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Background | Intrathecal dexmedetomidine, as an adjuvant to local anesthetics, has been reported to improve the quality of spinal anesthesia and reduce the required local anesthetic dose. However, the optimal dosage regimen for intrathecal dexmedetomidine combined with plain ropivacaine for cesarean section (CS) remains undetermined. The present study aimed to determine the median effective dose (ED | PMC10519004 | ||
Methods | Sixty parturients undergoing CS were randomly assigned to either group: plain ropivacaine 8 mg (Group Rop | PMC10519004 | ||
Results | The ED | PMC10519004 | ||
Conclusions | The present data suggested that the ED | PMC10519004 | ||
Trial registration | Chinese Clinical Trial Registry, identifier: ChiCTR2200055928. | PMC10519004 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12871-023-02275-x. | PMC10519004 | ||
Keywords | PMC10519004 | |||
Background | shivering, intraoperative nerve blockade, pain | Regional anesthesia (spinal or epidural anesthesia) has been recommended as the preferred option for elective cesarean section compared to general anesthesia. The main reason for the preference is the negligible maternal mortality associated with gastric acid aspiration of mothers. Spinal anesthesia for cesarean section is thought to be advantageous due to its rapid onset of nerve blockade and reliable performance [Dexmedetomidine has been increasingly used as a local anesthetic adjuvant for spinal anesthesia. The combination was associated with a long list of benefits, including reduced use of analgesics, improved intraoperative nerve blockade, shortened onset time of the sensory or motor block, lowered occurrence of shivering, prolonged postoperative analgesia, and reduced postoperative pain score in cesarean Sects. [Therefore, our primary aim was to determine the median effective dose (ED | PMC10519004 | |
Methods | PMC10519004 | |||
Study design and participants | Sixty parturients scheduled for elective cesarean section were enrolled in the present study. Patient inclusion criteria were ASA Physical Status II, aged 18 to 45 years, term gestation (≥ 37 weeks), singleton pregnancy, and scheduled for elective cesarean section under combined spinal-epidural anesthesia (CSEA). Exclusion criteria were contraindications to neuraxial anesthesia, BMI ≥ 40 kg·m | PMC10519004 | ||
Ethics | The study protocol was approved by the local ethics committee, the Guangzhou Women and Children’s Medical Centre Ethics Committee, Guangzhou, China, on March 11, 2022 (reference number 2021-232B00, Chairperson Professor Sitang Gong). The protocol was registered at the Chinese Clinical Trial Registry (Registration number: ChiCTR2200055928, Date of registration: 26/01/2022) before the start of enrollment on 14/03/2022. This study complied with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. All participants provided written informed consent prior to study commencement. | PMC10519004 | ||
Randomization and blinding | Consenting parturients were randomly allocated into Group Rop | PMC10519004 | ||
Anesthetic procedure | pain | STERILE, DECUBITUS | All patients fasted for 6 h and discontinued fluid intake 2 h before cesarean section. No patient was given premedication. After an intravenous catheter was placed, the patient was transported to the operating room, where standard ASA monitors were placed and a volume of 500 mL of Ringer’s lactate solution was started. With the patient in a left lateral decubitus position, a 25-gauge pencil-point needle was introduced into the subarachnoid space at the L3-L4 or L2-L3 interspace using the single-space needle-through-needle technique in a standard sterile fashion. After the return of clear cerebrospinal fluid, a 2.5 mL freshly prepared mixed solution containing plain ropivacaine (Naropin®, AstraZeneca AB Company, Sodertalje, Sweden) 8 mg + dexmedetomidine (Dexmedetomidine Hydrochloride Injection, 200 µg per 2 mL, Jiangsu Yangzi River Pharmaceutical Co., Ltd.; preservative-free and contains no additives or chemical stabilizers) (Group RopThe mixed solutions for spinal anesthesia were previously prepared by an independent anesthesiologist not involved further in the trial. A second anesthesiologist who was blinded to the details of the mixed solutions performed the CSEA procedure and intraoperative management as well as the subsequent assessments. A 1 mL insulin syringe was used for measuring volumes ≤ 1 mL. Dexmedetomidine for the present study was prepared by withdrawing 0.1 mL (10 µg) of dexmedetomidine from an ampoule of 100 µg·mLThe dose of dexmedetomidine for the first patient in each group was 5 µg. The dose of dexmedetomidine for the following patient was determined by the response of the previous patient to the intrathecal mixed solution in the same group according to the up-down sequential allocation method. If the response of the previous patient was effective, the dose of intrathecal dexmedetomidine for the subsequent patient was decreased by 1 µg. If the response of the patient was ineffective, the dose for the subsequent patient was increased by 1 µg. In case of an effective response in 1 µg or an ineffective response in 10 µg, the dose for the subsequent patients would remain the same until an ineffective response or an effective response prompted the anesthesiologist to increase or decrease the dose, respectively. An effective intrathecal block was defined as a bilateral sensory level to pinprick of T6 or above, which was achieved within 10 min after injection of spinal solution without the requirement of additional intraoperative epidural anesthetic. The ineffective intrathecal block was defined as failure to obtain a bilateral sensory level to pinprick of T6 within 10 min of intrathecal drug administration, or additional analgesia was required to complete surgery because of either a visual analog score (VAS; 0–10; 0 = no pain and 10 = worse pain imaginable) greater than 2, or the patient’s request for additional analgesia, despite achieving T6 sensory level block. In cases of ineffective response, supplemental epidural anesthesia consisting of 2% lidocaine was administered as 5 mL bolus injections, repeated every 5 min if necessary [ | PMC10519004 |
Measurements | Bradycardia, Hypotension, T10 dermatome sensory block | REGRESSION | The primary outcome was effective intrathecal block. Secondary outcomes included: the onset time of sensory block, which was defined as the time taken from intrathecal injection to T10 dermatome sensory block level being achieved; the highest level of sensory block within 10 min after intrathecal injection and the time taken to reach this maximal sensory block; the duration of sensory block, which was defined as the time to 2 segment regression checked every 10 min after achieving peak sensory block level; the onset time of motor block (assessed in both lower extremities using the Bromage scale [Hypotension (defined as systolic BP 20% less than the baseline value or less than 90 mmHg) was treated with 40 µg intravenous phenylephrine and was repeated as needed. Bradycardia, defined as HR < 50 beats·min | PMC10519004 |
Statistical analysis | Due to the nonindependence and unknown distribution of data associated with an up-down sequential allocation method, the exact sample size needed for a prespecified precision of the estimation of EDStatistical analyses were performed using SPSS (version 25.0, IBM Corp., Armonk, NY, USA). Data were presented as the mean ± standard deviation (SD), the median (interquartile range, IQR), or the number (proportion) as appropriate. Values for ED | PMC10519004 | ||
Discussion | cardiovascular and cerebrovascular diseases, Shivering, hypotension | MUSCLE RELAXATION | Our study showed that the EDThe ideal spinal anesthesia for cesarean section should provide adequate surgical conditions throughout the procedure with fewer side effects and earlier recovery of maternal motor functions and should not affect neonatal outcomes. Although a high dose of local anesthetics can achieve adequate intraoperative analgesia and muscle relaxation, it will inevitably lead to a higher incidence of hypotension and motor block [Several studies have explored intrathecal nonopioids as novel alternatives, such as αAlthough various factors influence the efficacy of nerve block during surgical anesthesia, the local anesthetic dose is the main determinant of its success [Khaw et al. [Earlier mobilization is important for parturients because it enables care for the newborn, reduces the incidence of venous thromboprophylaxis and facilitates early discharge from the hospital. Low-dose local anesthetics in spinal anesthesia permit earlier recovery from motor block and lower maternal side effects [Shivering, associated with spinal anesthesia during cesarean section, is an uncomfortable experience for the parturient; it may lead to increased oxygen consumption, increased peripheral vascular resistance, increased risk of cardiovascular and cerebrovascular diseases, and compromised wound healing [In our study, no newborn had an Apgar score < 9 in either group, indicating that the dosages of intrathecal dexmedetomidine were safe for neonates. These findings were in line with the results of previous randomized controlled trials [Our study also has limitations. First, we did not use intrathecal opioids as a control to examine the superiority or inferiority of intrathecal dexmedetomidine vs. opioids. Second, we did not detect the ED | PMC10519004 |
Conclusions | In conclusion, the ED50 of intrathecal dexmedetomidine as an adjuvant to 8 mg and 10 mg plain ropivacaine in spinal anesthesia during cesarean section was approximately 6 µg and 3 µg, respectively. | PMC10519004 | ||
Acknowledgements | Assistance with the study: We would like to thank Chongyang Duan, PhD of the Department of Biostatistics, School of Public Health, Southern Medical University, China, for his statistical analysis guidance during this project. | PMC10519004 | ||
Authors’ contributions | Xiaofei Mo, Fa Huang, and Jinghui Chen contributed to the conception and design of the study. Xiaoying Wu, Jumian Feng, and Jiequn Zeng contributed to the acquisition of data. Data analysis was primarily conducted by Fa Huan. Xiaofei Mo and Jinghui Chen contributed to the interpretation of data. Xiaofei Mo drafted the manuscript. All coauthors have contributed to the revision of the manuscript. | PMC10519004 | ||
Funding | Financial support and sponsorship: This work was supported by the National Science Foundation of China (grant number 81870823) and Guangzhou Institute of Pediatrics/Guangzhou Women and Children’s Medical Center funds (GCP-2018-001 and GCP-2019-002). | PMC10519004 | ||
Data Availability | The datasets used and/or analyzed during this study are available from the corresponding author upon reasonable request. | PMC10519004 | ||
Declarations | PMC10519004 | |||
Competing interests | The authors declare that there are no competing interests associated with the manuscript. | PMC10519004 | ||
Ethics approval and consent to participate | This study was approved by the Ethics Committee of Guangzhou Women and Children’s Medical Centre. Written informed consent was obtained from all legal representatives prior to data collection or study intervention. The trial was performed according to the Declaration of Helsinki. Our study complies with the CONSORT guidelines. | PMC10519004 | ||
Consent for publication | Not applicable. | PMC10519004 | ||
Abbreviations | analysis of varianceblood pressureconfidence intervalcesarean sectioncombined spinal-epidural anesthesiaheart ratemedian effective dosestandard deviationvisual analog score | PMC10519004 | ||
References | PMC10519004 | |||
Abstract | APPENDIX | Members of the NIHR Global Health Research Unit on Global Surgery are co-authors of this study and are listed under the heading Collaborators. Contributions of each collaborating author are detailed in Appendix S1.Data from TALON-1 were presented to the virtual UK National Institute of Health Research Academy Members Conference 2021 and the 6th UK Annual National PROMS 2022 conference where it was awarded the best overall abstract prize. | PMC10364512 | |
Background | surgical-site infection | The Bluebelle Wound Healing Questionnaire (WHQ) is a universal-reporter outcome measure developed in the UK for remote detection of surgical-site infection after abdominal surgery. This study aimed to explore cross-cultural equivalence, acceptability, and content validity of the WHQ for use across low- and middle-income countries, and to make recommendations for its adaptation. | PMC10364512 | |
Methods | TALON-1 | This was a mixed-methods study within a trial (SWAT) embedded in an international randomized trial, conducted according to best practice guidelines, and co-produced with community and patient partners (TALON-1). Structured interviews and focus groups were used to gather data regarding cross-cultural, cross-contextual equivalence of the individual items and scale, and conduct a translatability assessment. Translation was completed into five languages in accordance with Mapi recommendations. Next, data from a prospective cohort (SWAT) were interpreted using Rasch analysis to explore scaling and measurement properties of the WHQ. Finally, qualitative and quantitative data were triangulated using a modified, exploratory, instrumental design model. | PMC10364512 | |
Results | redness, fever, pain | SEPARATION | In the qualitative phase, 10 structured interviews and six focus groups took place with a total of 47 investigators across six countries. Themes related to comprehension, response mapping, retrieval, and judgement were identified with rich cross-cultural insights. In the quantitative phase, an exploratory Rasch model was fitted to data from 537 patients (369 excluding extremes). Owing to the number of extreme (floor) values, the overall level of power was low. The single WHQ scale satisfied tests of unidimensionality, indicating validity of the ordinal total WHQ score. There was significant overall model misfit of five items (5, 9, 14, 15, 16) and local dependency in 11 item pairs. The person separation index was estimated as 0.48 suggesting weak discrimination between classes, whereas Cronbach’s α was high at 0.86. Triangulation of qualitative data with the Rasch analysis supported recommendations for cross-cultural adaptation of the WHQ items 1 (redness), 3 (clear fluid), 7 (deep wound opening), 10 (pain), 11 (fever), 15 (antibiotics), 16 (debridement), 18 (drainage), and 19 (reoperation). Changes to three item response categories (1, not at all; 2, a little; 3, a lot) were adopted for symptom items 1 to 10, and two categories (0, no; 1, yes) for item 11 (fever). | PMC10364512 |
Conclusion | This study made recommendations for cross-cultural adaptation of the WHQ for use in global surgical research and practice, using co-produced mixed-methods data from three continents. Translations are now available for implementation into remote wound assessment pathways.This mixed-methods study within the FALCON trial across six low-and middle-income countries used qualitative and state-of-the-art psychometric methods with Rasch analysis. The authors make recommendations for adaptation of a Wound Healing Questionnaire (originally published in | PMC10364512 | ||
Introduction | Surgical-site infection, TALON-1, SSI | COMPLICATION | Surgical-site infection (SSI) is the most common complication of abdominal surgery, and has a cross-societal, global impact on patients and their familiesTimely identification of SSI is essential in maintaining patient safety after hospital discharge. Missed SSI diagnoses or misclassification of SSI can directly and indirectly affect patient safetyThe Bluebelle Wound Healing Questionnaire (WHQ) was developed and validated in the UK in the English language to support postdischarge surveillance for SSI after abdominal surgeryThe aims of this mixed-methods study (TALON-1) were: to explore cross-cultural and cross-language equivalence, acceptability, and content validity of the WHQ across several LMICs; to assess the scaling and psychometric properties of the WHQ when used across different patient populations and subgroups using Rasch analysis; and to consolidate recommendations for adaptation of the WHQ for use in global surgical research by triangulating qualitative and quantitative data. | PMC10364512 |
Methods | TALON-1 was a mixed-methods study embedded in an international randomized trial, conducted according to best practice guidelines, and co-produced with community and patient partnersOverview of TALON-1 study methodsSummary of Wound Healing Questionnaire adaptation methodologyAdapted from Oxford University Innovation outcomes centre checklist, and Mapi process for cross-cultural and cross-language adaptation. SWAT, study within a trial; WHQ, Wound Healing Questionnaire. | PMC10364512 | ||
Reporting and registration | This study was reported with reference to recommendations from the Global Health Network for qualitative research in LMICs, the COREQ framework | PMC10364512 | ||
Ethics and ethical approvals | SSI | This study within a trial (SWAT) was first approved within the pragmatic multicentre factorial RCT testing measures to reduce SSI in LMICs (FALCON trial) protocol by a University of Birmingham Research Ethics Committee (v1_0_substudies_v1_0. Reference: ERN_18-0230A). Additional approvals were then obtained from national, regional, and/or hospital-level ethics committees for selected centres in all participating countries, in accordance with local protocols. Written (or fingerprint) informed consent to participate was obtained from all participants. In the qualitative phase, an information sheet for was provided to all participants. Verbal consent was taken and recorded. Participant data were pseudonymized for storage securely within a password-protected NVivo® V12 data management system. In the quantitative phase, written (or fingerprint) informed consent to participate was obtained from all participants. Quantitative data were stored in a secure REDCap server | PMC10364512 | |
Host trial | skin infection | SKIN INFECTION | FALCON was a stratified, pragmatic, multicentre, 2 × 2 factorial trial testing two measures (skin preparation and antimicrobial sutures) to reduce superficial or deep skin infection after abdominal surgery in seven LMICs (NCT03700749) | PMC10364512 |
Study instrument | SSI | The WHQ was developed with the aim of detecting postdischarge SSI after abdominal surgery, and validated in a large feasibility study within a pilot RCT (Bluebelle) in the UK, as summarized in | PMC10364512 | |
Qualitative phase | PMC10364512 | |||
Cross-cultural and cross-contextual adaptation | Owing to the number of target languages for questionnaire in the host trial, cross-cultural adaptation was initially performed in English language. Structured interviews were conducted with two to three research staff in each country, according to a template from the Social Research Association based on WillisThe topic guide was structured around four predefined categories (To check trustworthiness, one or two focus groups were then held with investigators from each country to review and discuss the thematic coding. The focus groups were held after the interviews had been completed to explore consensus and contrasting opinions between different stakeholders around themes emerging in the semistructured interviews. The overall objective was to obtain a single cross-culturally adapted questionnaire to move into cross-language adaptation | PMC10364512 | ||
Cross-language adaptation | SECONDARY | In some countries, English was a primary or prevalent secondary language among the host trial participants. In these countries, the feasibility of single-language administration of the questionnaire was tested at sites during the cohort study. Where translation of the WHQ was required, this was performed according to the Mapi process for standard linguistic validation to verify conceptual equivalence across languages | PMC10364512 | |
Quantitative phase | trauma | Data for the quantitative phase were collected during a prospective, international cohort SWAT. Consecutive adult patients (aged over 18 years) recruited to the FALCON trial were eligible. These included a broad range of abdominal operations with a predicted clean-contaminated, contaminated or dirty operating field, and a planned skin incision of greater than 5 cm. Operations could be performed for benign, malignant, trauma, or obstetric indications. Consent for an additional telephone follow-up call to administer the WHQ was taken at the same time as trial consent, using a targeted Informed Consent Form and Patient Information Sheet. Patient and community partners supported co-production of these resources to ensure culturally attuned language and delivery.Telephone administration of the translated WHQ was undertaken 28–30 days after surgery (in the 72 h before in-person follow-up) integrated into the host trial pathway. The telephone WHQ was administered by a researcher, doctor, or research nurse (non-consultant or attending grade), who was independent of the assessment for the trial primary outcome at 30 days after surgery. Optimization and quality assurance of WHQ administration is described in | PMC10364512 | |
Psychometric testing using Rasch analysis | anomalies | WOUND INFECTION | A simple summary of Rasch methodology for the general reader is provided in The Rasch unidimensional measurement model was fitted to examine the psychometric properties of the WHQ, identify anomalies in the data, and evaluate the extent to which the WHQ items are measuring the latent trait of wound infection | PMC10364512 |
Triangulation | Qualitative and quantitative data were triangulated using data (between countries) and methodological (between qualitative interviews and psychometric analysis of quantitative data) triangulation, adopting a modified, exploratory, instrumental design model. Triangulation was performed item by item to enable a final version of the instrument in both source (English) and target languages to be finalized and consolidated | PMC10364512 | ||
Community engagement and involvement | Patients and community members from LMICs were engaged in all phases of the design and delivery of this study. The interview topic guide was co-designed with input from a representative global surgery patient forum. Practicable methods for conducting interviews, and patient compensation for time in participation, were determined with the support of local community leaders. The Guidance for Reporting Involvement of Patients and the Public (GRIPP-2) short form was used to track and report the impact of CEI | PMC10364512 | ||
Results | PMC10364512 | |||
Qualitative phase | SSI | In total, 10 structured interviews and six focus groups were arranged with a total of 47 investigators across six countries. They included 34 surgeons, five anaesthetists, and eight research staff caring for patients in both urban and rural populations, and across a range of abdominal surgery disciplines. Interview duration ranged from 34 to 112 min, and focus groups lasted from 92 to 126 min. There was a median of 11 (range 6–16) participants involved in the focus groups. Interview and focus group data from site investigators confirmed that the assumption of a universalist approach to SSI was acceptable, and that symptomology and treatment paradigms were shared across settings. No divergence from this was identified during thematic analysis. This was also explored with the CEI partners; together, they confirmed content validity across settings. No new domains or concepts related to symptoms or treatment of SSI arose, suggesting content validity across contexts. A summary of qualitative data are presented for symptom items in Translation was successfully completed in five target languages after the qualitative phase: French (Benin), Hindi (India), Kinyarwanda (Rwanda), Punjabi (India), and Tamil (India). For some potential languages of delivery, there was no written version of the dialect (for example, Goun in Benin, Fante in Ghana), and, on rare occasions, patients would travel a very long distance for treatment and spoke a language that was uncommon to the local area (for example, Malayam in Northern India). Here, the questionnaire was translated ad hoc from English (source language) by the assessor in the cohort study. | PMC10364512 | |
Quantitative phase | An attempt was made to contact 655 patients in the cohort study across five countries, of whom five had died by 30 days (15 missing status). Of the 635 confirmed to be alive, 537 (84.5 per cent) were contactable for WHQ completion. Features of included patients are summarized in Patient characteristics (quantitative phase)Values are | PMC10364512 | ||
Unidimensionality of scale | The exploratory Rasch model was fitted using these data from 537 patients (369 excluding extremes) across five class intervals ( | PMC10364512 | ||
Model fit and targeting | Overall, the model did not fit well, with a high probability of item–trait interaction (χPerson–threshold distribution map of the Wound Healing QuestionnaireItem location map for the adapted Wound Healing Questionnaire | PMC10364512 | ||
Individual item fit and dependency | Five items (5, 9, 14, 15, 16) displayed significant misfit to the model (mean(s.d.) item fit residual −1.61(1.75)) ( | PMC10364512 | ||
Differential item functioning | There was significant evidence of uniform differential item functioning (DIF) by country in items 1, 3, 5, 8, 10, and 13, and non-uniform DIF by country in items 4, 10, 13, 16, 17, and 19 ( | PMC10364512 | ||
Triangulation | Triangulation of qualitative and quantitative data was performed item by item for the 11 symptom items (10 items and 1 subitem) and eight pathway items (Category probability curves for items with an overlapping response thresholdThreshold map for Wound Healing QuestionnaireSummary of recommendations for adaptation of Wound Healing Questionnaire (English language) | PMC10364512 | ||
Measurement procedures | Junior | A summary of measurement procedures is shown in ‘People were very impressed that I was calling them and still following up on the surgeries and were willing to talk very happily.’ (Research nurse, Focus group IN002F, India)Measurement processes (quantitative phase)Values are In total, 533 of 537 patients (99.2 per cent) reported the telephone WHQ pathway to be very satisfactory or satisfactory:‘Early feedback that the questionnaire is highly acceptable to patients. Patients say they are receiving a ‘VIP’ treatment.’ (Junior doctor, Focus group GH001F, Ghana)Often the telephone owner was a friend or relative (who was then able to connect the researcher directly to the patient) rather than the patient themselves (189 of 537, 35.2 per cent), and commonly this was a mobile phone (534 of 537, 99.5 per cent). In total, 154 of 537 (28.7 per cent) had a mobile phone with video capability. Feedback from CEI partners alongside interview data supported optimization of the telephone follow-up pathway for future implementation; this is presented in a toolkit available in | PMC10364512 | |
Discussion | SSI | CARDIOVASCULAR DISEASE, COMPLICATIONS | Pathways for remote assessment of common complications after surgery in low-resource settings are essential in improving the safety and resilience of surgical care systems. This mixed-methods study made recommendations for cross-cultural and cross-language adaptation of the WHQ for use in LMICs, and improved its relevance across cultures and for patients with lower levels of health literacy. Conceptual equivalence, and content and construct validity was confirmed across languages using qualitative and translation methods. Unidimensionality, measurement properties, and use of the total WHQ score were seen to be valid within the Rasch framework, although the overall power of fit was low. The telephone pathway was demonstrated to be feasible and highly acceptable. Working with CEI partners, recommendations were made for optimization of telephone follow-up in research and postoperative surveillance programmes. This study provides a large, international, high-quality proof of concept for rapid adaptation and implementation of patient-reported measures in emerging global health arenas such as surgery.The use of mixed methods here added strength and depth. The qualitative data were used primarily to inform cross-cultural adaptation ahead of translation. Although this was based on cognitive theory, data were collected indirectly about patient experience from frontline clinicians involved in wound assessment. The Rasch analysis supplemented this, and allowed patient-level data to enrich and inform final recommendations for adaptation. In a majority of instances, the qualitative and quantitative data were supportive of one another, demonstrating coherence during triangulation. Where conflict arose, qualitative findings were softened and/or caveated (that is, changes were recommended where there was coherence on triangulation, and further exploration recommended where there was conflict between the qualitative and quantitative data).Rasch analysis is an established method for instrument development and cross-cultural refinementExploring complex relationships between items and optimizing the measurement properties using subtesting and adjusting for DIF was not the aim here, but warrants further investigation. It is feasible that the instrument could be simplified, or its diagnostic accuracy could be improved using Rasch by better accounting for differences in the symptomology and health-seeking behaviours of patients with SSI across countries. DIF by country observed for several items here supports methods to ensure balance in randomized trials, such as stratification or minimization of randomization by country.This study has several limitations. Owing to safety and ethical concerns during the SARS-CoV-2 pandemic, cognitive interviewing could not be undertaken directly with patients. Instead, aggregate perspectives of frontline clinicians involved in the care of surgical patients were explored. This meant that the data represented clinicians’ impressions of patients’ responses, and challenges in retrieval and judgement, rather than direct exploration with patients in typical cognitive interviewingThe use of patient-reported outcome measures (PROMs) in low-income settings is complex; many instruments have not yet undergone cross-cultural and cross-language adaptation, and there is uncertainty about the feasibility of remote, digital methods. Although examples exist from established global health fields, such cardiovascular disease, few studies in global surgery have adopted PROMs to date | PMC10364512 |
Collaborators | René, Ademuyiwa, Ramos de la Medina, Parth Dhamija, Olufunmilade, Claudia, Antonio Ramos De la Medina, Lawal Abdullahi, Corinne Dzemta, Wilson Adenikinju, Adjei-Acquah, Dokponou, Donna Smith, Thomas, Adagrah, Pierre Sodonougbo, Godsway, Abdul-Hafiz | BRUCE, OGO, GIBERT, MOREL, BROWN, MOORE, FRANK, ROBLES, LISSAUER, DEL, DARLING, FRANCIS, HORTON | NIHR Global Health Research Unit on Global Surgery: James Glasbey, Adesoji Ademuyiwa, Alisha Bhatt, Bruce Biccard, Jane Blazeby, Peter Brocklehurst, Sohini Chakrabortee, JC Allen Ingabire, Francis Moïse Dossou, Irani Durán, Rohini Dutta, Dhruva Ghosh, Frank Gyamfi, Parvez Haque, Pollyanna Hardy, Mike Horton, Gabriella Hyman, Ritu Jain, Oluwaseun Ladipo-Ajayi, Ismail Lawani, Souliath Lawani, Mwayi Kachapila, Rachel Lillywhite, Rhiannon Macefield, Laura Magill, Janet Martin, Jonathan Mathers, Kenneth McLean, Punam Mistry, Rohin Mittal, Mark Monahan, Rachel Moore, Dion Morton, Moyo Ojo, Faustin Ntirenganya, Emmanuel Ofori, Rupert Pearse, Alberto Peón, Thomas Pinkney, Antonio Ramos de la Medina, Tubasiime Ronald, David Roman, Emmy Runingamugabo, Alice Sitch, Anita Slade, Donna Smith, Stephen Tabiri, Aneel Bhangu, James Glasbey, Anita Slade, Mike Horton, Rhiannon Macefield, Aneel Bhangu, Pollyanna Hardy, Adesoji O Ademuyiwa, Lawani Ismail, Dhruva Ghosh, Antonio Ramos de la Medina, Rachel Moore, Faustin Ntirenganya, Stephen Tabiri, Emmy Runingamugabo, Simin Patrawala, Angela Prah, Christian Oko, Karolin Kroese, Ismaïl Lawani, Francis Moïse Dossou, Corinne Dzemta, Covalic Melic Bokossa Kandokponou, Souliath Lawani, Hulrich Behanzin, Cyrile Kpangon, Bernard Appiah Ofori, Stephen Tabiri, Abdul-Hafiz Saba, Gbana Limann, Daniel Kwesi Acquah, Shamudeen Mohammed Alhassan, Sheriff Mohammed, Owusu Abem Emmanuel, Yakubu Musah, Yenli Edwin, Sheba Kunfah, Yakubu Mustapha, Abantanga Atindaana Francis, Emmanuel Ayingayure, Gbana Limann, Forster Amponsah-Manu, Eric Agyemang, Vera Agyekum, Esther Adjei-Acquah, Emmanuel Yaw Twerefour, Barbra Koomson, Ruby Acheampong Boateng, Ato Oppong Acquah, Richard Ofosu-Akromah, Leslie Issa Adam-Zakariah, Nii Armah Adu-Aryee, Theodore Wordui, Coomson Christian Larbi, Akosa Appiah Enoch, Mensah Elijah, Kyeremeh Christian, Addo Gyambibi Kwame, Boakye Percy, Kontor Effah Bismark, Gyamfi Brian, Manu Ruth, Romeo Hussey, Samuel Dadzie, Akosua Dwamena Appiah, Grace Yeboah, Cynthia Yeboah, James Amoako, Regina Acquah, Naa Anyekaa Sowah, Atta Kusiwaa, Esther Asabre, Cletus Ballu, Charles Gyamfi Barimah, Frank Owusu, Clement Sie-Broni, Vivian Adobea, Prince Yeboah Owusu, Marshall Zume, Abdul-Hamid Labaran, Raphael Adu-Brobbey, Martin Tangnaa Morna, Samuel A. Debrah, Patrick Opoku Manu Maison, Michael Nortey, Donald Enti, Mabel Pokuah Amoako-Boateng, Anthony Baffour Appiah, Emmanuel Owusu Ofori, Richard Kpankpari, Benedict Boakye, Elizabert Mercy Quartson, Patience Koggoh, Anita Eseenam Agbeko, Frank Enoch Gyamfi, Joshua Arthur, Joseph Yorke, Christian Kofi Gyasi-Sarpong, Charles Dally, Agbenya Kobla Lovi, Michael Amoah, Boateng Nimako, Robert Sagoe, Anthony Davor, Fareeda Galley, Michael Adinku, Jonathan Boakye-Yiadom, Jane Acquaye, Juliana Appiah, Dorcas Otuo Acheampong, Iddrisu Haruna, Edward Amoah Boateng, Emmanuel Kafui Ayodeji, Samuel Tuffuor, Naa Kwarley, Yaa Tufuor, Ramatu Darling Abdulai, Fred Dankwah, Ralph Armah, Doris Ofosuhene, Dorcas Osei-Poku, Arkorful Ebenezer Temitope, Delali Akosua Gakpetor, Victoria Sena Gawu, Christopher Asare, Enoch Tackie, James Ankomah, Isaac Omane Nyarko, Zelda Robertson, Serbeh Godwin, Appiah Anthony Boakye, Godfred Fosu, Frank Assah-Adjei, Parvez Haque, Ritu Jain, Alisha Bhatt, Jyoti Dhiman, Rohini Dutta, Dhruva Ghosh, Esther Daniel, Priyadarshini K, Latha Madankumar, Rohin Mittal, Ida Nagomy, Soosan Prasad, Arpit Jacob Mathew, Danita Prakash, Priya Jacob, Jeremiah Zain Ally*, Margot Flint, Bruce Biccard, Adesoji O Ademuyiwa, Adewale O. Adisa, Aneel Bhangu, Peter Brocklehurst, Sohini Chakrabortee, Pollyanna Hardy, Ewen Harrison, JC Allen Ingabire, Parvez D Haque, Lawani Ismail, James Glasbey, Dhruva Ghosh, Frank Enoch Gyamfi, Elizabeth Li, Rachel Lillywhite, Antonio Ramos de la Medina, Rachel Moore, Laura Magill, Dion Morton, Dmitri Nepogodiev, Faustin Ntirenganya, Thomas Pinkney, Omar Omar, Joana Simoes, Donna Smith, Stephen Tabiri, Adesoji O Ademuyiwa, Lawani Ismail, Dhruva Ghosh, Antonio Ramos de la Medina, Rachel Moore, Faustin Ntirenganya, Stephen Tabiri, Adesoji Ademuyiwa, Aneel Bhangu, Felicity Brant, Peter Brocklehurst, Sohini Chakrabortee, Dhruva Ghosh, James Glasbey, Pollyanna Hardy, Ewen Harrison, Emily Heritage, Lawani Ismail, Karolin Kroese, Carmela Lapitan, Rachel Lillywhite, David Lissauer, Laura Magill, Antonio Ramos de la Medina, Punam Mistry, Mark Monahan, Rachel Moore, Dion Morton, Dmitri Nepogodiev, Faustin Ntirenganya, Omar Omar, Thomas Pinkney, Tracy Roberts, Donna Smith, Stephen Tabiri, Neil Winkles, Pollyanna Hardy, Omar Omar, Emmy Runigamugabo, Azmina Verjee, Pierre Sodonougbo, Pamphile Assouto, Michel Fiogbe, Houenoukpo Koco, Serge Metchinhoungbe, Hodonou Sogbo, Hulrich Behanzin, Djifid Morel Seto, Yannick Tandje, Sosthène Kangni, Cyrile Kpangon*, Marcelin Akpla, Hugues Herve Chobli, Blaise Kovohouande, Gérard Agboton, Rene Ahossi, Raoul Baderha Ngabo, Nathan Bisimwa, Covalic Melic Bokossa Kandokponou, Mireille Dokponou, Francis Moïse Dossou, Corinne Dzemta, Antoine Gaou, Roland Goudou, Emmanuel Hedefoun, Sunday Houtoukpe, Felix Kamga, Eric Kiki-Migan, Souliath Lawani, Ismaïl Lawani, René Loko, Afissatou Moutaïrou, Pencome Ogouyemi, Fouad Soumanou, Pia Tamadaho, Mack-Arthur Zounon, Luke Aniakwo Adagrah, Bin Baaba Alhaji Alhassan, Mabel Pokuah Amoako-Boateng, Anthony Baffour Appiah, Alvin Asante-Asamani, Benedict Boakye, Samuel A Debrah. Donald Enti, Rahman Adebisi Ganiyu, Patience Koggoh, Richard Kpankpari, Isabella Naa M. Opandoh, Meshach Agyemang Manu, Maison Patrick Opoku Manu, Samuel Mensah, Martin Tangnaa Morna, John Nkrumah, Michael Nortey, Emmanuel Owusu Ofori, Elizaberth Mercy Quartson, Esther Adjei-Acquah, Vera Agyekum, Eric Agyemang, Rebecca Adjeibah Akesseh, Forster Amponsah-Manu, Richard Ofosu-Akromah, Ato Oppong Acquah, Leslie Issa Adam-Zakariah, Esther Asabre, Ruby Acheampong Boateng, Barbara Koomson, Ataa Kusiwaa, Emmanuel Yaw Twerefour, James Ankomah, Frank Assah-Adjei, Anthony Appiah Boakye, Godfred Fosu, Godwin Serbeh, Kofi Yeboah Gyan, Isaac Omane Nyarko, Zelda Robertson, Ralph Armah, Christopher Asare, Delali Akosua Gakpetor, Victoria Sena Gawu, Ambe Obbeng, Doris Ofosuhene, Dorcas Osei-Poku, Diana Puozaa, Enoch Tackie, Arkorful Ebenezer Temitope, Regina Acquah, James Amoako, Akosua Dwamena Appiah, Mark Aseti, Charles Banka, Samuel Dadzie, Derick Essien, Frank Enoch Gyamfi, Romeo Hussey, Jemima Kwarteng, Naa Anyekaa Sowah, Grace Yeboah, Cynthia Yeboah, Kwame Gyambibi Addo, Enoch Appiah Akosa, Percy Boakye, Christian Larbi Coompson, Brian Gyamfi, Bismark Effah Kontor, Christian Kyeremeh, Ruth Manu, Elijah Mensah, Friko Ibrahim Solae, Gideon Kwasi Toffah, Dorcas Otuo Acheampong, Jane Acquaye, Michael Adinku, Kwabena Agbedinu, Anita Eseenam Agbeko, Emmanuel Gyimah Amankwa, Michael Amoah, George Amoah, Juliana Appiah, Joshua Arthur, Alex Ayim, Emmanuel Kafui Ayodeji, Jonathan Boakye-Yiadom, Edward Amoah Boateng, Charles Dally, Anthony Davor, Christian Kofi Gyasi-Sarpong, Naabo Nuhu Noel Hamidu, Iddrisu Haruna, Naa Kwarley, Agbenya Kobla Lovi, Boateng Nimako, Bertina Beauty Nyadu, Dominic Opoku, Anita Osabutey, Robert Sagoe, Samuel Tuffour, Yaa Tufour, Francis Akwaw Yamoah, Abiboye Cheduko Yefieye, Joseph Yorke, Nii Armah Adu-Aryee, Faisal Adjei, Erica Akoto, Elikem Ametefe, Joachim Kwaku Amoako, Godsway Solomon Attepor, George Darko Brown, Benjamin Fenu, Philemon Kwame Kumassah, David Olatayo Olayiwola, Theodore Wordui, Nelson Agboadoh, Fatao Abubakari, Cletus Ballu, Charles Gyamfi Barimah, Guy Casskey Boateng, Prosper Tonwisi Luri, Abraham Titigah, Frank Owusu, Raphael Adu-Brobbey, Christian Larbi Coompson, Abdul-Hamid Labaran, Junior Atta Owusu, Vivian Adobea, Amos Bennin, Fred Dankwah, Stanley Doe, Ruth Sarfo Kantanka, Ephraim Kobby, Kennedy Kofi Korankye Hanson Larnyor, Edwin Osei, Prince Yeboah Owusu, Clement Ayum Sie-Broni, Marshall Zume, Francis Atindaana Abantanga, Darling Ramatu Abdulai, Daniel Kwesi Acquah, Emmanuel Ayingayure, Imoro Osman, Sheba Kunfah, Gbana Limann, Shamudeen Alhassan Mohammed, Sheriff Mohammed, Yakubu Musah, Bernard Ofori, Emmanuel Abem Owusu, Abdul-Hafiz Saba, Anwar Sadat Seidu, Stephen Tabiri, Mustapha Yakubu, Edwin Mwintiereh Taang Yenli, Arun Gautham, Alice Hepzibah, Grace Mary, Deepak Singh, Dimple Bhatti, William Bhatti, Karan Bir, Swati Daniel, Tapasya Dhar, Jyoti Dhiman, Dhruva Ghosh, Sunita Goyal, Ankush, Goyal, Monika Hans, Parvez Haque, Samuel Konda, Anil Luther, Amit Mahajan, Shalini Makkar, Kavita Mandrelle, Vishal Michael, Partho Mukherjee, Reuben Rajappa, Prashant Singh, Atul Suroy, Ravinder Thind, Alen Thomas, Arti Tuli, Sreejith Veetil, Esther Daniel Mark Jesudason, Priyadarshini K, Latha Madankumar, Rohin Mittal, Ida Nagomy, Rajesh Selvakumar, Bharat Shankar, Moonish Sivakumar, Rajeevan Sridhar, Cecil Thomas, Devabalan Titus, Manisha Aggarwal, Parth Dhamija, Himani Gupta, Vinoth Kanna, Ashwani Kumar, Gurtaj Singh, Philip Alexander, Josy Thomas, Pradeep Zechariah, Amos Dasari, Priya Jacob, Elizabeth Kurien, Arpit Mathew, Danita Prakash, Anju Susan, Rose Varghese, Rahul Alpheus, Ashish Choudhrie, Hemanth Kumar, Nitin Peters, Subrat Raul, Rajeev Sharma, Rakesh Vakil, Wenceslao Ángeles Bueno, Francisco Barbosa Camacho, Aldo Bernal Hernández, Ana Bogurin Arellano, Edgar Cortes Torres, Clotilde Fuentes Orozco, Erick González García de Rojas, Alejandro González Ojeda, Bertha Guzmán Ramírez, Michel Hernández Valadez, Diego Luna Acevedo, Rubén Morán Galaviz, Oscar Olvera Flores, José Pérez Navarro, Kevin Pintor Belmontes, Fernando Ramirez Marbello, Luis Ramírez-González, Laura Reyes Aguirre, Ramona Rojas García, Eduardo Valtierra Robles, Reyes Cervantes Ortiz, Gonzalo Hernandez Gonzalez, Rosa Hernandez Krauss, Luis Hernández Miguelena, Marco Hurtado Romero, Isaac Baltazar Gomez, Celina Cuellar Aguirre, Alejandro Cuevas Avendaño, Luis Dominguez Sansores, Hector Ortiz Mejia, Laura Urdapilleta Gomez del Campo, Claudia Caballero Cerdan, David Dominguez Solano, Rafael Toriz Garcia, Mariana Barreto Gallo, Ana Cortes Flores, Alejandro Gonzalez Ojeda, Monica Jimenez Velasco, Rozana Reyes Gamez, Roque Lincona Menindez, Alberto Navarrete Peón, Maria Paz Muñoz, Irán Irani Durán Sánchez, Diana Samantha González Vázquez, María José Martínez Lara, Laura Martinez Perez Maldonado, Alejandra Nayen Sainz de la Fuente, Antonio Ramos De la Medina, Lawal Abdullahi, Khadija Ado, Mohammed Aliyu, Lofty-John Anyanwu, Mahmoud Magashi, Abubakar Muhammad, Saminu Muhammad, Bello Muideen, Idris Takai, Onyekachi Ukata, Opeoluwa Adesanya, David Awonuga, Olushola Fasiku, Chidiebere Ogo, Moruf Abdulsalam, Abimbola Adeniran, Olalekan Ajai, Olukemi Akande, Kazeem Atobatele, Grace Eke, Omolara Faboya, Zainab Imam, Esther Momson, Francisca Nwaenyi, Ayokunle Ogunyemi, Mobolaji Oludara, Olufunmilade Omisanjo, Olabode Oshodi, Yusuf Oshodi, Yemisi Oyewole, Omotade Salami, Omolara Williams, Victoria Adeleye, Adesoji Ademuyiwa, Oluwafunmilayo Adeniyi, Opeyemi Akinajo, David Akinboyewa, Iyabo Alasi, Felix Alakaloko, Oluwole Atoyebi, Olanrewaju Balogun, Orimisan Belie, Christopher Bode, Andrew Ekwesianya, Olumide Elebute, Francis Ezenwankwo, Adedeji Fatuga, George Ihediwa, Adesola Jimoh, Jubril Kuku, Oluwaseun LadipoAjayi, Ayomide Makanjuola, Olayanju Mokwenyei, Samuel Nwokocha, Olubunmi Ogein, Rufus Ojewola, Abraham Oladimeji, Thomas Olajide, Oluwaseun Oluseye, Justina Seyi-Olajide, Adaiah Soibi-Harry, Aloy Ugwu, Emmanuel Williams, Ochomma Egwuonwu, Okechukwu Ekwunife, Victor Modekwe, Chukwuemeka Okoro, Chisom Uche, Kenneth Ugwuanyi, Chuka Ugwunne, Akeem Adeleke, Wilson Adenikinju, Olumide Adeniyi, Akinfolarin Adepiti, Adewale Aderounmu, Abdulhafiz Adesunkanmi, Adewale Adisa*, Samuel Ajekwu, Olusegun Ajenjfuja, Jerrie Akindojutimi, Akinbolaji Akinkuolie, Olusegun Alatise, Olubukola Allen, Lukmon Amosu, Micheal Archibong, Olukayode Arowolo, Deborah Ayantona, Ademola Ayinde, Olusegun Badejoko, Tajudeen Badmus, Amarachukwu Etonyeaku, Emeka Igbodike, Omotade Ijarotimi, Adedayo Lawal, Fayowole Nana, Tunde Oduanafolabi, Olalekan Olasehinde, Olaniyi Olayemi, Stephen Omitinde, Owolabi Oni, Chigozie Onyeze, Ernest Orji, Adewale Rotimi, Abdulkadir Salako, Olufemi Solaja, Oluwaseun Sowemimo, Ademola Talabi, Mohammed Tajudeen, Funmilola Wuraola, Francis Adebayo, Oseremen Aisuodionoe-Shadrach, Godwin Akaba, Lazarus Ameh, Ndubuisi Mbajiekwe, Felix Ogbo, Samson Olori, Olabisi Osagie, Abu Sadiq, Samuel Sani, Nancy Tabuanu, Martins Uanikhoba, Godwin Chiejina, Ekpo Edet, Akan Inyang, Mary Isa, Faith Iseh, Adams Marwa, Sunday Ogbeche, Edima Olory, Gabriel Udie, Joseph Udosen, Usang Usang, Olukayode Abayomi, Rukiyat Abdus-Salam, Sikiru Adebayo, Akinlabi Ajao, Olanrewaju Amusat, Omobolaji Ayandipo, Kelvin Egbuchulem, Hyginus Ekwuazi, Peter Elemile, Taiwo Lawal, Olatunji Lawal, Solomon Olagunju, Peter Osuala, Bamidele Suleman, Augustine Takure, Lukman Abdur-Rahman, Nurudeen Adeleke, Muideen Adesola, Rafiat Afolabi, Sulaiman Agodirin, Isiaka Aremu, Jibril Bello, Saheed Lawal, Abdulwahab Lawal, Hadijat Raji, Olayinka Sayomi, Asimiyu Shittu, Jude Ede, Sebastian Ekenze, Vincent Enemuo, Matthew Eze, Uchechukwu Ezomike, Emmanuel Izuka, Okezie Mbadiwe, Ngozi Mbah, Uba Ezinne, Matthew Francis, Iweha Ikechukwu, Okoi Nnyonno, Philemon Okoro, Igwe Patrick, John Raphael, Oriji Vaduneme, Abhulimen Victor, Salathiel Kanyarukiko, Francine Mukaneza, Deborah Mukantibaziyaremye, Aphrodis Munyaneza, Gibert Ndegamiye, Ronald Tubasiime, Moses Dusabe, Emelyne Izabiriza, Hope Lydia Maniraguha, Christophe Mpirimbanyi, Josiane Mutuyimana, Olivier Mwenedata, Elisee Rwagahirima, Francine Uwizeyimana, Job Zirikana, Aime Dieudonne Hirwa, Elysee Kabanda, Salomee Mbonimpaye, Christine Mukakomite, Piolette Muroruhirwe, Georges Bucyibaruta, Gisele Juru Bunogerane, Sosthene Habumuremyi, Jean de Dieu Haragirimana, Alphonsine Imanishimwe, JC Allen Ingabire, Violette Mukanyange, Emmanuel Munyaneza, Emmanuel Mutabazi, Isaie Ncogoza, Faustin Ntirenganya, Jeannette Nyirahabimana, Christian Urimubabo, Mary Augusta Adams, Richard Crawford, Chikwendu Jeffrey Ede, Maria Fourtounas, Gabriella Hyman, Zafar Khan, Morapedi Kwati, Mpho Nosipho Mathe, Rachel Moore, Ncamsile Anthea Nhlabathi, Hlengiwe Samkelisiwe Nxumalo, Paddy Pattinson, Nnosa Sentholang, Mmule Evelyn Sethoana, Maria Elizabeth Stassen, Laura Thornley, Paul Wondoh Edenvale Hospital, Johannesburg: Cheryl Birtles, Mathete Ivy, Cynthia Mbavhalelo, Zain Ally, Abdus-sami Adewunmi, Jonathan Cook, David Jayne, Soren Laurberg, Julia Brown, Simon Cousens, Neil Smart | PMC10364512 |
Supplementary Material | Click here for additional data file. | PMC10364512 | ||
Acknowledgements | The Bluebelle Wound Healing Questionnaire (WHQ) is copyright of the University of Bristol and was licensed for use in this study by Oxford University Innovation LTD (OUI). Enquiries for permission to use the WHQ should be directed to Oxford University Innovation. Special thanks to the Centre for Patient Reported Outcomes Research at the University of Birmingham, Leeds Psychometric Laboratory for Health Sciences at the University of Leeds, and the patients and community members who helped steer the global WHQ adaptation process. | PMC10364512 | ||
Funding | TALON-1 was funded through a doctoral research fellowship from the National Institute for Health Research (NIHR) Academy (NIHR300175). The FALCON trial was funded by a NIHR Global Health Research Unit Grant (NIHR 16.136.79). The funder and sponsor had no role in study design or writing of this report. The funder has approved the submission of this report for publication. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the UK Department of Health and Social Care. | PMC10364512 | ||
Disclosure | The authors declare no conflict of interest. | PMC10364512 | ||
Supplementary material | PMC10364512 | |||
Data availability | Anonymized interview and cohort study data are available on request to the TALON Study Management Group, upon successful completion of a Data Sharing Agreement | PMC10364512 | ||
References | PMC10364512 | |||
Supplementary Information | CKD, chronic kidney disease | The prevalence of chronic kidney disease (CKD) is steadily increasing, and it is a global health burden. Exercise has been suggested to improve physical activity and the quality of life in patients with CKD, eventually reducing mortality. This study investigated the change in physical performance after exercise in dialysis-dependent patients with CKD and analyzed differentially expressed proteins before and after the exercise. Plasma samples were collected at enrollment and after 3 months of exercise. Liquid chromatography with tandem mass spectrometry analysis and data-independent acquisition results were analyzed to determine the significantly regulated proteins. A total of 37 patients on dialysis were recruited, and 16 were randomized to exercise for 3 months. The hand grip strength and the walking speed significantly improved in the exercise group. Proteome analysis revealed 60 significantly expressed proteins after 3 months of exercise. In the protein functional analysis, the significantly expressed proteins were involved in the immune response. Also, some of the key significantly expressed proteins [(M Matrix metallopeptidase 9 (MMP-9), Activin A Receptor Type 1B (ACVR1B), Fetuin B (FETUB)] were validated via an enzyme-linked immunosorbent assay. Our results showed that exercise in dialysis-dependent patients with CKD could improve their physical performance. These results indicated that this beneficial effect of exercise in these populations could be associated with immune response.The online version contains supplementary material available at 10.1186/s12882-023-03146-w. | PMC10122383 | |
Keyword | PMC10122383 | |||
Introduction | CKD, chronic kidney disease | The global prevalence of chronic kidney disease (CKD) has increased, and it is considered the leading cause of public health problems [Recent studies have shown that high physical function and activity are associated with improved survival and decreased mortality in patients with CKD [Therefore, this study investigated the change in physical performance after exercise intervention in patients with CKD on dialysis. We also analyzed protein expression after exercise intervention using a proteomic approach. | PMC10122383 | |
Materials and methods | PMC10122383 | |||
Study population | ESRD | ESRD | This study prospectively enrolled ESRD patients in CHA bundang medical center in South Korea, and undergoing maintenance hemodialysis for at least 3 months was diagnostic criteria for ESRD. The overall scheme of this study is shown in Fig.
Schematic diagram summarizing the study design. (Initially, 37 adult patients were recruited, and 16 were randomized for three months of exercise during hemodialysis sessions (Fig. This study was approved by the Institutional Review Board of CHA Bundang Medical Center and was conducted in accordance with the Declaration of Helsinki and principles of Good Clinical Practice (CHAMC 2016-05-064-024). Written informed consent was obtained from all the patients. | PMC10122383 |
Exercise intervention | dyspnea, chest pain, vomiting, leg cramps, dizziness, intradialytic, nausea, | STRETCHES | The intradialytic exercise program consisted of aerobic exercises using a cycle ergometer. Each exercise phase consisted of a warm-up, main exercise, and cool-down phase. The warm-up consisted of stretches recommended by LORAC (2000), and was conducted for 5 min before the main exercise, sequencing from the upper body to lower body movements. In the main exercise phase, the patients were trained on a mechanically braked cycle ergometer (Mbike; Hong Jin Company, China), which was positioned in front of the dialysis recliner. The exercise was performed three times a week for every dialysis session and in the first 1–2 h of hemodialysis, with a total exercise time of 30–60 min. Using Borg’s 15-point scale for rating of perceived exertion, the patients were trained at a range of 7–9 for 5 min, range 12–15 for 20–50 min, and range 7–9 for 5 min. The cool-down phase was conducted in a manner similar to the warm-up phase for 5 min.The training was terminated if the patient’s blood pressure exceeded (above 230 mmHg systolic blood pressure or above 120 mmHg diastolic blood pressure) or if the patient experienced dizziness, chest pain, nausea, vomiting, leg cramps, or severe dyspnea. | PMC10122383 |
Physical performance and body composition | The physical performance test was performed at the time of enrollment and three months later in both patient groups. Handgrip strength was measured immediately before the dialysis session. Patients performed three tests of maximum hand grip strength with the hand without vascular access using a Jamar hand dynamometer (Sammons Preston Inc., Bolingbrook, IL, USA). Slow walking speed was assessed by measuring gait speed over a 4 m course [ | PMC10122383 | ||
Clinical variables | angina pectoris | CVD, MYOCARDIAL INFARCTION, CONGESTIVE HEART FAILURE | Patient demographics and clinical data, including age, sex, body mass index, and comorbidities, were obtained from medical records. CVD was defined as a medical history of congestive heart failure, angina pectoris, myocardial infarction, percutaneous transluminal coronary angioplasty, or coronary artery bypass surgery. Laboratory data were collected on hemoglobin, albumin, calcium, phosphorus, and creatinine levels at the time of patient enrolment and three months later in both patient groups. | PMC10122383 |
Sample preparation for proteomic analysis | To remove high-abundance proteins, 30 µL of plasma samples were diluted 1:4 with multiple affinity removal system (MARS) buffer A (Agilent Technologies, Santa Clara, CA, USA) and filtered with 0.22 μm Spin-X filters (Corning Costar, NY, USA). Individual plasma samples were depleted of six high-abundance human plasma proteins [albumin, Immunoglobulin (Ig) G, IgA, transferrin, haptoglobin, and antitrypsin) using a MARS column (Hu-6HC, 4.6 × 100 mm, Agilent Technologies, Santa Clara, CA, USA) on an Agilent 1260 HPLC system. Depleted plasma samples were concentrated by centrifugal filtration using a 3 kDa Amicon filter (Millipore, Burlington, MA, USA). Protein concentration was measured using the Bicinchoninic acid (BCA) assay.For protein digestion, 100 µg of each sample was precipitated by adding a 5-fold volume of ice-cold acetone prior to digestion. The dried samples were reconstituted in 50 µL of SDT buffer (2% sodium dodecyl sulphate, 0.1 M dithiothreitol in 0.1 M Tris HCl pH 8.0). The denatured proteins were heated at 95 °C, and subsequently digested using a filter-aided sample preparation (FASP) method, as previously described [ | PMC10122383 | ||
Liquid chromatography with tandem mass spectrometry analysis | Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) analysis was performed using quadrupole Orbitrap mass spectrometers, Q-exactive plus (Thermo Fisher Scientific, Waltham, MA, USA), coupled to an Ultimate 3000 RSLC system (Dionex, Sunnyvale, CA, USA) with a nano-electrospray source as previously described, with some modifications [ | PMC10122383 | ||
Proteomic data processing | To generate spectral libraries, 24 data dependent acquisition (DDA) measurements were performed on the urine samples. DDA spectra were searched using MaxQuant against the UniProt Human Database (December 2014, 88,657 entries) and the indexed retention time standard peptide sequence. A spectral library was generated using the spectral library generation feature from Spectronaut 10 (Biognosys, Schlieren-Zurich, Switzerland) and DIA data from individual samples were analyzed. First, the DIA raw files were converted into HTRMS format using the GTRMS converter tool provided by Spectronaut. The false discovery rate (FDR) was estimated using the mProphe [ | PMC10122383 | ||
Statistical analyses of proteomics data | Statistical analyses of the DIA data were performed using Perseus software [ | PMC10122383 | ||
Bioinformatics analysis | Functional gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEPs were performed using the DAVID bioinformatics tool ( | PMC10122383 | ||
Enzyme linked immunosorbent assay (ELISA) for the validation of proteomic data | MMP-9 (cat. no. MBS2880173), ACVR1B (cat. no. MBS7232818), and FETUB (cat. no. MBS454400) concentrations in the plasma samples were measured according to the manufacturer’s specifications using MyBioSource ELISA kits. The minimum levels of detection were as follows: WFDC3, 3.12 ng/mL; FGFR1, 0.094 ng/mL; MMP-9, 0.056 ng/mL, ACVR1B, 0.5 ng/mL, FETUB, 0.04125 ng/mL. | PMC10122383 | ||
Statistical analysis | Categorical variables were recorded as numbers and percentages, and continuous variables were presented as mean ± standard variation or median. The χ | PMC10122383 | ||
Results | PMC10122383 | |||
Baseline laboratory findings of included patients | Clinical characteristics and laboratory data are shown in Table
Baseline characteristics of study participantsData are presented as number of patients (%) or mean ± standard variationBMI, body mass index; HD, hemodialysis; URR, urea reduction ratio | PMC10122383 | ||
Effects of exercise on laboratory finding and physical performance | The results of laboratory findings and physical performance tests at baseline and three months follow-up exercise were compared using a paired t-test. In the exercise group, the change in serum creatinine levels (9.8 ± 2.4 vs. 9.8 ± 2.6 mg/dL,
3-months changes of laboratory outcomes and physical function for participantsCr(mg/dL)Albumin(g/dL)Grip strength(kg)Walking speed(m/s)Data are presented as mean ± standard variationCr, creatinine | PMC10122383 | ||
Protein functional annotation and enrichment analysis | PROLIFERATION, ADHESION | In the KEGG pathway analysis of DEPs, the significantly enriched proteins were those associated with processes, such as complement and coagulation cascades, extracellular matrix-receptor interactions, phagocytosis, cell adhesion, and protein digestion and absorption. The top 24 KEGG pathways are shown in Fig.
Plasma proteins that differentially expressed in before exercise and after 3 months exercise (In the enrichment analysis for DEPs using GO pathway analysis (Fig. The PPI network map showed that these proteins were involved in various biological processes such as neutrophil aggregation, regulation of membrane attack complex activation, regulation of chondrocyte proliferation, very-low-density lipoprotein particle clearance, and leukocyte aggregation and molecular functions, such as Toll-like receptor 4 binding, antioxidant activity, integrin binding, glycosaminoglycan binding, and sulfur compound binding (Fig.
The KEGG pathway and GO analysis of significantly expressed proteins. The vertical axis represents the pathway category and the horizontal axis represents the enrichment score [− log(P-value)] of the pathway. Significantly enriched pathways (P < 0.05) are presented. The data were analyzed by DAVID bioinformatics tools. ( | PMC10122383 | |
Proteomics-based protein identification and quantification | To analyze the protein expression in the 16 patients before and after three months of exercise, DIA was performed by analyzing the samples in a randomized order. Finally, 433 proteins (200 upregulated and 233 downregulated, Fig.
The protein–protein interaction network analysis was performed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software. The nodes reflect individual proteins enriched in the analysis, and the edges are the functional associations based on various online resources. (The plasma proteome profiles before and after exercise were compared, to determine significant differences in plasma protein expression, reflecting a significant effect of exercise in these patients. Paired t-test was performed to identify significantly DEPs between two intervals of three months of exercise. We found 60 significantly expressed proteins with a | PMC10122383 | ||
Validation of proteomics data for selected proteins by ELISA | CKD | Among the top 10 proteins that were significantly expressed and significantly enriched after exercise, MMP-9, ACVR1B, and FETUB were selected for the validation of proteomic data obtained using ELISA. The logThe baseline levels of MMP-9 and FETUB were higher in patients with CKD on dialysis than those in the healthy age-matched control group, and the expression level significantly decreased after exercise. In contrast, the level of ACVR1B was lower in patients on dialysis than that in healthy controls, and the level significantly increased from the baseline after three months of exercise (Fig.
Validation of proteomics results with ELISA. Age-matched healthy control, before exercise, and after 3 months exercise. *P < control vs. before exercise; **P < control vs. before exercise; ***P < before exercise vs. after exercise. Control, Age-matched healthy control; before, before exercise in dialysis patients; after, after 3 months exercise in dialysis patients | PMC10122383 | |
Discussion | CVDs, CKD, cancer, CVD, ESRD | CVD, CANCER, ESRD, INFLAMMATION | The present study investigated the effects of exercise training on protein expression in patients on hemodialysis by comparing the altered protein expression levels before and after the exercise intervention. The significantly enriched proteins were involved in the immune response on protein functional analysis. Some main proteins, which demonstrated significant changes, were also validated through ELISA. In addition, the protein expression levels of patients on dialysis were compared with those of a healthy age-matched control group, confirming the effect of exercise on improving the levels of these proteins.CKD is an independent risk factor for various adverse health issues, particularly CVDs. The age-adjusted mortality of CVD is much higher than the mortality of the general population, ranging approximately 15–30 times [Previous studies have reported a relationship between poor physical activity and high mortality in patients with CKD. Several trials have shown the effect of exercise on improving physical function and outcomes in patients with CKD. The largest randomized clinical trial conducted by Rossi et al. showed that 12-week/24-session renal rehabilitation exercise intervention improved the quality of life and physical function [Although studies investigating the effects of exercise on improving cardiovascular risk in patients with CKD are rare, some studies have reported beneficial cardiac outcomes observed in exercise interventions in this population [Recent studies have suggested that the immune system plays an important role in cardiac function and composition [Furthermore, previous studies have suggested that regular exercise could reduce pro-inflammatory cytokine secretion and even modulate the immune system, eventually reducing the risk of CVD and cancer [MMP-9 is secreted by different immune-related cells [The serum level of fetuin-B, the protein encoded by the Although studies investigating the effect of ACVR1B on CVD are scarce, it is known that ACVR1B belongs to the TGFT-b superfamily and contributes to the resolution of inflammation. In a gene analysis study, There are some limitations of the study that warrant discussion. First, the study population was small, and the duration of exercise intervention was relatively short. Further investigations involving a larger number of patients over a longer period of exercise intervention are needed to prove the immune response-related beneficial effects of exercise. Second, we could not analyze the protein expressions of the healthy age-matched control group. However, we strengthened the results by confirmation using ELISA validation with this control group. In addition, we could not investigate the direct correlation between improvement in physical function and the levels of expressed proteins. As no previous studies have investigated changes in protein levels after exercise using proteomic profiling, the present study, which evaluated the effect of exercise by analyzing molecular level changes using a high-confidence proteomic method, would be meaningful. We also used functional analysis to confirm the potential role of the significantly changed proteins and strengthened the results by confirmation using ELISA analysis.In conclusion, exercise in dialysis-dependent patients with CKD could enhance physical activity, which is a modifiable factor associated with reducing cardiovascular risk and mortality in the study population. The proteomic profiling results of protein expression changes after exercise might imply that the immune response is associated with this change in these patients. To investigate the beneficial effects of exercise on improving the outcomes of patients with ESRD on dialysis, we need more studies with longer intervention periods and larger patient populations. | PMC10122383 |
Electronic supplementary material | Below is the link to the electronic supplementary material.
Supplementary Material 1
Supplementary Material 2
Supplementary Material 3
Supplementary Material 4 | PMC10122383 | ||
Author Contribution | H.Y.J. and H-J.A. were involved in study design. M.J.S. and M.H.H helped in data collection. Y.H.L., T.Y.Y. and D.H.Y. contributed to data analysis. S-Y.L., D.H, and H.Y.J. helped in drafting manuscript. All authors read and approved the final manuscript. | PMC10122383 | ||
Funding | So-Young Lee received National Research Foundation Grant of Korea (NRF-2022R1A2C2006713), funded by the Korean government ( | PMC10122383 | ||
Data Availability | The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. | PMC10122383 | ||
Declarations | PMC10122383 | |||
Ethics approval and consent to participate | BLOOD | Collection and use human blood were approved by the Institutional Review Board (IRB) of CHA medical university (IRB; Permit No. BD2015-07117-005). The study was conducted in accordance with the Declaration of Helsinki. Blood was collected from donors after obtaining their informed consent. | PMC10122383 | |
Consent for publication | Not applicable. | PMC10122383 | ||
Competing interests | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10122383 | ||
References | PMC10122383 | |||
1. Introduction | stroke, stress, cognitive impairments | EVENTS, STROKE, CORTEX | Mental stress has been associated with cardiovascular events and stroke, and has also been linked with poorer brain function, likely due to its impact on cerebral vasculature. During periods of stress, individuals often increase their consumption of unhealthy foods, especially high-fat foods. Both high-fat intake and mental stress are known to impair endothelial function, yet few studies have investigated the effects of fat consumption on cerebrovascular outcomes during periods of mental stress. Therefore, this study examined whether a high-fat breakfast prior to a mental stress task would alter cortical oxygenation and carotid blood flow in young healthy adults. In a randomised, counterbalanced, cross-over, postprandial intervention study, 21 healthy males and females ingested a high-fat (56.5 g fat) or a low-fat (11.4 g fat) breakfast 1.5 h before an 8-min mental stress task. Common carotid artery (CCA) diameter and blood flow were assessed at pre-meal baseline, 1 h 15 min post-meal at rest, and 10, 30, and 90 min following stress. Pre-frontal cortex (PFC) tissue oxygenation (near-infrared spectroscopy, NIRS) and cardiovascular activity were assessed post-meal at rest and during stress. Mental stress increased heart rate, systolic and diastolic blood pressure, and PFC tissue oxygenation. Importantly, the high-fat breakfast reduced the stress-induced increase in PFC tissue oxygenation, despite no differences in cardiovascular responses between high- and low-fat meals. Fat and stress had no effect on resting CCA blood flow, whilst CCA diameter increased following consumption of both meals. This is the first study to show that fat consumption may impair PFC perfusion during episodes of stress in young healthy adults. Given the prevalence of consuming high-fat foods during stressful periods, these findings have important implications for future research to explore the relationship between food choices and cerebral haemodynamics during mental stress.Episodes of acute stress have been shown to trigger cardiovascular events [Acute laboratory mental stress has been evidenced to increase cerebral blood velocity [The impact of acute stress on vascular function is often measured in the fasted state, yet during periods of stress, individuals are more likely to overeat and consume unhealthy foods, i.e., fat [However, few studies have investigated how fat consumption can influence cerebrovascular function. Initial rodent-based research presented cognitive impairments following a chronic high-fat diet [Given the high prevalence of consumption of high-fat foods during stressful periods [ | PMC10534483 |
2. Materials and Methods | PMC10534483 | |||
2.1. Participants | Healthy, young (age range inclusion: 18–45 years) participants ( | PMC10534483 | ||
2.2. Procedure | The present study was a cross-over intervention study, with two laboratory visits at least a week apart for males, and approximately a month apart for females. The order of dietary conditions was randomised and counterbalanced. Participants visited the lab at 08:00 h and were asked to refrain from food 12 h before, and from alcohol, vigorous exercise, and caffeine 24 h before each testing session. We also requested that participants followed a similar diet for 24 h prior to each visit. Pre-intervention peripheral vascular measurements were assessed (data reported elsewhere: [ | PMC10534483 | ||
2.3. Meal Interventions | Both meals were prepared just before consumption, and fresh ingredients were bought within 24 h of each session. The calorie-matched meals consisted of a high-fat meal (HFM, 56.5 g fat) and a low-fat meal (LFM, 11.4 g fat). Nutrients were closely matched, apart from carbohydrate quantity ( | PMC10534483 | ||
2.4. Mental Stress Task | The 8-min paced-auditory-serial-addition-task (PASAT) was used to induce mental stress, shown to have good test–retest reliability and to perturb the cardiovascular system [ | PMC10534483 |
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