tasks that they need to implement from studying research literature, e.g., clustering of data points, making volcano plots given fold changes in gene expression and associated p-values, etc. Programmable functions in R are but an analogue of the buttons comprising a calculator’s keypad. To learn to “push the buttons” of the R system is an achievable goal in a short time frame, especially because R is designed to be a “smart” version of calculators (see the next section).\n\n3. To get good at arithmetic, it is important to know the method by which one adds, subtracts, multiplies, or divides by hand. Similarly, one must strive to understand what the algorithms implemented in R functions are doing. Learning to program in R is a good starting point towards that goal. Further, as we discuss later, there are ways in which one can achieve synergy by combining their beginner-level knowledge of programming with the statistical know-how of their collaborators and/or supervisors.\n\nLike the traditional hand-held calculators, R is a device for quantitative computations. However, R supports a myriad of quantitative operations that are required for modern biosciences. If the order of 100,000 R functions were to be accessed via push button keys, i.e., the same way as traditional calculators—one key per function, the device would be unwieldy. A programming language is a logical way to interact with a “smart calculator”.\n\n\nR is a smart version of calculators\n\nAnalogy between R and calculators stretches beyond them both being devices for quantitative computations. In fact, R may be viewed as a “smart” version of calculators. Among its many improved features, the version advance has been made possible by adoption of a new interface (programmable functions instead of push-button functions), utilization of internet connectivity (e.g., internet-enabled package installations for new functions), support to save analysis sessions to secondary memory, availability of functions for diverse applications, and support for literate programming. As described below, in our workshops, we presented some of the key elements that constitute the R system as logical designs to upgrade calculators to a “smart” version.\n\nNew interface via programming. Calculators perform only a few basic arithmetic operations accessible via push-button functions. In contrast, R is designed to perform a myriad of tasks. To enable this advance, R users must spell out the name of the functions that would otherwise be button labels if R functions were to be accessed via a keypad. Further, simple arithmetic performed by the push-button functions of calculators accept one or a few numeric inputs. In contrast, programmable functions in R can take a variety of inputs. These are passed to functions as named arguments enclosed in parentheses. The function and argument names are conventionally meaningful, utilize common language and context-specific words, and follow syntax patterns. These features make them easy to look up and remember. Hence, programmable functions have been the preferred way to interface with R.\n\nInternet-enabled updates to available options via packages. Software updates by installations of files obtained from internet is a defining feature of smart devices. A package is the R equivalent of apps on a smartphone. To understand why this is a logical feature of a smart calculator, it is helpful to consider the logic underlying smartphone apps, which is something that all postgraduate learners are familiar with. An app store is a digital platform that distributes a large number of apps— each app serving a specific need. If all these apps were pre-installed on a smartphone, they would occupy a lot of storage. Hence, in the age of internet connectivity, the smart solution is to have a single platform from which apps are available on demand. Similar solution exists in programming languages such as R. Users can install R packages from online repositories such as CRAN21 and Bioconductor.22 The packages provide access to a set of functions that have been written to facilitate a specific analysis, e.g., edgeR for differential expression analysis of RNA-seq data. There may be multiple packages that serve the same purpose, e.g., edgeR and DEseq2, which is analogous to there being multiple smartphone apps for the same purpose, e.g., Google Maps and Waze for navigation. Each R package may have its own distinguishing feature or selling point, which might make it more suitable for a particular use case. From an R user’s perspective, when faced with the task of processing biological data, a good starting point might be to do a literature search for current best practices in analysis of the kind of data they have, which would typically result in recommendations for R packages. Alternatively, the user might find such information in the methods sections of articles that may have used such data, or study literature and surf online discussion forums for reviews of different packages. These steps are analogous to those one might take in picking a smartphone app for their needs. It is important to hit these points in introductory workshops because we found that absolute beginners harbor a misconception that advanced bioinformaticians are always building methods for analysis from scratch for every task.\n\nSecondary memory for long-term storage. A typical calculator lacks secondary memory, and hence, does not support saving work sessions. In contrast, the modern devices that support access to R, typically provide ample secondary storage and access to large-scale remote storage via internet. In turn, R supports saving outputs of computations in a diverse range of file formats including image file formats and biological data file formats. R also allows saving images of the R environment to a compressed file. However, absolute beginners often struggle to grasp the notion of R environment. In our workshops, we conveyed this notion with the aid of an imagery of a traditional data analysis work space (see Figure 2). When one starts a new job, they may begin their work at an empty desk. As they proceed with their work, they would populate their work environment with objects that may store data, e.g., taskpads or other office stationery. Similarly, when one starts a new R session, they begin with an empty R environment. As they progress with analysis, they create R objects that have a name label and contain data. These are visible in the R environment. A smart feature of R is that it allows users to save the environment as a file and load at a later time in a new R session, which is analogous to packing up the books or printouts at one’s desk when a session of work ends and rearranging them on the desk whenever needed again.\n\n(a,b) An empty R environment is analogous to an empty desk at the start of analysis. (a,c) As analysis progresses, objects with data are stored in the current environment.\n\nHandling of diverse and complex use cases. A typical session of data analysis might involve feeding data that exists in paper or digital media such as text/image files to a computing device and saving desired results in a convenient format. R supports diverse file formats for both the input and output, which is a substantial advance over ordinary calculators that typically accept and output numeric values only. Further, there are flexible options to organize or structure data within an R session, and a number of functions to support sampling from existing data and reorganizing data in meaningful ways. In our workshops, when we were introducing data types and structures in R, and the functions called head, tail, colnames, etc. that display the first few entries, last few entries, column names (if applicable) of R data objects, respectively, we found the trainees wondering what the point of learning about these was. Although we were asked an explicit question about this only once out of ten sessions, we suspect that many more beginners may benefit from a motivation when discussing such concepts, which we communicated as follows. In a typical calculator, the allowed data type is predominantly single numeric value. In contrast, R can handle data structured in various formats. For example, in real life, sometimes our needs of storing data would be better served by a sticky note than by a notebook, or by a printer paper, etc. (see Figure 3). Similarly, in R, our needs are sometimes better served by tabular structures, at other times by an array, or at other times by a list structure. In fact, a smart feature of R is that package developers may define their own data structures for special purposes, e.g., DGElist in the edgeR package, SeuratObject in the Seurat package, which are analogous to special-purpose formats, e.g., lab notebooks, sheet music, ledger, etc. When handling a notebook containing data, one flips through the pages in many ways to examine how the data is organized. Similarly, functions such as head, tail, colnames, etc. enable us to examine R objects.\n\nDiverse data structures are used in R to store different kinds of data. This is analogous to the use of various objects as shown in the illustrations to store data in non-digital life.\n\nSupport for literate programming. A popular advice is to treat a program as a piece of literature, addressed to human beings rather than to a computer.23 Such practice facilitates reproducible research and enables open access, which are easily achievable goals in the digital age. To this end, R provides the option to include text and analysis results along with blocks of code in the same document, e.g., as RMarkdown documents. Additionally, comments and use of indentation in scripts make R documents easy for humans to read. Once again, in an age of smart devices, this is a desirable way to write and think about programs. Further, it has been suggested that programs and algebra play analogous roles in quantitative sciences.24 Highlighting these points may equip beginners with a framework to think about R scripting.\n\n\nIntroductory workshops should seamlessly integrate an understanding of the elements of R with participatory live coding\n\nWe delivered an understanding of the R system using analogies described above, and strove to present them in seamless integration with participatory live coding. In feedback, our trainees described participatory live coding as one of the best parts of our workshops. We conducted our workshops in person and via videoconferencing to support remote learning. To design the workshops, we studied tips suggested in literature by other instructors.25,26 In particular, we found it helpful to assess student learning periodically by asking them to guess what a line of code might do and to suggest code for some of the tasks. However, we kept our workshops informal and participation voluntary. Our goal in doing so was to accommodate individuals who are looking to learn passively by being present in workshops while also attending to other work, e.g., responding to emails. In our workshops, presence of passive learners did not interfere with the attention of other students actively following instruction. We allowed attendees to interrupt with questions at any time including by unmuting themselves in remote sessions. Our goal was to create a relaxed, no-judgement workshop environment where participants can feel free to ask any question and do as they please.\n\nThe feedback revealed that the choice of data for practice during the workshop is an important consideration. Most trainees prefer to work with a data type that they have experience with and is relevant to their research. Since our audience was almost all biomedical researchers, we switched to using a bulk RNA-seq counts matrix after using the Iris flower data27 for initial iterations of our workshop. For general audiences, we recommend pre-workshop surveys to identify datasets that most attendees might find interesting. In some of our workshops, we found it helpful to share a summary of a pre-workshop survey with the attendees. Awareness of the class composition helped with making the students with somewhat more advanced backgrounds (e.g., experience with other programming languages) patient while we answered questions from absolute beginners.\n\n\nIntroductory workshops should provide specific examples of what students can do after the workshop\n\nIndependent surveys have found that retention of skills taught in short workshops tends to be poor.9 Hence, it is important that introductory workshops give specific examples of how students can integrate R in their research practice. In our workshops, we recommended that students ask their computational collaborators (if any) for code, or download them for published papers they may read. At the very least, they should study them as part of their research, which can teach them about new functions and programming practices. Additionally, they could ask their collaborators for guidance in making minor modifications to the code for exploratory analysis. We browsed examples of RMarkdown documents and scripts available online to show that they can be studied the same way as research literature with code chunks having the same role as algebraic equations, only easier to understand because R function names are in many cases abbreviations of English words.\n\nAdditionally, it is important for beginners to have an awareness of things that they should explore in their own time. For example, in a four hour long introductory workshop, we could not cover concepts such as conditional statements, loops, and hypothesis tests via participatory live coding. We dedicated the last 5-10 minutes to discussing these and browsing the R graph gallery.28 These provide students with a concrete direction to continue learning and exploring R after the workshop.\n\n\nDiscussion and conclusion\n\nA major factor that shaped the thought process underlying our workshop design was the duration of workshop. This was set to four hours based on our assessment of availability of postgraduate learners in our community, the other workshops that we teach throughout the year, and our own research load. To provide something of practical utility to absolute beginners with advanced needs in this short time frame, we came up with a way to communicate the key ideas that will serve as a mental framework to guide self-learning after the workshop. However, this can have an unintended effect of making beginners feel that using R is as simple as using a calculator, i.e., it is not important to look under the hood for how R functions are processing data. Consequently, it is important to warn the beginners to be cautious and check the function documentation and relevant literature to ensure that the methods implemented in the function are suitable for their purpose. If the workshop duration permits, instructors could consider demonstrating cases of undesirable outcomes due to uninformed use of statistical or other functions. In feedback, some of our attendees suggested that the duration could be longer than four hours, include more advanced statistical analysis and visualization with packages such as ggplot2,29 and allow time for practicing on their own but in the presence of instructors. We found it challenging to include these in our introductory workshop and conduct separate workshops on these topics. Other instructors may find it beneficial for their communities to conduct workshops over longer duration, and include these components in their design.\n\nBesides providing analogies to enhance teaching effectiveness, one of our goals in writing this manuscript is to expose the conceptual chasm that exists between the instructors of introductory programming workshops and absolute beginners. To be effective, the instructors should be aware of the questions that beginners may have on their minds but may not ask. Many of our workshop attendees prefaced their questions with a statement such as “sorry for a stupid question”, which suggests that students have to overcome a sort of guilt feeling before they ask a question. In our opinion, all of their questions are valid and should be answered to welcome beginners into the fold of programming. Additionally, since our workshops were free-of-cost, our experience has been that there are always at least some individuals who stroll into a workshop without prior planning or any study on their own. Even though there are professional benefits from learning to program, instructors are competing with other online platforms for attention, which is only made more tough when the students do not feel a sunk cost in the form of payment for attending workshops. Yet, demanding payment for training from individual students can slow down the progress to a future when all bioscientists will be computational bioscientists. Hence, several institutions including ours sponsor free data science training workshops for their community members and/or facilitate access to online courses. In this article, we proposed that introducing R (or other languages for data analysis) as a smart version of calculators can capture the attention of absolute beginners and make learning to program feel like switching from first-generation mobile phones to smartphones—a logical and pleasant move to an intuitive way to interface with technology. For other instructors, when designing their workshops, important considerations should be to tell the story the way they have it in their head and customize for their audience. Whether they use the analogies presented in this article or not, a workshop should not be fragments of code presented in succession. It is important to have one unifying theme that is easy to remember and focuses on the R system in general instead of the specific data being analyzed. For our purpose, our proposition that R is a smart version of calculators worked well.\n\n\nData availability\n\nNo data is associated with this study.",
"appendix": "Acknowledgements\n\nWe thank Giovanni Maki for help with the illustrations, Gladstone Bioinformatics Core team for feedback on design of the introductory R training workshop, and John H. Morris for valuable feedback on the manuscript.\n\nWe are grateful for the generous support of our training program jointly sponsored by Gladstone Institutes and the UCSF Bakar Computational Health Sciences Institute.\n\n\nReferences\n\nSchuster SC: Next-generation sequencing transforms today’s biology. Nat Methods. 2008; 5(1): 16–18. PubMed Abstract | Publisher Full Text\n\nPegoraro G, Misteli T: High-throughput imaging for the discovery of cellular mechanisms of disease. Trends Genet. 2017; 33(9): 604–615. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang Z, Wu S, Stenoien DL, et al.: High-throughput proteomics. Annu Rev Anal Chem. 2014; 7: 427–454. PubMed Abstract | Publisher Full Text\n\nZampieri M, Sekar K, Zamboni N, et al.: Frontiers of high-throughput metabolomics. Curr Opin Chem Biol. 2017; 36: 15–23. PubMed Abstract | Publisher Full Text\n\nSmaglik P: The genetic microscope. Nature. 2017; 545(7654): S25–S27. PubMed Abstract | Publisher Full Text\n\nLeonelli S: Data-centric biology: A philosophical study. University of Chicago Press; 2016.\n\nMarx V: The big challenges of big data. Nature. 2013; 498(7453): 255–260. PubMed Abstract | Publisher Full Text\n\nStrasser BJ: Data-driven sciences: From wonder cabinets to electronic databases. Stud Hist Philos Biol Biomed Sci. 2012; 43(1): 85–87. PubMed Abstract | Publisher Full Text\n\nAttwood TK, Blackford S, Brazas MD, et al.: A global perspective on evolving bioinformatics and data science training needs. Brief Bioinform. 2019; 20(2): 398–404. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGoodman AL, Dekhtyar A: Teaching bioinformatics in concert. PLoS Comput Biol. 2014; 10(11): e1003896. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLibeskind-Hadas R, Bush E: A first course in computing with applications to biology. Brief Bioinform. 2013; 14(5): 610–617. PubMed Abstract | Publisher Full Text\n\nRubinstein A, Chor B: Computational thinking in life science education. PLoS Comput Biol. 2014; 10(11): e1003897. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWest JD, Portenoy J: The data gold rush in higher education. Big Data is Not a Monolith. 2016; page 129.\n\nDeMasi O, Paxton A, Koy K: Ad hoc efforts for advancing data science education. PLoS Comput Biol. 2020; 16(5): e1007695. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcGrath A, Champ K, Shang CA, et al.: From trainees to trainers to instructors: Sustainably building a national capacity in bioinformatics training. PLoS Comput Biol. 2019; 15(6): e1006923. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaput J, Noss R, Hoyles C: Developing new notations for a learnable mathematics in the computational era. Handbook of international research in mathematics education. 2002; pages 51–75.\n\nTreagust DF: The evolution of an approach for using analogies in teaching and learning science. Res Sci Edu. 1993; 23(1): 293–301. Publisher Full Text\n\nSanford JP, Tietz A, Farooq S, et al.: Metaphors we teach by. In: Proceedings of the 45th ACM technical symposium on Computer science education. 2014; pages 585–590.\n\nGuzdial M, Adams JC: Disputing Dijkstra, and birthdays in base 2. Communications of the ACM. 2021; 64(3): 12–13. Publisher Full Text\n\nCao Y, Porter L, Zingaro D: Examining the value of analogies in introductory computing. In: Proceedings of the 2016 ACM Conference on International Computing Education Research. 2016; pages 231–239.\n\nHornik K: The comprehensive R archive network. Wiley interdisciplinary reviews: Computational statistics. 2012; 4(4): 394–398.\n\nGentleman RC, Carey VJ, Bates DM, et al.: Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004; 5(10): 1–16. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKnuth DE: Literate programming. Computer J. 1984; 27(2): 97–111.\n\nSherin BL: A comparison of programming languages and algebraic notation as expressive languages for physics. Int J Computer Math Learn. 2001; 6(1): 1–61. Publisher Full Text\n\nBrown NCC, Wilson G: Ten quick tips for teaching programming. PLoS Comput Biol. 2018; 14(4): e1006023. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWilson G: Ten quick tips for delivering programming lessons. PLoS Comput Biol. 2019; 15(10): e1007433. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnderson E: The irises of the Gaspe peninsula. Bull Am Iris Soc. 1935; 59: 2–5.\n\nHoltz Y: The R Graph Gallery. [Online; accessed April 12, 2021]. Reference Source\n\nWickham H: ggplot2. Wiley Interdisciplinary Reviews: Computational Statistics. 2011; 3(2): 180–185."
}
|
[
{
"id": "126471",
"date": "23 Mar 2022",
"name": "Lex Nederbragt",
"expertise": [
"Reviewer Expertise Bioinformatics",
"Genomics",
"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 opinion piece suggests motivating researchers to use R by introducing the tool as an advanced calculator first. By making analogies to things new users are already familiar with, the authors aim to lower the barrier for getting started. The authors describe a 4-hour workshop where this approach is used successfully.\nI like the use of these analogies and enjoyed reading the article. I would suggest others also try this approach for other programming languages or computational tools. Often researchers will come to a workshop to learn a tool they have heard about and that seems to be important for their work, but are uncertain whether they will be able to master it. Connecting the tool to something familiar makes for a smoother introduction.\nI would support the indexing of the opinion article in its current state. I do, however, have a few comments and suggestions.\nFirst, although not strictly necessary, the article indirectly refers to concepts from the sciences of learning (e.g., cognitive psychology). For example, research has shown that connecting new knowledge to prior existing knowledge helps with learning. Another useful concept would be that of mental models: the authors are first providing a mental model of R close to the familiar one of a calculator, then expand on it to show the power of R as an analysis tool beyond calculations. A third example is that to \"assess student learning periodically\" is known as 'formative assessment', a way (for instructors and learners!) to check that learning actually has happened. Anchoring the approach taken by the authors to these phenomena from the learning sciences would strengthen their validity.\nSome more specific comments:\nCould the authors include a bit more on the intended audience of their workshops, for example how the workshop was announced? The reader would benefit from a brief explanation of what Participatory Live Coding is.\nIn the section \"Handling of diverse and complex use cases\", where data structures and tail, head, colnames are discussed: to me, using the analogy of a table of data in a spreadsheet program (Excel, Google Sheets) came up as a useful way to introduce R data objects. Have you considered using that?\nI found the section \"Support for literate programming\" a bit confusing. I agree that the use of RMarkdown and the creation of computational notebooks is a useful aspect of choosing a tool like R, but the arguments in this section are a bit vague and I wonder whether most readers will follow them. For example, I do not understand the connection to 'smart devices' or the reason for including the next sentence about the comparison of programs and algebra.\nFinally, when reading the article, I could not help thinking about how nicely this fits in with the 'philosophy' of The Carpentries, the international volunteer organization teaching coding and data analysis skills to researchers (https://carpentries.org). Are the authors aware of The Carpentries? The suggestions from this opinion article could be tried out in one of their workshops as well.\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? Yes\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? Yes",
"responses": [
{
"c_id": "8363",
"date": "21 Jun 2022",
"name": "Krishna Choudhary",
"role": "Author Response",
"response": "Thank you for the positive assessment of our submission and the thoughtful suggestions. Per your suggestions, we have: added text and references to mental models and formative assessment; described the intended audience and defined “participatory live coding”; included spreadsheet programs as another analogy; a citation to Software Carpentry."
}
]
},
{
"id": "119622",
"date": "01 Apr 2022",
"name": "Yasha Hasija",
"expertise": [
"Reviewer Expertise Computational Biology",
"Bioinformatics"
],
"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 of this opinion article have discussed the analogy of introducing the R programming language as a smart version of calculators in order to present the concept in a more simple and understandable manner. The article explains various analogies that can be derived while teaching the R programming language in a clear and concise manner. As a smart calculator R employs programmed functions, which are analogous to the calculator's push-button operations. These functions can be created through logical or arithmetic programming or downloaded from internet repositories such as CRAN and Bioconductor. Some of the advantages of R over traditional calculators have been discussed in terms of new interfaces via programming, Internet-enabled updates to available options via packages, secondary memory for long-term storage, and handling of diverse and complex use cases.\nIn addition, the authors have tried a few methods for introducing R to beginners via a webinar. They presented a concept of R programming using the analogies mentioned above, attempting to integrate them seamlessly with a participatory live coding webinar. The program was scheduled for four hours, and based on their evaluation, newbies were convinced that R is as simple to use as a calculator. While they were unable to cover conditional statements, loops, and hypothesis testing in a four-hour webinar. Overall, the authors addressed in this article how introducing R as a smarter version of calculators can spark a new interest in complete beginners. However, presenting an exploratory analysis of the feedback data may have made the article more conclusive.\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": [
{
"c_id": "8365",
"date": "21 Jun 2022",
"name": "Krishna Choudhary",
"role": "Author Response",
"response": "We thank the reviewer for their thoughtful summary of our article, and suggestion for further analysis."
}
]
},
{
"id": "128422",
"date": "05 Apr 2022",
"name": "Rayna M Harris",
"expertise": [
"Reviewer Expertise Genomics"
],
"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 opinion article \"Introducing R as a smart version of calculators enables beginners to explore it on their own\" provides practical advice for teaching R to trainees in the biological sciences. Designing workshops for beginners is challenging because trainees have diverse skills and learning objectives. The authors provide multiple analogies that could be used in an \"Introduction to R workshop\" to make R more accessible to beginners. The figures bring the analogies to life and could easily be inserted into a slide deck for a workshop (with permission) to teach these concepts. I think the article provides a unique perspective on teaching that is relevant to anyone teaching computational tools to diverse audiences.\nLike Reviewer 1, I would support the indexing of the opinion article in its current state. I do, however, have a few comments and questions.\nI noticed that you cited the iris dataset but not the RNA-seq data used for your workshop. A citation for that data would be useful to the reader and appreciated by the data generators. Also, do you teach edgeR and DESeq2 to beginners, or was this provided as an example? I think a citation here would be good to show how often these tools are being taught and used.\n\nIn the data availability section, it says that there is no data associated with this study. Would it be possible to link some of the files used in previous workshops (such as R scripts, slides) that could be used by instructors wishing to incorporate these suggestions into their classrooms? Also, you mentioned showing the results of pre-workshop surveys at the beginning of a workshop. Can you share those data summaries and/or survey questions (or is that private)? This could provide a nice overview of the target audience's field of study and prior knowledge.\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? Partly\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": [
{
"c_id": "8364",
"date": "21 Jun 2022",
"name": "Krishna Choudhary",
"role": "Author Response",
"response": "Thank you for the positive assessment of our submission and the suggestions. In the revision, we have cited the RNA-seq data we used, and the articles describing DESeq2 and edgeR. These libraries were covered in separate workshops later in the series and were indeed just provided here as examples. We have also provided a link to the workshop materials. We did not save the pre-workshop surveys, but the large majority of our workshop attendees self-identified as beginners to R scripting and programmatic data analysis, and consisted of graduate students and postdoctoral scholars pursuing biomedical research. Occasionally, faculty also attended the workshops."
}
]
}
] | 1
|
https://f1000research.com/articles/10-859
|
https://f1000research.com/articles/11-680/v1
|
21 Jun 22
|
{
"type": "Research Article",
"title": "Managing health care needs of the elderly through an elderly care manager: Thailand",
"authors": [
"Chanuttha Ploylearmsang",
"Chutamat Somboon",
"Utoomporn Namdee",
"Saithip Suttiruksa",
"Chutamat Somboon",
"Utoomporn Namdee",
"Saithip Suttiruksa"
],
"abstract": "Background: This mixed method research aimed to investigate health needs of older people and the attributes of the Elderly Care Managers (ECMs), and to evaluate the outcomes of two ECMs coordination. Methods: Three phases were: 1) a field survey of the health needs of 94 older persons; 2) group discussions between ten relevant persons involved in ECMs characteristics; 3) two ECMs coordinating with health-related agencies and measuring the outcomes of older people who needed assistance. Results: 63.1% of the participants had difficulties with their health, 12.8% of them had no caregiver, 26.6% of them had >1 health condition. Group talks dealt with the characteristics, role and attributes of ECMs. The two-month of ECMs coordination with health-related agencies according to older adults' needs, and made home visits encouraged the aged to acquire knowledge on their diseases. Conclusion: ECMs’s coordination with health-related agencies could support the needs of those of advanced age.",
"keywords": [
"Elderly Care Manager",
"Community",
"Older people",
"Health needs",
"Quality of life"
],
"content": "Introduction\n\nAn aging society is defined as one in which those who are 60 years of age or older make up more than 10% of the whole population of the country. In Thailand, the proportion of elderly persons in society has continuously increased as the birth rate continues to fall, and people live longer. By the year 2022, the number of Thai people who are 60 years of age and above will increase to 20 million, or 20% of the whole population (The National Statistical Office of Thailand, 2019). This change in the population characteristics is predicted to result in a dependency ratio, with regard to the elderly, will rise from 47.4% in 2019 to 99.8% in 2037 (Foundation of Thai gerontology research and development institute, 2020).\n\nAn elderly person faces both physical and mental changes. The immune system is weakened, resulting in generally more health problems than those in other age groups. It is also found that most aged individuals have chronic illnesses, especially dementia, which affect their daily lives and their quality of life (Barbe et al., 2018). As their ability to take care of themselves decreases, and as they are left alone (while the rest of their family members go out to work), people of advanced age often suffer from depression. Additionally, the environment that they live in is unsuitable to physical changes. experienced by elderly individuals.\n\nA long-term care system is extremely necessary for an aging society. The World Health Organization (WHO, 2020), has stipulated that long-term care is an indispensable part of the health system of society. There needs to be care activities by both formal caregivers, who are public officials, and medical practitioners in their areas, and informal caregivers, who are members of the family, friends and neighbors (Laranjeira, 2020). Important factors for the success of the long-term care system are the existence of supporting policies and regulations, a good, systematic, structure of services, channels of access to services, funding from various sources, flexible services and the ability to provide services to the residents of the older, participation from the community and relevant networks (Canadian Foundation for Healthcare Improvement, 2020). An Elderly Care Manager (ECM), at the level of the community, from the community itself, can play the role of a coordinator who addresses the various factors, and finds different ways to manage and solve different problems in response to the individual needs of the elderly in different cases. It may be said that the goals of care are to ensure that the basic factors in the daily lives of the older are meaningfully addressed, whether from the point of view of their expectations, or in terms of the existing standards of care (Yodpet, 2009).\n\nThus, the researchers were interested in exploring the health problems of the aged in a community, and that through conducting group discussions, getting the opinions of the relevant persons who are responsible for the care of the elderly in the community, and to investigate the outcome through ECM coordination. The aim of this research was to find out the outcomes when informal care in the community is carried out by members of the community themselves.\n\n\nMethods\n\nThis is mixed method research, using both quantitative methods for exploring the difficulties faced by the elderly and outcomes due to the ECM, and qualitative methods, based on focus group discussion. The relevant persons involved in elderly care, at this particular time, carried out their activities in Kruewan community1, city municipality, Maha Sarakham Province. The data collection in the field was carried out over a period of six months. The study was separated into three phases, each with a specific objective. The three phases were: 1) to explore the difficulties faced by older people in the community using an interview form (Ploylearmsang, 2022a) that the researchers had designed, and a trained team of researchers who used this form to collect the necessary information; 2) to conduct focus group discussions with the relevant persons involved in the system of long-term care for the elderly in the community. They consisted of representatives from the municipality, spokespersons of the community leaders, envoys of the older from the community, Village Health Volunteer (VHV), and health practitioners in the area; and 3) to study the two months short-term outcomes that were enhanced by two trained volunteer ECMs who coordinated with health-related agencies to provide contributions or interventions according to the needs of elderly, made at least two home visits over a period of two months, and informed the elderly about the diseases and some supportive help for improving quality of life of the elderly.\n\nThe three phases of the research had three different population and sample groups, as follows:\n\n1) The population in the first stage consisted of the elderly persons in Kruewan1 community. The subjects, consisting of both males and females, were ≥60 years on the day of the survey. They were also residents of the Kruewan1 community throughout the three months period, and were willing to provide the data. The results were calculated based on the size of the sample group for the survey, p=ratio of aging patients with chronic illnesses–53% (Gray, Hahn, Thongcharoenchupong, 2016) applying the Cochran formula (1953) as follows:\n\nn=the minimum number of sample groups needed\n\nZα/2=constant under α error where α=0.05 then Zα/2=1.96\n\ne=acceptable error, equivalent to 10% or 0.1\n\nThe research team conducted an interview of 45-60 minutes’ duration for each elderly person.\n\n2) The population in the second phase consisted of relevant persons involved in the health care of the elderly in Kruewan community1. Those who were able to give evidence, and willing to participate in group discussions, contributed to the investigation and ECM training. There were ten individuals in total, consisting of one community leader, one representative of the elderly, three VHV, one municipality official in charge of the maintenance and improvement of housing conditions, and four health personnel who had worked in the research area: a doctor, a nurse, a pharmacist, and a physiotherapist.\n\n3) The population in the third phase consisted of the elderly who participated in phase 1. Samples consisted of elderly persons who had made a request for healthcare and were willing to accept assistance from ECMs. The sample size was calculated using the effect size of paired data on quality of life.\n\nn = [(Zα/2 + Zβ)σ/Δ]2 when Zα/2 = 1.96, Zβ = 0.84, and Δ of EQ 5D = 0.15 (Comans et al., 2013), n=13.9 or 14. Fourteen elderly persons that fitted the inclusion criteria were recruited. The exclusion criteria were: 1) patients that ECMs were unable to access or collect the data, because they had moved out of the area or passed away during the data collection period; 2) those that requested for discontinuation.\n\n\n\n1. An interview form and a consent form were used for collecting information regarding issues faced by the elderly in the community.\n\n2. The questions were framed by the investigators for the group discussion. The subject matter included their view on ECM, the characteristics and roles of the ECM. The questions were checked for content validity by an expert on development of survey instruments and a local authority on health care for the elderly. The interview form was tested for reliability on ten elderly persons in other localities.\n\nThe 10 steps for the research were: 1) submission of a human research ethics form to the Ethical Committee of xxxxx University with the ethical approval number xxxxx submission of a letter of request for assistance to Burapha primary care unit (PCU) in order to collect research data from populations in Kruewan 1 community; 3) submission of a request for permission to access the study area to the Maha Sarakham city municipality; 4) conducting a field survey of older people in order to find out about their situation and any problems affecting their health; 5) collection of data by tape recorded interviews, analyzing the results, and categorizing the problems and the health needs of people of the elderly; 6) leading a group discussion in order to exchange information on the conditions and difficulties faced by the elderly in the community, and recording of opinions held by members of the community about the characteristics, roles and responsibilities of the ECMs; 7) gathering of evidence from group dialogues, identification of the subject matters discussed, and analysis of the resultant evidence; 8) categorization of the difficulties faced by the elderly based on the information obtained from the first phase of the survey, and training ECMs to coordinate with specific personnel or agencies who have the ability to resolve individual problems, together with suggestions and solutions to be applied by the relevant agency; 9) collecting paired data for the supportive effects of ECMs’ coordination on short-term outcomes among the elderly; 10) summarizing data and providing feedback to the community.\n\nApproval IRB protocol/human subjects approval numbers: Faculty of Pharmacy Mahasarakham University Ethics Board (REB: PD 014/2014).\n\nThe relevant general and health information of the participants during the first stage were described by descriptive statistics such as frequency, percent, average, and standard deviation. The paired data of pre-post supportive effects including score of disease knowledge (score 0-5) and quality of life (score 0-1) were analyzed by using Wilcoxon signed ranks tests.\n\n\nResults\n\nAccording to the information from Burapha Primary Care Unit (PCU), the population of Kruewan1 community consisted of 1,006 individuals. There were 149 elderly persons (9.34%) and 94 elderly persons were willing to participate in this survey, a response rate of 63.1%. There were 55 individuals whose information could not be obtained as they had moved, were not home at the time of the survey, or had passed away. Most of the older people in the Kruewan1 community were female (74.47%). As shown in Table 1, 53 individuals (56.38%) were 60-70 years old. 51 older persons (54.26%) were married and were together. In this community, there were forty aged persons (42.55%) who were widowed. The education level of most participants was at primary school level (93.62%). There were seventy-nine elderly persons (84.04%) who were no longer in any occupation. Eighty-two of the elderly had regular caregivers (87.23%), but as many as twelve elderly persons (12.77%) had no regular caregivers.\n\nThe status of the elderly in Kruewan1 community is shown in Table 2, and fifty-seven (60.64%) had underlying medical conditions. The three most common underlying diseases were high blood pressure (38.30%), diabetes (32.98%), and hyperlipidemia (19.15%). Other medical conditions which were found were: emphysema, migraine, hemorrhoids, Parkinson’s disease and partial paralysis. Five individuals were discovered to have them. Three were identified as having Alzheimer’s disease.\n\nHealth needs of the older people in the community\n\nFrom the interview about the need for health services among the aged in the community, we concluded that there are seven main needs, as follows: (1) income-generating occupations, (2) commodities for daily living, such as blankets, (3) monetary support, (4) basic knowledge on diseases and medication, (5) equipment to increase their quality of life, such as canes, walkers, and wheelchairs, (6) social activities such as aerobic exercise groups, (7) advice and suggestions to manage their mental health and depression after the loss of loved ones.\n\nVarious results (Ploylearmsang et al., 2022) were derived from the group discussions conducted among ten relevant persons who were involved in health care for the elderly (see Table 3). They consisted of five members of the community who were involved with the elderly, and five personnel from the public sector who were health care providers for elderly persons. The group discussion was held for them to give their opinions on the health problems faced by the elderly, and the characteristics, qualifications and work methods of the ECM. The opinions about the ECM in the community were shown in Table 2.\n\nData was obtained, over a two-month period, from fourteen elderly persons who were willing to participate in this research, during which two trained volunteer ECMs coordinated with health-related agencies which could provide contributions or interventions according to the needs of the elderly. The ECMs made home visits during the two months’ period. Five participants were missing during follow up, two elderly persons were reported as dead, and three had moved to their children’s homes in other areas and thus the response rate was 64.3%. Table 4 shows the activities that ECMs performed for the elderly in their community, and Table 4 shows outcomes of these activities among the elderly after the two-month period. The trend in terms of increased quality of life (EQ-5D-5L) among the elderly from pretest to posttest was 0.80±0.16, 0.82±0.15 (p=0.059), while that for knowledge about diabetes and hypertension increased significantly from 4.11±0.60 to 4.56±0.53 (p=0.046) and 4.11±0.60 to 4.89±0.33 (p=0.008), respectively.\n\na Wilcoxon signed ranks test.\n\n* statistical significance at p<0.05.\n\n\nDiscussion\n\nA study of the development of systems for long-term care service in the community, found that 67.6% of the elderly were female (Loskultong & Sritanyarat, 2012). Research investigating health problems, issues with the use of medications, and the behaviors of the elderly in the community of Phramongkutklao Hospital, with regard to the use of medications, also found that most of the residents of advanced age were female (Naiyapatana, 2010). The results of the current study are consistent with the two studies mentioned i.e. elderly female would be a group of concern in the future. It was found that the health problems of the elderly were chronic diseases including hypertension, diabetes, hyperlipidemia, gout and rheumatoid arthritis, heart disease, and asthma. Some of the elderly had more than one underlying medical condition. This is consistent with the findings of the survey on the six most common chronic illnesses suffered by people of advanced years in 2019, which was conducted by the National Statistical Office. It is also consistent with the study from home visits and the management of left-over medications in elderly persons with chronic illnesses. It was found that the five most common chronic illnesses, with the left-over medications, among the aged were high blood pressure, diabetes, stroke, hyperlipidemia, and cardiovascular diseases, (Chantra & Moungkan, 2020) Studies carried out on the development of systems for long-term care services for the elderly in the community found that the most common morbidity suffered by the elderly was high blood pressure (Loskultong & Sritanyarat, 2012; Naiyapatana, 2010). Additionally, the results of this study demonstrated that most of the elderly had more than one underlying condition, and long-term medications use was important.\n\nElderly persons, living without caregivers was one of main factors for the aggravation of health problems amongst elderly in Kruewan1 community. Most of their children worked in different areas, and thus the elderly had to live alone, without a caregiver. Physical changes experienced by advanced age also affect their health. The survey found problems relating to aches and pains in joints, knees and body. Additionally, there were problems with balance and dizziness, eyesight and visual acuity, oral and dental health, and the excretory system and this is similar to the findings of a study in Thailand (Jarutach, 2007). A large number of the elderly have orthopedic illnesses, and illnesses linked to joints/muscles/ligaments, and most elderly persons have problems with visual acuity. However, in terms of mental health, most of the elderly people in this study did not suffer from depression and this is consistent with the situation in Thailand as a whole where it was found that Thai elderly persons had average mental health scores of 32.3 out of 45 points – which was within the normal level of the mental health (Yiengprugsawan et al., 2012).\n\nEnvironmental factors may also play a role in the health problems of the elderly. This is because ideal environments for the elderly vary according to their individual limitations. If an environment allows an elderly person to help themselves, the consequence may be positive effects on such a person’s mental health. They can take pride in being able to fend for themselves, and do not feel that they are burdening their children. Research has been shown that elderly persons with mobility problems and whose difficulties have been managed, can move around more comfortably, and are able to perform more movements by themselves (Tongsiri et al., 2017). Similarly, it has been found that elderly persons living in urban areas need to use equipment, which are safe and not complicated to use, to assist with their mobility (Lertpradit & Jarutach, 2020).\n\nTeaching the elderly to have basic knowledge about illnesses and medications is important. Awareness about such issues needs to be created among them and their caregivers in order to prevent health problems that may result from a lack of such information. A study on the management of left-over medications among the elderly with chronic illnesses, found that the elderly needed knowledge with regards to use of medications, and the methods to use them appropriately. Most of the elderly tend to forget to take their medications or to take them at the appropriate time (Chantra & Moungkan, 2020). Thus, in this study, the elderly indicated their need for this information, and their caregivers also were of the opinion that they needed to know more in order to provide good support to the elderly person in the family. The results of our research also showed that after such educational activities the knowledge scores in this area had increased among the elderly.\n\nThere should be a system of management with continuity for the health problems of the elderly, especially for their long-term health care. Investigations into the development of systems for long-term older care services in the community found a lack of policy for long-term health care for the elderly (Loskultong & Sritanyarat, 2012). Thus, in this research, an attempt was made to introduce the working methods, roles and responsibilities of ECMs in the community, and to indicate how their work should be carried out. As Somkamlang & Kitreerawutiwong stated, the main roles and responsibilities of the ECM can be divided into two categories, according to whether they are care providers or care managers. In the system employed in Japan, there is an arrangement for elderly care service in the form of care management, with care managers as the persons who individually organize the format of care for older persons (Trakoolngamden et al., 2018). The voluntary elderly care managers have to be trained and certified by the state (Kelsey & Laditka, 2009). In Thailand, the Ministry of Social Development and Human Security (2014) stated that in order to substantially and systematically help with the daily lives of the elderly, and to understand them, voluntary care managers must be able to analyze the situation, the problems and the feelings of the elderly, and the relevant target groups, as well as conduct home visits, so as to follow up on relevant facts and information, in order to help with the planning of care for the elderly.\n\nIn terms of the outcomes of elderly by ECMs, in this present study found that the 2-month community supportive intervention for Thai elderly by ECMs has significantly effect on patients’ knowledge score but there was no significant improvement in elderly’s quality of life by EQ 5D, even an increasing trend of elderly quality of life was found. Whereas a study (Rachasrimuang, 2018) revealed that the 18-week home visit intervention by youth volunteers for the elderly in the Thai rural community showed the significant improvement in EQ 5D (p<0.001). Another study in Australia also found similar result that the discharge program for elderly had positive effect on the six-month quality of life from EQ 5D 0.75±0.16 to 0.84±0.25 within 6 months (Comans et al., 2013). Comparing with two references, the improvement of quality of life needs the suitable duration for implementing the intervention for the elderly.\n\n\nConclusion\n\nProblems affecting the health of the elderly in Kruewan1 community are underlying medical conditions, aches and pains, mobility problems, problems with eyesight and visual acuity, problems with oral and dental health, and not being able to be self-dependent. The needs of the elderly in the community are related to other problems which were identified such as the need to have an income-generating occupation, the need for essential commodities, financial support, knowledge about illnesses they suffered and the medications, equipment for mobility and for exercise groups, and to have consultation regarding mental health issues arising from depression due to the loss of loved ones.\n\nFrom the views which were expressed about ECMs by those involved in healthcare for the elderly in the community, members of the community, public sector personnel, and health professionals, it may be concluded that an ECM needed to be someone from the community who is healthy and responsible, who puts their heart into the work, is service-minded, is willing to take on their responsibilities, fully dedicates their time to their work, is flexible, able to travel in order to coordinate their work, understands the elderly, and can work alone or in a team. While the level of education attained by such individuals is not an issue, this person needs to be literate and have a basic knowledge of health care. They also need to know the situation and the needs of the elderly in the community, and the pertinent channels of coordination or communication with relevant agencies with regard to health care for the elderly. They need to have communication skills, the capability to plan well, and get along easily with those in their areas, or from relevant teams. They are required to use appropriate communication channels in order to coordinate with others both within and outside of the community. Additionally, they need to use the appropriate information technology and computing systems. Their main responsibilities are to coordinate with relevant agencies in order to be able to respond to the basic needs of the elderly in the community.\n\nThe information on the health of elderly persons who are on the public sector database is not up to date. Some of the elderly no longer live in the community but their names are still on the database. This caused problems in the collection of complete information in the survey of the elderly persons’ health problems. Additionally, the elderly person’s ability to recall is decreased and their recollection may be significantly limited on such matters as their medication use. Interviews, therefore, had to be conducted in the presence of others as well, such as the caregivers and the families. ECMs coordination with health-related agencies, which can provide contribution or intervention according to health needs of the elderly, provides a connection between the community and health-related agencies, and can be said to be one supporting components in terms of improving the situation of people of the elderly. However, it may not show up in terms of direct effects on such outcomes. There are other significant influencing factors, such as interventions by health-related agencies, the compliance displayed by the elderly themselves to instructions that are prescribed to them and the level of support that they receive from their families, all play a role.\n\n\n\n• The connection between health services and the elderly in the community is the crucial elements of the long-term care. Elderly Care Manager (ECM), a voluntary coordinator in the community, is a key person for making the smooth connection.\n\n• The opinions of the relevant persons, health-related officers and lay persons, about the ECMs, as well as the working process to recruit ECMs were created.\n\n• The supportive interventions coordinated by ECMs has significantly affected on elderly’s health needs.\n\n\n\n• Elderly participation in their own community to co-create, develop, and implement the health-related project with the local authorities, is significant strategy for enhancing both elderly empowerment and community engagement. It could be generalized in other aging community.\n\n• ECMs, recruited by community will be accepted and allowed to coordinate with elderly for improving their quality of life. They will be able to provide continuous help, manage problems, and respond to the elderly’s health needs.\n\n• Elderly home visit is an encouraging process to learn and understand their health needs. It could be applied for elderly in other area.\n\n\nData availability\n\nFigshare: Managing Health Care Needs of the Elderly through an Elderly Care Manager: Thailand, https://doi.org/10.6084/m9.figshare.19961522.v2 (Ploylearmsang et al., 2022).\n\nFigshare: Data coding, https://doi.org/10.6084/m9.figshare.20010527.v1 (Ploylearmsang, 2022b).\n\nFigshare: Questionnaire and Questions for group discussion, https://doi.org/10.6084/m9.figshare.20010536.v1 (Ploylearmsang, 2022a).\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 give thanks to all of the older patients, the health volunteers, and the health-related agencies in Kruewan Community1 for the co-operations during the research time. A sincere thank you to Professor Thomas Paraidathathu for proofreading the article.\n\n\nReferences\n\nBarbe C, Jolly D, Morrone I, et al.: Factors associated with quality of life in patients with Alzheimer’s disease. BMC Geriatr. 2018; 18(159): 159–159. PubMed Abstract | Publisher Full Text\n\nCanadian Foundation for Healthcare Improvement: Long-term success and Sustainability of Healthcare Improvement Guide. 2020, April 1.Reference Source\n\nChantra C, Moungkan J: Cause of Leftover Drugs in Elderly patients with Chronic disease at Ruamjai Community health care Wangthong Phitsanulok Province. Proceedings in the 11th Hatyai National and International Conference. 2020; 1957–1967.\n\nComans TA, Peel NM, Gray LC, et al.: Quality of life of older frail persons receiving a post-discharge program. Health Qual. Life Outcomes. 2013; 11: 58. PubMed Abstract | Publisher Full Text\n\nFoundation of Thai gerontology research and development institute (TGRI): Situation of the Thai elderly 2019. Nakhon Pathom:Printory Co. Ltd;2020.\n\nGray RS, Hahn L, Thapsuwan S, et al.: Strength and stress: Positive and negative impacts on caregivers for older adults in Thailand. Australas. J. Ageing. 2016; 35(2): E7–E12. Publisher Full Text\n\nHirakawa Y: Care manager as a medical information source for elderly people. Med. Res. Arch. 2016; 4(5): 1–12.\n\nLertpradit N, Jarutach T: Housing Conditions and Improvement Guidelines for the Elderly Living in Urban Areas. Nakhara: Journal of Environmental Design and Planning. 2020; 18(1): 117–138.\n\nJarutach T: The Minimum Standard of Environment and housing for Thai Elderly. Proceedings of The Eighth Pan-Pacific Conference on Occupational Ergonomics (PPCOE2007). 2007.Reference Source.\n\nKittirattanapaiboon P, Tanaree A: Trend and associated factors of mental health in Thailand: a national survey 2018. J. Ment. Health Thai. 2020; 28(2): 121–135.\n\nLaranjeira C: Quality of life of informal caregivers for elderly people with dementia: A comparative study. Alzheimers Dement. 2020; 16(Suppl. 7): e047273. Publisher Full Text\n\nNaiyapatana W: Health Problems, Medicine-Used Problems, and Medicine-Used Behaviors among Elderly in the Community of Phramongkutklao Hospital Personnel’s Residence. J. Nurs. Educ. 2010; 3(1): 2–14.\n\nLoskultong P, Sritanyarat W: Development of Long-Term Care Service System for Community Older Persons in the Context of a Secondary Care Hospital. Graduate Research Conference (GRC) 2012. Khon Kean University. 2012.Reference Source\n\nNational Statistical Office: Size and structure of the population by age and sex. Statistical Section. 2019, October 1.Reference Source\n\nRachasrimuang S, Kuhirunyaratn P, Bumrerraj S: Effectiveness of a Home Visit Programme by Youth Volunteers on Health-Related Quality of Life and Depression among Elderly Persons: Results from a Cluster Randomized Controlled Trial in Rural Thailand. J. Med. Assoc. Thail. 2018; 101(5): 189–195.\n\nSomkamlang S, Kitreerawutiwong N: Long Term Care Manager in District Health System. J. Nurs. Health Sci. 2019; 12(4): 1–8.\n\nSub-committee for the development of standards for elderly integrated care: Manual of Voluntary Elderly Care Manager. Thailand:Department of Older Persons, Ministry of Social Development and Human Security;2014.Reference Source\n\nKelsey SG, Laditka SB: Evaluating the Roles of Professional Geriatric Care Managers in Maintaining the Quality of Life for Older Americans. J. Gerontol. Soc. Work. 2009; 52(3): 261–276. PubMed Abstract | Publisher Full Text\n\nPloylearmsang C, Somboon C, Namdee U, et al.: Managing Health Care Needs of the Elderly through an Elderly Care Manager: Thailand. figshare. [Dataset].2022. Publisher Full Text\n\nPloylearmsang C: Questionnaire and Questions for group discussion. figshare. [Extended Dataset].2022a. Publisher Full Text\n\nPloylearmsang C: Data Coding. figshare. [Dataset].2022b. Publisher Full Text\n\nTakahashi T, Kaihara S: Introduction to the Status -Function-Care (SFC) Method. Journal of Japan Hospital Management Association. 1992; 29: 247.\n\nTongsiri S, Ploylearmsang C, Hawsutisima K, et al.: Modifying homes for persons with physical disabilities in Thailand. Bull. World Health Organ. 2017; 95(2): 140–145. PubMed Abstract | Publisher Full Text\n\nTrakoolngamden B, Mongkolsinh V, Srangthaisong D: The Evaluation of Care Manager Course on Elderly in Bangkok Metropolis of Kuakarun Faculty of Nursing, Navamindradhiraj University. Kuakarun J. Nurs. 2018; 25(2): 210–228.\n\nWorld Health Organization: Long-term-care systems. 2020, November 1.Reference Source\n\nYiengprugsawan V, Somboonsook B, Seubsman S, et al.: Happiness, Mental Health, and Socio-Demographic Associations Among a National Cohort of Thai Adults. J. Happiness Stud. 2012; 13(6): 1019–1029. PubMed Abstract | Publisher Full Text\n\nYodpet S: Integrations of Long-term Care System for the Elderly in Thailand. 1st edBangkok:J Print 2 Publishing House;2009."
}
|
[
{
"id": "141662",
"date": "01 Sep 2022",
"name": "Sawaeng Watcharathanakij",
"expertise": [
"Reviewer Expertise health services research",
"pharmacoepidemiology",
"drug utilization study",
"instrumental development",
"longitudinal design",
"and longitudinal statistical 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\nThis is a very interesting research article. However, the abstract needs a minor change to show attributes of ECMs rather than the method used (group talks). In addition, some changes are required e.g. statistical formula, the number in Table 1 is not consistent with narrative content, additional explanation at some points, and others as highlighted in the attached file. Overall, minor revision is required. Please see the attached file for 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?\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": "254035",
"date": "09 Mar 2024",
"name": "Roger E. Thomas",
"expertise": [
"Reviewer Expertise Geriatric polypharmacy",
"hospital readmissions"
],
"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 topic. There is a limited literature on the outcomes of care provided by home visits of physicians or visiting nurses or other health practitioners. Carefully conducted RCTs at low risk of bias and appropriately powered are needed.\nThe computations for phase 3 (those who consented to receive ECM) concluded 14!! respondents were needed. This computation does not take into account the need for generalizability of results and is speciously scientific. You stated 53% had a chronic medial issue. How many had 2, 3 .. such issues?\nYou commented that 87% had regular caregivers. What did these caregivers provide? provide compared to ECM? and did the caregivers and ECM work together? What were their combined results?\nAn interesting approach, but tiny sample, no RCT, and low generalizability.\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": []
},
{
"id": "184484",
"date": "14 Sep 2024",
"name": "Anne Wissendorff Ekdahl",
"expertise": [
"Reviewer Expertise Geriatrician"
],
"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 using ECMs to care for the growing older population in Thailand, of which more older people live alone. I don't understand the \"xxx\" in the research process, as the ethical approval number is later exposed. The findings of health needs seem plausible and relevant. I my opinion, the article could be indexed to support the growing health needs of the Thai population.\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": []
}
] | 1
|
https://f1000research.com/articles/11-680
|
https://f1000research.com/articles/11-675/v1
|
20 Jun 22
|
{
"type": "Research Article",
"title": "Prevalence of pulmonary tuberculosis in Al-Najaf governorate, Iraq",
"authors": [
"Saleem Khteer Al-Hadraawy",
"Kais Khudhair Alhadrawi",
"Israa Abduljabbar Jaloob Aljanaby",
"Ahmed Abduljabbar Jaloob Aljanaby",
"Rahman S Zabibah",
"Saleem Khteer Al-Hadraawy",
"Kais Khudhair Alhadrawi",
"Israa Abduljabbar Jaloob Aljanaby",
"Rahman S Zabibah"
],
"abstract": "Background: pulmonary tuberculosis (PTB) is one of the most global dangerous infectious diseases worldwide, particularly in developing countries. Mycobacterium tuberculosis (Mtb) is the most infectious agent that caused PTB transferred by air droplets from one person to other. In the present epidemiological study, we aimed to record the total numbers and percentages of patients infected with PTB caused by Mtb during 12 months in AL-Najaf Governorate, Iraq.\n\nMethods: This study has been done in 2019 from January to the end of December in the north and south region of AL-Najaf Governorate, Iraq. Sputum of PTB-patients has been stained by Ziehl–Neelsen to Mtb diagnosis according to World Health Organization (WHO) recommendation. Results: We recorded 174 PTB-patients in AL-Najaf Governorate 2019; 89 male and 85 female; 101 and 73 in the north and south sections respectively. The age group 16-24 was the highest infected. Quarter two recorded the highest numbers of PTB-patients; 33 (60%) in the north section and 22 (40%) in the south section. Conclusion: There was low PTB incidence in AL-Najaf Governorate 2019 but the Youngers were the most susceptible to infection. Infection in the north section was higher than in the south section and there were no high differences between genders. Seasons have no high effect on the number of infections.",
"keywords": [
"Pulmonary tuberculosis",
"Mycobacterium tuberculosis",
"AL-Najaf Governorate",
"North section",
"South section",
"2019",
"Iraq."
],
"content": "Introduction\n\nHealth awareness is one of the most important reasons to avoid different infection such as pulmonary-TB and COVID-19.1 The developing countries are the most infected with these types of infections.2,3 Pulmonary-TB considered as the most infection caused by Mtb and can cause many dangerous complicated in the lung lead to death in many times.4 Pulmonary-TB is a contagious disease that is a major cause of illness and one of the top causes of mortality around the world and was the biggest cause of mortality from a single infectious agent until the COVID-19 pandemic, ranking ahead of many infections such as acquired immunodeficiency syndrome (AIDS).5,6 More than 80% of pulmonary-TB patients can be successfully treated with a six to nine-month drug regimen. Many factors can lead to PTB progress such as smoking, malnutrition, diabetes, poverty and absent of health awareness.7,8 In 2020, milestone of about more than 30% reduction in the absolute number of PTB deaths between 2015 and 2020.9 Al-Najaf Governorate is one of the most important holy cities in Iraq, about 180 kilometers south of Baghdad capital of Iraq and its estimated population about 1,500,000 people and it is crowded Governorate as compared with other because of highly percentage of visitors came to it from inside and outside of Iraq over the year.2 This feature may be lead to fast transmit of different pandemic diseases in population such as COVID19 and PTB.10,11 According to important features above, the main goal of this study is to detect the prevalence of numbers and percentages of PTB-patients caused by Mtb in AL-Najaf Governorate during one year to find the most important ways to avoid this deadly disease in future.\n\n\nMethods\n\nThe authors confirm that they are getting verbal agreement from Mtb-patients in this study. We confirm that we have obtained all the original approvals from Specialized Center for Chest and Respiratory Disease in AL-Najaf Governorate (23895/2019) in order to collect samples and follow up on patients and all data that related with research.\n\nThis epidemiological study has been performed under supervisor of Specialized Center for Chest and Respiratory Disease in AL-Najaf Governorate during one year from the first January to end of December 2019. In this study, two main sections have been studied; north and south section. According to seasonal variation, study was divided to four quarters as follow: quarter one include January, February and March. Quarter two; April, May and June July. Quarter three; July, August and September. Quarter four; October, November and December.\n\nSputum has been collected from all suspected patient infected with PTB as follows; fasting sputum were collected from the same patient in three days respectively, and made slide stained with Ziehl-Neelsen. Appearance of red bacilli has been considered as positive infection with Mtb.12,13\n\nGraph-Pad Prism computer software has been used to detect the numbers and percentages of PTB-patients caused by Mtb according to ages, gender and seasonal variation.14–16\n\n\nResults\n\nThe results indicated in Table 1 there were 174 PTB-patients in AL-Najaf Governorate; 89 male 51.1% and 85 female 48.9%. Out of total 174, there were 101(58%) in north section and 73(42%) in south section of the Governorate. According to age groups, Table 2 shows the age group 16-24 was the most infected with PTB that recorded 52 patients 29.9% followed by 55-64 which recorded 45 patients 25.9%.\n\nThirty eight PTB-patients have been recorded in quarter one distributed as follows: 22 patients 57.9% in north section and 16 in south section 42.1%. Age group 16-24 was the highest infected with 13 cases 34.2% while the 25-34 was the lowest which recorded 5 cases 13.2% only (Table 3). Quarter two recorded the highest numbers of PTB-patients; 33 (60%) in north section and 22 (40%) in south section. Also, the age group 16-24 was the highest infected with 17 patients 31% while the 35-44 was the lowest which recorded 6 cases 11% (Table 4). As shown in Table 5 there were 44 PTB-patients in quarter three; 23 patients 52.3% and 21 patients 47.7% has been recorded in north and south section respectively, while the age group 55-64 registered 15 infections 34.1%, on the contrary, the age group 35-44 was the lowest infected with 4 cases 9.1%. The results proved in Table 6 there were 37 PTB-patients in quarter four; 23 (62.1%) and 14 (37.9%) in north and south section of Governorate respectively, age group 16-24 recorded 11 patients 29.7% while the 25-35 registered 3 cases 8.1%.\n\n\nDiscussion\n\nAl-Najaf is a tourist governorate in Iraq, attracting millions of tourists from within Iraq and abroad annually and inhabited by a high percentage of the population. Therefore, it is necessary to study the most important epidemic diseases that may be dangerously and quickly transmitted in this type of crowded population.17,18 In this epidemiological study we divided Al-Najaf Governorate in two sections: north and south (Table 1), the results demonstrated that north section was higher than south section according to total infection in 2019, this result is may be due to the increase in the population and the large number of rural and crowded areas in north section more than south section.2,19 Also, Table 1 proved that there was approximately equal frequency in numbers of male and female infected with PTB; 89 and 85 respectively, while other researchers proved that PTB rates are significantly higher in male than in female.20–22 In this study, the equal numbers of male and female infected with PTB may be due to there have their equal involvement in society and public life.23 Therefore, man and women are vulnerable to PTB in equal percentage. Male and female have different combinations of risk factors for PTB but the main reason still not fully unclear.24 Out of five age groups, we documented in Table 2 the age group 14-26 was the highest infected with 52 patients 29.9%. We think this is dangerous indicator in young age groups and the reason may be due to low health awareness, malnutrition and hookah smoking.25,26 Martinez et al. (2017)12 recommended that focusing PTB preventive efforts on home contacts is extremely beneficial. However, beyond the family, a significant portion of transmission may occur at the communal level.27 Therefore, we must increasing health awareness among young people and holding seminars to focus on the seriousness of this deadly disease to protecting children at risk for tuberculosis transmission in communities and households should be recommended. Poor health system development, scarcity of medical care and socio-economic factors and have been linked with increased risk of PTB on individual and population levels in developing countries.28,29 These factors cannot account for the seasonality of PTB incidence, which has been seen in many parts of the world. According seasonal variation, quarter two recorded 55 cases it is the highest numbers of PTB-patients. Much research recorded a high numbers in infections in the warm seasons.30,31 Al-Najaf Governorate has hot climate in most of year with hot shiny sun, therefore, most peoples try avoiding the sun light that lead to decrease in vitamin D that support innate immune responses to Mtb.32,33 Skin is the important source for Vitamin D synthesis dependent upon sunlight exposure. The low exposure to sunlight during summer and winter could lead to vitamin D deficiency and subsequent that leads to low innate immune response and may be increase to Mtb infection.34,35\n\n\nConclusion\n\nThere were low PTB-patients numbers in AL-Najaf Governorate in 2019 but the Youngers were the most susceptible to infected. Infection in north section was higher than south section and there were no high differences between genders. Seasons have no high effect on the number of infections.\n\n\nData availability\n\nAll data has been included in this manuscript.\n\n\nRaw data of patients infected with tuberculosis/2019\n\n",
"appendix": "Acknowledgment\n\nSpecial thanks to Specialized Center for Chest and Respiratory Disease in AL-Najaf Governorate for all assistance and all information that introduced to researchers to finish this study.\n\n\nReferences\n\nPluschke G, Röltgen K: Overview: Development of Drugs Against Mycobacterium ulcerans. Mycobacterium Ulcerans. 2022; 185–187. PubMed Abstract | Publisher Full Text\n\nAljanaby AA, Al-Faham QM, Aljanaby IA, et al.: Epidemiological study of mycobacterium tuberculosis in Baghdad governorate, Iraq. Gene Reports. 2022 Mar 1; 26: 101467. Publisher Full Text\n\nDarnton-Hill I, Mandal PP, de Silva A , et al.: Opportunities to prevent and manage undernutrition to amplify efforts to end TB. Int. J. Tuberc. Lung Dis. 2022 Jan 1; 26(1): 6–11. PubMed Abstract | Publisher Full Text\n\nPezzella AT: History of pulmonary tuberculosis. Thorac. Surg. Clin. 2019 Feb 1; 29(1): 1–7. Publisher Full Text\n\nMousquer GT, Peres A, Fiegenbaum M: Pathology of TB/COVID-19 co-infection: The phantom menace. Tuberculosis. 2021 Jan 1; 126: 102020. Publisher Full Text\n\nKhawbung JL, Nath D, Chakraborty S: Drug resistant tuberculosis: a review. Comp. Immunol. Microbiol. Infect. Dis. 2021 Feb 1; 74: 101574. Publisher Full Text\n\nPeloquin CA, Davies GR: The treatment of tuberculosis. Clin. Pharmacol. Ther. 2021 Dec; 110(6): 1455–1466. Publisher Full Text\n\nAli ZA, Al-Obaidi MJ, Sameer FO, et al.: Epidemiological profile of tuberculosis in Iraq during 2011–2018. Indian J. Tuberc. 2022 Jan 1; 69(1): 27–34. PubMed Abstract | Publisher Full Text\n\nMirzayev F, Viney K, Linh NN, et al.: World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update. Eur. Respir. J. 2021 Jun 1; 57(6): 2003300. PubMed Abstract | Publisher Full Text\n\nZaheen A, Bloom BR: Tuberculosis in 2020-new approaches to a continuing global health crisis. N. Engl. J. Med. 2020 Apr 2; 382(14): e26. PubMed Abstract | Publisher Full Text\n\nVan Kerkhove MD: COVID-19 in 2022: controlling the pandemic is within our grasp. Nat. Med. 2021 Dec; 27(12): 2070. PubMed Abstract | Publisher Full Text\n\nMartinez L, Shen Y, Mupere E, et al.: Transmission of Mycobacterium tuberculosis in households and the community: a systematic review and meta-analysis. Am. J. Epidemiol. 2017 Jun 15; 185(12): 1327–1339. PubMed Abstract | Publisher Full Text\n\nAljanaby AA, Al-Faham QM, Aljanaby IA, et al.: Immunological role of cluster of differentiation 56 and cluster of differentiation 19 in patients infected with mycobacterium tuberculosis in Iraq. Gene Reports. 2022 Jan 19; 26: 101514. Publisher Full Text\n\nAljanaby AA, Aljanaby IA: Prevalence of aerobic pathogenic bacteria isolated from patients with burn infection and their antimicrobial susceptibility patterns in Al-Najaf City, Iraq-a three-year cross-sectional study. F1000Res. 2018 Jul 30; 7(1157): 1157. Publisher Full Text\n\nHasan TH, Alasedi KK, Aljanaby AA: A Comparative Study of Prevalence Antimicrobials Resistance Klebsiella pneumoniae among Different Pathogenic Bacteria Isolated from Patients with Urinary Tract Infection in Al-Najaf City, Iraq. Lat. Am. J. Pharm. 2021 Apr 1; 40(SI): 174–178.Reference Source\n\nAbdulla NY, Aljanaby IJA, Hasan TH, et al.: Assessment of ß-lactams and Carbapenems Antimicrobials Resistance in Klebsiella Oxytoca Isolated from Patients with Urinary Tract Infections in Najaf, Iraq. Arch. Razi Inst. 2022; 77(2): 669–673.\n\nAlhasnawi HM, Aljanaby AA: The immunological role of CD4 and CD8 in patients infected with Helicobacter pylori and stomach cancer. Gene Reports. 2022 Mar 1; 26: 101500. Publisher Full Text\n\nAlhasnawi HM, Aljanaby AA: Evaluation of Galectin-3 and CD19 in Helicobacter pylori patients infected with stomach cancer. Gene Reports. 2022 Jan 21; 26: 101520. Publisher Full Text\n\nSadananda G, Knoblauch AM, Andriamiadanarivo A, et al.: Latent tuberculosis infection prevalence in rural Madagascar. Trans. R. Soc. Trop. Med. Hyg. 2020 Nov 1; 114: 883–885. PubMed Abstract | Publisher Full Text\n\nMason PH, Snow K, Asugeni R, et al.: Tuberculosis and gender in the Asia-Pacific region.2017. Publisher Full Text\n\nHertz D, Schneider B:Sex differences in tuberculosis. Seminars in Immunopathology. Berlin Heidelberg:Springer;2019 Mar; (Vol. 41(No. 2): pp. 225–237). Publisher Full Text\n\nJmaa MB, Ayed HB, Koubaa M, et al.: Is there gender inequality in the epidemiological profile of tuberculosis?. La Tunisie Medicale. 2020 Mar; 98(3): 232–240. PubMed Abstract\n\nSbayi A, Arfaoui A, Janah H, et al.: Epidemiological characteristics and some risk factors of extrapulmonary tuberculosis in Larache, Morocco. Pan Afr. Med. J. 2020 Aug 31; 36(1): 381. PubMed Abstract | Publisher Full Text\n\nGopalaswamy R, Shanmugam S, Mondal R, et al.: Of tuberculosis and non-tuberculous mycobacterial infections–a comparative analysis of epidemiology, diagnosis and treatment. J. Biomed. Sci. 2020 Dec; 27(1): 74–77. PubMed Abstract | Publisher Full Text\n\nDogar O, Jawad M, Shah SK, et al.: Effect of cessation interventions on hookah smoking: post-hoc analysis of a cluster-randomized controlled trial. Nicotine Tob. Res. 2014 Jun 1; 16(6): 682–688. PubMed Abstract | Publisher Full Text\n\nChu AL, Lecca LW, Calderón RI, et al.: Smoking Cessation in Tuberculosis Patients and the Risk of Tuberculosis Infection in Child Household Contacts. Clin. Infect. Dis. 2021 Oct 15; 73(8): 1500–1506. Publisher Full Text\n\nWard JL, Azzopardi PS, Francis KL, et al.: Global, regional, and national mortality among young people aged 10–24 years, 1950–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2021 Oct 30; 398(10311): 1593–1618. PubMed Abstract | Publisher Full Text\n\nWu J, Dalal K: Tuberculosis in Asia and the pacific: the role of socioeconomic status and health system development. Int. J. Prev. Med. 2012 Jan; 3(1): 8. Free Full Text\n\nBonell A, Contamin L, Thai PQ, et al.: Does sunlight drive seasonality of TB in Vietnam? A retrospective environmental ecological study of tuberculosis seasonality in Vietnam from 2010 to 2015. BMC Infect. Dis. 2020 Dec; 20(1): 181–184. PubMed Abstract | Publisher Full Text\n\nNarula P, Sihota P, Azad S, et al.: Analyzing seasonality of tuberculosis across Indian states and union territories. J. Epidemiol. Glob. Health. 2015 Dec 1; 5(4): 337–346. PubMed Abstract | Publisher Full Text\n\nMohammed SH, Ahmed MM, Al-Mousawi AM, et al.: Seasonal behavior and forecasting trends of tuberculosis incidence in Holy Kerbala, Iraq. Int. J. Mycobacteriol. 2018 Oct 1; 7(4): 361–367. PubMed Abstract | Publisher Full Text\n\nGou X, Pan L, Tang F, et al.: The association between Vitamin D status and tuberculosis in children: a meta-analysis. Medicine. 2018 Aug; 97(35): e12179. PubMed Abstract | Publisher Full Text\n\nGanmaa D, Uyanga B, Zhou X, et al.: Vitamin D supplements for prevention of tuberculosis infection and disease. N. Engl. J. Med. 2020 Jul 23; 383(4): 359–368. PubMed Abstract | Publisher Full Text\n\nBaeke F, Takiishi T, Korf H, et al.: Vitamin D: modulator of the immune system. Curr. Opin. Pharmacol. 2010 Aug 1; 10(4): 482–496. Publisher Full Text\n\nHammami F, Koubaa M, Mejdoub Y, et al.: The association between vitamin D deficiency and extrapulmonary tuberculosis: Case-control study. Tuberculosis. 2021 Jan 1; 126: 102034. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "142258",
"date": "08 Jul 2022",
"name": "Edinson Dante Meregildo Rodriguez",
"expertise": [
"Reviewer Expertise infectious diseases",
"tropical diseases",
"tuberculosis",
"Covid-19",
"emergency medicine",
"critical care",
"chronic diseases",
"mental health",
"endocrinology",
"public health",
"systematic review",
"metanalysis"
],
"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 entire manuscript needs extensive and in-depth English language revision by a professional language-editing service. Otherwise, it should be rejected.\nAbstract\nBackground: \"pulmonary tuberculosis (PTB) is one of the most global dangerous infectious diseases worldwide...\". Comment: This sentence is redundant because global and worldwide have similar meanings. It would be better to say: \"pulmonary tuberculosis (PTB) is one of the most dangerous infectious diseases worldwide...\".\nIntroduction Please define each abbreviation when it first appears. For example, Mtb, PTB, etc.\n“The developing countries are the most infected with these types of infections”. Comment: This sentence is redundant: It would be better to say: “The developing countries are the most affected by these types of infections”.\n“Pulmonary-TB considered as the most infection caused by Mtb and can cause many dangerous complicated in the lung leads to death in many times”.\n\nComment: This expression doesn't make much sense. Please check your correctness.\n\"...the main goal of this study is to detect..\" Comment: \"...the main goal of this study was to detect...\"\n\"... they are getting verbal agreement from Mtb-patients in this study.\" Comment: It would be better to say that informed consent was obtained.\nStudy design \"This epidemiological study has been performed under supervisor of...\" Comment: \"This epidemiological study has been performed under the supervision of...\"\n\n\"Quarter two; April, May and June July.\" Comment: \"Quarter two; April, May, and June\".\nDiagnosis of Mtb in PTB-patients \"Sputum has been collected from all suspected patient...\" Comment: \"Sputum was collected from all suspected patients...\"\n\nResults: Total PTB-patients In Table 1 the authors present absolute and relative frequencies and state: \"Out of total 174, there were 101(58%) in north section and 73(42%) in south section of the Governorate.\". Comment: It would be more useful and more clinically relevant if the authors showed (in the tables) some tests for comparison of proportions (also showing a level of significance and 95% CI) to specify whether these differences between the north and the south sections are statistically significant or not.\nDiscussion The authors state: “…Table 1 proved that there was approximately equal frequency in numbers of male and female infected with PTB; 89 and 85 respectively…In this study, the equal numbers of male and female infected with PTB may be due to there have their equal involvement in society and public life”. Comment: The authors should not make such an affirmation until they have applied a test to compare proportions and have shown that there are no statistically significant differences between the groups.\nConclusion The authors state: “There were low PTB-patients numbers in AL-Najaf Governorate in 2019 but the Youngers were the most susceptible to infected”. Comment: This statement is not true. The only thing the authors could say is that tuberculosis was more frequent in this age group. This is because tuberculosis infection and active tuberculosis are different stages of the same disease1. What the researchers studied is active tuberculosis disease, but not primary infection or susceptibility to tuberculosis infection. Tuberculosis infection depends more on exogenous factors such as host exposure, while active tuberculosis depends more on endogenous factors, such as immunity 1,2,3. In addition, in low-burden countries, a higher proportion of TB cases occurs due to reactivation of a latent focus of post-primary tuberculosis (remote infection among foreign-born residents); whereas worldwide, particularly in high-burden countries, most clinical TB reflects recently transmitted infection 2,3.\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? 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? Yes\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "8486",
"date": "11 Jul 2022",
"name": "ahmed abduljabbar jaloob aljanaby",
"role": "Author Response",
"response": "Warm greetings The research was subjected to an English language review. I think the scientific content is good. I respect your opinion, whatever it is. Please mention the scientific content, not the linguistic content Thanks a lot"
}
]
},
{
"id": "149163",
"date": "12 Sep 2022",
"name": "Sarman Singh",
"expertise": [
"Reviewer Expertise Tuberculosis"
],
"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's aim is not clear.\n\nThe introduction section mentions that reduction in case numbers was a priority of the government, but without comparing the data of several years, how any trend can be forecasted?\n\nMoreover, the methodology is extremely poor. The authors, on one hand, mention that sputum processing and reporting were done as per WHO criteria but in the same section they mention that 3 consecutive fasting samples were collected and stained with ZN staining. The authors seemingly are not aware of WHO's revised policy of 2 sputa (one morning and one spot).\n\nThe total population screened is not mentioned. So how without a numerator prevalence could be calculated?\n\nLanguage is poor with numerous spelling, grammatical and syntax errors.\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": []
}
] | 1
|
https://f1000research.com/articles/11-675
|
https://f1000research.com/articles/9-1099/v1
|
07 Sep 20
|
{
"type": "Research Article",
"title": "Investigating the effect of e-cigarette use on quitting smoking in adults aged 25 years or more using the PATH study",
"authors": [
"Peter N. Lee",
"John S. Fry",
"John S. Fry"
],
"abstract": "Background: Part of the evidence on harms and benefits of e-cigarettes concerns whether using e-cigarettes encourages smokers to quit. With limited results from controlled trials, and weaknesses in much epidemiological data, we addressed this using nationally representative prospective study data, with detailed accounting for factors associated with quitting. Methods: Analyses used data for adults aged 25+ years from Waves 1 to 3 of the US PATH study. Separate analyses concerned follow-up from Waves 1 to 2, 2 to 3 and 1 to 3. The main analyses related baseline ever e-cigarette use (or e-product use at Wave 2) to having quit at follow-up, adjusting for predictors of quitting derived from 55 candidates. Sensitivity analyses omitted adults who had never used other products, linked quitting to current rather than ever e-cigarette use, used modified values of some predictors using later recorded data, or (in Wave 1 to 3 analysis only) also adjusted for quitting by Wave 2. Results: In the main analyses, unadjusted odds ratios (ORs) of quitting for ever e-cigarette use were 1.29 (95% CI 1.01-1.66), 1.52 (1.26-1.83) and 1.47 (1.19-1.82) for the Wave 1 to 2, 2 to 3, and 1 to 3 analyses. These estimates reduced after adjustment, to 1.23 (0.94-1.61), 1.51 (1.24-1.85) and 1.39 (1.11-1.74). The final models, including between six and nine predictors, always included household income, everyday/someday smoking, wanting to smoke after waking and having tried quitting, with other variables included in specific analyses. Quitting rates remained elevated in e-cigarette users in all sensitivity analyses. ORs were increased where other product users were omitted. Adjusted ORs of quitting for current e-cigarette use were 1.41 (1.06-1.89), 1.30 (1.01-1.67) and 1.56 (1.21-2.00). Conclusions: The results suggest e-cigarettes may assist adult smokers to quit, particularly in individuals not using other nicotine products, and who are current e-cigarette users.",
"keywords": [
"Cigarettes",
"Confounding",
"Over-adjustment",
"E-cigarettes",
"Cessation",
"Modelling"
],
"content": "Introduction\n\nAlthough it is believed that e-cigarettes cause far less harm to their users than do cigarettes (Nutt et al., 2014), the introduction of e-cigarettes may theoretically have various adverse and beneficial effects (Lee et al., 2019). Adverse effects would occur if the use of e-cigarettes encouraged initiation of smoking, if smokers intending to quit take up e-cigarettes instead, or if smokers take up e-cigarettes without reducing their cigarette consumption. Beneficial effects would occur if individuals who would otherwise have continued cigarette smoking switch instead to e-cigarette use, if simultaneous use of e-cigarettes helps smokers to materially reduce their cigarette consumption, or if use of e-cigarettes helps established smokers to quit. Here we present results relating to the last of these possibilities, the effect of e-cigarette use on quitting.\n\nInformation on e-cigarette use as an aid to quitting comes from various sources. Evidence from randomised controlled trials comparing smokers assigned a nicotine e-cigarette or a placebo (Baldassarri et al., 2018; Bullen et al., 2013; Caponnetto et al., 2013; Caponnetto et al., 2019; Masiero et al., 2019), comparing e-cigarettes with nicotine replacement therapy (Hajek et al., 2019; Li et al., 2020) or comparing e-cigarettes with nicotine patches (Walker et al., 2020) generally indicates higher quit rates in the nicotine e-cigarette group, but this is not always the case (Halpern et al., 2018). A non-randomised study in which smokers were offered free e-cigarettes (Hajek et al., 2015) also found that those who accepted them were more likely to quit. While such evidence avoids uncontrolled confounding, it can be argued that such trials do not fully reflect what happens in the general population, where smokers choose to try or not try e-cigarettes without being allocated them.\n\nEvidence that smoking rates have declined in the US and UK over a period where e-cigarette use has been increasing (Beard et al., 2020; West et al., 2016b; Zhu et al., 2017) is suggestive of a beneficial effect of e-cigarette use on quitting, but is limited by the difficulty of taking account of other factors affecting smoking rates.\n\nEpidemiological studies are an alternative approach, but while most of such studies show a positive relationship between e-cigarettes and smoking cessation, a recent review considered that the evidence is inconclusive due to the low quality of the research (Malas et al., 2016). Problems involve the use of cross-sectional studies, the use of unrepresentative populations, failure to limit attention to established e-cigarette users, and the failure fully to take into account the many factors associated with quitting smoking. An expert reaction (West et al., 2016a) made clear that a meta-analysis perversely claiming that e-cigarette use was associated with a reduced risk of quitting (Kalkhoran & Glantz, 2016) suffered from such weaknesses. Restricting attention to cohort studies (other than the study we analyse here), which determine e-cigarette use at baseline and quitting at follow-up, it is clear that by now there are quite a number of studies that report somewhat higher quit rates in those using e-cigarettes, (e.g. (Jackson et al., 2019; Mantey et al., 2017; Piper et al., 2019; Snow et al., 2018; Weaver et al., 2018; Young-Wolff et al., 2018; Zhuang et al., 2016), and though there are also many that did not find any clear association, (e.g. (Bowler et al., 2017; Brose et al., 2015; Chiang et al., 2019; Comiford et al., 2020; Flacco et al., 2019; Grana et al., 2014; Harrington et al., 2015; Lozano et al., 2019; Pasquereau et al., 2017; Sweet et al., 2019; Wang et al., 2017; Wu et al., 2018), it is rare to find a study (Al-Delaimy et al., 2015) suggesting that e-cigarettes inhibits quitting.\n\nHere we describe results from a prospective study aimed at avoiding such weaknesses. It is based on the Population Assessment of Tobacco and Health (PATH) study, a nationally representative cohort study of tobacco use and how it affects the health of people in the US. Wave 1 was conducted from 12 September 2013 to 15 December 2014, and our analyses are based on data for this Wave and from two annual follow-ups (Waves 2 and 3). The data files made publicly available include extensive information on use of various types of tobacco products and on numerous variables linked to initiation of tobacco. In order to avoid complexities caused by consideration of younger adults who may only recently have initiated cigarette smoking, possibly only on a temporary basis, attention is limited to adults aged 25 years or more, an age when initiation of cigarettes is less common.\n\n\nMethods\n\nSeparate sets of analyses have been conducted for three periods, from Wave 1 to Wave 2 (period 1), from Wave 2 to Wave 3 (period 2) and from Wave 1 to Wave 3 (period 3). The analyses are based on individuals with relevant data available at Waves 1, 2 and 3 on smoking and e-cigarette use, and take account of the Wave 1 person-based weights. All analyses are limited to individuals aged 25 years or over at baseline.\n\nA current cigarette smoker is a “current established cigarette user” defined as “has ever smoked a cigarette, has smoked more than 100 cigarettes in life time, and currently smokes every day or some days”, while a former cigarette smoker is a “former established cigarette user” defined as “has ever smoked a cigarette, has smoked more than 100 cigarettes in life time, and now does not smoke at all”. Those who are neither current nor former cigarette smokers are not considered in the analyses.\n\nA current e-cigarette user is a “current established e-cigarette user” defined as “has ever used an e-cigarette, has used fairly regularly and uses every day or some days”, while a former e-cigarette user is a “former established e-cigarette user” defined as “has ever used an e-cigarette, has used fairly regularly, and currently does not use at all”. An ever e-cigarette user is either a current or former e-cigarette user. At Wave 2 those who smoked other e-products (such as e-cigars, e-pipes or e-hookahs) are also included, so the definition relates to e-product rather than e-cigarette use.\n\nThe main analysis for each period relates ever e-cigarette use at baseline to the probability of quitting, with adjustment for predictor variables measured at baseline. The predictor variables have been selected from a pre-defined list of candidates classified into eight groups: demographics (A); general aspects of smoking (B); aspects of smoking specifically related to quitting (C); smoking by family and friends (D); awareness of hazards of smoking (E); health status (F); alcohol and drugs (G); and others (H).\n\nThe specific predictor variables are listed in the Results section, with fuller details of their definition given in the Extended data.\n\nWhere the baseline of the period studied is Wave 1, the values of the predictor variables used are as recorded at Wave 1. Where it is Wave 2, the values of some variables are amended to take into account data from Wave 1, as described in the Extended data.\n\nFor each period, the main analysis was conducted in seven stages, preliminary counts and six further steps, each involving weighted logistic regression analyses.\n\nCounts Restricted to individuals who were current cigarette smokers at baseline, a frequency table was prepared, separated by quitting during follow-up and e-cigarette use at baseline by each of the adjustment variables. Missing values are shown, to indicate variables with high levels of missing values requiring special consideration in analysis.\n\nStep 1 This is conducted in eight parts, each part corresponding to a group of predictor variables (A to H). For each part, the regressions first relate each predictor variable individually to quitting, with stepwise forward multiple regressions then carried out, with the most significant predictor variable introduced first, then the next most significant, and so on, until no more variable can be added that is significant at p < 0.01.\n\nStep 2 This is in three sections, each involving stepwise forward multiple regressions. The first section considers all the variables found to be significant in Step 1 from groups A, B and C, the second considers those significant from groups D, E and F, and the third those significant from groups G and H.\n\nStep 3 A final stepwise regression considers all the predictor variables remaining as significant in step 2. This generates a final list of predictors to be considered when relating ever e-cigarette use to quitting.\n\nEach analysis in steps 1 to 3 is restricted to those with non-missing data for all the predictor variables considered in the particular analysis.\n\nThe final three steps are then based on all individuals with data on all the predictor variables in the final list.\n\nStep 4 An unadjusted analysis relates ever e-cigarette use to quitting.\n\nStep 5 Stepwise regression analyses are run, introducing the predictor variables in the final list first, and then adding ever e-cigarettes as a predictor.\n\nStep 6 Stepwise regressions similar to those in step 5 are run, but introducing ever e-cigarette use first rather than last.\n\nThe main results produced by the regression analyses are the odds ratios (ORs) and 95% confidence intervals (CIs) relating to each predictor of interest, and the significance of introducing that predictor into the model.\n\nWhile the main analyses relates quitting cigarettes during follow-up to ever e-cigarette use at baseline and the predictor variables considered include use of nicotine products other than cigarettes or e-cigarettes, four sensitivity analyses (S1 to S4) were also conducted, which are intended to give additional information on how dependent the ORs derived from the main analyses are on exactly how they are conducted. These are modifications of the main analyses:\n\nS1 restricts attention to individuals who have never used other nicotine products;\n\nS2 links quitting to current (rather than ever) e-cigarette use at baseline;\n\nS3 adjusts, where necessary, for variables which take account of data recorded at the end of follow-up rather than just at baseline; and\n\nS4, which applies only to the analyses based on quitting between Waves 1 and 3, additionally adjusts for whether the individual had already quit by Wave 2.\n\nIn each of S1 to S4 the analyses run were as in steps 4 to 6 of the main analyses and used the final set of predictor variables derived for the period they related to.\n\nFor most of the 55 predictor variables considered, there were relatively few missing values, and the regressions could be run excluding the individuals with missing values for the predictors considered without material loss of power. However, for two predictors, where there were about 8% of missing values, individuals with missing data were assigned average values. Thus, for household income in the past 12 months, where data were recorded in five increasing levels, individuals recorded as unknown were assigned an income in the third level, $25,000 to $49,999, while for poverty status, where data were recorded in three levels, <100%, 100–199% and 200+% of the poverty guideline, individuals recorded as unknown were assigned a status in the second level. For living with a regular smoker who smoked inside your home during childhood, where about 16% of individuals were classified as “not ascertained” rather than “yes” or “no”, this answer was included as a separate level, thus the predictor was treated in analysis as having three levels.\n\nFor some predictors with multiple levels, the regression analyses were based on a single trend variable. This was only appropriate where the predictor variable represented increasing (or decreasing) levels of a characteristic.\n\nGenerally, the analyses were based on predictors recorded at the baseline Wave. Where the baseline Wave was Wave 2, however, and data were not available at Wave 2, Wave 1 data were used if appropriate. Also, if the Wave 2 predictor related to ever having done something, particularly when the variable concerned action in the last 12 months, individuals were counted as ever having done so if this was reported at Wave 1 or 2.\n\nFurther details of the process are given in the Extended data.\n\nRelevant data were transferred for analysis to a ROELEE database, and analysed using the ROELEE program (Release 59, Build 49). All these analyses could be run using the R-program, using the “lm” function including the “weights=” option for weighted linear regression, and for stepwise regression using the “step” function specifying “method=forward” and test=”F”.\n\n\nResults\n\nTable 1 shows the predictor variables used in the final regression analysis or excluded at various stages of the preliminary analyses.\n\na C = continuous variable, T = treated as a linear trend variable in regressions\n\nFor the analyses based on Waves 1 and 2, for example, 54 predictors were considered, 11 in group A, 8 in B, 8 in C, 4 in D, 4 in E, 8 in F, 9 in G, and 2 in H. Of the 55 predictors listed in Table 1, there was one variable in group H with no Wave 1 data. Of the 54 predictors considered in the Wave 1 and 2 analyses, 37 were excluded at step 1, marked X1 in Table 1. A further 4 were excluded at step 2 (X2). This left 13 variables considered in step 3, of which 4 were excluded (X3), with 9 included in the final model (Y).\n\nFor the analyses based on Waves 2 and 3 there were data available for 51 predictors, with 45 excluded (34 X1, 3 X2 and 8 X3) and 6 included in the final model. For those based on Waves 1 and 3 there were data on 54 predictors, with 46 excluded (35 X1, 8 X2 and 3 X3) and 8 included in the final model.\n\nTable 2 summarizes the results of the main analysis. Each analysis was based on between 6,000 and 7,000 adults with the percentage quitting varying from 9.1% to 13.1%. The unadjusted gateway-out effect varied from 1.29 to 1.52 in the three analyses. Adjustment only slightly reduced the estimates, the fully adjusted ORs being 1.23 (95%CI 0.94-1.61) for Wave 1 to 2, 1.51 (1.24-1.85) for Wave 2 to 3, and 1.39 (1.11-1.74) for Wave 1 to 3.\n\naWhere the baseline is Wave 1, the predictor is ever regular e-cigarette use, where it is Wave 2, it is ever regular e-product use\n\nTable 3 shows the full models used, showing the effect estimates for each of the predictor variables used to adjust the relationship of ever regular e-cigarette use to quitting. Where the same adjustment variable was included in each model, the effect estimates were generally quite similar and always in the same direction. As regards aspects of smoking, smokers were found to be less likely to quit if they were everyday smokers, were more likely to smoke right after waking up, had not previously tried to quit, smoked more cigarettes per day, lived in a home with more relaxed rules about smoking, lived with a smoker in childhood, had a better opinion of tobacco, or had a lesser perception of cigarettes as harmful. Interestingly, they were also less likely to quit if they had ever used pharmaceutical aids for quitting, i.e. Chantix, varenicline or bupropion (Wellbutrin, Zyban). Smokers were also less likely to quit if they were worse off and worse educated. Higher age (particularly above age 74 years) and higher BMI were also associated with a greater likelihood to quit.\n\nTable 4 summarises the results of the sensitivity analyses, showing the estimated ORs in each case from the fully adjusted analysis. The first line of results (“Main model”) repeats the estimates shown in Table 3.\n\nN = total number quitting\n\nn = number of quitters among e-cigarette users (current users in sensitivity analysis 2, ever users otherwise)\n\nSensitivity analysis 1 excludes those who had ever used other nicotine products. The number of quitters is substantially reduced, as is the number using e-cigarettes (or e-products). However, the OR is increased, with ever regular users of e-cigarettes about twice as likely to quit cigarettes by the end of the follow-up period, though the confidence limits of the ORs are relatively wide.\n\nIn sensitivity analysis 2, quitting is linked to current rather than ever e-cigarette use. Here the ORs tend to be somewhat higher than in the main analysis (though not for the Wave 2 to 3 analysis).\n\nThe results for both sensitivity analyses 1 and 2 seem consistent with smokers being more likely to quit if, at baseline, e-cigarettes formed a more important part of the total tobacco use.\n\nSensitivity analysis 3 adjusts, where necessary, for variables which are modified to take account of data recorded at the end of follow-up, and not just at baseline, in an attempt to minimize “residual confounding”. The ORs were quite similar to those in the main analysis for Wave 1 to 2, or Wave 1 to 3 quitting, but were somewhat increased for Wave 2 to 3 quitting.\n\nSensitivity analysis 4, only applicable to the Wave 1 to 3 quitting analyses, adjusted also for having quit by Wave 2. This slightly increased the estimate from the main analysis.\n\nThis report summarizes evidence from Waves 1, 2 and 3 of the US PATH study relating to the possibility that e-cigarette use may increase the likelihood of smokers quitting cigarettes. All of the adjusted ORs estimated, which (as shown in Table 4) varied between 1.20 and 2.22, were consistent with this possibility, although not all the estimates were statistically significant at p < 0.05. Compared to the estimates from the main model, which related ever e-cigarette use at baseline to quitting by follow-up, ORs were increased (though based on far fewer quitters) when those who had ever used other products were omitted from the analysis. The ORs were also increased, in the analysis with Wave 1 as the baseline, when quitting was linked to current rather than ever e-cigarette use. In both the sensitivity analyses where the ORs were increased, e-cigarette use would have formed a greater proportion of current tobacco use at baseline.\n\nOther related analyses based on the PATH study have previously been published, all of which are consistent with e-cigarette use increasing the probability of quitting cigarettes.\n\nAn analysis of 3,093 quit attempters based on adult data from Waves 1 and 2 (Benmarhnia et al., 2018) considered two endpoints – abstinence from smoking for at least 30 days and reduced cigarette consumption – and reported a significant increase in both endpoints related to using e-cigarettes to quit during the previous year, but no significant increase in either endpoint related to the use of approved pharmaceutical aids.\n\nAnother analysis based on Waves 1 and 2 (Berry et al., 2019), here limiting attention to adults aged 25 years or more, studied factors related to 30-day cigarette cessation and to at least a 50% reduction in cigarette consumption in multivariable logistic regression analyses, which included a number of the variables included as predictors in our analyses. While the model included e-cigarette use, this was defined not at baseline, but as new e-cigarette use at Wave 2. In this analysis large ORs were reported for everyday e-cigarette use both for cessation (7.88, 95% CI 4.45-13.95) and for 50% reduction in cigarette consumption (5.70, 3.47-9.35).\n\nA further analysis based on Waves 1 and 2 (Verplaetse et al., 2019) considered adults aged 18+ years and reported that, compared to those who had never used e-cigarettes at Wave 1, quitting was increased in Wave 1 daily users (OR 1.56. 95%CI 1.12-2.18) but not in Wave 1 nondaily users (0.83, 0.68-1.02). Age, race and education were the only adjustment variables considered.\n\nAnalyses based on data from Waves 1, 2 and 3 (Watkins et al., 2020), conducted separately for adults aged 18–24 years and 25+ years, studied the relation of a variety of cessation strategies to short-term cessation (quit at Wave 2) and long-term cessation (quit at both Waves 2 and 3). Adjustments were made for a range of covariates. The authors reported that “substitution with e-cigarettes” did not predict long-term cessation but predicted short-term cessation for older daily smokers of 5 or more cigarettes a day.\n\nAn analysis based on data for adults from Waves 1, 2 and 3 (Kalkhoran et al., 2020), related current e-cigarette use at Wave 1 (defined as daily, non-daily or none) in cigarette smokers at Wave 1 to three cigarette abstinence endpoints: at Wave 2, at Wave 3 or at Waves 2 and 3 (prolonged abstinence). Adjustments were made for a fixed set of variables: age, sex, race/ethnicity, education, income, cigarettes per day, and having a first cigarette within 30 minutes of waking. Non-daily e-cigarette use was only associated with a small, non-significant increase in each of the abstinence endpoints, but daily e-cigarette use was associated with a clear increase in all three endpoints, with adjusted ORs of 1.53 (95%CI 1.04-2.23) for Wave 2 abstinence, 1.57 (1.12-2.21) for Wave 3 abstinence, and 1.77 (1.08-2.89). These results particularly seem quite similar to ours.\n\nStrengths of our work include the use of a prospective study design based on a study population representative of the US, and analyses which take account of a very large number of other predictors of quitting, and restrict attention to established e-cigarette use.\n\nLimitations relate to the relatively small number of quitters, leading to the decision not to study heterogeneity of the results by basic variables, such as sex, race or age group. Our decision to limit attention to those aged at least 25 years was based on the desire not to include young smokers whose smoking habits were not well established. We have also not studied persistent quitting, by relating Wave 1 e-cigarette use to quitting at both Waves 2 and 3. As our analyses were based on a pre-defined plan, and as data from Wave 4 are now available, we plan to address these issues in a further paper. This might, for example, relate Wave 1 e-cigarette use simultaneously to quitting at all subsequent waves, separating those who quit at all three waves, or at only one or two.\n\nFor the present, our results clearly suggest that among adults aged 25 years or more, most of whom would not have initiated smoking recently, e-cigarettes may assist in helping smokers to quit, particularly if, at baseline, e-cigarettes form an important part of total tobacco use – i.e. for individuals who at baseline did not use products other than cigarettes or e-cigarettes, and who were current rather than ever e-cigarette users.\n\nNational Addiction & HIV Data Archive Program: Population Assessment of Tobacco and Health (PATH) Study [United States] Public-Use Files (ICPSR 36498), https://doi.org/10.3886/ICPSR36498.v8 (United States Department of Health and Human Services (USDHHS), 2018).\n\nThe data are available under the Terms of Use as set out by ICPSR, which can be accessed when users start the process of downloading the data.\n\nOpen Science Framework: Investigating the effect of e-cigarette use on quitting smoking in adults aged 25 or more using the PATH study https://doi.org/10.17605/OSF.IO/F4WA7 (Lee & Fry, 2020).\n\nThis project contains the following extended data file:\n\nAdditional file_fuller details regarding the predictor variables used.docx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "Acknowledgements\n\nWe thank Esther Afolalu for assistance in acquiring the data from the PATH study, and Zheng Sponsiello-Wang and Christelle Chrea for providing technical comments at various stages. We also thank Jan Hamling for assistance in running the analyses, and Yvonne Cooper and Diana Morris for typing the various drafts of the paper.\n\n\nReferences\n\nAl-Delaimy WK, Myers MG, Leas EC, et al.: E-cigarette use in the past and quitting behavior in the future: a population-based study. Am J Public Health. 2015; 105(6): 1213–1219. Erratum appears in Am J Public Health. 2015 Sep;105(9):e7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaldassarri SR, Bernstein SL, Chupp GL, et al.: Electronic cigarettes for adults with tobacco dependence enrolled in a tobacco treatment program: A pilot study. Addict Behav. 2018; 80: 1–5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBeard E, West R, Michie S, et al.: Association of prevalence of electronic cigarette use with smoking cessation and cigarette consumption in England: a time-series analysis between 2006 and 2017. Addiction. 2020; 115(5): 961–974. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBenmarhnia T, Pierce JP, Leas E, et al.: Can e-cigarettes and pharmaceutical aids increase smoking cessation and reduce cigarette consumption? Findings from a nationally representative cohort of American smokers. Am J Epidemiol. 2018; 187(11): 2397–2404. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBerry KM, Reynolds LM, Collins JM, et al.: E-cigarette initiation and associated changes in smoking cessation and reduction: the Population Assessment of Tobacco and Health Study, 2013-2015. Tob Control. 2019; 28(1): 42–49. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBowler RP, Hansel NN, Jacobson S, et al.: Electronic cigarette use in US adults at risk for or with COPD: Analysis from two observational cohorts. J Gen Intern Med. 2017; 32(12): 1315–1322. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBrose LS, Hitchman SC, Brown J, et al.: Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction. 2015; 110(7): 1160–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBullen C, Howe C, Laugesen M, et al.: Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013; 382(9905): 1629–37. PubMed Abstract | Publisher Full Text\n\nCaponnetto P, Campagna D, Cibella F, et al.: EffiCiency and safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013; 8(6): e66317. Erratum appears in PLoS One. 2014;9(1)PLoS One. 2014;9(1). doi:10.1371/annotation/e12c22d3-a42b-455d-9100-6c7ee45d58d0. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCaponnetto P, DiPiazza J, Cappello GC, et al.: Multimodal smoking cessation in a real-life setting: Combining motivational interviewing with official therapy and reduced risk products. Tob Use Insights. 2019; 12: 1179173x19878435. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChiang SC, Abroms LC, Cleary SD, et al.: E-cigarettes and smoking cessation: a prospective study of a national sample of pregnant smokers. BMC Public Health. 2019; 19(1): 964. PubMed Abstract | Publisher Full Text | Free Full Text\n\nComiford AL, Rhoades DA, Spicer P, et al.: Impact of e-cigarette use among a cohort of American Indian cigarette smokers: associations with cigarette smoking cessation and cigarette consumption. Tob Control. 2020; tobaccocontrol-2019-055338. PubMed Abstract | Publisher Full Text\n\nFlacco ME, Ferrante M, Fiore M, et al.: Cohort study of electronic cigarette use: safety and effectiveness after 4 years of follow-up. Eur Rev Med Pharmacol Sci. 2019; 23(1): 402–412. PubMed Abstract | Publisher Full Text\n\nGrana RA, Popova L, Ling PM: A longitudinal analysis of electronic cigarette use and smoking cessation. JAMA Intern Med. 2014; 174(5): 812–3. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHajek P, Corbin L, Ladmore D, et al.: Adding e-cigarettes to specialist stop-smoking treatment: City of London Pilot Project. J Addict Res Ther. 2015; 6: 244. Publisher Full Text\n\nHajek P, Phillips-Waller A, Przulj D, et al.: A randomized trial of E-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019; 380(7): 629–637. PubMed Abstract | Publisher Full Text\n\nHalpern SD, Harhay MO, Saulsgiver K, et al.: A pragmatic trial of E-cigarettes, incentives, and drugs for smoking cessation. N Engl J Med. 2018; 378(24): 2302–2310. PubMed Abstract | Publisher Full Text\n\nHarrington KF, Cheong J, Hendricks S, et al.: E-cigarette and traditional cigarette use among smokers during hospitalization and 6 months later. Cancer Epidemiol Biomarkers Prev. 2015; 24(4): 762. Reference Source\n\nJackson SE, Kotz D, West R, et al.: Moderators of real-world effectiveness of smoking cessation aids: a population study. Addiction. 2019; 114(9): 1627–1638. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKalkhoran S, Chang Y, Rigotti NA: Electronic Cigarette Use and Cigarette Abstinence Over 2 Years Among U.S. Smokers in the Population Assessment of Tobacco and Health Study. Nicotine Tob Res. 2020; 22(5): 728–733. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKalkhoran S, Glantz SA: E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med. 2016; 4(2): 116–28. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee PN, Coombs KJ, Afolalu EF: Considerations related to vaping as a possible gateway into cigarette smoking: an analytical review [version 3; peer review: 2 approved]. F1000Res. 2019; 7: 1915. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee PN, Fry, JS: Investigating the effect of e-cigarette use on quitting smoking in adults aged 25 or more using the PATH study. F1000Res. Pending submission to F1000Research. 2020. Publisher Full Text\n\nLi J, Hajek P, Pesola F, et al.: Cost-effectiveness of e-cigarettes compared with nicotine replacement therapy in stop smoking services in England (TEC study): a randomized controlled trial. Addiction. 2020; 115(3): 507–517. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLozano P, Arillo-Santillán E, Barrientos-Gutiérrez I, et al.: E-cigarette use and its association with smoking reduction and cessation intentions among Mexican smokers. (Uso de cigarros electrónicos y su asociación con la reducción en el consumo de cigarros convencionales y la intencion de dejar de fumar entre fumadores mexicanos). Salud Publica Mex. 2019; 61(3): 276–285. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMalas M, van der Tempel J, Schwartz R, et al.: Electronic cigarettes for smoking cessation: A systematic review. Nicotine Tob Res. 2016; 18(10): 1926–1936. PubMed Abstract | Publisher Full Text\n\nMantey DS, Cooper MR, Loukas A, et al.: E-cigarette use and cigarette smoking cessation among Texas college students. Am J Health Behav. 2017; 41(6): 750–759. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMasiero M, Lucchiari C, Mazzocco K, et al.: E-cigarettes may support smokers with high smoking-related risk awareness to stop smoking in the short run: Preliminary results by randomized controlled trial. Nicotine Tob Res. 2019; 21(1): 119–126. Corrigendum appears in Nicotine Tob Res. 2020 Apr 17;22(4):594-595. PubMed Abstract | Publisher Full Text\n\nNutt DJ, Phillips LD, Balfour D, et al.: Estimating the harms of nicotine-containing products using the MCDA approach. Eur Addict Res.2014; 20(5): 218–225. PubMed Abstract | Publisher Full Text\n\nPasquereau A, Guignard R, Andler R, et al.: Electronic cigarettes, quit attempts and smoking cessation: a 6-month follow-up. Addiction. 2017; 112(9): 1620–1628. PubMed Abstract | Publisher Full Text\n\nPiper ME, Baker TB, Benowitz NL, et al.: Changes in use patterns over 1 year among smokers and dual users of combustible and electronic cigarettes. Nicotine Tob Res. 2019; 22(5): 672–680. Corrigendum appears in Nicotine & Tobacco Research, ntz164, https://doi.org/10.1093/ntr/ntz164. PubMed Abstract | Publisher Full Text\n\nSnow E, Johnson T, Ossip DJ, et al.: Does e-cigarette use at baseline influence smoking cessation rates among 2-year college students? J Smok Cessat. 2018; 13(2): 110–120. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSweet L, Brasky Theodore M, Cooper Sarah, et al.: Quitting behaviors among dual cigarette and e-cigarette users and cigarette smokers enrolled in the tobacco user adult cohort. Nicotine Tob Res. 2019; 21(3): 278–284. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUnited States Department of Health and Human Services (USDHHS): Population assessment of tobacco and health (PATH) Study [United States] Public-Use Files (ICPSR 36498-V8). 2018. Reference Source\n\nVerplaetse TL, Moore KE, Pittman BP, et al.: Intersection of e-cigarette use and gender on transitions in cigarette smoking status: Findings across Waves 1 and 2 of the Population Assessment of Tobacco and Health Study. Nicotine Tob. Res. 2019; 21(10): 1423–1428. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWalker N, Parag V, Verbiest M, et al.: Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial. Lancet Respir Med. 2020; 8(1): 54–64. PubMed Abstract | Publisher Full Text\n\nWang MP, Li WH, Wu Y, et al.: Electronic cigarette use is not associated with quitting of conventional cigarettes in youth smokers. Pediatr Res. 2017; 82(1): 14–18. PubMed Abstract | Publisher Full Text\n\nWatkins SL, Thrul J, Max W, et al.: Real-world effectiveness of smoking cessation strategies for young and older adults: Findings from a nationally representative cohort. Nicotine Tob Res. 2020; 22(9): 1560–1568. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWeaver SR, Huang J, Pechacek TF, et al.: Are electronic nicotine delivery systems helping cigarette smokers quit? Evidence from a prospective cohort study of U.S. adult smokers, 2015-2016. PLoS One. 2018; 13(7): e0198047. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWest R, Bauld L, O'Connor R, et al.: Expert reaction to meta-analysis looking at e-cigarette use and smoking cessation. 2016a. Reference Source\n\nWest R, Shahab L, Brown J: Estimating the population impact of e-cigarettes on smoking cessation in England. Addiction. 2016b; 111(6): 1118–9. PubMed Abstract | Publisher Full Text\n\nWu SYd, Wang MP, Li WH, et al.: Does electronic cigarette use predict abstinence from conventional cigarettes among smokers in Hong Kong? Int J Environ Res Public Health. 2018; 15(3): 400. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYoung-Wolff KC, Klebaner D, Folck B, et al.: Documentation of e-cigarette use and associations with smoking from 2012 to 2015 in an integrated healthcare delivery system. Prev Med. 2018; 109: 113–118. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhu SH, Zhuang YL, Wong S, et al.: E-cigarette use and associated changes in population smoking cessation: evidence from US current population surveys. BMJ. 2017; 358: j3262. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhuang YL, Cummins SE, Sun YJ, et al.: Long-term e-cigarette use and smoking cessation: a longitudinal study with US population. Tob Control. 2016; 25(Suppl 1): i90–i95. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "70981",
"date": "14 Sep 2020",
"name": "Ruifeng Chen",
"expertise": [
"Reviewer Expertise Behavioral Epidemiology",
"with a major focus on tobacco use behavior."
],
"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\nIn the background of the abstract, the authors state that their goal is to address the research question whether e-cigarettes encourage smokers to quit using a quality nationally representative cohort study from the United States.\nThe introduction presents a somewhat limited review of the literature. In the discussion of the randomized trials the authors infer that these trials reached statistically significant findings where e-cigarettes were favored. This is a misrepresentation of the literature.\nThe authors note the following problems that have been identified with observational studies addressing the target research question: studies in which the exposure measure does not precede the outcome measure (as happens in cross-sectional studies), the use of non-representative populations, and failure to fully account for the many potential confounding factors. While these are appropriate criticisms of some of the literature, they are far from complete. For example, in 2018, the US National Academies of Science, Engineering and Medicine put out a major report on e-cigarettes where they expressed concern about the quality of some of the papers addressing whether these products were cessation aids: In addition to these three concerns, this report noted the importance of the study focusing on quit attempts with a comparable control group – this issue has been highlighted in the 2019 paper by Pierce et al. in Nicotine and Tobacco Research1. This analysis showed that the likelihood of a quit attempt was much higher in e-cigarette users in the PATH study (many who started using e-cigarettes did so because they were trying to quit) than in was in the control population. Thus, the higher probability of making a quit attempt could explain the difference in smoking cessation and so the difference should not be attributed to the use of e-cigarettes.\nHowever, the authors go further and argue “Problems involve the …failure to limit attention to established e-cigarette users,” (Para 4 introduction). It is not clear what the authors mean by this? Do they mean that the study population need to have developed a consistent pattern of dual use of cigarettes and e-cigarettes? What is their justification for such a limitation when addressing the stated research question? It is apparent that they do not place such a limitation on their own analyses.\n\nIndeed, the authors have not laid out specific research questions or hypotheses that guide the analyses that they undertake in this paper. This is an important omission.\nIn the methods, the authors state that analyses are based on individuals with relevant data available at Waves 1, 2 and 3 on smoking and e-cigarette use. They do not mention that the population needed to have made a recent quit attempt. As noted above, unless they demonstrate that the populations that they choose are comparable on this variable, then their study is confounded.\nThe methods are not at all clear about the outcome measure used in this analysis. In their section outlining their main analyses, the authors use the term “quitting during follow-up”. What does this mean? A logical interpretation is that a quit attempt was made in the year prior to the follow-up survey. However, the authors have not addressed the quit attempt data in the methods. Do they use a point prevalence of former smoking at the follow-up survey? If so, how can this be described as successful smoking cessation? This is one of the most critical points in the paper. Most other papers discussing successful quitting require abstinence for either 6 of 12 months at follow-up (see, Gilpin et al. 19972). This is particularly important in an observational study when a person quit at follow-up could have quit only for the day before the survey, for example.\nThe potential confounders in this analysis include those variables that are associated with use of e-cigarettes as well as variables that are associated with successful cessation. The authors omit any discussion of variables associated with the probability of a smoker using an e-cigarette, thus seriously confounding their analyses. At least in a supplement, there should be a summary table of these predictors outlining how they are associated with e-cigarette use.\nAnalytic Plan: The analysis plan lays out a stepwise forward selection logistic regression, adjusted for selected covariates. What is unclear is how the authors use step 5 & 6 of their analytic plan in drawing their inferences.\nThere is a problem with the use of study weights. For their Wave 2 to Wave 3 analysis, it would seem that the appropriate weights would be the Wave 2 weights,\nA figure laying out the different analyses with samples sizes (including loss to follow-up) would be very helpful to the reader.\nResults: The unadjusted quitting rates by ever use of e-cigarettes should be presented a in table in the results section.\nAlso, the authors should report the percentage of subjects excluded in the multiple regressions.\nAny reworking of this manuscript should discuss the four recent analyses that address e-cigarettes and smoking using the PATH data. All these papers use appropriate analytic procedures and arrive at opposite conclusions to those of the authors3 - 6.\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? 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? No",
"responses": [
{
"c_id": "5993",
"date": "05 Oct 2020",
"name": "Peter Lee",
"role": "Author Response",
"response": "We thank the reviewers for their comments which we attempt to answer in detail below. Please note that, as advised by the journal, our proposed changes to the paper have not, at this stage, been made, pending comments from other reviewers on our paper. Please also note that, as explained in more detail below, some of the points raised by the reviewers will be dealt with more fully in a further paper we are currently preparing based on data from Waves 1 to 4, as mentioned in the penultimate paragraph of the conclusions section. As will be evident, the reviewers original comments are in normal type and our replies and suggested changes to the paper are in bold. We hope that our reply and the changes will affect the reviewers’ opinion of our work. In the background of the abstract, the authors state that their goal is to address the research question whether e-cigarettes encourage smokers to quit using a quality nationally representative cohort study from the United States. The introduction presents a somewhat limited review of the literature. The introduction was never intended to be a fully detailed and comprehensive review of the extensive literature relating e-cigarettes to quitting, the main purpose of the paper being to describe the results of our own analyses. Nevertheless the introduction includes as many as 39 references, and we feel gives a relatively succinct summary of the findings from the literature available at the time of writing. In the discussion of the randomized trials the authors infer that these trials reached statistically significant findings where e-cigarettes were favored. This is a misrepresentation of the literature. We made no reference to statistical significance and had not intended to imply this. We were merely summarizing the direction of the differences reported in the papers cited, virtually all of which indicated a higher quit rate in the nicotine e-cigarette group. However to avoid confusion, the second sentence of the second paragraph of the discussion will be amended so that it ends ‘…generally indicates higher quit rates in the nicotine e-cigarette group, although not all the differences cited were statistically significant (at p<0.05), and one study did not find such higher quit rates (Halpern et al., 2018).’The authors note the following problems that have been identified with observational studies addressing the target research question: studies in which the exposure measure does not precede the outcome measure (as happens in cross-sectional studies), the use of non-representative populations, and failure to fully account for the many potential confounding factors. While these are appropriate criticisms of some of the literature, they are far from complete. For example, in 2018, the US National Academies of Science, Engineering and Medicine put out a major report on e-cigarettes where they expressed concern about the quality of some of the papers addressing whether these products were cessation aids: We had already stated in the first sentence of paragraph 4 of the discussion that’…a recent review considered the evidence is inconclusive due to the low quality of the research’ citing Malas et al. (2016). We will amend this to start ‘…recent reviews have considered the evidence…’ and additionally cite the reference to the major report in 2018 that the reviewers mention. In addition to these three concerns, this report noted the importance of the study focusing on quit attempts with a comparable control group – this issue has been highlighted in the 2019 paper by Pierce et al. in Nicotine and Tobacco Research1. In the second sentence of paragraph 4 of the discussion we will add ‘the use of non-comparable control groups’ after ‘the use of unrepresentative populations’. This analysis showed that the likelihood of a quit attempt was much higher in e-cigarette users in the PATH study (many who started using e-cigarettes did so because they were trying to quit) than it was in the control population. Thus, the higher probability of making a quit attempt could explain the difference in smoking cessation and so the difference should not be attributed to the use of e-cigarettes. We already do adjust for aspects of smoking related to quitting in our analyses, as shown in Tables 1 and 3.However, the authors go further and argue “Problems involve the …failure to limit attention to established e-cigarette users,” (Para 4 introduction). It is not clear what the authors mean by this? Do they mean that the study population need to have developed a consistent pattern of dual use of cigarettes and e-cigarettes? What is their justification for such a limitation when addressing the stated research question? It is apparent that they do not place such a limitation on their own analyses. It does not seem sensible to include among e-cigarette users those who have in the past tried them once or twice and abandoned them as they did not like them. The reviewers state that we did not limit attention to established users. This is untrue; that we do limit attention to established users is very clearly stated in the third paragraph of the methods section. Indeed, the authors have not laid out specific research questions or hypotheses that guide the analyses that they undertake in this paper. This is an important omission. In the introduction, the first sentence of the final paragraph is ‘Here we describe results from a prospective study aimed at avoiding such weaknesses.’ which might be regarded as a statement of our objectives. However we will insert a sentence after this to read: ‘The main objective of our analyses is to quantify the relationship between e-cigarette use in smokers and subsequent cessation of smoking, with detailed adjustment for the multitude of factors that may differ between e-cigarette users and non-users.’ We will also amend the next sentence to start ‘Our analyses are based on’ rather than ‘It is based on…’.In the methods, the authors state that analyses are based on individuals with relevant data available at Waves 1, 2 and 3 on smoking and e-cigarette use. They do not mention that the population needed to have made a recent quit attempt. As noted above, unless they demonstrate that the populations that they choose are comparable on this variable, then their study is confounded. We did not say that the population needed to have made a recent quit attempt, as this was not a requirement in our study, and indeed was not a requirement of a number of the other studies we had cited in our discussion (Berry et al., 2019; Kalkhoran et al., 2019; Verplaetse et al., 2019), though it was in others (Benmarhnia et al., 2018; Watkins et al., 2019). Those who used e-cigarettes at baseline may not at that time have used them intending to quit, but may have found during follow-up that they could meet their nicotine needs without smoking cigarettes. Our analyses compared quit rates between e-cigarette users and non-users to try to answer the simpler, and highly relevant, question ‘are e-cigarette users more likely to quit?’ We prefer to present results based on the whole population of baseline smokers, thus using a larger sample size than if we restricted attention to quit attempters, and to try to avoid bias by taking into account a range of predictor variables related to quitting. However we will add a second paragraph in the methods section as follows. ‘Some studies of data from Waves 1 to 3 of the PATH study (Benmarhnia et al., 2018; Pierce et al., 2020a; Watkins et al., 2019) have limited analyses to quit attempters, but others (Berry et al., 2019; Kalkhoran et al., 2019; Verplaetse et al., 2019) have not. Although such a limitation more closely mimics randomized control trials (Pierce et al., 2020b) we prefer not to do so, and to avoid bias by adjusting for aspects of quitting in analyses. Our approach uses a larger sample size and provides results that are more representative of the whole population of baseline smokers’. As already noted, we intend to carry out some additional analyses limited to quit attempters in the paper being prepared based on data from Waves 1 to 4, though we do note for the reviewers’ information that a preliminary analysis we conducted, based on data from Waves 1 and 2 and limiting attention to those who at Wave 2 had ever made a quit attempt, produced an adjusted odds ratio of 1.20 (95%CI 0.91-1.57) which is very similar to the estimate we give in Table 2 of our paper of 1.23 (0.94-1.61). The methods are not at all clear about the outcome measure used in this analysis. In their section outlining their main analyses, the authors use the term “quitting during follow-up”. What does this mean? A logical interpretation is that a quit attempt was made in the year prior to the follow-up survey. However, the authors have not addressed the quit attempt data in the methods. Do they use a point prevalence of former smoking at the follow-up survey? If so, how can this be described as successful smoking cessation? This is one of the most critical points in the paper. Most other papers discussing successful quitting require abstinence for either 6 of 12 months at follow-up (see, Gilpin et al. 19972). This is particularly important in an observational study when a person quit at follow-up could have quit only for the day before the survey, for example.We certainly thought that we had made it clear enough in the methods that we were defining smoking status as at each Wave, and defining quitting based on being a current established smoker at baseline and a former established smoker at follow-up. While we agree that some former smokers may only have quit for a relatively short time, we believe that our method still provides meaningful results. However, we will extend the first sentence of the old fourth paragraph of the methods to read‘The main analysis for each period relates ever e-cigarette use at baseline to the probability of being an established former smoker at follow-up (referred to subsequently as either “quitting” or “quitting during follow-up”), with adjustment for predictor variables measured at baseline.’ Again, for the reviewers’ information, we repeated our Wave 1 to 2 analysis, redefining quitting as having quit for at least 30 days. This produced an adjusted estimate of 1.26 (95%CI 0.93-1.70) which is very similar to the estimate we give in Table 2 of our paper of 1.23 (0.94-1.61).The potential confounders in this analysis include those variables that are associated with use of e-cigarettes as well as variables that are associated with successful cessation. The authors omit any discussion of variables associated with the probability of a smoker using an e-cigarette, thus seriously confounding their analyses. At least in a supplement, there should be a summary table of these predictors outlining how they are associated with e-cigarette use. We will extend the fifth paragraph of the methods section to read as follows: ‘The specific predictor variables are listed in the Results section, with fuller details of their definition given in the Extended data. While the variables were chosen as being suggested by the literature as being related to smoking, the Extended data also provides information, based on Wave 1, of their association with ever e-cigarette use. As shown there, ever use was highly significantly (p < 0.001) more frequent in the young and in females, and after adjustment for age and sex, was also highly significantly related to a range of the predictor variables considered, being less frequent in Hispanics and Blacks, and more frequent in those with more income or education, those who ever use other tobacco products, those who have a perceived greater need for tobacco, those who have tried to quit more often, those who plan to quit, those who find it hard to stop smoking and those who have used quitting aids. Users were also clearly more likely to have significant problems more recently with sleeping, anxiety and distress, to see a doctor more often, to use the internet often, and to use various different types of drugs (but not cocaine or crack). At most weak relationships were seen with smoking by family and friends, awareness of the hazards of smoking, use of alcohol, body mass index, or self-perception of physical health or quality of life. Little relationship was also seen between ever e-cigarette use and daily cigarette consumption, a finding which was reported earlier (Lee et al., 2020), where it was suggested that it was explained by smokers taking up e-cigarettes having higher consumption initially, reduced by partial replacement of cigarettes by e-cigarettes.’ We will also, in due course, add to the Extended data a section describing and presenting the output from which the above results are summarized.Analytic Plan: The analysis plan lays out a stepwise forward selection logistic regression, adjusted for selected covariates. What is unclear is how the authors use step 5 & 6 of their analytic plan in drawing their inferences. Our inferences are drawn from the results of the step 5 and 6 analyses which, reassuringly, produced the same models. The results in Table 2 compare unadjusted odds ratios with those adjusted for the final (step 5/6) models shown in Table 3. There is a problem with the use of study weights. For their Wave 2 to Wave 3 analysis, it would seem that the appropriate weights would be the Wave 2 weights, In fact we did use Wave 2 weights for the Wave 2 to Wave 3 analysis. We will correct the end of the second sentence of the first paragraph of the Methods section to read ‘, and take account of the person-based weights of the baseline population’. A figure laying out the different analyses with samples sizes (including loss to follow-up) would be very helpful to the reader. Results: The unadjusted quitting rates by ever use of e-cigarettes should be presented in a table in the results section. Also, the authors should report the percentage of subjects excluded in the multiple regressions. We already present in Tables 1 and 2 sample sizes in each of the main analyses. We will add information on the proportion of the baseline population that were not followed up, but do not think that this merits a figure. We will also extend Table 2 to include additional lines to cover the other points made by the reviewers. Thus the revised tables will start with the following lines:Table 1.Table 2.Any reworking of this manuscript should discuss the four recent analyses that address e-cigarettes and smoking using the PATH data. All these papers use appropriate analytic procedures and arrive at opposite conclusions to those of the authors3 - 6. Of the four references which the reviewers cite, two (Dai and Leventhal, 2019; Everard et al., 2020) relate to relapse, which is outside the scope of the paper, and not quitting, and one of these (Dai and Leventhal, 2019) in any case states that ‘Baseline e-cigarette use was not associated with smoking relapse at follow-up after covariate adjustment.’ We do not propose to cite these two references, as our paper concerns quitting. One of the other two references the reviewers cite (Pierce et al., 2020a), not published at the time our paper was prepared, describes analyses based on Waves 1 to 3 of the PATH study. We have, in the discussion in paragraphs 3 to 7, already summarized findings from five other analyses based on the PATH study which are consistent with e-cigarette use increasing the probability of quitting cigarettes. To take into account this paper, and to provide further detail in the discussion, we propose to make the following two changes. First, we will extend the second paragraph of the discussion to read as follows: ‘Six other related analyses based on the first three Waves 1 of the PATH study have previously been published. The first five analyses summarized below (Benmarhnia et al., 2018; Berry et al., 2019; Kalkhoran et al., 2019; Verplaetse et al., 2019; Watkins et al., 2019) are consistent with e-cigarette use increasing the probability of quitting cigarettes, despite variation in whether Wave 3 data has been used or not, whether analyses are restricted to those attempting quitting at baseline, the definition of abstinence used, the confounding variables adjusted for, and other analytical details. However, the final analysis (Pierce et al., 2020a) only reported a small and non-significant increase in quitting related to e-cigarette use.’ Second, we will add a new paragraph about the latest study at the end of the paragraphs describing the results of the first five analyses as follows: ‘A third analysis based on data from Waves 1, 2 and 3 (Pierce et al., 2020a) restricted attention to adult (ages 18+) smokers identified at Wave 1 who reported a quit attempt before Wave 2 and completed Wave 3. 12 month abstinence at Wave 3 among e-cigarette users was slightly but non-significantly reduced as compared both to users of pharmacotherapy to quit or no product.’ The other reference cited by the reviewers (Chen et al., 2020) refers to analyses based on Waves 1 to 4 of the PATH study. Partly because our analyses relate to Waves 1 to 3, and partly because we are currently developing analyses based on Waves 1 to 4 for a further publication, we strongly prefer not to consider analyses that include Wave 4 data in our discussion. We will also add two extra sentences at the end of the penultimate paragraph of our discussion section, which refers to the planned further paper, as follows: ‘That paper might also consider different definitions of quitting, such as at least 30 day quitting, and investigate the effect of restricting attention to those attempting quitting at baseline. It will also describe and comment on other publications that have used data up to Wave 4’. Is the work clearly and accurately presented and does it cite the current literature?Partly It was never intended to consider literature based on analyses using PATH Wave 4 data, or considering relapse, and the huge literature on e-cigarettes from other studies is covered in fair detail.< >Is the study design appropriate and is the work technically sound?Are sufficient details of methods and analysis provided to allow replication by others?If applicable, is the statistical analysis and its interpretation appropriate? Are all the source data underlying the results available to ensure full reproducibility?Are the conclusions drawn adequately supported by the results?We confirm that we have read this submission and believe that we have an appropriate level of expertise to state that we do not consider it to be of an acceptable scientific standard, for reasons outlined above.We hope that our submission, when the revisions described are made, will now be considered of an acceptable scientific standard. ReferencesBenmarhnia, T., Pierce, J.P., Leas, E., White, M.M., Strong, D.R., Noble, M.L., Trinidad, D.R., 2018. Can e-cigarettes and pharmaceutical aids increase smoking cessation and reduce cigarette consumption? Findings from a nationally representative cohort of American smokers. Am. J. Epidemiol. 187, 11, 2397-2404. DOI:10.1093/aje/kwy129. Berry, K.M., Reynolds, L.M., Collins, J.M., Siegel, M.B., Fetterman, J.L., Hamburg, N.M., Bhatnagar, A., Benjamin, E.J., Stokes, A., 2019. E-cigarette initiation and associated changes in smoking cessation and reduction: the Population Assessment of Tobacco and Health Study, 2013-2015. Tob. Control. 28, 1, 42-49. DOI:10.1136/tobaccocontrol-2017-054108. Chen, R., Pierce, J.P., Leas, E.C., White, M.M., Kealey, S., Strong, D.R., Trinidad, D.R., Benmarhnia, T., Messer, K., 2020. E-cigarette use to aid long-term smoking cessation in the US: Prospective evidence from the PATH Cohort Study. Am. J. Epidemiol. Published online ahead of print July 27, 2020 (doi: 10.1093/aje/kwaa161). DOI:10.1093/aje/kwaa161. Erratum appears in Am J Epidemiol. 2020 Sep 12;kwaa193. doi: 10.1093/aje/kwaa193. Dai, H., Leventhal, A.M., 2019. Association of electronic cigarette vaping and subsequent smoking relapse among former smokers. Drug Alcohol Depend. 199, 10-17. DOI:10.1016/j.drugalcdep.2019.01.043. Everard, C.D., Silveira, M.L., Kimmel, H.L., Marshall, D., Blanco, C., Compton, W.M., 2020. Association of electronic nicotine delivery system use with cigarette smoking relapse among former smokers in the United States. JAMA Netw. Open. 3, 6, e204813. DOI:10.1001/jamanetworkopen.2020.4813. Halpern, S.D., Harhay, M.O., Saulsgiver, K., Brophy, C., Troxel, A.B., Volpp, K.G., 2018. A pragmatic trial of e-cigarettes, incentives, and drugs for smoking cessation. N. Engl. J. Med. 378, 24, 2302-2310. DOI:10.1056/NEJMsa1715757. Kalkhoran, S., Chang, Y., Rigotti, N.A., 2019. E-cigarettes and smoking cessation in smokers with chronic conditions. Am. J. Prev. Med. 57, 6, 786-791. DOI:10.1016/j.amepre.2019.08.017. Lee, P., Fry, J., Forey, B., Coombs, K.J., Thornton, A.J., 2020. Cigarette consumption in adult dual users of cigarettes and e-cigarettes: a review of the evidence, including new results from the PATH study [version 1; peer review: awaiting peer review] F1000Res. 9, 630. DOI:10.12688/f1000research.24589.1. Malas, M., van der Tempel, J., Schwartz, R., Minichiello, A., Lightfoot, C., Noormohamed, A., Andrews, J., Zawertailo, L., Ferrence, R., 2016. Electronic cigarettes for smoking cessation: A systematic review. Nicotine Tob. Res. 18, 10, 1926-1936. DOI:10.1093/ntr/ntw119. Pierce, J.P., et al., 2020a. Role of e-cigarettes and pharmacotherapy during attempts to quit cigarette smoking: The PATH Study 2013-16. PLoS One. 15, 9, e0237938. DOI:10.1371/journal.pone.0237938. Pierce, J.P., Messer, K., Leas, E.C., Kealey, S., White, M.M., Benmarhnia, T., 2020b. A source of bias in studies of e-cigarettes and smoking cessation. Nicotine Tob. Res. 22, 5, 861-862. DOI:10.1093/ntr/ntz143. Verplaetse, T.L., Moore, K.E., Pittman, B.P., Roberts, W., Oberleitner, L.M., Peltier, M.K.R., Hacker, R., Cosgrove, K.P., McKee, S.A., 2019. Intersection of e-cigarette use and gender on transitions in cigarette smoking status: Findings across Waves 1 and 2 of the Population Assessment of Tobacco and Health Study. Nicotine Tob. Res. 21, 10, 1423-1428. DOI:10.1093/ntr/nty187. Watkins, S.L., Thrul, J., Max, W., Ling, P.M., 2019. Real-world effectiveness of smoking cessation strategies for young and older adults: Findings from a nationally representative cohort. Nicotine Tob. Res. 22, 9, 1560-1568. DOI:10.1093/ntr/ntz223."
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https://f1000research.com/articles/9-1099
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https://f1000research.com/articles/11-673/v1
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20 Jun 22
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{
"type": "Research Article",
"title": "Consumption of food supplements: is there a risk of muscle dysmorphia?",
"authors": [
"Isaac Kuzmar",
"José Rafael Consuegra",
"María Calao",
"Andrea Florez",
"Angie Garcés",
"Nicolas Ibañez",
"Olga Harb",
"Karen Martínez",
"Nelson Martínez",
"Yiseth Castro",
"José Rafael Consuegra",
"María Calao",
"Andrea Florez",
"Angie Garcés",
"Nicolas Ibañez",
"Olga Harb",
"Karen Martínez",
"Nelson Martínez",
"Yiseth Castro"
],
"abstract": "Background. Bigorexia is an eating disorder and obsessive-compulsive disorder where the subject has an incorrect perception of their body image with exercise addiction. This study aims to determine whether there is a relationship between body mass index (BMI), food supplement consumption, dietary adherence, gender and risk of muscle dysmorphia in the individual and to provide information to build recommendation systems to monitor the health and mental state of the population. Methods. A cross-sectional descriptive observational study was conducted in Barranquilla (Colombia) between February – May 2020. A face-to-face survey of 200 individuals of both sexes was used in which users evaluated different variables that helped to identify their risk of muscle dysmorphia.\n\nResults. Of the 200 participants, 105 men: N=48, 45.7% vs. women: N=57, 54.3%) consume nutritional supplements. There is no relationship in the total population with the risk of muscle dysmorphia with the consumption of nutritional supplements nor with the feeling of guilt for non-adherence to the diet, nor with age, gender, or BMI (p<0.05). In contrast, gender, age and BMI are related to nutritional supplement consumption, and gender is related to feelings of guilt for non-adherence to the diet. In the population that consumes nutritional supplements the risk of muscle dysmorphia is increased and the frequency varies by risk group: low risk: N=16, 15.2%; medium risk: N=46, 43.8%; high risk: N=28, 26.7%; and very high risk: N=15, 14.3%. The consumption of food supplements is higher in the female gender (57, 54.3% vs. 48, 45.7%), and moderate the feeling of guilt for not completing the diet, BMI and the risk of muscle dysmorphia. Conclusions. Women consume more food supplements, but gender does not determine the risk of muscle dysmorphia. Food supplement consumption influences the feeling of guilt for not completing the diet, BMI and the risk of muscle dysmorphia.",
"keywords": [
"Physical Exercise",
"Muscle Dysmorphia",
"Body Mass Index",
"Bigorexia",
"Food Supplements",
"Diet"
],
"content": "Introduction\n\nDisorders are defined as changes or alterations that occur in the normal functioning of the body. According to the World Health Organization (WHO), mental health and mental disorders are currently not given the necessary importance in comparison to physical health; strictly speaking, they have been rather ignored or neglected.1 Mental health problems affect society as a whole, and not just a limited or isolated segment of it, and therefore constitute a major challenge for the integral development of human beings.1\n\nAbout 450 million people are affected by a mental or behavioural disorder.1,2 Among the mental disorders that affect people is bigorexia, which develops when people become obsessed with their physical state, directly affecting their eating behaviour.2 From childhood onwards, food preferences are influenced by the habits of choosing different dishes; eating should be a conscious and voluntary act that allows one to decide what and how to eat.3\n\nFeeding is linked to culture and begins to change once weaning takes place; the child is almost always given what is considered to be the best possible food: daily bread.4 In most cases, the child is conceived as a small adult and is fed accordingly; ingesting what his culture has taught him.4\n\nIn Bigorexia, eating is sometimes extreme in quantity but reduced in variety.5 The first references to this term are found in the research group of psychiatrist Harrison Pope in the United States, who first described the “disease” in 1993 while investigating steroid use and abuse; when the first cases were diagnosed it was called “reverse anorexia nervosa”, due to the common characteristics that in certain respects make up these disorders, although in the opposite direction.6\n\nBigorexia is an eating disorder (ED) and obsessive compulsive disorder (OCD) where the subject has an incorrect perception of their own body image (muscle dysmorphia) with exercise addiction: constant thoughts about the need to exercise and whose compulsion is the physical activity itself.7 Bigorexics tend to restrict their food intake, use drugs and excessive physical exercise; and as in anorexia nervosa, they share an excessive concern for their physical appearance, distortion of the body schema, obsession with weighing food, interest in food, calories and composition of what is eaten, self-observation, weighing themselves several times a day, fat suppression.8\n\nIn bigorexia, subjects show recurrent thoughts about their image, their lack of muscle and how to improve it; and they decide to “compulsively” do physical exercise to compensate for this “defect” in their body.8,9 Bigorexia in the past was characterised by a fear of being too small, and perceiving oneself as small and weak, even when one is really big and muscular.10 It is a multifactorial pathology involving genetic, biological, psychological and socio-cultural variables that can affect all people with a tendency towards low self-esteem, i.e. they are more perfectionist and have some difficulty in interpersonal relationships.11 Young people who are overweight or obese during childhood are more likely to suffer from this disorder, and it can also be seen in common with those who have been exposed to bullying because of their physical appearance or mannerisms during childhood.12\n\nThe use of ergogenic substances (ESU) is not restricted to consumption for the achievement of athletic performance in the case of athletes, it is nowadays also a behaviour used for body change and muscle development, but little is known about the relationship between ESU and the development of muscular dysmorphia (MD).13 There are factors that influence whether there is an EUS-MD relationship such as socio-cultural influences; men tend to read more magazines and are associated with the use of supplements to increase muscle mass, body image has been identified as the most significant concern, comparisons, and the use of supplements to increase muscle mass.13\n\nIn this situation, it is necessary to take into account some guidelines such as psychological help for adolescents, especially those who have been violated in this way, and additional physical examinations to determine the state of health, needs and capabilities of the individual to adapt the exercises they can perform in their daily lives.12\n\nSymptoms identified in people suffering from bigorexia include an obsession with their physical well-being, which may involve changes in eating habits, frequent preoccupation with reaching their daily protein intake target, comparing their fitness with others, and anxiety when skipping a training session or a meal.14 The diagnosis of this condition is made by health professionals supported by instruments for the identification of bigorexia.15\n\nMD could be framed within the framework of obsessive compulsive disorders, due to the verification behaviours experienced by the people who suffer from it, specifically associated with subjects who have a low self-concept, identity problems, depression and substance abuse.16\n\nThe Diagnostic and Statistical Manual of Mental Disorders (DSM-517) defines 4 essential features for the diagnosis of body dysmorphic disorder:\n\nA. Concern about one or more perceived defects or flaws in physical appearance that are not observable or appear minor to others.\n\nB. At some point during the course of the disorder, the individual has engaged in repetitive exercise behaviours (e.g., mirror gazing, excessive grooming, skin pinching, seeking reassurance) or mental acts (e.g., comparing her appearance to others) in response to appearance concerns.\n\nC. The preoccupation causes clinically significant distress or impairment in social, occupational or other important areas of functioning.\n\nD. Concern with appearance is not best explained by concerns with body fat or weight in an individual whose symptoms meet diagnostic criteria for an eating disorder.\n\nAt present there is no specific protocol for treating muscle dysmorphia; some authors emphasise the motivation of those suspected of having MD to seek help through techniques that are used for eating disorders.9 It is proposed that to help patients with cognitive and behavioural techniques, patients will be able to identify cognitive distortions and irrational beliefs, i.e. the patient is confronted with the beliefs without creating maladaptive behaviours.9 This research seeks to determine which variables are related to bigorexia disorder in a population of Barranquilla, Colombia.\n\nTo determine if there is a relationship between body mass index (BMI), consumption of food supplements, adherence to a diet, gender and risk of muscular dysmorphia in the individual and to provide information that will allow the construction of recommendation systems that monitor the health and mental state of the population.\n\n\nMethods\n\nThe study is consistent with the ethical principles of the Declaration of Helsinki and was approved by the Simón Bolívar University of Barranquilla and BiomediKcal – Advanced Medical Nutrition & Lifestyle Center on 14 January 2020 under identification number BK01-20. Written informed consent was received from all participants and data have been treated anonymously and in a strictly protected way.\n\nThe study design is a cross-sectional descriptive observational study conducted in the city of Barranquilla-Colombia (GPS coordinates: 10°58′6.74′′N -74°46′52.75′′W) during 12 weeks between February and May 2020. Participants were recruited from five gyms in areas with different socioeconomic levels (medium and high) spread out over different parts of the city of Barranquilla. Data collection was done directly through a face-to-face survey in which users had assessed their physical activity, dietary habits and some aspects that helped to identify their risk of muscle dysmorphia. Based on height and weight, participants chose the BMI group to which they belonged; we provided the formula for those who did not know it: BMI = kg/m2 where kg is a person's weight in kilograms and m2 is their height in metres squared. Because we used a scientifically validated questionnaire published in a previous study by Palazón-Bru A et al. with 180 participants, the sample size of the study was estimated according to the formula:\n\nConfidence level: 95%\n\nPopulation size: 180\n\nMargin of error: 5%\n\nIdeal sample size: 123\n\nFor our study, the calculated sample size was approximately 123, but we decided to increase the number of participants to improve the quality and efficiency of the survey. This study includes 200 individuals of both sexes, aged between 20 and 49 years. Inclusion criteria were people who are physically active, people who take food supplements, and older people. Exclusion criteria were people who are not physically active, BMI<20, and people who refused to participate. The dataset analysed in this study was previously published as a data article.18\n\nA scientifically validated questionnaire15 was used and the variables gender, age, weight, risk of muscle dysmorphia, consumption of food supplements, feelings of guilt for not adhering to the diet were statistically analysed. The risk of muscle dysmorphia was calculated using a scientifically validated computer application by entering the necessary data (age group, BMI, food supplements, feelings of guilt).15\n\nRaw data were transferred to IBM SPSS statistics version 26 for further analysis, testing for normality and comparative non-parametric statistics. A robust two-tailed equivalence analysis is performed by strengthening the t-test for comparative analysis. The Mann-Whitney U test was used to compare whether there is a difference in the dependent variable for independent groups. Kruskal-Wallis test was used to determine whether or not there is a statistically significant difference between the medians of independent groups. The significance level is 0.05.\n\n\nResults\n\nThere is a total population of 200 participants where the majority were women (N=107, 53.5%) as opposed to men (N=93, 46.5%).31 A second selection was carried out, choosing only those who consume food supplements, leaving a total population of 105, (men: N=48, 45.7% vs. women: N=57, 54.3%). See Table 1 and Figure 1. None of the participants withdrew or incompletely filled in the questionnaires; all surveys were recorded for data analysis.\n\nThere is no relationship in the total population (N=200) with the risk of muscle dysmorphia with the consumption of nutritional supplements nor with the feeling of guilt for non-adherence to the diet, nor with age, gender, or BMI (p<0.05). In contrast, gender, age and BMI are related to nutritional supplement consumption, and gender is related to feelings of guilt for non-adherence to the diet (see Table 2). To analyse the ages of the participants, they were grouped and stratified with a number: 1. < 20; 2. 20-29; 3. 30-34; 4. 35-44 and 5. > 45 (see the questionnaire18).\n\nWhen analysing only the population that consumes nutritional supplements (N=105; Female 57, 54.3% vs Male 48, 45.7%) we find that the risk of muscle dysmorphia is increased (Table 3).\n\nFigure 2 shows that the frequency varies by risk group: low risk: N=16, 15.2%; medium risk: N=46, 43.8%; high risk: N=28, 26.7% and very high risk: N=15, 14.3%.\n\nThe consumption of food supplements is higher in women (57, 54.3% vs. 48, 45.7%), and influences the feeling of guilt for not completing the diet, BMI and the risk of muscle dysmorphia (Table 4 and Figure 3); however, it does not influence the rest of the variables analysed (p<0.05).\n\n1 Significance values have been adjusted by the Bonferroni correction for multiple tests.\n\n\nDiscussion\n\nThis analysis was conducted to determine if there is a relationship between BMI, consumption of food supplements, adherence to a diet, gender and risk of muscular dysmorphia in the individual and to provide information that will allow the construction of recommendation systems that monitor the health and mental state of the population. Bigorexia is generally associated with male gym-goers19 but also occurs in women20; and although in the present study there are more women than men (53% vs 46.5%), the results show that gender does not condition the risk of muscle dysmorphia (p<0.05) consistent with findings from studies suggesting that women prefer a toned, slim female figure to an exclusively slim one, in line with figures commonly seen in fitness-inspiring media.21,22 Therefore, the inclusion of women in epidemiological studies of MD is critical for accurate estimation of the population burden of this disorder. Contesini et al.23 conclude that active individuals with muscle dysmorphia ingest dietary and ergogenic supplements to reduce weight; our study shows that in those individuals who go to the gym and consume nutritional supplements, these play a mediating role between guilt for not completing the diet, BMI and risk of muscle dysmorphia (Tables 3, 4, and Figure 3) and when analysed by the sex of the participants, women consume more (Table 1). 52.5% of the Colombian population who go to the gym consume nutritional supplements, similar to the results of other studies in other countries.24,25\n\nOur study shows that 86% of gym-going, overweight or obese individuals who consume food supplements have a medium, high or very high risk of muscle dysmorphia and guilt for dietary withdrawal (p<0.05). This result is similar to the results published by Martínez-Segura, A. et al.26 This data is really high if compared to other studies27–29 carried out in South America, in which the percentage varies between 25-60%; but they concede that they have been carried out before 2010, which means that at the present time this percentage is high. Pope et al. concluded that the use of dietary supplements and abuse of anabolic steroids were linked to a higher frequency of disorders like bulimia and anorexia nervosa and lack of adequate nutrition was associated with worsening psychopathology and engagement.30\n\nThis study has collected data using a scientifically valid questionnaire and from an adequate sample size. While the data collected is useful, it may lack depth and detail. More detailed variables could have provided more useful and in-depth data. Although 200 surveys can be done in two to three days; it took a little longer as movement restriction measures in the city were beginning to be enforced due to the recent pandemic. The study is well positioned to be generalisable to the Colombian population. While it may not be generalisable beyond that, neighbouring countries with the same economic and socio-cultural contexts can learn from the results of this study. Another limitation is that no other recent studies have been found that directly relate muscle dysmorphia to dietary supplement consumption in Colombia to make comparisons with our results. Our results have a theoretical-methodological implication of great contribution to dietary health research. We invite researchers in our region to replicate our study and compare their results.\n\n\nConclusion\n\nWomen consume more food supplements, but gender does not determine the risk of muscle dysmorphia. Food supplement consumption influences the feeling of guilt for not completing the diet, BMI and the risk of muscle dysmorphia.\n\n\nData availability\n\nfigshare: Dataset for estimation of muscle dysmorphia in individuals from Colombia, https://doi.org/10.6084/m9.figshare.12482516.v3.31\n\nThis project contains the following underlying data:\n\n- Muscle Dysmorphia Data.sav (raw data file)\n\nfigshare: Dataset for estimation of muscle dysmorphia in individuals from Colombia, https://doi.org/10.6084/m9.figshare.12482516.v3.31\n\nThis project contains the following extended data:\n\n- Questionary and Informed consent.pdf\n\n- Datakey.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nWHO: Factsheets. World Health Organization;2018. Accessed on: 22.05.2022.Reference Source\n\nWHO: The World health report: 2001: Mental health: new understanding, new hope. World Health Organization;2001. Accessed on: 25.02.2022.Reference Source\n\nUNICEF: Niños, alimentación y nutrición. Estado Mundial de la Infancia 2019. UNICEF;2019; 1–258. Accessed on: 25.05.2022.Reference Source\n\nUNESCO: Alimentación y cultura: El hombre y lo que come. El Correo.1987; 1–36. Accessed on: 25.05.2022Reference Source\n\nMuñoz-Sánchez R, Martínez-Moreno A: Ortorexia y vigorexia ¿nuevos trastornos de la conducta alimentaria?. Trastornos de la conducta alimentaria. 2007; 5: 457–482.\n\nGonzalez I, Fernandez J, Contreras O: Contribución para el criterio diagnóstico de la Dismorfia Muscular. (Vigorexia). Revista de Psicología del Deporte. 2012; 21(2): 351–358.\n\nRodríguez-Molina JM: Vigorexia: adicción, obsesión o dismorfia; un intento de aproximación. Rev Salud y drogas. 2007; 7(2): 289–308.\n\nGordillo-Montaño MJ, et al.: Vigorexia. ¿El ideal de belleza?. 17° Congreso Virtual de Psiquiatría. Interpsiquis.2016; 1–18. Accessed on: 22.05.2022.Reference Source\n\nCompte EJ, Sepúlveda AR; Dismorfia muscular: perspectiva histórica y actualización en su diagnóstico, evaluación y tratamiento. Behavioral Psychology. 2014; 22(2): 307–326.\n\nPope HG, Katz DL, Hudson JI: Anorexia nervosa and “reverse anorexia” among 108 male bodybuilders. Compr. Psychiatry. 1993; 34(6): 406–409. PubMed Abstract | Publisher Full Text\n\nSerrano E: 8. Cuando la relación con la comida cambia (anorexia y bulimia). Una mirada a la salud mental de los adolescentes, Claves para comprenderlos y acompañarlos. Cuaderno Faros. 2021; 12: 183–197. Accessed on: 22.05.2022.Reference Source\n\nAssociation, American Psychiatric: Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR). 4ª ed.Washington;2000.\n\nGarcía-Rodríguez J, et al.: Dismorfia muscular y uso de sustancias ergogénicas. Una revisión sistemática. Revista Colombiana de Psiquiatría. 2017; 46(3): 168–177. Publisher Full Text\n\nSalamanca JS: Una Guía para la Prevención: Insatisfacción Corporaly Trastornos de la Conducta Alimentaria Campaña de Sensibilización ante los Trastornos de la Conducta Alimentaria: “Vales más de lo que Pesas”. CJEX. 2008; 1–88. Accessed on: 22.05.2022.Reference Source\n\nPalazón-Bru A, et al.: Screening tool to determine risk of having muscle Dysmorphia symptoms in men who engage in weight training at a gym. Clin. J. Sport Med. 2018; 28(2): 168–173. Publisher Full Text\n\nCastro R, et al.: Dismorfia Muscular y su relación con los síntomas de los Trastornos Alimentarios. Mexican J. Eat. Disord. 2013; 4(1): 31–36.\n\nAmerican Psychiatric Association: Obsessive-Compulsive and Related Disorders. Body Dysmorphic Disorder. Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed.APA;2013; 242–247.\n\nKuzmar I, et al.: Dataset for estimation of muscle Dysmorphia in individuals from Colombia. Data Brief. , 2020; 31: 105967. Accessed on: 22.05.2022. Publisher Full Text Reference Source\n\nSandgren SS, et al.: Muscle Dysmorphia in Norwegian Gym-Going Men: An Initial Investigation. Kinesiology. 2019; 51(1): 12–21. Publisher Full Text\n\nSerro-Vargas C, et al.: Prevalence of muscle dysmorphia in women attending academy. Revista Brasileira de Nutrição Esportiva. 2012; 7(37): 28+.\n\nBenton C, Karazsia BT: The effect of thin and muscular images on women's body satisfaction. Body Image. 2015; 13: 22–27. PubMed Abstract | Publisher Full Text\n\nHoman K, McHugh E, Wells D, et al.: The effect of viewing ultra-fit images on college women's body dissatisfaction. Body Image. 2012; 9(1): 50–56. Publisher Full Text\n\nContesini et al.Nutritional strategies of physically active subjects with muscle dysmorphia. Int. Arch. Med. 2013; 6(1): 25–6. Publisher Full Text\n\nAlshammari SA, et al.: Use of hormones and nutritional supplements among gyms' attendees in Riyadh. J. Fam. Community Med. 2017; 24(1): 6–12. PubMed Abstract | Publisher Full Text\n\nAlhakbany MA, et al.: Knowledge, Attitudes, and Use of Protein Supplements among Saudi Adults: Gender Differences. Healthcare. 2022; 10(2): 394. PubMed Abstract | Publisher Full Text\n\nMartínez-Segura A, et al.: Factores de riesgo nutricionales para dismorfia muscular en usuarios de sala de musculación. Nutr. Hosp. 2015; 32(1): 324–329.\n\nHirschbruch MD, Fisberg M, Mochizuki L: Consumo de suplementos por jovens freqüentadores de academias de ginástica em São Paulo. Rev. Bras. Med. Esporte. 2008; 14(6): 539–543. Publisher Full Text\n\nRocha LP: Pereira MVL Consumo de suplementos nutricionais por praticantes de exercícios físicos em academias. Rev. Nutr. 1998; 11(1): 76–82. Publisher Full Text\n\nPereira RF, Lajolo FM, Hirschbruch MD: Consumo de suplementos por alunos de academias de ginástica em São Paulo. Rev. Nutr. 2003; 16(3): 265–272. Publisher Full Text\n\nPope CG, et al.: Clinical features of muscle dysmorphia among males with body dysmorphic. Body Image. 2005; 2: 395–400. Publisher Full Text\n\nKuzmar I: Dataset for estimation of muscle dysmorphia in individuals from Colombia. figshare. [Dataset].2020. Publisher Full Text"
}
|
[
{
"id": "145654",
"date": "04 Aug 2022",
"name": "Gianluca Rizzo",
"expertise": [
"Reviewer Expertise Nutrition and 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\nThe authors present the results of a cross-sectional observational study on 200 individuals who attend gyms in Colombia using investigation through individual interviews, to explore the correlation between the risk of muscle dysmorphia and other factors such as sex, age and the use of supplements. The study shows that about 50% of participants used supplements, more women than men, and that this use was correlated with the risk of muscle dysmorphia.\nThe topic is interesting but the manuscript is confusing at times and some aspects deserve attention. Furthermore, a linguistic revision would improve the paper.\nThe analyses carried out are unclear. It would be more effective to show correlation indices between elements with statistical significance (avoiding truncating the p-value below 0.01). Tables 2 and 3 are unclear. It is important to determine a correlation value, in addition to statistical significance, to judge whether the correlation is still clinically relevant. In addition, a more detailed analysis such as a multivariate analysis that considers other elements that may act as confounders in the correlation between muscle dysmorphia and the use of supplements would be helpful.\n\nThe inclusion criteria are confused. As they are described, it seems that the use of supplements is necessary to participate in the study while it is evident that it is not a necessary prerogative, therefore it does not represent an inclusion criterion (being only half of the participants consuming supplements). Furthermore, it is specified that individuals from 20 to 49 years of age are included, but later on, it is specified “and older people”. Does this mean that age is also not a criterion for inclusion?\n\nImages and tables should have a caption that adequately describes their content.\n\nIt is not very clear to me why the authors argue that there is no correlation between muscle dysmorphia and the use of supplements in the reference sample and then say that this correlation is present among supplement-users.\n\nThere is no clear description of the types of supplements referred to.\n\nThere is no description of the characteristics of the participants. Furthermore, in the discussion (on page 8) the authors highlight aspects of stratification by BMI not presented in the results (overweight and obese).\n\nIt is not clear on which factor the sample size was calculated in the power analysis. The authors refer to 180 individuals but are these enough to identify a correlation between supplement use and muscle dysmorphia?\n\nThe study is over-interpreted. As this is an exploratory study, it is unlikely that these results can already be codified into recommendations.\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": []
},
{
"id": "243547",
"date": "08 Feb 2024",
"name": "Shervin Assari",
"expertise": [
"Reviewer Expertise gender differences",
"BMI",
"mental health",
"body dismorphia"
],
"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 paper titled \"Consumption of Food Supplements: Is There a Risk of Muscle Dysmorphia?\" aims to investigate the correlation between body mass index (BMI), food supplement consumption, dietary adherence, gender, and the risk of muscle dysmorphia by employing a survey on a sample of 200 individuals. While the study provides valuable insights, there are certain aspects that require attention for a more robust analysis. Firstly, the sample size of 200 individuals might be considered low for drawing definitive conclusions, potentially leading to underpowered results. It is crucial to acknowledge that some negative outcomes may be attributed to this limitation, and cautious interpretation is advised. Moreover, the paper utilizes present tense in presenting results, which is unconventional for a peer-reviewed publication. Adjusting the language to past tense would align the manuscript with standard practices in scientific writing, enhancing its overall professionalism. Additionally, the language employed in the results, conclusion, and discussion sections is somewhat casual and deterministic. To align with the conventions of peer-reviewed papers, it would be advisable to consolidate bullet points into a coherent paragraph format, fostering a more seamless flow of information. Furthermore, the tables in the manuscript lack a standard format, and Table 4 proves challenging to comprehend. Providing clarity in the presentation of data is crucial for readers to grasp the findings effectively. Additionally, reducing the decimal places for p-values to three instead of two would enhance readability. Finally, the inclusion of a histogram depicting the risk may not be necessary and could be omitted to streamline the visual elements of the paper. In summary, addressing these concerns, such as increasing the sample size, adjusting verb tense, refining language, improving table formatting, and reconsidering visual elements, would contribute to the overall quality and adherence to standard practices of a peer-reviewed 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? 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": "243551",
"date": "22 Feb 2024",
"name": "Sebastian S. Sandgren",
"expertise": [
"Reviewer Expertise Muscle dysmorphia and eating 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\nThank you for the opportunity to review this manuscript. The topic (muscle dysmorphia) is of great scientific interest in the field and there are some useful insights in this paper. However, I have several concerns with the way the paper is presented, and the way the findings have been interpreted in its current form. Please see my overall comments and suggestions below:\nThe authors refer to both “bigorexia” and “muscle dysmorphia” which is confusing. The correct term is muscle dysmorphia and should be used consistently throughout the manuscript. Secondly, bigorexia is not an eating disorder and muscle dysmorphia is a specifier for body dysmorphic disorder in the DSM-5. These details are very important, and readers should not be misguided. What is meant by “a protocol for treating MD”? (p. 4). The authors are recommended to include some of the literature around muscle dysmorphia interventions, and where the evidence-base is currently at. This would strengthen the rationale, in addition to more clearly demonstrating why we need more knowledge about the associations between MD, BMI, food supplements, diet and gender. Aren’t these relationships already fairly well established in the cross-cultural literature? A total sample size of n=200 is relatively small in a cross-sectional design with the purpose of exploring associations between MD and other variables. Could this have affected the statistical power in the analysis and subsequently the conclusions made? Where is the number “180” from in the sample size calculation? Please state the name of the measure used for determining risk of MD. Also, what is the validity and reliability of this measure? More details around the measure is needed. Has it been tested with only men or with both sexes? Are the psychometric properties the same for both, or are they different? I would recommend the authors test for this. There are some details lacking in the results (e.g., what are the correlation coefficients in the correlation matrix that you performed, and what are the Z statistics from the KW test?). P values are not enough for interpretation. The tables also do not follow standard reporting of statistical results. What is meant by “More detailed variables could have provided more useful and in-depth data”? Please elaborate on the “how” and “why” for the following statement “Our results have a theoretical-methodological implication of great contribution to dietary health research”. The discussion should be revised in line with any changes and revisions made to the other parts of the manuscript. I agree with the other reviewers’ comments around language and readability. The manuscript would benefit from proof reading and further editing.\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/11-673
|
https://f1000research.com/articles/11-195/v1
|
16 Feb 22
|
{
"type": "Opinion Article",
"title": "Brain death debates: from bioethics to epistemology",
"authors": [
"Alberto Molina Pérez"
],
"abstract": "50 years after its introduction, brain death remains controversial among scholars. The debates focus on one question: is brain death a good criterion for determining death? This question has been answered from various perspectives: medical, metaphysical, ethical, and legal or political. Most authors either defend the criterion as it is, propose some minor or major revisions, or advocate abandoning it and finding better solutions to the problems that brain death was intended to solve when it was introduced. In short, debates about brain death have been characterized by partisanship, for or against. Here I plead for a non-partisan approach that has been overlooked in the literature: the epistemological or philosophy of science approach. Some scholars claim that human death is a matter of fact, a biological phenomenon whose occurrence can be determined empirically, based on science. We should take this claim seriously, whether we agree with it or not. The question is: how do we know that human death is a scientific matter of fact? Taking the epistemological approach means, among other things, examining how the determination of human death became an object of scientific inquiry, exploring the nature of the brain death criterion itself, and analysing the meaning of its core concepts such as “irreversibility” and “functions”.",
"keywords": [
"Death criteria",
"Brain death",
"Bioethics",
"Epistemology",
"Philosophy of Science",
"Functions",
"Irreversibility",
"Uniform Death Determination Act"
],
"content": "Introduction\n\nMore than 50 years after the neurological determination of death—also known as “brain death”—was admitted as a new criterion of death (Beecher et al., 1968), and despite its broad acceptance in medical practice (Wahlster et al., 2015; Lewis et al., 2020b; Greer et al., 2020), brain death continues to raise confusion (Dalle Ave & Bernat, 2018; Rodríguez-Arias et al., 2020), disagreement among scholars (Joffe et al., 2007, 2012; Youngner et al., 1989), and opposition among the general public (Skowronski et al., 2021; Shah et al., 2015). Brain death has been and still remains debated. In 2018, the Harvard School of Medicine organised a three-day conference on current controversies related to determining death (Hastings Center Report, 2018). In 2020, the World Brain Death Project published consensus recommendations on determination of brain death (Greer et al., 2020). The same year, the US Uniform Law Commission (ULC) appointed a Study Committee on updating the 1981 Uniform Determination of Death Act (UDDA), which is the legal statute adopted in more than 40 states in the United States of America and which has had a significant influence in the laws throughout the world. In 2021, more than 100 scholars endorsed the Statement in Support of Revising the UDDA and in Opposition to a Proposed Revision (Shewmon, 2021).\n\nAccording to the current neurological criterion, as defined in the UDDA and other laws around the world, death is determined by the “irreversible cessation of all functions of the entire brain, including the brainstem”. Recent proposals to revise this criterion focus on the cessation of a limited number of functions, especially consciousness and some brainstem functions, including spontaneous respiration, and require the permanent (i.e. will not reverse)—but not necessarily irreversible (i.e. cannot reverse)—cessation of these functions (Gardiner et al., 2020; Lewis et al., 2020a).\n\nForeseeable advances in medicine and neurosciences may completely challenge our current concept of human death by opening yet unknown possibilities to restore or reactivate consciousness, cognition, and other brain functions. Current and future technology, such as brain–computer interfaces (Kübler, 2019; Abdalmalak et al., 2020) linked to brain-stimulation technology (Xia et al., 2019; Fox et al., 2020; Hakon et al., 2020) and machine learning (Iturrate et al., 2020), may allow us to detect brain activity and function unnoticed today (Owen, 2019), and to artificially restore some brain functions, for example through neural stem cell transplantation therapy (Otsuki & Brand, 2018; Zhang et al., 2019) or other therapeutic interventions (Thibaut et al., 2019), thus challenging the irreversibility of death (Brummitt, 2018).\n\nIn 2019, researchers recirculated pigs’ brains, through a device called BrainEx, four hours after their decapitation (Vrselja et al., 2019). Glial cells were still able to maintain their inflammatory responses and neurons were responding to depolarizing current stimulation. Would such a device be able to restore human brain activities in similar conditions, stretching our knowledge on irreversibility of seemingly lost brain function? If so, would these patients be considered alive? It depends on whether those neural activities are mere activities or if they exert specific functions, like cognition or perception. Indeed, human death is usually determined by the irreversible cessation of either respiratory and circulatory functions, or all brain functions (President’s Commission, 1981), while simple neuronal activities are ignored. However, the notions of activity and function are not clearly defined in the literature, and these notions are often used interchangeably, while their distinction may be key to define death.\n\nIn transplantation medicine, a clear and unambiguous determination of death is mandatory. Indeed, one of the main ethical norms in transplantation is the dead donor rule (Dalle Ave et al., 2020), which states that an individual should be declared dead before the procurement of any vital organs. This norm ensures that individuals will not be killed for transplantation purposes, and that they won’t suffer during organ recovery. What would happen if there were no clear criteria for determining death? Are certainty and universality required for the determination of death or could some degree of uncertainty and diversity be acceptable?\n\nAdvances in medical technology may enable perception, motricity, cognition, or communication, to be artificially prolonged beyond a state in which they would normally be irreversibly destroyed. What would that mean for our understanding of what it is to be a human person? What kind of quality of life would such technology offer? Would that life be worth living? How would it impact social justice and equality? How would it affect personal identity and human rights? What would be the future of humankind if, in our quest to surmount mortality, we could eliminate the very concept of death through technology and neurosciences (Sandberg et al., 2008; Bamford & Danaher, 2017; Harari, 2018)?\n\nThese questions are of a philosophical nature and belong, in particular, to the domain of moral philosophy. To this day, most academic debates around brain death have been and are bioethical. However, I believe that a different philosophical approach can shed light on old controversies and help either settle open disputes or, on the contrary, raise new questions. I am talking about epistemology or, to be more accurate, about the philosophy of science. Death criteria are supposed to have an epistemic or scientific value. Some scholars claim, and most physicians certainly agree, that human death is a matter of fact, a biological phenomenon whose occurrence can be determined empirically, based on scientific knowledge and methods, and that medicine has epistemic authority over it. We should take this claim seriously, whether we agree with it or not, and analyse it from the perspective of the philosophy of science.\n\n\n50 years of bioethical controversies around death determination\n\nSince it was introduced in 1968, the brain criterion of death is at the centre of a heated debate that has produced a vast and complex literature. The debate among bioethicists has had some key recurring features (Belkin, 2018): first and foremost, argument over alleged flaws in the conceptual logic and consistency of the rationale for equating brain death with human death; second, efforts to fix perceived limitations of brain death-based practices to optimize transplantation; and third, a basic unease provoked by the experience of using the criteria and managing a warm and heart-beating body in a state previously known as “irreversible coma.”\n\nWith regard to the second feature, the 2018 special Hastings Center Report illustrates the central role played by the dead donor rule in bioethical debates (see also: Arnold & Youngner, 1993; Veatch, 2004; Nair-Collins et al., 2015; Rodríguez-Arias, 2018; Dalle Ave et al., 2020).\n\nWith regard to the first feature, one of the first and still open controversies concerns the nature of the justification of introducing brain death as a criterion of death, some claiming it had been initially proposed to solve practical and moral problems, including the opportunity of recovering organs without violating the “dead donor rule” (Pernick, 1999; Rodríguez-Arias, 2017).\n\nIn 1981, Bernat, Culver and Gert proposed the “whole-brain” concept of death, a scientific and philosophical justification based on the idea that life requires the integration of the organism and that the brain is the organ responsible for its integration (Bernat et al., 1981). Apart from the UK and a handful of nations, most developed countries soon adopted the whole-brain rationale (Wijdicks, 2002). However, Bernat and colleagues’ claim that individuals with a cessation of all brain functions are not integrated organisms but merely a group of artificially maintained subsystems has been challenged repeatedly and decisively (Youngner & Bartlett, 1983; Gervais, 1986; Halevy & Brody, 1993; Lizza, 1993; Seifert, 1993; Veatch, 1993; Taylor, 1997; Truog, 1997; Brody, 1999; Halevy, 2001; Potts et al., 2001; Shewmon, 1998, 2001; Byrne & Weaver, 2004; Zamperetti et al., 2004; Joffe, 2007; Shemie et al., 2014; Brugger, 2016; Verheijde et al., 2018). As a consequence, some advocates of the brain criterion have proposed refined versions of this rationale in terms of “organism-as-a-whole” (President’s Council, 2008; Moschella, 2019; Bernat, 2019; Huang & Bernat, 2019; Omelianchuk, 2021) while others have proposed alternatives in terms of “embodied consciousness” (Veatch, 2005; Veatch & Ross, 2016), personhood (Green & Wikler, 1980; Bartlett & Youngner, 1988; Lizza, 2006), or homeostasis (Nair-Collins, 2018). Most of these propositions are compatible with a single brain-based criterion of death, although for different reasons and with varying implications for the boundary between life and death.\n\nA different way of addressing the issue of determining death is to focus on its intrinsically legal, ethical, and political nature, by arguing that brain death is a legal fiction (Shah et al., 2011), advocating for a pluralistic policy that would allow stakeholders to choose among several definitions of death (Veatch, 1976; Bagheri, 2007; Molina-Pérez et al., 2008; Ross, 2018), requiring consent for brain death testing (Berkowitz & Garrett, 2020), and calling for an open public conversation on end-of-life practices (Youngner & Arnold, 2001; Rodríguez-Arias & Veliz, 2013).\n\n\nTaking the epistemological approach to human death\n\nDeath debates focus on a single question: Are death criteria, and especially the brain criterion, good criteria? They may be good in a scientific or medical sense because patients declared dead according to these criteria are actually dead, although there may be false positives and false negatives (Bernat & Dalle Ave, 2019). They may be good in a moral or policy sense because, for instance, they allow practices that are ethically and socially valuable, such as organ procurement. They may be good for a combination of both reasons. These reasons have their advocates and opponents. Almost all authors have either defended the death criteria, proposed some minor or major revisions and improvements of the criteria, or plead to abandon them—especially the brain criterion—and promoted better solutions to the problems these criteria were meant to solve. In sum, the death debates have been characterised by partisanship, either in favour or against the criteria.\n\nRegardless of whether the death criteria are true or accurate, or whether they are good policy, we should examine the determination of death as an object of scientific inquiry. This is the epistemological or philosophy of science approach that I am advocating. Taking this approach means examining how the determination of human death became a scientific issue and why medicine claims epistemic authority over it. It means asking what a death criterion is: is it a heuristic or a definition? Is it descriptive, stipulative or performative? Is it a rule of inference, and if so, what is its logical structure? For example, is the determination of the death of an individual the conclusion of a syllogism? To adopt this approach is also to analyse the meaning of the core concepts of death criteria, such as “irreversibility” and “functions”.\n\nEpistemological analyses of death definitions and criteria are scarce (Nair-Collins, 2015). In addition to the question of whether the main justification for brain death is rather scientific/epistemic or moral/practical, debates with a more epistemological orientation have revolved around two central questions: the nature of death as an event or a process (Morison, 1971; Pallis, 1983), and the requirement of irreversibility (as opposed to permanence) for the loss of functions (Bernat, 2010; Dalle Ave & Bernat, 2016; Gardiner & McGee, 2017). To my knowledge, few other publications have adopted what I consider an epistemological or philosophy of science approach, with some notable exceptions (e.g.: Walton, 1981; Meier, 2020).\n\nTaking the epistemological approach may help settle old debates and also bring novel insights. For example, death is characterised in medicine and described or defined in most legislations as the irreversible cessation of specific functions: either circulatory and respiratory functions or all brain functions. However, the meaning of the concepts used, especially the concept of function, requires clarification. These concepts are rarely defined in the medical literature and their interpretation varies between professionals. Hence, the consistent interpretation of the death criteria that rely on these concepts is not warranted, which may cause a lack of uniformity in death determination.\n\nBy applying to the criteria of death an analysis similar to the one used in the philosophy of biology to define biological functions (Molina-Pérez, 2017), Anne Dalle Ave, James Bernat and I revealed that the current US law is conceptually inconsistent (Molina-Pérez et al., forthcoming). Indeed, the UDDA uses the phrase “cessation of functions” with two different and conflicting meanings for its two criteria. On the one hand, it means the cessation of spontaneous functions, i.e. the cessation of the organ’s spontaneous functioning. On the other hand, it means the cessation of either spontaneous or artificially supported functions. We also showed that this inconsistency in the UDDA—and other laws throughout the world that acknowledge both criteria—derives from the conceptual assumptions underlying James Bernat’s 1981 “Whole-Brain” rationale for equating brain death with death. By conducting a logical deconstruction of the rationale, we showed that its premises are false and that, therefore, its conclusions cannot be drawn.\n\nThis type of analysis leads to policy recommendations and ethical considerations. After exploring possible ways to address the inconsistency, we found only two viable options: one is to keep the law as it is while admitting that death is a legal fiction, and the other is to pick a single criterion of death, either a circulatory-respiratory criterion, which would imply that “brain dead” patients maintained in the ICU are not dead, thus disrupting organ procurement (DBD) programmes, or a single brain criterion, which may affect medical practice and hinder programmes of organ recovery after circulatory death (DCDD) (see Rodríguez-Arias et al., 2013; Dalle Ave et al., 2016; Ortega-Deballon & Rodríguez-Arias, 2018).\n\nIn order to better assess death determination criteria, further analyses of the concept of function are needed. On the one hand, brain functions are at the intersection of three different but related scientific fields: biology, psychology, and neurology. While functions in general have been very much discussed in philosophy of biology (Garson, 2016; Molina-Pérez, 2017) and to some extent in philosophy of psychology (Ariew et al., 2002; Parot, 2008), they have received much less attention from either physicians or philosophers of medicine (Roux, 2014; Shewmon & Verheijde, 2020). A distinction needs to be made between the brain’s functions, as considered by physiology, and the brain’s functionality, as considered by neuroscience (Northoff & Tumati, 2019). In the context of neurophilosophy and brain-computer interfaces, brain’s functionality requires visible and coordinated behavioural responses in reference to specific environmental contexts. In other words, brain functions are not merely considered as physiological mechanisms, but also viewed in terms of whether they serve their intended behavioural purpose.\n\nOn the other hand, as critical care medicine keeps pushing forward its resuscitation capabilities, we still do not know where to find—and whether there are—absolute limits to the reversibility of functional losses. The cessation of brainstem functions, such as the initiation of respiration, can now be reversed with life-support technologies such as mechanical ventilation. This means that, although the spontaneous control of these functions by the brain is lost, the functions themselves can still be executed and controlled by artificial means (Meier, 2020; Molina-Pérez et al., forthcoming). Future advances, including BCIs, might help support, restore or replace not only brainstem functions, but also those necessary for cognition, and may, consequently, alter the threshold of irreversibility. This raises the question of the limits and meaning of irreversibility in the determination of death.\n\nIrreversibility can be interpreted as either absolute, relative, or permanent (Tomlinson, 1993; Bernat, 2010). Absolute irreversibility means that the cessation of functions cannot be reversed under any circumstances, regardless of any medical and technological interventions. Relative irreversibility means that the cessation of functions cannot be reversed in some context, but might be reversed in a different one. Most circulatory and respiratory arrests were irreversible in the 19th century, before the development of resuscitation techniques, but can now be reversed because these means now exist. Irreversibility, thus, depends on when and where the capacity to reverse the loss of functions is available and feasible, which in turn depends on other considerations, including the ethical, social, economic, and political framework. However, it is not always clear which of these two interpretations of the notion of irreversibility (absolute or relative) is used in current definitions and criteria of death. This also is a task to be conducted from an epistemological or philosophy of science perspective.\n\n\nData availability\n\nNo data are associated with this article.",
"appendix": "Acknowledgments\n\nThis article is inspired and partly derives from the introduction of a research project application, coordinated by Anne Dalle Ave, with contributions by Anne Dalle Ave, Ralf Jox, Andrea Kübler, Georg Northoff, Bernabé Robles del Olmo, Fernando Vidal, and myself. This article was written as part of the project PID2020-119717GA-100 funded by Spain’s Ministry of Science and Innovation.\n\n\nReferences\n\nAbdalmalak A, Milej D, Yip LCM, et al.: Assessing Time-Resolved fNIRS for Brain-Computer Interface Applications of Mental Communication. Front. Neurosci. 2020; 14. PubMed Abstract | Publisher Full Text\n\nAriew A, Cummins R, Perlman M: Functions: New essays in the philosophy of psychology and biology. Oxford University Press; 2002.\n\nArnold RM, Youngner SJ: The Dead Donor Rule: Should We Stretch It, Bend It, or Abandon It?. Kennedy Inst. Ethics J. 1993; 3: 263–278. Publisher Full Text\n\nBagheri A: Individual choice in the definition of death. J. Med. 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}
|
[
{
"id": "123954",
"date": "21 Mar 2022",
"name": "Michael Nair-Collins",
"expertise": [
"Reviewer Expertise Bioethics",
"philosophy",
"brain death"
],
"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 “Brain death debates: from bioethics to epistemology,” Alberto Molina Pérez argues that the debates on brain death have been characterized by a partisan nature: authors are, roughly, either for or against brain death as an appropriate criterion for death. In place of partisanship, Molina Pérez suggests a non-partisan, epistemological or philosophy of science-based approach to the topic, which would involve examining how the nature of death became an object of scientific inquiry, exploring the brain death criterion, and analyzing the core concepts of “irreversibility” and “function”.\nOverall, I think the article has the potential to contribute something of value to the brain death literature. Its key point – that the brain death literature can benefit from an examination rooted in philosophy of science – is well-taken. Is death something that can be studied empirically, is it a matter of physiology? Can there be an objective, rationally defensible answer to the question of what is human death, as a matter of physiology? Alternatively, is the nature of death necessarily a “social construction” or fundamentally a matter of agreement rather than discovery? Are all biological categories necessarily vague? Are pluralistic concepts always appropriate, such as how, some argue, the species concept is appropriately pluralistic and different species concepts can be marshalled for different scientific purposes – and so too for the concept of function, irreversibility, and death? And so on… These are all fundamentally situated in theories from the philosophy of science and philosophy of biology, and as such, these areas of research have much to offer the bioethical debates about brain death.\nMy main suggestions for revision involve the concept of partisanship and the terminology of “epistemology” vs. “philosophy of science”.\nTo suggest partisanship is to suggest a strong commitment to a cause (or political party), which is grounded in noncognitive reasons of affiliation with one’s “team”, rather than a commitment to truth and quality scholarship. This rendering of the debate seems to suggest that there aren’t any standards by which we might say that one view has better evidence and reasons in support of it; it also suggests that it is not the case that at least one side is, in fact, correct.\nOf course, brain death is a very longstanding debate, and it is very complex, drawing on metaphysics, philosophy of science, physiology, ethics, and much else besides, and it may well be true that we are unable to determine – as an epistemic matter – which side, if any, is actually right. But those considerations demand epistemic and moral humility. They do not lead quite so far as to suggest that this is a partisan issue of affiliation and persuasion, and that there aren’t any standards we could appeal to in evaluating distinct views. One could attempt to defend the view that all debates in scientific domains are characterized by something like incommensurability and as such, adherents are, in fact, partisan, and reason and evidence would not arbitrate such disputes. However I don’t think that broader thesis is being made here.\nSecond, the notion that taking a bioethical approach leads to partisanship, while taking a philosophy of science approach is non-partisan, doesn’t make sense to me. Why would simply approaching the issues from one perspective render one partisan, but approaching them from a different perspective render one non-partisan? Furthermore, any conclusions drawn from a philosophy of science approach are going to have implications for questions regarding brain death anyway, which would seem to lead back to partisanship on this view anyway.\nOverall I don’t get the sense that the concept of partisanship does a lot of work in the paper. My recommendation is to remove it entirely, or if not, clarify its use in light of the above comments.\nRegarding the terms “epistemology” and “philosophy of science”, I am a little uncertain about how they are used here. My understanding is that epistemology is the study of knowledge, while philosophy of science is a field that studies many aspects of science and its practice, drawing on epistemology, metaphysics, formal logic, philosophy of language, and so on. I am certain that I would not be alone in this interpretation of these terms, so I would suggest just rephrasing in terms of “philosophy of science” throughout and removing “epistemology” to avoid creating unnecessary confusion for readers.\nWhat follows are a number of comments; this should be read simply as having a conversation, rather than any particular requests for revisions based on the text below. The author should make any changes they think important or interesting enough, but need not reply to every point.\nSome comments on the term “function”: It is stated in the paper that “the notions of activity and function are not clearly defined in the literature” (p. 3). Perhaps their definitions are motivated, and bad definitions, but they are defined in the literature. The World Brain Death Project (Greer et al. 2020) and the International Guidelines for Determination of Death group (Shemie et al 2014) both explicitly define these terms, where “function” means something like “measurable on bedside neurological examination” and “activity” means “cellular phenomena recordable by technology”.\nGranted, I think that their definitions are bizarre, and clearly motivated by the goal of pretending that clinical practices in the diagnosis of brain death are consistent with the UDDA and the whole-brain criterion of death, when they are certainly not, since some brain function in the form of osmoregulation can continue in patients declared brain dead, and hence it is not true that “all functions of the entire brain” have ceased.\nIt is interesting to ask about the field within which we should address the question of function (cf. p. 5 discussion of biology, psychology, neurology definitions of function). Quite obviously, in this context the field is clinical medicine. And in clinical medicine, physicians assess cardiac, renal, hepatic (etc.) function using laboratory tests and imaging technology. It would be absolutely bizarre to suggest that a physician cannot assess their patient’s kidney function by evaluating lab measurements of urine and blood, because this only shows “activity and not function”. It would be similarly bizarre to suggest that a physician cannot assess their patient’s heart function with an EKG because this reflects the electrical activity of cells “recordable by technology”. This is what Greer et al 2020 and Shemie et al 2014 are saying with their definitions. The purpose is to be able to claim is that osmoregulation is not a function because it cannot be assessed at the bedside (which isn’t true anyway – normal urine output signals osmoregulation and hypothalamic function).\nIn any case, on any reasonable understanding of how physicians can and do assess the function of organs, there must be a variety of ways to do that, including bedside assessment, questionnaires, laboratory tests, imaging, and so on.\nFinally, the notion that “brain functions are not merely considered as physiological mechanisms, but also viewed in terms of whether they serve their intended behavioral purpose” (p. 5) seems incorrect, or to build in illicit assumptions, even within the context of neurophilosophy and brain-computer interface. First, any theory of function that makes it come out that all brain functions must have an overt, 3rd-person observable, behavioral manifestation does not seem right. There are many functions the brain is involved in that involve managing the homeostatic environment of the physiochemical milieu, even as simple as shunting blood from the periphery to the core, or causing blood vessels to constrict or dilate, and so on. In locked-in syndrome, the entire suite of normal cognitive functions are maintained, and occur without behavioral manifestation. Some of these cognitive functions become apparent through blinking, for sure, but not all. To assume that brain functions must have an overt behavioral manifestation seems to take an unjustified behaviorist approach to mentation.\nAnd then second, a function as understood within the context of natural selection would not have any “intended” purpose, behaviorally manifested or not. A function is something that had some advantage in an environment of evolutionary origin, and was reproduced, and that is it, at least on this view. For example, the intrinsic automaticity of the sinoatrial node manifests a clear function in preserving the heartbeat, but it does not “intend” anything, nor does it have an “intended purpose”. Who could have intended such a purpose?\nOn the dead donor rule: The manuscript states [death criteria] “may be good in a moral or policy sense because … they allow … organ procurement” (p. 4). This is a common thing to say, but I think it is confused. The criteria for death neither allow nor prohibit any policy or practice. In the case of organ procurement, it is the dead donor rule that prohibits organ procurement, not death criteria. If we as a society agree that donors should be dead first – we support the dead donor rule – then they should be dead. The criteria for what constitutes being dead cannot then be derived in such a way that it bypasses the entire point of the dead donor rule, which is to restrict organ procurement. If the dead donor rule matters, then the criteria for death must be independent of the dead donor rule itself, otherwise it becomes trivial, and is not a genuine constraint on behavior at all. On the other hand, if it’s ok to take organs from patients in state X, AND it turns out that patients in state X are still living, then it follows that the dead donor rule need not be adhered to. Either way, death criteria do not prohibit or allow anything.\nNair-Collins does not defend the brain criterion (p. 4): “As a consequence, some advocates of the brain criterion …, or homeostasis (Nair-Collins 2018)”.\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": [
{
"c_id": "8069",
"date": "20 Jun 2022",
"name": "Alberto Molina Pérez",
"role": "Author Response",
"response": "Comment: “To suggest partisanship is to suggest a strong commitment to a cause…” Response: With regard to the use of the term “partisanship”, I really appreciate your comment because I was not aware that this term could be interpreted in this context as it is in the political sphere. This was not the intention. As you say, this rendering of the debate would suggest “that there aren’t any standards by which we might say that one view has better evidence and reasons in support of it” and “that it is not the case that at least one side is, in fact, correct”. However, this is not the way I see the debate; quite the contrary. On the one hand, I think that all parties involved are strongly committed to truth and quality scholarship, and that their views are based on good evidence and well-considered reasons. On the other hand, I also believe that it is possible to critically assess the distinct views and show that some of them are based on flawed, inconsistent or unsatisfying arguments from a scientific and/or philosophical perspective. To do so in a useful way, we need to agree on the standards of evaluation and on the meaning of the concepts used. Some disagreements may be based on the fact that the different parties do not speak the same language, although they think they do. Other disagreements may stem from the fact that the parties have different objectives or different interpretations of what a “good” criterion means to them, although they are not necessarily aware that this is the root of their disagreement. This is why I think a “neutral” approach is needed to be on the same page. This would not solve all disagreements, but it would enable more fruitful debates based on more solid ground. C: “Second, the notion that taking a bioethical approach…” R: I agree with you. However, (bio)ethics refers to well-founded standards of right and wrong that prescribe what we ought to do. In this case, the question is whether or not we should keep using brain death (as it is or some modified version of it) to determine human death. Some support using brain death because they consider it is a good/right criterion for varying reasons (scientifically, ethically, as a policy, etc.) while others oppose it because they consider it is a bad/wrong criterion (scientifically, ethically, as a policy, etc.). The approach I am advocating for in this article means taking a step back, setting aside the question of whether brain death is good/right or bad/wrong, and asking more general questions to understand the very nature of a (any) death criterion. This is similar to your own proposition: “An objective and unbiased investigation of the biology of death is independent of, and should be undertaken prior to, an analysis of the normative questions engendered by debate about determination of death.” (Nair-Collins 2015) Perhaps the main difference is that you emphasize the scientific questions about the biology of death and dying, which I totally agree with, whereas I emphasize the (more general?) philosophical questions about the science of death determination. In some cases, both approaches coincide. For example, with regard to the distinction between activities and functions, you show how the definition of “function” in terms of clinical observability by the IGDD group is an ad hoc strategy to rule out neuroendocrine functions (op. cit.). This is real philosophy of science and it's beautifully done. However, a more general question remains unanswered: how does/should medicine define functions and distinguish them from mere activities? I think it is (ideally) possible to come to an agreement on this issue regardless of where everyone stands on brain death. But it is true (hopefully) that the conclusions drawn from this—objective and unbiased, to use your words—approach of functions in medicine can have implications for the debates on brain death and the question of whether we should keep using it as is, revise it, or abandon it. C: “Overall I don’t get the sense that the concept of partisanship does a lot of work in the paper.” R: I have removed any reference to partisanship from the abstract and the text. I have also tried to emphasized that discrepancies between scholars are not based on mere opinions or ideological affiliations: “They [death criteria] may be good for a combination of reasons. These reasons have their advocates and opponents, both committed to truth and quality scholarship and based on good evidence and well-considered scientific and/or philosophical arguments.” (p.3) “Ideally, the answers to these questions could be shared by most scholars, regardless of their position on the issue of brain death.” (p.3) C: “Regarding the terms ‘epistemology’ and ‘philosophy of science’…” R: I understand your confusion with regard to the use of the term “epistemology”. In France and in Spain, where I trained as a philosopher, “epistemology” and “history and philosophy of science” are used as synonyms. This is not the case elsewhere. In the first draft of the manuscript, I used “epistemology” alone because it felt more natural to me, then I added “or philosophy of science” to try to convey this equivalent meaning. Following your advice, to avoid any confusion for readers, I removed the term “epistemology”. C: “Some comments on the term ‘function’…” R: Definitions of activity and function are scarce and, when available, suboptimal (to say the least). I have included in the manuscript the two references you mention so that the reader can make their own opinion. C: “Granted, I think that their definitions are bizarre…” R: I agree. Still, I think it should be possible to find a more charitable interpretation. I am increasingly convinced that some disagreements, especially between philosophers and clinicians, are just misunderstandings based on different mental frameworks—not only with different ways of approaching the same questions but also different views on what it means to give these questions a satisfactory answer. This does not necessarily mean that these particular definitions are correct or even justifiable, but it means that we should (also) assess their validity/justification against the internal logic of functional attributions in medicine. What is this internal logic? That's the question I ask myself. C: “It is interesting to ask about the field within which we should address the question of function…” R: Your comment prompted me to adopt the role of the devil’s advocate and seek alternative interpretations. First, the distinction between “measurable on bedside” vs. “recordable by technology” reminded me of debates about theory and observation in science and whether the use of instruments to augment the human senses counts as an observation. Second, we could reverse the reasoning. Let’s suppose that Greer, Shemie, and colleagues make the following implicit assumption: only living organisms have functions. Based in it, we could argue that if brain dead patients are dead (and I am sure they truly believe it) and if, despite being dead, there is still osmoregulation and other hypothalamic activity, then these activities are not functional. These lines of argumentation are just two sketchy examples that could be further developed and improved. Personally, I find them unconvincing, but at least they make sense (kind of). C: “Finally, the notion that “brain functions are not merely considered as physiological mechanisms…” I don't have a clear idea on this yet. I would need to think about it more. C: “And then second, a function as understood within the context of natural selection would not have any “intended” purpose, behaviorally manifested or not…” Obviously, functions (and biological traits in general) don’t have intentions. The notions of intention, purpose, design, etc., are controversial in biology and are usually considered as informal ways of talking. The intended purpose of a biological trait (organ, structure, process, etc.), in the context of natural selection, is what this trait (an occurrence of it) is supposed to do according to the type it belongs to, and this type is constituted by its etiology. In other words, the sinoatrial node of a particular heart in a particular individual is supposed to preserve the heartbeat (and thus contribute to the circulation of blood) because it belongs to a type of cells (or group of cells) who, because they have had in the past (previous generations) the consequence of preserving the heartbeat, have contributed to the reproductive success of their ancestor organisms. In simpler words, the function of a trait is what this trait has been selected for. This is what, in the context of an etiological conception of functions (e.g. Larry Wright, Karen Neander, Ruth Garrett Millikan), we can consider as being the “intended purpose” of a trait, although there is nobody or nothing to actually intend it nor any actual purpose into it, but it is an easier way of talking. I have now put the expression “intended behavioural purpose” between quotation marks to indicate that it must not be taken literally. C: “On the dead donor rule…” R: Indeed, it is the dead donor rule that prohibits organ procurement, not the criterion itself, and I agree that both things must be independent. However, we can consider death criteria from at least two different perspectives. One is medical, the other is legal. Medical criteria are supposed to determine whether the patient is dead or not as a matter of fact in the biological realm (I am not sure whether this characterisation is accurate and, if so, whether I would agree with it, but let’s assume it), whereas legal criteria determine whether the patient is dead or not as a matter of law in the social and legal realms. Legal death allows social and legal practices beyond organ donation: autopsies, burial, mourning, inheritance, payment of life insurances, etc. Legal death and biological death do not necessarily coincide. For instance, an individual who has been missing for many years can be declared dead in absentia, without any actual proof of their death. This is a good policy because families and society as a whole need such a mechanism (although there may be false positives). Similarly, we could consider the UDDA (i.e. the current legal criteria of death, including the brain criterion) as good policy regardless of the issue of organ procurement. C: “Nair-Collins does not defend the brain criterion…” R: Indeed. I corrected the wording of the sentence to avoid any confusion: “As a consequence, some advocates of the brain criterion…, whereas critics…, or homeostasis (Nair-Collins 2018)”."
}
]
},
{
"id": "123955",
"date": "31 Mar 2022",
"name": "Milena Maglio",
"expertise": [
"Reviewer Expertise Milena Maglio: moral philosophy",
"bioethics and clinical ethics. Vivien García: moral and political philosophy",
"ethics and philosophy of 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\nIn “Brain death debates: from bioethics to epistemology”, Alberto Molina Pérez recalls the still controversial character of the neurological determination of death. He also maintains that “to this day, most academic debates around brain death have been and are bioethical”. To support this claim, he draws on extensive literature on the topic; this is undoubtedly one of the great qualities of his contribution. But the main thesis of this opinion article goes further, Molina Pérez argues for a shift of the debate toward “epistemology or, to be more accurate, … philosophy of science”. More exactly, he suggests examining “the determination of death as an object of scientific inquiry”. Aiming at illustrating the relevance of the change of approach he pleads for, Molina Pérez briefly analyses two core concepts of death criteria — “irreversibility” and “functions” — and shows that each of them bear meaning which are different and possibly conflicting.\nThe main strength of the paper lies in this demonstration, in particular, in the analysis of the concept of “functions”. The distinction between “brain functions” and “brain functionality” is quite convincing and original. Although promising, the analysis of the concept of “irreversibility” is not so clear. Here come the first suggested revision. On page 3 (§2), the author refers to a distinction between “permanent” and “irreversible” cessation of “functions”. In the first case, he says, the cessation “will not reverse” but it is “not necessarily irreversible”. In the second case, the cessation “cannot reverse”. However, on page 5 (last §). Molina Pérez presents 3 possible interpretations of “irreversibility”: “as either absolute, relative, or permanent”. Presented this way, the permanent cessation of a functions seems to be one type of irreversibility. Moreover, only 2 of the 3 terms are explained, so it is not clear if relative and permanent “irreversibility” can be taken as synonyms. We suggest that the author clarify the formulations of these two paragraphs.\nAnother possible criticism (which leads to the suggestion of a second minor revision) could be that the author raises many interesting questions without addressing them, i.e: “What a death criterion is: is it a heuristic or a definition? Is it descriptive, stipulative or performative? Is it a rule of inference, and if so, what is its logical structure? For example, is the determination of the death of an individual the conclusion of a syllogism?”\nThis is problematic because:\nthese questions are clearly related to the main goal of this paper: “examining how the determination of human death became a scientific issue and why medicine claims epistemic authority over it”;\n\naccording to the author, here lies all the interest of his “epistemological or philosophy of science approach”.\nIf the author has already addressed these questions elsewhere, or plans to do so, he should at least provide references. If not, he could reduce the number of questions and focus on the relevant ones for the present article.\nAs pointed out in Michael Nair-Collins' review, Molina Pérez should make clear what he means by “epistemology” and “philosophy of science”. As non-native English speakers, and academics trained in continental philosophy, our understanding of how Molina Pérez uses these words is probably different from Nair-Collins' one. To prevent misunderstandings (and this is the third revision suggested), the author should definitely clarify his take on the matter.\nBeyond these terminological concerns, and without suggesting any revision this time, we would like to stress that the core thesis of the paper — the need for a shift “from bioethics to epistemology” — is not self-evident. As a matter of fact, after reporting the outcomes of a forthcoming study, Molina Pérez argues that the “type of analysis [he supports] leads to policy recommendations and ethical considerations”. In a provocative way, one could say that the author finally moves from “epistemology” to bioethics, or assert that this epistemological “digression” fundamentally serves (normative) ethical purposes.\nThe brain death debates could certainly benefit from taking more seriously the “epistemological” approach. But the latter will hardly eliminate, in particular in the medical field, a haunting ethical question: why do we value human life? This is not a mere theoretical problem. In some medical practices, in end-of-life decisions, before the determination of death comes into play (and whatever criteria we choose for this purpose) this question frequently reappears, either implicitly or explicitly. For example, in Controlled Donation After Cardiac Arrest — even if the Dead Donor Rule remains a fundamental moral norm for organ retrieval — the issues related to futile treatments and the decision to withdraw life-sustaining treatments can be far more relevant than the definition of death.\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": [
{
"c_id": "8070",
"date": "20 Jun 2022",
"name": "Alberto Molina Pérez",
"role": "Author Response",
"response": "Comment: “the analysis of the concept of ‘irreversibility’ is not so clear” Response: I appreciate your comment on the lack of clarity of the term “irreversibility”. In the first paragraph you mention, the focus is on the requisite of permanence (i.e. will not reverse) as opposed to irreversibility (i.e. cannot reverse). Although briefly explicated, both terms remain quite vague but I would prefer not to enter into further details there. In the second paragraph you mention, further clarification is indeed necessary. I have made a series of changes to better explain absolute irreversibility, relative irreversibility, and permanence. C: “Another possible criticism…” R: With regard to your comment on unaddressed questions, my objective was to show a sample of the questions that can be asked from a philosophy of science perspective and for which, as far as I know, no one has yet proposed an answer, neither have I. This article is a way to draw the attention of researchers like you to a field of research that is still underexplored and to lay the foundations for future work; a work that will require the collaboration of many. To avoid the accumulation, I have rephrased the passage as follows: “It means asking, for example, whether death criteria are heuristics or definitions, and whether the determination of the patient’s death is the conclusion of a syllogism.” C: “Molina Pérez should make clear what he means by ‘epistemology’ and ‘philosophy of science’…” R: To avoid any confusion, I have removed the term “epistemology”. C: “Beyond these terminological concerns…” R: It is true that after conducting a conceptual and logical analysis of death criteria from a philosophy of science perspective, my colleagues and I moved back to bioethics. I sincerely hope that this back and forth may prove useful to address normative questions. However, I would not say that the epistemological approach is a digression at the service of ethical purposes. In my opinion, these are two autonomous and complementary ways to approach and address some of the issues raised by the determination of human death. C: “The brain death debates could certainly benefit from taking more seriously the “epistemological” approach. But…” R: I agree that some end-of-life ethical issues, such as the dead donor rule and the decision to withdraw life-sustaining treatments, are independent from the epistemic issues raised by the definition and determination of death. I believe it is important to distinguish, as much as possible, facts from values, ‘is’ from ‘ought’. One of the criticisms formulated against brain death is that it is a way of disguising normative questions under the appearance of a factual question. If we are not careful, the same strategy could be used for other end-of-life issues."
}
]
}
] | 1
|
https://f1000research.com/articles/11-195
|
https://f1000research.com/articles/11-669/v1
|
17 Jun 22
|
{
"type": "Data Note",
"title": "Data on antibiograms and resistance genes of Enterobacterales isolated from ready-to-eat street food of Ambato, Ecuador",
"authors": [
"Jessica Tubón",
"Gabriela Barragán-Fonseca",
"Liliana Lalaleo",
"William Calero-Cáceres",
"Jessica Tubón",
"Gabriela Barragán-Fonseca",
"Liliana Lalaleo"
],
"abstract": "Foodborne pathogens represent a significant cause of negative impacts on human health and the economy worldwide. Unfortunately, information about epidemiological insights in Latin American countries is scarce. The consumption of ready-to-eat street food in Ecuador is extensive, and information about the presence of foodborne pathogens, their virulence factors, and antimicrobial resistance is negligible. This data includes the occurrence, phenotypic antibiotic resistance profiles, and antibiotic resistance genes of Enterobacterales isolated from ready-to-eat street food in Ambato, central Ecuador during 2020 and 2021. The most common genera detected were Escherichia coli, Klebsiella spp., and Cronobacter spp. Agar disk diffusion assays were performed to determine their phenotypic resistance. The presence of antibiotic resistance genes conferring resistance against colistin, β-Lactams, aminoglycosides, tetracyclines, sulfonamides, fluoroquinolones, and amphenicols was detected via polymerase chain reaction (PCR) amplification.",
"keywords": [
"antibiotic resistance",
"enterobacterales",
"escherichia coli",
"street food",
"food microbiology"
],
"content": "Introduction\n\nThis data contributes information about the antibiotic resistance profiles of Enterobacterales strains isolated from street food that will facilitate pathogen surveillance in Ecuador and Latin America. This data is useful for the scientific community to determine the presence of pathogenic Escherichia coli isolates and antibiotic resistance genes, including mobile colistin resistance genes, carbapenemases, quinolone resistance genes, and extended-spectrum β-lactamases present on Enterobacterales strains isolated from street food. Researchers and policymakers involved with the work related to the One Health initiative could also benefit from this data for retrospective and comparative analysis or epidemiological surveillance projects.1,2\n\n\nMethods\n\nReady-to-eat street food was obtained in the streets of the city of Ambato, Ecuador, and processed the same day. A sharp sterile blade was used to cut the samples on sterile surfaces. 10 g of each sample was placed in sterile brain heart infusion broth (BHIB) (Merck, Darmstadt, Germany) in 90 ml, shaken on a rotator for 8-10 min, and incubated for 24 h at 37 °C. A large amount of broth was inoculated on MacConkey agar plates (Merck, Darmstadt, Germany), Cromocult Coliforms Agar (Merck KGaA, Darmstadt, Germany), and CHROMagar mSuperCARBA were incubated overnight at 37 °C under aerobic conditions. Further purification was performed on Macconkey agar.\n\nThe isolates were amplified by polymerase chain reaction (PCR), analysed using agarose gel electrophoresis and visualised with Sybr Safe DNA Gel Stain.3 For the identification of the isolated Enterobacterales, biochemical tests such as catalase, oxidase, TSI agar, Simmons citrate, lactose test, indole production, urea agar, methyl red test, and Voges-Proskauer were carried out and their interpretation was performed based on Bergey's manual.4 Additionally, the software for Automated Biometric Identification Systems (ABIS) was used to confirm the biochemical identification results.\n\nAgar disk diffusion assays (Thermo Scientific Oxoid and Bioanalyse) on Mueller-Hinton Agar (Thermo Scientific Oxoid) were performed. Antibiograms tests were based on the measured diameter of the zones of inhibition and interpreted as sensible, intermediate or resistant by referring to CLSI breakpoints.5\n\nThe PCR test was performed according to the standardized protocol of the UTA RAM One Health research group6,7: 2.5 μL of DNA from each sample and 22.5 μL of PCR mix containing 12.5 μL DreamTaq PCR Master Mix (ThermoFisher Scientific, USA), 9 μL Nuclease-free water, 0.5 μL Primer 1 and 0.5 μL Primer 2 (final concentration of primers: 0.5 μM) were mixed to run PCR. The PCR conditions are reported in Supplementary Table S4. PCR products were analyzed by 1.2% agarose gel electrophoresis stained by Sybr Safe DNA Gel Stain (ThermoFisher Scientific, USA).\n\nHierarchical clustering\n\nHierarchical clustering was performed using the Euclidean correlation method and clustered by affinity.2 The MeV Multiexperiment Viewer software version 4.8.1 was used in this study.\n\nThe data presented show the frequency of isolation of Enterobacterales in 151 samples of ready-to-eat street food in Ambato, Ecuador (Figure 1). The specific characteristics (date of sampling, type of street food, location) of the samples were reported in Supplementary Table S1. A total of 145 isolates were analyzed, and the results of the biochemical tests were reported in Supplementary Table S2. Among them, 86 isolates corresponded to E. coli and 59 isolates to other Enterobacterales.\n\nTo visualize the relative similarity of the antimicrobial resistance patterns of the isolates, a hierarchical cluster analysis was performed using the results of the antibiograms, where the phenotypes ‘resistant’, ‘intermediate’, and ‘susceptible’ were observed as red, white, and blue colors respectively. Dendrograms and clustered data were assembled using the complete linkage method through Pearson correlation and sample leaf organization.7 For this purpose, the MeV Multiexperiment Viewer software version 4.8.1 was used.8 Figures 2 and 3 represent the resistance profiles and the hierarchical clustering of E. coli and the rest of Enterobacterales, respectively. The complete information is shown in Supplementary Table S3.\n\nRed: resistant, White: intermediate, Blue: sensitive.\n\nRed: resistant, White: intermediate, Blue: sensitive.\n\nAbbreviations: TE: Tetracycline 30 μg, AM: Ampicilin 10 μg, KF: cephalotin 30 μg, C: chloramphenicol 30 μg, CIP: Ciprofloxacin 5 μg, CTX: Cefatoxime 30 μg, LEV: Levofloxacin 5 μg, FOX: Cefoxitin 30 μg, STX: Trimethoprim/sulphamethoxazole 25 μg, AMC: Amoxicyllin/ClavulanicAcid 30 μg, CN: Gentamicin 10 μg, CRO: Ceftriaxione 30 μg, FEP: Cefepime 30 μg, ATM: Aztreonam 30 μg, IPM: Imipenem 10 μg, TPZ: Piperacillin/Tazobactam 110 μg, ETP: Ertapenem 10 μg, MEM: Meropenem 10 μg, CAZ: Ceftazidime 30 μg.\n\nThe presence of diarrheagenic E. coli pathotypes present in ready-to-eat food was assessed in this study through the analysis of virulence genes related to the pathotypes. Only one isolate (C2.1c) was positive for the eae gene, suggesting the potential presence of enteropathogenic E. coli (EPEC) or enterohemorrhagic E. coli (EHEC). The β-lactamase resistance genes of Enterobacterales isolated in this study are reported in Table 1. Mobile colistin resistance genes or quinolone resistance genes were not found in the Enterobacterales isolates. The complete information about virulence genes and antibiotic resistance genes are available in Supplementary Table S5. The information about primers and PCR conditions were shown in Supplementary Table S4. The gel electrophoresis images are available at Supplementary figure S6. The disk difussion assays figures were shown at Supplementary figure S7.\n\n\nData availability\n\nFigshare project: https://figshare.com/projects/Data_on_antibiograms_and_resistance_genes_of_Enterobacterales_isolated_from_Ready-to-eat_street_food_of_Ambato_Ecuador/137014\n\nThis collection contains the following underlying data:\n\nFigure 1. Occurrence of Enterobacterales on 151 samples of ready-to-eat street foods in Ambato, Ecuador. figshare. Figure. https://doi.org/10.6084/m9.figshare.19579087.v19\n\nTable 1. Beta-lactamase resistance genes of Enterobacterales isolated from ready-to-eat food. figshare. Dataset. https://doi.org/10.6084/m9.figshare.19579099.v110\n\nFigure 2 and 3. Antibiotic resistance profiles and hierarchical trees of Enterobacterales isolated from ready-to-eat street food in Ambato, Ecuador. figshare. Dataset. https://doi.org/10.6084/m9.figshare.19579267.v111\n\nThis collection contains the following extended data:\n\nSupplementary table S1. Characteristics (Sample type, date, treatment type, location, coordinates) of the ready-to-eat food samples. figshare. Dataset. https://doi.org/10.6084/m9.figshare.19579108.v112\n\nSupplementary table S2. Biochemical tests performed on Enterobacterales isolates from Ready-to-eat Street Food in Ambato, Ecuador. figshare. Dataset. https://doi.org/10.6084/m9.figshare.19579177.v113\n\nSupplementary table S3. Antibiogram of Enterobacterales isolated from ready-to-eat Street food of Ambato, Ecuador. figshare. Dataset. https://doi.org/10.6084/m9.figshare.19579189.v114\n\nSupplementary table S4. Primers used in this study and PCR conditions. figshare. Dataset. https://doi.org/10.6084/m9.figshare.19579198.v115\n\nSupplementary table S5. Antibiotic resistance genes and virulence genes harbored by Enterobacterales isolates from ready-to-eat street food in Ecuador. figshare. Dataset. https://doi.org/10.6084/m9.figshare.19579207.v116\n\nSupplementary figure S6. PCR results (positive electrophoresis images). figshare. Figure. https://doi.org/10.6084/m9.figshare.19729618.v117\n\nSupplementary figure S7. Disk diffusion assay images-Antibiotic resistance evaluation of Enterobacterales isolated from ready-to-eat street food of Ambato, Ecuador. figshare. Figure. https://doi.org/10.6084/m9.figshare.19729630.v118\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgments\n\nThe authors would like to thank to the Directorate of Postgraduate Studies of the Department of Food and Biotechnology Science and Engineering, Universidad Técnica de Ambato.\n\n\nReferences\n\nF. and A.O. of the U.N: (FAO) and W.O. for A.H. (OIE) World Health Organization (WHO), Monitoring and evaluation of the global action plan on antimicrobial resistance: framework and recommended indicators.2019.\n\nGuardabassi L, Butaye P, Dockrell DH, et al.: One Health: a multifaceted concept combining diverse approaches to prevent and control antimicrobial resistance. Clin. Microbiol. Infect. 2020; 26: 1604–1605. PubMed Abstract | Publisher Full Text\n\nSalazar GA, Guerrero-López R, Lalaleo L, et al.: Prevalence and diversity of Salmonella isolated from layer farms in central Ecuador. F1000Res. 2019; 8: 235. Publisher Full Text\n\nBernner D, Farmer J: Enterobacteriaceae, Bergey’s Man. Syst. Archaea Bact. 2015. Publisher Full Text\n\nCLSI, Clinical and Laboratory Standards Institute: Performance standards for antimicrobial susceptibility testing, 31th ed., in: 2021.2021.\n\nChandra M, Cheng P, Rondeau G, et al.: A single step multiplex PCR for identification of six diarrheagenic E. coli pathotypes and Salmonella. Int. J. Med. Microbiol. 2013; 303: 210–216. PubMed Abstract | Publisher Full Text\n\nSánchez-Salazar E, Gudiño ME, Sevillano G, et al.: Antibiotic resistance of Salmonella strains from layer poultry farms in central Ecuador. J. Appl. Microbiol. 2019; 128: 1347–1354. PubMed Abstract | Publisher Full Text\n\nBerrazeg M, Drissi M, Medjahed L, et al.: Hierarchical clustering as a rapid tool for surveillance of emerging antibiotic-resistance phenotypes in Klebsiella pneumoniae strains. J. Med. Microbiol. 2013; 62: 864–874. PubMed Abstract | Publisher Full Text\n\nCalero-Cáceres W: Fig. 1. Occurrence of Enterobacterales on 151 samples of ready-to-eat street foods in Ambato, Ecuador. figshare. Figure.2022. Publisher Full Text\n\nCalero-Cáceres W: Table 1. Beta-lactamase resistance genes of Enterobacterales isolated from ready-to-eat food. figshare. Dataset.2022. Publisher Full Text\n\nCalero-Cáceres W: Antibiotic resistance profiles and hierarchical trees of Enterobacterales isolated from ready-to-eat street food in Ambato, Ecuador. figshare. Dataset.2022. Publisher Full Text\n\nCalero-Cáceres W: Characteristics (Sample type, date,treatment type,location, coordinates) of the ready-to-eat food samples. figshare. Dataset.2022. Publisher Full Text\n\nCalero-Cáceres W: Biochemical tests performed on Enterobacterales isolates from Ready-to-eat Street Food in Ambato, Ecuador. figshare. Dataset.2022. Publisher Full Text\n\nCalero-Cáceres W: Antibiogram of Enterobacterales isolated from ready-to-eat Street food of Ambato, Ecuador. figshare. Dataset.2022. Publisher Full Text\n\nCalero-Cáceres W: Primers used in this study and PCR conditions. figshare. Dataset.2022. Publisher Full Text\n\nCalero-Cáceres W: Antibiotic resistance genes and virulence genes harbored by Enterobacterales isolates from ready-to-eat street food in Ecuador. figshare. Dataset.2022. Publisher Full Text\n\nCalero-Cáceres W: PCR results (positive electrophoresis images). figshare. Figure.2022. Publisher Full Text\n\nCalero-Cáceres W: Disk diffusion assay images-Antibiotic resistance evaluation of Enterobacterales isolated from ready-to-eat street food of Ambato, Ecuador. figshare. Figure.2022. Publisher Full Text"
}
|
[
{
"id": "141529",
"date": "23 Jun 2022",
"name": "Laura Sala-Comorera",
"expertise": [
"Reviewer Expertise water microbiology",
"food microbiology",
"microbial source tracking"
],
"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 note article, Turbón and colleagues examined the antibiograms and resistance genes profiles of Enterobacterales order strains isolated in ready-to-eat street food in Ecuador. A larger number of samples and types of food have been selected, resulting in a solid database of Enterobacterales strains (n=151).\nI suggested a few points to be clarified.\nMethods\nEnterobacterales strains- Section\n“A larger amount of broth”. The authors can specify the volume used for the analysis.\n\nAdd the reference for the “software for Automated Biometric Identification Systems (ABIS)”.\n\nPhenotypic antibiotic resistance profiles – Section.\n\nInclude the full reference for these companies (Thermo Scientific Oxoid and Bioanalyse) following the same style as the previous ones.\n\nDetection of E. coli pathotypes and antibiotic resistance genes detection via PCR - Section.\nInclude the method/kid used for the DNA extraction.\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": "141528",
"date": "05 Jul 2022",
"name": "Edgar Gonzalez-Villalobos",
"expertise": [
"Reviewer Expertise antibiotic resistance",
"microbiology",
"phages"
],
"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 Latin American countries the consumption of street food represents in the majority the alimentary base, due to the conditions that present the most countries belonging to Latin American, for this reason, the information generated by Turbón et al., could facilitate the epidemiology surveillance and allow action before the emergence of foodborne pathogens outbreak. The authors carry out a complete characterization of a significant number of strains (n=151), highlighting the distribution of pathogens, antibiotic resistance profiles, presence of antibiotic resistance genes.\nI suggest reviewing next points:\nThe sentence that refers to \"The isolates were amplified by polymerase chain reaction (PCR)\" confuses a bit since later it is specified that the identification is carried out with conventional biochemicals, just to clarify well, why PCR was used in this section.\n\nAdd information about how to DNA was obtained for PCR assays.\n\nWas there any pathogen that predominated in the sampling areas? If so, the results could show a strain that is already distributed in the community with outbreak potential.\nBoth articles (that are referenced below) are related with the importance of a good epidemiological surveillance system in a possible outbreak of foodborne pathogens. These are closely related to the study presented by the authors, where they carry out the isolation and complete characterization, anticipating of the emergence of foodborne pathogens in an area such as Latin America where epidemiological data usually are limited.\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": "141527",
"date": "19 Jul 2022",
"name": "Erika A. Rodriguez",
"expertise": [
"Reviewer Expertise Bacterial Antibiotic Resistance",
"Molecular Microbiology",
"Molecular Epidemiology",
"Medical 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\nThe data note by Tubón J et al. aims to give information about the antibiotic resistance profiles of Enterobacterales strains isolated from street food in Ecuador. The work is relevant because, usually in Latin American countries, street food consumption is typical, it has little sanitary regulation, and in some towns, potable water access is limited, which could favor the presence of resistant bacteria in foods. On the other hand, the research gives information about antibiotic resistance in settings different from hospitals and contributes information from Latin American countries where the data is limited. Another relevant point is that the work detects antibiotic resistance Enterobacterales strains in cooked food differently from other studies on lettuce and raw vegetables. The manuscript is well structured and written. The protocols are appropriate and provide acceptable methods and details to allow replication.\nI have provided comments/suggestions as follows:\nI suggest to future reports, the author gives information about the bacteria typification, such as ERIC, PFGE, MLST, or WGS. This information could be help to understand what clones to type of strains are circulating in the region.\n\nWhat is the resistance behavior in the Ambato hospitals where the project was carried out? The results could help to understand the resistance problem in the city?\n\nAny limitations related to this manuscript and/or methods you want to bring up to the reader?\n\nIn the profiles of antibiotic resistance, there are Enterobacterales isolates resistant to carbapenems, and you did not detect carbapenemases. Could you give information about the reason to this resistance, for example, intrinsic mechanisms or other beta-lactamases not detected?\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/11-669
|
https://f1000research.com/articles/11-668/v1
|
17 Jun 22
|
{
"type": "Research Article",
"title": "Educating delinquent youths: A qualitative approach to understand the Malaysian story",
"authors": [
"Jowati Juhary",
"Ahmad Thamrini Fadzlin Syed Mohamed",
"Erda Wati Bakar",
"Ahmad Thamrini Fadzlin Syed Mohamed",
"Erda Wati Bakar"
],
"abstract": "Background: This paper reports on the first stage of a larger research project on the education of delinquent youths in Malaysia. Specifically, this paper addresses the challenges of educating delinquent youths in the country. As a developing nation, Malaysia faces various issues pertaining social and youth development. The question explored in this study is whether delinquent youths in Malaysia are neglected in terms of systematic and adequate education. In Malaysia, delinquent youths are sent to correctional facilities all around the country, where they are separated from school systems, their families and communities; it can be argued that these youths are deprived of moral support from society. This paper aims to identify the challenges around educating delinquent youths in Malaysia and to recommend potential solutions to these challenges. Methods: The research approaches adopted for this paper included content analysis of printed documents and preliminary informal interviews with the staff at one correctional facility. Content analysis data were gathered from departmental and government documents made public as well as past research on delinquent youths. Meanwhile, a curtesy visit was made to a correctional facility in Kuala Lumpur to obtain preliminary input into the education and training provided at the facility. Results: The authors found that there are three main challenges to sufficiently educating delinquent youths in Malaysia. These include unclear policy on the education of youths at correctional facilities; the lack of frameworks facilitating the education of these youths; and the lack of awareness and understanding on the need for educating these youths, despite their behaviors. Conclusions: The paper ends with two solutions to these challenges and future directions for the education of delinquent youths in Malaysia.",
"keywords": [
"correctional facilities",
"delinquent youths",
"disruptive behaviors",
"educating delinquent youths",
"juveniles",
"social development",
"youth development"
],
"content": "Introduction\n\nAs a developing nation, the education system in Malaysia plays a critical role in its economic and social development. The education system is not just about providing academic aptness; most importantly, the system assists in the development of self-efficacy and self-worth through value learning that promotes good-moral conduct (Budin, 2013). To date, the government has given tremendous support to gifted and talented students by nurturing and bringing forth their talents through various programs; one of those is PERMATA, a national program to mold and educate Malaysian children (see Adnan et al., 2016; Mohd. Sharif et al., 2020). PERMATA is an Early Childhood Guide and Education and has several categories such as PERMATA Pintar (for inculcating intellectual capacity) and PERMATA Seni (for inculcating cultural performance capacity). The government has designed and developed these programs in order to nurture these young talents because they are the assets of the country.\n\nDespite these efforts and programs created for talented youths, does Malaysia have a systematic program for those not so talented and delinquent students? To date, the Malaysian government has been working hard to overcome the increasing national concern about youth violence, which is considered from a social perspective, a significant public health issue (Reffien et al., 2020). Hassan et al. (2016) indicated in their work that the Ministry of Education, Malaysia, and the Department of Education at the state level have been taking proactive measures to overcome such cases. These include the enforcement of numerous laws such as acts under Articles 19 and 37 of the Child Act 2001 and Child Protection Plan 2009; intervention programs; and the distribution of circulars that detailed out a clear preventive measure to abdicate bully cases in schools. In addition, Nasrul and Zarina (2017) listed six official guidebooks and over 40 periodic circulars from the Ministry of Education, Malaysia on the procedures to be adhered to by the school management in handling students’ disciplinary problems.\n\nThis paper uses the term delinquent youths and juveniles interchangeably throughout the discussion; thus, it is important to set the parameter of these terms. The authors adopt the definition of delinquent youths as that offered by Abdullah et al. (2015). They refer to delinquent youths as youths associated with juvenile delinquency, juvenile offending, or youth crime, and argue that these can be considered normative teen behaviors and that most young people commit non-violent crimes during adolescence. Further, Siegel and Welsh (2005) defined delinquent youths as those participating in illegal behavior, and that in most countries the age of these youths is no more than 19 years old. Therefore, the authors opine that, in this paper, the term delinquent youths suggest youths between the ages of 10 to 19 years old, who commit non-violent acts that are not considered normal behavior and are not acceptable in Malaysian society.\n\nIt is argued that there are two sets of arrangement for the education system in Malaysia: inclusion and exclusion (see Ozel et al., 2017). The first educational arrangement, according to OECD (2012), caters for the development of model-citizens, in which the mainstream schools are not for those students with disruptive behaviors. This then creates the second arrangement for those students who are labelled as possessing disruptive behaviors and cannot follow the normal educational programs. The separation from society and the regular education system unfortunately results in marginalization in adult life. Furthermore, these youths with so-called disruptive behaviors are often displaced by society and hence decentralized from the mainstream educational system (or even reality) which further reinforces their disruptive behavior and can lead to further social problems. Faruqee (2016) argued that youth prisons are an outdated approach plagued by physical and sexual abuse, neglect, and segregation. This is because the approach further keeps the youth from society, family, and friends, who could be the best source of support.\n\nThis paper addresses the challenges of educating delinquent youths in Malaysia, or to follow the previous argument, educating students in the second arrangement system. This paper explores whether delinquent youths in Malaysia are neglected in systematic and adequate education systems. In Malaysia, delinquent youths are sent to correctional facilities across the country, where they are separated from the mainstream school systems, their families and communities; it can be argued that these youths are deprived of moral support from society, and especially their loved ones. To fulfil the objective of this paper, two research questions will be answered. These are, firstly, to identify the challenges of educating delinquent youths in Malaysia and, secondly, to recommend possible solutions to these challenges.\n\nThere are several main sections in this paper. The first section frames the context for discussion of educating delinquent youths in Malaysia. The second section presents the main data. Challenges around educating delinquent youths are then synthesized and arranged according to their importance. This is then followed by the methodology section which explains the methodology adopted to complete this paper, including content analysis and informal interviews with staff at one correctional facility in Kuala Lumpur. The fourth section presents the data of this paper, triangulation of what is evident in the departmental and government documents and excerpts from the preliminary interviews at the correctional facility. Lastly, a concluding section offers solutions to the challenges of educating delinquent youths and summarizes the findings.\n\n\nThe need to educate delinquent youths systematically\n\nThis section presents selected literature on educating delinquent youths globally and in Malaysia. There are two sub sections that correspond to the nature of educating these youths, the current situation surrounding delinquent youths and the past, present, and future challenges.\n\nBased on reports on delinquent youths, disruptive behaviors have not only damaged these youths physically, emotionally, and mentally, but have also affected the well-being of the country. According to Holbrook et al. (2018), the well-being of a country is affected because more money is required to create suitable prevention and corrective programs. Further, Faruqee (2016) also reported that, in Virginia, it costs USD142,000 per year to incarcerate just one young person, where 75 percent of them will relapse within a few years. Cases on delinquent behaviors in Malaysia are narrated by Sayuti et al. (2020), Mustafa et al. (2017) and Hassan et al. (2016). These researchers concluded that delinquent teenagers in Malaysia were involved in cases such as bullying, running away from home, cutting school, stealing, smoking, substance abuse, pre-marital sex, and child abandonment. As illustrated in Tables 1 and 2, the age group with the highest rates of drug addiction among youths in Malaysia is between 16 and 19 years old and most of the youths involved in substance abuse received education at the LCE/SRP/PMR/PT3 level.\n\nDespite a gradual decline in the number of delinquency cases from 2010 to 2013 (see Tables 1 and 2), there is an alarming increase in the number of drug addicts below the legal age each passing year. Furthermore, the data also show an increase of 55 percent of unschooled children since 2010. Nonetheless, Figures 1 and 2 illustrate a different scenario of the delinquent cases in Malaysia after 2016, where it is observed that the number of youths involved in disruptive behaviors reflect the number of cases, and that from 2016 to 2020, the overall number of cases has decreased tremendously (Figure 1). In addition, there has been a slight decline from 2017 to 2018 in the number of first offenders and an increase of 184 cases of repeated offenders from 2017 to 2018 (Figure 2). The factors effecting the decrease in numbers for both cases and youths are aplenty, including effective measures taken by the authority and preventive programs adopted by society. However, these factors will not be examined in this paper.\n\nSource: Malaysia Youth Data Bank System (2019).\n\nSource: Department of Statistics, Malaysia (2019).\n\nDespite the reduction in the number of cases of delinquent youths, the authors argue that there is an urgent need for Malaysians to provide suitable education and/or training for those students labelled as delinquent youths. The Malaysia Education Blueprint does not fully cater for these students; there is a small portion covering schools to house delinquent youths, but no elaboration is given on this matter. Instead of nurturing responsible citizens, there is a concern that the current system systemically traumatizes youths and leaves them less able to find employment, have healthy relationships, receive adequate education, and lead productive lives. Furthermore, these delinquents will have a permanent criminal record that may hinder them from applying for jobs in the future. This situation suggests that the nation is neglecting some of its talents who may require more support in order to be molded into model citizens that can contribute productively to develop the nation.\n\nIsmail and Rahman (2012) in their analysis suggested that currently, measures taken by schools are too dependent on the behavioral, biological, social, familial, and cognitive and do not give much attention to the aspect of human spirituality. Furthermore, Nasir et al. (2010) suggested that to nurture self-esteem and facilitate better intervention programs, there should be more involvement from the families of youths as family relationships are a viable variable in Eastern societies. In this case Eastern societies such as Malaysia, Indonesia, or Thailand have a stronger sense of belonging in the community, more respect towards the elderly, and value family relations more as they are high context culture groups. Andreou et al. (2013) promoted the use of the Evidence-Based Psycho-social Treatments (EBTS) that target bullying behavior among students who have special educational needs in Greek schools. In the program, participants were required to self-reflect in groups as these students were associated with loneliness and social dissatisfaction that led to their delinquency. Further, the findings of this study suggest that it is important to promote social inclusion among children with special educational needs and disabilities.\n\nIsmail and Rahman (2012) further argued that not only is research on school violence and juvenile delinquency prevention still relatively small in the body of literature; past research also did not take into consideration the role of religion and faith as a possible behavior modification tool.\n\nAccording to Kassim (2006), in Malaysia, the Prison Department is among the organizations responsible for caring for the delinquent youths. The department has developed and implemented a rehabilitation module that is specially targeted at young prisoners known as the Putra Module and a rehabilitation plan targeted at juveniles in Henry Gurney schools for attitude building, knowledge, and skills development as the main objectives. Kassim (2006) further stated that these two rehabilitation initiatives are targeted at reshaping these juveniles to become functional individuals again. The Putra Module is structured into four phases: Discipline Building Program (three months); Character Reinforcement Program (six to 12 months); Skills Program (the duration depends on the skills taken); and Community Program. Meanwhile, the Rehabilitation Plan is divided into three modules: Rehabilitation Module for Juveniles Aged 18 years and below; Rehabilitation Module for Juveniles Aged 18 years and above; and Rehabilitation Module for Juveniles with no basic education (Taib, 2012).\n\nMoreover, educational programs for the delinquents can also be directed into two pathways – prevention and correction. Prevention programs are carried out by schools through different programs, campaigns, and enforcement of certain rules and regulations as permitted by certain acts and regulations under the supervision of the Ministry of Education, Malaysia. Meanwhile, to habilitate and rehabilitate youths’ disruptive behavior, the efforts are led by the Department of Social Welfare through different rehabilitation institutions such as Asrama Akhlak, Tunas Bakti Schools, and Taman Seri Puteri. Known as community-based rehabilitation, the delinquents, and their families, together with the local community, work collectively during the rehabilitation process. At these facilities, delinquents will only be separated from their families and enrolled in rehabilitation hostels if their family cannot support these teenagers.\n\nIf the community treatment fails, the juveniles will then be institutionalized and sent to two types of institutional rehabilitation: Henry Gurney Schools (educational programs for juveniles) and Integrity Schools (educational programs for younger detainees). Currently, there are five Henry Gurney Schools in Malaysia: Henry Gurney School, Telok Mas, Malacca (for boys and girls); Henry Gurney School, Kota Kinabalu, Sabah (for all-girls); Henry Gurney School, Keningau, Sabah (for all-boys); Henry Gurney School, Puncak Borneo, Sarawak (for all-boys); and Henry Gurney School, Batu Gajah, Perak (for all-girls) (Taib, 2012). In addition, there are currently eight Integrity Schools located all over Malaysia: Integrity School, Sungai Petani, Kedah; Integrity School, Kajang, Selangor; Integrity School, Marang, Terengganu; Integrity School, Kluang, Johor; Integrity School, Kota Kinabalu, Sabah; Integrity School, Kuching, Sarawak; Integrity School, Muar, Johor; and Integrity School, Bentong, Pahang. All these Integrity Schools are for boys only except for the one in Bentong, Pahang.\n\nUnder the supervision of the Prison Department, Malaysia, entrants to these facilities are young adolescents under the age of 21, who have been convicted by the judiciary (Wan Mohamed and Yunus, 2009). According to Budin (2013), not much is known about the existence of such programs as the institutions are all well-guarded and secluded from the general population. However, Wan Mohamed and Yunus (2009) did describe in their paper that the department utilizes two treatment models – treatment within the community and institutional treatment. At the institution, delinquent students or these juveniles will be assigned either to follow the Academic Track or Skills Track after following a stringent process of selection to these tracks. All students are interviewed and then they sit for a diagnostic test that inevitably decides whether they qualify to follow the corrective class, skills class, or academic class. Budin (2013) further argued that the objective of this education system is for these students to correct and restore, reinforce their morale, combat illiteracy, provide educational opportunity, inculcate the culture of lifelong learning, and convince the juveniles that education can change their lives.\n\nUp until now, the existing literature suggest that all efforts in educating delinquents are well concerted by different departments of the government. However, there are some fundamental issues that are in dire need of attention. Farrell et al. (2003), for example, argued that the implementation of school-based intervention programs may provide one important focus for such efforts, but its implementation may be limited and may produce little success. Furthermore, the usual intervention practices – harsh disciplinary procedures, temporary suspension, transferal to another school, or expulsion – invigorate the situation more as these students will experience social marginalization caused by the stigma attached to the label of delinquent and this may increase the likelihood of subsequent involvement in deviant activities (Bernburg and Krohn, 2003). It is interesting to consider Mustafa et al.’s (2017) report which found that these delinquents usually have low self-acceptance, low self-emotional awareness, are not able to control their emotions, and have low levels of motivation. These youths have even posited that factors such as their inability to manage stress, their loose understanding of religion, and influence from friends, influence their delinquency. Kassim (2006) added that among the main factors that lead to delinquent behaviors in Malaysia are loose family ties, overcrowded residences, and lack of or no religious education.\n\nThere are various approaches to examine the above-mentioned debates and discussions. According to Sharpe et al. (1995), the authorities may view such programs as an effort to habilitate and rehabilitate youths’ disruptive behavior. Meanwhile, the courts view them as a final opportunity for these youth to avoid imprisonment. In contrast, students view it as a form of punishment and banishment from society. Local schools view it as a dumping ground for the most problematic adolescents. Politicians view it as a relatively inexpensive way to maintain an environment of care, custody, and control. Families of these students remain ambivalent depending on whether they prefer to have their children remain at home or be sent away. Local merchants view the programs with suspicion and fear because they know who, among the youngsters, are involved in the neighborhood gangs. Furthermore, the situation worsens due to the decline in influence of traditional socializing agents such as religion and family. In other words, instead of providing an education program that provides an opportunity to change their lives, the available system unintentionally produces angrier individuals who are more demotivated to learn. As suggested by Nasir et al. (2010), some juveniles are suffering from cognitive distortion that may lead them to rationalize their delinquent behaviors as acceptable and rational. As a result, the system that is expected to modify the delinquents’ behavior, has been fueling the young offenders’ motivation for aggressive behavior.\n\n\nMethods\n\nAs this paper reports a small part of a larger research work, the methodology adopted was simpler. There were two research approaches. Firstly, content analysis was done on printed departmental, government and research works relating to the issues surrounding delinquent students. Data from this approach provide important insights into the existing situations regarding Malaysian delinquent youths. Secondly, preliminary informal interviews were conducted with a teacher (hence referred to as RT) and an administrator (hence referred to as RA) at a correctional facility in Kuala Lumpur. This correctional facility houses youngsters, who are considered to demonstrate disruptive behaviors, and whose families consented to their admission to this correctional facility. The facility was established under the Department of Social Welfare, the Ministry of Women, Family and Community Development, Malaysia. It was established under Section 55 of the Child Act 2001 for the care and rehabilitation of children. The duration of rehabilitation is for the period of three years from the date of order, but the period may be shortened by the approval of the Minister or Board of Visitors or by amending, varying, or revoking the order of the Court of Children.\n\nTwo respondents were involved in the preliminary informal interviews, one was the teacher, RT and the other was the administrator, who is also the Headmistress of the facility, RA. Convenience sampling was used since both respondents were the ones who met the authors during the curtesy visit. For the documents that were analyzed, the authors use several important keywords to search for journal articles on Google, including delinquent youths, education for delinquents, and delinquency theory. Further, the departmental and government documents include policies and guides regarding the Child Act 2001 (Juhary, 2022).\n\nContent analysis\n\nFor the first section of the data collection, issues that emerge from the printed documents were categorized according to themes. These themes then form the challenges of educating delinquent youths in Malaysia and will be further examined in the next section. There were two stages used during content analysis. First the authors searched for articles on Google using several key words: delinquent youths, education for delinquent youths, crime and teenagers, and teenagers’ disruptive behaviors. 27 articles were found, and 20 were used in writing this paper as they provided discussions and arguments relevant for the objectives of this paper; all were documented in the references at the end of this paper. Second, the authors searched for relevant national policies to support findings in the first stage. Three departmental and government papers were analyzed, and it was found that firstly, there are vague policies on educating delinquent youths in Malaysia; secondly, there is no single authority to take charge of these youths; and finally, there is no framework that provides direction for the education of delinquent youths. These strengthen the findings from the first phase of content analysis.\n\nInformal interviews\n\nThe second research approach collected preliminary data from a curtesy and introductory visit to a correctional facility (Juhary, 2022). The visit took place on 5th August 2020, and lasted for about two hours. The objective of the visit was to introduce the research purposes and the team members that would be coming for data collection for the larger research project. In so doing, this courtesy visit sought preliminary consent from the Headmistress or RA of the correctional facility for the members to collect data through observations as well as interviews in the coming months. This correctional facility is located in Kuala Lumpur, Malaysia and houses female teenagers only. During the visit, there were approximately 60 students residing in the facility between the ages of 12 to 18 years old. Two staff (RA and RT) received the authors for the visit and these were the ones whom the authors had informal conversations, or interviews with. During the conversations, they were asked five questions each, with some variations of other sub questions depending on their answers (Juhary, 2022). The conversations or interviews were not recorded as this was done during the courtesy visit; these serve as the background information on the learning situations at the correctional facility. Their responses were then triangulated with the themes found in the content analysis phase; these will be further explored in the next section.\n\nContent analysis\n\nContent analysis in this paper adopted a qualitative approach, where the focus is on understanding and interpreting the selected written documents. The analysis was done manually based on the steps below.\n\na. selection of the articles or documents using Google\n\nb. defining the units of analysis: the units of meaning that were counted based on frequency they appeared in the selected articles and documents\n\nc. developing the codes: based on the frequency, key terms were identified\n\nd. coding the articles and documents according to themes: for the identified key terms from the articles and documents, the authors then organized them into the identified themes\n\ne. analyzing the results and drawing conclusions: three themes emerged that were the challenges of educating delinquent youths in Malaysia\n\nInformal interviews\n\nQuestions were based on the literature review conducted for the main research and from the content analysis performed earlier. Seven questions were prepared, but only five were asked due to the responses provided. Further, both RA and RT were also probed on matters about educating delinquent youths at the correctional facility; nonetheless, nothing of significance was documented on these responses for the sub questions. The responses were analyzed manually and key terms that were found similar to the ones in the content analysis phase were added to the triangulation process done later.\n\n\nEthical approval and consent\n\nThe main research has been granted a Certificate of Ethical Research Approval (Control Number 02/2019) by the National Defence University of Malaysia (NDUM) Research Ethics Committee on 21st March 2019.\n\nParticipants gave informed verbal consent to take part in the interview and their data to be shared for research purposes.\n\n\nResults and discussion\n\nBased on the content analysis and the informal interviews at the correctional facility, three challenges emerge. They are unclear policies on the education of youths at correctional facilities; the lack of frameworks in facilitating the education of these youths; and the lack of awareness and understanding on the need for educating these youths.\n\nThe authors find that there are unclear policies on the education of youths at the facilities. The educational programs and existing modules are based on the National Education Policy, aimed at Malaysian students in general (see Budin, 2013). The basis of the education provided at the correctional facilities is that all children between the ages of 12 to 17 years old must be given appropriate education; it is compulsory for all children and teenagers to attend school or to be given the opportunities to learn regardless of the logistics, socio-cultural or socio-economic backgrounds. The fourth edition of the National Education Policy, published in 2017, states that there exist two types of schools (Henry Gurney and Integrity Schools) for delinquent youths, which are supported by the government (see Dasar Pendidikan Kebangsaan, 2017). Alas, information about these educational programs is limited to the public. Since 2017 up until the writing of this paper, the policy, Dasar Pendidikan Kebangsan, that binds education of these delinquent youths is arguably just a policy that is still implemented, and the results have yet to be seen or have not been publicized. Notwithstanding this, the policy on educating delinquent youths is not reflected in the Malaysia Education Blueprint 2013-2025 (Pre-School and Post-Secondary Education).\n\nNonetheless, RA at the correctional facility argued that Henry Gurney offers an effective education system to the youth that it houses. According to RA, these youngsters follow the national curriculum, and they are also allowed to take the national examination for pursuing higher education after they leave Henry Gurney. The information about the education and training activities at these correctional facilities is not made public and it is not common knowledge; perhaps, if this changes, these delinquent youths can return to society successfully as the public would be more aware of the positive system in the facilities and may provide relevant assistance to these youths.\n\nDespite some modules and initiatives by various governing bodies in Malaysia, the fact that too many bodies are taking charge of delinquent youths is baffling. On the one hand, there is this system of education by the Prison Department, and on the other hand, the Department of Social Welfare too has its own system. At the Ministry of Education level, officers in charge are monitoring the education provided to these youths, without taking an active role in ensuring that the guidelines are followed. What can be discerned from this is that because the rules and regulations apply to different groups or categories of delinquent youths, different authorities are given the responsibilities to oversee cases depending on the seriousness of the disruptive behaviors. The authors argue that this scenario reflects the need to have a clearer overall framework for educating delinquent youths; a framework that can house all youths under the care of one authority, which can prepare, plan, implement, monitor, and improve education and/or training programs for these youths. Further deliberation on this will be in the last section of this paper.\n\nRA and RT at the correctional facility agreed that what the teenagers undergo at the facility follows the module given. This is illustrated in the summaries of the conversations below.\n\n“Despite following all the modules given by the ministry, we could see that they are not enough and may not be effective to these residents.” (RA)\n\n“But this facility follows the standard module for teaching and learning. The module is provided by the Ministry of Education, and it is in accordance with the level of studies for the youngsters.” (RT)\n\nThe main concern is to ensure that these youngsters are given sufficient skills before their release. The main activities and lessons at this facility include cooking, sewing and religious education. RA put forth that as much as the teachers at the correctional facility want to follow up on the youngsters after they leave, they simply could not afford the time and that some of these youths are not willing to have a prolonged relation with the teachers. As summarized based on the informal interview, RA put forth that,\n\n“Further, we are not able to trace and track the progress of the residents who leave the facility; this is rather crucial because we do not want them to revert to their old self.”\n\nOne may wonder on the reasons for this; the authors opine that perhaps the youngsters do not want to be reminded of their time at the facility for unknown reasons to others.\n\nLastly, because of the lack of framework in educating these youths, society at large has an inaccurate perception of these youths and how they are educated and trained in the correctional facilities. According to RT, trainees face difficulties when they exit the facility because the community does not understand the functions and responsibilities of these facilities. The youths are kept separated for a duration that may or may not ensure that they are independent after rehabilitation. Despite being guilty of disruptive behaviors, these youths are young, and they arguably should be given the chance to redeem and improve themselves. The lack of awareness and understanding on the need for educating these delinquents may also be contributed to the laws that protect their cases. The authors agree that the youths and their cases should be protected but the activities and training modules must be broadcasted to the public more often. By doing so, society can process the information and education provided to these delinquents and society at large may be also able to offer suggestions on how to integrate these youths into the community.\n\n\nRecommendations and conclusions\n\nGiven the discussions in the previous section, the authors propose two recommendations to face the challenges. The authors consider these recommendations long term solutions to educating delinquent youths in Malaysia. First, various responsible agencies and authorities must come together and decide on only one sole agency that will oversee the education and training of the delinquent youths. The main reason why this should be the case is that all planning, implementation, and monitoring will be done more systematically and effectively because there is only one caretaker. Second, when there is only one caretaker for these students, it is easier to properly work and perhaps improve on the implementation of the existing policy. The policy outlines what should be provided to delinquent youths, but not on how to work on or around it. Preparing a more workable framework based on the policy allows for clearer actions to be taken in ensuring that students can receive proper education and training that they deserve. The findings from this paper suggest that educating delinquent youths in Malaysia requires improvement in order to support these youths during and after their stay at correctional facilities. The authors opine that the best way to rectify this is to conduct an extended study on educating these youths. As a preliminary work, this paper has provided directions for the bigger research project in ensuring that delinquent youths are educated appropriately. This paper is not without its limitations. In explaining the current issue of educating delinquent youths, this paper serves as a groundwork for the bigger research project. The methodology itself was limited to content analysis of selected journal articles, documental and government policies, as well as conversations with only two staff at one correctional facility.\n\nTo conclude, this paper has identified three challenges and presented two possible solutions to solve these. To work on the challenges, all stakeholders must accept that these challenges do exist and be prepared to face these challenges. Then only these two solutions could be applied accordingly, and as mentioned earlier, these two are long term solutions that eventually will strengthen the process of educating and training delinquent youths, who are housed in correctional facilities in Malaysia. There is much to be done by relevant stakeholders, including choosing the sole caretaker for these youths and working out the acts and regulations related to the disruptive behaviors and educating these students. The authors opine that there is no better time than now to work on the framework of educating delinquent youths in Malaysia because the foundation has been laid; it is the matter of properly planning, implementing, monitoring, and improving what is missing in the education of delinquent youths.\n\n\nData availability\n\nDANS: COMPLETE DATASET FOR EDUCATING DELINQUENT YOUTHS: A QUALITATIVE APPROACH TO UNDERSTAND THE MALAYSIAN STORY. https://doi.org/10.17026/dans-xc7-4uq3 (Juhary, 2022).\n\nThis project contains the following underlying data:\n\n- Repository Data Availability F1000_24 May 2022_DOI.csv\n\n- Repository Data Availability F1000_24 May 2022_URL.csv (contains all references cited in the content analysis)\n\n- Repository Data Availability_Notes_RA_24 May 2022.pdf\n\n- Repository Data Availability_Notes_RT_24 May 2022.pdf (responses from informal interviews)\n\nThis project contains the following extended data:\n\n- Repository Data Availability_Blank_Items_24 May 2022.pdf (Questionnaire/interview guide)\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 contributions\n\nBoth JJ and ATFSM contribute 40 percent each for the write up of this paper, and EWB contributes 20 percent. JJ is involved in data curation, writing the original draft preparation and writing for review and editing. ATFSM prepares the conceptualization and methodology of this paper, and he secures the funding of this research. Lastly, EWB oversees the planning and execution of this research grant, including supervises the writing of this paper.",
"appendix": "Acknowledgements\n\nThe authors thank the National Defence University of Malaysia (NDUM) for the environmental support given to complete this paper.\n\n\nReferences\n\nAbdullah H, Ortega A, Ahmad N: Aggressive and Delinquent Behavior among High-Risk Youth in Malaysia. Asian Soc. Sci. 2015; 11(16): 62–73. Publisher Full Text\n\nAdnan M, Ayob A, Ong AET, et al.: Memperkasa Pembangunan Modal Insan Malaysia di Peringkat Kanak-kanak: Kajian Kebolehlaksanaan dan Kebolehintegrasian Pendidikan STEM dalam Kurikulum PERMATA Negara. GEOGRAFIA OnlineTM Malaysian Journal of Society and Space. 2016; 12(1): 29–36. Accessed 29 August 2021.Reference Source\n\nAndreou E, Didaskalou E, Vlachou A: Bully/Victim Problems Among Greek Pupils with Special Educational Needs: Associations with Loneliness and Self-Efficacy for Peer Interactions. J. Res. Spec. Educ. Needs. 2013; 15(4): 235–246. Publisher Full Text\n\nBernburg JG, Krohn MD: Labelling, Life Chances, and Adult Crime: The Direct and Indirect Effects of Official Intervention in Adolescence on Crime in Early Adulthood. Criminology. 2003; 41: 1287–1318. Publisher Full Text\n\nBudin D: Pendidikan Juvana di Jabatan Penjara Malaysia: Dasar, Hala Tuju, Pelaksanaan dan Cabaran. Jurnal Hadhari. 2013; 6(1): 87–104. Accessed 5 May 2021.Reference Source\n\nDasar Pendidikan Kebangsaan: Kementerian Pendidikan Malaysia, 4th Edition.2017. Accessed 24 February 2021.Reference Source\n\nDepartment of Statistics, Malaysia:2019. Accessed 29 August 2021.Reference Source\n\nFarrell AD, Meyer AL, Sullivan TN, et al.: Evaluation of the Responding in Peaceful and Positive Ways (RIPP) Seventh Grade Violence Prevention Curriculum. J. Child Fam. Stud. 2003; 12(1): 101–120. Publisher Full Text\n\nFaruqee M: Youth Prisons Don’t Work. Here’s What Does.2016. Accessed 16 July 2018.Reference Source\n\nHassan J, Rashid SA, Sufahani SF, et al.: Bully Among Rural Primary School Students: A Case Study of North Kedah-Perlis Felda Territory, Malaysia. Jurnal Psikologi Malaysia. 2016; 30(1): 113–125. Accessed 16 July 2018.Reference Source\n\nHolbrook AM, Hunt SR, See MR: Implementation of Dialectical Behavior Therapy in Residential Treatment Programs: A Process Evaluation Model for a Community-based Agency. Community Ment. Health J. 2018; 54: 921–929. PubMed Abstract | Publisher Full Text\n\nIsmail ZM, Rahman NSNA: School Violence and Juvenile Delinquency in Malaysia: A Comparative Analysis between Western Perspectives and Islamic Perspectives. Procedia Soc. Behav. Sci. 2012; 69: 1512–1521. Publisher Full Text\n\nJuhary J; (National Defence University of Malaysia): Complete Dataset for Educating Delinquent Youths: A Qualitative Approach to Understand the Malaysian Story. DANS;2022. Publisher Full Text\n\nKassim AW: Juveniles of Remand: Trends and Practices in Malaysia. Resource Material No. 68. Work Product of the 129th International Senior Seminar – Crime Prevention in the 21st Century: Effective Prevention of Crime associated with Urbanization based upon Community Involvement and Prevention of Youth Crime and Juvenile Delinquency. United Nations Asia and Far East Institute for the Prevention of Crime and the Treatment of the Offenders.March 2006. Accessed 5 May 2021.Reference Source\n\nMalaysia Youth Data Bank System:2019. Accessed 15 April 2020.Reference Source\n\nMustafa MN, Suandi T, Hamzah AH, et al.: Fenomena Delinkuen dalam kalangan Remaja yang Berisiko di Sebuah Sekolah Menengah Kebangsaan Agama di Luar Bandar Malaysia. Jurnal Kemanusiaan. 2017; 14(2): 10–34. Accessed 24 February 2021.Reference Source\n\nNasir R, Zamani ZA, Yusooff F, et al.: Cognitive Distortion and Depression among Juvenile Delinquents in Malaysia. Procedia Soc. Behav. Sci. 2010; 5: 272–276. Publisher Full Text\n\nNasrul HNM, Zarina AR: Peraturan dan Undang-Undang Kawalan Displin Murid di Malaysia. Malaysian Online Journal of Education. 2017; 1(1): 1–11. Accessed 24 February 2021.Reference Source\n\nOzel E, Zhagan M, Md Nor M, et al.: The Human Rights to Inclusive Education under International Law: Malaysian Concepts. Journal of Global Business and Social Entrepreneurship. 2017; 1(3): 234–243. Accessed 22 April 2022. Reference Source\n\nOECD: Equity and Quality in Education: Supporting Disadvantaged Students and Schools. OECD Publishing;2012. Publisher Full Text\n\nReffien MAM, Shah SA, Lim KH: Violence-Related Behaviors Among School Going Adolescents in Peninsular Malaysia. Malaysian. J. Public Health Med. 2020; 2: 65–73. Publisher Full Text\n\nSayuti AB, Awang MM, Ahmad AR, et al.: Fenomena Buli dan Gangsterisme: Satu Kajian Empirikal. Kuala Lumpur:Penerbit UPNM;2020.\n\nSharif MHM, Sidek NA, Saharuden SS, et al.: PERMATA Childcare Course: The Implication for Childcare Practices Quality. Southeast Asia Early Childhood Journal. 2020; 9(1): 15–27. Accessed 3 March 2021.Reference Source\n\nSiegel LJ, Welsh BC: Juvenile Delinquency: The Core. Wadsworth;2005.\n\nSharpe T, Brown M, Crider K: The Effects of a Sportsmanship Curriculum Intervention on Generalized Positive Social Behavior of Urban Elementary School Students. J. Appl. Behav. Anal. 1995; 28(4): 401–416. Publisher Full Text\n\nTaib R: Empowering Young Inmates Through Lifelong Learning Programs in Malaysia: Prospects and Challenges. Int. Business Educ. J. 2012; 5(1): 69–77. Accessed 23 April 2022. Reference Source\n\nWan Mohamed WA, Yunus MH: The Inculcation of Generic Skills among Juveniles through Technical and Vocational Education. US-China Education Review. 2009; 6(4): 56–61. Accessed 24 February 2021. Reference Source"
}
|
[
{
"id": "172526",
"date": "05 Mar 2024",
"name": "Theresa Ochoa",
"expertise": [
"Reviewer Expertise juvenile delinquency",
"special education laws",
"international special education"
],
"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\nThank you for providing the opportunity to review the manuscript titled “Education of Delinquent Youths: A Qualitative Approach to Understanding the Malaysian Context”. The significance of the topic cannot be overstated. I commend the authors for their efforts in shedding light on the variance between governmental policies and actual practices in the rehabilitation of incarcerated youths. It is crucial to give voice to the personnel directly involved in serving these high-needs populations, documenting their daily challenges and success. Regrettably, despite the importance of the subject matter, I am unable to recommend the manuscript for approval. I will outline my comments and reservations below.\nFirstly, a comprehensive literature review regarding juvenile incarceration is imperative. While I acknowledge that the manuscript was not intended to serve as a literature review, the current introduction lacks depth in capturing the known characteristics and needs of this youth demographic. Upon conducting a thorough review, the focus of the study should be confined to describing he Malaysian context, rather than incorporating statistics from disparate countries (USA, Greece, Thailand) without sufficient justification. Regarding the definition of the youth age group, inconsistency arises as different age ranges are provided (e.g., 12-19, 17, 21). It is advisable to specify a range encompassing the youngest to the oldest age discussed. Furthermore, Table 1 provides data on the number of youths with drug addiction, yet its discussion is limited in relation to the extensive list of characteristics outlined in the text. Typically, tables should complement the information presented in the text. Additionally, the content in Figures 1 and 2 appears more fitting for inclusion in the introduction. Another notable limitation is the inadequacy of the methodology section. Which requires significant enhancement in clarity and detail. The inclusion of the process of searching for articles on juvenile delinquency and incarceration may be better suited for the introduction as part of the missing literature review. Alternatively, if these articles are to be included in the methodology, the manuscript should adopt a scoping review approach. Moreover, if governmental documents were analyzed, explicit details regarding the documents and the methodology employed are necessary for replication purposes. Additionally, the interview methodology should be expanded upon, detailing the questions posed and whether an interview protocol was utilized to ensure consistency. The recommendation advocating for a single agency to oversee the incarcerated youth population contradicts best-practice guidelines, which emphasize collaboration and communication among various service providers for effective rehabilitation and reentry. Lastly, the manuscript suffers from difficulties in comprehension and requires substantial reorganization. In summary, a comprehensive copy-editing and restructuring of the entire manuscript is warranted.\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?\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? No",
"responses": []
},
{
"id": "147037",
"date": "25 Mar 2024",
"name": "Hadijah Jaffri",
"expertise": [
"Reviewer Expertise Educational Psychology"
],
"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 is no reference about content analysis. Thus, it seems there is misconception about content analysis. Content analysis is perceived as a method to collect data whereas it is used as data analysis of documents. Refer to [1] and [2]. Insufficient citations to back up descriptions, decisions, or actions pertaining to research processes. For example, there is no justification given for the use of convenience sampling. This article can be improved with additional supporting references. Description of ethical considerations with regards to data collection (involvement of officer/personnel of correctional facilities) can be improved with more detailed explanations about ethical procedures that the researchers have undertaken. Is there any ethical committee that approved the data collection process etc.? Explanation given under sub-heading (Ethical approval and consent) does not explicitly explain how the data is collected and managed. There is no explanation about philosophical background of content analysis. Refer to [3]. There are three typologies of content analysis. In this article, the specific typology used is unclear. Refer to [4]. The levels of content analysis in this article are not described in detail. Thus, it could create doubt among readers about the validity of the data analysis which has been undertaken. For more understanding about the levels of analysis for content analysis, refer to [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? 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/11-668
|
https://f1000research.com/articles/10-356/v1
|
07 May 21
|
{
"type": "Brief Report",
"title": "Brain structural abnormalities in six major psychiatric disorders: shared variation and network perspectives",
"authors": [
"Euclides José de Mendonça Filho",
"Márcio Bonesso Alves",
"Patricia Pelufo Silveira",
"Euclides José de Mendonça Filho",
"Márcio Bonesso Alves"
],
"abstract": "Common brain abnormalities are a possible explanation for comorbidities in psychiatric disorders. Challenges in understanding these conditions are likely due to the paucity of studies able to analyze the extent and regional distribution of shared morphometric abnormalities between disorders. Recently, Opeal et al. presented an elegant rationale to investigate shared and specific morphometric measures of cortical thickness and subcortical gray matter volume between healthy individuals and subjects across six major psychiatric disorders. Although their approach has the potential to systematically portrait shared brain alterations, the chosen principal component analysis solution may not address the central question of the observed shared versus specific brain alterations due to misspecification of the number of components. Given how this misspecification can lead to different conclusions, we reanalyzed Opel et al. data to thoroughly determine the number of factors to be considered, explore the alternative solution, and visualize the patterns of shared brain matter correlations using network analysis. Our approach suggests that a unidimensional solution was appropriate in this situation. The unidimensional solution indicated that brain alterations in autism spectrum disorder (ASD) had a significant negative component loading, suggesting that brain abnormalities found in ASD carry more similarities with major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) than demonstrated by the original work. Network analysis indicated that SCZ had the highest strength, BD the highest closeness, and BD and MDD had the highest betweenness in the network. This work highlights how different component solutions can lead to different conclusions, with important implications for the understanding of overlapped patterns of symptoms among six major psychiatric diseases. The network approach is complementary in indicating central markers of specific psychopathology domains. Investigations using shared-variation and network perspectives are promising for the study of pathophysiological patterns of common brain alterations.",
"keywords": [
"Cross-disorder",
"ENIGMA",
"Psychiatric disorders",
"Structural MRI",
"Principal Component Analysis",
"Network Analysis"
],
"content": "Introduction\n\nChallenges to the understanding of heterogeneity and comorbidity of psychiatric disorders have long been acknowledged in medicine. The National Institute of Mental Health’s Research Domain Criteria (RDoC) initiative acknowledges that common brain abnormalities can potentially explain psychiatry comorbidities,1 but few studies were able to systematically investigate the extent and regional distribution of shared morphometric abnormalities between disorders.\n\nUsing published meta- and mega-analyses of the Enhancing Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) consortium, Opel et al.2 present an elegant rationale to investigate shared and specific morphometric measures of cortical thickness and subcortical gray matter volume between typical control individuals and subjects with six of the major psychiatric disorders (major depressive disorder [MDD], bipolar disorder [BD], schizophrenia [SCZ], obsessive-compulsive disorder [OCD], attention-deficit/hyperactivity disorder [ADHD], and autism spectrum disorder [ASD]). To address whether brain-structural alterations related to these disorders loaded onto latent variables, shared brain abnormalities among them were examined using principal component analysis (PCA) across all cortical and subcortical regions. Then component scores were compared with the empirical regional effect sizes, allowing the definition of regions in each disorder that were better predicted by a shared variance component. The authors retained three principal components across disorders with a solution defined by MDD, BD, SCZ, and OCD loading on the first component, ADHD on the second, and ASD on the third component, leading to the conclusion that MDD, BD, SCZ, and OCD shared neuro-abnormality patterns, whereas ASD and ADHD exhibited disease-specific alterations.\n\nAlthough the rationale used to investigate shared and specific morphometric measures of brain matter consists of an opportune strategy for improving the understanding of the pathophysiologic mechanisms of psychiatric disorders,3 the number of components retained in the analysis, in this case, may not address the central question of the observed shared versus specific brain alterations. The three-factor solution parcels out the weaker residual correlation into minor components that might be of theoretical importance. We recognize that it is often a challenge to define the appropriate number of factors for data reduction, but common recommendations assume that retaining components with eigenvalues >1.0 usually indicates an excessive number of components. Moreover, the consideration of weak or poorly identified factors (i.e., components defined by only one or two variables) is an indication that the number of factors extracted should be reconsidered.4\n\nThe over-extraction and under-extraction of factors retained in data reduction can have deleterious effects on the results.5 Given the importance of the number of factors in data reduction and how different component solutions can lead to different conclusions, we leveraged the cross-disease effect sizes reported in Opel et al.2 to thoroughly determine the number of factors to be considered, explore the appropriate solution, and visualize the patterns of shared brain matter correlations using network analysis.\n\n\nMethods\n\nWe reanalyzed the underlying structure of 41 regional measures of cortical thickness and subcortical volumes across the six psychiatric disorders compiled by Opel et al.2 The data consisted of effect sizes obtained by contrasting healthy controls (N = 33,146) and patients (N = 19,578) of published structural neuroimaging mega- and meta-analyses of the ENIGMA consortium in the years 2016 to 2019.2 The data selection criteria included the availability of effect sizes of psychiatric disorders for all 34 cortical brain regions based on the Desikan-Killiany atlas automated labeling system,6 and 7 subcortical regions included in the standardized probabilistic information, modeled using the Markov random fields imaging pipeline7 applied by the ENIGMA consortium. This criteria identified 11 studies of six psychiatric disorders: MDD (N = 2), BD (N = 2), SCZ (N = 2), OCD (N = 2), ADHD (N = 2), and ASD (N = 1). The effect size measures consisted of Cohen’s d mean differences in each cortical or subcortical region after age, sex, scanner adjustment, and in case of subcortical volume, total intracranial volume.2\n\nThe object of analysis is a dataset comprised of the effect size estimates for six psychiatric disorders and 41 regions of interest – hippocampus, amygdala, thalamus, accumbens, caudate, putamen, pallidum, isthmus cingulate cortex, posterior cingulate cortex, rostral anterior cingulate cortex, caudal anterior cingulate cortex, lateral orbit frontal cortex, pars opercularis of inferior frontal gyrus, rostral middle frontal gyrus, superior frontal gyrus, medial orbital frontal cortex, pars orbitalis of inferior frontal gyrus, pars triangularis of inferior frontal gyrus, caudal middle frontal gyrus, precentral gyrus, frontal pole, paracentral lobule, insula, lateral occipital cortex, lingual gyrus, cuneus, pericalcarine cortex, inferior parietal cortex, supramarginal gyrus, precuneus, superior parietal, postcentral gyrus fusiform gyrus, middle temporal gyrus, inferior temporal gyrus, banks superior temporal sulcus, superior temporal gyrus, parahippocampal gyrus, transverse temporal gyrus, entorhinal cortex, and temporal pole. This dataset was obtained by copying the effect sizes estimates reported by Opel et al2 on Supplementary Table S2 of their manuscript.2 The full manuscript was accessed in https://doi.org/10.1016/j.biopsych.2020.04.027 via the McGill Library Portal (https://www.mcgill.ca/library/) on September 19, 2020. The data extracted from Opel’s manuscript2 Supplementary Table S2 was prepared for statistical manipulation in the SPSS (V.21, IBM Corp., Armonk, NY) statistical environment and is available upon request.\n\nThe number of principal components retained was determined using the scree plot criteria and Horn’s parallel analysis.8 The scree plot shows how much variation each component captures from the data and allows to determine the inflection point in the data where additional components are unnecessary. The number of data points above the inflection is usually the number of components to retain. Horn’s parallel analysis compares the eigenvalues randomly generated from the data using Monte-Carlo simulation with the original data. The number of components retained consists of the original eigenvalues that are higher than the simulated eigenvalues.8 We also verified the number of components in the cross-disease correlation matrix with eigenvalues greater than 1.0, although this procedure is considered one of the least accurate methods for selecting the number of components.5 At this stage, we used the functions implemented by the psych package9 from the R statistical language (V. 4.0.2). At a second stage, we used the SPSS software to conduct exploratory factor analysis. The principal components algorithm was used for dimensional extraction, and component scores obtained using the regression method.9\n\nTo investigate specific patterns of residual correlations between the psychiatric disorders, we fitted a Gaussian graphical model with a Least Absolute Shrinkage and Selection Operator (gLASSO)10 to the data using the qgraph11 R package. This procedure yields parsimonious partial-correlations of the brain alterations for each pair of psychiatric diseases here represented as nodes. Edges between diseases indicate a regularized partial correlation, after conditioning on all other diseases in the dataset. To assess the importance of nodes in the network, we computed the following centrality measures: strength, a measure of how well a node is directly connected to other diseases, closeness, how well a node is indirectly connected to other diseases, and betweenness, quantification of how important a node is in the average path between two other diseases.\n\n\nResults\n\nInspection of the scree plot and Horn’s parallel analysis indicated the consideration of one component instead of the original three-component solution. Figure 1 shows a steeper decrease from the first to the second eigenvalues, followed by a flatter pattern for the remaining components. In addition, only the first actual eigenvalue was higher than the resampled eigenvalues (depicted in red) suggesting a unidimensional solution. It can be noticed that the third component obtained an eigenvalue of .98, violating the liberal eigenvalues greater than the 1.0 cut-off. Therefore, we opted to retain one component for subsequent analysis.\n\nThe unidimensional solution indicated that the effect size of the differences in brain structure between ASD patients and controls shared a significant negative component loading (λ = -0.30, p = 0.04) with the brain abnormalities of the remaining five diseases (Figure 2). While in the original analysis SCZ had the highest shared correlation (indicated by the highest component loading) of the four conditions (MDD, BD, SCZ, and OCD), the unidimensional solution showed that the BD (λ = 0.89, p < 0.001) followed by SCZ (λ = 0.88, p < 0.001), and OCD (λ = 0.87, p < 0.001) had the highest shared correlation with all six disorders (Figure 2B), illustrating how different dimensional reduction solutions are implied in different patterns of covariance. Similar to the original report, ADHD did not load into the PCA, indicating low shared brain abnormalities with the other disorders.\n\nWe also calculated a regional component score (M = 0.0, SD = 1.0) to identify which brain areas were more affected in a cross-disease manner. The hippocampus (-1.64) and the fusiform gyrus (-1.40) exhibited a more prominent shared reduction, whereas the pallidum (2.94) and putamen (2.09) showed a stronger shared increase. In order to explore shared- and disorder-specific morphometric abnormalities, we computed regional effect-sizes residuals from the component score. In contrast to the original work, this allowed the inclusion of ASD and ADHD in the analysis, although ADHD was not further explored due to its non-significant component loading. Regional specificities for MDD, BD, SCZ, and OCD were similar to Opel et al.2 results (Figure 2C). ASD showed large residuals especially for the rostral middle (residual [res] = .18) and superior frontal gyrus (res = .15), as well as fusiform (res = -.22) and entorhinal gyrus (res = -.17).\n\nNetwork analysis indicated that ASD showed a stronger negative association with BD, suggesting that BD is a bridge node between ASD and the other diseases. Interestingly, after controlling for the other diseases, ASD exhibited a positive correlation with SCZ in contrast with the PCA and Opel et al.2 results. ADHD had a weaker partial correlation with the other nodes that were linked by MDD. SCZ, BD, and OCD maintained the pattern of strong positive associations (Figure 2D). Centrality measures of the network indicated that SCZ had the highest strength (direct connections to other diseases), BD had the highest closeness (indirect connection to other diseases). BD and MDD had the highest betweenness (the average path between two other diseases),5 see Figure 2E.\n\n(A) Predicted component scores mapped onto brain regions; (B) Path diagram of the principal component unidimensional solution; (C) Residuals from the regional effect sizes accounting for the predicted shared principal component. As in Opel et al.,2 the absolute size of residuals encompasses the degree of representation through the shared unidimensional component. Lower (negative) residuals represent underestimation and higher (positive) residuals represent overestimation based on the brain-regional shared variance. (D) gLASSO correlations network of brain structural alterations in the six psychiatric disorders. Edges represent parsimonious partial-correlations between psychiatric disorders. A stronger correlation (positive = blue; negative = red) results in a thicker and darker edge. (E) Network centrality measures. ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; BD, bipolar disorder; MDD, major depressive disorder; OCD, obsessive-compulsive disorder; SCZ, schizophrenia. All effect sizes used in these results are taken from Opel et al.2\n\n*p < 0.05; **p < 0.001.\n\n\nDiscussion and conclusion\n\nOur approach suggests that the brain abnormalities found in ASD carry more similarities with MDD, BD, SCZ, and OCD than demonstrated by the original three-component solution in Opel et al.2 Indeed, the well-observed pattern of co-occurrence and clinical overlap among ASD and other psychiatric disorders indicates that they share important pathogenic brain mechanisms and risk factors.12,13 The small association of ASD and the specificity of ADHD abnormalities might be explained by the fact that these are neurodevelopmental disorders, although recent work has supported the idea that the etiology of BD and SCZ also involves a substantial neurodevelopmental basis.14,15 An alternative and interesting view argue that these disorders could be conceptualized as a neurodevelopmental continuum, in which the symptoms would reflect the severity, timing, and pattern of brain abnormalities, as well as the modulatory effects of genetic and environmental factors.14 The results we obtained here seem to partially reflect Owen and O’Donavan’s14 theoretical understanding of this phenomenon.\n\nTo summarize, Opel et al.2 advance our understanding of brain morphometric features in highly debilitating psychiatric conditions. Notably, different component solutions can lead to different conclusions, but both approaches were categorical in demonstrating the strong alterations of the hippocampus, fusiform gyrus, pallidum, and putamen. These findings may be of special interest given that the overlapped pattern of symptoms among the major psychiatric diseases usually makes it difficult to accurately diagnose and to prescribe tailored treatment. Moreover, the network approach might help to understand specific disease domains of psychopathology. With more neuroimaging studies of psychiatric disorders becoming available, investigations via shared variation and network perspectives are promising venues for understanding the subtypes of shared pathophysiological patterns.\n\n\nData availability:\n\nThe underlying data of the present study is based on Opel et al.2 work and are available on https://doi.org/10.1016/j.biopsych.2020.04.027. The dataset was obtained by copying the effect sizes estimates reported by Opel et al2 on Supplementary Table S2 of their manuscript.2 The full manuscript was accessed via the McGill Library Portal (https://www.mcgill.ca/library/) on September 19, 2020.\n\n© 2020 Society of Biological Psychiatry.",
"appendix": "References\n\nXia CH, Ma Z, Ciric R, et al.: Linked dimensions of psychopathology and connectivity in functional brain networks. Nat Commun. 2018; 9(1): 1–14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOpel N, Goltermann J, Hermesdorf M, et al.: Cross-Disorder Analysis of Brain Structural Abnormalities in Six Major Psychiatric Disorders: A Secondary Analysis of Mega- and Meta-analytical Findings From the ENIGMA Consortium. Biol Psychiatry. 2020; 88(9): 678–686. PubMed Abstract | Publisher Full Text\n\nEckstrand KL: Shared Versus Disorder-Specific Brain Morphometric Features of Major Psychiatric Disorders in Adulthood. Biol Psychiatry. 2020; 88(9): e41–e43. PubMed Abstract | Publisher Full Text\n\nIzquierdo I, Olea J, Abad FJ: Exploratory factor analysis in validation studies: uses and recommendations. Psicothema. 2014; 26(3): 395–400. PubMed Abstract | Publisher Full Text\n\nCostello AB, Osborne JW: Best practices in exploratory factor analysis: Four recommendations for getting the most from your analysis. Pract Assessment, Res Eval. 2005; 10(7). Publisher Full Text\n\nDesikan RS, Ségonne F, Fischl B, et al.: An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006; 31(3): 968–980. PubMed Abstract | Publisher Full Text\n\nFischl B, Salat DH, Busa E, et al.: Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain. Neuron. 2002; 33(3): 341–355. PubMed Abstract | Publisher Full Text\n\nHorn JL: A rationale and test for the number of factors in factor analysis. Psychometrika. 1965; 30(2): 179–185. PubMed Abstract | Publisher Full Text\n\nRevelle W: psych: Procedures for Personality and Psychological Research.2020. Reference Source\n\nEpskamp S, Borsboom D, Fried EI: Estimating psychological networks and their accuracy: A tutorial paper. Behav Res Methods. 2018; 50(1): 195–212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEpskamp S, Cramer AOJ, Waldorp LJ, et al.: Borsboom D. qgraph: Network Visualizations of Relationships in Psychometric Data. J Stat Softw. 2015; 48(4). Publisher Full Text\n\nGuan J, Cai JJ, Ji G, et al.: Commonality in dysregulated expression of gene sets in cortical brains of individuals with autism, schizophrenia, and bipolar disorder. Transl Psychiatry. 2019; 9(1). PubMed Abstract | Publisher Full Text | Free Full Text\n\nLai MC, Kassee C, Besney R, et al.: Prevalence of co-occurring mental health diagnoses in the autism population: a systematic review and meta-analysis. Lancet Psychiatry. 2019; 6(10): 819–829. PubMed Abstract | Publisher Full Text\n\nOwen MJ, O’Donovan MC: Schizophrenia and the neurodevelopmental continuum: evidence from genomics. World Psychiatry. 2017; 16(3): 227–235. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKloiber S, Rosenblat JD, Husain MI, et al.: Neurodevelopmental pathways in bipolar disorder. Neurosci Biobehav Rev. 2020; 112(February): 213–226. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "139204",
"date": "06 Jun 2022",
"name": "Takahiro Osada",
"expertise": [
"Reviewer Expertise neuroimaging"
],
"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 by de Mendonça Filho et al. reanalyzed the data presented in Opel et al. to investigate the common brain abnormalities for various psychiatric disorders. Specifically, the authors reconsidered the number of factors in the principal component analysis and demonstrated that a solution of one factor was appropriate while the original study adopted three factors. Based on the unidimensional solution, brain abnormalities in ASD showed a negative component loading, whereas those in MDD, BD, SCZ, and OCD showed positive component loadings. The authors concluded that the same component could explain ASD as well as MDD, BD, SCZ, and MDD. Understanding brain abnormalities related to psychiatric disorders is clinically important, and using a large database of the ENIGA consortium is a plausible way for investigation. However, I have some concerns with the analyses and interpretations of the results in this manuscript.\nMajor comments:\nThe authors compared the number of components in the principal component analysis solely based on eigenvalues (Figure 1). I wonder whether the unidimensional analysis explained sufficiently the variance of brain regional effect sizes. According to the original study by Opel et al., the three factors explained 85.14 % of the variance in total. To what extent did this unimodal solution could explain the variance?\n\nIn the unidimensional analysis, ASD showed a negative component loading while MDD, BD, SCN, and OCD showed positive component loadings. Based on this finding, the authors stated in the Abstract and Discussion that brain abnormalities in ASD had more similarities with the four disorders than the original study. The authors should describe this conclusion with caution. The pattern of brain abnormalities in ASD was not “similar”, but rather opposite to that in the four disorders because of the negative and positive values. The same component could explain ASD and the four disorders rather than the two distinct factors suggested in the original study.\n\nThe authors calculated the partial correlations among the residuals and conducted network analyses (Figures 2D and 2E). I wonder whether these analyses were valid. It would be reasonable to examine the relationships between the residuals after the component with the same tendency was extracted (i.e., the same sign and nearly the same amount of loading). However, the authors compared the residuals between the disorders for negative loadings (ASD and ADHD) and positive loadings (MDD, BD, SCN, and OCD). The network analysis seems interesting, but what is the rationale for examining the residuals from data with different tendencies?\n\nMinor comments:\nFigure 2A was not cited in the text, and how was the “predicted component score” calculated?\n\nFor evaluating component loadings, why was “λ” used rather than “r”? Is this different from a simple correlation coefficient?\n\nIt would be helpful to provide a figure for the regional component score map.\n\nIn the third paragraph in the Results section, the authors stated, “Regional specificities for MDD, BD, SCZ, and OCD were similar to Opel et al. results”. Could you elaborate on this?\n\nIn the fourth paragraph in the Results section, the authors stated, “BD is a bridge node between ASD and the other disease”. Please elaborate on this.\n\nFigure 2B: it would be helpful to explain the numbers in the figure legend. I assume these are component loadings.\n\nFigure 2C and 2D: the color coding is somewhat counterintuitive. In Figure 2A, red means represents while blue represents negative. In Figure 2D, it would be helpful to add a color scale bar.\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? Partly\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": "8377",
"date": "17 Jun 2022",
"name": "Euclides Jose de Mendonca Filho",
"role": "Author Response",
"response": "We thank the reviewer for the thorough revision of our manuscript. Bellow, we address the comments to improve readers’ understanding of our findings. Major comments: 1. The authors compared the number of components in the principal component analysis solely based on eigenvalues (Figure 1). I wonder whether the unidimensional analysis explained sufficiently the variance of brain regional effect sizes. According to the original study by Opel et al., the three factors explained 85.14% of the variance in total. To what extent did this unimodal solution could explain the variance? Although the unimodal solution explains less of the variance, the consideration of a unidimensional solution was based on three criteria:1) the scree plot of eigenvalues, 2) the exhaustive parallel analysis procedure that identified one component as a recurrent robust solution, and 3) the inspection of the Opel et al. solution that indicated that the second and third components were defined by only one variable each. The inspection of the original 3-factors solution was the motivator for the reanalysis presented in our manuscript. Since principal component analysis is a data reduction technique, considering components with only one variable seemed redundant, and an indication that the number of factors extracted should be reconsidered. We added the explained variance in the text. Now it reads: \"The unidimensional solution explained 48.3% percent of the six-brain structural alterations and indicated that the effect size of the differences in brain structure between ASD patients and controls shared a significant negative component loading (λ = -0.30, p = 0.04) with brain abnormalities of the remaining five diseases (Figure 2). Although the unimodal solution explains less of the variance than the original work (the three-factor solution explained 85.14% of variance), the consideration of a unidimensional solution was based on several criteria. Namely, the scree plot of eigenvalues, the exhaustive parallel analysis procedure that identified one component as a recurrent robust solution, and the inspection of the Opel et al.2 solution that indicated additional second and third components defined by only one variable each. Since principal component analysis is a data reduction technique, considering components with only one variable seemed redundant, and an indication that the number of factors extracted should be reconsidered.\" 2. In the unidimensional analysis, ASD showed a negative component loading while MDD, BD, SCN, and OCD showed positive component loadings. Based on this finding, the authors stated in the Abstract and Discussion that brain abnormalities in ASD had more similarities with the four disorders than the original study. The authors should describe this conclusion with caution. The pattern of brain abnormalities in ASD was not “similar”, but rather opposite to that in the four disorders because of the negative and positive values. The same component could explain ASD and the four disorders rather than the two distinct factors suggested in the original study. We agree with the reviewer that the observed pattern is not similar but is negatively associated with alterations in SCZ, BD, MDD, and OCD. We clarified this information throughout the manuscript. 3. The authors calculated the partial correlations among the residuals and conducted network analyses (Figures 2D and 2E). I wonder whether these analyses were valid. It would be reasonable to examine the relationships between the residuals after the component with the same tendency was extracted (i.e., the same sign and nearly the same amount of loading). However, the authors compared the residuals between the disorders for negative loadings (ASD and ADHD) and positive loadings (MDD, BD, SCN, and OCD). The network analysis seems interesting, but what is the rationale for examining the residuals from data with different tendencies? Our framework is based on the RDoC initiative that acknowledges that common brain abnormalities can potentially explain psychiatry comorbidities. We aimed at investigating patterns of shared variance independently of the direction of observed brain alterations. PCA and Network analysis are both appropriate for modelling opposite tendencies, and the use of network analysis is aimed at further interrogating the relationship between brain alterations by investigating the function of the observables in the network. This allowed us to obtain information about which observables are dominant in the network in terms of the strength of relations with other observables, for instance. Minor comments: Figure 2A was not cited in the text, and how was the “predicted component score” calculated? Thank you for bringing this to our attention, we added Figure2A to the 11th paragraph. We also added information about the estimation of the component score. Now it reads: \"The principal components algorithm was used for dimensional extraction, and component scores were obtained using the regression weights (Thurstone method), which are obtained by multiplying the inverse of the observed variable correlation matrix by the matrix of factor loadings.\" 1. For evaluating component loadings, why was “λ” used rather than “r”? Is this different from a simple correlation coefficient? The λ symbol represents a factor or component loading, thus it is not a Pearson correlation coefficient, although λ reported are standardized yielding a similar interpretation to a simple correlation coefficient. 2. It would be helpful to provide a figure for the regional component score map. This information is depicted in Figure 2A, we added a sentence to clarify this. 3. In the third paragraph in the Results section, the authors stated, “Regional specificities for MDD, BD, SCZ, and OCD were similar to Opel et al. results”. Could you elaborate on this? Thank you for bringing this to our attention. The sentence now reads: \"Regional specificities for MDD, BD, SCZ, and OCD were similar to Opel et al. results, in which large absolute residuals were found in the rostral ACC and the medial orbito frontal cortex (OFC) for MDD, parahippocampal gyrus and pallidum for BD and superior temporal gyrus and medial OFC for SCZ.\" 4. In the fourth paragraph in the Results section, the authors stated, “BD is a bridge node between ASD and the other disease”. Please elaborate on this. Thank you for bringing this to our attention. The sentence now reads: \"Network analysis indicated that ASD showed a stronger negative association with BD, suggesting that BD is a bridge node between ASD and the other diseases. Thus, the brain alterations in BD may connect ASD alterations to the other nodes, and if the BD node is removed, the observed shared variance with SCZ, OCD, and MDD is likely to decrease\" 5. Figure 2B: it would be helpful to explain the numbers in the figure legend. I assume these are component loadings. The reviewer is correct, we added a sentence to grant a better understanding of Figure 2A 6. Figure 2C and 2D: the color coding is somewhat counterintuitive. In Figure 2A, red means represents while blue represents negative. In Figure 2D, it would be helpful to add a color scale bar. Thank you for your suggestion, we altered Figures 2C and 2D for clarity."
}
]
}
] | 1
|
https://f1000research.com/articles/10-356
|
https://f1000research.com/articles/11-666/v1
|
16 Jun 22
|
{
"type": "Research Article",
"title": "Teledentistry: a new oral care delivery tool among Indian dental professionals – a questionnaire study",
"authors": [
"Kishan Paul Raja",
"Aindrila Pal",
"Sangeeta Umesh Nayak",
"Keshava Pai",
"Ramya Shenoy",
"Kishan Paul Raja",
"Aindrila Pal",
"Keshava Pai",
"Ramya Shenoy"
],
"abstract": "Background: The sudden massive spread of coronavirus disease 2019 (COVID-19) has led to a major public health emergency and changed the scene of the health care globally. During the COVID-19 pandemic, most dental treatment procedures were considered as major sources of infection transmission. Thus, the current survey aimed at evaluating knowledge, awareness and attitude of dental professional of India towards teledentistry. Methods: A pre structured questionnaire was framed and distributed among 600 dental professionals of India using email, WhatsApp and other social media modes. SPSS version 17 was used for data analysis. The Chi-Square, student t test and one way ANOVA test were applied to assess the association between qualification, type of practice and participant response. Logistic regression analysis was also carried out. Results: In total, 431 dental professionals completed the survey. Overall, 94.7% of dental professionals were aware about teledentistry and agreed it is useful in fulfilling needs of the community at great amount. A statistically significant difference was found for questions related to the application of teledentistry for all branches, whether it is a good tool to assess oral hygiene in remote areas and its usefulness in training in primary health care centre when comparison was done among dental professionals and specialist in different branches of dentistry. Conclusions: Within the limits of the study, findings show that study participants exhibited good knowledge and awareness regarding teledentistry. The participants exhibited positive attitude towards teledentistry but at the same time expressed the uncertainty in challenges which they may face in teledentistry. Lack of training, advanced infrastructure, good connectivity and network are main issues they were concerned about. The other important point of concern is many participants felt teledentistry cannot be applied for all branches of dentistry. Future research should focus on this aspect of teledentistry.",
"keywords": [
"Tele dentistry",
"Telemedicine",
"Health education",
"Oral care in rural area"
],
"content": "Introduction\n\nComputers and tele-communications are playing an important role in health care. Dental manpower shortages, remoteness, funding challenges, reduction of cost and technical developments, have led to increased awareness in the utilisation of telemedicine services.1\n\nThe term “telehealth” and “e-health” came into reality because of advances in communication technologies and use of electronic information in health care services at a distance.1,2\n\nTelemedicine is a fragment of telehealth, and makes use of communication networks to deliver healthcare services and medical education from one geographical location to another. Teledentistry deals specifically with dental health and related issues, and is a combination of digital/telecommunication technology and dentistry. The use of teledentistry and its application in oral health services is of utmost importance in rural and distant locations. With the help of teledentistry one can recognize high risk populations, arrange referral to a dental surgeon or specialist, and encourage locally based treatment. Together all these leads to reduction in waiting period, unnecessary travel and loss of productivity.2,3\n\nThe sudden and rapid spread of coronavirus disease 2019 (COVID-19) caused an unrivalled public health crisis which has altered the landscape of the health system globally, and thus teledentistry gained popularity during the COVID-19 pandemic. During this time, dental clinics and medical facilities were considered as spots of cross infection. A majority of dental treatment procedures deal with saliva, aerosol and droplet production which were considered as major sources of infection transmission. It was thus only emergency treatment that was permitted during the pandemic. This led to subsequent delay in diagnosis and management of dental diseases which caused devastating consequences in oral health conditions.3,4\n\nTo overcome this, teledentistry consultation was encouraged so that with minimum contact between dentists and patients, the problems were addressed and both dentist and patient were benefited too.4\n\nIn today’s era, a strong communication between dental professionals and patients can be achieved using high-speed mobile data, and good internet connectivity. The term “teledentistry,” is a mode of providing dental care across different regions. It has evolved with the use of smartphones, laptops, and various video conferencing software applications. It has totally reformed the traditional practice as it encourages a virtual mode of consultations and follow-up instead of direct one-to-one consultation.5,6\n\nIn the management of patients with dental emergencies teledentistry can be of great help for patients. It can be delivered in two ways:\n\n(i) Real-time consultation\n\n(ii) Store and forward\n\nReal-time consultation comprises a video conference connecting dentist and the patient, at different locations. During this time the dental professional can discuss with the patient about their problems and see their problems. The advanced telecommunication tools and high-speed internet connections makes this possible.7,8\n\nIn the store and forward method, the telecommunication equipment is used to collect case material involving the clinical information and static images (clinical/radiographic/laboratory) and is stored. Then for consultant opinion and treatment planning this stored data is utilized. Thus in a quicker and cost effective manner treatment can be delivered to the targeted population.7,9\n\nRemote and new health care workers can utilize teledentistry as a strategy to support rural populations. It makes it possible to increase access to, and provision of oral care in rural and undeveloped areas.2 Higher degree of acceptance for tele dentistry is seen among clinicians and patients compared to traditional direct consultation.5,6,7 Very few studies have been done in this aspect in the Indian population.1,10 Thus the current research aims at assessing the knowledge, awareness, and attitude regarding teledentistry among dental professionals of India.\n\n\nMethods\n\nThe present survey used an online pre structured questionnaire among the dental professionals in India.\n\nThe permission from the Institutional Ethics and Review Board of the Manipal College of Dental Sciences, Mangalore. India (protocol no: 21016) was obtained prior to commencement of the research. All participants gave informed consent through the Google form.\n\nThe sample size was calculated using statistical software, considering 95% confidence interval, and an assuming 50% level of knowledge on teledentistry and its usefulness. The estimated sample size was 431 participants.\n\nInclusion criteria and Exclusion criteria\n\nAll the dental professionals whose dental degree was recognized by the Indian regulatory body and willing to participate in the survey by giving the consent were included in the study.\n\nThe dental students and interns whose internship is not complete or degree is not registered to governing body during the survey period were excluded.\n\nBased on the available previous data the questionnaire was formulated. A preliminary pilot study was conducted among 40 dental professionals and this data were not included during the survey. The survey tool was validated.\n\nThe survey explained the objectives of the current research and the participants were asked to provide inform consent if there are willing to participate in the survey. A set of 20 questions were divided into three sections. The demographic information such as name, age, qualification, type of practices, year of experience were recorded in first section of the survey.\n\nThe knowledge and awareness regarding teledentistry was assessed in the second section using eight questions in that aspect. In the third section dental professional’s attitude was evaluated using five-point Likert scale. The two extremes of the Likert scale were strongly agree = 1 and strongly disagree = 5. The tool can be found as Extended data.22\n\nAn electronic form - A google form with study information, informed consent and questionnaire was developed. The study team identified Email, WhatsApp, and Instagram groups of practicing dentists in India. The sharing of the questionnaire was done through the assigned social media platforms to a randomly selected sample of dental professionals in India (n = 600). This step helped us to control the potential selection bias. The data was collected from July 2021 to October 2021, and the survey was stated closed by November 2021.Two reminders were sent in an interval of two weeks to all the selected candidates.\n\nThe SPSS statistical package was used for data analysis (IBM SPSS Statistics for Windows, Version 17.0, Released 2011, IBM Corp., Armonk, NY, USA, RRID:SCR_016479). Descriptive statistics were tabulated. Chi-Square, student’s t test and one way ANOVA tests were applied to assess the association between qualification, type of practice and participant response. Logistic regression analysis was also carried out. Professional qualification was kept as the dependent variable and questions (1-8) pertaining to knowledge of teledentistry were kept as independent variables. A p-value < 0.05 was considered significant.\n\n\nResults\n\nIn total, 600 google forms were emailed to dental surgeons all around India. Among which 431 complete filled forms we received.22 Out of 431 participants, 378 (87.7%) were aware of the term “teledentistry” and 408 (94.7%) were aware of the use of teledentistry, its method of use and its usefulness in dental practice. 403 (93.5%) study participants felt teledentistry is useful in seeking opinion about disease diagnosis with a specialist. 349 (81.2%) study participants felt tele-dentistry can be a good educational tool. This can be used to create awareness and educate the primary care dental professionals in an effective way. 343 (79.6%) study participants felt teledentistry can be a good way to track the oral health of the patient. 258 (59.9%) study participants felt tele dentistry is difficult or challenging to apply to all branches of dentistry. Majority of study participants felt teledentistry can be used as effective tool in teaching oral care, to create awareness among health professionals and patients and circulate the information regarding the access to information pertaining to oral hygiene facility (Figure 1).\n\nA questionnaire (set of 12 questions) was used to access the attitude towards tele-dentistry (Figure 2). A mixed response was obtained from the study participants. The responses ranged from strongly agree, agree and neutral.\n\nCategorization of different qualifications was done using student’s t test. Out of 431 participants 281 participants were dental surgeons with a BDS degree and 150 participants were specialist in various branches of dentistry. The distribution was statistically significant with a P value of 0.036. One way ANOVA showed uniform distribution among the type of practice (private, academician or both) (Table 1).\n\nThe chi square test and logistic regression analysis showed a statistically significant difference among dental surgeons (BDS) and specialists (MDS) regarding teledentistry as an educational tool to train dental professionals in primary care centres in remove/rural areas (question no 4), it is an effective tool in monitoring patient’s oral health (question no 5) and can be applied to all branches of dentistry (question 6). A statistically significant difference with p value of 0.005 was found for the questions regarding teledentistry as an effective tool for oral hygiene training (question8) (Tables 2, 3 & 4).\n\n* P value stastically significant ≥ 0.005, df - degrees of freedom.\n\n* P value stastically significant ≥ 0.005, df - degrees of freedom.\n\na Variable(s) entered on step 1: Q1, Q2, Q3, Q4, Q5, Q6, Q7, Q8, TOTAL SCORE.\n\n* P value stastically significant ≥ 0.005.\n\n\nDiscussion\n\nWith the advancement in technology, the world is changing in all directions. Dental practitioners also should be aware about the changing trends in their field. They should be updated with knowledge which will assist them to face the challenges in their filed. They should be updated with knowledge and skills so that they will be able to fulfil the necessary oral health care and the ongoing requirements of their community.\n\nTeledentistry is a mode of delivery of oral care in which dental care is provided to the patient without direct contact or with minimal contact. This all is possible because of usage information technology and high speed internet facility.\n\nSince there are limited challenges in clinical examination of the oral cavity, intraoral photographing can be carried out with little knowledge or guidance by patients or by -standers.11\n\nAlthough tele dentistry is not a new treatment modality, the COVID-19 pandemic did raise the attention of the dental community towards teledentistry and the important role it can play as a tool for the delivery of a wide range of dental services in near distant places with zero risk of infection.12\n\nIn the present study a large section of respondents did agree that teledentistry would help to minimise the waiting time period. They were also of the opinion that teledentistry can improve the interaction among colleagues to seek advice regarding patients. Teledentistry is also believed to manage patient referral effectively and in providing a safe atmosphere for practicing dentistry.\n\nIn the present study 94.7% study participants were aware about teledentistry which is in contrast to earlier studies.1,12–14 In the earlier studies it was opined that a smaller number of dentists were aware of teledentistry because of a lack of knowledge in this field. This was mainly attributed to having no didactic and practical training in this field as it was not a part of the dental curricula, and also a lack of continuous education programs on teledentistry. Hence, integrating teledentistry in the undergraduate and postgraduate curricula and organising lectures and hands on workshops as a part of continuing dental education is of paramount importance to fill the knowledge gap. In the present study the participants were found to be aware about the concept of teledentistry. This is probably due to the involvement of technology in dental curriculum (paperless exams, online teaching, webinars by dental regulatory bodies (dental council of India). Nowadays in the health care system, application of computers and internet has become common. In the field of teledentistry a link is created between dental health care providers and patients so that there is improvement in communication, exchange of health-related information and access to dental care dental health records in different locations.15,16 In the present study, 93.5% of participants felt teledentistry is useful in seeking opinion about disease diagnosis with a specialist. 81.2% study participants felt tele-dentistry can be a good educational tool and this is similar to earlier studies.12,17 The study participants showed a positive attitude towards teledentistry and this was similar to earlier studies.12,17 It was seen that 59.9% study participants felt that teledentistry is difficult or challenging to apply to all branches of dentistry, and this was in accordance with earlier studies.12,17 Disagreement among dentists exists regarding the accuracy and reliability of diagnosis through teledentistry.12,18–20 The reliability of examination via the application of teledentistry should be assessed and supported by more research directed in this direction.\n\nAbout 60% of dentists accepted the potential helpfulness of teledentistry for patients. In addition, its usefulness among patients in rural and remote areas was expressed by more than 70% of the dentists. The benefit of teledentistry in terms of patient education, patient monitoring and a reduction of the need to travel to the dental clinic was expressed by 70% of the responding dentists.1 A study by Fernandez C E in 2021, also stated teledentistry as an effective means for oral health improvement in terms of prevention and promotion.21 The application of teledentistry to help detect and diagnose dental caries has also been reported in a systematic review of 10 studies.18\n\nLimitation of the study: Around 169 forms (39%) were not included in the data analysis due to lack of clarity and incomplete details. The study included both practitioners and academicians which may be some amount of impact on their knowledge regarding teledentistry.\n\n\nConclusion\n\nWithin the limits of the study, participants exhibited good knowledge and awareness regarding teledentistry. The participants exhibited positive attitudes towards teledentistry but at the same time expressed the uncertainty in challenges which they may face in teledentistry. Lack of training, advanced infra structure, good connectivity and network are main issues which they were concerned about. The other important point of concern is many participants felt teledentistry cannot be applied for all branches of dentistry. Future research should focus on this aspect of teledentistry.\n\n\nData availability\n\nFigshare: Teledentistry: New Oral Care Delivery Tool among Indian Dental Professionals –A questionnaire Study. https://doi.org/10.6084/m9.figshare.19915021.22\n\nThis project contains the following underlying data:\n\n- teledentistry- data.ods\n\nFigshare: Teledentistry: New Oral Care Delivery Tool among Indian Dental Professionals –A questionnaire Study. https://doi.org/10.6084/m9.figshare.19915021.22\n\nThis project contains the following extended data:\n\n- Case proforma.docx (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": "References\n\nNagarajappa R, Aapaliya P, Sharda AJ, et al.: Teledentistry: Knowledge and Attitudes among Dentists in Udaipur, India. Oral Health Dent. Manag. 2013; 12: 502.\n\nFricton J, Chen H: Using teledentistry to improve access to dental care for the underserved. Dent. Clin. N. Am. 2009; 53(3): 537–548. PubMed Abstract | Publisher Full Text\n\nSanchez Dils E, Lefebvre C, Abeyta K: Teledentistry in the United States: a new horizon of dental care. Int. J. Dent. Hyg. 2004; 2: 161–164. PubMed Abstract | Publisher Full Text\n\nObeidat L, Masarwa N, AlWarawreh A, El-Naji W. Dental Treatments During the COVID-19 Pandemic in Three Hospitals in Jordan: Retrospective Study. Interact. J. Med. Res. 2020; 9(4): e24371. Published 2020 Dec 29. PubMed Abstract | Publisher Full Text\n\nGhai S: Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14 (2020) 933e935 Alabdullah JH, Daniel SJ. A systematic review on the validity of teledentistry. Telemed. J. E Health. 2018; 14: 933–935. Publisher Full Text\n\nEstai M, Kanagasingam Y, Tennant M, et al.: A systematic review of the research evidence for the benefits of teledentistry. J. Telemed. Telecare. 2018; 24: 147–56. PubMed Abstract | Publisher Full Text\n\nDeshpande S, Patil D, Bhanushali MDP, et al.: Teledentistry: A Boon Amidst COVID -19 Lockdown- A Narrative Review. Int. J. Telemed. Appl. 2021; Vol 2021: 6pages. Article ID8859746. PubMed Abstract | Publisher Full Text\n\nSubramanyam VR: Telepathology: virtually a reality. J. Oral Pathol. Med. 2002; 1: 1–15.\n\nChang SU, Plotkin DR, Mulligan R, et al.: Teledentistry in rural California: a USC initiative. J. Calif. Dent. Assoc. 2003; 31(8): 601–608. PubMed Abstract\n\nChandra G, Rao J, Singh K, et al.: Teledentistry in India: Time to deliver. J Educ Ethics Dent. 2012[Cited 2022 mar 24]; 2: 61–64.Reference Source\n\nPetruzzi M, De Benedittis M: WhatsApp: a telemedicine platform for facilitating remote oral medicine consultation and improving clinical examinations. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2016; 121(3): 248–254. PubMed Abstract | Publisher Full Text\n\nNassani MZ, Al-Maweri SA, AlSheddi A, et al.: Teledentistry—Knowledge, Practice, and Attitudes of Dental Practitioners in Saudi Arabia: A Nationwide Web-Based Survey. Dent. Health. 2021; 9(12): 1682. PubMed Abstract | Publisher Full Text\n\nSubhan R, Ismail WA, Musharraf S, et al.: Teledentistry as a Supportive Tool for Dentists inPakistan. Biomed. Res. Int. 2021; 2021: 1–6. [CrossRef] [PubMed]. Publisher Full Text\n\nRaucci-Neto W, de Souza Pereira M , Cerqueira NM, et al.: Knowledge, perception, and experience of dentists about teledentistry. Int. Dent. J. 2021. in press. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text\n\nChhabra N, Chhabra A, Jain RL, et al.: Role of Teledentistry in Dental Education: Need of the Era. J. Clin. Diagn. Res. 2011; 5: 1486–1488.\n\nAta S, Ozkan S: Information technology in oral health care: attitudes of dental professionals on the use of teledentistry in Turkey. European and Mediterranean conference on information system 2009.2009.\n\nAlSheikh R: Teledentistry awareness among dental professionals in Saudi Arabia. PLoS One. 2020; 15(10): e0240825. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEstai M, Bunt S, Kanagasingam Y, et al.: Diagnostic accuracy of teledentistry in the detection of dental caries: A systematic review. J. Evid. Based Dent. Pract. 2016; 16: 161–172. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text\n\nAlShaya MS, Assery MK, Pani SC: Reliability of mobile phone teledentistry in dental diagnosis and treatment planning in mixed dentition. J. Telemed. Telecare. 2020; 26: 45–52. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text\n\nMandall NA, O’Brien KD, Brady J, et al.: Teledentistry for screening new patient orthodontic referrals. Part 1: A randomised controlled trial. Br. Dent. J. 2005; 199: 659–662. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text\n\nFernández CE, Maturana CA, Coloma SI, et al.: Teledentistry and Health for promotion and prevention of oral health: A systematic review and meta-analysis. J. Dent. Res. 2021; 100: 914–927. [CrossRef] [PubMed]. PubMed Abstract | Publisher Full Text\n\nNayak S: Teledentistry: a new oral care delivery tool among Indian dental professionals – a questionnaire study. figshare. [Dataset].2022. Publisher Full Text"
}
|
[
{
"id": "141715",
"date": "12 Jul 2022",
"name": "Melwin Mathew",
"expertise": [
"Reviewer Expertise Dentistry",
"Periodontics",
"Dental Implants",
"Laser dentistry",
"Dental Radiology",
"Dental disinfection and decontamination",
"Practice management"
],
"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 study has been conducted with the current issue faced by the community during the pandemic lockdown and when patients were unable to visit a clinic due to movement restrictions or fear of transmission of COVID-19 while visiting a medical/dental clinic. The study design is well structured and a well-balanced validated questionnaire has been used to assess the knowledge and attitude of dental practitioners towards teledentistry.\nIn this study, a total of 431 participants responded out of 600 questionnaires sent out online, the awareness regarding the term \"Teledentistry\" and applications of teledentistry was highly significant among the participants however, the knowledge and awareness of applicability for all branches of dentistry in teledentistry was not significant as 59.9% answered \"NO\".\n\nMeanwhile, assessing their attitude, the participants strongly agreed teledentistry was useful for improving patients' awareness and attitude toward oral health and providing the comfort of online consultation with a specialist. Apparently, the response was more neutral about patients' acceptance of online oral examinations using computers and intraoral cameras.\nLimitations of the study, that could be addressed in the future is, in assessing the practicality of the use of Teledentistry in rural, semi-urban and urban areas equally based on the accessibility of the internet by identifying participants in each of these areas and also assessing the agreement from the participants about setting up a large database to store the clinical data collected from teledentistry.\nThis study has concluded by adequately supporting their 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? 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": "148514",
"date": "13 Sep 2022",
"name": "Harsh Priya",
"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\nThis is a good initiative to utilize the social media platform for evaluating knowledge, awareness and attitude of dentists towards teledentistry.\nA few concerns regarding the questionnaire, if the validity was assessed. An explanation regarding the content validity of the questionnaire will be appreciated. It would also be helpful to explain the online consent form a little more. Now, many studies will be performed online hence a clarification for readers would reinforce the procedure.\nUtilization of teledentistry in the primary health centres in rural areas should be elaborated on in the discussion. The preventive and public healthcare aspects may be discussed. This is a very important aspect here.\nHow can the inclusion of practitioners and academicians change the results?\nThank you Best Regards Harsh Priya\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": "144019",
"date": "13 Sep 2022",
"name": "Vidya Shenoy",
"expertise": [
"Reviewer Expertise Dentistry",
"oral health",
"geriatric oral 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 current survey aimed at evaluating knowledge, awareness and attitude of dental professional of India towards teledentistry. In total, 431 dental professionals completed the survey. Overall, 94.7% of dental professionals were aware of teledentistry and agreed it is useful in fulfilling the needs of the community at great amount. Within the limits of the study, findings show that study participants exhibited good knowledge and awareness regarding teledentistry. The participants exhibited a positive attitude towards teledentistry but at the same time expressed the uncertainty in challenges that they may face in teledentistry. Lack of training, advanced infrastructure, good connectivity and network are the main issues they were concerned about. The other important point of concern is many participants felt teledentistry cannot be applied to all branches of dentistry. Future research should focus on this aspect of teledentistry.\nWork is clearly and accurately presented with a technically sound design which will help the readers in reproducibility. Conclusions are drawn based on the results obtained.\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": []
}
] | 1
|
https://f1000research.com/articles/11-666
|
https://f1000research.com/articles/11-662/v1
|
16 Jun 22
|
{
"type": "Systematic Review",
"title": "Performance measurement of university-industry collaboration in the technology transfer process: A systematic literature review",
"authors": [
"Darminto Pujotomo",
"Syed Ahmad Helmi Syed Hassan",
"Azanizawati Ma’aram",
"Wahyudi Sutopo",
"Syed Ahmad Helmi Syed Hassan",
"Azanizawati Ma’aram",
"Wahyudi Sutopo"
],
"abstract": "Background To fostering organizational improvement, the performance must be assessed. In the context of university-industry collaboration (UIC) in the technology transfer process, the performance of also must be assessed. However, the performance covers complex aspects which makes it difficult to be measured. This indicates the need to have a better understanding of the methods used. Therefore, this study presents a systematic literature review on the performance measurement of UIC in the technology transfer process that can give to the researchers an easy and quick overview of the literature about (mainly) the methods used for the performance measurement. Methods We used two major scientific databases, i.e., Scopus and Web of Science. We defined four groups of keywords to restrict the search criteria. We only consider articles published in the last decade, during 2010 to November 2021. The search procedure contains four phases following the PRISMA framework: (i) identification, (ii) screening, (iii) eligibility, and (iv) inclusion. Results The final screening process resulted in 24 articles that satisfied the criteria for inclusion in this review. The collected articles are categorized according to two classifications. The first is about type of the collaboration, while the second is about the methods used. We investigated three types of collaboration, i.e., at the level of technology transfer office (TTO), the academic (university) spin-offs, and joint-research. There are several methods for assessing performance, ranging from qualitative, quantitative, to mixed methods. Conclusion The literature review leads us to the following conclusions. First, most studies are conducted at the TTO level, in which it is anticipated since it is the most common form UIC. Second, the application of data envelopment analysis is still preferable than other method in measuring the performance. This study also provides possible research directions that can facilitate scholars to uncover gaps in the literature.",
"keywords": [
"performance measurement",
"PRISMA framework",
"systematic literature review",
"technology transfer process",
"university-industry collaboration"
],
"content": "Introduction\n\nPolicymakers and researchers have prioritized collaboration between academia and businesses since the implementation of the Bayh Dole Act of 1980 (Miller et al., 2018). It has been observed from the active efforts from universities to improve their relationships with industry due to the increased demand to have a positive influence on society as well as the diminishing funding streams (Miller et al., 2014). It further led to the growing push to build university-industry collaborations (UICs) to improve institutional innovation and economic competitiveness through information exchange across academic and commercial spheres (Perkmann et al., 2013). Universities now have additional obligations to assist their researchers in transforming knowledge to value in terms of socio-economic growth (Fayolle and Redford, 2014). This has been indicated by the aggressive creation of relationships with business sector groups as part of the third-mission activities to assist institutions in connecting with society (Rantala and Ukko, 2018). Moreover, universities are also seen as desirable partners in aiding industrial organizations’ innovation efforts (Mäkimattila et al., 2015).\n\nIn the technology transfer process, as in the UIC context, the university may supply ideas and expertise to the business, which the industry would then use and put into practice (Prabhu, 1999). There are seven phases of the UIC in the technology transfer process, which include scientific discovery, dissemination of the invention, evaluation of the invention for patenting, registration of the patent, marketing/supply of the technology to companies or entrepreneurs, negotiations of the license, and formal (or informal) commercialization (Lopes et al., 2018). To foster organisational improvement, the performance of the collaboration must be assessed. Performance measurement is the process of measuring all achievable goals (Sutopo et al., 2019). Although the significance of performance measurement is not always easy to justify, the measurement might help organisations discover their strengths and weaknesses as well as areas for improvement. However, the performance of technology transfer process covers complex aspects which makes it difficult to measure (Stankevičienė et al., 2017). This indicates a need to have a better understanding of the methods used in performance measurement of technology transfer process in the UIC context.\n\nThe objective of this study is to systematically review the academic articles regarding performance measurement of UIC in the technology transfer process. We searched the articles by using Scopus and Web of Science databases through the PRISMA framewotk. The collected articles were then categorized according to two classifications. The first was the type of the collaboration, while the second referred to the methods used for assessing the performance. It will give to the researchers a quick and easy overview of the literature about the level of analysis, the methods, and selection of variables used for performance measurement. According to the insights of the review, this study also provides some potential research directions that might facilitate scholars to uncover gaps in the literature.\n\nThe remaining of this paper is organized as follows. The methodology is presented in the next section. The third section presents the result of the search, including the classification of the collected articles. Possible research directions are offered in the Discussion. Finally, the last section concludes.\n\n\nMethods\n\nThe steps to conducting this literature review are described in Figure 1. In the first step, the research objective was defined. In this case, this study aimed to systematically review the academic articles regarding performance measurements of UIC in the technology transfer process. To get a widespread coverage of the literature, we used two major scientific databases, i.e., Scopus by Elsevier and Web of Science by Clarivate Analytics.\n\nStep 2 was conducted to restrict the search criteria. As such, the relevant search keywords for the query process were determined. With the aid of Boolean operators, we used four groups of keywords as follows: (i) university-industry collaboration OR university-industry linkages OR university-industry relationship OR university-industry partnership OR university-industry alliance OR knowledge and technology exchange OR university-industry knowledge transfer OR university-industry technology transfer OR community knowledge transfer OR technology transfer office OR office of technology transfer OR knowledge transfer office OR technology transfer center OR technology licensing office; AND (ii) performance OR effectivity OR efficiency OR accomplishment OR achievement OR efficacy; AND (iii) assessment OR evaluation OR appraisal OR analysis OR rating OR measurement; AND (iv) research development OR invention OR scientific discovery OR initial development OR product development OR product manufacturing OR commercialization process OR commercialization OR transferring OR technology acquisition OR product manufacturing OR market development OR valley of death OR death valley OR Darwinian seas. Thus, articles which contain those keywords in the title, abstract, or keywords were extracted. We included several “variations” of UIC in the first group of keywords to get wider results of articles discussing UIC. While the second and third groups of keywords are self-explanatory, we added the context in the last group, i.e., stages in the technology transfer process.\n\nThe next step was conducting the search. The search procedure contained four phases following the PRISMA framework (Page et al., 2021): (i) identification, (ii) screening, (iii) eligibility, and (iv) inclusion, as shown in Figure 2. PRISMA has potential benefits due to the fact that complete reporting allows readers to assess the appropriateness of the methods and subsequently, the trustworthiness of the findings. Using the previously mentioned inclusion criteria, the search yielded 264 articles (63 from Scopus and 201 from the Web of Science database). We then removed 22 duplicate articles. For the sake of insuring quality, the document type was restricted to (peer-reviewed) research article published in a journal as these sources are the most useful for literature reviews (Saunders et al., 2012). Therefore, other types of documents such as books or book chapters, conference proceedings, short communications, letters or editorial materials were excluded. From a pragmatic point of view, only articles published in English were included. We only considered articles published in the last decade, from 2010 to November 2021, including old literature would be misleading and irrelevant. This way, 75 articles were excluded, leaving only 167 articles to be further investigated. The titles and abstracts were then read to verify whether the articles were relevant to this study’s theme and objective. The second-round inspection was performed by carefully reading the full text of each article to address their eligibility for inclusion in this study. Following this procedure, 49 articles did not meet the criteria and were not considered for final extraction. Note that the ineligible articles did not discuss the addressed main topic in this research domain (the articles discussed e.g., partners’ selection for UIC, barriers of UIC management, the relationship within UIC, among others). Ultimately, the final screening process resulted in 24 articles that satisfied the criteria for inclusion in this review.\n\nIn analyzing and presenting the included 24 articles, we used qualitative approach to categorize articles according to the type of collaboration and methods of performance measurement.\n\n\nResults and discussion\n\nThe final screening process resulted in 24 articles published in 16 different journals (see Figure 3) that met the refinement criteria and became the object of this study. Figure 4 illustrates the number of articles published annually from 2010-2021. This section devotes to articles classification. Each article was classified according to the type of collaboration and methods of performance measurement. Classifying extracted articles from literature review allows readers to validate what has been studied and can also allow to find gaps in this research domain.\n\nWe investigated three types of collaboration according to the insights of the literature review: see Table 1. Several elements of UIC performance can be influenced by the type of collaboration. This is shown by the fact that organizational structure has an impact on the stakeholder relationships, information flow, as well as how relational components allow knowledge sharing (Ribeiro and Nagano, 2021).\n\nThe first and most common type of collaboration is technology transfer office (TTO). It is a kind of organization which supports universities in dealing with their intellectual assets and transforming them to benefit the society (Carlsson and Fridh, 2002). The roles of TTO are commonly offering support in the area of intellectual property and entrepreneurship, creating relationships with industries and communities, enabling the establishment of firms (or start-ups) from UIC, and generating net income from sponsored research, collaborating partners, or consulting opportunities. Note that there are several variations for the term “TTO” in the literature, including knowledge transfer office, university technology transfer office, offices of technology licensing, and industrial liaison office (Brescia et al., 2016).\n\nOne of the most important mechanisms of TTO and the one that is expected to have the highest impact at the local level, is the formation of academic spin-offs (ASO) or university spin-offs (USO); thus, ASO is a new firm formed by the utilization of university’s core technology or technology-based idea (Smilor et al., 1990). The establishment of ASOs results from the technology transfer policy of a university. ASOs also take part in accelerating technology innovation and promoting economic development (Block et al., 2017; Guerrero et al., 2015; Visintin and Pittino, 2014). ASOs have distinguished features compared to other start-ups, i.e., being created within a university and offering products resulting from university research. For these reasons, ASOs characteristically have huge potential in terms of research and innovation.\n\nWhile ASOs might be considered as having the highest impact, joint research probably reflects the lowest quality of collaboration (Guimón, 2013). This type of collaboration does not create such a new formal organization, often in the form of temporary (short-term) contract or agreement between university and industry partners. This collaboration commonly involves on-demand problem solving with predefined results and tends to be expressed as consulting, contract research, and licensing. In addition, it might include joint supervision and postdoctoral or doctoral positions offered within alliance (Perkmann et al., 2011; Seppo and Lilles, 2012), co-owned patents (Hong and Su, 2013; Lei et al., 2011), joint publications (Lundberg et al., 2006; Tijssen et al., 2009), joint public lectures, and joint training (Al-Ashaab et al., 2011; Ramos-Vielba et al., 2010).\n\nThe next classification relates to methods used to measure the performance of the collaboration:see Table 2. One measure of performance evaluations which is widely used is efficiency (Cornali, 2012). In a broader view, efficiency refers to the ratio of output to input (Cooper et al., 2006). In this sense, efficiency is used to describe the ability of the collaboration to generate output (s) with available input(s). In the literature, efficiency is largely measured by two most popular frontier methods: i.e., data envelopment analysis (DEA), and stochastic frontier analysis (SFA). In this review, DEA is preferable to SFA (DEA was applied in seven studies while SFA was used in only two studies). Compared to SFA, DEA can manage multiple inputs and outputs more easily. There is no assumption about the functional form in DEA. However, DEA assumes that all differences from the frontier (or the most efficient) are due to inefficiency. It means that DEA does not discriminate between inefficiency from statistical noise; thus, it results that DEA might overestimate inefficiency level. On the other hand, DEA’s drawback can be eluded in the SFA procedure because SFA does discriminate between inefficiency and statistical noise. In SFA, we also can identify the effect of inputs on the outputs, something that we cannot observe in DEA. SFA also can be used in a panel data setting (Ulkhaq, 2021). Despite several benefits as have been showed previously, research on applying SFA are the minority compared to DEA. It seems very fruitful to undertake more research regarding measuring efficiency of the collaboration using SFA.\n\nRegression analysis is used as an alternative to the frontier methods, as observed in only two studies. Although it cannot measure efficiency, it can be used to identify the determinants of UIC performance. The outcome of the collaboration would serve as dependent variable. Caldera and Debande (2010) used five measure of performance, i.e., the number of research and development (R&D) contracts, R&D contracts income, the number of spin-offs, licensing income, and the number of licensing agreements (the last two also have been used by Conti and Gaule, 2011). Latent growth model (LGM), which is a regression-based model, was used by Hung et al. (2015) for assessing the use of knowledge created by universities. The LGM consists of two sub-models: the level-1 model describes the individual change over time measured by the number of cumulative patent citations, while the level-2 model describes inter-university differences in citation growth. They showed how the influence of knowledge use for patented inventions is subject to research impact, UIC, and the university location.\n\nPerformance metrics have been proposed to evaluate the performance of the collaboration. Gianiodis and Meek (2020) proposed performance metrics to assess entrepreneurial education initiatives inside of the entrepreneurial university. They argued that a profit-oriented framework model (which commonly includes two performance matrices: revenues from licensing and other activities, and new ventures or start-ups) only favors elite universities and undervalues resource-constrained universities. Tseng and Raudensky (2014) used two normalized metrics, i.e., overall performance metric (OPM) and patenting control ratio (PCR) to assess the performances of TTO activities of twenty US major universities. The OPM which is developed based on outcome instead of process, is a combination of patents issued, disclosures submitted, patent applications filed, TTO revenue and the numbers of licenses agreed, and start-ups launched, associated with different weighting factors. On the other hand, PCR which is a dimensionless metric, is the number of patents granted normalized by the number of patent applications. Albats et al. (2018) presented specific key performance indicators (KPIs) of UIC. They broke down the UIC measures across the collaboration lifecycle which implies four stages of UIC and its assessment, i.e., inputs, in-process activities, outputs and impact. Weis et al. (2018) characterized the performance of research organizations across different steps of the technology transfer process. They proposed the commercialization pipeline that can be used to assess and compare relative levels of technology transfer activity at different institutions, and at different steps along the pipeline. They defined seven steps in the pipeline (i.e., research expenditure, invention disclosure, patent application, patent issued, licenses and option executed, start-up, and adjusted gross income), in which each step corresponds to a specific metric.\n\nLafuente and Berbegal-Mirabent (2019) investigated the productivity level of TTO. They analyzed the productivity of TTOs in Spain from 2006 to 2011 by calculating the Malmquist index, a total factor productivity index. After the productivity level was identified, its relationship with aspiration performance was investigated by using a random-effects model in a panel data setting. Results of the study confirm that productivity is influenced by changes in the configuration of the TTO’s outcome portfolio.\n\nSeveral studies tried to employ multi-criteria decision making tools. Aragonés-Beltrán et al. (2017) presented the analytic network process (ANP) by Saaty (1996) to assess whether the TTO activities are contributing to meeting the third mission goals set by the university in its strategic plans and to what extent. They implemented the ANP in Universitat Politècnica de València (UPV)-TTO and found that TTO’s objective “facilitate the participation of the UPV in sponsored R&D and innovation (R&D&I) programmes” should be prioritized first; and “support services to justify expenditure incurred in the development of subsidised R&D&I activities” obtained the highest weight among other TTO activities, meaning that this activity should be prioritized first. Stankevičienė et al. (2017) used factor relationship model (FARE) to identify the relationship among criteria that influence TTO performance and weights of each criterion. After implementing FARE, the TOPSIS method by Hwang and Yoon (1981) was utilized to rank the seven biggest Lithuanian universities to find out how much, based on the chosen criteria, universities were influenced in their value creation process through TTO performance assessment.\n\nSeveral scholars proposed other quantitative methods to evaluate the performance of the collaboration. Kireyava et al. (2020) derived 11 success factors of scientific project implementation in TTO, which consist of e.g., finance, infrastructure, human resource, communication system, among others. Venturini and Verbano (2017) identified resources used in the various stages of development of an ASO, i.e., opportunity recognition, entrepreneurial commitment, threshold of credibility, and threshold of sustainability (Vohora et al., 2004) as well as indicators for the performance evaluation, i.e., revenue, employee numbers, number of patents, quality certification, R&D investments, total liabilities and equity, prizes and awards, and return on equity index. Cartalos et al. (2018) derived three dimensions which consist of several criteria for the assessment. The dimensions are technology–innovation, market opportunities, and exploitation team. Each criterion in those dimensions are scored with a 4-level Likert-type scale (1: to a low, very low extent; 2: to some extent; 3: to a considerable extent; 4: to a high/very high extent), except for the criterion of technology maturity (of the technology–innovation dimension), which is marked using the technology readiness level scale (EARTO, 2014).\n\nApart from the quantitative approach, although less popular, Resende et al. (2013) used a qualitative analysis tool, named best transfer practices that can be utilized to improve efficiency and effectiveness of TTO. They used interviews, participative observation, document analysis, and survey to investigate the performance of TTO and where the improvements can be performed.\n\nIazzolino et al. (2020) proposed the spin-off lean acceleration, which constitutes a combination of the quantitative and qualitative aspects to assess ASO. They argued that most of the traditional methods of assessment are designed for firms which operate in an organized manner; on the contrary, start-ups are far from that organized manner. In particular, the features of ASOs are more multifaceted compared a common start-up firm, including involved stakeholders, barriers and drivers, as well as key success factors (Hossinger et al., 2020; Mathisen and Rasmussen, 2019). The starting point is that before measuring performance quantitatively, the critical point of an ASO is to realize as quick as possible if the key risk areas are sufficiently controlled, which can be identified through qualitative analysis.\n\nEfficiency and effectiveness are two common terms which are widely exploited in assessing the performance of organisations (Cornali, 2012; Mouzas, 2006), and therefore we believe these terms are highly relevant to be discussed in this study. One of the challenges for organisations to be managed is to balance efficiency with effectiveness. In many cases, they often are unsuccessful in doing this; instead, they might do by dealing with efficiency but neglecting effectiveness. Leaders of organisations are often looking for efficiency indicators, such as cost reduction, resources usage minimization, and operational margins improvement; however, those indicators are not measures of effectiveness (Ambler, 2003). The tendency to pursue efficiency may be credited to the fact that business is more applicable to efficiency gains than to the effectiveness of a business (Moran and Ghoshal, 1999). We confirm the argument with the fact that none of the performance measurement methods observed in this review was related to effectiveness (or impact) evaluation.\n\nAlthough tightly related, those concepts are distinct from each other. The Britannica Dictionary gives effective definition as “producing a result that is wanted” while efficient means “capable of producing desired results without wasting resources”. Efficiency is quantitatively determined by the ratio of output(s) to total input(s) (Cooper et al., 2006). In the literature, evaluating effectiveness is often referred to impact evaluation, that can be used to answer such specific question: “What is the impact of a program on an outcome of interest?” (Gertlet et al., 2016), see Figure 5. The focus is only on the impact (not the resources): that is, the changes directly attributable to a program. This section is divided into two subsections, each discussing possible research directions related to efficiency and effectiveness (or impact) concepts.\n\nSource: Ulkhaq (2022).\n\nEven though there is abundant research in the field of efficiency measurement, the efficiency is largely measured by the frontier methods: parametric, e.g., SFA; and non-parametric approach, e.g., DEA. Despite several benefits as has been showed previously, research on applying SFA in this research domain are the minority compared to its non-parametric counterpart, i.e., DEA. It seems fruitful to undertake more research regarding measuring efficiency of the collaboration using SFA. In addition, in some cases, the aim of the study is not only identifying the inefficiency level, but also factors that describe inefficiency, called the determinants of inefficiency. DEA cannot handle this issue, yet SFA can easily incorporate the determinants of inefficiency into the so-called heteroscedastic model. Accordingly, SFA can model both cross-sectional and panel data, different to DEA that only can be applied in cross-sectional data. In this review, only two studies used SFA to assess efficiency: Bertoletti and Johnes (2021) who used cross-sectional data, and Lee and Jung (2021) who used panel data. Compared to cross-sectional data, the benefit of using panel (or longitudinal) data is that more information on inefficiency (as well as the changes in efficiency) can be explained; whereas the cross-sectional data can only give a static picture of inefficiency.\n\nPanel data also enables researchers to consider heterogeneity that may exist and to observe whether inefficiency has been persistent over time (time-invariant) or time-varying. The persistent inefficiency is defined as a long-term or structural inability of an institution (in this case is the type of collaboration) to achieve the desired output. On the other hand, time-varying inefficiency refers to a short-run shortage that can be removed swiftly without a huge structural change. Distinguishing between persistent and time-varying inefficiency is vital since they might have different policy implications (Lai and Kumbhakar, 2018). The most recent model in SFA is called the “four-component model”, which was proposed by Colombi et al. (2011), Kumbhakar et al. (2014), Tsionas and Kumbhakar (2014). The model separates producer effects, random noise, persistent, and time-varying inefficiency as follows\n\nNot a single article in this review used this model. Therefore, it is suggested to conduct research measuring performance of UIC by using the four-component model of SFA. The determinants of inefficiency then can be investigated by applying the heteroscedastic model. Caudill and Ford (1993), Caudill et al. (1995), and Hadri (1999) proposed that the heteroscedasticity can be parameterized by a vector of observable variables and corresponding parameters. If uit is assumed to follow half-normal distribution, then σu2 — i.e., the variance of uit — is the (only) variable to be parameterized. Further, the exponential function is used to ensure positivity. Therefore, the parameterization is as follows\n\nHow to estimate the marginal effect of zu on E [uit] given the half-normal assumption of ui can be seen in Kumbhakar et al. (2015).\n\nImpact evaluation seeks to evaluate the effect of a program on an outcome (Imbens and Rubin, 2008; Rubin, 1974). Mathematically, it can be written as:\n\nHowever, such evaluation is unmanageable, as we know that it is impossible to evaluate identical unit in two different states at the same time. This is called the “counterfactual” problem. The vital point to estimate this problem is to shift from the individual level to the group level. From a statistical point of view, if the number of individuals in a group is large enough, the individuals are statistically undifferentiated from each other at the group level. To accommodate this, we now have to form two groups: (i) the group that partakes in the program, known as the treatment group, and (ii) the control group, which does not participate in the program.\n\nOne of the challenges to conduct this research is to recognize a control group and a treatment group which are statistically similar, on average, in the absence of the program. In the vocational training program, we have to find a group of TTO which does not conduct the training (as control group) and other TTO group which does conduct the training (as treatment group). Then, we can compare those groups’ income to evaluate whether the training effectively affects the income. This simple example might be expanded to some real applications in UIC context. Conducting a particular program in the UIC context and evaluating it to observe the outcome that might or might not be benefited from is a very promising branch in this research domain. Readers are encouraged to see for instance Gertlet et al. (2016) that discusses impact evaluation in more detail.\n\n\nConclusions\n\nThis study has systematically reviewed literature (from the Scopus and Web of Science databases) on the performance measurement of UIC in the technology transfer process. It represents a unique opportunity to contribute to the literature by mapping articles systematically in this research domain. Through the PRISMA framework, the review collected 24 articles published in 16 different journals, which were thoroughly analyzed. The collected articles were categorized according to two classifications. The first was the type of collaboration, in which authors might conduct their studies at TTO, ASO, or joint-research level, while the second was the methods used for assessing the performance.\n\nThe literature review lead us to the following conclusions: first, most studies were conducted at the TTO level, in which was anticipated since it is the most common form of UIC. Second, the application of DEA for measuring efficiency is still preferable to SFA. Although DEA has several benefits over SFA (see previous section), it cannot identify the influence of inputs on the outputs, does not distinguish inefficiency from statistical noise, and cannot analyze panel data. Therefore, this study explored the use SFA more deeply to measure efficiency as one of possible research directions. We argue that it is suggested to conduct research on measuring performance of UIC by applying the four-component model of SFA, i.e., the most recent SFA model. Another research direction lies in the field of impact evaluation. Since none of the articles in this review conducted impact evaluation research, we suggest a simple example of how to conduct the evaluation in the context of UIC that might be beneficial for the future research.\n\nThis study also highlights several implications. It represents a unique opportunity to contribute to the research domain by mapping the type of collaboration in UIC and methods to measure the performance of UIC. As has been previously mentioned, this study provides possible research directions that are highly beneficial for researchers to find gaps in the literature. Another theoretical implication comes from the methodology used, as this study presents a robust and structured methodology using the PRISMA workflow in the area of UIC research.\n\nOne of the limitations of this study was the use Scopus and Web of Science databases as we cannot claim that we covered all published articles falling in this research domain since other databases, including Google Scholar and EBSCO, can be used. The other limitation is to include only journal papers as document types in the search. It I possible that different types of documents could contain more useful information. Finally, the search was guided by a set of keywords that provided us with a certain confidence level that we have synthesized an extensive knowledge base on this research domain. It is possible that relevant articles did not put the set of keywords used in this study in their title, abstract, and keywords.\n\n\nData availability\n\nFigshare: Dataset for “Performance Measurement of University-Industry Collaboration in the Technology Transfer Process A Systematic Literature Review”, https://doi.org/10.6084/m9.figshare.19731553.v4\n\nThis project contains the following underlying data:\n\n- PRISMA_2020_checklist\n\n- Framework Prisma\n\n- Dataset Scopus\n\n- Dataset WoS\n\n\nReporting guidelines\n\nFigshare: PRISMA_2020_checklist for “Performance Measurement of University-Industry Collaboration in the Technology Transfer Process A Systematic Literature Review”, https://doi.org/10.6084/m9.figshare.19731553.v4\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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}
|
[
{
"id": "171812",
"date": "16 Aug 2023",
"name": "Chunyan Zhou",
"expertise": [
"Reviewer Expertise University-industry relations",
"university technology transfer",
"university-industry-government triple helix innovation model",
"entrepreneurial university"
],
"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\nSuggestions and Comments:\nSuggest to change the title into “Types and performance measurement methods of university-industry collaboration in the technology transfer process: A systematic literature review”.\n\nSome important literatures are missing, for example, Henry Etzkowitz’s study on university-industry interaction based on the university-industry-government triple helix innovation model; Johan Bruneel et al Investigating the factors that diminish the barriers to university–industry collaboration; Karolin Sjöö and Tomas Hellström， University–industry collaboration: A literature review and synthesis.\n\nSpelling problems, e.g., on page 11 of 14, “It I possible that …”\n\nOn page 7 of 14, what are non-financial effects?\n\nOn page 5 of 14, in “we used qualitative approach to categorize articles according to …” , what is the “qualitative approach”? And on this page, it is repeating that “This section devotes to articles classification. Each article was classified according to the type of collaboration and methods of performance measurement. Classifying extracted articles from literature review allows readers to validate what has been studied and can also allow to find gaps in this research domain.” Need to be reorganized.\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? I cannot comment. A qualified statistician is required.\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/11-662
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https://f1000research.com/articles/11-661/v1
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16 Jun 22
|
{
"type": "Systematic Review",
"title": "The effect of dietary modification on executive function domains in adult individuals with obesity: A systematic review and meta-analysis of randomized controlled trials",
"authors": [
"Junita Maja Pertiwi",
"Adriyan Pramono",
"Martha Marie Kaseke",
"Nelly Mayulu",
"David Susanto",
"Andisty Ate",
"Mochammad Rizal",
"Ahmad Syauqy",
"William Ben Gunawan",
"Fahrul Nurkolis",
"Junita Maja Pertiwi",
"Martha Marie Kaseke",
"Nelly Mayulu",
"David Susanto",
"Andisty Ate",
"Mochammad Rizal",
"Ahmad Syauqy",
"William Ben Gunawan",
"Fahrul Nurkolis"
],
"abstract": "Background: Recent study suggests that obesity is associated with a broad executive function decline. Several dietary intervention studies may improve executive function domains. This meta-analysis aimed to determine the effect of dietary modification on executive function domains in adult patients with obesity. Methods: This systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Pubmed/Medline, Cochrane Library, Science Direct/SCOPUS, and Google Scholar were systematically searched to obtain articles until April 30th, 2022. The main outcome of interest was the change in executive function domains (inhibition, cognitive flexibility, working memory, verbal fluency, decision making, and planning). We extracted data on the standardized mean difference (SMD) between the dietary intervention and control groups in change from baseline executive function domains. The meta-analysis with a random effect model was performed using STATA, and the Risk of Bias (RoB 2.0) tool was used to determine the quality of the included studies. Subsequently, to assess the quality of evidence, we used GRADE tools. Results: A total of 10 randomized controlled trials (RCTs) that met the objectives were obtained. This meta-analysis showed that dietary modification improved cognitive flexibility [SMD=0.303 (-0.527 to -0.079), P=0.008, I2= 0%], working memory [SMD=0.601 (0.076 to 1.125), P=0.025, I2=83.6%], and verbal fluency [(SMD=0.223 (0.002 to 0.428), P=0.033, I2=16.3%]. However, most RCTs (six out of 10) had some concerns due to allocation concealment, unclear blinding assessment or participants, and a high dropout rate. Thus, further well-controlled RCTs are needed to confirm these results. Conclusions: Dietary modification might improve executive function domains in adult individuals with overweight/obesity. Registration: This systematic review is registered in the PROSPERO database (CRD42022332572; registered 24 May 2022).",
"keywords": [
"Obesity",
"executive function",
"cognitive flexibility",
"working memory",
"verbal fluency",
"diet",
"meta-analysis"
],
"content": "Introduction\n\nAccording to the 2017 global disease burden report, more than four million people die yearly from being overweight or obese. The prevalence of obesity continues to rise in adult individuals, with a global trend of 4% to 18% between 1975 and 2016 (World Health Organization, 2018). Of note, the rise of obesity prevalence is irrespective of sex, social, and economic status (Blüher, 2019). Indeed, a recent review pointed out that the economic growth and urbanization experienced by many Low Middle-Income Countries (LMICs) were significant drivers of obesity trends as they promoted unhealthy dietary patterns and sedentary physical activity (Malik et al., 2020). In general, obesity status can be defined using body mass index (BMI), although this measure is not sensitive to determine the amount of body fat (Nuttall, 2015; World Health Organization, 2018).\n\nThe effects of obesity are usually deleterious on several organ systems. Furthermore, metabolic syndrome, an obesity disorder, is often characterized by several comorbid conditions, such as large waist size, high triglyceride levels, glucose intolerance, and hypertension, has contributed to metabolic disorders. This condition is also a risk factor for developing type 2 diabetes (T2D), systemic hypertension, coronary arterial disease, and heart failure. Obesity further increases the incidence of gastrointestinal and musculoskeletal disorders, thromboembolism, stroke, cancer, and respiratory diseases, such as obstructive sleep apnea (Blüher, 2019). This disease affects the central nervous system, namely the subregions essential to learning, memory, and executive functions (EFs) (Nguyen et al., 2014; Nuttall, 2015).\n\nNotably, a recent meta-analysis has suggested that deficits in EF domains have already been observed in adult individuals with obesity. It has been indicated that adult individuals with obesity performed inhibition tasks worse as compared to normal-weight individuals. According to pieces of literature on EF (Miyake et al., 2000; Miyake & Friedman, 2012), inhibition is defined as the ability to suppress impulsive responses. Next to that, obese individuals had impairment on tasks that require cognitive flexibility, which refers to the ability to shift attention when situationally appropriate (Yang et al., 2018). Furthermore, obese individuals lacked working memory performance, known as the ability to monitor the incoming stimuli and update information in memory as required (Yang et al., 2018). In addition to that, other EF domains have also been investigated in that meta-analysis (Collins & Koechlin, 2012; Lezak et al., 2012; Suchy, 2009; Testa et al., 2012), including i) decision making (Rangel et al., 2008), ii) verbal fluency (Troyer et al., 1997), and iii) planning (Lezak et al., 2012) suggesting that healthy individuals performed tasks related to EF domains better than obese individuals (Yang et al., 2018).\n\nRecently, it has been proposed that weight loss may be associated with improvement in EF in obesity (Eichen et al., 2021). Various lifestyle modification approaches could be used for individuals to lose weight or overcome obesity problems, including calorie reduction and macronutrient composition balancing. The Mediterranean diet (MD) is an example of one of these methods used to treat obesity. In addition, Rodrigues et al. (2020) stated that this regimen was associated with higher structural connectivity between the left hemisphere brain regions, specifically the amygdala, lingual, middle occipital gyrus, and calcarine area (Rodrigues et al., 2020). The benefits of this diet are also positively associated with brain health, namely EFs, and white matter integrity, which are associated with taste processing and integration, reward, and decision making (Devere, 2016; Martin & Davidson, 2014). However, the effect of dietary intervention (modification) on EF domains in adult individuals with obesity remains unknown. Therefore, this systematic review and meta-analysis aimed to determine the effect of dietary modification on several EF domains in adult individuals with overweight/obesity.\n\n\nMethods\n\nThis systematic review and meta-analysis are reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) updated guidelines (Page et al., 2021) (completed PRISMA checklist (Gunawan, 2022) and flow chart (Gunawan, 2022)). This systematic review is registered in the PROSPERO database (CRD42022332572; 24 May 2022).\n\nThe main outcome of interest was the change in EF domains based on a previous study (Yang et al., 2018), including i) inhibition measured by several tests such as the Stroop task, the Stop Signal Task or Reaction Time Tasks, ii) cognitive flexibility as determined by Trail Making Test or Wisconsin Card Sorting Test (WCST) or Modified WCST, iii) working memory as assessed by the Digit span tasks, or the Letter–number sequencing task or memory performance test, iv) decision making as determined by Tower of London Task or Iowa Gambling Task or Delay Discontinuing Task, v) verbal fluency as measured by verbal learning test or verbal fluency test or verbal paired associates or word list fluency or verbal free recalls, and vi) planning as determined by The Wechsler Memory Scale – Fourth Edition (WMS-IV) or Tower of London Task following dietary intervention (dietary modification).\n\nComprehensive literature searches on Pubmed (RRID: SCR_004846)/Medical Literature Analyses and Retrieval System Online (MEDLINE) (RRID: SCR_002185), Cochrane Library (RRID: SCR_013000), Science Direct (SCOPUS), and Google Scholar (RRID: SCR_008878) were performed to identify articles from 1980 until 30 April 2022. The main keywords used were as follows: ‘overweight’, ‘obesity’, ‘EF’, ‘cognitive flexibility’, ‘inhibition’, ‘working memory’, ‘decision making’, ‘verbal fluency’, ‘planning’, ‘dietary intervention’, ‘dietary modification’, ‘Caloric restriction’, ‘Mediterranean diet’, ‘Diet’. These keywords were combined with Boolean operators (e.g., ‘OR’, ‘AND’, ‘NOT’), and all fields or Medical Subject Heading (MeSH) terms or Title/Abstract (TIAB). This set of search terms was slightly modified when we searched in every database due to a different system and technical limitations.\n\nEligible studies met the Patients/participants, Intervention, Comparison/control group, outcome, and Study design (PICOS) criteria: i) study was a randomized controlled trial (RCT); ii) study population consisted of individuals with overweight/obesity (without complications); iii) interventions were dietary modifications (any modes of dietary interventions) versus the appropriate control; iv) no limit of the duration for intervention (weekly, or monthly); v) measured outcomes of EF domains (inhibition and/or cognitive flexibility and/or working memory and/or decision making and/or verbal fluency and/or planning); vi) RCT; and vii) study was published in English.\n\nExclusion criteria were as follows: i) non-clinical trial studies; ii) studies without the outcome of EF domains (inhibition and/or cognitive flexibility and/or working memory and/or decision making and/or verbal fluency and/or planning); iii) study populations with end-stage renal disease (kidney disease), cancers, gestational diabetes mellitus (GDM), nonalcoholic steatohepatitis, cardiovascular diseases complications, and infectious diseases; iv) intervention periods of < 4 weeks; and v) study performed in children or adolescents (<18 years old).\n\nFollowing the search, duplicates were removed. Titles and abstracts were screened by two authors (A.P. and W.B.G.). Based on the inclusion criteria, the final study selection was done by two authors (A.P. and W.B.G.) and approved by another author (J.M.P.). Any disagreements between the authors were resolved through discussion with other authors.\n\nData were extracted by two authors (A.P. and W.B.G.). Extracted data were approved by the other authors. Data extracted from each study included the following items: first author, reference, year of publication, country of study, study design, sample size, age, BMI, dietary interventions, duration, participants’ characteristics [n, sex (% male)], outcome measures of EF domains [as described i) inhibition measured by several tests such as the Stroop task, the Stop Signal Task or Reaction Time Tasks, ii) cognitive flexibility as determined by Trail Making Test or WCST or Modified WCST, iii) working memory as assessed by the Digit span tasks, the Letter–number sequencing task, memory performance test, iv) decision making as determined by Tower of London Task, Iowa Gambling Task, Delay Discontinuing Task, v) verbal fluency as measured by verbal learning tests or verbal fluency tests, verbal paired associates, word list fluency, verbal free recalls, and vi) planning as determined by WMS IV-VWMIS, Tower of London Task] (Table 1).\n\n\n\n▪ Sustained attention (Bakan vigilance task),\n\n▪ Short-term memory (word recall task),\n\n▪ Simple reaction time (inhibition domain),\n\n▪ Motor performance (two finger tapping task),\n\nand focused attention (Ericksen effect)\n\n\n\n▪ The Digit Symbol-Coding subtest of the Wechsler Adult Intelligence Scale III\n\n▪ The Trail Making Test\n\n▪ The Stroop Test\n\n▪ The Self-Ordered Pointing Task\n\n▪ Two measures of verbal fluency: initial letter fluency and excluded letter fluency\n\n\n\n▪ Grammatical Reasoning\n\n▪ Four Choice Reaction Time\n\n▪ Repeated Acquisitions\n\n▪ Visual Vigilance\n\n\n\n▪ Trail making test B-A\n\n▪ The Stroop Interference\n\n▪ Digit Span Task\n\n▪ Verbal Fluency Test (Animal naming)\n\n▪ Verbal Paired Associates\n\n▪ Word Association Test\n\n▪ Ruff 2 and 7 Test (total correct)\n\n▪ Digit Symbol Substitution Test\n\n\n\n▪ Two-Finger Tapping Task (motor speed)\n\n▪ Verbal Free Recall Task (phonological loop)\n\n▪ Bakan Vigilance Task (sustained attention and general working memory)\n\n▪ Simple Reaction Time\n\n▪ Tower London Task\n\n\n\n▪ Trail making test B\n\n▪ Trail making test A\n\n▪ Word Lists Fluency\n\n\n\n▪ Memory Performance Test\n\n\n\n▪ Digit Span\n\n▪ Trail Making Test (TMT) part A and B\n\n▪ Stroop Color-word Test\n\n▪ Verbal Fluency Tasks\n\n\n\n▪ The RAVLT\n\n▪ The Rey-Osterrieth complex figure Test (RCFT)\n\n▪ The Symbol Digit Modalities Test (SDMT)\n\n▪ The Stroop Color-Word Interference Test\n\n▪ The Iowa Gambling Task (IGT)\n\n▪ The CPT\n\n\n\n▪ The Trail Making Test A-B\n\n▪ Verbal short memory composite included the score of Forward Digit Span Task (FDST) and Backward Digit Span Task (BDST)\n\n▪ The Letter Number Sequencing Task (LNST)\n\n▪ The SDMT\n\n▪ Auditory Verbal Learning Test (AVLT)\n\nThe quality of selected RCTs was assessed independently by two authors (A.P. and W.B.G.) using the risk of bias checklist (RoB 2.0) from the Cochrane Collaboration (Sterne et al., 2019). The quality assessments of the checklist included: i) bias from the randomization process, ii) bias due to deviations from intended interventions, iii) bias due to missing outcome data, iv) bias from measurements of the outcome, v) bias from the selection of reported result. Each criterion could be answered in three ways: yes (adequate information), no (inadequate information), or unclear (some concerns). Study quality and the risk of bias in the eligible RCTs were systematically assessed using RoB 2.0 tools (MS Excel format).\n\nTo calculate the effect size of each study, we used the mean change and standard deviation (SD) change of the outcome measures from baseline to the end of the intervention in the control and intervention groups. When the outcome measure was reported as median and range or 95% confidence interval (CI), mean and SD values were estimated using the method described previously (Wan et al., 2014). If the standard error of the mean (SEM) was reported, the SD was estimated using the following formula: SD = SEM x square root (n), where n is the number of subjects (Wan et al., 2014). SDs of the mean difference were estimated using the following formula: SD = square root [(SD pre-treatment)2 + (SD post-treatment)2) - (2R * SD pre-treatment * SD post-treatment)]. Because the pretest-posttest correlation coefficients (r) were not reported in studies, an r-value of 0.5 was assumed throughout this meta-analysis.\n\nA meta-analysis was conducted to combine the individual study results using Stata version 16 software (RRID:SCR_012763; StataCorp LLC). Alternatively, RStudio (RRID:SCR_000432) can be used as a free alternative. If a study included more than two intervention groups (e.g., diet modification and exercise), groups were included compared to the placebo (control) group is exercise. If the outcome measurement was performed multiple times after the intervention period, we only used the endpoint after the intervention.\n\nRandom-effects models (DerSimonian-Laird method) were used to estimate outcomes. Heterogeneity was assessed using the I2 index, with values above 60% indicating substantial heterogeneity. The Egger test’s funnel plot followed by a meta-bias analysis was performed to detect publication bias. The effect size is reported as the standardized mean difference with its 95% confidence interval (Higgins et al., 2022). A p-value < 0.05 is considered statistically significant. The forest plots and funnel plots will be produced using Stata version 16 software.\n\nThe sensitivity and/or subgroup analyses were performed to try to gain insight into the source of the heterogeneity. Sensitivity analysis was performed using the leave-one-out method (removing one study each time and repeating the analysis).\n\nThe Grading of Recommendations Assessments, Development, and Evaluation (GRADE) was further used to qualify this meta-analysis’s evidence. All outputs were evaluated for quality, based on the components of bias risk, inconsistency, indirectness, and impressions.\n\n\nResults\n\nIn the initial search, a total of 956 publications have been reported in PubMed (340); Cochrane library (400); SCOPUS (190); and Google Scholar (26). After removing duplicate and unrelated titles and screening the titles and abstracts, about 71 articles were selected. The authors read the full text of these selected articles and selected 10 eligible articles (Arjmand et al., 2022; Boraxbekk et al., 2015; Bryan & Tiggemann, 2001; Cheatham et al., 2009; Green & Elliman, 2013; Kretsch et al., 1997; Napoli et al., 2014; Prehn et al., 2017; Smith et al., 2010; Soldevila-Domenech et al., 2021) to be qualitatively and quantitatively synthesized. The detail of the study selection process can be seen in Figure 1.\n\nCharacteristics of these studies (10 studies) are shown in Table 1. The age and mean BMI of participants were comparable between studies. The types of dietary intervention (diet modification) varied between studies. The duration of studies ranged between eight weeks and six years (Arjmand et al., 2022; Boraxbekk et al., 2015; Bryan & Tiggemann, 2001; Cheatham et al., 2009; Green & Elliman, 2013; Kretsch et al., 1997; Napoli et al., 2014; Prehn et al., 2017; Smith et al., 2010; Soldevila-Domenech et al., 2021). The outcomes of EF domains varied between studies. There are limited data on the ethnicity of subjects within the study intervention. However, the study’s country of origin was described as The United States of America (three studies), Australia (two studies), The United Kingdom (two studies), Spain, Sweden, Japan, and Iran.\n\nAll 10 studies (Arjmand et al., 2022; Boraxbekk et al., 2015; Bryan & Tiggemann, 2001; Cheatham et al., 2009; Green & Elliman, 2013; Kretsch et al., 1997; Napoli et al., 2014; Prehn et al., 2017; Smith et al., 2010; Soldevila-Domenech et al., 2021) reported the use of several types of dietary modifications such as caloric restriction (Bryan & Tiggemann, 2001; Kretsch et al., 1997; Prehn et al., 2017), The Paleolithic Diet (Boraxbekk et al., 2015), The MD (Soldevila-Domenech et al., 2021), the Dietary Approaches to Stop Hypertension (DASH) Diet (Smith et al., 2010) as well as modified Mediterranean – DASH Diet (Arjmand et al., 2022). Dietary modification (dietary intervention) was designed for weight loss in all studies (Arjmand et al., 2022; Boraxbekk et al., 2015; Bryan & Tiggemann, 2001; Cheatham et al., 2009; Green & Elliman, 2013; Kretsch et al., 1997; Napoli et al., 2014; Prehn et al., 2017; Smith et al., 2010; Soldevila-Domenech et al., 2021). The duration of intervention ranged from eight weeks to six years. Most of the studies (except Arjmand et al., 2022) have reported a higher dropout rate, whereas those who left the study either did not comply with the dietary protocol during dietary modification (dietary intervention) or left for personal reasons. More importantly, no major adverse effect of the dietary modification (intervention) program was reported. This suggests that all dietary modifications are considered safe for adult individuals with overweight/obesity.\n\nFurthermore, changes in EF domains were determined by varied tasks of inhibition domain, cognitive flexibility, working memory, decision making, verbal fluency, and planning (Arjmand et al., 2022; Boraxbekk et al., 2015; Bryan & Tiggemann, 2001; Cheatham et al., 2009; Green & Elliman, 2013; Kretsch et al., 1997; Napoli et al., 2014; Prehn et al., 2017; Smith et al., 2010; Soldevila-Domenech et al., 2021). Among these outcomes, the decision-making and planning domains were not quantitatively synthesized because the data from included studies could not be extracted. Based on qualitative analysis, the decision-making domain tested by Iowa Gambling Task (IGT) by (Soldevila-Domenech et al., 2021) suggests an improvement following three years of the MD trial. Of interest, the planning domain assessed by The Tower of London task (Green & Elliman, 2013) showed no differences between a supervised-diet group and the control group.\n\nThe effect of dietary modification (diet interventions) on EF domain inhibition\n\nIn this meta-analysis, the domain inhibition of EF was determined based on the Stroop test and reaction time test. About eight RCTs described the outcome of the Stroop test (five studies) (N dietary intervention 361 vs. N control 279) and reaction time test (three studies) (N dietary intervention 44 vs. N control 37). Based on a random-effect model in this meta-analysis, dietary modification (dietary intervention) did not improve the inhibition domain of EF as measured by the Stroop test and Reaction Time Test (the Stroop test SMD: −0.055; 95% CI: −0.356 to 0.246, P=0.721; Reaction Time Test SMD −0.527; 95% CI: −1.423 to 0.369, P=0.249) (Figure 2a and 2b, respectively).\n\n(a) Forest plots of SMD of inhibition domain measured by Stroop test between intervention and control groups (represented as Diamond). Horizontal lines span individual study 95% confidence intervals. (b) Forest plots of SMD of inhibition domain measured by reaction time tests between intervention and control groups (represented as Diamond). Horizontal lines span individual study 95% confidence intervals.\n\nThe effect of dietary modification (diet interventions) on EF domain cognitive flexibility\n\nAbout six RCTs described the outcome of the cognitive flexibility domain of EF (N dietary intervention 161 vs. N control 154) was determined based on the Trail Making Test. Based on a random-effect model in this meta-analysis, dietary modification (dietary intervention) decreases the score of the Trail Making Test (SMD: −0.303; 95% CI: −0.527 to −0.079, P=0.008), with no heterogeneity observed (I2=0%, P=0.513) (Figure 3). This result implies that dietary modification (dietary intervention) resulted in an improvement of the cognitive flexibility domain of EF.\n\nHorizontal lines span individual study 95% confidence intervals.\n\nThe effect of dietary modification (diet interventions) on EF domain working memory\n\nIn this meta-analysis, about seven RCTs described the outcome of EF’s working memory domain, which was determined based on the Digit Span test, the Letter Number Sequencing Task. Based on a random-effect model in this meta-analysis, dietary modification (dietary intervention) (N dietary intervention 260 vs. N control 193) improves the working memory domain of EF (SMD: 0.601; 95% CI: 0.076 to 1.125, P=0.025), with substantial heterogeneity observed (I2=83.6%, P=0.000) (Figure 4).\n\nHorizontal lines span individual study 95% confidence intervals.\n\nThe effect of dietary modification (diet interventions) on EF domain verbal fluency\n\nAbout six RCTs described the outcome of the verbal fluency domain of EF that was measured based on verbal learning test (Auditory Verbal Learning Test, Verbal initial and excluded letter fluency, Verbal Fluency test, Animal naming, Verbal paired associates, and control oral word association). Based on a random-effect model in this meta-analysis, dietary modification (dietary intervention) (N dietary intervention 274 vs. N control 234) enhances the verbal fluency domain of EF (SMD: 0.223; 95% CI: 0.002 to 0.428, P=0.033), with low heterogeneity observed (I2=16.3%, P=0.297) (Figure 5).\n\nHorizontal lines span individual study 95% confidence intervals.\n\nThe output of the improved EF domains from most included studies suggests that the effect of all dietary modification (dietary intervention) may be similar and not superior to other dietary modification regimes. Due to the limited number of selected articles, we could not perform a subgroup analysis to determine that question. However, perhaps a varied improvement of EF domains may also suggest that more specific approaches might be taken into account when implementing a dietary modification to improve specific domains of EF in adult patients with overweight/obesity.\n\nVisually inspected funnel plot symmetry did not indicate any potential publication bias for the comparison of EF domains, inhibition domain, cognitive flexibility, and verbal fluency, between the dietary modification (intervention) groups and control groups (Figures 6-9). Regarding the outcome of working memory, the further inspection of the funnel plot, including a meta-bias analysis using the Egger test, illustrates publication bias from included studies (Egger test Root MSE=2.021 P=0.049).\n\nSMD, standardized mean difference.\n\nSMD, standardized mean difference.\n\nSMD, standardized mean difference.\n\nSMD, standardized mean difference.\n\nHorizontal lines span individual study 95% confidence intervals.\n\nWe excluded the study in which the outcome had the highest effect size, and the interpretation was slightly changed to address that issue. We found that working memory was slightly improved in the dietary intervention (dietary modification) group as compared to the control group (SMD=0.306; 95% CI −0.024 to 0.635, P=0.069) with moderate heterogeneity (I2=56.6%, P=0.018). Further funnel plot inspection and the Egger-test analysis revealed no publication bias was observed (Root MSE=1.457, P=0.235) (Figures 10 and 11).\n\nRisk of bias assessment (RoB 2.0)\n\nOverall, the RoB assessment using RoB 2.0 tools of the included studies using the Cochrane risk of bias tool 2020 showed some concerns in six out of 10 studies (Figure 12). This assessment illustrated only four out of 10 studies with a low risk of bias. Several domains such as “randomization processes”, “allocation concealment” and “deviations from intended intervention” were recognized as sources of concern. In addition, this type of study (i.e., dietary intervention/dietary modification) trials, the domains that mostly contributed to concern were the “blinding of participants and personal (performance bias)” as well as “blinding of outcome assessment (detection bias)”. These can be attributed due to the nature of this type of intervention (dietary modification/dietary intervention).\n\nQuality of evidence assessment\n\nThe study’s quality assessment was evaluated using the GRADE assessment based on the Cochrane Handbook 2022 (Higgins et al., 2022) in a narrative format with overall analysis results on all selected articles. This software assessed the article results, which are following the initially set research outputs according to PICOS, such as changes in several domains (inhibition, cognitive flexibility, working memory, verbal fluency, decision-making, and planning) of the EF after dietary intervention (dietary modification). All outputs were measured for quality in each selected article by assessing the risk components of bias, inconsistency, indirectness, and impressions. Subsequently, the outputs were grouped based on the outcome priorities. We also determined whether each output had a very low, low, medium, or high certainty level (Schünemann et al., 2013) (Table 2). Table 2 describes the quality of evidence assessment based on GRADE. We evaluated the assessment of each effect of dietary modification on several domains of the EF. No serious issues were observed concerning the components of inconsistency and indirectness since the results were relatively consistent between studies and all participants were adults with overweight/obesity. Regarding impression, four (inhibition, cognitive flexibility, working memory, and verbal fluency) out of six domains in the EF domains can be determined with meta-analyses. We could not perform meta-analyses for outcome decision-making and planning. Furthermore, the majority of included studies had some concerns, as depicted in Figure 12. Therefore, the intervention treatment (dietary modification) might be implemented and with careful attention on some concerns such as randomization, allocation concealment and high rate of dropout. Table 2 shows that all outcomes had distinct certainty values of the selected articles.\n\nBased on the risk of bias assessment, the two outputs did not pose a serious risk because a randomization technique was conducted in the study design. The output assessment was also evaluated with an objective tool to minimize the risk of bias. No serious issue was observed concerning the components of inconsistency and indirectness since the results were relatively consistent between studies and all participants were adults with overweight/obesity. Regarding impression, four (inhibition, cognitive flexibility, working memory, and verbal fluency) out of six domains in the EF domains could be determined with meta-analyses. We could not perform meta-analyses for the outcome of decision-making and planning. Furthermore, the majority of included studies had some concerns, as depicted in Figure 6. Therefore, the intervention treatment (dietary modification) may be implemented with low-risk precision. Table 1 shows that all outcomes had distinct certainty values in the selected articles.\n\n\nDiscussion\n\nThis systematic review and meta-analysis reported findings regarding the effect of dietary modification (dietary intervention) on the EF domains in adult individuals with overweight/obesity. This meta-analysis determined the EF domains as described in literature such as inhibition, cognitive flexibility, working memory, verbal fluency, decision-making, and planning. Overall, this meta-analysis showed that the dietary intervention (dietary modification) was safe to implement in adult individuals with overweight/obesity. Furthermore, we observed improvements in cognitive flexibility, working memory, and verbal fluency after dietary intervention in the treatment groups as compared to control groups. By contrast, we did not see any dietary intervention effects on the EF inhibition domain. We could not draw results from the decision-making and planning domains due to a limited number of studies to perform a meta-analysis.\n\nA growing body of evidence suggests that being overweight and obese are linked to cognitive decline and an increased risk of vascular dementia and Alzheimer’s disease, particularly in middle-aged people (Pedditizi et al., 2016). Notably, the incidence of dementia in those under the age of 65 years was associated with obesity according to a previous meta-analysis (Pedditizi et al., 2016). Furthermore, in another systematic review and meta-analysis, there was a clear association between overweight/obesity and the EF domains (Favieri et al., 2019). Supporting this evidence, a recent meta-analysis also demonstrated that overweight/obesity had the worse response regarding several domains of the EF (Yang et al., 2018).\n\nA recent review has indicated that the EF domains may be associated with lower weight loss (Eichen et al., 2021). Losing bodyweight is still recognized as the main target of treatments for overweight/obesity. There are several weight loss treatment programs; bariatric surgery, pharmacological treatment, and behavioral weight loss (BWL), including dietary modification (National Institute for Health and Care Excellence, 2020; Tchang et al., 2021). Currently, behavioral weight loss is still the recommended behavioral treatment for obesity. One strategy to establish behavioral weight loss is by implementing dietary modifications. The majority of human trials on dietary modification-induced weight loss are by implementing caloric restriction. Indeed, it has been shown that caloric restriction may reduce visceral adipose tissue (VAT) (Ard et al., 2018). The optimum weight reduction as a result of dietary modification strategy is varied for each individual. Several reports determine that a 5 to 10% weight loss is adequate enough to influence the clinical outcomes (Haase et al., 2021).\n\nIn this meta-analysis, we found that dietary modification rules varied between studies. Notably, several included studies employed a combination of specific diets such as MD or DASH diet and caloric restriction (Arjmand et al., 2022; Soldevila-Domenech et al., 2021). A meta-analysis determined that adherence to the MD increased working memory and verbal cognition compared to the control group (Loughrey et al., 2017). Of note, populations in that meta-analysis were individuals with relatively healthy/normal BMI.\n\nIn addition, several studies have reported that the direct effect of weight reduction on cognition is biologically plausible (Horie et al., 2016; Siervo et al., 2011). Accordingly, BMI reduction during the intervention period might be associated with improvements in working memory. It may also be that cognitive improvements accumulate based on time course. Our results also suggest that weight loss is often accompanied by the dietary intervention (dietary modification) and was associated with the EF domains.\n\nThe EF consists of several domains (Miyake et al., 2000; Miyake & Friedman, 2012), inhibition is defined as the ability to suppress impulsive responses. Next to that, obese individuals had impairment on tasks that require cognitive flexibility, which refers to the ability to shift attention when situationally appropriate (Yang et al., 2018). Furthermore, obese individuals lacked working memory performance, known as the inability to monitor the incoming stimuli and update information in memory as required (Yang et al., 2018). In addition to that, other EF domains have also been investigated in that meta-analysis (Collins & Koechlin, 2012; Lezak et al., 2012; Suchy, 2009; Testa et al., 2012), including i) decision making (Rangel et al., 2008), ii) verbal fluency (Troyer et al., 1997), and iii) planning (Lezak et al., 2012), suggesting that healthy individuals performed tasks related to EF domains better than obese individuals (Yang et al., 2018).\n\nSeveral tools were used in the assessment of cognitive performance, such as Rey’s auditory verbal learning test (RAVLT) for evaluating short-term and long-term auditory memory. The Rey-Osterrieth complex figure test (RCFT) was used to assess visuospatial function, the symbol digit modalities test (SDMT) to measure thinking speed, and the Stroop color-word interference test to evaluate inhibitory and attentional functions. Furthermore, the IGT was another tool used to assess decision-making abilities, the conner’s continuous auditory test of attention (CPT) evaluated attention, impulsivity, and alertness, while the screening assessment of general cognitive function was examined with a mini-mental state examination (MMSE) (Soldevila-Domenech et al., 2021).\n\nThe EF outputs in the selected articles showed improvements in the attention, decision-making, and speed of thinking performances through the CPT – commission errors, IGT, and SDMT examinations, respectively. Meanwhile, the inhibition function through the Stroop test did not show any statistically significant changes. This finding is in accordance with several hypotheses, which showed that cognitive function and obesity have a two-way relationship, where this condition results in mental decline and vice versa. According to Kamijo et al. (2014), an impaired inhibitory control function in the prefrontal cortex can lead to excessive caloric consumption, which significantly results in weight gain (Kamijo et al., 2014). Volkow et al., 2011 further revealed that imaging studies in obese patients indicate hypoactivation of dopamine D2 receptors and decreases neural metabolism in areas involved in EF. Dopamine also plays a role in the “reward system”, therefore, disruption of its production can impact excessive calorie consumption (Schiff et al., 2015; Volkow et al., 2011). Another hypothesis by Gonzales et al. (2010) depicted that obesity can affect insulin resistance, inflammatory processes, changes in cerebral areas related to analytical functions, and cerebrovascular blood flow, resulting in structural modifications (Gonzales et al., 2010).\n\nStinson et al. (2018) mentioned that prolonged incorrect food consumption is connected with excessive body weight maintenance, which leads to decreased EF performance and impaired behaviors. Furthermore, these factors are linked to an increased risk of cognitive impairment in old age (Sanderlin et al., 2017) and trouble reacting correctly to external stimuli. These traits are indicative of impaired EFs, which will have a detrimental impact on the lives of overweight people (Favieri et al., 2019). Dohle et al. (2018) also revealed that dietary behavior influences brain performance, and that healthy eating habits can increase cognitive function maintenance throughout life (Morris et al., 2005; Smith & Blumenthal, 2015). Other research, however, tends to disagree with this viewpoint, claiming that cognitive functions are regarded as separate entities. On the other hand, several disagree with this viewpoint, claiming that cognitive abilities predict eating behavior connected to weight change. According to this viewpoint, decreased brain function is the underlying of disordered eating behavior, causing alterations in adults with overweight/obesity (Dassen et al., 2018; Dohle et al., 2018; Favieri et al., 2019).\n\nThis study had several strengths; first, we performed a systematic review and meta-analyses of RCTs, which is considered high-quality evidence. Second, we determined detailed domain analysis regarding the EF e.g., inhibition, cognitive flexibility, working memory, verbal fluency, decision-making, and planning. There were several limitations in this meta-analysis. First, even though the dietary intervention (dietary modification) is considered safe, the majority of included studies had low adherence to the dietary intervention, and other personal circumstances exist during dietary interventions. Second, whether the dietary modification directly affects the EF domains or due to the mediator effect of weight loss remains unclear. Third, while measuring the six domains of the EF (inhibition, cognitive flexibility, working memory, verbal fluency, decision-making, and planning), included studies employed varied tasks. Nevertheless, these meta-analyses showed that dietary modification might influence the changes in some of the EF domains.\n\n\nConclusions\n\nThis meta-analysis highlights the effects of dietary modification on several domains of the EF such as cognitive flexibility, working memory, and verbal fluency. However, we did not find any effects of dietary intervention on the inhibition domain of the EFs. In addition, the effects of dietary modification on decision-making and planning domains remain unclear. Nevertheless, dietary modification may have beneficial effects on improving the EF domains. More large, well-controlled studies are needed to confirm these findings.\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\nReporting guidelines\n\nFigshare: PRISMA checklist for ‘The effect of dietary modification on executive function domains in adult with obesity: A systematic review and meta-analysis of randomized controlled trials’. https://doi.org/10.6084/m9.figshare.19843111 (Gunawan, 2022).\n\nFigshare: PRISMA flow diagram for ‘The effect of dietary modification on executive function domains in adult with obesity: A systematic review and meta-analysis of randomized controlled trials’. https://doi.org/10.6084/m9.figshare.19843873 (Gunawan, 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\nAuthor contributions\n\nJunita Maja Pertiwi, Adriyan Pramono, Martha Marie Kaseke, David Susanto, Andisty Ate, Ahmad Syauqy, and William Ben Gunawan: Conceptualization, Formal Analysis, Writing – Original Draft Preparation and Writing – Review & Editing. Adriyan Pramono, Nelly Mayulu, Mochammad Rizal, and Fahrul Nurkolis: Supervision, Validation, Writing – Review & Editing.",
"appendix": "Acknowledgments\n\nJ.M.J., M.M.K., D.S., and A.A. thank the Faculty of Medicine, Sam Ratulangi University, Manado for supporting this research. A.P., A.S., and W.B.G. also thank the Faculty of Medicine, Diponegoro University, Semarang.\n\n\nReferences\n\nArd JD, Gower B, Hunter G, et al.: Effects of Calorie Restriction in Obese Older Adults: The CROSSROADS Randomized Controlled Trial. The Journals of Gerontology: Medical Sciences. 2018; 73(1): glw237–glw280. Publisher Full Text\n\nArjmand G, Abbas-Zadeh M, Eftekhari MH: Effect of MIND diet intervention on cognitive performance and brain structure in healthy obese women: a randomized controlled trial. Sci. Rep. 2022; 12(1): 2814–2871. PubMed Abstract | Publisher Full Text\n\nBlüher M: Obesity: global epidemiology and pathogenesis. Nat. Rev. Endocrinol. 2019; 15(5): 288–298. 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Publisher Full Text\n\nLezak MD, Howieson DB, Bigler ED, et al.: Neuropsychological assessment. 5th ed.Oxford University Press;2012.\n\nLoughrey DG, Lavecchia S, Brennan S, et al.: The Impact of the Mediterranean Diet on the Cognitive Functioning of Healthy Older Adults: A Systematic Review and Meta-Analysis. Adv. Nutr. 2017; 8: 571–586. PubMed Abstract | Publisher Full Text\n\nMalik VS, Willet WC, Hu FB: Nearly a decade on — trends, risk factors and policy implications in global obesity. Nat. Rev. Endocrinol. 2020; 16(11): 615–616. Publisher Full Text\n\nMartin AA, Davidson TL: Human cognitive function and the obesogenic environment. Physiol. Behav. 2014; 136: 185–193. PubMed Abstract | Publisher Full Text\n\nMiyake A, Friedman NP: The nature and organization of individual differences in executive functions: Four general conclusions. Curr. Dir. Psychol. Sci. 2012; 21(1): 8–14. PubMed Abstract | Publisher Full Text\n\nMiyake A, Friedman NP, Emerson MJ, et al.: The Unity and Diversity of Executive Functions and Their Contributions to Complex “Frontal Lobe” Tasks: A Latent Variable Analysis. Cogn. Psychol. 2000; 41(1): 49–100. PubMed Abstract | Publisher Full Text\n\nMorris MC, Evans DA, Tangney CC, et al.: Fish consumption and cognitive decline with age in a large community study. Arch. Neurol. 2005; 62(12): 1849–1853. PubMed Abstract | Publisher Full Text\n\nNapoli N, Shah K, Waters DL, et al.: Effect of weight loss, exercise, or both on cognition and quality of life in obese older adults. Am. J. Clin. Nutr. 2014; 100(1): 189–198. Publisher Full Text\n\nNational Institute for Health and Care Excellence: Identifying and assessing people who are overweight or obese (flowchart). 2020.Reference Source\n\nNguyen JCD, Killcross AS, Jenkins TA: Obesity and cognitive decline: Role of inflammation and vascular changes. Front. Neurosci. 2014; 8(OCT): 1–9. PubMed Abstract | Publisher Full Text\n\nNuttall FQ: Body mass index: Obesity, BMI, and health: A critical review. Nutr. Today. 2015; 50(3): 117–128. PubMed Abstract | Publisher Full Text\n\nPage MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. The BMJ. 2021; 372. PubMed Abstract | Publisher Full Text\n\nPedditizi E, Peters R, Beckett N: The risk of overweight/obesity in mid-life and late life for the development of dementia: A systematic review and meta-analysis of longitudinal studies. Age Ageing. 2016; 45(1): 14–21. Publisher Full Text\n\nPrehn K, von Schwartzenberg RJ , Mai K, et al.: Caloric restriction in older adults-differential effects of weight loss and reduced weight on brain structure and function. Cereb. Cortex. 2017; 27(3): 1765–1778. Publisher Full Text\n\nRangel A, Camerer C, Montague PR: A framework for studying the neurobiology of value-based decision making. Nat. Rev. Neurosci. 2008; 9(7): 545–556. Publisher Full Text\n\nRodrigues B, Asamane EA, Magalhães R, et al.: The association of dietary patterns with cognition through the lens of neuroimaging—a Systematic review. Ageing Res. Rev. 2020; 63: 101145. PubMed Abstract | Publisher Full Text\n\nSanderlin AH, Todem D, Bozoki AC: Obesity and co-morbid conditions are associated with specific neuropsychiatric symptoms in mild cognitive impairment. Front. Aging Neurosci. 2017; 9(MAY): 1–8. PubMed Abstract | Publisher Full Text\n\nSchiff S, Amodio P, Testa G, et al.: Brain and Cognition Impulsivity toward food reward is related to BMI: Evidence from intertemporal choice in obese and normal-weight individuals. Brain Cogn. 2015; 110: 112–119. PubMed Abstract | Publisher Full Text\n\nSchünemann H, Brożek J, Guyatt G, et al.:GRADE Handbook.Schünemann H, Brożek J, Guyatt G, et al., editors. Cochrane Training. 2013 (October 20).Reference Source\n\nSiervo M, Arnold R, Wells JCK, et al.: Intentional weight loss in overweight and obese individuals and cognitive function: A systematic review and meta-analysis. Obes. Rev. 2011; 12(11): 968–983. PubMed Abstract | Publisher Full Text\n\nSmith PJ, Blumenthal JA: Dietary Factors and Cognitive Decline. J. Prev Alzheimers Dis. 2015; 3(1): 53–64. PubMed Abstract | Publisher Full Text\n\nSmith PJ, Blumenthal JA, Babyak MA, et al.: Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure. Hypertension. 2010; 55(6): 1331–1338. PubMed Abstract | Publisher Full Text\n\nSoldevila-Domenech N, Forcano L, Vintró-Alcaraz C, et al.: Interplay between cognition and weight reduction in individuals following a Mediterranean Diet: Three-year follow-up of the PREDIMED-Plus trial. Clin. Nutr. 2021; 40(9): 5221–5237. PubMed Abstract | Publisher Full Text\n\nSterne JAC, Savović J, Page MJ, et al.: RoB 2: A revised tool for assessing risk of bias in randomised trials. The BMJ. 2019; 366: 1–8. PubMed Abstract | Publisher Full Text\n\nStinson EJ, Krakoff J, Gluck ME: Depressive symptoms and poorer performance on the Stroop Task are associated with weight gain. Physiol. Behav. 2018; 186(August 2017): 25–30. PubMed Abstract | Publisher Full Text\n\nSuchy Y: Executive functioning: Overview, assessment, and research issues for non-neuropsychologists. Ann. Behav. Med. 2009; 37(2): 106–116. Publisher Full Text\n\nTchang BG, Saunders KH, Igel LI: Best Practices in the Management of Overweight and Obesity. Med. Clin. N. Am. 2021; 105(1): 149–174. Publisher Full Text\n\nTesta R, Bennett P, Ponsford J: Factor analysis of nineteen executive function tests in a healthy adult population. Arch. Clin. Neuropsychol. 2012; 27(2): 213–224. PubMed Abstract | Publisher Full Text\n\nTroyer AK, Moscovitch M, Winocur G: Clustering and switching as two components of verbal fluency: Evidence from younger and older healthy adults. Neuropsychology. 1997; 11(1): 138–146. PubMed Abstract | Publisher Full Text\n\nVolkow ND, Wang GJ, Baler RD: Reward, dopamine and the control of food intake: Implications for obesity. Trends Cogn. Sci. 2011; 15(1): 37–46. PubMed Abstract | Publisher Full Text\n\nWan X, Wang W, Liu J, et al.: Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med. Res. Methodol. 2014; 14(1): 1–13. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: World health statistics 2018: Monitoring health for the SDGs, sustainable development goals. Geneva:World Health Organization;2018.\n\nYang Y, Shields GS, Guo C, et al.: Executive function performance in obesity and overweight individuals: A meta-analysis and review. Neurosci. Biobehav. Rev. 2018; 84(2): 225–244. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "145957",
"date": "25 Aug 2022",
"name": "Michael D. Kendig",
"expertise": [
"Reviewer Expertise Diet",
"cognition",
"neuroscience",
"psychology"
],
"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 and meta-analysis tests for changes in measures of executive function in people with obesity who undergo a diet intervention. Ten studies are selected for consideration. Random effects models find improvements in working memory, cognitive flexibility and verbal fluency, but not inhibition. Heterogeneity is mixed across domains, and there is evidence of some bias for working memory. Overall quality of the studies is found to be moderate.\nThe manuscript provides a thorough assessment of the quality of the included studies, but omits discussion of weight changes and diet intervention length, two key variables that could explain at least as much variance in cognition as the diet itself. It would have been ideal to model the effects of these variables; without them, the conclusions that can be drawn are limited. Greater discussion of these would have improved the manuscript.\nFurther minor comments are provided below:\nIn the introduction the phrase ‘die yearly from being overweight or obese’ is a bit simplistic, and could be revised to clarify that deaths are associated with overweight/obesity.\n\nMetabolic syndrome is not ‘an obesity disorder’. It is a cluster of metabolic symptoms that correlates with obesity, but MetS can be diagnosed without obesity (waist circumference is only one of 5 criteria). Please revise.\n\nThe phrase ‘lacked working memory performance’ implies people with obesity had no working memory, which is of course not true. Presumably the paper found lower scores of working memory in people with obesity; if so, please rephrase accordingly.\n\nAfter the phrase ‘…other EF domains have also been investigated in that meta-analysis’, four papers are cited. Which of these papers was the meta-analysis that the authors are describing?\n\nThe introduction should cite a previous meta-analysis by Veronese et al published in Neuroscience & Biobehavioral Reviews1.\n\nResults from the BRIDGE RCT2 published in 2021 appear relevant and seem to meet the inclusion criteria. Was there a reason they were not included?\n\nThe data analysis section states that the meta-analysis was conducted in Stata, but also that ‘Alternatively, RStudio…can be used as a free alternative.’ Please clarify which analyses, if any, used RStudio.\n\nThe number of reports not retrieved seems quite high (47 studies). Why was this the case?\n\nThe results state that ‘…changes in EF domains were determined by varied tasks of …’ followed by a list of tasks and the 10 papers. It would be more helpful to cite the relevant studies after each measure so readers can identify which papers tested which outcome.\n\nDid the degree of weight loss differ between the studies? Ideally this would be incorporated into analyses; if not possible, it would be pertinent to at least comment on the differences across studies, given the wide variety of diet interventions employed.\n\nSimilarly, it was surprising that the duration of the diet intervention was not discussed. Did this vary substantially between studies? Was cognition tested at similar times on the diet and could this explain heterogeneity in the results?\n\nWhen reporting effects on working memory, a p-value of 0 is provided. Please correct to < .0001\n\nThe authors state that ‘About six RCTs’ tested verbal fluency effects. Please clarify how many tests were made.\n\nWas the study with the highest working memory effect size underpowered? It would be worth commenting on any methodological features that may have produced bias.\n\nThe phrase ‘incorrect food consumption’ is unclear. Please revise to clarify what foods or dietary patterns the Stinson paper is describing.\n\nThere are two very similar sentences back-to-back in the discussion. The first could be deleted for clarity: “Other research, however, tends to disagree with this viewpoint, claiming that cognitive functions are regarded as separate entities. On the other hand, several disagree with this viewpoint, claiming that cognitive abilities…”\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? I cannot comment. A qualified statistician is required.\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "148330",
"date": "15 Sep 2022",
"name": "Yong Zhang",
"expertise": [
"Reviewer Expertise nutrition and 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\nThis systematic review is trying to confirm if dietary modification can improve EF in obese adults. But the topic is not well justified, because both weight and diet may have direct impact on EF according to other published studies. Therefore this study can not separate the effects from diet and weight loss. When the author is making conclusions, they also mixed them together without probing the changes of weight loss. Some other problems are listed below:\n1. The test methods of outcomes for most of readers are unfamiliar, so author needs to do a brief introduction and indicate which direction of change is good or bad to EF in figures.\n2. On page 8, the first sentence, ‘the groups were included compared to the placebo group is exercise’ is not clear about which group was included.\n\n3. On page 9 the title ‘qualitative analysis…’ is the same as another one on page 8.\n\n4. Letters for abbreviations in tables need to be annotated.\n5. On page 16, above discussion, ‘as depicted in figure 6’ and ‘table 1 shows’, are the numbers of figure/table correct? And this paragraph seems like a repetition of the one above it.\n6. On page 18, ‘our result also suggested that weight loss is often…and was…associated with EF domains’. This conclusion was not supported by results in this study, because weight loss was not studied, and the association between weight loss and EF was not analyzed. On the contrary, authors analyzed the dietary intervention and EF domain. Therefore, in discussion, author need to address this issue i.e. whether the diet itself or diet related weight loss caused EF changes in this study.\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? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-661
|
https://f1000research.com/articles/11-252/v1
|
01 Mar 22
|
{
"type": "Research Article",
"title": "The differentiation of mesenchymal bone marrow stem cells into nerve cells induced by Chromolaena odorata extracts",
"authors": [
"Kartini Eriani",
"Desriani Desriani",
"Suhartono Suhartono",
"Miftahul Jannah Br Sibarani",
"Ichsan Ichsan",
"Dedy Syafrizal",
"Hadhymulya Asmara",
"Desriani Desriani",
"Suhartono Suhartono",
"Miftahul Jannah Br Sibarani",
"Ichsan Ichsan",
"Dedy Syafrizal",
"Hadhymulya Asmara"
],
"abstract": "Background: Mesenchymal stem cells (MSCs) can differentiate into nerve cells with an induction from chemical compounds in medium culture. Chromolaena odorata contains active compounds, such as alkaloids and flavonoids, that can initiate the transformation of MSCs into nerve cells. The aim of this study was to determine the potential of methanol extracted C. odorata leaf to induce the differentiation of bone marrow MSCs into nerve cells. Methods: A serial concentration of C. odorata leaf extract (0.7–1.0 mg/mL) with two replications was used. The parameters measured were the number of differentiated MSCs into nerve cells (statistically analyzed using ANOVA) and cell confirmation using reverse transcription polymerase chain reaction (RT-PCR). Results: The results showed that the C. odorata extract had a significant effect on the number MSCs differentiating into nerve cells (p < 0.05) on the doses of 0.8 mg/ml with 22.6%. Molecular assay with RT-PCR confirmed the presence of the nerve cell gene in all of the samples. Conclusions: In conclusion, this study showed the potential application of C. odorata leaf extract in stem cell therapy for patients experiencing neurodegeneration by inducing the differentiation of MSCs into nerve cells.",
"keywords": [
"Chromolaena odorata",
"mesenchymal stem cell",
"nerve cell",
"cell differentiation"
],
"content": "Introduction\n\nStem cells have received significant attention in the medical field because of their extended growth characteristics and ability to differentiate into other cell types. Neural stem cells (NSCs) can repair damaged brain cells by undergoing differentiation into nerve cells and glial cells.1 In adults, NSCs are found in the subventricular zone (SVZ) of the lateral ventricles and the sub-granular zone (SGZ) of the hippocampus. In the SVZ, the differentiation of NSCs into nerve cells occurs through migration along the rostral migration stream to the olfactory bulb. While in the SGZ, NSCs migrate to the granule cell layer.2 However, the capacity of NSCs to replace lost cells is limited and the regeneration of nerve cells in the mammalian brain, despite spontaneous regeneration, does not compensate for all lost nerve cells.3 As an alternative to NSCs, mesenchymal stem cells (MSCs) could be employed to repair damaged nerve cells. MSCs can differentiate into various mesenchymal cells comprising fibroblasts, chondrocytes, osteoblasts, myoblasts, and adipocytes.4\n\nBone marrow derived MSCs become the most potent stem cells for cell replacement because of their efficiency, high proliferative capacity, and immunological naivety. A suitable media is required as a habitat for nerve growth for the successful differentiation of MSCs into nerve cells. The media can be modified by adding fibroblast growth factor-2 (FGF-2), FGF-8, brain-derived neurotrophic factor (BDNF), or particular substrates.5 However, there are some challenges in the differentiation process of MSCs because of the low resistance of nerve cells during the culture process. To overcome this, an inducer is needed during the MSC differentiation process. Genetics, epigenetic, and chemical inducers have been used.6,7 Recently, researchers have utilized plant extracts to increase cell production by enhancing proliferation and protecting stem cells during the growing phase.8\n\nChromolaena odorata has pharmacological efficiency in wound healing by involving cell proliferation, inhibiting cell apoptosis, and contracting the collagen lattice.9 The plant extract contains flavonoids and alkaloids, which contribute to establishing proper growth of nerve cells, protecting the extracellular environment in the nervous system, inducing glial cell secretion of nerve growth factors, and protecting neurons from oxidative stress-induced apoptosis.10 In this study, we investigated the potential of C. odorata leaf extract as an inducer for MSC differentiation from bone marrow into nerve cells, where its expression was then detected using reverse transcription polymerase chain reaction (RT-PCR).\n\n\nMethods\n\nAn in vitro experiment study was conducted to assess the potential of C. odorata leaf extract as an inducer for MSC differentiation into nerve cells. The MSCs were isolated from the bone marrow of a Mus musculus (the house mouse) and four concentrations of C. odorata extract were tested. Randomization and blinding of the animals were not required in this study. Two control groups (positive and negative) were used. The effect of C. odorata extract on MSC differentiation into nerve cells were measured after nine days of incubation.\n\nExtraction was conducted using a maceration method with methanol as the solvent. First, C. odorata leaves were washed using water and sun-dried for three days. Dried leaves were then crushed into simplicial powder using a DF-15 grinder (CGOLDENWALL). Then 500 grams of simplicial powder were mixed with 1 liter of 96% methanol for five days, filtered and stored for two days at room temperature. The filtrate was evaporated using a BUCHI R-300 Rotary Evaporator (BÜCHI Labortechnik AG, Meierseggstrasse, Postfach, Germany) at 40°C with 80–90 rpm before the extract was kept in a container.\n\nA stock culture medium of 1000 ml mDMEM was prepared by mixing 1 g of DMEM powder with aquadest and was homogenized. Then 0.37 g of NaHCO3, 100 μL of non-essential amino acids (Sigma-Aldrich Pte Ltd, Singapore), 100 μL of insulin transferrin selenium (Thermo Fisher Scientific, Carlsbad, CA, US), 100 μl of gentamicin (Sigma-Aldrich Pte Ltd, Singapore), and 10 mL of 10% fetal calf serum (Sigma-Aldrich Pte Ltd, Singapore) were added to the solution. The mixture was then sterilized using microfiltration with a diameter of 0.22 μm.11\n\nThe male M. musculus mice of the strain BALB/c (eight weeks of age) were acclimated and fed ad libitum with standardized feed for one week under laboratory conditions with a 12 h light-dark cycle, 60% of humidity with 23oC. To minimize the number of animals, six mice were used with assumption that the number of MSCs from one mouse was enough for one set of repetitions (i.e., with four repetitions in this study, two other mice were prepared for any unexpected event such as if the MSCs did not grow).\n\nThe animal facility was cleaned and disinfected regularly. During the acclimation the animal facility was kept quiet with controlled environmental conditions. If there were abnormal behaviors (apathy or increased aggression), the animals were excluded from the study and returned to the breeding center of the Faculty of Veterinary Medicine, Universitas Syiah Kuala. The mice were anesthetized with 0.01 mL of ketamine (Troy Laboratories PTY Limited) and 0.01 mL of xylazine (Troy Laboratories PTY Limited) and the animals were sacrificed using a cervical dislocation technique per protocol.12 It was ensured that all animals were dead before any autopsy was conducted. The autopsies were conducted by a certificated veterinarian.\n\nThe femur and tibia were removed from the mice and washed using FBS solution to remove muscle and fat tissue. Both ends of the bone were cut, then the marrow contents were removed using a syringe and stored in a culture dish containing FBS and NBCS. The bone marrow suspension was pipetted and centrifuged at 3,000 rpm for 10 min and then rinsed four times with FBS and once with mDMEM to remove as many single cells as possible.10 Before incubation, the number of cells (cells/mL) was counted using a hemocytometer.\n\nA 1 mL of bone marrow suspension containing 1 × 106 cells was placed in a petri dish containing mDMEM medium and cultured in an incubator humidified with 5% CO2 at 37°C. After one day of incubation, the media was replaced and 10 μL of plant extract was added with a concentration of 0.7 mg/mL (group M1), 0.8 mg/mL (M2), 0.9 mg/mL (M3), and 1.0 mg/mL (M4) as treatments group and no extract was added as the negative control. The cells were incubated for nine days with media replacement every two days.11\n\nEnumeration of differentiation nerve cells\n\nCells were observed under a CKX41 inverted microscope (Olympus Life Science, Tokyo, Japan) with 100x magnification in 16 fields of view. The enumeration was performed in three replications and the results averaged.\n\nNerve cell gene confirmation using reverse transcription polymerase chain reaction (RT-PCR)\n\nThe gene of nerve-like cells was detected using RT-PCR. The RNA was extracted using Z6011 ReliaPrep RNA Cell Miniprep System following the manufacturers’ protocol (Promega, Madison, WI, USA). Then 1 μL RNA was converted into a reverse transcription template cDNA using GoScript Reverse Transcriptase and random primer (Promega, Madison, WI, USA). The reaction condition was maintained at 25°C for 5 min, 37°C for 60 min, and 70°C for 15 min. The amplification of the cDNA was carried out using GoTaq qPCR Master Mix (Promega, Madison, WI, USA) and 2 μL forward and reverse primers (β-actin and β-tubulin 3). The detailed primer sequences are presented in Table 1.13 The PCR product was then analyzed on 1% agarose gel electrophoresis with TAE buffer run at 80 V for 60 min then visualized using UV light at 312 nm.\n\nTo compare the differentiation of the nerve cells among different doses of C. odorata, the data were analyzed using analysis of variance (ANOVA) followed by Duncan’s post hoc test with a significance level of 5%. All analyses were conducted using SPSS software version 20 (IBM SPSS, Chicago, IL, USA) (RRID:SCR_019096).\n\nEthical clearance was obtained from the Research Ethics Committee of the Faculty of Veterinary Medicine, Universitas Syiah Kuala (No 110/KEPH/VI/2021) - PT Bimana Indomedical (No.R.07-20-IR). All efforts were made to ameliorate any suffering of animals. Efforts were made to minimize the pain, suffering and distress experienced by the research animals. The animals were provided with appropriate housing with ad libitum feeding, the appropriate anesthesia was used to minimize pain before the animals were sacrificed and all procedures were conducted by a certificated veterinarian with the animal care training.\n\n\nResults and discussion\n\nThe leaf extract of C. odorata with a concentration of 0.8 mg/mL was the most optimum concentration for inducing cell growth with mean total cells of 147.67. Therefore, the morphology examination of differentiated MSCs into nerve-like cells was conducted using this optimal dose. The observations focused on differentiated nerve-like cells with cytoplasmic appendages. The cell's cytoplasm consisted of dendrites and axons, which indicated the cells were similar to nerve cells. Herein, it was observed that there were some variations of the nerve-like cells, such as nerve cells (neuroblast) with apolar (Figure 1A), bipolar (Figure 1B), and multipolar (Figure 1C) forms. Some undifferentiated MSCs (Figure 1D and E) were also observed.\n\nThe differentiation process of nerve-like cells in medium culture showed the development steps of nerve-like cell formation, followed by dendrite extension and enlargement of the cytoplasm and dendritic bodies. Apolar nerve-like cells (Figure 1A) are the first development step of nerve cells, indicated by round and undeveloped extension of dendrites. The nerve-like cells then developed into bipolar form with two dendritic appendages (Figure 1B). The bipolar nerve-like cells then differentiated into multipolar forms characterized by multi dendritic extensions (Figure 1C).14 Bipolar nerve-like cells are classified as young nerve-like cells and multipolar as mature nerve-like cells.15\n\nThe mean number of nerve-like cells showed that the doses of C. odorata extracts had a significant implication on the differentiation (Table 2 and Figure 2). The M2 group (0.8 mg/mL) had a higher number of differentiated nerve-like cells compared to other treatments (i.e., M1 (0.7 mg/mL), M3 (0.9 mg/mL), and M4 (1.0 mg/mL) and control groups. This suggested that 0.8 mg/mL was the most optimum concentration for inducing the differentiation of MSCs into nerve-like cells.\n\n* Significant at p < 0.05 compared to the negative control group.\n\nBased on the statistical analysis, there was no significant difference between the control and M4 (1.0 mg/ml) group on inducing differentiated MSC into nerve cells. This indicated that 1.0 mg/mL had an inhibition effect on the cell culture. The decrease in the number of differentiated cells may be due to the use of excessive concentration. Extracts with excessive concentrations can cause cytotoxic effects on cells, so that cell growth becomes inhibited.16 Based on these results, the induction by C. odorata leaf extract on the differentiation of MSCs into nerve cells was better carried out at concentrations ranging from 0.7 to 0.9 mg/ml.\n\nThe leaf extract of C. odorata used in this study has active chemical compounds, such as flavonoids and alkaloids. Flavonoids are compounds that may also trigger nerve cell formation (neurodegeneration) by increasing the production of nitric oxide (NO). NO is used as a potent activator of the soluble guanyl cyclase enzyme. This enzyme is responsible for forming cyclic-guanosine monophosphate (cGMP).17 The concentration of cGMP can also decrease the conversion of cGMP into GMP by adding phosphodiesterase-5 (PDE-5), an inhibitor enzyme.18 The presence of NO might assist the conversion of cGMP into sildenafil. Sildenafil can lead to the increased protein expression of phosphatidylinositol 3-kinase (PI3K)-Akt. PI3K-Akt is one of the essential regulation factors for the neurodegeneration process and transmission of information to neuronal progenitor cells.19 Moreover, cGMP activates cGMP-phosphokinase G (PKG) pathways leading to the increasing cycle-adenosine monophosphate (cAMP) and element-binding protein (CREB) response that is essential for neuroblast viability.20 BDNF, cGMP, and P13K activity use Wnt signaling, which is the primary pathway in the differentiation process by increasing the number of receptors.21,22\n\nA study found that alkaloids had an essential role in leading to neuroprotective effects by the inhibition of oxidative stress and the up regulation of BDNF expression.23 BDNF is one of the factors that can trigger the expression of nerve cells, which is essential in regulating plasticity, immune, and nerve formation (neuro-regeneration).24 BDNF can affect the survival and development of nerve cells by activating kinase receptor B enzyme in nerve cells and ganglia cells.25\n\nIn this study, the existence of nerve cells was (β-tubulin 3) confirmed using the RT-PCR. The control primer used in this study was β-actin. The β-actin primer was used to detect the actin gene, which is one of the housekeeping genes and the gene that is expressed within the cells in any tissue at any development stage of nerve cells.26 At the same time, β-tubulin 3 primer was used to confirm nerve cell gene expression.13 Figure 3 shows the DNA RT-PCR product of β-actin and β-tubulin.\n\n1: leaders; 2: β-actin of M4 group; 3: β-actin of M3 group; 4: β-actin of M2 group; 5: β-actin of M1 group; 6: β-actin of control; 7: β-tubulin 3 of M4 group; 8: β-tubulin 3 of M3 group; 9: β-tubulin 3 of M2 group; 10: β-tubulin 3 of M1 group; 11: β-tubulin 3 of negative control.\n\nFor the β-actin gene, PCR product was found in lanes two, three, four, five and six representing M4 (1.0 mg/mL), M3 (0.9 mg/mL), M2 (0.8 mg/mL), M1 (0.7 mg/mL), and the control group, respectively. DNA bands in lanes two, three, four and five are similar to those in the control (lane six). This indicated that RNA extraction was successful and no PCR inhibitor was found in the RNA solution extraction product.\n\nFor the β-tubulin 3 gene, there were positive DNA bands in lanes seven, eight, nine and 10 that represented M4 (1.0 mg/mL), M3 (0.9 mg/mL), M2 (0.8 mg/mL), and M1 group (0.7 mg/mL), respectively. Each band had clear and clean PCR product at the same size, while there was no PCR product in the negative control which suggests that the cells were nerve cells. The control band was not clear, perhaps due to a pipetting error. The size of the DNA band of the primer β-actin was about 443bp as expected, and the primer β-tubulin 3 was about 700bp, while according to Wang et al.,11 the size of targeted β-tubulin 3 was 55bp. This size difference was probably because the primer design was based on Rattus novergicus, the brown rat, while in this study we used M. musculus. Based on sequence data DNA similarity of the rat and mouse are high (90%), the primer also has potential for β-tubulin 3 detection in the mouse. However, confirmation of the PCR product with sequencing is required.\n\n\nConclusions\n\nThe application of C. odorata extract containing flavonoids and alkaloids increased the differentiation of MSCs into nerve cells at the optimum concentration of 0.8 mg/ml. Identification with RT-PCR targeting β-actin and β-tubulin 3 confirmed the presence of nerve cell genes.\n\n\nData availability\n\nFigshare: Underlying data for ‘The differentiation of mesenchymal bone marrow stem cell into nerve cell induced by Chromolaena odorata extracts’. https://doi.org/10.6084/m9.figshare.19126544.27\n\nThis project contains the following underlying data:\n\n• Master table.xlsx [Table containing the raw data of the study]\n\n• PCR gel.jpg [Raw picture of the PCR gel]\n\nFigshare: ARRIVE checklist for ‘The differentiation of mesenchymal bone marrow stem cell into nerve cell induced by Chromolaena odorata extracts’. https://doi.org/10.6084/m9.figshare.19126544.27\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 would like to thank Narra Studio Jurnal and Universitas Syiah Kuala.\n\n\nReferences\n\nOkano H: Neural stem cells and strategies for the regeneration of the central nervous system. Proc Jpn Acad Ser B Phys Biol Sci. 2010; 86(4): 438–50. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBond AM, Ming GL, Song H: Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later. Cell Stem Cell. 2015 Oct 1; 17(4): 385–95. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGeorge S, Hamblin MR, Abrahamse H: Differentiation of Mesenchymal Stem Cells to Neuroglia: in the Context of Cell Signalling.Stem Cell Rev Rep.2019 Dec; 15(6): 814–26. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen Q, Shou P, Zheng C, et al.: Fate decision of mesenchymal stem cells: adipocytes or osteoblasts?. Cell Death Differ. 2016 Jul; 23(7): 1128–39. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi M, Zhao W, Gao Y, et al.: Differentiation of Bone Marrow Mesenchymal Stem Cells into Neural Lineage Cells Induced by bFGF-Chitosan Controlled Release System. Biomed Res Int. 2019; 2019: 5086297. Epub 20190327. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLai PL, Lin H, Chen SF, et al.: Efficient Generation of Chemically Induced Mesenchymal Stem Cells from Human Dermal Fibroblasts. Sci Rep. 2017 Mar 17; 7: 44534. Epub 20170317. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSrinageshwar B, Maiti P, Dunbar GL, Rossignol J: Role of Epigenetics in Stem Cell Proliferation and Differentiation: Implications for Treating Neurodegenerative Diseases. Int J Mol Sci. 2016 Feb 2; 17(2). Epub 20160202. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUdalamaththa VL, Jayasinghe CD, Udagama PV: Potential role of herbal remedies in stem cell therapy: proliferation and differentiation of human mesenchymal stromal cells. Stem Cell Res Ther. 2016 Aug 11; 7(1): 110. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVijayaraghavan K, Rajkumar J, Bukhari SN, et al.: Chromolaena odorata: A neglected weed with a wide spectrum of pharmacological activities (Review). Mol Med Rep. 2017 Mar; 15(3): 1007–16. PubMed Abstract | Publisher Full Text\n\nCui X, Lin Q, Liang Y: Plant-Derived Antioxidants Protect the Nervous System From Aging by Inhibiting Oxidative Stress. Front Aging Neurosci. 2020; 12: 209. Epub 20200714. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEriani K, Suryani I, Azhar A, et al.: Neurogenic Differentiation of Bone Marrow Mesenchymal-Like Stem Cell Induced by Delonix regia Flowers Extract. Biosaintifika: Journal of Biology & Biology Education. 2018; 10(2): 417–23. Publisher Full Text\n\nCCAC: CCAC guidelines on: euthanasia of animals used in science. Ottawa, Canada: Canadian Council on Animal Care; 2010. Reference Source\n\nWang B, Zou X, Zhang H, et al.: Establishment of an immortalized GABAergic neuronal progenitor cell line from embryonic ventral mesencephalon in the rat. Brain Res. 2008 May 19; 1210: 63–75. PubMed Abstract | Publisher Full Text\n\nBeale LS, editor. On the structure of the so-called apolar, unipolar, and bipolar nerve-cells of the frog. Proceedings of the Royal Society of London. 1997.\n\nJurić M, Zeitler J, Vukojević K, et al.: Expression of Connexins 37, 43 and 45 in Developing Human Spinal Cord and Ganglia. Int J Mol Sci. 2020 Dec 8; 21(24). Epub 20201208. eng. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJang MH, Piao XL, Kim JM, et al.: Inhibition of cholinesterase and amyloid-beta aggregation by resveratrol oligomers from Vitis amurensis. Phytother Res. 2008 Apr; 22(4): 544–9. PubMed Abstract | Publisher Full Text\n\nPan W, Quarles LD, Song LH, et al.: Genistein stimulates the osteoblastic differentiation via NO/cGMP in bone marrow culture. J Cell Biochem. 2005 Feb 1; 94(2): 307–16. PubMed Abstract | Publisher Full Text\n\nFrancis SH, Busch JL, Corbin JD, et al.: cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev. 2010 Sep; 62(3): 525–63. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGhofrani HA, Osterloh IH, Grimminger F: Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov. 2006 Aug; 5(8): 689–702. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen C, Nakamura T, Koutalos Y: Cyclic AMP diffusion coefficient in frog olfactory cilia. Biophys J. 1999 May; 76(5): 2861–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWestendorf JJ, Kahler RA, Schroeder TM: Wnt signaling in osteoblasts and bone diseases. Gene. 2004 Oct 27; 341: 19–39. eng. PubMed Abstract | Publisher Full Text\n\nBodine PV: Wnt signaling control of bone cell apoptosis. Cell Res. 2008 Feb; 18(2): 248–53. PubMed Abstract | Publisher Full Text\n\nMao QQ, Huang Z, Zhong XM, et al.: Piperine reverses the effects of corticosterone on behavior and hippocampal BDNF expression in mice. Neurochem Int. 2014 Jul; 74: 36–41. PubMed Abstract | Publisher Full Text\n\nBathina S, Das UN: Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci. 2015 Dec 10; 11(6): 1164–78. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlöcker N, Kermer P, Weishaupt JH, et al.: Brain-derived neurotrophic factor-mediated neuroprotection of adult rat retinal ganglion cells in vivo does not exclusively depend on phosphatidyl-inositol-3'-kinase/protein kinase B signaling. J Neurosci. 2000 Sep 15; 20(18): 6962–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGu W, Pan F, Zhang H, et al.: A predominantly nuclear protein affecting cytoplasmic localization of beta-actin mRNA in fibroblasts and neurons. J Cell Biol. 2002 Jan 7; 156(1): 41–52. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEriani K: The differentiation of mesenchymal bone marrow stem cell into nerve cell induced by Chromolaena odorata extracts. Dataset. 2022. Publisher Full Text"
}
|
[
{
"id": "125785",
"date": "14 Mar 2022",
"name": "Sharun Khan",
"expertise": [
"Reviewer Expertise Regenerative medicine",
"Stem cell therapy",
"Animal 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\nThe authors have attempted to evaluate the potential of C. odorata leaf methanol extract to induce the differentiation of bone marrow MSCs into nerve cells using an in vitro experiment. The manuscript is well written, presented and discussed, and understandable to a specialist readership. The findings are promising and the authors can further conduct studies to identify the specific constituent(s) that contribute to the differentiation potential of C. odorata leaf methanol extract. In general, the organization and the structure of the article are satisfactory and in agreement with the journal instructions for authors.\nMinor comments:\nMesenchymal stem cells exposure with C. odorata extract - please correct \"106 cells\" to \"106 cells\".\n\n2The mice were anesthetized with 0.01 mL of ketamine (Troy Laboratories PTY Limited) and 0.01 mL of xylazine - please mention the dose in mg/kg.\n\nThe authors are advised to comment on whether they have characterized the isolated mice MSCs according to the minimal criteria set by the International Society for Cellular Therapy (ISCT)1,2.\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": "8369",
"date": "15 Jun 2022",
"name": "Kartini Eriani",
"role": "Author Response",
"response": "Thank you for reviewing our manuscript. We believe the comments and suggestions improve the quality of our current manuscript. 1. We have corrected the concentration of the cells from 106 to 106 cells within the subheading, Mesenchymal stem cells exposure with C. odorata extract. 2. We have changed the amount of ketamine and xylazine from ml to mg/kg within the Housing and husbandry of animals subheading. 3. We have added the information that the characterization of isolated MSCs according to the criteria by the International Society for Cellular Therapy (ISCT). Can be found within the subheading, Number of differentiated mesenchymal stem cells into nerve like cells"
}
]
},
{
"id": "128658",
"date": "08 Jun 2022",
"name": "Arief Boediono",
"expertise": [
"Reviewer Expertise Cell culture",
"stem cell",
"embryo engineering"
],
"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 reported the influence of C. odorata leaf methanol extract to induce the differentiation of bone marrow MSCs into nerve cells using an in vitro experiment. In general, the manuscript provided good information, but some revisions need to be done before it can be indexed.\nThe dose used must match the content of the chemicals used (gentamicin, ketamine, xylazine, etc).\n\nCell concentration: please use 106 instead of 106.\n\nWhether the method for enumeration of differentiation nerve cells is standard, needs to be given reference. Table 2, Cell numbers (Mean + SD) need to be explained per 16 fields of view.\n\nDelete Figure 2, it is a repetition of the data in Table 2.\n\nIn the conclusion: remove the words ‘containing flavonoids and alkaloids’ because in this study there was no identification of these active substances.\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? Partly",
"responses": [
{
"c_id": "8368",
"date": "15 Jun 2022",
"name": "Kartini Eriani",
"role": "Author Response",
"response": "Thank you for reviewing our manuscript. We believe the comments and suggestions improve the quality of our current manuscript. 1. We have provided the actual concentration of the drugs used in this study. We also have change the amount of ketamine and xylazine from ml to mg/kg within the Housing and husbandry of animals subheading. 2. We have corrected the concentration of the cells from 106 to 106 cells within the subheading, Mesenchymal stem cells exposure with C. odorata extract. 3. We have provided the reference for enumeration of differentiation nerve cells within the subheading, Enumeration of differentiation nerve cells. We have provided the note on Table 2 that the number of cell numbers and the means based on measurements in 16 fields of view with 100x magnification. 4. We have deleted the Figure 2 since the data is repetitive with Table 2. 5. We have deleted the words of “containing flavonoids and alkaloids” within the heading Conclusion."
}
]
}
] | 1
|
https://f1000research.com/articles/11-252
|
https://f1000research.com/articles/11-660/v1
|
15 Jun 22
|
{
"type": "Research Article",
"title": "Actual and potential drug interactions of psychotropic drugs in patients of the COVID-19 medicine service of the emergency hospital-Lima, 2021",
"authors": [
"Ambrocio Teodoro Esteves Pairazaman",
"Emma Caldas Herrera",
"Gabriel Leon Apac",
"Jesús Daniel Collanque Pinto",
"María Evelina Caldas Herrera",
"Daniel Ñañez del Pino",
"Javier Francisco Martínez Carreras",
"Ricardo Robles Huaranca",
"Emma Caldas Herrera",
"Gabriel Leon Apac",
"Jesús Daniel Collanque Pinto",
"María Evelina Caldas Herrera",
"Daniel Ñañez del Pino",
"Javier Francisco Martínez Carreras",
"Ricardo Robles Huaranca"
],
"abstract": "Background: Actual and potential drug–drug interactions of psychotropic drugs in patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital during the months of February to July, 2021. Methods: The study is deductive, retroprospective, quantitative, applied, cross-sectional observational. The instrument used was a collection card for 86 pharmacotherapeutic follow-ups where psychotropic drugs for anxiety, depression and insomnia were registered. Results: In the actual and potential drug interactions of psychotropic drugs, according to the degree of severity dimension, it was identified that the important indicator represented the highest frequency of 89% of the interactions; according to the type of interaction dimension, it was identified that the pharmacodynamic indicator presented a higher frequency with 53%; according to the clinical evidence dimension, it was identified that the fair indicator had a higher frequency with 73% interactions; in the manifestation dimension, it was identified that the potential indicator presented a higher frequency with 92.2% interactions. In its moment of appearance dimension, it was identified that the quick indicator had a higher prevalence with 5.5% of real interactions. In its causality algorithm dimension, the probable indicator was identified as having the highest frequency with 7.25% of actual interactions. With respect to sex, the male presented 49.9% of potential interactions and in the real interactions, the female sex presented a higher incidence with 4.3% interactions. The average age of the potential interactions was 48.83 years, and the average age of the real interactions was 45.67 years. Sertraline presented 53.2% of potential interactions and in relation to real drug interactions the one that presented the highest frequency was mirtazapine with 3.5% interactions. Conclusion: We conclude that the increase in the prescription of psychotropic drugs is related to a higher probability of interactions.",
"keywords": [
"Drug interactions",
"real",
"potential",
"psychotropic drugs",
"Covid-19",
"Hospital",
"patients",
"clinical pictures."
],
"content": "Introduction\n\nOn January 30, 2020, the World Health Organization (WHO) Emergency Committee declared COVID-19 a global emergency disease and to date it has claimed thousands of lives in most countries of the world.1\n\nCOVID-19 generates a wide variety of symptomatology ranging from mild symptoms to severe complications such as respiratory failure, cardiac and cardiovascular complications, thrombolytic, inflammatory, skin and neurological complications.2,3\n\nAmong the neuropsychiatric symptoms presented by patients hospitalized for COVID-19 are depression, anxiety, insomnia, agitation and delirium, which affect their mental health. Rogers et al. conducted a systematic review and meta-analysis and revealed that during the acute phase of the disease, hospitalized patients presented symptoms of confusion (27.9%), depressed mood (32.6%), anxiety (35.7%), memory impairment (34.1%) and insomnia (41.9%). And among patients admitted to the intensive care unit (ICU), delirium (65%) and agitation (69%) were evidenced.2–5\n\nThe increase in cases of anxiety, depression and insomnia in COVID-19 patients has led to an increase in the prescription of psychotropic drugs. Sanchez and Calvo6 indicated that the consumption of anxiolytics increased in Spain during the pandemic from 55.25 to 57.36 defined daily doses per 1,000 inhabitants per day (DHD) during 2019 to 2021 and Shahad et al.7 indicated that, during the COVID-19 pandemic, there was an increase in prescribing of Antidepressant prescriptions and costs increased significantly during the pandemic compared to the pre-pandemic period, with 4 million additional prescription items dispensed in 2020 costing NHS England £139 million more than in 2019.\n\nIncreased prescribing of psychotropic drugs may contribute to the manifestation of drug–drug interactions and increase the risk of having an adverse reaction due to toxicity and/or therapeutic failure of pharmacotherapeutic treatment due to lower plasma concentrations.\n\nIn Germany, Kirilochev et al.,8 in their study identified 52 adverse reactions in a psychiatric hospital attributed to drug–drug interactions between antipsychotic drugs and those used for cardiac disorders.\n\nIn Peru, Lovera, in his study conducted at the Carlos Lanfranco La Hoz Hospital, evaluated 450 prescriptions where 226 dispensed prescriptions presented potential drug–drug interactions, of which 248 had drug–drug interactions.9\n\nIn the Villa El Salvador Emergency Hospital, there was an increase in prescriptions of psychotropic drugs indicated for anxiety depression and insomnia in the COVID-19 medicine service, in 2019 there were 911 prescriptions, in 2020 there were 9686 prescriptions and in 2021 there were 14005 prescriptions. Where the increase in the prescriptions of psychotropic drugs can interact with the medication indicated to treat other frequent pathologies in the patient of the COVID-19 medicine service such as arterial hypertension, diabetes mellitus, obesity and over-aggregated infections, which can cause a greater occurrence of drug interactions that produce therapeutic failure, appearance of toxic effects and adverse reactions, increasing the hospital stay and even endangering the patient's life.\n\nThe work is justified because, during the pandemic caused by COVID-19, the prescription of psychotropic drugs used in the treatment of anxiety, depression and insomnia has been increasing. The patients of the COVID-19 medicine service present various pathologies such as diabetes, hypertension, obesity, asthma, dyslipidemia, etc. For this reason, they are receiving several medications, which can interact with psychotropic drugs, causing an increase in drug-drug interactions, which can end up putting drug therapy at risk and generate reactions. For this reason, the following work will allow to deepen and update the information on drug-drug interactions of psychotropic drugs that are presented in the COVID-19 medical service and generate a contribution for future research. The study will provide a protocol and instrument, which will be validated by experts, this will allow further research aimed at identifying potential and actual drug–drug interactions in the various hospital services prescribed by the treating physician and will also allow to know what are the main potential and actual drug–drug interactions that occur in psychotropic drugs prescribed for anxiety, depression and insomnia in the COVID-19 medicine service. This will make it possible to reduce and prevent drug–drug interactions.\n\nFinally, the aim of this study is to analyze the actual and potential drug interactions of psychotropic drugs in patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital during the months of February to July 2021 and to identify the actual and potential drug interactions of psychotropic drugs in terms of degree of severity, type of interaction, clinical evidence, manifestation in patients, time of appearance, causality algorithm and to evaluate the actual and potential drug interactions of psychotropic drugs in patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital, according to sex and age, with the highest potential and actual frequency.\n\n\nMethods\n\nThe research methodology is deductive and applied-observational. The approach was quantitative because the analysis was observational based on a documentary analysis. At the same time, it was applied and of non-experimental and cross-sectional design. Ethical approval was not required for this section because no humans and/or animals were used.\n\nThe population consisted of 86 pharmacotherapeutic follow-ups carried out by the pharmacy unit, where psychotropic drugs for the treatment of anxiety, depression and insomnia were registered for hospitalized patients of the COVID-19 medicine service of the Villa El Salvador Emergency Hospital. Some inclusion and exclusion criteria were applied:\n\nInclusion criteria:\n\n• Pharmacotherapeutic follow-ups performed by the pharmacy unit on adult patients over 18 years of age.\n\n• Pharmacotherapeutic follow-ups performed by the pharmacy unit during the period from February to July, 2021.\n\n• Pharmacotherapeutic follow-ups performed by the pharmacy unit for patients on the COVID-19 medicine service.\n\n• Pharmacotherapeutic follow-ups carried out by the pharmacy unit where psychotropic drugs for anxiety, depression and insomnia with indications authorized by the National Essential Drug Formulary (sertraline, mirtazapine, clonazapine, clonidine, and other drugs for anxiety, depression and insomnia) are registered, mirtazapine, clonazepam, alprazolam, fluoxetine, amitriptyline, clobazam, diazepam and levomepromazine) and psychotropic drugs approved by the pharmacotherapeutic committee of the Villa El Salvador Emergency Hospital (quetiapine, olanzapine and paroxetine).\n\nExclusion criteria:\n\n• Pharmacotherapeutic follow-ups performed by the pharmacy unit on patients under 18 years of age.\n\n• Pharmacotherapeutic follow-ups performed by the pharmacy unit on patients who do not correspond to the COVID-19 medicine service.\n\n• Pharmacotherapeutic follow-ups performed by the pharmacy unit that do not correspond to the period of February to July, 2021.\n\n• Pharmacotherapeutic follow-ups performed by the pharmacy unit where no psychotropic drugs for anxiety, depression and insomnia with an indication authorized by the National Essential Drug Formulary (sertraline, mirtazapine, clonazapine, clonidine) have been registered in the pharmacy unit, mirtazapine, clonazepam, alprazolam, fluoxetine, amitriptyline, clobazam, diazepam and levomepromazine) and the psychotropic drugs approved by the pharmacotherapeutic committee of the Villa El Salvador Emergency Hospital (quetiapine, olanzapine and paroxetine).\n\nThe sample consisted of 87 pharmacotherapeutic follow-ups carried out by the pharmacy unit, which were chosen by non-probabilistic convenience sampling. The sample consisted of 87 pharmacotherapeutic follow-ups carried out by the pharmacy unit. psychotropic drugs for the treatment of anxiety, depression and insomnia in hospitalized patients of the COVID-19 medicine department of the Villa El Salvador Emergency Hospital.\n\nPharmacotherapeutic follow-ups were carried out during the period February to July 2021 on patients in the medicine department at the study site.\n\nThe instrument used was the data recording form, which consists of the following parts: pharmacotherapeutic follow-up, where the number of pharmacotherapeutic follow-ups will be recorded, age, where the number of years completed will be recorded, interacting drugs, where the drugs will be recorded and whether they present drug interaction with two items (1: Yes; and 2: No): and the score was obtained manually.\n\nDimension according to type of interaction with four items:\n\n1. Does not present\n\n2. Pharmacokinetics,\n\n3. Pharmacodynamics\n\n4. Unknown.\n\nDimension according to its degree of severity with six items:\n\n1. Not presented.\n\n2. Contraindicated\n\n3. Important\n\n4. Moderate\n\n5. Minor\n\n6. Unknown\n\nDimension according to its clinical evidence with five items:\n\n1. Does not present\n\n2. Fair\n\n3. Good\n\n4. Excellent\n\n5. Unknown\n\nDimension according to its manifestation with two items:\n\n1. Potential\n\n2. Actual\n\nDimension according to its moment of presentation with four items:\n\n1. No presentation\n\n2. Immediate from 0 to 12 hours\n\n3. Rapid from 12 to 72 hours\n\n4. Delayed more than 72 hours\n\nDimension according to severity with four items:\n\n1. Does not present\n\n2. Mild\n\n3. Moderate\n\n4. Severe\n\nDimension according to its causality algorithm with five items:\n\n1. Does not present\n\n2. Highly probable\n\n3. Likely\n\n4. Possible\n\n5. Doubtful\n\nThe instrument used was reviewed and approved under the judgement of three experts, who vouched for and validated the form used for its subsequent application.\n\nThe method used to estimate the reliability of the instrument was the Cronbach's Alpha Coefficient test, whose alpha value must be between 0.7 and 0.9, which allows the reliability of the questionnaire to be measured. A reliability of 0.702 was obtained according to Cronbach's Alpha Coefficient test.\n\nAfter collecting the information, all of it was emptied and processed using the SPSS program version 28, and where the interpretation of the results was performed according to the variable and proposed objectives, with the Microsoft Excel 2019 program, frequency tables and graphs were made. The statistical tests used in this research were cross tables and frequencies.\n\nThe research project was approved under Resolution N°059-2022-DFFB/UPNW issued by the Faculty of Pharmacy and Biochemistry of the Norbert Wiener University.\n\nFor the development of the study, the document “Approval of Research Project N°005-2022” was issued to request authorization from the ethics and research committee of the Villa El Salvador Emergency Hospital. A positive response was received with document \"N°61-2022-OGRH-DE-HEVES\". With this authorization, we coordinated with the pharmaceutical chemist from the pharmacy service to collect data and draw up a work schedule for the study.\n\nIt should be noted that the development of the research project complied with the ethical principles of the Norbert Wiener University's current regulations and the confidentiality and privacy of the people who were taken as samples for the development of the research will be maintained.\n\nIt should also be noted that each person was notified and an informed consent document was received from the patients or relatives who formed part of the study sample, indicating that they are aware of and authorize the provision of data from their medical records for the research.\n\n\nResults\n\nIn Table 1, in relation to the degree of severity of the actual and potential drug interactions of psychotropic drugs, we observed that the important indicator represented the highest frequency with 307 (89%) interactions, followed by the moderate indicator with 22 (6.4%) interactions, then the contraindicated indicator with 16 (4.6%) interactions and the minor and unknown indicators did not present interactions, in patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nIn Table 2, in relation to actual and potential drug interactions of psychotropic drugs in their interaction type dimension, we observed that the pharmacodynamic indicator had the highest frequency with 183 (53%) interactions, followed by the pharmacokinetic indicator with 93 (27%) interactions and in last place unknown with 69 (20%) interactions, in the patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nIn Table 3, in relation to actual and potential drug interactions of psychotropic drugs in its clinical evidence dimension, we observed that the indicator fair had a higher frequency with 252 (73%) interactions, followed by the indicator good with 72 (20.9%) interactions, then excellent with 21 (6.1%) interactions and in last place to unknown with 0 (0%) interactions, in patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nIn Table 4, in relation to actual and potential drug interactions of psychotropic drugs in its manifestation dimension, we observed that the potential indicator presented a higher frequency with 318 (92.2%) interactions, compared to the actual indicator with 23 (7.8%) interactions, in patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nIn Table 5, in relation to real and potential drug interactions of psychotropic drugs in their time of appearance dimension, we observed that the indicator did not present a higher frequency with 318 (92.2%) potential interactions, followed by the fast indicator with 19 (5.5%) real interactions, then late with 8 (2.32%) real interactions and in last place immediate with 0 (0%) real interactions, in the patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nIn Table 6, in relation to actual and potential drug interactions of psychotropic drugs in its causality algorithm dimension, the indicator does not present a higher frequency with 318 (92.2%) potential interactions, in second place the probable indicator with 25 (7.25%) actual interactions, in third place possible with 2 (0.58%) actual interactions and the indicators highly probable and doubtful in last place with 0 (0%) actual interactions each, in the patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nIn Table 7, in relation to actual and potential drug interactions of psychotropic drugs according to sex, it was observed that the male sex presented a higher frequency in potential interactions with 172 (49.9%) interactions compared to the female sex with 146 (42.3%) interactions and in actual interactions the female sex presented a higher incidence with 15 (4.3%) interactions compared to the male sex that presented 12 (3.5%) interactions, in the patients of the COVID-19 Medicine Service of the Emergency Hospital of Villa El Salvador.\n\nIn Table 8, in relation to real and potential drug interactions of psychotropic drugs according to age, showed that the average age was 48.58 years, the average age of potential interactions was 48.83 years, and the average age of real interactions was 45.67 years, in the patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nIn Table 9, in relation to the psychotropic drugs with the highest frequency of potential drug interactions it was observed that sertraline in first place with 184 (53.2%) interactions, in second place, mirtazapine with 56 (16. 2%) interactions, in third place, clonazepam with 41 (11.9%) interactions and in fourth, fifth, sixth, seventh, eighth and ninth alprazolam, quetiapine, levomepromazine, fluoxetine, amitriptyline and olanzapine. In relation to actual drug interactions, mirtazapine had 12 (3.5%) interactions in first place, clonazepam and sertraline had 7 (2%) interactions each, olanzapine had 1 (0.3%) interaction in third place, and alprazolam, quetiapine, levomepromazine, fluoxetine and amitriptyline had no interactions in the patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nIn Table 10, in relation to the psychotropic drugs with the highest frequency of actual and potential drug interactions of psychotropic drugs it was evidenced that sertraline with enoxaparin ranked first with 50 (14.49%) interactions, in second place mirtazapine with clonazepam 6.40%, in third place clonazepam with gabapentin with 11 (3.19%) interactions, in fourth place alprazolam with codeine 4 (1.16%) hospitalizations, in fifth place quetiapine with gabapentin and quetiapine with metoclopramide with 3 (0.87%) interactions each, in seventh place fluoxetine with sulpiride with 2 (0.58%) interactions and seventh place amitriptyline with dextromethorphan and olanzapine with valproic acid with 1 (0.29%) interaction, in patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nIn Table 11, in relation to the actual drug interactions that were manifested, it can be seen that somnolence presented the highest frequency with 18 (66.7%) actual interactions, followed by depression with 3 (11.1%) actual interactions and anxiety, muscular weakness, INR elevation, hematochezia, hemoptysis and dizziness in third place with 1 (3.7%) actual interaction for each one, in patients of the COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\n\nDiscussion and conclusion\n\nThe most significant constraint during the research process was the limited time taken to collect the data, as the hospital did not authorise the document in a timely manner.\n\nRegarding actual and potential drug interactions of psychotropic drugs in their degree of severity dimension, the important indicator represented the highest frequency with 307 (89%) interactions, followed by the moderate indicator with 22 (6.4%) interactions, then the contraindicated indicator with 16 (4.6%) interactions and the minor and unknown indicators did not present interactions, similar results were obtained in the studies Lovera,9 Palomino and Rojas,10 Candia Bruno and Candia Bruno,11 Kirilochev et al.,12 Zapelini et al.13 Where the important indicator also presented greater frequency, different values were obtained in the study of Escarza and Salas14 where the indicator with greater frequency was moderate, this difference is probably since all the psychotropic drugs prescribed in the hospital center were included, as opposed to this study which only included psychotropic drugs indicated for anxiety, depression, and insomnia.\n\nIn relation to real and potential drug interactions of psychotropic drugs in its interaction type dimension, the pharmacodynamic indicator obtained a higher frequency with 183 (53%) interactions, followed by the pharmacokinetic indicator with 93 (27%) interactions and in the last place unknown with 69 (20%) interactions, similar results were obtained in the studies Lovera,9 Palomino, Rojas,10 Escarza and Salas14 and Montes and Ramos.15 Where the pharmacodynamic indicator presented higher prevalence, a different result was obtained by Zapelini et al.13 where the most frequent indicator was pharmacokinetics, this difference is probably due to the sample size of 2320 clinical histories and all psychotropic drugs prescribed in a hospital center were included, unlike this study which only included psychotropic drugs indicated for anxiety, depression and insomnia, and the sample size was 86 pharmacotherapeutic follow-ups.\n\nRegarding actual and potential drug interactions of psychotropic drugs in its clinical evidence dimension, we observed that the indicator fair had a higher frequency with 252 (73%) interactions, followed by the indicator good with 72 (20.9%) interactions, then excellent with 21 (60.1%) interactions and lastly unknown with 0 (0%) interactions. This difference is probably due to the size of the sample of 450 prescriptions, unlike this study which only included psychotropic drugs indicated for anxiety, depression and insomnia, and the sample size of 86 pharmacotherapeutic follow-ups.\n\nIn relation to actual and potential drug interactions of psychotropic drugs in their manifestation dimension, we observed that the potential indicator presented a higher frequency with 318 (92.2%) interactions, compared to the actual indicator with 23 (7.8%) interactions, a similar result was obtained in the study conducted by Montes and Ramos15 where potential interactions had a higher prevalence.\n\nRegarding the image in relation to actual and potential drug interactions of psychotropic drugs in their time of onset dimension, we observed that the indicator did not present a higher frequency with 318 (92.2%) potential interactions, followed by the fast indicator with 19 (5.5%) actual interactions, then late with 8 (2.32%) actual interactions and lastly immediate with 0 (0%) actual interactions. A different result was obtained by Zevallos16 where slow had a higher prevalence of 48% and fast 16.3%, this difference is probably due to the fact that this study was carried out on all drugs prescribed in the medical service, unlike this study which only included psychotropic drugs indicated for anxiety, depression and insomnia.\n\nIn relation to the actual and potential drug interactions of psychotropic drugs in its causality algorithm dimension, the indicator did not present the highest frequency with 318 (92.2%) potential interactions, in second place, the probable indicator with 25 (7.25%) actual interactions, third place, possible with 2 (0.58%) actual interactions and the immediate highly probable and doubtful indicators in last place with 0 (0%) actual interactions each. 25%) real interactions, in third place, possible with 2 (0.58%) real interactions and the immediate indicators highly probable and doubtful in last place with 0 (0%) real interactions each, a different result obtained by Castro and Monroy17 where the indicator with the highest presence was possible with 8.3%. This difference is probably due to the fact that the sample of this study is smaller, with seven follow-ups, compared to this study, where the sample is made up of 86 follow-ups.\n\nRegarding the actual and potential drug interactions of psychotropic drugs according to sex, it was observed that the male sex presented higher frequency in the potential interactions with 172 (49.9%) interactions compared to the female sex with 146 (42.3%) interactions and in the actual interactions the female sex presented higher incidence with 15 (4.3%) interactions compared to the male sex that presented 12 (3.5%) interactions, unlike the studies conducted by Palomino and Rojas10 and Jan Wolff et al.18 where the female sex presented a higher frequency; however, similarity was found in the results obtained in the studies by Montes and Ramos15 and Candía Bruno and Candia Bruno11 where the male sex presented a higher frequency. This difference between the results obtained and this study is probably since COVID-19 affects the male sex more.\n\nIn relation to real and potential drug interactions of psychotropic drugs according to their age, it was found that the average age was 48.58 years, of the potential interactions the average age was 48.83 years and of the real interactions it was 45.67, a different result obtained by Montes and Ramos15 where the average age was in the range of 24 and maximum of 36 years, probably because COVID-19 affects older adults more.\n\nAs for the psychotropic drugs that presented the highest frequency of potential drug interactions was sertraline with 184 (53.2%) and in relation to real drug interactions, the one that presented the highest frequency was mirtazapine with 12 (3.5%) interactions. Different results were obtained by Palomino and Rojas,10 Kirilochev et al.12 and Escarza and Salas,14 where sertraline was in third place, in the second study sertraline was in seventh place and in the second study sertraline was in second place with 13.5%.\n\nThe most frequent drug-drug interaction was sertraline with enoxaparin with 50 (14.49%) interactions. A different result was obtained by Lovera9 and Escarza and Salas14 where clonazepam-sertraline was the most frequent interaction in both studies, probably due to the symptomatic treatment indicated for COVID-19 where enoxaparin is indicated for hypercoagulability.\n\nAnd in relation to real drug interactions, somnolence presented the greatest frequency with 18 (66.7%) real interactions, in second place, depression with 3 (11.1%) real interactions and anxiety, muscular weakness, INR elevation, hematochezia, hemoptysis and dizziness in third place with 1 (3.7%). Similar results were obtained by Montes and Ramos15 where extrapyramidal and sedation effects were more frequent, probably due to the central nervous system depressant effect of psychotropic drugs.\n\nIn conclusion, it was identified that the male sex presented a higher frequency in the potential interactions with 172 (49.9%) interactions and in the real interactions the female sex presented a higher incidence with 15 (4.3%) interactions, it was also identified that the average age was 48.58 years, in the potential interactions the average age was 48.83 years and in the real interactions it was 45.67 years. In turn, it was identified that the psychotropic drug that presented the highest frequency in potential drug interactions was sertraline with 184 (53.2%) and in relation to real drug interactions the one that presented the highest frequency was mirtazapine with 12 (3.5%) interactions and that the most frequent interaction was sertraline with enoxaparin with 50 (14.49%) interactions and finally it was identified that somnolence was the main adverse event that occurred with 18 (66.7%) cases.\n\n\nData availability\n\n[Repository name: ZENODO] [Data file title: Actual and potential drug interactions of psychotropic drugs in patients of the covid-19 medicine service of the Hospital de Emergencia-Lima, 2021] [DOI: 10.5281/zenodo.6499337. https://zenodo.org/record/6499337#.Ymmo89pBy3A] [License details: Open Access].19",
"appendix": "References\n\nCarlos C: Universidad Privada Antenor Orrego Facultad De Medicina Humana Escuela Profesional De Medicina Humana Tesis Para Optar El Título Profesional De Médico Cirujano.Reference Source\n\nMcintosh K: UPTODATE. Martin S hirsch, MD. 2021.Reference SourceReference Source\n\nJiménez V: Uso de psicofármacos para síntomas neuropsiquiátricos en pacientes hospitalizados con covid-19. Horizonte médico (Lima). 2021 May 21; 21(2): e1272. Publisher Full Text\n\nB Stein M: UPTODATE.2021 [cited 2021 nov 21].Reference SourceReference Source\n\nApaza MV: Tesis para optar el título profesional de médico cirujano autora vicerrectorado de investigación.2020 [cited 2021 Nov 21].Reference Source\n\nDíaz S, Calvo M: ml. Trends in the use of anxiolytics in castile and leon, spain, between 2015–2020: evaluating the impact of covid-19. Int. J. Environ. Res. Public Health. 2021 Jun 1 [cited 2021 Nov 21]; 18(11): 5944. PubMed Abstract | Publisher Full Text Reference Source\n\nShahad AR, Hamid AM: Surging trends in prescriptions and costs of antidepressants in england amid covid-19. DARU J. Pharm. Sci. 2021 Mar 13.\n\nChesney E: Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the covid-19 pandemic. Lancet Psychiatry. 2020 May; 7(7): 611–627. Publisher Full Text\n\nLovera TM: Identificación de interacciones medicamentosas potenciales en recetas médicas atendidas en la farmacia ambulatoria del hospital carlos lanfranco la hoz, periodo setiembre - noviembre 2018.2019 [cited 2021 Nov 21].Reference Source\n\nPalomino Torres E, Rojas CE: Interacciones medicamentosas potenciales en las prescripciones médicas de los fármacos psicotrópicos atendidas en la farmacia universal sede lima periodo enero – julio 2016.2018.Reference Source\n\nCandia Bruno N, Candia Bruno Y: Interacciones Medicamentosas Potenciales En El Departamento De Medicina Del Hospital Militar Central Enero - Setiembre 2019 tesis para optar el título profesional de químico farmacéutico autores.2020 [cited 2021 Nov 21].Reference Source\n\nKirilochev OO: Interacciones fármaco-fármaco en el tratamiento de pacientes en condiciones.hospital psiquiátrico.2017 [cited 2021 Nov 21].Www.mediasphera.ruReference Source\n\nZapelini Do Nascimento D, Gm M, Schuelter-Trevisol F: Potential psychotropic drug interactions among drug-dependent people. J. Psychoactive Drugs. 2020 Nov 22; 30: 1–9. Publisher Full Text\n\nEscarza Aquino K, Salas MK: Interacciones medicamentosas potenciales en prescripciones médicas de pacientes ambulatorios del servicio de psiquiatría Del Hospital III De Emergencias Grau Essalud, periodo abril - noviembre del 2017.2021.Reference Source\n\nMontes Sence MM, Ramos Quispe CR: Evaluación del uso de psicofármacos en pacientes con trastornos mentales del Hospital De Salud Mental “SAN JUAN PABLO II EN EL PERIODO 2014-2015 Universidad Nacional De San Antonio Abad Del Cusco Facultad De Ciencias De La Salud Escuela Profesional De Farmacia y Bioquímica Tesis.2017 [cited 2021 Nov 21].Reference Source\n\nZevallos S: Interacciones medicamentosas de relevancia clínica en el Servicio de Medicina del Hospital Regional de Ayacucho de febrero a julio 2019. Edu.pe.2019 [citado el 9 de marzo de 2022].Reference Source\n\nCastro MJ, Monroy J: Interacciones medicamentosas potenciales en pacientes crónicos con esquizofrenia hospitalizados en una clínica de bogotá d.c., durante el período enero a febrero del año 2018. Edu.co.2018 [citado el 9 de marzo de 2022]. Reference Source\n\nWolff J, Kaier K, Toto S: Polypharmacy and the risk of drug–drug interactions and potentially inappropriate medications in hospital psychiatry. Pharmacoepidemiol. Drug Saf. 2021 Jun 24; 30(9): 1258–1268. PubMed Abstract | Publisher Full Text\n\nPAIRAZAMAN ATE, et al.: Underlying data for: Actual and potential drug interactions of psychotropic drugs in patients of the covid-19 medicine service of the Hospital de Emergencia-Lima, 2021. [data].2022. Publisher Full Text"
}
|
[
{
"id": "175595",
"date": "10 Sep 2024",
"name": "Aybeniz Civan Kahve",
"expertise": [
"Reviewer Expertise Psychopharmacology"
],
"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\nFirst of all, thank you for giving me the opportunity to review the article. Researchers have investigated drug-drug interactions in psychotropics used in the emergency department over a five-month period during the COVID-19 pandemic. Here are my suggestions that I think will help the authors:\nThe summary of the article needs to be rewritten. What system did the authors use to evaluate drug interactions? By which analysis were the rates given in the findings obtained? What are the targeted drug groups? I suggest you write them in the summary. It is more important that they give the interactions rather than the ratios of the findings.\n\nIntroduction: “Increased prescribing of psychotropic drugs may contribute to the manifestation of drug–drug interactions and increase the risk of having an adverse reaction due to toxicity and/or therapeutic failure of pharmacotherapeutic treatment due to lower plasma concentrations.”. The decrease in drug level is not the only reason for the decrease in pharmacotherapeutic efficacy. Pharmacodynamic interactions at the receptor level may also lead to decreased efficacy. Therefore, I suggest saying that there may be a loss of efficacy due to pharmacokinetic and pharmacodynamic interactions.\n\nIntroduction: “In the Villa El Salvador Emergency Hospital, there was an increase in prescriptions of psychotropic drugs indicated for anxiety depression and insomnia in the COVID-19 medicine service, in 2019 there were 911 prescriptions, in 2020 there were 9686 prescriptions and in 2021 there were 14005 prescriptions. Where the increase in the prescriptions of psychotropic drugs can interact with the medication indicated to treat other frequent pathologies in the patient of the COVID-19 medicine service such as arterial hypertension, diabetes mellitus, obesity and over-aggregated infections, which can cause a greater occurrence of drug interactions that produce therapeutic failure, appearance of toxic effects and adverse reactions, increasing the hospital stay and even endangering the patient's life.” It may make it more understandable if you write the sentences in this paragraph shorter and in splits.\n\nIntroduction: “The work is justified because, during the pandemic caused by COVID-19, the prescription of psychotropic drugs used in the treatment of anxiety, depression and insomnia has been increasing. The patients of the COVID-19 medicine service present various pathologies such as diabetes, hypertension, obesity, asthma, dyslipidemia, etc. For this reason, they are receiving several medications, which can interact with psychotropic drugs, causing an increase in drug-drug interactions, which can end up putting drug therapy at risk and generate reactions. For this reason, the following work will allow to deepen and update the information on drug-drug interactions of psychotropic drugs that are presented in the COVID-19 medical service and generate a contribution for future research. The study will provide a protocol and instrument, which will be validated by experts, this will allow further research aimed at identifying potential and actual drug–drug interactions in the various hospital services prescribed by the treating physician and will also allow to know what are the main potential and actual drug–drug interactions that occur in psychotropic drugs prescribed for anxiety, depression and insomnia in the COVID-19 medicine service. This will make it possible to reduce and prevent drug–drug interactions.” The entry contains too much repetitive information. The fact that patients have additional medical conditions may increase the number of drugs used and cause more drug-drug interactions. That's enough to write. In addition, the purpose of the study has already been stated in the next paragraph. I think that it is not suitable for a portable introduction to the end of the discussion to guide future studies.\n\nIt was said that there is no need for ethical approval, but the research approval has already been obtained from the university. People and their relatives were also informed that their data was used. This data is not open data. It is obtained by examining the drug treatment records of people from hospital information systems. Therefore, ethical compliance decision is needed. “Ethical approval was not required for this section because no humans and/or animals were used.” Could this sentence be written in methods mistakenly??\n\nIlluminate in the method of operation. Is approval required for the use of psychotropic medication in your hospital's emergency department? How does the Pharmacy unit work? For whom does he follow up? Which unit is this approval made by? Have you considered all psychotropics approved by that unit?\n\nI think this paragraph is unnecessary in exclusion criteria. “Pharmacotherapeutic follow-ups performed by the pharmacy unit where no psychotropic drugs for anxiety, depression and insomnia with an indication authorized by the National Essential Drug Formulary (sertraline, mirtazapine, clonazepam, clonidine) have been registered in the unit, mirtazapine, clonazepam , alprazolam, fluoxetine, amitriptyline, clobazam, diazepam and levomepromazine) and the psychotropic drugs approved by the pharmacotherapeutic committee of the Villa El Salvador Emergency Hospital (quetiapine, olanzapine and paroxetine).”\n\nAre the specified scales and questions evaluated and filled by the pharmacologist over all the drugs and recorded data of the patients? Explain this a little.\n\nWhat are the unknown interactions in Table 1? Can you explain what is called unknown under the table and in the text? Unknown if there is interaction or not??\n\nThe difference between table 1 and table 2 cannot be understood. The two tables can be combined and the difference in table 2 compared to table 1 can be explained.\n\nTable 3 – according to what is the categorization called fair good excellent etc.? Here, it should be explained what is taken into consideration in scoring the method.\n\nI think there is no need to mention the location in every finding and table: COVID-19 Medicine Service of the Villa El Salvador Emergency Hospital.\n\nFor what hour/day was the word fast late immediate for Table 5?\n\nHow was causality evaluated in Table 6? We do not know the evaluation conditions of any scale. In Table 8, which one is real and which potential is decided based on what?\n\nThe way of evaluating the evaluation dimensions of drug interaction is very inadequate. I did not find the article understandable. Tables can be combined I think 11 tables make it difficult to follow.\n\nThe discussion was data repetition. It needs rewriting.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-660
|
https://f1000research.com/articles/11-657/v1
|
15 Jun 22
|
{
"type": "Research Article",
"title": "The objectivity requirement in crimes related to electronic or magnetic records containing unauthorized commands",
"authors": [
"Kouya Takara"
],
"abstract": "The crime of electromagnetic records under unauthorized instruction (Article 168-2 and 3 of the Penal Code) requires that the program or the instruction code in question is against the intention of the computer user (counterintentionality) and socially unacceptable (unauthorized), as the requirements of objectivity. The significance or factors to be considered in the requirements of “counterintentionality” and “unauthorized” have not been clarified in practice. This paper examines the requirements of “counterintentionality” and “unauthorized” intent in crimes related to electromagnetic records with the Coinhive case as material, by means of a literature survey and case study. In addition, the significance and scope of the Supreme Court’s decision in the Coinhive case will be clarified.\n不正指令電磁的記録に関する罪（刑法168条の２および３）においては、客体性の要件として、当該コンピュータの利用者の意図に反すること（反意図性）および当該プログラム等が社会的に許容されないこと（不正性）が要求される。反意図性及び不正性の要件においてその意義あるいは考慮要素について、実務上は明確化されていなかった。本稿は、コインハイブ事件を素材に、文献調査と判例研究の方法で、不正指令電磁的記録に関する罪における反意図性と不正性の要件について検討する。加えてコインハイブ事件最高裁判決の意義と射程を明らかにするものである。",
"keywords": [
"Coinhive",
"crimes related to electronic or magnetic records containing unauthorized commands",
"counterintentionality",
"unauthorized",
"cryptojacking"
],
"content": "I. はじめに\n\n2011 年 6 月 17 日に、第 177 回国会において「情報処理の高度化等に対処するための刑法等の一部を改正する法律」が成立してから 10 年余りが経過した。かかる法案は、「サイバー犯罪その他の情報処理の高度化に伴う犯罪及び強制執行を妨害する犯罪の実情に鑑み、情報処理の高度化に伴う犯罪に適切に対処するため、及びサイバー犯罪に関する条約の締結に伴い、処罰規定の整備や電磁的記録に係る記録媒体に関する証拠収集手続の規定の整備等を行い、並びに悪質な強制執行妨害事犯等に適切に対処するために処罰規定の整備等を行うべく刑法等を改正したもの」であり1、本改正により、マルウェアなどを含むコンピュータ・ウイルスなどに関連する犯罪を規制する、不正指令電磁的記録に関する罪（刑法第 19 章の 2）として、不正指令電磁的記録作成等罪（同第 168 条の 2）、不正指令電磁的記録取得等罪（同第 168 条の 3）が新設されている。不正指令電磁的記録に関する罪においては、該当する電磁的記録が、人が電子計算機を使用するに際してその「意図に沿うべき動作をさせず、又はその意図に反する動作をさせるべき不正な指令を与える」もの（168 条の 2 第 1 項 1 号）であることが構成要件として要求されている。すなわち「反意図性」と「不正性」の要件である。\n\n反意図性と不正性の認定基準については、従来必ずしも明確ではなく、裁判所の立場も不明確であった。ここで、反意図性と不正性をめぐっては近時注目すべき裁判例がある。いわゆるコインハイブ事件である。これはウェブサイト閲覧者の通信機器の中央処理装置 (CPU) の計算機能を一部用いることで暗号通貨のマイニングを行わせるプログラムを呼び出すプログラムコードを、ウェブサイトへ設置したことが不正指令電磁的記録の保管罪に該当するかが問題になった事案である。当該事案においては、原原審の横浜地裁、原審の東京地裁、および最高裁がそれぞれ異なる判断基準の下、判決を下しており、不正指令電磁的記録に関する罪の構成要件を明確化する上で参考になる。\n\n本稿は、コインハイブ事件の各裁判例を分析・検討することを通して、不正指令電磁的記録に関する罪における反意図性と不正性の判断基準を明らかにすることを目的とするものである。\n\n方法\n\n本稿は、文献調査および判例研究の方法で行うものである。文献および判例は、裁判所ウェブサイト、Westlaw Japan、Google Scholar、CiNii Research、LexisNexis、Beck Online を使用し調査を行った。\n\n\nII. コインハイブ事件\n\n本章においては、前述のコインハイブ事件における事案の概要及び、各裁判経過の内容について述べる。事案の概要は次の通りである。\n\nウェブサイト「Ｘ」を運営していた被告人は、Ｘ閲覧を通じて利益を得るため、平成 29 年 9 月 21 日、マイニングプログラムコードを提供しているサービスであるコインハイブ3に登録し、提供されたプログラムコードに、被告人に割り当てられたサイトキーを記述したもの（本件プログラムコード）を、サーバコンピュータ上のＸ内に設置し、本件公訴事実の期間中、Ｘを構成するファイル内に蔵置して保管した。本件当時、一般の使用者に、ウェブサイトの収益方法として閲覧者の電子計算機にマイニングを行わせるという仕組みは認知されていなかったが、被告人は、Ｘに、閲覧中にマイニングが行われることについて同意を得る仕様を設けたり、マイニングに関する説明やマイニングが行われていることの表示をしたりすることなく、本件プログラムコードを保管していた。なお被告人は、本件プログラムコードにおいて、閲覧者の電子計算機の CPU 使用率を調整する値を 0.54と設定していた。\n\n・第一審（横浜地判平成 31 年 3 月 27 日判時 2446 号 78 頁）5: 無罪\n\n本件第一審は、反意図性を認定したものの、不正性を否定して無罪としている。\n\n反意図性は、「個別具体的な使用者の実際の認識を基準とするのではなく，当該プログラムの機能の内容や機能に関する説明内容，想定される利用方法等を総合的に考慮して，当該プログラムの機能につき一般的に認識すべきと考えられるところ」を判断基準とする。\n\nその上で、Ｘには本件マイニングプログラムについての一般的な認知や、マイニングについての同意を得る仕組みがないといった、上述の事実から、一般的に認知されず点から、「一般的なユーザーが認識すべきと考えられるものということはできない」として反意図性を認定する。\n\n不正性については、「ウェブサイトを運営するような特定のユーザー及びウェブサイト閲覧者等の一般的なユーザーにとっての有益性や必要性の程度，当該プログラムのユーザーへの影響や弊害の度合い，事件当時における当該プログラムに対するユーザー等関係者の評価や動向等の事情を総合的に考慮し，当該プログラムの機能の内容が社会的に許容し得るものであるか否か」を判断基準とした上で、①「（運営者が得た利益が）ウェブサイトのサービスの質を維持・向上させるための資金源になり得るのであるから，現在のみならず将来的にも閲覧需要のある閲覧者にとっては利益とな」り、②「消費電力の増加，処理速度の低下等の影響が生じるが，その程度は広告表示プログラム等の場合と大きく変わることがな」く、「サイト閲覧中に限定され」ることを基礎に、本件プログラムコードが社会的に許容されていなかったとはいえないとして、不正性を否定した。\n\n・原審（東京高判令和 2 年 2 月 7 日判時 2446 号 78 頁）6: 破棄自判・有罪\n\n反意図性について、「当該プログラムの機能について一般的に認識すべきと考えられるところを基準とした上で，一般的なプログラム使用者の意思に反しないものと評価できるかという観点から規範的に判断されるべき」とし、第一審の検討については、規範的検討を行っていない点で判断手法には問題があるとする。その上で、本件プログラムコードについては、「プログラム使用者に利益をもたらさないものである上，プログラム使用者に無断で電子計算機の機能を提供させて利益を得ようとするものであり，このようなプログラムの使用を一般的なプログラム使用者として想定される者が許容しないことは明らか」として、反意図性を認定した結論においては第一審を支持している。\n\n不正性については、「一般的なプログラム使用者の意に反するプログラムであっても，使用者として想定される者における当該プログラムを使用すること自体に関する利害得失や，プログラム使用者に生じ得る不利益に対する注意喚起の有無などを考慮した場合，プログラムに対する信頼保護という観点や，電子計算機による適正な情報処理という観点から見て，当該プログラムが社会的に許容されることがある」ことから、反意図性のある場合に処罰範囲を限定するための要件であるとする。\n\nその上で、本件プログラムコードは、「その使用によって，プログラム使用者（閲覧者）に利益を生じさせない一方で，知らないうちに電子計算機の機能を提供させるものであって，一定の不利益を与える類型のプログラムといえる上，その生じる不利益に関する表示等もされていない」から、「プログラムに対する信頼保護という観点から」、社会的に許容できないする。\n\n加えて、第一審が挙げた閲覧者の利益 (①) については、「意に反するプログラムの実行を，使用者が気づかないような方法で受忍させた上で，実現されるべきものでない」上、広告表示プログラムとの類似性(②) については、「広使用者のウェブサイトの閲覧に付随して実行され，また，実行結果も表示されるものが一般的であり，その点で，閲覧者の電子計算機の機能を閲覧者に知らせないで提供させる機能のある本件プログラムコードとは，大きな相違があ」るとして、不正性を否定する要素にはならないことを認めている。第一審は、コインハイブについての賛否があることを社会的許容性を肯定する評価に用いているが、この点についても否定をしている。\n\n以上により、不正性を認定し、第一審を破棄し有罪とした。これを受けて弁護人が上告したのが本件である。\n\n・最（一）判令和 4 年 1 月 20 日（裁判所ウェブサイト掲載）7 : 破棄自判・無罪\n\n不正指令電磁的記録に関する罪の保護法益および反意図性と不正性要件を設けた目的について「電子計算機において使用者の意図に反して実行される不正プログラムが社会に被害を与え深刻な問題」であり、「電子計算機において使用者の意図に反して実行される不正プログラムが社会に被害を与え深刻な問題となっていることを受け、電子計算機による情報処理のためのプログラムが、『意図に沿うべき動作をさせず、又はその意図に反する動作をさせるべき不正な指令』を与えるものではないという社会一般の信頼を保護し、ひいては電子計算機の社会的機能を保護するために、反意図性があり、社会的に許容し得ない不正性のある指令を与えるプログラムの作成、提供、保管等を、一定の要件の下に処罰するものである」ことであるとする。\n\n反意図性については、「当該プログラムについて一般の使用者が認識すべき動作と実際の動作が異なる場合に肯定される」のであり、「一般の使用者が認識すべき」か否かは、「当該プログラムの動作の内容」、「プログラムに付された名称」、「動作に関する説明の内容」、「想定される当該プログラムの利用方法」などを判断の基底におくとする。\n\n不正性については、「電子計算機による情報処理に対する社会一般の信頼を保護し、電子計算機の社会的機能を保護するという観点から、社会的に許容し得ないプログラムについて肯定される」か否かを判断するのであり、「当該プログラムの動作の内容」、「その動作が電子計算機の機能や電子計算機による情報処理に与える影響の有無・程度」、「当該プログラムの利用方法」などが考慮要素となるとする。\n\n以上の点から、「閲覧中にマイニングが行われることについて同意を得る仕様になっておらず、マイニングに関する説明やマイニングが行われていることの表示もなかった」のであり、「ウェブサイトの収益方法として閲覧者の電子計算機にマイニングを行わせるという仕組みは一般の使用者に認知されていなかった」といった事情から、本件プログラムコードを一般の閲覧者の「認識すべき」ものではなく、反意図性を肯定している。\n\n一方で不正性については、「本件プログラムコードによるマイニングは、閲覧者の同意を得ることなくその電子計算機に一定の負荷を与え、これに関する報酬を閲覧者が取得することができないものであるのに、閲覧者にマイニングの実行を知る機会やこれを拒絶する機会が保障されていないなど、プログラムに対する信頼という観点から、より適切な利用方法等が採り得た」としつつも、「（上記の）保護法益に照らして重要な事情である電子計算機の機能や電子計算機による情報処理に与える影響は、Ｘ閲覧中に閲覧者の電子計算機の中央処理装置を一定程度使用することにとどまり、その使用の程度も、閲覧者の電子計算機の消費電力が若干増加したり中央処理装置の処理速度が遅くなったりするが、閲覧者がその変化に気付くほどのものではなかった」こと、「ウェブサイトの運営者が閲覧を通じて利益を得る仕組みは、ウェブサイトによる情報の流通にとって重要であるところ、被告人は、本件プログラムコードをそのような収益の仕組みとして利用したものである上、本件プログラムコードは、そのような仕組みとして社会的に受容されている広告表示プログラムと比較しても、閲覧者の電子計算機の機能や電子計算機による情報処理に与える影響において有意な差異は認められ」ないものとし、「事前の同意を得ることなく実行され、閲覧中に閲覧者の電子計算機を一定程度使用するという利用方法等も同様であって、これらの点は社会的に許容し得る範囲内といえる」として、本罪の保護法益に照らし、社会的許容性を認定する。またマイニング自体の社会的許容性も認めている。\n\n以上の点から、「本件プログラムコードの動作の内容、その動作が電子計算機の機能や電子計算機による情報処理に与える影響、その利用方法」などを考慮しても、不正性は認定できないとして、無罪とした。\n\nコインハイブ事件をめぐる一連の判決において、論点となるのは反意図性および不正性についての判断基準である。不正指令電磁的記録に関する罪においては、その客体性要件である反意図性と不正性の認定基準が不明確であり、従前の裁判例においてもこの点を詳細に検討判断したものは見受けられない。上記3判決においては、次の点が注目できる。\n\n・保護法益:規範的判断の基礎となる保護法益の理解\n\n・反意図性:反意図性の判断における規範的評価\n\n・不正性:考慮要素と判断の妥当性\n\n以上、3 点において、コインハイブ最高裁判決を検討したい。その前提として、次章において、従来の議論を整理する。\n\n\nIII. 不正指令電磁的記録に関する罪\n\n不正指令電磁的記録に関する罪8は前述の通り、2011 年刑法改正により新設されたものであり、マルウェアやコンピュータ・ウイルスにかかる犯罪に対応するための犯罪類型である。本罪の新設以前においては、不正なプログラムである電磁的記録によってコンピュータが破壊あるいはそれにより業務が妨害された際に、器物損壊罪（刑法第 261 条）や公電磁的記録損壊罪（刑法第 258 条）、電子計算機損壊等業務妨害罪（刑法第 234 条の 2）が成立する場合を除けば、不正プログラムの作成、提供、供用、取得、保管の各段階は規制対象ではなかった。本罪成立より前では、例えば、ファイル共有ソフトを通じてウイルスファイルを送付し、他者のハードディスク内のファイルを使用できない状態にした事案につき、器物損壊罪で起訴したものがある9。\n\n本罪の保護法益は、「コンピュータ・プログラムがコンピュータに意図せざる不正な動作をさせるものではないことに対する信用・信頼」であり10、社会的法益であると理解されてきた。法務省作成の解説においても、「「人が電子計算機を使用するに際してその意図に沿うべき動作をさせず、又はその意図に反する動作をさせるべき不正な指令」を与えるものではないという、電子計算機のプログラムに対する社会一般の者の信頼」11とされ、通説的には社会的法益として分類されるとともに、個人的法益に対する罪である電子計算機損壊等業務妨害罪あるいは公電磁的記録損壊罪の予備罪としての構成も否定されている12。\n\n個人的法益に対する罪の予備罪として構成することが否定された理由は、立案担当者の「個人情報を流出させるウイルスや電子メールを勝手に送信するウイルス、画像データなど権利・義務に関するものでない私電磁的記録を勝手に消去・改変するウイルスを作成、供用する行為が処罰対象に含まれないことになり、相当性を欠く」13との指摘にあるように、マルウェアやコンピュータ・ウイルスにかかる構成要件を不当に狭めることを避けるためであったと考えられる。マルウェアやコンピュータ・ウイルスは、「個々の電子計算機被害を与えるにとどまらず、それを超えて社会一般に重大な損害を与える」14のであって、例えば、これらプログラムの設置・送信が継続する間、国境を越えた被害の拡散の危険性も継続し、プログラムが発信元から削除されても、すでにかかるプログラムに感染した受信者から他のユーザーへの被害の拡散もあるなど、インターネットが普及した状況下における危険なプログラムの被害発生可能性等に鑑みれば、本罪の保護法益を社会的法益とする考え方は妥当である15。また、かかる理解は本罪が 19 章の 2 として、文書等に対する「社会一般の信頼」を保護法益とする 16 章以下の偽造罪類型の後に位置している関係からも自然である。\n\nなお、本罪は、「正当な理由がないのに」（正当な理由の不存在）、「人の電子計算機における実行の用に供する目的で」（目的犯）、客体となる電磁的記録を作成、提供 （168 条の 2 第 1 項）、供用（同第 2 項）、取得または保管 (168 条の 3) する行為が構成要件に該当する。本罪の客体は、「人が電子計算機を使用するに際してその意図に沿うべき動作をさせず、又はその意図に反する動作をさせるべき不正な指令を与える電磁的記録」（168 条の 2 第 1 項 1 号）および「（1 号の）不正な指令を記述した電磁的記録その他の記録」（同 2 号)16 であり、反意図性および不正性は、当該電磁的記録が不正指令電磁的記録に関する罪における客体性の要件である。情報セキュリティの検査や情報漏洩防止のための技術が同時に犯罪にも利用可能なもの17については、当該プログラムがコンピュータや電磁的記録を毀損しうるものであったとしても、不正指令電磁的記録に該当するかについては確定せず18、主観的構成要件としての「不正な目的」とならび、適法に使用される当該プログラムを除外する要件となる。\n\n「その意図に沿うべき動作をさせず、又はその意図に反する動作をさせる」すなわち反意図性は、立法立案者解説19 や大コンメンタール20 の記述によれば、社会一般の信頼を保護法益とする以上、その「意図」についても、そのような信頼を害するものであるか否かという点から規範的に判断されるべきであるとされる。この点、および法務省解説21 に「規範的」という文言は用いられておらず、「反意図」である場合の具体例が示されているのみである。\n\nこの点、大コンメンタールの記述と法務省解説の齟齬について、198 回国会において質問主意書22 が提出されている。本質問主意書への回答において、「意図」についても「そのような信頼を害するものであるか否かという観点から、すなわち、個別具体的な使用者の実際の認識を基準とするのではなく、当該プログラムの機能の内容や機能に関する説明内容、想定される利用方法等を総合的に考慮して、その機能につき一般に認識すべきと考えられるところを基準として、規範的に判断されるべきもの」23 であるとされ、「一般に認識すべき」ところを基準とした「規範的」判断が法務省の見解であることが示されている。かかる見解は、「一般に認識すべき」か否、すなわち一般人の認識可能性の有無を、単なる事実判断ではなく、法益侵害性を有するものか否かという価値判断を含ものである24。\n\n反意図性が認められない場合として、立法立案者解説においては、電子計算機の利用者が、「そのプログラムの指令によって電子計算機が行う基本的な動作については当然に認識している上、それ以外の詳細な機能についても、使用説明書に記載されるなどして、通常、使用者が認識しうる」市販のソフトウェアや、説明書が付与されていない場合であっても「当該ソフトウェアの機能は、その名称や公開されているサイト上での説明等により、通常、使用者が認識しうる」ようなフリーソフトの場合が挙げられ、ポップアップ広告についても「通常、インターネットの利用に随伴するものであることに鑑みると、そのようなものとして一般的に認識すべき」場合であるとする25。いずれの場合も一般人の認識可能性が判断基準である。ただし、かかる文言だけでは、一般人が特に知ることができるか、広く周知されているかというある意味事実的判断のみで判断可能であるようにも読める。\n\n情報リテラシーについては利用者において差があり、当該プログラムについて個々人としてみた場合、例えばエンジニアにおいて一般的に知りうる情報を、情報機器に疎い者はもちろん通常のユーザーですら知りえないことは当然にあることである。この点、日々開発されるプログラムについて通常人においては知りえず、常に「一般的に認識すべき」場合ではなく、反意図性が認められうるのであり26、一般人の認識可能性のみを基礎とするのであれば、反意図性の範囲は規範的判断によって限定した意味を失してしまうであろう。仮に「一般人に認識すべき」プログラムであったとしても、当該プログラムが多大な負担を強いるのであれば、一般人がこれを望まないことは当然にありうる。かかる判断においては、実質的な負担の存否・軽重などに鑑み、どの程度の負担であれば一般に許容できるのか、つまりは、社会的許容性を観念せざるを得ないと思われる27。\n\n立法立案者の解説によれば、「「意図に反するか」否かの判断と「不正」か否かの判断は、別個の観点からなされるものであり、両者は必ずしも完全に重複するものではな」いとされ、前者が利用者にとって「一般に認識すべき」か、後者が「社会的に許容しうる」かが判断の際の観点となるとされるが28、両者は重なりあうものであり、形式的な分類はともかくとして、実質的な判断においては区別困難となろう29。\n\nなお、コインハイブ事件については、全ての裁判経過において反意図性と不正性を認定する判断枠組みは維持されている。反意図性が認められる場合においては、多くの事例で当該プログラムが社会の信頼を害するといえるが、不正性の要件によって社会的に例外的に許容しうるものを除外することが、かかる要件の目的である30ともいえる。\n\n不正性判断において、社会的許容性を考慮するに際して、単に「有害性」のみを基準として判断することは立法段階で否定されており31、「プログラムの客観的な性質だけで「不正」か否かを決することは難しく、理論的には、プログラムの客観的な性質に加えて、犯罪を行うために使用する意図の有無により処罰の対象となるか否かを判断する」32との言及に見られる通り、不正性判断においても「意図」あるいはそれを支える認識可能性の要素は排除されるものではない。「一般に認識すべき」動作や機能でないことは、本件最高裁の様に一般に認識できないほどの軽微な損害という観点からは、社会的許容性を認定する要素となる一方で、ユーザーの認識の外でマルウェア等が起動することは、ユーザーやネットワークへの潜在的なリスクという意味で不正性の認定要素33ともなりうる。\n\n不正性判断において、国際的動向についても言及しておきたい。クリプトジャッキング (Cryptojacking) とは、他人のコンピュータを密かに利用して、暗号通貨をマイニングする行為である34。本件最高裁判決に関する「WLJ 判例コラム第 254 号」においても、「その後、種々の態様のサイバー攻撃が登場し、「不正な指令」の範囲が拡張していく。膨大な数の他人のパソコンを「ボット」として使うことにより、サイバーアタックが実行されている。スパムメールやフィッシングメールが蔓延し、他人のパソコンを乗っ取りマイニングを行って利益を得る行為が世界中で問題視されている」との指摘がある35。\n\nドイツ連邦刑事庁 (BKA) の報告書によれば、計算上、2017 年 10 月上旬時点で、TOP10 万サイトのうち約 220 サイトがコインハイブのスクリプトを搭載し、これらのサイトを合計すると、1 ヶ月に約 5 億人のユーザーの利用があるとされる36。セキュリティウェア企業などの定義によればクリプトジャッキングに該当するとするものがみられる。なお、クリプトジャッキングについては、インストール型とウェブサイト閲覧型があり、コインハイブは後者である。前者はいわゆるマルウェアに分類されうる37。コインハイブが 2019 年にサービスを停止した後、すでに多くのウェブサイトが、ウェブサイト閲覧型のクリプトジャッキングから撤退したもののなおも、複数のサイトにクリプトジャッキングのスクリプトを搭載しているとされる38。\n\n先のドイツの例でいえば、コインハイブのように javascript を用いて、データ自体の変更を伴わないようなプログラムの場合には、データの変更に関する規定（ドイツ刑法 303a 条）の適用はない。また、他者のコンピュータへの介入について、DDoS はコンピュータの妨害（ドイツ刑法 303b 条）の対象となるが、ウェブサイト閲覧型のクリプトジャッキングは処理の中断を伴わないため対象とはならない39。\n\nなお、諸外国の動向を見るに、現在のところ、ウェブサイト閲覧型クリプトジャッキングについてのコインハイブ事件と同様の事案は見受けられず40、マルウェアを用いたクリプトジャッキングについては複数の検挙事案がみられるところである41。ウェブサイト閲覧型のクリプトジャッキングサービスのプライバシーリスクあるいは、暗号通貨自体が犯罪利用リスクの存在については問題となりうるが、かかるサービスを契約し利用する者に可罰的な違法性まで存するのかについては、議論が成熟していないのが現状であろう。\n\nとはいえ、クリプトジャッキングが許容しえない損害を利用者あるいは社会全体に与えうるのだとすれば、これを国家として容認するには当然に問題がある。当該国家の住民対象のウェブサイトであれば、合法的に他者の CPU を利用することができるとの誤ったメッセージを与え、サイバー攻撃の誘引につながる危険性もあり得る。コインハイブにかかるプログラムコードが不正指令電磁的記録に該当するかどうかとは別論、クリプトジャッキング自体を明確に「適法」であるということは困難である。\n\n\nIV. コインハイブ事件最高裁判決の検討\n\n本件最高裁判所は、反意図性を肯定しつつ不正性を否定して、有罪判決としていた原審東京高裁判決を破棄し、被告人を無罪とした。本章においては、最高裁判所における、不正指令電磁的記録に関する罪の保護法益、反意図性および不正性の判断についての見解について検討を行う。\n\n・保護法益について\n\nまず、反意図性および不正性の判断を保護法益を侵害するか否かの規範的判断によって行うのであれば、まず最高裁が本罪の保護法益をいかに理解しているかに言及する必要がある。ここでは、電子計算機で用いられるプログラムが、「意図に沿うべき動作をさせず、又はその意図に反する動作をさせるべき不正な指令」を与えるものではないという「社会一般の信頼」とするように、立法時からの理解が維持されている。この点、「ひいては電子計算機の社会的機能を保護」に言及する点、かかる社会的機能を重視した判断であり、「抽象的な信頼にとどまらないこのような機能自体、即ち電子計算機による適正な情報処理という具体的状態自体への着目は不正指令電磁的記録不正指令電磁的記録概念の要件解釈の重要な指標」42 となりうるとの指摘がある。立法担当者においても、当初より電子計算機の社会的機能の重要性については言及されていたところである43。もちろん最高裁が「社会一般の信頼」保護の結果ないし反射的効果として保護されるものとして、「電子計算機の社会的機能」を明示した点には意義がある。ただし、本件最高裁は、「閲覧者の電子計算機の機能や電子計算機による情報処理」への影響の社会的許容性を問題としているのであり、電子計算機自体の社会的機能ではなく、生じうる損害への社会的評価に重点を置いている様に思われる。「電子計算機の社会的機能」への影響を重視するのであれば、不正性を認定する方向に傾くとも考えられよう。\n\n・反意図性について\n\n反意図性については、「一般の使用者が認識すべき動作と実際の動作が異なる場合に肯定される」とし、一般の認識可能性を判断基準としつつ、文言上は一般人の認識と現実の齟齬を判断している事実的判断であるようにも見える44。一般の使用者が「認識すべき」か否かを判断基準とする点においては、一審からの一貫した判断であるが、「規範的」との文言が反意図性判断においては第一審と最高裁判決においては用いられていない。高裁判決は「規範的判断」に言及し、立法立案者の見解に立つことが明確であることと相違する。\n\nこの点、先の保護法益についての文言である「意図に沿うべき…保護するために、」という文言は、文脈上、反意図性と不正性双方にかかるものであり、反意図性判断においても、単なる認識と現実の齟齬といった事実的判断だけではなく、法益侵害性についての判断を行うことが前提であろう。本件が、ある種の事実的判断のみで反意図性が認定可能であるのは、本件が法益侵害性についての価値判断を行うまでもなく、反意図性が認定できる事案であったと思われる。本件において、「不正性」判断において規範的評価の中心がおかれているとはいえ、本件最高裁が反意図性の判断における規範的判断を放棄したとまではいえないであろう。\n\n・不正性について\n\n第一審及び原審において反意図性判断の要素であった「閲覧者の同意」「閲覧者にマイニングの実行を知る機会やこれを拒絶する機会」の保障といったものが、不正性判断の段階で検討されており、この点、反意図性と不正性は不可分であるとの私見によれば妥当な判断であると思われる45。不正性については、原審において「閲覧者に利益を生じさせない一方で一定の不利益を与えるものである上、不利益に関する表示等もされない」点で、「閲覧者の電子計算機を、閲覧者以外の利益のために無断で使用する点を基礎に 不正性、本罪の保護法益である、「社会一般の信頼」保護という原則により依拠したものであるといえる。\n\n不正性判断において、「社会一般の信頼」を侵害する危険性があるか否かを判断基準にすることについては、異論はない。しかし、同意を得ずに他者のコンピュータに介入操作するクリプトジャッキングの潜在的な危険性に鑑みれば、「社会一般の信頼」を害する危険性は少なくない。「本件プログラムコードの動作の内容であるマイニング自体は、仮想通貨の信頼性を確保するための仕組みであり、社会的に許容し得ないものとはいい難い」ことは、暗号通貨のマイニングによって報酬をえることそのものが適法であるのは当然のことであるが、かかる閲覧者の同意を得ない手法が「社会一般の信頼」を害しないといえるかには疑問が残る。本件最高裁の結論自体には異をとなえるものではないが、理由付けとしては、損害が軽微ゆえに、本件プログラムコードの掲載自体の社会的許容性あるとする方が妥当だったのではなかろうか。\n\nまた、社会的許容性を判断するにあたり、そもそも広告表示プログラムはその動作が閲覧者に秘匿されるものではなく、そのウェブ利用時の付随性も一般的に知られ、当該プログラムによる動作もかかる広告を画面表示させるにとどまる46。一方で、マイニングプログラムは閲覧者の認識なくCPU を利用した計算処理を行った上、継続的かつ一方的に処理能力を奪い、電力を消費する。その上、計算結果の抜き取りについても本人の同意なく行われる。当該プログラムが与えうる侵害の危険性と、個人領域への干渉は小さくない。本件行為対応が社会的に許容される範囲に収まるとしても、マイニングプログラムにおいては潜在的なリスクが存する。その点を過小評価しているのではないかとの評価はなしうるところである。\n\n\nV. おわりに\n\n以上、本稿においては不正指令電磁的記録に関する罪における反意図性と不正性を中心に若干の検討を行った。なお、コインハイブ事件に関して、本稿においては刑法構成要件の観点で検討を行ったが、コンピュータ・プログラムへの規制は研究開発への過度の制約となりえ、また、これにより表現の自由の侵害の危険性もあるものである。この点、本稿で挙げた評釈においても憲法的論点から論じる者が少なくない47。この点、今後さらなる検討を行いたい。\n\n結びに変えて、本稿で扱ったコインハイブ事件の射程と意義を述べたい。本稿は従来明らかでなかった反意図性と不正性について最高裁判所がはじめて判断した事案であり、今後の本罪にかかる事案について参考になるものである。ただし、反意図性は事実的判断、不正性については規範的判断であると、その判断方法について明確に区別したものとまでは言えないと考える。反意図性が認められる場合の処罰範囲を限定するものとして不正性の要件があり、反意図性判断が不正性判断の前段階におかれることが明示された点は評価できる。私論であるが、裁判所が反意図性判断における規範的判断を放棄していないと考えるのであれば、(1) 反意図性にかかる事実判断、(2) 反意図性にかかる規範的判断、(3) 不正性判断との流れで検討がなされ、処罰範囲を限定していくとも考えられる。ただし、判例における判断基準については、今後事案の蓄積を要し、本稿において断言することは難しい。\n\nなお、付言すれば、プログラムを実装するに際し、情報流通の国境がなくなり、データプライバシーが重視される昨今においては、プライバシー・バイ・デザインを意識して技術の企画から実装までの各段階においてプライバシーへの尊重が求められるのであり、利用者や閲覧者の同意を得る仕組みを組み込んだ上で技術実装がなされることが望ましいことはいうまでもない。\n\n\nデータ可用性\n\n本論文は法学の論文であり、「生データ (raw data)」は存在しない。書籍や論文として公開されている学説、判例等に基づいている。",
"appendix": "Footnotes\n\n1 第 177 回国会法務大臣による趣旨説明。第177回国会法務委員会第 13 号（平成 23 年 5 月 25 日） （江田五月）。\n\n2 事案の概要および、最高裁判旨については、裁判所ウェブサイトを参照。\n\n3 最高裁の認定事実（前掲注 2）参照）によれば、「その内容は、登録したウェブサイトの運営者（以下「登録者」という。）に対し、ウェブサイト閲覧者が閲覧中に使用する電子計算機の中央処理装置に同閲覧者の同意を得ることなく仮想通貨 Monero （モネロ）の取引台帳へ取引履歴を追記する承認作業等の演算を行わせ、その演算が成功すると、報酬として仮想通貨の取得が可能になるというマイニングを実行するプログラムコードを取得するためのプログラムコードを提供し、報酬の 7 割を登録者に分配し、 3 割をコインハイブチーム側が取得するというもの」である。コインハイブ自体は 2019 年にサービスを終了している。\n\n4 裁判所認定事実（前掲注 3）参照）によれば、「マイニングを実行すると、閲覧者の電子計算機の消費電力が若干増加したり中央処理装置の処理速度が遅くなったりするが、極端に遅くはならず、これらの影響の程度は、閲覧者が気付くほどではなく、また、一般的なウェブサイトで広く実行されている広告を表示するプログラム（以下「広告表示プログラム」という。）と有意な差異はなかった」とされる。そのため、個々のサイト閲覧者が被る実害自体は軽微であった。\n\n5 第一審の解説及び評釈また先行研究としては、以下のようなものがある。板倉陽一郎「解題 コインハイブ事件[横浜地裁平31.3.27 判決]」 Law & Technology 85 号 (2019) 15-19 頁、高木浩光「コインハイブ事件で否定された不正指令電磁的記録該当性とその論点[横浜地裁平成 31.3.27 判決]」Law & Technology 85 号 (2019) 20-30 頁、永井善之「判批」法セ増（新判例解説Watch) 26 号 (2020) 187-190 頁。\n\n6 原審の解説及び評釈としては、以下のようなものがある。品田智史「判批」法セ 787 号 (2020) 134 頁、永井善之「不正指令電磁的記録概念について」金沢法学 63 巻 1 号 (2020) 79-146 頁、三重野雄太郎「不正指令電磁的記録の解釈と該当性判断枠組:コインハイブ事件を素材に」社会学部論集 71 号 (2020) 127-148 頁、白鳥智彦「判批」警察学論集 73 巻 9 号 (2020) 206 頁、木下昌彦「コンピュータ・プログラム規制と漠然性故に無効の法理（上）コインハイブ事件を契機とした不正指令電磁的記録に関する罪の憲法的考察」NBL1181 号 (2020) 4-12 頁、木下昌彦「コンピュータ・プログラム規制と漠然性故に無効の法理（下）コインハイブ事件を契機とした不正指令電磁的記録に関する罪の憲法的考察」NBL1182 号 (2020) 39-50 頁、西貝吉晃「技術と法の共進化を企図した法解釈の実践: コインハイブ高裁判決を素材に」法セ 792 号 (2021) 40-46 頁、板倉陽一郎「解題 コインハイブ事件控訴審」Law & Technology 91 号 (2021) 40-45 頁、高木浩光「コインハイブ不正指令事件の控訴審逆転判決で残された論点」Law & Technology 91 号 (2021) 46-57 頁、永井善之「判批」法セ増（新判例解説 Watch) 27号 (2021) 153 頁、岡田好史「判批」刑事法ジャーナル 68 号 (2021) 159-164 頁、小田啓太=西貝吉晃「アプリ開発の実務を踏まえた不正指令電磁的記録に関する罪の一考察: コインハイブ事件を契機として」千葉大学法学論集 36 巻 (2021) 1 号 105-136 頁。\n\n7 本稿執筆時点において、解説として、永井善之「判批」新・判例解説 Watch 刑法 No.176 https://www.lawlibrary.jp/pdf/z18817009-00-071762137_tkc.pdf (2022-4-4参照）、コインハイブ事件にコメントするものとして、前田雅英「判批」WLJ判例コラム 254 号 (2022) (2022WLJCC006)、河津博史「判批」銀行法務 21 881 号 (2022) 70 頁がある。なお、本稿の執筆後、今井猛嘉 「判批」法教 500 号 (2022) 33-39 頁、西貝吉晃「判批」法セ 808 号 (2022) 46-55 頁に接した。\n\n8 なお、不正指令電磁的記録に関する罪の立法経緯や解説については、立案担当者の解説である杉山徳明=吉田雅之「 『情報処理の高度化等に対処するための刑法等の一部を改正する法律』について（上） 」法曹時報 64 巻 4 号 (2012) 64 頁以下を参照。\n\n9 いわゆる「イカタコウイルス事件」東京地判平成 23 年 7 月 20 日判タ 1393 号 366 頁。\n\n10 山口厚「サイバー犯罪に対する実体法的対応」ジュリスト 1257 号 (2013) 18 頁、嶋矢貴之「第 19 章の 2 不正指令電磁的記録に関する罪」西田典之他編『注釈刑法 第 2 巻』（有斐閣、2016) 545 頁ほか。\n\n11 杉山=吉田・前掲注 8) 65頁。\n\n12 法務省「 いわゆるコンピュータ・ウイルスに関する罪について 」(2012) 1 頁 http://www.moj.go.jp/content/001267498.pdf(2022-4-4参照）。\n\n13 杉山=吉田・前掲注 8) 66 頁。\n\n14 杉山=吉田・前掲注 8) 66 頁。\n\n15 この点、法益の抽象化によって事実上の処罰の早期化につながるとの批判がある。渡邊卓也『ネットワーク犯罪と刑法理論』（成文堂、2018） 266 頁以下。\n\n16 2 号類型については、「人が電子計算機を使用するに際してその意図に沿うべき動作をさせず、又はその意図に反する動作をさせるべき不正な指令を与える」ものとして実質的には完成しているものの、そのままでは電子計算機において動作をさせる状態にないものをいうとされ、不正な指令を与えるプログラムコードを記述した電磁的記録や紙媒体がこれに該当しうる。法務省文書・前掲注12) 5頁。なお、 2 号の客体は「プログラムの機能ないし構造上、「不正指令」を与えるものとして設計されているもの」に限定すべきであるとの主張もある。石井徹哉「いわゆる「デュアル・ユース・ツール」の刑事的規制について（中） 」千葉大学法学論集 26 巻 4 号 (2012) 17 頁以下。\n\n17 いわゆるデュアルユース。石井徹哉「いわゆる「デュアル・ユース・ツール」の刑事的規制について（上） 」千葉大学法学論集 26 巻 1-2 号 (2012) 66 頁。\n\n18 例えば、ハードディスク内のファイルを全て消去するプログラムが、その機能を適切に説明した上で公開されるなどしており、ハードディスク内のファイルを全て消去するという動作が使用者の「意図に反する」ものでない場合は、処罰対象とはならない。法務省文書・前掲注 12) 4 頁。\n\n19 杉山=吉田・前掲注 8) 。\n\n20 立法立案者の一人の執筆による。吉田雅之「第 19 章の2 不正指令電磁的記録に関する罪」大塚仁他編『大コンメンタール刑法第 8 巻（第三版） 』（青林書院、2014） 345 頁。\n\n21 法務省文書・前掲注 12)。\n\n22 松平浩一「不正指令電磁的記録に関する罪の解釈に関する質問主意書」（令和元年 6 月 21 日提出 質問第 294 号）。\n\n23 「衆議院議員松平浩一君提出不正指令電磁的記録に関する罪の解釈に関する質問に対する答弁書」（令和元年 7 月 5 日受領 答弁第二九四号）。吉田・前掲注 20) 345 頁に同旨。\n\n24 この点、「現実にその機能を認識したらその実行を許していたか?という判断も「べき」か否かの規範的判断に混入しうる点で処罰範囲が恣意的に決定されうる」 との危惧も指摘される。西貝吉晃「不正指令電磁的記録に関する罪の解釈論」罪と罰 58 巻 3 号 (2021) 21 頁。\n\n25 杉山=吉田・前掲注 8) 71 頁参照。この点「なぜ一般に認識「すべき」なのかは判然としない。同広告を鬱陶しく感じるものが相当数いることが容易に想定できる以上、反意図性を定型的に否定するのは難しい」との批判もある。西貝・前掲注 24) 22 頁。\n\n26 永井・前掲注 5) 189 頁に同旨。\n\n27 永井（金沢法学） ・前掲注 7) 103 頁は「結局これは、反意図性についても不正性についても、その肯否の判断に際しては使用者一般により、即ち社会的に許容されるものであるかが基準とされざるをえないためであるように思われる」とする。\n\n28 杉山=吉田・前掲注 8) 83 頁参照。\n\n29 「意図に反する」か否かの判断と「不正」か否かの判断は連動すると解するのが自然であるとの見解として、渡邊・前掲注 15) 269 頁。\n\n30 吉田・前掲注 20) 346 頁参照。この点、左記吉田の大コンメンタールにおける記述は、「「意図に反する動作をさせる」の解釈を保護法益に照らして信頼を害するものに限定」しており、「「意図に反する動作をさせるものなら」その時点で「信頼を害するものとして……当罰性がある」という当然のことを述べたに過ぎない」とする見方もある。高木・前掲注 5) 26 頁。\n\n31 「法制審議会刑事法（ハイテク犯罪関係）部会第 3 回会議議事録 」（平成 15 年 5 月 15 日開催） https://www.moj.go.jp/shingi1/shingi_030515-1.html(2022-4-4 閲覧）。\n\n32 経済産業省「サイバー刑事法研究会報告書「欧州評議会サイバー犯罪条約と我が国の対応について」」21 頁。\n\n33 この点、西貝・前掲注 24) 22 頁以下は、サイバー犯罪条約準拠の情報セキュリティ（CIA=機密性、完全性及び可溶性）観点から、CIAを侵害するか否かの観点から不正性要件、保護法益の理解の修正を検討している。\n\n34 これをサイバー犯罪の一種であるとする記述もみられる。Interpol. “Cryptojacking”. https://www.interpol.int/Crimes/Cybercrime/Cryptojacking （2022-04-04閲覧）。ただ、当該記述においてはインストール型を想定してる。\n\n35 前田・前掲注 7) 5 頁。\n\n36 Rainer Franosch. “Sicherheit in einer offenen und digitalen Gesellschaft”. BKA Herbsttagung 21, 22. November 2018, 2018. p.5.\n\n37 例えば、Norton「 クリプトジャッキングとは?その基本から撃退方法まで 」ノートンウェブサイト、https://jp.norton.com/internetsecurity-general-security-cryptojacking.html（2022-4-4閲覧）参照。\n\n38 この点、Said Varlioglu et al. “Is Cryptojacking Dead After Coinhive Shutdown?”. 2020 3rd International Conference on Information and Computer Technologies (ICICT). 2020, pp. 385 - 389 参照。\n\n39 Franosch. op.cit. p. 5.\n\n40 Google Scholar および LexisNexis 、Beck-Online の各文献検索サービスを用いて調査を行った。\n\n41 例えば、ルーマニアの犯罪組織に属する被告人らが、共謀の上、電信詐欺、加重 ID 窃盗、マネーロンダリングへの関与、マルウェアを用いた暗号通貨のマイニングを行った事案につき合衆国において有罪となった事案がある。United States v. Nicolescu, 17 F.4th 706.\n\n42 永井・前掲注 7) 3 頁。\n\n43 杉山=吉田・前掲注 8) 65 頁。\n\n44 永井・前掲注 7) 3 頁。この点、左記では、第一審についてもプログラムの機能との齟齬という事実的判断に立つとする。\n\n45 原判決の様に、「反意図性につき形式的、事実的な判断ではなく、より実質的な規範的判断をなすとすると、それにより不正性要件の判断の先取りないし、それとの一体化となる」とし、本件最高裁の判断はこれを回避しうるとの見解もある。永井・前掲注7) 3頁以下。\n\n46 仮に他の機能が当該広告表示プログラムに付随している場合においては個別の機能や動作において社会的に許容されるか否かを判断する必要があろう。\n\n47 例えば、木下・前掲注 6)。"
}
|
[
{
"id": "140926",
"date": "27 Jun 2022",
"name": "Osamu Magata",
"expertise": [
"Reviewer Expertise 法学・刑事法"
],
"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\nⅠ. 本論稿の概要 1. ［全体の概略］ 本論稿は、いわゆる「コインハイブ事件」上告審判決(最判令和4・1・20)を素材に、不正指令電磁的記録に関する罪(刑法168条の2および3)の客体性要件たる「反意図性」および「不正性」について論じたものです。また、本判決に対して批判的な観点から検討が加えられています。 2. ［筆者の問題意識］ これまでの裁判例において、本罪の反意図性要件・不正性要件について詳細に検討したものはなく、これらの要件の認定基準はいまだ明確ではないという点に、筆者の問題意識が向けられているものと思われます。 3. ［筆者の見解］ 本罪の保護法益は、一般に、電子計算機のプログラムに対する社会一般の者の信頼という社会的法益であると理解されており、筆者はこれを妥当としています。そのうえで、反意図性要件につき、これも(不正性要件に同じく)法益侵害性と関係する要件であることから、規範的に判断されるものであり、その判断は社会的許容性の観点を入れてなされるべきであるとの主張が示されています。すなわち、反意図性要件は、社会的許容性判断が中心となる不正性要件と「重なり合う」のであり、両要件は「実質的な判断においては区別困難となろう」とするわけです。 こうした前提から、本件最高裁判決の結論に関しては同調しつつも、結論を導く論理や事案の特性に関する前提理解において、不十分な点がある旨、指摘がなされています。すなわち「損害が軽微ゆえに、本件プログラムコードの掲載自体の社会的許容性あるとする方が妥当だったのではなかろうか。」、「マイニングプログラムにおいては潜在的なリスクが存する。その点を過小評価しているのではないか」などとの叙述が展開されています。\n\nⅡ. 評価 1.［結論］ 条件付き承認 2.［理由］ 不正指令電磁的記録に関する罪は、2011年(平成23年)の刑法一部改正により新設された、比較的新しい処罰規定です。そのため、保護法益や成立要件に関する議論は進展過程にあるといえるでしょう。そのような状況のなか、webサイトにアクセスした人の電子計算機のCPUを同意なく使用して暗号資産のマイニングを実行させる行為が、不正指令電磁的記録保管罪(刑法168条の3、168条の２第1項)に当たるとして立件されました。この事案は「コインハイブ事件」として耳目を集めてきましたが、特に問題となったのは、同罪の客体性要件たる「反意図性」・「不正性」の充足いかんです。上記最高裁判決は、この争点に関して一定の判断を示し、無罪との結論を示したものであり、その意義は大きいといえます。 筆者、高良氏による本論稿は、そのような新しい重要な最高裁判断を扱い、分析したものである点で、少なくない意義があります。また、反意図性要件および不正性要件をめぐる解釈のあり方について検討がなされているとともに、ドイツにおける類似事案の取扱いについての言及もあり、参照価値があります。さらに、反意図性要件および不正性要件に関し、実質判断において区別し難いものであり、重なり合う要件であるとする筆者の主張は興味深く、議論の活性化を促しうるものといえます。 もっとも、いくつかの点で不明確な点が見受けられるため、条件付き承認と判定します。 ・全体を通しての留意点は、「Ⅲ. コメント」として記載します。参考になさってください。 ・具体的な要修正箇所は、「Ⅳ. 要修正箇所」(1)-(9)として記載します。これらに関しては、適切に修正を行ってください(承認条件)。 ・修正は必須ではありませんが、参考にしていただきたい点を「Ⅴ. 参考意見」(a)-(d)として挙げます。\nⅢ. コメント(全体を通しての留意点) 筆者によれば、本稿は「コインハイブ事件の各裁判例を分析・検討することを通して、不正指令電磁的記録に関する罪における反意図性と不正性の判断基準を明らかにすることを目的とするもの」であるかことから、論文として執筆されたものと思われます。 しかし、反意図性要件・不正性要件それぞれの内容に関する筆者自身の見解の全体像が、必ずしも明確に叙述されていません。その意味で、反意図性・不正性の判断基準を明らかにするという筆者の目的が達せられていないきらいがあります。両要件の内容をいかに解するのかは本論文のコアとなる部分ですから、より充実し、整理された論述が求められます。\nⅣ. 要修正箇所 (1) Ⅲ・2・第4段落: 「情報リテラシーについては利用者において差があり、当該プログラムについて個々人としてみた場合、例えばエンジニアにおいて一般的に知りうる情報を、情報機器に疎い者はもちろん通常のユーザーですら知りえないことは当然にあることである。この点、日々開発されるプログラムについて通常人においては知りえず、常に「一般的に認識すべき」場合ではなく、反意図性が認められうるのであり、一般人の認識可能性のみを基礎とするのであれば、反意図性の範囲は規範的判断によって限定した意味を失してしまうであろう。」の部分について。\n\n(1-1)「限定した意味を失してしまう」は、過度な否定的評価と思われます。仮に、一般人の認識可能性のみを基準としたとしても(一般人の認識可能性と実際との形式的な齟齬のみから反意図性を判断したとしても)、たとえば、プログラム送信を受けた実際のユーザーは情報機器に疎かったことから認識できかったものの一般ユーザーならば認識することができたといえるプログラムの動作が問題となった場合に、反意図性を規範的に否定できるのですから、規範的判断による限定機能はその意味で有効に働きます。「限定した意義が弱まってしまう」など、少なくとも表現を変えることを含め、検討してください。\n\n(1-2)おそらく筆者は、高度な知識をもつ特別なユーザーのみが知りうるプログラムが問題となるケース(一般ユーザには認識できないケース)であっても、場合によっては、反意図性を否定すべきだと考えるのでしょう。しかし、どういう場合がそれに当たるのかについて具体的な叙述がなく、主張が伝わりにくくなっています。この部分について加筆等を行ってください。 (筆者の立場はおそらく控訴審が展開した論理に近いにように思われるので、加筆に当たってはその点にも留意するとよいでしょう。)\n(2) Ⅲ・2・第4段落:「仮に「一般人に認識すべき」プログラムであったとしても、当該プログラムが多大な負担を強いるのであれば、一般人がこれを望まないことは、当然にありうる。かかる判断においては、実質的な負担の存否・軽重などに鑑み、どの程度の負担であれば一般に許容できるのか、つまりは、社会的許容性を観念せざるを得ないと思われる。」の部分について。\n\n(2-1)「多大な負担」、「実質的な負担」、「どの程度の負担」というように「負担」という語が多用されていますが、用語として適切か再検討し、より適切な表現に変えてください。\n\n(2-2) 筆者は、「どの程度の負担であれば一般に許容できるのか」という(社会的許容性の)観点を、反意図性の要件判断において(も)用いるべきであるとしています。この観点は、(本件最高裁判断が示すように、)もっぱら不正性要件に関わるものとして位置づけることも十分可能であるため、なぜ反意図性の要件に(も)かかわらしめるのかについて、より立ち入った説明が求められます。\n(3) Ⅲ・2・第5段落:「両者は重なりあうものであり、形式的な分類はともかくとして、実質的な判断においては区別困難となろう。」の部分について。\n\n(3-1) 両者(反意図性要件と不正性要件)が「重なり合う」とは、より詳しくはどういうことか、またなぜそうなるのか、もう少し説明を付してください。\n\n(3-2) また、両者は「実質的な判断において区別困難となろう」としていますが、これは、そうなってしかるべきだ(本来そういうものだ)という趣旨であるのか、そうであってはならないという意からのものか、判然としません。他の叙述部分から推測しますに、おそらく前者に近いものと思われますが〔Ⅳ・「不正性について」の部分に「反意図性と不正性は不可分であるとの私見」とある〕、やはり主張の趣旨が明確でないので、書きぶりを改善することを検討なさってください。\n(4) Ⅲ・2・第6段落: (4-1) この段落において「意図」という語が複数回用いられていますが、行為者の主観面としての意図と、一般ユーザーの規範的主観面としての意図とを、同じ扱いにしているように読めます。このような書き方でよいのか再検討なさってください。\n(5) Ⅳ・「反意図性について」: 「反意図性については、「一般の使用者が認識すべき動作と実際の動作が異なる場合に肯定される」とし、一般の認識可能性を判断基準としつつ、文言上は一般人の認識と現実の齟齬を判断している事実的判断であるようにも見える。」の部分について。\n\n(5-1)「一般人の認識と現実の齟齬を判断」する手法を「事実的判断」と呼ぶのは、ミスリードとなりえます。具体的な個々のユーザーの実際の認識でなく、通常ユーザーの認識可能性というものを想定し、それと現実との齟齬の有無を判断基準としようとしている時点で、すでにそれは規範的判断です。「事実的判断」ではなく、異なる表現を用いることを検討してください。\nひょっとすると、筆者において、「規範的判断」・「事実的判断」の意について誤解があるかもしれませんので、以下、参考までに若干説明しておきます。 反意図性要件をめぐって使用される「規範的判断」という語は、二通りに使用されています。すなわち、第一は、個別具体的な使用者の実際の認識を基準とするのではなく、一般に認識すべきと考えられるところを基準にするという意味〔一般人であれば知りうるプログラムの動作かという観点〕として使用されており、第二は、当該プログラムの機能の内容や機能に関する説明内容、想定される利用方法等を考慮に入れて、一般ユーザーであれば許容するプログラムの動作かどうかを基準にするという意味〔一般人基準で見たときの当該プログラムの許容可能性〕として使用されています。 1審も最高裁も、一般人の認識可能性を問題にし、それと現実との齟齬の有無を基準にする判断手法に依拠していますので、その限りでやはり規範的判断(第一の意味における規範的判断)を展開しているといえます (ただ、第二の意味における規範的判断はしておらず、その点で控訴審の判断方法と相違がありますので、そうしたところを押さえた論評をすべきでしょう)。\n\n(5-2) 如上の観点からしますと、「本件最高裁が反意図性の判断における規範的判断を放棄したとまではいえないであろう。」という分析内容は不可解に映ります。この部分の叙述についても再検討なさってください。\n(6) Ⅳ・「不正性について」: 「この点、反意図性と不正性は不可分であるとの私見によれば妥当な判断であると思われる。」の部分について。\n\n(6-1) 反意図性と不正性が「不可分」とはどういう趣旨であるか、説明を付してください。\n(7) Ⅳ・「不正性について」:「しかし、同意を得ずに他者のコンピュータに介入操作するクリプトジャッキングの潜在的な危険性に鑑みれば、「社会一般の信頼」を害する危険性は少なくない。」の部分について。\n\n(7-1) そうなのであれば、最高裁の結論とは異なり、不正性を肯定すべきではないかとの疑問が生じます。この点、筆者は、「損害が軽微ゆえに…社会的許容性〔が〕ある」と説いていますが、何をもって損害が軽微であるというのか、説明が欲しいところです。この点について説明を付してください。\n(8) Ⅴ・第2段落: 「結びに変えて、本稿で扱ったコインハイブ事件の射程と意義を述べたい。」の部分について。\n\n(8-1) 本判決の意義は述べられていますが、射程について実質的な明確な記述が見当たりません。本判断は具体的にどういう事案に判断拘束性を及ぼすのか、言及してください。 (なおその際、本件が、閲覧者の電子計算機のCPU使用率調整値を0.5と設定していた事案であることにも留意するとよいでしょう。)\n(9) Ⅴ・第2段落: 「反意図性が認められる場合の処罰範囲を限定するものとして不正性の要件があり、反意図性判断が不正性判断の前段階におかれることが明示された点は評価できる。」の部分について。\n\n(9-1) 上記は、本件最高裁判断に対する筆者の評価ですが、筆者はⅣ・「不正性について」のなかで、「反意図性と不正性とは不可分である」と主張しており、「評価できる」の趣旨が必ずしも明らかではありません。いかなる趣旨であるのか述べてください。\nⅤ. 参考意見 (a) Ⅲ・2・第2段落・最後の一文\n\n(a-1)伝えたいことが伝わる文になっているか再検討してください。\n(b) Ⅲ・2・第4段落:「仮に「一般人に認識すべき」プログラムであったとしても、当該プログラムが多大な負担を強いるのであれば、一般人がこれを望まないことは当然にありうる。かかる判断においては、実質的な負担の存否・軽重などに鑑み、どの程度の負担であれば一般に許容できるのか、つまりは、社会的許容性を観念せざるを得ないと思われる。」の部分について。\n\n(b-1) 話題はここで、直前までの叙述内容(一般人に認識できないプログラムの話題)とは逆のケース、すなわち一般人が認識すべきプログラムの話題に切り替わっていますが、書きぶりからそうだとは分かりにくく、読者を混乱させる恐れがあります。上記部分の直前に、「反対に」とか、「逆に」など、適切な接続詞を入れるとよいように思われます。\n\n(b-2) 筆者は、「どの程度の負担であれば一般に許容できるのか」という(社会的許容性の)観点を、反意図性の要件判断において(も)用いるべきであるとしています。しかし、そうすると、すでに論者によって指摘されているように(永井善之「判批」新・判例解説 Watch 刑法 No.176、4頁参照)、反意図性要件の判断は不正性要件の判断の先取りまたはそれとの一体化に至りうるかもしれません。筆者はこの点についてどう考えるでしょうか。読み手が関心をもつこととなりうるので、可能であればこの点に言及されると、説得性が増すでしょう。\n(c) Ⅳ・「不正性について」:「不正性については、原審において「閲覧者に利益を生じさせない一方で一定の不利益を与えるものである上、不利益に関する表示等もされない」点で、「閲覧者の電子計算機を、閲覧者以外の利益のために無断で使用する点を基礎に不正性、本罪の保護法益である、「社会一般の信頼」保護という原則により依拠したものであるといえる。」の部分について。\n\n(c-1) 読み手に伝わる表現になっているか、確認なさってください。\n(d) Ⅴ・第2段落: 「私論〔試論?〕であるが、裁判所が反意図性判断における規範的判断を放棄していないと考えるのであれば、(1) 反意図性にかかる事実判断、(2) 反意図性にかかる規範的判断、(3) 不正性判断との流れで検討がなされ、処罰範囲を限定していくとも考えられる。」の部分に関して。\n\n(d-1) (前述のように、)そもそも、裁判所が反意図性判断における規範的判断を放棄しているとは思えないので、「放棄していないと考えるならば」という論の進め方には違和感があります。\n\n以上\n\n本研究は明確かつ正確に提示されたものであり、最新の文献を引用していますか。 一部該当\n\n研究設計は適切で学術的価値がありますか。 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。 対象外（統計を使っていない\n\n結果の基礎となるソースデータはすべて入手可能で再現性を十全に保証していますか。 はい\n\n結論は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": "8479",
"date": "07 Jul 2022",
"name": "Kouya Takara",
"role": "Author Response",
"response": "中央大学 曲田統 先生 この度はお忙しい中、査読依頼をお引き受けいただきありがとうございます。 また、詳細なご指摘をいただきました点につきましても御礼申し上げます。 ご指摘いただきました点を反映し、近日中に修正版を投稿いたします。 何卒よろしくお願いいたします。 髙良幸哉"
}
]
},
{
"id": "140928",
"date": "30 Jun 2022",
"name": "Takashi Hikasa",
"expertise": [
"Reviewer Expertise 刑法 独占禁止法 サイバー犯罪 AI 自動運転"
],
"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\n本論文は、コインハイブ事件の最高裁判決を素材に、不正指令電磁的記録に関する罪の、①保護法益、②反意図性、③不正性について検討し、同罪の内実を明らかにするものである。 原審では、反意図性に関して「規範的評価」が要求されているものの、最高裁ではこれに関する文言が見受けられない点につき、筆者は、保護法益についての文言部分との対比等を踏まえ、規範的評価自体を否定したとまではいえない旨の指摘をする。かかる指摘は、技術的・社会的背景（CPUの使用程度や消費電力、ウェブサイトにおける広告表示プログラムとの異同）を分析する筆者の根拠づけと相まって、妥当であると考えられる。 反意図性および不正性が区分けとして不明確であることやその内容が漠然としていること、両者の関係が独立なのか、反意図性が認められると原則不正性は推定されるのか、など、従来の争点に対し、本論文では、保護法益論（「社会一般の信頼」）との関係性および、クリプトジャッキングの社会的意味を分析することで、これらの問題に対する的確な回答を呈示している。\n\n本研究は明確かつ正確に提示されたものであり、最新の文献を引用していますか。 はい\n\n研究設計は適切で学術的価値がありますか。 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。 対象外（統計を使っていない\n\n結果の基礎となるソースデータはすべて入手可能で再現性を十全に保証していますか。 はい\n\n結論は結果により妥当な裏付けを得ていますか。 はい",
"responses": [
{
"c_id": "8480",
"date": "07 Jul 2022",
"name": "Kouya Takara",
"role": "Author Response",
"response": "多摩大学 樋笠尭士 先生 この度は、お忙しい中、査読依頼をお引き受けいただきありがとうございます。 近日中に、先生方からのご指摘を反映した修正版を投稿いたします。 何卒、よろしくお願いいたします。 髙良幸哉"
}
]
},
{
"id": "140924",
"date": "05 Jul 2022",
"name": "Yoshifumi Okada",
"expertise": [
"Reviewer Expertise 刑法"
],
"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\n本論文では、暗号資産をマイニングするスクリプトの利用を巡り問題となった不正指令電磁的記録に関する罪の成立要件、とりわけ反意図性と不正性の関係について、最高裁として初めて判断を示した判例をもとに明らかにし、その判断基準について検討している。マイニングツールの利用の適否は社会的関心事でもあり、この問題を扱った意義は非常に大きい。しかし、用語の理解が十分でない、構成にわかりにくい点等が見受けられた。詳細は、以下のコメントを参考にしていただきたい。 ・マルウエアは、不正プログラム全般を指すものであり、コンピュータ・ウイルス、ワームなどを含んだ概念です。 ・crypto-assetを指す語として日本の資金決済法では「暗号資産」としています。判決文中の引用を除き、暗号通貨よりも、暗号資産という語を使用した方がよいと思います。 ・不正指令電磁的記録の客体該当性が問われた先行裁判例としては、仙台地判平成30年7月2日LEX/DB文献番号25560905、東京高判令和元年12月17日高検速報（令1）号362頁があるので、触れておく必要があるのではないでしょうか。 ・最高裁は、不正指令電磁的記録の該当性を認める要件として反意図性と不正性を明確に区別することを明らかにし、両者の関係を並列的に捉えていると解されます。この点について、反意図性と不正性の関係について不可分であるという自説からの検討があるとより論旨が明確になると思います。 ・プライバシー・バイ・デザインは注で説明がある方がよいと思います。また、この点に触れるのであれば、プライバシー・バイ・デザインがGDPRにより法的要求事項になったことや、GDPR違反による高額の制裁金が科された事例が生たことでグローバルスタンダードな設計思想になってきていることを示すとよいのではないでしょうか。 ・脚注で、法学セミナー、法学教室のみ略称表記となっていますので、他の注同様に正式名とするか、略称で統一するのであれば「法律時報文献月報」を基にするとよいと思います。 ・構成としては、不正指令電磁的記録に関する罪の概要を示した上で、先行事例の紹介、コインハイブ事件の概要、最高裁判決の分析、反意図性と不正性の要件についての検討とした方が理解しやすくなるように思います。\n\n本研究は明確かつ正確に提示されたものであり、最新の文献を引用していますか。 はい\n\n研究設計は適切で学術的価値がありますか。 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。 対象外（統計を使っていない\n\n結果の基礎となるソースデータはすべて入手可能で再現性を十全に保証していますか。 はい\n\n結論は結果により妥当な裏付けを得ていますか。 はい",
"responses": [
{
"c_id": "8481",
"date": "07 Jul 2022",
"name": "Kouya Takara",
"role": "Author Response",
"response": "専修大学 岡田好史 先生 この度は、お忙しい中、急な査読依頼をお引き受けいただきありがとうございます。 また、詳細なご指摘をいただきましたことにつきましても御礼申し上げます。 ご指摘いただきました点を反映させ、近日中に修正版を投稿予定です。 何卒、よろしくお願いいたします。 髙良幸哉"
}
]
},
{
"id": "140927",
"date": "07 Jul 2022",
"name": "Ko Shikata",
"expertise": [
"Reviewer Expertise 刑事法学、社会安全政策論"
],
"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\n本稿は、刑法の不正指令電磁的記録に関する罪の客体要件について、本罪の著名事件であるコインハイブ事件に対する最近の最高裁判決の評価を中心に検討したものである。本稿のような判例の評価という規範的な判断に関する客観性は、自然科学的な意味での客観性ではなく、多方面の視点や価値観を参照して得られるものと言える。その意味で本稿の特徴は、本判決の判例評釈の多くが指摘している技術開発の自由の視点を紹介するのはもちろん、他の評釈ではあまり顧みられてこなかった一般ユーザーの視点や、コインハイブというサービスやその技術的基礎となっているクリプトジャッキングに対する海外の視点をも紹介し、客観的でバランスのとれた評釈がなされている点にあるといえる。\n本罪の客体である不正指令電磁的記録の要件に関する論点としては、本稿も示しているように、一般に、本罪の保護法益、いわゆる反意図性要件、不正性要件が挙げられるが、前2者については論者による評価の差は比較的小さい。論者により評価が分かれ、本事件でも第一審・最高裁と高裁とで見解が分かれたのは不正性要件であった。\n反意図性要件は広く理解され本罪の処罰範囲を広げ得るものだけに、本罪が過剰な規制とならないためには不正性要件が適切な限定をかける機能を果たす必要があるのは、他の多くの評釈が指摘しているとおりである。他方で、本件をはじめとする一連のコインハイブ関連事件には、自己の端末の空き容量を知らない間に利用された多数の一般ユーザーが存在する。一人一人のユーザーにしてみると、その受けた影響は確かに被害と認識できない程度に軽微なものである。しかし、現在のインターネット空間においては極めて多数の者を相手に瞬時に行動を起こすことができ、個々人には微小な影響しか与えないプログラムであっても、ネットワークを通じれば多数の者の端末をその知らない間に利用して、全体としては大規模な利益をあげることができる可能性がある。個別の端末に対する影響を中心的な考慮要素とした本判決の枠組みでは、例えばボットネットを用いて個々のユーザーに対しては本件と同様に至極軽微な影響しか与えないが、数千、数万の一般ユーザーの端末を勝手に利用することによって莫大な利益をあげるような活動が許されることになりかねないのではないかという疑念がぬぐい切れない。\nこのように考えると、我が国法体系が保護すべき情報セキュリティには、サイバーセキュリティ基本法第2条が示しているように、個々の端末のセキュリティだけでなく「情報通信ネットワークの安全性及び信頼性」が含まれるべきであり、本罪の保護法益である「電子計算機のプログラムに対する社会一般の者の信頼」にも情報通信ネットワークが公正に利用される信頼性の観点が含まれるべきではなかろうか。したがって不正性要件の判断においても、個々の端末への影響だけでなく情報通信ネットワークの信頼性・公正性を考慮して判断されるべきものであろう。\n査読者と同様の問題意識からであるかは分からないが、本稿は、「ユーザーの認識の外でマルウェア等が起動することは、ユーザーやネットワークへの潜在的なリスクという意味で不正性の認定要素ともなりうる」ことを指摘し、一般ユーザーや情報通信ネットワーク全体の信頼性に通ずる視点を示している。さらに、コインハイブに対する国際的評価やウェブサイト閲覧型のクリプトジャッキングの技術的危険性についても指摘している。\nその上で本稿は、本判決について、本件に使われた「当該プログラムが与えうる侵害の危険性と、個人領域への干渉は小さくない。本件行為対応が社会的に許容される範囲に収まるとしても、マイニングプログラムにおいては潜在的なリスクが存する。その点を過小評価しているのではないかとの評価はなしうるところである」と結論付けている。\nこのように、本稿は、他の多くの評釈が指摘する技術開発の自由に十分配意しつつも、一般ユーザーや情報通信ネットワークの信頼、国際的社会の視点といった幅広い視野に立って、客観的で妥当な結論に達しているものと評価することができる。\n\n本研究は明確かつ正確に提示されたものであり、最新の文献を引用していますか。 はい\n\n研究設計は適切で学術的価値がありますか。 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。 対象外（統計を使っていない\n\n結果の基礎となるソースデータはすべて入手可能で再現性を十全に保証していますか。 はい\n\n結論は結果により妥当な裏付けを得ていますか。 はい",
"responses": [
{
"c_id": "8681",
"date": "14 Sep 2022",
"name": "Kouya Takara",
"role": "Author Response",
"response": "中央大学 四方光先生 この度はお忙しい中、査読をお引き受けいただきありがとうございます。 近日中に、他の査読者の先生方からのご指摘も踏まえ、ver. 2を投稿予定です。 よろしくお願い申し上げます。 髙良幸哉"
}
]
}
] | 1
|
https://f1000research.com/articles/11-657
|
https://f1000research.com/articles/11-651/v1
|
14 Jun 22
|
{
"type": "Research Article",
"title": "Investigating audible and ultrasonic noise in modern animal facilities",
"authors": [
"Andrew Parker",
"Liane Hobson",
"Rasneer Bains",
"Sara Wells",
"Michael Bowl",
"Andrew Parker",
"Liane Hobson",
"Rasneer Bains",
"Sara Wells"
],
"abstract": "Background: The environmental housing conditions of laboratory animals are important for both welfare and reliable, reproducible data. Guidelines currently exist for factors such as lighting cycles, temperature, humidity, and noise, however, for the latter the current guidelines may overlook important details. In the case of the most common laboratory species, the mouse, the range of frequencies they can hear is far higher than that of humans. The current guidelines briefly mention that ultrasonic (>20 kHz) frequencies can adversely affect mice, and that the acoustic environment should be checked, though no recommendations are provided relating to acceptable levels of ultrasonic noise. Methods: To investigate the ultrasonic environment in a large mouse breeding facility (the Mary Lyon Centre at MRC Harwell), we compared two systems, the Hottinger Bruel and Kjaer PULSE sound analyser, and an Avisoft Bioacoustics system. Potential noise sources were selected; we used the PULSE system to undertake real-time Fourier analysis of noise up to 100 kHz, and the Avisoft system to record noise up to 125 kHz for later analysis. The microphones from both systems were positioned consistently at the same distance from the source and environmental conditions were identical. In order to investigate our result further, a third system, the AudioMoth (Open Acoustic Devices), was also used for recording. We used DeepSqueak software for most of the recording analysis and, in some cases, we also undertook further spectral analysis using RX8 (iZotope, USA). Results: We found that both systems can detect a range of ultrasonic noise sources, and here discuss the benefits and limitations of each approach. Conclusions: We conclude that measuring the acoustic environment of animal facilities, including ultrasonic frequencies that may adversely affect the animals housed, will contribute to minimising disruption to animal welfare and perturbations in scientific research.",
"keywords": [
"Noise",
"Mouse",
"Welfare"
],
"content": "Introduction\n\nEnvironmental factors, such as temperature, light cycle humidity and noise can have significant impacts on the physiology, behaviour and health of animals.1–5 It is therefore key for both animal welfare and the quality and reproducibility of scientific findings that animals are housed in suitable conditions. Considerable research effort has focussed on determining the environmental conditions most appropriate for each species most commonly used in scientific studies; the basis of legislation regarding the use of animals in many countries is informed by these data.6–9\n\nThe importance of the maintenance of certain environmental parameters within strict limits is not underestimated by those working with and caring for animals. Animal facilities have systems and procedures in place to prevent deviations from the limits outlined in animal use legislation, and have contingency plans in place in the event of a failure.9,10 The conditions in which animals are housed are also stated in scientific publications and, if a system failure did occur during the study, the potential consequences are typically discussed therein. However, not all environmental factors are considered to be of equal importance to animal welfare and phenotype. In some cases, this is because current evidence does not show an impact of these environmental factors on welfare or phenotype. In others, there is emerging evidence of an impact, and potential reason for stricter control of these parameters, but research remains in relatively early stages and this has yet to transition fully to the legislature.\n\nMice are the most commonly used animals in scientific research.11 Recent research has shown that the acoustic environment can have significant impacts on hearing,12–20 anxiety,21–24 cardiovascular function,25,26 glucose tolerance27,28 and reproductive success,29,30 among others. The need for stricter control of the acoustic environment for mouse welfare and to ensure the production of high quality scientific data has been highlighted in previous reviews.31,32 Other publications have made recommendations about how the acoustic environment might be controlled in animal housing facilities.31,33 In response, governmental bodies and special interest groups released guidelines for monitoring and controlling the acoustic environment.6–8,10 For example, the Home Office in the UK recommends that noise levels are assessed at a range of frequencies and that extraneous noise is minimised.10\n\nThe current guidelines on monitoring the acoustic environment encourages animal housing facilities to monitor noise levels and highlights the importance of this for mouse welfare. However, as research continues to emerge on the impact of noise and the importance of ultrasonic vocalisations (USVs) in social communication in mice,34–38 it is becoming increasingly clear that the current guidelines may lack the specificity required to minimise detrimental impacts on welfare and scientific quality. For example, there are no specifications regarding the length of surveys to assess noise levels or the frequencies of sound that should be considered in such surveys. This means that there is likely greater inter-facility variation in the acoustic environment compared to other factors known to impact welfare and phenotype. Facilities conducting longer surveys might be more likely to detect, and subsequently mitigate, periodic noises, and those assessing frequencies spanning the entire range audible to mice (1–100 kHz39) could act to minimise extraneous noise from a greater range of sources. Any potential consequence of variation is difficult to detect though, because neither the methods used in sound surveys or noise levels are typically reported in publications.\n\nGiven the varied potential impacts of the acoustic environment on mouse welfare and phenotype,31,32 it is crucial that methods are standardised between facilities. It is likely that facilities housing mice are primarily focussed on minimising extraneous noise audible to humans (human audible frequency range 0.02–20 kHz39), as the majority of research investigating the impact of the acoustic environment on mice has examined the impacts of noise within this frequency range.31,32 Further, those working with animals are able to detect such noise and note any possible impact on studies. Ultrasonic sounds (those with frequencies >20 kHz) have received less attention, because their impact on mice has not been investigated and they cannot be detected by humans. However, although mice have peak hearing sensitivity at 10–20 kHz, they also have increased hearing sensitivity at ~50 kHz,40 so are able to hear ultrasonic sounds clearly. Indeed, the importance of ultrasonic vocalisations for social communication in mice is gaining research interest.34–38 Taken together, this suggests that mouse welfare and phenotype could be impacted by extraneous ultrasonic noise in housing facilities.\n\nThe importance of implementing a framework for the maximum acceptable levels of audible and ultrasonic noise, as well as vibration within animal facilities has recently been proposed.41 Whilst we do not report on vibration assessment here, we provide a comparison of ways that facilities may detect ultrasonic noise and show that mitigation is often easily and economically achieved.\n\nDetection of ultrasonic noise is the first step in being able to assess the potential impact on mice and minimise extraneous noise. In this paper we evaluate the use of two different pieces of equipment (an Avisoft ultrasonic microphone and the Hottinger Brüel & Kjær (HBK) PULSE system) that can be used to monitor ultrasonic noise in animal housing facilities. We aim to raise awareness of the importance of standardising noise surveys between facilities and make recommendations for potential changes in legislation regarding control of the acoustic environment.\n\n\nMethods\n\nMultiple systems are capable of detecting and measuring ultrasonic sound. We selected two commercially available systems to identify sources of ultrasonic noise at the Mary Lyon Centre: 1) The Avisoft system - an Avisoft condenser microphone CM16/CMPA connected to an Avisoft UltraSoundGate 116Hb (Avisoft Bioacoustics, Berlin), and 2) the HBK PULSE system with a type 4939 ¼” measuring microphone attached to a high frequency 3110 processing module (Hottinger, Bruel & Kjaer UK).\n\nThese systems were selected as both can detect ultrasound and are of a very high quality. The Avisoft system is designed to monitor ultrasonic vocalisations (USVs) used in social communication and the PULSE system is a sound analysis platform designed for accurate noise and vibration measurement and analysis. Although the objective of both systems is to detect audible and ultrasonic noise, the intended purposes result in distinct differences between the two systems. The microphones differ in sensitivity: the Avisoft microphone CM16/CMPA (500 mV/Pa) is orders of magnitude higher than the HBK 4939 (4 mV/Pa), but by design, the HBK 4939 microphone has a much flatter frequency response, allowing single frequency calibration for accurate measurement. An AudioMoth (Open Acoustic Devices) full spectrum recorder was also used for one of the noise sources.\n\nAll recordings were completed using Avisoft Bioacoustics RECORDER software (Version 4.2.27) running on a Dell laptop computer. The sampling rate for recordings was 250 kHz, unless otherwise stated, enabling sounds with frequencies of up to 125 kHz to be detected. Recordings were stored as uncompressed 16-bit PCM .wav files.\n\nThe PULSE system can be user configured from a number of optional hardware and software modules according to the requirements of the noise under investigation. Our system was configured to measure accurately in one second epochs up to 100 kHz; however, our system lacked the optional recording functionality, which can be added with a software licence, also we did not have the capability to measure vibration.\n\nThe type 4939 microphone has a frequency range of 4 Hz–100 kHz, and was calibrated before each measurement session using a 1 kHz test tone at 94 dB SPL from a pistonphone calibrator (Aco-Pacific type 511e). The flat response of this microphone allows single frequency calibration to be accurate across the stated frequency range. The A-weighting scale, normally used for noise assessments concerning humans, would not have been suitable as it only covers the acoustic range. Therefore, linear (unweighted) measurements were used. Fast Fourier Transform (FFT) analysis was performed in real time using the PULSE type 7700 sound analyser software running on a Hewlett Packard laptop computer. The FFT analyser was set to measure 6400 lines spanning the frequency range of 0 Hz–100 kHz, and stored measurements in a multi-buffer that refreshed every second. Whilst noise levels were analysed over this range, frequencies lower than 4 Hz were ignored due to the frequency range of the microphone. All sound pressure levels measured are in dB SPL (dB re. 20 μPa).\n\nThe AudioMoth is a standalone full spectrum recorder; 16-bit PCM.wav files were written directly to a removable SanDisk microSD card. A sample rate of 384 kHz was used, enabling recording of noise up to 192 kHz, and the gain was set to high.\n\nMultiple potential sources of extraneous ultrasonic noise were identified in the Mary Lyon Centre. Possible sources that were considered included computers, air ventilation systems, ventilated hoods and changing station cabinets, equipment/procedures involving contact between two metal surfaces, walkie-talkie radios and light sources, among others. This is not a report of all the measurements taken, rather a comparison of the output of both systems to different types of potential ultrasonic noise sources: ceiling lights, commercially available walkie-talkie radios, and, contact between metal surfaces.\n\nUnless stated otherwise, for data collection, microphones were positioned both inside a closed individually ventilated cage (IVC) (Tecniplast IVC 1284L) or on a tripod outside of an IVC. This enabled us to evaluate whether the mice would be exposed to the noise when housed in an IVC, such as exposure occurring under normal housing conditions, or only when removed from the IVC (e.g. during cage cleaning). For recordings taken inside the cage, the microphones associated with each system were inserted through holes made in the IVC, a PVC grommet was used to maintain an airtight seal. For recordings/measurements taken outside of the cage, the microphones were placed horizontally in a tripod stand. The microphone was positioned facing the noise source under investigation, at a distance of 20 cm.\n\nThe .wav files resulting from recordings made using the Avisoft system were high-pass filtered at 10 kHz and processed using DeepSqueak (version 2.6.0). All neural networks available on this version of DeepSqueak were applied to detect ultrasonic frequencies within the recordings and the default settings for detections were used. Measures of frequency and spectrograms of the structure of sounds were taken from DeepSqueak directly. Spectral analysis of the Avisoft recordings and the AudioMoth recordings was also performed in iZotope RX8.\n\nData from the recordings from the Avisoft system, and measurements from the PULSE system are both presented in spectrogram form. These plot time against frequency, with the level/amplitude of the noise being denoted by a colour gradient scale adjacent to individual plots; however, only the PULSE system displays a calibrated measurement of noise in dB SPL. Spectrograms from the two systems are not directly comparable, but are presented to highlight the output from each system in response to different noise sources. The DeepSqueak spectrogram plots frequency vertically and time horizontally, whereas the PULSE spectrogram does the opposite. Another difference is the time scale: as mentioned the PULSE data is measured consistently in one-second epochs; the DeepSqueak system is a continuous recording and the timeframe used to present the data is in fractions of a second. However, the exact scale is variable due to software scaling dependent on the duration of noise. With a digital recording such as a.wav, there are numerous software options to analyse the data. In addition to the DeepSqueak software designed to automatically identify USVs within an audio recording, in one case iZotope RX8 was used. This analysis is again presented as a spectrogram, however the colours used to denote level are different from the other systems. The same spectral analysis could be performed using the open-source Audacity software.\n\n\nResults\n\nMultiple sources of extraneous ultrasonic noise are likely to be present in any given animal facility. Rather than attempt to provide an exhaustive list of all potential noise sources, we have provided example sources for the three different types of ultrasonic noise identified in this study and evaluated the capacity of each system to detect and or measure each type of noise.\n\nSome ceiling lights within the animal facility have been updated to include LEDs, but those that have not been updated produced continuous ultrasonic noise. To confirm that the lights were the source of the noise and to assess background noise level, the lights were turned on and off during tests (Figure 1).\n\nA) Noise produced by the lights is highlighted in the red box. Spectrogram produced using DeepSqueak (2.6.0)36. B) Full frequency range Fast Fourier Transform (FFT) autospectrum from the PULSE system highlighting the ultrasonic noise produced by the fluorescent ceiling lights. The periods when the lights were turned on or turned off are marked. The noise in the lower frequency bands was a result of background noise and movement in the adjacent corridor. C) FFT autospectrum from the PULSE system focused on the frequency range containing the ultrasound produced by the lights. D & E) The delta cursor, indicated in yellow, set to the frequencies spanned by the noise (40.3 kHz–47.4 kHz) measured 33.1 dB SPL when the lights were on (D) and 29 dB when off (E).\n\nThe Avisoft system detected low-level noise with a frequency just below 50 kHz (Figure 1A). Consistent with this finding, measurements taken from recordings made by the PULSE system using a delta cursor showed that the lights produced ultrasonic noise with frequencies between 40.3 kHz and 47.4 kHz (Figure 1B & C). Further measurements were taken using the PULSE system to confirm the source, and to calculate the sound pressure level using a delta cursor covering this frequency range. A level of 33.1 dB SPL was present in the delta cursor when the lights were on (Figure 1D), compared to ~29 dB SPL when the lights were switched off (Figure 1E). A change of 3 dB SPL equates to a doubling of sound pressure; this does not mean it is twice as loud but if it were audible noise, humans would be able to detect the change. Using the standard background noise correction calculation, we calculated that the lights were producing ultrasonic noise in the specified frequency range at a level of 30.8 dB SPL.\n\nWhen measuring from inside the IVC, neither system detected any change from background levels, suggesting that the cage is sufficient to attenuate the noise and therefore mice will not be exposed to this sound under normal housing conditions. However, both systems detected the sound when positioned on a tripod outside of the IVC, so when removed from the cage during handling, or if housed in conventional caging in facilities without IVCs, this would be audible for mice.\n\nWhen using the Avisoft system, a noise related to the use of commercially available walkie-talkie radios was identified. The results were similar for multiple brands of radio, suggesting that this noise is inherent to this technology.\n\nThe Avisoft Bioacoustics system reliably detected the noise produced by the radios. The spectrograms produced by DeepSqueak indicated the noise was repetitive, highly transient and frequency modulated (FM) with multiple components. One element modulated at 48–50 kHz and another at 98–102 kHz (Figure 2A, C). Both components would therefore potentially be audible to mice,39 with the former component, like the ceiling lights, within the frequency range at which mice display an elevated sensitivity to ultrasonic sound.40\n\nA) The Avisoft system detected a multi component frequency modulated noise centred at approximately 50 kHz and 100 kHz. B) The PULSE system did not detect any noise at 100 kHz. The red boxes in (A) and (B) highlight comparable frequency ranges in each spectrogram. Whilst the PULSE system did measure a low-level noise in this range, it is likely related to harmonics of the higher-level audible beep in the 1–7 kHz range.\n\nIn contrast, the PULSE system did not detect the noise from the walkie-talkie radios as efficiently. The PULSE system could detect a component centred on 50 kHz. The FFT autospectrum indicated low-level noise with frequency content spreading from 20 kHz to 50 kHz, coinciding with the audible beep produced by the operation of the radio (Figure 2B). The frequency spread seen in the spectrogram suggests that this noise could be harmonic frequencies related to the high-level noise of the audible beep from the radio below 7 kHz. Interestingly, the PULSE system did not detect any noise in the 100 kHz range (Figure 2B).\n\nFurther experiments were undertaken to investigate the disparity between the results obtained from the two systems. The Avisoft system detected this noise even when the microphone was housed within the IVC, at a distance of 10 metres and through a wall within the animal facility. In contrast, the noise could not be detected by the PULSE system outside of the IVC with the radio a short distance (20 cm) from the microphone. Ultrasonic sound is readily absorbed by surfaces and is very unlikely to pass through walls, therefore, this suggested that the DeepSqueak spectrogram was potentially displaying an artefact.\n\nUpon audio playback of the unfiltered .wav file recorded by the Avisoft system, it was apparent that some sort of interference was present in the recording. The audible beep from the radio could be heard, but a clicking sound was also present that was not heard when using the walkie-talkie at the time of recording. Spectral analysis of the unfiltered, full spectrum recording (iZotope RX8) showed that the clicking noise was concurrent with the higher frequency noise detected by DeepSqueak (Figure 3Bi).\n\nA) Spectrograms of the AudioMoth recordings of the radio being used in an isolated room (i), and in close proximity to an active monitor speaker (ii). The black arrows denote the audible beep produced when the transmit button was pressed. The white arrows in (ii) show the RF interference picked up by the active monitor speaker, while the absence of these in (i) shows that the noise did not arise from the walkie-talkie alone. B) Comparison of the spectrograms from the Avisoft recording (i) and the AudioMoth recording of the radio by the speaker (ii). The white arrows again denote the audible clicks in both recordings, which are not produced by the walkie-talkie itself (as shown in [Ai]); note the ultrasonic noise picked up the Avisoft system are bordered by these clicks. C) The same comparison as (B) using a logarithmic frequency scale to highlight the temporal similarities between the noise from the Avisoft system and the radio being operated in close proximity to the speaker. D) FFT spectrogram using the PULSE software to analyse the recording made by the Avisoft system. Noise can clearly be seen at the same frequencies that were originally detected by the Avisoft system, indicating that if the noise was not an artefact, the PULSE system would have also detected it.\n\nWalkie-talkie radios use FM radio frequencies (RF) in the MHz range. Ultrasonic sound propagates as a mechanical wave and requires a medium such as air to travel. Radio waves are electromagnetic waves, which can travel great distances and can easily pass through walls, as they do not require a medium to travel. As electromagnetic waves do not cause fluctuations in air pressure, they cannot be recorded using microphones in the normal way, however, poorly shielded microphones and cables can act as an aerial and pick up interference from RF sources.42 It is possible that the extremely sensitive Avisoft CM16 microphone, or indeed the cable used could also potentially be acting as an aerial, and the spectrogram was showing this as an intermittent FM signal.\n\nA third device, an AudioMoth (Open Acoustic Devices), was utilised in an attempt to determine if the noise detected by the Avisoft system was indeed due to RF interference. The AudioMoth is a full spectrum audio-logger which contains a Micro-Electromechanical Systems (MEMS) microphone, and is capable of producing full-spectrum recordings at a maximum sample rate of 384 kHz. By design, MEMS microphones are much less sensitive to RF or electromagnetic interference. Whilst the audible beep was picked up by the AudioMoth, the additional ultrasonic component was not (Figure 3A, Bii and Cii). Operation of the radio in close proximity to a pair of active monitor speakers (Alesis, USA), produced a noise similar to ‘GSM Buzz’, the noise produced by RF interference with speaker coil/cables, that can sometimes be heard when a mobile (cell) phone is in use in close proximity. The spectrogram of this noise shows it occurs in a similar temporal pattern to that of the clicking noise seen in the Avisoft recording (Figure 3C).\n\nFurthermore, when the recording from the Avisoft microphone was used as the input for the PULSE analysis software, noise in both regions of 50 kHz and 100 kHz could be identified (Figure 3D). Taken together, these findings strongly suggest that the noise picked up by the Avisoft system was in fact RF interference; therefore, it would not be audible to, or affect mice.\n\nPerhaps the most common cause of noise within an animal facility are impacts, in particular those involving contact between metal objects. We detected high-level noise with a widespread frequency content when a pair of metal forceps, commonly used for checking copulatory plugs, were dropped from normal working height onto the metal surface of a laminar air flow (LAF) cabinet. Although relatively transient, this noise was detected using both systems when the microphones were placed on a tripod outside of an IVC. The spectrogram for the Avisoft system can be seen in Figure 4D.\n\nA) Fast Fourier Transform (FFT) autospectrum from the PULSE software showing the noise measured by dropping metal forceps on a metal LAF cabinet surface. B) Similar measurements taken using a neoprene mat as a noise control measure. C) Measurements from inside the modified individual ventilated cage (IVC) when the forceps were dropped on the metal surface of the LAF cabinet. The black arrows indicate the records used for analysis shown in Table 1, background readings in (A), (B) and (C) were taken from records where the forceps were not dropped. D) Spectrogram from DeepSqueak of the recording made outside the LAF cabinet with the Avisoft system to highlight that it was able to detect the noise. Again, a 10 kHz high-pass filter was used on the recording so much of the high-level sound in the human audible range is not displayed. However, the ultrasonic frequency content was similar to that measured by the PULSE system.\n\nIn an attempt to approximate the exposure of a mouse to this noise during copulatory plug checks, the microphone for the PULSE system was positioned inside the LAF cabinet approximate to that of a mouse during this routine husbandry procedure. Given that it is not possible to perform repeated impacts in a uniform manner, and the fact that the highest levels are likely to have the greatest effect on the mice, measurements of sound pressure level from the highest level of impact were used. Background noise correction is not necessary for the calculation of the impact noise level; the measured sound pressure level was sufficiently high in each case to be equivalent to that of the impact. However, the level increase over background levels for each frequency band were used to highlight where mice may have heightened sensitivity to the sound due to normally low background levels. Sound pressure levels were also measured within the modified IVC inside the LAF cabinet to analyse noise audible to mice in the cage. The Avisoft system was not used inside the LAF cabinet as it could detect the sound from outside and is not able to measure sound pressure levels.\n\nMeasured noise levels for the different frequency ranges are shown in Table 1. At their peak, noise levels from the impact of the forceps on the base of the LAF cabinet reached a total of 112.11 dB SPL across the full frequency range of 4Hz–100 kHz (Figure 4A and Table 1). The majority (112.03 dB SPL) was concentrated within the human audible range (20 Hz–20 kHz),39 which includes the range of mouse peak hearing sensitivity (10 kHz–20 kHz),40 although noise levels were highest below 10 kHz. In addition, very high-level noise was also detected at frequencies within the ultrasonic range (20 kHz–100 kHz) (Figure 4A and Table 1). The impact noise caused an increase of 49.34 dB SPL relative to background noise, both across the range of mouse peak hearing sensitivity and the ultrasonic frequency range. This increase in sound pressure level relative to background across those frequencies was greater than that evident at frequencies <10 kHz (~26.1 dB SPL increase) (Figure 4A and Table 1). This indicates that metal on metal impacts of this kind may expose mice to a substantial increase in noise across a wide range of frequencies audible to them, for which background levels of noise are typically very low (~45 dB SPL).\n\nMeasurements of background noise levels, noise produced when dropping metal forceps in different circumstances as described, the difference between background and measured impact noise and the reduction when using a neoprene mat as a noise control measure. IVC: individual ventilated cage; BG: Background.\n\nAs these metal-on-metal impacts occur frequently in the animal unit, we repeated the test using conditions identical in every way, except that a neoprene mat was placed on the metal LAF cabinet base, to cushion the impact of the forceps. The neoprene mat prevented the metal-on-metal impact, resulting in a substantial attenuation of noise (Figure 4B and Table 1), most importantly a relative reduction of ~36 dB SPL in both the ultrasonic and the mouse peak hearing sensitivity frequency ranges (Figure 4B and Table 1).\n\nMeasurements taken from inside the IVC showed that the cage provided ~10 dB SPL attenuation across the 4 Hz–100 kHz range investigated; however, the metal on metal impact was of a sufficiently high level to be easily audible to mice inside the cage. The measurement in the ultrasonic range was still very high, an increase over background of 36.2 dB SPL (Figure 4C and Table 1). These data combined with the findings from the ceiling lights, show that whilst the plastic cage is sufficient to shield mice from low-level ultrasonic noise, higher levels can still pass through.\n\n\nDiscussion\n\nIn recent years, it has become increasingly apparent that exposure to noise, particularly high-level noise within the range audible to humans (20 Hz–20 kHz), can impact mouse welfare and influence multiple aspects of phenotype (see e.g. Refs. 15, 21, 22), thus potentially confounding studies. While current guidelines have been beneficial in encouraging the monitoring of the acoustic environment in animal housing facilities, they lack specificity, enabling variation between animal housing facilities. In this paper, we wanted to draw attention to the importance of monitoring ultrasonic noise sources, for two reasons in particular:\n\n1. Ultrasonic noise is inaudible to humans, so those working with mice are unlikely to perceive the noise and take subsequent steps to mitigate it. By contrast, they are likely to take steps to minimise noise at frequencies audible to both humans and mice, preventing prolonged exposure to high level noise at these frequencies, which is known to be harmful to both humans and mice.15,21,22\n\n2. There is considerable evidence that animals can be detrimentally affected by noise within their audible range.25,43 However, whilst we know that ultrasonic frequencies are audible to mice,39 the potential impacts of such noise on welfare and phenotype have not been explored to date. To our knowledge, only two studies have explicitly considered ultrasonic noise when examining the impact of noise on mice, and neither tested the impact of ultrasonic frequencies in isolation of those audible to humans.39,44\n\nWe used two commercially available systems to examine potential ultrasonic noise sources at the Mary Lyon Centre at MRC Harwell; the Avisoft Bioacoustics system and the HBK PULSE system. Both systems detected the continuous ultrasonic (e.g. from the ceiling lights) and metal-on-metal impact noises; however, the increased sensitivity and gain used for the microphone of the Avisoft system introduced artefacts. If we had not used both systems to investigate the noise made by walkie-talkie radios in this instance, we would have not discovered this was an artefact. It is advised that measures are taken to minimise exposure if a noise is identified, either audible or ultrasonic, which could therefore potentially unnecessarily impact resources. It is recommended that detected ultrasonic noise is investigated thoroughly and measured accurately where possible.\n\nWhilst both systems could be used to detect ultrasonic noise, in our study, only the PULSE system could be used to obtain accurate and reliable measures of frequency and sound pressure level. The Avisoft system in the configuration used here could only provide relative measures. A calibrator could be used to improve the accuracy of measurements obtained from the Avisoft system, but due to the flat frequency response of the type 4939 microphone, the PULSE system would nonetheless remain the most suitable system in this area. Thus, whilst the Avisoft system, and likely other ultrasonic microphones intended for a similar purpose, could be used to identify ultrasonic noise sources, accurate measurement equipment such as the PULSE system is preferable for precisely quantifying frequency content and sound pressure level. The PULSE system is, however, far less accessible (>£20k) than ultrasonic microphones typically used to record USVs (price range ~-£250–~£5k). Other options such as the MEMS-based AudioMoth full spectrum logger may be useful as an alternative option to the more RF-sensitive, high-gain ultrasonic condenser microphones such as the CM16, for routine detection or periodical monitoring of ultrasonic (and audible) noise; however, they also have the disadvantage of not being easy to calibrate for measurement over the required frequency range.\n\nIf animal facilities possess the equipment to record USVs we suggest it would be beneficial for them to perform an in-house investigation to identify potential sources of noise. The frequency range of this investigation should be determined according to the reported audible range of the species contained within. Our findings also indicate that proper measurement of detected noise sources is essential when looking at mitigating measures. Equipment to perform these investigations is available to hire, however, operation and interpretation of data may require specialist consultation.\n\nUltrasonic noise detected in this study could potentially impact mouse welfare and phenotype. This is an area that certainly warrants further investigation, as actions to mitigate ultrasonic noise are most likely to occur only when a detrimental effect has been identified. However, we strongly feel that, especially given the importance of mouse USVs in social communication34–38 and evidence of how impactful other frequencies can be to welfare,15,21,22 steps should be taken to minimise noise wherever possible. Although harder to detect, ultrasonic noise is comparably easier to attenuate by shielding than noise with a lower frequency content. We observed that ultrasonic noise from the ceiling light was not detected by either system from inside the IVC, so the cage itself will probably protect mice from low level ultrasonic sources. However, as the aim of this type of investigation is to find noise sources that specifically affect the animals, measurements should always be taken from both inside a modified cage and outside to confirm this. Actions to minimise ultrasonic noise that is high-level and can be detected within a sealed IVC in particular should be a priority, as mice will be exposed under normal housing conditions. Such noise could conceivably hinder social communication and impact other traits related to health, welfare and behaviour even when mice are not exposed to any other form of stress outside of routine husbandry procedures.\n\nWhilst noises detected outside of the IVC may not be of a high level, the ultrasonic frequencies will normally be readily attenuated by the cage. This may make mice more sensitive to these frequencies when they are exposed. The presence of ultrasonic noise whilst performing behavioural testing could be particularly impactful; the mice are infrequently exposed to the noise, and sources may vary from room to room. Steps should be taken to investigate and minimise such noises in experimental areas to reduce potential negative effects on the reliability of data. Mitigation of impact noise, such as that produced in copulatory plug checking, may be relatively simple. As shown in this study, it can be substantially controlled with cost-effective and easy-to-implement modifications; in some cases simple procedural refinements may be sufficient. As mice can also hear the sound very clearly inside the cage, this should be a priority.\n\nCurrent guidelines for noise surveys in animal facilities recommend that multiple frequencies are considered, and typically mention that mice can hear ultrasonic frequencies.6–8,10 However, the guidelines do not make specific recommendations regarding the range of frequencies to consider, the ideal length of surveys or the distance from potential noise sources that measurements should be performed. This lack of specificity prevents standardisation, meaning that mice in different facilities may have vastly different acoustic environments. Ideally, noise surveys should consider all frequencies audible to the animals housed in that facility but, whilst a good starting point, this alone could be insufficient to minimise exposure to extraneous noise. For example, facilities that conduct longer sound surveys are more likely to detect periodic noises, such as those from equipment that is not constantly running or procedures that are conducted relatively infrequently. Such facilities are thus more likely to act to minimise exposure to periodic noise. Further, since ultrasonic sound is highly directional and travels a shorter distance than lower frequency sound, noise measurements undertaken in one part of a room may fail to detect ultrasonic noise that mice housed elsewhere in that room are exposed to.\n\nThe potential consequences of exposure to ultrasonic noise have not been studied to date but could be profound. Mice use USVs for social communication,37,38 and whilst they are able to distinguish between USVs and noise,45,46 it is perceivable that ultrasonic noise could hinder social communication. This could be detrimental to welfare by leading to increased levels of aggression or simply preventing normal social behaviour. Whilst unlikely under IVC housing conditions, exposure of higher levels of ultrasonic noise could also lead to hearing loss, as with exposure to noise with lower frequencies,19,20 which could prevent mice from detecting USVs, at least at particular frequencies. Further, human studies have shown that exposure to audible noise, particularly at high levels, can affect multiple traits, including stress, cardiovascular function and anxiety.25,43 As ultrasonic frequencies are audible to mice, it follows that exposure to them may have similar effects. Any such effect could be detrimental to welfare, increase mortality, reduce productivity and/or confound studies, particularly those which require phenotyping outside of the home cage. Exposure to ultrasonic noise could therefore be a source of unnecessary stress for animals in animal housing facilities and could lead to the need for greater numbers of animals in studies for sufficient statistical power, and because of the lack of standardisation of sound surveys, this could lead to reduced study reproducibility. These consequences are in direct conflict with the principles of the 3Rs, aimed at performing more humane animal research by minimizing the pain, suffering, distress or lasting harm experienced by the animals in research, via “Replacement, Reduction and Refinement” and steps taken to reduce noise exposure, audible or otherwise would constitute a refinement.41\n\n\nConclusions\n\nMultiple systems, including those discussed here, can be used to identify sources of ultrasonic noise. When selecting a system to use, it is important to consider the relative advantages and disadvantages of each. Sound analysis systems such as the PULSE system, when combined with a suitable calibrated microphone, can provide accurate measurements of sound pressure level and frequency. Recordings from ultrasonic microphones like the Avisoft and AudioMoth systems used in this study can also be employed to detect ultrasonic frequencies that are inaudible to humans; as long as gain settings and processing remain consistent, they could also be useful for comparing relative levels as an initial investigation, and can be more accessible. Furthermore, in some cases the ability to visualise the spectrogram of these recordings with high temporal resolution could be helpful in identifying the source of an ultrasonic noise. It is also important to remember that measurement and detection are distinct when selecting a system. Thus, if the purpose of testing is to examine noise sources that affect animals and reduce the chance of exposure, and the hire or acquisition of accurate measurement equipment is not currently financially possible, using a cheaper method of detection is likely more important than measuring exact levels. However, as with workplace surveys of audible noise, accurate measurement is important to assess exposure and environmental impact. If the current guidelines surrounding the acoustic environment of the animals were to be changed to include ultrasonic frequencies, accurate measurement would almost certainly be required.\n\nDue to the nature of scientific research involving animals, animal house staff normally spend more time in the facility with the animals than the researchers. As such, they are arguably best placed to identify potential sources or causes of noise (i.e. through noticing changes in animal behaviour). Animal staff are also dedicated to maintaining the highest standards of welfare for the animals in their care, and as such they should be made aware of the potential exposure of mice to ultrasonic noise, which could potentially have adverse effects. Attention should also be drawn to the ultrasonic frequency content of some impact noises, in particular those involving metal such as forceps or wire cage tops. Any simple procedural or material changes that would minimise this noise will only benefit the animals.\n\nIt would be a positive step for animal facilities to be more aware of noise, audible and ultrasonic, and try to implement local policies for identifying and mitigating any noise sources relevant to the species housed within. We would advise that noise surveys should be sufficiently long to identify periodic noise (e.g. from equipment that is not in constant use) and tests should be undertaken at the minimum distance that the equipment will be used from mice (both inside and outside of an IVC, where this is the housing used). A particular emphasis should be placed on assessing areas with the highest potential of exposure, such as phenotyping rooms where mice are frequently handled outside of their home-cage. Ideally, all new equipment would be tested as a potential noise source when it is first introduced into an animal housing facility, so that appropriate precautions can be taken to minimise noise exposure. We also recommend that studies are undertaken to evaluate the impact of ultrasonic noise on mice. Unless there is conclusive evidence that there is no detrimental effect, steps should be taken to minimise ultrasonic noise wherever possible; this can usually be achieved simply at no or minimal cost either by operational changes or simple shielding methods; however sources must first be identified. We encourage scientists to disclose sound profiles of their facilities and the testing environment in publications. This would not only enable the potential impact to be assessed at a later date, but also raise awareness of the issue.\n\n\nData availability\n\nHarvard Dataverse: Investigating Audible and Ultrasonic Noise in Modern Animal Facilities. https://doi.org/10.7910/DVN/QSCYBS\n\nThis project contains the following underlying data:\n\n- Audio moth away from speaker.wav (recording of the walkie-talkie operation not in proximity to a speaker using the AudioMoth)\n\n- Audio moth near speaker.wav (recording of the walkie-talkie operation in close proximity to a speaker using the AudioMoth)\n\n- Avisoft.wav (original recording of walkie-talkie being operated using the Avisoft system)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "Acknowledgements\n\nThe authors would like to thank Mark Dowie from Hottinger, Bruel & Kjaer UK for analysing the recording of the walkie-talkie radio, and for technical advice. In addition, the authors would like to thank all the animal care, and estates and engineering staff at the Mary Lyon Centre at Harwell for their assistance during the collection of data.\n\n\nReferences\n\nHansen PJ: Effects of heat stress on mammalian reproduction. Philosophical Transactions of the Royal Society B: Biological Sciences. 2009; 364: 3341–3350. PubMed Abstract | Publisher Full Text\n\nDaskalov PI, Arvanitis KG, Pasgianos GD, et al.: Non-linear adaptive temperature and humidity control in animal buildings. Biosyst. Eng. 2006; 93: 1–24. Publisher Full Text\n\nKeijer J, Li M, Speakman JR: What is the best housing temperature to translate mouse experiments to humans?. Mol. Metab. 2019; 25: 168–176. 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Cardiol. 2018; 71: 688–697. Publisher Full Text\n\nMünzel T, et al.: Effects of noise on vascular function, oxidative stress, and inflammation: Mechanistic insight from studies in mice. Eur. Heart J. 2017; 38: 2838–2849. PubMed Abstract | Publisher Full Text\n\nLiu L, et al.: Effects of noise exposure on systemic and tissue-level markers of glucose homeostasis and insulin resistance in male mice. Environ. Health Perspect. 2016; 124: 1390–1398. PubMed Abstract | Publisher Full Text\n\nLiu L, et al.: The effect of noise exposure on insulin sensitivity in mice may be mediated by the JNK/IRS1 pathway. Environ. Health Prev. Med. 2018; 23: 4–11.\n\nRasmussen S, Glickman G, Norinsky R, et al.: Construction noise decreases reproductive efficiency in mice. J. Am. Assoc. Lab. Anim. Sci. 2009; 48: 363–370. PubMed Abstract\n\nShafiei A, et al.: The effect of chronic noise stress on serum levels of cortisol, gonadotropins, and sexual hormones at implantation time of mice. Comp. Clin. Path. 2017; 26: 779–784. Publisher Full Text\n\nTurner JG, Parrish JL, Hughes LF, et al.: Hearing in laboratory animals: Strain differences and nonauditory effects of noise. Comp. Med. 2005; 55: 175–182. PubMed Abstract\n\nTurner JG, Bauer CA, Rybak LP: Noise in animal facilities: Why it matters. J. Am. Assoc. Lab. Anim. Sci. 2007; 46: 10–13. PubMed Abstract\n\nHughes LF: The Fundamentals of Sound and its Measurement. J. Am. Assoc. Lab. Anim. Sci. 2007; 46: 14–19. PubMed Abstract\n\nArmstrong EC, et al.: Assessing the developmental trajectory of mouse models of neurodevelopmental disorders: Social and communication deficits in mice with Neurexin 1α deletion. Genes Brain Behav. 2019; 19: e12630. PubMed Abstract | Publisher Full Text\n\nEgnor SER, Seagraves KM: The contribution of ultrasonic vocalizations to mouse courtship. Curr. Opin. Neurobiol. 2016; 38: 1–5. PubMed Abstract | Publisher Full Text\n\nCoffey KR, Marx RG, Neumaier JF: DeepSqueak: a deep learning-based system for detection and analysis of ultrasonic vocalizations. Neuropsychopharmacology. 2019; 44: 859–868. 0–10. PubMed Abstract | Publisher Full Text\n\nSangiamo DT, Warren MR, Neunuebel JP: Ultrasonic signals associated with different types of social behavior of mice. Nat. Neurosci. 2020; 23: 411–422. PubMed Abstract | Publisher Full Text\n\nFerhat AT, et al.: Recording mouse ultrasonic vocalizations to evaluate social communication. J. Vis. Exp. 2016. PubMed Abstract | Publisher Full Text\n\nReynolds RP, Kinard WL, Degraff JJ, et al.: Noise in a laboratory animal facility from the human and mouse perspectives. J. Am. Assoc. Lab. Anim. Sci. 2010; 49: 592–597.\n\nEhret G: Frequency and intensity difference limens and nonlinearities in the ear of the housemouse (Mus musculus). J. Comp. Physiol. 1975; 102: 321–336. Publisher Full Text\n\nTurner JG: Noise and Vibration in the Vivarium: Reccomendations for Developing a Measurement Plan. J. Am. Assoc. Lab. Anim. Sci. 2020; 59: 665–672. PubMed Abstract | Publisher Full Text\n\nBrown J, Josephson D: Radio Frequency Susceptibility of Capacitor Microphones.2003; 1–14.\n\nLe TN, Straatman LV, Lea J, et al.: Current insights in noise-induced hearing loss: a literature review of the underlying mechanism, pathophysiology, asymmetry, and management options. J. Otolaryngol. Head Neck Surg. 2017; 46: 41. PubMed Abstract | Publisher Full Text\n\nTrindade Madeira Araújo F, et al.: Low welfare impact of noise: assessment in an experimental model of mice infected by Herpes simplex-1. Appl. Anim. Behav. Sci. 2018; 207: 79–88. Publisher Full Text\n\nWöhr M, Schwarting RKW: Maternal Care, Isolation-Induced Infant Ultrasonic Calling, and Their Relations to Adult Anxiety-Related Behavior in the Rat. Behav. Neurosci. 2008; 122: 310–330. PubMed Abstract | Publisher Full Text\n\nAsaba A, Kato M, Koshida N, et al.: Determining Ultrasonic Vocalization Preferences in Mice using a Two-choice Playback Test. J. Vis. Exp. 2015: 2–9. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "142997",
"date": "18 Jul 2022",
"name": "Markus Brielmeier",
"expertise": [
"Reviewer Expertise Laboratory Animal Science",
"Microbiology",
"Sound and Vibration measurement",
"home cage technologies"
],
"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 manuscript shows how to measure sound and ultrasound in an experimental animal facility. The advantages and disadvantages of 2 measurement systems available on the market are reported and possible artifact sources are discussed.\nI agree with the authors that too little attention is paid to the disturbance of laboratory animals by inaudible ultrasound. As mice communicate with ultrasound, it is likely that they are disturbed by ultrasound at high sound levels. The authors suggest that suitable equipment should be used to identify and, if possible, attenuate the sources of ultrasound. Using the example of impact noises (e.g. noises made by tweezers during transfer), they show that simple measures can be taken to attenuate the sound. Although mice are almost only kept in individually ventilated cages and the plastic attenuates ultrasound very well, the authors show that ultrasound at high levels does reach into the cage. Moreover, most of the tests still take place outside the protective cage and there the mice are exposed to the various ultrasound sources. If ultrasound affects phenotypes, it will contribute to de-standardization, which is unsatisfactory from a scientific point of view.\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": []
},
{
"id": "140878",
"date": "28 Jul 2022",
"name": "Leonardo Restivo",
"expertise": [
"Reviewer Expertise Behavioural Neuroscience"
],
"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\nBiomedical scientists working with research animals are becoming increasingly aware of factors affecting animal welfare and experimental procedures. Animal facilities must follow strict guidelines determining acceptable ranges of potentially disruptive factors such as light, noise, temperature, and humidity. Currently, there are no guidelines dictating standards of acceptable noise range in the ultrasonic domain for rodent facilities. Knowing the negative impact that noise may exert on rodents' welfare and experimental procedures, this manuscript sets out to implement novel and refined techniques to assess sources of ultrasonic and audible noise commonly found in rodent housing facilities. The authors present a detailed analysis of the benefits and caveats of the two systems deployed to capture the sources of ultrasonic noise.\nThe manuscript is a significant step toward the definition of a \"systemic\" approach to biomedical research. The \"experiment\" is commonly defined as the interval of time during which the subject is under direct experimentation (e.g., application of selected assays), often neglecting that living creatures experience time as a continuum. Therefore, factors affecting animal welfare outside of the limited time covered by the experimental procedure are bound to impact the quality of the data collected throughout the experiment. For this reason, it is critical to design guidelines that regulate factors present in the housing facility (e.g., light, temperature, humidity, noise), including sources outside the perceptual range of human operators (e.g., ultrasonic noise). The authors performed ultrasonic noise analysis both outside and inside the home cage (IVC), leading to the critical finding that some noise sources can reach mice inside their air-sealed home cage. Critically, the authors show that simple and inexpensive procedures can be deployed to minimize ultrasonic noise disruptions. As correctly stated in the manuscript, we do not know yet the consequences of exposure to ultrasonic noise. Therefore, this manuscript is also a call to action for animal welfare scientists to further investigate the effects of ultrasonic noise on rodents. Nonetheless, I support the authors when they state that in the absence of conclusive evidence, all animal facilities must be encouraged to check their noise landscapes, including ultrasonic noise, and to take action to eliminate or dampen the sources of this potentially disruptive noise.\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": []
}
] | 1
|
https://f1000research.com/articles/11-651
|
https://f1000research.com/articles/11-649/v1
|
13 Jun 22
|
{
"type": "Research Article",
"title": "Metabolic changes in chronic hepatitis C patients receiving direct acting antivirals",
"authors": [
"Nehal K. Abdel Fattah",
"Sara M. Shaheen",
"Osama A. Ahmed",
"Kadry Elsaeed",
"Nagwa A. Sabri",
"Sara M. Shaheen",
"Osama A. Ahmed",
"Kadry Elsaeed",
"Nagwa A. Sabri"
],
"abstract": "Background: Treatment of chronic hepatitis C (CHC) with direct acting antivirals (DAAS) improves the rates of sustained virological response (SVR). However, derangements with lipid profile and glycemic status have been observed. This study aimed to compare the effect of sofosbuvir/daclatasvir (SOF/DAC) versus sofosbuvir/ledipasvir (SOF/LED) regimens on metabolic status of CHC patients. Methods: An observational prospective study was conducted on a total of 140 easy-to-treat treatment-naïve genotype-4 chronic hepatitis C virus (HCV) infected Egyptian patients. Patients received either 400 mg SOF/60 mg DAC or SOF 400 mg/90 mg LED daily for 12 weeks. Patients were followed-up for 12 weeks after end-of-treatment. Total lipid profile, fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) were measured at baseline, four weeks (during treatment), and 12 weeks post-treatment (24 weeks). Clinical laboratory tests and treatment side effects during the treatment period were assessed to ensure safety. Complete blood picture, liver function tests, fibrosis-4 index (FIB-4) were performed at baseline and week 12. Results: Both groups had 100% SVR. In both groups, no significant difference in body mass index was found after treatment. FIB-4 decreased significantly after treatment in the SOF/LED group. Regarding lipid profile, total cholesterol (TC) and low-density lipoproteins (LDL) were significantly increased then slightly decreased between week four and week 24 respectively in both groups with higher percentage change in the SOF/LED group. On the other hand, high-density lipoprotein (HDL) decreased throughout the follow-up period in both groups with no significant difference between two groups. Regarding glycemic status, HbA1c and FBS were significantly decreased in both groups throughout the study period with significant difference in the percentage change of HbA1c and FBS between two groups. Conclusions: SOF/LED regimen showed a significant change in lipid profile parameters more than the SOF/DAC regimen, while both regimens showed favorable outcomes in HbA1C and FBS levels.",
"keywords": [
"sofosbuvir",
"daclatasvir",
"ledipasvir",
"chronic hepatitis C",
"lipid profile",
"glycemic status",
"sustained virological response",
"end of treatment"
],
"content": "Abbreviations\n\nAEs: adverse effects\n\nALT: alanine aminotransferase\n\nAPO B: apolipoprotein B\n\nAST: aspartate aminotransferase\n\nASV: asunaprevir\n\nBMI: body mass index\n\nCBC: complete blood picture\n\nCHC: chronic hepatitis C\n\ncm: centimeters\n\nCT: computerized tomography\n\nDAAS: directing acting antivirals\n\nDAC: daclatasvir\n\ndL: deciliters\n\nEOT: end of treatment\n\nFBS: fasting blood sugar\n\nFIB-4: fibrosis-4 index\n\nHbA1c: gylcated hemoglobin\n\nHBV: hepatitis B virus\n\nHCC: hepatocellular carcinoma\n\nHCV: hepatitis C virus\n\nHDL: high-density lipoproteins\n\nHOMA-IR: homeostatic model assessment of insulin resistance.\n\nIFN: interferon\n\nINR: international normalized ratio\n\nIR: insulin resistance\n\nIRS-1: insulin receptor substrate-1\n\nIU: international units\n\nkg: kilograms\n\nLDL: low-density lipoproteins\n\nLED: ledipasvir\n\nmg: milligrams\n\nmm3: cubic millimeters\n\nMRI: magnetic resonance imaging\n\nNCCVH: National Committee for the Control of Viral Hepatitis\n\nPCR: polymerase chain reaction\n\nPEG-IFN: pegylated interferon\n\nRBV: ribavirin\n\nRNA: ribonucleic acid\n\nSD: standard deviation\n\nSIM: simeprevir\n\nSOF: sofosbuvir\n\nSVR12: sustained virological response week 12\n\nT2DM: type-2 diabetes mellitus\n\nTC: total cholesterol\n\nTG: triglycerides\n\nTLC: total leucocytic count\n\nVLDL: very low-density lipoproteins\n\n\nIntroduction\n\nHepatitis C virus (HCV), a blood borne disease, is a primary causative agent of chronic liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) that lead to related high mortality and morbidity.1 Several lipid and lipoprotein metabolic pathway disorders such as hypocholesterolemia, hepatic steatosis, hypobetalipoproteinemia that cause fatty liver and insulin resistance (IR), are associated with chronic HCV infection.2 IR occurs in the early phases of HCV infection and can manifest later on as type-2 diabetes mellitus (T2DM), which can accelerate the progression of liver fibrosis into cirrhosis and later on into HCC.3\n\nGlobally, about 170 million patients with HCV chronic liver disease have been reported.1 Egypt has the greatest prevalence of HCV globally with approximations more than 10% amongst the overall inhabitants with genotype-4 being the most dominant type in 91% of the cases.4 The HCV large infection pool in Egypt was believed to be caused by the national parenteral anti-schistosomiasis campaign in the late 1860s–1980s. Moreover, 24.3% of HCV transmission was due to a history of previous blood transfusions, 20.6% due to needle reuse, medical procedures, and household transmissions.5\n\nThe treatment of chronic HCV disease has shifted from interferon (IFN)-based into IFN-free regimens consisting of directly acting antiviral agents. Second generation direct acting antivirals show sustained virological response (SVR) rates ≥ 90% with reduced side effects and increased tolerability.6–10 Treatment with direct acting antiviral (DAA) leads to improvement in the rates of SVR and decreases the predictive aptitude of baseline metabolic characteristics for SVR with IFN-based treatment, even though baseline low-density lipoprotein (LDL) is still a predictor in some direct acting antiviral (DAA) studies.7\n\nHepatitis C virus replication and maturation have shown a robust interaction between the virus and host intracellular lipids, indicating that host lipid metabolism and cholesterol homeostasis have a crucial role in HCV circulation and HCV replication cycle stages including entry, replication, assembly, and secretion.11,12\n\nPathophysiological mechanisms for IR by HCV include direct and indirect pathways. HCV proteins have a direct influence on inhibiting the insulin-signaling pathway stimulating central IR through increasing the insulin receptor substrate-1 (IRS-1) degradation by preventing IRS1 from binding to insulin receptors and hence impairing glucose metabolism.7,12 Peripheral IR occurs as a result of indirect pathways due to overproduction of inflammatory cytokines and high lipolysis by HCV.7,13\n\nChronic hepatitis C (CHC) is associated with decreased serum levels of LDL, total cholesterol (TC), and apolipoprotein B (APO B) since HCV utilizes host circulating lipids for their replication causing hypolipidemia. In addition, it is associated with increased IR and T2DM rates.14,15 In the era of pegylated interferon (PEG-IFN) plus ribavirin (RBV), several studies reported an increase in LDL, TC, and triglycerides (TG) after achieving SVR suggesting that HCV has a significant role in baseline hypolipidemia.16–20\n\nLipid and glucose metabolic changes data are controversial regarding direct acting antivirals (DAAS).15 Some studies reported a significant increase in TC and LDL irrespective of DAAS treatment regimen type and HCV genotype suggesting an interrelationship between HCV and host lipid metabolism which reverses to baseline levels after failure of treatment.9,21\n\nHowever, this was opposed by other studies22,23 where they found significant differences in lipid changes between different DAA regimens. This finding indicates that successful viral elimination is not the only factor that affects lipid levels during treatment with DAAS, but DAAS themselves may have pharmacological effects on host lipid metabolism. Hence, increases in lipids are strongly dependant on antiviral DAAS type.22,23\n\nSuccessful viral eradication by DAAS showed improvements in glycemic control with worsening of lipid parameters due to alterations of glucose and lipid metabolic pathways by HCV. Increase in lipid profile might be due to the return of lipids to normal pre-virological levels since HCV is known to cause hypolipidemia. However, these alterations might have a potential cardiovascular risk that might require monitoring during DAA treatment.15\n\nSeveral studies investigated metabolic changes in lipid metabolism and glycemic control for other genotypes, but it has not been studied extensively in genotype-4 patients. This observational study aimed to assess the outcome of using sofosbuvir/daclatasvir and sofosbuvir/ledipasvir as treatment regimens for chronic hepatitis C genotype-4 infected non-diabetic non-cirrhotic Egyptian patients and their impact on lipid profile and glycemic control.\n\n\nMethods\n\nThis prospective observational cohort study was conducted on 140 easy-to-treat treatment-naïve genotype-4 chronic HCV infected patients diagnosed by a positive test of anti-HCV antibodies and HCV RNA. Patients were recruited from the outpatient clinics of Al-Demerdash Ain Shams University Hospital hepatitis viral unit (one of the centers of the National Committee for the Control of Viral Hepatitis) between the periods of October 2019 to April 2020.\n\nThe study protocol was approved by the ethical committee of Ain Shams University, Faculty of Pharmacy, Cairo, Egypt (ID number 164). This study was conducted according to the Declaration of Helsinki ethical guidelines for medical research involving humans and good clinical practice standards.24 A written informed consent was obtained from each patient without any obligations and the patients were able to withdraw at any time if they wanted to.25\n\nPatients were diagnosed with chronic HCV infection by showing continuous anti-HCV antibody and HCV-RNA positivity by quantitative polymerase chain reaction (PCR) for six months or more. Patients included in the study were those who fulfilled the criteria of the National Committee for the Control of Viral Hepatitis (NCCVH) in Egypt for treatment. It included male or female easy-to-treat, treatment-naïve patients with an age range between 18 and 75 years old. Treatment-naïve was defined as patients who had not undergone any previous HCV treatment or relapsed from previous DAAS or pegylated-interferon plus ribavirin treatment. Easy-to-treat was defined as patients who were treatment-naïve, non-cirrhotic chronic HCV with compensated biochemical liver parameter26 categorized by certain labs according to the National Committee for the Control of Viral Hepatitis such as serum biliribun ≤ 1.2 mg/dL, serum albumin ≥ 3.5g/dL, international normalized ratio (INR) ≤ 1.2, and platelet count ≥ 150,000/mm3. Patients’ liver condition was assessed by fibrosis-4 index (FIB-4) where FIB-4 index score of > 3.25 predicts significant liver fibrosis (F3–F4). Pelvic abdominal ultrasonography was routinely performed on all patients to assess hepatic status and further advanced imaging modalities, such as computerized tomography (CT) or magnetic resonance imaging (MRI), were performed when needed.\n\nPatients not eligible for HCV treatment according to the National Committee for the Control of Viral Hepatitis with any of the following criteria were excluded: Child’s C cirrhotic patients (score ≥ 9); platelet count < 50,000/mm3; patients with active hepatocellular carcinoma (HCC) except for those who were cured for more than six months with no active evidence of HCC by dynamic imaging (CT or MRI); patients with active extra-hepatic malignancies except for those who were malignancy free for a time period of two years or patients who were cured from lymphomas and chronic lymphocytic leukemia and could start treatment immediately after remission based on the oncology report; pregnancy or patients who were unable to use contraceptives; uncontrolled diabetes mellitus with glycated hemoglobin levels (HbA1c > 9%).\n\nExclusion criteria in this study also included patients with factors that may affect lipid profiles or glycemic control. Factors that were excluded by examination and medical history profile included lipid lowering medications (statins); endocrine diseases such as hyperthyroidism or hypothyroidism; diabetes mellitus; Cushing’s disease; patients receiving hypertensive medication or corticosteroids that may induce insulin resistance; other comorbidities such as renal disease. Chronic HCV patients suffering from comorbid liver diseases such hepatitis B virus (HBV) or human immunodeficiency (HIV) coinfections, hepatocellular carcinoma or autoimmune hepatitis were also excluded from our study.25 Diabetic patients were defined by the American Diabetes Association guidelines as those with fasting glucose of ≥ 126 mg/dL or HbA1C of ≥ 6.5%.27\n\nThree hundred patients were assessed and only one hundred and forty patients fulfilled the inclusion criteria and were included in the study. Patients included received either SOF/DAC regimen 400 mg sofosbuvir (Sovaldi® by Gilead Sciences INC., Foster City, CA) plus daclatasvir 60 mg (Daclavirocyrl by MARCYRL pharmaceutical industries, Egypt) daily for 12 weeks28 or SOF/LED regimen 400 mg sofosbuvir plus ledipasvir 90 mg (a fixed-dose combination tablet named Harvoni® by Gilead Sciences, Foster City, CA) daily for 12 weeks.28 Treatment regimens were determined and prescribed by physicians in charge at Al-Demerdash Ain Shams University hospital. Both treatment regimens are readily available and prescribed at Al-Demerdash Ain Shams University Hospital. No intervention was done regarding HCV treatment plan decided for patients by hospital physicians. Figure 1 shows the study flow chart methodology.\n\nBMI: body mass index; CBC: complete blood picture; INR: international normalized ratio; AST: aspartate aminotransferase; ALT: alanine aminotransferase; HCV: hepatitis C virus, RNA: ribonucleic acid, PCR: polymerase chain reaction, LDL: low-density lipoproteins, TC: total cholesterol, TG: triglycerides, HDL: high density lipoproteins, VLDL: very low-density lipoproteins, FBS: fasting blood sugar, HbA1c: glycated hemoglobin, LFTs: liver function tests.\n\nBefore starting treatment, all patients underwent a full medical assessment, medication history, and family history. Patient demographics such as age, sex, body weight (kg), height (cm), and calculated BMI (body mass index) were collected. Complete laboratory investigations including complete blood count (CBC); liver function tests such as alanine aminotransferase (ALT), aspartate aminotransferase (AST); international normalized ratio (INR); serum bilirubin; serum creatinine; serum albumin; baseline quantitative HCV-RNA PCR; calculated fibrosis-4 (FIB-4) index; complete lipid profile including fasting low-density lipoprotein (LDL), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL); glycated hemoglobin (HbA1c); fasting blood sugar (FBS).25\n\nPatients were followed-up during treatment for 12 weeks and after the end of treatment (EOT) for 12 weeks (total duration of 24 weeks follow-up). Total lipid profile, fasting blood sugar, and HbA1c were measured at four weeks (during treatment), and 12 weeks post-treatment (at 24 weeks). CBC, liver function tests, serum albumin, serum bilirubin, serum creatinine, and INR were measured at week 12. BMI and FIB-4 were calculated at EOT at week 12 of treatment.25\n\nSustained virological response 12 (SVR 12) is defined as undetectable HCV ribonucleic acid (RNA) by polymerase chain reaction (PCR) after 12 weeks of completion of HCV therapy.29 HCV-RNA was obtained at baseline (before the start of therapy) and at week 24 after completion of therapy by 12 weeks. HCV-RNA levels were quantified using Roche Diagnostics TaqMan PCR V.2.0, Mannheim, Germany (lower detection limit: 15 IU/ml).30 The study main end point was considered undetected HCV-RNA after the EOT by 12 weeks known as SVR 12.25\n\nPatients were asked to report any adverse effects (AEs) due to treatment during the entire study period and follow-up. Safety end points that would stop continuation of a patient’s treatment included severe AEs, laboratory abnormalities, discontinuation of treatment due to AEs intolerance, and death. Safety was ensured during the study period by assessing monthly laboratory hematological and biochemical parameters along with AEs reporting.\n\nEnrolment was dependent on the clinical need for medication rather than on statistical factors. Sample size was estimated using nQuery statistical package, version 7.0 (Los Angeles, CA); an open-access alternative is G*Power software (RRID: SCR_013726). Statistical analysis was done using IBM SPSS® Statistics version 22 (IBM® Corp., Armonk, NY, USA) (RRID:SCR_019096); an open-access alternative is JASP version 0.16.1 (RRID: SCR_015823). Numerical data were tested for normality using Kolmogorov-Smirnov test and Shapiro-Wilk test. For quantitative data, comparison between two groups was done using the Student t-test for normally distributed data; while for non-normally distributed data, the Mann-Whitney test (non-parametric t-test) was used. Comparison between two groups was done using the Kruskal-Wallis test (non-parametric ANOVA) then the post-Hoc test was used for pair-wise comparison based on the Kruskal-Wallis distribution. Wilcoxon-signed ranks test (non-parametric paired t-test) was used to compare two consecutive measures of numerical variables. Friedman’s test (non-parametric ANOVA with repeated measures) was used to compare more than two consecutive measures of numerical variables. All tests were two-tailed. A p-value < 0.05 was considered significant.\n\nIn previous studies, Hashimoto et al., 2016 and Jain et al., 201923,31 showed a difference in ΔLDL (percentage change LDL) between SOF/LED and SOF/DAC of 13 mg/dL with a pooled standard deviation of 21. Based on these findings, a minimal sample size of 42 subjects in each group was required at an alpha level of 0.05 and power of 80%. To compensate for loss to follow-up, the sample size was increased by 70% to 70 subjects in each group with a total sample size of 140 subjects.\n\n\nResults\n\nOut of 140 patients who fulfilled the inclusion criteria and started the study, only 110 patients completed the whole study period and were included in the final analysis. The first group included 60 patients who received the SOF/DAC regimen and the second group included only 50 patients who received the SOF/LED regimen. The reason for the patients’ withdrawal or exclusion after starting participation was noncompliance to study protocol due to personal reasons (as shown in Figure 1). Patients in both groups achieved a 100% sustained virological response (SVR).25\n\nIn the SOF/DAC group, the mean age was 46.7 years. The 60 patients who received SOF/DAC were 23 (38.3%) males and 37 (61.7%) females, and their mean BMI was 30.1. While the mean age of the 50 patients who received SOF/LED treatment was 54.8. The males represented 24 (48.0%) patients and 26 (52.0%) were females, and their mean BMI was 25.1. The baseline demographic and laboratory parameters are presented in Table 1. A significant difference was found between the patients in the two groups regarding many baseline characteristics and laboratory parameters. Therefore, further comparisons were done using percentage change between both groups.\n\n* means significance when p-value is less than 0.05.\n\na Student’s T-Test.\n\nb Chi-square test.\n\nc Mann-Whitney U-test.\n\nTwelve weeks after treatment, the two groups showed a significant decrease in hemoglobin concentration with p-value < 0.001 and 0.002 in SOF/DAC and SOF/LED respectively. Meanwhile, no significant change of TLC or platelet count after treatment in both groups was detected. The body mass index did not change significantly at end of treatment in both groups with p-value 0.871.\n\nOn the other hand, ALT, AST, and FIB-4 score decreased significantly with baseline 43.5 (7–150) versus end of treatment 18 (8–70), 42 (12–234) versus 21 (9–54), and 1.91 (0.45–5.61) versus 1.3 (0.42–6.58) respectively at the end of treatment in the SOF/LED group. Moreover, this reduction was significantly higher in the SOF/LED group compared to the SOF/DAC group with p-value < 0.001 (as shown in Table 2).\n\n* means significance when p-value is less than 0.05. Percentage change = [(before-after)/before]×100.\n\nThe two groups experienced a similar pattern of change in total cholesterol levels throughout the treatment period. In the SOF/DAC and SOF/LED groups, cholesterol increased significantly after four weeks from baseline levels with (150.1 ± 31.9) versus (143.7 ± 21.8) and (175.1 ± 23.0) versus (157.6 ± 24.8) respectively with p-value < 0.001. In week 24, the TC decreased significantly in both groups compared to week four with (143.0 ± 28.8) and (169.9 ± 21.5) with p-value < 0.001 in SOF/DAC and SOF/LED groups respectively but remained higher than baseline levels. Moreover, the percentage change of TC levels was significantly different between the two groups (as shown in Table 3).\n\n* means significance when p-value is less than 0.05. Percentage change= [(before-after)/before]×100.\n\nRegarding the change in TG levels in the SOF/DAC group, TG increased significantly after four weeks (113.4 ± 28.4) from the baseline levels (107.3 ± 24.4) with p-value < 0.028, then decreased significantly after 24 weeks (99.2 ± 18.5) with p-value < 0.001. In the SOF/LED group, TG did not change significantly after four weeks of treatment (123.7 ± 36.8) compared to baseline readings (124.7 ± 37.2) with p-value = 1.00, but it increased significantly after 24 weeks (130.7 ± 40.2) compared to the week-four reading with p-value 0.032. The percentage change of triglyceride levels was significantly different between the two groups (as shown in Table 3).\n\nThe change in LDL levels was also similar in both groups where in the SOF/DAC group, LDL increased after four weeks (81.6 ± 31.1) from the baseline levels (76.4 ± 21.6) but not significantly with p-value = 0.215. While in week 24, the LDL decreased significantly (79.3 ± 27.9) compared to week four with p-value = 0.01. In the SOF/LED group, LDL increased significantly after four weeks (106.7 ± 20.0) versus the baseline levels (88.6 ± 20.6) with p-value < 0.001 and then decreased significantly after 24 weeks (101.8 ± 17.4) with p < 0.015 but remained higher than the baseline levels. Also, the percentage change of LDL was significantly different between the two groups (as shown in Table 3).\n\nIn the SOF/DAC group, HDL levels did not change significantly after four weeks (45.8 ± 3.1) from the baseline levels (46.2 ± 3.5) with p-value = 1.00, but it decreased significantly after 24 weeks (43.9 ± 2.3) with p-value < 0.001. In the SOF/LED group, HDL levels did not change significantly after four weeks of treatment (43.6 ± 10.4) or after treatment at week 24 (41.9 ± 9.0) from the baseline levels (44.0 ± 12.4) with p-value = 0.127. Also, the percentage change of HDL levels was comparable between the two groups (as shown in Table 3).\n\nRegarding the glycemic parameters, both HbA1c and FBS decreased throughout the study period in both groups (as shown in Figures 2 and 3). In the SOF/DAC group, HbA1c did not decrease significantly after four weeks (5.2 ± 0.6) from baseline levels (5.4 ± 0.68) with p-value = 0.166, but it decreased significantly at week 24 (5.0 ± 0.57) from baseline with p-value < 0.001. In the SOF/LED group, there was a significant decrease at week four and week 24 (5.3 ± 0.35) and (5.2 ± 0.33) respectively compared to baseline levels (5.9 ± 0.21) with p-value <0.001. Regarding FBS, the SOF/DAC group showed no significant decrease at week four (99.2 ± 12.2) with p-value = 0.32 from baseline (106.4 ± 13.2), but significantly decreased at week 24 (91.2 ± 12.5) with p-value < 0.001. In the SOF/LED group, FBS showed no significant decrease at week four (96.4 ± 12.5) with p-value = 1, but significantly decreased from baseline at week 24 (91.9 ± 11.3) with p-value = 0.049. There was a significant difference between the two groups in both percentage change of HbA1c and FBS. There was a significant percentage change of HbA1c between both groups at week four and week 12 with p-value < 0.001 and p-value = 0.032 respectively from baseline values with higher change in the SOF/LED group. Regarding FBS, there was a significant percentage change between both groups at week four and week 24 with p-value = 0.014 and p-value < 0.001 respectively from baseline values with higher percentage change in the SOF/DAC group.25\n\nSOF/DAC: sofosbuvir/daclatasvir, SOF/LED: sofosbuvir/ledipasvir, week 4: during treatment, week 24: 12 weeks post end of treatment. Data is expressed as mean ± SD. Friedman’s test is used for statistical significance non-parametric data comparisons with repeated measures. P-value < 0.05 is statistically significant.\n\nSOF/DAC: sofosbuvir/daclatasvir, SOF/LED: sofosbuvir/ledipasvir, week 4: during treatment, week 24: 12 weeks post end of treatment. Data is expressed as mean±SD. Friedman’s test is used for statistical significance in non-parametric data comparisons with repeated measures. P-value <0.05 is statistically significant.\n\n\nDiscussion\n\nChronic HCV treatment has shifted from an IFN-based to an IFN-free regimen combination consisting of direct acting antivirals (DAAS). Twelve weeks of DAA combinations revolutionized the treatment of chronic hepatitis C virus (HCV) due to high sustained virological response (SVR) rates of 95%–100% with tolerable side effects.22,32 Successful treatment using DAAS showed overall improvements in quality of life with decreased mortality due to HCV-related complications, hepatocellular carcinoma, and the need for liver transplantations.22,31,33 Several studies have shown that HCV is associated with impaired metabolic factors such as lipid metabolism and insulin resistance (IR). Successful reversal of chronic of HCV has shown reversal of those metabolic factor alterations.7,9,31 In the present study, significant changes in both lipid profile and glycemic parameters, along with other parameters, were demonstrated in both IFN-free regimens.\n\nSustained virological response of 100% by quantitative PCR at week 24 was achieved by both groups receiving sofosbuvir/daclatasvir (SOF/DAC) and sofosbuvir/ledipasvir (SOF/LED) regimens in the current study. All 110 patients continued the study without discontinuation due to treatment side effects showing no significant differences between efficacy and safety of both treatment regimens. These results were in concordance with Abdelaty et al. and Nouh et al. where they studied the efficacy and safety of both SOF/DAC and SOF/LED treatment regimens in treatment-naïve genotype-4 chronic HCV Egyptian patients with SVR rates of 98% and 96% respectively and 98% for both groups in the Nouh et al. study with no discontinuation of therapy due to any reported side effects.34,35 Similarly, Essawy et al. achieved 100% SVR in chronic HCV Egyptian patients receiving the SOF/DAC regimen.36\n\nRegarding anthropometric measurements, both groups showed no significant difference in change of body mass index (BMI) after the end of treatment (EOT) when compared to baseline values. These results were similar to Attia et al. who studied the effects of DAAS on glycemic control in HCV diabetic patients; where no difference in body weight or waist circumference were found at EOT when compared to baseline values.37 Also, the results of Allam et al. showed no significant difference in BMI change during the entire study and that obesity had no significant effects on SVR to sofosbuvir-based regimens in chronic HCV Egyptian patients.38\n\nHowever, Kassas et al. showed an increase in overall BMI in Egyptian patients undertaking several DAAS regimens, including SOF/DAC and SOF/LED, after achieving SVR. The mechanism for increasing BMI with SVR is unclear but they suggested that the increase in BMI might be due to the psychological state improvement which leads to increased patient appetite and taste for food after achieving SVR.39 Non-significant changes of BMI in the results of this study may be due to patients being overweight or obese at the start of the study with baseline BMI values for SOF/DAC and SOF/LED 30.1 ± 6.7 and 25.1 ± 4 respectively.\n\nSuccessful viral clearance results in liver fibrosis regression due to decrease in hepatic inflammatory markers, which causes deactivation of hepatic stellate cells and myofibroblasts apoptosis.10 A significant decrease in calculated FIB-4 index in the SOF/LED group at EOT compared to baseline values was found, while there were no significant changes in the SOF/DAC group. However, Nouh et al. reported a significant decrease in FIB-4 at SVR 12 with both SOF/DAC and SOF/LED in easy-to-treat patients, while no significant difference was found in FIB-4 in patients receiving the same regimens with advanced liver fibrosis. They concluded that DAAS therapy showed little to no improvement in liver fibrosis in advanced liver disease.35\n\nThe interrelationship between host lipid metabolism and HCV was proved by previous clinical studies,21 where HCV uses host cell pathways to produce chronic infection which disrupts the host lipid metabolism.40 Regarding lipid profile, the current study results showed that low-density lipoproteins (LDL) and total cholesterol (TC) levels were increased at week four then decreased at week 24, but at levels higher than baselines levels in both treatment groups. However, comparing the two groups, these changes were more significant in SOF/LED than SOF/DAC. This was in agreement with Mohamed et al. where LDL and TC increased at one month with the SOF/DAC regimen followed by a gradual decrease of lipids at different serial measurements, but at levels higher than baseline.41\n\nRegarding triglycerides (TG) change, SOF/LED showed a significant increase in TG values at SVR 12 compared to baseline (p-value 0.023). However, in the SOF/DAC group, there was a significant increase in TG in week four (p-value = 0.028), which later significantly decreased at week 24 to a level lower than baseline levels.\n\nHigh-density lipoproteins (HDL) decreased in both groups during the entire study period compared to baseline. However, it was not significant in SOF/LED. This decrease in HDL might be explained by reverse cholesterol transport (RCT) where HDL acts as a transporter of excess cholesterol in peripheral tissue and plasma. HDL carries it to the liver where it can be either metabolized into bile salts to be excreted or directly excreted into bile.42\n\nThese results indicate that HCV clearance has a direct effect on host lipid metabolism. This was confirmed by Graf et al. who stated that DAAS are very efficient in eradication of HCV with excellent SVR rates, which leads to increased serum lipid levels during treatment and at SVR. This increase is a reflection of lipid metabolism reversal due to successful HCV eradication.43 Another possible reason for increased lipid levels after HCV clearance could be due to returning of lipids to normal levels pre-HCV infection.20\n\nThese findings indicate that successful viral elimination is not the only factor that affects lipid levels during treatment with DAAS, but DAAS themselves may have pharmacological effects on host lipid metabolism. Hence, increases in lipids are strongly dependant on antiviral DAAS type. This is in agreement with Endo et al. and Hashimoto et al. where they found an increase in LDL and TC levels after treatment in both SOF/LED and sofosbuvir/asunaprevir (SOF/ASV) but with a greater increase in the SOF/LED group than the SOF/ASV group. They suggested that DAA type might have different effects on HCV elimination affecting HCV viral kinetics or DAAS themselves may have pharmacological action on serum cholesterol during HCV eradication.22,23 Also, several studies done on Egyptian patients with genotype-4 chronic HCV infection were in agreement with the current study results where the Kamal et al. prospective study found significant increases in TC, TG, and LDL (p-value < 0.001) after treatment with DAAS.44 While El Sagheer et al. found a significant increase in serum LDL and TC at SVR 12 post treatment with sofosbuvir/simeprevir (SOF/SIM).7 In addition, Menesy et al. found a significant increase in serum LDL and TC levels in patients treated with SOF/DAC, SOF/LED, and SOF/SIM regimens, but no significant changes in TG and HDL levels were found.45\n\nMorales et al. did a retrospective study on patients taking SOF/LED, SOF/SIM, and sofosbuvir/ribavirin/interferon (SOF/RBV/IFN) regimens where they found increases in LDL and TC with minimal decrease in HDL irrespective of HCV genotype and HCV antiviral therapy. SOF/LED showed a higher increase in LDL than other SOF regimens; however, it was not significant (p-value = 0.157).9 Moreover, Ozdogan et al. suggested that an increase in LDL and TC is due to direct antiviral inhibition and elimination of DAAS on HCV and that DAAS themselves have no direct effects on lipid metabolism.46\n\nIncreases in lipid profiles after treatment with DAAS could be atherogenic, which can predict risk for cardiovascular effects. Hence, it is recommended to long-term monitor lipid profiles after treatment success with DAAS along with cardiological assessment to make sure that lipid increase is simply a pre-infection return of normal lipid levels and ensure that it has no impact on cardiovascular risk.\n\nRegarding glycemic control, this study showed a significant decrease in fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) in both treatment regimens at week four and week 24 compared to baseline in non-diabetic Egyptian patients. An explanation for glycemic control improvement might be due to the direct and indirect effects of HCV on glucose metabolism that promotes IR and inflammatory cascade which increases the risk of developing type-2 diabetes mellitus (T2DM). These alterations are successfully reversed by eradicating HCV with anti-HCV therapy through decreasing systemic inflammation that in return leads to insulin resistance (IR) improvement.47\n\nWhen comparing both groups, the SOF/LED group had a higher significant drop in HbA1c than the SOF/DAC group. This was in agreement with Morales et al. where they found a higher significant decrease in HbA1c in both diabetic and non-diabetic genotype-1 patients taking SOF/LED when compared to SOF/SIM and SOF/RBV. They suggested that this difference might be due to different DAA interactions with different targets.9\n\nIn addition, Jain et al. observed a significant improvement of HbA1c in non-diabetic patients when achieving SVR with the SOF/DAC regimen. They suggested that DAAS are responsible for improvement of glycemic parameters in non-diabetics which in return would prevent the risk of coronary heart disease in patients infected with HCV.31 Also, Adinolfi et al., who included genotype-1 non-diabetic HCV patients, reported that a significant improvement of IR was mainly due to HCV clearance which decreases stress on β-cell and prevents IR-related conditions such as T2DM, cardiovascular disorders, worsening of liver fibrosis, and metabolic syndrome.48\n\nRegarding the effect of different DAA regimens on glycemic parameters, the results of several studies conducted in HCV genotype-4 infected Egyptian patients were in accordance with the results of the current study. All the studies reported significant reductions in FBS and HbA1c after using SOF-based regimens compared to baseline values in either diabetics or non-diabetics who achieved SVR.41,44,47,49\n\nIn contrast, other studies didn’t observe a significant change in IR until six months post end of treatment (EOT) and no significant changes in FBS during and at EOT of DAAS were found.43,46,50 Meissner et al. found only a small difference in HbA1c in patients undergoing a SOF/RBV regimen over the period of 24 weeks. However, RBV can have an effect on HbA1c and so it cannot be taken as a marker for glycemic control.21\n\nHigh BMI is known to be associated with increased IR and hepatic steatosis which can later develop into hepatic fibrosis.47,51 Significant improvement in FBS and HbA1c were reported in the current study even though there were no changes in BMI before and after treatment with DAAS. This suggests that BMI is independent of changes in glycemic control, which supports the role of HCV in IR development. This was in agreement with several studies, where they found no changes or even increases in BMI before and after treatment with DAAS suggesting that improvement in IR is independent of BMI and that it is a consequence of HCV eradication by DAAS.43,47,48,50,52–54 However, Abdel Alem et al. and Attia et al. suggested that improvements in IR and HbA1c are significantly associated with decreased BMI, and recommended lifestyle changes and weight reduction during treatment with DAAS.37,47\n\nHbA1c is a crucial biomarker for long-term determination of glycemic control and plays an important role in diabetic patients’ management. Homeostatic model assessment for insulin resistance (HOMA-IR) is a viable measure of IR. However, HbA1c can be a cheaper practical measure of glycemic control to assess IR by improvements in HbA1c when achieving SVR.9,47 Moreover, the use of HOMA-IR to define IR can be problematic since there are different cut-off insulin resistance levels.3\n\nPatients would benefit from early management of HCV since it can cause early improvements in glycemic control in non-diabetics. This can prevent the future development of IR and T2DM which can alter the course of development of diabetes-related complications.\n\nOur study included a small sample size with a non-cirrhotic non-diabetic study population, which makes our findings not extendable to all HCV-infected population. Moreover, short-term follow-up of both lipid profile and glycemic control after EOT does not allow us to determine if those changes persist beyond the treatment follow-up.\n\n\nConclusions\n\nSofosbuvir-based regimens are highly effective anti-HCV therapy with excellent SVR rates and high tolerability that can improve metabolic and hepatic functions of chronically HCV genotype-4 infected Egyptian patients. It was demonstrated that DAAS had no impact on BMI. However, DAAS resulted in a significant increase in LDL, TC, and TG with decrease in HDL when achieving SVR. Rapid increase in serum lipids during treatment with DAAS is associated with HCV elimination and the type of HCV therapy regimen. Similarly, significant improvement in HbA1c and FBS were also associated with HCV elimination. Moreover, SOF/LED showed higher lipid increases with higher improvements in glycemic control than SOF/DAC.\n\n\nData availability\n\nFigshare: Underlying data for ‘Metabolic changes in chronic hepatitis C patients receiving direct acting antivirals’. https://doi.org/10.6084/m9.figshare.19097063.v125\n\nThis project contains the following underlying data:\n\n▪ Data file: Study Subjects Results (Demographics data; baseline, week 4, week 12, and week 24 Laboratory data in the study groups).xlsx\n\nFigshare: Extended data for ‘Metabolic changes in chronic hepatitis C patients receiving direct acting antivirals’. https://doi.org/10.6084/m9.figshare.19097063.v125\n\nThis project contains the following extended data:\n\n▪ Data file 1: Patient data sheet.docx\n\n▪ Data file 2: Study protocol.docx\n\n▪ Data file 3: Ethics committee approval.docx\n\n▪ Data file 4: Enrolment method with inclusion and exclusion criteria.docx\n\nFigshare: STROBE checklist for ‘Metabolic changes in chronic hepatitis C patients receiving direct acting antivirals’. https://doi.org/10.6084/m9.figshare.19097063.v125\n\nData are available under the terms of Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nConsent\n\nWritten informed consent for publication of the patients’ details was obtained from the patients.",
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PubMed Abstract | Publisher Full Text\n\nMohamed H, Sabri N, Zaki H, et al.: Clinical effects of simvastatin in chronic hepatitis C patients receiving sofosbuvir/daclatasvir combination. A randomized, placebo-controlled, double-blinded study. Clinical and Experimental. Hepatology. 2020; 6(2): 99–105.\n\nOuimet M, Barrett TJ, Fisher EA: HDL and Reverse Cholesterol Transport. Circ. Res. 2019; 124(10): 1505–1518. PubMed Abstract | Publisher Full Text\n\nGraf C, Welzel T, Bogdanou D, et al.: Hepatitis C Clearance by Direct-Acting Antivirals Impacts Glucose and Lipid Homeostasis. J. Clin. Med. 2020; 9(9).\n\nKamal EM, El-Sayed AM, Mohammed MA: Effect of Direct-Acting Antivirals on Lipid and Glucose Metabolism in Chronic HCV Patients. MJMR. 2019; 30(3): 120–123.\n\nMenesy A, Ehab A, Abbas N: Impact of Direct-Acting Antiviral Agents Treatment on Body Mass Index and Lipid Profile in Egyptian Chronic Hepatitis C Patients. Medical. J. Viral Hepat. 2021; 5.2(2): 21–26.\n\nOzdogan O, Yaras S, Ates F, et al.: The impact of direct-acting antiviral treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients: temporary? permanent?. Turk. J. Gastroenterol. 2020; 31(5): 384–392. PubMed Abstract | Publisher Full Text\n\nAbdel Alem S, Elsharkawy A, Fouad R, et al.: Improvement of glycemic state among responders to Sofosbuvir-based treatment regimens: Single center experience. J. Med. Virol. 2017; 89(12): 2181–2187. PubMed Abstract | Publisher Full Text\n\nAdinolfi LE, Nevola R, Guerrera B, et al.: Hepatitis C virus clearance by direct-acting antiviral treatments and impact on insulin resistance in chronic hepatitis C patients. J. Gastroenterol. Hepatol. 2018; 33(7): 1379–1382. PubMed Abstract | Publisher Full Text\n\nElhelbawy M, Abdel-Razek W, Alsebaey A, et al.: Insulin resistance does not impair response of chronic hepatitis C virus to direct-acting antivirals, and improves with the treatment. Eur. J. Gastroenterol. Hepatol. 2019; 31(1): 16–23. PubMed Abstract | Publisher Full Text\n\nRusso FP, Zanetto A, Gambato M, et al.: Hepatitis C virus eradication with direct-acting antiviral improves insulin resistance. J. Viral Hepat. 2020; 27(2): 188–194. PubMed Abstract | Publisher Full Text\n\nTakahashi H, Nakahara T, Kogiso T, et al.: Eradication of hepatitis C virus with direct-acting antivirals improves glycemic control in diabetes: A multicenter study. JGH Open. 2021; 5(2): 228–234. PubMed Abstract | Publisher Full Text\n\nCiancio A, Bosio R, Bo S, et al.: Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents. J. Med. Virol. 2018; 90(2): 320–327. PubMed Abstract | Publisher Full Text\n\nDawood AA, Nooh MZ, Elgamal AA: Factors Associated with Improved Glycemic Control by Direct-Acting Antiviral Agent Treatment in Egyptian Type 2 Diabetes Mellitus Patients with Chronic Hepatitis C Genotype 4. Diabetes Metab. J. 2017; 41(4): 316–321.\n\nKassem A, Mahmoud Aboelenin M, Abdelhamid Khedr M: Outcome of Eradication of Chronic Hepatitis C Virus Infection with Direct Acting Antiviral Agents on Blood Sugar Control and Insulin Resistance in Patients with Type 2 Diabetes Mellitus. Al-Azhar Medical Journal. 2018; 47(2): 241–256.\n\nMada PK, Malus ME, Parvathaneni A, et al.: Impact of Treatment with Direct Acting Antiviral Drugs on Glycemic Control in Patients with Hepatitis C and Diabetes Mellitus. Int. J. Hepatol. 2020; 2020: 6438753."
}
|
[
{
"id": "163033",
"date": "17 May 2023",
"name": "Luciana Diniz Silva",
"expertise": [
"Reviewer Expertise Sarcopenia and chronic viral hepatitis"
],
"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 specific queries and comments are below:\nThe subject studied by the authors is very relevant; however, there are three relevant points that should be evaluated. First, the small number of patients limited the statistical power of this study [sofosbuvir/daclatasvir (n = 60); sofosbuvir/ledipasvir (n = 50)]. Is there robust data from this study to support the conclusion that the “SOF/LED regimen showed a significant change in lipid profile parameters more than the SOF/DAC regimen”? Secondly, among patients who received the SOF/LED regimen and those who received the SOF/DAC regimen, several variables in addition to antiviral therapy may have had an impact on the alteration of the lipid profile, such as age, BMI, degree of necroinflammatory activity. Did the authors perform logistic regression models to assess the interaction of these independent variables with lipid profile changes? Finally, was the presence of metabolic syndrome assessed among patients who received the SOF/LED regimen and those who received the SOF/DAC regimen?\nTitle\nPlease, the title should be reviewed. The title should be focused on the objective of the study.\nAbstract\nDue to the influence of the degree of hepatic dysfunction on the lipid profile, the authors must clarify the meaning of “easy-to-treat treatment-naïve genotype-4 chronic hepatitis C virus (HCV)”.\nIntroduction:\nThe Introduction Section and the Discussion Section are conflated.\nThis section would have been strengthened by a thorough review of the literature. There is insufficient information in the Introduction to make a case for why SOF/LED regimen would impact lipid profile parameters more than the SOF/DAC. It would be important to cite previous research demonstrating this finding. What has been examined to date? To reiterate, what does the current study add to what is available in the extant literature? A succinct and clear description of the hypotheses is needed.\nMethods\nThe initial sample consisted of 300 patients; 160 were excluded. Considering the 140/110 patients included in the study, do the authors believe there may be significant differences between the initial sample and those who remained in the study? In this way, would the 110 patients reflect the patients followed at the reference service?\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?\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": "168387",
"date": "17 May 2023",
"name": "Tatsuo Kanda",
"expertise": [
"Reviewer Expertise Hepatology and viral hepatitis"
],
"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\nAuthors reported that metabolic changes in chronic hepatitis C patients receiving DAAs.\nIn Introduction section, “Globally, about 170 million patients with HCV chronic liver diseases have been reported.” WHO reported “Globally, an estimated 58 million people have chronic hepatitis C virus infection, with about 1.5 million new infections occurring per year. There are an estimated 3.2 million adolescents and children with chronic hepatitis C infection.”(https://www.who.int/news-room/fact-sheets/detail/hepatitis-c, accessed on 4/2/2023).\n\nAs cholesterol is synthesized in the liver, DAA improves liver function and then hyperlipidemia occurs.\n\nIn table 3, triglyceride levels seem better in the SOF/DAC groups. Ref. 22,23, these references did not support your description. You may make change from “SOF/ASV” to “DAC/ASV”.\n\nThe limitation of this study is that: the follow-up period is too short. Authors should follow-up for SVR-patients for their dyslipidemia and/or post-SVR HCC occurrence.\n\nData should be analyzed by absolute values not but %.\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?\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? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-649
|
https://f1000research.com/articles/10-541/v1
|
06 Jul 21
|
{
"type": "Research Article",
"title": "The number of osteoblasts and osteoclasts in hypofunctional teeth during orthodontic tooth movement in rats",
"authors": [
"Adibah Maulani",
"Cendrawasih Andusyana Farmasyanti",
"Darmawan Sutantyo",
"Cendrawasih Andusyana Farmasyanti",
"Darmawan Sutantyo"
],
"abstract": "Background: When moved orthodontically, hypofunctional teeth will have a decreased tooth movement rate compared to normal teeth. This study aimed to determine the number of osteoblasts in the tension side and the number of osteoclasts in the pressure side of the hypofunctional teeth during orthodontic tooth movement. Method: 18 male Wistar rats were given a palatal coil spring application on the maxillary incisors. Rats were divided into two groups, the orthodontic group with normal occlusion (NO) and hypofunctional occlusion (HO). The number of osteoblasts on the tension side and osteoclasts on the pressure side on days zero (D0), five (D5), and 10 (D10) were tested with two-way ANOVA. Observations were made by hematoxylin eosin staining.\nResult: The results showed that the number of osteoblasts on the tension side of the HO group was the same at the NO group (p> 0.05). The number of osteoblasts on the tension side in the NO and HO groups at D5 was the same at D10 (p = 0.99), but significantly higher (p = 0.002), than D0. The number of osteoclasts on the pressure side in the HO group was significantly lower than the NO group (p <0.05). The number of osteoclasts in the NO D5 group was significantly higher than the other groups (p <0.05).\nConclusions: The number of osteoblasts on the tension side was not affected by the hypofunctional state but decreased the number of osteoclasts on the pressure side during orthodontic tooth movement.",
"keywords": [
"Tooth movement",
"osteoblast",
"osteoclast",
"hypofunctional"
],
"content": "Introduction\n\nTooth movement in orthodontic treatment is a biological response to mechanical forces characterized by remodeling processes in dental and paradental tissue, including pulp tissue, periodontal ligaments, alveolar bone, and gingiva.1 Osteoblasts, osteoclasts, and osteocytes play an essential role in bone remodeling in orthodontic tooth movement.2\n\nClinicians often encounter cases which need to move the teeth that functionally never have occlusal pressure or hypofunctional teeth, such as open bite, ectopic canine, linguioversion and bucoversion teeth.3 Open bite malocclusion occurs when maxillary and mandibular teeth are not in contact.4\n\nHypofunctional teeth cause atrophic changes in the periodontal ligament, a decrease in the number of periodontal fibers and blood vessels, and the periodontal space's narrowing. Periodontal space's narrowing occurs due to the apposition of the alveolar bone by an increase in Transforming Growth Factor β (TGFβ), causing tooth elongation.5 Changes in the paradental structure of hypofunctional teeth cause different reactions when orthodontically moved than normal teeth, especially in periodontal ligament tissue. Hypofunctional teeth when orthodontically moved have less heparan sulfate proteoglycan exposure, which plays a role in the osteoclastic activity, compared to normal teeth.5 Expression of Vascular Endothelial Growth Factor (VEGF) in hypofunctional teeth also decreases during orthodontic movement leading to vascular constriction and endothelial cell apoptosis. The expression of VEGF has an important role in the resorption and apposition processes of alveolar bone because it affects the proliferation and differentiation of osteoblasts and osteoclasts in vitro.6 Research on the number of osteoblasts on the tension side and osteoclasts on the pressure side in hypofunctional teeth during orthodontic movement has never been done before. This study aimed to determine the number of osteoblasts on the tension side and osteoclasts on the pressure side on hypofunctional teeth, respectively, during orthodontic tooth movement.\n\nWistar rats are considered a good research model for this study into orthodontic tooth movement because rats are cheap, making them easy to use as a large quantity sample, and the histological profiles of rats are easy to compare, especially in incisor teeth. Incisor teeth of Wistar rats have a gingival structure that almost resembles humans’, and is easy to install the orthodontic appliance into.\n\n\nMethods\n\nAll experimental procedures were performed according to the Institutional Animal Care and Usage Committee (ARRIVE guidelines). The Ethical Clearance was approved by Ethical Committee of the Faculty of Dentistry of Universitas Gadjah Mada Yogyakarta, Indonesia, with Ethical Clearance number 00288/KKEP/FKG-UGM/EC/2019. All procedures involving rats were carried out with consideration to eliminate any suffering in the rats by using anesthetic drugs and euthanasia procedures during rats’ tissue collection.\n\nThis study used 18 five-month-old, male, healthy rats weighing ± 400 grams, which had never been used in any procedures before. Rats adapted beforehand for seven days on a standard diet, including pellets. Rats were placed in cages at room temperature, which was 26C. Inclusion criteria related to body weight, sex, age, and health condition of the rats. Exclusion criteria included any technical issues that could disrupt orthodontic tooth movement, such as trapped bonding inside palatal coil.\n\nExperimental animals were divided into two groups: the normal occlusion (NO) and the hypofunctional occlusion group (HO), both were moved orthodontically. This study was done without a control group in order to examine orthodontic tooth movement with and without occlusion over a period of time. In the hypofunctional group, the mandibular left incisors were cut to the gingival margin level every two days to obtain consistent spacing throughout the study. The sample size was determined using the Federer formula. Each group consisted of three rats with three groups of observation days: day zero (D0), day five (D5), and day 10 (D10). Rats were allocated to their groups using a simple randomization method: each rat was labelled, and a blindfolded researcher drew corresponding labels from a hat for each group. Researchers were aware of which group was which during the experiment.\n\nAnimals were anesthetized using 10% ketamine 35 mg/kg and 2% xylazine 5 mg/kg intramuscularly during spring installation and reduction of left lower incisor. The upper incisors were separated using a customized palatal coil spring of 0.012 mm stainless steel wire (Ortho Prime Inc. USA: A 85021201; orthoshape SS 0,012”) connected to two metal bands (Dentaurum) with the arm length is 5 mm and the coil diameter is 2 mm. The customized coil spring was deflected for 3.4 mm to deliver an orthodontic force of 17.5 cN per upper incisor before being installed.7 The palatal coil spring was cemented using GIC Fuji IX, as shown in Figure 1. Then the left lower incisor was cut.\n\nAll experimental animals in day zero, day five, and day 10 groups were euthanized using an overdose solution of ketamine and xylazine (lethal dose: ketamine (KEPRO.BV production), 300 mg/kg BW and brand xylazine (Xyla) 30 mg/kg BW) intraperitoneally. Cross sections were taken on alveolar crest region of the upper incisor, shown in Figure 2. The number of osteoblasts were counted on the tension side and osteoclasts were counted on the pressure side using hematoxylin eosin staining and observed using an optical microscope (Olympus) with 400 times magnification in three fields of view every slide. Osteoblast cells appear cuboidal or columnar, purple, and single-nucleated. Osteoclast cells appear multinucleated with random boundaries, and purple in the resorption lacunae.\n\nThe program used to perform statistical analysis was SPSS version 17.0 for Windows. Cohen's Kappa test value from two observers showed more than 0.50, which means there was good agreement between the two observers. All data were normally distributed and homogeneous. The research data were then analyzed using the two-way ANOVA test followed by the Post Hoc test, Multiple Comparison (LSD). The confidence level used in this study is 95%.\n\n\nResults\n\nThe results in Table 1 show that the number of osteoblasts on the tension side of the hypofunctional group is higher than the normal group, but the difference is not significant (p = 0.187). The number of osteoblasts in the normal occlusal contact group (NO) increased significantly on day five and continued to increase until day 10, as seen in Table 2, in contrast to the hypofunctional group, which increased until day five but slightly decreased on day 10.\n\nAbbreviations: SD, standard deviations; NO, normal occlusion group; HO, hypofunctional occlusions group; D0, day zero; D5, day five; D10, day 10.\n\nAbbreviations: D0, day zero; D5, day five; D10, day 10.\n\nThe highest number of osteoblasts on the tension side was seen in the hypofunctional group on day five. The lowest number of osteoblasts on the tension side was seen in the orthodontic tooth movement group with normal occlusion on day zero.\n\nThe number of osteoblasts in the normal occlusion group (A) and the number of osteoblasts in the hypofunctional group (B) in the tension side during tooth movement is shown in Figure 3. Figure 4 showed the number of osteoclasts in the normal occlusion (C) and the hypofunctional groups (D) in the pressure side during orthodontic treatment.\n\nAB: Alveolar Bone, PDL: Periodontal Ligament.\n\nAB: Alveolar Bone, PDL: Periodontal Ligament.\n\nThe results in Table 3 showed that the number of osteoclasts in the hypofunctional group was significantly lower than the normal occlusion group on each day of observation (p = 0.014). The number of osteoclasts on the pressure side during orthodontic tooth movement in the normal occlusion group began to significantly increase until day five, as seen in Table 4, then decreased on day 10. This pattern was the same as in the hypofunctional group, which increased until day five, then decreased on day 10. The highest number of osteoclasts on the pressure side was seen in the normal occlusion group on day five.\n\nAbbreviations: SD, standard deviations; NO, normal occlusion group; HO, hypofunctional occlusions group; D0, day zero; D5, day five; D10, day 10.\n\nAbbreviations: D0, day zero; D5, day five; D10, day 10.\n\n\nDiscussion\n\nThe study showed that the number of osteoblasts in the normal occlusion group had increased significantly on day five and then showed no significant difference until day 10, as seen in Table 2. This result was in line with Herniyati’s8 research, which stated that the formation of preosteoblasts from mesenchymal cells had occurred 10 hours after applying force, followed by the differentiation of osteoblasts 40-48 hours later. The maximum number of osteoclasts was reached on the 6th day of orthodontic tooth movement.9 This osteoblast differentiation and proliferation lasted up to 10 days.10\n\nThe increasing number of osteoblasts on the tension side during 10 days of observation occurs because in the early phase of orthodontic tooth movement there will be an acute inflammatory response characterized by periodontal tissue vasodilation and prostaglandin secretion and growth factors such as TGFβ.1 TGFβ is also produced by fibroblasts on the tension side. TGFβ is an important factor in osteoblastogenesis and bone formation by recruiting osteoblast progenitors and stimulating the differentiation of bone matrix. An increase in TGFβ will increase osteoblast proliferation on the tension side.11 This acute inflammatory response will lead to an increasing number of osteoblasts in the early phase. One to two days later, the acute phase of inflammation is replaced by a chronic inflammatory process that is more proliferative, involving fibroblasts, endothelial cells, and osteoblasts.1\n\nThe number of osteoblasts on the tension side during orthodontic movement of teeth with normal occlusion is influenced by several growth factors that are sensitive to mechanical stimuli, such as the expression of TGFβ, VEGF, Fibroblast Growth Factor (FGF), and Insulin-like Growth Factor (IGF). The increase in growth factor on the tension side will cause an increase in the number of osteoblasts. Hypofunctional teeth, without orthodontic force, will experience an increase in TGFβ expression, which simultaneously decreases VEGF, IGF, and FGF expression in the periodontal tissue.5,6,12,13 Transforming Growth Factor β has a role in stimulating osteoblast differentiation and osteoclast apoptosis.5 Decreased FGF will lead to osteoblast differentiation in hypofunctional teeth because FGF works to inhibit osteoblast differentiation.13 The decrease in IGF causes a decrease in osteoblast proliferation because IGF is dominant in providing osteogenic effects.14\n\nTeeth that are hypofunctional when moved orthodontically will tend to experience decreased VEGF expression on both the tension and pressure sides.6 Decreased VEGF expression will cause apoptosis of endothelial cells, causing vascular constriction and decreased permeability. This will reduce the migration of osteoblasts on the tension side.6 Increased TGF and decreased FGF in hypofunctional teeth will increase osteoblasts.\n\nThe results showed the number of osteoblasts on the tension side of the hypofunctional teeth was the same as normal teeth during orthodontic movement (p > 0.05). This was possible because before orthodontic movement there was an increase in osteoblasts due to the interaction of increasing TGFβ and decreasing FGF and IGF, but simultaneously when hypofunctional teeth were given orthodontic force, there was a decrease in VEGF which tended to decrease osteoblast differentiation and migration, so that the number of osteoblasts became the same as the normal group. This needs further research.\n\nThe results showed the number of osteoclasts on the pressure side of the normal group began to increase on the first day after the installation of a palatal coil spring and continued increasing until the fifth day, then decreased. on day 10. This result was almost the same as in the hypofunctional group, which increased up to day five, then decreased on day 10. This result is in line with the study by Miyoshi15 which states that orthodontic movements immediately after force application are almost absent in osteoclasts. After the third day of mechanical strength application, several osteoclasts appeared. The maximum number of osteoclasts was reached on day six of orthodontic tooth movement.9 The increase in osteoclasts on day three was in line with the increase in VEGF expression, which also increased sharply.16\n\nAn increasing number of osteoclasts occur because, in the early phase, the mechanical stress in the compression area will stimulate mechanoreceptors on osteocytes and cause changes in flow and blood vessels, causing tissue hypoxia that activates VEGF.17 VEGF plays an essential role in the angiogenesis process in the area of hyalinization.16 VEGF also plays a role in vascular permeability and activates endothelial cells. Active endothelial cells in the area of compression will cause chemoattraction of acute inflammatory cells such as leukocytes, monocytes, and macrophages. Leukocytes will stimulate prostaglandins and macrophage-colony stimulating factor (M-CSF). Increased prostaglandins in the area of compression will stimulate osteoblast differentiation and receptor activator of nuclear factor-kappa B ligand (RANKL) expression, whereas M-CSF can induce osteoclast differentiation by attaching to the c-Fms receptor on monocytic lineage cells. RANKL and M-CSF play an essential role in the process of osteoclast differentiation and bone resorption.17\n\nThe number of osteoclasts on the pressure side in the hypofunctional group was smaller than the normal occlusion group on each observation day. This result was probably because VEGF expression in hypofunctional teeth decreases during orthodontic movement leading to vascular constriction and endothelial cell apoptosis.6 Endothelial cell apoptosis will cause decreased osteoclast differentiation and bone resorption.17 The decrease in VEGF will also cause a decrease in vascular permeability so that it will significantly imply a decrease in the number of osteoclasts.18\n\nOrthodontic tooth movement involves osteoblastic activity on the tension side and osteoclastic activity on the pressure side.1 The decrease in the number of osteoclasts on the pressure side in the orthodontic tooth movement of this hypofunctional tooth group suggests a possible decrease in the rate of orthodontic tooth movement. This is in line with the research of Usumi-Fujita6 which states that there is a decrease in the rate of orthodontic movement in hypofunctional teeth.\n\n\nConclusion\n\nIn conclusion, the number of osteoblasts on the tension side was not affected by the hypofunctional condition but decreased the number of osteoclasts on the pressure side during orthodontic tooth movement. The number of osteoclasts in hypofunctional teeth is lower compared to the normal group during orthodontic tooth movement. It is possible that this is because of the decrease in VEGF and heparan sulfate proteoglycan.\n\n\nData availability\n\nFigshare: The Number of Osteoclast and Osteoblast in Hypofunctonal Teeth during orthodontic tooth movement. https://doi.org/10.6084/m9.figshare.14515740.v8.\n\nThis project contains the following underlying data:\n\n- osteoclasts.xlsx\n\n- osteoblasts.xlsx\n\n- table of statistic analysis.docx\n\n- Figure 1. jpg\n\n- Figure 2. jpg\n\n- Figure 3 A.jpg\n\n- Figure 3 B.jpg\n\n- Figure 4 C.jpg\n\n- Figure 4 D.jpg\n\n\nReporting guidelines\n\nFigshare: ARRIVE Checklist, Maulani et al. https://doi.org/10.6084/m9.figshare.14515740.v8.\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "References\n\nKhrisnan V, Davidovitch Z: Cellular, Molecular, and Tissue-level Reactions to Orthodontic Force. Am J Orthod Dentofacial Orthop. 2006; 129(4): 469e1–469e32. PubMed Abstract | Publisher Full Text\n\nMaleeh I, Robinson J, Wadhwa S: Role of Alveolar Bone in Mediating Orthodontic Tooth Movement and Relapse. Biology of Orthodontic Tooth Movement. Springer, Switzerland; 2016. Publisher Full Text\n\nEsashika M, Kaneko S, Yanagishita M, et al.: Influence of Orthodontic Force on the Distribution of Proteoglycans in Rat Hypofunctional Periodontal Ligament. J Med Dent Sci. 2003; 50: 183–194. PubMed Abstract\n\nTasanapanont J, Wattanachai T, Apisariyakul J, et al.: Biochemical and Clinical Assessments of Segmental Maxillary Posterior Tooth Intrusion. Int J Dent. 2017; vol. 2017(2689642): 1–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nItohiya K, Kazaki H, Ishikawa M, et al.: Occlusal Hypofunction Mediates Alveolar Bone Apposition via Relative Augmentation of TGF-β Signaling by Decreased Asporin Production in Rats. Dental Oral Craniofacial Res. 2016; 3(1): 1–8.\n\nUsumi-Fujita R, Hosomichi J, Ono N, et al.: Occlusal Hypofunction Causes Periodontal Atrophy and VEGF/VEGFR Inhibition in Tooth Movement. Angle Orthodontist. 2013; 83(1): 48–56. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFarmasyanti CA, Kujipers-Jagtman AM, Susilowati H, et al.: Effects of Pentagamavunon-0 (PGV-0) as Alternative Analgesics on Orthodontic Tooth Movement in Rats. Padjajaran J Dentistry. 2019; 31(3): 152–160.\n\nHerniyati H: The increased number of osteoblasts and capillaries in orthodontic tooth movement post-administration of Robusta coffee extract. Dental J (Majalah Kedokteran Gigi). 2017; 50(2): 91–96.\n\nArias OR, Marquez-Orozco MC: Aspirin, Acetaminophen, and Ibuprofen:Their Effects on Orthodontic Tooth Movement. Am J Orthod Dentofacial Orthop. 2006; 130(3): 364–370. PubMed Abstract | Publisher Full Text\n\nd’Apuzzo F, Cappabianca S, Ciavarella D, et al.: Biomarkers of Periodontal Tissue Remodelling during Orthodontic Tooth Movement in Mice and Men: Overview and Clinical Relevance. ScientificWorldJournal. 2013: 1–8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIndriasari V, Suparwitri S, Christnawati C, et al.: Different Effects of Soybean Isoflavone Genistein on Transforming Growth Factor Levels during Orthodontic Tooth Movement among Young and Old Rabbits. F1000Res. 2020: 1–14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTermsuknirandorn S, Hosomichi J, Soma K: Occlusal Stimuli Influence on the Expression of IGF-1 and IGF-1 Receptor in the Rat Periodontal Ligament. Angle Orthodontist. 2008; 78(4): 610–616. PubMed Abstract | Publisher Full Text\n\nBoonpratham S, Kanno S, Soma K: Occlusal Stimuli Regulate IL-1β and FGF-2 Expression in Rat Periodontal Ligament. J Med Dent Sci. 2007; 54(1): 71–77. PubMed Abstract\n\nTokimasa C, Kawata T, Kaku M, et al.: Effects of Insulin-like Growth Factor-I on the Expression of Osteoclasts and Osteoblasts in the Nasopremaxillary Suture under Different Masticatory Loading Conditions in Growing Mice. Arch Oral Biol. 2003; 48: 31–38. PubMed Abstract | Publisher Full Text\n\nMiyoshi K, Igarashi K: Tooth Movement and Changes in Periodontal Tissue in Response to Orthodontic Force in Rats Vary Depending on the Time of Day the Force is Applied. Eur J Orthod. 2001; 23(4): 329–338. PubMed Abstract | Publisher Full Text\n\nSalomao MFL, Reis SRA, Vale VLC, et al.: Immunolocalization of FGF-2 and VEGF in Rat Periodontal Ligament During Experimental Tooth Movement. Dental Press J Orthod. 2014; vol. 19, no. 3, pp. 67–74. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi Y, Laura A, Jacox SH: Orthodontic Tooth Movement:The Biology and Clinical Implications. Kaohsiung J Med Sci. 2018; 34(4): 207–214. PubMed Abstract | Publisher Full Text\n\nKaku M, Kohno S, Kawata T, et al.: Effects of Vascular Endothelial Growth Factor on Osteoclast Induction during Tooth Movement in Mice. J Dent Res. 2001; 80(10): 1880–1883. PubMed Abstract | Publisher Full Text\n\nMaulani A: The Number of Osteoclasts and Osteoblasts in Hypofunctional teeth during orthodontic tooth movement. figshare, Thesis. 2021. Publisher Full Text"
}
|
[
{
"id": "89164",
"date": "15 Jul 2021",
"name": "Erliera Sufarnap",
"expertise": [
"Reviewer Expertise cellulars in the orthodontic tooth movement 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\nPlease allow me to congratulate the authors to perform this research study which I found quite interesting and useful as a reference for further study in the orthodontics field. We have been reviewing the manuscript.\nHowever, I may require some clarifications on the following issues. My reviews recommend reconsideration to have some minor revisions which I will addressing the inquiries below.\nGeneral comment:\nThe paper is well organized and easy to follow. It also well-written and well-structured but unfortunately there were had some typos, inconsistent of using words or abbreviation, had an ambiguous comprehension in reporting the analysis results, and many statement didn’t follow with references. I suggest the revision of the English grammar structures by an expert and also to the statistician to interpret the result.\n\nA. Abstract:\n- Background:\n“When moved orthodontically, hypofunctional teeth will have a decreased tooth movement rate compared to normal teeth” - This background already described the results indirectly which can correlated to lower osteoclast production and increased osteoblast. Please find another reason as a research gap which doesn’t comprehend to the OTM, maybe from the periodontal point of view.\n- Results:\n\nPlease describe the exact numbers of the p-value of each osteoblast and osteoclast, and compare mean between groups as the result.\n\nOsteoblast: The post hoc analysis which had been analysed to “compare” between each time points (internally) for both groups and please further describe with statistically words and maintain the chronological time points, i.e., significantly increased at D0-D5, D0-D10 and not significantly changed at D5-D10.\n\nB. Introduction:\nAt the last chapter, the research gap and the objective of the study clearly mentioned but We couldn’t see any hypothesis described in the introduction.\n\nDescribe the reference of why the animal model being used\n\nC. M&M:\n1. Animals:\nPlease explain scientifically with refference the rationale to choose the male Wistar rats. The hypofunctional teeth could be happened to all genders.\n\n“…without a control group”; In my opinion, the NO already intervened as a control group.\n\nThe teeth were cut to the gingival margin level every 2 days. Explain about the teeth and pulp anatomical condition. Please also mention why the teeth were cut every 2 days.\n2. Procedures:\nFigure 1: We couldn’t see properly the palatal coil spring.\n\nMicroscope (Olympus); please provide the type of the Olympus microscope.\n\nPlease provide the reference which were mentioned for the osteoblast and osteoclast characteristics\n\n3. Statistical analysis:\n\nWho were the two observers? Please mention in the manuscript.\n\nD. Results:\nThe post hoc analysis were compared the differences between each time point for both HO and NO groups. Please describe those results based on the data, i.e, at D0 to D5, D0 to D10 and D5 to D10.\n\nPlease consistent of using “the group’s name”; with or without abbreviation. As if it will choose without abbreviation please further consistent of using complete group’s name. For some journal, they would prefer mention with abbreviation though.\n\nE. Discussion:\nAt the first sentence for osteoblast discussion it discussed about time interval analysis, the author described only NO group unfortunately from Table 2 only had 1 result, did it mean that the statistic aimed to compare between time for both groups together? It supposed that the HO and NO increased together significantly at D0-D5 and D0-D10. Please, it would be more satisfy as if the author would ask the statistician whether the post hoc analysis results addressed for each group or for both group.\n\nThe first paragraph described all about osteoblast, but at the second last sentence it described about osteoclast. It has been incompatible discussion.\n\nThe second and third paragraphs describes slightly about Growth factors. Please describes first from the general (all GF) and then followed to each GF discussion.\n\nTypos found in the TGF abbreviation supposed to be TGFb.\n\nSome discussion for several paragraph didn’t have references.\n\nWe couldn’t find any study’s limitation. As if the study were flawless it would be accepted.\n\nF. Conclusion:\nPlease conclude the study based on the results.\n\nPlease be consistent in using the groups name.\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": [
{
"c_id": "8073",
"date": "29 Apr 2022",
"name": "Adibah Maulani",
"role": "Author Response",
"response": "Dear Dr. Erliera Sufarnap Thank you for your kind assistance in reviewing our manuscript and providing us with valuable advices. Please allow us to comment as follows : Background: “When moved orthodontically, hypofunctional teeth will have a decreased tooth movement rate compared to normal teeth” - This background already described the results indirectly which can correlated to lower osteoclast production and increased osteoblast. Please find another reason as a research gap which doesn’t comprehend to the OTM, maybe from the periodontal point of view. Hypofunctional teeth would have less VEGF expression and decreased heparan sulfate proteoglycan production during orthodontic tooth movement. The study about periodontal structure of hypofunctional teeth that moved orthodontically is never been done before. Results: Please describe the exact numbers of the p-value of each osteoblast and osteoclast, and compare mean between groups as the result. p-value of osteoblast between NO and HO group is 0.187 p-value of osteoclast between NO and HO group is 0.014 Osteoblast: The post hoc analysis which had been analysed to “compare” between each time points (internally) for both groups and please further describe with statistically words and maintain the chronological time points, i.e., significantly increased at D0-D5, D0-D10 and not significantly changed at D5-D10. Osteoblast significantly increased at D0 to D5 with p-value 0.002, and so is at D0 to D10. However, at D5 to D10, the number of osteoblast is not significantly different, with p-value 0.99. B. Introduction: At the last chapter, the research gap and the objective of the study clearly mentioned but We couldn’t see any hypothesis described in the introduction. Hypotheses of the study are: The number of osteoblasts on the tension side of the hypofunctional teeth is higher than normal teeth during orthodontic tooth movement. There is an increase in the number of osteoblasts and osteoclast of the hypofunctional teeth during 5 and 10 days of orthodontic tooth movement. The number of osteoclasts on the pressure side of the alveolar bone in hypofunctional teeth lower than normal teeth during orthodontic tooth movement. Describe the reference of why the animal model being used This study used animal model because we would like to see histologically during orthodontic tooth movement in hypofunctional teeth. The histological profiles of rats are easy to compare, especially in incisor teeth. Incisor teeth of Wistar rats have a gingival structure that almost resembles humans (Ren et al., 2004). Thank you for your kind assistances. We would complete the references in new version of the article. C. M&M: 1. Animals: Please explain scientifically with refference the rationale to choose the male Wistar rats. The hypofunctional teeth could be happened to all genders. The reason why we choose male Wistar rats is because we avoid hormonal influences in female Wistar rats during orthodontic tooth movement. “…without a control group”; In my opinion, the NO already intervened as a control group. Thank you very much for your insight. The teeth were cut to the gingival margin level every 2 days. Explain about the teeth and pulp anatomical condition. Please also mention why the teeth were cut every 2 days. Wistar rats is a rodent, so the incisor teeth will erupt continuously. To maintain the space between maxillary incisor teeth and mandible incisor teeth, the teeth were cut to the gingival margin every 2 days. The teeth and pulp was still in good condition even after being cut every 2 days. This method was done based on previous study by Silva and Merzel (2004). 2. Procedures: Figure 1: We couldn’t see properly the palatal coil spring. Thank you very much for your suggestion, I have revised it in recent article. Microscope (Olympus); please provide the type of the Olympus microscope. Olympus CX-22 (Olympus, Germany). Please provide the reference which were mentioned for the osteoblast and osteoclast characteristics Osteoblast characteristic was based on previous study by Alhasyimi et al., (2018) which mentioned that osteoblast is cuboid cell with single and deep-blue nucleus. Osteoclast cells appear multinucleated with random boundaries, and purple in the resorption lacunae (Florencia-silva et al., 2015). Thank you for your kind assistances. We would complete the references in new version of the article. 3. Statistical analysis: Who were the two observers? Please mention in the manuscript. The two observer were two-trained person who performed the measurement of osteoblast and osteoclast cell histologically. They were blinded to the applied sample. Thank you very much for your suggestion, I have revised it in recent article. D. Results: The post hoc analysis were compared the differences between each time point for both HO and NO groups. Please describe those results based on the data, i.e, at D0 to D5, D0 to D10 and D5 to D10. Osteoblast significantly increased at D0 to D5 with p-value 0.002, and so is at D0 to D10. However, at D5 to D10, the number of osteoblast was not significantly different, with p-value 0.99. Osteoclast significantly increased at D0 to D5 with p-value 0.011. However, osteoclast significantly decreased at D5 to D10 with p-value 0.004. The number of osteoclast between D0 to D10 was not significantly different, with p-value 0.626. Please consistent of using “the group’s name”; with or without abbreviation. As if it will choose without abbreviation please further consistent of using complete group’s name. For some journal, they would prefer mention with abbreviation though. Thank you very much for your suggestion, I have revised it in recent article. E. Discussion: At the first sentence for osteoblast discussion it discussed about time interval analysis, the author described only NO group unfortunately from Table 2 only had 1 result, did it mean that the statistic aimed to compare between time for both groups together? It supposed that the HO and NO increased together significantly at D0-D5 and D0-D10. Please, it would be more satisfy as if the author would ask the statistician whether the post hoc analysis results addressed for each group or for both group. Thank you very much for your suggestion. The result between HO and NO group is not significantly different. Increasing number of osteoblast from D0 to D5 and then D10 on HO group has the same pattern with NO group, so the Post Hoc analysis is aimed to compare between time for both group together. The first paragraph described all about osteoblast, but at the second last sentence it described about osteoclast. It has been incompatible discussion. Thank you for your kind assistance, I apologize for the typo. I have revised it in recent article. The second and third paragraphs describes slightly about Growth factors. Please describes first from the general (all GF) and then followed to each GF discussion. Growth factors are proteins that attach to receptors on the cell surface, thereby activating a signal transduction, and subsequently affecting cell proliferation, differentiation, and apoptosis. Most growth factors have a specific effect on certain cell types on the process of proliferation and differentiation. For example, Fibroblast Growth Factor (FGF), Transforming Growth Factor (TGF)-β, and Insulin-like Growth Factor (IGFs), required for growth of bone, muscle, and other cells (Stone et al., 2022). TGF-β (Transforming Growth Factor β) is growth factor that can affect bone metabolism. This mediator regulates bone remodeling by modulating osteoblasts and osteoclasts (Fox and Lovibond, 2005). Transforming Growth Factor has the role of stimulating differentiation osteoblasts and osteoclast apoptosis (Itohiya et al., 2016). FGF (Fibroblast Growth Factor) is a representative growth factor which has shown the potential effects on the repair and regeneration of tissues (Moya et al, 2010). Basic fibroblast growth factor (bFGF) also involved in stimulation of osteoblasts and osteoclasts (Seifi et al., 2013). IGF, induced by growth hormone and parathyroid hormone, is reproduced by osteoblast, chondrocytes and other bone cells, and plays an essential part as a local modulator in cell differentiation and proliferation in either an autocrine or paracrine manner. Igf-I stimulates not only osteoblast proliferation but also osteoclast formation (Tokimasa et al., 2003). VEGF (Vascular Endhotelial Growth Factor) is an essential mediator during the process of angiogenesis, bone remodelling by stimulating osteoblast differentiation, and osteoclastic recruitment (Yang et al., 2012).. Typos found in the TGF abbreviation supposed to be TGFb. Thank you very much for your suggestion, we have revised the typos in new version of the article. Some discussion for several paragraph didn’t have references. Thank you for your kind assistances. We would complete the references in new version of the article. We couldn’t find any study’s limitation. As if the study were flawless it would be accepted. Thank you for your kind suggestions, this study’s limitations including days of observations which was limited for 10 days. Further study should provide longer time, at least 14 days up to 21 days, to observe further effect of hypofunctional condition in the number of osteoblast and osteoclast cell during orthodontic tooth movement. F. Conclusion: Please conclude the study based on the results. The number of osteoblasts on the tension side was not affected by the hypofunctional condition but the number of osteoclasts on the pressure side was lower during orthodontic tooth movement under hypofunctional condition. Please be consistent in using the groups name Thank you very much for your suggestion, we have revised the groups name recent article. References Stone WL, Leavitt L, Varacallo M. Physiology, Growth Factor. StatPearls Publishing. 2022. https://www.ncbi.nlm.nih.gov/books/NBK442024/ Fox SW, Lovibond AC. Current insights into the role of transforming growth factor-beta in bone resorption. Mol Cell Endocrinol. 2005;243(1-2):19–26. Itohiya K, Kazaki H, Ishikawa M, et al.: Occlusal Hypofunction Mediates Alveolar Bone Apposition via Relative Augmentation of TGF-β Signaling by Decreased Asporin Production in Rats. Dental Oral Craniofacial Res. 2016;3(1):1–8. Moya ML, Cheng MH, Huang JJ, Francis-Sedlak ME, Kao SW, Opara EC, Brey EM Biomaterials. 2010 Apr; 31(10):2816-26. Seifi M, Badiee MR, Abdolazimi Z, Amdjadi P. Effect of basic fibroblast growth factor on orthodontic tooth movement in rats. Cell J. 2013;15(3):230-237. Tokimasa, C., Kawata, T., Kaku, M., Kohno, S., Tsutsui, K., Tenjou, K., Ohtani, J., Motokawa, M., Tanne, K., 2003, Effects of Insulin-like Growth FactorI on the Expression of Osteoclasts and Osteoblasts in the Nasopremaxillary Suture under Different Masticatory Loading Conditions in Growing Mice, Arch Oral Biol, 48:31-8 Yang YQ, Tan YY, Wong R, Wenden A, Zhang LK, Rabie AB. The role of vascular endothelial growth factor in ossification. Int J Oral Sci. 2012 Jun;4(2):64-8. doi: 10.1038/ijos.2012.33. PMID: 22722639; PMCID: PMC3412670."
}
]
},
{
"id": "119271",
"date": "28 Jan 2022",
"name": "Masaru Yamaguchi",
"expertise": [
"Reviewer Expertise Dental",
"Orthodontics",
"bone metabolism",
"inflammation"
],
"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 describes that the number of osteoblasts and osteoclasts in hypofunctional teeth during orthodontic tooth movement in rats. Generally, this manuscript is interesting. However, there are some concerns as presented and some of these are discussed below.\nMajor Comments:\nWas the force in this study optimal? The optimal force for molar tooth movement in rat may be 10g. The 25cN may induce an undermining bone resorption. In incisor, 17.5 cN force may be strong.\n\nHow much was the amount of tooth movement? Please add the results of them.\n\nI think that research on Hypofunction is generally more suitable for molars, but how about it?\n\nThe authors concluded that the number of osteoblasts on the tension side was not affected by the hypofunctional state but decreased the number of osteoclasts on the pressure side during orthodontic tooth movement. However, this statement seems inconsistent. Did the number of osteoblasts on the tension side in hypofunction group also decreased?\n\nI think that immunostaining such as TGF-b, VEGF, FGF, and IGF will be a better 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? 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": "8074",
"date": "29 Apr 2022",
"name": "Adibah Maulani",
"role": "Author Response",
"response": "Dear Dr. Masaru Yamaguchi Thank you for your kind assistance in reviewing our manuscript and providing us with valuable advices. Please allow us to comment as follows : Was the force in this study optimal? The optimal force for molar tooth movement in rat may be 10g. The 25cN may induce an undermining bone resorption. In incisor, 17.5 cN force may be strong. Thank you very much for your insight. The force in this study was moderate force and already used in previous study about the rate of orthodontic tooth movement in rat incisor. How much was the amount of tooth movement? Please add the results of them. Thank you very much for your suggestion. We already revised in new version by adding the rate of orthodontic tooth movement of this study. I think that research on Hypofunction is generally more suitable for molars, but how about it? Hypofunctional research is usually done on molar because the hypofunctional state is easier to obtain by removing the upper molar teeth of rats. However, in this study, we chose incisors in order to facilitate the installation of orthodontic appliances and the anatomical structure of the periodontal tissue of the rat incisor was almost similar to humans. The hypofunctional state in this study was obtained by cutting the lower incisors of rats every two days. The authors concluded that the number of osteoblasts on the tension side was not affected by the hypofunctional state but decreased the number of osteoclasts on the pressure side during orthodontic tooth movement. However, this statement seems inconsistent. Did the number of osteoblasts on the tension side in hypofunction group also decreased? The number of osteoblast on the tension side in hypofunction group was actually increase, but not significant. Because it was not significant, we conclude that the number of osteoblast on tension side was not effected. I think that immunostaining such as TGF-b, VEGF, FGF, and IGF will be a better paper. Thank you very much for your suggestion. We would continue the study to know deeper using immunostaining."
}
]
}
] | 1
|
https://f1000research.com/articles/10-541
|
https://f1000research.com/articles/11-647/v1
|
13 Jun 22
|
{
"type": "Research Article",
"title": "Consumers’ behavior in conversational commerce marketing based on messenger chatbots",
"authors": [
"Reena Mehta",
"Jose Verghese",
"Shriya Mahajan",
"Sergey Barykin",
"Svetlana Bozhuk",
"Nelli Kozlova",
"Irina Vasilievna Kapustina",
"Alexey Mikhaylov",
"Elena Naumova",
"Natalia Dedyukhina",
"Reena Mehta",
"Jose Verghese",
"Shriya Mahajan",
"Svetlana Bozhuk",
"Nelli Kozlova",
"Irina Vasilievna Kapustina",
"Alexey Mikhaylov",
"Elena Naumova",
"Natalia Dedyukhina"
],
"abstract": "Background: The increasing penetration of smartphones and the Internet in developing countries caused the rise of e-retail. Conversational commerce is highly increasing via interaction through messengers. To extract the benefits of both trends, companies have adopted messenger chatbots. These chatbots use Artificial intelligence and natural language processing to give live responses to the customer and assist online shopping on the messenger interface. This research aims to discover the factors that affect the use of messenger chatbots and their influence on attitude and behavior intention. Methods: The research methodology includes the Technology Acceptance Model (TAM) with the variables of perceived usefulness, perceived ease of use, consumer trust, and anthropomorphism. The authors used an online survey for collecting the responses from 192 respondents and analyzed structural equation modelling. Results: Customer trust has shown the most decisive influence on customer attitude followed by Perceived Usefulness, Perceived Ease of Use. Also, the use of chatbots to make online shopping faster significantly affects the use of messenger chatbots for online shopping in the future. The authors explore various factors resulting in consumers’ favor of accepting chatbots as an interface for m-commerce. Conclusions: The findings indicate that organizations should design strategies to improve interaction with the customer by developing messenger chatbots for more trusting conversations. Further research could include a theoretical digital marketing approach to conversational commerce based on anthropomorphic digital technologies.",
"keywords": [
"Messenger Chatbots",
"Conversational Commerce",
"M-Commerce",
"Technology Acceptance Model",
"Artificial Intelligence",
"Online Shopping Experience",
"Anthropomorphism"
],
"content": "Introduction\n\nChatbots are computer programs that can “converse” with users via voice or text and mimic human conversation. Voice assistants and chatbots operate due to speech recognition technologies, a decision-making service, and conversion into a voice message. ELIZA was the first kind of chatbot introduced in the 1960s, although in the 1960s, the awareness of chatbots among the public was limited. Corporations have now adopted this technology to enhance customer service and develop consumer-brand solid relationships with the growing awareness. The IT giant companies conduct research and developments in automated communications, and the robots are getting more and more intelligent every day. Authors suppose that by 2025, the global market for speech recognition technologies should exceed $30 billion. More than 8 billion chatbots will be operating (for comparison, in 2018 — 2.5 billion). Chatbots seem to have a bright future as the industry predicts that 90% of banking and 75% of health care customer interactions will involve chatbots without human intervention by 2022. The underlying fact supports millennials’ natural affinity for technologies.1 These young, tech-savvy consumers are expected to adopt chatbots for multiple purposes, including shopping for products, customer service, or making reservations.\n\nAs of January 2021, GlobalWebIndex reports that 76,8% of Internet users in the world aged 16 to 64 make online purchases every month, 55,4% do it from mobile devices. Similar indicators in developing countries are not far behind. Developing countries are making efforts to reduce the backlog. For example, Russia has a “Digital Economy” program to distribute digital services. Driven by the digital India initiative, there is a significant increase in India’s number of internet connections. In Russia, the share of Internet users is 60% (32% for m-commerce), in India – 74% (55% for m-commerce). The chatbot is a promising means of solving marketing problems of interaction with consumers and increasing the response rate to solve current consumer problems. At the same time, it is necessary to understand how consumers in developing countries react to interaction with chatbots what consumer requirements chatbots should meet. Therefore, the topic of this study is relevant. Chatbots have already been widely accepted and have risen for several years. Various companies associate messenger apps with providing services in response to this trend. Chatbots enhance customer experiences and fulfill expectations through real-time interactions.2 They bring forth the concept of conversational commerce and offer new ways of communication between the companies and their customers. They constitute a channel through which companies can connect with their customers anytime through commonly used social messenger platforms like Facebook Messenger, WhatsApp, etc. The latest trend in artificial intelligence is utilizing applications that interact with consumers in a casual setting, mimicking human conversation “chatbots, conversational agents, or simply bots”.3\n\nThe use of messenger chatbots can shorten the stages in the buying process, and is thus; companies are inclined towards it as it can be a \"one-stop shopping\" channel. Chatbots do not require a separate platform as they rely on the interface of the messenger platform, and there is no need to download other apps. They also cost less than actual humans for customer support.4 Retailers are increasingly using conversational artificial intelligence (chatbots) to serve customers due to this new technology’s perceived benefits and reduced operating costs.5 However, our understanding of how consumers perceive interaction with chatbots and how this interaction may affect other consumer service programs remains limited.\n\nThe main results show that reliability and perceived usefulness are the most important criteria influencing the intention to reuse a chatbot. Contrary to expectations, empathy had no significant effect. The study suggests that when interacting with a chatbot for a purpose that may include an economic transaction, customers prefer the chatbot for its practical value since reliability and usefulness are considered more important than empathy. In addition, tangible elements play an essential role in increasing the perceived ease of use.\n\nSince this concept is still new, there is insufficient research on chatbots for trading. This study aims to determine how users agree with using messenger chatbots for e-commerce. This study aims to determine whether consumers will use messenger chatbots for online purchases and what factors influence messenger bots.\n\nThe growth of the chatbot market relates to high Internet penetration and the E-commerce and m-commerce industry development. As of January 2021, more than 4.66 billion people already use the Internet (60% of the world’s population), 92% of them connect to the Internet using mobile devices.\n\nThe development of chatbots as a way of communication is directly related to the deep penetration of social networks and messengers. In the context of a pandemic, consumers use social networks as a tool for interacting. The use of social networks and messengers as communication channels remains high. GlobalWebIndex reports that as of January 2020, the average person in the world spends 2 hours 24 minutes a day on social networks. This time is close to the average (2 hours 26 minutes in Russia and India 2 hours 24 minutes).\n\nAs of January 2021, WhatsApp has 2 billion active users, followed by Facebook Messenger with 1.3 billion users, followed by WeChat and Instagram with 1.2 billion users each (We Are Social 2020).\n\nAccording to Mediascope, 73% of the population uses social networks in Russia, 49% daily. According to PWC, in 2020, 86% of global consumers plan to use social networks frequently in the future, and 91% of them use messengers (in Russia, this trend continues: 86% and 89%, respectively).\n\nThe usage of voice interfaces has grown by more than 9% over the past year, according to GlobalWebIndex2020. Globally, 43% of Internet users aged 16 to 64 use voice search and voice commands on any device every month. In India, the share of such users is 54%, and in Russia, only 25%. However, today chatbots are already actively used by businesses — about 57% of companies in Russia plan or use chatbots to interact with consumers. For example, at Tinkoff Bank, the voice assistant «Oleg» solves 35% of all customer requests without human intervention. Users find this communication format convenient — 34% prefer to interact while asking and answering questions with chatbots or virtual assistants.\n\nFor humans to feel they are talking to an actual human being or make them experience anthropomorphic chatbots, they are programmed using natural language processing with human-like dialogue.6,7\n\nHan8 obtains results confirming that anthropomorphism positively shapes consumers’ intentions to purchase using chatbots. Anthropomorphism is beneficial for transaction results, but it also leads to a significant increase in consumers’ sensitivity to the amount of offer. As the chatbot becomes more human-like, consumers move on to evaluating fairness or negotiating.9\n\nConsumers’ perception of both empathy and friendliness of a chatbot positively influences their trust in it.10 The anthropomorphic design of brand chatbots and communication strategies of social presence can improve the outcomes of consumer evaluation.11\n\nFolstad and Taylor12 give an idea of critical drivers of user experience, including the relevance of responses and the usefulness of the dialogue. The privacy issues on the Internet negatively affect the relationship between the attitude towards chatbots and the behavioral intention to use this technology.13\n\nZarouali et al.14 propose and test a model based on consumer acceptance of a technological model (CAT model), including three cognitive dimensions (i.e., perceived usefulness, perceived ease-of-use, and perceived helpfulness) and three affective determinants (pleasure, arousal, and dominance; PAD-dimensions).\n\nThe perceived usefulness and ease of use of chatbots have positively affected the attitude of online consumers, leading to impulse buying and the repurchase intention behavior of customers.15\n\nAlt et al.16 identify the factors influencing consumers’ intention to use chatbot technology applied in the banking industry. Researchers used the measurement based on the technology acceptance model extended with compatibility, customers’ perceived privacy risk, and service awareness. The findings highlight the importance of perceived compatibility and usefulness in adopting banking chatbot technology. Understanding the service affects perceived ease of use and perceived privacy risk, and it indirectly affects usage intention of banking chatbots through perceived usefulness. Also, perceived ease of use influences perceived benefit, and perceived compatibility affects perceived ease of use and service. Perceived ease of use and perceived privacy risk show no effect on intention.\n\nSoni17 presents Technology Adoption Model (TAM) and states that chatbots have an excellent influence on the modern generation “z,” which has grown in the current conditions of widespread mobile communications. The youngsters adopt chatbots as a communicating agents. The analysis outcomes demonstrate chatbots as effective in building customer relationships.\n\nMeyer-Waarden et al.18 examined consumer acceptance and intention to reuse the chatbot in the context of automated customer service in the airline industry.\n\nThe authors use the TAM as the primary model considering it as one of the most widely used models for understanding adoption and use by users in various fields. TAM is among the most commonly applied model for understanding user acceptance and usage in multiple domains.19–21 The TAM is empirically supported through validations, applications, and replications. TAM considers two beliefs to impact the customer’s behavioral intention to use technology. First, is perceived Usefulness (PE), which is the extent to which user feels the use of specific technology will increase their job performance. Second, Perceived ease of use (POEU), which is a user’s probability that the use of particular technology will be free of effort. As per TAM, higher PU and PEOU positively influence users’ attitudes towards this system. Attitude is an individual’s positive or negative feelings about performing the target behavior.22 Further, attitude leads to a higher intention to use the system, which has a cascading effect on the actual use of the system.23,24\n\nAuthors describe intention to use as “the strength of one’s intention to perform a specified behavior”.22\n\nSo,the authors have made the following hypothesis:\n\nH1: Perceived usefulness (PE) influences the attitude of the customers.\n\nH2: Perceived ease of use (POEU) will affect the attitude of the customers.\n\nAnthropomorphism assigns human features to non-human beings or things like products, brands, and nature.25 It usually makes people more connected and increases engagement. It enhances the quality of discussions by making them more exciting and influences consumers’ decision-making behaviors. According to research, products that show more human-like traits are more trustworthy. Empirical studies indicate that people are more inclined to engage with websites as humans through anthropomorphic esthetic cues. Anthropomorphic website design (e.g., a website with human-like eyes) has helped increase the trust and intentions of a potential customer to purchase from such sites.26 Social presence is when a person feels a personal human contact within a medium as if other humans are present too.27 E-commerce considers the lack of human warmth and connection compared to offline commerce. Previous research suggests that social presence is an essential factor influencing users’ trust and intention to use or make an online purchase.28,29 So it is hypothesized that:\n\nH3: Anthropomorphism & Social presence (AS) will influence the customers’ attitude.\n\nAs per various studies and research conducted in the past and numerous information systems (IS) studied, authors suppose that, in e-commerce sets, trust and purchase behavior have a powerful link.28 Many researchers have also claimed that belief becomes a significant factor for predicting machine/technology success. Researchers have started to believe that it is essential to investigate the consumers’ confidence in this new technology as the adoption of chatbot usage depends on trust. Disclosing the full potential of chatbots considers the customers’ trust. It is logical now to state:\n\nH4: Customer Trust (CT) influences the attitude of the customers.\n\nSeveral authors considered the dependence of the behavioral intentions from the general attitudes.30–33 So, the authors assume that:\n\nH5: The attitude of the customers will influence their Behavioral intentions.\n\n\nMethods\n\nA quantitative research approach was adopted in the study. An online survey35 was conducted through Google forms, through which 192 responses were recorded. A judgmental sampling method is employed to identify the respondents. As the concept of messenger chatbot is relatively new, the respondents were first shown a video of a conversation with messenger chatbot, after which there were asked to answer specific questions related to chatbots. There are two sections in the questionnaire; the first section included questions to understand the demographics of the respondents, insights on their mobile phone usage, and frequency of online shopping. The second section had queries based on the factors in the technology acceptance model. These questions were designed as 5 point scale (1 = strongly disagree and 5 = strongly agree).\n\nThe authors selected a Structural Equation Modeling (SEM) approach to analyze the cause-effect relationships among constructs. Using SEM allows assessing causal relationships based on statistical data and qualitative causal assumptions.\n\nInstitutional review board permission was taken for this study (Approval Number F-2-Q1-2022). All the participants of this study were informed and written consent was taken. Participation in the study was solely based on the voluntary consent of the participants.\n\n\nResults\n\nThe data34 collected was from people above 16 years of age. Most of the respondents were of 16 to 35 years of age (82.8%) as they were the main focus of the research. 59.9% of the respondents were male, and 40.1% were female. 65% of the respondents had completed their post-graduation or even higher studies, and nearly 35% had completed their education until graduation. 33% of the respondents were heavy mobile phone users who used it for more than 5 hours. Also, another 33% of the respondents used it for 3 to 5 hours a day. So more than three-quarters of the respondents are regular mobile users, and 95.5% used mobile messenger chats. 24.6% of respondents were heavy online shoppers who shopped more than once a month, and 38.7 % of them shopped at least once a month.\n\nThe SEM technique consists of two parts: the structural model that describes the latent variables and their relationships among themselves and the measurement model that describes the indicators to be measured. All the parameters associated with the measurement and structural models need to be calculated using appropriate estimation methods to estimate the model. The research was analyzed using the Partial Least Square (PLS) software, Warp PLS 7.0.\n\nThe PLS regression algorithm with the bootstrapping method of re-sampling was used to estimate the model that maximizes the variance explained in the latent variable scores by the latent variable indicators. The estimates included path coefficients with ‘p’ values, indicators’ weights, loadings, and factor scores.\n\nThe validity and reliability criteria vary depending on the nature of the construct. The guidelines are shown in Table 1. After estimation, it is recommended to load/weight measurements above 0.5 and compute p values less than 0.01. Causality assumptions were verified only based on a valid model. The pre-processing of data as part of Warp PLS 7.0 analysis confirmed the data quality for further research about missing values zero variance.\n\nThe estimated model with path coefficients and corresponding ‘p’ values are illustrated in Figure 1.\n\nDifferent fit indices were used to evaluate the model’s validity. The ‘p’ values for both the average path coefficient (APC) and the average R-squared (ARS) should be below 0.05. Moreover, the average variance inflation factor (AVIF) should be below 5. As the model was well-represented data, all three fit criteria were satisfied, and the model had acceptable predictive and explanatory qualities. Each reflective indicator had factor loadings greater than 0.5 with a ‘p’ of less than 0.01. The composite reliability, Cronbach alpha, and average variance extracted (AVE) were above the threshold limits. Model parameters included R-squared and Q-squared that were satisfying for predictive validity. The square root of AVE for all constructs was more significant than any correlation involving the latent variable. All these observations confirm reliability and validity and allow for causal inference (Tables 2, 3).\n\n\nDiscussion\n\nThe authors suggested discussion over the relevant influencers of philosophy concerning the online purchase. They identified Perceived Usefulness (PE), Perceived ease of use (POEU), Anthropomorphism & Social presence (AS), Customer Trust (CT) as the primary influencers. Of the four variables, customer trust has shown the most decisive influence on customer attitude (β = 0.42), followed by perceived ease of use (β = 0.40) and perceived usefulness (β = 0.30). Authors suppose that the research could not establish the significance of the relationship between Anthropomorphism & Social presence and the customer’s (p = 0.40). This study highlights the positive influence of the customer’s attitude on their behavioral intentions (β = 0.33).\n\n\nConclusions\n\nThe research highlights the importance of trust, ease of use, and usefulness of chatbots. Authors consider anthropomorphic chatbots to act as intermediaries of parasocial interaction and perceived dialogue. Chatbots potentially influence consumer attitudes towards chatbot-providing brands and their likelihood of using and recommending a chatbot. These findings indicate that organizations should design strategies to improve customer trust with messenger chatbots.\n\nThe authors tried to achieve the results by providing relevant and truthful customer queries. Authors suppose the customer profiling with improved precision. Researchers could anticipate possible objections and confusion of the customer in advance. This study also indicates that consumers prefer the ease of use of the chatbots and evaluate their usefulness. This finding suggests that the firms can incorporate user-friendly features and interfaces in the platform, enhancing customer involvement and providing a joyful experience.\n\nThis study suggests that educated young people show a positive attitude towards mobile messenger chatbots usage and are likely to shop. Thus, consumers will adopt the concept of messenger chatbots for m-commerce. Brands can think of it as the next big thing in the e-retail space and potential expansion to reach more consumers. As most consumers are heavy internet users, social media and messengers are lucrative spaces to do business. Various companies are already adopting chatbots in the customer service domain; messenger chatbots to help people find products online and shorten their purchase time will benefit the brands. While designing the messenger chatbots, the brands need to consider the rising concern of internet privacy as it affects consumers’ the most. Also, the chatbots need to be easier to use and help consumers find products faster, make their shopping convenient, and make it easier for customers to follow up and provide personalized support to consumers.\n\n\nData availability\n\nFigshare: Responses.xlsx, https://doi.org/10.6084/m9.figshare.19626882.v1.34\n\nFigshare: Questionnair Chatbot.docx, https://doi.org/10.6084/m9.figshare.19626879.v1.35\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgments\n\nWe are thankful to the Ministry of Science and Higher Education of the Russian Federation for the financial support of this project.\n\n\nReferences\n\nKlein A, Sharma VM: German Millennials’ Decision-Making Styles and Their Intention to Participate in Online Group Buying. J. Internet Commer. 2018; 17: 383–417. Publisher Full Text\n\nChung M, Ko E, Joung H, et al.: Chatbot E-Service and Customer Satisfaction Regarding Luxury Brands. J. Bus. Res. 2020; 117: 587–595. Publisher Full Text\n\nRam K, Satyendra U, Feba J, et al.: Prospects for artificial intelligence implementation to design personalized customer engagement strategies. J. Leg. Ethical Regul. Issues. 2021; 24.\n\nMott B, Lester J, Branting L: Conversational Agents.2004.\n\nTran A, Pallant J, Johnson L: Exploring the Impact of Chatbots on Consumer Sentiment and Expectations in Retail. J. Retail. Consum. Serv. 2021; 63: 102718. Publisher Full Text\n\nShawar B, Atwell E: Chatbots: Are They Really Useful?. LDV Forum. 2007; 22: 29–49.\n\nShawar BA, Atwell E: ALICE Chatbot: Trials and Outputs. Computacion y Sistemas. 2015; 19: 625–632. Publisher Full Text\n\nHan MC: The Impact of Anthropomorphism on Consumers’ Purchase Decision in Chatbot Commerce. J. Internet Commer. 2021; 20: 46–65. Publisher Full Text\n\nSchanke S, Burtch G, Ray G: Estimating the Impact of “Humanizing” Customer Service Chatbots. Inf. Syst. Res. 2021; 32: 736–751. Publisher Full Text\n\nCheng X, Bao Y, Zarifis A, et al.: Exploring Consumers’ Response to Text-Based Chatbots in e-Commerce: The Moderating Role of Task Complexity and Chatbot Disclosure. Internet Res. 2021; 32: 496–517. Publisher Full Text\n\nTsai W, Liu Y, Chuan C-H: How Chatbots’ Social Presence Communication Enhances Consumer Engagement: The Mediating Role of Parasocial Interaction and Dialogue. J. Res. Interact. Mark. 2021; 15: 460–482. Publisher Full Text\n\nFølstad A, Taylor C: Investigating the User Experience of Customer Service Chatbot Interaction: A Framework for Qualitative Analysis of Chatbot Dialogues. Qual. User Exp. 2021; 6. Publisher Full Text\n\nde Cosmo LM , Piper L, di Vittorio A : The Role of Attitude toward Chatbots and Privacy Concern on the Relationship between Attitude toward Mobile Advertising and Behavioral Intent to Use Chatbots. Ital. J. Mark. 2021; 2021: 83–102. Publisher Full Text\n\nZarouali B, den Broeck E , Walrave M, et al.: Predicting Consumer Responses to a Chatbot on Facebook. Cyberpsychol. Behav. Soc. Netw. 2018; 21: 491–497. PubMed Abstract | Publisher Full Text\n\nThanh Khoa B: The Impact of Chatbots on the Relationship between Integrated Marketing Communication and Online Purchasing Behavior in The Frontier Market. Jurnal The Messenger. 2021; 13: 19. Publisher Full Text\n\nAlt M, Vizeli I, Saplacan Z: Banking with a Chatbot – A Study on Technology Acceptance. Studia Universitatis Babes-Bolyai Oeconomica. 2021; 66: 13–35. Publisher Full Text\n\nSoni R: Trust in Chatbots: Investigating Key Factors Influencing the Adoption of Chatbots by Generation Z.2020.\n\nMeyer-Waarden L, Pavone G, Poocharoentou T, et al.: How Service Quality Influences Customer Acceptance and Usage of Chatbots?. J. Serv. Manag. Res. 2020; 4: 35–51. Publisher Full Text\n\nMcCoy S, Galletta D, King W: Applying TAM across Cultures: The Need for Caution. EJIS. 2007; 16: 81–90. Publisher Full Text\n\nLai PC: The literature review of technology adoption models and theories for the novelty technology. J. Inf. Syst. Technol. Manag. 2017; 14: 21–38. Publisher Full Text\n\nCalantone R, Griffith D, Yalcinkaya G: An Empirical Examination of a Technology Adoption Model for the Context of China. J. Int. Marketing. 2006; 14: 1–27. Publisher Full Text\n\nAjzen I, Fisbbein M: Factors Influencing Intentions and the Intention-Behavior Relation. Hum. Relat. 1974; 27: 1–15. Publisher Full Text\n\nVenkatesh V, Morris MG, Davis GB, et al.: User Acceptance of Information Technology: Toward a Unified View. MIS Q.: Manag. Inf. Syst. 2003; 27: 425–478. Publisher Full Text\n\nDavis FD: Perceived Usefulness, Perceived Ease of Use, and User Acceptance of Information Technology. MIS Q.: Manag. Inf. Syst. 1989; 13: 319–339. Publisher Full Text\n\nAggarwal P, Mcgill AL: When Brands Seem Human, Do Humans Act like Brands? Automatic Behavioral Priming Effects of Brand Anthropomorphism. J. Consum. Res. 2012; 39: 307–323. Publisher Full Text\n\nWölfl S, Feste J: Do You Trust Me? Facial Width-to-Height Ratio of Website Avatars and Intention to Purchase from Online Store. Proceedings of the International Conference on Information Systems 2018, ICIS 2018. 2018.\n\nYoo Y, Alavi M: Media and Group Cohesion: Relative Influences on Social Presence, Task Participation, and Group Consensus. MIS Q.: Manag. Inf. Syst. 2001; 25: 371–390. Publisher Full Text\n\nGefen D, Straub DW: Consumer Trust in B2C E-Commerce and the Importance of Social Presence: Experiments in e-Products and e-Services. Omega. 2004; 32: 407–424. Publisher Full Text\n\nKumar BVD: An Empirical Study on Impact of Chatbots in Digital Marketing Communication.2021; 2455–6211.\n\nFazio R, Olson M: The MODE Model: Attitude-Behavior Processes as a Function of Motivation and Opportunity. Dual Process Theories of the Social Mind. 2014; 155–171.\n\nFazio R: Attitudes as Object-Evaluation Associations: Determinants, Consequences, and Correlates of Attitude Accessibility.2021.\n\nFazio RH: Multiple Processes by Which Attitudes Guide Behavior: The Mode Model as an Integrative Framework 1990; Vol. 23.\n\nFazio R: How Do Attitudes Guide Behavior.2021.\n\nMehta R: Responses.xlsx. figshare. [Dataset].2022. Publisher Full Text\n\nMehta R: Questionnair Chatbot.docx. figshare. [Dataset].2022. Publisher Full Text"
}
|
[
{
"id": "152655",
"date": "24 Oct 2022",
"name": "Dominika Kaczorowska-Spychalska",
"expertise": [
"Reviewer Expertise Digital transformation",
"digital technologies",
"especially the Internet of Things (IoT) and artificial intelligence (AI) and their impact on society and business",
"Society 5.0",
"Business 4.0",
"digital consumer (homo cyber - homo digitalis - posthuman)."
],
"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 issue discussed in the article is important and fits in with the currently observed market trends. Therefore, it is important not only in the scientific dimension, but also in practice. The text is written in a logical and understandable way. However, the presented justification to address the discussed issue is, in my opinion, insufficient. There is no systematic (according to the applicable rules) review of the literature (bibliometric analysis of the scientific achievements of other authors and their research) that would allow to identify the existing research gaps to which the article should refer. In some cases, the authors forgot to indicate the source, e.g. the definition of a chatbot, \"The growth of the chatbot market relates to high Internet penetration and the e-commerce and m-commerce industry development. As of January 2021, more than 4.66 billion people already use the Internet (60% of the world’s population), 92% of them connect to the Internet using mobile devices ” etc.\nThe text only refers to the market and programs implemented in Russia and India, where the authors of the article come from. It is worth emphasizing in the title of the article, which currently suggests a broad look at the analyzed issues and/ or to show and discuss the situation also in other markets, which are mentioned in the introductory section.\nWhere did the respondents come from (Russia, India, other countries)? It is a pity that among the variables describing the respondents’ profile only such factors as age, gender, education level were included.\nI suggest that the purpose of the study should be clarified, focusing on identifying factors that have a key impact on the use of Messenger chatbots by consumers. It is worth emphasizing the aspect of anthropomorphism.\nThe following aspects would be advisable to emphasize in the content of the article: research, practical implications and limitations, which are currently in the section entitled Conclusions and their development. It is worth remembering that the sample of 192 respondents is not broad enough to generalize the obtained results for the entire population.\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? 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": []
},
{
"id": "175515",
"date": "02 Jun 2023",
"name": "Roberta De Cicco",
"expertise": [
"Reviewer Expertise Digital marketing",
"digital technologies",
"influencer marketing",
"chatbots",
"conversational marketing"
],
"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\nThanks for the opportunity to read and comment on this paper.\nThe study aims to discover the factors that affect the use of messenger chatbots and their influence on attitude and behavior intention. The Technology Acceptance Model (TAM) was applied, including perceived usefulness, perceived ease of use, consumer trust, and anthropomorphism/social presence. 192 valid responses were collected through an online survey and data analyzed with structural equation modelling. Customer trust has a major effect on attitude, followed by Perceived Usefulness and Perceived Ease of Use. Attitude, in turn, is positively related to behavioral intention. Contrary to expectations, anthropomorphism has no significant effect on attitude. The findings indicate that companies should design strategies to improve the practical value of the chatbot by developing conversational agents that are reliable, useful, and easy to use.\nThe topic addressed in the article holds significant relevance and aligns with the prevailing market trends. As a result, its significance might extend beyond the realm of academia and hold practical implications. In my opinion, the paper is a good effort in the area of chatbots, however, some additional information is needed to justify the significance and implication of the study. I hope that my comments will be useful for improving this work.\n- Is the work clearly and accurately presented and does it cite the current literature? (No)\nThe literature review of the paper is not developed enough, and sources and references are missing. For example, I think it is worth mentioning all that studies have already tested TAM for e-retailing chatbots (Rose et al. 20201; De Cicco et al. 20222; Araujo & Casais, 20203).\n\nThe paper would benefit from a clear separation of introduction and theoretical framework. Authors should be more efficient in the introduction as there are passages of the introduction that belong to the literature review or there are passages that are not well connected with each other. For example, the information regarding the market, the forecasts, and the levels of technology and internet adoption should be put together and placed in the same paragraph while they should not be scattered here and there in the text. The introduction is the place to concisely establish the relevance and novelty of the research question(s). For the introduction, try the following flow with one or two succinct points for each of the following: industry relevance, clarification of where messenger chatbots are in the conversational ecosystem, why your research topic/question(s) is relevant, why your research question is novel, how you go about answering your question.\n- Are sufficient details of methods and analysis provided to allow replication by others? (No)\nThe most interesting result is probably the not significant relation; however, it is not clear whether the authors measured anthropomorphism or social presence. Anthropomorphism and social presence are different constructs, they should not be placed in a single hypothesis. The methodology section misses some important information: what is the source of the scales adopted? What are the items? When was the data collected?\n- Are the conclusions drawn adequately supported by the results? (Partly)\nMore emphasis should be placed on the discussions of results, how current results tie to past research, as well as implications both for the industry and academia.\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? 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": []
}
] | 1
|
https://f1000research.com/articles/11-647
|
https://f1000research.com/articles/11-645/v1
|
13 Jun 22
|
{
"type": "Software Tool Article",
"title": "eXNVerify: coverage analysis for long and short-read sequencing data in clinical context",
"authors": [
"Sebastian Porębski",
"Tomasz Stokowy",
"Sebastian Porębski"
],
"abstract": "Accurate identification of genetic variants to a large extent is based on the type of experimental technology, quality of the material and coverage of sequencing data obtained. The latter, coverage quality, highly influences variant calling accuracy and final diagnosis. Our motivation was to create a tool that will evaluate genome coverage and accelerate the introduction of long-read sequencing to medical diagnostics and clinical practice. The implementation was guided by the ease of use of the tool by users who are not proficient in using complex software. A Docker container is perfect for this purpose. Using Docker’s advantages (flexibility, mobility and ease of use of the proposed tools), we created eXNVerify. This is a tool for inspection of clinical data in the context of pathogenic variants search. The tool calculates clinical depth coverage (CDC) – a measure of coverage which we introduce to evaluate loci with pathogenic germline and somatic variants reported in ClinVar. The tool additionally provides visualization options for user-defined genes of interest. Finally, we present examples of BRCA1, TP53, CFTR application and results of a test conducted in the Extensive Sequence Dataset of Gold-Standard Samples for Benchmarking and Development. eXNVerify improves the diagnostic process of patients related to important genetic diseases and facilitates the assessment of genetic samples by diagnosticians. The use of Docker allows to run an analysis package and does not require any special technical preparation. Detailed examples are included in the GitHub project documentation and the package can be downloaded directly from DockerHub using the command: docker pull porebskis/exnverify:1.0.",
"keywords": [
"long-read technology",
"whole genome sequencing",
"single nucleotide variants",
"sequencing coverage"
],
"content": "Introduction\n\nAccurate identification of clinically relevant genomic variants strictly depends on sequencing coverage of sequencing data. Long-read (LR) sequencing covers a higher percentage of the human genome than short-read (SR) sequencing and results in more stable coverage1. Consequently, single nucleotide, indel2, and structural variants3 are detected more accurately. Recent benchmarks evaluate the accuracy, precision, and recall of variant calling in long-read genome data4; however, the introduction of new findings in the clinical and diagnostic setting requires more time. To accelerate the development of clinical genomics we present eXNVerify (named from “exon and single nucleotide variant verification”), a standalone tool that evaluates and visualizes genome coverage in a clinical context. While the available software approaches can analyze the sequencing data, none of them focuses on evaluating single nucleotide variant (SNV) coverage in the context of diagnostic procedures. This gap is filled by eXNVerify. The comprehensive quality control of medically relevant genes can be now adjusted to the diagnostic procedure. Moreover, the tool helps to verify the sequencing sample in terms of coverage of selected genes or to evaluate the overall genome/exome in terms of variant coverage.\n\n\nMethods\n\neXNVerify consists of two procedures prepared in Python 3.8 with utilization of well-known numerical data-related libraries: numpy, pandas and matplotlib. Hence, for proper utilization of our tool, the user needs to install above packages in their Python distribution on their computer system. Source codes can be executed with the python command on Windows or Unix systems. However, we decided to publish a ready-to-go Docker container that includes all dependencies. If the potential user chooses the container, only the Docker application needs to be prepared and then our container can be pulled from the DockerHub repository with one line command: docker pull porebskis/exnverify:1.0.\n\nThe eXNVerify tool is designed to run clinically relevant coverage analysis for SR and LR data, providing integration with the ClinVar database. The software is designed as two standalone procedures: geneCoverage and snvScore. The primary input file for both procedures is the coverage record (BED format) obtained from processing BAM files. To create an input file, the user can use dependencies such as bedtools5, mosdepth6, or samtools7 (see our GitHub documentation).\n\nThe first procedure is geneCoverage. According to the location of exons of the selected gene, it presents coverage in a graphical form (coverages of exons are light blue fragments in Figure 1, Figure 2 and Figure 3) with the location of pathogenic SNVs. Germline and somatic variants are shown as red and dark blue dots, respectively. Moreover, geneCoverage counts the coverage of these SNVs and summarizes the results in a tabular form. The geneCoverage script, in addition to the exon list, pathogenic germline, and pathogenic somatic SNV list, also takes the names of the genes and the coverage threshold as a parameter. The latter is set to evaluate the sample if the gene-related variants are sufficiently covered. Thus, geneCoverage reports the percentage of SNV covered for a given gene and includes insufficient coverage in the generated figure. That is, specific exons that are poorly covered (which may contain key variants) are highlighted in red (see Figure 1, Figure 2 and Figure 3). This design helps to evaluate the reliability of the data before and after specific variant calling. Importantly, it is possible to prepare their own reference files with desired exon regions and SNV positions by following the examples provided in the referenced GitHub repository (Underlying data8).\n\nThe upper panel demonstrates the distribution of coverage in the region of the gene (exons and introns). The lower panel depicts coverage of exons. X-axis is a genomic locus, specified by the user. Dots highlight positions where pathogenic germline (red) and somatic (dark blue) ClinVar variants are located. If coverage of exons is lower than the threshold specified by the user, they are highlighted by the software in red color.\n\nCoverage of more than 40% of the gene did not reach expected 20x coverage. In such case diagnostic lab should consider optimization of the sequencing protocol, especially in exons 1, 2, 5 and 6, which include germline and somatic pathogenic variants.\n\neXNVerify scales visualization to correctly illustrate genes with large number of exons. In this case, CFTR gene, responsible for development of cystic fibrosis consist of 27 exomes.\n\nAn additional element of eXNVerify that focuses on the overall evaluation of sequence coverage is snvScore. It is used to check the coverage of all SNVs downloaded from the ClinVar database. The snvScore script checks variant coverage by all chromosomes and provides basic statistics. Finally, snvScore calculates a proposed measure of variant coverage, called clinical depth coverage (CDC), calculated as:\n\nwhere C(vi(t)) is the coverage of the i-th SNV and N(t) is the number of all referenced variants. Germline and somatic variants are analyzed separately; hence t equals g or s for germline and somatic, respectively. We created examples for highly relevant genes for medical genetics and cancer genomics (see Supplementary Files 1 and 2, Extended data8).\n\nThe sample BED file contains exclusive fragments of a gene sequence. Each fragment is related to one value of coverage. An exome reference list is also a BED format file, but it is different since it contains the location of all exons. It means that each row usually expresses a large fragment of sequence. Therefore, one fragment may be covered in a different number of reads. During the implementation, the task was to locate all fragments in the sample BED file that are in one exon fragment from the reference BED. In this way, coverages in one exon fragment are extracted. Next, if SNV location is available, it is possible to extract coverage information in formerly extracted exon coverage information. Coverage of SNVs is also presented graphically. Moreover, SNV coverage information is aggregated and summarized in table form in a report file. These operations are the core of the geneCoverage procedure.\n\nThe second procedure, snvScore explores the whole genome/exome and extracts coverage of all referenced SNVs coverage. Hence, snvScore requires a sample BED file and two ClinVar SNV tables. Exome reference and gene name are not necessary. The sample BED may be a large file, hence snvScore iteratively loads one-chromosome fragments, and extracts and aggregates information about SNV coverage. When finished, it reports CDC (1) for the whole sample with a via-chromosome table of germline and somatic pathogenic SNV coverage statistics. Supplementary File 1 (Extended data)8 provides a detailed example of snvScore execution.\n\n\nResults\n\neXNVerify is a new tool created to evaluate and visualize gene coverage in a clinical context. The tool consists of two methods implemented in Python: geneCoverage and snvScore. The first tool, geneCoverage looks for a gene (or multiple genes) of interest and evaluates it, integrating the coverage with the ClinVar pathogenic variant information. It demonstrates exons in a gene of interest, highlighting positions of pathogenic variants in the ClinVar database (Figure 1, BRCA1 gene). The tool includes both germline pathogenic and somatic pathogenic SNVs. The tool is flexible and suitable for both oncology project (Figure 2, TP53 gene) and rare disease projects (Figure 3, CFTR gene). Processing the samples with the pandas and numpy libraries as well as visualization of the results with the matplotlib library is enough to provide intuitive support for the diagnostician. Moreover, geneCoverage indicates positions in which desired coverage has not been achieved and therefore variant analysis may lead to false negative/positive calls. The tool is suitable for LR and SR data providing novel insights and analysis options for all technologies used currently in clinical laboratories. To address the spectrum of technology-dependent coverage differences we present results for LR whole genome, SR whole genome and SR exome in Supplementary Figures 1 A, B, and C (Extended data),8; respectively. The second method, snvScore calculates coverage statistics for pathogenic variants, allowing the user to estimate the percentage of all SNVs that are covered above the defined threshold. Table 1 summarizes the essentials of its execution for test samples (Supplementary File 3, Extended data8).\n\nCDC: clinical depth coverage; s: somatic; g: germline.\n\n\nUse cases\n\ngeneCoverage.py performs detailed verification of pathogenic germline and somatic SNVs for chosen gene(s) in a graphical from. Execution of the procedure require parameters in following order:\n\n\n\nThe crucial result of abovementioned procedure is graphical file with coverage analysis results of BRCA1 genome sequence (see Figure 1). More examples and results can be directly downloaded from 8.\n\nsnvScore.py analyses the whole genome sequence coverage and evaluate all pathogenic germline and somatic SNV coverage quality. Its execution needs to fit the procedure positional arguments as follows:\n\n\n\nExemplar snvScore.py execution within eXNVerify Docker container for sample coverage BED file is as follows:\n\n\n\nThe aim of snvScore.py is to prepare coverage analysis of all referenced SNVs in the tabular form (Table 1). summarizes the results of snvScore execution of different genome sequence data. In the project documentation8, the reader may find snvScore results in tabular via-chromosome qualitative results.\n\n\nConclusions\n\nThe tool can be used to inspect structural variants observed in the sample, especially deletions and copy number changes. This approach can be helpful in a manual verification of structural variants, which is still a recommended practice in medical genetics9.\n\nFinally, eXNVerify gives insights into the sample’s usefulness in a hypothesis-free analysis of pathogenic variants. The proposed CDC measure provides a percentage of variants covered above the desired threshold in a specified case (Table 1 and Supplementary File 3, Extended data,8). This measure is useful for everyday laboratory practice to maintain and maximize the quality of experiments. Results of such analyses are provided in Table 1, which indicates the percentage of germline and somatic pathogenic variants specified above the desired threshold. It can also be observed that pathogenic variant coverage differs from median coverage and mean coverage of the sample. For the HG003 PacBio Long Read sample, clinical depth coverage equaled 20x, while global median coverage was 22x. A user of the software can also see that 81% of germline pathogenic variants were covered at least 15x.\n\nWe conclude that CDC measures and the percentage of variants covered above the threshold are useful for medical genetics and cancer diagnostics. In summary, our new tool introduces new, easily applicable options for medical genome analysis.\n\n\nSoftware availability\n\nReady-to-go Docker container can be pulled from https://hub.docker.com/r/porebskis/exnverify. Source code available from: https://github.com/porebskis/eXNVerify. Archived source code as at time of publication: https://doi.org/10.5281/zenodo.6541899\n\nLicense: MIT\n\n\nData availability\n\nTest samples were taken from the public repository provided by Google Cloud Storage. The only requirement for users to browse this repository is to have Google account. These data are released under CC-0 license and introduced by Baid et al., 20204. Instructions for accessing this public data can be found in Google Cloud Storage documentation. For user consideration, we provide the following public links to HG003 samples, generated with three different sequence technologies: PacBio Long Read (42.1 GB), Illumina WGS (38.9 GB), and Illumina Exome Agilent (8.4 GB)\n\nGitHub: https://github.com/porebskis/eXNVerify/tree/main/suppdata This project contains the following extended data:\n\nS1 Fig BRCA1 coverage for samples: A – PacBio Long Read, B – Illumina WGS, C – Illumina Exome Agilent. Detail description as for Fig 1.\n\nS1 File Supplementary Data – exemplar use cases of eXNVerify with quantitative and graphical results\n\nS2 File geneCoverage report for HG003 PacBio LR, Illumina WGS, Illumina Exome Agilent\n\nS3 File snvScore report for HG003 PacBio LR, Illumina WGS, Illumina Exome Agilent",
"appendix": "Acknowledgments\n\nWe would like to acknowledge SnotraBio for sharing computational resources which were used to develop the study. We are thankful for constructive insights from employees of the Medical Genetics Department, Haukeland University Hospital, Bergen Norway, especially from Aashish Srivastava, Rita Holdhus and Sigrid Erdal.\n\n\nReferences\n\nWenger AM, Peluso P, Rowell WJ, et al.: Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome. Nat Biotechnol. 2019; 37(10): 1155–1162. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKolesnikov A, Goel S, Nattestad M, et al.: DeepTrio: Variant Calling in Families Using Deep Learning. bioRxiv. 2021; 2021.04.05.438434. Publisher Full Text\n\nMahmoud M, Gobet N, Cruz-Dávalos DI, et al.: Structural variant calling: the long and the short of it. Genome Biol. 2019; 20(1): 246. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaid G, Nattestad M, Kolesnikov A, et al.: An Extensive Sequence Dataset of Gold-Standard Samples for Benchmarking and Development. bioRxiv. 2020; 2020.12.11.422022. Publisher Full Text\n\nQuinlan AR: Bedtools: the swiss-army tool for genome feature analysis. Curr Protoc Bioinformatics. 2014; 47: 11.12.1–34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPedersen BS, Quinlan AR: Mosdepth: quick coverage calculation for genomes and exomes. Bioinformatics. 2018; 34(5): 867–868. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi H, Handsaker B, Wysoker A, et al.: The sequence alignment/map format and samtools. Bioinformatics. 2009; 25(16): 2078–2079. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPorębski S: porebskis/eXNVerify, Exon and SNV coverage verification, software, v1.0.1. 2022. http://www.doi.org/10.5281/zenodo.6541899\n\nMinoche AE, Lundie B, Peters GB, et al.: ClinSV: clinical grade structural and copy number variant detection from whole genome sequencing data. Genome Med. 2021; 13(1): 32. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "140681",
"date": "27 Jun 2022",
"name": "Zebin Zhang",
"expertise": [
"Reviewer Expertise Bioinformatics"
],
"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\nPorębski S and Stokowy T provide a software, “eXNVerify,” which evaluates and visualizes genome and variations coverage for long and short reads sequencing data in the clinical context. This software is useful, especially for users who are not proficient in bioinformatics, as it is easy to install, use, and visualize results. It also filled the gap in evaluating the coverage of SNV in the context of diagnostic procedures.\nWhile much of the descriptions and results are clear, there are some minor concerns about this paper. These concerns are laid out below:\n1. The authors declare that their software can work on long and short reads sequencing data in the title. I believe this as the authors exhibited long-read results in the results section and short-read results in the supplementary section. However, in the abstract, the authors describe, “Our motivation was to create a tool that will evaluate genome coverage and accelerate the introduction of long-read sequencing to medical diagnostics and clinical practice,” without mentioning short-read sequencing. Is this implying that the result for the short read is not as reliable as the long read?\n2. Methods - operation section. The source codes seem only work on Windows and Linux systems. Because many people work on this system, especially those who are not proficient in bioinformatics or can’t access any servers. So my question is, does the eXNVerify work on the macOS system? If not, please explain why.\n3. The function of highlighting the insufficient coverage is pretty good, and the authors give some examples of the coverage thresholds 15x and 20x. Why did the authors choose those two values? Are these values arbitrary or selected based on some statistical consideration? Can the software give users a recommended value for the threshold?\n4. In fig 3 and 4, the threshold line of 20 doesn’t match the y-axis.\n5. Given the importance of de novo mutation in clinical, is that possible for authors to add another function of output the coverage of those variations?\n6. Mapping quality is also critical in variants calling, do the authors ever consider quality in variants evaluation and CDC calculation?\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": []
},
{
"id": "228033",
"date": "02 Jan 2024",
"name": "Xueyi Dong",
"expertise": [
"Reviewer Expertise bioinformatics"
],
"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 introduced their software tool eXNVerify, which provides functions to visualize and check variant coverage of genes.\nOverall, the functions and usage of eXNVerify are introduced clearly in this article. The software tool shows good practical value in making it easier to investigate SNV coverage from sequencing data. The format of visualization that eXNVerify takes is also clear and helpful. However, I have several minor comments:\n1. In the exon-only coverage plots (Figure 1-3 bottom panels), the x-axis is scaled to skip the intron regions and highlight the exon regions. It helps show more details of SNVs in exon regions, especially for genes with lots of exons. However, the starting and ending point labels on the x-axis are misleading. It should be reflected on the plots of how the axis was scaled, such as including a scale bar of genomic positions.\n2. The software tool is provided as a docker image, which simplifies the installation procedure. However, some institution computers and/or servers don't support docker. Are alternative installation methods available?\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": []
},
{
"id": "228027",
"date": "24 Jan 2024",
"name": "Wouter De Coster",
"expertise": [
"Reviewer Expertise bioinformatics",
"data visualization",
"sequencing data 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\nThe authors describe eXNVerify, a tool to assess the coverage in sequencing data. This is relevant, as coverage is a crucial parameter for variant detection and accuracy. The tool is well developed and the plots are mostly clear, but overall the scope of this tool is relatively narrow - focusing on one sample at a time. Please find my detailed comments below.\nIn the introduction, the authors mention that long-read sequencing covers a higher percentage of the human genome and results in more stable coverage. While the stable coverage is probably mostly a feature of the absence of PCR amplification, I would mainly warrant some caution about the sentence following that statement: 'Consequently, single nucleotide, indel, and structural variants are detected more accurately'. I believe this statement to be incorrect, specifically in the case of short indels - as such variants are the dominant error mode of nanopore sequencing. While long reads enable alignment in highly repetitive regions, and thus variant calling there, some more nuance is warranted with regard to which variants are more accurately detected. I am a bit unsure if the focus on long-read sequencing in the introduction is relevant, as your tool appears to be broadly applicable.\nI am a bit confused by the bottom panels of Figures 1 and 3 and both panels in Figure 2. Do these plots contain two samples, with the blue lines of exon coverage at y=0? Why are variants shown twice, once in the plot at different heights and once at y=1/-1? The legend of Figure 3 mentions that it consists of \"27 exomes\". which should presumably be 27 exons.\nCan the authors elaborate on what the coverage threshold of 15x was chosen for Figure 1, and 20x for Figure 2? I also think that the converge threshold line in Figure 2 is not at 20x but just above that.\nI think distributing your tool via docker might make it easier for some people, as installation becomes easier, but then requires that docker is already installed, which may not be the case. I would suggest that you include installation instructions (using pip or conda) for those users that cannot use docker. Regrettably, not all sysadmins will allow users to use docker. I see in the GitHub documentation that the tool requires a 'Path to Clivar-generated table with pathogenic germline SNVs,' but it is not clear how that one needs to be generated. Example files are provided in the repository, which is highly appreciated, but it is unclear to which reference genome they correspond. It would however be most useful if your tool included a command to download such a table automatically from the clinvar database. The same argument could be made for the exome bed file. In addition, the authors recommend Mosdepth, which is an excellent choice, but I would also suggest including optimal parameters for this tool in your documentation, as it has various options. I see the SNVSomaticTXT is a required argument, but I can imagine that somatic variants are not necessarily relevant for everyone. Maybe that could be an optional input, and maybe a suitable default could already be set for the threshold. In addition, if users have many genes of interest, they will have to provide them all one by one on the command line, which is probably frustrating. The example docker command for geneCoveray.py in the GitHub documentation misses a trailing slash '\\', and thus yields a confusing error. It also appears the coverage bed file cannot be (b)gzip compressed? That is very unfortunate and something I would suggest adding.\nWhile not critical, I think it would be interesting if users could provide multiple samples as input (e.g. a trio), for comparison, rather than having to run the tool multiple times and open multiple separate plots. That said, after downloading all files, the tool ran as expected and the plots provided a useful representation of the coverage.\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? Partly\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-645
|
https://f1000research.com/articles/8-322/v1
|
22 Mar 19
|
{
"type": "Research Article",
"title": "Impact of pathogenic mutations of the GLUT1 glucose transporter on channel dynamics using ConsDYN enhanced sampling",
"authors": [
"Halima Mouhib",
"Akiko Higuchi",
"Sanne Abeln",
"Kei Yura",
"K. Anton Feenstra",
"Halima Mouhib",
"Akiko Higuchi",
"Sanne Abeln",
"Kei Yura"
],
"abstract": "Background: The solute carrier (SLC) family of membrane proteins is a large class of transporters for many small molecules that are vital for the cell. Several pathogenic mutations are reported in the glucose transporter subfamily SLC2, causing Glut1-deficiency syndrome (GLUT1DS1, GLUT1DS2), epilepsy (EIG2) and cryohydrocytosis with neurological defects (Dystonia-9). Understanding the link between these mutations and transporter dynamics is crucial to elucidate their role in the dysfunction of the underlying transport mechanism. Methods: Predictions from SIFT and PolyPhen provided an impression of the impact upon mutation in the highly conserved RXGRR motifs, but no clear differentiation could be made by these methods between pathogenic and non-pathogenic mutations. Therefore, to identify the molecular effects on the transporter function, insight from molecular dynamic simulations is required. We studied a variety of pathogenic and non-pathogenic mutations, using a newly developed coarse-grained simulation approach ‘ConsDYN’, which allows the sampling of both inward-open and outward-occluded states. To guarantee the sampling of large conformational changes, we only include conserved restraints of the elastic network introduced upon coarse-graining, which showed similar reference distances between the two conformational states (≤1 Å difference). Results: We capture the ‘conserved dynamics’ between both states using ConsDYN. Simultaneously, it allowed us to considerably lower the computational costs of our study. This approach is sufficiently sensitive to capture the effect of different mutations, and our results clearly indicate that the pathogenic mutation in GLUT1, G91D, situated at the highly conserved RXGRR motif between helices 2 and 3, has a strong impact on channel function, as it blocks the protein from sampling both conformational states. Conclusions: Using our approach, we can explain the pathogenicity of the mutation G91D when we observe the configurations of the transmembrane helices, suggesting that their relative position is crucial for the correct functioning of the GLUT1 protein.",
"keywords": [
"GLUT1 glucose transporter deficiency syndrome",
"Human glucose transporters",
"SLC transporter family",
"transport mechanism",
"molecular dynamics simulation",
"Martini force field",
"coarse-grained simulations",
"enhanced sampling method"
],
"content": "Introduction\n\nThe solute carrier (SLC) transporter superfamily is known to play a key role in the transport of small molecules. The superfamily comprises 52 families, and at least 386 different transporter genes have so far been identified in humans (Hediger et al., 2013; Higuchi et al., 2018). This family of membrane proteins is a large class of transporters for many small molecules such as glucose that are vital for the cell, and can be found in all kingdoms of life. Of particular interest are the glucose transporters SLC2A1 from the SLC2 subfamily; GLUT1 mutations are associated with GLUT1 deficiency syndrome (GLUT1DS1 and GLUT1DS2), and some forms of spasticity (Dystonia-9) and epilepsy (EIG2) (Klepper et al., 2016; Mongin et al., 2016). Shedding light on the molecular mechanism of the channel transport function, can enable us to understand the difference between pathogenic and benign mutations that have been observed in human subjects. Glucose transporter GLUT1 is built of 12 transmembrane helices (TMs) and exhibits a two-fold symmetry plane joining the two times six TM helices over a bridging helix on the cytoplasmic side of the membrane (see Figure 1A). Throughout the SLC transporters, a highly conserved RXGRR-motif is found between TM2 and TM3 and between TM8 and TM9 at the intracellular side of the corresponding loops (Pao et al., 1998; Sato & Mueckler, 1999). Several mutations at these anchor points are known to be disease-related, such as G91D and R92W which are known to cause GLUT1DS1 (Klepper et al., 2001; Klepper & Voit, 2002), whereas R93W is associated with GLUT1DS2 (Joshi et al., 2008).\n\n(A) Pipe representation of the inward-open (IO) conformation (PDB-ID: 5EQI) of GLUT1 situated in the lipid bilayer. Note that the protein structure has a two-fold rotational symmetry and the two conserved RXGRR-motifs are located at the junctions of the transmembrane (TM) helices 2 and 3 and TM8-TM9. The red arrows symbolize the inside and outside distances. Note that we number the helices starting from TM1 at the beginning of the N-terminus of the transporter (dark blue in the pipe representation). (B) Pipe representation of the IO conformation (PDB-ID: 5EQI) of GLUT1 viewing on the outward facing part of the channel inside the periplasm. The four main mutation sites, G91, R92, R333, and R334, are highlighted in magenta. (C) Definition of the order parameters to follow the motion of the helices over the ConsDYN simulations.\n\nHere, we investigate the effect of different mutations on the dynamic of the human GLUT1 protein. As the dynamic response upon mutation may depend on the conformational state, we aimed to simulate both the outward-occluded state (OO) and inward-open state (IO). For GLUT1, however, only the IO state is available; therefore, simulations of GLUT3, which is evolutionarily quite close to GLUT1, in the OO state were analysed. GLUT3 is also suspected to be associated with neurological disorders such as Alzheimer (An et al., 2018; Gu et al., 2018; Simpson et al., 1994; Szablewski, 2017).\n\n\nMethods\n\nThe crystal structures of both Io and Oo states are available in the PDB; 5EQI for GLUT1 IO state (Deng et al., 2015), and 4ZW9 for GLUT3 OO state (Kapoor et al., 2016); these were used as starting points for the simulations. Based on the reported pathogenic mutations of GLUT1 in the conserved RXGRR motif region, we searched for additional mutations at the corresponding positions of GLUT3 and included them in our study. The selected mutations are situated in the conserved RXGRR-motif distal to the channel. An overview of all mutations for GLUT1 and GLUT3 studied in this work is provided in Table 1. Due to the high sequence identify (~70%) between the proteins, we intentionally did not build a homology model for one or the other protein. This is justified, as our main aim is to characterize the global opening and closing mechanism rather than to look into atomistic details such as protonation states. Moreover, we now avoid additional uncertainties about details of the structure as would be inevitably introduced during the homology building process. Our composite scheme using coarse-grained molecular dynamics with a conserved elastic network ConsDYN is explained in the approach below and further details are supplied in the supporting methods, available in the deposited code (Feenstra, 2019b).\n\nThe pathogenic mutations in GLUT1 are underlined.\n\n* References given to literature describing clinical appearance, OMIM entries, and dbSNP entries given, if available.\n\nIn this study, we employ molecular dynamics (MD) simulations using the GROMACS 4.0.5 programme package (Hess et al., 2008). For efficiency reason, we investigated the applicability of the MARTINI coarse-grained (CG) force field (Arnarez et al., 2015; de Jong et al., 2013; Hsu et al., 2017; Monticelli et al., 2008; Periole et al., 2009), which is about 500-fold faster than the full-atomistic GROMOS (May et al., 2014). In addition, we modified the elastic network that is used in MARTINI based on our starting conformations, including only elastic network constraints that differed less than 1Å between the IO and OO states. This allows transition between both states, while maintaining protein structure stability. This composite scheme will henceforward be referred to as ConsDYN (CONServed DYNamics). The detailed computational set-up is provided in the Supporting Methods (Feenstra, 2019b).\n\nEssential dynamics analysis was performed on the GLUT1 and GLUT3 simulations using built-in analysis tools on GROMACS. To allow this comparison between these two homologous proteins, and allow for focusing on overall motions of the channel region, we selected the structurally conserved helical segments, as summarized in Supporting Table S2, available as extended data (Feenstra, 2019a). Then, the covariance and eigenvalue calculation was performed on the ensemble of both wild-type systems, using the full atomistic (AT), coarse-grained (CG) and ConsDYN simulations.\n\nTo analyse the channel dynamics from the ConsDYN, we defined several order parameters as previously proposed by Nagarathinam et al. (2018) by measuring distances between adjacent TM helices, at the intracellular (in)- and extracellular (out)sides of the protein (see Figure 1B, C). For each of the ring of six central helices that make up the channel, TM2, TM1, TM5, TM8, TM7, TM11 (and back to TM2), we defined an ‘inside’ and ‘outside’ segment of ten residues (See Figure 1 and extended data, Supporting Figure S3 (Feenstra, 2019a)). Comparing the distances of the mutations to both wild types allows us to capture abnormal behaviour and identify the mutations that have the highest impact on the opening and closing mechanism (see Results and Discussion).\n\n\nResults and discussion\n\nFor each of the mutants of GLUT1 and GLUT3 considered here, Table 1 lists the predicted impact upon mutation obtained from SIFT (Sim et al., 2012) and PolyPhen-2 (Adzhubei et al., 2010). Most mutations are classified as likely pathogenic by both methods, with the exception of GLUT1 R93Q, and GLUT3 R91C and R91H. However, these methods are trained on the dbSNP database which also includes these known mutations, so this should be no surprise. Moreover, these predictions do not allow us to gain any insights into the mechanism by which these mutations may affect transporter function.\n\nFirstly, we want to verify if our conservation-based constraining approach for coarse-grained MD simulations (ConsDYN) is able to sample both IO and OO states. We performed essential dynamics (ED) analysis (Amadei et al., 1993; Van Aalten et al., 1997) to compare AT, traditional CG MARTINI, and ConsDYN simulations, as described in the Methods. Figure 2 shows 2D plots of the first two (largest) ED eigenvectors, representing the extracted correlated motions over the ensemble of our simulations. The sampling of the different states, inward-open and outward-occluded, in AT simulation hardly converges. The regular CG simulations already sample more intermediate conformations, but there is no overlap. The ConsDYN simulations, on the other hand, sample many states intermediate to the inside-open and outside-open starting states, compared to other simulations. This means our goal of improved sampling of large conformational transitions has been attained.\n\nNote that the time-scale of the full-atomistic simulations only samples conformations around the IO and OO states, while the ConsDYN samples a large number of conformations between both states. AT, full-atomistic; CG, coarse-grained; ConsDYN, conserved CG; IO, inward open state (PDB-ID: 5EQI); OO, outward occluded state (PDB-ID: 4ZW9).\n\nTo probe for the degree of the conformational changes during the simulations of the wild types and the mutants in more detail than done with the ED analysis, two distances were used to describe the opening and closing of the periplasmic and cytoplasmic sides of the transporter. Nagarathinam et al. (2018) studied a bacterial homolog of GLUT1 and GLUT3, and analysed the movement between TM5 and TM8. In the extended data, Figure S4 (Feenstra, 2019a), we can see that the distributions obtained from our ConsDYN simulations, resemble those reported by Nagarathinam et al. (2018), providing an independent validation that our ConsDYN approach is able to sample biologically relevant conformational states for large scale motions, such as those involved in the glucose transporter mechanism. Nevertheless, there are differences between the distance distributions in our work and that of Nagarathinam et al. (2018), which is not surprising when comparing human glucose transporters with a bacterial multidrug transporter (see also extended data, Figure S4 and Table S3 (Feenstra, 2019a)).\n\nTherefore, in addition to the TM5-TM8 distances, we extended the analysis to other helices along and across the channel rim that make up for the entire SLC channel architecture, allowing us to monitor changes in their position (see Figure 1B, C). For each of these order parameters, we calculate the distance at the inside and outside of the protein with respect to the membrane. Using this analysis, we can immediately observe the changes occurring between the inward-open and outward-occluded states. We see several distances changing significantly during this process: TM1/TM2(in), TM1/TM5(out), TM1/TM7(out), TM1/TM8(in), and TM5/TM11(in) are all closing, while TM1/TM2(out), TM1/TM5(in), TM1/TM7(in), TM2/TM11(in), TM2/TM8(out), and TM5/TM11(out) are opening (see extended data, Table S3 and Figure S4 for more details (Feenstra, 2019a)); these motions are also schematically summarised in extended data, Figure S3 (Feenstra, 2019a). Table 2 summarises the overlap between the observed distribution of distances between the wild type and each of the mutants for TM5 and TM11 that exhibited the strongest effects and conformational changes during the simulations. The direction of change is quantified by the difference in the position (‘shift’) of the maximum of the distribution; negative being a ‘closing’ motion, and positive ‘opening’ (the complete table of the distributions for all order parameters are available in the extended data, Table S3 (Feenstra, 2019a)). The corresponding conformational distributions from the ConsDYN simulations, calculated as a function of the inner and outer distances between TM5 and TM7 are given in Figure 3.\n\nThe pathogenic mutations are underlined. All the large shifts (above 0.5) and small overlaps (below 0.6) are set to bold. For a visual aid, the shifts are set in italic.\n\nColour code: wild types IO in purple (PDB-ID: 5EQI), OO in green (PDB-ID: 4ZW9), mutants in orange. Pathogenic mutants are highlighted in red. It should be noted that in contrast to the benign R93Q mutant, the pathogenic mutants do not sample the IO and OO states during the simulation, which strongly indicates that the mutation blocks the proper opening and closing mechanism.\n\nNot all mutations have a high impact on the overall dynamics (extended data, Table S3 and Figure S4 (Feenstra, 2019a)). However, in GLUT1, the reported pathogenic mutation G91D has a profound effect on the dynamics of the protein (i.e., a low overlap and large shift, see Table 2). Also when we consider the distance of TM5-TM11, as shown in Figure 3, the strongest effect is observed for the pathogenic G91D mutant: its distribution varies strongest from the wild types, and hardly visits the inward-open and outward-occluded states. Furthermore, Figure 3 shows that for the pathogenic R92W and R333W mutations, only one state or small parts from both can be accessed. For the benign mutant R93Q, in contrast, it can be seen that both states, inward-open and outward-occluded, are sampled thoroughly during the simulations. Assuming that the relative distance between the two helices is crucial for the correct functioning, this strongly suggests that the pathogenic mutations directly affect the opening and closing mechanism of the GLUT1 transporter.\n\nMutations in GLUT3 show similar behaviour in TM dynamics compared to those in GLUT1. Here, two mutants with strong abnormal behaviour can be identified: G89V and R91H (Table 2; extended data Figure S4 (Feenstra, 2019a) shows the corresponding distance distribution plots). Additionally, similar to the observations for pathogenic mutations on GLUT1, these mutations no longer sample intermediate states associated with the transport function, unlike the wild type and many of the other mutations. This strongly suggests that the corresponding mutations between GLUT1 and GLUT3 also have the same direct blocking effects on the opening and closing mechanism of the GLUT3 transporter. However, it should be noted that we cannot make any conclusions about the clinical significance of these GLUT3 mutants, as none have been reported to be pathogenic.\n\n\nConclusion\n\nUsing extensive ConsDYN simulations of GLUT1 and GLUT3 wild type and several clinically relevant mutations, we provide an effective way to study dynamic effects of mutations on the molecular mechanism of human glutamate transporter proteins. Without using full-atomistic details, we were able to get insight into the opening and closing mechanisms, which may account for the (dys)function of the SLC family caused by pathogenic mutations around the conserved RXGRR-motif. Through these mutations (especially G91D, R92W and R333W in GLUT1), the distances between TM5 and TM11, across the rim of the transporter channel structure, are affected the strongest and can be used as order parameters to elucidate abnormal behaviour in the dynamics of the transporter opening and closing mechanism. Comparing atomistic (AT), coarse-grained MARTINI (CG), and ConsDYN simulations, our work shows that our CG ConsDyn simulations are sufficiently accurate to sample between the conformational states and capture the effect of the mutations on the dynamic and function of these transporter proteins.\n\n\nData availability\n\nCrystal structures for GLUT1 IO state (Deng et al., 2015) and for GLUT3 OO state (Kapoor et al., 2016) were obtained from the Protein Data Bank, under accession numbers 5EQI and 4ZW9, respectively.\n\nOpen Science Framework: ConsDYN. https://doi.org/10.17605/OSF.IO/F82H5 (Feenstra, 2019a).\n\nThe following extended data are available:\n\nData.tgz. data files accompanying analyses performed in this study.\n\nTable S1. Summary of the molecular composition of simulated systems.\n\nTable S2. Structurally conserved helical segments between 4ZW9 and 5EQI.\n\nTable S3. Wild-type and Mutant simulations compared by Overlap and shift between TM helix distance distributions.\n\nFigure S1. Sequence alignment between E. coli multi-drug transporter MDFA, and human glucose transporters GLUT1 and GLUT3.\n\nFigure S2. Pipe representation of the inward-open conformation of the channel.\n\nFigure S3. Schematic view of the observed pore mechanism going from the inward-open state to the outward-occluded state.\n\nFigure S4. Distribution of inside and outside helix distances for all examined mutants in GLUT1 and GLUT3.\n\nExtended data are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).\n\n\nSoftware availability\n\nScripts used to setup and analyze the ConsDYN simulations available from:\n\nhttps://github.com/ibivu/ConsDYN.\n\nArchived source code at time of publication: https://doi.org/10.5281/zenodo.2591477 (Feenstra, 2019b).\n\nLicense: GNU General Public License 3.0.",
"appendix": "Grant information\n\nAH was supported through the Program for Leading Graduate Schools, “Global Leader Program for Social Design and Management,” by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. HM would like to thank the European Molecular Biology Organization for a personal grant (EMBO short-term fellowship).\n\nThe funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n\n\nAcknowledgments\n\nThis research (in part) used computational resources of COMA and HA-PACS provided by Multidisciplinary Cooperative Research Program in Center for Computational Sciences, University of Tsukuba, Japan.\n\n\nReferences\n\nAdzhubei IA, Schmidt S, Peshkin L, et al.: A method and server for predicting damaging missense mutations. Nat Methods. 2010; 7(4): 248–249. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmadei A, Linssen AB, Berendsen HJ: Essential dynamics of proteins. Proteins. 1993; 17(4): 412–425. PubMed Abstract | Publisher Full Text\n\nAn Y, Varma VR, Varma S, et al.: Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement. 2018; 14(3): 318–329. PubMed Abstract | Publisher Full Text | Free Full Text\n\nArnarez C, Uusitalo JJ, Masman MF, et al.: Dry Martini, a coarse-grained force field for lipid membrane simulations with implicit solvent. J Chem Theory Comput. 2015; 11(1): 260–275. PubMed Abstract | Publisher Full Text\n\nde Jong DH, Singh G, Bennett WF, et al.: Improved Parameters for the Martini Coarse-Grained Protein Force Field. J Chem Theory Comput. 2013; 9(1): 687–697. PubMed Abstract | Publisher Full Text\n\nDeng D, Sun P, Yan C, et al.: Molecular basis of ligand recognition and transport by glucose transporters. Nature. 2015; 526(7573): 391–396. PubMed Abstract | Publisher Full Text\n\nFeenstra KA: ConsDYN. 2019a. http://www.doi.org/10.17605/OSF.IO/F82H5\n\nFeenstra KA: ibivu/ConsDYN v1.1b (Version v1.1b). Zenodo. 2019b. http://www.doi.org/10.5281/zenodo.2591477\n\nGu J, Jin N, Ma D, et al.: Calpain I Activation Causes GLUT3 Proteolysis and Downregulation of O-GlcNAcylation in Alzheimer’s Disease Brain. J Alzheimers Dis. 2018; 62(4): 1737–1746. PubMed Abstract | Publisher Full Text\n\nHediger MA, Clémençon B, Burrier RE, et al.: The ABCs of membrane transporters in health and disease (SLC series): introduction. Mol Aspects Med. 2013; 34(2–3): 95–107. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHess B, Kutzner C, van der Spoel D, et al.: GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. J Chem Theory Comput. 2008; 4(3): 435–447. PubMed Abstract | Publisher Full Text\n\nHiguchi A, Nonaka N, Yura K: iMusta4SLC: Database for the structural property and variations of solute carrier transporters. Biophys Physicobiol. 2018; 15: 94–103. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHsu PC, Bruininks BMH, Jefferies D, et al.: CHARMM-GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides. J Comput Chem. 2017; 38(27): 2354–2363. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJoshi C, Greenberg CR, De Vivo D, et al.: GLUT1 deficiency without epilepsy: yet another case. J Child Neurol. 2008; 23(7): 832–834. PubMed Abstract | Publisher Full Text\n\nKapoor K, Finer-Moore JS, Pedersen BP, et al.: Mechanism of inhibition of human glucose transporter GLUT1 is conserved between cytochalasin B and phenylalanine amides. Proc Natl Acad Sci U S A. 2016; 113(17): 4711–4716. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlepper J, Leiendecker B, Eltze C, et al.: Paroxysmal Nonepileptic Events in Glut1 Deficiency. Mov Disord Clin Pract. 2016; 3(6): 607–610. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlepper J, Voit T: Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain-- a review. Eur J Pediatr. 2002; 161(6): 295–304. PubMed Abstract | Publisher Full Text\n\nKlepper J, Willemsen M, Verrips A, et al.: Autosomal dominant transmission of GLUT1 deficiency. Hum Mol Genet. 2001; 10(1): 63–68. PubMed Abstract | Publisher Full Text\n\nLeen WG, Klepper J, Verbeek MM, et al.: Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. Brain. 2010; 133(Pt 3): 655–70. PubMed Abstract | Publisher Full Text\n\nMay A, Pool R, van Dijk E, et al.: Coarse-grained versus atomistic simulations: realistic interaction free energies for real proteins. Bioinformatics. 2014; 30(3): 326–334. PubMed Abstract | Publisher Full Text\n\nMongin M, Mezouar N, Dodet P, et al.: Paroxysmal Exercise-induced Dyskinesias Caused by GLUT1 Deficiency Syndrome. Tremor Other Hyperkinet Mov (N Y). 2016; 6: 371. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMonticelli L, Kandasamy SK, Periole X, et al.: The MARTINI Coarse-Grained Force Field: Extension to Proteins. J Chem Theory Comput. 2008; 4(5): 819–834. PubMed Abstract | Publisher Full Text\n\nNagarathinam K, Nakada-Nakura Y, Parthier C, et al.: Outward open conformation of a Major Facilitator Superfamily multidrug/H+ antiporter provides insights into switching mechanism. Nat Commun. 2018; 9(1): 4005. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPao SS, Paulsen IT, Saier MH Jr: Major facilitator superfamily. Microbiol Mol Biol Rev. 1998; 62(1): 1–34. PubMed Abstract | Free Full Text\n\nPeriole X, Cavalli M, Marrink SJ, et al.: Combining an Elastic Network With a Coarse-Grained Molecular Force Field: Structure, Dynamics, and Intermolecular Recognition. J Chem Theory Comput. 2009; 5(9): 2531–2543. PubMed Abstract | Publisher Full Text\n\nSato M, Mueckler M: A conserved amino acid motif (R-X-G-R-R) in the Glut1 glucose transporter is an important determinant of membrane topology. J Biol Chem. 1999; 274(35): 24721–24725. PubMed Abstract | Publisher Full Text\n\nSchneider SA, Paisan-Ruiz C, Garcia-Gorostiaga I, et al.: GLUT1 gene mutations cause sporadic paroxysmal exercise-induced dyskinesias. Mov Disord. 2009; 24(11): 1684–1688. PubMed Abstract | Publisher Full Text\n\nSim NL, Kumar P, Hu J, et al.: SIFT web server: predicting effects of amino acid substitutions on proteins. Nucleic Acids Res. 2012; 40(Web Server issue): W452–7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSimpson IA, Chundu KR, Davies-Hill T, et al.: Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer’s disease. Ann Neurol. 1994; 35(5): 546–551. PubMed Abstract | Publisher Full Text\n\nSzablewski L: Glucose Transporters in Brain: In Health and in Alzheimer’s Disease. J Alzheimers Dis. 2017; 55(4): 1307–1320. PubMed Abstract | Publisher Full Text\n\nVan Aalten DMF, De Groot BL, Findlay JBC, et al.: A comparison of techniques for calculating protein essential dynamics. J Comput Chem. 1997; 18(2): 169–181. Publisher Full Text"
}
|
[
{
"id": "46135",
"date": "15 Apr 2019",
"name": "Lucie Delemotte",
"expertise": [
"Reviewer Expertise Membrane proteins",
"ion channels",
"molecular dynamics simulations",
"enhanced sampling"
],
"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 paper describes a computational study of the effect of mutations on GLUT transporter dynamics. The work consists of atomistic and coarse grained simulations, including some using a protocol called ConsDYN which imposes constraints on distances conserved across conformational transitions. The study identifies that several pathogenic and other mutations modify the structural ensemble visited by the protein.\nWhile the topic is important and computational methods are well-suited to answer the question, I have reservations about the study design and the conclusions reached:\n\nA pathogenic mutation modifies the function of the protein such that cellular and organism function are altered. Glucose transporters carry out their function, i.e. importing sugars, via an alternating access cycle in which the transporter transits between outward-open and inward-open states via occluded states; whereas sugar binding from the extracellular medium promotes a transition to the inward facing state, sugar release to the inside intracellular medium promotes a return to the outward facing state. Other than the intrinsic dynamics of interconversion between states, the fact that the sugar modifies the stability of states and the kinetics of interconversion is key for function. Thus pathogenicity of a mutation could be due to many factors: among others, sugar binding, unbinding, (de)stabilization of one or more states on the functional cycle, modification of the rate of conversion between states, in the presence and/or absence of sugar. In this paper, the authors investigate the effect of mutations on the dynamics of interconversion between states. I believe the assumption should be spelled out more clearly, and the omission of all other possible effects on the sugar transport cycle should be explained.\nRelatedly, were the simulations performed in the presence or absence of sugar? Comparing both cases could lead to increased insights.\n\nWhy was the analysis limited to outward occluded and inward open states, when high-resolution structures of other states are available? If only two states should be considered, why not consider the inward open and outward open since they are the two end-points of the transport cycle?\n\nThe ConsDYN method can be an interesting way to promote conversion between states using coarse grained simulations. However, whereas the stated aim on p5 is “to check that ConsDYN is able to sample both Io and Oo states”, Figure 2 reveals that ConsDYN simulations only sample intermediate states, instead of bridging between states. I would thus disagree with the conclusion according to which the method allows to capture the “conserved dynamics” and to “sample between the conformational states”.\n\nWould lowering the force constant of the constraints imposed lead to further exploration of the landscape?\nThe method also seems to have a serious conceptual drawback, in that it assumes that when switching from a state to another, common contacts are conserved, and additional ones are formed in either states. This does not seem to be a general feature of conformational changes in biological molecules and should be discussed.\n\nTable 2 reports changes in distance between helices in the presence and absence of mutations, including pathogenic ones. Whereas the pathogenic G91D seems to cause major changes to the dynamics of the transporter, the other pathogenic mutations only alter some of the distance distributions. It does not appear that applying this methodology and measuring the difference in distance distributions as is done in Table 2 allows to predict pathogenicity. I thus disagree with the conclusions: “the distances between TM5 and TM11 can be used as order parameters to elucidate abnormal behavior in the dynamics of the transporter” and “ConsDYN simulations capture the effect of the mutations on the dynamic and function of the transporter proteins”.\n\nMinor comments:\n\nThe authors refer to a “channel” in the title and later in the manuscript. Do they mean the transporter lumen? In an alternating access mechanism, a channel is never observed.\n\np5: The difference between Nagarathinam et al. (2018) and this work is ascribed to differences in the transporter protein studied (bacterial vs human) but the authors cannot rule out that the differences can come from differences in the sampling protocol.\n\nWere the CG or AA simulations of Io and Oo analyzed in Figure 3, Table 2 and SI figures?\n\np6: “outer distances between TM5 and TM7 are given in Figure 3” should be replaced by “outer distances between TM5 and TM11 are given in Figure 3”.\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? No",
"responses": [
{
"c_id": "8316",
"date": "13 Jun 2022",
"name": "K. Anton Feenstra",
"role": "Author Response",
"response": "We thank the reviewer for the attention and time spent on our work, and respond to each of their comments in detail below: Reply: All the simulations were carried out without glucose or any other ligand, we only consider the ligand-free states of the transporters. This implies that the pathogenicity of a mutant might already be stated through the intrinsic dynamics of the transporter without explicitly considering the effect of the mutation in the ligand-bound state. This does indeed not exclude that pathogenicity linked to a specific mutant might arise from a dysfunction of the binding mechanism. In this study we focus on the first part of the transport mechanism of SLC transporters, and introduce the ComDYN method, which is designed to capture conformational changes between different states. We have now added this point to the manuscript and explicitly mention that, to guarantee the study of all the relevant effects, simulations including the ligand-bound states might yield additional insight on the structure and dynamic of different mutants. However, this would only be feasible using full-atomistic simulations, since sugars are not well parametrized in the Martini force field. As this would pose strong limits on the time scales we could practically attain in our simulations, it is out of the scope of the current study. Reply: We want to focus on the first part of the transport mechanism: moving from the inward open to the outward occluded state. The next step to elucidate the complete pathway will be to extend this to the outward-open conformation which is available in the PDB. For the present work, we focus on the impact of some mutations on the intrinsic dynamics of the protein (without considering the impact of any ligand) and show in this case study that ComDYN is able to sample these large conformational changes between states. We have now clarified this point in the manuscript. Reply: We mostly agree, we have rephrased “sample both IO and OO states” to “sample the intermediate states between IO and OO states” throughout the manuscript. Reply: A lower force constant would indeed lead to more sampling, just like a wider cut-off which we discuss in our response to question 3 of Reviewer 1, but it would not necessarily lead to a better sampling or better exploration of the landscape. At low force constants for the constraints, in the MARTINI forcefield it becomes increasingly likely that too large conformational changes become permissible, even up to the point of unfolding of the transporter proteins. Reply: The elastic network used in the MARTINI forcefield captures all residue contacts in the tertiary structure. In the case of SLC about 40% of contacts are conserved between both states, in our definition of less than 1 Å difference in the elastic network distance. Except in the case of (complete) unfolding, the vast majority of these contacts will exist in multiple conformational states of a solute carrier protein. However, it should be noted that we used the word ‘conserved’ in two different meanings: the specific evolutionary conservation, and the more general meaning of preservation, in this case of the contacts between two conformational states. We now clarified this throughout the text by referring to ‘common constraints’, and also changed the name ConsDYN to ComDYN accordingly. Reply: Indeed, from the dynamics observed we cannot predict pathogenicity. However, we can ‘elucidate’ the known pathogenicity, in the sense of clarifying where previously effects were not understood. We have made the limitations of the method more explicit in the manuscript. In particular, this sentence now reads “For this reason, we chose them as our order parameter to explain the abnormal behavior in the dynamics of the transporter opening and closing mechanism for some of the observed mutants.” In future approaches, sugar binding will certainly need to be considered in order to fully understand the altered dynamics and behavior of the pathogenic mutants. Minor comments: Reply: Indeed, we have now changed the title and appropriate sections in the text to refer to ‘transporter’ in stead of ‘channel’. Reply: Indeed we cannot. We have clarified this in the text. Reply: The CG ComDYN simulations are analyzed in Figure 3, Table 2 and SI figures. We now mention this explicitly in the captions of Fig 3 and Table 2 and Figure S3. Reply: We thank the reviewer for pointing out this mistake, which we have now corrected."
}
]
},
{
"id": "47253",
"date": "08 May 2019",
"name": "Jocelyne Vreede",
"expertise": [
"Reviewer Expertise Molecular simulation of proteins and DNA"
],
"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 reports a molecular dynamics simulation study of the glucose transporter GLUT1 using all-atom and coarse grained force fields, in combination with a conserved elastic network. Using essential dynamics analysis and comparison of various distances the authors compared the dynamics of the wild type protein to pathogenic variants in the outward occluded and inward open states. This procedure enabled the prediction of the effect of mutations on the dynamics of GLUT1 and GLUT3.\n\nThe manuscript requires a few clarifications to improve my understanding:\nAs I am not very familiar with the mechanism of glucose transporters, I would like a few sentences describing how these proteins work, thus giving more context to the different conformational states Io and Oo. Also in the conclusion, a bit more context as to how the states interconvert and the impact of the mutations on these transitions would aid my understanding tremendously.\n\nThe manuscript reports results on mutations at positions 92, 93, 333 and 334, which are highlighted in Fig. 1. Only mutations 92 and 93 are discussed in the introduction. For more context, the mutations at 333 and 334 should be discussed in the introduction as well.\n\nWhat motivates the cut-off of 1 angstrom for including constraints in the elastic network? Would 1.5 angstrom or 2 angstrom work as well?\n\nAs essential dynamics analysis is performed on both all-atom and coarse grained simulations, I assume only C-alpha positions are included. Is this assumption correct?\n\nWhat do the two eigenvectors shown in Fig. 2 mean? My interpretation is that EV1 is the transition from the Oo to the Io state, and that EV2 is the transition from the all-atom to coarse grained-constrained description. If this interpretation is correct, would the conclusion be correct that the dynamics sampled in the different force fields overlap?\n\nThe Oo and Io states as sampled with the consdyn and the AT approach seem quite different in Fig. 2. What could be the explanation for this difference?\n\nSnapshots of the conformations at the maxima of the probability histograms would help my understanding of the differences as introduced by the mutations.\n\nI do not understand how the overlap in the distributions in Table 2 is computed.\n\nWhat is the unit of the shift in Table 2 and of the distances in Fig. 3?\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": "8317",
"date": "13 Jun 2022",
"name": "K. Anton Feenstra",
"role": "Author Response",
"response": "We thank the reviewer for the attention and time spent on our work, and respond to each of their comments in detail below: Reply: We have added a short explanation of the basics of the SLC glucose transport and how the process cycles through the various states in the Introduction, and now also emphasize the main changes arising from the pathogenic mutations in the Conclusion. Reply: We have added a discussion on the mutations at the R333 and R334 positions in the Introduction. Reply: The 1Å cutoff retains 40% of the constraints, which is already relatively little. Shorter cut-offs would yield more restricted sampling. A wider cut-off would not necessarily provide better sampling, but would very likely lead to too large conformational changes or even unfolding of the transporter protein. This is now explicitly mentioned in the methods section under Molecular Dynamics. Reply: Indeed, the ED analysis uses C-alpha for AT and backbone particles at C-alpha position for CG. We have now clarified this in the Analysis of transporter dynamics section in the Methods. Reply: Indeed, transitions between Oo and Io are visible on EV1 in Figure 2; we have now added this explicitly in the figure caption. The sampled states do overlap between the different forcefield approaches. Moreover, as we also discuss in our reply to question 3 of Reviewer 2, the CG sampling partly overlaps the AT sampling on both sides of the Oo to Io transition, and partly with the ComDYN sampling more to the middle of the transition. Furthermore, the Oo ComDYN sampling overlaps considerably with the Io ComDYN sampling. We have also added the starting conformations in Fig 2 as an aid to the reader to better navigate this projected sampling space. We cannot exclude that EV2 may represent conformational changes due to differences between the forcefields, however as we are also sampling far longer timescales in the CG and ComDYN simulations, these differences may also genuinely be part of the transition between the Oo and Io states. Reply: Both ComDYN simulations start at or near the conformations from the AT simulations, but this is not quite visible in the plot in Fig 2. We have now added spheres to indicate the respective starting conformations, as well as triangles to show the corresponding crystal structures. The CG simulations sample much longer timescales, so allow conformational transition that cannot be reached during the sampling time of the AT simulations. We have now clarified this in results, Section “Verification of constraining approach”. Reply: The outcome of such a visualization would not be informative for a protein of this size. The differences in conformation (namely the distances between the transmembrane helices) are small and therefore difficult to visualize. Superpositioning snapshot does therefore not help to understand the differences occurring through the mutations. To capture molecular motions during our simulations, we use the defined inter-helix distances (cf. Figure 1D.) as order parameters, which are directly interpretable. Reply: ‘Overlap’ is the fraction of overlap between both distributions of sampled conformations, calculated as the integral of the minimum of both functions, i.e., the volume (normalized to a maximum of one) that represents the amount of sampling between two distributions. We have now clarified this in the section Analysis of transporter dynamics in Methods, with a reference to the relevant python script and now provide the ‘overlap’ in percentage to make this explicit. Reply: They are all in nanometers (nm), we have added this now explicitly to the table and figure captions."
}
]
}
] | 1
|
https://f1000research.com/articles/8-322
|
https://f1000research.com/articles/11-644/v1
|
13 Jun 22
|
{
"type": "Research Article",
"title": "Reporting characteristics of allergic rhinitis trials registered on ClinicalTrials.gov and in publications: an observational study",
"authors": [
"Ivan Paladin",
"Shelly Pranić",
"Shelly Pranić"
],
"abstract": "Background: Data from randomized controlled trials (RCTs) on Allergic rhinitis (AR) should be complete and consistent throughout multiple sources to ensure accurate evidence-based information. The aim of this study was to determine whether there are discrepancies in the reported data from AR trials. Methods: This cross-sectional study retrospectively analyzed completed RCTs on AR registered in ClinicalTrials.gov and last updated between 9/27/2009 and 10/4/2019 with results and corresponding publications. Completeness, informativeness and major changes to World Health Organization Trial Registration Data Set items as well as completeness of results data in ClinicalTrials.gov and corresponding publications were analyzed. Results: Omitted items were present in 35 (46.1%) of the 76 trials at initial registration, 15 (19.7%) at last registration, and in 22 (56.4%) of the 39 publications. All 76 trials between first and last registration and all 39 publications had major changes in registration items. Uninformative reporting of analyzed items were present both in ClinicalTrials.gov and publications. Completeness of results in ClinicalTrials.gov was satisfactory. In contrast, publications reported fewer adverse events. Conclusions: Discrepancies in data elements of AR trials are common both in ClinicalTrials.gov and subsequent publications. To ensure transparent data reporting from AR trials, multiple stakeholders should control the accuracy, consistency, and completeness of AR trial data to notice discrepancies before publication.",
"keywords": [
"Allergic rhinitis",
"ClinicalTrials.gov",
"Completeness",
"Informativeness",
"Trial Registration Data Set"
],
"content": "List of abbreviations\n\nAE: Adverse Event\n\nAR: Allergic rhinitis\n\nCONSORT: Consolidated Standards of Reporting Trials\n\nFDAAA: The Food and Drug Administration Amendment Act\n\nICMJE: International Committee of Medical Journal Editors\n\nMeSH: Medical Subject Headings\n\nNCT: National Clinical Trial\n\nOAE: Other Adverse Event\n\nRCT: Randomized controlled trials\n\nSAE: Serious Adverse Event\n\nSTROBE: Strengthening the Reporting of Observational Studies in Epidemiology\n\nTRDS: Trial Registration Data Set\n\nU.S.: United States\n\nWHO: World Health Organization\n\n\nIntroduction\n\nAllergic rhinitis (AR) is a global health problem with a 10% to 30% prevalence in adults and up to 40% in children.1,2 The total cost of AR in the U.S. is estimated at $9 billion annually through direct health expenditures and lost productivity due to absence from work and school.3,4 Studies that test interventions, drug efficacy or behavioral factors that may stop the increase in prevalence or reduce the costs of AR are imperative. Therefore, data from such studies should be complete and consistent throughout multiple sources to ensure accurate evidence-based information that may be used by patients, clinicians, researchers, and professional organizations for decisions regarding therapy, establishing guidelines, or other.5–9 The accuracy and completeness of data from studies can be assessed from the presence of standardized data elements registered in a public registry such as ClinicalTrials.gov.5,10\n\nFor adequate trial registration and a precondition for publication in International Committee of Medical Journal Editors (ICMJE) member journals, the World Health Organization (WHO) and ICMJE, since 2005, require the completion of WHO Trial Registration Data Set (TRDS) items for basic, mandatory trial information.11–14 Two years later, on 9/27/2007, Section 801 of the Food and Drug Administration Amendment Act (FDAAA 801) went into effect and mandated the registration of clinical trials and reporting of basic results from them within 1 year of trial completion.15 Furthermore, the Final Rule of Clinical Trials Registration and Results Information Submission, implemented in January 2017, clarified which trials the FDAAA covers as well as requirements concerning registration and results submission.16,17 Additionally, in November 2017, WHO TRDS has been expanded with 4 new items and currently contains 24 items.18 As a result, the registration of trials in ClinicalTrials.gov as well as the consistency of information with corresponding publications has improved; however, discrepancies remain between trial information and results reported in ClinicalTrials.gov and corresponding publications more than a decade since the implementation of the FDAAA 801.19,20\n\nThus, we aimed to assess completed randomized controlled trials (RCTs) on AR registered in ClinicalTrials.gov for completeness, informativeness and major changes to WHO TRDS items as well as completeness of results data in ClinicalTrials.gov and corresponding publications.\n\n\nMethods\n\nAll methods were performed in accordance with the relevant guidelines and regulations and there was no need for approval from an institutional review board (Ethics Committee of the University of Split School of Medicine), as this study is cross-sectional and historical cohort database study. We neither collected patient data nor performed experimental procedures.\n\nFurthermore, all data used in this study are publicly available in the ClinicalTrials.gov registry and therefore no permission was required to access the data.\n\nThis study neither studied nor analyzed the raw data of other studies. We analyzed their data which were publicly registered in ClinicalTrials.gov and published in publicly available scientific journals. So no permission was needed here either.\n\nData from other studies registered in the ClinicalTrials.gov registry, which we analyzed, were anonymized by their authors, so no anonymization was required on our study.\n\nFigure 1 shows our retrospective analysis. The start date (9/27/2009) of the search allowed at least two years for the study to post in ClinicalTrials.gov and publish results in journals. The last search date (10/4/2019) allowed more than 10 years from first to last posting and publishing of results.\n\nFlow diagram of retrospective cross-sectional study with inclusion and exclusion criteria. FDAAA: The Food and Drug Administration Amendment Act, FDA: The Food and Drug Administration.\n\nWe accessed the history of all changes in registration elements through the ClinicalTrials.gov Archive site. We searched ClinicalTrials.gov for completed RCTs using the following keywords: “allergic rhinitis”, “nasal allergies”, “rhinoconjunctivitis”, “hay fever”, and “atopic rhinitis”. We did not use Medical Subject Headings (MeSH) terms.\n\nFor trials with publications provided on ClinicalTrials.gov, we selected only those that reported the results of the current trial to find corresponding publications to our sample of AR RCTs. For trials without publications provided, we searched PubMed, Web of Science, Scopus, and Google Scholar with the National Clinical Trial (NCT) identifier provided by ClinicalTrials.gov in the trial record that is usually listed in the abstract or main text of published articles.21 If the initial search failed, we searched using the principal investigator's name and study title. Only full publications were compared with registered data. Publication dates were determined from online publication dates for articles made available ahead of print.22\n\nInclusion criteria are shown in Figure 1. Requirements for an applicable clinical trial according to the FDAAA 801 were verified according to the “Elaboration of definitions of responsible party and applicable clinical trial (ACT)” from 3/9/2009 for trials initiated after 9/27/2007 and according to the “Checklist for evaluating whether a clinical trial or study is an ACT” for those initiated after 1/18/2017.23\n\nDifferences between first and last registration were assessed from 20 out of 24 extracted WHO TRDS items, while we assessed differences between last registration and publications from 15 out of 24 items. The “Contact for Public Queries” and “Contact for Scientific Queries” items were excluded from both analyzes due to their unavailability in ClinicalTrials.gov while “Recruitment Status” item was excluded due to it's transient nature. Furthermore, the “Date of Registration in Primary Registry”, “Secondary Identifying Numbers”, “Secondary Sponsor(s)” and “Public Title” items were excluded from the analysis of the differences between last registration and publications due to their exclusion from journals. The “IPD Sharing Statement” and “Ethics review” items added to the WHO TRDS in November 2017 were not included in the analysis for trials started before the WHO TRDS extension. Also the “IPD Sharing Statement” was not included in the analysis for publications before the mandatory data sharing statement from July 1, 2018.24 In contrast, the “Completion Date” and “Basic Results” (comprises the current “Summary Results” item) items were required by the FDAAA 801 in ClinicalTrials.gov15 and were therefore analyzed. Additionally, the “All-cause Mortality” item in the Adverse Events (AEs) section was required by the Final Rule of the FDAAA, so we did not analyze this item for trials with a primary completion date before its implementation in 2017. We studied the reporting of deaths of such trials from other elements of the outcome data, primarily from Serious AEs (SAEs).\n\nWe determined the completeness and informativeness, i.e., missing information or uninformative terminology (unspecified or unclear information for the relevant registry item such as a code instead of a generic name of a drug), respectively, at first and last registration and in publications of WHO TRDS items.8,25 We used previous methods25 to evaluate the history of changes in WHO TRDS items from first to last registration and changes between last registration and corresponding publications. Changes were defined as qualitative (difference in the meaning of the provided information) or quantitative (difference in a numerical entry).25 We modified criteria developed by Chan et al.8 to describe discrepancies between registered and published outcomes as: a new primary outcome introduced in the article, an omitted registered primary or secondary outcome in the article, a registered primary or secondary outcome switched in the article or vice versa, a new secondary outcome introduced in the article, a registered primary or secondary outcome changed in the article, a new outcome methodology introduced or the registered one changed in the article, the timing of assessment changed in the article, and a new primary or secondary outcome introduced in the article as a combination of registered outcomes.\n\nThe completeness of results reporting from first to last registration and from last registration to the publication were determined by the presence of Participant Flow elements, Baseline Characteristics elements, Outcome Measures elements, and AEs.\n\nAdditionally, we analyzed these discrepancies in data reporting between trials with prospective and retrospective trial registration in ClinicalTrials.gov as well as between industry vs. non-industry sponsored trials. Trials with prospective registration started during or after first registration, and trials with retrospective registration started before it. We also analyzed the time differences between several points in the registration and publication.\n\nTwo investigators (IP and SP) independently extracted data in parallel from the entire cohort of trials for completeness, informativeness and changes to avoid potential data collector bias from possible subjective interpretation. Inter-rater reliability was high for changes in the WHO TRDS items (kappa range 0.83 to 1.00). We resolved through consensus discussion the differences in our interpretation of the secondary outcome changes, which had the lowest kappa in any single category (0.83, 95% confidence interval (CI) 0.73 to 0.94). We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for reporting observational studies.26 There was no need for approval from an institutional review board (Ethics Committee of the University of Split School of Medicine), as this study is a cross-sectional and historical cohort database study. We neither collected patient data nor performed experimental procedures.\n\nData extracted from ClinicalTrials.gov were coded and then entered into a Microsoft Excel spreadsheet. Dichotomous variables were registration period (retrospective or prospective), sponsorship (industry or non-industry) and completeness of registration (trial with or without missing registration items). The number of major changes and trial duration in months were treated as nonparametric, and were categorized based on a median split, where values were dichotomized as 0, when less than or equal to their respective median, and as 1 when greater than their respective medians. Differences in the trials, completeness, and major changes to the WHO TRDS items were compared using the Chi-square test. Frequencies, medians with the 95% CI were presented. Frequencies were compared using Chi-squared tests. We used IBM SPSS Statistics 21 (SPSS, Inc., an IBM company, Chicago, IL, USA, RRID:SCR_002865) for the analyses. Differences were considered significant at a P<.05.\n\n\nResults\n\nA total of 76 trials were analyzed and 42 (55.3%) were published, two of which were in Japanese and one was only available as a Supplement. Thus, 39 (51.3%) publications were available for analysis. All were published in journals that follow ICMJE recommendations and only one (2.6%) was an ICMJE member.24 Further, there were 16 (41.0%) out of the 39 published trials where the corresponding publication was published before the results were posted in ClinicalTrials.gov[1]. Most trials in ClinicalTrials.gov were phase 3 (n=41 [53.9%]), quadruple-blind (n=33 [43.4%]), parallel group (n=64 [84.2%]) and placebo controlled (n=57 [75.0%]). In contrast, most published trials were double-blind (n=32 [82.1%]) (Table 1).\n\nAll 76 trials started before the implementation of the Final Rule and there were 22 (28.9%) trials with retrospective registration in ClinicalTrials.gov. Table 2 shows the median elapsed time between several points in the registration and publication of the trials. Most trials (n=64 [84.2%]) as well as most publications (n=36 [92.3%]) were industry-sponsored. We found that industry-sponsored compared to non-industry funded trials had a statistically significant shorter duration (χ2=6.848, P=.009).\n\nTable 3 shows which WHO TRDS items are most often missing at first and last registration and in publications. At least 1 WHO TRDS item was missing in 35 (46.1%) trials at first registration, in 15 (19.7%) at last registration and in 22 (56.4%) publications. There were statistically significantly more incomplete first registrations in trials with prospective registration than in those with retrospective (n=32 [91.4%] vs. n=3 [8.6%]); χ2=13.096, P≤.001.\n\na For trials that started after November 6, 2017 and for publications that were submitted to journals after July 1, 2018.\n\nb 6 publications were submitted after July 1, 2018.\n\nAll registered trials had major changes in WHO TRDS items in the period between first and last registration as well as all publications (Tables 4-5 and Supporting Tables 1-3 in Extended data). The median major changes per trial between first and last registration was 31 (95% CI 35.73 to 65.29), and per publication it was 28 (95% CI 24.6 to 32.2) (Table 4). There was no difference in the number of major changes to WHO TRDS items per trial between first and last registration. as well as between last registration and publication according to prospective or retrospective trial registration; χ2=3.003, P=.083 and χ2=2.820, P=.093, respectively.\n\nPredominantly, methodological details were changed in both primary and secondary outcomes between first and last registration as well as in publications (Table 5). Furthermore, primary outcome changes between first and last registration and in publications included the addition of new outcomes and changes to existing ones. According to prospective or retrospective trial registration, we found no difference in the number of major changes to primary and secondary outcomes between first and last registration as well as between last registration and publication; χ2=0.616, P=.433; χ2=2.758, P=.097; χ2=2.201, P=.138 and χ2=2.820, P=.093, respectively.\n\nWe found uninformative reporting of WHO TRDS items in ClinicalTrials.gov and publications (Table 6). The median uninformative WHO TRDS items per trial at first registration was 3 (95% CI 3.1 to 3.8), 1 (95% CI 1.3 to 1.9) at last registration, while in publications it was 0 (95% CI 0.08 to 0.43). At first registration, most trials had uninformative “Primary and Key Secondary Outcomes” and “Intervention(s)” items. The outcomes were uninformative mainly due to their unclear methodology that was clarified by last registration, and the interventions mainly due to a missing time frame (Table 6). Table 6 also shows that registered and published interventions from RCTs on AR had uninformative descriptions. 28 (71.8%) publications had a less informative “Study Type” than in ClinicalTrials.gov, mostly due to omitted study phase (Supporting Table 3 in Extended data).\n\na Multiple uninformativeness present in single WHO TRDS item.\n\nRegarding participant characteristics, all trials in ClinicalTrials.gov reported Participant overall flow and Baseline population descriptions while only 1 (2.6%) out of 39 publications did not. All 76 trials reported SAEs and Other AEs (OAEs) in ClinicalTrials.gov. In contrast, 30 (76.9%) publications reported SAEs and 38 (97.4%) OAEs. Due to primary completion dates after 2017, the reporting of the “All-cause Mortality” item was analyzed for only nine (11.8%) trials, all of which have a reported item in ClinicalTrials.gov. Of these, four were published and two of them reported deaths. There were only two (2.6%) trials that reported deaths, both as an SAE. Of these, both were published, and only one publication reported it. Overall, deaths were reported in 20 (51.3%) publications.\n\n\nDiscussion\n\nOur novel cross-sectional study on the discrepancies in the reporting of data from RCTs on AR showed that most of the analyzed trials were phase 3 and 4. These studies, especially if published in high-impact journals, have the greatest impact on clinical care and formulate clinical practice guidelines.20 For most trials in ClinicalTrials.gov (n=45 [59.2%]) masking/blinding was listed as quadruple and triple. In contrast, most publications were double-blind (n=34 [87.2%]), and only one (2.6%) publication was listed as triple-blind, while none were listed as quadruple. This discrepancy in the reporting of masking/blinding between registered protocol data and corresponding publications and insufficient descriptions of the blinding process in publications is contrary to the updated Consolidated Standards of Reporting Trials (CONSORT) guidelines, which require transparent reporting of this process.27,28\n\nAlmost half of the registered trials had incomplete first registration. Furthermore, more than a quarter of trials had retrospective registration in ClinicalTrials.gov, and those trials also had a more complete first registration. Perhaps researchers or sponsors perceive a greater incentive to fully register when the trial is progressing significantly or about to be published rather than to prospectively register the trial.29\n\nMore than half of the publications also had missing registration items that differed significantly from those in ClinicalTrials.gov. In addition to poor reporting of deaths, also almost a quarter of the publications were missing explicit reporting of SAEs. The analysis of discrepancies in the reporting of deaths between ClinicalTrials.gov and publications is deficient due to the fact that the item \"All-cause Mortality\" was required by the implementation of the Final Rule and therefore included only nine (11.8%) trials. In contrast, we could not associate the implementation of the Final Rule with the publication of trial results prior to their posting in ClinicalTrials.gov due to the fact that only two (5.1%) trials were published before April 2017 from which responsible parties have been required to be compliant, and the posting of the corresponding results in ClinicalTrials.gov was after that date.23\n\nAll trials in ClinicalTrials.gov as well as published trials had major changes to registration items mainly due to the aggregate nature of the changes (e.g., deletions, additions, or changes to the outcome's methodology). A concerning fact is that changes in outcomes, study design and interventions were among the most common. We expected changes to the WHO TRDS items for prospectively registered trials,25,29 but if without approval from an ethics committee, changes to primary and secondary outcomes in more than 80% of the trials between first and last registration as well as changes to primary outcomes in 26% and secondary in 82% of the corresponding publications are unjustifiable.\n\nThe presence of uninformative WHO TRDS items clearly declined between first registration and publication, especially between last registration and publication. Of particular concern is the significant prevalence of uninformative outcomes as well as interventions at first registration.\n\nAccordingly, it can be concluded that journals following ICMJE recommendations do not consider registration data inadequate if any WHO TRDS item is missing or uninformative.12 To address this issue, Talebi et al. proposed the introduction of a registration checklist for researchers that would provide an explanation in the publication of any discrepancy related to registered information and request a link to the corresponding ClinicalTrials.gov record to help journal editors find discrepancies between registered data and data in submitted manuscripts.20\n\nConcerning the primary sponsor, our findings that most of the trials (n=64 [84.2%]) were industry-sponsored and significantly shorter are consistent with the results of a cross-sectional study conducted on a sample of 245,999 registered interventional studies in ClinicalTrials.gov.30 Although we found a predominance of industry-sponsored trial publications, less than half (n=36 [47.4%]) of them were published, while slightly higher percentages (55-68%) of industry-sponsored publications were reported in the literature.31,32 Notably in ClinicalTrials.gov, the primary sponsor data item is inseparable from the funding source, a WHO data item that is not included in the current Administrative Information section of a trial record. Thus, administrators at ClinicalTrials.gov may need to introduce a separate “Source(s) of Monetary or Material Support” field to improve comparison and reduce the risk of misclassification of funders.30\n\nWe analyzed trials only registered in ClinicalTrials.gov, which is a limitation to the study. There are currently 17 other primary registries in the WHO registry network that meet ICMJE requirements and therefore our analyzed data may not have external validity to trials registered outside of ClinicalTrials.gov.33 However, we used ClinicalTrials.gov, which is the largest clinical trial registry.5,10 Another limitation could be the oversight of some of the existing publications despite different search methods. Furthermore, data interpretation may be subjective, particularly regarding major changes in the WHO TRDS items and results due to data collector characteristics and bias. Therefore, a second reviewer (SP) independently extracted data and we performed inter-rater agreement, and through discussion and consensus, we determined clear rules for data entry to minimize subjective data interpretation. Finally, our samples regarding RCTs and publications were small so the changes or discrepancies recorded should be viewed with caution.\n\n\nConclusions\n\nDespite the WHO and ICMJE registration requirements and US legal provisions, the completeness and consistency of WHO TRDS items of RCTs on AR registered in ClinicalTrials.gov as well as in the corresponding publications is mostly poor. The informativeness of the analyzed items is higher in publications than in ClinicalTrials.gov. Whichever of the WHO TRDS items are applicable to trials, trialists should ensure that the registered data is accurate and subsequent checks could ensure this before the publication of AR trial data. Checking the accuracy of trial data through multiple sources and resolving any discrepancies before final approval for publication would help prevent publication bias and improve the transparency of data reporting.\n\n\nData availability\n\nOpen Science Framework: Cross-sectional study on the reporting of allergic rhinitis trials registered in ClinicalTrials.gov and in corresponding publications.\n\nhttps://DOI: doi.org/10.17605/OSF.IO/YMHC2.\n\nThis project contains the following underlying data:\n\n- Data file 1: Paladin_Database_OSF\n\n- Data file 2: ClinicalTrials.gov database coding key\n\n- Data file 3: Extended data/Supporting Tables\n\nData associated with the article are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAuthors’ contributions\n\nAll authors meet the ICMJE authorship criteria.\n\nIvan Paladin: data acquisition and interpretation, statistical analysis, writing and revising of the manuscript, approval of the final version.\n\nShelly Melissa Pranić: design and supervision of the study, data acquisition and interpretation, critical review, revision and approval of the final version of the manuscript.",
"appendix": "References\n\nSeidman MD, Gurgel RK, Lin SY, et al.: Clinical practice guideline: Allergic rhinitis. Otolaryngol. Head Neck Surg. 2015; 152(1 Suppl): S1–43. Publisher Full Text Publisher Full Text\n\nMims JW: Epidemiology of allergic rhinitis. Int. Forum Allergy Rhinol. 2014; 4(Suppl 2): S18–S20. Publisher Full Text\n\nMeltzer EO, Bukstein DA: The economic impact of allergic rhinitis and current guidelines for treatment. Ann. Allergy Asthma Immunol. 2011; 106(2 Suppl): S12–S16. PubMed Abstract | Publisher Full Text\n\nBlaiss MS: Allergic rhinitis: Direct and indirect costs. Allergy Asthma Proc. 2010; 31(5): 375–380. Publisher Full Text\n\nClinicalTrials.gov: ClinicalTrials.gov background. Bethesda, MD:U. S. National Library of Medicine; National Institutes of Health;2018 [October 3, 2019].Reference Source\n\nViergever RF, Ghersi D: The quality of registration of clinical trials. PLoS One. 2011; 6(2): e14701. PubMed Abstract | Publisher Full Text\n\nDwan K, Gamble C, Williamson PR, et al.: Systematic review of the empirical evidence of study publication bias and outcome reporting bias - an updated review. PLoS One. 2013; 8(7): e66844. PubMed Abstract | Publisher Full Text\n\nChan AW, Hrobjartsson A, Haahr MT, et al.: Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA. 2004; 291(20): 2457–2465. PubMed Abstract | Publisher Full Text\n\nAl-Marzouki S, Roberts I, Evans S, et al.: Selective reporting in clinical trials: analysis of trial protocols accepted by The Lancet. Lancet. 2008; 372(9634): 201. PubMed Abstract | Publisher Full Text\n\nClinicalTrials.gov: ClinicalTrials.gov home. U. S. National Library of Medicine; National Institutes of Health;2021 [Accessed 2021 May 30].Reference Source\n\nFredrickson MJ, Ilfeld BM: Prospective trial registration for clinical research: what is it, what is it good for, and why do I care?. Reg. Anesth. Pain Med. 2011; 36(6): 619–624. Publisher Full Text\n\nDe Angelis CD, Drazen JM, Frizelle FA, et al.: Is this clinical trial fully registered? A statement from the International Committee of Medical Journal Editors. Ann. Intern. Med. 2005; 143(2): 146–148. Publisher Full Text\n\nDe Angelis C, Drazen JM, Frizelle FA, et al.: Clinical trial registration: a statement from the International Committee of Medical Journal Editors. CMAJ. 2004; 171(6): 606–607. PubMed Abstract | Publisher Full Text\n\nTse T, Williams RJ, Zarin DA: Reporting “basic results” in ClinicalTrials.gov. Chest. 2009; 136(1): 295–303. PubMed Abstract | Publisher Full Text\n\nU.S. Food and Drug Administration: Food and Drug Administration Amendments Act of 2007, U.S. Food and Drug Administration;2007. 21 U.S.C. Public Law 110-85. Sect. 801.Reference Source\n\nNational Institutes of Health: Clinical trials registration and results information submission, US Department of Health and Human Services, Federal Register, 2016-22129.2016; 81: p. 64981–65157.Reference Source\n\nZarin DA, Tse T, Sheehan J: The proposed rule for U.S. clinical trial registration and results submission. N. Engl. J. Med. 2015; 372(2): 174–180. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: The Trial Registration Data Set (TRDS) has been expanded Geneva. Switzerland:World Health Organization; 2017. [Accessed 2022 February 9].Reference Source\n\nPhillips AT, Desai NR, Krumholz HM, et al.: Association of the FDA Amendment Act with trial registration, publication, and outcome reporting. Trials. 2017; 18(1): 333. PubMed Abstract | Publisher Full Text\n\nTalebi R, Redberg RF, Ross JS: Consistency of trial reporting between ClinicalTrials.gov and corresponding publications: one decade after FDAAA. Trials. 2020; 21(1): 675. PubMed Abstract | Publisher Full Text\n\nU.S. National Library of Medicine: Clinical Trial Registry Numbers in MEDLINE/PubMed Records. Bethesda, MD:U.S. National Library of Medicine;2019 [October 3, 2019].Reference Source\n\nRoss JS, Mocanu M, Lampropulos JF, et al.: Time to publication among completed clinical trials. JAMA Intern. Med. 2013; 173(9): 825–828. PubMed Abstract | Publisher Full Text\n\nClinicalTrials.gov: FDAAA 801 and the Final Rule: ClinicalTrials.gov.2021 [updated January 2021; Accessed 2021 May 22].Reference Source\n\nInternational Committe of Medical Journal Editors: Recommendations for the conduct, reporting, editing, and publication of scholarly work in medical journals.[updated 2021; Accessed 2021 May 22].Reference Source\n\nPranic S, Marusic A: Changes to registration elements and results in a cohort of Clinicaltrials.gov trials were not reflected in published articles. J. Clin. Epidemiol. 2016; 70: 26–37. PubMed Abstract | Publisher Full Text\n\nSTROBE Statement: Strengthening the reporting of observational studies in epidemiology. STROBE checklists: University of Bern, Institute of Social and Preventive Medicine. Clinical Epidemiology & Biostatistics. 2014. [Accessed 2021 May 22].Reference Source\n\nMoher D, Hopewell S, Schulz KF, et al.: CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ. 2010; 340: c869. PubMed Abstract | Publisher Full Text\n\nPenic A, Begic D, Balajic K, et al.: Definitions of blinding in randomised controlled trials of interventions published in high-impact anaesthesiology journals: a methodological study and survey of authors. BMJ Open. 2020; 10(4): e035168. PubMed Abstract | Publisher Full Text\n\nHuic M, Marusic M, Marusic A: Completeness and changes in registered data and reporting bias of randomized controlled trials in ICMJE journals after trial registration policy. PLoS One. 2011; 6(9): e25258. PubMed Abstract | Publisher Full Text\n\nGresham G, Meinert JL, Gresham AG, et al.: Assessment of Trends in the Design, Accrual, and Completion of Trials Registered in ClinicalTrials.gov by Sponsor Type, 2000-2019. JAMA Netw. Open. 2020; 3(8): e2014682. PubMed Abstract | Publisher Full Text\n\nTurer AT, Mahaffey KW, Compton KL, et al.: Publication or presentation of results from multicenter clinical trials: evidence from an academic medical center. Am. Heart J. 2007; 153(4): 674–680. Publisher Full Text\n\nJones CW, Handler L, Crowell KE, et al.: Non-publication of large randomized clinical trials: cross sectional analysis. BMJ. 2013; 347: f6104. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: Primary registries in the WHO registry network. Geneva, Switzerland:World Health Organization;2021 [Accessed 2021 May 3, 2021].Reference Source\n\n\nFootnotes\n\n1 NCT02696850, NCT01861522, NCT01783548, NCT01700192, NCT01697956, NCT01644617, NCT01586091, NCT01424397, NCT01380327, NCT01307319, NCT01270256, NCT01185080, NCT01134705, NCT01010971, NCT01007253, NCT01003301."
}
|
[
{
"id": "141557",
"date": "25 Jul 2022",
"name": "Andrew Jull",
"expertise": [
"Reviewer Expertise Venous leg ulcers",
"trial 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 opportunity to review this paper. I have three relatively simple comments.\n1. It is insufficiently descriptive to denote a trial as double, triple or quadruple blinded as per table 1. It would be useful if the authors could distinguish who was considered blinded in category of blinding.\n2. There appeared to be a considerable percentage of trials that changed the sample size and primary outcome (both about 9 out of every 10 trials) after first trial registration along with a smaller percentage that changed sample size or primary outcome at publication. These findings could bear some commentary in the discussion as good practice for determining sample size is a priori calculation based on the primary outcome. Changes to one or both especially between last registration entry and publication are inconsistent with good practice.\n3. While the discussion section addresses some issues arising from the findings, it does not make comparisons with other studies of similar investigations and thus it is hard to put trials of AR in context with trials in other fields.\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/11-644
|
https://f1000research.com/articles/11-199/v1
|
16 Feb 22
|
{
"type": "Case Report",
"title": "Case Report: Hydranencephaly in a female newborn with congenital cytomegalovirus infection",
"authors": [
"Lilia Dewiyanti",
"Andrew Robert Diyo",
"Jonathan Edbert Afandy",
"Jennefer .",
"Cipta Pramana",
"Lilia Dewiyanti",
"Andrew Robert Diyo",
"Jonathan Edbert Afandy",
"Jennefer ."
],
"abstract": "Background: Hydranencephaly is a congenital abnormality of the central nervous system characterized by massive hemispheric necrosis and ventricular dilatation with most of the cerebral hemispheres being replaced by membranous sacs filled with cerebrospinal fluid (CSF). Cytomegalovirus (CMV) infection can be one of the causes of hydranencephaly. The choice of therapy for hydranencephaly is a challenge because of poor prognosis, but now neural stem cell (NSC) transplantation may give new hope. Case report: We report a case of a female newborn born at term by cesarean section from a gravida 5, para 3, abortus 1 (G5P3A1) mother with suspected hydrocephalus. Head circumference was 35 cm at birth. The baby was born crying immediately, looked active, and did not appear cyanotic, but on the second day, the baby looked less active, moaned, showed acral cyanosis, and had a large fontanelle that was dilated and soft. Signs of hydrocephalus such as Macewen’s sign, setting sun phenomenon, and transillumination were found to be positive. Echocardiographic examination showed floppy interatrial septum and mild mitral regurgitation. Non-contrast computerized tomography (CT) scan of the head showed hydranencephaly. The toxoplasmosis, rubella, CMV, and herpes simplex virus (TORCH) screening showed positive anti-CMV immunoglobulin G (IgG). The baby underwent a ventriculoperitoneal (VP) shunt procedure with a head circumference of 36 cm before surgery. VP shunt was performed with an opening pressure of 15 cmH2O. Conclusions: After the VP shunt procedure, the baby's general condition improved with the head circumference within normal limits. The baby was discharged from the hospital after 16 days of treatment.",
"keywords": [
"Hydranencephaly",
"Cytomegalovirus infection",
"Ventriculoperitoneal shunt"
],
"content": "Introduction\n\nHydranencephaly is an uncommon congenital abnormality of the central nervous system. It is characterized by massive hemispheric necrosis and ventricular dilatation with most of the cerebral hemispheres being replaced by membranous sacs filled with cerebrospinal fluid (CSF).1,2 This abnormality is very rare and unique with an incidence rate of less than one per 10,000 births in the world.1\n\nAlthough there are many studies on hydranencephaly, some aspects of hydranencephaly are still being debated in terms of pathogenesis, onset, clinical manifestations, and prognosis.2 Intrauterine lesions to the bilateral supra-clinoid internal carotid arteries are thought to be the underlying pathophysiology of hydranencephaly, which leads to resorption of brain tissue usually supplied by the anterior circulation. Intrauterine infections and toxin exposure have been suggested as possible causes of these vascular damages.3 Congenital cytomegalovirus (CMV) infection can be one of the causes of hydranencephaly, but it is very rare.4 In a retrospective cohort study, macrocephaly (92%) was the most common clinical manifestation of hydranencephaly, followed by seizures or myoclonic movements (41%), and signs of increased intracranial pressure (ICP) (25%).3\n\nThe choice of therapy for hydranencephaly including CSF diversion surgery is a challenge in itself because the prognosis is quite poor.3,5 Neural stem cell (NSC) transplantation therapy may be a new hope as an option for hydranencephaly therapy.6,7\n\nWe report a case of a female newborn with hydranencephaly and congenital cytomegalovirus infection and underwent a ventriculoperitoneal (VP) shunt procedure.\n\n\nCase report\n\nA female Javanese newborn was born from a 35-year-old mother, gravida 5, para 3, abortus 1 (G5P3A1), at the gestational age of 38 weeks. The baby was born by cesarean section on indication of suspected hydrocephalus with a birth weight of 3000 grams, body length 49 cm, head circumference 35 cm and chest circumference 32 cm, and an Appearance, Pulse, Grimace response, Activity, Respiration (APGAR) score of 8-9-10 at 1.5 and 10 minutes. The baby was born crying immediately, looked active, and did not appear cyanotic. The infant's primitive reflexes were intact at birth. The baby care after birth was performed in the perinatology room.\n\nThe mother did not partake in any antenatal care during pregnancy. She admitted that she did not have any complaints or flu-like syndrome during pregnancy. A family history of congenital abnormalities was denied. From her previous obstetric history, the mother had experienced abortion once during her second pregnancy with unknown causes.\n\nOn the second day, the baby looked less active, moaned, showed acral cyanosis, and had a large fontanelle that was dilated and soft. Signs of hydrocephalus such as Macewen’s sign, setting sun phenomenon, and transillumination were found to be positive. From the babygram examination, neonatal pneumonia was suspected, while the echocardiographic examination indicated a floppy interatrial septum and mild mitral regurgitation (Figure 1). The non-contrast computerized tomography (CT) scan of the head showed a hypodense lesion according to the density of CSF filling the right and left hemicrania, while the hemi-cerebral cortex and lateral and third ventricles were not visible. Structures of the right thalamus, mesencephalon, pons and posterior fossa, and falx cerebri were still visible. The non-contrast CT scan of the head indicated hydranencephaly (Figure 2). From the toxoplasmosis, rubella, CMV, and herpes simplex virus (TORCH) screening examination, the results of anti-CMV immunoglobulin G (IgG) were 22 aU/ml (positive if the value ≥6) and anti-CMV IgM were 0.156 COI (negative if the value ≤0.7).\n\nThe structures of the right thalamus, mesencephalon, pons and posterior fossa, and the falx cerebri are still visible. CT, computerized tomography.\n\nOn the 6th day, the baby had bradypnea and then apnea. The baby was then intubated with no. 3.5 endotracheal tube (ETT), 9 cm deep, and attached to mechanical ventilation with pressure control mode, inspiratory pressure (Pinsp) 13 cmH2O, positive end-expiratory pressure (PEEP) 8 cmH2O, respiratory rate (RR) 40, fraction of inspired oxygen (FiO2) 80%, and inspiratory expiratory ratio (I/E) 1:2. The baby care was moved to the neonatal intensive care unit (NICU) room. The baby seemed to have jitteriness.\n\nAfter discussions with the patient's family, we decided to perform a VP shunt procedure. Head circumference before surgery was 36 cm (large for gestational age based on the Lubchenco curve). The VP shunt was performed with an opening pressure of 15 cmH2O. CSF was taken for macroscopic, chemical (protein, glucose, albumin), and microscopic (erythrocyte, leukocyte, foreign cell) analysis and the results were within normal limits.\n\nAfter the VP shunt procedure was performed, the baby's general condition improved. The baby's head circumference was within normal limits according to the Lubchenco curve with an average of 33 cm. Oxygen weaning was done gradually until the baby could breathe in room air on the 15th day of treatment. On day 16, the baby was discharged from the hospital with 3000 grams of body weight.\n\n\nDiscussion\n\nHydranencephaly is a condition in which there is no cerebral tissue because most of the brain's lining is damaged, fluid, and reabsorbed. The cerebral hemispheres are largely replaced by the thin-walled leptomeningeal sacs filled with CSF, preserving the structures of the midbrain and cerebellum. In hydranencephaly, there is a partial or complete falx cerebri structure with brainstem atrophy and the cerebellum is almost always normal, distinguishing it from holoprosencephaly.8,9 According to the patient in this case, brain structures other than the cerebral cortex were still visible.\n\nIn the absence of most of the cerebral cortex, the fetal head should be small. However, in some cases, the head is more often normal or enlarged because the choroid plexus in the lateral ventricles continues to produce CSF that cannot be adequately absorbed, causing an increase in pressure that can expand and impair the integrity of the ventricles and other intracranial structures.10\n\nSeveral studies have stated that the onset of hydranencephaly is still debated and has not been proven. Most refer to the second trimester of pregnancy at 13 to 26 weeks after the hemispheres, ventricles, and falx cerebri are formed, followed by ischemic damage occurring in the third trimester, which usually causes multicystic encephalomalacia.2,8,11,12 However, there are also some case reports of hydranencephaly diagnosed before the 12th week of gestation, so hydranencephaly may occur in the first trimester of pregnancy.2,13–15\n\nThe cause of hydranencephaly remains unclear. Several hypotheses suggest vascular occlusion and infection be the causes of hydranencephaly.8 Occlusion of the supra-clinoid segment of the bilateral internal carotid artery is the most common cause, but this has not been confirmed because in some autopsies of hydranencephaly cases, the internal carotid arteries are not always occluded.5,8 Other causes include extensive tissue necrosis with cavitation, resorption of necrotizing tissue, and necrotic vasculitis caused by maternal exposure to carbon monoxide or butane gas. Intrauterine infections, such as congenital toxoplasmosis, CMV, and herpes simplex, can also cause local brain tissue damage.16 Hydranencephaly is not a malformation, but rather a secondary disorder of some pathological event, which causes ischemia in the uterus in the carotid artery area.5\n\nThe screening result of the patient in our case found evidence of congenital CMV infection. CMV target cells are immature cells of the germinal matrix that result in extensive periventricular inflammation, tissue necrosis, and dystrophic calcifications. In early pregnancy, neuronal migration anomalies can occur and subsequent infection can cause encephalopathic disorders, such as subependymal paraventricular cysts, hydranencephaly, and microencephaly.17\n\nAfter CMV infects the fetus, several types of fetal cells allow CMV to replicate, including endothelial, epithelial, smooth muscle, and mesenchymal cells, as well as hepatocytes, monocytes or macrophages, and granulocytes. In further studies, CMV infection was also identified in several organs, such as the adrenal glands, bone marrow, diencephalon, small intestine, spleen, and heart.18 From the case presented in the current report, the patient also had cardiac abnormalities, which may have been caused by congenital CMV infection.\n\nCMV-immunoglobulin M (IgM) antibodies are used as an indicator of acute infection, whereas IgG antibodies begin to appear after the onset of infection for several months. However, in cases of congenital infection, detection of CMV-IgG antibodies is complicated by the transplacental transfer of maternal antibodies.19 The results of the CMV antibody examination of the patient in this case report showed positive anti-CMV IgG with negative anti-CMV IgM, which supports the possibility that this infection was not an acute episode and was associated with the process of hydranencephaly. According to research from Chen et al., acquired anti-CMV IgG in infants disappears before the age of 8 months.20\n\nAntiviral treatment should be given to infants with virologically confirmed congenital CMV infection. Intravenous ganciclovir and its orally available prodrug, valganciclovir, is the antiviral agent recommended for the treatment of congenital CMV disease.21 The patient in this case was not given antiviral treatment for CMV because the infection was not an acute episode.\n\nMost babies with hydranencephaly die before birth. Infants that survive usually do not show visible neurological or clinical signs at first; primitive reflexes such as the sucking and swallowing reflexes, movements of the legs and arms are frequently present at birth. More specific symptoms, such as moaning, difficulty eating, hypotonia, or a dilated fontanelle, may also be present. After a few days, symptoms such as severe hypotonia, irritability, and seizures become more noticeable.5 The patient's initial signs found in this case report were that the baby looked normal at birth, but on the second day the large fontanelle dilated, movement became less active and on the 6th day, the patient appeared to have jitteriness.\n\nHydranencephaly has a poor prognosis because of the loss of most brainstem functions. Patients generally die before birth or within the first year of life.1 Treatment of hydranencephaly is only supportive and symptomatic, and the choice of therapy should be discussed with the family in detail. The failure of surgery to improve cognitive function must be balanced with stabilization of increased ICP and head size. The VP shunt procedure is an option but may require some repairs because there may be leakage from the hole site and absorption problems in the peritoneum.22 In this patient a VP shunt procedure was performed with consideration for stabilization of increased ICP and head size.\n\nThe risk of complications of a VP shunt in infants with extreme macrocephaly is increased because of thinning and fragility of the scalp, malnutrition, and infected scalp ulcers. In infants with this condition, the choroid plexus coagulation procedure may be an option with a success rate of about 40%, but it is still rarely performed in developing countries.23\n\nNSC transplant therapy that has been successful in animal models is a new hope.7 Success is also seen in cerebral palsy patients with an effectiveness of about 50%.24,25 Hypothetically, cell junction pathology is the final common pathway of various genetic and environmental factors that cause disturbances in the ventricular zone (VZ). VZ disorders in the cerebral aqueduct cause hydrocephalus, while VZ disorders in the telencephalon cause abnormal neurogenesis.6 NSCs are known to have self-sustaining and pluripotent properties.7\n\nProliferation and migration of neurons occur between the 12th and 30th weeks of gestation in humans, whereas in fetuses with hydrocephalus, VZ disturbances begin around the 16th week of gestation and continue throughout the second and third trimesters of gestation.6 NSC transplant surgery is generally performed ex-utero after the child is born, but ideally, NSC transplantation is performed at an early stage of fetal development during the process of forming neurons in the cortex during VZ disruption. In-utero fetal surgery is a recent advancement that allows the operation to be safer by considering the safety of the mother and fetus, as well as avoiding premature delivery.7 Unfortunately, there are no facilities available at this time to accommodate the implementation of NSC transplantation at our location.\n\n\nConclusions\n\nWe report a case of hydranencephaly in a newborn with congenital CMV infection who underwent a VP shunt procedure. Hydranencephaly in our patient was a congenital central nervous system abnormality that may have been caused by intrauterine CMV infection. Despite having a poor prognosis, the patient improved after undergoing a VP shunt procedure. The success of NSC transplantation therapy in animal models and cerebral palsy patients may be a new hope for the treatment of hydranencephaly. Unfortunately, there are no facilities available at this time to accommodate the implementation of NSC transplantation at our location.\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 parent of the patient.",
"appendix": "References\n\nWijerathne BT, Rathnayake GK, Ranaraja SK: A rare variation of hydranencephaly: case report. F1000Res. 2014; 1: 22. PubMed Abstract | Publisher Full Text\n\nCecchetto G, Milanese L, Giordano R, et al.: Looking at the Missing Brain: Hydranencephaly Case Series and Literature Review. Pediatr. Neurol. 2013; 48(2): 152–158. PubMed Abstract | Publisher Full Text\n\nOmar AT, Manalo MKA, Zuniega RRA, et al.: Hydranencephaly: Clinical Features and Survivorship in a Retrospective Cohort. World Neurosurg. 2020; 144: e589–e596. PubMed Abstract | Publisher Full Text\n\nde Juan GA , Alemany Albert M, Marco Hernández AV, et al.: Neurological sequelae in patients with congenital cytomegalovirus. An Pediatría Engl Ed. 2020; 93(2): 111–117. Publisher Full Text\n\nPavone P, Praticò AD, Vitaliti G, et al.: Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital. J. Pediatr. 2014; 40(1): 79. PubMed Abstract | Publisher Full Text\n\nRodríguez EM, Guerra MM: Neural Stem Cells and Fetal-Onset Hydrocephalus. Pediatr. Neurosurg. 2017; 52(6): 446–461. PubMed Abstract | Publisher Full Text\n\nGuerra M: Neural stem cells: are they the hope of a better life for patients with fetal-onset hydrocephalus?. Fluids Barriers CNS. 2014; 11(1): 7. PubMed Abstract | Publisher Full Text\n\nTaori KB, Sargar KM, Disawal A, et al.: Hydranencephaly associated with cerebellar involvement and bilateral microphthalmia and colobomas. Pediatr. Radiol. 2011; 41(2): 270–273. PubMed Abstract | Publisher Full Text\n\nChinsky JM: Hydranencephaly: Transillumination may not illuminate diagnosis. NeoReviews. 2012; 13(4): e233–e240. Publisher Full Text\n\nPinar H: Hydranencephaly. Pathol Case Rev. 2011; 16(5): 186–188. Publisher Full Text\n\nVaneckova M, Seidl Z, Goldova B, et al.: Post-mortem magnetic resonance imaging and its irreplaceable role in determining CNS malformation (hydranencephaly) – Case report. Brain Dev. 2010; 32(5): 417–420. PubMed Abstract | Publisher Full Text\n\nHahn JS, Lewis AJ, Barnes P: Hydranencephaly Owing to Twin—Twin Transfusion: Serial Fetal Ultrasonography and Magnetic Resonance Imaging Findings. J. Child Neurol. 2003; 18(5): 367–370. PubMed Abstract | Publisher Full Text\n\nLam YH, Tang MHY: Serial sonographic features of a fetus with hydranencephaly from 11 weeks to term: Sonographic features of hydranencephaly. Ultrasound Obstet. Gynecol. 2000; 16(1): 77–79. PubMed Abstract | Publisher Full Text\n\nLaurichesse-Delmas H, Beaufrère AM, Martin A, et al.: First-trimester features of Fowler syndrome (hydrocephaly-hydranencephaly proliferative vasculopathy): Fowler syndrome. Ultrasound Obstet. Gynecol. 2002; 20(6): 612–615. PubMed Abstract | Publisher Full Text\n\nLin Y-S, Chang F-M, Liu C-H: Antenatal detection of hydranencephaly at 12 weeks, menstrual age. J. Clin. Ultrasound. 1992; 20(1): 62–64. PubMed Abstract | Publisher Full Text\n\nKhalid S, Zaheer S, Redhu N, et al.: Hydranencephaly: A rare cause of an enlarging head size in an infant. North. Am. J. Med. Sci. 2012; 4(10): 520. Publisher Full Text\n\nSener RN: Congenital cytomegalovirus infection and hydranencephaly. Radiography. 1996; 2(3): 229–232. Publisher Full Text\n\nJones CA: Congenital cytomegalovirus infection. Curr. Probl. Pediatr. Adolesc. Health Care. 2003; 33(3): 70–93. Publisher Full Text\n\nRoss SA, Novak Z, Pati S, et al.: Diagnosis of Cytomegalovirus Infections. Infect. Disord. Drug Targets. 2011; 11(5): 466–474. PubMed Abstract | Publisher Full Text\n\nChen J, Hu L, Wu M, et al.: Kinetics of IgG antibody to cytomegalovirus (CMV) after birth and seroprevalence of anti-CMV IgG in Chinese children. Virol. J. 2012; 9(1): 304. PubMed Abstract | Publisher Full Text\n\nHarrison GJ: Current controversies in diagnosis, management, and prevention of congenital cytomegalovirus: Updates for the pediatric practitioner. Pediatr. Ann. 2015; 44(5): e115–e125. PubMed Abstract | Publisher Full Text\n\nSedain G, Rajbhandari B: Hydranencephaly: Insights into Pathophysiology and Management. Nepal J. Neurosci. 2020; 17(1): 5–9. Publisher Full Text\n\nShitsama S, Wittayanakorn N, Okechi H, et al.: Choroid plexus coagulation in infants with extreme hydrocephalus or hydranencephaly: Clinical article. J. Neurosurg. Pediatr. 2014; 14(1): 55–57. Publisher Full Text\n\nChen G, Wang Y, Xu Z, et al.: Neural stem cell-like cells derived from autologous bone mesenchymal stem cells for the treatment of patients with cerebral palsy. J. Transl. Med. 2013; 11(1): 21. PubMed Abstract | Publisher Full Text\n\nHe S, Luan Z, Qu S, et al.: Ultrasound guided neural stem cell transplantation through the lateral ventricle for treatment of cerebral palsy in children. Neural Regen. Res. 2012; 7(32): 2529–2535. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "124076",
"date": "20 May 2022",
"name": "Nobuyuki Akutsu",
"expertise": [
"Reviewer Expertise Pediatric neurosurgery"
],
"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\nHydranencephaly is an uncommon congenital abnormality of the central nervous system. This article reported a rare case of a female newborn with hydranencephaly and congenital cytomegalovirus infection, who underwent a ventriculoperitoneal (VP) shunt procedure successfully. This article was very interesting, but I think it needs some modifications and answers to the questions:\nDid the patient need medical care at the time of discharge?\n\nIt is true that the prognosis of hydranencephaly is poor, but recently there have been many reports of prolonged survival. I would like you to mention that point, see the following article of mine: Akutsu et al., 2020.\n\nThe author described that choroid plexus coagulation (CPC) is still rarely performed in developing countries. However, isn't it difficult in developing countries to manage VP shunts? There are reports recommending CPC over VP shunts for the treatment of hydrocephalus in developing countries. (Warf, 2005).\nTaking all these things into account, this paper will require minor revisions before indexing.\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": "8313",
"date": "17 Jun 2022",
"name": "Cipta Pramana",
"role": "Author Response",
"response": "Dear reviewer, Thank you for taking the time to review our manuscript entitled \"Case Report: Hydranencephaly in a female newborn with congenital cytomegalovirus infection\". We appreciate the time and effort dedicated by reviewers to provide feedback on our manuscript and are grateful for insightful comments and valuable improvements to our paper. We have included most of the suggestions made by reviewers in our revised version. Please see below, for point-by-point responses to reviewer comments. \"Did the patient need medical care at the time of discharge?\" Authors response: Yes. The patient fully recovered and was later discharged from the hospital weighing 3000 grams and scheduled for a follow-up examination and routine physical rehabilitation. \"It is true that the prognosis of hydranencephaly is poor, but recently there have been many reports of prolonged survival. I would like you to mention that point, see the following article of mine: Akutsu et al., 2020.\" Author response: Yes. Hydranencephaly generally has a poor prognosis, however, there are several reports showing hydranencephaly patients able to survive for more than 5 years. The patient survival depends on the integrity of their brainstem function which controls cardiorespiratory function as well as temperature regulation. \"The author described that choroid plexus coagulation (CPC) is still rarely performed in developing countries. However, isn't it difficult in developing countries to manage VP shunts? There are reports recommending CPC over VP shunts for the treatment of hydrocephalus in developing countries. (Warf, 2005).\" Author response: According to several studies comparing CPC and ventriculoperitoneal shunt, it is shown that CPC has a higher success rate, however, due to the lack of neuroendoscopic facilities in developing countries such as Indonesia, especially in a rural area, a ventriculoperitoneal shunt was chosen in our study and showed improvement in patient's condition. It is not difficult to manage VP shunt in developing countries because the function and complication of the procedure are able to be closely monitored. The development of infrastructure, communication technology, and transportation allowed after-implant management to be performed well."
}
]
}
] | 1
|
https://f1000research.com/articles/11-199
|
https://f1000research.com/articles/11-643/v1
|
13 Jun 22
|
{
"type": "Research Article",
"title": "The demographic effects and public health infrastructure dearth of COVID-19 in Ghana",
"authors": [
"Andrew Kweku Conduah"
],
"abstract": "Background: Over the last two years, the world has been experiencing a worldwide health catastrophe. The Corona Virus (COVID-19) struck at the heart of societies and is a major health-care infrastructure problem. Infrastructure has been characterised as the basic requirement for carrying out productive and relevant public health actions. Mortality has direct and indirect relationship, with the former causing short and long-term mortality, resulting in a short life expectancy. Reduced accessibility and quality of health care, isolation, loneliness, and poverty were some of the indirect repercussions. The outcomes were sad and deeply felt when the two collided with ageing and persons with co-morbidities. The fertility effect of COVID-19 in the short-term on contraception presented itself in increased difficulties in accessing services and disruptions in the supply chain. Migration was mainly affected due to travel bans and restriction of movements through stay-at-home instructions. Methods: This paper uses the qualitative paradigm of research that used corpus construction in the selection of material to represent a whole and this make it functionally equivalent to sampling but structurally different. It used secondary data to ascertain the demographic effects and the extent of health infrastructure deficit and ingenious ways to curb the challenges as exposed by the COVID -19. Results: The study underscores how demographic factors can be disrupted by pandemics to bring about high rates of mortality. Global health function is under-funded and under-produced, as a study by the World Health Organization suggests. Conclusions: The study brings to bear that anthropogenic activities, air greenhouse gases, lifespan and hospital beds are key drivers of COVID-19 growth. The path forward to mitigate such pandemics is international harmony and alliances in the distribution of vaccines, strengthening of international health systems ability to hold back major infectious disease, addressing service quality and providing key financial injection.",
"keywords": [
"Demographic effects",
"public health",
"infrastructure",
"public health dearth",
"corona virus and Ghana."
],
"content": "Introduction\n\nA mysterious pneumonia was discovered in Wuhan, the capital of Hubei province in China and later brought to the attention of the World Health Organisation on December 31, 2019 in China. Huang et al. (2020) submits that 41 people with confirmed infections had been admitted to hospitals in China as at January 2020. Officials in Wuhan declared a mainly quarantine measures which brought the case numbers around 80,000 in mid-February 2020 (ECDC 2020). Prior to this juncture, the World Health Organisation had called out the outbreak as a “a global public health emergency” on January 11, 2020, and a pandemic on March 11, 2020. All this while, the aviation industry had been very active due to the new year traditional/cultural festivities of various parts of the world. Thus, the global air travel had spread the virus all over the continents of the world and there were confirmed cases in 146 nations of the world in mid-March. As at 12:39 p.m. CET on March 17, 2021, there have been 120,164,106 confirmed cases of COVID-19 reported to WHO, with 2,660,422 deaths. Also, 363,691,238 vaccination doses had been delivered as of March 16, 2021. There are 88,228 confirmed cases in Ghana, including 698 deaths (Covidttracker.bsg.ox.ac.uk, March 2021). Presently, the Ghana Health Service reports that a total number of 13, 842,945 doses has been administered as at 20th April, 2022 (www.ghs.gov.gh/covid19/) out of a total population of 30,823,019 (Ghana 2121 Population and Housing Census Report). This constitutes 45% of the population that has been vaccinated.\n\nThe virus had infected 188 countries as of May 13, 2020. At the time, there were no vaccines, drugs and the virus were very adept at quickly mutating and spreading (Ferguson et al., 2020; Imai et al., 2020). Almost every country implemented nonpharmaceutical interventions (NPI), such as non- pharmaceutical interventions (NPI) such as restrictions on movements of goods and services, closure of land, sea and air boarders except for key essential cargos, closures of all educational facilities at all levels, then work places as well as a ban on all public gatherings including conferences, religious activities and festivals. These were aimed at evening out the epidemiological curvature by cancellation of outdoor events and meetings, orders to the security agencies to enforce confinement at home rules and disruptions/cancellation of domestic and international travels. All these became essential as there was no known vaccine/drugs at the time and the virus had the capacity to multiply swiftly (Ibid). Apparently, this intervention at the superficial level may not seemed “water tight” but a study by Nussbaumer-Streit et al. (2020) and Sjödin et al. (2020) asserted that any holistic intervention in such an emergencies control disease. The battle over COVID-19 was country led governed by various socio-economic and political factors pertaining to each country.\n\nThe rondure in the last four decades has seen a number of great epidemics, but none have had the same economic impact as the COVID-19 pandemic. The tourism industry has shown resilience to a variety of shocks in the past, but current evidence suggested that the impacts and attempts at recovery from the pandemic will be a herculean task. Throughout the twenty-first century, growing pandemic threats as a result of population explosion, the dawn of an urban millennium (UNFP, 2007); the global chain value of industrialized food production, excessive patronage of processed foods; biophysical drivers such as vegetation, rock and soil type, livestock, military training, and recreational facilities; and biophysical drivers such as vegetation, rock and soil type, livestock, military training, and recreational facilities (Labonte et al., 2011; Pongsiri et al., 2009). Recent emerging viruses like Ebola, Marburg, Sars, are all the upshot of anthropogenic influence.\n\nApart from different public health responses to the pandemic, a variety of climatic, social, and demographic variables reacts to make to make containments efforts difficult. These are pollution, temperature and variabilities of the weather (Copat et al., 2020; Ricc et al., 2020), the level of sustainable development in a country, income, and gross domestic product (Lippi et al., 2020; Mukherji, 2020), and population ageing (Lippi et al., 2020; Petretto & Pili, 2020). In terms of meteorological factors, COVID-19 and a delayed in 14-days temperature moved in tandem (positively correlated), but when a 14-day lagged in wind speed occurred, a negative correlation between COVID-19 cases occurred. Moreso, at absolute humidity between ranging from 5–10 g/m3 range, an increased rate of COVID-19 was detected (Islam et al., 2020). As such, pollutants notably PM2.5 and NO2, but to a lesser amount PM10 are all triggers of COVID-19 and high rates of mortality (Copat et al., 2020). Economic indicators particularly Gini’s inequality index link with COVID-19 induced death rate (Mukherji, 2020). Furthermore, COVID-19 death rates have been connected to socioeconomic and health characteristics such as old age, males, ethnic backgrounds, and comorbidities (diabetes, cancer, and other chronic-degenerative illnesses) are all linked to COVID-19 rate of fatality.\n\nThese outbreaks have underlined the motivation for governments to establish a resilient system to mitigate health emergencies which has been mostly linked to a weak health system, sluggish emergency response systems, and climate change. The goal is to broaden our infrastructure knowledge base in Ghana’s public health sector, allowing us to better evaluate previous efforts, prioritise current finance needs, and follow future progress.\n\nThe paper is part of a qualitative research paradigm in which Corpus Construction was used to select material to represent a whole, making it operationally similar to sampling but structurally different from sampling. To identify the scale of the health infrastructure gap and propose creative solutions to the concerns identified by COVID -19, it relies on secondary sources, primarily archival data, and documentary approaches, primarily document analysis. Aside from this, the demographic effects of the COVID-19 are also assessed and policy prescription are proposed.\n\n\nEspousing literature\n\nIn order to promote health care policy and welfare mechanisms inside a country, health infrastructure is an important indicator. A healthy work force is created by a well-developed health infrastructure, which typically includes specialist doctors, nurses, and paramedical personnel, as well as machinery and a well-developed pharmaceutical sector. World Health Organisation classify a health care system as “all the organisations, institutions, resources, and individuals whose primary goal is to enhance health” (2020). The availability of essential infrastructure is key for the provision of public health service (Public Health Infrastructure, 2020).\n\nCommunities to stop the occurrences of diseases, encourage healthy living and plan for and respond to both acute (emergency) and chronic (ongoing) threats to their health. Therefore, infrastructure becomes the spring board to initiate public health planning, delivery evaluation and improvement. All public health programmes- infectious disease surveillance, cancer and asthma prevention, drinking of quality water, immunization etc., rely on health professionals with cross cutting and technical skill, access to modern information equipment and the ability of such professionals to intervene in community needs. The “nerve center” of the health-care system. In the film Turnock, Turnock is a character (2001).\n\n\nSystem thinking concepts\n\nThis postulates the need to understand an entire system and the significant interplay of all the factors that make up that system in an ever-changing and complex world (Pidwiny, 2006; Checkland, 1981; Von Bertalanffy, 1976). Systems theory had a significant impact on how the world perceives and changes organisational performance (Best, 2007; Atun & Manade, 2006) One of the key instruments of the theory, which is described as a broad science of wholeness (Von Bertalanffy, 1976), is system thinking (Pidwimy, 2006). It aims to assist an individual in viewing systems from a wide perspective, including their structures, patterns, and cycles, rather than focusing on isolated events (Pidwiny, 2006; Atun & Manade, 2006).\n\nEngineering, economics, and ecology are just a few of the domains where systems thinking has been used (Paina & Peters, 2012; Pidwimy, 2006). They have a non-linear relationship with a degree of unpredictability, are generally difficult to change, and solutions can sometimes exacerbate the situation (Best 2007; and Checkland 1981). In recent projects, system thinking has been applied to address some risk factors and health challenges in order to determine its functionality as a system. In the works of Paina and Peters (2012), Diane, Finegood and Carrie (2008) and Best (2007), programmes such as tuberculosis and obesity research and tobacco control are some classic examples. Nevertheless, it application in health infrastructure to a large extent is either immaculate or limited (WHO, 2009). In addition to these are tobacco control, obesity research, and tuberculosis research, to name a handful (Paina and Peters, 2012; Diane, Finegood and Carrie 2008; Best 2007). Its use to health infrastructure on a larger scale is either immaculate or limited (WHO, 2009).\n\nSystem thinking is able to help identify and resolve health system difficulties as reported by WHO in 2009. The report further endorses it to be a fundamental component that enhances health system or infrastructure. Thus, it should be applied to critical paths in service delivery, financing, governance, information dissemination, workforce in the health sector, medical products and technologies (Paina & Peters 2012; Agyapong, Kodua, Adjei & Adam 2012). This critical paths by these authors ought to be adopted by Ghana Health Service (GHS) to better place it in the event of future pandemics.\n\n\nTheory of health and development\n\nIn 1975, Preston asserted that long-life is a panacea to increased human productivity and has the potential to spur a country (Ghana) into higher Gross Domestic Product (GDP). Going further, he postulated that those born in higher income countries tend to have a longer life span when juxtaposed with their counter parts from poorer regions of the world. The relationship is viewed as causal and levels of income. Otherwise stated, a causal relationship as far as the returns on income is concern will diminish life expectancy. Therefore, the Preston curve shifts upwards as health- care technology improves.\n\nTo influence development, Preston adds that a healthier work force means physically and technically, they are more likely to be resilient, active and equip with long life span. To put it in another way, the health of the population is critical for national economic success. In Ghana as a sub-Sahara African (SSA) country, poor health caused by a high disease burden has a detrimental impact on productivity, education, demography, and finally economic development. For example, economic growth loss according to projections in Africa due to high malaria prevalence is roughly 1% each year. A country’s population’s poor health can stymie its economic well-being, growth, and development by reducing longevity and increasing disability adjusted life years (DALYS). As a result, a healthy population is key for poverty reduction, economic development, and overall societal expansion (CMH, 2001). As a result, it is critical that every country’s health system and infrastructure receive adequate funding.\n\n\nAdopting\n\nAs COVID-19 persist, it was obvious that global workforce is compelled to work remotely, but at first, it was unclear whether the workforce could complete most jobs remotely without a major reduction in productivity or quality. With what is now the new normal, such as a hybrid workforce and scattered workplace, has been re-calibrated. Thus, the workplace is now split between home, office, and satellite offices. These teams must be virtual-ready, and managers must be able to coach and find innovative means to inspire employees entrusted to them to work from a distance.\n\nWith the support of video communications, healthcare, those in educational and financial institution, as well as large, medium and small enterprises all endured while some prospered from the pandemic. This was as a result of utilising video to interact with clients. A hybrid work paradigm emerged with the use of communication technology, working from home while some have maintained the remote working paradigm even after post COVID-19. In a business report of British Broadcasting Company (BBC) on May 2, 2022, a London Law Firm Stephenson Harwood is prepared to allow staff work from home permanently, but the convenience come at a price of 20% less the current salary (www.bbc.com/news/business-61298394).\n\nLooking back at the onset of the COVID-19, 37.5% of business began or raised usage of mobile money while a tenth of business (9.0%) commenced or surged their use of the internet for business activities (Brem, Viardot & Nylund, 2021; Naeem, 2020).\n\n\nCOVID-19 effects on mortality and health\n\nCOVID-19 had a direct impact on the population, as measured by case counts or the number of people infected. The infected person’s age and co-morbidities were important factors in survival or long-term disability and fatality, including mental health. The indirect consequences were apparent in health-care accessibility and quality interventions, as well as health-care and old people’s rights and long-term care services.\n\nImpact on older people’s health, rights, and long-term care services: COVID-19 confirmed cases puts the median age at 51 (according to the COVID Intel database as of October 2020). This means death cases of people aged over the age of 80 are five times higher than the global average. In Europe, over 95% deaths related to COVID-19 are those over age 60. Adults aged 60 and up account for nearly 95 percent of COVID-19 induced mortality in Europe while adults aged 65 and up accounted for 80% of deaths in the United States. In China, persons aged 60 and more accounted for nearly 80% of all deaths. For older people, this reality offered a number of direct and indirect obstacles.\n\nAccess to health care: This was a threatening disease and older people particularly struggled to get medical attention. The other side is that a large chunk of people in poorer regions of the globe lack access to basic health (Lu, Kong & Shelley, 2021), due to underdeveloped health systems. Lockdowns and a focus on COVID-19 appear to have disenfranchised older people and created impediments to their receiving health care for their underlying problems, make them even more vulnerable to COVID-19 (Ibid). Access to medical care for older people with impairments and chronic conditions at the time became more difficult, and some were marginalised. Workforce shortages have hampered the delivery of care and have a direct impact on the elderly, further isolating them. Access to health-care for older people with disabilities and chronic diseases may become more difficult, and they may become more marginalised (Campbell, 2020; Aikins et al., 2021; Dovie, 2021; Boateng et al., 2022).\n\nIn the midst of the pandemic, over burdened hospitals were confronted with various delinmas about decisions on the use of limited resources. Advocates in human rights were concerned that in some situations, the use of ventilators were decided using age or broad assumptions of prevailing underlying Conditions such as dementia, general outcome with respect to survival of patient. This, they argued, flies in the face of triage rules which upholds medical ethics, application of scientific knowledge and the right to consent or refusal, as well as the ability to express their preferences in advance. There are allegations of elderly persons not being given the opportunity to provide consent to medical treatment and other inducement such as being made to sign forms not to be resuscitated under compulsión during this pandemic. See Figure 1.\n\nSource: Author’s Construct, 2022.\n\n\nCOVID-19 effects on fertility\n\nCOVID-19’s influence on contraception will manifest itself in increasing difficulty in getting services and supply chain interruptions in the near and long term. The long-term ramifications of this are currently impossible to predict, however they are changing. Sexual and reproductive health rights (SRHR) may have an impact on fertility and death. Family planning is the second most affected service (WHO, August 2020), and early data from Ghana during the school lockdown showed that adolescent pregnancy rose. Increased fertility or abortions, as well as linked reproductive health issues such as unwanted pregnancy, which is one of the main causes of maternal mortality and morbidity in the world, will be the overall consequence (Singh et al., 2010; Abbasi-Shavazi et al., 2004). As a result, if SRHR coverage drops by 10%, up to 15 million unplanned pregnancies and 3.3 million unsafe abortions could occur (Guttmacher, April 2020).\n\nTeenage pregnancy during the COVID-19 lockdown, according to World Vision International, might jeopardize the education of one million African girls (World Vision International, May 2020). During the lockdown in Ghana, the Krachi West district in the Volta region had a nearly nine-fold increase in teen pregnancy, according to the same research. Thus, 51 teenage pregnancies were reported between March and May 2020, compared to only six incidences of teenage pregnancy in 2018. According to data from the Kenyan government, 4,000 adolescent girls attended health institutions for prenatal treatments in Machekos County between January and May 2020. As a result, the national figure might be in the tens of thousands.\n\nOn nuptiality and COVID-19, the likely short term could be marriage postponement which may result in decrease fertility. However, over the medium to long term, mortality may remain low due to job losses and bleak world economic outlook for the future of most national economies. In this way, without a return to normalcy at the economic front, fertility may decline, while long period outside school also increase fertility representing an oxymoron for demographers.\n\nIn the case of nuptiality and COVID-19, the most likely short-term outcome was marriage postponement, which led to lower fertility. However, due to employment losses and a grim global economic outlook for the foreseeable future of most national economies, mortality remained low in the medium to long- term. In this way, if the economy does not return to normal and drag as we are presently experiencing, fertility may stall or even drop, while long periods outside of school boost fertility at the height of the pandemic which is an oxymoron for demographers. With schools at all level now opened, and adopting various internet platforms to compliment in-person teaching and learning, a gradual reversal of the situation may be on the horizon. See Figure 2.\n\nSource: Author’s Construct, 2022.\n\n\nCOVID-19 effects on mobility and migration\n\nThe main consequences were a decline in mobility and migration, as well as a contraction in economic and social interaction within and between countries. Passengers also decreased in the transportation industry from the on-set to the peak of the pandemic until a gradual return to semblance of normality when vaccines were rolled out. Between March and May, 2020, commuter minibuses were at 70 percent, and intercity buses were at 50 percent capacities. Monthly revenue for Metro-Mass Transport in the Country fell from GH5.5 million to GH2.1 million, according to government estimates. Since March 2020, the Intercity STC Company had lost planned income of GH5.0 million in preceding months, averaging GH3.0 million These among other factors forced most of these institutions to resort to financial institutions to honour their pay roll obligations in their bid to avoid layoffs (Mid - Year Review and Supplementary Estimate, 2020). See Figure 3.\n\nSource: Author’s Construct, 2022.\n\n\nCOVID-19 effects on demographic dividend\n\nFertility, population growth, age composition and dependency ration will impact demographic dynamics which could lead to higher fertility and mortality as well as less initial migration. As a result, in order to empower the general public, social and economic interventions in the areas of education and employment are required. This could take the form of a concentration on youth employment, educational support with a focus on the poor, such as Ghana’s free senior high school, technological training, expanded access to family planning, and gender equity policies that promote empowerment and increased work prospects. The first is that investments in family planning and health are critical because they affect Ghanaian youth’s education, employment, labor force participation, and poverty. The second point is that infrastructure expenditures, such as housing, sanitation, and drinking water, should be prioritized because safe living is a fundamental human right, especially for young people and women. Third, Ghana must prepare for an aging population, which necessitates a greater focus on healthcare, pensions, and elderly care. See Figure 4.\n\nSource: Author’s Construct, 2022.\n\n\nDiscussion\n\nCOVID-19 has wreaked havoc on society and businesses around the world in recent months, exposing flaws in medical care infrastructure. Although the epidemic continues to spread over the world, infections have peaked and fallen in some areas. With time, countries have eased social and economic restrictions with the view of achieving recovery.\n\nDemographic, ecological, and communal dynamics all play a role in infection rates of COVID-19. Studies affirmed population of urban axes, air greenhouse gasses, lifespan and clinic beds are key drivers of COVID-19 growth.\n\nIn metropolitan clusters of more than 1 million people, the COVID-19 growth rate exhibits a positive association and a considerable effect on population. This is particularly the case for large continents like Americas and Australia. The CDC COVID-19 Response Team, explained it is mostly spread through droplets from respiratory so the plausibility for densely populated areas to experience high transmission (CDC COVID Response Team, 2020). Social distancing is very challenging in densely populated areas so this may explain the high fatality rates from other people becomes more difficult with higher population densities, and contact rates (Rocklöv & Sjödin, 2020). This finding is in consonance with the works of Bhadra et al. (2021) and Kadi and Khelfaoui (2020) that indicated a moderate relationship between population density and COVID-19 dissemination (Rader et al., 2020). Other research, on the other hand, were unable to duplicate these findings, instead finding an inverse (Hamidi et al., 2020) or no connection (Carozzi et al., 2020).\n\nThere are fewer urban clusters in Ghana with a population density as at 2019 being 134 people per km2 (346 people per mi2), computed on 227,540 km2 (87,854 sq.miles) (Worldometer). This could perhaps explain why the Government could better managed the rate of infections which stands at 161,124 as at April 25, 2020 with the total fatality of 1,445 as at April 25, 2022\n\nAir pollution has a positive relationship with growth rate and has a major impact on it. The transmission of COVID-19 is aided by air pollution. Pollutants can operate as a virus carrier, spreading the infection over a distance of 2 meters (Sharma & Balyan, 2020). Particular places having a high concentration of air pollution, like India, China, Italy, Russia, Chile, and Qatar have reported increased fatality cases, when compared with areas per lower levels of pollution (Paital & Agrawal, 2020). Ghana is not an even a moderately industrialised country as industry contributes to 29.74% of our Gross National Product (GNP) (www.statista.com). This could perhaps also explain the low rate of infections compared to others in the sub region and Africa as a whole.\n\nAt the time, the growing rate of COVID-19 had a promising link and a significant effect on life expectancy. This can be explained when comparing high-income and low-income countries. Despite the fact that high-income countries have longer life expectancies, their populations are aging, with many more persons over 70 (Schellekens & Sourrouille, 2020). Elderly adults are affected by a greater septicity and fatality rate (Chen et al., 2020), but younger folks, on the other hand, have milder symptoms and may even have a quiet infection (Chen et al., 2020; Velavan & Meyer, 2020). A new meta-analysis of almost half a million COVID-19 cases from various nations (China, Italy, Spain, the United Kingdom, and New York State, USA) demonstrated the impact of age on death, finding the key age as larger than 50 years and, in particular, greater than 60 years. This is consistent with our findings, which reveal a positive relationship between life expectancy and COVID-19 increase rate, particularly in North America, Europe, China, and Australia. The propagation of the virus, on the other hand, is projected to adversely effect on lifespan, reversing the materialistic upward trend (Marois et al., 2020).\n\nAgain, Ghana and indeed the whole African continent has a youthful population. Indeed, the new census in Ghana project the youthful population to be 37.13% Which is 114,479, 29 of the total population of 30,832,019 (www.statista.com).\n\nQuantity of available hospital beds has a considerable impact on COVID-19 growth rate and is also strongly associated. On the one hand, countries with more beds for every hospital experienced a reduced amount of burden and tension, necessitating the implementation of more radical and stringent procedures. On the other side, it has been demonstrated that having additional hospital beds as well as extra health-care means easily accessible helped COVID-19 spread faster. This may also result in a drop in care quality, resulting in insufficiency means of opportunity for ventilators cases of infection usage and upward trend in the cases of infection (Li et al., 2020). In areas like Russia, Australia, North America and China, this might explain why the death tools were high as the hospital infrastructure got overwhelmed. This is consistent with a study undertaken in the United States (Karaca-Mandic et al., 2020), which found that a surge in patients who were cared for in the non-intensive care unit (ICU) bed use greatly increased COVID-19 mortality. In Ghana, efforts were made to established more centers, the country was just fortunate the numbers were somehow under controlled else a public health catastrophe would have emerged.\n\nOne key priority area for rebuilding is the need to strengthen Ghana’s health care infrastructure by the Government of Ghana. Admittedly, the COVID-19 pandemic exposed the fault lines of global health systems. Thus, for a robust and resilient recovery to be achieved, intercontinental improvements in health systems cannot be ruled out particularly when it comes to investing in global public goods.\n\n\nGlobal public goods in health\n\nPublic goods meet critical societal needs and play a critical role in ensuring its security. However, because of the “free rider” dilemma, profit-seeking private enterprises are unable to produce them. Furthermore, compared to individual consumers, public products have beneficial \"spill-over effects\" that does not translate to market value. Due to this, the market has historically underproduced public goods, the Ghanaian government must assume responsibility for supplying them domestically.\n\nOn a global scale, the international propagation of the coronavirus produced consequences by way of state reaction to the pandemic which highlight the value of universal mode of interaction of interaction between countries and coordination. This could take the shape of multiple frontier roles or involvements that aid in the advancement of health, but it has received little attention. Virus surveillance and control, infectious disease centers, research into illness causes and treatments, local vaccine production, giving out information, outbreak readiness and principles and procedures are just a few examples.\n\nIn today’s global community, health hazards and diseases can spread across national borders, with substantial health, social, and economic consequences. As proven by the present epidemic and previous health catastrophes, it is possible that national health capacities and measures are insufficient. Kaki (2004) underscored the relevance of the interplay of endogenous as well as exogenous structures. “On the endogenous level, state agencies alone are not capable of bringing about economic growth and political change. On the exogenous level, historically and currently established relations of interdependence bind national systems with supranational systems. Interdependence … . significantly shapes the course of a nation’s development experience” (Kaki, 2004:29). Therefore, global health interventions address crucial needs that cut across countries and brings about societal benefits to all. At the height of the Ebola outbreak in West Africa in 2014-2016, the problem of underinvestment in global well-being of health was highlighted. Generally, there was a state of being without test kits, treatment, or vaccines, as well as inadequate surveillance and preparedness procedures (Yamey and others, 2019). The situation at the time revealed the woefully unprepared nature of all countries to effectively handle competently epidemics and pandemics, as well as other significant public emergency health issues which will inevitably arise as a result of climate change in the future.\n\nThe international reaction to COVID-19 was besiege with years of under- funding in the global public health system. According to research (Schäfer and others, 2019), 25% of the fund’s donors gave go into the areas of health of the population in the worldwide context. In 2017, there was $24 billion in donor financing for health out of which $7 billion (about 25%) went into areas of health of the population. Some authors point out a further need of $9.5 billion per year extra funding (Yamey and others, 2019). When compared to the scale of the COVID-19, such estimations are small when compared to the effects of challenging global health emergencies. Preceding to the COVID-19, a study projected annual losses from pandemic risk at $500 billion, or 0.6 percent of global revenue (Fan, Jamison and Summers, 2018). The IMF predicted a worldwide GDP fall of 4.9 percent in 2020, whereas UN (2020) estimations suggested output losses of $8.5 trillion in 2020 and 2021, wiping out the previous four years’ gains and resulting in 2,660,422 fatalities as of March 17, 2021.\n\nCOVID-19, as well as previous epidemics, clearly demonstrate the necessity for global public health goods. To limit outbreaks across borders, this should include comprehensive surveillance and preparedness mechanisms. Furthermore, inter-country cooperation and resource mobilization will be facilitated through the African Center for Disease Control, the European Center for Disease Control, and the United States Center for Disease Control will make inter-country cooperation and resource mobilisation easier. When epidemics strike, this will drastically minimise the time it takes for international response measures to be implemented. As particular countries are not generating them alone, global knowledge sharing and research resources will bridge treatment disparities, and economies of scale will lower costs. These public goods will serve to augment national public health systems in combating infections and meliorating the general physical, social and mental well- being of people and so contributing to the achievement of SDG 3 on health.\n\n\nThe path forward is based on international harmony and multi-alliances\n\nOn February 17, 2021, the World Health Organization (WHO) held an African Health Ministers Conference to mark the transition from planned to action in the introduction of COVID-19 vaccinations. This was in anticipation of a rapid vaccination release for emergency usage of two versions of the AstraZeneca-Oxford COVID-19 vaccine. An independent regional review committee approved vaccinations from 190 participating economies, of which 35 are from African. The framework applied in accessing the vaccines was developed by WHO with GAVI as a Co- Leader to COVAX. Others were the Vaccine Alliance, and the Coalition for Epidemic Preparedness Innovations who provided fair access to COVID-19 vaccines.\n\nThough an excellent long-term global public goods effort and after the Ebola epidemic, foreign donor money for global health functions soared but was not sustained (Schäfer and others, 2019). This trap should be avoided, and long-term financing arrangements must be established. As the Decade of Action for achieving the SDGs for everyone gains traction, more investment is needed in this direction.\n\nBy its mandate, the WHO should act as a springboard for countries to collaborate, coordinate, and manage the world’s health system’s future in order to foster direction and stewardship that will result in information exchange, which is crucial to defeating COVID-19. To have an integral global community, more state actors and intergovernmental organizations, the scientific community, the corporate sector, and civil society, should all be marshalled in research and production. For this reason, most of us may be unaware of the availability of global public goods in health. The impact of its non-availability is felt particularly during crisis periods. COVID-19 can be defeated by a united world, restoring normalcy and preparing the world to be more resistant to viruses and epidemics.\n\n\nClosing the infrastructure dearth in public health in Ghana\n\nWeak health system capacity, ambulance services, as well as clinical and public health critical care facility, quality issues in service delivery, financing health sector, health workforce management, low number of health centers/inadequate number of infectious disease centers, blood safety at blood banks, health-care concentration in cities and non-availability are all areas of health infrastructure that need to be improved.\n\n\nInternational health systems’ ability to hold back the pandemic\n\nThe nature of the fragile health units that previously held back major infectious diseases like cholera and Ebola showed that Africa, and indeed Ghana are vulnerable. Accessibility to hospitals is also a problem. Table 1 displays available hospital beds in 1000 population in seven African nations with the most COVID19 cases as of May 29, 2020. An overview of the bed-to-population ratio can be found elsewhere.\n\nNotwithstanding this, the United States had 34 intensive care units (ICUs) per 100,000 inhabitants yet it suffered. Since there were no particular treatments for COVID19 then, the current standard of care was supportive care. If a patient suffered respiratory distress, this involves antipyretics, hydration, and ventilator assistance.\n\nMost African countries that were severely afflicted by the virus had already faced a shortage of ventilators. One of the main causes of the ventilator shortage was problems with the worldwide supply chain. Exports of medical equipment, particularly ventilators, were halted because all manufacturing countries were battling the COVID-19 intensively and were not prepared for exports of ventilators. This peaked in March, 2020 where 54 countries had ceased the exploration of ventilators. Simply put, given the rising infection rate at the time, health-care systems in African nations lacked the ability to contain a pandemic. See Table 1.\n\n\nAmbulance service, as well as clinical and public health emergency services\n\nIn Ghana, medical emergency care is in short supply. In 2015, there were 214 operational ambulances, with 300 expected by 2017. The service’s expected response time is 50 minutes, however, this may differ depending on the area. In 2015, around 5000 patients/casualties were treated. Pandemics and large epidemics such as avian and pandemic influenzas, cholera, and Ebola have all been seen around the world over the years.\n\nGlobalisation, deplorable hygiene and veterinary practices, outmoded surveillance technology for early detection, confirmation, and reaction, and an already overstretched health systems coping with other widespread diseases are all contributing to its gravity and diffusion in poorer nations. The Ghanaian government purchased 307 new ambulances for the Ministry of Health in 2019, yet this was grossly inadequate.\n\nThe government’s purchase and subsequent deployment of 307 additional ambulances to the country’s previously deficient National Ambulance Service has improved emergency medical services. Hence, the fact that the total number of operational public ambulances has increased from 50 to 357 in the last few years, representing a 600% increase. The government’s action has also pushed Ghana closer to meeting the world’s requirement for ambulance-to-population ratio. According to WHO, every country’s ambulance to population ratio must be at least 1:50,000 for effective emergency care delivery. Thus, for every 50,000 people in a nation should be serviced by one ambulance for their emergency situations.\n\nIn time past, population-to-ambulance ratio in Ghana was 1:524,000, with only 50 ambulances. The ratio has improved substantially with the deployment of the 307 new ambulances, to 1:84,000. To achieve WHO requirements, Ghana, with a population of little over 30 million people, requires 600 operable ambulances. The coming of the extra 307 ambulances to add to the status quo of 50 fleet presupposes the current government requires 243 more ambulances to meet the WHO requirement (www.abcnewsgh.com).\n\nAs the COVID-19 disruptions have shown, emergency medical services that provide the first line of response to urgent healthcare requirements within a community are critical. Emergency care should be a top priority for the Ghanaian government, and it should be incorporated into the development of public health systems. In order to organize emergency care services, a system approach with interconnected components must be used. Pre-hospital care, transportation, and hospital treatment should all be included. Ghana’s district hospitals are ideally positioned to organize these services in a synchronized fashion. Following that, a foundation for an urgent reaction structure must be built.\n\n\nIssues with service delivery quality\n\nThere is a distinction to be made between medical and overall quality of service. The former refers to aspects of the healthcare system that result in an improved result, such as surgical expertise, drug availability, logistics, and other factors. On the other hand, the latter refers to a variety of factors that influence patients’ experiences and satisfaction, including hospital comfort, physician assistance, waiting time, appointments, and visits, as well as the facility’s physical surroundings. It is critical for healthcare executives to continually assess the factors that influence patient satisfaction with the quality of care they receive in order to understand what patients value, how they perceive quality of care, and where, when, and how service changes and improvement can be implemented (Ford, Bach, & Fottler,1997; Raposo, Alves, & Duarte, 2009).\n\n\nFinancing the health sector\n\nIn order to improve health outcomes, it is necessary to support appropriate, sustainable, equitable, and effective health financing. The “role of a health system dealing with the mobilisation, accumulation, and allocation of money to cover the health demands of the people, individually and collectively, in the health system” is referred to as health financing (WHO, 2005). With the introduction of COVID-19, it is now more important than ever to provide the correct financial stimulus for suppliers while putting in organising structures to make everyone easily access medical care.” Raising revenue, risk pooling, and purchasing are the three major roles of health financing proposed by the World Health Organisation (WHO). See Table 2.\n\nGhana must pay particular attention to efficiently executing the three health financing functions, particularly in the aftermath of COVID-19 disruptions and setbacks, in order to achieve the fundamental goals of enhancing health outcomes, maintaining financial security, and responding to customers in a fair, efficient, and long-term manner.\n\n\nHealth workforce management\n\nHealth workforce management is an integral component of the health-care system. Human resources, including their number, professional competence, skill mix, and incentive, are essential to Ghana’s health-care sector’s ability to function and provide the essential healthcare services to achieve the best possible health outcomes.\n\nIn terms of both quantity and quality, the Ghanaian government must invest in health worker training and specialisation. According to some studies, surgeons play a less role in influencing how treatment prescriptions and drugs are use and the general consumption of healthcare resources (Appiah-Denkyira, Herbst, Soucat, Lemiere, & Saleh, 2013; World Health Organisation, 2016a; and World Health Organisation (human resources for health observer, 17) 2016b). Their official and informal functions create an enabling atmosphere that improves health-care practices and performance.\n\nOther research on health-care system performance and clinical governance (Appiah-Denkyira et al., 2013; Andersen, Davidson, & Baumeister, 2007; Nyoni & Gedik, 2012), highlights the need of good clinical management in driving improvement efforts and initiatives. As a result, there is a favorable association between hospital performance and medical specialists taking on job that is not directly related to patient care, as this will result in executive board cooperation. Even while the medical profession has a special standing, it is also crucial to remember that when other professionals’ leadership is included in the decision-making process, health systems generally improve.\n\nCOVID-19 demonstrated once again how important it is for the government of Ghana to spend more in the training of physicians, paramedics, and other caregivers who worked on the front lines during the disturbances.\n\n\nLow number of health centres/inadequate number of infectious disease centre\n\nIn response to the COVID-19 epidemic, a new 100-bed hospital in Accra, Ghana’s Infectious Disease Center (GIDC), was established. The GIDC will provide critical healthcare services to residents of Ghana’s capital as the country’s first infectious disease center. The urgent necessity for an infectious disease center at the height of global spikes in the pandemic resulted in the hospital being completed in a record span of 100 days. To make patient recovery as satisfying as possible, almost 700 square meters of water-efficient landscaping were built around the hospital. To reduce the hospital’s utility expenses, measures such as insulation, energy-saving lighting, and low-flow plumbing fixtures were implemented.\n\nIncorporating the green features’ operating savings allowed for a straightforward payback period of less than a year. The Ghana COVID-19 Business Sector Fund, a private sector-led initiative aimed to promptly reacting to the agony and suffering caused by the COVID-19 pandemic, established the GIDC. The GIDC final EDGE certification has been issued by Think step-SGS. The project was completed within three months and commissioned in July, 2020 which costed USD 7.5 million (https://ghanacovid19fund.com). To achieve this crucial national task, the Ghana Armed Forces, the Architectural Institute of Ghana, the Institute of Engineers, and all other related professionals, as well as Corporate Ghana, should all be marshalled once more. The Ghanaian government should build similar facilities in the Western, Ashanti, and Northern regions of the country, with the goal of completing them by 2023.\n\nThe government has already expressed its willingness to construct 110 new district hospitals with the introduction of six new regions, bringing the total number of regions to 16. When fully implemented, this will vastly improve the health sector’s infrastructure, allowing it to better satisfy Ghanaians’ health requirements while also improving the management of future epidemics and pandemics.\n\n\nBlood safety at blood banks\n\nAs a result of the country’s general lack of financial resources, this area of Ghana’s health infrastructure is suffering. Again, in many countries, including Ghana, a high prevalence of transfusion transmissible illnesses, a lack of quality systems, and a significant reliance on family/replacement donations create ongoing issues that threaten the sustainability of national blood programs (Chigurupati, & Murthy, 2015; Tagny, Mbanya, Tapko, & Lefrère, 2008; Adjei, Kuma, Tettey, Ayeh-Kumi, Opintan, Apeagyei, & Narter-Olaga, 2009; Mohammed & Essel, 2018). For transfusion safety, Ghana needs increase vigilance and surveillance measures.\n\n\nRemove obstacles and allow immediate access to research results and local production of urgently needed vaccines\n\nVaccination against COVID-19 is progressing across Africa, despite the continent obtaining immunizations later and in smaller amounts, with more than 7 million doses delivered so far than other parts of the world (African Centre for Disease Control, 2021). South Africa, Tunisia, Egypt, Senegal and Morocco. are the five African countries that produce vaccines. Most local enterprises focus entirely on packaging and labeling, therefore upstream production is extremely limited. Because immediate facilities cannot be adjusted for large-scale production through strategic partnerships, the COVID-19 disruptions had exposed the constraints in vaccine availability during disease emergencies. As a result, it is critical that vaccine makers in Africa shape supply chains in order to export their goods to new markets.\n\nIn 2014, a five-year clinical trial on malaria vaccine ended with seven nations where nearly 2,500 Ghanaian adolescents took part in facilities at Agogo and Kintampo. Participants were drawn from the Ghana Health Service Kintampo Health Research Centre, Agogo Presbyterian Hospital and The School of Medical Sciences at Kwame Nkrumah University of Science & Technology. This vaccine is a watershed occasion in Ghana’s history where eventually malaria will be curbed and eradicated.\n\nThe School of Medical Sciences at Kwame Nkrumah University of Science and Technology, Agogo Presbyterian Hospital, and the Ghana Health Service’s Kintampo Health Research Centre were among the participants. The release of a malaria vaccine in Ghana will be a watershed moment in history, indicating the path to a future where malaria will be curbed and eventually eradicated.\n\nSimilarly, Sibiri, Zankawah, and Prah (2020) highlighted Ghana’s scientific and technological advances during the peak of the pandemic. Despite a severe lack of healthcare and scientific facilities, Ghanaian scientists were among the first to decode the novel coronavirus genome in Africa (SARS-CoV-2). Some of the well-known laboratories in Ghana’s Universities were at the forefront of the fight and developed some novel testing procedures that allowed the country to test at a larger scale per million than its peers in Africa. Other auxiliaries used were drones for delivery of samples for testing at designated laboratories. Rapid test kits, ventilators and solar powered hand- washing machines were created by local scientists and developers.\n\nThe country’s laboratories, which are at the forefront of the fight, had also developed some novel testing procedures that allowed the country to test on a far larger scale per million than the rest of Africa. Drones were also used to deliver samples to the laboratory for testing. Local scientists and developers created rapid diagnostic test kits, ventilators, and solar-powered hand-washing machines.\n\nVaccine production is complicated, and it necessitates significant financial investments as well as a long-term strategy. Ghana must begin with the objective in mind, concentrating on the African vaccine market and the present procurement and distribution of vaccinations. Prioritize concerns like creative funding, enabling local and regional regulatory authority to ensure quality. This must be laced with skills development, technical transfer, product development and collaborations. A good manufacturing etiquette and standard facility designs are important as well.\n\n\nCOVID-19 is speeding up the digital transformation process\n\nGovernment-imposed lockdowns and confinement measures to combat the virus. COVID-19’s spread is hastening the rate of information and communications technology (ICT) advances. According to recent projections, the number of employees working remotely throughout the world would double by 2021 (Chavez-Dreyfuss, 2020). People are increasingly turning to the internet to work, interact, socialise, consume, and find pleasure resulting in an increase in Internet traffic (OECD, 2020).\n\nCompanies and industries have responded by speeding up the digitisation of their product portfolios, basic internal operations (McKinsey, Sneader & Sternfels, 2020). Business registration, tax filing, birth certificates, and other forms of identification are among the services that national and municipal governments are expanding their online offerings (UNDESA, 2020b).\n\nRapid technological change that is not accompanied by sustainable development exacerbates existing inequities while also introducing new ones. As a result, as stated by Heads of State and Government in the Declaration on the 75th Anniversary of the United States, adopted on September 21, 2020, all nations should prioritise a vision for future digitised collaboration. Given the increased reliance on digital tools for wealth and connectedness in our society, only a shared vision for a digital world that is secure, open, and free can unleash technology’s full potential and address concerns about digital trust and security. As Ghana emerges from the COVID-19 crisis, closing the digital divide will be key to resuscitate socio-economic activities.\n\nTo bridge the digital divide, all must ensure that everyone has affordable Internet access by 2030. The government must proactively promote access to ICT infrastructure especially in all second and tertiary cycles educational institutions, use technology transfer to make it affordable and improve digital skill and literacy and raise awareness of the advantages of being online. Again, this process will provide the government with a once-in-a-lifetime opportunity to combine all of the various cards currently in circulation, such as the Driver’s License, Health Insurance Card, Social Security and National Insurance Trust Card (SSNIT), Voter’s Identity Card, and Tax Identification Card (TIN), into The Ghana Identity Card, thereby expanding the country’s tax net. This process has commenced and is ending in June 2022 where non-compliant citizens cannot transact banking business, purchase land, acquired driving license or passport or indeed register any movable or immovable property in once name as well the exercise of franchise.\n\nWomen, elderly people, people with debilities, displaced people, and native peoples, among other disadvantaged as well as marginalised groups, require specific and varied efforts to achieve digital inclusion. Recognising and reforming discriminatory stratagem and practices, as well as a general sensitization of the digital divide and contesting labels in the digital realm by presenting extra inspiring images of women, elderly persons, and other exploited groups are among them. National broadband plans that cater for women, educating people to close the digital skills gap and building gender-friendly training venues are all examples of policies that are specifically aimed to close gender disparities.\n\nNevertheless, digital inclusion can never be ascribed as the “magic bullet” in the crusade to eradicate poverty and inequality, rather it is at the nerve of the process. As a result, digital inclusion is at the heart of Member States’ resolve to ensuring that, as the 2030 Agenda is implemented, no one is left behind and to facilitate a socially just evolution to a more comprehensive, impartial, robust, and sustainable future for all.\n\n\nFuture health and demographic implications\n\nIn national and local emergency response activities, such as infectious disease outbreaks, hospitals and other healthcare facilities are critical. Therefore, the Ghana Health Service must ensure and enforce the undernoted key issues. Firstly, that there is an effective management in place in all hospitals, infection prevention and control policies, a communication plan, human resources policy that is actively being carried out, logistical support being available in sufficient quantities. There must also be the availability of the undernoted facilities such as hospital pharmacy, laboratory, concurrent emergencies, essential support services, continuity of essential care services, psychological and social support services, patient management and surge capacity.\n\nThe future demographic implication is mirrored by the demographic dividend- the potential for economic growth when an age structure shifts from young people with large families to older people with small families. The shift in age distribution, brings about less investments in younger age groups that gives opportunity to move resources to the “economic gift.”\n\nIt indicates a faster growing working population than non-economic active population that it serves, allowing for higher economic growth and improved family well-being. In theory, this transformation can result in higher per capita incomes and better living standards for families at the household levels, but may create standards of living and per capita incomes at the macro level. This can result in major advances in a country’s economic progress. The advantages usually fall into four categories: labor supply, human capital, and economic growth.\n\nThe economy can absorb and employ more individuals in terms of labour supply and women will have the chance to work outside their immediate home. As a result, personal savings rise and can be used to drive the economy. Reduced general fertility rates make women healthier and reduce domestic economic stressors. Parents can invest more resources per child, improving health and educational outcomes. Finally, a reduced dependency ratio can stimulate economic growth.\n\nHowever, there may be some concomitants to reaching the demographic rewards. To achieve the dividend, these are normally predicated on the implementation of proper social, political, and economic policies. This means that, in addition to entering a period of decreased fertility. Therefore, demographic advantages inure to countries that have implemented policies and programmes especially in family planning, reproductive health, quality education, job creation and opportunities, investments in girls and women as well as good governance.\n\n\nConclusion\n\nIn the end, the demographic dividend’s benefits are not automatic. Reduced fertility is not a guarantee of prosperity in and of itself. The size of the demographic dividend is thus determined by the rate of fertility decline and population increase, the ability to profitably employ the extra people, and the nature of Ghana’s political, economic, and social reforms.\n\nCOVID-19 has demonstrated that state agencies cannot bring about economic growth and political transformation on their own. Established interdependence binds national systems with supranational systems, both historically and lately, to ensure that global health interventions meet critical needs that cut across countries and provide social benefits to all. The COVID-19 outages have underlined the need of emergency services, particularly in providing first-line responses to critical healthcare requirements at all levels of society. It is recommended that Ghana’s government prioritizes emergency care requirements and plans for them as an integral part of public health system planning.\n\nPre-hospital care, transportation, and hospital treatment should all be included. District hospitals are in a unique position to organize these services in a synchronized fashion. Furthermore, it is critical to concentrate on executing the three health funding tasks in order to respond to future disruptions in an equitable, efficient, and long-term manner. Health infrastructure, such as well-equipped medical facilities, a well-trained workforce, regulatory capacity to ensure quality, technology transfers through the use of digital applications, and collaboration with the private sector, will help prepare the groundwork for more comprehensive robust, and viable healthcare systems in the future.\n\n\nEthics approval and consent to participate\n\nNot applicable as this was mainly a documentary study.\n\n\nData availability\n\nAll data/articles underlying the work are available from the following sources.\n\n- Bacterial Contamination of Blood and Blood Components in Three Major Blood Transfusion Centers, Accra, Ghana. https://www.researchgate.net/profile/Theophilus-Adiku/publication/26692181_Bacterial_Contamination of Blood\n\n- The Four Habits of High-Value Health Care Organizations. Richard M.J. 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PubMed Abstract | Publisher Full Text\n\nPaital B, Agrawal PK: Air pollution by NO2 and PM2.5 explains COVID-19 infection severity by overexpression of angiotensin-converting enzyme 2 in respiratory.2020.\n\nPetretto DR, Pili R: Ageing and COVID-19: what is the role for elderly people?. Geriatrics. 2020; 5(2): 25. PubMed Abstract | Publisher Full Text\n\nPidwimy M: Definitions of Systems and Models: Fundamentals of Physical Geography, 2nd edn.2006. (last accessed March 9 2021).Reference Source\n\nPolicy Brief: Education During COVID-19 and beyond:August 2020. UN (2020b).\n\nPongsiri MJ, Roman J, Ezenwa VO, et al.: Biodiversity loss affects global disease ecology. Bioscience. 2009; 59(11): 945–954. Publisher Full Text\n\nPreston SH: The Changing Relation between Mortality and Level of Economic Development. Population Studies. 1975; 29(2): product. Acta Bio Med 91 (2). 224–225.\n\nPublic Health Infrastructure:2020.Retrieved March 23, 2021. Reference Source\n\nRader B, Scarpino SV, Nande A, et al.: Crowding and the shape of COVID-19 epidemics. Nature Medicine. 2020; 26(12): 1829–1834. PubMed Abstract | Publisher Full Text\n\nRaposo ML, Alves HM, Duarte PA: Dimensions of service quality and satisfaction in healthcare: a patient’s satisfaction index. Service Business. 2009; 3(1): 85–100. Publisher Full Text\n\nRocklöv J, Sjödin H: High population densities catalyse the spread of COVID-19. Journal of Travel Medicine. 2020; 27(3): taaa038. PubMed Abstract | Publisher Full Text\n\nSchäfer MS, Kessler SH, Fähnrich B, et al.: Analyzing science communication through the lens of communication science: Reviewing the empirical evidence. Handbooks of Communication Science .2019; 17:77–104. Publisher Full Text\n\nSchellekens P, Sourrouille DM: COVID-19 mortality in rich and poor countries: a tale of two pandemics?. World Bank Policy Research Working Paper, (9260). 2020.\n\nSharma AK, Balyan P: Air pollution and COVID-19: Is the connect worth its weight?. Indian Journal of Public Health. 2020; 64(6): 132–S134. PubMed Abstract | Publisher Full Text\n\nSibiri H, Zankawah SM, Prah D, et al.: COVID-19 response: Highlights of Ghana’s scientific and technological innovativeness and breakthroughs. Ethics, Medicine and Public Health (2020). 2019; 14: 100537.\n\nSingh A, Agrawal M, Marshall FM: The role of organic vs. inorganic fertilizers in reducing phytoavailability of heavy metals in a wastewater-irrigated area. Ecological Engineering .2010; 36(12):1733–1740. Publisher Full Text\n\nSjödin H, Wilder-Smith A, Osman S, et al.: Only strict quarantine measures can curb the coronavirus disease (COVID-19) outbreak in Italy, 2020. Eurosurveillance .2020; 25(13):2000280. Publisher Full Text\n\nTagny CT, Mbanya D, Tapko JB, et al.: Blood safety in sub-Saharan Africa: a multifactorial problem. Transfusion. 2008; 48(6): 1256–1261. PubMed Abstract | Publisher Full Text\n\nThe World Bank: Hospital beds (per 1000).Accessed March 3, 2021.Reference Source\n\nTowards improved access to broadband Internet in support of Africa’s transformation: Eca Policy Brief, no. ECA/18/003.2020.Reference Source\n\nTurnock BJ: Public Health—What It Is and How It Works. 2nd ed.Gaithersburg, Md.:Aspen Publishers;2001.\n\nUnited Nations Department of Economic and Social Affairs (UNDESA): World Social Report 2020: Inequality in a Rapidly Changing World.\n\nVelavan TP, Meyer CG: The COVID-19 epidemic. Tropical Medicine and International Health. 2020; 25(3): 278–280. PubMed Abstract | Publisher Full Text\n\nVerity R, Okell LC, Dorigatti I, et al.: Estimates of the severity of coronavirus disease 2019: a model-based analysis. The Lancet Infectious Diseases. 2020; 20(6): 669–677. PubMed Abstract | Publisher Full Text\n\nVon Bertalanffy L: General System Theory: Foundations, Development, Applications. New York.1976.\n\nWagner G, Siebert U, Ledinger D, et al.: Quarantine Weight?. Indian Journal of Public Health. 2020.\n\nWHO: Systems thinking for health systems strengthening. Geneva:World Health Organization:2009; with COVID-19. Disaster Medicine and Public Health Preparedness. 1–6. Retrieved on April 14, 2022.\n\nWorld Bank: Air transport, passengers carried.2020a.Retrieved March 4, 2021. Reference Source\n\nWorld Bank: Air transport, passengers carried.2020b.Retrieved April 4, 2020. Reference Source\n\nWorld Bank: International tourism, number of arrivals.2020c.Retrieved March 4, 2021. Reference Source\n\nWorld Bank: International tourism, number of arrivals.2020d.Retrieved April 4, 2020. Reference Source\n\nWorld Health Organization. Department of Mental HealthAbuse S; World Health Organization, World Health Organization. Department of Mental Health, Substance Abuse. Mental Health, World Health Organization. Mental Health Evidence, & Research Team: Mental health atlas 2005. World Health Organization;2005.\n\nWHO, 2012.Reference Source\n\nWHO, 2014.Reference Source\n\nWHO, 2016.Reference Source\n\nWorld Health Organization (WHO):Retrieved 28 May 2020.\n\nWorld Health Organisation: Global strategy on human resources for health: workforce 2030.2016a. Accessed on May 1, 2022.\n\nWorld Health Organisation: Health workforce requirements for universal health coverage and the sustainable development goals (human resources for health observer, 17).2016b.\n\nYamey G, Jamison D, Hanssen O, et al.: Financing Global Common Goods for Health: When the World is a Country Health Systems & Reform.2019; 5(4): 334–349. Publisher Full Text"
}
|
[
{
"id": "140688",
"date": "21 Jul 2022",
"name": "Osamah Shihab Albahri",
"expertise": [
"Reviewer Expertise AI",
"Decision science",
"medical informatics",
"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\nThis paper uses the qualitative paradigm of research that used corpus construction in the selection of material to represent a whole and this makes it functionally equivalent to sampling but structurally different. It used secondary data to ascertain the demographic effects and the extent of health infrastructure deficit and ingenious ways to curb the challenges as exposed by COVID-19. Some limitations were found, as follows:\nThe abstract is not clear. re-write it considering the context, challenges, aim, method, results and implications.\n\nAdd research questions.\n\nNovelty and contribution should be clarified.\n\nMotivation behind the work should be discussed.\n\nMore discussion is essential.\n\nComparison analysis with more articles should be discussed.\n\nLimitations and future directions should be highlighted.\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?\nPartly\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/11-643
|
https://f1000research.com/articles/11-109/v1
|
28 Jan 22
|
{
"type": "Study Protocol",
"title": "Extension of the PRISMA 2020 statement for living systematic reviews (LSRs): protocol",
"authors": [
"Lara A Kahale",
"Vanessa Piechotta",
"Joanne E McKenzie",
"Elena Dorando",
"Claire Iannizzi",
"James M Barker",
"Matthew J Page",
"Nicole Skoetz",
"Elie A Akl",
"Lara A Kahale",
"Vanessa Piechotta",
"Joanne E McKenzie",
"Elena Dorando",
"Claire Iannizzi",
"James M Barker",
"Matthew J Page",
"Nicole Skoetz"
],
"abstract": "Background: While the PRISMA 2020 statement is intended to guide the reporting of original systematic reviews, updated systematic reviews, and living systematic reviews (LSRs), its explanation and elaboration document notes that additional considerations for updated systematic reviews and LSRs may need to be addressed. This paper reports the protocol for developing an extension of the PRISMA 2020 statement for LSRs. Methods: We will follow the EQUATOR Network’s guidance for developing health research reporting guidelines. We will review the literature to identify possible items of the PRISMA 2020 checklist that need modification, as well as new items that need to be added. Then, we will survey representatives of different stakeholder groups for their views on the proposed modifications of the PRISMA 2020 checklist. We will summarize, present, and discuss the results of the survey in an online meeting, aiming to reach consensus on the content of the LSR extension. We will then draft the checklist, explanation and elaboration for each item, and flow diagram for the PRISMA 2020 extension. Then, we will share these initial documents with stakeholder representatives for final feedback and approval. Discussion: We anticipate that the PRISMA 2020 extension for LSRs will benefit LSR authors, editors, and peer reviewers of LSRs, as well as different users of LSRs, including guideline developers, policy makers, healthcare providers, patients, and other stakeholders.",
"keywords": [
"PRISMA",
"extension",
"living systematic reviews",
"reporting",
"flow diagram",
"checklist",
"statement"
],
"content": "Introduction\n\nSystematic reviews (SRs) need to include all relevant primary studies to validly answer clinical or public health questions. To meet this goal, SRs need to be updated on a frequent basis, particularly in areas with a fast pace of research generation and publication (e.g., treatments for COVID-19). Living systematic reviews (LSRs) attempt to achieve this through continual searching of the literature and incorporation of relevant new evidence, soon after it becomes available.1 In addition to the frequency of the search update, LSRs differ from traditional SRs in a number of other aspects, e.g., reporting on the change in eligibility criteria in results, conclusion, authorship, and the publication process. Also, unlike traditional SRs, LSRs should consider how to avoid inadvertent type I and II errors arising from repeated updating. It is not clear whether LSRs are reporting on how they have addressed this issue.\n\nThe ‘Preferred Reporting Items for Systematic reviews and Meta-Analyses’ (PRISMA) statement is widely used to report SRs.2 The statement is intended to facilitate transparent, complete, and accurate reporting of SRs. While the PRISMA 2020 statement is intended to guide the reporting of original systematic reviews, updated systematic reviews, and LSRs, its explanation and elaboration document notes that additional considerations for updated and LSRs may need to be addressed.3\n\nA recent methodological survey of LSRs identified variability in reporting the flow of studies through the different phases of the review for the different update versions.4 Another mixed-methods study found that authors of LSRs have adopted different approaches to communicating the LSR findings to readers.5 One of the stated reasons for variability was that little or no guidance exists as to which approach is best for reporting LSRs. At the moment, there appears to be a lot of variation in how LSRs are reported. An extension to the current PRISMA 2020 statement is needed to better address the unique aspects of LSR reporting.\n\nThe objective of this study is to develop an extension of the PRISMA 2020 statement for LSRs. The aim of this paper is to report the details of the protocol for that study.\n\n\nProtocol\n\nWe will develop an extension to the PRISMA 2020 statement for LSRs by following the EQUATOR Network’s guidance for developing health research reporting guidelines (Figure 1).6 We have registered our project on the EQUATOR Network website.7 We will obtain ethical approval for the study and will inform participants that any collected information will be de-identified and that findings will be reported in aggregate.\n\nEstablishment of the executive committee\n\nThe executive committee members, who are the authors of this protocol, will lead, organize, and author this extension. The executive committee consists of individuals with various backgrounds, including systematic review methodologists, LSR authors, co-leads and authors of the PRISMA 2020 statement, publishers, clinicians, and practice guideline methodologists.\n\nIdentify the need for a guidance\n\nAs noted earlier, there are a number of aspects of LSRs that the guidance from the PRISMA 2020 statement does not address, or where we believe modification is needed. Furthermore, we are not aware of any reporting guidance for LSRs published outside of the PRISMA banner.\n\nReview the literature\n\nTo identify possible items of the PRISMA 2020 checklist that need to be added or modified for the reporting of LSRs, we will make use of the cumulative information arising from five methodological studies examining aspects of LSRs, and led by members of the executive committee:\n\n• Methodological survey of published LSR flow diagrams4\n\nThis survey examined how authors of all LSRs published since 2014 until April 2021 reported the flow of studies through the different phases of the review for each update. We noted six different ways of reporting study flow, none of which are currently required in the PRISMA 2020 flow diagram.\n\n• Concept paper on methodological challenges with COVID-19 LSRs8\n\nThis concept paper reviews the methodological challenges of conducting LSRs during the COVID-19 pandemic. The paper identified several reporting challenges including, for example, how to transparently report methodological changes when updating an LSR. We will consider how to address these challenges in the extension of the PRISMA 2020 checklist.\n\n• Methodological survey of published LSRs9\n\nThis survey of published LSRs (published between 2014 until April 2021) describes their general characteristics, the methods of conduct and reporting, and how the methods change across updates. Also, it examined how and when the different versions of an LSR were being published. The practice of authors aids in identifying relevant items that may not have been addressed in the PRISMA 2020 checklist.\n\n• Scoping review of the methodological literature on LSRs10\n\nThis scoping review examines methodological guidance for conducting, reporting, and publishing LSRs (protocol available10). Results from this review will be used to identify issues pertinent to the reporting of LSRs. These issues will be mapped against the 27 items of the PRISMA 2020 checklist, thus allowing identification of items that need modification, and the items that need to be added.\n\n• Qualitative study with LSR authors\n\nWe will interview LSR authors and journal editors to explore their views and their experiences with conducting, reporting, and publishing LSRs. We will use the findings to identify potential modifications to the PRISMA 2020 checklist items.\n\nIdentify participants\n\nWe will identify representatives of different stakeholders groups, including the authors of PRISMA 2020; authors of published PRISMA extensions11–18; editors of journals that have published LSRs; representatives of organizations that have published LSRs (e.g., Cochrane, Campbell); publishers and editors of preprint platforms; practice guideline developers (e.g., the World Health Organization); practice guideline end-users (e.g., health care professionals, patients); end-users of the PRISMA LSR extension (i.e., LSR authors); systematic review methodologists; statisticians; information specialists; and research funders.\n\nWe will invite one to three representatives for each type of stakeholder (listed above). We will aim to have adequate gender and geographic representation.\n\nDevelop the first draft of the extension\n\nWe will develop the first draft of the checklist extension based on the results of the background studies (see ‘Review of the literature’ section). Then, the executive committee members will complete a survey to propose the items of the 2020 PRISMA checklist that may be modified. They will also propose new items that may be added.\n\nSurvey stakeholders about the extension’s first draft\n\nIn preparation for this step, we will summarize the findings of the background studies (see ‘review of the literature’ section) and share them with stakeholders. Then, we will survey the stakeholders for their views on each of the items included in the draft extension of the PRISMA 2020 checklist. For each item currently included in the PRISMA 2020 checklist, we will present its wording, its explanation and elaboration, and possibly a suggestion on how the item may be modified for LSRs. Then, for each item, we will seek stakeholders’ views on whether the item should be kept without changes or modified. We will ask similar questions for new items proposed by the executive committee. In addition, we will ask stakeholders to propose additional items to include in the checklist. We will calculate descriptive statistics using frequencies and percentages of responses to each item.\n\nDevelop the second draft of the extension\n\nWe will use the results of the survey to develop a second draft of the extension. Similar to the development process used for the PRISMA 2020 checklist, we will consider that an item has reached consensus when one of its response options is selected by more than 66% of the stakeholders.19 Items for which no consensus is reached will be considered for discussion at a consensus meeting.\n\nConduct an online consensus meeting\n\nWe will conduct an online meeting to try and reach consensus on the content of the LSR extension. We will electronically share the second draft of the extension ahead of the meeting. The meeting will be held via an online meeting platform with enough sessions to cover the tasks to be completed and to accommodate the different time zones of those attending. Members of the executive team will chair the meeting and take minutes.\n\nDuring the consensus meeting, we will give short presentations on the background, rationale, the scope of the project, the results of the survey. We will discuss the proposed list of modifications to the checklist (any new items and modifications of existing items of the PRISMA 2020 statement), and to the PRISMA flow diagram.\n\nWe will prioritize items for discussion for which there is a lack of consensus. The discussion will revolve around the different arguments for inclusion or exclusion of a specific item with the aim of reaching consensus. If outstanding issues are not resolved (not discussed, consensus not reached), we will re-work them post-meeting and share them via email with the meeting attendees for their comments.\n\nIf time allows, we will discuss the strategy for writing the manuscript, task assignment, authorship, and ideas regarding piloting and knowledge translation.\n\nDevelop the guidance statement and explanatory document\n\nMembers of the executive committee will draft initial documents including (1) the modified PRISMA 2020 checklist for LSRs, (2) explanation and elaboration for each item, and (3) modified flow diagram. These initial documents will then be circulated to all members of the executive committee and to all meeting attendees for feedback and approval. We will seek their views on the layout, clarity of the terminology, and the comprehensiveness of the set of items covered. Any proposed revision arising from these comments will be assessed by the executive committee as to whether further changes are required.\n\nDevelop a publication strategy\n\nWe will publish the extension in an open-access, peer reviewed journal and upload a pre-print and the material which informed the extension (e.g., de-identified survey data) to the Open Science Framework repository.\n\nPlan post- publication activities\n\nWe will post this extension on the PRISMA statement website and will develop an application that facilitates the development/creation of a PRISMA 2020 flow diagram for LSRs. We will encourage readers and users to submit any comments or feedback via the website.\n\nWe will welcome and support any initiative to translate the extension or any part of it to a different language. We will contact editors of journals that publish LSRs to inform them about the extension and to seek their endorsement. Specifically, we will encourage journal editors and publishers to raise awareness of the extension by referring to it in journal “Instructions to authors”, endorsing its use, advising editors and peer reviewers to evaluate the reporting of submitted LSRs against this extension, and making changes to journal policies to accommodate the extension.\n\nCurrently, we are reviewing the literature, identifying the participants, and developing the first draft of the extension.\n\n\nDiscussion\n\nThe number of LSRs has substantially increased over time, and this is set to keep growing. Complete and accurate reporting of the methods and results of these reviews is necessary for readers to understand the findings, and identify any methodological weaknesses, that may compromise those findings. In this protocol we have outlined the steps we will take to develop a reporting extension to PRISMA 2020 specific to LSRs.\n\nConducting online meetings to try reach consensus might have some advantages and challenges. An advantage is that such meetings are more feasible and convenient for attendees with busy schedules and ensures equity, especially for those who do not have funding to attend in-person meetings. On the other hand, there are time zone challenges when participants are attending from around the globe. To address this, we will try to accommodate the attendees’ different time zones. A further challenge relates to technical issues associated with Internet connection or other software failures. To address these challenges, we will ask the attendees to secure an alternative to the primary Internet connection in case the latter fails. A further strength is that members of the executive committee have diverse backgrounds and expertise at all levels that will enrich and facilitate completion of the extension.\n\nWe anticipate that the PRISMA 2020 extension for LSRs will benefit LSR authors, editors, and peer reviewers of LSRs, and different users of LSRs, including guideline developers, policy makers, healthcare providers, patients, and other stakeholders. We hope that implementation of the reporting guidance will lead to more transparent, complete, and accurate accounts of LSRs, thus providing the necessary synthesized evidence to underpin healthcare decisions.\n\n\nData availability\n\nNo data are associated with this article.",
"appendix": "Acknowledgments\n\nThe authors thank Neal Haddaway for contributing to earlier discussions about the design of the study.\n\n\nReferences\n\nElliott JH, et al.: Living systematic review: 1. Introduction-the why, what, when, and how. J. Clin. Epidemiol. 2017; 91: 23–30. PubMed Abstract | Publisher Full Text\n\nPage MJ, Moher D: Evaluations of the uptake and impact of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement and extensions: a scoping review. Syst. Rev. 2017; 6(1): 263. PubMed Abstract | Publisher Full Text\n\nPage MJ, et al.: PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021; 372: n160. Publisher Full Text\n\nKahale LA, et al.: Tailored PRISMA flow diagrams for living systematic reviews: a methodological survey and a proposal. F1000Res. 2021; 10(192): 192. Publisher Full Text\n\nMillard T, et al.: Feasibility and acceptability of living systematic reviews: results from a mixed-methods evaluation. Syst. Rev. 2019; 8(1): 1–14. Publisher Full Text\n\nMoher D, et al.: Guidance for developers of health research reporting guidelines. PLoS Med. 2010; 7(2): e1000217. PubMed Abstract | Publisher Full Text\n\nEquator Network: PRISMA for LSR – Extension of PRISMA 2020 for living systematic reviews. 2021. Reference Source\n\nIannizzi C, et al.: Methodological challenges for living systematic reviews conducted during the COVID-19 pandemic: a concept paper. J. Clin. Epidemiol. 2022; 141(82-9): 82–89. PubMed Abstract | Publisher Full Text\n\nKhamis AM, et al.: Methods of conduct and reporting of living systematic reviews: a protocol for a living methodological survey. F1000Res. 2019; 8: 221. Publisher Full Text\n\nIannizzi C, et al.: Methods and guidance on conducting, reporting, publishing and appraising living systematic reviews: a scoping review protocol. F1000Res. 2021; 10(802): 802. Publisher Full Text\n\nWelch V, et al.: PRISMA-Equity 2012 extension: reporting guidelines for systematic reviews with a focus on health equity. PLoS Med. 2012; 9(10): e1001333. PubMed Abstract | Publisher Full Text\n\nBeller EM, et al.: PRISMA for Abstracts: reporting systematic reviews in journal and conference abstracts. PLoS Med. 2013; 10(4): e1001419. PubMed Abstract | Publisher Full Text\n\nHutton B, et al.: The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann. Intern. Med. 2015; 162(11): 777–784. PubMed Abstract | Publisher Full Text\n\nStewart LA, et al.: Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD Statement. JAMA. 2015; 313(16): 1657–1665. Publisher Full Text\n\nZorzela L, et al.: PRISMA harms checklist: improving harms reporting in systematic reviews. BMJ. 2016; 352: i157. Publisher Full Text\n\nGuise JM, et al.: AHRQ series on complex intervention systematic reviews-paper 6: PRISMA-CI extension statement and checklist. J. Clin. Epidemiol. 2017; 90: 43–50. PubMed Abstract | Publisher Full Text\n\nMcInnes MDF, et al.: Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement. JAMA. 2018; 319(4): 388–396. Publisher Full Text\n\nTricco AC, 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\nPage MJ, et al.: Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J. Clin. Epidemiol. 2021; 134: 103–112. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "125876",
"date": "06 Apr 2022",
"name": "Meera Viswanathan",
"expertise": [
"Reviewer Expertise Systematic review methodologist"
],
"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 have a few suggestions for improvement; please use or discard as you like.\nIt may be that you intend on doing this when you present the results of your scoping review, but a first step that I didn’t see explicitly was ensuring that all your participants are working from a common definition of a living systematic review. You’ll be able to come together more easily on required PRISMA items if all participants share a common conceptual understanding of the boundaries between living systematic reviews and frequently updated systematic reviews. Do all participants share a common understanding of how much change in core methods or scope is permissible?\nI also think you might benefit from including two more groups: (1) programmers for large databases and systematic review software and (2) science communication experts. I suggest the former group because large databases are changing methods. NLM, for example, is switching to automated indexing (MEDLINE 2022 Initiative: Transition to Automated Indexing. NLM Technical Bulletin. 2021 Nov–Dec (nih.gov)); these changes may have implications for how searches should be reported in LSRs. Similarly, systematic review software (and AI tools within them) is likely to play a significant role in LSRs, and these software developers may have insights on upcoming technological changes with implications for reporting. As for the latter group, I think it would be interesting to learn what types of reporting enhance trust in the findings of LSRs, when results are updated (and perhaps prior errors are corrected) on an ongoing basis.\nFinally, I think that even after the consensus meeting, you may have to do some lumping and splitting, and it’s best to anticipate that activity and be transparent about it.\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? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": [
{
"c_id": "8327",
"date": "10 Jun 2022",
"name": "Lara Kahale",
"role": "Author Response",
"response": "The Reviewers’ comments are in bold font and our replies in regular font. Extracts from the text are in italic fonts with changes underlined. We have indicated the sections where revisions have been made in our manuscript. Reviewer 1: Meera Viswanathan, RTI International, Research Triangle Park, NC, USA I have a few suggestions for improvement; please use or discard as you like. 1. It may be that you intend on doing this when you present the results of your scoping review, but a first step that I didn’t see explicitly was ensuring that all your participants are working from a common definition of a living systematic review. You’ll be able to come together more easily on required PRISMA items if all participants share a common conceptual understanding of the boundaries between living systematic reviews and frequently updated systematic reviews. Do all participants share a common understanding of how much change in core methods or scope is permissible? Authors' response: Thank you so much for your suggestion. We have added the following to our objectives section: “We adopt the definition of an LSR as being “a systematic review that is continually updated, incorporating relevant new evidence as it becomes available”. 2. I also think you might benefit from including two more groups: (1) programmers for large databases and systematic review software and (2) science communication experts. I suggest the former group because large databases are changing methods. NLM, for example, is switching to automated indexing (MEDLINE 2022 Initiative: Transition to Automated Indexing. NLM Technical Bulletin. 2021 Nov–Dec (nih.gov)); these changes may have implications for how searches should be reported in LSRs. Similarly, systematic review software (and AI tools within them) is likely to play a significant role in LSRs, and these software developers may have insights on upcoming technological changes with implications for reporting. As for the latter group, I think it would be interesting to learn what types of reporting enhance trust in the findings of LSRs, when results are updated (and perhaps prior errors are corrected) on an ongoing basis. Authors' response: Per your suggestion, we have now invited programmers for large databases and systematic review software. We had already invited science communication experts and have invited one more. 3. Finally, I think that even after the consensus meeting, you may have to do some lumping and splitting, and it’s best to anticipate that activity and be transparent about it. Authors response: thank you. We have added text referring to that point: ‘Any proposed revision arising from these comments will be assessed by the executive committee as to whether further changes are required, including lumping and splitting’."
}
]
},
{
"id": "121603",
"date": "28 May 2024",
"name": "Zhao-Xiang Bian",
"expertise": [
"Reviewer Expertise Reporting guideline methodology",
"Clinical Trial Design and implementation",
"Evidence-based 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 protocol for developing the extension of Living systematic reviews to PRISMA 2020 is a good one. The topic is important during pandemics such as COVID-19. Some suggestions are as follows:\nProvide the detailed methods to the survey for the stakeholders. The survey process is crucial to get the consensus of the reporting guideline. Currently, the methods to decide whether the items are included, excluded, or discussed at the meeting are not clear.\n\nAdd the pilot test after the consensus meeting. The pilot testing will provide practical feedback for the use of the checklist.\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? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/11-109
|
https://f1000research.com/articles/11-637/v1
|
10 Jun 22
|
{
"type": "Research Article",
"title": "Pharmaceutical advertising and the consumption of over the counter (OTC) medicines in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.",
"authors": [
"Ambrocio Teodoro Esteves Pairazaman",
"Walter Gregorio Ibarra Fretell",
"Jessica Noelia Huapaya Cuzcano",
"Ronald Alan De La Cruz Rojas",
"Veronica Liset Esteves Cardenas",
"Jose Rincon Chavez",
"Leydi Ochoa Ayvar",
"Francisco Palacios Valverde",
"Walter Gregorio Ibarra Fretell",
"Jessica Noelia Huapaya Cuzcano",
"Ronald Alan De La Cruz Rojas",
"Veronica Liset Esteves Cardenas",
"Jose Rincon Chavez",
"Leydi Ochoa Ayvar",
"Francisco Palacios Valverde"
],
"abstract": "Background: To determine the relationship between pharmaceutical advertising and the consumption of over-the-counter (OTC) medicines in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022. Methods: The methodology used was a quantitative approach, non-experimental, cross-sectional, descriptive-correlational design. The sample consisted of 269 users, who were administered a questionnaire with 20 questions; the technique used was the survey. The results were obtained using SPSS Version 22 and Spearman's correlation statistical test with a significance level of 5%. Results: The correlation for the general hypothesis was determined with a P value of 0.000 and a Spearman's Rho value of r=0.729 indicating a strong and direct correlation between Variable 1 pharmaceutical advertising and Variable 2 consumption of over-the-counter (OTC) drugs. For the pharmaceutical advertising message dimension, a P value of 0.000 was obtained, Spearman's Rho value of r=0.597 indicating a moderate and direct correlation, for the mass media dimension (P value is 0.000), Spearman's Rho value of r=0.525 indicating a moderate and direct correlation, for the pharmaceutical product promotion dimension (P value 0.000) Spearman's Rho value of r=0.637 showing a moderate and direct correlation and for the dimension of excessive consumption of medicines under the influence and responsibility of the pharmaceutical industry (P value 0.000) was obtained. Spearman's Rho value of r=0.670 indicating a moderate and direct correlation. Conclusion: The conclusion is that there is a significant relationship between the variables pharmaceutical advertising and drug consumption.",
"keywords": [
"Pharmaceutical advertising",
"pharmacy",
"medicines",
"drugs",
"over-the-counter",
"OTC",
"consumer"
],
"content": "Introduction\n\nThere seems to be a problem with pharmaceutical advertising and the consumption of over-the-counter (OTC) medicines, which supposedly present alternatives for the prevention and/or cure of mild or moderate illnesses. The bad habits of the users of the SUPERFAR drugstore, Barrios Altos-Cercado de Lima, could be harming them when consuming these medicines, all this because of misleading and exaggerated pharmaceutical advertising, with little information about the adverse reactions that they could cause. Self-medication as a form of self-care would have consequences on the health of these people that would be evidenced by the masking of diseases, aggravation of diseases (renal, hepatic, gastric, others), increased expenses at the time of acquiring these advertising products.\n\nLooking to other countries, Castro (2016) says that in Ecuador in the area of Quito Norte, pharmaceutical advertising affects the practice of self-medication of people because, through media, such as television, print media and even the internet, messages about the advantages and benefits of pharmaceuticals are disseminated and that makes people obtain pharmaceutical products quickly and without attending a consultation with a healthcare professional.1 On the other hand, Viña and Debesa (2017) tell us that in Havana Cuba, thanks to the intervention of the Ministry of Public Health (Minsap) and the Center for State Control of Medicines, Equipment and Medical Devices, the promotion of medicines is well regulated and controlled. Thanks to these institutions, the phenomenon of drug promotion as a source of profit for the pharmaceutical industry does not exist in Cuba.2 Likewise, Villada and Sanchez (2019) tell us that, in the City of Pereira, Colombia, unregulated web spaces, social network platforms and smartphone applications are directly involved in the consumption of poor quality, counterfeit and/or illegal medical products.3\n\nAt the national level, Ortiz (2020) tells us that in the district of Trujillo-Iquitos, the consumption of medicines during the health emergency was mainly affected by social, cultural, personal, and psychological factors.4 Meanwhile, according to Socican (2013), in Peru the lack of oversight of pharmaceutical advertising, laws, regulations, and codes of conduct causes the media to breach several ethical violations and illegal practices that are undermining the rights of Customers.5 On the other hand, in the journal Tsafiqui et al. (2021) titled “Regulation of pharmaceutical products in Peru” indicates that pharmaceutical advertising is a tool used by the competition in the market providing information such as characteristics, advantages and disadvantages, constituting a dynamic and competitive information channel for consumers to make better consumption decisions about a drug.6\n\nRegionally, Sosa (2019) tells us that, in the A.A.H.H. 12 de agosto-San Martin de Porres, Lima, the lack of time, low level of knowledge, the difficulty of access to health services, dissatisfaction with health services and acceptance of the sale without prescription leads to self-medication, and that on the contrary consumers are not influenced by media to obtain OTC drugs.7 Meanwhile, Digemid and Minsa (2014) made a bulletin on promotion and pharmaceutical advertising applied since 1946 indicating that they are actions promoted to persuade the selection, acquisition, prescription and use of a certain pharmaceutical product, inducing users to acquire a lot of units, based on communicative policies.8 On the other hand, J. Fernandez (2020) recommends allowing certain drugs to be advertised and promoted without restrictions, although they can only be dispensed with medical prescription in the same way as OTC drugs, but taking into account the prior approval of the DIGEMID.9\n\nAt the local level, Mayma et al. (2013) in Cercado de Lima conducted 11-question surveys of people aged 18 to 65 years old, classified by gender (male and female) and socioeconomic level. The users agree that 70% of them buy medicines influenced by pharmaceutical advertising and 55% do so because of their socioeconomic level.10 This information has been confirmed when users approach pharmacies requesting one or another drug without having had any level of diagnosis or information about their ailment based only on pharmaceutical advertising or on the recommendation of an acquaintance or relative.\n\nThe present study focuses on the pharmaceutical advertising that users perceive in order to request OTC drugs without having had any medical review or diagnostic level by a medical professional.\n\nThis research is carried out with the purpose of contributing to the knowledge that exists on pharmaceutical advertising and the consumption of OTC drugs, whose results will be systematized in a proposal, to adhere it as knowledge and evolution to the health sciences, since it will be possible to demonstrate that there is a relationship between pharmaceutical advertising and the consumption of OTC drugs.\n\nIn order to obtain the objectives of the present study, it is descriptive and observational in nature, providing results that can contribute to research with current data and of great relevance for subsequent research studies.\n\nThis study is justified in practice because it helps to measure the relationship that will exist between pharmaceutical advertising and the consumption of OTC drugs, and the results of this study will also help to determine how pharmaceutical advertising is related to and influences the consumption of OTC drugs.\n\nThe following general question was posed: What is the relationship between pharmaceutical advertising and the consumption of OTC drugs among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022?\n\nFinally, the purpose of this study was to determine the relationship between pharmaceutical advertising and the consumption of OTC drugs among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\n\nMethod\n\nThe research was of the hypothetico-deductive type, with a quantitative approach. The type of research was basic, and the level was descriptive and correlational; finally, the design was non-experimental.11–13\n\nThe study population is a defined, limited and accessible set of cases, which will be indicated for the selection of the sample, which has to meet many predetermined criteria. In addition, the population is finite.14 The following study is made up of 900 users who attended the pharmacy. SUPERFAR de Barrios Altos-Cercado de Lima, during the month of February on weekdays from Monday to Friday.\n\nTo define the sample size, a formula for finite populations was used, with a confidence level of 95% and a margin of error of 5%.\n\nWhere:\n\nn = Sample size in finite populations.\n\nN = Size of the population to be studied.\n\np y q = Statistical values for the population, when the indicators are unknown (p = 0.5 and q = 0.5).\n\nE = Error 0.05%\n\nZ = Reliability margin\n\nThis is the calculation used to obtain the sample size in the population of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima.\n\n• The study sample consisted of 269 users considered during the month of February (2022), from Monday to Friday of each week, until the indicated number of users was reached.\n\nInclusion criteria:\n\no Users of both genders.\n\no Users over 18 years of age.\n\no Voluntary acceptance of the surveys.\n\no Users who come to shop at the SUPERFAR drugstore.\n\nExclusion criteria:\n\no Persons under 18 years of age.\n\no Do not accept the questionnaire\n\no Do not buy medicines in the SUPERFAR drugstore.\n\nA simple random probability sampling was carried out, where all the people had the same possibility of being chosen and being part of our research. This is a basic sampling procedure, its main characteristic guaranteeing that the selection is carried out from a list of the population, giving each element an equal chance.15\n\nThe technique used was personal surveys, which were used to evaluate the users who went to the SUPERFAR drugstore in Barrios altos-Cercado de Lima. For this research, the questionnaire instrument was used, for which the Likert scale was used. The instrument is made up of 11 questions for variable 1: Pharmaceutical advertising and nine questions for variable 2: Consumption of OTC drugs. Below, we present the technical data sheet of the survey instrument, where we will observe a general summary of the instrument and the research.16\n\nThe validation of the instrument for this study was carried out through the judgment of experts who validated the content, this is because they are professionals with a higher university degree; they were the methodologists; Antonio Guillermo Ramos Jaco, Gabriel Enrique León Apac, and Orlando Juan Márquez Caro.\n\nThe reliability of the instrument used for this study was the Cronbach's alpha coefficient method, this coefficient will allow us to determine the internal consistency and homogeneity within the dimensions, using as a pilot test approximately 27 subjects, with a zero value “0”: null reliability and a “1” total reliability, these results indicate whether the questionnaire instrument is reliable to determine the relationship between pharmaceutical advertising and consumption of OTC drugs in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022. The Cronbach's alpha coefficient method obtained is 0.937, providing total reliability.\n\nA normality test was also performed on the pharmaceutical advertising message dimension, the mass media dimension, the pharmaceutical product promotion dimension, the dimension of excessive consumption of drugs under the influence and responsibility of the pharmaceutical industry, and the OTC drug consumption variable, obtaining a value of 0.000 for all of them. Therefore, it can be inferred that the sample data present a non-normal distribution, and the Spearman's Rho non-parametric statistic should be used.17,18\n\nThe research work was developed through the survey technique and the questionnaire was used as an instrument, which was validated by three experts in the research topic, the surveys are divided into variable 1, pharmaceutical advertising, consisting of 11 questions and variable 2, OTC drug consumption, consisting of nine questions for a total of 20 items. The results will be organized in the Microsoft Excel 2019 program (RRID:SCR_016137) and will allow us to analyze, manage and share decision making. They will then be transferred to IBM SPSS Statistics version 22 (Statistical package for social sciences) (RRID:SCR_002865). The descriptive statistical analysis allowed us to summarize the information in graphs and tables, which were illustrated with images. To analyze our research hypothesis, we used Spearman's correlation coefficient. Likewise, the SPSS version 22 program indicated that the data had a non-normal distribution with a P-value of less than 0.05.\n\nFor this study, we took into account the regulations of the code of ethics for research at the Norbert Wiener Private University, taking into account the ethical criteria for research, which indicates that we must ensure the protection of the rights, safety and well-being of human beings who, in the use of their faculties and free will, accept to be subjects of the study(47); for this reason, informed consent was obtained in a CIE-VRI research study so that the user could express his intention to participate in the survey voluntarily. The consent of the SUPERFAR drugstore, which provided its facilities to conduct the surveys, was also authorized.\n\n\nConsent\n\nRegarding the consent for the participation in the research, it should be indicated that the instrument applied, had a written informed consent for the application of this, which was intended to provide information to the person about the survey. Information such as the use of the potential answers, the duration of the survey, the receipt of an incentive for answering the questionnaire and the assurance that the identity of each person would be protected, always keeping them anonymous.\n\nLikewise, the survey was approved by the ethics committee of the Universidad Norbert Wiener with the resolution of document N°138-2022-DFFB/UPNW issued by the Faculty of Pharmacy and Biochemistry.\n\n\nResults\n\nTable 2 shows that of the 269 users surveyed, 16.7% (45) indicate that no one is influenced by pharmaceutical advertising to consume OTC medicines, 59.5% (160) are some and 23.8% (64) represent the range all are influenced by pharmaceutical advertising to consume OTC medicines.\n\nTable 3 shows that of the 269 users surveyed, 21.9% (59) indicate that no one is influenced by the pharmaceutical advertising message to consume OTC medicines, 65.1% (175) are some and 23.8% (64) represent the range all are influenced by the pharmaceutical advertising message to consume OTC medicines.\n\nTable 4 shows that of the 269 users surveyed, 27.5% (74) indicate that no one is influenced by pharmaceutical mass media to consume OTC medicines, 61.0% (164) are some and 11.5% (31) represent the range all are influenced by pharmaceutical mass media to consume OTC medicines.\n\nTable 5 shows that of the 269 users surveyed, 22.7% (61) indicate that no one is influenced by pharmaceutical product promotion to consume OTC medicines, 61.0% (164) are some and 11.5% (31) represent the range all are influenced by pharmaceutical advertising to consume OTC medicines.\n\nTable 6 shows that of the 269 users surveyed, 38.3% (103) indicate that no one practices excessive consumption of drugs under the influence and responsibility of the pharmaceutical industry 50.6% (136) are some and 11.2% (30) indicate that all practice excessive consumption of medicines under the influence and responsibility of the pharmaceutical industry.\n\nTable 7 shows that of the 269 users, 21.2% (57) do not consume OTC medicines induced by pharmaceutical advertising, 55.8% (150) represent the range of some and 23.0% (62) all consume OTC medicines induced by pharmaceutical advertising.\n\nTable 8 shows that the P value is less than 0.05, which indicates that there is a correlation, with a Spearman's Rho value of r = 0.729 indicating that the correlation is strong and direct between variable 1 pharmaceutical advertising and variable 2 consumption of OTC drugs in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH0: There is no significant relationship between pharmaceutical advertising and the consumption of OTC medicines among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH1: There is a significant relationship between pharmaceutical advertising and the consumption of OTC medicines among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nTable 9 shows that the P value is less than 0.05, which indicates that there is a correlation, with a Spearman's Rho value of r = 0.597 indicating that the correlation is moderate and direct between dimension 1 the pharmaceutical advertising message and variable 2 the consumption of over-the-counter (OTC) drugs in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH0: There is no significant relationship between the pharmaceutical advertising message and the consumption of OTC drugs among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH1: There is a significant relationship between the pharmaceutical advertising message and the consumption of OTC drugs in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nTable 10 shows that the P value is less than 0.05, which indicates that there is a correlation, with a Spearman's Rho value of r = 0.525 indicating that the correlation is moderate and direct between dimension 2 mass media and variable 2 consumption of over-the-counter (OTC) drugs among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH0: There is no significant relationship between the mass media and the consumption of OTC drugs among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH1: There is a significant relationship between mass media and the consumption of OTC drugs among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nTable 11 shows that the P value is less than 0.05, which indicates that there is a correlation, with a Spearman's Rho value of r = 0.637 indicating that the correlation is moderate and direct between dimension 3, Promotion of the pharmaceutical product, and the consumption of OTC drugs in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH0: There is no significant relationship between the promotion of the pharmaceutical product and the consumption of OTC drugs among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH1: There is a significant relationship between the promotion of the pharmaceutical product and the consumption of OTC drugs in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nTable 12 shows that the P value is less than 0.05, which indicates that there is a correlation, with a Spearman's Rho value of r = 0.670 indicating that the correlation is moderate and direct between dimension 4, excessive consumption of drugs under the influence and responsibility of the pharmaceutical industry, and variable 2, the consumption of OTC drugs among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH0: There is no significant relationship between the excessive consumption of medicines under the influence and responsibility of the pharmaceutical industry and the consumption of OTC medicines among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\nH1: There is a significant relationship between the excessive consumption of medicines under the influence and responsibility of the pharmaceutical industry and the consumption of OTC medicines in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.\n\n\nDiscussion and conclusion\n\nThe main limitations of this research were the access and lack of information in Spanish that exists in the relevant pages for our research, which often require registration or payment to access their information. On the other hand, the time limited by the SUPERFAR Pharmaceutical establishment in barrios altos-cercado de lima to carry out the surveys with the established opening hours to carry out the surveys to the users.\n\nIn the general hypothesis, there is a significant correlation between pharmaceutical advertising and the consumption of OTC drugs in users of the SUPERFAR pharmacy in Barrios Altos-Cercado de Lima, 2022, because a P value of 0.000 less than 0.05 and Spearman's Rho of r = 0.729 were found, indicating that the strength of correlation is high and direct between the two variables, thus rejecting the null hypothesis and approving the alternative hypothesis. Coinciding with Gamarra19 who pointed out in his research that there is a relationship between misleading advertising and the violation of consumer rights, evidencing in his results a positive relationship with a Pearson's percentage of 0.857 being the significant value (0.000 < 0.05) considered positive and direct relationship between pharmaceutical advertising and the violation of the buyer's rights. As mentioned by Domingo et al.,20 advertising has an important influence on the public and these advertisements should contribute to making rational decisions on OTC drugs; however, the information is very limited and almost always omits the dosage, duration of treatment, adverse effects and contraindications.\n\nAnalyzing the specific Hypothesis 1 There is a significant relationship between the pharmaceutical advertising message and the consumption of OTC medicines in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022, we found a P value of 0.000 less than 0.05 and Spearman's Rho of r = 0.597 which indicates that the strength of correlation is moderate and direct between dimension 1 and variable 2, thus rejecting the null hypothesis and approving the alternative hypothesis. In this way, we can contradict the research conducted by Cancho and Echevarría21 who determined the relationship between factors associated with self-medication and classes of drugs in users of the Botica Biofarma, indicating that the Family factor and convincing by the pharmaceutical staff are the most influential means for the acquisition of over-the-counter drugs with a margin of error of 16.60%, indicating that there is no relationship between the variables. Unlike Rodriguez J.22 states that the pharmaceutical advertising message aims to inform, remind about the products or services that are intended to provide to the population, or potential consumers who have needs to soothe or persuade some discomfort immediately.\n\nConsidering the specific hypothesis 2, there is a significant relationship between mass media and the consumption of over-the-counter (OTC) medicines in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022, the results were obtained with a P value of 0.000 less than 0.05 and Spearman's Rho of r = 0.525, indicating that the strength of correlation is moderate and direct between dimension 2 and variable 2, thus rejecting the null hypothesis and approving the alternative hypothesis. Therefore, in relation to their research by López and Reátegui23 to discover opportunities for improvement for the pharmaceutical sector, they point out that the most influential pharmaceutical advertisements are the Social Networks with entertaining, shocking and credible contents, this was determined by means of surveys which they then proceeded to analyze in IBM statistics SPSS version 25, providing a correlation coefficient of 0.249 with a significance of 0.000 considering it to be positive. Agreeing with Gutiérrez A. and Mora E.24 consider that the most influential means of communication in the population is the audiovisual media because they fix the products in the mind of the consumers unconsciously and these do not consume them for their therapeutic properties in themselves, but for the added values provided by pharmaceutical advertising.\n\nWith respect to specific hypothesis 3, there is a significant relationship between the promotion of the pharmaceutical product and the consumption of over-the-counter (OTC) medicines among users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022. A P value of 0.000 less than 0.05 and Spearman's Rho of r = 0.637 were found, indicating that the correlation is moderate and direct between dimension 3 and variable 2, thus rejecting the null hypothesis and approving the alternative hypothesis. In such a way we can support what was exposed by Lopez25 who determined the factors that influence the acquisition of brand and/or generic drugs in the pharmacy of the San Juan de Dios Cusco Clinic, calculating Pearson's Chi-squared for dimension 2 external factors has a P value = 0.000 is less than α = 0.05, leaving evidence of a positive result for its indicators price, advertising and pharmacotherapeutic alternatives. As mentioned by Tipan, et al., drug promotion is a persuasive activity carried out by manufacturers and distributors that generate conflicts of interest by giving free gifts or lowering their prices unconsciously, users have consumed products from that laboratory.26\n\nFinally, in the specific hypothesis 4, there is a relationship between the excessive consumption of medicines under the influence and responsibility of the pharmaceutical industry and the consumption of OTC medicines in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022. A P value of 0.000 less than 0.05 and Spearman's Rho of r = 0.670 were found, indicating that the correlation strength is moderate and direct between dimension 4 and variable 2, thus rejecting the null hypothesis and approving the alternative hypothesis, Therefore, in relation to their research by Bastos and Garcia27 to identify the habits of consumption of OTC drugs by university students in the health area, it was obtained that self-medication is not harmful to health with a P value of 0.0015 lower than 0.05, indicating that there is an association between the values and in criteria at the time of consuming or buying a medicine has a P value = 0.0463 < 0.05 it was evidenced that more than half of the student population agrees that self-medication practices are harmful to health, but they consider that the symptoms treated are not serious and that they are familiar with these OTC medicines. As mentioned by Lobo F.28 states that drug advertising is largely responsible for the education on the excessive consumption of drugs by placing in the media images of doctors or health personnel recommending their products and providing the assurance that a product is good for their therapy and creating a vicious circle that is difficult to break.\n\nIn conclusion, in relation to the general objective: the relationship between pharmaceutical advertising and the consumption of OTC medicines in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022, was determined, based on the result of Spearman's Rho value of r = 0.729, indicating that the correlation is strong and direct. In relation to specific objective 1: the relationship between dimension 1 (pharmaceutical advertising message) and variable 2 (consumption of over-the-counter medicines) was determined, based on the result of Spearman's Rho value r = 0.597 indicating that the correlation strength is moderate and direct. In relation to specific objective 2: the relationship between dimension 2 (pharmaceutical mass media) and variable 2 (consumption of OTC medicines) was determined, based on the result of Spearman's Rho value r = 0.525, indicating that the strength of correlation is moderate and direct. In relation to specific objective 3: the relationship between dimension 3 (promotion of the pharmaceutical product) and variable 2 (consumption of over-the-counter medicines) was determined, based on the result of Spearman's Rho value of r = 0.637, indicating that the correlation is moderate and direct. In relation to specific objective 4: the relationship between dimension 4 (excessive consumption of medicines under the influence and responsibility of the pharmaceutical industry) and variable 2 (consumption of OTC medicines) was determined, based on the result of Spearman's Rho value of r = 0.670 indicating that the correlation strength is moderate and direct.\n\n\nData availability\n\nZenodo: Pharmaceutical advertising and the consumption of over the counter (OTC) medicines in users of the Superfar drugstore in Barrios Altos-Cercado de Lima, 2022, https://doi.org/10.5281/zenodo.6544660.29\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nCastro K: La influenciade la publicidad farmacéutica en las prácticas de automedicación [tesis]. Ecuador: Universidad Politécnica Salesiana- Sede Quito.2016.Reference Source\n\nViña-Pérez G, Debesa-García F: La industria farmacéutica y la promoción de los medicamentos. Una reflexión necesaria. Gac Méd Espirit. 2017 Ago. [citado 2021 Sep. 26].Reference Source\n\nVillada S, Sánchez J: Factores clave en la comercialización online de medicamentos [tesis]. Colombia: Universidad Católica de Pereira Facultad de Ciencias Económicas y Administrativas Administración de Empresas, Pereira.2019.Reference Source\n\nOrtiz S: Comportamiento del consumidor de productos farmacéuticos en el distrito de Trujillo durante la emergencia sanitaria COVID -19, 2020. [tesis]. Perú-Iquitos: Universidad Privada de la Selva Peruana- Facultad De Ciencias Empresariales Carrera Profesional de Administración.2020.Reference Source\n\nSocican: Promoción Ética de Medicamentos en el Perú [tesis], Aspec, Mayo-2009.Reference Source\n\nHuapaya: Regulación de publicidad de productos farmacéuticos en Perú.2021; pág. 83–93.Reference Source\n\nSosa: Determinación de factores asociados a la automedicación san martín de porres-lima-Perú [tesis], 2019. Perú: Universidad María Auxiliadora (UMA) Facultad De Ciencias De La Salud Escuela Profesional De Farmacia Y Bioquímica.2019.Reference Source\n\nDigemid, Minsa L: Promoción y publicidad farmacéutica [boletin].2014Reference Source\n\nFernández J: Problemáticas de la prohibición de publicidad directa de medicamentos con receta médica: descripción y recomendaciones [tesis]. Universidad de Lima Escuela de Posgrado Maestría en Derecho Empresarial, Lima-Peru.2020.Reference Source\n\nAguirre C, Orellana G: Influencia de la publicidad en la decisión de compra de productos farmacéuticos antiinflamatorios no esteroideos de venta libre (AINE) en consumidores en Lima Metropolitana durante el mes de setiembre de 2012[tesis], Lima-Peru.2013Reference Source\n\nCabezas E, Andrade D, Torres J: Introducción a la Metodología de la investigación científica com.ed. F.F.A.A. ESPE. Ecuador.2018 [citado 21 noviembre 2021]. Prim. Edic.Reference Source\n\nMestanza A, Tirado L: Automedicación con antigripales y riesgo de reacciones medicamentosas en personas mayores de 18 años en boticas y farmacias del distrito de baños del inca – Cajamarca 2020. Perú.2021. [citado 21 noviembre 2021].Reference Source\n\nMogollón G, Montañez T: Publicidad y relación con el consumo de medicamentos de venta libre en botica INKAFARMA Lince – 1047, Perú 2020.2020 [citado 21 noviembre 2021].Reference Source\n\nArias-Gómez J, Villasís-Keever MÁ, Novales M, et al.: El protocolo de investigación III: la población de estudio. Rev. Alerg. Mex. 2016; [citado 24 noviembre 2021]; 63(2): 201–206. Publisher Full Text Recuperado de:Reference Source\n\nOtzen T, Manterola C: Técnicas de Muestreo. Int. J. Morphol. 2017 [citado 26 noviembre de 2021]; 35(1): 227–232. Publisher Full Text Reference Source\n\nÑaupas, et al.: Metodología de la investigación cuantitativa-cualitativa. Colombia:edicionesdelau;2018. [citado 26 noviembre 2021].Reference Source\n\nRomero M: Pruebas de bondad de ajuste a una distribución normal. Rev. Enf. del trabajo. 2016 julio [citado 16 marzo de 2022]; 6(3): 105–114.Reference Source\n\nGonzález C: Estrategias De Aprendizaje Y Rendimiento Académico De Los Estudiantes Del Curso De Aprendizaje Investigativo Del Instituto De Lima, 2017- I. [tesis]. Lima: Universidad Privada Norbert Wiener, Escuela De Posgrado.2017.Reference Source\n\nGamarra A: “Publicidad engañosa y vulneración a los derechos del consumidor en las boticas de Canto Grande, San Juan de Lurigancho- 2017” [Tesis],Universidad Cesar Vallejo, Facultad de derecho, Escuela ´profesional de Derecho, Lima-Peru.2018.Reference Source\n\nDomingo P, Tenllado M, Martínez P, et al.: Estrategias para fomentar un adecuado compromiso del farmacéutico. Rev. de la Fac. Cienc. Méd. Córdoba. 2018 [citado 18 nov. 2021]; 75(4).Reference Source\n\nCancho L, Echevarría G: Factores asociados a la automedicación en usuarios de la botica biofarma de la ciudad de Huancavelica- 2015[Tesis], Universidad Nacional de Huancavelica Facultad de Enfermeria, Peru-Huancavelica.2015.Reference Source\n\nCenteno R, Carlos J: La publicidad como herramienta de las distintas modalidades de comunicación persuasiva. Global Media Journal México. 2018 [citado 18 nov. 2021]; 1 (1). 2004.Reference Source\n\nLópez V, Reategui A: Actitud, Comportamiento e Intención de Compra de los Consumidores Finales hacia la Publicidad en Redes Sociales de Productos Farmacéuticos OTC en San Borja Lima. Caso Aplicado: MiFarma, Inkafarma, Boticas y Salud y Universal, Universidad Peruana de Ciencias Aplicadas (UPC),Perú.2019.Reference Source\n\nGutiérrez A, Mora E: Los medicos y la industria farmacéutica: Una relación de vulnerabilidad vista desde la Bioética.2004 [citado 18 nov. 2021]. Bogotá.Reference Source\n\nLopez L: Factores que influyen en la adquisición de medicamentos de marca y genéricos en la farmacia de la Clínica San Juan de Dios Cusco [Tesis], Universidad Cesar Vallejo, escuela de posgrado, Peru-2018.Reference Source\n\nTipán J, Zavala A, Estévez L: Bioética y la promoción de medicamentos. Rev. Médica Ateneo. 2021[citado 18 nov. 2021]; 23(1): 89–100.Reference Source\n\nBastos H, García J: Hábitos de consumo de medicamentos OTC en estudiantes del área de la salud de tres Universidades de la ciudad de Cartagena durante el primer periodo académico del 2017. [Tesis]. Montevideo, Uruguay: Universidad de la República.2017. [citado 10 noviembre 2021].Reference Source\n\nLobo F: El sistema de desinformación Farmacéutica. Ed. 5.Universidad de Oviedo;82–117.Reference Source\n\nAMBROCIO TEODORO ESTEVES PAIRAZAMAN: Underlying data for “Pharmaceutical advertising and the consumption of over the counter (OTC) medicines in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022.” [DATA].2022. Publisher Full Text"
}
|
[
{
"id": "143788",
"date": "25 Jul 2022",
"name": "Renly Lim",
"expertise": [
"Reviewer Expertise Drug utilisation",
"medication safety",
"quality use of medicines",
"pharmacy practice"
],
"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\nThank you for the opportunity to review the manuscript. The topic is very interesting, however, the methodology and findings are questionable. More specific comments below:\nThere’s limited details in the abstract methods section. It is unclear what the authors actually did. How did the authors define pharmaceutical advertising. Similarly how did the authors define consumption? How was this measured?\n\nThe introduction section is written rather informally more like a news article instead of a journal article.\n\nThe last few paragraphs in the introduction section are also confusing – why did the authors have separate justification, general question and purpose?\n\nIn the methods section, the authors presented methods and results of validation of the tool, I am not sure why this was included? Shouldn’t this be reported separately in another paper, for example?\n\nIt is also unclear how the authors defined “influence by pharmaceutical companies”\n\nThe results section is really difficult to follow, with 12 tables presented one after the other.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "165092",
"date": "20 Mar 2023",
"name": "Ashenafi Kibret Sendekie",
"expertise": [
"Reviewer Expertise Quality use of medicines",
"pharmacy practice",
"chronic medication care"
],
"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\nThank you for giving me the opportunity to review a paper entitled “Pharmaceutical advertising and the consumption of over the counter (OTC) medicines in users of the SUPERFAR drugstore in Barrios Altos-Cercado de Lima, 2022”\nThe authors came up with an interesting area, pointing out the importance of providing evidence and literature in the area. However, the manuscript could be carefully revised unless it is difficult to publish in its current form.\nGeneral comments to the authors\nThere is unnecessary repetition of words and unclear and ambiguous statements throughout the manuscript.\n\nNeeds some English editing\n\nAvoid unnecessary and uncommon abbreviations.\n\nUse the full length and abbreviations together for abbreviated phrases when they come up for the first time. And then, use the abbreviation form consistently.\n\nUse words and phrases consistently, particularly for major objectives.\nSpecific comments\nAbstract\n\nHow were the outcomes for each objective measured? At least some measuring methods and techniques for pharmaceutical advertising and consumption could be mentioned in the abstract.\n\nAnd please verify whether the abstract is written per the journal standard.\n\nIntroduction\n\nIt is written just as normal, not organized well.\n\nThere are statements without reference. Please ensure that the sources of all statements need to be acknowledged by citing them.\n\nYou are mentioning the title, the journal, etc. of some of the reference papers. Mentioning this much detail may not be necessary. Enough to mention the study setting, including country, design, or author, and focus on the issue and what they did or found.\n\nThe research questions and hypotheses are disorganized, and it is better to reorganize your research questions and hypotheses.\nMethods\nWhere is Table 1 cited in the manuscript? I didn’t find its importance, and it is not clear.\n\n\"Persons under 18 years of age: Do not accept the questionnaire; do not buy medicines in the SUPERFAR drugstore.\" These are mentioned in the exclusion criteria. But these were totally excluded from the beginning. Subjects who need to be excluded should be eligible to include first; then they might be excluded for different reasons. Thus, there is no need to exclude this population because it is not already included.\n\nThere are proposal-like statements in the method section that need to be changed.\n\nYou stated that the outcome measurement of pharmaceutical advertising was determined using 11 items, and similarly, OTC drug consumption was measured using 9 items using a Likert scale score. Then what is final? How the score was counted? What was the value of each scale? Is an increase or decrease in score to be counted as good on the outcome measures? These issues need to be presented in detail and clearly.\n\nOutcome (pharmaceutical advertising and OTC drug consumption) measures need to be clearly presented.\nResults\nThe study had a total of 269 participants, according to the results. How could a 100% response rate be achieved? It is preferable to share any data collection experience; it will be beneficial to others as well.\n\nThe result should be reorganized and presented based on the objectives.\n\nThe description of the tables should be concise and focused on the main variables of the study.\nDiscussion\n\nNeed to focus on the major objectives and findings.\n\nThe gaps mentioned in the methods and results sections need to be clear and correspond to the discussion.\nConclusion\n\nNeed to be concise and focused on the major findings.\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? 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? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-637
|
https://f1000research.com/articles/11-635/v1
|
09 Jun 22
|
{
"type": "Review",
"title": "Hyperoside: a review of pharmacological effects",
"authors": [
"Qi Li",
"Fuchen Song",
"Meidong Zhu",
"Qianzhu Wang",
"Yan Han",
"Yinlu Ling",
"Lirui Qiao",
"Ni Zhong",
"Lei Zhang",
"Qi Li",
"Fuchen Song",
"Meidong Zhu",
"Qianzhu Wang",
"Yan Han",
"Yinlu Ling",
"Lirui Qiao",
"Ni Zhong"
],
"abstract": "Hyperoside, also known as quercetin-3-O-β-D-galactopyranoside, belongs to the class of flavonol glycosides. Its aglycon is quercetin, and the sugar base is galactopyranoside. It is made of quercetin. The O atom at the 3rd position of the element is connected to the sugar group by a β-glycosidic bond. Hyperoside, which is widely present in the planted objects, such as the fruits and whole plants of Hypericaceae, Rosaceae, Campanulaceae, Lamiaceae, and Berberis spp., has received extensive attention due to its anti-inflammation, anti-oxidation, anti-tumor, and other disease activities, as well as its protective effects on the cardiovascular system, nervous system, digestive system and immune system. While glycosides are a commonly researched topic, there are very few studies on the metabolic pathways, and its overuse and adverse reactions are rarely reported. This article provides a comprehensive review of the pharmacological research results of hyperoside, and a new perspective on the limitations of the existing research on metabolic pathways and toxicology. It provides new ideas for further research and clinical application of hyperoside.",
"keywords": [
"hyperoside",
"natural product",
"effect",
"therapy",
"pharmacology",
"review."
],
"content": "1. Introduction\n\nPlants have been used as folkloric sources of medicinal agents since the beginning of humankind. Following the emergence of modern medicine and single pure drugs, plant-derived active principles and their semi-synthetic and synthetic analogs have served as a major route to new pharmaceuticals (Lee, 1999). Hyperoside, a flavonoid compound (Magnus et al., 2020), is isolated from Hypericaceae (Figure 1), Rhododendron ponticum L. Rosaceae, Campanulaceae, Lamiaceae, and Berberis (Guo et al., 2020). Hyperoside, which is the main active ingredient of many Hypericum and Crataegus plants, has anti-inflammatory, anti-oxidant, anti-tumor, anti-bacterial and anti-viral, anti-coagulant, anti-platelet and lipid-lowering, hypoglycemic, and other pharmacological activities. It can protect the liver, kidney, and nervous, cardio-cerebrovascular, and cardio-cerebrovascular systems. Over recent years, the antidepressant, anti-neurodegenerative, and bone protective effects of hyperoside have also attracted people’s attention. Clinically, several drugs containing hyperoside or made from hyperoside have been widely used (Chen et al., 2020; He et al., 2016; Qian et al., 2007; Wang et al., 2011; Wei et al., 2009; Wu et al., 2019; Zou et al., 2004).\n\nWith the continuous development of scientific research, numerous comprehensive studies have been conducted for hyperoside, including those addressing many pharmacological effects. Hyperoside can effectively prevent age-related kidney damage, protect human primary melanocytes from oxidative damage induced by H2O2, and liver fibrosis induced by heart failure in rats (Guo et al., 2019b; Liu et al., 2018a; Yang et al., 2016). Hyperoside can also effectively induce the apoptosis of breast cancer cells, autophagy, and apoptosis of non-small cell lung cancer cells, and inhibit the survival and proliferation of lung cancer cells induced by hypoxia (Chen et al., 2020; Fu et al., 2016; Qiu et al., 2019). Considering anti-inflammatory effects, hyperoside glycosides can effectively reduce allergic airway inflammation, inhibit lipopolysaccharide-induced inflammation of microglia, and depress pro-inflammatory cytokines in human lung epithelial cells infected with Mycoplasma pneumonia (Fan et al., 2017; Liu et al., 2019a; Ye et al., 2017), all of which show the great potential of hyperoside for the development of a new drug. Therefore, this article reviews the existing pharmacological effects of hyperoside to provide references for further research on hyperoside.\n\n\n2. Source and chemistry of hyperoside\n\nThe chemical structure of hyperoside (Figure 2) is composed of two phenyl rings (A ring and B ring), a hexaoxy heterocyclic ring (C ring), and a galactoside (D ring). It is a pale-yellow needle crystal with a melting point of 227–229°C. The rotation rate is −83°C (C=0.2, pyridine), which is easily soluble in ethanol, methanol, acetone, and pyridine. It reacts with magnesium hydrochloric acid powder by producing fuchsia color, ferric chloride by producing green color, and naphthol by positive reaction (Lavie et al., 1995; Liu et al., 2019b). Compared with synthetic drugs, natural plant drugs have fewer side effects and higher economic value. Hyperoside is found in a variety of plants. For example, the content range of hyperoside is 2.790–6.502 mg/g in Cuscuta chinensis (Lin et al., 2007), 3.64 μg/100 mg in the dried Geranii robertiani herba (Fodorea et al., 2005), 0.85–2.7 mg/g in the hawthorn buds (Jakstas et al., 2004), and 4.6–4.9 mg/g in St. John’s Wort (Bertoli et al., 2008). However, the content is relatively low in plants, where it is mainly synthesized from rutin.\n\n\n3. Pharmacological effects\n\nAs early as 1996, Wang et al. (1996) found that hyperoside has a protective effect on myocardial ischemia/reperfusion injury. After years of follow-up studies by other scholars, the effect has been reaffirmed. Hyperoside has a protective effect on cardiomyocyte injury induced by hypoxia/reoxygenation through anti-oxidant properties. After hyperoside preconditioning, the activities of Bnip3, Bax, and caspase3 decrease, and the expression of Bcl-2 increases (Xiao et al., 2017). Hyperoside can alleviate heart failure by inducing autophagy, inhibiting apoptosis, changing the level of apoptosis-related proteins, and promoting the autophagy of H9C2 cells induced by angiotensin II. Most importantly, hyperoside can reduce the heart/body weight ratio and the cross-sectional area of cardiomyocytes (Guo et al., 2020). Recent studies proved that (Wang et al., 2018b) hyperoside can also prevent cardiac hypertrophy by blocking the activation of the AKT signal pathway and protecting heart remodeling caused by pressure overload. In the model of oxidative injury induced by high glucose, hyperoside protects cardiomyocytes from oxidative stress induced by high glucose by activating PI3K/AKT/Nrf2 signal pathway (Wang et al., 2018a). After the hyperoside intervention, cardiac function parameters of cardiomyocytes injured by ischemia-reperfusion injury obtained significant improvements. The possible mechanism is that hyperoside-activated anti-oxidant Nrf2 signal pathway and decreased the level of endoplasmic reticulum stress and oxidative stress (Hou et al., 2016). However, some studies suggested that the protective effect of hyperoside on ischemia–reperfusion injury of isolated rat cardiomyocytes may be related to the activation of the ERK signal pathway, thus promoting the phosphorylation of extracellular signal-regulated protein kinase, improving myocardial contractile function, and reducing the myocardial infarct size (Li et al., 2013).\n\nThe effect of hyperoside on cerebral ischemia–reperfusion injury has also been previously reported. Hyperoside was administered to rats at doses of 6.25, 12.5, and 25 mg·kg−1, which can significantly improve abnormal neurological symptoms. Among them, 12.5 and 25 mg·kg−1 significantly reduced infarct weight, inhibited the increase of MDA and NO in rats’ cerebral cortex, increased the CBF of the cerebral cortex, and protected cerebral infarction by reducing lipid peroxidation and NO (Chen et al., 1998). Liu et al. (2012) studied primary cultured rat neurons and created ischemia–reperfusion cell model (OGDR), reporting that hyperoside could significantly reduce the damage caused by OGDR to neurons and that internal mechanisms were related to the NO signal pathway. The regulation of hyperoside may be related to the BKC a channel by activating TRPV4, reducing the concentration of Ca2+ in cells, relaxing blood vessels, forming a new therapeutic target for protecting ischemic brain injury, and participating in brain protection (Han et al., 2018).\n\nThe inhibitory effect of hyperoside on tumor has been confirmed in various human malignant tumor cells such as lung, breast, liver, prostate, colon, gastric, and similar. The important reason for the unrestricted growth of tumor cells is the loss of their active and physiological apoptotic ability. Therefore, inducing tumor cell apoptosis and inhibiting tumor cell proliferation are the main purposes of most anti-tumor drugs (Shi et al., 2014). Hyperoside can affect tumor cells through different mechanisms of action, including depressing proliferation, promoting apoptosis, blocking cell cycle.\n\nHyperoside could inhibit the survival and proliferation of hypoxia-induced non-small cell lung cancer cell line A549 in a dose-dependent manner, possibly through iron accumulation on the AMPK/HO-1 axis to combat hypoxia-induced survival and proliferation of A549 (Chen et al., 2020). In vitro experiments revealed that hyperoside could induce autophagy and apoptosis in human non-small cell lung cancer by inhibiting the activation of the Akt/mTOR/p70S6K signaling pathway (Fu et al., 2016). By inducing the inactivation of the NF-kB signaling pathway, activating caspase3 regulated by Bcl-2/Bax, and increasing lung cancer malignant tumor cell apoptosis, hyperoside can also inhibit lung cancer growth. Regulating caspase-3 and p53 inhibits the proliferation, migration, and invasion of lung cancer cells, promotes the expression of pro-apoptotic factors, and suppresses the expression of anti-apoptotic factors (Liu et al., 2016; Lü, 2016). Apoptosis is closely related to the activation of p38MAPK and JNK-induced mitochondrial death pathway (Yang et al., 2017c). Further studies proved that hyperoside mediates p38MAPK and AKT/PI3K signaling pathways, regulates the expression of genes related to migration and invasion and inhibits the invasion and migration of A549 cells (Yang et al., 2017b). Some studies have shown that hyperoside can also work synergistically with some drugs to exert its anti-tumor effect. Hyperoside can inhibit the proliferation of A549 cells by inducing cell apoptosis and G1/S phase arrest. Let-7a-5p can inhibit the proliferation of A549 cells by blocking the cell cycle in G1/S phase. At the same time, microRNA-let-7a-5p directly regulates the expression of CCND1 in A549 cells. Hyperoside combined with let-7a-5p can effectively inhibit the proliferation of A549 cells (Li et al., 2018a).\n\nAccording to breast cancer research, hyperoside can reduce the production of ROS, inhibit the transcription activity of NF-kB and the expression of Bcl-2 and XIAP, promote the expression of Bax and cleaved caspase-3, and induce breast cancer cells MCF-7 and the apoptosis of 4T1 that can scavenge free radicals and has a cytotoxic effect on breast cancer MCF-7 cells (Qiu et al., 2019). Hyperoside can inhibit the viability of breast cancer cells without being cytotoxic to normal breast mammary epithelial cell lines (Agar et al., 2015). It also increases cell apoptosis and caspase-3 activity, inhibits the activation of TLR4-NF-κB signal transduction caused by paclitaxel, reduces the expression of anti-apoptotic protein Bcl-2, enhances the expression of pro-apoptotic protein Bax and pro-inflammatory cytokines IL-6, and IL-6 protein levels increase the sensitivity of paclitaxel to breast cancer cells MDA-MB-231 (Sun et al., 2020). In other types of cancer, hyperoside can also exert its anti-cancer effect. Guo et al found that hyperoside can reduce the expression of the C-Myc gene in cervical cancer C-33A and HeLa cells and promote the expression of TFRC. To inhibit the proliferation of cervical cancer cells (Guo et al., 2019a), hyperoside may induce the apoptosis of human endometrial RL952 cells through the Ca2+-related mitochondrial apoptosis pathway, and it can induce death receptor-mediated and mitochondrial-mediated apoptosis. The apoptotic pathway induces apoptosis of HT-29 human colon cancer cells, thereby inhibiting tumor growth (Guon and Chung, 2016; Li et al., 2012a). Hyperoside can inhibit GSH-Px and CAT mRNA expression by inducing caspase-dependent apoptosis and p53 signaling pathway and participating in the pro-apoptotic signal transduction of SW620 human colorectal cancer cells (Zhang et al., 2017a). It can also induce apoptosis of SW579 human thyroid squamous cell carcinoma cells, partly by up-regulating Fas during apoptosis And FasL mRNA expression and down-regulating survivin protein expression to induce apoptosis (Liu et al., 2017). Hyperoside inhibits the cycle of INS-1 and MIA PaCa-2 pancreatic cancer cells in the G2/M phase and activates caspase-3 protein expression, induces apoptosis of tumor cells, and inhibits the proliferation of osteosarcoma cells by inducing G0/G1 block in the cell cycle (Boukes and van de Venter, 2016; Zhang et al., 2014). It may also reactivate caspase-9 and caspase-9 by inhibiting BAD phosphorylation, increase the level of p27 by up-regulating LC-II in the HL-60 AML cell line; it can induce autophagy, and enhance the apoptosis-inducing effect of As2O3 on acute myeloid leukemia cells (Zhang et al., 2015). Hyperoside can also down-regulate β1-adrenergic receptors in rat C6 glioblastoma cells, reduce the β1AR density in the plasma membrane, and subsequently reduce downstream signal transduction, thus inhibiting the growth of tumor cells (Jakobs et al., 2013). High glycosides use PGRMC1-dependent autophagy to induce apoptosis and cell death of ovarian cancer cells and increase tumor cells’ sensitivity to cisplatin drugs. In combination with quercetin, it can inhibit prostate cancer cells and kidney cancer by regulating microRNA-21 Cell growth and metastasis (Li et al., 2014; Yang et al., 2015; Zhu et al., 2017).\n\nGrowing evidence has suggested that hyperoside has anti-inflammatory, anti-oxidant stress, anti-swelling, anti-bacterial and anti-viral effects in vivo and in vitro. Due to the anti-inflammatory effect, hyperoside is commonly applied in the treatment of a variety of inflammatory-related diseases.\n\nHyperoside can inhibit the release of lipopolysaccharide (LPS)-mediated HMGB1 and HMGB1-mediated cytoskeletal rearrangement and inhibit the HMGB1 signaling pathway to treat vasculitis (Ku et al., 2015). Zhou et al. (2018) explored the effects of hyperoside on inflammation and apoptosis of human umbilical vein endothelial cells induced by endotoxin. They found that 20 μg/L and 50 μg/L hyperoside could significantly increase the survival rate of human umbilical vein endothelial cells induced by LPS. In addition, hyperoside could decrease the mRNA expression of IL-1β, IL-6, TNF-α, and iNOS in umbilical vein endothelial cells in a dose-and time-dependent manner. Furthermore, some studies showed that hyperoside could inhibit vascular inflammation mediated by TNF-α, which is characterized by the drop of VCAM-1 expression in vascular smooth muscle cells and the adhesion ability of monocytes to vascular smooth muscle cells, where hyperoside (10, 50, 100 μmol/L) dose-dependently inhibited the proliferation and migration of human RAFLSs induced by LPS, reduced the production of TNF-α, IL-6, IL-1 and MMP-9 in LPS-stimulated cells and inhibited lipopolysaccharide. Moreover, it induced p65 and IκBα phosphorylation, lipopolysaccharide-induced p65 nuclear translocation, and NF-κB DNA adhesion at 3 weeks after administration, thus significantly reducing the clinical score of collagen-induced arthritis (CIA) in mice, reduced synovial hyperplasia, inflammatory cell infiltration, and cartilage damage (Fan et al., 2017; Jang et al., 2018; Jin et al., 2016; Yang et al., 2017a). In another study, hyperoside significantly inhibited the loss of cell viability and the increase in endothelial Ca2+ content and apoptosis in HUVEC induced by H2O2, and reduced B-cell lymphoma (Bcl)-2 related X Protein (Bax). It also cleaved caspase-3 and phosphorylated p38 mRNA expression levels while increasing the mRNA expression of Bcl-2 in H2O2-induced HUVEC, thus indicating that it has a certain anti-H2O2-induced HUVEC apoptosis effect, as well as a key role in preventing cardiovascular diseases (Hao et al., 2016). Hyperoside could decrease skin inflammation by inhibiting inflammatory pathways and repairing DNA damage (Kurt-Celep et al., 2020). Animal experiments demonstrated that hyperoside could lower TNF-α and IL-1β in rat cerebral ischemia-reperfusion injury models and play an anti-inflammatory role (He et al., 2019). Hyperoside also has a protective effect on ovalbumin-induced allergic airway inflammation in mice by decreasing the levels of IL-4, IL-5, IL-1β, and IgE and reducing inflammatory cell infiltration (Ye et al., 2017).\n\nHyperoside can selectively block the activation of AIM2 and NLRC4 inflammatory bodies and inhibit inflammatory response. In vitro experiments illustrated that hyperoside inhibited the production of TNF-α and IL-1β and inhibited the activation of AKT, NF-κB, and extracellular regulated kinase (ERK1/2) that are mediated by HMGB1 in lipopolysaccharide-induced vascular endothelial cells (Jung et al., 2012). In rat peritoneal macrophages, hyperoside inhibited the expression of pro-inflammatory cytokines and iNOS, and significantly decreased the levels of inflammatory cytokines such as TNF-α and IL-6 (Kim et al., 2011). Hyperoside can also be applied to treat allergic inflammation aggravated by TSLP, thus reducing the expression of IL-1β, IL-6, and their mRNA, down-regulating Ca2+/RIP2/Caspase-1/NF-κB signal pathway and inhibiting the level of TSLP in human mast cell lines (Han et al., 2014).\n\nThe role of oxidative stress in cardiovascular diseases, malignant tumors, liver and kidney injury, and autoimmune diseases has been extensively verified. Hyperoside has a protective effect on oxidative stress and apoptosis of granulosa cells induced by H2O2, which is potentially exerted by reducing the expression of Bax and up-regulating the expression of Bcl-2 in granulosa cells (Wang et al., 2019). After intraperitoneal injection of hyperoside (50 mg/kg/d) into the rat model of ischemia–reperfusion injury, the activity of malondialdehyde decreased, the activity of superoxide dismutase and glutathione peroxidase increased, the expression of heme oxygenase-1 and NADPH quinone oxidoreductase-1 increased, and the apoptosis index decreased. Hyperoside could remarkably reduce the levels of ALT and AST after reperfusion and reduce the histological injury score (Shi et al., 2019). Similarly, polyphenols in the lotus chamber, including hyperoside and other compounds, were also reported to display strong anti-oxidant and anti-proliferation activity and to have the ability to effectively scavenge many kinds of free radicals such as superoxide anion (Shen et al., 2019).\n\nIn a rat model of cerebral ischemia–reperfusion injury, He et al. (Kurt-Celep et al., 2020) found that hyperoside could increase the levels of SOD, MDA, and GSH-Px, improve the total anti-oxidant capacity of the rat brain, and inhibit oxidative stress and anti-apoptosis. Gao et al. (2019) applied Saccharomyces cerevisiae as a model to study the anti-oxidant activity of hyperoside, revealing that hyperoside can reduce the level of intracellular reactive oxygen species and lipid peroxidation, and improve cell survival rate. Chen et al. (2019) proposed that hyperoside improves the activity of free radical scavenging (or power reduction) in a dose-dependent manner and has an anti-oxidant role through the REDOX reaction and covalent pathway of lyophilized water extract and phenolic components of Hyalocin. Hyperoside promotes the expansion of cord blood hematopoietic cells in vitro by reducing the level of intracellular ROS. The expansion ability of cord blood hematopoietic cells that are pretreated with hyperoside (1 μM) was 54.9±9.6 times higher than that of the control group (42.0±8.1 times), which was a noticeable difference (Zhang et al., 2018a). Hyperoside exerts a protective effect on apoptosis of retinal pigment epithelial cells by inhibiting blue light-induced poly ADP-ribose polymerase cleavage and complement C3 activation of PARP (Kim et al., 2018). Similarly, hyperoside has a protective effect on oxidative damage and cytotoxicity of renal cells simulated by oxalate, and the ability of hyperoside to enhance endogenous antioxidation and detoxification may be closely related to Nrf2/HO-1/NQO1 pathway (Chen et al., 2018b). In vitro experiments revealed that hyperoside could enhance the activity of anti-oxidant enzyme SOD/CAT/GSH-Px (Zou et al., 2017).\n\nYang et al. (2016) demonstrated that hyperoside protects melanocytes from oxidative damage by inhibiting p38 phosphorylation and mitochondrial apoptosis signals and activating AKT, which provides vital value for the treatment of vitiligo. By inducing an endogenous oxidation system, hyperoside up-regulates the level of Nrf2 and the binding activity of anti-oxidant response elements and increases the expression of HO-1 mRNA and protein in a time- and dose-dependent manner (Park et al., 2016). Additionally, hyperoside in hawthorn extract has been shown to have an immunomodulatory effect through its antioxidant activity, including spleen cells, NK cells, CTL cells, and macrophages; however, the specific mechanism remained unclear (Mustapha et al., 2016). Li et al. (2012b) argued that the underlying mechanism might be correlated with the activation of the ERK signal pathway. According to a recent study, hyperoside can attenuate H2O2-induced oxidative stress damage in L02 cells by inhibiting the KAP1-activated NRF2-ARE signal pathway and increasing serine kinase-3β to inhibit phosphorylation (Xing et al., 2015). The anti-oxidant activity of hyperoside is also reflected in its inhibitory effect on cell injury induced by H2O2 that up-regulates the expression of HO-1 and increases the activity of heme oxygenase-1 through the interaction of Keap1-Nrf2-ARE signal pathway (Xing et al., 2011). Hyperoside depends on the regulation of NMDA receptors of NR2A and NR2B, and significantly attenuates NMDA-induced neuronal apoptosis and prevents neuronal injury (Zhang et al., 2010). Previous studies revealed that H2O2 could induce apoptosis of hamster lung fibroblasts (V79-4). Through the intervention of hyperoside, the activity of antioxidant enzymes in V79-4 cells significantly increases, while the content of reactive oxygen species obviously decreases (Piao et al., 2008).\n\nNumerous studies indicated that hyperoside has a neuroprotective effect. Hyperoside has a protective effect on human dopaminergic neurons, and it can inhibit 6-hydroxydopamine induced oxidative stress of dopaminergic neurons by activating Nrf2/HO-1 signal. It can also improve the loss of neuronal vitality, lactate dehydrogenase release, excessive accumulation of ROS, and abnormal mitochondrial membrane potential induced by 6-OHDA (Ramesh et al., 2018). Most importantly, hyperoside treatment activates nuclear erythroid 2-related factor 2 that is the upstream molecule of heme oxygenase-1. Simultaneously, Nrf2-dependent HO-1 signal activation is a potential target for preventing and treating Parkinson’s disease (Kwon et al., 2019).\n\nAmyloid protein, which is thought to have an important role in Alzheimer’s disease’s pathogenesis, produces neurotoxicity by destroying the blood-brain barrier (Kumaran et al., 2018). Liu et al. (2018b) stated that hyperoside could alleviate the damage of a blood-brain barrier induced by Aβ1–42 and may be a potential drug for AD treatment. Furthermore, hyperoside can reverse mitochondrial dysfunction induced by Aβ25-35, inhibit its toxicity and apoptosis, and protect primary cultured cortical neurons by regulating PI3K/AKT/Bad/BclXL pathway (Zeng et al., 2011). Based on the in vitro ischemia model of hypoxia–glucose deprivation–reperfusion injury, it was obvious that hyperoside has a protective effect on primary cultured cortical neurons against OGD-R injury and that NO signal pathway is involved in this regulatory process (Liu et al., 2012).\n\nAs the most important detoxification organ of the human body, the metabolism of most drugs depends on the liver, and liver injury caused by drugs is inevitable. Paracetamol is widely used in clinics due to its good antipyretic and analgesic effect; however, liver injury caused by acetaminophen is unavoidable. In vitro experiments proved that hyperoside could effectively reduce the indexes of acute liver injury induced by acetaminophen. The possible mechanisms of ALT, AST, and ALP are related to hyperoside that can increase the level of glutathione and reduce the content of ROS (Jiang et al., 2019). Xie et al. (2016) proposed that Hyperoside accelerates the harmless metabolism of APAP by inhibiting the activity of CYP2E1 and increasing the expression and activity of detoxifying enzymes Sults and UGTS.\n\nHyperoside has a protective effect on liver fibrosis and liver injury induced by heart failure in rats, such as the decrease of hydroxyproline content and liver fibrosis area, the decrease of ALT, AST, and ALP levels, and the relief of hepatocyte edema and vacuolar degeneration (Guo et al., 2019b). By inhibiting inflammation and strengthening the anti-oxidant defense system, the protein and mRNA expression of iNOS, COX-2, and TNF-α are inhibited (Choi et al., 2011). Recently, Wang et al. (2016) suggested that hyperoside can effectively inhibit the DNA binding activity of transcription factor NF-κB, change the expression of apoptosis-related genes regulated by it, and induce HSC apoptosis in hepatic stellate cells to reduce hepatic fibrosis.\n\nDiabetic nephropathy is one of the diabetic microvascular complications. Early selective loss of glomerular permeability has an essential role in the pathogenesis of microalbuminuria in diabetic nephropathy. Oral administration of hyperoside to 30 mg/kg/day DN mice for 4 weeks can significantly reduce microalbumin excretion and glomerular filtration but has no significant effect on glucose metabolism and lipid metabolism (Zhang et al., 2016a). Moreover, hyperoside may delay the progression of diabetic nephropathy by down regulating the phosphorylation levels of p38MAPK, IL-β, and pERK1/2 in glomerular Mesangial cells of diabetic rats and reducing the expression of TGF-κ1 and AGE/RAGE binding (Kim et al., 2016). Hyperoside can inhibit the activity of heparanase gene promoter and heparanase expression induced by ROS or high glucose in podocytes (An et al., 2017).\n\nWang et al. (Wu et al., 2018) proposed that Huangkui capsule and its active ingredient hyperoside could improve the proteinuria and renal dysfunction of the mouse model of early diabetic nephropathy, reduce glomerular basement membrane thickening, glomerular hypertrophy and mesangial dilatation, and alleviate the pathological changes of early DN by inhibiting Akt/mTOR/p70S6K signal activity, which was consistent with results reported in another study (Cai et al., 2017). Huangkui capsule significantly improves the renal function of rats with chronic renal failure induced by adenine and significantly inhibits Scr, BUN, UP, p-ERK1/2, α-SMA, and similar. It was recently reported that hyperoside could alleviate D-galactose-induced renal injury and delay renal aging by inhibiting AMPK-ULK1 signal-mediated autophagy (Liu et al., 2018a). Hyperoside can block ADR-induced mitochondrial division and improve renal injury in both ADR-induced nephrotic mice and cultured human podocytes (Chen et al., 2017).\n\nFurther studies revealed that hyperoside could alleviate glomerulosclerosis and improve renal function in diabetic nephropathy mice, which may be related to its promotion of the expression of MMP-2 and MMP-9 and the inhibition of the expression of TIMP-1 and Col IV, FN (Zhang et al., 2016b). Yan et al. (2014) proposed the renal fibrosis model of Wistar rats based on unilateral ureteral obstruction, reporting that the combination of hyperoside and quercetin (H:Q=1:1) could significantly inhibit the expression of smooth muscle actin and fibronectin in Mesangial cells induced by interleukin-1β (IL-1β), thus effectively interfering with the progression of renal fibrosis. As the main active component of total flavonoids of Abelmoschus, hyperoside could inhibit caspase-3 and caspase-8 expression induced by advanced glycation end product, reduce podocyte apoptosis induced by sAGEs and prevent renal injury (Lei et al., 2012). Furthermore, the combination of hyperoside and quercetin (20 mg/kg/day) can inhibit the formation of calcium oxalate stones induced by ethylene glycol in rats and significantly increase catalase levels superoxide dismutase (Zhu et al., 2014).\n\nHyperoside, which decreases the levels of MC3T3-E1 phosphorylated Jun N-terminal kinases and p38 induced by H2O2 in osteoblasts, has a protective effect on MC3T3-E1 of osteoblasts induced by hydrogen peroxide (Qi et al., 2020). Hyperoside can induce MC3T3-E1 differentiation of mouse preosteoblasts, and it participates in the process of promoting and inhibiting osteoclast formation (Hou et al., 2020).\n\nAfter an artificial joint replacement, joint aseptic loosening often occurs, which maybe related to titanium particles’ effect on osteoblast apoptosis and autophagy. Hyperoside effectively intervenes by improving the vitality and proliferation of MC3T3-E1 cells to protect MC3T3-E1 cells from titanium particles. At the same time, the activation of the TWEEP-p38 pathway is involved in this repair process (Zhang and Zhang, 2019). Further studies revealed that hyperoside has an anti-osteoporotic effect on ovariectomized mice, which may be correlated with its inhibition of TRAF6-mediated RANKL/RANK/NF-κB signal pathway and the increase of OPG/RANKL value (Chen et al., 2018a). Artemisia annua extracts’ active components include chlorogenic acid, hyperoside, and artemisia lactone, which together inhibit osteoclast differentiation and bone resorption-related acidification that is partly achieved by down-regulating the interaction between V-ATPase and TRAF6 to reduce acidification (Lee et al., 2017). Hyperoside reduces the expression of osteopontin, sclerosin, TNF, and IL6, thereby reducing osteoblastic activity (Nash et al., 2016).\n\nA previous experimental study in mice showed that hyperoside could exert an antidepressant effect through the monoaminergic system and up-regulation of brain-derived neurotrophic factor (Wang et al., 2016b). Hyperoside also has an antidepressant effect on CNS after intraperitoneal administration (Liu et al., 2019b). The main active components of Apocynum venetum leaves include hyperoside and isoquercitrin. Recent studies proved that the antidepressant effect of Apocynum venetum leaf extract (AVLE) on rats exposed to CUMS is similar to that of fluoxetine (10 mg/kg), which may be related to its up-regulation of hippocampal BDNF level and the inhibition of hippocampal neuronal apoptosis and oxidative stress (Li et al., 2018b; Orzelska-Górka et al., 2019). Gong et al. (2017) proposed that hyperoside can increase the expression of brain-derived neurotrophic factor BDNF in the hippocampus of rats induced by chronic mild stress, thus reversing the cognitive impairment caused by CMS and improving cognitive function. In the in vitro model of depression induced by corticosterone, hyperoside reduces the expression of BDNF and CREB genes up-regulated by Ca2+ through cAMP-CREB signaling pathway, which protects PC12 cells from corticosterone-induced neurotoxicity. The cellular mechanism of hyperoside protecting PC12 cells from corticosterone-induced neurotoxicity is closely correlated with the cAMP signaling pathway (Zheng et al., 2012). In the FST model, hyperoside displayed strong antidepressant activity by mediating and activating D2-like receptors through the dopaminergic system (Haas et al., 2011). It has recently been proposed that the extract of Hawthorn fruit can improve memory impairment in mice with Alzheimer’s disease induced by β-amyloid protein. Different from the general drug action, CPE can block the accumulation of Aβ in a concentration-dependent manner (Lee et al., 2019).\n\nHu et al. (Liu et al., 2012) agreed that Hawthorn ethanol extract containing hyperoside could affect lipid metabolism and significantly reduce the levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol in hyperlipidemic rats. Totally, 15 lipid metabolites, including threonine, aspartic acid, and glutamine, were identified as potential biomarkers of hyperlipidemia. Berkoz (Hu et al., 2019) discovered that hyperoside could inhibit the transformation of early fat to mature fat as 10 μM hyperoside has an inhibitory effect in the late stage of adipogenesis, 5 μM hyperoside has an anti-lipid effect in the early stage of adipogenesis, and high dose hyperoside could reduce lipid accumulation in mature adipocytes, while low dose hyperoside could inhibit adipogenesis. Zhang et al. (Berkoz, 2019) proved that hyperoside extracted from Zanthoxylum bungeanum leaves also have a certain lipid-lowering effect and can reduce LDL-C and increase HDL-C.\n\nPlatelet aggregation and thrombosis are the common pathogenesis of many vascular diseases, so anticoagulation and inhibition of platelet aggregation are the focus of many new drug researches and development. Although there are few reports on the anti-platelet effect of hyperoside, this does not negate its role in the vascular system. A simultaneous experiment in vivo and in vitro revealed that (Lee et al., 2019) hyperoside could inhibit platelet aggregation induced by collagen or thrombin in vitro, while it had enhanced antithrombotic effect in the model of arterial thrombosis and pulmonary embolism in vivo. Both isorhamnetin-3 murine O-galactose and hyperoside in water celery extract could inhibit the activity of thrombin and activator FXa and partially prolong activated thromboplastin time and plasma prothrombin time (PT). At the same time, both of them could inhibit the production of plasminogen activator inhibitor-1 induced by TNF-α; however, the anticoagulant effect and fibrinolytic activity of hyperoside were lower than those of isorhamnetin-3 murine O-galactose (Ku et al., 2014). In the model of vascular smooth muscle cells cultured with oxidized low-density lipoprotein in vitro, hyperoside could inhibit the proliferation of vascular smooth muscle cells through the oxLDL-LOX-1-ERK pathway and the activation of VSMCs and ERK (Zhang et al., 2017b).\n\nThe above-reported studies on the pharmacological effects of various aspects of hyperoside revealed that hyperoside has many pharmacological properties, different mechanisms of action, and different dosages in the treatment of various diseases. The pharmacological mechanism of hyperoside, its effect on the different cells or animals, and the dosage are summarized in Table 1 and Figure 3.\n\n\n4. Conclusion and future direction\n\nIn recent years, the research on hyperoside has been greatly increased, mainly focusing on its pharmacological activity. For example, hyperoside can significantly increase the activity of antioxidant enzymes, while protecting the heart and cerebral ischemia/reperfusion injury, but also enhance immunity, liver protection, anti-depression, prevention of cardiac hypertrophy by blocking the activation of AKT signaling pathway and protecting heart remodeling caused by pressure overload (Wang et al., 2018a), inhibiting tumor cell proliferation, promoting tumor cell apoptosis, and preventing tumor cell cycle, etc. On the contrary, there are few studies on the toxicology and pharmacokinetics of hyperoside. Consequently, more clinical trials are needed for the accumulation of reliable research data under the guidance of clinical applications and medical practices. Chinese herbal medicine has been proven to be effective in the field of traditional medicine. However, its effectiveness and safety have not been globally accepted, as its mechanism remains unclear. Therefore, future studies should pay attention to the pharmacological activity of a single active ingredient and address the interaction among multiple components in the same drug.\n\nAlthough the current pharmacological research of hyperoside has made great progress, due to the lack of systematic pharmacokinetic studies, the dosage of hyperoside in different research protocols is quite different, and some experimental evidence is contradictory (Guo et al., 2012). At the same time, there are few studies on the toxicology and safety of the substance, and different administration methods have also led to differences in the bioavailability and pharmacological activity of the drug. Therefore, this article makes a comparison of the pharmacological effects of hyperoside, provides a complete summary and a new perspective on the limitations of current hyperoside metabolism and toxicology studies, as well as a reference for further research on hyperoside.\n\nIn conclusion, hyperoside has multiple bio-activities, including anti-inflammatory, anti-viral, anti-cancer, and hepatoprotective effects. Further pharmacokinetic studies on hyperoside and the systematic evaluation of its metabolites’ biological activity, the dose-time-pharmacology/toxicity relationship, and the determination of biological targets and interaction modes are urgently needed.\n\n\nAuthor contributions\n\nQL and Fengxian Wang researched the article and wrote the manuscript. LZ modified and reviewed the manuscript before submission. All authors provided substantial contribution to the discussion of content.\n\n\nData availability\n\nThere are no data associated with this article.",
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PubMed Abstract | Publisher Full Text\n\nLi X, Wu T, Yu Z, et al.: Apocynum venetum leaf extract reverses depressive-like behaviors in chronically stressed rats by inhibiting oxidative stress and apoptosis. Biomed. Pharmacother. 2018b; 100: 394–406. PubMed Abstract | Publisher Full Text\n\nLi Y, Wang Y, Li L, et al.: Hyperoside induces apoptosis and inhibits growth in pancreatic cancer via Bcl-2 family and NF-κB signaling pathway both in vitro and in vivo. Tumor Biol. 2016; 37(6): 7345–7355. Publisher Full Text\n\nLi ZL, Hu J, Li YL, et al.: The effect of hyperoside on the functional recovery of the ischemic/reperfused isolated rat heart: potential involvement of the extracellular signal-regulated kinase 1/2 signaling pathway. Free Radic. Biol. Med. 2013; 57: 132–140. PubMed Abstract | Publisher Full Text\n\nLi ZL, Liu JC, Hu J, et al.: Protective effects of hyperoside against human umbilical vein endothelial cell damage induced by hydrogen peroxide. J. Ethnopharmacol. 2012b; 139(2): 388–394. PubMed Abstract | Publisher Full Text\n\nLin HB, Lin JQ, Lu N, et al.: Study of quality control on Cuscuta chinensis and C. australia. Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. 2007; 30(11): 1446–1449.\n\nLiu B, Tu Y, He W, et al.: Hyperoside attenuates renal aging and injury induced by D-galactose via inhibiting AMPK-ULK1 signaling-mediated autophagy. Aging-Us. 2018a; 10(12): 4197–4212. PubMed Abstract | Publisher Full Text\n\nLiu CY, Bai K, Liu XH, et al.: Hyperoside protects the blood-brain barrier from neurotoxicity of amyloid beta 1-42. Neural Regen. Res. 2018b; 13(11): 1974–1980. PubMed Abstract | Publisher Full Text\n\nLiu D, Yu X, Sun H, et al.: Flos lonicerae flavonoids attenuate experimental ulcerative colitis in rats via suppression of NF-κB signaling pathway. Naunyn Schmiedeberg’s Arch. Pharmacol. 2020; 393(12): 2481–2494. PubMed Abstract | Publisher Full Text\n\nLiu F, Zhao Y, Lu J, et al.: Hyperoside inhibits proinflammatory cytokines in human lung epithelial cells infected with Mycoplasma pneumoniae. Mol. Cell. Biochem. 2019a; 453(1-2): 179–186. Publisher Full Text\n\nLiu J, Zhang Z, Yang L, et al.: Molecular structure and spectral characteristics of hyperoside and analysis of its molecular imprinting adsorption properties based on density functional theory. J. Mol. Graph. Model. 2019b; 88: 228–236. Publisher Full Text\n\nLiu RL, Xiong QJ, Shu Q, et al.: Hyperoside protects cortical neurons from oxygen-glucose deprivation-reperfusion induced injury via nitric oxide signal pathway. Brain Res. 2012; 1469: 164–173. PubMed Abstract | Publisher Full Text\n\nLiu YH, Liu GH, Mei JJ, et al.: The preventive effects of hyperoside on lung cancer in vitro by inducing apoptosis and inhibiting proliferation through Caspase-3 and P53 signaling pathway. Biomed. Pharmacother. 2016; 83: 381–391. Publisher Full Text\n\nLiu Z, Liu G, Liu X, et al.: The effects of hyperoside on apoptosis and the expression of Fas/FasL and survivin in SW579 human thyroid squamous cell carcinoma cell line. Oncol. Lett. 2017; 14(2): 2310–2314. Publisher Full Text\n\nLiu Z, Tao X, Zhang C, et al.: Protective effects of hyperoside (quercetin-3-o-galactoside) to PC12 cells against cytotoxicity induced by hydrogen peroxide and tert-butyl hydroperoxide. Biomed. Pharmacother. 2005; 59(9): 481–490. Publisher Full Text\n\nLü P: Inhibitory effects of hyperoside on lung cancer by inducing apoptosis and suppressing inflammatory response via caspase-3 and NF-κB signaling pathway. Biomed. Pharmacother. 2016; 82: 216–225. Publisher Full Text\n\nMagnus S, Gazdik F, Anjum NA, et al.: Assessment of Antioxidants in Selected Plant Rootstocks. Antioxidants (Basel, Switzerland). 2020; 9(3). Publisher Full Text\n\nMustapha N, Mokdad-Bzéouich I, Sassi A, et al.: Immunomodulatory potencies of isolated compounds from Crataegus azarolus through their antioxidant activities. Tumour Biol. 2016; 37(6): 7967–7980. PubMed Abstract | Publisher Full Text\n\nNash LA, Peters SJ, Sullivan PJ, et al.: Supraphysiological Levels of Quercetin Glycosides are Required to Alter Mineralization in Saos2 Cells. Int. J. Environ. Res. Public Health. 2016; 13(5). PubMed Abstract | Publisher Full Text\n\nOrzelska-Gorka J, Szewczyk K, Gawronska-Grzywacz M, et al.: Monoaminergic system is implicated in the antidepressant-like effect of hyperoside and protocatechuic acid isolated from Impatiens glandulifera Royle in mice. Neurochem. Int. 2019; 128: 206–214. Publisher Full Text\n\nPark JY, Han X, Piao MJ, et al.: Hyperoside Induces Endogenous Antioxidant System to Alleviate Oxidative Stress. J. Cancer Prev. 2016; 21(1): 41–47. PubMed Abstract | Publisher Full Text\n\nPiao MJ, Kang KA, Zhang R, et al.: Hyperoside prevents oxidative damage induced by hydrogen peroxide in lung fibroblast cells via an antioxidant effect. Biochim. Biophys. Acta. 2008; 1780(12): 1448–1457. PubMed Abstract | Publisher Full Text\n\nQi XC, Li B, Wu WL, et al.: Protective effect of hyperoside against hydrogen peroxide-induced dysfunction and oxidative stress in osteoblastic MC3T3-E1 cells. Artif. Cells Nanomed. Biotechnol. 2020; 48(1): 377–383. PubMed Abstract | Publisher Full Text\n\nQian ZM, Li HJ, Li P, et al.: Simultaneous qualitation and quantification of thirteen bioactive compounds in Flos lonicerae by high-performance liquid chromatography with diode array detector and mass spectrometry. Chem. Pharm. Bull. 2007; 55(7): 1073–1076. PubMed Abstract | Publisher Full Text\n\nQiu J, Zhang T, Zhu X, et al.: Hyperoside Induces Breast Cancer Cells Apoptosis via ROS-Mediated NF-κB Signaling Pathway. Int. J. Mol. Sci. 2019; 21(1). PubMed Abstract | Publisher Full Text\n\nRamesh P, Thida S, Jungwon S: Protective Effects of Hyperoside from Juglans sinensis Leaves against 1-methyl-4-phenylpyridinium-Induced Neurotoxicity %J Korean. J. Pharmacogn. 2018; 49(3).\n\nShen Y, Guan Y, Song X, et al.: Polyphenols extract from lotus seedpod (Nelumbo nucifera Gaertn.): Phenolic compositions, antioxidant, and antiproliferative activities. Food Sci. Nutr. 2019; 7(9): 3062–3070. PubMed Abstract | Publisher Full Text\n\nShi S, Tang A, Yin S, et al.: [Inhibitive effect of matrine modification X on the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice]. Lin chuang er bi yan hou tou jing wai ke za zhi =. Journal of Clinical Otorhinolaryngology, Head, and Neck Surgery. 2014; 28(21): 1697–1700.\n\nShi Y, Qiu X, Dai M, et al.: Hyperoside Attenuates Hepatic Ischemia-Reperfusion Injury by Suppressing Oxidative Stress and Inhibiting Apoptosis in Rats. Transplant. Proc. 2019; 51(6): 2051–2059. PubMed Abstract | Publisher Full Text\n\nSun T, Liu Y, Li M, et al.: Administration with hyperoside sensitizes breast cancer cells to paclitaxel by blocking the TLR4 signaling. Mol. Cell. Probes. 2020; 53: 101602. PubMed Abstract | Publisher Full Text\n\nSun Y, Sun F, Feng W, et al.: Hyperoside inhibits biofilm formation of Pseudomonas aeruginosa. Exp. Ther. Med. 2017; 14(2): 1647–1652. PubMed Abstract | Publisher Full Text\n\nWang C, Li X, Liu Z, et al.: The Effect and Mechanism of Hyperoside on High Glucose-induced Oxidative Stress Injury of Myocardial Cells. Sichuan da xue xue bao Yi xue ban = Journal of Sichuan University Medical science edition. 2018a; 49(4): 518–523. PubMed Abstract\n\nWang CH, Wang YX, Liu HJ: Validation and application by HPLC for simultaneous determination of vitexin-2″-O-glucoside, vitexin-2″-O-rhamnoside, rutin, vitexin, and hyperoside. J. Pharm. Anal. 2011; 1(4): 291–296. PubMed Abstract | Publisher Full Text\n\nWang L, Yue Z, Guo M, et al.: Dietary Flavonoid Hyperoside Induces Apoptosis of Activated Human LX-2 Hepatic Stellate Cell by Suppressing Canonical NF-κB Signaling. Biomed. Res. Int. 2016a; 2016: 1–10. Publisher Full Text\n\nWang WQ, Ma CG, Xu SY: Protective effect of hyperin against myocardial ischemia and reperfusion injury. Zhongguo yao li xue bao = Acta pharmacologica Sinica. 1996; 17(4): 341–344. PubMed Abstract\n\nWang X, Fan G, Wei F, et al.: Hyperoside protects rat ovarian granulosa cells against hydrogen peroxide-induced injury by sonic hedgehog signaling pathway. Chem. Biol. Interact. 2019; 310: 108759. PubMed Abstract | Publisher Full Text\n\nWang X, Liu Y, Xiao L, et al.: Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway. Cell. Physiol. Biochem. 2018b; 51(2): 827–841. PubMed Abstract | Publisher Full Text\n\nWang Y, Lin H-Q, Xiao C-Y, et al.: Using molecular docking screening for identifying hyperoside as an inhibitor of fatty acid binding protein 4 from a natural product database. J. Funct. Foods. 2016b; 20: 159–170. Publisher Full Text\n\nWei Y, Xie Q, Ito Y: Preparative separation of axifolin-3-glucoside, hyperoside and amygdalin from plant extracts by high-speed countercurrent chromatography. J. Liq. Chromatogr. Relat. Technol. 2009; 32(7): 1010–1022. PubMed Abstract | Publisher Full Text\n\nWu L, Li Q, Liu S, et al.: Protective effect of hyperoside against renal ischemia-reperfusion injury via modulating mitochondrial fission, oxidative stress, and apoptosis. Free Radic. Res. 2019; 53(7): 727–736. PubMed Abstract | Publisher Full Text\n\nWu W, Hu W, Han WB, et al.: Inhibition of Akt/mTOR/p70S6K Signaling Activity With Huangkui Capsule Alleviates the Early Glomerular Pathological Changes in Diabetic Nephropathy. Front. Pharmacol. 2018; 9: 443. PubMed Abstract | Publisher Full Text\n\nXiao R, Xiang AL, Pang HB, et al.: Hyperoside protects against hypoxia/reoxygenation induced injury in cardiomyocytes by suppressing the Bnip3 expression. Gene. 2017; 629: 86–91. PubMed Abstract | Publisher Full Text\n\nXie W, Jiang Z, Wang J, et al.: Protective effect of hyperoside against acetaminophen (APAP) induced liver injury through enhancement of APAP clearance. Chem. Biol. Interact. 2016; 246: 11–19. PubMed Abstract | Publisher Full Text\n\nXing HY, Cai YQ, Wang XF, et al.: The Cytoprotective Effect of Hyperoside against Oxidative Stress Is Mediated by the Nrf2-ARE Signaling Pathway through GSK-3β Inactivation. PloS One. 2015; 10(12): e0145183. PubMed Abstract | Publisher Full Text\n\nXing HY, Liu Y, Chen JH, et al.: Hyperoside attenuates hydrogen peroxide-induced L02 cell damage via MAPK-dependent Keap1-Nrf2-ARE signaling pathway. Biochem. Biophys. Res. Commun. 2011; 410(4): 759–765. PubMed Abstract | Publisher Full Text\n\nYan Y, Feng Y, Li W, et al.: Protective effects of quercetin and hyperoside on renal fibrosis in rats with unilateral ureteral obstruction. Exp. Ther. Med. 2014; 8(3): 727–730. PubMed Abstract | Publisher Full Text\n\nYang B, Yang Q, Yang X, et al.: Hyperoside protects human primary melanocytes against H2O2-induced oxidative damage. Mol. Med. Rep. 2016; 13(6): 4613–4619. PubMed Abstract | Publisher Full Text\n\nYang FQ, Liu M, Li W, et al.: Combination of quercetin and hyperoside inhibits prostate cancer cell growth and metastasis via regulation of microRNA-21. Mol. Med. Rep. 2015; 11(2): 1085–1092. Publisher Full Text\n\nYang L, Shen L, Li Y, et al.: Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway. Journal of inflammation (London, England). 2017a; 14: 25. PubMed Abstract | Publisher Full Text\n\nYang Y, Sun Y, Guo X, et al.: Hyperoside inhibited the migration and invasion of lung cancer cells through the upregulation of PI3K/AKT and p38 MAPK pathways. Int. J. Clin. Exp. Pathol. 2017b; 10(9): 9382–9390. PubMed Abstract\n\nYang Y, Tantai J, Sun Y, et al.: Effect of hyperoside on the apoptosis of A549 human non-small cell lung cancer cells and the underlying mechanism. Mol. Med. Rep. 2017c; 16(5): 6483–6488. PubMed Abstract | Publisher Full Text\n\nYe P, Yang XL, Chen X, et al.: Hyperoside attenuates OVA-induced allergic airway inflammation by activating Nrf2. Int. Immunopharmacol. 2017; 44: 168–173. PubMed Abstract | Publisher Full Text\n\nZeng KW, Wang XM, Ko H, et al.: Hyperoside protects primary rat cortical neurons from neurotoxicity induced by amyloid β-protein via the PI3K/Akt/Bad/Bcl (XL)-regulated mitochondrial apoptotic pathway. Eur. J. Pharmacol. 2011; 672(1-3): 45–55. PubMed Abstract | Publisher Full Text\n\nZhang F, Zhu FB, Li JJ, et al.: Hyperoside enhances the suppressive effects of arsenic trioxide on acute myeloid leukemia cells. Int. J. Clin. Exp. Med. 2015; 8(9): 15290–15295. PubMed Abstract\n\nZhang J, Fu H, Xu Y, et al.: Hyperoside reduces albuminuria in diabetic nephropathy at the early stage through ameliorating renal damage and podocyte injury. J. Nat. Med. 2016a; 70(4): 740–748. PubMed Abstract | Publisher Full Text\n\nZhang L, He S, Yang F, et al.: Hyperoside ameliorates glomerulosclerosis in diabetic nephropathy by downregulating miR-21. Can. J. Physiol. Pharmacol. 2016b; 94(12): 1249–1256. PubMed Abstract | Publisher Full Text\n\nZhang N, Ying MD, Wu YP, et al.: Hyperoside, a flavonoid compound, inhibits proliferation and stimulates osteogenic differentiation of human osteosarcoma cells. PLoS One. 2014; 9(7): e98973. PubMed Abstract | Publisher Full Text\n\nZhang Q, Zhang X-F: Hyperoside decreases the apoptosis and autophagy rates of osteoblast MC3T3-E1 cells by regulating TNF-like weak inducer of apoptosis and the p38mitogen activated protein kinase pathway. Mol. Med. Rep. 2019; 19(1): 41–50. PubMed Abstract | Publisher Full Text\n\nZhang W, Zhang W, Zhang X, et al.: Hyperoside promotes ex vivo expansion of hematopoietic stem/progenitor cells derived from cord blood by reducing intracellular ROS level. Process Biochem. 2018a; 72: 143–151. Publisher Full Text\n\nZhang X-N, Li J-M, Yang Q, et al.: Anti-apoptotic effects of hyperoside via inhibition of NR2B-containing NMDA receptors. Pharmacol. Rep. 2010; 62(5): 949–955. PubMed Abstract | Publisher Full Text\n\nZhang Y, Dong H, Zhang J, et al.: Inhibitory effect of hyperoside isolated from Zanthoxylum bungeanum leaves on SW620 human colorectal cancer cells via induction of the p53 signaling pathway and apoptosis. Mol. Med. Rep. 2017a; 16(2): 1125–1132. PubMed Abstract | Publisher Full Text\n\nZhang Y, Wang M, Dong H, et al.: Anti-hypoglycemic and hepatocyte-protective effects of hyperoside from Zanthoxylum bungeanum leaves in mice with high-carbohydrate/high-fat diet and alloxan-induced diabetes. Int. J. Mol. Med. 2018b; 41(1): 77–86. PubMed Abstract | Publisher Full Text\n\nZhang Z, Sethiel MS, Shen W, et al.: Hyperoside downregulates the receptor for advanced glycation end products (RAGE) and promotes proliferation in ECV304 cells via the c-Jun N-terminal kinases (JNK) pathway following stimulation by advanced glycation end-products in vitro. Int. J. Mol. Sci. 2013; 14(11): 22697–22707. PubMed Abstract | Publisher Full Text\n\nZhang Z, Zhang D, Du B, et al.: Hyperoside inhibits the effects induced by oxidized low-density lipoprotein in vascular smooth muscle cells via oxLDL-LOX-1-ERK pathway. Mol. Cell. Biochem. 2017b; 433(1-2): 169–176. PubMed Abstract | Publisher Full Text\n\nZheng M, Liu C, Pan F, et al.: Antidepressant-like effect of hyperoside isolated from Apocynum venetum leaves: possible cellular mechanisms. Phytomedicine. 2012; 19(2): 145–149. PubMed Abstract | Publisher Full Text\n\nZhou L, An XF, Teng SC, et al.: Pretreatment with the total flavone glycosides of Flos Abelmoschus manihot and hyperoside prevents glomerular podocyte apoptosis in streptozotocin-induced diabetic nephropathy. J. Med. Food. 2012; 15(5): 461–468. PubMed Abstract | Publisher Full Text\n\nZhou YQ, Zhao YT, Zhao XY, et al.: Hyperoside Suppresses Lipopolysaccharide-induced Inflammation and Apoptosis in Human Umbilical Vein Endothelial Cells. Curr. Med. Sci. 2018; 38(2): 222–228. PubMed Abstract | Publisher Full Text\n\nZhu W, Xu YF, Feng Y, et al.: Prophylactic effects of quercetin and hyperoside in a calcium oxalate stone forming rat model. Urolithiasis. 2014; 42(6): 519–526. PubMed Abstract | Publisher Full Text\n\nZhu X, Ji M, Han Y, et al.: PGRMC1-dependent autophagy by hyperoside induces apoptosis and sensitizes ovarian cancer cells to cisplatin treatment. Int. J. Oncol. 2017; 50(3): 835–846. PubMed Abstract | Publisher Full Text\n\nZou L, Chen S, Li L, et al.: The protective effect of hyperoside on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2. Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft fur Toxikologische Pathologie. 2017; 69(7): 451–460. PubMed Abstract | Publisher Full Text\n\nZou Y, Lu Y, Wei D: Antioxidant activity of a flavonoid-rich extract of Hypericum perforatum L. in vitro. J. Agric. Food Chem. 2004; 52(16): 5032–5039. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "269925",
"date": "07 May 2024",
"name": "Francesca Aiello",
"expertise": [
"Reviewer Expertise natural compounds extraction",
"design",
"and synthesis of pharmacological active molecules",
"antioxidants",
"vasorelaxants"
],
"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 abstract of this review needs to be rewritten, correctly and in line with style used in the whole manuscript. Mainly, the name of hyperoside must be correctly reported: so the O, meaning oxygen, is usually written in italic capital letter O-galactoside, not O-galactoside. Anti-oxidation effect is wrong! The antioxidant effect is fine.\nThe partition of the paragraphs is well-conducted, and the content is easy to read and comprehensive. The authors analyzed all the main findings regarding Hyperoside, and most interesting, they added some future perspectives. I suggest minor revision\n\nIs the topic of the review discussed comprehensively in the context of the current literature? Yes\n\nAre all factual statements correct and adequately supported by citations? Yes\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-635
|
https://f1000research.com/articles/11-111/v1
|
28 Jan 22
|
{
"type": "Research Article",
"title": "A quantitative study exploring the acceptance of the eHealth model for mental wellness among digital workers",
"authors": [
"Choon Hong Tan",
"Ah Choo Koo",
"Hawa Rahmat",
"Wei Fern Siew",
"Alexius Weng Onn Cheang",
"Elyna Amir Sharji",
"Ah Choo Koo",
"Hawa Rahmat",
"Wei Fern Siew",
"Alexius Weng Onn Cheang",
"Elyna Amir Sharji"
],
"abstract": "Background: eHealth makes use of information and communication technologies (ICT) to improve health. In the digital age, the use of eHealth applications and other health-related applications has gained popularity, particularly during the COVID-19 pandemic. As a result of the pandemic, many uncertainties have arisen, causing stress and affecting the mental health of many skilled workers in the digital industry, particularly in the ICT, computing, and creative media industries. eHealth applications have the potential to benefit people's health. As a prerequisite for effective implementation of eHealth for mental wellness (EHMW), this paper examines the acceptance of EHMW among digital workers in Malaysia. The objectives of this research are two-fold: 1) To explore the acceptance of EHMW among digital workers in a local Premier Digital Tech Institution (PDTI), and 2) To explore how these talents' demographic profiles, mental health literacy and workplace wellness influence their acceptance of EHMW.\n\nMethods: This research surveyed 41 digital workers who played vital roles in providing digital skills at a tertiary education level.\n\nResults: Most respondents agreed that eHealth was appropriate for managing mental wellness. Among the three eHealth domains for managing mental wellness, the acceptance level is the highest for the application domain of \"interacting for health\", with male respondents more likely to accept the use of EHMW. Conclusions: This small-scale survey could not fully examine the acceptance of eHealth and its usage patterns for mental wellness among digital workers in Malaysia. Future research will target more digital workers in Malaysia. This research addresses the research gap on the eHealth perspectives of digital workers on their acceptance, and the potential influence of demographic profiles, mental health literacy, and workplace wellness on EHMW's acceptance of digital health tools/platforms to promote their mental wellness.",
"keywords": [
"eHealth",
"digital talents",
"mental wellness",
"survey",
"quantitative analysis"
],
"content": "Introduction\n\nFollowing the COVID-19 pandemic, increasing amounts of working adults in Malaysia are facing general health and mental health problems due to concerns such as personal finances and health problems.4 Since the introduction of the Movement Control Order (MCO), most workers, especially digital workers who are working in digital industries and involved in ICT-related work areas,8 have moved to working from home (WFH) using various digital technologies and platforms. Therefore, digital skills have become essential, and digital literacy has become a critical subset of the skills acquired by digital workers. WFH has the advantage of flexibility in terms of working hours and location, but there are also disadvantages, such as the blurring of boundaries between work and personal life, the increase in workload and working hours caused by constant connectivity, leading to increased work pressure and a higher likelihood of developing other psychosocial problems.14 While digital workers have the critical skills to lead digital transformation in WFH, their mental health is at risk and must be protected.\n\nThere is stigma surrounding mental health in Malaysia, which often leads to patients suffering in silence. Close physical contact and travel was prohibited during the MCO, which made it difficult to seek mental health care. eHealth is able to bridge this gap by using information and communication technology (ICT) to help patients access and manage their health, enable remote communication between doctor and client and integrate data collection and analysis into useful information for more accurate diagnosis.13 eHealth for mental wellness (EHMW), such as Telehealth, can overcome many of the restrictions in seeking health information/care following the MCO, as it eliminates the need for travel and is cost effective. Therefore, higher acceptance of the use of EHMW has great potential to ensure mental wellbeing. As a prerequisite for the effective implementation of EHMW, this research discusses the acceptance of EHMW among digital workers.\n\nThe objectives of this research were: 1) to examine the acceptance of EHMW among digital workers in a local premier digital technology institution, and 2) to examine how these talents’ demographic profiles, mental health literacy and workplace wellness influence their acceptance of EHMW.\n\n\nLiterature review\n\nIn addition to physical health, mental health is essential for achieving overall well-being. Therefore, the promotion of mental wellness should also be a priority.\n\nAccording to Shaw et al., thematic analyse interviews with experts involved in health care research revealed that eHealth consists of three general domains: ‘1) Health in our hands is the use of technologies to monitor, track, and inform health status; 2) Interacting for health involves the use of technologies to communicate between stakeholders in health; 3) Data enabling health is the use of technology to collect, manage, and use health data for a more precise diagnostic’.13\n\nThe central overlap of three domains indicates the optimum point of eHealth, which is most effective for promoting mental wellness.\n\nAlthough EHMW is widely accessible and has been shown to be effective, it is still in its early stages, with the acceptability and potential uptake of EHMW still unclear. Previous studies have shown that poor acceptance prevents the uptake of internet-based therapies and results in individuals with mental health problems not seeking professional help.3 The level of interest and real-world uptake remains very low.1 Utilisation and adoption are essential for these technologies to be implemented effectively.6 Furthermore, acceptance of eHealth interventions is highly subjective and often influenced by internal and external factors. Previous research has identified demographic characteristics, such as age and education level, as predictors of eHealth intervention use.5,7\n\nKnowledge of eHealth has been associated with higher levels of its acceptance.5,13 Inadequate mental health literacy was identified as a key barrier to seeking help among those with mental health issues. Severity of stress symptoms can be a key determinant of the acceptance of stress-management apps.1 However, there is no clear evidence to link stress to the acceptance of e-mental health.2 The evidence on the influence of eHealth intervention acceptance is inconsistent and differs for various reasons, such as the culture of the study target groups. To address this research gap, we examined the acceptance of EHMW among digital workers in Malaysia and how demographic profiles, mental health literacy and workplace wellness influence acceptance of EHMW. The conceptual framework of this study is depicted in Figure 2.\n\n\nMethods\n\nThis study employed a survey targeted to digital workers from a Premier Digital Tech Institution (PDTI). Data were collected using a questionnaire created through Google Forms that included questions about demographic profiles such as gender, age group, education level, and work experience, as well as acceptance of eHealth. Some of the questions in this questionnaire were adapted from previous research. Following the development of the questionnaire, it was tested for face and content validity by members of the research group who are psychology practitioners, psychology lecturers, and experienced social sciences researchers. The questionnaire was revised in terms of the structure and wording of the questions based on the suggestions. The questionnaire was then sent to four external reviewers for face and content validity testing. These reviewers included lecturers with experience in e-mental health, social science researchers, and data analysis experts. The questionnaire was revised once more to improve the structure and wording of the questions, as well as to remove redundant questions. Finally, the questionnaire was sent to a lecturer who specialises in teaching English language for proofreading. The questionnaire was revised to improve the consistency and accuracy of the questions' grammar, spelling, and punctuation. The survey was conducted online between December 2020 and February 2021. Respondents were recruited via email invitation one month before data collection.\n\nThe key variables of this research were measured as follows:\n\n• Mental Health Literacy Scale (MHLS) adapted from the eHealth Literacy Scale (eHEALS)6\n\n• Workplace wellness scale (WWS) adapted from WHO (five-item) Well-Being Questionnaire and ‘Utrecht Work Engagement Scale’ (UWES)11\n\n• Acceptance of EHMW was measured using the three domains of eHealth.13 Items measuring acceptance of ‘health in our hands’ (ACC-HIOH), ‘interacting for health’ (ACC-IFH) and ‘data enabling health’ (ACC-DEH) were adapted from the ‘Unified theory of acceptance and use of technology’ (UTAUT) by Venkatesh et al. (2003). Wording of items was adapted into the context of ‘application for mental wellness’\n\nThe MHLS consists of five questions with a five-point scale ranging from ‘Strongly disagree’ (1) to ‘Strongly agree’ (5), and a total score ranging between 5 and 25. The WWS consists of five questions with a seven-point scale ranging from ‘At no time’ (0) to ‘All of the time’ (6), and the total score ranging between 0 and 30. The domains ACC-HIOH, ACC-IFH and ACC-DEH each consist of three questions with a five-point scale ranging from ‘Strongly disagree’ (1) to ‘Strongly agree’ (5), and total score ranging between 3 and 15.\n\nCronbach’s alpha (a) was used to test the item reliability of MHLS-5, WWS, ACC-HIOH, ACC-IFH and ACC-DEH. All scales had acceptable reliability coefficients, with Cronbach’s alpha > 0.7, MHLS-5 = 0.83, WWS = 0.92, ACC-HIOH = 0.83, ACC-IFH = 0.90 and ACC-DEH = 0.89.\n\nThe study population were employees of a local university that provide digital, computing and multimedia education. It is one out of the 11 premier digital technology universities in Malaysia, where digital workers can be sourced. A purposive sample of 67 employees were selected and invited to participate in an online survey between December 2020 and February 2021. These participants were selected because of their experience of three and more years in teaching IT, computing and multimedia courses or managing computing systems and lab systems.\n\n46 out of 67 respondents responded and participated in this survey. The collected data was exported into Microsoft Excel for data cleaning. Responses that did not provide consent to participate in this survey were removed, leaving 41 valid responses for further analysis. IBM SPSS Statistics Version 23 was used to analyse the data. Descriptive statistics such as mean and standard deviation, independent samples t-test and Pearson’s correlation were used to examine group differences and relationships of data. Because the questionnaire only contains positive coded items, common method bias (CMB) may arise from similar response tendencies caused by similarities in item structure.9 Harman’s single-factor test is used to test CMB, and the results show that the data collected does not contain CMB and is ready for further analysis.10\n\nEthical approval and clearance for data collection in this study were obtained from Multimedia University (MMU) (Approval number: EA2652021). The questionnaire included an initial option for participants to confirm they consent to participate. Before starting the survey, participants were informed that all identifying information would be kept private, all answers would be collected anonymously and the research report would only present the collective results, and data collected would be held confidentially and used for research purposes only. Only those who responded “Yes” to this question were able to begin the questionnaire.\n\n\nResults\n\nThe survey results describe the digital workers’ demographic information, mental health literacy, workplace wellness and acceptance of the EHMW. All responses for the MHLS, WWS, ACC-HIOH, ACC-IFH and ACC-DEH were summarised and averaged to get the mean score, then further categorised into ‘Low’ (1–2.34), ‘Moderate’ (2.35–3.67) and ‘High’ (3.68–5) scores. The WWS was further categorised by the mean score into ‘Low’ (0–1.99), ‘Moderate’ (2–3.99) and ‘High’ (4–6) scores, and the frequency of each score category was calculated. There were 54% (n = 22) females and 46% (n = 19) males; the majority of them, 83% (n = 34), were between the ages of 35 and 54 years old; half of them (n = 21) were Malay and 39% (n = 16) were Chinese, with 5% (n = 2) Indian and 5% (n = 2) other. The majority of respondents, 81% (n = 33), were talents with many years of work experience, ranging from 9–25 years. Most were from Creative Technology and Design (39%, n = 16), followed by Computer Science (20%, n = 8) and IT (17%, n = 7) departments. A total of 44% (n = 18) had a master’s degree, and 39% (n = 16) had a doctorate (PhD). Half of the respondents, 54% (n = 22), had incomes ranging from Ringgit Malaysia (RM)5,880–RM10,959. Most respondents presented with moderate to high levels of mean scores in the MHLS, WWS, ACC-HIOH, ACC-IFH and ACC-DEH, as outlined in Figure 3. The mean score for ACC-IFH (mean = 3.75, SD = 0.68) was the highest compared to ACC-HIOH (mean = 3.69, SD = 0.64) and ACC-DEH (mean = 3.65, SD = 0.66).\n\nMHLS, WWS, ACC-HIOH, ACC-IFH and ACC-DEH were normally distributed, with skewness between −0.54 to 0.08 and kurtosis between −0.46 to 0.50.\n\nAn independent samples t-test was used to identify differences between gender, age group and education level and work experience regarding acceptance of the EHMW. There were significant differences in the acceptance of all three eHealth domains for mental wellness between different genders, as depicted in Table 1. For ACC-HIOH, mean scores for males (M = 3.96, SD = 0.63) were higher than females (M = 3.45, SD = 0.56) (t[39] = 2.75, p = 0.009). For ACC-IFH, mean scores for males (M = 4.00, SD = 0.68) were higher than females (M = 3.53, SD = 0.61) (t[39] = 2.33, p = 0.025). For ACC-DEH, mean scores for males (M = 3.93, SD = 0.56) were higher than females (M = 3.41, SD = 0.66) (t[39] = 2.70, p = 0.010).\n\nThere were no significant differences in acceptance of all three eHealth domains for mental wellness between different education levels, as depicted in Table 2. For ACC-HIOH, mean scores for those without a PhD (M = 3.79, SD = 0.59) were slightly higher than for those with a PhD (M = 3.54, SD = 0.70) (t[39] = 1.21, p = 0.24). For ACC-IFH, mean scores for those without a PhD (M = 3.79, SD = 0.64) were slightly higher than for those with a PhD (M = 3.68, SD = 0.75) (t[39] = 0.45, p = 0.65). For ACC-DEH, mean scores for those without a PhD (M = 3.63, SD = 0.63) were slightly lower than for those with a PhD (M = 3.69, SD = 0.72) (t[39] = −0.28, p = 0.78).\n\nThere were no significant differences in acceptance of all three eHealth domains for mental wellness between different age groups, as depicted in Table 3. For ACC-HIOH, mean scores for 25-39-year-olds (group 1; M = 3.86, SD = 0.55) were slightly higher than 40-59-year-olds (group 2; M = 3.60, SD = 0.67) (t[39] = 1.21, p = 0.24). For ACC-IFH, mean scores for age group 1 (M = 3.95, SD = 0.63) were slightly higher than group 2 (M = 3.64, SD = 0.69) (t[39] = 1.41, p = 0.17). For ACC-DEH, mean scores for age group 1 (M = 3.74, SD = 0.68) were slightly higher than group 2 (M = 3.60, SD = 0.66) (t[39] = 0.61, p = 0.55).\n\nThere were no significant differences in acceptance of all three eHealth domains for mental wellness between different work experience groups, as depicted in Table 4. For ACC-HIOH, mean scores for those with 3-15 years of work experience (group 1; M = 3.74, SD = 0.61) were slightly higher than for those with 16-25 years of work experience (group 2; M = 3.65, SD = 0.67) (t[39] = 0.42, p = 0.68). For ACC-IFH, mean scores for group 1 (M = 3.70, SD = 0.55) were slightly lower than group 2 (M = 3.79, SD = 0.78) (t[39] = −0.40, p = 0.69). For ACC-DEH, mean scores for group 1 (M = 3.74, SD = 0.59) were slightly higher than group 2 (M = 3.58, SD = 0.72) (t[39] = 0.77, p = 0.44).\n\nPearson’s correlation (r) analysis was conducted to analyse the bivariate correlations of the MHLS, WWS, ACC-HIOH, ACC-IFH and ACC-DEH, and significant correlations were found. MHLS and WWS were negatively correlated (Pearson’s r (41) = −0.33, p = 0.036). ACC-HIOH was positively correlated with ACC-IFH (Pearson’s r(41) = 0.78, p <0.001) and ACC-DEH (Pearson’s r(41) = 0.70, p <0.001). ACC-IFH was positively correlated with ACC-DEH (Pearson’s r(41) = 0.71, p <0.001). However, there were no significant correlations between MHLS and ACC-HIOH, ACC-IFH or ACC-DEH, and no significant correlations between WWS and ACC-HIOH, ACC-IFH or ACC-DEH, as depicted in Table 5.\n\n\nDiscussion\n\nThis research provided information on the acceptance of EHMW among digital workers in Malaysia and showed moderate to high acceptance of EHMW. The purposively selected respondents were digitally experienced talents, who seem to have high acceptance, similar to previous findings showing that frequent internet users are more willing to use the internet for mental health purposes.2 A deeper understanding of EHMW acceptance was examined by adopting the three eHealth domains, which showed that acceptance of ‘interaction for health’ (IFH) was highest among the other eHealth domains. This is consistent with previous studies showing that IFH applications, such as Tele-mental Health, that use communication technologies to deliver mental health care remotely are widely accepted in mental health treatment, especially during MCOs, as they eliminate the need for travel while maintaining the quality of health care, which is cost- effective.15\n\nThe three domains of eHealth showed strong correlations, implying that acceptance of any one of the eHealth domains may be a strong predictor of acceptance of the other domains. In this study, there was a significant difference in the acceptance of EHMW between genders, with males having a higher acceptance rate of EHMW than females, which is supported by previous findings indicating that males with a more technology-friendly orientation have a higher acceptance rate of e-mental health6 and implies that it is important to promote the acceptance of EHMW among female digital workers. There was no significant difference in the acceptance of EHMW among different age groups, education levels and level of work experience. Mental health literacy and wellness at work did not have a strong influence on EHMW acceptance, reflecting the findings of previous research, which indicated that EHMW literacy was only indirectly related to EHMW acceptance6 and that perceived stress was not a meaningful predictor of acceptance.2\n\n\nConclusion\n\nThe prevention of mental health problems is important during the COVID-19 crisis, and EHMW has played an important role in providing mental health-related support during the MCO. Nevertheless, it is predicted that social distancing measures coupled with awareness among policy and decision makers in the context of the pandemic will lead to significant attitudinal and behavioural change and result in greater long-term acceptance of EHMW. As the acceptance of EHMW in this paper was researched using a small survey of digital workers, it was not possible to fully examine acceptance and the determinants that might influence acceptance of EHMW among digital workers in Malaysia. A larger study by this research group is currently underway to capture further aspects regarding the determining factors of EHMW acceptance.\n\n\nData availability\n\nDANS-EASY: Exploring acceptance of the eHealth model for mental wellness among digital workers. https://doi.org/10.17026/dans-xwz-5x6s12\n\nThis project contains the following underlying data:\n\n- Dataset.xlsx (This file consists all 41 responses that were collected from respondents that participated in the survey for this study)\n\nThis project contains the following extended data:\n\n- Survey Questionnaire_EN.pdf (Respondents were required to answer this questionnaire to participate in the survey)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).",
"appendix": "Acknowledgements\n\nThe main author would like to express appreciation to the anonymous reviewers for their highly constructive comments and their help in reviewing the survey instrument.\n\n\nReferences\n\nApolinário-Hagen J, Hennemann S, Fritsche L, et al.: Determinant factors of public acceptance of stress management apps: Survey study. J. Med. Internet Res. 2019; 6(11). PubMed Abstract | Publisher Full Text\n\nApolinário-Hagen J, Hennemann S, Kück C, et al.: Exploring User-Related Drivers of the Early Acceptance of Certified Digital Stress Prevention Programs in Germany. Health Services Insights. 2020; 13: 117863292091106. PubMed Abstract | Publisher Full Text\n\nApolinário-Hagen J, Vehreschild V, Alkoudmani RM: Current Views and Perspectives on E-Mental Health: An Exploratory Survey Study for Understanding Public Attitudes Toward Internet-Based Psychotherapy in Germany. JMIR Mental Health. 2017; 4(1): e8. PubMed Abstract | Publisher Full Text\n\nAzuddin A: MCO and Mental Well-Being: Home Sweet Home ? Part 1: Housing and crowding during the MCO.2020; 1–42.\n\nEichenberg C, Wolters C, Brähler E: The internet as a mental health advisor in Germany - Results of a national survey. PLoS One. 2013; 8(11): e79206. PubMed Abstract | Publisher Full Text\n\nHennemann S, Witthöft M, Bethge M, et al.: Acceptance and barriers to access of occupational e-mental health: cross-sectional findings from a health-risk population of employees. Int. Arch. Occup. Environ. Health. 2018; 91(3): 305–316. PubMed Abstract | Publisher Full Text\n\nKontos E, Blake KD, Chou WYS, et al.: Predictors of ehealth usage: Insights on the digital divide from the health information national trends survey 2012. J. Med. Internet Res. 2014; 16(7): e172–e116. PubMed Abstract | Publisher Full Text\n\nMalaysian Digital Economic Corporation, (MDEC): Digital talent report. Cyberjaya: Frost & Sullivan; 2017; 2017.\n\nPodsakoff PM, MacKenzie SB, Podsakoff NP: Sources of method bias in social science research and recommendations on how to control it. Annu. Rev. Psychol. 2012; 63: 539–569. PubMed Abstract | Publisher Full Text\n\nPodsakoff PM, MacKenzie SB, Lee JY, et al.: Common Method Biases in Behavioral Research: A Critical Review of the Literature and Recommended Remedies. J. Appl. Psychol. 2003; 88(5): 879–903. PubMed Abstract | Publisher Full Text\n\nSchaufeli WB, Bakker AB, Salanova M: The measurement of work engagement with a short questionnaire: A cross-national study. Educ. Psychol. Meas. 2006; 66(4): 701–716. Publisher Full Text\n\nTan, Mr CHOON HONG (Multimedia University Cyberjaya, Malaysia): Exploring acceptance of the eHealth model for mental wellness among digital workers. DANS; 2020. Publisher Full Text\n\nShaw T, et al.: What is eHealth (6)? Development of a Conceptual Model for eHealth: Qualitative Study with Key Informants Corresponding Author.2017; vol. 19(no. 6): pp. 1–12.\n\nVargas-Llave O, Mandl I, Weber T: Telework and ICT-based mobile work: Flexible working in the digital age.2020. Publisher Full Text\n\nWhaibeh E, Mahmoud H, Naal H: Telemental Health in the Context of a Pandemic: the COVID-19 Experience. Curr. Treat. Options Psych. 2020; 7: 198–202. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "124565",
"date": "18 Mar 2022",
"name": "Eugene Boon Yau Koh",
"expertise": [
"Reviewer Expertise psychiatry",
"mental health",
"digital mental 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\nThis is a fundamental study that explores the acceptance of the eHealth model for mental health. The study aimed to explore the association of acceptance with participants demographic data, mental health literacy and workplace wellness. They found that participants were agreeable with the idea of eHealth for mental health. They also found that the acceptance level was the highest for the application domain of \"interacting for health\", with male respondents more likely to accept the use of eHealth in Mental Health.\nThe study design and data collection appear to be sound. However, there are other confounding factors such as internet access availability, gender bias in workplace (if relevant in sample population), salary gap and other external factors that can have a huge impact on the current study result. These factors should be briefly addressed by the authors to present a more holistic description of the results.\nAs this is a fundamental study, I believed that the results presented, while limited in interpretation, provides an early view on how eHealth can be associated within the field of mental health. This study serve as the stepping stone so that more robust study methodology should be explored in the future.\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": "7983",
"date": "22 Mar 2022",
"name": "Choon Hong Tan",
"role": "Author Response",
"response": "Dear Eugene Boon Yau Koh, Thank you very much for your reviews."
}
]
},
{
"id": "129667",
"date": "09 May 2022",
"name": "Karin Ahlin",
"expertise": [
"Reviewer Expertise e-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 study is of interest and should be tested in other work groups or other contexts. The interesting part of the study is the combination of various aspects on accepting e-health and the relation to the pandemic situation with the working-from-home situation.\nWhat I want you to consider is to describe why you have started by using this group of people. Why are they of interest as a focal point? Is it related to easy access or any other specific factor? I also would like to know how you want to continue with other groups, declaring a step-wise declaration on how to move on with them. This would make the study of further interest, declaring how scale it. I would also like to have more information about the group, i.e., in the introduction or even in the article’s headline.\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": [
{
"c_id": "8245",
"date": "09 Jun 2022",
"name": "Choon Hong Tan",
"role": "Author Response",
"response": "Thank you for your thoughtful and highly constructive comments and efforts towards improving our manuscript. In the following, we highlight your general concerns by addressing to each comments. The study is of interest and should be tested in other work groups or other contexts. Future study will be addressed to larger group of digital workers from various digital and ICT related industry/firms/institutions. This larger study has been conducted and is in the process of data analysis and reporting. Further planning of future studies for other high stress working groups, such as blue collar workers involved in electronics manufacturing organizations who are exposed to high work stress; young trainee doctors who are still conducting housemanship procedures in Malaysia’s government hospitals that experience high burnout rate due to huge workload, and huge mental burden due to workplace violence and bullying. The issue of high prevalence of workplace bullying among young doctors was recently brought to attention following a shocking and sad incident of death of a young doctors which is claimed to be the result of bullying and harassment. The study should also be addressed to these group of workers in order to reveal more findings which would help the future implementation of eHealth to be more relevant and beneficial to these groups of workers who are in need of these eHealth innovations. What I want you to consider is to describe why you have started by using this group of people. Why are they of interest as a focal point? The study implement purposive sampling from a chosen multimedia and ICT based higher education institution that offer mostly ICT, computing and multimedia related academic programmes. This group of users / respondents were chosen mainly because they have the experience, background, and technical knowledge in the areas of ICT, computing and multimedia, and are often works with digital technologies to carry out their daily task. The target respondents include, 1) in-house system developer, system admin who are under the Technical and ICT Division of the institution, 2) an academician group who are teaching in multimedia and ICT field. These groups of the respondents have more exposure to digital technologies and have been expecting (more ready) to have higher digital literacy and acceptance for new technologies such as e-mental health. Another reason is due to higher education industry in Malaysia is highly competitive and greatly affected by the COVID-19 pandemic. The shifting of workstyle to a new normal, especially in teaching online, and many other stressful situations (such as the increase of student intakes) due to pandemic situation, has affected their mental wellness. Their experience during this period also have made them as an important stakeholder which needs to be a targeted respondents of this study. Is it related to easy access or any other specific factor? This research was conducted mainly as purposive sampling (of choosing digital workers), influence partly by the easy access of the sample. This is because the second and the third author is close to the targeted respondent group, and they were able to assist in data collection in a tight schedule given under this study. I also would like to know how you want to continue with other groups, declaring a step-wise declaration on how to move on with them. This would make the study of further interest, declaring how scale it. After this study was concluded, another study was conducted to reach out to more digital workers from various digital and ICT related industry/firms and ICT divisions/department from various companies. This study has started and currently in the analysis and reporting stage. Future study also planned to reach out to other high stress worker groups such as blue collar workers involved in electronics manufacturing organizations; young trainee doctor who are still conducting housemanship procedures in Malaysia’s government hospitals, and to different workplaces, or different employers who are concerned about their employees’ wellbeing and subsequently promoting health in their workplaces. These target groups are chosen because they are familiar with the concept of workplace wellness, and therefore their inputs will be highly beneficial for the development of knowledge in this field. Lastly, a more comprehensive research would need to be participatory in nature by including different stakeholders (developers, health care providers, and users) in a more formal and structured program. The program can involve various processes of developing, implementing, and evaluating eHealth for mental wellness and to increase the likelihood of the intervention to be appeal, and to be accepted and meet the users’ need. An innovation’s full potential can only be exploited for better wellness when it is well accepted and is being used for a long period of time. I would also like to have more information about the group, i.e., in the introduction or even in the article’s headline. More information of the target group will be included in the introduction of the new version of this paper after revision is completed."
}
]
}
] | 1
|
https://f1000research.com/articles/11-111
|
https://f1000research.com/articles/11-634/v1
|
09 Jun 22
|
{
"type": "Case Report",
"title": "Case Report: Hyperemesis gravidarum, high transaminases level and prolonged prothrombin time: is it an acute liver injury?",
"authors": [
"Rym Ennaifer",
"Yosr El Mouldi",
"Bochra Bouchabou",
"Abdelwahab Nakhli",
"Nesrine Hemdani",
"Amel Triki",
"Rym Ennaifer",
"Bochra Bouchabou",
"Abdelwahab Nakhli",
"Nesrine Hemdani",
"Amel Triki"
],
"abstract": "Background: Hyperemesis gravidarum (HG) is a severe form of nausea and vomiting in the first trimester of pregnancy. It is considered a benign condition, but severe complications, fortunately rare, have been reported. Frequently, this condition is associated with a perturbed liver function tests, which remains without severe consequences. The clinical presentation may be suggestive of an acute liver injury (ALI), especially as the end of the first trimester approaches, pregnancy specific and non-specific liver diseases should be considered. Case: A 28-year-old primigravida, 14-week pregnant woman affected by hyperemesis gravidarum, developed high transaminases level and spontaneously low prothrombin time (PT) ratio. An ALI was suspected as transaminases were very high and our patient was at the end of the first trimester. An exhaustive etiological work-up was negative. In the second line, the factor V assay was conducted, which showed a normal activity, and the vitamin K level was low. We therefore concluded that it was hyperhemesis gravidarum complicated by fluid and electrolyte disorders and vitamin K deficiency. She had parenteral rehydration and a proton pump inhibitor. She received intravenous vitamin K 10 mg daily for three days. The outcome was excellent without any maternal or fetal impact. Conclusion: Hyperhemesis gravidarum is a common condition in the first trimester of pregnancy that usually has a favourable outcome. However, it is important to be attentive to possible complications, including vitamin K deficiency with its maternal and fetal consequences. On the other hand, in case of major disturbance of the liver function tests, we should not overlook acute liver injury and should not hesitate to initiate an adequate etilogical investigation.",
"keywords": [
"Hyperemesis",
"Acute liver injury",
"prothrombin time",
"vitamin K"
],
"content": "Editorial note\n\nEditorial note (14th June 2023): Following internal discussion and communication with the author, the F1000 Editorial Team have determined that oral informed consent to publish is acceptable in this instance; the anonymity of the patient is maintained and the oral informed consent to publish was documented in the patient’s medical records. Peer review will now resume for this article.\n\nEditorial note (28th March 2023): Since publication, it has been brought to the attention of the Editorial Team that only oral informed consent was obtained from the patient for publication of this case report. As per our research involving humans policy, case reports require written informed consent to be obtained as they contain potentially identifying information about individuals. We have requested that the authors obtain written informed consent to publish from the patient. Peer review activity has been suspended for this article until written informed consent is confirmed.\n\n\nIntroduction\n\nNausea and vomiting are common in the first trimester of pregnancy and usually have an excellent outcome: most cases recover around week 20. However, some patients present a more severe form: hyperemesis gravidarum (HG). It is defined by incoercible vomiting leading to a weight loss of more than 5%, hydro-electrolytic disorders and ketosis. Frequently, this condition is associated with a perturbed liver function tests, mainly a mild elevation of transaminases and more rarely jaundice, which remains without severe consequences, particularly without hepatocellular failure.\n\n\nCase report\n\nA 24 year-old primigravida patient, with no familial or personal medical history, was admitted at week 14 of pregnancy for severe vomiting refractory to the usual symptomatic treatment since one month with asthenia and recent bodyweight loss.\n\nOn admission, she presented an altered general condition, signs of extracellular dehydration, and epigastric sensitivity in abdominal examination. Her axillary temperature was normal, the skin and mucous membranes were normal, the haemodynamic status was stable and there was no palpable goiter. The patient has no active bleeding and no abnormalities on neurological examination. Obstetrical examination was also normal. The urine test showed ketonuria without proteinuria.\n\nAbdominopelvic ultrasound ruled out anomalies of the biliary tract, hepatic veins thrombosis and obstetric emergencies.\n\nLaboratory analysis showed hypokalaemia at 2.4 mmol/l without other electrolyte disorder, elevated transaminases: serum aspartate aminotransferase (ASAT) 201 IU/l and serum alanine aminotransferase (ALAT) 648 IU/l (normal value < 40) without cholestasis, total bilirubin 32 umol/l, spontaneously low prothrombin time (PT) ratio 40%, haemoglobin 10 g/dl. Thyroid function tests were normal. Bacterial urine sampling was negative in culture. Serum markers for viral hepatitis (A, B, C, E, EBV, CMV and HSV) were not detectable. Autoimmune antibodies were absent.\n\nDrug-induced hepatotoxicity was also ruled out, as the patient did not ingest any recent medicine or pharmacological therapy.\n\nAcute liver injury (ALI) was suspected. However, Factor V assay showed a normal activity, with low vitamin K levels. The diagnosis of HG complicated by fluid and electrolyte disorders and vitamin K deficiency was retained.\n\nAs her PT continued to decrease, she received intravenous vitamin K 10 mg daily for 3 days. She had parenteral rehydration with correction of hypokalaemia. For vomiting, a proton pump inhibitor was prescribed.\n\nThe outcome was excellent, with regression of vomiting, correction of water-electrolyte balance and a normal PT of 85%. On the other hand, liver function tests normalization was slower.\n\n\nDiscussion\n\nHG is the most severe form of nausea and vomiting in the first trimester of pregnancy. Its prevalence is 0.3 to 1% of pregnancies.1 Its pathophysiology remains unclear, but it is certainly multifactorial. This condition is considered a first trimester pregnancy-related liver disease as it is associated with liver function abnormalities in half of the cases.2 The transaminase elevation is usually moderate but can reach 1000 IU/L in rare cases. It predominates over ALAT.2 Alkaline phosphatase may double, and bilirubin increases up to 4 mg/dL. However, synthetic liver function remains intact, with normal coagulation profile and serum albumin levels, except in case of severe malnutrition.3 Usually, these disorders disappear after the vomiting has stopped and the fluid and electrolyte disorders have been resolved.2\n\nThe aetiology of liver damage during HG is not well known, but several factors may be involved: dehydration, malnutrition, human chorionic gonadotropin (HCG) and placental-derived cytokines such as tumor necrosis factor-alpha.4\n\nNormal pregnancy has no effect on ASAT and ALAT. Therefore, in case of liver enzymes anomalies, other causes, both non-specific and specific to pregnancy, should be ruled out, in particular those that can lead to hepatocellular failure and that require urgent treatment.4 It has to be emphasized that most pregnancy-related liver diseases occur in the second and third trimesters. The diagnosis of liver disease secondary to HG remains a diagnosis of exclusion. Our patient was at the end of the first trimester (week 14), we were therefore alarmed at the fall of PT ratio, fearing other pregnancy specific liver diseases.\n\nSevere complications, fortunately rare, have also been reported in HG.5 Mallory-Weiss syndrome, oesophageal rupture, inhalation pneumonitis, splenic avulsion, retinal haemorrhage and vitamin deficiency due to malabsorption secondary to incoercible vomiting: Gayet-Wernicke encephalopathy and a coagulopathy secondary to vitamin K deficiency. The latter was first described in 19985 in a patient admitted for management of HG, who presented with profuse epistaxis and whose various investigations of blood haemostasis and liver function concluded that she was vitamin K deficient.\n\nIn our patient’s case, an ALI was suspected based on the significant elevation of transaminases and the low PT. We therefore performed the standard work-up. We also tested for factor V activity to be sure that liver synthetic functions were correct. Then we confirmed the diagnosis of vitamin K deficiency by determining vitamin K blood level.\n\nVitamin K is a fat-soluble vitamin, absorbed in the small intestine, mainly the jejunum, in the presence of bile salts. Reserves are low and are mainly in the liver. It has a key role in coagulation. Recommended intakes are usually largely covered by the diet. The aetiologies of vitamin K deficiency are diverse: lack of intake, intestinal malabsorption, liver dysfunction or the use of anti-vitamin K drugs (warfarin). In HG, vitamin K deficiency due to inadequate intake secondary to incoercible vomiting may be present in 26% of patients.6\n\nIt can have serious consequences for both the mother and the foetus: vitamin K deficiency embryopathy, maternal haemorrhage and neonatal cranial haemorrhage.6 Vitamin K deficiency embryopathy includes Binder phenotype and chondrodysplasia punctata.\n\nScreening for haemostasis disorders by performing a PT could allow early diagnosis and correction of the deficiency by vitamin K supplementation before the onset of these consequences.\n\nHG management usually includes fluid and electrolyte correction, intravenous antiemetic therapy and vitamin supplementation. Indeed, vitamin B1 supplementation to prevent Wernicke’s encephalopathy is recommended and commonly practiced. Several studies suggest prophylactic vitamin K supplementation for hyperemesis gravidarum with severe malnutrition or weight loss. It remains to be proven whether early prophylactic vitamin K supplementation is safe and effective in preventing complications, especially embryopathy.6\n\nFor our patient, no foetal anomalies were detected on perinatal ultrasound. PT was not performed in the context of a bleeding complication or embryopathy, but rather systematically. She did not receive initially prophylactic supplementation.\n\n\nConclusion\n\nHG is generally considered as a benign condition. However, it should be kept in mind that HG could lead to coagulopathy by means of vitamin K deficiency, in order to avoid maternal and foetal complications. In this context, the disturbance of liver function tests associated with a low PT must lead to the suspicion of ALI and therefore initiate an appropriate etiological investigation. Collaboration between the hepatologist and gynaecologist is essential for better management.\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\nOral informed consent for publication of their clinical details and/or clinical images was obtained from the patient during her hospital stay and noted in her medical record.",
"appendix": "References\n\nBacq Y: Hépatopathies gravidiques. Hépato-Gastro & Oncologie Digestive. 2013; 20(8): 583–592. Publisher Full Text\n\nGaba N, Gaba S: Study of Liver Dysfunction in Hyperemesis Gravidarum. Cureus. 2020 Jun 20; 12(6): e8709. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVarlas VN, Bohîltea R, Gheorghe G, et al.: State of the Art in Hepatic Dysfunction in Pregnancy. Healthcare. 2021; 9: 1481. PubMed Abstract | Publisher Full Text\n\nSasamori Y, Tanaka A, Ayabe T: Liver disease in pregnancy. Hepatol. Res. 2020 Sep; 50(9): 1015–1023. PubMed Abstract | Publisher Full Text\n\nRobinson JN, Banerjee R, Thiet MP: Coagulopathy secondary to vitamin K deficiency in hyperemesis gravidarum. Obstet. Gynecol. 1998 Oct; 92(4 Pt 2): 673–675. PubMed Abstract | Publisher Full Text\n\nNijsten K, van der Minnen L , Wiegers HMG, et al.: Hyperemesis gravidarum and vitamin K deficiency: a systematic review. Br. J. Nutr. 2021 Jul; 30: 1–13. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "236742",
"date": "23 Jan 2024",
"name": "Jone Trovik",
"expertise": [
"Reviewer Expertise gynecology",
"hyperemesis gravidarum",
"nutritional treatment in early pregnancy"
],
"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 describe a woman with severe nausea and vomiting in pregnancy; hyperemesis gravidarum, hospitalized with weight loss (not stated amount of weight loss) prescribed \"usual symptomatic treatment\" (not specified) and at admission detected elevated liver enzymes. Acute liver injury was suspected and during evaluation (no time frame noted) she was diagnosed with vitamin-K deficiency and prescribed vitamin-K intravenously.\n\nThe description of treatment provided is insufficient. What was provided as antiemetics? Did this relieve her nausea and vomiting? But most important for this patient history: did she receive any nutritional therapy apart from vitamins (parenteral or enteral, not only fluids to correct dehydration/electrolyte imbalance). And with regard to any nutritional treatment; was her food intake monitored? What about noting her weight loss initially (from prepregnant weight until admission) and was any weight gain during hospital stay noted or further weight gain until end of pregnancy/until delivery? What was the length of pregnancy (gestational length) when she delivered? What was the baby's weight at birth? What was the maternal weight at delivery/end of pregnancy?\n\nAs an obstetrician these information's are very important in assessing health during pregnancy!\n\nThe discussion regarding etiology is sufficient.\n\nThis case point to an important aspect of hyperemesis; insufficient nutritional intake, and also point to the general lack of health carers assessing and providing adequate nutritional treatment for a woman with nausea and vomiting 24/7! I would very much like the authors to provide additional information regarding these aspects.\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? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-634
|
https://f1000research.com/articles/9-1493/v1
|
21 Dec 20
|
{
"type": "Software Tool Article",
"title": "HGNChelper: identification and correction of invalid gene symbols for human and mouse",
"authors": [
"Sehyun Oh",
"Jasmine Abdelnabi",
"Ragheed Al-Dulaimi",
"Ayush Aggarwal",
"Marcel Ramos",
"Sean Davis",
"Markus Riester",
"Levi Waldron",
"Sehyun Oh",
"Jasmine Abdelnabi",
"Ragheed Al-Dulaimi",
"Ayush Aggarwal",
"Marcel Ramos",
"Sean Davis",
"Markus Riester"
],
"abstract": "Gene symbols are recognizable identifiers for gene names but are unstable and error-prone due to aliasing, manual entry, and unintentional conversion by spreadsheets to date format. Official gene symbol resources such as HUGO Gene Nomenclature Committee (HGNC) for human genes and the Mouse Genome Informatics project (MGI) for mouse genes provide authoritative sources of valid, aliased, and outdated symbols, but lack a programmatic interface and correction of symbols converted by spreadsheets. We present HGNChelper, an R package that identifies known aliases and outdated gene symbols based on the HGNC human and MGI mouse gene symbol databases, in addition to common mislabeling introduced by spreadsheets, and provides corrections where possible. HGNChelper identified invalid gene symbols in the most recent Molecular Signatures Database (mSigDB 7.0) and in platform annotation files of the Gene Expression Omnibus, with prevalence ranging from ~3% in recent platforms to 30-40% in the earliest platforms from 2002-03. HGNChelper is installable from CRAN.",
"keywords": [
"gene symbols",
"molecular biology",
"HGNC",
"MGI"
],
"content": "Introduction\n\nGene symbols are widely used in biomedical research because they provide descriptive and memorable nomenclature for communication. However, gene symbols are constantly updated through the discoveries and re-identification of genes, resulting in new names or aliases. For example, GCN5L2 (General Control of amino acid synthesis protein 5-Like 2) is a gene symbol that was later discovered to function as a histone acetyltransferase and therefore renamed as KAT2A (K(lysine) Acetyl Transferase 2A))1. In addition to the rapid and constant updates on valid gene symbols, commonly used spreadsheet software, such as Microsoft Excel, modify some gene symbols, converting them into dates or floating-points numbers2,3. For example, ‘DEC1’, a symbol for ‘Deletion in Esophageal Cancer 1’ gene, can be exported in date format, ‘1-DEC’. There have been attempts to rectify gene symbol issues, but they have largely been limited to Excel-modified gene symbols. Also the suggested solutions often reference static files with the corrections curated at the time of publication3 or comprise scripts for detecting the existence of Excel-modified gene symbols without correction2. In recognition of the importance of the spreadsheet modification issues, HGNC recently announced that all symbols that auto-convert to dates in Excel have been changed4. However, much literature and public data still contains outdated and incorrect gene symbols, motivating a convenient method of systematic detection and correction. To systematically identify historical aliases, correct for capitalization differences, and simultaneously correct spreadsheet-modified gene symbols, we built the HGNChelper R package. HGNChelper maps different aliases and spreadsheet-modified gene symbols to approved gene symbols maintained by The HUGO Gene Nomenclature Committee (HGNC) database5. HGNChelper also supports mouse gene symbol correction based on the Mouse Genome Informatics (MGI) database6.\n\n\nMethods\n\nSource data. Human gene symbols are accessed from HGNC Database ftp site (ftp://ftp.ebi.ac.uk/pub/databases/genenames/new/tsv/hgnc_complete_set.txt)7 and mouse gene symbols are acquired from MGI Database (http://www.informatics.jax.org/downloads/reports/MGI_EntrezGene.rpt)6. These URLs, and their access and processing, are handled by HGNChelper so the user does not interact directly with them.\n\nAlgorithm. Human gene symbol correction is processed in three steps. First, capitalization is fixed: all letters are converted to upper-case, except the open reading frame (orf) nomenclature, which is written in lower-case. Second, dates or floating-point numbers generated via Excel-modification are corrected using a custom index generated by importing all human gene symbols into Excel, exporting them in all available date formats, and collecting any gene symbols that are different from the originals. In the last and most commonly applied step, aliases are updated to approved gene symbols in the HGNC database. Mouse gene symbol correction follows the same three steps as in human gene symbol correction, except the capitalization step since mouse gene symbols begin with an uppercase character, followed by all lowercase.\n\nUser interface. The user interface of HGNChelper does not include any local input or output files; instead it uses R data structures as function arguments and output. Base R data export functions such as write.table can be used to write results to file in whichever format required. The input arguments to the main function, checkGeneSymbols, are:\n\n1. x: A character vector of gene symbols to check for modified or outdated values\n\n2. chromosome: An optional integer vector the same length as x, providing chromosome numbers for each gene\n\n3. unmapped.as.na: A logical value, if TRUE (default), unmapped symbols will appear as NA in the Suggested.Symbol output column. If FALSE, the original unmapped symbol will be kept.\n\n4. map: An optional user-updated or non-standard gene map. The default maps can be updated by running the interactive example provided in the help page to checkGeneSymbols.\n\n5. species: A required character vector of length 1, either \"human\" (default) or \"mouse\".\n\ncheckGeneSymbols returns an R data.frame with one row per input gene and three columns:\n\n1. The first column of the data frame shows the input gene symbols.\n\n2. The second column indicates whether the input symbols are valid\n\n3. The third column provides a corrected gene symbol where possible.\n\nA message is printed indicating when the package’s built-in map was last updated. Because the gene symbol databases are updated as frequently as every day, we provide the getCurrentHumanMap and getCurrentMouseMap functions for updating the reference map without requiring an HGNChelper software update. These functions fetch the most up-to-date version of the map from HGNC and MGI, respectively, and users can provide the output of these functions through the map argument of checkGeneSymbols function. However, fetching a new map requires internet access and takes longer than using the package’s built-in index.\n\nHGNChelper is an R package installable from CRAN on Linux, Windows, and OSX. It requires a base installation of R (> 3.5.0) and no other dependencies, and has minimal hardware requirements that should be met by any computer capable of installing the R dependency.\n\n\nResults\n\nTo evaluate the performance of HGNChelper, we quantified the extent of invalid gene symbols present in platform annotation files in the Gene Expression Omnibus (GEO) database from 2002 to 2020. We downloaded 20,716 GEO platform annotation (GPL) files using GEOquery::getGEO8, of which 2,044 platforms were suspected to contain gene symbol information based on matching to valid symbols. There is a clear trend of increasing proportion of invalid gene symbols with age of platform submission (Figure 1), ranging from an average of ~3% for recent platforms and increasing with age to ~20% in 2010 and 30–40% in the earliest platforms from 2002–03. The overall proportion of valid gene symbols was 79%, increasing to 92% after HGNChelper correction. The 8% remaining, invalid gene symbols were mostly long non-coding RNA (lncRNA), pseudogenes, commercial product IDs such as probe ID, missing data, and gene symbols from non-human species, erroneously included together with human gene symbols. We also checked the validity of gene symbols in the Molecular Signatures Database (MSigDB 7.0)9. Out of 38,040 gene symbols used in MSigDB version 7.0, 850 were invalid, and this number reduces to 453 after HGNChelper correction, of which the majority were lncRNA and a few withdrawn symbols.\n\nEach dot represents a unique GPL. Older entries show a smaller fraction of valid gene symbols than more recent entries (Before, white box), but many of which are successfully corrected by HGNChelper (After, grey box).\n\n\nDiscussion\n\nGene symbols are error-prone and unstable, but remain in common use for their memorability and interpretability. Our analysis of public databases containing gene symbols emphasizes the need for gene symbol correction particularly when using symbols from older datasets and reported results. Such correction should be routinely done when gene symbols are part of high-throughput analysis, such as re-analysis of targeted gene panels for precision medicine, which tend to be annotated with gene symbols (e.g. 10), in Gene Set Enrichment Analysis using the gene symbol versions of popular databases such as MSigDB9 or GeneSigDB11, or when performing systematic review or meta-analysis of published multi-gene signatures (e.g. 12). HGNChelper implements a programmatic and straightforward approach to the routine identification and correction of invalid gene symbols.\n\n\nSoftware availability\n\nPackage available from CRAN: https://cran.r-project.org/package=HGNChelper\n\nSource code available from: https://github.com/waldronlab/HGNChelper/\n\nArchived source code as at time of publication: https://doi.org/10.5281/zenodo.430998513\n\nLicense: GPL (≥ 2.0)",
"appendix": "Acknowledgements\n\nAn earlier version of this article can be found on bioRxiv (doi: https://doi.org/10.1101/2020.09.16.300632)\n\nSupported by National Cancer Institute (NCI) grant U24-CA180996 to L.W.\n\n\nReferences\n\nPoux AN, Cebrat M, Kim CM, et al.: Structure of the GCN5 histone acetyltransferase bound to a bisubstrate inhibitor. Proc Natl Acad Sci U S A. 2002; 99(22): 14065–70–70. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZeeberg BR, Riss J, Kane DW, et al.: Mistaken identifiers: gene name errors can be introduced inadvertently when using Excel in bioinformatics. BMC Bioinformatics. 2004; 5: 80. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZiemann M, Eren Y, El-Osta A: Gene name errors are widespread in the scientific literature. Genome Biol. 2016; 17(1): 177. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBruford EA, Braschi B, Denny P, et al.: Guidelines for human gene nomenclature. Nat Genet. 2020; 52(8): 754–758. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYates B, Braschi B, Gray KA, et al.: Genenames.org: the HGNC and VGNC resources in 2017. Nucleic Acids Res. 2017; 45(D1): D619–D625. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBult CJ, Blake JA, Smith CL, et al.: Mouse Genome Database (MGD) 2019. Nucleic Acids Res. 2019; 47(D1): D801–D806. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHome | HUGO Gene Nomenclature Committee. [cited 2 May 2020]. Reference Source\n\nDavis S, Meltzer PS: GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor. Bioinformatics. 2007; 23(14): 1846–1847. PubMed Abstract | Publisher Full Text\n\nLiberzon A, Subramanian A, Pinchback R, et al.: Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011; 27(12): 1739–1740. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcCabe MJ, Gauthier MEA, Chan CL, et al.: Development and validation of a targeted gene sequencing panel for application to disparate cancers. Sci Rep. 2019; 9(1): 17052. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCulhane AC, Schwarzl T, Sultana R, et al.: GeneSigDB--a curated database of gene expression signatures. Nucleic Acids Res. 2010; 38(Database issue): D716–25. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWaldron L, Haibe-Kains B, Culhane AC, et al.: Comparative meta-analysis of prognostic gene signatures for late-stage ovarian cancer. J Natl Cancer Inst. 2014; 106(5): dju049. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWaldron L, Oh S, Aggarwal A: waldronlab/HGNChelper: Release for Zenodo (Version v1.0.1). Zenodo. 2020. http://www.doi.org/10.5281/zenodo.4309985"
}
|
[
{
"id": "76531",
"date": "18 Jan 2021",
"name": "Mikhail G. Dozmorov",
"expertise": [
"Reviewer Expertise Bioinformatics",
"genomics"
],
"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 manuscript \"HGNChelper: identification and correction of invalid gene symbols for human and mouse\" by Oh S. et al. describes the HGNChelper R package that corrects the common problem of misformatted gene symbols and aliases. The package works with both human and mouse gene symbols. The manuscript describes the procedure for obtaining current gene symbols and creating a mapping between the correct and invalid gene symbols. Analysis of >20K GEO datasets demonstrated the pervasive presence of invalid gene symbols, with the proportion of such symbols decreasing over time. Applied to the recent version of MSigDB, it shows the presence of 850 invalid gene symbols; half of them can be corrected with HGNChelper. The manuscript is well-written, and the package is made using R best practices.\n\nMinor comments about the manuscript include:\nThe limma R package has the alias2Symbol function with similar functionality. How the functionality of HGNChelper differs or improves upon this function?\n\nFigure 1 - Before/after boxplots look identical in the black and white version. Please, correct.\nThe following comments about the package interface are suggestive.\nThe current output of the checkGeneSymbols() function returns a data frame with three columns (x, Approved, Suggested.Symbol). Suggesting including an argument \"simplify\" (TRUE by default) that will return one vector of the same length and order as the original vector of gene symbols, with NAs replacing non-mappable symbols. The rationale is to use this function as a wrapper around the original vector of gene symbols, e.g., checkGeneSymbols(my_genes), returning a drop-in replacement vector of corrected gene symbols. An example is the p.adjust() function that, given a vector of p-values, returns a vector of p-values corrected for multiple testing.\n\nThe package provides separate functions to update gene maps. These updated gene maps can then be used in the checkGeneSymbols() function. Suggesting including an argument \"update.map\" (FALSE by default) to checkGeneSymbols(), that, if TRUE, will automatically update gene maps.\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": "8160",
"date": "09 Jun 2022",
"name": "Levi Waldron",
"role": "Author Response",
"response": "Thank you for reviewing our manuscript and for your constructive comments. Below are our responses to the individual comments. Comment 1: The limma R package has the alias2Symbol function with similar functionality. How does the functionality of HGNChelper differ or improve upon this function? The biggest difference is that limma::alias2Symbol and limma::alias2SymbolTable are intended only to translate known gene aliases, whereas HGNChelper is intended for heterogeneous input that may include aliases, valid symbols, Excel-modified symbols, incorrect capitalization, and unmappable symbols, and to provide a map between input and output. limma::alias2SymbolTable maintains the length of the output vector as same as the input, but if there are multiple aliases, it displays only the one with the lowest Entrez ID number, whereas HGNChelper returns a delimited vector of all aliases. The following example demonstrates these differences: > library(HGNChelper) > input = c(\"FN1\", \"TP53\", \"UNKNOWNGENE\", + \"7-Sep\", \"9/7\", \"1-Mar\", + \"Oct4\", \"4-Oct\", \"OCT4-PG4\", + \"C19ORF71\", \"C19orf71\", \"NIP\") > checkGeneSymbols(input) Maps last updated on: Mon Sep 28 18:31:21 2020 x Approved Suggested.Symbol 1 FN1 TRUE FN1 2 TP53 TRUE TP53 3 UNKNOWNGENE FALSE 4 7-Sep FALSE SEPTIN7 5 9/7 FALSE SEPTIN7 6 1-Mar FALSE MARCHF1 /// MTARC1 7 Oct4 FALSE POU5F1 8 4-Oct FALSE POU5F1 9 OCT4-PG4 FALSE POU5F1P4 10 C19ORF71 FALSE C19orf71 11 C19orf71 TRUE C19orf71 12 NIP FALSE CRPPA /// DUOXA1 /// GIPC1 Warning messages: 1: In checkGeneSymbols(input) : Human gene symbols should be all upper-case except for the 'orf' in open reading frames. The case of some letters was corrected. 2: In checkGeneSymbols(input) : x contains non-approved gene symbols > library(limma) > library(org.Hs.eg.db) > alias2Symbol(alias = input) [1] \"FN1\" \"TP53\" \"C19orf71\" \"GIPC1\" \"DUOXA1\" > alias2SymbolTable(alias = input) [1] \"FN1\" \"TP53\" NA NA NA NA [7] NA NA NA NA \"C19orf71\" \"GIPC1\" Warning message: In alias2SymbolTable(alias = input) : Multiple symbols ignored for one or more aliases Additionally, limma::alias2Symbol uses Bioconductor org*.db packages to map aliases for multiple organisms. org*.db packages in turn pull data from NCBI and update it with each Bioconductor release. HGNChelper is a CRAN package with no dependency on non-base packages, and instead downloads aliases directly from the HUGO and MGI projects. limma::alias2Symbol however provides an advantage of supporting any organism for which an org*.db package is available, whereas HGNChelper supports only human and mouse. Comment 2: Figure 1 - Before/after boxplots look identical in the black and white version. Please, correct. We apologize for the confusing color display. The color schema for Figure 1 is fixed in the updated manuscript. Comment 3: The current output of the checkGeneSymbols() function returns a data frame with three columns (x, Approved, Suggested.Symbol). Suggesting including an argument \"simplify\" (TRUE by default) that will return one vector of the same length and order as the original vector of gene symbols, with NAs replacing non-mappable symbols. The rationale is to use this function as a wrapper around the original vector of gene symbols, e.g., checkGeneSymbols(my_genes), returning a drop-in replacement vector of corrected gene symbols. An example is the p.adjust() function that, given a vector of p-values, returns a vector of p-values corrected for multiple testing. This is a good use case, but we are reluctant to allow a function argument to change the class (and the contract) of what the function returns. Motivated by arguments for “Type consistency” such as by Gillespie and Lovelace (Efficient R programming, https://csgillespie.github.io/efficientR/, section 3.5.2), we think it is less error-prone to require a simple but explicit step to change data class. We’ve added an example to the checkGeneSymbols help page to provide a straightforward solution in this use case: > human [1] \"FN1\" \"TP53\" \"UNKNOWNGENE\" \"7-Sep\" \"9/7\" \"1-Mar\" [7] \"Oct4\" \"4-Oct\" \"OCT4-PG4\" \"C19ORF71\" \"C19orf71\" > checkGeneSymbols(human)$Suggested.Symbol Maps last updated on: Thu Mar 25 08:36:49 2021 [1] \"FN1\" \"TP53\" NA \"SEPTIN7\" [5] \"SEPTIN7\" \"MARCHF1 /// MTARC1\" \"POU5F1\" \"POU5F1\" [9] \"POU5F1P4\" \"C19orf71\" \"C19orf71\" Warning messages: 1: In checkGeneSymbols(human) : Human gene symbols should be all upper-case except for the 'orf' in open reading frames. The case of some letters was corrected. 2: In checkGeneSymbols(human) : x contains non-approved gene symbols Comment 4: The package provides separate functions to update gene maps. These updated gene maps can then be used in the checkGeneSymbols() function. Suggesting including an argument \"update.map\" (FALSE by default) to checkGeneSymbols(), that, if TRUE, will automatically update gene maps. We are reluctant to add an argument that automatically updates the data resource first because results from the same code and the same version of HGNChelper would produce different results at any time since the HGNC and MGI databases change frequently, and secondly because the potential for unnecessary heavy load on the HGNC database could result in restrictions on the bulk downloads we rely on. To maintain reproducibility by default we require the user to download and save the map if they want a version newer than what HGNChelper has, an approach also compatible with caching programs like BiocFileCache. We have added the following explanation to the vignette under the title, “Updating maps of aliased gene symbols”: We intentionally avoid automatic update of the map to maintain reproducibility, because the same code from the same version of HGNChelper could produce different results at any time with automatic map update."
}
]
},
{
"id": "76418",
"date": "20 Jan 2021",
"name": "Susan Tweedie",
"expertise": [
"Reviewer Expertise Gene nomenclature",
"Genomics"
],
"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 describes an R package for that checks whether human and mouse symbols match an HGNC or MGI approved symbol and if not suggests a replacement by, correction of capitalization, correction of Excel date and floating-point transformations and matching to alias symbols.\nThe rationale for developing the new software tool is generally clearly explained. As the authors point out, symbols do change (although the HGNC are now committed to making as few symbol changes as possible) and there is a need to check symbols are valid. As the human symbols that convert to dates in Excel have all been changed, this should be less of a problem going forward. However, these mangled symbols persist in historic data sets and some authors will undoubtedly continue to use problematic aliases such as OCT3 so that aspect of the tool is helpful. It may be worth adding that conversion of gene symbols to floating-point numbers in Excel is more of an issue for mouse genes with RIKEN identifiers than human gene symbols.\nThe authors should also address whether there are any other R packages that have similar functionality. The name HGNChelper could lead some to think this is an HGNC endorsed tool; given that a symbol checking tool is already available from the HGNC (https://www.genenames.org/tools/multi-symbol-checker/) (albeit not an R package) the authors should mention this exists and ideally compare the functionality of their tool versus the HGNC tool.\nWhile this is likely to be a useful tool for R users it should come with a few words of caution given that you cannot always be completely sure which gene a symbol refers to in the absence of confirmation via an ID or other additional information. For example, FHL1 is both an approved symbol and an alias of CFH so while FHL1 is a valid symbol the input data may refer to CFH. There are also cases where a symbol is an alias for several genes but not an approved symbol itself e.g. NIP (or Nip) which not an approved symbol but is an alias of GIPC1, DUOXA1, and CRPPA. The authors should clarify how the algorithm deals with cases where an input symbol matches more than one gene. This would address my concerns about whether this is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool.\nI note that the input contains optional chromosome information but there is no mention of how this is used – does the algorithm take this information into account when determining whether a symbol is valid or not?\nThe authors note that some symbols in their test that could not be updated were lncRNAs and pseudogenes. As both of these classes of gene are named by HGNC it would be good to expand on why the tool failed with these genes – do these particular genes lack an HGNC symbol?\nFigure 1 is hard to interpret - it is unclear what the white boxes mentioned in the legend refer to. Improving the clarity of the figure would address my concerns about whether the conclusions about the tool and its performance adequately supported by the findings presented in the article.\n\nIs the rationale for developing the new software tool clearly explained? Partly\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? Yes\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? Partly",
"responses": [
{
"c_id": "8161",
"date": "09 Jun 2022",
"name": "Levi Waldron",
"role": "Author Response",
"response": "Thank you for reviewing our manuscript and for your constructive comments. Below are our responses to the individual comments. Comment 1: It may be worth adding that conversion of gene symbols to floating-point numbers in Excel is more of an issue for mouse genes with RIKEN identifiers than human gene symbols. The reviewer is correct that human gene symbols prone to Excel conversion have now been changed, but many still exist in the literature and public databases as demonstrated in Figure 1. HGNChelper does not currently fix RIKEN identifiers, so we don’t draw this comparison in the manuscript. Comment 2: The authors should also address whether there are any other R packages that have similar functionality. The name HGNChelper could lead some to think this is an HGNC endorsed tool; given that a symbol checking tool is already available from the HGNC (https://www.genenames.org/tools/multi-symbol-checker/) (albeit not an R package) the authors should mention this exists and ideally compare the functionality of their tool versus the HGNC tool. We now compare HGNChelper with the function alias2Symbol from the limma package. This is described in the response to comment 1 from Reviewer 1. Thank you for pointing us to the HGNC’s own tool, the Multi-symbol checker. We understand that our package name, HGNChelper, can potentially imply the endorsement from HGNC, so we clarified in the manuscript that Multi-symbol checker is the tool supported by HGNC. We also compared the HGNChelper and Multi-symbol checker from HGNC. Here are the major points that differentiate these tools: Implementation: Multi-symbol checker is a web-based UI tool. Users can provide an input as a comma- or space- separated list of gene symbols, directly typing-in or uploading the file. Outputs are displayed in the interface as a sortable table and users can choose to download it as a csv file. HGNChelper is a R package, which takes an input as a character vector and outputs the result as a data frame, which can be saved and exported in a different format, such as csv, tsv, rds, etc. Excel-modified gene symbols: HGNChelper corrects inputs in a potentially excel-modified format (e.g. “9/7”, “1-Mar”, “Oct4”), and suggest the original symbol (e.g. “SEPTIN7”, “MARCHF1 /// MTARC1”, “POU5F1”). This functionality is not part of multi-symbol checker - it marks them as ‘Unmatched’ as with any other unmatchable symbol. Chromosome location: Multi-symbol checker provides the chromosome location as a part of the default output, if the approved symbol is available for a given input. HGNChelper provides the chromosome information only if it is provided with the input gene symbol - it validates whether the input chromosome information is correct or not, and if it’s wrong, gives the correct chromosome location. Comment 3: While this is likely to be a useful tool for R users it should come with a few words of caution given that you cannot always be completely sure which gene a symbol refers to in the absence of confirmation via an ID or other additional information. For example, FHL1 is both an approved symbol and an alias of CFH so while FHL1 is a valid symbol the input data may refer to CFH. In this example, FHL1 will be returned as a valid symbol, unless the chromosome of CFH is specified. For example: > checkGeneSymbols(\"FHL1\") x Approved Suggested.Symbol 1 FHL1 TRUE FHL1 > checkGeneSymbols(c(\"FHL1\", \"FHL1\"), chromosome = c(\"X\", \"1\")) x Approved Suggested.Symbol Input.chromosome Correct.chromosome 1 FHL1 TRUE FHL1 X X 2 FHL1 FALSE CFH 1 1 We have added this discussion to the “Limitations” section. Comment 4: There are also cases where a symbol is an alias for several genes but not an approved symbol itself e.g. NIP (or Nip) which is not an approved symbol but is an alias of GIPC1, DUOXA1, and CRPPA. The authors should clarify how the algorithm deals with cases where an input symbol matches more than one gene. This would address my concerns about whether this is sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool. When an input symbol matches ambiguously to more than one gene, HGNChelper displays all the matching genes. For example, HGNChelper::checkGeneSymbols(“NIP”) will return “CRPPA /// DUOXA1 /// GIPC1'' as the suggested symbols. If there is only one valid gene symbol matched with the input, HGNChelper simply evaluates whether the provided chromosome information is correct or not, and if it’s incorrect, outputs the correct chromosome location under the ‘Correct.chromosome’ column. For example, HGNChelper::checkGeneSymbols(“NIP”, chromosome = 1) will return “CRPPA /// DUOXA1 /// GIPC1'' as the suggested symbol and “7 /// 15 /// 19'' as the correct chromosome. If the input matches more than one gene, the chromosome information is used to specify the suggested gene symbol. For example, HGNChelper::checkGeneSymbols(“NIP”, chromosome = 7) will return “CRPPA'' as the suggested symbol and “7'' as the correct chromosome. lncRNAs and pseudogenes can be updated as long as they are not ‘uncharacterized genes’, whose symbols start with ‘LOC’. Based on NCBI, when a published symbol is not available and orthologs have not yet been determined, gene will provide a symbol that is constructed as ‘LOC’ + the GeneID. So HGNChelper can not update them because there are no approved gene symbols for them. Comment 5: Figure 1 - Improve the clarity of the figure We apologize for the confusing color display. Color schema for Figure 1 is fixed in the updated manuscript."
}
]
},
{
"id": "76417",
"date": "02 Feb 2021",
"name": "Marcin Cieślik",
"expertise": [
"Reviewer Expertise Cancer Genetics"
],
"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\nHGNChelper is a particularly valuable tool in the toolbox of a bioinformatics practicioneer. It addresses a real problem, which while superficially trivial, actually affects the quality of analyses.\n\nI use HGNChelper ALL THE TIME especially if a dataset ends up being garbled by Excel. It is easy to use, in most recent versions reasonably fast, and frankly just gets the job done\nThe paper is a short description of the motivation and implementation. With a short study detailing the evolution of gene symbolss.\nWhat I miss in the paper is an assessment of HGNChelper failures (to increase my confidence in the tool). For example how often are symbols converted incorrectly because the same gene symbol was used, at different times, to denote different genes.\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? Partly",
"responses": [
{
"c_id": "8162",
"date": "09 Jun 2022",
"name": "Levi Waldron",
"role": "Author Response",
"response": "Thank you for reviewing our manuscript and for your encouraging comments. Comment 1: The main issue raised is when HGNChelper fails to map symbols, it is important for users to understand the limitations of what the tool can and cannot map. To address this point we manually reviewed many cases where HGNChelper correction efficiency is low in Figure 1 and almost all unmapped symbols fell into one of the following categories: Long non-coding RNAs (e.g. “lnc-ARMCX4-1”, “lnc-SOX11-1”) Withdrawn symbol (e.g. “OCLM”) Uncharacterized gene (e.g. “LOC644669”): Symbols beginning with LOC. When a published symbol is not available, and orthologs have not yet been determined, this may be represented as ‘LOC’ + the GeneID. Non-human gene symbol Missing data Commercial product name (e.g. Probe ID) We have added this to the manuscript section “Limitations”."
}
]
}
] | 1
|
https://f1000research.com/articles/9-1493
|
https://f1000research.com/articles/11-630/v1
|
08 Jun 22
|
{
"type": "Research Article",
"title": "Stress and its association with involvement in online classes: a cross-sectional study among undergraduate students of a medical college in South India",
"authors": [
"Rohith Motappa",
"Malavika Sachith",
"Pracheth Raghuveer",
"Rohith Motappa",
"Malavika Sachith"
],
"abstract": "Background: With the implementation of lockdown and all students restricted to their houses, medical education has shifted towards the online mode. The objective of this study was to assess stress during the pandemic and the association between stress and involvement in online classes among students of a medical college in Mangalore, Karnataka, South India. Methods: A cross-sectional study was conducted among 324 undergraduate students at a medical college in Mangalore, Karnataka, South India. The extent of stress was assessed using a perceived stress scale (PSS), and a questionnaire was used to identify different stressors and to understand the participant’s involvement in online classes. Results: In this study, the mean perceived stress score was 21.66 ± 4. Moderate stress was observed in 262 (85%) students. The main stressors noted were inability to focus (173 (56.4%)) and fear of exams (153 (49.8%)). A significant association was noted between stress and involvement in online classes. Conclusions: This study thereby highlights the need for more attention to the various stressors among students and for making online classes student friendly.",
"keywords": [
"Online classes",
"Perceived stress",
"COVID 19"
],
"content": "Introduction\n\nCoronavirus disease 2019 (COVID-19) was first reported in Wuhan, Hubei Province, China. On January 27th, 2020, the first case in India was reported in the state of Kerala. Thereafter, on March 11th, 2020, the World Health Organisation declared it a pandemic.\n\nCOVID-19 is a novel organism that spreads rapidly among people. Countries feared the doubling rate of the disease and the number of deaths due to it. Although people were being educated to practise preventive measures such as social distancing, wearing masks and sanitising hands, in countries such as India, the rates were still climbing. Hence, to break the chain of this infection, a nationwide complete lockdown was imposed in India on March 24th 2020.\n\nLockdown is an emergency protocol that prevents people from leaving a given area. In the case of complete lockdown, only essential supplies such as grocery stores, pharmacies and banks continued to serve people.\n\nIndia is the country with the largest proportion of the population at a young age. Hence, when lockdown was imposed, they were the worst hit, as this was a generation that has never sat idle but was always on the go. Additionally, the last pandemic faced by India was the 2009 Swine flu,1 so this subject population is totally new to this disease and its preventive measures. As part of the lockdown, all educational institutions, including medical colleges, were shut down, and students were sent back home. Students are most affected by this, as they are losing out on their valuable school and college days. They are confined to the four walls of their households and are exposed to the outer world only virtually via the internet.\n\nIt was found that psychological symptoms such as depression and anxiety were elevated during the period of lockdown and isolation.2 Student suicide was noted during this period, with the first case occurring in Kerala being a 15-year-old who committed suicide.3\n\nIn studies conducted during the pandemic, it was found that stress, anxiety and depression due to COVID-19 were prevalent among the general population.4 Among students, medical students were generally found to have higher stress than nonmedical students.5 With the implementation of the lockdown, all the students were sent home, and online teaching was the only way to continue education.\n\nOnline education is an electronic learning tool that relies on the internet for teacher/student interaction and the distribution of class material. In this way, a student can turn anywhere with internet access and electricity into a virtual classroom. Although this method was introduced as an add on to traditional teaching and learning experience, with COVID-19 still prevalent throughout the world, it has become the new normal for generation Z.\n\nMedical students are the upcoming doctors. Being at home and with an indefinite closure of colleges, there is a prevailing fear of the future among students. For the past 7–8 months, they were attending online classes. This has affected medical education with no more practical classes. This study aimed to assess stress during the pandemic and the association between stress and involvement in online classes among students of a medical college in Mangalore, Karnataka, South India.\n\n\nMethods\n\nInstitution Ethics Committee approval (Yenepoya Ethics Committee-2, Protocol number: YEC2/622, dated 26/12/2020) and permission from the institutional head were obtained before conducting the study. This is a cross-sectional study conducted among medical students studying Bachelor of Medicine and Bachelor of Surgery (MBBS) at Yenepoya Medical College situated in Mangalore taluk, Dakshina Kannada district, Karnataka, South India. The study was conducted from November to December 2020. Complete enumeration was used to enrol participants in this study, including participants studying in the first to final year in the medical college and the total sample size was 600. Approximately six attempts were made to reach out the participants through their online classes and WhatsApp groups, but we did not receive the desired response from the students. Thereby, the final sample size was accounted to 324.\n\nA predesigned, validated, semi-structured questionnaire was used to capture information.6 Demographic variables such as age, sex, religion, year of study and current place of stay were included. The Perceived Stress Scale (PSS), a classic instrument to assess stress, was also incorporated into the questionnaire.7 The questions here ask about the feelings and thoughts of the participants during the last month. It is a 10-item questionnaire with responses in the form of how often participants did experience certain situations from 0-never to 4-very often. Scores ranging from 0 to 13 were considered low stress. Scores ranging from 14 to 26 were considered moderate stress. Scores ranging from 27 to 40 were considered high perceived stress. Questions pertaining to the participants’ involvement in online classes conducted by the college were also included. The Google Form also included a participant information sheet and informed consent.8 All participants were voluntary, and it was described that the identity and the information given would remain strictly confidential. The Google Form responses were downloaded in a coma separated value (CSV) format, and the data captured were then cleaned. Data collected were analysed using SPSS Version 23. Descriptive statistics such as the mean, frequency and proportion were applied. The chi-square test was used to study the association between stress and involvement in online classes.\n\n\nResults\n\nA total of 324 students responded to the survey, and 17 (5%) students did not give consent. The mean age of the students was 21 ± 2 years. The characteristics of the students are depicted in Table 1.\n\nThe mean perceived stress score was 21.66 ± 4. Out of 307 students, moderate stress was observed in 262 (85%) students (Figure 1).\n\nAmong the various stressors identified, inability to focus and fear of exams were the most common stressors (173 (56.4%) and 153 (49.8%), respectively) (Table 2), and other stressors were record completions, phone addiction, etc.\n\n* Multiple response questions.\n\nOn assessing the preference for the mode of teaching among medical students pre- and post-pandemic, it was observed that the offline mode of teaching was preferred during both periods (226 (73.6%) and 170 (55.4%), respectively).\n\nThe association between perceived stress score and online classes is depicted in Table 3. There was a statistically significant association between perceived stress score and remembering content of online classes (p < 0.05), between perceived stress score and hours of classes attended (p < 0.05), and between perceived stress score and difficulty in concentrating online classes (p < 0.05).\n\n\nDiscussion\n\nThis study explored stress among 307 medical undergraduates of a medical college in South India and its association with involvement in online classes.\n\nAlthough there are many studies assessing the stress level among medical students, this is one of the few studies conducted in South India aimed at identifying different stressors and their association with involvement in online classes during this COVID pandemic.\n\nIn this study, the mean perceived stress score was 21.66 ± 4, with moderate stress in 262 (85%) students. These findings were contrary to a study conducted by Joseph et al in which the mean stress score was 13.3 ± 4.2.9 This could be attributed to the fact that our study was conducted during a period of pandemic with the whole world in immense stress.\n\nThe newer stressors due to online learning found in our study were inability to focus on studies, fear of exams, prolonged stay at home, etc., while previous studies suggest that potential stressors for medical students are academic workload and poor time management.10,11 These findings were similar to those of a study conducted by Abdulghani et al.12 COVID-related stressors were also noted, such as fear of infection and inadequate information on the disease, and these were consistent with a study conducted by Luberto et al.13\n\nOut of the 307 students who participated, 170 (55%) students experienced a decrease in overall time spent in studies after the implementation of online classes, which was consistent with the findings of previous studies.14\n\nThe association between perceived stress score and remembering contents of online classes was found to be statistically significant in our study (p < 0.05). Among the 78 students who did not remember the contents of online classes, moderate stress was noted among 67 (85%) students.15\n\nIn the present study, it was found that before the COVID pandemic and lockdown, only 55 (17.9%) students preferred the blended mode of classes with both online and offline modes. After the implementation of the lockdown, the number increased to 109 (35.5%). This is similar to a study conducted by Suryawanshi DM et al.16\n\nThe study results highlight the fact that issues related to online teaching have become a new stressor for already stressed medical students. As online medical education is a new and evolving concept, the education system should make specific modules to help students. Additionally, students should be properly oriented for these classes, and individual-level monitoring must be done not just by teachers but also by parents. Tailor-made coping strategies must be developed for students to ease their stress. In the long run, colleges should modify the learning experience for each student with access to current technologies and the availability of resources for effective learning.\n\nThe strength of this study was that perceived stress scale, a standardised stress scale, was used in this study to access the stress level among the medical students and open-ended questions were asked to identify the different stressors. This study is reported according to the STROBE statement for reporting cross-sectional studies.\n\nThe study had several limitations. The study cannot be completely generalised, as it was conducted in a single private medical college. Here, most of the students were financially secure; hence, the study did not gather information about the needs of students with disabilities during the transition to online courses. As the study was based on a self-administered questionnaire, the chance of reporting bias could not be eliminated. Since the PSS questions are based on the experience of the students in the previous month, there is also a chance for memory or recall bias.\n\nFurther research is advocated for on stress among medical students and its association with online classes. In the “new normal” arena, research should also be directed toward teaching, learning, and evaluation strategies that can maximise learning results while minimising anxiety and negative psychological effects among students.\n\n\nConclusion\n\nModerate perceived stress was observed in approximately 85.3% of students. Inability to focus on studies, fear of exams, and difficulty grasping are the key stressors. Due to this long-term lockdown as a result of the COVID-19 pandemic, the online mode of learning was the only way to continue medical education, which may cause further worsening of the psychological and learning behaviours of these students. Despite these difficulties, students’ faith in the efficiency of online medical education has grown as a result of their experiences during the first few weeks of the pandemic. While pandemics have historically posed difficulties, recognising these difficulties is the first step toward turning them into possibilities.\n\n\nData availability\n\nFigshare: Stress and its association with involvement in online classes: a cross-sectional study among undergraduate students of a medical college in South India. https://doi.org/10.6084/m9.figshare.19375205.v1.17\n\nThis project contains the following underlying data:\n\n• Appraisal of stress V2.xlsx (This is the study participants data in the form of an excel sheet)\n\nFigshare: Stress and its association with involvement in online classes: a cross-sectional study among undergraduate students of a medical college in South India-Questionnaire. https://doi.org/10.6084/m9.figshare.19431500.v1.6\n\nThis project contains the following extended data:\n\n• Questionnaire.docx (This is the questionnaire in word format)\n\nFigshare: Consent form.docx. https://doi.org/10.6084/m9.figshare.19524058.18\n\nThis project contains the following extended data:\n\n• Consent form.docx (Blank copy of the consent form)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nChoudhry A, Singh S, Khare S, et al.: Emergence of pandemic 2009 influenza A H1N1, India. Indian J. Med. Res. 2012 Apr [cited 2021 May 10]; 135(4): 534–537. PubMed Abstract | Free Full Text\n\nBrooks SK, Webster RK, Smith LE, et al.: The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020 [cited 2021 May 10]; 395: 912–920. Lancet Publishing Group. PubMed Abstract | Publisher Full Text\n\nLathabhavan R, Griffiths M: First case of student suicide in India due to the COVID-19 education crisis: A brief report and preventive measures. Asian J. Psychiatr. 2020 [cited 2021 May 10]; 53: 102202. Elsevier B.V. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSalari N, Hosseinian-Far A, Jalali R, et al.: Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: A systematic review and meta-analysis. Global. Health. BioMed Central. 2020 [cited 2021 May 10]; 16: 1–11. PubMed Abstract | Publisher Full Text\n\nAamir IS: Stress Level Comparison of Medical and Nonmedical Students: A Cross Sectional Study done at Various Professional Colleges in Karachi, Pakistan. Acta Psychopathol. 2017 Mar 31 [cited 2021 May 10]; 03(02). Publisher Full Text Reference Source\n\nMotappa R, Raghuveer P: Stress and its association with involvement in online classes: a cross-sectional study among undergraduate students of a medical college in South India-Questionnaire. figshare.2022. Publisher Full Text\n\nState of New Hampshire Employee Assistance Program: Perceived Stress Scale Score Cut Off. State New Hampsh Empl Assist Progr. 1983; 2.\n\nMotappa R, Raghuveer P: Stress and its association with involvement in online classes: a cross-sectional study among undergraduate students of a medical college in South India- Consent form.docx. figshare.2022. Publisher Full Text\n\nJoseph N, Joseph N, Panicker V, et al.: Assessment and determinants of emotional intelligence and perceived stress among students of a medical college in south India. Indian J. Public Health. 2015; 59(4): 310–313. PubMed Abstract | Publisher Full Text\n\nChowdhury R, Mukherjee A, Mitra K, et al.: Perceived psychological stress among undergraduate medical students: Role of academic factors. Indian J. Public Health. 2017; 61(1): 55–57. PubMed Abstract | Publisher Full Text\n\nHill MR, Goicochea S, Merlo LJ: In their own words: stressors facing medical students in the millennial generation. Med. Educ. Online. 2018; 23(1). PubMed Abstract | Publisher Full Text\n\nAbdulghani HM, Sattar K, Ahmad T, et al.: Association of covid-19 pandemic with undergraduate medical students’ perceived stress and coping [response to letter]. Psychol. Res. Behav. Manag. 2020; 13: 1101–1102. PubMed Abstract | Publisher Full Text\n\nLuberto CM, Goodman JH, Halvorson B, et al.: Stress and Coping Among Health Professions Students During COVID-19: A Perspective on the Benefits of Mindfulness. Glob. Adv. Heal. Med. 2020; 9: 2164956120977827. PubMed Abstract | Publisher Full Text\n\nKapasia N, Paul P, Roy A, et al.: Impact of lockdown on learning status of undergraduate and postgraduate students during COVID-19 pandemic in West Bengal, India. Child Youth Serv. Rev. 2020; 116(June): 105194. PubMed Abstract | Publisher Full Text\n\nMeo SA, Abukhalaf AA, Alomar AA, et al.: COVID-19 Pandemic: Impact of Quarantine on Medical Students’ Mental Wellbeing and Learning Behaviors. Pak. J. Med. Sci. 2020 [cited 2020 Oct 7]; 36: S43–S48. PubMed Abstract | Publisher Full Text\n\nSuryawanshi DM, Venugopal R: Preferences, perceptions and barriers to E-learning among medical students during COVID-19 pandemic lockdown in India. Int. J. Community Med. Public Heal. 2020; 7(10): 4100. Publisher Full Text\n\nRaghuveer P, Motappa R: Stress and its association with involvement in online classes: a cross-sectional study among undergraduate students of a medical college in South India. figshare. [Dataset].2022. Publisher Full Text"
}
|
[
{
"id": "140148",
"date": "20 Jun 2022",
"name": "Chonnakarn Jatchavala",
"expertise": [
"Reviewer Expertise Psychiatry",
"mental health",
"suicide",
"students"
],
"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\nIntroduction: -Paragraph 1, not necessary to mention Wuhan, when 1st detected in India and your area. -Before indicating online education, please briefly explain your curriculum of medicine (MBBS?) for years 1,2,3, and 4. What about studying pre-clinic and clinical practice study? -Speaking about \"online education or digital psychiatry\", please reference and describe \"For example, implementing digital training programs may significantly improve the level of knowledge in psychiatry in Asia-pacific region\" Please ref: https://onlinelibrary.wiley.com/doi/full/10.1111/appy.12501 -How long did the lockdown your medical students experienced that year last? -Do you have any rate of Covid-19 infection in medical students/ university students in the area?\nMethods: -Please identify the validity of the tools.\nResults: -It is quite short, with many results you can describe interestingly. Data in Table 3 is confusing, you should explain every item's result and discuss it.\nDiscussion: -What is your suggestion for your medical students from your paper and other research? It will be very good if you can sum it up in a box. Please reference: https://ps.psychiatryonline.org/doi/abs/10.1176/appi.ps.202000774 https://link.springer.com/article/10.1007/s40596-021-01482-3\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? 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? Yes",
"responses": [
{
"c_id": "8420",
"date": "24 Jun 2022",
"name": "Pracheth Raghuveer",
"role": "Author Response",
"response": "Thank you very much for the detailed review. Please find our response to your comments. Introduction: -Paragraph 1, not necessary to mention Wuhan, when 1st detected in India and your area. Response: It will be modified as commented. -Before indicating online education, please briefly explain your curriculum of medicine (MBBS?) for years 1,2,3, and 4. What about studying pre-clinic and clinical practice study? Response: In India, the MBBS curriculum is structured in this way. In the first professional year, pre-clinical subjects like Anatomy, Physiology and Biochemistry are the core subjects. In the second professional year, para-clinical subjects like Pathology, Microbiology, Pharmacology are the core subjects and in the third professional year, Community Medicine, ENT, Ophthalmology and Forensic Medicine are the core-subjects. In the final year, clinical subjects like Medicine, Surgery, OBG and Pediatrics are the core subjects. The teaching involves an integrated approach with emphasis on small group teaching and early clinical exposure. This is as per the latest Competency Based Medical Education mandated by the National Medical Commission of India in the year 2019. -Speaking about \"online education or digital psychiatry\", please reference and describe \"For example, implementing digital training programs may significantly improve the level of knowledge in psychiatry in Asia-pacific region\" Please ref: https://onlinelibrary.wiley.com/doi/full/10.1111/appy.12501 Response: Thanks. This suggestion will be incorporated. -How long did the lockdown your medical students experienced that year last? Response: In India, the nation-wide lockdown lasted from 25 March 2020 to 31 May 2020. This was followed by a gradual ease of restrictions. -Do you have any rate of Covid-19 infection in medical students/ university students in the area? Response: Yes, we do have the data of COVID-19 infection among the medical students in our area. The data may be available on request from the district health officials. However, this study was carried out during the time when the students were off-campus, that is, the lockdown period of 25 March-31 May, 2020. Methods: -Please identify the validity of the tools. Response: A pre-tested, pre-designed and validated proforma was used to collect the data. Results: -It is quite short, with many results you can describe interestingly. Data in Table 3 is confusing, you should explain every item's result and discuss it. Response: Thanks for this comment. Table 3 denotes the association of perceived stress categories with the involvement of online classes. Detailed description will be given in the subsequent version. Discussion: -What is your suggestion for your medical students from your paper and other research? It will be very good if you can sum it up in a box. Please reference: https://ps.psychiatryonline.org/doi/abs/10.1176/appi.ps.202000774 https://link.springer.com/article/10.1007/s40596-021-01482-3 Response: Thanks. This will be summed up in a box as suggested."
}
]
},
{
"id": "141242",
"date": "07 Jul 2022",
"name": "Padmini Thalanjeri",
"expertise": [
"Reviewer Expertise Medical education",
"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 study is a cross sectional study done on undergraduate medical students to determine the academic stress due to online curricular transactions during COVID times. It has shown that the online mode of learning created a significant increase in stress scores thus highlighting the need for more studies on various stressors and to pave the way forward for making online learning more student friendly.\nMinor comments:\nIn the results section of the abstract, please add more findings relevant to the study objectives.\n\nThe introduction may be further strengthened by adding studies carried out on stress among medical students particularly during the COVID pandemic.\n\nKindly modify the conclusion and make it specific to the study objectives.\n\nWhat are the recommendations based on the study findings?\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/11-630
|
https://f1000research.com/articles/11-629/v1
|
08 Jun 22
|
{
"type": "Research Article",
"title": "Effects of the COVID-19 pandemic on the management of ST-Segment elevation myocardial infarction in Indonesia: a cohort study",
"authors": [
"Eka Ginanjar",
"Arif Mansjoer",
"Lusiani Rusdi",
"Rizky Ramadantie",
"Hadiki Habib",
"Lies Dina Liastuti",
"Sally Aman Nasution",
"Idrus Alwi",
"Abdul Rashid Abdul Rahman",
"Arif Mansjoer",
"Lusiani Rusdi",
"Rizky Ramadantie",
"Hadiki Habib",
"Lies Dina Liastuti",
"Sally Aman Nasution",
"Idrus Alwi",
"Abdul Rashid Abdul Rahman"
],
"abstract": "Background: ST-segment elevation myocardial infarction (STEMI) is a form of acute coronary syndrome with high mortality rate. Management of STEMI should be performed as soon as possible to prevent further damage. With the emergence of coronavirus disease 2019 (COVID-19), it may face obstacles. To overcome those problems, some changes in policy focusing on fibrinolytic therapy in STEMI patients have been applied. This study aimed to identify the effects of COVID-19 in management of STEMI patients in Indonesia. Methods: This retrospective study was conducted in Dr. Cipto Mangunkusumo Hospital (CMH), the national referral center in Indonesia. We compared data between 2018 to 2019 and 2020 to 2021 as before and during COVID-19 pandemic period, respectively. We analyzed the effects of COVID-19 on STEMI patients' visits to hospital i.e., monthly hospital admission and symptoms-to-hospital, management of STEMI i.e., the strategies and time of reperfusion, and clinical outcomes of STEMI patients i.e., major adverse coronary event and mortality. Results: There was a significant statistically reduced mean of monthly hospital admissions from 11 to 7 (p = 0.002) and prolonged duration of symptoms-to-hospital during COVID-19 from 8 to 12 hours (p = 0.005). There was also a decrease in primary percutaneous coronary intervention (PPCI) procedures during COVID-19 (65.2% vs. 27.8%, p<0.001), which was accompanied by an increased number of fibrinolytic (1.5% vs. 9.5%, p<0.001) and conservative therapy (28.5% vs. 55.6%, p <0.01). Moreover, there was also a prolonged duration of diagnosis-to-wire-crossing time (160 vs. 186 minutes, p = 0.005), meanwhile, percentage of urgent PCI, door-to-needle time, and clinical outcomes were not statistically significant. Conclusions: During COVID-19 pandemic, the number STEMI patients declined in monthly hospital admission, delays in symptoms-to-hospital time, changes in type of reperfusion strategy, and delays in PPCI procedures in CMH. Meanwhile, fibrinolytic time and clinical outcomes were not affected.",
"keywords": [
"COVID-19",
"STEMI",
"hospital admission",
"symptoms-to-hospital time",
"reperfusion strategy",
"reperfusion time",
"mortality rate",
"MACE"
],
"content": "Introduction\n\nST-segment elevation myocardial infarction (STEMI) as one of the acute coronary syndromes is a condition of acute transmural myocardium ischemia, which causes injury or necrosis of the myocardium with a high mortality rate.1 The management of STEMI including identification, triage, and reperfusion must be performed as soon as possible to prevent further damage to the myocardium. Reperfusion therapy as the main therapy of STEMI plays an important role to improve patients’ clinical outcomes.2 Reperfusion therapy may include fibrinolytic and primary percutaneous coronary intervention (PPCI). However, PPCI is more preferably recommended since it has been proven to provide better clinical results.3\n\nThe emergence of coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has made some impact on healthcare services. The high rate of disease transmission of SARS-CoV-2 has created changes in the algorithm of diagnosis and therapy in hospitals.4–6 Additional screening COVID-19 tests, wearing personal protective equipment, and performing disinfection of medical equipment and wards must be done to prevent the possibility of transmission.7,8 These conditions have potential to hamper treatment response in managing patients with emergency conditions including STEMI.5,9 Additionally, reperfusion therapy using PPCI may need more time considering the high risk of transmission whenever the procedure should be done with the unidentified status of their COVID-19 infection.10\n\nIn response to those obstacles, some countries have changed their policy on the management of STEMI patients by prioritizing fibrinolytic therapy.4–6,11,12 This policy has also been applied in Dr. Cipto Mangunkusumo Hospital (CMH). Therefore, this study aimed to provide knowledge about the effects of the COVID-19 pandemic on the management of STEMI patients in Indonesia.\n\n\nMethods\n\nThis research was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia with number KET-883/UN2.F1/ETIK/PPM.00.02/2021. The Ethics Committee also waived participants consent due to the inconsiderable risk nature of data collection through retrospective datasets already stored on electronic health records, including demographic data, signs and symptoms, pre-existent comorbidity, the duration from symptoms to hospital, the duration of reperfusion strategies, type of reperfusion, and clinical outcomes. The personal information such as medical records numbers and names of patients were deidentified to protect confidentiality.\n\nThis study was a cohort retrospective study conducted at CMH in Jakarta, which serves as the national referral hospital in Indonesia. Information obtained from medical records was collected from all patients with STEMI diagnosis, who had fulfilled inclusion criteria, including patients admitted to CMH who were diagnosed with STEMI according to the diagnostic criteria from European Society of Cardiology (ESC) 2020 and American Heart Association/American College of Cardiology (AHA/ACC) 2014.3,13 The data were retrieved from medical records taken between March 15, 2018 and March 15, 2020 for “before COVID-19 pandemic” period and between March 16, 2020 and September 14, 2021 for “COVID-19 pandemic” period.25 The cut-off point between before COVID-19 and COVID-19 pandemic period was the same day when the Indonesian government announced the COVID-19 as a national disaster in Indonesia. Before the announcement, there were no policies related to lockdown and other official regulations. The exclusion criteria of this study included patients who came with major adverse coronary events (MACE) and severe comorbidities such as acute stroke, hepatic cirrhosis, chronic inflammation, sepsis, autoimmune disorders, and malignancy. As one of the complications of STEMI, MACE was excluded because it can influence the therapy and outcomes that are observed. The sampling technique was total sampling and calculated using sample size determination in health studies by S.K. Lawanga and S. Lameshow.14 The confidence interval (CI) was 5% and the power of test was 20%. The minimum sample size was 167 subjects.\n\nIn this study, we compared the characteristics of STEMI patients before and during COVID-19 pandemic. The outcomes of the study were STEMI patients’ visits to the hospital, including monthly hospital admission and symptoms-to-hospital time; the management of STEMI, including the strategies reperfusion such as PPCI, fibrinolytic, conservative, and urgent PCI; the timeline of reperfusion therapy, including door-to-diagnosis time, door-to-wire crossing time, door-to-needle time, diagnosis-to-wire crossing time, and diagnosis-to-needle time; and the clinical outcomes including MACE and mortality. Patients who underwent PPCI were analyzed specifically about door-to-diagnosis time, door-to-wire-crossing time, diagnosis-to-wire-crossing time, and ischemic time. Patients who administered fibrinolytic agents were analyzed specifically in regards to the door-to-diagnosis time, door-to-needle time, diagnosis-to-needle time, and ischemic time. We also analyzed clinical outcomes including mortality and MACE.\n\nMonthly hospital admission was defined as the number of STEMI patients who visited the emergency department (ED) after experiencing symptoms of STEMI every month, while the strategy of reperfusion included some optional therapies received by the STEMI patients, which were PPCI, fibrinolytic, conservative, and urgent PCI. The definition of symptoms-to-hospital time was the time taken for patients experiencing STEMI symptoms to be admitted to the ED.\n\nPatients who underwent PPCI or received fibrinolytic therapy were assessed for door-to-diagnosis time. This was defined as the time from when the patients came to the ED until they were diagnosed with STEMI. Specifically, door-to-wire crossing time was defined as the duration from the patients came to the ED until they had wire crossing during PPCI, and diagnosis-to-wire crossing time was defined as the duration from when the patients were diagnosed until they underwent wire crossing during PPCI. Meanwhile, door-to-needle time was defined as the duration from the time patients came to the ED until they received fibrinolytic therapy and diagnosis-to-needle time was defined as the duration from the time patients were diagnosed until the fibrinolytic agent was administered. Ischemic time was defined as the duration from the onset of symptoms until the patients received the therapy, either PPCI or fibrinolytic.\n\nData were collected into excel datasheets and codes were made for further analysis using STATA 15.1 program (StataCorp. 2017) (RRID: SCR_012763). The chi-square (X2) test, Mann-Whitney test, and Fisher’s exact test were performed to compare the variables. Continuous variables were presented as median and mean. Categorical variables are presented as frequency and percentage.\n\n\nResults\n\nThere were 712 STEMI patients reported during the sampling period. Among those cases, 393 (55%) of them fulfilled inclusion criteria and the study was conducted retrospectively. The first group consisted of 267 STEMI patients who were included in the “before COVID-19 pandemic” period (mean age of 55 years; 84% were male) and the second group consisted of 126 STEMI patients included in the “COVID-19 pandemic” period (mean age was 58 years and 83% were male).20 Risk factors for cardiovascular diseases such as diabetes mellitus, hypertension, dyslipidemia, obesity, acute renal injury, and chronic kidney failure were distributed similarly in both groups. The detailed baseline characteristics are shown in Table 1.\n\n* p < 0.05.\n\nDuring the COVID-19 pandemic period, there was a reduced number of monthly hospital admission, i.e., from an average visit of 11 patients to 7 patients (p = 0.002). The percentage of STEMI patients who came with a duration of symptoms-to-hospital of <12 hours had found reduced from 68.1% to 49.2%, while symptoms-to-hospital of >12 hours increased from 31.9% to 50.8% (p < 0.001). The average symptoms to hospital time of STEMI patients before COVID-19 pandemic was 8 hours, while during the COVID-19 pandemic, it prolonged to 12 hours (p = 0.005) (Figure 1).\n\nThe significantly prolonged duration of symptoms-to-hospital was found during COVID-19 pandemic compared to before COVID-19 pandemic.\n\nWe found a statistically significant decrease in the use of PPCI procedure from 65.2% to 27.8% (p < 0.001) and increase in the use of fibrinolytic (1.5% vs. 9.5%, p < 0.001) and conservative therapy (28.5% vs. 55.6%, p < 0.001). However, the number of patients who underwent urgent PCI was not statistically significant (4.9% vs. 7.1%, p = 0.360) (Figure 2). The door-to-wire crossing time showed a statistically significant increase during COVID-19 pandemic (160 minutes vs. 186 minutes, p = 0.005). Furthermore, we also found the difference in door-to-diagnosis time for PPCI was statistically significant (15 minutes vs. 35 minutes, p = 0.004), but the difference in diagnosis-to-wire crossing time and ischemic time for PPCI were not statistically significant [(136 minutes vs. 134.5 minutes, p = 0.382), (521 minutes vs. 488 minutes, p = 0.421), respectively]. The duration of fibrinolytic therapy, including door-to-needle time (151 minutes vs. 158 minutes, p = 0.953), door-to-diagnosis time for fibrinolytic (16 minutes vs. 12 minutes, p = 0.571), diagnosis-to-needle time (130 minutes vs. 155 minutes, p = 0.851), and ischemic time (321.5 minutes vs. 400.5 minutes, p = 0.599) showed no statistically significant difference.\n\nPanel A shows monthly hospital admission of STEMI patients seems to have decreased during the pandemic and it was accompanied by the strategies of reperfusion. Panel B shows a decreased significantly the percentage of PPCI and fibrinolytic as well as conservative increased, meanwhile, urgent PCI was not statistically affected. Abbreviation: PPCI: percutaneous coronary intervention, urgent PCI: urgent percutaneous coronary intervention. Panel A i.e., the COVID-19 daily new cases has been reproduced with permission from Ministry of Health of the Republic of Indonesia [https://covid19.go.id/].\n\nThe difference in clinical outcomes, including mortality and MACE, were not statistically significant during COVID-19 from 6.7% to 11% (p = 0.220) and from 10.9% to 16.5% (p = 0.107), respectively. The detailed outcomes of this study were shown in Table 2.\n\n* p < 0.05.\n\n\nDiscussion\n\nThis study found that during the COVID-19 pandemic, there was a significant decrease in the average number of monthly of STEMI related hospital admissions compared to before the COVID-19 pandemic period (11 patients vs. 7 patients, p = 0.002). We also found that the STEMI patients who came to the hospital were dominated by those who experienced the onset of symptoms >12 hours earlier with a median time of 12 hours. Some hypotheses can explain those findings: first, during the pandemic, STEMI patients hesitate to visit hospitals as they may be afraid of COVID-19 exposure when they come to the healthcare facilities; second, there is the large-scale social restriction or emergency public activity restriction in Indonesia, therefore, patient access to healthcare facilities becomes limited; third, the lack of cost to visit healthcare facilities and other socio-economic reasons. Although Indonesia has implemented a national health insurance system, some patients have not register to that system yet. Moreover, the cost of some aspects are not covered, such as transportation to CMH because not every patients is transported with ambulance facilities. The accommodation for the families and relatives who accompany the patients is also not covered by this insurance. In COVID-19 pandemic era, the patients could not be accompanied by other relatives due to the risk of transmission thus, the relatives often stayed outside the hospital, in local homestays provided by government and non-government organization.\n\nThe reduced number of patients who came to ED during COVID-19 has also occurred in numerous places for extremely varying reasons and these reasons are still speculative.9,15–18 A study conducted in France has suggested that the reason for reduced patient visits to ED was that the patients were afraid to get exposed to COVID-19 when they must visit the hospital or they were worried that they would become a burden to healthcare personnel during the difficult time of fighting the pandemic.16 In addition, the factor of persuasion on “stay at home” or lockdown during a pandemic may also have a great contribution to the decrease of patient visits.16 A study in Italy has suggested some other hypotheses on the reduced number of visits, i.e. changes to a healthier lifestyle due to the policy to stay at home; therefore, the stress and air pollution levels, which are one of the triggering factors of the coronary event, become less and on the contrary, the feeling of scared being exposed to COVID-19 or misinterpretation of the “stay at home” instruction may also cause patients to not visit hospital although they experience myocardial infarct symptoms.17 Changes in hospital policy that gives a greater priority to COVID-19 patients and executes deferral for patients without any emergency may also become a reason for reduced admission of STEMI patients.19 Lack of education associated with symptoms of heart attack and COVID-19 may also become a factor that can affect the reduced number of visits of STEMI patients who came to the hospital during the COVID-19 pandemic.20\n\nThe number of PPCI procedures in CMH showed a significant decrease during pandemic when compared to before the COVID-19 pandemic period (65.2% vs. 27.8%, p < 0.001), while the number of patients who had fibrinolytic (1.5% vs. 9.5%, p < 0.001) and conservative therapy (28.5% vs. 55.6%, p < 0.001) increased. The illustration of COVID-19 daily new cases in Indonesia and STEMI patients with different reperfusion strategies in CMH is depicted in Figure 2. These changes in reperfusion strategies during COVID-19 in STEMI patients were influenced by new policies that were applied in CMH.26 These included a recommendation for using fibrinolytic therapy as first-line treatment for STEMI patients with an onset of <12 hours without any contraindications for fibrinolytic agents and the hemodynamic is stable. The policy is established by considering the status of COVID-19 infection in STEMI patients, which is mostly unidentified before admission and it takes a long time for the COVID-19 test results to be confirmed. Three days were required to get the result of the COVID-19 test and other regions need to wait even longer (up to 8 days).21 Additionally, the absence of a negative-pressure catheterization room and other obstacles may occur because the process of establishing a COVID-19 diagnosis takes place before the reperfusion procedure is performed. Polymerase chain reaction (PCR) tests, the standard diagnostic tool of COVID-19, were scarce, particularly at the beginning of the pandemic in Indonesia when there were only the Ministry of Health’s Research and Development Agency and other three institutions designated as COVID-19 test referral lab.21 Therefore, a significant amount of time was needed to establish the diagnosis of COVID-19, and the PPCI procedure for STEMI patients can be potentially delayed. This policy has also been applied by some countries such as China, Taiwan, Palestine, Iran, and India.4–6,11,12 Fibrinolytic therapy is considered as it can reduce the delay time that occurs in STEMI patients during COVID-19 pandemic.\n\nIn STEMI patients who underwent PPCI, it was observed that the door-to-diagnosis time and door-to-wire crossing time were significantly longer during COVID-19 pandemic (Figure 3). This can be explained by the occurrence of additional screening COVID-19 tests and procedures to prevent nosocomial infection in ED, from the patients came until the diagnosis can be established. These new procedures include using personal protective equipment, performing disinfection of equipment including electrocardiogram before its usage, and screening the status of COVID-19 infection, i.e including radiology examination, laboratory tests, and questionnaire COVID-19 screening (Figure 4). Meanwhile, the difference in door-to-needle time was found to be not statistically significant. This indicates that basic management for fibrinolytic therapy has not been changed. Patients with STEMI can receive fibrinolytic therapy without waiting for the establishment of COVID-19 status. Right after STEMI was established, patients who fulfill the criteria can receive the fibrinolytic agent. Hence, there are no differences between before and during COVID-19 period for fibrinolytic therapy. The condition of prolonged reperfusion time, both door-to-needle time and door-to-wire crossing time, during COVID-19 pandemic has been reported in previous studies.5,9,22–24 Two studies from China have demonstrated a significantly prolonged time between before and during the pandemic.5,9 However, other studies in Turkey, England, and Canada have suggested results that are not significantly different, before and during the pandemic.22–24 These differences may occur since there are some differences in determining policy for reperfusion therapy and the availability of equipment, facility, and catheterization room during the COVID-19 pandemic.\n\nThe prolonged duration of door-to-wire-crossing time was significantly observed during COVID-19 pandemic compared to before COVID-19 pandemic.\n\nAccording to the policy, there is an additional screening for COVID-19 status for all patients that may delay the treatment.26\n\nAnother finding that we observed was the patient's clinical outcome during hospitalization. In this study, it was found that there was no significant difference in mortality and MACE in STEMI patients during the COVID-19 pandemic period. This indicates that there is no substantial difference in terms of the quality to give treatment for STEMI patients.\n\nOur study was conducted in CMH which serves as the national referral hospital that may provide a general profile of the STEMI patient population in Indonesia during the COVID-19 pandemic.\n\nThere is a time gap between before and during the COVID-19 pandemic period regarding the response of the Indonesian government to the COVID-19 pandemic situation that creates uncertainty in determining the cut-point.\n\n\nConclusions\n\nIn conclusion, this study found that the number of STEMI patients in CMH declined in monthly hospital admission. There were delays in symptoms-to-hospital time, changes in the type of reperfusion strategy, and delays in door-to-diagnosis time in PPCI and door-to-wire-crossing time. Meanwhile, the duration of fibrinolytic therapy and clinical outcomes were not affected. This study was a retrospective cohort study by analyzing the electronic medical records from our institution. More clinical and basic research is needed in the future to provide the assessment, risk factors, and treatment of STEMI patients during the COVID-19 pandemic.\n\n\nData availability\n\nDaily COVID-19 cases in Indonesia: https://covid19.go.id/peta-sebaran (March 2020 to September 2021).\n\nFigshare: Supplementary File: Effects of COVID-19 Pandemic on the Management of ST-Segment Elevation Myocardial Infarction in Indonesia, https://doi.org/10.6084/m9.figshare.19558969.v2.25\n\nThis project contains the following underlying data:\n\n- STEMI Patients Data during COVID-19.xlsx\n\nFigshare: The policy of acute coronary syndrome patients during COVID-19 pandemic in Dr. Cipto Mangunkusumo Hospital, https://doi.org/10.6084/m9.figshare.19728016.v1.26\n\nThis project contains the following extended data:\n\n- The policy of acute coronary syndrome management in CMH during COVID-19 pandemic.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgments\n\nNone.\n\n\nReferences\n\nAkbar H, Foth C, Kahloon RA, Mountfort S: Acute ST Elevation Myocardial Infarction. StatPearls:Treasure Island (FL):StatPearls Publishing; 2021 [cited 2021 Aug 23].Reference Source\n\nBoersma E, Steyerberg EW, Van der Vlugt MJ, et al.:Reperfusion therapy for acute myocardial infarction. Which strategy for which patient?. Drugs. 1998 Jul; 56(1): 31–48. Publisher Full Text\n\nThiele H, Barbato E, Barthelemy O, et al.:ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.2020; 2020: 79.\n\nSadeghipour P, Talasaz AH, Eslami V, et al.:Management of ST-segment-elevation myocardial infarction during the coronavirus disease 2019 (COVID-19) outbreak: Iranian “247” National Committee’s position paper on primary percutaneous coronary intervention. Catheter. Cardiovasc. Interv. 2020 Apr 22; 97: E346–E351. PubMed Abstract | Publisher Full Text\n\nXiang D, Xiang X, Zhang W, et al.:Management and Outcomes of Patients With STEMI During the COVID-19 Pandemic in China. J. Am. Coll. Cardiol. 2020 Sep; 76(11): 1318–1324. PubMed Abstract | Publisher Full Text\n\nDaralammouri Y, Azamtta M, Hamayel H, et al.:Recommendations for safe and effective practice of interventional cardiology during COVID-19 pandemic: expert opinion from Jordan and Palestine. Palest Med. Pharm. J. (5): 65–73.\n\nCDC:Healthcare Workers. Centers for Disease Control and Prevention.2020 [cited 2021 Aug 8].Reference Source\n\nKementerian Kesehatan RI:Panduan Teknis Pelayanan Rumah Sakit pada Masa Adaptasi Kebiasaan Baru.2020.\n\nLeng WX, Yang JG, Li XD, et al.:Impact of the shift to a fibrinolysis-first strategy on care and outcomes of patients with ST-segment–elevation myocardial infarction during the COVID-19 pandemic—The experience from the largest cardiovascular-specific centre in China. Int. J. Cardiol. 2021 Apr; 329: 260–265. PubMed Abstract | Publisher Full Text\n\nHan Y, Zeng H, Jiang H, et al.:CSC Expert Consensus on Principles of Clinical Management of Patients With Severe Emergent Cardiovascular Diseases During the COVID-19 Epidemic. Circulation. 2020 May 19; 141(20): e810–e816. PubMed Abstract | Publisher Full Text\n\nChopra H, Wander GS, Kumar AS, et al.:Consensus on STEMI Management in the Era of COVID-19.8.\n\nLi YH, Wang MT, Huang WC, et al.:Management of acute coronary syndrome in patients with suspected or confirmed coronavirus disease 2019: Consensus from Taiwan Society of Cardiology. J. Formos. Med. Assoc. 2021 Jan; 120(1): 78–82. PubMed Abstract | Publisher Full Text\n\nAmsterdam EA, Wenger NK, Brindis RG, et al.:2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes. Circulation. 2014; 130: e344–e426. PubMed Abstract | Publisher Full Text\n\nLwanga SK, Lemeshow S, Organization WH: Sample size determination in health studies: a practical manual. World Health Organization;1991 [cited 2022 May 5].Reference Source\n\nShowkathali R, Yalamanchi R, Sankeerthana MP, et al.:Acute Coronary Syndrome admissions and outcome during COVID-19 Pandemic–Report from large tertiary centre in India. Indian Heart J. 2020 Nov; 72(6): 599–602. PubMed Abstract | Publisher Full Text\n\nMesnier J, Cottin Y, Coste P, et al.:Hospital admissions for acute myocardial infarction before and after lockdown according to regional prevalence of COVID-19 and patient profile in France: a registry study. Lancet Public Health. 2020 Oct; 5(10): e536–e542. PubMed Abstract | Publisher Full Text\n\nCampo G, Fortuna D, Berti E, et al.:In- and out-of-hospital mortality for myocardial infarction during the first wave of the COVID-19 pandemic in Emilia-Romagna, Italy: A population-based observational study. The Lancet Regional Health - Europe. 2021 Apr; 3: 100055. PubMed Abstract | Publisher Full Text\n\nRattka M, Dreyhaupt J, Winsauer C, et al.:Effect of the COVID-19 pandemic on mortality of patients with STEMI: a systematic review and meta-analysis. Heart. 2021 Mar; 107(6): 482–487. PubMed Abstract | Publisher Full Text\n\nDe Rosa S, Spaccarotella C, Basso C, et al.:Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era. Eur. Heart J. 2020 May 15; ehaa409.\n\nHammad TA, Parikh M, Tashtish N, et al.:Impact of COVID-19 pandemic on ST-elevation myocardial infarction in a non-COVID-19 epicenter. Catheter. Cardiovasc. Interv. 2021; 97(2): 208–214. PubMed Abstract | Publisher Full Text\n\nSucahya PK:Barriers to Covid-19 RT-PCR Testing in Indonesia: A Health Policy Perspective. J INDO HEALTH POLICY ADM. 2020 May 10 [cited 2022 May 5]; 5(2). Publisher Full Text Reference Source\n\nAbdelaziz HK, Abdelrahman A, Nabi A, et al.:Impact of COVID-19 pandemic on patients with ST-segment elevation myocardial infarction: Insights from a British cardiac center. Am. Heart J. 2020 Aug; 226: 45–48.\n\nErol MK:Treatment Delays and In-Hospital Outcomes In Acute Myocardial Infarction During The Covid-19 Pandemic: A Nationwide Study. Anatol. J. Cardiol. 2020 [cited 2021 Dec 31]; 24: 334–342. PubMed Abstract | Publisher Full Text Reference Source\n\nClifford CR, Le May M, Chow A, et al.:Delays in ST-Elevation Myocardial Infarction Care During the COVID-19 Lockdown: An Observational Study. CJC Open. 2020 Dec 15; 3(5): 565–573. Publisher Full Text\n\nGinanjar E:Supplementary File: Effects of COVID-19 Pandemic on the Management of ST-Segment Elevation Myocardial Infarction in Indonesia. figshare. Dataset.2022. Publisher Full Text\n\nGinanjar E:The policy of acute coronary syndrome patients during COVID-19 pandemic in Dr. Cipto Mangunkusumo Hospital. figshare. Figure.2022. Publisher Full Text"
}
|
[
{
"id": "141551",
"date": "04 Jul 2022",
"name": "Doni Firman",
"expertise": [
"Reviewer Expertise interventional cardiology"
],
"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 COVID-19 Pandemic has significantly impacted the healthcare system all over the world including Indonesia. This single center report interestingly reported what happened in Indonesia - a developing country in dealt with Covid-19 focused in STEMI management. Ginanjar et al showed reduced mean of monthly hospital admissions, prolonged duration of symptoms-to-hospital, decrease in primary percutaneous coronary intervention (PPCI) procedures, increased number of fibrinolytic, conservative therapy and prolonged duration of diagnosis-to-wire-crossing time.\nThere are some points that I would like to address:\n\nIn deciding between fibrinolytic and PPCI, I do not see clearly the explanation or the reason for choosing between those two in ED.\n\nConsidering prolonged ischemic time, is there data regarding cardiogenic shock?\n\nMortality between before and during pandemic is statistically significant; even the ischemic time was prolonged, is there any explanation?\n\nIt is better to compare this report to other report from Indonesia1\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": "8500",
"date": "12 Jul 2022",
"name": "Eka Ginanjar",
"role": "Author Response",
"response": "Dear Dr. Doni Firman, Thank you for reviewing our article. Here are some responses to your points: The reasons for choosing therapy for STEMI patients were enclosed in the 3rd paragraph in the discussion section. Generally, patients who came to ER with the onset less than 12 hours and no contraindications for fibrinolytic agents, patients will receive fibrinolytic therapy. We enclose the detail of this policy in the references.26 We included cardiogenic shock in the MACE outcome, thus the data is available, but we published it as the general term under “MACE variable”. The data is attached through this link.25 Based on our analysis, the mortality was not statistically significant as well as the ischemic time. We concluded that there may be no quality difference for STEMI patients to receive therapy, either fibrinolytic or PPCI. We found the article you enclosed interesting to compare with our study. We'll add the report to our study in the second version. Kindly look forward to hearing from you in due time regarding our second version and to responding to any further questions and comments you may have. Best Regards, Eka Ginanjar References: 25. Ginanjar E:Supplementary File: Effects of COVID-19 Pandemic on the Management of ST-Segment Elevation Myocardial Infarction in Indonesia. figshare. Dataset.2022. https://doi.org/10.6084/m9.figshare.19558969.v2 26. Ginanjar E:The policy of acute coronary syndrome patients during COVID-19 pandemic in Dr. Cipto Mangunkusumo Hospital. figshare. Figure.2022. https://doi.org/10.6084/m9.figshare.19728016.v1"
}
]
},
{
"id": "172531",
"date": "30 May 2023",
"name": "Dafsah Arifa Juzar",
"expertise": [
"Reviewer Expertise Acute coronary syndrome",
"Cardiogenic shock",
"acute and intensive cardiovascular."
],
"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 congratulate for writing the impact of COVID pandemic on the STEMI performance and outcome.\n\nSimilar outcome for different reperfusion strategy in this study is novel findings. Several RCTs & registry reported that difference reperfusion strategy lead to different outcome: specifically in hospital and 30 days mortality. In this study, the conservative treatment and fibrinolysis treatment are significantly higher during pandemic as compared to pre-pandemic. Despite higher inferior strategy of reperfusion there is no difference in outcome.\nThe novel findings is worth to be elaborated.\nSuggestion to differentiate between the quality of treatment and the difference in stratification or others\n\nCongratulations once again\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? No source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-629
|
https://f1000research.com/articles/11-628/v1
|
08 Jun 22
|
{
"type": "Research Article",
"title": "Outcomes in intervention research on snakebite envenomation: a systematic review",
"authors": [
"Soumyadeep Bhaumik",
"Deepti Beri",
"Jyoti Tyagi",
"Mike Clarke",
"Sanjib Kumar Sharma",
"Paula R Williamson",
"Jagnoor Jagnoor",
"Deepti Beri",
"Jyoti Tyagi",
"Mike Clarke",
"Sanjib Kumar Sharma",
"Paula R Williamson",
"Jagnoor Jagnoor"
],
"abstract": "Introduction:\nA core outcome set (COS) is a minimal list of consensus outcomes that should be used in all intervention research in a specific domain. COS enhance the ability to undertake meaningful comparisons and to understand the benefits or harms of different treatments. A first step in developing a COS is to identify outcomes that have been used previously. We did this global systematic review to provide the foundation for development of a region-specific COS for snakebite envenomation. Methods:\nWe searched 15 electronic databases, eight trial registries, and reference lists of included studies to identify reports of relevant trials, protocols, registry records and systematic reviews. We extracted verbatim data on outcomes, their definitions, measures, and time-points. Outcomes were classified as per an existing outcome taxonomy, and we identified unique outcomes based on similarities in the definition and measurement of the verbatim outcomes. Results:\nWe included 107 records for 97 studies which met our inclusion criteria. These reported 538 outcomes, with a wide variety of outcome measures, definitions, and time points for measurement. We consolidated these into 88 unique outcomes, which we classified into core areas of mortality (1, 1.14 %), life impact (6, 6.82%), resource use (15, 17.05%), adverse events (7, 7.95%), physiological/clinical (51, 57.95%), and composite (8, 9.09%) outcomes. The types of outcomes varied by the type of intervention, and by geographic region. Only 15 of the 97 trials (17.04%) listed Patient Related Outcome Measures (PROMS). Conclusion:\nTrials evaluating interventions for snakebite demonstrate heterogeneity on outcomes and often omit important information related to outcome measurement (definitions, instruments, and time points). Developing high quality, region-specific COS for snakebite could inform the design of future trials and improve outcome reporting. Measurement of PROMS, resource use and life impact outcomes in trials on snakebite remains a gap.",
"keywords": [
"Snakebite",
"Systematic Review",
"Clinical Trials",
"Outcome Assessment",
"Treatment Outcome",
"Patient Reported Outcome Measures"
],
"content": "Background\n\nSnakebite is a major public health problem in South Asia, Africa, and South America with an estimated 5.4 million people being bitten by snakes annually. It is estimated that snakebite causes up to 138,000 deaths worldwide each year, with three times as many people experiencing permanent disabilities.1 In 2017, the World Health Organization (WHO) classified snakebite envenoming as a neglected tropical disease and this was followed by the launch of the WHO global strategy to reduce the mortality and morbidity by 50% by 2030.2 One of the four key pillars of this strategy is to “ensure safe, effective treatment of snakebite”.2 However, clinical practice guidelines, including those from the WHO, have been found to have quality issues, including in the use of evidence to inform recommendations for snakebite management.3 These issues in guidelines is linked to the poor evidence base for interventions for snakebite management. We had previously found that systematic reviews on snakebite were of critically low quality.4 Investment in treatments for snakebite, including in the identification of new therapies, has increased in recent years, and this trend is expected to continue.5 Our earlier overview of systematic reviews on snakebite management has also highlighted the limitation of non-standardised measurement and reporting of outcomes.4 This non standardisation of outcomes limits the ability of researchers, healthcare providers, decision makers, and patients to undertake meaningful comparisons and understand the potential benefits or harms of different treatment modalities.6,7 Thus, there is an identified need for a core outcome set (COS)8 for intervention research on snakebite management including trials and systematic reviews. A COS is a minimal list of consensus outcomes that should be used in all clinical trials and evidence synthesis in a specific area or setting of health or health care.\n\nThe objective of this study is to identify what outcomes have been used in intervention research on snakebite through a global systematic review of outcomes. This conduct of a robust and comprehensive systematic review of outcomes is an essential first step in the development of a COS.8\n\n\nMethods\n\nThis systematic review is a part of a larger project to develop a COS for intervention research on snakebite in South Asia. The protocol for the entire project, including the current systematic review was registered a priori (https://doi.org/10.17605/OSF.IO/PEKSJ). The COS development was registered a priori in the COMET database (https://cometinitiative.org/Studies/Details/1849). A summary of the methods for this systematic review is provided below.\n\nThe PRISMA checklist for this report of the review is available in Extended Dataset: Appendix 1.9\n\nWe included studies which met the following criteria:\n\n• Health condition/Population: people with snakebite, irrespective of their sex/gender, species of snake, region, or any other factor.\n\n• Intervention: any intervention regarding management of snakebite.\n\n• Comparators: an active comparator or control group.\n\n• Outcomes: the outcomes measured and reported, given the objective of identifying the full range of all outcomes.\n\n• Study Design: we included studies with the following designs:\n\no Randomised trials.\n\no Non-randomised controlled trials.\n\no Secondary analysis of randomised or non-randomised controlled trials.\n\no Systematic reviews that included randomised or non-randomised controlled trials.\n\nWe excluded systematic reviews which solely included non-trial designs. Protocols and trial registry records pertaining to the above were also included.\n\n• Other criteria: there were no limits based on date of publication.\n\nWe searched 15 electronic databases (PubMed, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, ACP Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment, NHS Economic Evaluation Database, Campbell Library, Epistemonikos, Scielo and Open dissertations) on 29th October 2021, with no language restrictions. The search strategies for all databases are presented in Extended Dataset: Appendix 2.9\n\nWe hand-searched nine trial registries (Australia New Zealand Trial Clinical Registry, Brazilian Clinical Trials Registry, Clinical Trial Registry of India, US trial registry (clinicaltrials.gov), Iranian Registry of Clinical Trials, Thai Clinical Trials Registry, Peruvian Clinical Trial Registry, Sri Lanka Clinical Trials Registry, and WHO International Clinical Trial Registry Platform) in November 2021. We also screened the reference lists of included studies and contacted snakebite experts to identify additional eligible studies.\n\nAt least two reviewers (SB and DB or JT) independently screened the records retrieved based on titles and abstracts (where available) in the first phase and subsequently screened the full texts of potentially eligible studies. Disagreements, if any, were resolved by consensus between three reviewers (SB, DB, and JT).\n\nWe extracted data using a standardised data extraction form in REDCap (a secure web application for building and managing online surveys and databases) containing key information pertaining to participant details (number and demographics: age, sex/gender, country and time period of the study), details on the bite (species information), study design, intervention and comparator group, reported outcomes (together with their definitions, measurement instruments and timepoints). The outcomes from trials were supplemented by additional outcomes from systematic reviews. All details pertaining to outcomes were extracted verbatim as recommended by the COMET Handbook.8\n\nWe analysed the verbatim information pertaining to reported outcomes. If we found multiple reports for the same study, we included these, but outcomes duplicated across these reports were only counted once. Outcomes which were not reported in the included trials, but which were defined or searched for in systematic reviews were also extracted verbatim. We classified the verbatim outcomes as per a taxonomy structure for outcomes in medical research10 which has been validated for various health conditions. As such, we mapped outcomes areas (mortality, physiological or clinical, life impact, resource use and adverse events) and sub-domains within these. We had an additional domain for composite outcomes, recognising that their individual elements might not be categorised as “unique” under the other domains so that information on composite outcomes could be used in the next steps in the COS development. We consolidated the outcomes based on similarity of outcome measures and definitions to create a set of the unique outcomes that had been used in intervention studies on snakebite envenomation. We summarized the results using frequencies and percentages for these unique outcomes.\n\nOur protocol envisaged inclusion of studies published from 1990 onwards. However, we searched for studies irrespective of date of publication and removed this time limit. We also searched electronic databases and trial registries that were not listed in our protocol to enhance comprehensiveness. On a post-hoc basis, we included secondary analysis of trials because some outcomes are not reported as a part of the main publication of a trial. This inclusive approach helped capture maximal evidence. We did not separate outcomes by different age-groups and special populations as originally planned because of the lack of studies. The decision to retain composite outcomes was post-hoc.\n\nNo ethical approval is required for this study because it is a systematic review of existing studies and does not include any human or animal participants.\n\n\nResults\n\nWe found 3277 records in our search in electronic databases, 69 in trial registries and another two records through hand-searching relevant websites. After removing duplicates, obtaining, and evaluating full texts, 107 records from 97 studies met our eligibility criteria and are included in this review. A detailed PRISMA flowchart showing the inclusion of studies is presented in Figure 1.\n\nReasons for exclusion of records that were assessed at the full text level are shown in Extended Dataset: Appendix 3.9\n\nWe included nine systematic reviews,4,11–18 and 88 trials and registry records. Out of the 88 trials and registry records, 84 are randomised trials,19–98 and 4 are non-randomised controlled trials.99–102 We found 10 post-hoc or secondary analysis of trials.103–112 Out of the 84 randomised trials, there was one adaptive,68 one factorial67 and one cross-over trial.66\n\nThe sample size ranged from eight to 1007 participants. Among the included trials, (26, 29.50%) were multicentric.19–23,26–28,34,41,49,50,55,64,66–68,70,74,81,85,89,90,99,113,114 Three (3.41%) trials were exclusively on children.23,25,76 Most of the studies (72, 81.8%) had only two arms of comparison. In 16 (18.2%) trials20,27,30,34,38,41,42,60,67,69,71,80–83,115 with more than two comparison arms, the number of arms ranged from three to eight. A total of 49 (55.7%) trials19–56,77,78,80,82,85,88,93,98,101,102 were restricted to participants with bites of a specific snake species/genus. Most of the trials started recruitment after the year 2000 (58, 65.91%).\n\nA summary of the characteristics of the included studies is presented in Table 1 below.\n\n\n\n• Randomised trials: 84 (and 10 post-hoc or secondary analysis from these)\n\n• Non-randomised controlled trials: 4\n\n• Systematic reviews: 9\n\n\n\n• Range is 80 to 1007 (median=80)\n\n• 0-50 participants: 24 (27.27%)\n\n• 51-100 participants: 27 (30.68%)\n\n• 101-200 participants: 26 (29.54%)\n\n• >200 participants: 11 (12.50%)\n\n\n\n• ≤1990:14\n\n• 1991-2000: 13\n\n• 2001-2010: 27\n\n• 2011-2020: 27\n\n• ≥2021: 4\n\n• Unclear/not reported: 3\n\n\n\n• Multicentre: 26 (29.5%)\n\n• Single centre: 62 (70.5%)\n\n\n\n• Restricted to bites of specific snake species/genus: 49 (55.7%)\n\n• Not restricted to bites of specific snake species/genus: 39 (44.3%)\n\nWe extracted verbatim data for 538 outcomes and categorised them into the following core areas: death/mortality (26, 4.83%), life impact (19, 3.53%), resource use (96, 17.84%), adverse events (80, 14.87%), physiological/clinical (288, 53.53%), and composite outcome (29, 5.39%). The proportionate frequency of outcomes by domain and sub-domains of physiological/clinical outcomes varied both by the type of intervention being evaluated and by geographic region (Extended Dataset: appendix 49). Trials from South Asia seldom measured life impact outcomes (0.47% of trials in contrast to 17.05% of North American trials which reported on life impact outcomes), but they frequently (29.28%) reported resource use outcomes. The focus of trials from South America, Southeast Asia and the rest of Asia is overwhelmingly in physiological/clinical outcomes. Blood and lymphatic system outcomes were proportionately much higher in African trials (64.00%) compared to South Asian (35.63%) trials. South Asian trials measured renal outcomes more (in 18.39% trials) compared to trials in other regions. Reporting of respiratory outcomes were uncommon except in Australia and Papua New Guinea (11.11%) trials.\n\nOnly 48 trials (54.54%) specifically identified their primary outcomes, out of which 10 (11.37%)47,60–62,67,77,84,89,97,98 had adverse events or effects as a primary outcome.\n\nWe consolidated the verbatim outcomes into 88 unique outcomes which we categorised as: mortality (1, 1.14%), life impact (6, 6.82%), resource use (15, 17.05%), adverse event (7, 7.95%), physiological/clinical (51, 57.95%), and composite (8, 9.09%).\n\nThe long list of the unique outcomes with summary information on their measurement and definitions is provided in Table 2 and discussed below.\n\n\n\n1. Functional life impact: Patient Specific Functional Scale, and the physical function domain of the SF-36 questionnaire\n\n2. Disability: Sheehan Disability Inventory and American Medical Association (AMA) disability rating score.\n\n3. Quality of life: Patient's Global Impression of Change Scale, Clinical Global Impression - Improvement (CGI-I), and Patient-reported outcome measurement information system physical function-10 score (PROMIS PF-10).\n\n4. Time to functional recovery: defined as time to full functional status recovery as measured by the Patient-Specific Functional Scale, or complete resolution of swelling and ability to run and jump (for lower extremity bites) or equal hand-grip (for upper extremity bites).\n\n5. Lower extremity function: Scores on Lower Extremity Functional Scale, and walking speed.\n\n6. Upper extremity function: Scores on the Disorders of the Arm, Shoulder, and Hand (DASH) and grip strength through a dynamometer.\n\n\n\n1. Duration of hospital stay: no clear criterion for discharge except in one study.\n\n2. Duration of Intensive Care Unit (ICU) stay: no clear criterion.\n\n\n\n1. Requirement of a blood product (unspecified or any).\n\n2. Requirement of FFP (fresh frozen plasma).\n\n3. Requirement of PRBC (packed red blood cell).\n\n4. Requirement of platelets.\n\n5. Requirement of cryoprecipitate.\n\n6. Requirement of mechanical ventilation.\n\n7. Requirement for non-invasive ventilation or reintubation (Post- extubation).\n\n8. Requirement of antibiotic.\n\n9. Requirement of analgesic.\n\n10. Requirement of dialysis/renal replacement therapy.\n\n11. Requirement of antivenom.\n\n\n\n1. Cost of antivenom (average compared).\n\n2. Any cost-related outcome.\n\n\n\n1. Adverse event unclassified: proportion and time from antivenom infusion to reaction with or without classification of severity or frequency/proportion of treatment emergent adverse event.\n\n2. Anaphylaxis: incidence and time from antivenom infusion to anaphylaxis with or without classification (Brown 2004 criterion) of severity.\n\n3. Anaphylactoid syndrome: incidence of anaphylactoid syndrome, pyrogenic reaction alone and urticaria alone.\n\n4. Early antivenom reaction (EAR): incidence and time from antivenom infusion to EAR.\n\n5. Late antivenom reaction: incidence.\n\n6. Adverse events specific to FFP: incidence.\n\n7. Capillary leak syndrome: incidence.\n\n\n\n1. Conjunctival oedema.\n\n\n\n1. Cardiac rhythm abnormalities.\n\n2. Hypotension.\n\n3. Shock.\n\n\n\n1. Anxiety: Hopkins somatic symptoms checklist.\n\n2. Depression: modified Sinhala version of the Beck depression inventory.\n\n3. Post-Traumatic Stress Disorder: Post-traumatic Stress Symptom Scale-Self Report Scale.\n\n4. Suicidal ideation and behaviour: Columbia-Suicide Severity Rating.\n\n\n\n1. Respiratory distress: measured as airway obstruction, respiratory failure, and acute respiratory distress syndrome; no specific definition reported.\n\n2. Negative inspiratory pressure: standard methods.\n\n3. Forced vital capacity: standard methods.\n\n\n\n1. Paralysis: proportion or duration; assessed clinically, no clear definition.\n\n2. Ophthalmoplegia/Ptosis: days for resolution of ptosis/ophthalmoplegia, endurance of upward gaze, and proportion of the iris uncovered.\n\n3. Anosmia: as reported by patient.\n\n4. Motor strength: no clear definition.\n\n5. Neurotoxicity overall: incidence/frequency and time to complete resolution of all neuroparalytic features.\n\n\n\n1. Venom concentration: standard methods.\n\n2. Anti-venom concentration: standard methods.\n\n3. Varisyllabic-methyl levels: standard methods.\n\n\n\n1. Immunogenicity profile: standard methods.\n\n2. profile of antibodies: standard methods.\n\n3. COVIP-Plus induced sera: standard methods.\n\n\n\n1. Pain: intensity measured by Visual Analogue Scale, time for complete resolution of the local pain with or without induration.\n\n2. Non-specific systemic symptoms: no definition provided.\n\n\n\n1. Myotoxicity as an outcome was measured clinically, levels of creatine kinase, and levels of lactate dehydrogenase, creatine phosphokinase, metalloproteinases.\n\n\n\n1. Necrosis: assessed clinically, no clear definition.\n\n2. Blistering: assessed clinically, no clear definition.\n\n3. Oedema: measured as circumference difference between the affected limb and the normal limb; circumference measurements of the affected limb alone; remission time of limb swelling; cessation of local swelling progression; time to swelling resolution; oedema progression; measurement of decrease of oedema-scaled dish.\n\n4. Swelling: measured based on the number of segments affected (extent) and increase in circumference of the bitten limb (intensity); proximal length of swelling from bite site; criteria developed by Warell et al 1977; criteria based on physical appearance of swelling; swelling is confirmed to bitten segment or crosses 1 or 2 joints; and % increase in volume compared to contralateral (non-envenomated) limb.\n\n5. Wound cosmesis: measured by any validated cosmesis score.\n\n6. Any other wound related outcome, including but not limited to cosmesis.\n\n\n\n1. Abscess.\n\n2. Blister.\n\n3. Cellulitis.\n\n4. Inflammatory markers.\n\n5. Pneumonia.\n\n6. Ventilator associated pneumonia.\n\n7. Wound infection.\n\n\n\n1. Blood urea nitrogen (BUN) and creatinine levels measures in serum.\n\n2. Acute Kidney Injury defined as per Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) Criteria, Kidney Disease Improving Global Outcomes (KDIGO) Criteria, measurement of surrogate markers (Neutrophil gelatinase-associated lipocalin, beta2-microglobulin, Kidney Injury Molecule-1, serum creatinine), estimated glomerular filtration rate and oliguria.\n\n3. Abnormalities in urine: proteinuria or haematuria.\n\n4. Chronic kidney disease: no definition provided.\n\n5. Renal angle tenderness: no definition provided.\n\n6. Ferryl-haem derivatives: detected in urine sample.\n\n\n\n1. Blood coagulability -by 20 min whole blood clotting test (WBCT20)/Lee -White method, or standard laboratory measures of international normalized ratio (INR), bleeding time (BT), clotting time (CT), Prothrombin Time (PT), aPTT (activated partial thromboplastin time).\n\n2. Platelet count- standard laboratory measures.\n\n3. Clotting Factors- Clotting factor panel or specific factors like fibrinogen, Factor V, VII, VIII, Fibrinogen degradation products/D-dimer.\n\n4. Bleeding – defined clinically using various criterion.\n\n5. Clot Quality- measures as per a method developed by Reid\n\n6. Other Haematological parameters – complete blood count, packed cell volume.\n\n7. Lymphadenopathy/lymphadenitis – no clear clinical criteria provided.\n\n\n\n1. Clinical recovery as a composite outcome: seven unique definitions were used.\n\n2. Complications as a composite outcome: four different definitions were used or not clearly reported.\n\n3. Envenoming manifestations: measured compositely as improvement in signs and symptoms of envenoming (systematic alone or together with local).\n\n4. Snakebite Severity Score (SSS): either the complete SSS or the pulmonary, cardiovascular, hematologic symptoms, and nervous system sub scores of the SSS, and as defined in the US FDA-approved information for Crotaline Polyvalent Immune Fab antivenom (FabAV) prescription.\n\n5. Haemolysis: measured using haemolysis markers (visual haemolysis score level and abnormal lactate dehydrogenase - LDH levels).\n\n6. Local Inflammation: Reduction in local inflammatory manifestations such as pain, oedema, and temperature (flushing).\n\n7. Prognosis: no clear definition.\n\n8. Treatment failure: measured as a composite outcome based on clinical features.\n\nDeath/mortality outcomes\n\nWe found one unique outcome (1.14%) for mortality from 26 verbatim outcomes (4.83%) in 26 trials and five systematic reviews. Time points at which death was measured were until discharge from hospital, 28 days from discharge, 60 days from recruitment/intervention and 90 days from bite.\n\nMore detailed information tabulating this unique outcome, together with measures, definitions and time-points, is reported in Extended Dataset: Appendix 5.9\n\nLife impact outcomes\n\nWe found six unique outcomes (6.82%) from 19(3.53%) verbatim outcomes from six trials and one systematic review. No trials or systematic reviews measured any life impact outcome related to social functioning, emotional functioning/well-being, cognitive functioning, perceived health status, compliance (including withdrawal from treatment), delivery of care or personal circumstances.\n\nA clear definition with clear details on the outcome measurement instruments used was provided for all but one verbatim life impact outcome. Disability outcomes were measured long term (six months from discharge and 12 months from intervention). Serial measurement from baseline through 28 days (from bite) was common. More detailed information about these unique outcomes, together with their measures, definitions and time-points for measurements is provided in Extended Dataset: Appendix 5.9\n\nResource use outcomes\n\nWe found 15 unique (17.05%) resource use outcomes from 96 verbatim (17.84%) outcomes: two (2.27%) hospital use outcomes from 30 verbatim (5.58%) outcomes in 25 trials; 11 (12.5%) outcomes related to the need for further intervention from 65 verbatim (12.08%) outcomes in 25 trials, and two (2.27%) economic outcomes from two verbatim outcomes (0.37%) from one trial and one systematic review. No trials or systematic reviews reported on outcomes of societal or carer economic burden.\n\nFor almost all the resource use outcomes, the specific clinical criterion associated with the outcome was not reported. For example, none of the outcomes relating to the need for further intervention reported the specific clinical criteria that would lead to further intervention. More detailed information about these unique outcomes together with their measures, definitions and time-points for measurement is provided in Extended Dataset: Appendix 5.9\n\nAdverse effect/events outcomes\n\nOur synthesis led to seven (7.95%) unique adverse event outcomes from a total of 80 (14.87%) verbatim outcomes from 52 trials and six systematic reviews. There was substantial heterogeneity in the definitions used for these outcomes. Adverse effects and events were almost always measured in the acute setting with no long-term measurement of these outcomes. More detailed information about these unique outcomes together with their measures, definitions and time-points for measurement is provided in Extended Dataset: Appendix 6.9\n\nPhysiological or clinical outcomes\n\nThe 288 (53.53%) verbatim physiological/clinical outcomes from trials were consolidated into 51(57.95%) unique physiological/clinical outcomes and were classified as per the taxonomy into the following:\n\n• Eye: one unique (1.14%) outcome from one (0.19%) verbatim outcome from one trial. Outcomes were assessed clinically with no clear criteria reported in the trials.\n\n• Cardiac: three (3.41%) unique outcomes from seven (1.30%) verbatim outcomes from six trials. Outcomes were assessed clinically with no clear criteria reported in the trials.\n\n• Psychiatric: four (4.55%) unique outcomes from four (0.74%) verbatim outcomes from two trials and one systematic review. psychiatric outcomes were measured with validated instruments and had good reporting of time points.\n\n• Respiratory, thoracic, and mediastinal: three (3.41%) unique outcomes from four (0.74%) verbatim outcomes from three trials. Two of the outcomes are related to standard spirometry tests while the other was assessed clinically with no clear definition provided.\n\n• Nervous system: five (5.68%) unique outcomes from 16(2.97%) verbatim outcomes from 13 trials and one systematic review. Many of the outcomes were measured clinically with no specific criteria mentioned.\n\n• Injury and poisoning outcomes: three (3.41%) unique outcomes from 28(5.20%) verbatim outcomes from 20 trials. All the outcomes were laboratory measured.\n\n• Immune system: three (3.41%) unique outcomes from three verbatim outcomes from one trial. All were laboratory measures.\n\n• General: two (2.27%) unique outcomes from 16 (2.97%) verbatim outcomes from 14 trials. A standardised tool was used for one outcome and a clear definition was not provided for the other. Time points were not clear for both.\n\n• Musculoskeletal and connective tissue: one (1.14%) unique outcome from eight (1.49%) verbatim outcomes from seven trials. Clear definitions were provided for the outcome measures and pertained to use of standard laboratory tests.\n\n• Skin and subcutaneous tissue outcomes: six (6.82%) unique outcomes from 41 (7.62%) verbatim outcomes from 29 trials and one systematic review. Outcomes were assessed clinically with no clear criteria or time points reported for many outcome measures.\n\n• Renal and urinary: six (6.82%) unique outcomes from 26(4.83%) verbatim outcomes from 14 trials and one systematic review. Outcome definitions were clearly reported (except for one outcome) and validated criteria or standard laboratory methods were used.\n\n• Infection, infestation, and inflammation: seven (7.95%) unique outcomes from 21(3.90%) verbatim outcomes from 15 trials and 1 systematic review. There was substantial heterogeneity in outcome measures and definition with reporting being poor when clinical assessment was the basis of outcome measurement.\n\n• Blood and lymphatic system: seven (7.95%) unique outcomes from 122(22.68%) verbatim outcomes from 49 trials and five systematic reviews. Laboratory tests were the basis of six of these outcomes with clinical assessment being the basis of outcome measurement in the other three.\n\nNo trial or systematic review measured endocrine outcomes, ear and labyrinth outcomes, gastrointestinal outcomes, hepatobiliary outcomes, puerperium, and perinatal outcomes, or vascular outcomes. We considered the following taxonomy sub-categories to be not relevant to the snakebite: familial, and genetic outcomes, metabolism and nutrition outcomes, outcomes relating to neoplasms: benign, malignant, and unspecified (including cysts and polyps), reproductive system and breast outcomes.\n\nIn general, reporting of time points was poor in many trials. More detailed information about these unique outcomes together with their measures, definitions and time-points for measurement is provided in Extended Dataset: Appendix 7.9\n\nComposite outcomes\n\nOur synthesis led to eight (9.09%) unique composite outcomes from 29(5.39%) verbatim outcomes from 21 trials and one verbatim outcome from two systematic reviews. There was substantial heterogeneity in outcome definitions as well as in the time points for measurement.\n\nMore detailed information on these unique outcomes together with measures, definitions and time-points for measurement is provided in Extended Dataset: Appendix 8.9\n\nOnly 15 trials22,66,78,82,88,90,116 included Patient Reported Outcome Measures (PROMs). The PROMs used in snakebite trials (with related citations on the measurement tools, where relevant) is presented in Table 3.\n\n\n\n• Pain related\n\no Visual Analog Scale128\n\no Numeric Pain Rating Scale128\n\n• Physical Function/disability related\n\no Patient Specific Functional Scale110,129\n\no Physical function domain of the SF-36 questionnaire130\n\no Sheehan Disability Inventory131,132\n\no American Medical Association disability rating score133\n\no Patient's Global Impression of Change Scale134\n\no Patient-reported outcome measurement information system physical function-10135\n\no Lower Extremity Functional Scale136\n\no Disorders of the Arm, Shoulder, and Hand137\n\no Anosmia-as reported by patient\n\n• Mental Health related\n\no Hopkins somatic symptoms checklist131,138\n\no Beck depression inventory131,139(modified Sinhala version)\n\no Post-traumatic Stress Symptom Scale-Self Report Scale131,140\n\no Columbia-Suicide Severity Rating141\n\n* Details on PROMS is within different Extended Dataset appendices.\n\n\nDiscussion\n\nThis systematic review of outcomes captured a total of 538 verbatim outcomes, which were consolidated into 88 unique outcomes, which had a wide variety of measures, definitions, and time points for their measurement. Outcome definitions and time points were infrequently or poorly reported. Outcomes related to resource use and life impact were included in few trials, with no trials using outcome related, societal or carer burden, social functioning, emotional functioning or well-being, cognitive functioning, perceived health status, compliance, and delivery of care or personal circumstances. The only trial which captured economic outcomes reported the average cost of antivenom without any comprehensive calculation of other direct or indirect costs. No trials had outcomes related to pregnancy. We also found that the primary outcome was explicitly stated in only a few of the trials. Outcome types (by the taxonomy domains) varied for both different geographic regions and different types of intervention being evaluated.\n\nHeterogeneity in outcomes, their measures, definitions, and time points prevents comparison of effectiveness data, thus limiting the usefulness of trials and reviews to clinical practice.8 The major reason for evidence synthesis specialists not being able to conduct meta-analyses is heterogeneity in the ways in which outcomes are reported and measured.8,117 This systematic review has shown that this is likely to be a major problem for snakebite research. Therefore, if high-quality trials are to be done to develop a robust evidence base for the management of snakebite,4 this needs to be preceded by the development of COS for use in intervention research.\n\nThe variation in outcomes (by taxonomically domains) across geographic regions and types of intervention indicates the need for development of COS with a focus on specific regions. This is to be expected because the clinical features of envenomation and the consequent choice of type of intervention largely depends on the type of snake and this largely depends on the geographic region. As such, this review has confirmed the appropriateness of our intention to develop a COS with a specific South Asia focus. This is also in keeping with the WHO’s work to develop targeted therapeutic profiles for snakebite envenomation therapies on a geographic region basis.118 The scarce use of PROMs, resource use and life impact outcomes in snakebite research to date is a gap that needs to be filled. These outcomes have high relevance for, for example, patients, clinicians, and hospital administrators. Our systematic review identified several outcome measurements instruments, but their measurement properties (structural validity, internal consistency, cross-cultural validity, and reliability) and the feasibility of using them is unknown. We will address this in future steps of our COS development, which will not only involve public health professionals, social workers, health economists, but also patients and caregivers of people with snakebite. This would enhance the clinical and public health relevance of the COS. To achieve this, the inventory of outcomes from this systematic review will be supplemented by additional outcomes identified by stakeholders participating in the consensus development process in the next steps of COS development.8\n\nThere is also a need for better reporting of outcome definitions (including outcome measurement instruments) and time points of measurement in clinical trials for snakebite. While the uptake of COS in future trials119 will address this issue to some extent, there is also a need for funders, trialists, and journal editors to take this into account through the lifecycle of a trial, from its design stage to publication. The lack of specific mention of primary outcomes also needs to be addressed.120 Trialists should also ensure that their outcome measurement instruments are valid for their own setting or use ones which are validated in their geographic region, such that their cross-cultural validity and feasibility is enhanced.121 Improvements in trial outcome transparency and reporting should also arise from the forthcoming Outcome extensions for the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) and CONsolidated Standards of Reporting Trials (CONSORT) statements.122 Beyond improvements in how outcomes are used in trials, there is also a need to conduct more trials in children, since we identified only three trials exclusively on children.\n\nStrengths of this review include that we searched 15 electronic databases and eight trial registries to comprehensively capture outcomes from as many studies as possible, not only including those trials which have completed but also including trials that are not published, not completed, or were terminated early. We have used standard evidence synthesis methods to maintain quality and used a validated taxonomy to classify outcomes. In keeping with guidance on the use of the taxonomy, this standardised outcome classification system allowed us to remove “inconsistencies due to ambiguity and variation in how outcomes are described across different studies”.10 We acknowledge the limitation that, although we were able to successfully manage records in English and Spanish, we were unable to extract information from five records123–127 that were available in Portuguese and Chinese.\n\n\nConclusion\n\nWe have shown that trials evaluating therapies for snakebite envenoming have heterogeneity of outcomes and often omitted key information related to their measurement. Developing high quality region-specific COS for snakebite would facilitate improvements in the design and reporting of future trials and thereby strengthen their ability to have a positive impact on policy, practice, patient care and overall health. Particular attention also needs to be paid to improve the reporting of outcomes, and to include PROMs, resource use and life impact outcomes in trials on snakebite.\n\n\nData availability\n\nFigshare. Outcomes in intervention research on snakebite envenomation: a systematic review. DOI: https://doi.org/10.6084/m9.figshare.19777921.v1\n\nThis project contains the following underlying data in the extended dataset:\n\n• Data file Appendix 1. PRISMA checklist\n\n• Data file Appendix 2. Search strategies of all databases\n\n• Data file Appendix 3. Reasons for exclusion at full text level\n\n• Data file Appendix 4. Outcome core categories by region and intervention\n\n• Data file Appendix 5. Detailed data on outcomes in categories of death, life impact and resource use\n\n• Data file Appendix 6. Detailed data on outcomes in categories of adverse event\n\n• Data file Appendix 7. Detailed data on outcomes in categories of physiological/clinical\n\n• Data file Appendix 8. Detailed data on composite outcomes\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
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PubMed Abstract | Publisher Full Text\n\nGerardo CJ, Keyler DE, Rapp-Olson M, et al.: Control of venom-induced tissue injury in copperhead snakebite patients: a post hoc sub-group analysis of a clinical trial comparing F (ab')2 to Fab antivenom. Clin. Toxicol. (Phila.). 2021; 60: 521–523. PubMed Abstract | Publisher Full Text\n\nFreiermuth C, Gerardo CJ, Lavonas EJ, et al.: Antivenom administration was associated with shorter duration of opioid use in copperhead envenomation patients. Acad. Emerg. Med. 2018; 25: S89.\n\nAnderson VE, Gerardo CJ, Rapp-Olsson M, et al.: Early administration of Fab antivenom resulted in faster limb recovery in copperhead snake envenomation patients. Clin. Toxicol. (Phila.). 2019; 57(1): 25–30. PubMed Abstract | Publisher Full Text\n\nTheophanous RG, Vissoci JRN, Wen FH, et al.: Validity and reliability of telephone administration of the patient-specific functional scale for the assessment of recovery from snakebite envenomation. PLoS Negl. Trop. Dis. 2019; 13(12): e0007935. PubMed Abstract | Publisher Full Text\n\nGerardo CJ, Vissoci JRN, de Oliveira LP , et al.: The validity, reliability and minimal clinically important difference of the patient specific functional scale in snake envenomation. PLoS One. 2019; 14(3): e0213077. PubMed Abstract | Publisher Full Text\n\nGreene S: Clinical features and outcomes of copperhead envenomations treated with either crotalidae polyvalent immune fab (ovine) or placebo in adolescents. Clin. Toxicol. 2020; 58(11): 1138.\n\nMullins ME, Gerardo CJ, Bush SP, et al.: Adverse Events in the Efficacy of Crotalidae Polyvalent Immune Fab Antivenom vs Placebo in Recovery from Copperhead Snakebite Trial. South. Med. J. 2018; 111(12): 716–720. PubMed Abstract | Publisher Full Text\n\nIsbister GK, Jayamanne S, Mohamed F, et al.: A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming. J. Thromb. Haemost. 2017; 15(4): 645–654. PubMed Abstract | Publisher Full Text\n\nCastano MFT, Castillo JCQ, Cadavid AD, et al.: Bothrops bites in Colombia: A multicenter study on the efficacy and safety of Antivipmyn-Tri. A polyvalent antivenom produced in Mexico. Iatreia. 2007; 20(3): 244–262.\n\nWijesinghe CA, Williams SS, Kasturiratne A, et al.: A Randomized Controlled Trial of a Brief Intervention for Delayed Psychological Effects in Snakebite Victims. PLoS Negl. Trop. Dis. 2015; 9(8): e0003989. PubMed Abstract | Publisher Full Text\n\nSagar P, Bammigatti C, Kadhiravan T, et al.: Comparison of two Anti Snake Venom protocols in hemotoxic snake bite: A randomized trial. J. Forensic Legal Med. 2020; 73: 101996. PubMed Abstract | Publisher Full Text\n\nMcKenzie JE, Brennan SE: Synthesizing and presenting findings using other methods. Cochrane Handbook for Systematic Reviews of Interventions. 2019: 321–347. Publisher Full Text\n\nWHO: Call for public consultation ̶ Development of Target Product Profiles (TPPs) for Snake Antivenom Products in Sub-Saharan Africa. Geneva:World Health Organization;2021 [cited 2022 28 Jan].accessed 28 Jan 2022. Reference Source\n\nHughes KL, Clarke M, Williamson PR: A systematic review finds Core Outcome Set uptake varies widely across different areas of health. J. Clin. Epidemiol. 2021; 129: 114–123. PubMed Abstract | Publisher Full Text\n\nAndrade C: The primary outcome measure and its importance in clinical trials. J. Clin. Psychiatry. 2015; 76(10): e1320–e1323. Publisher Full Text\n\nPrinsen CA, Vohra S, Rose MR, et al.: How to select outcome measurement instruments for outcomes included in a “Core Outcome Set” - a practical guideline. Trials. 2016; 17(1): 449. PubMed Abstract | Publisher Full Text\n\nButcher N, Monsour A, Mew E, et al.: SPIRIT-Outcomes and CONSORT-Outcomes: Enhanced trial outcome transparency, less bias, improved systematic reviews, better health. Advances in Evidence Synthesis: special issue Cochrane Database of Systematic Reviews. 2020; 9(Suppl 1). Publisher Full Text\n\nMiao YN, Chen MC, Huang Z: Clinical observation on treatment of snake bite induced disseminated intravascular coagulation by qinwen baidu decoction. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2003; 23(8): 590–592. PubMed Abstract\n\nFang ZM, Hu GH, He BX, et al.: Study on clinical efficacy of combination of traditional Chinese medicine and western medicine in treatment of pit viper bites and peripheral blood inflammatory factors. Zhongguo Zhong Yao Za Zhi. 2013; 38(7): 1087–1090. PubMed Abstract\n\nZheng Z, Chen G, Liang W, et al.: Clinical application of VSD negative pressure aspiration and detoxification in severe snake bite. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017; 29(11): 1026–1029. PubMed Abstract | Publisher Full Text\n\nLuo Y, Zhang J, Zhai C, et al.: Clinical study on the application of covered vacuum sealing drainage technology to the bite of venomous snakes of Trimeresurus stejnegeri in Guangxi. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020; 32(10): 1241–1246. PubMed Abstract | Publisher Full Text\n\nJorge MT, Ribeiro LA: Effect of reduction in the Bothrops antivenin dose administrated in patients bitten by the Bothrops snake. Rev. Assoc. Med. Bras. (1992). 1994; 40(1): 59–62. PubMed Abstract\n\nWilliamson A, Hoggart B: Pain: a review of three commonly used pain rating scales. J. Clin. Nurs. 2005; 14(7): 798–804. PubMed Abstract | Publisher Full Text\n\nStratford P: Assessing Disability and Change on Individual Patients: A Report of a Patient Specific Measure. Physiother. Can. 1995; 47(4): 258–263. Publisher Full Text\n\nSaris-Baglama RN, Dewey CJ, Chisholm GB, et al.: QualityMetric health outcomes™ scoring software 4.0: installation guide. Lincoln (RI):QualityMetric Incorporated;2010.\n\nHollifield M, Hewage C, Gunawardena CN, et al.: Symptoms and coping in Sri Lanka 20-21 months after the 2004 tsunami. Br. J. Psychiatry. 2008; 192(1): 39–44. PubMed Abstract | Publisher Full Text\n\nSheehan DV: The anxiety disease. New York:Charles Scribner & Sons;1986.\n\nAmerican Medical Association: AMA Guides Sixth 2022: Current medicine for permanent impairment ratings. American Medical Association;2022 [cited 2022 Jan 3].accessed Jan 3 2022. Reference Source\n\nFerguson L, Scheman J: Patient global impression of change scores within the context of a chronic pain rehabilitation program. J. Pain. 2009; 10(4): S73. Publisher Full Text\n\nFries JF, Krishnan E, Rose M, et al.: Improved responsiveness and reduced sample size requirements of PROMIS physical function scales with item response theory. Arthritis Res. Ther. 2011; 13(5): R147. PubMed Abstract | Publisher Full Text\n\nBinkley JM, Stratford PW, Lott SA, et al.: The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. North American Orthopaedic Rehabilitation Research Network. Phys. Ther. 1999; 79(4): 371–383. PubMed Abstract\n\nJester A, Harth A, Wind G, et al.: Disabilities of the arm, shoulder and hand (DASH) questionnaire: Determining functional activity profiles in patients with upper extremity disorders. J. Hand Surg. Br. 2005; 30(1): 23–28. PubMed Abstract | Publisher Full Text\n\nVeijola J, Jokelainen J, Laksy K, et al.: The Hopkins Symptom Checklist-25 in screening DSM-III-R axis-I disorders. Nord. J. Psychiatry. 2003; 57(2): 119–123. PubMed Abstract | Publisher Full Text\n\nBeck AT, Steer RA, Ball R, et al.: Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J. Pers. Assess. 1996; 67(3): 588–597. PubMed Abstract | Publisher Full Text\n\nFoa EB, Riggs DS, Dancu CV, et al.: Reliability and validity of a brief instrument for assessing post-traumatic stress disorder. J. Trauma. Stress. 1993; 6(4): 459–473. Publisher Full Text\n\nSalvi J: Calculated Decisions: Columbia-Suicide Severity Rating Scale (C-SSRS). Emerg. Med. Pract. 2019; 21(5): CD3-4. PubMed Abstract"
}
|
[
{
"id": "144412",
"date": "20 Jul 2022",
"name": "Harry Williams",
"expertise": [
"Reviewer Expertise Snakebite research",
"human-wildlife conflict",
"toxicology"
],
"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\nGenerally this is a superb review. The authors have carried out an incredibly detailed systematic review and this article meets all the criteria f1000 set for acceptable publications and has hopefully paved the way for their goal of a South Asian Core Outcome Set to be developed. The article is well written with very impressive tables of results and as a precursor to the eventual COS is exemplary for the methodology to be used in this process. Overall Bhaumik et al. have done a great job at reviewing the vast and varied snakebite literature and I look forward to reading the eventual COS. They have reviewed the literature to identify the full range of outcomes associated with snakebite envenomation. They identify the need to homogenise outcome reports so as to easily compare cases and act fast following the admission of a previously documented outcome. This would enable future clinical trials to be designed more methodically.\nMajor Points:\nAt no point in their review do they mention any of the snake species involved or any means for diagnosing the bites and ensuring they are indeed snake bites.\n\nNone of the toxins found within snake venoms are mentioned or attributed to any of the effects seen in these cases. I understand this was not the purpose of the review but it would have added greatly to my personal enjoyment if there was at least some level of discussion surrounding each of the unique outcomes regarding the snakes or toxins to blame.\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": "9210",
"date": "16 Jan 2023",
"name": "Soumyadeep Bhaumik",
"role": "Author Response",
"response": "We thank the reviewer for the kind comments and appreciating the work. We conducted a review of existing trials and systematic reviews on any intervention on outcomes with the explicit objective to look at outcomes for developing a core outcome set. We did not capture data on diagnosis. We have already noted that 55.7% of studies were restricted to bites of specific snake species/genus in Table 1. We have provided the reference for all studies of this type in the text of Characteristic of included studies section. Since the studies we reviewed were trials or systematic reviews, aiming to clinically evaluate specific therapeutic agents the included studies did not report on the effect of specific toxins within snake venoms."
}
]
},
{
"id": "153142",
"date": "18 Oct 2022",
"name": "Julien Potet",
"expertise": [
"Reviewer Expertise Antivenom development",
"antivenom access"
],
"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 have conducted a thorough review of published clinical trial studies and have meticulously listed all the outcomes used in these studies. This review demonstrates heterogeneity on outcomes. This review will be helpful to support efforts to determine a minimal list of consensus outcomes (aka a Core Outcome Set) that should be used in forthcoming trials of interventions against snakebite.\n\nMy only criticism is that authors have omitted to mention and discuss a very similar review of existing clinical outcomes for snakebite trials that was published in PLoS-NTD in 2021 (Abouyannis et al. 2021)1. It would be interesting to compare the results of the authors' review with the results of this other PLoS-NTD review.\nApart from that, I want to commend the authors for this impressive work!\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": "9209",
"date": "16 Jan 2023",
"name": "Soumyadeep Bhaumik",
"role": "Author Response",
"response": "We thank the reviewer of the kind comment. We have now taken note of another systematic review for development of a global core outcome set (COS) on snakebite. In our review, as already noted, we used a standard taxonomy for classifying snakebite outcomes [1] which the other review did not. We also included non-randomised trials and systematic reviews. A comparison, when the both the regional and global COS is completed will be valuable, as it will provide methodological insight for future COS development, beyond snakebite. 1. Dodd S, Clarke M, Becker L, et al. A taxonomy has been developed for outcomes in medical research to help improve knowledge discovery. J Clin Epidemiol 2018; 96:84-92"
}
]
}
] | 1
|
https://f1000research.com/articles/11-628
|
https://f1000research.com/articles/10-848/v1
|
25 Aug 21
|
{
"type": "Research Article",
"title": "Cost and pollution by the use of xylene in cervical cytology in four Peruvian hospitals",
"authors": [
"Jeel Moya-Salazar",
"Richard Salazar-Hernández",
"Victor Rojas-Zumaran",
"Gloria Cruz-Gonzales",
"Hans Contreras-Pulache",
"Richard Salazar-Hernández",
"Victor Rojas-Zumaran",
"Gloria Cruz-Gonzales"
],
"abstract": "Background: Cytological samples are cleared with xylene in two or three baths during a Pap test, however, this solvent has a high degree of toxicity, and being a controlled reagent infers high costs for its purchase and implications for environmental pollution. We estimated the impact of xylene during the Pap test in terms of the number of liters and cost of two baths of xylene, and also estimated the impact with three baths Methods: This cross-sectional study was carried out in four hospitals of EsSalud in Peru in two stages. First, the analysis of the impact due to the use of two baths of xylene was conducted during the period 2015–2019, and second, the estimates were calculated based on the assumption of three baths of xylene for the years 2020–2025. The assumption was based on the recommendations of the 2018 EsSalud cytology guideline. The monthly amount of xylene was ~10 liters per bath/month and the cost per liter was estimated at 8.13 USD (27 soles). Results: For the staining of 594,898 cytology tests, 7,848 liters of xylene were necessary, resulting in a cost of 60,861 USD (202,068 soles) during the period 2015–2019. The estimates showed a maximum assumption of 9,483 liters and 77,110 USD (256,040 soles) for the use of three baths of xylene in the four EsSalud hospitals (p = 0.0025) during the period 2020–2025.\n\nConclusions: We determined that there was a high economic impact of using xylene with two baths from 2015 to 2019 and a dramatic increase in costs with the possible use of three baths of xylene in the Pap test for the following five years.",
"keywords": [
"xylene",
"polycyclic aromatic hydrocarbon",
"cervical cancer",
"Pap test",
"pollution",
"Peru"
],
"content": "Introduction\n\nXylene (C6H4(CH3)2) is a polycyclic aromatic hydrocarbon (PAHs) part of the aromatic BTXs (benzene, toluene, and xylenes) obtained from petroleum, from the dry distillation of wood, and from coke gases. Xylene can have one of the three isomers of dimethylbenzene or a combination thereof, which are used as solvents (in fuel formulations, and glue in plastic model kits etc.).1 In medical practice, xylene is used in cellular clarification in the final phase of tissue processing.2,3\n\nSince George Papanicolaou’s research began in 1914 at Weill Cornell University, these PAHs have been used as part of the Papanicolaou (Pap) stain to clear cells at the end (clearing) of the process.4 The preliminary Pap protocol as well as the modifications that he made in 1953 and 1959 indicates the use of three xylene baths (~350 ml each) during the process.5 These protocols, and several modifications6,7 suggest the use of one or three xylene baths, causing high exposure to workers (as several hospitals do not have adequate protection barriers), bioaccumulation, and environmental pollution (due to the incorrect handling of these wastes).8\n\nEven though there are techniques for the biodegradation of xylene such as the use of iron and manganese from underground aquifers, the biofiltration of xylene by microorganisms adhered to a Nylon support,9,10 and modifications of the Pap stain that avoid the use of xylene (and other pollutants),8,11,12 laboratories in many countries continue using xylene as a cellular clarifier in two or three baths during the process. According to the standardized operating procedures of each cytology laboratory, these baths are replaced every thousand slides or once a week.12\n\nIn this study, we aimed to estimate the impact of xylene during the Pap test in terms of number of liters and costs for two baths of xylene, and also estimated the impact with three baths for the next five years (2020–2025) following the 2018 Peruvian Social Security cytology guideline.\n\n\nMethods\n\nThis was a retrospective longitudinal study that used a model for estimating xylene prices and quantities through logistic regression and the Bayes test. This study was approved by the Ethics Committee of Universidad Norbert Wiener (UNW-N° 072-2020). The study was conducted in two stages with data on costs and quantities (in liters) of xylene used in cytology over a five-year period (2015–2019) in four hospitals (Figure 1) of Social Security (EsSalud) of Peru.13\n\nHospital Nacional Guillermo Almenara Irigoyen, Hospital Nacional Edgardo Rebagliati Martins, and Hospital Nacional de Emergencias Grau in Lima, and the Hospital Nacional Alberto Sabogal Sologuren in Callao province. Maps by ©Jeel Moya-Salazar.\n\n\n\no Hospital Nacional Guillermo Almenara Irigoyen (HNGAI)\n\no Hospital Nacional Edgardo Rebagliati Martins (HNERM)\n\no Hospital Nacional Alberto Sabogal Sologuren (HNASS)\n\no Hospital Nacional de Emergencias Grau (HNEG)\n\nThe EsSalud cytology guide, Chapter 9. Cervical cytology procedures in the laboratory: Section 9.5.1. Manual staining describes the process, which includes three xylene baths (10 minutes each) at the end of the staining procedure (https://ww1.essalud.gob.pe/compendio/pdf/0000003706_pdf.pdf).14,15\n\nIn the first stage we collected the data on xylene use for the period 2015–2019 in the four hospitals.13 The amount of xylene used for exfoliative cytology was ~10 liters per bath/month (with two xylene-baths),14,15 and the global cost (EsSalud) per liter of xylene was 8.13 US dollars (USD) per liter (27 soles). We estimated the number of cytology tests and the amount of xylene per year used as part of the routine Pap test, which follows the second protocol of Papanicolaou.4\n\nFor the second stage, we followed the recommendations of the 2018 EsSalud cytology guidelines14,15 that establishes the addition of a third xylene bath during Papanicolaou staining. We considered the use of three xylene baths for each cervical smear, estimating the monthly usage in each hospital. As in the previous stage, the cost of xylene was estimated.\n\nWe used the direct costs of purchasing xylene without considering the indirect costs of processing, logistics management and usage (man-hours) during the Pap test. The cost of one liter of xylene was determined according to the contract between the manufacturer and EsSalud, which is a standardized contract for all hospitals in Lima.\n\nHence, we estimate the impact of pollution of xylene, initially by the amount of xylene used by the workers who were exposed daily to xylene under the biosafety conditions available in each hospital (Figure 2). Then, we estimated the pollution load based on the bioaccumulation of xylene during use, because the waste collection cycle is once every two months (hospital accumulation process). The quantity of liters and the costs (in USD) for xylene were estimated only for the Pap tests (we exclude the amount of xylene used in histology).\n\n(A) Guillermo Almenara Irigoyen National Hospital, (B) Hospital Nacional de Emergencias Grau, (C) Edgardo Rebagliati Martins National Hospital. Note that all staining centers are manual and are exempt from basic protection barriers such as the laminar flow chamber and air filtration systems.\n\nIn this sense, the monthly amount of xylene used in each hospital was estimated to establish the annual and the total cost (in liters). In the second stage, these costs and contamination estimates were made for the next five years (2020-2025) under the same parameters. The maximum and minimum amounts of xylene per year were used to estimate the costs and future quantities of xylene.\n\nStatistical analysis was performed with descriptive statistics and frequency measures. To estimate the cost, directly purchased xylene was used, with an estimated price of USD 8.13 (27 soles) per liter. In order to assess the impact of contamination (two baths for cytological clearance), the annual reagent usage and the annual xylene bioaccumulation rate of four hospitals in Lima were considered. To estimate the impact of pollution and direct costs (between 2020–2025), of using three xylene baths, multiple logistic regression with Bayesian analysis was used, with a p-value <0.05 and a 95% confidence interval (CI) as significant. We used IBM Statistical Package for the Social Sciences (SPSS) v25.0 (Armork, US) for Linux for all data analysis.\n\n\nResults\n\nWe included 131,456 cytology tests in the HNGAI, 254,106 in the HNERM, 110,858 in the HNASS, and 98,478 in the HNEG. The use of xylene during for the HNGAI, HNERM, HNASS and HNEG was 2,369, 2,299, 1,637, and 1,179 liters, respectively. Overall, a total of 7,484 liters of xylene were used for Pap stains in four EsSalud hospitals during a five-year period in Lima, Peru (Table 1). The mean rate of xylene use was 473.8 ± 88.1 liters (95%CI 396.5 to 551.1) for HNGAI, 459.8 ± 63.5 liters (95%CI 404.1 to 515.5) for HNERM, 327.4 ± 136.3 liters (95%CI 207.9 to 446.9) for the HNASS, and 235.8 ± 111.9 liters (95% CI 137.7 to 333.9) for the HNEG (Figure 3). Using this amount of xylene in four hospitals resulted in a cost of USD 60,853 (202,068 soles).\n\nThese data were estimated according to the amount of annual Pap tests during 2015–2019.\n\nAbbreviations: HNGAI: Hospital Nacional Guillermo Almenara Irigoyen, HNERM: Hospital Nacional Edgardo Rebagliati Martins, HNASS: Hospital Nacional Alberto Sabogal Sologuren, HNEG: Hospital Nacional de Emergencias Grau. Costs: 8.13 US dollars (USD) per liter (27 soles).\n\nWithin the study period, the mean xylene used is shown for each year according to color. HNGAI: Hospital Nacional Guillermo Almenara Irigoyen, HNERM: Hospital Nacional Edgardo Rebagliati Martins, HNEG: Hospital Nacional de Emergencias Grau, HNASS: Hospital Nacional Alberto Sabogal Sologuren in Callao province.\n\nWhen estimating future costs for the five-year period from 2020 to 2025, the biggest assumption is that the use of three xylene baths in four hospitals is estimated at 9,483 liters and 77,110 USD (256040 soles). The lowest assumption for the use of three xylene baths in the next five years is estimated to be 5,485 liters and 44,590 USD (148,080 soles) (p = 0.0025) (Table 2). For HNGAI, HNERM, HNASS and HNEG, the maximum volume of the three xylene baths used is 561.9, 523.3, 463.7 and 347.7 liters, respectively. For HNGAI, HNERM, HNASS and HNEG, the minimum volume of the three xylene baths used is 385.7, 396.3, 191.1, 123.9 liters, respectively.\n\nWe describe the quantities and, maximum and minimum costs estimated in this study at four EsSalud hospitals during 2015–2019 in Lima, Peru.\n\nAbbreviations: HNGAI: Hospital Nacional Guillermo Almenara Irigoyen, HNERM: Hospital Nacional Edgardo Rebagliati Martins, HNASS: Hospital Nacional Alberto Sabogal Sologuren, HNEG: Hospital Nacional de Emergencias Grau. Costs: 8.13 US dollars (USD) per liter (27 soles).\n\nThese estimates of future costs showed increases and decreases according to the hospitals (Figure 4). In the four hospitals, the liter and cost of xylene increased by 30.4% and 30.3% USD on average, respectively. The average reduction in the cost and liters of xylene was 25.3% liters and 24.3% USD, respectively. A difference was determined between the increases in xylene use among EsSalud hospitals (p = 0.0001).\n\nA. Hospital Nacional Guillermo Almenara Irigoyen, B. Hospital Nacional Edgardo Rebagliati Martins, C. Hospital Nacional Alberto Sabogal Sologuren, D. Hospital Nacional de Emergencias Grau. The increase indicates the maximum percentage of increase in the 2020–2025 periods in liters and costs of xylene. The reduction indicates the minimum percentage of reduction in the five-year period 2020–2025 in liters and costs of xylene.\n\n\nDiscussion\n\nWe determined that xylene had a high impact during the Pap test with two baths in four EsSalud hospitals, and a dramatic increase in costs and xylene contamination in the next five years (2020–2025) with the use of three xylene baths on the Pap smear according to the recommendations of the 2018 EsSalud cytology guidelines.\n\nIn the environment, xylene can cause air pollution due to the production of toxic gases (when it is thermally decomposed), polluting water, soil, and subsoil.16 Inhalation of xylene can irritate the mucous membranes of the nose and throat, and high concentrations can cause nausea, vomiting, headache, respiratory failure, cough, heart abnormalities, proteinuria, and hematuria.17 Cancer, leukemia, brain tumors and tissue changes (pulmonary long-term exposure and long-term high concentration) are also related to xylene contamination.18,19 Other effects include fetal kidney disease, infertility and miscarriage in children whose mothers have been in contact with xylene for a long time.20\n\nOur estimates of xylene use in hospitals indicate that 594,898 cervical smears analyzed by Pap staining use >7,000 liters of xylene every five years. The same estimation of the use and contamination by xylene can be applied in other realities such as the 243,374 smears of the Hospital Nacional Docente Madre Niño San Bartolomé in Lima during two periods [118,016 for the conventional Pap staining (2011–2013 years) and 125,358 for the prolonged Pap staining (2013–2014 years)],11,21 to the 3,276,045 cervical smears of the Instituto Mexicano del Seguro Social in Mexico,22 and in the 60 million cervical smears performed annually in the United States.23 We can infer that in every country, cervical cancer screening will involve a large amount of xylene, which will threaten the health of laboratory workers and global environmental health.\n\nImplementing a third xylene bath to the Pap test would undoubtedly have even more counterproductive results. As our findings indicate, there will be an increase in the overall costs of the tests (77,110 USD), the time to stain each sample, and the daily exposure of workers to higher amounts of xylene (9,483 liters). A previous study demonstrated that 37 national guidelines on prevention measures for the use of xylene in South American cytology laboratories were of little importance.24 In this sense, under the actual conditions of cytological screening in low-and-middle-income countries, adding an additional xylene bath to the Pap stain is unsustainable and therefore should not be considered.\n\nCurrently, there are xylene substitutes that allow diagnostic activities to be carried out in the pathology laboratory in a less toxic and eco-friendly environment. These substitutes are mainly the solution of Neo-Clear (Merck, Darmstadt, Germany), Pathoclear (Biopack, Buenos Aires, Argentina), Master clear (American MasterTech Scientific, CA, USA), UltraClear™ (Avantor’s JT Baker, Deventer, Netherlands), Shandon™ (Thermo Scientific, Walthman, MA, USA), and Ottix Plus (DiapathS.pA, Martinengo, Italy), which have shown different degrees of performance and health risks.25–27 Regardless of the opportunities these surrogates offer, they come with costs for Pap processing that many cytology labs cannot afford. In view of this, Eco-Pap (patent application pending) brings an alternative to ecological staining, which can reduce the number of reagents, staining time and cost without reducing test performance.8,12\n\nOn the other hand, our estimated analysis model for three xylene baths shows that the cost of the Pap stain and the liters of xylene solvent are reduced. However, this assumption could not be further from reality, given that exfoliative cytology has a new stage.28 This fact is partly due to the co-testing in which the Human Papilomavirus test and cytology are used as a strategy with better performance and diagnostic accuracy.29 It is also because many countries, mainly low- and middle-income countries, have strategies based on exfoliative cytology due to the benefits that this technique offers and for the economic limitations that these countries face.30,31\n\nAnother component that distances this assumption of reducing quantities and costs of xylene from reality is undoubtedly the alarming increase in the incidence and mortality from cervical cancer between 2012 and 2018 according to the International Agency for Research on Cancer (IARC) from 527,624 and 569,847 cases for the former, and from 265,672 to 311,365 cases for the second.32\n\nIn this sense, the use of cytology as a cervical cancer strategy will continue to develop and grow around the plausibility of other techniques such as molecular biology. Therefore, if a xylene bath is added to the Pap test, the amount and cost of xylene in Peru’s EsSalud Hospitals will increase by an average of 16.6% in the next five years.\n\nThis study had limitations. 1) The analysis was conducted in four EsSalud hospitals in Lima, however, there are other hospitals that have not been included. Further studies that include other Social Security hospitals are needed; and 2) The analysis evaluated the xylene used in the Pap tests; however, it is necessary to evaluate its impact on histopathology.\n\n\nConclusions\n\nWe demonstrated a high economic impact of xylene during the Pap test with two xylene baths in four EsSalud hospitals, in Lima, Peru. Our three-bath estimates for 2020–2025 indicate that the economic growth of xylene use is significant, which is why the 2018 EsSalud cytology guidelines are not applicable.\n\nNowadays, there are some alternative methods that can make Pap smears free of xylene during the clearing process, thereby becoming ecofriendly, which is beneficial to occupational health and global environmental health.\n\n\nData availability\n\nFigshare: ‘Cost and pollution by the use of xylene in cervical cytology in four Peruvian hospitals’,\n\nhttps://doi.org/10.6084/m9.figshare.14615508.v113\n\nThis project contains the following underlying data:\n\n\n\n• Table 1. Xylene database used in EsSalud hospitals 2015–19\n\nFigshare: ‘Cost and pollution by the use of xylene in cervical cytology in four Peruvian hospitals’, https://doi.org/10.6084/m9.figshare.15048903.v1.14\n\nThis project contains the following underlying data:\n\n\n\n• 2018 EsSalud Cytology Guideline – Chapter 9 (English translation)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY-4.0)",
"appendix": "References\n\nDepartment of Health and Human Services public health service: Agency for Toxic Substance and Disease Registry. Toxicological profile for Xylene. Atlanta: ASTDR, CDC; 2007.\n\nCulling CFA: Handbook of Histopathological and Histochemical Techniques . 3rd ed. London: Butterworth; 1974.\n\nProphet EB, Mills B, Sobin LH: Armed Forces Institute of Pathology Laboratory Methods in Histotechnology. Washington, D.C.: American Registry of Pathology Press; 1992.\n\nPapanicolaou GN: A new procedure for staining vaginal smears. Science. 1942; 95(2469): 438–439. PubMed Abstract | Publisher Full Text\n\nChantziantoniou N, Donnelly AD, Mukherjee M, et al.: Inception and Development of the Papanicolaou Stain Method. Acta Cytol. 2017; 61(4-5): 266–280. PubMed Abstract | Publisher Full Text\n\nShinde PB, Pandit AA: Application of modified ultrafast Papanicolaou stain in cytology of various organs. Diagn Cytopathol. 2006; 34(2): 135–139. PubMed Abstract | Publisher Full Text\n\nGupta S, Chachra KL, Bhadola P, et al.: Modified Papanicolaou staining protocol with minimum alcohol use: a cost-cutting measure for resource-limited settings. Cytopathology. 2010; 21(4): 229–233. PubMed Abstract | Publisher Full Text\n\nMoya-Salazar J, Rojas-Zumaran V: Eco-Pap: an ecological Papanicolaou stain for sustainable cervical cancer diagnosis. Acta Cytol. 2019; 63(1): 35–43. PubMed Abstract | Publisher Full Text\n\nVillatoro-Monzón WR, Mesta-Howard AM, Razo-Flores E: Anaerobic biodegradation of BTX using Mn (IV) and Fe (III) as alternative electron acceptors. Water Sci Technol. 2003; 48(6): 125–131. PubMed Abstract\n\nOrtega-González DK, Zaragoza D, Aguirre-Garrido J, et al.: Degradation of benzene, toluene, and xylene isomers by a bacterial consortium obtained from rhizosphere soil of Cyperus sp. grown in a petroleum-contaminated area. Folia Microbiol (Praha). 2013; 58(6): 569–577. PubMed Abstract | Publisher Full Text\n\nMoya-Salazar J, Rojas-Zumaran V: Validation of the modification of the prolonged Papanicolaou stain for the diagnosis of cervical cancer. Acta Cytol. 2016; 60(1): 79–84. PubMed Abstract | Publisher Full Text\n\nMoya-Salazar JJ, Rojas-Zumaran VA: Environmental Performance of xylene, hydrochloric acid and ammonia solution during Pap stain for diagnosing cervical cancer. J Health Pollution. 2016; 6(11): 58–65. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoya-Salazar J: Xylene data base used in EsSalud hospitals. Dataset. Figshare. 2021. Publisher Full Text\n\nMoya-Salazar J: 2018 EsSalud Cytology Guideline - Chapter 9. Online resource. Figshare. 2021. Publisher Full Text\n\nSeguro Social de Salud (EsSalud): Resolución de gerencia central de prestaciones de salud n.04 – GCPS-ESSALUD-2018. Documento Técnico: Procedimiento de Citología cervical.Lima: EsSalud; 2018.\n\nWorld Health Organization (WHO): International Programme on Chemical Safety: Environmental Health Criteria. Geneva: WHO; 1997.\n\nDergovics FL, Moura TP, Shirata NK, et al.: Avaliação do desempenho da mistura verniz/xilol na diafanização de lâminas de citopatologia coradas com a técnica de Papanicolaou. RBAC. 2012; 44(1): 35–38.\n\nTiburtius ER, Peralta-Zamora P, Lea LE: Contaminação de águas por BTXs e procesos utilizados na remediação de sítios contaminados. Quím Nova. 2004; 27(3): 441–446.\n\nSandikci M, Seyrek K, Aksit H, et al.: Inhalation of formaldehyde and xylene induces apoptotic cell death in the lung tissue. Toxicol Ind Health. 2009; 25(7): 455–461. PubMed Abstract | Publisher Full Text\n\nOccupational Safety and Health Administration (OSHA): U.S. Department of Health and Human Services, Public Health Services, Centers for Disease Control. Ocupational Health Guideline for Xylene. Georgia, Atlanta; 1978.\n\nMoya-Salazar J, Pio DL: Prevalence of Cervical- Uterine Abnormalities associated with Poverty levels at “Hospital Nacional Docente Madre Niño San Bartolome” between 2011-2013. Rev Invest Universidad Norbert Wiener. 2014; 3(1): 89–99. PubMed Abstract | Publisher Full Text\n\nRamos-Ortega G, Díaz-Hernández MC, Rodríguez-Moctezuma JR, et al.: Satisfactory cervical cytologic smear against longitudinal exocervical smears. Rev Med Inst Mex Seguro Soc. 2014; 52(6): 696–703. PubMed Abstract\n\nWheeler CM: Natural history of human papillomavirus infections, cytologic and histologic abnormalities, and cancer. Obstet Gynecol Clin North Am. 2008; 35(4): 519–536. PubMed Abstract | Publisher Full Text\n\nMoya-Salazar J, Rojas-Zumaran V: Análisis de la problemática del xileno en los laboratorios Sudamericanos de citología. Rev Latinoam Patol Clin Med Lab. 2018; 65(3): 150–158.\n\nAlwahaibi N, Aljaradi S, Alazri H: Alternative to xylene as a clearing agent in histopathology. J Lab Physicians. 2018; 10(2): 189–193. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKunhua W, Chuming F, Tao L, et al.: Novel Non-Toxic Xylene Substitute (SBO) for histology. Afr J Tradit Complement Altern Med. 2012; 9(1): 43–49. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBuesa RJ, Peshkov MV: Histology without xylene. Ann Diag Pathol. 2009; 13(4): 246–256. PubMed Abstract | Publisher Full Text\n\nHarjes U: Pap seeking new challenges. Nat Rev Cancer. 2018; 18(6): 338–339. PubMed Abstract | Publisher Full Text\n\nWright TC, Stoler MH, Behrens CM, et al.: Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol. 2015; 136(2): 189–197. PubMed Abstract | Publisher Full Text\n\nAlonso de Ruiz P, Lazcano Ponce EC, Hernández Ávila M: Cáncer cervicouterino. Diagnóstico, prevención y control . Medica Panamericana: Buenos Aires; 2000.\n\nMoya-Salazar J, Rojas-Zumaran V: Tendencias en la investigación del Virus de Papiloma Humano en Latinoamérica y en los en los países de altos ingresos. Rev Colomb Obstet Ginecol. 2017; 68(3): 202–217.\n\nBray F, Ferlay J, Soerjomataram I, et al.: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer Clin. 2018; 68(6): 394–424. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "92919",
"date": "08 Sep 2021",
"name": "Nasar Yousuf Alwahaibi",
"expertise": [
"Reviewer Expertise Histopathology"
],
"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\nAlthough the study has academic merit, however, it lacks some important information:\nIn the methodology, there are no inclusion and exclusion criteria for this retrospective study.\n\nXylene details are missing.\n\nThe manual staining for cervical cytology procedures in the laboratory (Section 9.5.1) is written in a different language but not in English. Please have a translation or a brief summary for the procedure.\n\nMany low and middle-income countries recycle xylene and other chemical solutions used in histopathology to overcome the high cost of those solutions as well as to provide a pollution-prevention solution for the laboratory, the discussion section does not discuss this issue.\n\nHow do you get rid of xylene in Peru? Usually, the management of xylene is carried out by means of specific legislation created by the specific regulatory agency for this purpose.\n\nPlease justify the choice of only those four hospitals in Peru.\n\nIn Figure 2 and in all mentioned laboratories, there is no safety cabinet to cover the xylene containers, which is a concern for biomedical scientists working in the laboratory.\n\nPlease note that the title for the tables should be up, and the title for the figures should be underneath the figures.\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?\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? Yes",
"responses": [
{
"c_id": "8016",
"date": "21 Apr 2022",
"name": "Jeel Moya-Salazar",
"role": "Author Response",
"response": "Dear Reviewer, We welcome feedback. We have made modifications to the study on the following points: In the methodology, there are no inclusion and exclusion criteria for this retrospective study. Response: Criteria of inclusion/exclusion have been included. The manual staining for cervical cytology procedures in the laboratory (Section 9.5.1) is written in a different language but not in English. Please have a translation or a brief summary for the procedure. Response: A short version of the procedure is included in reference 13. It's on Figshare Many low and middle-income countries recycle xylene and other chemical solutions used in histopathology to overcome the high cost of those solutions as well as to provide a pollution-prevention solution for the laboratory, the discussion section does not discuss this issue. Response: We added in the discussion. How do you get rid of xylene in Peru? Usually, the management of xylene is carried out by means of specific legislation created by the specific regulatory agency for this purpose. Response: We added in the discussion. Please justify the choice of only those four hospitals in Peru. Response: We selected four hospitals because they are the main ones of EsSalud and they were the ones that agreed to be part of the study. In Figure 2 and in all mentioned laboratories, there is no safety cabinet to cover the xylene containers, which is a concern for biomedical scientists working in the laboratory. Response: We agree with what you say, it is important to note that the four main hospitals in Lima do not yet have security booths. This is why, based on our research, we believe that adding one more xylene bath is not enough. Please note that the title for the tables should be up, and the title for the figures should be underneath the figures Response: It is an editorial issue that we already adjusted. Sincerely"
}
]
},
{
"id": "122077",
"date": "22 Feb 2022",
"name": "Alexandre Rieger",
"expertise": [
"Reviewer Expertise Molecular biology",
"Genetics",
"Genotoxicity"
],
"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 manuscript brings a relevant theme, but I believe it is not suitable for indexing, according to the following comments:\nWhat were the criteria for choosing the hospitals included in the study?\n\nA very important information is missing. What are the reasons why the 2018 EsSalud cytology guidelines recommend using three baths of xylene? I didn't find this information. I believe this is important to mention, as clearly the addition of one more xylene bath increases costs and environmental impact. Therefore, there must be a coherent reason for this recommendation, which perhaps outweighs the harm of adding one more bath.\n\nThe cost analyzed should include factors other than the value of a liter of xylene, such as: time, need for skilled labor, possibility of automation, generation and disposal of waste.\n\nSubstitutes for the use of xylene are suggested. It is important, however, to compare the costs and also the quality of the results, in addition to illustrating them better. This would bring more impact to the conclusion, which unfortunately did not add many scientific gains, because, if only the cost and environmental impact are compared, certainly using three xylene baths instead of two will have more impact.\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? Yes",
"responses": [
{
"c_id": "8017",
"date": "21 Apr 2022",
"name": "Jeel Moya-Salazar",
"role": "Author Response",
"response": "Dear reviewer, We welcome feedback. We made the following modifications in our study: What were the criteria for choosing the hospitals included in the study? Response: We include the inclusion criteria in the methodology section. Very important information is missing. What are the reasons why the 2018 EsSalud cytology guidelines recommend using three baths of xylene? I didn't find this information. I believe this is important to mention, as clearly the addition of one more xylene bath increases costs and environmental impact. Therefore, there must be a coherent reason for this recommendation, which perhaps outweighs the harm of adding one more bath. Response: We have included this information in our methods. Basically, the purpose is to improve cytology procedures, without proposing an analysis of cost-effectiveness or environmental impact of the use of xylene. The cost analyzed should include factors other than the value of a liter of xylene, such as: time, need for skilled labor, possibility of automation, generation and disposal of waste. Substitutes for the use of xylene are suggested. It is important, however, to compare the costs and also the quality of the results, in addition to illustrating them better. This would bring more impact to the conclusion, which unfortunately did not add many scientific gains, because, if only the cost and environmental impact are compared, certainly using three xylene baths instead of two will have more impact. Response: We want to do a more structured analysis, but we don't have access to the data to include more variables. Therefore, we limit our study to a cost/liter analysis as a preliminary approximation to the topic. These features are added in the limitations section. Sincerely,"
}
]
}
] | 1
|
https://f1000research.com/articles/10-848
|
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