The Commercial Determinants of Health and Evidence Synthesis (CODES): methodological guidance for systematic reviews and other evidence syntheses.

BACKGROUND: The field of the commercial determinants of health (CDOH) refers to the commercial products, pathways and practices that may affect health. The field is growing rapidly, as evidenced by the WHO programme on the economic and commercial determinants of health and a rise in researcher and funder interest. Systematic reviews (SRs) and evidence synthesis more generally will be crucial tools in the evolution of CDOH as a field. Such reviews can draw on existing methodological guidance, though there are areas where existing methods are likely to differ, and there is no overarching guidance on the conduct of CDOH-focussed systematic reviews, or guidance on the specific methodological and conceptual challenges. METHODS/RESULTS: CODES provides guidance on the conduct of systematic reviews focussed on CDOH, from shaping the review question with input from stakeholders, to disseminating the review. Existing guidance was used to identify key stages and to provide a structure for the guidance. The writing group included experience in systematic reviews and other forms of evidence synthesis, and in equity and CDOH research (both primary research and systematic reviews). CONCLUSIONS: This guidance highlights the special methodological and other considerations for CDOH reviews, including equity considerations, and pointers to areas for future methodological and guideline development. It should contribute to the reliability and utility of CDOH reviews and help stimulate the production of reviews in this growing field.

Gender equity in health research publishing in Africa.

INTRODUCTION: Women researchers find it more difficult to publish in academic journals than men, an inequity that affects women's careers and was exacerbated during the pandemic, particularly for women in low-income and middle-income countries. We measured publishing by sub-Saharan African (SSA) women in prestigious authorship positions (first or last author, or single author) during the time frame 2014-2016. We also examined policies and practices at journals publishing high rates of women scientists from sub-Saharan Africa, to identify potential structural enablers affecting these women in publishing. METHODS: The study used Namsor V.2, an application programming interface, to conduct a secondary analysis of a bibliometric database. We also analysed policies and practices of ten journals with the highest number of SSA women publishing in first authorship positions. RESULTS: Based on regional analyses, the greatest magnitude of authorship inequity is in papers from sub-Saharan Africa, where men comprised 61% of first authors, 65% of last authors and 66% of single authors. Women from South Africa and Nigeria had greater success in publishing than those from other SSA countries, though women represented at least 20% of last authors in 25 SSA countries. The journals that published the most SSA women as prominent authors are journals based in SSA. Journals with overwhelmingly male leadership are also among those publishing the highest number of SSA women. CONCLUSION: Women scholars in SSA face substantial gender inequities in publishing in prestigious authorship positions in academic journals, though there is a cadre of women research leaders across the region. Journals in SSA are important for local women scholars and the inequities SSA women researchers face are not necessarily attributable to gender discrepancy in journals' editorial leadership.

Low-carbohydrate versus balanced-carbohydrate diets for reducing weight and cardiovascular risk.

BACKGROUND: Debates on effective and safe diets for managing obesity in adults are ongoing. Low-carbohydrate weight-reducing diets (also known as 'low-carb diets') continue to be widely promoted, marketed and commercialised as being more effective for weight loss, and healthier, than 'balanced'-carbohydrate weight-reducing diets. OBJECTIVES: To compare the effects of low-carbohydrate weight-reducing diets to weight-reducing diets with balanced ranges of carbohydrates, in relation to changes in weight and cardiovascular risk, in overweight and obese adults without and with type 2 diabetes mellitus (T2DM). SEARCH METHODS: We searched MEDLINE (PubMed), Embase (Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 25 June 2021, and screened reference lists of included trials and relevant systematic reviews. Language or publication restrictions were not applied. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults (18 years+) who were overweight or living with obesity, without or with T2DM, and without or with cardiovascular conditions or risk factors. Trials had to compare low-carbohydrate weight-reducing diets to balanced-carbohydrate (45% to 65% of total energy (TE)) weight-reducing diets, have a weight-reducing phase of 2 weeks or longer and be explicitly implemented for the primary purpose of reducing weight, with or without advice to restrict energy intake.  DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and full-text articles to determine eligibility; and independently extracted data, assessed risk of bias using RoB 2 and assessed the certainty of the evidence using GRADE. We stratified analyses by participants without and with T2DM, and by diets with weight-reducing phases only and those with weight-reducing phases followed by weight-maintenance phases. Primary outcomes were change in body weight (kg) and the number of participants per group with weight loss of at least 5%, assessed at short- (three months to < 12 months) and long-term (≥ 12 months) follow-up. MAIN RESULTS: We included 61 parallel-arm RCTs that randomised 6925 participants to either low-carbohydrate or balanced-carbohydrate weight-reducing diets. All trials were conducted in high-income countries except for one in China. Most participants (n = 5118 randomised) did not have T2DM. Mean baseline weight across trials was 95 kg (range 66 to 132 kg). Participants with T2DM were older (mean 57 years, range 50 to 65) than those without T2DM (mean 45 years, range 22 to 62). Most trials included men and women (42/61; 3/19 men only; 16/19 women only), and people without baseline cardiovascular conditions, risk factors or events (36/61). Mean baseline diastolic blood pressure (DBP) and low-density lipoprotein (LDL) cholesterol across trials were within normal ranges. The longest weight-reducing phase of diets was two years in participants without and with T2DM. Evidence from studies with weight-reducing phases followed by weight-maintenance phases was limited. Most trials investigated low-carbohydrate diets (> 50 g to 150 g per day or < 45% of TE; n = 42), followed by very low (≤ 50 g per day or < 10% of TE; n = 14), and then incremental increases from very low to low (n = 5). The most common diets compared were low-carbohydrate, balanced-fat (20 to 35% of TE) and high-protein (> 20% of TE) treatment diets versus control diets balanced for the three macronutrients (24/61). In most trials (45/61) the energy prescription or approach used to restrict energy intake was similar in both groups. We assessed the overall risk of bias of outcomes across trials as predominantly high, mostly from bias due to missing outcome data. Using GRADE, we assessed the certainty of evidence as moderate to very low across outcomes.  Participants without and with T2DM lost weight when following weight-reducing phases of both diets at the short (range: 12.2 to 0.33 kg) and long term (range: 13.1 to 1.7 kg).  In overweight and obese participants without T2DM: low-carbohydrate weight-reducing diets compared to balanced-carbohydrate weight-reducing diets (weight-reducing phases only) probably result in little to no difference in change in body weight over three to 8.5 months (mean difference (MD) -1.07 kg, (95% confidence interval (CI) -1.55 to -0.59, I2 = 51%, 3286 participants, 37 RCTs, moderate-certainty evidence) and over one to two years (MD -0.93 kg, 95% CI -1.81 to -0.04, I2 = 40%, 1805 participants, 14 RCTs, moderate-certainty evidence); as well as change in DBP and LDL cholesterol over one to two years. The evidence is very uncertain about whether there is a difference in the number of participants per group with weight loss of at least 5% at one year (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31, I2 = 17%, 137 participants, 2 RCTs, very low-certainty evidence).  In overweight and obese participants with T2DM: low-carbohydrate weight-reducing diets compared to balanced-carbohydrate weight-reducing diets (weight-reducing phases only) probably result in little to no difference in change in body weight over three to six months (MD -1.26 kg, 95% CI -2.44 to -0.09, I2 = 47%, 1114 participants, 14 RCTs, moderate-certainty evidence) and over one to two years (MD -0.33 kg, 95% CI -2.13 to 1.46, I2 = 10%, 813 participants, 7 RCTs, moderate-certainty evidence); as well in change in DBP, HbA1c and LDL cholesterol over 1 to 2 years. The evidence is very uncertain about whether there is a difference in the number of participants per group with weight loss of at least 5% at one to two years (RR 0.90, 95% CI 0.68 to 1.20, I2 = 0%, 106 participants, 2 RCTs, very low-certainty evidence).  Evidence on participant-reported adverse effects was limited, and we could not draw any conclusions about these.  AUTHORS' CONCLUSIONS: There is probably little to no difference in weight reduction and changes in cardiovascular risk factors up to two years' follow-up, when overweight and obese participants without and with T2DM are randomised to either low-carbohydrate or balanced-carbohydrate weight-reducing diets.

'Building on shaky ground'-challenges to and solutions for primary care guideline implementation in four provinces in South Africa: a qualitative study.

OBJECTIVES: Clinical guidelines support evidence-informed quality patient care. Our study explored perspectives of South African subnational health managers regarding barriers to and enablers for implementation for all available primary care guidelines. DESIGN: We used qualitative research methods, including semistructured, individual interviews and an interpretative perspective. Thematic content analysis was used to develop data categories and themes. SETTING: We conducted research in four of nine South African provinces with diverse geographic, economic and health system arrangements (Eastern Cape, Western Cape, KwaZulu-Natal, Limpopo). South Africa is a middle-income country with high levels of inequality. The settings represented public sector rural and peri-urban health facilities. PARTICIPANTS: Twenty-two participants with provincial and district health management roles, that comprised implementation and/or training on primary care guidelines, were included. RESULTS: Participants recommended urgent consideration of health system challenges, particularly financial constraints, impacting on access to the guidelines themselves and to medical equipment and supplies necessary to adhere to guidelines. They suggested that overcoming service delivery gaps requires strengthening of leadership, clarification of roles and enhanced accountability. Participants suggested that inadequate numbers of skilled clinical staff hampered guideline use and, ultimately, patient care. Quality assurance of training programmes for clinicians-particularly nurses-interdisciplinary training, and strengthening post-training mentorship were recommended. Furthermore, fit-for-purpose guideline implementation necessitates considering the unique settings of facilities, including local culture and geography. This requires guideline development to include guideline end users. CONCLUSIONS: Guidelines are one of the policy tools to achieve evidence-informed, cost-effective and universal healthcare. But, if not effectively implemented, they have no impact. Subnational health managers in poorly resourced settings suggested that shortcomings in the health system, along with poor consultation with end users, affect implementation. Short-term improvements are possible through increasing access to and training on guidelines. However, health system strengthening and recognition of socio-cultural-geographic diversity are prerequisites for context-appropriate evidence-informed practice.

Reporting of health equity considerations in cluster and individually randomized trials.

BACKGROUND: The randomized controlled trial (RCT) is considered the gold standard study design to inform decisions about the effectiveness of interventions. However, a common limitation is inadequate reporting of the applicability of the intervention and trial results for people who are "socially disadvantaged" and this can affect policy-makers' decisions. We previously developed a framework for identifying health-equity-relevant trials, along with a reporting guideline for transparent reporting. In this study, we provide a descriptive assessment of health-equity considerations in 200 randomly sampled equity-relevant trials. METHODS: We developed a search strategy to identify health-equity-relevant trials published between 2013 and 2015. We randomly sorted the 4316 records identified by the search and screened studies until 100 individually randomized (RCTs) and 100 cluster randomized controlled trials (CRTs) were identified. We developed and pilot-tested a data extraction form based on our initial work, to inform the development of our reporting guideline for equity-relevant randomized trials. RESULTS: In total, 39 trials (20%) were conducted in a low- and middle-income country and 157 trials (79%) in a high-income country focused on socially disadvantaged populations (78% CRTs, 79% RCTs). Seventy-four trials (37%) reported a subgroup analysis across a population characteristic associated with disadvantage (25% CRT, 49% RCTs), with 19% of included studies reporting subgroup analyses across sex, 9% across race/ethnicity/culture, and 4% across socioeconomic status. No subgroup analyses were reported for place of residence, occupation, religion, education, or social capital. One hundred and forty-one trials (71%) discussed the applicability of their results to one or more socially disadvantaged populations (68% of CRT, 73% of RCT). DISCUSSION: In this set of trials, selected for their relevance to health equity, data that were disaggregated for socially disadvantaged populations were rarely reported. We found that even when the data are available, opportunities to analyze health-equity considerations are frequently missed. The recently published equity extension of the Consolidated Reporting Standards for Randomized Trials (CONSORT-Equity) may help improve delineation of hypotheses related to socially disadvantaged populations, and transparency and completeness of reporting of health-equity considerations in RCTs. This study can serve as a baseline assessment of the reporting of equity considerations.

Stuck in the middle: a systematic review of authorship in collaborative health research in Africa, 2014-2016.

BACKGROUND: Collaborations are often a cornerstone of global health research. Power dynamics can shape if and how local researchers are included in manuscripts. This article investigates how international collaborations affect the representation of local authors, overall and in first and last author positions, in African health research. METHODS: We extracted papers on 'health' in sub-Saharan Africa indexed in PubMed and published between 2014 and 2016. The author's affiliation was used to classify the individual as from the country of the paper's focus, from another African country, from Europe, from the USA/Canada or from another locale. Authors classified as from the USA/Canada were further subclassified if the author was from a top US university. In primary analyses, individuals with multiple affiliations were presumed to be from a high-income country if they contained any affiliation from a high-income country. In sensitivity analyses, these individuals were presumed to be from an African country if they contained any affiliation an African country. Differences in paper characteristics and representation of local coauthors are compared by collaborative type using χ² tests. RESULTS: Of the 7100 articles identified, 68.3% included collaborators from the USA, Canada, Europe and/or another African country. 54.0% of all 43 429 authors and 52.9% of 7100 first authors were from the country of the paper's focus. Representation dropped if any collaborators were from USA, Canada or Europe with the lowest representation for collaborators from top US universities-for these papers, 41.3% of all authors and 23.0% of first authors were from country of paper's focus. Local representation was highest with collaborators from another African country. 13.5% of all papers had no local coauthors. DISCUSSION: Individuals, institutions and funders from high-income countries should challenge persistent power differentials in global health research. South-South collaborations can help African researchers expand technical expertise while maintaining presence on the resulting research.

Ready-to-use therapeutic food (RUTF) for home-based nutritional rehabilitation of severe acute malnutrition in children from six months to five years of age.

BACKGROUND: Management of severe acute malnutrition (SAM) in children comprises two potential phases: stabilisation and rehabilitation. During the initial stabilisation phase, children receive treatment for dehydration, electrolyte imbalances, intercurrent infections and other complications. In the rehabilitation phase (applicable to children presenting with uncomplicated SAM or those with complicated SAM after complications have been resolved), catch-up growth is the main focus and the recommended energy and protein requirements are much higher. In-hospital rehabilitation of children with SAM is not always desirable or practical - especially in rural settings - and home-based care can offer a better solution. Ready-to-use therapeutic food (RUTF) is a widely used option for home-based rehabilitation, but the findings of our previous review were inconclusive. OBJECTIVES: To assess the effects of home-based RUTF used during the rehabilitation phase of SAM in children aged between six months and five years on recovery, relapse, mortality and rate of weight gain. SEARCH METHODS: We searched the following databases in October 2018: CENTRAL, MEDLINE, Embase, six other databases and three trials registers. We ran separate searches for cost-effectiveness studies, contacted researchers and healthcare professionals in the field, and checked bibliographies of included studies and relevant reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, where children aged between six months and five years with SAM were, during the rehabilitation phase, treated at home with RUTF compared to an alternative dietary approach, or with different regimens and formulations of RUTF compared to each other. We assessed recovery, deterioration or relapse and mortality as primary outcomes; and rate of weight gain, time to recovery, anthropometrical changes, cognitive development and function, adverse outcomes and acceptability as secondary outcomes. DATA COLLECTION AND ANALYSIS: We screened for eligible studies, extracted data and assessed risk of bias of those included, independently and in duplicate. Where data allowed, we performed a random-effects meta-analysis using Review Manager 5, and investigated substantial heterogeneity through subgroup and sensitivity analyses. For the main outcomes, we evaluated the quality of the evidence using GRADE, and presented results in a 'Summary of findings' table per comparison. MAIN RESULTS: We included 15 eligible studies (n = 7976; effective sample size = 6630), four of which were cluster trials. Eight studies were conducted in Malawi, four in India, and one apiece in Kenya, Zambia, and Cambodia. Six studies received funding or donations from industry whereas eight did not, and one study did not report the funding source.The overall risk of bias was high for six studies, unclear for three studies, and low for six studies. Among the 14 studies that contributed to meta-analyses, none (n = 5), some (n = 5) or all (n = 4) children were stabilised in hospital prior to commencement of the study. One small study included only children known to be HIV-infected, another study stratified the analysis for 'recovery' according to HIV status, while the remaining studies included HIV-uninfected or untested children. Across all studies, the intervention lasted between 8 and 16 weeks. Only five studies followed up children postintervention (maximum of six months), and generally reported on a limited number of outcomes.We found seven studies with 2261 children comparing home-based RUTF meeting the World Health Organization (WHO) recommendations for nutritional composition (referred to in this review as standard RUTF) with an alternative dietary approach (effective sample size = 1964). RUTF probably improves recovery (risk ratio (RR) 1.33; 95% confidence interval (CI) 1.16 to 1.54; 6 studies, 1852 children; moderate-quality evidence), and may increase the rate of weight gain slightly (mean difference (MD) 1.12 g/kg/day, 95% CI 0.27 to 1.96; 4 studies, 1450 children; low-quality evidence), but we do not know the effects on relapse (RR 0.55, 95% CI 0.30 to 1.01; 4 studies, 1505 children; very low-quality evidence) and mortality (RR 1.05, 95% CI 0.51 to 2.16; 4 studies, 1505 children; very low-quality evidence).Two quasi-randomised cluster trials compared standard, home-based RUTF meeting total daily nutritional requirements with a similar RUTF but given as a supplement to the usual diet (213 children; effective sample size = 210). Meta-analysis showed that standard RUTF meeting total daily nutritional requirements may improve recovery (RR 1.41, 95% CI 1.19 to 1.68; low-quality evidence) and reduce relapse (RR 0.11, 95% CI 0.01 to 0.85; low-quality evidence), but the effects are unknown for mortality (RR 1.36, 95% CI 0.46 to 4.04; very low-quality evidence) and rate of weight gain (MD 1.21 g/kg/day, 95% CI - 0.74 to 3.16; very low-quality evidence).Eight studies randomised 5502 children (effective sample size = 4456) and compared standard home-based RUTF with RUTFs of alternative formulations (e.g. using locally available ingredients, containing less or no milk powder, containing specific fatty acids, or with added pre- and probiotics). For recovery, it made little or no difference whether standard or alternative formulation RUTF was used (RR 1.03, 95% CI 0.99 to 1.08; 6 studies, 4188 children; high-quality evidence). Standard RUTF decreases relapse (RR 0.84, 95% CI 0.72 to 0.98; 6 studies, 4188 children; high-quality evidence). However, it probably makes little or no difference to mortality (RR 1.00, 95% CI 0.80 to 1.24; 7 studies, 4309 children; moderate-quality evidence) and may make little or no difference to the rate of weight gain (MD 0.11 g/kg/day, 95% CI -0.32 to 0.54; 6 studies, 3807 children; low-quality evidence) whether standard or alternative formulation RUTF is used. AUTHORS' CONCLUSIONS: Compared to alternative dietary approaches, standard RUTF probably improves recovery and may increase rate of weight gain slightly, but the effects on relapse and mortality are unknown. Standard RUTF meeting total daily nutritional requirements may improve recovery and relapse compared to a similar RUTF given as a supplement to the usual diet, but the effects on mortality and rate of weight gain are not clear. When comparing RUTFs with different formulations, the current evidence does not favour a particular formulation, except for relapse, which is reduced with standard RUTF. Well-designed, adequately powered, pragmatic RCTs with standardised outcome measures, stratified by HIV status, and that include diarrhoea as an outcome, are needed.

Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference.

IMPORTANCE: Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs. OBJECTIVE: To develop a set of evidence-based recommendations for patient blood management (PBM) and for research. EVIDENCE REVIEW: The scientific committee developed 17 Population/Intervention/Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018. FINDINGS: From 17 607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23 143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration <7 g/dL) as well as for patients undergoing cardiac surgery (recommended threshold for RBC transfusion, hemoglobin concentration <7.5 g/dL). For implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and to use electronic decision support systems (both conditional recommendations) to improve appropriate RBC utilization. CONCLUSIONS AND RELEVANCE: The 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.

Using the behavior change wheel to identify barriers to and potential solutions for primary care clinical guideline use in four provinces in South Africa.

BACKGROUND: Clinical practice guidelines risk having little impact on healthcare if not effectively implemented. Theory informed, targeted implementation may maximise their impact. Our study explored barriers to and facilitators of guideline implementation and use by South African primary care nurses and allied healthcare workers in four provinces in South Africa. We also proposed interventions to address the issues identified. METHODS: We used qualitative research methods, comprising focus group discussions using semi-structured topic guides. Seven focus group discussions were conducted (48 providers) in four South African provinces (Eastern Cape, Western Cape, Kwazulu-Natal, Limpopo). Participants included mostly nurses, dieticians, dentists, and allied health practitioners, from primary care facilities in rural and peri-urban settings. The analysis proceeded in three phases. Firstly, two analysts conducted inductive thematic content analysis to develop themes of data. This was followed by fitting emergent themes to the Theoretical Domains Framework and finally to the associated Behaviour Change Wheel to identify relevant interventions. RESULTS: Participants are knowledgeable about guidelines, generally trust their credibility and are receptive and motivated to use them. Guidelines are seen by nurses to provide confidence and reassurance, as well as professional authority and independence where doctors are scarce. Barriers to guideline use include: inadequate systems for printed book distribution, insufficient and substandard photocopies, linguistic inappropriateness (e.g. complicated language, lack of summaries, unavailable in local languages), unsupportive auditing procedures, limited involvement of end-users in guideline development, and patchy training that may not filter back to all providers. Future aspirations identified include: improving the design features of guidelines, accessible places to find guidelines, making digitally-formatted versions available, more supplementary materials (e.g. posters) to support patient engagement, accessible clinical support following training, and in-facility training for all professional cadres to ensure fair access, similar levels of capability and interdisciplinary consistency. CONCLUSIONS: South African primary care nurses and allied health practitioners have high levels of motivation to use guidelines, but face many systemic barriers. We used the Behaviour Change Wheel to suggest relevant, implementable interventions addressing identified barriers. This theory-informed approach may improve clinical guideline implementation and impact healthcare for South Africa.

National stakeholders' perceptions of the processes that inform the development of national clinical practice guidelines for primary healthcare in South Africa.

BACKGROUND: There is increased international focus on improving the rigour of clinical practice guideline (CPG) development practices. However, few empirical studies on CPG development have been conducted in low- and middle-income countries. This paper explores national stakeholders' perceptions of processes informing CPG development for primary healthcare in South Africa, focusing on both their aspirations and views of what is actually occurring. METHODS: A qualitative study design was employed including individual interviews with 37 South African primary care CPG development role-players. Participants represented various disciplines, sectors and provinces. The data were analysed through thematic analysis and an interpretivist conceptual framework. RESULTS: Strongly reflecting current international standards, participants identified six 'aspirational' processes that they thought should inform South African CPG development, as follows: (1) evidence; (2) stakeholder consultation; (3) transparency; (4) management of interests; (5) communication/co-ordination between CPG development groups; and (6) fit-for-context. While perceptions of a transition towards more robust processes was common, CPG development was seen to face ongoing challenges with regards to all six aspirational processes. Many challenges were attributed to inadequate financial and human resources, which were perceived to hinder capacity to undertake the necessary methodological work, respond to stakeholders' feedback, and document and share decision-making processes. Challenges were also linked to a complex web of politics, power and interests. The CPG development arena was described as saturated with personal and financial interests, groups competing for authority over specific territories and unequal power dynamics which favour those with the time, resources and authority to make contributions. These were all perceived to affect efforts for transparency, collaboration and inclusivity in CPG development. CONCLUSION: While there is strong commitment amongst national stakeholders to advance CPG development processes, a mix of values, politics, power and capacity constraints pose significant challenges. Contrasting perspectives regarding managing interests and how best to adapt to within-country contexts requires further exploration. Dedicated resources for CPG development, standardised systems for managing conflicting interests, and the development of a political environment that fosters collaboration and more equitable inclusion within and between CPG development groups are needed. These initiatives may enhance CPG quality and acceptability, with associated positive impact on patient care.

Translating research into action: an international study of the role of research funders.

BACKGROUND: It is widely accepted that research can lead to improved health outcomes. However, translating research into meaningful impacts in peoples' lives requires actions that stretch well beyond those traditionally associated with knowledge creation. The research reported in this manuscript provides an international review of health research funders' efforts to encourage this process of research uptake, application and scaling, often referred to as knowledge translation. METHODS: We conducted web-site review, document review and key informant interviews to investigate knowledge translation at 26 research funding agencies. The sample comprises the regions of Australia, Europe and North America, and a diverse range of funder types, including biomedical, clinical, multi-health domain, philanthropic, public and private organisations. The data builds on a 2008 study by the authors with the same international sample, which permitted longitudinal trend analysis. RESULTS: Knowledge translation is an objective of growing significance for funders across each region studied. However, there is no clear international consensus or standard on how funders might support knowledge translation. We found that approaches and mechanisms vary across region and funder type. Strategically tailored funding opportunities (grants) are the most prevalent modality of support. The most common funder-driven strategy for knowledge translation within these grants is the linking of researchers to research users. Funders could not to provide empirical evidence to support the majority of the knowledge translation activities they encourage or undertake. CONCLUSIONS: Knowledge translation at a research funder relies on context. Accordingly, we suggest that the diversity of approaches uncovered in our research is fitting. We argue that evaluation of funding agency efforts to promote and/or support knowledge translation should be prioritised and actioned. It is paradoxical that funders' efforts to get evidence into practice are not themselves evidence based.

Exploring the Relationship Between Surgical Capacity and Output in Ghana: Current Capacity Assessments May Not Tell the Whole Story.

OBJECTIVE: Capacity assessments serve as surrogates for surgical output in low- and middle-income countries where detailed registers do not exist. The relationship between surgical capacity and output was evaluated in Ghana to determine whether a more critical interpretation of capacity assessment data is needed on which to base health systems strengthening initiatives. METHODS: A standardized surgical capacity assessment was performed at 37 hospitals nationwide using WHO guidelines; availability of 25 essential resources and capabilities was used to create a composite capacity score that ranged from 0 (no availability of essential resources) to 75 (constant availability) for each hospital. Data regarding the number of essential operations performed over 1 year, surgical specialties available, hospital beds, and functional operating rooms were also collected. The relationship between capacity and output was explored. RESULTS: The median surgical capacity score was 37 [interquartile range (IQR) 29-48; range 20-56]. The median number of essential operations per year was 1480 (IQR 736-1932) at first-level hospitals; 1545 operations (IQR 984-2452) at referral hospitals; and 11,757 operations (IQR 3769-21,256) at tertiary hospitals. Surgical capacity and output were not correlated (p > 0.05). CONCLUSIONS: Contrary to current understanding, surgical capacity assessments may not accurately reflect surgical output. To improve the validity of surgical capacity assessments and facilitate maximal use of available resources, other factors that influence output should also be considered, including demand-side factors; supply-side factors and process elements; and health administration and management factors.

Next generation clinical guidance for primary care in South Africa - credible, consistent and pragmatic.

BACKGROUND: Agreed international development standards underpin high quality de novo clinical practice guidelines (CPGs). There is however, no international consensus on how high quality CPGs should 'look'; or on whether high quality CPGs from one country can be viably implemented elsewhere. Writing de novo CPGs is generally resource-intensive and expensive, making this challenging in resource-poor environments. This paper proposes an alternative, efficient method of producing high quality CPGs in such circumstances, using existing CPGs layered by local knowledge, contexts and products. METHODS: We undertook a mixed methods case study in South African (SA) primary healthcare (PHC), building on findings from four independent studies. These comprised an overview of international CPG activities; a rapid literature review on international CPG development practices; critical appraisal of 16 purposively-sampled SA PHC CPGs; and additional interrogation of these CPGs regarding how, why and for whom, they had been produced, and how they 'looked'. RESULTS: Despite a common aim to improve SA PHC healthcare practices, the included CPGs had different, unclear and inconsistent production processes, terminology and evidence presentation styles. None aligned with international quality standards. However many included innovative succinct guidance for end-users (which we classified as evidence-based summary recommendations, patient management tools or protocols). We developed a three-tiered model, a checklist and a glossary of common terms, for more efficient future production of better quality, contextually-relevant, locally-implementable SA PHC CPGs. Tier 1 involves transparent synthesis of existing high quality CPG recommendations; Tier 2 reflects local expertise to layer Tier 1 evidence with local contexts; and Tier 3 comprises tailored locally-relevant end-user guidance. CONCLUSION: Our model could be relevant for any resource-poor environment. It should reduce effort and costs in finding and synthesising available research evidence, whilst efficiently focusing scant resources on contextually-relevant evidence-based guidance, and implementation.

Consumption of processed food dietary patterns in four African populations.

OBJECTIVE: To identify predominant dietary patterns in four African populations and examine their association with obesity. DESIGN: Cross-sectional study.Setting/SubjectsWe used data from the Africa/Harvard School of Public Health Partnership for Cohort Research and Training (PaCT) pilot study established to investigate the feasibility of a multi-country longitudinal study of non-communicable chronic disease in sub-Saharan Africa. We applied principal component analysis to dietary intake data collected from an FFQ developed for PaCT to ascertain dietary patterns in Tanzania, South Africa, and peri-urban and rural Uganda. The sample consisted of 444 women and 294 men. RESULTS: We identified two dietary patterns: the Mixed Diet pattern characterized by high intakes of unprocessed foods such as vegetables and fresh fish, but also cold cuts and refined grains; and the Processed Diet pattern characterized by high intakes of salad dressing, cold cuts and sweets. Women in the highest tertile of the Processed Diet pattern score were 3·00 times more likely to be overweight (95 % CI 1·66, 5·45; prevalence=74 %) and 4·24 times more likely to be obese (95 % CI 2·23, 8·05; prevalence=44 %) than women in this pattern's lowest tertile (both P<0·0001; prevalence=47 and 14 %, respectively). We found similarly strong associations in men. There was no association between the Mixed Diet pattern and overweight or obesity. CONCLUSIONS: We identified two major dietary patterns in several African populations, a Mixed Diet pattern and a Processed Diet pattern. The Processed Diet pattern was associated with obesity.

Interventions for treating tuberculous pericarditis.

BACKGROUND: Tuberculous pericarditis can impair the heart's function and cause death; long term, it can cause the membrane to fibrose and constrict causing heart failure. In addition to antituberculous chemotherapy, treatments include corticosteroids, drainage, and surgery. OBJECTIVES: To assess the effects of treatments for tuberculous pericarditis. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register (27 March 2017); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2017, Issue 2); MEDLINE (1966 to 27 March 2017); Embase (1974 to 27 March 2017); and LILACS (1982 to 27 March 2017). In addition we searched the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal using 'tuberculosis' and 'pericard*' as search terms on 27 March 2017. We searched ClinicalTrials.gov and contacted researchers in the field of tuberculous pericarditis. This is a new version of the original 2002 review. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-RCTs. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search outputs, evaluated study eligibility, assessed risk of bias, and extracted data; and we resolved any discrepancies by discussion and consensus. One trial assessed the effects of both corticosteroid and Mycobacterium indicus pranii treatment in a two-by-two factorial design; we excluded data from the group that received both interventions. We conducted fixed-effect meta-analysis and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Seven trials met the inclusion criteria; all were from sub-Saharan Africa and included 1959 participants, with 1051/1959 (54%) HIV-positive. All trials evaluated corticosteroids and one each evaluated colchicine, M. indicus pranii immunotherapy, and open surgical drainage. Four trials (1841 participants) were at low risk of bias, and three trials (118 participants) were at high risk of bias.In people who are not infected with HIV, corticosteroids may reduce deaths from all causes (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.09; 660 participants, 4 trials, low certainty evidence) and the need for repeat pericardiocentesis (RR 0.85, 95% CI 0.70 to 1.04; 492 participants, 2 trials, low certainty evidence). Corticosteroids probably reduce deaths from pericarditis (RR 0.39, 95% CI 0.19 to 0.80; 660 participants, 4 trials, moderate certainty evidence). However, we do not know whether or not corticosteroids have an effect on constriction or cancer among HIV-negative people (very low certainty evidence).In people living with HIV, only 19.9% (203/1959) were on antiretroviral drugs. Corticosteroids may reduce constriction (RR 0.55, 0.26 to 1.16; 575 participants, 3 trials, low certainty evidence). It is uncertain whether corticosteroids have an effect on all-cause death or cancer (very low certainty evidence); and may have little or no effect on repeat pericardiocentesis (RR 1.02, 0.89 to 1.18; 517 participants, 2 trials, low certainty evidence).For colchicine among people living with HIV, we found one small trial (33 participants) which had insufficient data to make any conclusions about any effects on death or constrictive pericarditis.Irrespective of HIV status, due to very low certainty evidence from one trial, it is uncertain whether adding M. indicus pranii immunotherapy to antituberculous drugs has an effect on any outcome.Open surgical drainage for effusion may reduce repeat pericardiocentesis In HIV-negative people (RR 0.23, 95% CI 0.07 to 0.76; 122 participants, 1 trial, low certainty evidence) but may make little or no difference to other outcomes. We did not find an eligible trial that assessed the effects of open surgical drainage in people living with HIV.The review authors found no eligible trials that examined the length of antituberculous treatment needed nor the effects of other adjunctive treatments for tuberculous pericarditis. AUTHORS' CONCLUSIONS: For HIV-negative patients, corticosteroids may reduce death. For HIV-positive patients not on antiretroviral drugs, corticosteroids may reduce constriction. For HIV-positive patients with good antiretroviral drug viral suppression, clinicians may consider the results from HIV-negative patients more relevant.Further research may help evaluate percutaneous drainage of the pericardium under local anaesthesia, the timing of pericardiectomy in tuberculous constrictive pericarditis, and new antibiotic regimens.

Primary care clinical practice guidelines in South Africa: qualitative study exploring perspectives of national stakeholders.

BACKGROUND: Clinical practice guidelines (CPGs) are common tools in policy and clinical practice informing clinical decisions at the bedside, governance of health facilities, health insurer and government spending, and patient choices. South Africa's health sector is transitioning to a national health insurance system, aiming to build on other primary health care initiatives to transform the previously segregated, inequitable services. Within these plans CPGs are an integral tool for delivering standardised and cost effective care. Currently, there is no accepted standard approach to developing, adapting or implementing CPGs efficiently or effectively in South Africa. We explored the current players; drivers; and the context and processes of primary care CPG development from the perspective of stakeholders operating at national level. METHODS: We used a qualitative approach. Sampling was initially purposeful, followed by snowballing and further sampling to reach representivity of primary care service providers. Individual in-depth interviews were recorded and transcribed verbatim. We used thematic content analysis to analyse the data. RESULTS: We conducted 37 in-depth interviews from June 2014-July 2015. We found CPG development and implementation were hampered by lack of human and funding resources for technical and methodological work; fragmentation between groups, and between national and provincial health sectors; and lack of agreed systems for CPG development and implementation. Some CPG contributors steadfastly work to improve processes aiming to enhance communication, use of evidence, and transparency to ensure credible guidance is produced. Many interviewed had shared values, and were driven to address inequity, however, resource gaps were perceived to create an enabling environment for commercial interests or personal agendas to drive the CPG development process. CONCLUSIONS: Our findings identified strengths and gaps in CPG development processes, and a need for national standards to guide CPG development and implementation. Based on our findings and suggestions from participants, a possible way forward would be for South Africa to have a centrally coordinated CPG unit to address these needs and aspects of fragmentation by devising processes that support collaboration, transparency and credibility across sectors and disciplines. Such an initiative will require adequate resourcing to build capacity and ensure support for the delivery of high quality CPGs for South African primary care.

Prevalence of chronic kidney disease and association with cardiovascular risk factors among teachers in Cape Town, South Africa.

Background: There is a need to determine the feasibility of conducting studies of chronic diseases among large cohorts of African patients. One aim of the South African feasibility study was to determine the prevalence of chronic kidney disease (CKD) and its association with cardiovascular disease (CVD) risk factors among school teachers. Methods: In a cross-sectional survey of 489 teachers we captured data on demographics, CVD risk factors, anthropometry and blood pressure. Serum glucose, creatinine, cholesterol and urine protein/creatinine ratio was measured. Glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease study equations. Results: The mean (± standard deviation) age of the participants was 46.3 ± 8.5 years, with 70.3% being female and 74.6% of mixed ethnicity. The crude prevalence of CKD using the CKD-EPI equation was 6.1% while the age-adjusted prevalence was 6.4% (95% confidence interval 3.2-9.7%). CKD was associated with the presence of diabetes and higher diastolic blood pressures. Conclusions: In our study population of relatively young, working individuals CKD was common, clinically silent and associated with cardiovascular risk factors. The long-term complications of CKD are serious and expensive to manage and this, therefore, constitutes an important public health problem for South Africa.

Scope and quality of Cochrane reviews of nutrition interventions: a cross-sectional study.

BACKGROUND: All countries face significant challenges from complex manifestations of malnutrition, which affects one in three people globally. Systematic reviews provide ready-to-use syntheses of quality-appraised evidence to inform decision-making for actions. To enhance the utility and quality of future Cochrane nutrition evidence, we described the scope and quality of all nutrition systematic reviews in the Cochrane Database of Systematic Reviews (CDSR). METHODS: We screened all active CDSR records (31 July 2015) to identify reviews and protocols using pre-specified eligibility criteria and definitions. Duplicate, independent data extraction included criteria for inclusion of studies in completed reviews (PICOS). We assessed methodological quality (AMSTAR), use of GRADE, mapped reviews against 2013 Global Burden of Disease data, and categorised the paradigm (medical, lifestyle and socio-ecological) of the review question. We analysed our results using descriptive statistics. RESULTS: We screened 8484 records, and included 470 (8%) completed reviews (in 45 Cochrane Review Groups (CRGs)) and 169 (7%) protocols (in 41 CRGs) published by 47 of 53 CRGs with reviews. Most completed reviews were produced by the Pregnancy and Childbirth (n = 73), Neonatal (n = 64), Metabolic and Endocrine Disorders (n = 33), Developmental, Psychosocial and Learning Problems (n = 26), Kidney and Transplant (n = 18) and Heart (n = 18) CRGs. Only 27% (n = 129) of reviews had searches for new studies in 2013 or thereafter. Supplementation/supplement interventions were most common (50%; n = 235; majority with micronutrients; 73%, n = 173), followed by food interventions (20%; n = 95). All reviews included randomised controlled trials; about 5% included other designs; 25% used GRADE; the median AMSTAR score was 9 (interquartile range: 7 to 10), 51% were high (AMSTAR 9-11) and 49% moderate (AMSTAR 5-8) quality. More than 80% framed questions using a medical paradigm. For top causes of years-of-life-lost, most reviews addressed preterm birth, diabetes and ischaemic heart disease; for leading risk factors for disability-adjusted-life-years, most targeted childhood undernutrition and high body mass index. CONCLUSIONS: Nutrition reviews comprised 8% of active CDSR records, were widely distributed across nearly all CRGs and reflected the double nutrition burden. This analysis presents a comprehensive description of the scope and quality of Cochrane nutrition reviews, and identifies gaps for future activities to support actions to address the nutrition burden, in line with the current nutrition agenda and impetus.