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      Barriers and facilitators to the conduct of critical care research in low and lower-middle income countries: A scoping review

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          Abstract

          Background

          Improvements in health-related outcomes for critically ill adults in low and lower-middle income countries need systematic investments in research capacity and infrastructure. High-quality research has been shown to strengthen health systems; yet, research contributions from these regions remain negligible or absent. We undertook a scoping review to describe barriers and facilitators for the conduct of critical care research.

          Methods

          We searched MEDLINE and EMBASE up to December 2021 using a strategy that combined keyword and controlled vocabulary terms. We included original studies that reported on barriers or facilitators to the conduct of critical care research in these settings. Two reviewers independently reviewed titles and abstracts, and where necessary, the full-text to select eligible studies. For each study, reviewers independently extracted data using a standardized data extraction form. Barriers and facilitators were classified along the lines of a previous review and based on additional themes that emerged. Study quality was assessed using appropriate tools.

          Results

          We identified 2693 citations, evaluated 49 studies and identified 6 for inclusion. Of the included studies, four were qualitative, one was a cross-sectional survey and one was reported as an ‘analysis’. The total number of participants ranged from 20–100 and included physicians, nurses, allied healthcare workers and researchers. Barriers identified included limited funding, poor institutional & national investment, inadequate access to mentors, absence of training in research methods, limited research support staff, and absence of statistical support. Our review identified potential solutions such as developing a mentorship network, streamlining of regulatory processes, implementing a centralized institutional research agenda, developing a core-outcome dataset and enhancing access to low-cost technology.

          Conclusion

          Our scoping review highlights important barriers to the conduct of critical care research in low and lower-middle income countries, identifies potential solutions, and informs researchers, policymakers and governments on the steps necessary for strengthening research systems.

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          Most cited references33

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          PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation

          Scoping reviews, a type of knowledge synthesis, follow a systematic approach to map evidence on a topic and identify main concepts, theories, sources, and knowledge gaps. Although more scoping reviews are being done, their methodological and reporting quality need improvement. This document presents the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist and explanation. The checklist was developed by a 24-member expert panel and 2 research leads following published guidance from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. The final checklist contains 20 essential reporting items and 2 optional items. The authors provide a rationale and an example of good reporting for each item. The intent of the PRISMA-ScR is to help readers (including researchers, publishers, commissioners, policymakers, health care providers, guideline developers, and patients or consumers) develop a greater understanding of relevant terminology, core concepts, and key items to report for scoping reviews.
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            Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results

            Abstract Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)
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              Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit.

              Global epidemiological data regarding outcomes for patients in intensive care units (ICUs) are scarce, but are important in understanding the worldwide burden of critical illness. We, therefore, did an international audit of ICU patients worldwide and assessed variations between hospitals and countries in terms of ICU mortality. 730 participating centres in 84 countries prospectively collected data on all adult (>16 years) patients admitted to their ICU between May 8 and May 18, 2012, except those admitted for fewer than 24 h for routine postoperative monitoring. Participation was voluntary. Data were collected daily for a maximum of 28 days in the ICU and patients were followed up for outcome data until death or hospital discharge. In-hospital death was analysed using multilevel logistic regression with three levels: patient, hospital, and country. 10,069 patients were included from ICUs in Europe (5445 patients; 54·1%), Asia (1928; 19·2%), the Americas (1723; 17·1%), Oceania (439; 4·4%), the Middle East (393; 3·9%), and Africa (141; 1·4%). Overall, 2973 patients (29·5%) had sepsis on admission or during the ICU stay. ICU mortality rates were 16·2% (95% CI 15·5-16·9) across the whole population and 25·8% (24·2-27·4) in patients with sepsis. Hospital mortality rates were 22·4% (21·6-23·2) in the whole population and 35·3% (33·5-37·1) in patients with sepsis. Using a multilevel analysis, the unconditional model suggested significant between-country variations (var=0·19, p=0·002) and between-hospital variations (var=0·43, p<0·0001) in the individual risk of in-hospital death. There was a stepwise increase in the adjusted risk of in-hospital death according to decrease in global national income. This large database highlights that sepsis remains a major health problem worldwide, associated with high mortality rates in all countries. Our findings also show a significant association between the risk of death and the global national income and suggest that ICU organisation has an important effect on risk of death. None. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – review & editing
                Role: InvestigationRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 May 2022
                2022
                : 17
                : 5
                : e0266836
                Affiliations
                [1 ] Department of Critical Care Medicine, Apollo Hospitals, Chennai, India
                [2 ] Department of Pulmonary and Critical Care Medicine, Einstein Health Network, Philadelphia, Pennsylvania, United States of America
                [3 ] Mahidol-Oxford Tropical Research Unit, Bangkok, Thailand
                [4 ] Department of Anaesthesia and Critical Care Medicine, University College London, London, United Kingdom
                [5 ] Usher Institute, University of Edinburgh, Edinburgh, United Kingdom
                [6 ] Department of Medical Informatics, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
                [7 ] Interdepartmental Division of Critical Care Medicine, Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
                Stellenbosch University, SOUTH AFRICA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-1801-0667
                https://orcid.org/0000-0003-2707-2779
                https://orcid.org/0000-0002-6651-1730
                https://orcid.org/0000-0003-4038-5382
                Article
                PONE-D-21-24699
                10.1371/journal.pone.0266836
                9071139
                35511911
                228d61ae-f9c8-438e-ae7d-b437f4c4dfde
                © 2022 Tirupakuzhi Vijayaraghavan et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 July 2021
                : 28 March 2022
                Page count
                Figures: 1, Tables: 3, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100004440, wellcome trust;
                Award ID: 215522
                Award Recipient :
                Authors RH and AB were co-applicants on the grant. Wellcome Trust, U.K. (grant number WT215522/Z19/Z). https://wellcome.org/ The funder had no role in the design, conduct, analysis of this scoping review or in the decision to submit for publication
                Categories
                Research Article
                Social Sciences
                Economics
                Economic Geography
                Low and Middle Income Countries
                Earth Sciences
                Geography
                Economic Geography
                Low and Middle Income Countries
                Research and Analysis Methods
                Research Design
                Science Policy
                Science and Technology Workforce
                Careers in Research
                Research and Analysis Methods
                Database and Informatics Methods
                Database Searching
                Medicine and Health Sciences
                Health Care
                Socioeconomic Aspects of Health
                Medicine and Health Sciences
                Public and Occupational Health
                Socioeconomic Aspects of Health
                Science Policy
                Research Funding
                Government Funding of Science
                Medicine and Health Sciences
                Research and Analysis Methods
                Research Design
                Qualitative Studies
                Custom metadata
                All data are available in the manuscript file and the supplementary files.

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