Efficacy and Safety of Propolis for Treating Recurrent Aphthous Stomatitis (RAS): A Systematic Review and Meta-Analysis.

The systematic review assessed the efficacy and safety of propolis for treating recurrent aphthous stomatitis (RAS). The review adopted the PICO framework to examine the effects of topical and systemic propolis on RAS while also comparing it to established treatments, placebos, or no treatment. The main focus was on the healing time, pain levels, adverse effects, the likelihood of ulcer recurrence, and accompanying symptoms such as redness. The team included randomised controlled trials (RCTs) and quasi-randomised trials, excluding case reports and studies on oral ulcers other than RAS. In May 2022, the review team comprehensively searched nine databases and trial registries following the PRISMA guidelines. The protocol was registered in the PROSPERO database under the registration number CRD42022327123. Two review authors conducted a comprehensive and autonomous search for pertinent papers and extracted essential data. Where data permitted, the team utilised Review Manager 5 to conduct a random-effects meta-analysis, assessing the risk of bias and heterogeneity of the included studies. Where possible, the GRADE Pro programme was used to assess the certainty of the evidence for all the outcomes. This review included 10 RCTs, comprising 825 participants aged between 18 and 69 years. Seven studies evaluated the efficacy and safety of propolis when applied topically, all of which used different formulations, concentrations, and carriers. The remaining three studies assessed systemic administration in tablet form. The duration of investigations ranged from 5 days to 3 years. The review team classified two studies as having an overall 'high risk' of bias, while the remaining studies were categorised as having an overall 'uncertain risk'. The overall certainty of the evidence was 'very low'. The results indicate that topical and systemic propolis may decrease the duration of healing, alleviate pain, and reduce redness in patients with RAS compared to a placebo. However, the certainty of the evidence is very low. These may be due to the high risk of bias, substantial heterogeneity, and limited sample sizes in the included studies. For these reasons, the results of this review should be interpreted with caution. Nevertheless, the limited number of adverse effects observed suggests that propolis may have a favourable safety profile when used for a short period in treating RAS.

Obesity intervention evidence synthesis: Where are the gaps and which should we address first?

Health professionals and policymakers rely on evidence synthesized from high quality research studies. Yet, there remain unanswered questions about how to prevent and treat obesity. In this research project, international practice guidelines and Cochrane systematic reviews were examined in order to identify gaps in the synthesized obesity intervention evidence base. One hundred and forty-two partial or complete gaps were found. Systematic review questions to address these gaps were formulated and subjected to a prioritization consultation process with 36 international obesity expert stakeholders. Forty-three review questions were priority-assessed. The top 10 ranked review questions received support from at least 75.0% of stakeholders. The leading questions focused on preventive and community-based approaches, including those delivered through primary-care. Children within the context of their families were a highly-prioritized target group, as were persons with diabetes or disabilities. Experts also prioritized reviews to determine which elements of programs are the most effective, and by which mode they are best delivered. Experts recommended that negative, psycho-social, and longer-term outcomes be captured in reviews. We request reviewers and funders to strongly consider addressing the top 10 leading prioritized review questions presented here.

Obesity as an independent risk factor for COVID-19 severity and mortality.

BACKGROUND: Since December 2019, the world has struggled with the COVID-19 pandemic. Even after the introduction of various vaccines, this disease still takes a considerable toll. In order to improve the optimal allocation of resources and communication of prognosis, healthcare providers and patients need an accurate understanding of factors (such as obesity) that are associated with a higher risk of adverse outcomes from the COVID-19 infection. OBJECTIVES: To evaluate obesity as an independent prognostic factor for COVID-19 severity and mortality among adult patients in whom infection with the COVID-19 virus is confirmed. SEARCH METHODS: MEDLINE, Embase, two COVID-19 reference collections, and four Chinese biomedical databases were searched up to April 2021. SELECTION CRITERIA: We included case-control, case-series, prospective and retrospective cohort studies, and secondary analyses of randomised controlled trials if they evaluated associations between obesity and COVID-19 adverse outcomes including mortality, mechanical ventilation, intensive care unit (ICU) admission, hospitalisation, severe COVID, and COVID pneumonia. Given our interest in ascertaining the independent association between obesity and these outcomes, we selected studies that adjusted for at least one factor other than obesity. Studies were evaluated for inclusion by two independent reviewers working in duplicate.  DATA COLLECTION AND ANALYSIS: Using standardised data extraction forms, we extracted relevant information from the included studies. When appropriate, we pooled the estimates of association across studies with the use of random-effects meta-analyses. The Quality in Prognostic Studies (QUIPS) tool provided the platform for assessing the risk of bias across each included study. In our main comparison, we conducted meta-analyses for each obesity class separately. We also meta-analysed unclassified obesity and obesity as a continuous variable (5 kg/m2 increase in BMI (body mass index)). We used the GRADE framework to rate our certainty in the importance of the association observed between obesity and each outcome. As obesity is closely associated with other comorbidities, we decided to prespecify the minimum adjustment set of variables including age, sex, diabetes, hypertension, and cardiovascular disease for subgroup analysis.  MAIN RESULTS: We identified 171 studies, 149 of which were included in meta-analyses.  As compared to 'normal' BMI (18.5 to 24.9 kg/m2) or patients without obesity, those with obesity classes I (BMI 30 to 35 kg/m2), and II (BMI 35 to 40 kg/m2) were not at increased odds for mortality (Class I: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.94 to 1.16, high certainty (15 studies, 335,209 participants); Class II: OR 1.16, 95% CI 0.99 to 1.36, high certainty (11 studies, 317,925 participants)). However, those with class III obesity (BMI 40 kg/m2 and above) may be at increased odds for mortality (Class III: OR 1.67, 95% CI 1.39 to 2.00, low certainty, (19 studies, 354,967 participants)) compared to normal BMI or patients without obesity. For mechanical ventilation, we observed increasing odds with higher classes of obesity in comparison to normal BMI or patients without obesity (class I: OR 1.38, 95% CI 1.20 to 1.59, 10 studies, 187,895 participants, moderate certainty; class II: OR 1.67, 95% CI 1.42 to 1.96, 6 studies, 171,149 participants, high certainty; class III: OR 2.17, 95% CI 1.59 to 2.97, 12 studies, 174,520 participants, high certainty). However, we did not observe a dose-response relationship across increasing obesity classifications for ICU admission and hospitalisation. AUTHORS' CONCLUSIONS: Our findings suggest that obesity is an important independent prognostic factor in the setting of COVID-19. Consideration of obesity may inform the optimal management and allocation of limited resources in the care of COVID-19 patients.

Replacing salt with low-sodium salt substitutes (LSSS) for cardiovascular health in adults, children and pregnant women.

BACKGROUND: Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium contribute to elevated blood pressure. The WHO recommends decreasing mean population sodium intake through effective and safe strategies to reduce hypertension and its associated disease burden. Incorporating low-sodium salt substitutes (LSSS) into population strategies has increasingly been recognised as a possible sodium reduction strategy, particularly in populations where a substantial proportion of overall sodium intake comes from discretionary salt. The LSSS contain lower concentrations of sodium through its displacement with potassium predominantly, or other minerals. Potassium-containing LSSS can potentially simultaneously decrease sodium intake and increase potassium intake.  Benefits of LSSS include their potential blood pressure-lowering effect and relatively low cost. However, there are concerns about potential adverse effects of LSSS, such as hyperkalaemia, particularly in people at risk, for example, those with chronic kidney disease (CKD) or taking medications that impair potassium excretion. OBJECTIVES: To assess the effects and safety of replacing salt with LSSS to reduce sodium intake on cardiovascular health in adults, pregnant women and children. SEARCH METHODS: We searched MEDLINE (PubMed), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 18 August 2021, and screened reference lists of included trials and relevant systematic reviews. No language or publication restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and prospective analytical cohort studies in participants of any age in the general population, from any setting in any country. This included participants with non-communicable diseases and those taking medications that impair potassium excretion. Studies had to compare any type and method of implementation of LSSS with the use of regular salt, or no active intervention, at an individual, household or community level, for any duration. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-text articles to determine eligibility; and extracted data, assessed risk of bias (RoB) using the Cochrane RoB tool, and assessed the certainty of the evidence using GRADE. We stratified analyses by adults, children (≤ 18 years) and pregnant women. Primary effectiveness outcomes were change in diastolic and systolic blood pressure (DBP and SBP), hypertension and blood pressure control; cardiovascular events and cardiovascular mortality were additionally assessed as primary effectiveness outcomes in adults. Primary safety outcomes were change in blood potassium, hyperkalaemia and hypokalaemia. MAIN RESULTS: We included 26 RCTs, 16 randomising individual participants and 10 randomising clusters (families, households or villages). A total of 34,961 adult participants and 92 children were randomised to either LSSS or regular salt, with the smallest trial including 10 and the largest including 20,995 participants. No studies in pregnant women were identified. Studies included only participants with hypertension (11/26), normal blood pressure (1/26), pre-hypertension (1/26), or participants with and without hypertension (11/26). This was unknown in the remaining studies. The largest study included only participants with an elevated risk of stroke at baseline. Seven studies included adult participants possibly at risk of hyperkalaemia. All 26 trials specifically excluded participants in whom an increased potassium intake is known to be potentially harmful. The majority of trials were conducted in rural or suburban settings, with more than half (14/26) conducted in low- and middle-income countries. The proportion of sodium chloride replacement in the LSSS interventions varied from approximately 3% to 77%. The majority of trials (23/26) investigated LSSS where potassium-containing salts were used to substitute sodium. In most trials, LSSS implementation was discretionary (22/26). Trial duration ranged from two months to nearly five years.  We assessed the overall risk of bias as high in six trials and unclear in 12 trials. LSSS compared to regular salt in adults: LSSS compared to regular salt probably reduce DBP on average (mean difference (MD) -2.43 mmHg, 95% confidence interval (CI) -3.50 to -1.36; 20,830 participants, 19 RCTs, moderate-certainty evidence) and SBP (MD -4.76 mmHg, 95% CI -6.01 to -3.50; 21,414 participants, 20 RCTs, moderate-certainty evidence) slightly.  On average, LSSS probably reduce non-fatal stroke (absolute effect (AE) 20 fewer/100,000 person-years, 95% CI -40 to 2; 21,250 participants, 3 RCTs, moderate-certainty evidence), non-fatal acute coronary syndrome (AE 150 fewer/100,000 person-years, 95% CI -250 to -30; 20,995 participants, 1 RCT, moderate-certainty evidence) and cardiovascular mortality (AE 180 fewer/100,000 person-years, 95% CI -310 to 0; 23,200 participants, 3 RCTs, moderate-certainty evidence) slightly, and probably increase blood potassium slightly (MD 0.12 mmol/L, 95% CI 0.07 to 0.18; 784 participants, 6 RCTs, moderate-certainty evidence), compared to regular salt.  LSSS may result in little to no difference, on average, in hypertension (AE 17 fewer/1000, 95% CI -58 to 17; 2566 participants, 1 RCT, low-certainty evidence) and hyperkalaemia (AE 4 more/100,000, 95% CI -47 to 121; 22,849 participants, 5 RCTs, moderate-certainty evidence) compared to regular salt. The evidence is very uncertain about the effects of LSSS on blood pressure control, various cardiovascular events, stroke mortality, hypokalaemia, and other adverse events (very-low certainty evidence). LSSS compared to regular salt in children: The evidence is very uncertain about the effects of LSSS on DBP and SBP in children. We found no evidence about the effects of LSSS on hypertension, blood pressure control, blood potassium, hyperkalaemia and hypokalaemia in children. AUTHORS' CONCLUSIONS: When compared to regular salt, LSSS probably reduce blood pressure, non-fatal cardiovascular events and cardiovascular mortality slightly in adults. However, LSSS also probably increase blood potassium slightly in adults. These small effects may be important when LSSS interventions are implemented at the population level. Evidence is limited for adults without elevated blood pressure, and there is a lack of evidence in pregnant women and people in whom an increased potassium intake is known to be potentially harmful, limiting conclusions on the safety of LSSS in the general population. We also cannot draw firm conclusions about effects of non-discretionary LSSS implementations. The evidence is very uncertain about the effects of LSSS on blood pressure in children.

Hypoglycaemia due to insulin therapy for the management of hyperkalaemia in hospitalised adults: A scoping review.

INTRODUCTION: Hyperkalaemia is a very common electrolyte disorder encountered in hospitalised patients. Although hypoglycaemia is a frequent complication of insulin therapy, it is often under-appreciated. We conducted a scoping review of this important complication, and of other adverse effects, of the treatment of hyperkalaemia in hospitalised adults to map existing research on this topic and to identify any knowledge gaps. MATERIALS AND METHODS: We followed the PRISMA-ScR guidelines. Studies were eligible for inclusion if they reported on any adverse effects in hospitalised patients ≥18-years-old, with hyperkalaemia receiving treatment that included insulin. All eligible research from 1980 to 12 October 2021 were included. We searched Medline (PubMed), Embase (Ovid), the Cochrane Library, CINHAL, Africa-Wide Information, Web of Science Core Collection, LILACS and Epistemonikos. The protocol was prospectively registered with the Open Science Framework (https://osf.io/x8cs9). RESULTS: Sixty-two articles were included. The prevalence of hypoglycaemia by any definition was 17.2% (95% CI 16.6-17.8%). The median timing of hypoglycaemia was 124 minutes after insulin administration (IQR 102-168 minutes). There were no differences in the prevalence of hypoglycaemia when comparing insulin dose (<10 units vs. ≥10 units), rate of insulin administration (continuous vs. bolus), type of insulin (regular vs. short-acting) or timing of insulin administration relative to dextrose. However, lower insulin doses were associated with a reduced prevalence of severe hypoglycaemia (3.5% vs. 5.9%, P = 0.02). There was no difference regarding prevalence of hypoglycaemia by dextrose dose (≤25 g vs. >25 g); however, prevalence was lower when dextrose was administered as a continuous infusion compared with bolus administration (3.3% vs. 19.5%, P = 0.02). The most common predictor of hypoglycaemia was the pre-treatment serum glucose concentration (n = 13 studies), which ranged from < 5.6-7.8 mmol/L. CONCLUSION: This is the first comprehensive review of the adverse effects following insulin therapy for hyperkalaemia. Hypoglycaemia remains a common adverse effect in hospitalised adults. Future randomised trials should focus on identifying the optimal regimen of insulin therapy to mitigate the risk of hypoglycaemia.

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.

Cochrane corner: community-level interventions to increase access to food in low- and middle-income countries.

Food insecurity and hunger is a continuing problem in Africa, with access to food being critical to address it. Community-level interventions may help to increase access to food, specifically, nutritious food. We highlight a Cochrane review that assessed community level interventions aiming to increase access to nutritious food in low- and middle-income countries (LMICs), including those that improve buying power, address food prices, and the social environment. Randomised controlled trials and prospective controlled studies that assessed the effects of these interventions on food security and nutritional status were included, providing relevant implications for practice in LMICs. Findings suggest that unconditional cash transfers (UCTs) are important for improving food security, and that UCTs and food vouchers may increase dietary diversity and reduce stunting. This highlights the importance of current programmes in Africa, the need to reflect and refine where needed, and expand their capacity. A holistic approach to address food insecurity in the region.

Publication practices of sub-Saharan African Cochrane authors: a bibliometric study.

INTRODUCTION: Cochrane Africa (https://africa.cochrane.org/) aims to increase Cochrane reviews addressing high priority questions in sub-Saharan Africa (SSA). Researchers residing in SSA, despite often drawing on Cochrane methods, training or resources, conduct and publish systematic reviews outside of Cochrane. Our objective was to investigate the extent to which Cochrane authors from SSA publish Cochrane and non-Cochrane reviews. METHODS: We conducted a bibliometric study of systematic reviews and overviews of systematic reviews from SSA, first by identifying SSA Cochrane authors, then retrieving their first and last author systematic reviews and overviews from PubMed (2008 to April 2019) and using descriptive analyses to investigate the country of origin, types of reviews and trends in publishing Cochrane and non-Cochrane systematic reviews over time. To be eligible, a review had to have predetermined objectives, eligibility criteria, at least two databases searched, data extraction, quality assessment and a first or last author with a SSA affiliation. RESULTS: We identified 657 Cochrane authors and 757 eligible systematic reviews. Most authors were from South Africa (n=332; 51%), followed by Nigeria (n=126; 19%). Three-quarters of the reviews (71%) were systematic reviews of interventions. The intervention reviews were more likely to be Cochrane reviews (60.3% vs 39.7%). Conversely, the overviews (23.8% vs 76.2%), qualitative reviews (14.8% vs 85.2%), diagnostic test accuracy reviews (16.1% vs 83.9%) and the 'other' reviews (11.1% vs 88.9%) were more likely to be non-Cochrane reviews. During the study period, the number of non-Cochrane reviews increased more than the number of Cochrane reviews. About a quarter of the reviews covered infectious disease topics. CONCLUSION: Cochrane authors from SSA are increasingly publishing a diverse variety of systematic reviews and overviews of systematic reviews, often opting for non-Cochrane journals.

Pine bark (Pinus spp.) extract for treating chronic disorders.

BACKGROUND: Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review. OBJECTIVES: To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders. SEARCH METHODS: We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress. MAIN RESULTS: This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV1) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV1 % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events. AUTHORS' CONCLUSIONS: Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.

Community-level interventions for improving access to food in low- and middle-income countries.

BACKGROUND: After decades of decline since 2005, the global prevalence of undernourishment reverted and since 2015 has increased to levels seen in 2010 to 2011. The prevalence is highest in low- and middle-income countries (LMICs), especially Africa and Asia. Food insecurity and associated undernutrition detrimentally affect health and socioeconomic development in the short and long term, for individuals, including children, and societies. Physical and economic access to food is crucial to ensure food security. Community-level interventions could be important to increase access to food in LMICs. OBJECTIVES: To determine the effects of community-level interventions that aim to improve access to nutritious food in LMICs, for both the whole community and for disadvantaged or at-risk individuals or groups within a community, such as infants, children and women; elderly, poor or unemployed people; or minority groups. SEARCH METHODS: We searched for relevant studies in 16 electronic databases, including trial registries, from 1980 to September 2019, and updated the searches in six key databases in February 2020. We applied no language or publication status limits. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster randomised controlled trials (cRCTs) and prospective controlled studies (PCS). All population groups, adults and children, living in communities in LMICs exposed to community-level interventions aiming to improve food access were eligible for inclusion. We excluded studies that only included participants with specific diseases or conditions (e.g. severely malnourished children). Eligible interventions were broadly categorised into those that improved buying power (e.g. create income-generation opportunities, cash transfer schemes); addressed food prices (e.g. vouchers and subsidies); addressed infrastructure and transport that affected physical access to food outlets; addressed the social environment and provided social support (e.g. social support from family, neighbours or government). DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts, and full texts of potentially eligible records, against the inclusion criteria. Disagreements were resolved through discussion or arbitration by a third author, if necessary. For each included study, two authors independently extracted data and a third author arbitrated disagreements. However, the outcome data were extracted by one author and checked by a biostatistician. We assessed risk of bias for all studies using the Effective Practice and Organization of Care (EPOC) risk of bias tool for studies with a separate control group. We conducted meta-analyses if there was a minimum of two studies for interventions within the same category, reporting the same outcome measure and these were sufficiently homogeneous. Where we were able to meta-analyse, we used the random-effects model to incorporate any existing heterogeneity. Where we were unable to conduct meta-analyses, we synthesised using vote counting based on effect direction. MAIN RESULTS: We included 59 studies, including 214 to 169,485 participants, and 300 to 124, 644 households, mostly from Africa and Latin America, addressing the following six intervention types (three studies assessed two different types of interventions). Interventions that improved buying power: Unconditional cash transfers (UCTs) (16 cRCTs, two RCTs, three PCSs): we found high-certainty evidence that UCTs improve food security and make little or no difference to cognitive function and development and low-certainty evidence that UCTs may increase dietary diversity and may reduce stunting. The evidence was very uncertain about the effects of UCTs on the proportion of household expenditure on food, and on wasting. Regarding adverse outcomes, evidence from one trial indicates that UCTs reduce the proportion of infants who are overweight. Conditional cash transfers (CCTs) (nine cRCTs, five PCSs): we found high-certainty evidence that CCTs result in little to no difference in the proportion of household expenditure on food and that they slightly improve cognitive function in children; moderate-certainty evidence that CCTs probably slightly improve dietary diversity and low-certainty evidence that they may make little to no difference to stunting or wasting. Evidence on adverse outcomes (two PCSs) shows that CCTs make no difference to the proportion of overweight children. Income generation interventions (six cRCTs, 11 PCSs): we found moderate-certainty evidence that income generation interventions probably make little or no difference to stunting or wasting; and low-certainty evidence that they may result in little to no difference to food security or that they may improve dietary diversity in children, but not for households. Interventions that addressed food prices: Food vouchers (three cRCTs, one RCT): we found moderate-certainty evidence that food vouchers probably reduce stunting; and low-certainty evidence that that they may improve dietary diversity slightly, and may result in little to no difference in wasting. Food and nutrition subsidies (one cRCT, three PCSs): we found low-certainty evidence that food and nutrition subsidies may improve dietary diversity among school children. The evidence is very uncertain about the effects on household expenditure on healthy foods as a proportion of total expenditure on food (very low-certainty evidence). Interventions that addressed the social environment: Social support interventions (one cRCT, one PCS): we found moderate-certainty evidence that community grants probably make little or no difference to wasting; low-certainty evidence that they may make little or no difference to stunting. The evidence is very uncertain about the effects of village savings and loans on food security and dietary diversity. None of the included studies addressed the intervention category of infrastructure changes. In addition, none of the studies reported on one of the primary outcomes of this review, namely prevalence of undernourishment. AUTHORS' CONCLUSIONS: The body of evidence indicates that UCTs can improve food security. Income generation interventions do not seem to make a difference for food security, but the evidence is unclear for the other interventions. CCTs, UCTs, interventions that help generate income, interventions that help minimise impact of food prices through food vouchers and subsidies can potentially improve dietary diversity. UCTs and food vouchers may have a potential impact on reducing stunting, but CCTs, income generation interventions or social environment interventions do not seem to make a difference on wasting or stunting. CCTs seem to positively impact cognitive function and development, but not UCTs, which may be due to school attendance, healthcare visits and other conditionalities associated with CCTs.

Community-level interventions for improving access to food in low- and middle-income countries.

BACKGROUND: After decades of decline since 2005, the global prevalence of undernourishment reverted and since 2015 has increased to levels seen in 2010 to 2011. The prevalence is highest in low- and middle-income countries (LMICs), especially Africa and Asia. Food insecurity and associated undernutrition detrimentally affect health and socioeconomic development in the short and long term, for individuals, including children, and societies. Physical and economic access to food is crucial to ensure food security. Community-level interventions could be important to increase access to food in LMICs. OBJECTIVES: To determine the effects of community-level interventions that aim to improve access to nutritious food in LMICs, for both the whole community and for disadvantaged or at-risk individuals or groups within a community, such as infants, children and women; elderly, poor or unemployed people; or minority groups. SEARCH METHODS: We searched for relevant studies in 16 electronic databases, including trial registries, from 1980 to September 2019, and updated the searches in six key databases in February 2020. We applied no language or publication status limits. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster randomised controlled trials (cRCTs) and prospective controlled studies (PCS). All population groups, adults and children, living in communities in LMICs exposed to community-level interventions aiming to improve food access were eligible for inclusion. We excluded studies that only included participants with specific diseases or conditions (e.g. severely malnourished children). Eligible interventions were broadly categorised into those that improved buying power (e.g. create income-generation opportunities, cash transfer schemes); addressed food prices (e.g. vouchers and subsidies); addressed infrastructure and transport that affected physical access to food outlets; addressed the social environment and provided social support (e.g. social support from family, neighbours or government). DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts, and full texts of potentially eligible records, against the inclusion criteria. Disagreements were resolved through discussion or arbitration by a third author, if necessary. For each included study, two authors independently extracted data and a third author arbitrated disagreements. However, the outcome data were extracted by one author and checked by a biostatistician. We assessed risk of bias for all studies using the Effective Practice and Organization of Care (EPOC) risk of bias tool for studies with a separate control group. We conducted meta-analyses if there was a minimum of two studies for interventions within the same category, reporting the same outcome measure and these were sufficiently homogeneous. Where we were able to meta-analyse, we used the random-effects model to incorporate any existing heterogeneity. Where we were unable to conduct meta-analyses, we synthesised using vote counting based on effect direction. MAIN RESULTS: We included 59 studies, including 214 to 169,485 participants, and 300 to 124, 644 households, mostly from Africa and Latin America, addressing the following six intervention types (three studies assessed two different types of interventions). Interventions that improved buying power: Unconditional cash transfers (UCTs) (16 cRCTs, two RCTs, three PCSs): we found high-certainty evidence that UCTs improve food security and make little or no difference to cognitive function and development and low-certainty evidence that UCTs may increase dietary diversity and may reduce stunting. The evidence was very uncertain about the effects of UCTs on the proportion of household expenditure on food, and on wasting. Regarding adverse outcomes, evidence from one trial indicates that UCTs reduce the proportion of infants who are overweight. Conditional cash transfers (CCTs) (nine cRCTs, five PCSs): we found high-certainty evidence that CCTs result in little to no difference in the proportion of household expenditure on food and that they slightly improve cognitive function in children; moderate-certainty evidence that CCTs probably slightly improve dietary diversity and low-certainty evidence that they may make little to no difference to stunting or wasting. Evidence on adverse outcomes (two PCSs) shows that CCTs make no difference to the proportion of overweight children. Income generation interventions (six cRCTs, 11 PCSs): we found moderate-certainty evidence that income generation interventions probably make little or no difference to stunting or wasting; and low-certainty evidence that they may result in little to no difference to food security or that they may improve dietary diversity in children, but not for households. Interventions that addressed food prices: Food vouchers (three cRCTs, one RCT): we found moderate-certainty evidence that food vouchers probably reduce stunting; and low-certainty evidence that that they may improve dietary diversity slightly, and may result in little to no difference in wasting. Food and nutrition subsidies (one cRCT, three PCSs): we found low-certainty evidence that food and nutrition subsidies may improve dietary diversity among school children. The evidence is very uncertain about the effects on household expenditure on healthy foods as a proportion of total expenditure on food (very low-certainty evidence). Interventions that addressed the social environment: Social support interventions (one cRCT, one PCS): we found moderate-certainty evidence that community grants probably make little or no difference to wasting; low-certainty evidence that they may make little or no difference to stunting. The evidence is very uncertain about the effects of village savings and loans on food security and dietary diversity. None of the included studies addressed the intervention category of infrastructure changes. In addition, none of the studies reported on one of the primary outcomes of this review, namely prevalence of undernourishment. AUTHORS' CONCLUSIONS: The body of evidence indicates that UCTs can improve food security. Income generation interventions do not seem to make a difference for food security, but the evidence is unclear for the other interventions. CCTs, UCTs, interventions that help generate income, interventions that help minimise impact of food prices through food vouchers and subsidies can potentially improve dietary diversity. UCTs and food vouchers may have a potential impact on reducing stunting, but CCTs, income generation interventions or social environment interventions do not seem to make a difference on wasting or stunting. CCTs seem to positively impact cognitive function and development, but not UCTs, which may be due to school attendance, healthcare visits and other conditionalities associated with CCTs.

Agricultural and nutritional education interventions for reducing aflatoxin exposure to improve infant and child growth in low- and middle-income countries.

BACKGROUND: Aflatoxins are carcinogenic mycotoxins that contaminate many food crops. Maize and groundnuts are prone to aflatoxin contamination, and are the major sources of human exposure to aflatoxins, due to their high intake as staple foods, particularly in low- and middle-income countries (LMICs). Observational studies suggest an association between dietary exposure to aflatoxins during pregnancy and early childhood and linear growth in infants and young children. OBJECTIVES: To assess the effects on pre- and postnatal growth outcomes when agricultural and nutritional education interventions during the post-harvest period that aim to reduce aflatoxin exposure are compared to usual support or no intervention. We assessed this in infants, children, and pregnant and lactating women at the household or community level in LMICs. SEARCH METHODS: In July and August 2019, we searched: CENTRAL, MEDLINE, Embase, CINAHL, Web of Science Core Collection, Africa-Wide, LILACS, CAB Abstracts, Agricola, and two trials registers. We also checked the bibliographies of the included studies and contacted relevant mycotoxin organisations and researchers for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-RCTs of agricultural education and nutritional education interventions of any duration, at the household or community level, aimed at reducing aflatoxin intake by infants, children, and pregnant and lactating women, in LMICs during the post-harvest period, compared to no intervention or usual support. We excluded studies that followed participants for less than four weeks. We assessed prespecified prenatal (at birth) and postnatal growth outcomes (during infancy, childhood, and adolescence), with linear growth (as the primary outcome), infectious disease morbidity, and unintended consequences. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility using prespecified criteria, extracted data, and assessed risk of bias of included RCTs. We evaluated the certainty of the evidence using GRADE, and presented the main results in a 'Summary of findings' table. MAIN RESULTS: We included three recent cluster-RCTs reporting the effects of agricultural education plus post-harvest technologies, compared to usual agricultural support or no intervention. The participants were pregnant women and their children, lactating women and their infants (< 6 months), women of childbearing age, and young children (< 59 months), from rural, subsistence maize-farming communities in Kenya, Zimbabwe, and Tanzania. Two trials randomised villages to the intervention and control groups, including a total of at least 979 mother-child pairs from 60 villages. The third trial randomised 420 households, including 189 mother-child pairs and 231 women of childbearing age. Duration of the intervention and follow-up ranged between five and nine months. Due to risk of attrition bias, the overall risk of bias was unclear in one trial, and high in the other two trials. None of the included studies addressed the effects of nutritional education on pre- and postnatal growth. One trial reported outcomes not prespecified in our review, and we were unable to obtain unpublished growth data from the second trial, even after contacting the authors. The third trial, in lactating women and their infants in Tanzania, reported on the infants' weight-for-age z-score (WAZ) after six months. This trial found that providing agricultural education aimed at changing farmers' post-harvest practices to reduce aflatoxin exposure, by using demonstrations (e.g. handsorting, de-hulling of maize, drying sheets, and insecticides), may improve WAZ in infants from these farmers' households, on average, by 0.57 (95% confidence interval (CI) 0.16 to 0.98; 1 study; 249 participants; very low-certainty evidence), compared to infants from households where the farmers received routine agricultural extension services. Another way of reporting the effect on WAZ is to compare the proportion of underweight infants (WAZ > 2 SD below the reference median value) per group. This trial found that the intervention may reduce the proportion of underweight infants in the intervention households by 6.7% (95% CI -12.6 to -1.4; 249 participants; very low-certainty evidence) compared to control households. No studies reported on unintended effects of agricultural and nutritional education. AUTHORS' CONCLUSIONS: Evidence on the effects on child growth in LMICs of agricultural or nutritional education interventions that reduce aflatoxin exposure was very limited; no included study reported on linear growth. Very low-certainty evidence suggested that agricultural education aimed at changing farmers' post-harvest practices to reduce aflatoxin exposure by using demonstrations, may result in an increase in WAZ, when compared to usual or no education.

Caregiver involvement in interventions for improving children's dietary intake and physical activity behaviors.

BACKGROUND: Poor diet and insufficient physical activity are major risk factors for non-communicable diseases. Developing healthy diet and physical activity behaviors early in life is important as these behaviors track between childhood and adulthood. Parents and other adult caregivers have important influences on children's health behaviors, but whether their involvement in children's nutrition and physical activity interventions contributes to intervention effectiveness is not known. OBJECTIVES: • To assess effects of caregiver involvement in interventions for improving children's dietary intake and physical activity behaviors, including those intended to prevent overweight and obesity • To describe intervention content and behavior change techniques employed, drawing from a behavior change technique taxonomy developed and advanced by Abraham, Michie, and colleagues (Abraham 2008; Michie 2011; Michie 2013; Michie 2015) • To identify content and techniques related to reported outcomes when such information was reported in included studies SEARCH METHODS: In January 2019, we searched CENTRAL, MEDLINE, Embase, 11 other databases, and three trials registers. We also searched the references lists of relevant reports and systematic reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of interventions to improve children's dietary intake or physical activity behavior, or both, with children aged 2 to 18 years as active participants and at least one component involving caregivers versus the same interventions but without the caregiver component(s). We excluded interventions meant as treatment or targeting children with pre-existing conditions, as well as caregiver-child units residing in orphanages and school hostel environments. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures outlined by Cochrane. MAIN RESULTS: We included 23 trials with approximately 12,192 children in eligible intervention arms. With the exception of two studies, all were conducted in high-income countries, with more than half performed in North America. Most studies were school-based and involved the addition of healthy eating or physical education classes, or both, sometimes in tandem with other changes to the school environment. The specific intervention strategies used were not always reported completely. However, based on available reports, the behavior change techniques used most commonly in the child-only arm were "shaping knowledge," "comparison of behavior," "feedback and monitoring," and "repetition and substitution." In the child + caregiver arm, the strategies used most commonly included additional "shaping knowledge" or "feedback and monitoring" techniques, as well as "social support" and "natural consequences." We considered all trials to be at high risk of bias for at least one design factor. Seven trials did not contribute any data to analyses. The quality of reporting of intervention content varied between studies, and there was limited scope for meta-analysis. Both validated and non-validated instruments were used to measure outcomes of interest. Outcomes measured and reported differed between studies, with 16 studies contributing data to the meta-analyses. About three-quarters of studies reported their funding sources; no studies reported industry funding. We assessed the quality of evidence to be low or very low. Dietary behavior change interventions with a caregiver component versus interventions without a caregiver component Seven studies compared dietary behavior change interventions with and without a caregiver component. At the end of the intervention, we did not detect a difference between intervention arms in children's percentage of total energy intake from saturated fat (mean difference [MD] -0.42%, 95% confidence interval [CI] -1.25 to 0.41, 1 study, n = 207; low-quality evidence) or from sodium intake (MD -0.12 g/d, 95% CI -0.36 to 0.12, 1 study, n = 207; low-quality evidence). No trial in this comparison reported data for children's combined fruit and vegetable intake, sugar-sweetened beverage (SSB) intake, or physical activity levels, nor for adverse effects of interventions. Physical activity interventions with a caregiver component versus interventions without a caregiver component Six studies compared physical activity interventions with and without a caregiver component. At the end of the intervention, we did not detect a difference between intervention arms in children's total physical activity (MD 0.20 min/h, 95% CI -1.19 to 1.59, 1 study, n = 54; low-quality evidence) or moderate to vigorous physical activity (MVPA) (standard mean difference [SMD] 0.04, 95% CI -0.41 to 0.49, 2 studies, n = 80; moderate-quality evidence). No trial in this comparison reported data for percentage of children's total energy intake from saturated fat, sodium intake, fruit and vegetable intake, or SSB intake, nor for adverse effects of interventions. Combined dietary and physical activity interventions with a caregiver component versus interventions without a caregiver component Ten studies compared dietary and physical activity interventions with and without a caregiver component. At the end of the intervention, we detected a small positive impact of a caregiver component on children's SSB intake (SMD -0.28, 95% CI -0.44 to -0.12, 3 studies, n = 651; moderate-quality evidence). We did not detect a difference between intervention arms in children's percentage of total energy intake from saturated fat (MD 0.06%, 95% CI -0.67 to 0.80, 2 studies, n = 216; very low-quality evidence), sodium intake (MD 35.94 mg/d, 95% CI -322.60 to 394.47, 2 studies, n = 315; very low-quality evidence), fruit and vegetable intake (MD 0.38 servings/d, 95% CI -0.51 to 1.27, 1 study, n = 134; very low-quality evidence), total physical activity (MD 1.81 min/d, 95% CI -15.18 to 18.80, 2 studies, n = 573; low-quality evidence), or MVPA (MD -0.05 min/d, 95% CI -18.57 to 18.47, 1 study, n = 622; very low-quality evidence). One trial indicated that no adverse events were reported by study participants but did not provide data. AUTHORS' CONCLUSIONS: Current evidence is insufficient to support the inclusion of caregiver involvement in interventions to improve children's dietary intake or physical activity behavior, or both. For most outcomes, the quality of the evidence is adversely impacted by the small number of studies with available data, limited effective sample sizes, risk of bias, and imprecision. To establish the value of caregiver involvement, additional studies measuring clinically important outcomes using valid and reliable measures, employing appropriate design and power, and following established reporting guidelines are needed, as is evidence on how such interventions might contribute to health equity.

Priority setting for new systematic reviews: processes and lessons learned in three regions in Africa.

Priority setting to identify topical and context relevant questions for systematic reviews involves an explicit, iterative and inclusive process. In resource-constrained settings of low-income and middle-income countries, priority setting for health related research activities ensures efficient use of resources. In this paper, we critically reflect on the approaches and specific processes adopted across three regions of Africa, present some of the outcomes and share the lessons learnt while carrying out these activities. Priority setting for new systematic reviews was conducted between 2016 and 2018 across three regions in Africa. Different approaches were used: Multimodal approach (Central Africa), Modified Delphi approach (West Africa) and Multilevel stakeholder discussion (Southern-Eastern Africa). Several questions that can feed into systematic reviews have emerged from these activities. We have learnt that collaborative subregional efforts using an integrative approach can effectively lead to the identification of region specific priorities. Systematic review workshops including discussion about the role and value of reviews to inform policy and research agendas were a useful part of the engagements. This may also enable relevant stakeholders to contribute towards the priority setting process in meaningful ways. However, certain shared challenges were identified, including that emerging priorities may be overlooked due to differences in burden of disease data and differences in language can hinder effective participation by stakeholders. We found that face-to-face contact is crucial for success and follow-up engagement with stakeholders is critical in driving acceptance of the findings and planning future progress.

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.

Effects of total fat intake on bodyweight in children.

BACKGROUND: As part of efforts to prevent childhood overweight and obesity, we need to understand the relationship between total fat intake and body fatness in generally healthy children. OBJECTIVES: To assess the effects and associations of total fat intake on measures of weight and body fatness in children and young people not aiming to lose weight. SEARCH METHODS: For this update we revised the previous search strategy and ran it over all years in the Cochrane Library, MEDLINE (Ovid), MEDLINE (PubMed), and Embase (Ovid) (current to 23 May 2017). No language and publication status limits were applied. We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing and unpublished studies (5 June 2017). SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children aged 24 months to 18 years, with or without risk factors for cardiovascular disease, randomised to a lower fat (30% or less of total energy (TE)) versus usual or moderate-fat diet (greater than 30%TE), without the intention to reduce weight, and assessed a measure of weight or body fatness after at least six months. We included prospective cohort studies if they related baseline total fat intake to weight or body fatness at least 12 months later. DATA COLLECTION AND ANALYSIS: We extracted data on participants, interventions or exposures, controls and outcomes, and trial or cohort quality characteristics, as well as data on potential effect modifiers, and assessed risk of bias for all included studies. We extracted body weight and blood lipid levels outcomes at six months, six to 12 months, one to two years, two to five years and more than five years for RCTs; and for cohort studies, at baseline to one year, one to two years, two to five years, five to 10 years and more than 10 years. We planned to perform random-effects meta-analyses with relevant subgrouping, and sensitivity and funnel plot analyses where data allowed. MAIN RESULTS: We included 24 studies comprising three parallel-group RCTs (n = 1054 randomised) and 21 prospective analytical cohort studies (about 25,059 children completed). Twenty-three studies were conducted in high-income countries. No meta-analyses were possible, since only one RCT reported the same outcome at each time point range for all outcomes, and cohort studies were too heterogeneous to combine.Effects of dietary counselling to reduce total fat intake from RCTsTwo studies recruited children aged between 4 and 11 years and a third recruited children aged 12 to 13 years. Interventions were combinations of individual and group counselling, and education sessions in clinics, schools and homes, delivered by dieticians, nutritionists, behaviourists or trained, supervised teachers. Concerns about imprecision and poor reporting limited our confidence in our findings. In addition, the inclusion of hypercholesteraemic children in two trials raised concerns about applicability.One study of dietary counselling to lower total fat intake found that the intervention may make little or no difference to weight compared with usual diet at 12 months (mean difference (MD) -0.50 kg, 95% confidence interval (CI) -1.78 to 0.78; n = 620; low-quality evidence) and at three years (MD -0.60 kg, 95% CI -2.39 to 1.19; n = 612; low-quality evidence). Education delivered as a classroom curriculum probably decreased BMI in children at 17 months (MD -1.5 kg/m2, 95% CI -2.45 to -0.55; 1 RCT; n = 191; moderate-quality evidence). The effects were smaller at longer term follow-up (five years: MD 0 kg/m2, 95% CI -0.63 to 0.63; n = 541; seven years; MD -0.10 kg/m2, 95% CI -0.75 to 0.55; n = 576; low-quality evidence).Dietary counselling probably slightly reduced total cholesterol at 12 months compared to controls (MD -0.15 mmol/L, 95% CI -0.24 to -0.06; 1 RCT; n = 618; moderate-quality evidence), but may make little or no difference over longer time periods. Dietary counselling probably slightly decreased low-density lipoprotein (LDL) cholesterol at 12 months (MD -0.12 mmol/L, 95% CI -0.20 to -0.04; 1 RCT; n = 618, moderate-quality evidence) and at five years (MD -0.09, 95% CI -0.17 to -0.01; 1 RCT; n = 623; moderate-quality evidence), compared to controls. Dietary counselling probably made little or no difference to HDL-C at 12 months (MD -0.03 mmol/L, 95% CI -0.08 to 0.02; 1 RCT; n = 618; moderate-quality evidence), and at five years (MD -0.01 mmol/L, 95% CI -0.06 to 0.04; 1 RCT; n = 522; moderate-quality evidence). Likewise, counselling probably made little or no difference to triglycerides in children at 12 months (MD -0.01 mmol/L, 95% CI -0.08 to 0.06; 1 RCT; n = 618; moderate-quality evidence). Lower versus usual or modified fat intake may make little or no difference to height at seven years (MD -0.60 cm, 95% CI -2.06 to 0.86; 1 RCT; n = 577; low-quality evidence).Associations between total fat intake, weight and body fatness from cohort studiesOver half the cohort analyses that reported on primary outcomes suggested that as total fat intake increases, body fatness measures may move in the same direction. However, heterogeneous methods and reporting across cohort studies, and predominantly very low-quality evidence, made it difficult to draw firm conclusions and true relationships may be substantially different. AUTHORS' CONCLUSIONS: We were unable to reach firm conclusions. Limited evidence from three trials that randomised children to dietary counselling or education to lower total fat intake (30% or less TE) versus usual or modified fat intake, but with no intention to reduce weight, showed small reductions in body mass index, total- and LDL-cholesterol at some time points with lower fat intake compared to controls. There were no consistent effects on weight, high-density lipoprotein (HDL) cholesterol or height. Associations in cohort studies that related total fat intake to later measures of body fatness in children were inconsistent and the quality of this evidence was mostly very low. Most studies were conducted in high-income countries, and may not be applicable in low- and middle-income settings. High-quality, longer-term studies are needed, that include low- and middle-income settings to look at both possible benefits and harms.

Effects of total fat intake on bodyweight in children.

BACKGROUND: As part of efforts to prevent childhood overweight and obesity, we need to understand the relationship between total fat intake and body fatness in generally healthy children. OBJECTIVES: To assess the effects of total fat intake on measures of weight and body fatness in children and young people not aiming to lose weight. SEARCH METHODS: For this update we revised the previous search strategy and ran it over all years in the Cochrane Library, MEDLINE (Ovid), MEDLINE (PubMed), and Embase (Ovid) (current to 23 May 2017). No language and publication status limits were applied. We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing and unpublished studies (5 June 2017). SELECTION CRITERIA: We included randomised controlled trials (RCTs) in children aged 24 months to 18 years, with or without risk factors for cardiovascular disease, randomised to a lower fat (30% or less of total energy (TE)) versus usual or moderate-fat diet (greater than 30%TE), without the intention to reduce weight, and assessed a measure of weight or body fatness after at least six months. We included prospective analytical cohort studies in these children if they related baseline total fat intake to weight or body fatness at least 12 months later. We duplicated inclusion decisions and resolved disagreement by discussion with other authors. DATA COLLECTION AND ANALYSIS: We extracted data on participants, interventions or exposures, controls and outcomes, and trial or cohort quality characteristics, as well as data on potential effect modifiers, and assessed risk of bias for all included studies. We extracted outcome data using the following time point ranges, when available: RCTs: baseline to six months, six to 12 months, one to two years, two to five years and more than five years; cohort studies: baseline to one year, one to two years, two to five years, five to 10 years and more than 10 years. We planned to perform random-effects meta-analyses with relevant subgrouping, and sensitivity and funnel plot analyses where data allowed. MAIN RESULTS: We included 24 studies comprising three parallel-group RCTs (n = 1054 randomised) and 21 prospective analytical cohort studies (about 25,059 children completed). Twenty-three were conducted in high-income countries. No meta-analyses were possible, since only one RCT reported the same outcome at each time point range for all outcomes, and cohort studies were too heterogeneous.For the RCTs, concerns about imprecision and poor reporting limited our confidence in our findings. In addition, the inclusion of hypercholesteraemic children in two trials raised concerns about applicability. Lower versus usual or modified total fat intake may have made little or no difference to weight over a six- to twelve month period (mean difference (MD) -0.50 kg, 95% confidence interval (CI) -1.78 to 0.78; 1 RCT; n = 620; low-quality evidence), nor a two- to five-year period (MD -0.60 kg, 95% CI -2.39 to 1.19; 1 RCT; n = 612; low-quality evidence). Compared to controls, lower total fat intake (30% or less TE) probably decreased BMI in children over a one- to two-year period (MD -1.5 kg/m2, 95% CI -2.45 to -0.55; 1 RCT; n = 191; moderate-quality evidence), with no other differences evident across the other time points (two to five years: MD 0.00 kg/m2, 95% CI -0.63 to 0.63; 1 RCT; n = 541; greater than five years; MD -0.10 kg/m2, 95% CI -0.75 to 0.55; 1 RCT; n = 576; low-quality evidence). Lower fat intake probably slightly reduced total cholesterol over six to 12 months compared to controls (MD -0.15 mmol/L, 95% CI -0.24 to -0.06; 1 RCT; n = 618; moderate-quality evidence), but may make little or no difference over longer time periods. Lower fat intake probably slightly decreased low-density lipoprotein (LDL) cholesterol over six to 12 months (MD -0.12 mmol/L, 95% CI -0.20 to -0.04; 1 RCT; n = 618, moderate-quality evidence) and over two to five years (MD -0.09, 95% CI -0.17 to -0.01; 1 RCT; n = 623; moderate-quality evidence), compared to controls. However, lower total fat intake probably made little or no difference to HDL-C over a six- to 12-month period (MD -0.03 mmol/L, 95% CI -0.08 to 0.02; 1 RCT; n = 618; moderate-quality evidence), nor a two- to five-year period (MD -0.01 mmol/L, 95% CI -0.06 to 0.04; 1 RCT; n = 522; moderate-quality evidence). Likewise, lower total fat intake probably made little or no difference to triglycerides in children over a six- to 12-month period (MD -0.01 mmol/L, 95% CI -0.08 to 0.06; 1 RCT; n = 618; moderate-quality evidence). Lower versus usual or modified fat intake may make little or no difference to height over more than five years (MD -0.60 cm, 95% CI -2.06 to 0.86; 1 RCT; n = 577; low-quality evidence).Over half the cohort analyses that reported on primary outcomes suggested that as total fat intake increases, body fatness measures may move in the same direction. However, heterogeneous methods and reporting across cohort studies, and predominantly very low-quality evidence, made it difficult to draw firm conclusions and true relationships may be substantially different. AUTHORS' CONCLUSIONS: We were unable to reach firm conclusions. Limited evidence from three trials that randomised children to a lower total fat intake (30% or less TE) versus usual or modified fat intake, but with no intention to reduce weight, showed small reductions in body mass index, total- and LDL-cholesterol at some time points with lower fat intake compared to controls, and no consistent differences in effects on weight, high-density lipoprotein (HDL) cholesterol or height. Associations in cohort studies that related total fat intake to later measures of body fatness in children were inconsistent and the quality of this evidence was mostly very low. Twenty-three out of 24 included studies were conducted in high-income countries, and may not be applicable in low- and middle-income settings. High-quality, longer-term studies are needed, that include low- and middle-income settings and look at both possible benefits and risks.

Evaluating evidence-based health care teaching and learning in the undergraduate human nutrition; occupational therapy; physiotherapy; and speech, language and hearing therapy programs at a sub-Saharan African academic institution.

BACKGROUND: It is important that all undergraduate healthcare students are equipped with evidence-based health care (EBHC) knowledge and skills to encourage evidence-informed decision-making after graduation. We assessed EBHC teaching and learning in undergraduate human nutrition (HN); occupational therapy (OT); physiotherapy (PT); and speech, language and hearing therapy (SPLH) programs at a sub-Saharan African university. METHODS: We used methodological triangulation to obtain a comprehensive understanding of EBHC teaching and learning: (1) through a document review of module guides, we identified learning outcomes related to pre-specified EBHC competencies; we conducted (2) focus group discussions and interviews of lecturers to obtain their perspectives on EBHC and on EBHC teaching and learning; and we (3) invited final year students (2013) and 2012 graduates to complete an online survey on EBHC attitudes, self-perceived EBHC competence, and their experience of EBHC teaching and learning. RESULTS: We reviewed all module outlines (n = 89) from HN, PT and SLHT. The OT curriculum was being revised at that time and could not be included. Six lecturers each from HN and OT, and five lecturers each from PT and SLHT participated in the focus groups. Thirty percent (53/176) of invited students responded to the survey. EBHC competencies were addressed to varying degrees in the four programs, although EBHC teaching and learning mostly occurred implicitly. Learning outcomes referring to EBHC focused on enabling competencies (e.g., critical thinking, biostatistics, epidemiology) and were concentrated in theoretical modules. Key competencies (e.g., asking questions, searching databases, critical appraisal) were rarely addressed explicitly. Students felt that EBHC learning should be integrated throughout the four year study period to allow for repetition, consolidation and application of knowledge and skills. Lecturers highlighted several challenges to teaching and practising EBHC, including lack of evidence relevant to the African context and lack of time within curricula.

Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis.

BACKGROUND: Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases METHODS: We searched four electronic databases, four conference proceedings and two clinical trial registries in August 2014, without language restrictions. Experimental and observational studies with control groups that examined the efficacy and safety of abacavir-containing regimens in comparison with other NRTIs as first-line treatment for HIV-infected children and adolescents aged between one month and eighteen years were eligible. Two authors independently screened search results, extracted data and assessed the risk of bias of included studies using a pre-specified, standardised data extraction form and validated risk of bias tools. We also assessed the quality of evidence per outcome with the GRADE tool. RESULTS: We included two randomised controlled trials (RCTs) and two analytical cohort studies with a total of 10,595 participants. Among the RCTs we detected no difference in virologic suppression after a mean duration of 48 weeks between abacavir- and stavudine-containing regimens (2 trials; n = 326: RR 1.28; 95 % CI 0.67-2.42) with significant heterogeneity (P = 0.02; I(2) = 81 %). We also found no significant differences between the two groups for adverse events and death. After five years of follow-up, virologic suppression improved with abacavir (1 trial; n = 69: RR 1.96; 95 % CI 1.11-3.44). For cohort studies, we detected that the virologic suppression activity of abacavir was less effective than stavudine in both the lopinavir/ritonavir (1 study, n = 2165: RR 0.79, 95 % CI 0.67-0.92) and efavirenz sub-groups (1 study, n = 3204: RR 0.79, 95 % CI 0.67-0.92) respectively. The quality of evidence from RCTs was moderate for virologic suppression but low for death and adverse events, while that of cohort studies was low for all three these outcomes. CONCLUSIONS: Available evidence showed little or no difference between abacavir-containing regimen and other NRTIs regarding efficacy and safety when given to children and adolescents as a first-line antiretroviral therapy.