Search

Problem: Many national child health guidelines in Malawi, Nigeria and South Africa are outdated and score poorly on rigorous methods and stakeholder participation., Approach: In line with the World Health Organization's (WHO) emphasis on local guideline contextualization, the Global Evidence-Local Adaptation (GELA) project supported multistakeholder processes to adapt evidence-informed recommendations for child health in Malawi, Nigeria and South Africa. The GELA project team convened national steering groups, which conducted structured, iterative priority-setting exercises to identify priority topics. We identified appropriate source guidelines by systematically searching and screening available guidelines. We then matched recommendations in potential source guidelines to the relevant questions, and assessed the guidelines for timeliness and quality. Drawing on WHO's guideline process, we applied the GRADE-ADOLOPMENT process to develop contextualized recommendations from existing guidelines. If no source guideline or reviews were identified, we conducted new evidence syntheses., Local Setting: Malawi, Nigeria and South Africa are countries with varying health priorities and systems, all transitioning to universal health coverage. Guideline structures differ between countries, with processes largely led from national health ministries., Relevant Changes: National guideline groups, supported by GELA researchers and government-academic partners, developed five contextually-tailored child health recommendations. For most of these recommendations, additional evidence was required to inform contextually appropriate national decision-making. Formal capacity-building and on-the-job learning enhanced the competencies of national contributors and researchers in evidence-informed decision-making., Lessons Learnt: Developing context-relevant recommendations requires considerable resources and time. Further investment in strengthening local capacity is needed for sustainable national guideline development., ((c) 2024 The authors; licensee World Health Organization.)

Background and Objective: The Grading of Recommendations, Assessment, Development and Evaluations (GRADE)-ADOLOPMENT methodology has been widely used to adopt, adapt, or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. The objective of this guidance is to refine the operationalization for applying GRADE-ADOLOPMENT., Methods: Through iterative discussions, online meetings, and email communications, the GRADE-ADOLOPMENT project group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE working group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people), and twice in September 2023 (approximately 60 and 90 people) for approval., Results: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by doing the following: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing evidence-to-decision (EtDs), when available or developing new EtDs, if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others., Conclusion: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over 6 years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources., Competing Interests: Declaration of competing interest The authors are members or contributors to the GRADE working group. Zachary Munn is supported by an NHMRC investigator grant APP 1195676. Alexander G. Mathioudakis was supported by the National Institute for Health and Care Research Manchester Biomedical Research Centre (NIHR Manchester BRC, NIHR203308) and by an NIHR Clinical Lectureship in Respiratory Medicine. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: COVID-19 showed that countries must strengthen their operational readiness (OPR) capabilities to respond to an imminent pandemic threat rapidly and proactively. We conducted a rapid scoping evidence review to understand the definition and critical elements of OPR against five core sub-systems of a new framework to strengthen the global architecture for Health Emergency Preparedness Response and Resilience (HEPR)., Methods: We searched MEDLINE, Embase, and Web of Science, targeted repositories, websites, and grey literature databases for publications between 1 January 2010 and 29 September 2021 in English, German, French or Afrikaans. Included sources were of any study design, reporting OPR, defined as immediate actions taken in the presence of an imminent threat, from groups who led or responded to a specified health emergency. We used prespecified and tested methods to screen and select sources, extract data, assess credibility and analyse results against the HEPR framework., Results: Of 7005 sources reviewed, 79 met the eligibility criteria, including 54 peer-reviewed publications. The majority were descriptive reports (28%) and qualitative analyses (30%) from early stages of the COVID-19 pandemic. Definitions of OPR varied while nine articles explicitly used the term 'readiness', others classified OPR as part of preparedness or response. Applying our working OPR definition across all sources, we identified OPR actions within all five HEPR subsystems. These included resource prepositioning for early detection, data sharing, tailored communication and interventions, augmented staffing, timely supply procurement, availability and strategic dissemination of medical countermeasures, leadership, comprehensive risk assessment and resource allocation supported by relevant legislation. We identified gaps related to OPR for research and technology-enabled manufacturing platforms., Conclusions: OPR is in an early stage of adoption. Establishing a consistent and explicit framework for OPRs within the context of existing global legal and policy frameworks can foster coherence and guide evidence-based policy and practice improvements in health emergency management., Competing Interests: Competing interests: None declared., (© World Health Organization 2024. Licensee BMJ.)

Background: Poverty-related diseases (PRD) remain amongst the leading causes of death in children under-5 years in sub-Saharan Africa (SSA). Clinical practice guidelines (CPGs) based on the best available evidence are key to strengthening health systems and helping to enhance equitable health access for children under five. However, the CPG development process is complex and resource-intensive, with substantial scope for improving the process in SSA, which is the goal of the Global Evidence, Local Adaptation (GELA) project. The impact of research on PRD will be maximized through enhancing researchers and decision makers' capacity to use global research to develop locally relevant CPGs in the field of newborn and child health. The project will be implemented in three SSA countries, Malawi, South Africa and Nigeria, over a 3-year period. This research protocol is for the monitoring and evaluation work package of the project. The aim of this work package is to monitor the various GELA project activities and evaluate the influence these may have on evidence-informed decision-making and guideline adaptation capacities and processes. The specific project activities we will monitor include (1) our ongoing engagement with local stakeholders, (2) their capacity needs and development, (3) their understanding and use of evidence from reviews of qualitative research and, (4) their overall views and experiences of the project., Methods: We will use a longitudinal, mixed-methods study design, informed by an overarching project Theory of Change. A series of interconnected qualitative and quantitative data collections methods will be used, including knowledge translation tracking sheets and case studies, capacity assessment online surveys, user testing and in-depth interviews, and non-participant observations of project activities. Participants will comprise of project staff, members of the CPG panels and steering committees in Malawi, South Africa and Nigeria, as well as other local stakeholders in these three African countries., Discussion: Ongoing monitoring and evaluation will help ensure the relationship between researchers and stakeholders is supported from the project start. This can facilitate achievement of common goals and enable researchers in South Africa, Malawi and Nigeria to make adjustments to project activities to maximize stakeholder engagement and research utilization. Ethical approval has been provided by South African Medical Research Council Human Research Ethics Committee (EC015-7/2022); The College of Medicine Research and Ethics Committee, Malawi (P.07/22/3687); National Health Research Ethics Committee of Nigeria (01/01/2007)., (© 2024. The Author(s).)

Background: South Africa has a high HIV incidence and oral pre-exposure prophylaxis (PrEP) is available as public-sector standard of care. Access to alternative prevention methods for women may further reduce HIV acquisition., Setting: South African public sector., Methods: We performed a systematic search for high-quality up-to-date guidelines recommending dapivirine rings as PrEP using the Grading of Recommendations Assessment, Development, and Evaluation -Adolopment process. We appraised the systematic review and randomized controlled trial (RCT) evidence underpinning the selected guideline's recommendations and conducted a cost-effectiveness analysis. The Grading of Recommendations Assessment, Development, and Evaluation evidence-to-decision framework guided the adaptation of source guideline recommendations, according to our local context., Results: We identified the 2021 World Health Organization PrEP Guidelines, informed by 2 placebo-controlled RCTs, which were included in a contemporaneous systematic review. There were 23 fewer HIV acquisitions per 1000 clients with dapivirine ring vs placebo (95% confidence interval: 10 to 34), with no increase in adverse events (moderate certainty evidence). We found no RCTs comparing dapivirine to oral PrEP or among adolescent/pregnant/breastfeeding clients. Dapivirine is less cost-effective than oral PrEP at $14.59/ring, at the current price., Conclusions: The source guideline recommendation was adapted for the local context. Dapivirine ring seems to be less efficacious than oral PrEP, although comparative studies are lacking. Data on adolescents and pregnancy are also lacking, currently limiting the use of dapivirine as an alternative for women unable to take oral PrEP. At the current price, dapivirine is not cost-effective and unaffordable for inclusion in the South African Essential Medicines List., Competing Interests: H.D. was an investigator of the HPTN077 trial. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Professional nurses provide self-management support to adults (18 years and older) living with tuberculosis (TB) and human immunodeficiency virus (HIV) coinfection to enable them to mitigate its impact on their lives. However, the experiences of professional nurses providing self-management support to adults with TB-HIV coinfection remain unclear., Aim: This study explored and described the experiences of professional nurses on the provision of self-management support to adults living with TB-HIV coinfection in Greater Accra, Ghana., Setting: Three public primary health facilities in Greater Accra, Ghana., Methods: An exploratory, descriptive qualitative design was used. Twenty-two purposively sampled professional nurses were interviewed face-to-face individually using an interview guide. Interviews were recorded with participants' permission, transcribed and analysed thematically using MAXQDA software., Results: The three themes generated revealed that the: (1) self-management problems of adults living with TB-HIV coinfection included their recurring physical, mental and social problems, (2) the support provided to adults with TB-HIV coinfection included symptom, nutritional, medication and psychosocial self-management support, (3) the factors related to providing self-management support showed that self-management support was influenced by patient, nurse and health facility-related factors but was feasible, equitable and acceptable to patients and stakeholders., Conclusion: Professional nurses' self-management support practice entailed improvising limited resources to address the recurring problems of adults living with TB-HIV coinfection. Nurses require adequate resources to provide comprehensive self-management support., Contribution: The contextual evidence provides insight into the self-management problems of adults with TB-HIV coinfection and the factors influencing professional nurses' self-management support., Competing Interests: The author(s) declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Background: Sub-Saharan Africa is the region with the highest under-five mortality rate globally. Child healthcare decisions should be based on rigorously developed evidence-informed guidelines. The Global Evidence, Local Adaptation (GELA) project is enhancing capacity to use global research to develop locally relevant guidelines for newborn and child health in South Africa (SA), Malawi, and Nigeria. The first step in this process was to identify national priorities for newborn and child health guideline development, and this paper describes our approach., Methods: We followed a good practice method for priority setting, including stakeholder engagement, online priority setting surveys and consensus meetings, conducted separately in South Africa, Malawi and Nigeria. We established national Steering Groups (SG), comprising 10-13 members representing government, academia, and other stakeholders, identified through existing contacts and references, who helped prioritise initial topics identified by research teams and oversaw the process. Various stakeholders were consulted via online surveys to rate the importance of topics, with results informing consensus meetings with SGs where final priority topics were agreed., Results: Based on survey results, nine, 10 and 11 topics were identified in SA, Malawi, and Nigeria respectively, which informed consensus meetings. Through voting and discussion within meetings, and further engagement after the meetings, the top three priority topics were identified in each country. In SA, the topics concerned anemia prevention in infants and young children and post-discharge support for caregivers of preterm and LBW babies. In Malawi, they focused on enteral nutrition in critically ill children, diagnosis of childhood cancers in the community, and caring for neonates. In Nigeria, the topics focused on identifying pre-eclampsia in the community, hand hygiene compliance to prevent infections, and enteral nutrition for LBW and preterm infants., Conclusions: Through dynamic and iterative stakeholder engagement, we identified three priority topics for guideline development on newborn and child health in SA, Malawi and Nigeria. Topics were specific to contexts, with no overlap, which highlights the importance of contextualised priority setting as well as of the relationships with key decisionmakers who help define the priorities., (© 2024. The Author(s).)

Background: Low and middle-income countries remain disproportionately affected by high rates of child mortality. Clinical practice guidelines are essential clinical tools supporting implementation of effective, safe, and cost-effective healthcare. High-quality evidence-based guidelines play a key role in improving clinical management to impact child mortality. We aimed to identify and assess the quality of guidelines for newborn and child health published in South Africa, Nigeria and Malawi in the last 5 years (2017-2022)., Methods: We searched relevant websites (June-July 2022), for publicly available national and subnational de novo or adapted guidelines, addressing newborn and child health in the three countries. Pairs of reviewers independently extracted information from eligible guidelines (scope, topic, target population and users, responsible developers, stakeholder consultation process, adaptation description, assessment of evidence certainty). We appraised guideline quality using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument., Results: We identified 40-guidelines from the three countries. Of these, 8/40 reported being adopted from a parent guideline. More guidelines (n = 19) provided guidance on communicable diseases than on non-communicable diseases (n = 8). Guidelines were most often developed by national health ministries (n = 30) and professional societies (n = 14). Eighteen guidelines reported on stakeholder consultation; with Nigeria (10/11) and Malawi (3/6) faring better than South Africa (5/23) in reporting this activity. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used in 1/7 guidelines that reported assessing certainty of evidence. Overall guidelines scored well on two AGREE II domains: scope and purpose median (IQR) score 68% (IQR 47-83), and clarity of presentation 81% (67-94). Domains critical for ensuring credible guidance scored below 20%: rigour of development 11% (4-32) and editorial independence 6% (0-27)., Conclusion: National ministries and professional societies drive guideline activities in Malawi, Nigeria and South Arica. However, the methods and reporting do not adhere to global standards. We found low AGREE II scores for rigour of guideline development and editorial independence and limited use of GRADE or adaptation methods. This undermines the credibility of available guidelines to support evidence-informed care. Our findings highlight the importance of ongoing efforts to strengthen partnerships, capacity, and support for guideline development., (© 2024. The Author(s).)

Objectives: Guidelines and essential medicine lists (EMLs) bear similarities and differences in the process that lead to decisions. Access to essential medicines is central to achieve universal health coverage. The World Health Organization (WHO) EML has guided prioritization of essential medicines globally for nearly 50 years, and national EMLs (NEMLs) exist in over 130 countries. Guideline and EML decisions, at WHO or national levels, are not always coordinated and aligned. We sought to explore challenges, and potential solutions, for decision-making to support trustworthy medicine selection for EMLs from a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group perspective. We primarily focus on the WHO EML; however, our findings may be applicable to NEML decisions as well., Study Design and Setting: We identified key challenges in connecting the EML to health guidelines by involving a broad group of stakeholders and assessing case studies including real applications to the WHO EML, South Africa NEML, and a multiple sclerosis guideline connected to a WHO EML application for multiple sclerosis treatments. To address challenges, we utilized the results of a survey and feedback from the stakeholders, and iteratively met as a project group. We drafted a conceptual framework of challenges and potential solutions. We presented a summary of the results for feedback to all attendees of the GRADE Working Group meetings in November 2022 (approximately 120 people) and in May 2023 (approximately 100 people) before finalizing the framework., Results: We prioritized issues and insights/solutions that addressed the connections between the EML and health guidelines. Our suggested solutions include early planning alignment of guideline groups and EMLs, considering shared participation to strengthen linkage, further clarity on price/cost considerations, and using explicit shared criteria to make guideline and EML decisions. We also provide recommendations to strengthen the connection between WHO EML and NEMLs including through contextualization methods., Conclusion: This GRADE concept article, jointly developed by key stakeholders from the guidelines and EMLs field, identified key conceptual issues and potential solutions to support the continued advancement of trustworthy EMLs. Adopting structured decision criteria that can be linked to guideline recommendations bears the potential to advance health equity and gaps in availability of essential medicines within and between countries., Competing Interests: Declaration of competing interest Tamara Kredo is a member of the South African National Essential Medicines List Committee and Standard Treatment Guidelines; Co-lead of South African GRADE Network; Cochrane Board member; Member of the National Advisory Group on Immunisation. Trudy Leong is a member of the SA GRADE Network. Michael McCaul is a Member of the South African Primary Health Care and Adult Hospital Level Expert Review Committee; Founding member of the SA GRADE Network. The remaining authors are all members of the GRADE Working Group, however, have no other interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: The global research response to the COVID-19 pandemic was impressive, but also led to an infodemic and considerable research waste. Registered, but unpublished trials added to this noise. We aimed to determine the proportion of registered randomised trials of common COVID-19 treatments that were published and to describe the characteristics of these trials to examine the association between trial characteristics, publication status and research waste., Methods: This meta-epidemiological cohort study used a sample of randomised trials of corticosteroids, hydroxychloroquine or vitamin D as treatments for COVID-19, registered between 1 November 2019 and 31 December 2021 and available via the WHO ICTRP portal. We searched for the trials' published results up to 20 October 2022. We extracted the trial characteristics, analysing with descriptive statistics. We performed univariate logistic regression to examine the association between trials' characteristics and publication status, followed by multiple logistic regression using significant characteristics to assess the association between trial characteristics and publication status., Results: We identified 357 eligible trials on ICTRP. Of these, 107 (30%) had published or made their results available publicly by 20 October 2022, while 250 (70%) had not been published or shared their results publicly. Multiple logistic regression analysis showed that a larger target sample size was a significant positive predictor of publication with target sample sizes above 300 almost tripling the odds of publication (aOR: 2.75, 95% CI: 1.35 to 5.62)., Conclusions: Less than one third of registered trials made their results public and our findings identified that many trialists had not updated their trial registry entry with the trial status, results or both. Failure to share trial results publicly is a disservice to patients, clinicians and policy makers and adds to research waste., (© 2024. The Author(s).)

Abstract: "Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR: 1.56, 95% confidence interval [95% CI] [1.13-2.15]) and reducing (HR: 1.35, 95% CI [1.13-1.62]) drinking frequency, as well as reducing HED frequency (HR: 1.58, 95% CI [1.20-2.09]) versus robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control., (Copyright © 2024 Association of Nurses in AIDS Care.)

Background and Objective: Clinical practice guidelines (CPGs) are evaluated for quality with the Appraisal of Guidelines for Research and Evaluation (AGREE) tool, and this is increasingly done for different countries and regional groupings. This scoping review aimed to describe, map, and compare these geographical synthesis studies, that assessed CPG quality using the AGREE tool. This allowed a global interpretation of the current landscape of these country-wide or regional synthesis studies, and a closer look at its methodology and results., Study Design and Methods: A scoping review was conducted searching databases Medline, Embase, Epistemonikos, and grey literature on 5 October 2021 for synthesis studies using the later versions of AGREE (AGREE II, AGREE-REX and AGREE GRS) to evaluate country-wide or regional CPG quality. Country-wide or regional synthesis studies were the units of analysis, and simple descriptive statistics was used to conduct the analysis. AGREE scores were analysed across subgroups into one of the seven Sustainable Development Goal regions, to allow for meaningful interpretation., Results: Fifty-seven studies fulfilled our eligibility criteria, which had included a total of 2918 CPGs. Regions of the Global North, and Eastern and South-Eastern Asia were most represented. Studies were consistent in reporting and presenting their AGREE domain and overall results, but only 18% (n = 10) reported development methods, and 19% (n = 11) reported use of Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Overall scores for domains Rigor of development and Editorial independence were low, notably in middle-income countries. Editorial Independence scores, especially, were low across all regions with a maximum domain score of 46%. There were no studies from low-income countries., Conclusion: There is an increasing tendency to appraise country-wide and regionally grouped CPGs, using quality appraisal tools. The AGREE tool, evaluated in this scoping review, was used well and consistently across studies. Findings of low report rates of development of CPGs and of use of GRADE is concerning, as is low domain scores globally for Editorial Independence. Transparent reporting of funding and competing interests, as well as highlighting evidence-to-decision processes, should assist in further improving CPG quality as clinicians are in dire need of high-quality guidelines., (© 2023. The Author(s).)

Background: Tobacco smoking increases frailty risk among the general population and is common among people with HIV (PWH) who experience higher rates of frailty at younger ages than the general population., Methods: We identified 8608 PWH across 6 Centers for AIDS Research Network of Integrated Clinical Systems sites who completed ≥2 patient-reported outcome assessments, including a frailty phenotype measuring unintentional weight loss, poor mobility, fatigue, and inactivity, and scored 0-4. Smoking was measured as baseline pack-years and time-updated never, former, or current use with cigarettes/day. We used Cox models to associate smoking with risk of incident frailty (score ≥3) and deterioration (frailty score increase by ≥2 points), adjusted for demographics, antiretroviral medication, and time-updated CD4 count., Results: The mean follow-up of PWH was 5.3 years (median: 5.0), the mean age at baseline was 45 years, 15% were female, and 52% were non-White. At baseline, 60% reported current or former smoking. Current (HR: 1.79; 95% confidence interval: 1.54 to 2.08) and former (HR: 1.31; 95% confidence interval: 1.12 to 1.53) smoking were associated with higher incident frailty risk, as were higher pack-years. Current smoking (among younger PWH) and pack-years, but not former smoking, were associated with higher risk of deterioration., Conclusions: Among PWH, smoking status and duration are associated with incident and worsening frailty., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adults with tuberculosis-human immunodeficiency virus coinfection require professional nurses' support to manage their illness, treatment and its effect on their daily lives. This scoping review maps recommendations in clinical or best practice guidelines that guide professional nurses to provide self-management support to adults with tuberculosis-human immunodeficiency virus coinfection in primary healthcare settings., Methods: We conducted a scoping review by searching for guidelines in six online databases, guideline clearing houses and search engines from 16th April 2022 to 25th May 2022. The title, abstract and full-text screening of guidelines were conducted independently and in duplicate by two reviewers based on predetermined eligibility criteria. The guidelines were critically appraised with the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument. Relevant data regarding the characteristics of the guideline, recommendations and underlying evidence were extracted, analysed and reported., Results: The six guidelines on self-management support found were developed in four high-income countries. Five of the guidelines recorded <60% across all six domains of the AGREE II instrument. One high-quality guideline scored >60% in all AGREE II domains but was informed by outdated evidence produced between 1977 to 2010. Twenty-five practice, education and organisational/policy recommendations were extracted from the high-quality guideline. The guidelines did not report evidence-to-decision frameworks and the strength of the recommendations. The guidelines also lacked direct underlying evidence on the effectiveness and cost of self-management support. Lastly, the review found a paucity of contextual (equity, acceptability and feasibility) evidence on self-management support among adults with tuberculosis-human immunodeficiency virus in the guidelines., Conclusion: There is a dearth of updated and relevant high-quality guidelines that guide healthcare professionals to provide self-management support to adults with tuberculosis-human immunodeficiency virus coinfection in primary healthcare settings. Systematic reviews of effectiveness, economic and contextual evidence related to self-management support interventions are required for guideline production., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tornu 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.)

Introduction: The global antiretroviral therapy era has led to a decline in the number of children newly acquiring HIV and an increase in the number of children who are HIV-exposed and uninfected (HEU). This shift has prompted extensive research focussing on health and survival outcomes of children who are HEU. Study findings, particularly in relation to adverse birth outcomes, have been disparate, inconclusive and have not always been generalisable. Thus, the objectives of this scoping review are (1) to identify and extract definitions used for the adverse birth outcome terms 'low birth weight', 'small for gestational age', 'stillbirth' and 'preterm birth'; (2) to compare the characteristics of studies from which birth outcome definitions were extracted by (a) temporal periods and (b) study country setting (high-income vs low-income and middle-income countries); (3) to use content analysis to map and describe the temporal and geographic distribution of the definitions used and construct a logical model of their evolution., Methods and Analysis: The online databases of PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library and CINHAL/EBSCOhost will be used to identify published and grey literature from 2011 to 2022 to identify definitions for the adverse birth outcome terms 'low birth weight', 'small for gestational age', 'stillbirth' and 'preterm birth'. A three-step process of (1) duplicate removal, (2) title and abstract screening and (3) full text screening will be used to select included studies. The extracted data will be used to conduct a comparative analysis, content analysis and construct a logic model., Ethics and Dissemination: This review will be used to inform a consensus process around the development of harmonised definitions for the specified adverse birth outcomes. Our dissemination plan includes presentations, publications as well as the development infographics and a resource hub. The study is approved by the Human Research Ethics Committee of Stellenbosch University., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Frailty is common among people with HIV (PWH), so we developed frail risk in the short-term for care (RISC)-HIV, a frailty prediction risk score for HIV clinical decision-making., Design: We followed PWH for up to 2 years to identify short-term predictors of becoming frail., Methods: We predicted frailty risk among PWH at seven HIV clinics across the United States. A modified self-reported Fried Phenotype captured frailty, including fatigue, weight loss, inactivity, and poor mobility. PWH without frailty were separated into training and validation sets and followed until becoming frail or 2 years. Bayesian Model Averaging (BMA) and five-fold-cross-validation Lasso regression selected predictors of frailty. Predictors were selected by BMA if they had a greater than 45% probability of being in the best model and by Lasso if they minimized mean squared error. We included age, sex, and variables selected by both BMA and Lasso in Frail RISC-HIV by associating incident frailty with each selected variable in Cox models. Frail RISC-HIV performance was assessed in the validation set by Harrell's C and lift plots., Results: Among 3170 PWH (training set), 7% developed frailty, whereas among 1510 PWH (validation set), 12% developed frailty. BMA and Lasso selected baseline frailty score, prescribed antidepressants, prescribed antiretroviral therapy, depressive symptomology, and current marijuana and illicit opioid use. Discrimination was acceptable in the validation set, with Harrell's C of 0.76 (95% confidence interval: 0.73-0.79) and sensitivity of 80% and specificity of 61% at a 5% frailty risk cutoff., Conclusions: Frail RISC-HIV is a simple, easily implemented tool to assist in classifying PWH at risk for frailty in clinics., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Globally, millions of people die and many more develop disabilities resulting from injuries each year. Most people who die from injuries do so before they are transported to hospital. Thus, reliable, pragmatic, and evidence-based prehospital guidance for various injuries is essential. We systematically mapped and described prehospital clinical practice guidelines (CPGs) for injuries in the global context, as well as prioritised injury topics for guidance development and adolopment., Methods: This study was sequentially conducted in three phases: a scoping review for CPGs (Phase I), identification and refinement of gaps in CPGs (Phase II), and ranking and prioritisation of gaps in CPGs (Phase III). For Phase I, we searched PubMed, SCOPUS, and Trip Database; guideline repositories and websites up to 23 rd May 2021. Two authors in duplicate independently screened titles and abstract, and full-text as well as extracted data of eligible CPGs. Guidelines had to meet 60% minimum methodological quality according to rigour of development domain in AGREE II. The second and third phases involved 17 participants from 9 African countries and 1 from Europe who participated in a virtual stakeholder engagement workshop held on 5 April 2022, and followed by an online ranking process., Results: Fifty-eight CPGs were included out of 3,427 guidance documents obtained and screened. 39/58 (67%) were developed de novo compared to 19 that were developed using alternative approaches. Twenty-five out of 58 guidelines (43%) were developed by bodies in countries within the WHO European Region, while only one guideline was targeted to the African context. Twenty-five (43%) CPGs targeted emergency medical service providers, while 13 (22%) targeted first aid providers (laypeople). Forty-three CPGs (74%) targeted people of all ages. The 58 guidance documents contained 32 injury topics. Injuries linked to road traffic accidents such as traumatic brain injuries and chest injuries were among the top prioritised topics for future guideline development by the workshop participants., Conclusion: This study highlights the availability, gaps and priority injury topics for future guideline development/adolopment, especially for the African context. Further research is needed to evaluate the recommendations in the 58 included CPGs for possible adaptation to the African context., (© 2023. The Author(s).)

Introduction: Much is known around public health preparedness and response phases. However, between the two phases is operational readiness that comprises the immediate actions needed to respond to a developing risk or hazard. Currently, emergency readiness is embedded in multiple frameworks and policy documents related to the health emergency cycle. However, knowledge about operational readiness' critical readiness components and actions required by countries to respond to public health eminent threat is not well known. Therefore, we aim to define and identify the critical elements of 'operational readiness' for public health emergencies, including COVID-19, and identify lessons learnt from addressing it, to inform the WHO Operational Readiness Framework., Methods and Analysis: This is a scoping review following the Joanna Briggs Institute guidance. Reporting will be according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist. MEDLINE, Embase and Web of Science databases and grey literature will be searched and exported into an online systematic review software (eg, Rayyan in this case) for review. The review team, which apart from scoping review methodological experts include content experts in health systems and public health and emergency medicine, prepared an a priori study protocol in consultation with WHO representatives. ATLAS.ti V.9 will be used to conduct thematic data analysis as well as store, organise and retrieve data. Data analysis and presentation will be carried out by five reviewers., Ethics and Dissemination: This review will reveal new insights, knowledge and lessons learnt that will translate into an operational framework for readiness actions. In consultation with WHO, findings will be disseminated as appropriate (eg, through professional bodies, conferences and research papers). No ethics approvals are required as no humans will be involved in data collection., Protocol Registration: This rapid scoping review has been registered on Open Science Framework (doi:10.17605/OSF.IO/6SYAH)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: The World Health Organization (WHO) recommends parasitological testing of all suspected malaria cases using malaria rapid diagnostic tests (mRDTs) or microscopy prior to treatment. Some governments have extended this responsibility to community health workers (CHWs) to reduce malaria morbidity and mortality through prompt and appropriate treatment. This is an update of a Cochrane Review first published in 2013., Objectives: To evaluate community-based management strategies for treating malaria or fever that incorporate both a definitive diagnosis with an mRDT and appropriate antimalarial treatment., Search Methods: We searched CENTRAL, MEDLINE, Embase, five other databases, and three trials registers up to 14 September 2021., Selection Criteria: We included individually randomized trials and cluster-randomized controlled trials (cRCTs), controlled before-after studies, and controlled interrupted time series studies in people living in malaria-endemic areas, comparing programmes that train CHWs and drug shop vendors to perform mRDTs and provide appropriate treatment versus similar programmes that do not use mRDTs, and versus routine health facility care., Data Collection and Analysis: We used standard Cochrane methods. For each dichotomous outcome, we extracted the number of participants with the event and the total number of participants in each group, unless studies presented results at a population level only. Primary outcomes were all-cause mortality, hospitalizations, and number of people receiving an antimalarial within 24 hours. Secondary outcomes were malaria-specific mortality, severe malaria, outcomes related to antimalarial treatments, antibiotic prescribing to people with a negative microscopy or polymerase chain reaction (PCR) result, parasitaemia, anaemia, and all adverse events., Main Results: We included eight studies from several African countries, Afghanistan, and Myanmar. Staff included CHWs and drug shop vendors.  Community use of malaria rapid diagnostic tests compared to clinical diagnosis Compared to clinical diagnosis, mRDT diagnosis results in reduced prescribing of antimalarials to people who are found to be malaria parasite-negative by microscopy or PCR testing (71 fewer per 100 people, 95% confidence interval (CI) 79 to 51 fewer; risk ratio (RR) 0.17, 95% CI 0.07 to 0.40; 3 cRCTs, 7877 participants; moderate-certainty evidence). This reduction may be greater among CHWs compared to drug shop vendors. People diagnosed by mRDT are more likely to receive appropriate treatment; that is, an antimalarial if they are microscopy- or PCR-positive and no antimalarial if they are microscopy- or PCR-negative (RR 3.04, 95% CI 2.46 to 3.74, 3 cRCTs, 9332 participants; high-certainty evidence). Three studies found that a small percentage of people with a negative mRDT result (as read by the CHW or drug shop vendors at the time of treatment) were nevertheless given an antimalarial: 38/1368 (2.8%), 44/724 (6.1%) and 124/950 (13.1%). Conversely, in two studies, a few mRDT-positive people did not receive an antimalarial (0.5% and 0.3%), and one small cross-over study found that 6/57 (10.5%) people classified as non-malaria in the clinical diagnosis arm received an antimalarial. Use of mRDTs probably increases antibiotic use compared to clinical diagnosis (13 more per 100 people, 95% CI 3 to 29 more; RR 2.02, 95% CI 1.21 to 3.37; 2 cRCTs, 5179 participants; moderate-certainty evidence). We were unable to demonstrate any effect on mortality. Community use of malaria rapid diagnostic tests compared to health facility care Results were insufficient to reach any conclusion., Authors' Conclusions: Use of mRDTs by CHWs and drug shop vendors compared to clinical diagnosis reduces prescribing of antimalarials to people without malaria. Deaths were uncommon in both groups. Antibiotic prescribing was higher in those with a negative mRDT than in those with a negative clinical diagnosis., (Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Introduction: Appropriate and efficient staffing is a cornerstone of emergency centre performance. There is however a paucity of literature describing clinician output in low- and middle-income countries with current staffing models based on anecdotal evidence. This study aimed to assess clinician output at a district level emergency centre, and how it varied depending on shift, clinician, and workload factors., Methods: We conducted a retrospective cross-sectional study using an existing electronic patient registry, to determine the patients consulted per hour (PPH) during each clinician shift and how this is affected by various clinician, shift, and workload factors. Data was collected over three non-contiguous randomly selected four-week cycles from Mitchells Plain Hospital's electronic patient registry. Associations between PPH and various factors were assessed using ANOVA with post-hoc adjustments where appropriate. The correlation between PPH and workload metrics was calculated with the Pearson's Rank correlation test. Statistical significance was defined as p<0.05., Results: A total of 1 289 clinician shifts were analysed with an overall PPH of 0.7. A significant association between PPH and shift type (p=0.021), clinician category (p<0.001) and cumulative shifts (p<0.001) were shown. There was a decline in clinician output during a shift and output was significantly decreased by the number of boarders in the emergency centre but increased with higher numbers of patients waiting at the start of the shift., Conclusion: This study describes a relatively low clinician output as compared to evidence from high-income countries and has highlighted several associations with various shift, clinician, and workload factors. The results from this study will form the basis of quality improvement interventions to improve patient throughput and will inform staff scheduling and surge planning strategies., Competing Interests: Both CH and MM are editors of the African Journal of Emergency Medicine. CH and MM were not involved in the editorial workflow for this manuscript. The African Journal of Emergency Medicine applies a double blinded process for all manuscript peer reviews. The authors declared no further conflicts of interest., (© 2022 The Authors. Published by Elsevier B.V. on behalf of African Federation for Emergency Medicine.)

Background: Carbon dioxide pneumoperitoneum during laparoscopy changes cardiorespiratory physiology and contributes to post-op pain. We studied outcomes before and after implementing low-pressure pneumoperitoneum QI project., Methods: Forty-two patients were insufflated at standard pressures (15 mmHg) while 41 were insufflated using low (8-12 mmHg) during laparoscopic procedures. These variables were obtained from the patient chart: pain scores, intravenous morphine milligram equivalents (MME), peak inspiratory pressures (PIP), end-tidal CO 2 (EtCO 2 ), surgery duration, and patient demographics. The study was conducted after IRB approval., Results: Low-pressure pneumoperitoneum is feasible and the surgeon can increase to 10-12 mmHg as needed. The mean post-op IV MME was significantly decreased in the low-pressure group (11.75 ± 10.41) compared to the standard pressure group (17.36 ± 18.1) (t-test, P = .047). Mean peak inspiratory pressures during insufflation were significantly higher for procedures conducted at standard pressure (31.40 ± 4.82) compared to the 8 mmHg (24.68 ± 4.19) and 12 mmHg (27.33± 3.85) low pressure groups (one-way ANOVA, P < .0001). During insufflation, there was a significant increase in the average EtCO 2 in the standard pressure group (42.07 ± 5.60) compared to the 8 mmHg low pressure group (37.59 ± 5.05) (ANOVA, P = .0096). Constant flow insufflation was more likely to be performed at low pressure than demand mode (58% v. 33%)., Conclusion: Low pressure pneumoperitoneum decreases PIP pressure and CO2 absorption evidenced by lower ETCO2 intra-operatively. Patients have significant improvement in postoperative pain evidenced by decreased narcotics needed. Low pressure pneumoperitoneum using a constant flow insufflator is safe and results in improved patient outcomes.

Background: The burden of diabetes mellitus (DM) and its associated complications continue to burgeon, particularly in low- and middle-income countries (LMICs). Lower limb amputation (LLA) is one of the most life-altering complications of DM, associated with significant morbidity, mortality and socio-economic impacts. High-income countries have reported a decreasing incidence of DM-associated LLA, but the situation in many LMICs is unknown. We aim to conduct a systematic review to determine the incidence and prevalence of DM-associated LLA in LMICs to better inform appropriate interventions and health system response., Methods and Analysis: A systematic search of the literature will be conducted on five databases: MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus and African Journal Online (AJOL). Only observational, quantitative studies reporting the incidence and/or prevalence of DM-related LLA will be considered. A validated study design-specific critical appraisal tool will be used to assess the risk of bias in individual studies. We will determine the incidence of LLA by examining the number of new cases of LLA among individuals with confirmed DM diagnosis during the specified period, while the prevalence will be based on the total number of all new and existing LLAs in a population. LLA will be considered as the resection of the lower limb from just above the knee to any point down to the toe. If heterogeneity is low to moderate, a random-effects meta-analysis will be conducted on extracted crude prevalence/incidence rates, with the median and interquartile range also reported. The systematic review will be performed in accordance with the JBI guideline for prevalence and incidence review. Study reporting will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guideline., Prospero Registration Number: CRD42021238656., Competing Interests: The authors have declared that no competing interests exist.

Postgraduate training is moving from face-to-face workshops or courses to online learning to help increase access to knowledge, expertise and skills, and save the cost of face-to-face training. However, moving from face-to-face to online learning for many of us academics is intimidating, and appears even more difficult without the help of a team of technologists. In this paper, we describe our approach, our experiences and the lessons we learnt from converting a Primer in Systematic Reviews face-to-face workshop to a 6-week online course designed for healthcare professionals in Africa. We learnt that the team needs a balance of skills and experience, including technical know-how and content knowledge; that the learning strategies needed to achieve the learning objectives must match the content delivery. The online approach should result in both building knowledge and developing skills, and include interactive and participatory approaches. Finally, the design and delivery needs to keep in mind the limited and expensive internet access in some resource-poor settings in Africa., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Prehospital care is integral in addressing sub-Saharan Africa's (SSA) high injury and illness burden. Consequently, robust, high-quality prehospital guidance documents are needed to inform care. These guidance documents include, but are not limited to, clinical practice guidelines (CPGs), protocols and algorithms that are contextually appropriate for SSA. However, SSA prehospital guidance mostly originates from the 'Global North,' with limited guidance for Africa by Africans. To strengthen prehospital clinical practice in SSA, we described and appraised all prehospital SSA guidance documents informing clinical decision making., Methods: We conducted a scoping review of prehospital-relevant guidance documents, including CPGs, algorithms, protocols and position statements originating from SSA. We performed a comprehensive literature search in various databases (PUBMED and SCOPUS), guideline clearing houses (Scottish Intercollegiate Guidelines Network, Trip, and Guidelines International Network), journals, various forms of grey literature and contacted experts. Guidance document screening and data extraction was done independently, in duplicate and reviewed by a third author. Guidance quality was then determined using the AGREE II tool and data were analysed using simple descriptive statistics., Results: We included 51 guidance documents from 13 countries across SSA after screening 2320 potential documents. The majority of guidance documents lacked an evidence foundation, made recommendations based on expert input, and were predominantly end-user presentations such as algorithms or protocols. Overall, reporting quality was poor, specifically for critical domains such as rigour of development; however, clarity of presentation was generally strong. Guidance topics were focused around resuscitation and common diseases (both communicable and non-communicable) with major gaps identified across a variety of topics; such as mental health for example., Conclusion: The majority of prehospital clinical guidance from SSA provides clinicians with excellent ready to use end-user material. Conversely, most of the guidance documents lack an appropriate evidence foundation and fail to transparently report the guidance development process, highlighting the need to strengthen and build guideline development capacity to promote the transition from eminence-based to evidence-based guidance for prehospital care in SSA. Guideline developers, professional societies and publishers need to be aware of international and local guidance document development and reporting standards in order to produce guidance we can trust., Competing Interests: PM was supported by the Stellenbosch University Undergraduate Conference Presentation Fund for conference attendance linked to this manuscript. KS was supported by the Queen Elizabeth Scholarship in Strengthening Health and Social Systems during the time of this study. MM was involved as a methodologist in the AFEM 2016 CPGs for the Health Professions Council of South Africa (HPCSA). MM was removed from any decision, data collection or AGREE scoring for those guidelines. MM is an editor of the African Journal of Emergency Medicine. MM was not involved in the editorial workflow for this manuscript. The African Journal of Emergency Medicine applies a double blinded process for all manuscript peer reviews. The authors declared no further conflict of interest., (© 2020 African Federation for Emergency Medicine. Publishing services provided by Elsevier.)

Introduction: De novo (new) guideline development methods are well described and supported by numerous examples, including comprehensive checklists. However, alternative guideline development methods, which draw from existing up to date, high quality clinical practice guidelines instead of re-inventing the wheel, have not been adopted so readily, despite the potential efficiencies of such methods compared to de novo development. In Africa, guideline quality and rigour of development, especially for prehospital care, remains poor. This paper firstly describes the opinions of international guideline experts on the African Federation for Emergency Medicine guideline project, and secondly updates a framework for South African prehospital guideline development., Methods: We conducted a qualitative study of expert reviews of an evidence-based guideline development project led by the African Federation for Emergency Medicine in 2016 for prehospital care in South Africa. We purposefully sampled key international and regional guideline experts from a range of organisations. Comments and voice memos, following a terms of reference guide, were thematically analysed through manual coding., Results: A total of seven experts gave feedback. Key themes revolved around existing international clinical practice guidelines not being enough to cover context specific evidence, blurring of guideline responsibilities and output, and transparency of guideline decisions and conflicts of interest. We showcase three fit-for-purpose guideline development approaches and provide an updated alternative guideline development roadmap for low-resource settings., Conclusion: In order to create clinical practice guidelines that clinicians trust and use on a daily basis to change lives, guideline developers need rigorous yet pragmatic approaches that are responsive to end-user needs. Reflecting on the African Federation for Emergency Medicine prehospital guideline development project in 2016, this paper presents key guiding themes to strengthen guideline development in low- and middle-income countries and other low-resource settings and provides an updated hybrid guideline development approach., Competing Interests: MM was involved as a guideline methodologist and evidence reviewer in the original AFEM CPG commissioned via the Health Professions Council of South Africa Professional Board of Emergency Care. TY was involved as a consultant. Neither AFEM nor the Health Professions Council of South Africa Professional Board of Emergency Care were involved with the interpretation or final write up of this manuscript. MM is an editor of the African Journal of Emergency Medicine. MM was not involved in the editorial workflow for this manuscript. The African Journal of Emergency Medicine applies a double blinded process for all manuscript peer reviews., (© 2020 African Federation for Emergency Medicine. Publishing services provided by Elsevier.)

Objectives: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields., Study Design and Setting: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group., Results: A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan., Conclusion: An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Developing a clinical practice guideline (CPG) is expensive and time-consuming and therefore often unrealistic in settings with limited funding or resources. Although CPGs form the cornerstone of providing synthesised, systematic, evidence-based guidance to patients, healthcare practitioners and managers, there is no added benefit in developing new CPGs when there are accessible, good-quality, up-to-date CPGs available that can be adapted to fit local needs. Different approaches to CPG development have been proposed, including adopting, adapting or contextualising existing high-quality CPGs to make recommendations relevant to local contexts. These approaches are attractive where technical and financial resources are limited and high-quality guidance already exists. However, few examples exist to showcase such alternative approaches to CPG development. The South African Guidelines Excellence project held a workshop in 2017 to provide an opportunity for dialogue regarding different approaches to guideline development with key examples and case studies from the South African setting. Four CPGs represented the topics: mental health, health promotion, chronic musculoskeletal pain and prehospital emergency care. Each CPG used a different approach, however, using transparent, reportable methods. They included advisory groups with representation from content experts, CPG users and methodologists. They assessed CPGs and systematic reviews for adopting or adapting. Each team considered local context issues through qualitative research or stakeholder engagement. Lessons learnt include that South Africa needs fit-for-purpose guidelines and that existing appropriate, high-quality guidelines must be taken into account. Approaches for adapting guidelines are not clear globally and there are lessons to be learnt from existing descriptions of approaches from South Africa., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The SwEatch platform, a wearable sensor for sampling and measuring the concentration of electrolytes in human sweat in real time, has been improved in order to allow the sensing of two analytes. The solid contact ion-sensitive electrodes (ISEs) for the detection of Na + and K + have been developed in two alternative formulations, containing either poly(3,4-ethylenedioxythiophene) (PEDOT) or poly(3-octylthiophene-2,5-diyl) (POT) as a conductive polymer transducing component. The solution-processable POT formulation simplifies the fabrication process, and sensor to sensor reproducibility has been improved via partial automation using an Opentron® automated pipetting robot. The resulting electrodes showed good sensitivity (52.4 ± 6.3 mV/decade (PEDOT) and 56.4 ± 2.2 mV/decade (POT) for Na + ISEs, and 45.7 ± 7.4 mV/decade (PEDOT) and 54.3 ± 1.5 mV/decade (POT) for K + ) and excellent selectivity towards potential interferents present in human sweat (H + , Na + , K + , Mg 2+ , Ca 2+ ). The 3D printed SwEatch platform has been redesigned to incorporate a double, mirrored fluidic unit which is capable of drawing sweat from the skin through passive capillary action and bring it in contact with two independent electrodes. The potentiometric signal generated by the electrodes is measured by an integrated electronics board, digitised and transmitted via Bluetooth to a laptop. The results obtained from on-body trials on athletes during cycling show a relatively small increase in sodium (1.89 mM-2.97 mM) and potassium (3.31 mM-7.25 mM) concentrations during the exercise period of up to 90 min., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Diet is one of the modifiable lifestyle factors in management of kidney disease. We explored perceptions on adherence to dietary prescriptions for adults with chronic kidney disease on hemodialysis. This was a qualitative descriptive study. Participants were purposively selected at renal clinics/dialysis units at national referral hospitals in Kenya. Data were collected using in-depth interviews, note-taking and voice-recording. The data were managed and analyzed thematically in NVIV0-12 computer software. Study participants were 52 patients and 40 family caregivers (42 males and 50 females) aged 20 to 69 years. Six sub-themes emerged in this study: "perceived health benefits"; "ease in implementing prescribed diets"; "cost of prescribed renal diets"; "nutrition information and messages"; "transition to new diets" and "fear of complications/severity of disease". Both patients and caregivers acknowledged the health benefits of adherence to diet prescriptions. However, there are mixed messages to the patients and caregivers who have challenges with management and acceptability of the prescriptions. Most of them make un-informed dietary decisions that lead to consumption of unhealthy foods with negative outcomes such as metabolic waste accumulation in the patients' bodies negating the effects of dialysis and undermining the efforts of healthcare system in management of patients with chronic kidney disease.

Objective: The aim of this paper was to provide a systematic review and update on the pharmacotherapy of social anxiety disorder (SAD), including the efficacy and tolerability of these agents, the ranking of interventions, and the grading of results by quality of evidence., Methods: The Common Mental Disorder Controlled Trial Register and two trial registries were searched for randomised controlled trials (RCTs) comparing any pharmacological intervention or placebo in the treatment of SAD. We performed a standard pairwise meta-analysis using a random effects model and carried out a network meta-analysis (NMA) using the statistical package, R. Quality of evidence was also assessed., Results: We included 67 RCTs in the review and 21 to 45 interventions in the NMA. Paroxetine was most effective in the reduction of symptom severity as compared to placebo. Superior response to treatment was also observed for paroxetine, brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline. Higher dropout rates were found for fluvoxamine. Brofaromine, escitalopram, fluvoxamine, paroxetine, pregabalin, sertraline, and venlafaxine performed worse in comparison to placebo for the outcome of dropouts due to adverse events. Olanzapine yielded a relatively high rank for treatment efficacy and buspirone the worse rank for dropouts due to any cause., Conclusion: The differences between drugs and placebo were small, apart from a significant reduction in symptom severity and response for paroxetine. We suggest paroxetine as a first-line treatment of SAD, with the consideration of future research on the drug olanzapine as well as brofaromine, bromazepam, clonazepam, escitalopram, fluvoxamine, phenelzine, and sertraline because we observed a response to treatment.

Background: Poor stock management has been identified as one of the causes of vaccine stock-outs in health facilities. This study assessed the occurrence of vaccine stock-outs and vaccine stock management practices in primary health care facilities in OR Tambo district of the Eastern Cape province, South Africa., Methods: Descriptive cross-sectional study design was used in this study to assess both the stock management practices and the availability of vaccines in the facilities. The study was conducted in 64 primary health care facilities across all sub-districts in OR Tambo. Data were collected using a questionnaire administered by the researcher, record checks and through observation. The occurrence of stock-outs of six tracer vaccines on the day of the visit and in the preceding 24 months were assessed. The data were captured into REDCap tool and analysed using STATA version 14., Results: Most standard stock management procedures were not adhered to, as these procedures were mostly handled by health care workers who either required formal training or refresher training on vaccine management. Cold chain capacity was not adequate and some vaccines were exposed to freezing. Both stock cards and the stock visibility solution (SVS) device were used in all the facilities for vaccine stock management. Less than half of the facilities visited 27 (44%) filled their stock cards regularly. Delays in receiving supplies from the pharmaceutical depot were commonly reported by facilities, which contributed to stock-outs. A total of 49 (77%) health facilities had at least one stockout for at least one vaccine on the day of the visit. Furthermore, BCG and OPV were the most affected vaccines in 37 (58%) and 28 (44%) of facilities, respectively., Conclusion: Interventions for improving vaccine availability should be considered, especially those targeting human resources and the entire stock management system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Use of good quality, evidence-informed and up-to-date clinical practice guidelines (CPGs) has the potential to impact health outcomes. This paper describes the development, implementation and evaluation of a dedicated CPG training course to address the training needs of CPG stakeholders in South Africa., Methods: We first reviewed the content and teaching strategies of existing CPG courses. This review consisted of a systematic review of teaching and learning strategies for guideline teams and a document review of existing courses offered by international guideline groups, universities and professional groups. We then strengthened an existing CPG course and evaluated it., Results: We found no studies on teaching and learning strategies for guideline teams. We identified six CPG courses being offered as full courses (part of a postgraduate degree program) by universities or as independent training for continuing professional education by professional groups. Contents focused on new guideline development. One course included alternative methods of guideline approaches such as contextualization and adaptation. The format varied from face-to-face sessions, to online sessions, group exercises and discussions, seminar format and project based activities. The revised CPG four-month long course that we implemented was designed to be pragmatic, reflective and contextually relevant. It used local guideline examples, authentic tasks, and an online forum for discussions and resources. It covered de novo CPG development, alternative methods of development (adopting, contextualising, adapting), and implementing CPGs. Course evaluation identified strengths and areas for improvement., Conclusion: Dedicated capacity development has potential to positively influence CPG development and implementation., Competing Interests: The authors declare no competing interests., (© Taryn Young et al.)

Background: Methods on developing new (de novo) clinical practice guidelines (CPGs) have received substantial attention. However, research into alternative methods of CPG development using existing CPG documents (CPG adaptation) - a specific issue for guideline development groups in low- and middle-income countries - is sparse. There are only a few examples showcasing the pragmatic application of such alternative approaches in settings with time and budget constraints, especially in the prehospital setting. This paper aims to describe and strengthen the methods of developing prehospital CPGs using alternative guideline development methods through a case study design., Methods: We qualitatively explored a CPG development project conducted in 2016 for prehospital providers in South Africa as a case study. Key stakeholders, involved in various processes of the guideline project, were purposefully sampled. Data were collected from one focus group and six in-depth interviews and analysed using thematic analysis. Overarching themes and sub-themes were inductively developed and categorised as challenges and recommendations and further transformed into action points., Results: Key challenges revolved around guideline implementation as opposed to development. These included the unavoidable effect of interest and beliefs on implementing recommendations, the local evidence void, a shifting implementation context, and opposing end-user needs. Guideline development and implementation strengthening priority actions included: i) developing a national end-user document; ii) aligning recommendations with local practice; iii) communicating a clear and consistent message; iv) addressing controversial recommendations; v) managing the impact of interests, beliefs and intellectual conflicts; and vi) transparently reporting implementation decisions., Conclusion: The cornerstone of a successful guideline development process is the translation and implementation of CPG recommendations into clinical practice. We highlight key priority actions for prehospital guideline development teams with limited resources to strengthen guideline development, dissemination, and implementation by drawing from lessons learnt from a prehospital guideline project conducted in South Africa.

Background: The neurologic manifestations of HIV include a spectrum of HIV-associated neurocognitive disorders, as well as a cluster of neurologic symptoms and signs. The neurologic manifestations have been modified but not eradicated by antiretroviral therapy (ART). We describe the neurologic phenotype in South African patients with predominant HIV-1 subtype C infection on ART and its association with neurocognitive impairment and efavirenz and 8-hydroxy-efavirenz concentrations., Methods: We conducted a cross-sectional analysis of the neurologic examination findings of HIV+ patients with neurocognitive impairment and used multiple linear regression to explore associations with neurocognitive impairment, efavirenz, and 8-hydroxy-efavirenz pharmacokinetics (plasma and CSF)., Results: We included 80 participants established on ART (median 40 months) of which 72 (90%) were female. The median age was 35 (interquartile range [IQR], 32-42) and the median Global Deficit Score was 0.94 (IQR 0.63-1.36). We found associations between neurocognitive impairment and neurologic signs: gait (slow walking speed [ p = 0.03; R 2 = 0.06], gait ataxia [ p < 0.01; R 2 = 0.21], and abnormal gait appearance [ p < 0.01; R 2 = 0.18]); coordination (upper limb bradykinesia [ p < 0.01; R 2 = 0.10] and lower limb bradykinesia [ p = 0.01; R 2 = 0.10]); reflexes (jaw jerk [ p = 0.04; R 2 = 0.05] and palmomental response [ p = 0.03; R 2 = 0.06]); ocular signs (impaired smooth pursuit [ p = 0.01; R 2 = 0.09] and impaired saccades [ p < 0.01; R 2 = 0.15]); and motor signs (spasticity [ p ≤ 0.01; R 2 = 0.15] and muscle weakness [ p = 0.01; R 2 = 0.08]). No significant associations were found between plasma and CSF efavirenz or 8-hydroxy efavirenz concentrations and any neurologic sign., Conclusion: We found that individual neurologic signs were associated with neurocognitive impairment in South African HIV+ patients with predominant HIV-1 subtype C infection on ART and could be used in clinical practice to assess severity., Registration Number: PACTR201310000635418., (© 2019 American Academy of Neurology.)

Background: Significant individual variation in bone loss associated with aromatase inhibitors (AIs) emphasizes the importance of identifying postmenopausal breast cancer patients at high risk for this adverse effect. The study explores the clinical relevance of genetic variation in the Cytochrome P450 19A1 (CYP19A1) gene in a subset of South African patients during the first year of taking AIs for estrogen receptor (ER)-positive breast cancer., Methods: The study population consisted of ER-positive breast cancer patients on AIs, followed in real-life clinical practice. Body mass index was measured and bone mineral density (BMD) was determined at baseline and at month 12. CYP19A1 genotyping was performed using real-time polymerase chain reaction analysis of rs10046, extended to Sanger sequencing and whole exome sequencing in 10 patients with more than 5% bone loss at month 12 at the lumbar spine., Results: After 12 months of AI treatment, 72 patients had completed BMD and were successfully genotyped. Ten patients (14%) experienced more than 5% bone loss at the lumbar spine over the study period. Genotyping for CYP19A1 rs10046 revealed that patients with two copies of the A-allele were 10.79 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase at the lumbar spine, compared to patients with the GA or GG genotypes (CI of 1.771- 65.830, p=0.01). None of the 34 patients without lumbar spine bone loss at month 12 were homozygous for the functional CYP19A1 polymorphism. At the total hip region, patients with the AA genotype were 7. 37 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase (CI of 1.101- 49.336, p=0.04)., Conclusion: Homozygosity for the CYP19A1 rs10046 A-allele may provide information, in addition to clinical and biochemical factors that may be considered in risk stratification to optimize bone health in postmenopausal breast cancer women on AIs. Further investigation is required to place the clinical effect observed for a single CYP19A1 gene variant in a genomic context., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The fabrication of highly reliable and rugged fluidic chips designed for use in autonomous analyses for nutrient monitoring is described. The chips are based on a two-layer configuration with the fluidic channels produced in one layer using precision micromilling. The second capping layer contains through holes for sample/standard and reagent addition and waste removal post-analysis. Two optically clear polymethyl methacrylate (PMMA) windows are integrated into the opaque PMMA chip, orthogonal to a 22.5 mm-long section of the channel downstream from a serpentine reagent and sample/standard mixing region. An LED source is coupled into the channel through one of the windows, and the light intensity is monitored with a photodiode located at the distal end of the channel outside the second optically clear window. Efficient coupling of the source through the channel to the detector is achieved using custom-designed alignment units produced using 3D printing. In contrast to fluidic chips produced using solvent adhesion, the thermal-/pressure-bonded simplified method presented removes the need for surface treatment. Optimization of the thermal/pressure conditions leads to very strong adhesion between the PMMA layers, requiring forces in the region of 2000 N to separate them, which is necessary for the use in long-term deployments. Profilometry imaging shows minimal evidence of channel distortion after bonding. Finally, we show the potential of these techniques for environmental applications. The fluidic chips were integrated into prototype nutrient analyzers that display no evidence of leakage in extensive lab tests involving 2500 phosphate measurements using the yellow (vanadomolybdophosphoric acid) method. Similarly, excellent analytical performance (LOD is 0.09 μM) is reported for a 28-day field trial comprising 188 in situ autonomous phosphate measurements (564 measurements) in total including calibration., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Introduction: Trauma scoring systems are widely used in emergency settings to guide clinical decisions and to predict mortality. It remains unclear which system is most suitable to use for patients with gunshot injuries at district-level hospitals. This study compares the Triage Early Warning Score (TEWS), Injury Severity Score (ISS), Trauma and Injury Severity Score (TRISS), Kampala Trauma Score (KTS) and Revised Trauma Score (RTS) as predictors of mortality among patients with gunshot injuries at a district-level urban public hospital in Cape Town, South Africa., Methods: Gunshot-related patients admitted to the resuscitation area of Khayelitsha Hospital between 1 January 2016 and 31 December 2017 were retrospectively analysed. Receiver Operating Characteristic (ROC) analysis were used to determine the accuracy of each score to predict all-cause in-hospital mortality. The odds ratio (with 95% confidence intervals) was used as a measure of association., Results: In total, 331 patients were included in analysing the different scores (abstracted from database n = 431, excluded: missing files n = 16, non gunshot injury n = 10, <14 years n = 1, information incomplete to calculate scores n = 73). The mortality rate was 6% (n = 20). The TRISS and KTS had the highest area under the ROC curve (AUC), 0.90 (95% CI 0.83-0.96) and 0.86 (95% CI 0.79-0.94), respectively. The KTS had the highest sensitivity (90%, 95% CI 68-99%), while the TEWS and RTS had the highest specificity (91%, 95% CI 87-94% each)., Conclusions: None of the different scoring systems performed better in predicting mortality in this high-trauma burden area. The results are limited by the low number of recorded deaths and further studies are needed., Competing Interests: The authors declare no conflicts of interest., (2019 African Federation for Emergency Medicine. Publishing services provided by Elsevier.)

A low cost, UV absorbance detector incorporating a 235 nm light emitting diode (LED) for portable ion chromatography has been designed and fabricated to achieve rapid, selective detection of nitrite and nitrate in natural waters. The optical cell was fabricated through micromilling and solvent vapour bonding of two layers of poly (methyl methacrylate) (PMMA). The cell was fitted within a 3D printed housing and the LED and photodiode were aligned using 3D printed holders. Isocratic separation and selective detection of nitrite and nitrate was achieved in under 2.5 min using the 235 nm LED based detector and custom electronics. The design of the new detector assembly allowed for effective and sustained operation of the deep UV LED source at a low current (<10 mA), maintaining consistent and low LED temperatures during operation, eliminating the need for a heat sink. The detector cell was produced at a fraction of the cost of commercial optical cells and demonstrated very low stray light (0.01%). For retention time and peak area repeatability, RSD values ranged from 0.75 to 1.10 % and 3.06-4.19 %, respectively. Broad dynamic linear ranges were obtained for nitrite and nitrate, with limits of detection at ppb levels. The analytical performance of the IC set up with optical cell was compared to that of an ISO-accredited IC through the analysis of five various water samples. Relative errors not exceeding 6.86% were obtained for all samples. The detector was also coupled to a low pressure, low cost syringe pump to assess the potential for use within a portable analytical system. RSD values for retention time and peak area using this simple configuration were <1.15% and <3.57% respectively, highlighting repeatability values comparable to those in which a commercial HPLC pump was used., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: In 2016 the first African emergency care clinical practice guideline (CPG) was developed for national uptake in the prehospital sector in South Africa, with implementation starting in 2018. Comprehensive uptake of CPGs post development is not a given, as this requires effective and efficient dissemination and implementation strategies that take into account the perceptions, barriers and facilitators of the local end-users. This study aimed to identify prehospital end-users' perceptions of the emergency care guidelines, including barriers and facilitators for national decision makers, to strengthen CPG uptake in South Africa., Methods: Our study employed a descriptive qualitative research design, including nine focus groups with 56 operational emergency care providers across four major provinces in South Africa. Data was analysed using thematic analysis in ATLAS.ti. Ethics approval was provided by Stellenbosch University., Results: Themes related to provider perceptions, expectations and guideline uptake emerging from the data was unofficial and unclear communication, broadening versus limiting guideline expectations, conflicted personal reactions and spreading the word. Challenges to dissemination and implementation included poor communication, changes to scope of practice, and limited capacity to upskill existing providers. Facilitators included using technology for end-user documents, local champions to support change, establishing online and modular training, and implementation by independent decision makers., Conclusion: This study provides an overview of the perceptions of operational emergency care providers and how their experiences of hearing about and engaging with the guidelines, in their industry, can contribute to the dissemination, implementation and uptake of emergency care guidelines. In order to disseminate and implement an emergency care CPG, decision makers must take into account the perceptions, barriers, and facilitators of local end-users., Competing Interests: MM was involved as a guideline methodologist in the original AFEM CPG commissioned via the HPCSA PBEC. Neither AFEM or the HPCSA PBEC was involved with the interpretation or final write-up of the manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Background: Acute pain is a common reason for seeking prehospital emergency care. Regrettably, acute pain is often underestimated and poorly managed in this setting. The scoping review was conducted to gain insight into existing research on the topic and to make recommendations for future work., Objectives: To identify all available evidence related to acute pain assessment and management in the African prehospital setting, describe the extent of the evidence, encapsulate findings, and identify research gaps., Methods: The scoping review considered primary and secondary research related to acute pain assessment and management of both medical and traumatic origins in all age groups in the African prehospital setting. The search strategy aimed to identify published, unpublished, and ongoing research which met the inclusion criteria. Potentially eligible studies were identified by a comprehensive search of electronic databases, trial registers, dissertation/thesis databases, grey literature databases, and conference proceedings. Screening and data extraction were conducted independently and in duplicate., Results: The comprehensive search identified 3823 potential studies, duplicate titles were removed, and 3358 titles/abstracts were screened. Full text of 66 potentially eligible titles was screened, 60 were excluded, and six publications met the inclusion criteria. Despite recommendations for pain assessment during general patient care, most studies reported no/limited pain assessment. In general, pain management was concluded to be insufficient and not conforming to best practice., Conclusions: Only six publications addressing prehospital acute pain care in Africa could be identified, possibly indicative of a knowledge gap. Future research is indicated to enable a better understanding of the epidemiology of acute pain and barriers and enablers of acute pain care and to develop evidence-based clinical practice guidelines (CPGs) catering for all EMS systems in Africa. Additionally, educational initiatives should be implemented to improve the quality of acute pain care and to monitor quality through continuous quality improvement (CQI) programs.

Introduction: Osteoporosis (OP) risk factor assessment and bone mineral density (BMD) testing are frequently omitted at baseline in aromatase inhibitor (AI) studies, which may lead to misinterpretation of AI associated bone loss. The present study describes bone health of South African postmenopausal women of predominantly Mixed Ancestry, prior to AI treatment., Methods: This descriptive baseline study, nested in a prospective AI cohort study, included postmenopausal women with endocrine sensitive breast cancer, aged 50 to 80 years. A baseline questionnaire documented demographic-, medical-, lifestyle- and fracture history. Body weight was assessed clinically, and body composition and BMD measured via dual energy absorptiometry (DXA). Data was analysed in STATA 14 using descriptive and inferential statistics., Results: 101 participants were recruited, with a mean age of 61±7 years. Nearly a third (n = 32) of women at baseline fulfilled global criteria for bone protection (BMD T-score ≥-2SD (n = 18); BMD T-score -1.5SD to < -2SD with risk factors (n = 14). Lower body weight, body mass index (BMI), fat mass index and lean mass index were significantly associated with the participants with a BMD measurement in keeping with a diagnosis of OP (p <0.001). Low vitamin D was present in 93% of the cohort tested (n = 95), whilst deficient vitamin D status (<20ng/ml) was documented in 52 women (55%)., Conclusions: In this study, a third of postmenopausal women considered for AI therapy fulfilled international criteria for bone protective pharmacological intervention. This emphasizes the need for clinical risk and BMD assessment in postmenopausal breast cancer patients at baseline. Body composition and bone health associations highlight bone fragility associated with lower body weight., Competing Interests: Prof. MJ Kotze is a director and shareholder of Gknowmix (Pty) Ltd.