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Abstract 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).

Abstract 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.

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.

Abstract 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.

Abstract Robust, relevant, comprehensive, and up-to-date evidence syntheses are the cornerstone for evidence-informed healthcare decisions. When considering multiple treatment options, network meta-analysis (NMA) systematic reviews play a key role in informing impactful decisions and clinical practice guidelines. However, the capacity and literacy to conduct NMA systematic reviews and interpret its results remains out of reach for many clinicians and review authors, especially in low-to-middle-income countries. Despite ample resources and guides, NMA capacity and training opportunities remain limited to non-existent in Sub-Saharan Africa. Towards solutions and strengthening evidence synthesis and NMA capacity in the Sub-Saharan African region, we describe and reflect on two courses that build NMA capacity and aim to address NMA literacy in Sub-Saharan Africa. The Primer in NMA systematic reviews aimed for participants to be able to find, appraise, interpret, and consider the use of NMA SRs of intervention effects. It is a 6-week online course for clinicians, policy-makers, and researchers wanting to learn more about using NMA systematic reviews. The Global NMA Masterclass workshop aimed for participants to be able to understand and apply pairwise and NMA in STATA and R, evaluate NMA assumptions and confidence in NMA results, and appropriately report NMA results. This course was offered over 5 weeks to clinicians, biostatisticians, and researchers with basic knowledge of epidemiology and biostatics. Although the bulk of learning occurred through self-study, we had weekly, synchronous question-and-answer sessions for both courses. Using relevant examples throughout the courses helped to enable an authentic learning environment. This was the first NMA training developed in Africa for Africa. Development of the courses was a collaborative effort from a multi-disciplinary team. Both NMA courses were well received and attended by a diverse group of participants spread across Sub-Saharan African countries. Participants felt the courses were applicable to their setting. Although most participants appreciated the benefits of online learning, we also experienced some challenges. There is great potential to conduct NMA systematic reviews in Sub-Saharan Africa. The NMA Primer and NMA workshop can play an essential role in expanding and developing NMA SR capacity and literacy in SSA.

Abstract 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.

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.

Abstract 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.

Abstract 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 23rd 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.

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

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.

BackgroundAdults 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.MethodsWe 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.ResultsThe six guidelines on self-management support found were developed in four high-income countries. Five of the guidelines recorded 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.ConclusionThere 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.

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).

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.

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.

Abstract 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 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.

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,

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.

Introduction: An adaptive guideline development method, as opposed to a de novo guideline development, is dependent on access to existing high-quality up-to-date clinical practice guidelines (CPGs). We described the characteristics and quality of CPGs relevant to prehospital care worldwide, in order to strengthen guideline development in low-resource settings for emergency care. Methods: We conducted a descriptive study of a database of international CPGs relevant to emergency care produced by the African Federation for Emergency Medicine (AFEM) CPG project in 2016. Guideline quality was assessed with the AGREE II tool, independently and in duplicate. End-user documents such as protocols, care pathways, and algorithms were excluded. Data were imported, managed, and analysed in STATA 14 and R. Results: In total, 276 guidelines were included. Less than 2% of CPGs originated from low- and middle income-countries (LMICs); only 15% (n = 38) of guidelines were prehospital specific, and there were no CPGs directly applicable to prehospital care in LMICs. Most guidelines used de novo methods (58%, n = 150) and were produced by professional societies or associations (63%, n = 164), with the minority developed by international bodies (3%, n = 7). National bodies, such as the National Institute for Health and Care Excellence (NICE) and the Scottish Intercollegiate Guidelines Network (SIGN), produced higher quality guidelines when compared to international guidelines, professional societies, and clinician/academic-produced guidelines. Guideline quality varied across topics, subpopulations and producers. Resource-constrained guideline developers that cannot afford de novo guideline development have access to an expanding pool of high-quality prehospital guidelines to translate to their local setting. Discussion: Although some high-quality CPGs exist relevant to emergency care, none directly address the needs of prehospital care in LMICs, especially in Africa. Strengthening guideline development capacity, including adaptive guideline development methods that use existing high-quality CPGs, is a priority. Keywords: Emergency care, Prehospital, Guideline development, Scoping, Guideline quality

Abstract Objectives Methods on developing new (de novo) clinical practice guidelines (CPGs) have received substantial attention. However, the volume of literature is not matched by research into alternative methods of CPG development using existing CPG documents—a specific issue for guideline development groups in low- and middle-income countries. We report on how we developed a context specific prehospital CPG using an alternative guideline development method. Difficulties experienced and lessons learnt in applying existing global guidelines’ recommendations to a national context are highlighted. Results The project produced the first emergency care CPG for prehospital providers in Africa. It included > 270 CPGs and produced over 1000 recommendations for prehospital emergency care. We encountered various difficulties, including (1) applicability issues: few pre-hospital CPGs applicable to Africa, (2) evidence synthesis: heterogeneous levels of evidence classifications and (3) guideline quality. Learning points included (1) focusing on key CPGs and evidence mapping, (2) searching other resources for CPGs, (3) broad representation on CPG advisory boards and (4) transparency and knowledge translation. Re-inventing the wheel to produce CPGs is not always feasible. We hope this paper will encourage further projects to use existing CPGs in developing guidance to improve patient care in resource-limited settings.

Introduction: Emergency Medical Services are ideally placed to provide relief of acute pain and discomfort. The objectives of this study were to describe pre-hospital pain management practices by Emergency Medical Services in the Western Cape, South Africa. Methods: A retrospective, descriptive survey was undertaken of analgesic drug administration by advanced life support paramedics. Patient care records generated in the City of Cape Town during an 11-month period containing administrations of morphine, ketamine, nitrates and 50% nitrous oxide/oxygen were randomly sampled. Variables studied were drug dose, dose frequency, and route of administration, patient age, gender, disorder and call type as well as qualification and experience level of the provider. Results: A total of 530 patient care records were included (n = 530). Morphine was administered in 371 (70%, 95% CI 66–74) cases, nitrates in 197 (37%, 95% CI 33–41) and ketamine in 9 (1.7%, 95% CI 1–3) cases. A total of 5 mg or less of morphine was administered in 278 (75%, 95% CI 70–79) cases, with the median dose being 4 mg (IQR 3–6). Single doses were administered to 268 (72.2%, 95% CI 67–77) morphine administrations, five (56%, 95% CI 21–86) ketamine administrations and 161 (82%, 95% CI 76–87) of nitrate administrations. Chest pain was the reason for pain management in 226 (43%) cases. Advanced Life Support Providers had a median experience level of two years (IQR 2–4). Discussion: Pre-hospital acute pain management in the Western Cape does not appear to conform to best practice as Advanced Life Support providers in the Western Cape use low doses of morphine. Chest pain is an important reason for drug administration in acute pre-hospital pain. Multimodal analgesia is not a feature of care in this pre-hospital service. The development of a Clinical Practice Guideline for and training in pre-hospital pain should be viewed as imperative.

BackgroundIn 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.MethodsOur 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.ResultsThemes 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.ConclusionThis 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.

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.

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.

We identify concerns pertinent to establishing trust necessary to support adoptees’ confidence in and uptake of genetic testing that might allow them to benefit from early screening and medical intervention. Using principles of community-based participatory research, our study sought to build a foundation of trust to document such perspectives. Three focus groups were held with 12 adult adoptees. Transcripts were analyzed using thematic content analysis. Comments highlighted aspects related to genomics and health history in the context of adoption, specifically: (1) trust in the intention of the research study; (2) trust that the adoption community will benefit from the results of research; and (3) trust in the protection from misuse and abuse of genomic data. Results reinforce the call for proper security of data and oversight of the ways it is used and point to the value of including researchers who are a part of the community under study.

Chlamydia trachomatis forms membrane-bound inclusions inside the host cell that are decorated with IncA, a SNARE-like protein that promotes the fusion of inclusions. Here, Cingolani et al. show that the protein folds into a non-canonical four-helix bundle and identify an intramolecular clamp required for membrane fusion.

Autoimmune diseases such as rheumatoid arthritis are caused by immune system recognition of self-proteins and subsequent production of effector T cells that recognize and attack healthy tissue. Therapies for these diseases typically utilize broad immune suppression, which can be effective, but which also come with an elevated risk of susceptibility to infection and cancer. T cell recognition of antigens is driven by binding of T cell receptors to peptides displayed on major histocompatibility complex proteins (MHCs) on the cell surface of antigen-presenting cells. Technology for recombinant production of the extracellular domains of MHC proteins and loading with peptides to produce pMHCs has provided reagents for detection of T cell populations, and with the potential for therapeutic intervention. However, production of pMHCs in large quantities remains a challenge and a translational path needs to be established. Here, we demonstrate a fusion protein strategy enabling large-scale production of pMHCs. A peptide corresponding to amino acids 259–273 of collagen II was fused to the N-terminus of the MHC_II beta chain, and the alpha and beta chains were each fused to human IgG4 Fc domains and co-expressed. A tag was incorporated to enable site-specific conjugation. The cytotoxic drug payload, MMAF, was conjugated to the pMHC and potent, peptide-specific killing of T cells that recognize the collagen pMHC was demonstrated with tetramerized pMHC-MMAF conjugates. Finally, these pMHCs were incorporated into MMAF-loaded 3DNA nanomaterials in order to provide a biocompatible platform. Loading and pMHC density were optimized, and peptide-specific T cell killing was demonstrated. These experiments highlight the potential of a pMHC fusion protein-targeted, drug-loaded nanomaterial approach for selective delivery of therapeutics to disease-relevant T cells and new treatment options for autoimmune disease.