How Can Nutrition Research Better Reflect the Relationship Between Wasting and Stunting in Children? Learnings from the Wasting and Stunting Project.

Childhood wasting and stunting affect large numbers of children globally. Both are important risk factors for illness and death yet, despite the fact that these conditions can share common risk factors and are often seen in the same child, they are commonly portrayed as relatively distinct manifestations of undernutrition. In 2014, the Wasting and Stunting project was launched by the Emergency Nutrition Network. Its aim was to better understand the complex relationship and associations between wasting and stunting and examine whether current separations that were apparent in approaches to policy, financing, and programs were justified or useful. Based on the project's work, this article aims to bring a wasting and stunting lens to how research is designed and financed in order for the nutrition community to better understand, prevent, and treat child undernutrition. Discussion of lessons learnt focuses on the synergy and temporal relationships between children's weight loss and linear growth faltering, the proximal and distal factors that drive diverse forms of undernutrition, and identifying and targeting people most at risk. Supporting progress in all these areas requires research collaborations across interest groups that highlight the value of research that moves beyond a focus on single forms of undernutrition, and ensures that there is equal attention given to wasting as to other forms of malnutrition, wherever it is present.

Anthropometric criteria for best-identifying children at high risk of mortality: a pooled analysis of twelve cohorts.

OBJECTIVE: To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications. DESIGN: A multiple cohort individual data meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled. SETTING: Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread. PARTICIPANTS: Children aged 6 to 59 months. RESULTS: Of the twelve anthropometric case definitions examined, four (weight-for-age Z-score (WAZ) <-2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < -3) and (WAZ < -3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < -3) was better at predicting deaths associated with weight-for-height Z-score <-3 and concurrent wasting and stunting (WaSt) than the single WAZ < -3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < -3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone. CONCLUSIONS: A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.

Sensitivity to behavioral stress impacts disease pathogenesis in dystrophin-deficient mice.

Mutation to the gene encoding dystrophin can cause Duchenne muscular dystrophy (DMD) and increase the sensitivity to stress in vertebrate species, including the mdx mouse model of DMD. Behavioral stressors can exacerbate some dystrophinopathy phenotypes of mdx skeletal muscle and cause hypotension-induced death. However, we have discovered that a subpopulation of mdx mice present with a wildtype-like response to mild (forced downhill treadmill exercise) and moderate (scruff restraint) behavioral stressors. These "stress-resistant" mdx mice are more physically active, capable of super-activating the hypothalamic-pituitary-adrenal and renin-angiotensin-aldosterone pathways following behavioral stress and they express greater levels of mineralocorticoid and glucocorticoid receptors in striated muscle relative to "stress-sensitive" mdx mice. Stress-resistant mdx mice also presented with a less severe striated muscle histopathology and greater exercise and skeletal muscle oxidative capacity at rest. Most interestingly, female mdx mice were more physically active following behavioral stressors compared to male mdx mice; a response abolished after ovariectomy and rescued with estradiol. We demonstrate that the response to behavioral stress greatly impacts disease severity in mdx mice suggesting the management of stress in patients with DMD be considered as a therapeutic approach to ameliorate disease progression.

The relationship between wasting and stunting in young children: A systematic review.

In 2014, the Emergency Nutrition Network published a report on the relationship between wasting and stunting. We aim to review evidence generated since that review to better understand the implications for improving child nutrition, health and survival. We conducted a systematic review following PRISMA guidelines, registered with PROSPERO. We identified search terms that describe wasting and stunting and the relationship between the two. We included studies related to children under five from low- and middle-income countries that assessed both ponderal growth/wasting and linear growth/stunting and the association between the two. We included 45 studies. The review found the peak incidence of both wasting and stunting is between birth and 3 months. There is a strong association between the two conditions whereby episodes of wasting contribute to stunting and, to a lesser extent, stunting leads to wasting. Children with multiple anthropometric deficits, including concurrent stunting and wasting, have the highest risk of near-term mortality when compared with children with any one deficit alone. Furthermore, evidence suggests that the use of mid-upper-arm circumference combined with weight-for-age Z score might effectively identify children at most risk of near-term mortality. Wasting and stunting, driven by common factors, frequently occur in the same child, either simultaneously or at different moments through their life course. Evidence of a process of accumulation of nutritional deficits and increased risk of mortality over a child's life demonstrates the pressing need for integrated policy, financing and programmatic approaches to the prevention and treatment of child malnutrition.

Striated muscle activator of Rho signalling (STARS) overexpression in the mdx mouse enhances muscle functional capacity and regulates the actin cytoskeleton and oxidative phosphorylation pathways.

NEW FINDINGS: What is the central question of this study? Striated muscle activator of rho signalling (STARS) is an actin-binding protein that regulates transcriptional pathways controlling muscle function, growth and myogenesis, processes that are impaired in dystrophic muscle: what is the regulation of the STARS pathway in Duchenne muscular dystrophy (DMD)? What is the main finding and its importance? Members of the STARS signalling pathway are reduced in the quadriceps of patients with DMD and in mouse models of muscular dystrophy. Overexpression of STARS in the dystrophic deficient mdx mouse model increased maximal isometric specific force and upregulated members of the actin cytoskeleton and oxidative phosphorylation pathways. Regulating STARS may be a therapeutic approach to enhance muscle health. ABSTRACT: Duchenne muscular dystrophy (DMD) is characterised by impaired cytoskeleton organisation, cytosolic calcium handling, oxidative stress and mitochondrial dysfunction. This results in progressive muscle damage, wasting and weakness and premature death. The striated muscle activator of rho signalling (STARS) is an actin-binding protein that activates the myocardin-related transcription factor-A (MRTFA)/serum response factor (SRF) transcriptional pathway, a pathway regulating cytoskeletal structure and muscle function, growth and repair. We investigated the regulation of the STARS pathway in the quadriceps muscle from patients with DMD and in the tibialis anterior (TA) muscle from the dystrophin-deficient mdx and dko (utrophin and dystrophin null) mice. Protein levels of STARS, SRF and RHOA were reduced in patients with DMD. STARS, SRF and MRTFA mRNA levels were also decreased in DMD muscle, while Stars mRNA levels were decreased in the mdx mice and Srf and Mrtfa mRNAs decreased in the dko mice. Overexpressing human STARS (hSTARS) in the TA muscles of mdx mice increased maximal isometric specific force by 13% (P < 0.05). This was not associated with changes in muscle mass, fibre cross-sectional area, fibre type, centralised nuclei or collagen deposition. Proteomics screening followed by pathway enrichment analysis identified that hSTARS overexpression resulted in 31 upregulated and 22 downregulated proteins belonging to the actin cytoskeleton and oxidative phosphorylation pathways. These pathways are impaired in dystrophic muscle and regulate processes that are vital for muscle function. Increasing the STARS protein in dystrophic muscle improves muscle force production, potentially via synergistic regulation of cytoskeletal structure and energy production.

Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial.

BACKGROUND: The prevalence of anaemia and iron deficiency (ID) among children with severe acute malnutrition (SAM) and their correction during nutritional rehabilitation are not well documented. This study assessed anaemia and ID prevalence and their predictors at start of SAM treatment, and the efficacy of their treatment and effect on gut health of two novel Ready-To-Use Therapeutic foods (RUTF) prepared from soybean, maize and sorghum (SMS) with (MSMS-RUTF) or without added milk (FSMS-RUTF) compared to those of the standard formulation prepared from peanut and milk (PM-RUTF). METHODS: This was a 3-arms parallel groups, simple randomised, controlled non-inferiority trial in 6-59 months old Central Malawian children with SAM. Anaemia was defined using altitude- and ethnicity-adjusted haemoglobin. Iron status was defined using soluble transferrin receptor (sTfR) and body iron stores (BIS). We used Pearson's chi-square test, t-test for paired or unpaired data, Kruskal-Wallis test for between-arm differences as appropriate and logistic regression to identify independent predictors of anaemia or iron deficiency anaemia (IDA). RESULTS: The sample size was 389. At admission, the prevalence [%(95%CI)] of anaemia was 48.9(41.4-56.5)% while that of ID and IDA were 55.7(48.6-62.5)% and 34.3(28.2-41.0)% when using sTfR criterion and 29.1(24.4-34.4)% and 28.9(23.7-34.9)% when using BIS criterion, respectively. At discharge, nutrition rehabilitation with SMS-RUTF was associated with the lowest prevalence of anaemia [12.0(6.9-20.3)% for FSMS-RUTF, 18.2(11.9-26.8)% for MSMS-RUTF and 24.5(15.8-35.9)% for PM-RUTF; p = 0.023] and IDA [7.9(3.4-17.3)% for FSMS-RUTF, 10.9(4.8-22.6)% for MSMS-RUTF and 20.5(10.7-35.5)% for PM-RUTF; p = 0.028]. SMS-RUTF was also associated with the highest increase in BIS [Change in BIS (95%CI)] among the iron deplete at admission [6.2 (3.7; 8.6), 3.2 (0.8; 5.6), 2.2 (0.2; 4.3) for the same study arms; Anova p = 0.045]. Compared to P-RUTF, FSMS-RUTF had the highest adjusted recovery rate [OR (95%CI = 0.3 (0.2-0.5) with p < 0.001 for FSMS-RUTF and 0.6 (0.3-1.0) with p = 0.068 for MSMS-RUTF]. No effect of iron content on risk of iron overload or gut inflammation was observed. CONCLUSIONS: Anaemia and ID are common among children with SAM. FSMS-RUTF is more efficacious in treating anaemia and correcting BIS among this group than PM-RUTF. TRIAL REGISTRATION: This study was registered on 15 April 2015 ( PACTR201505001101224 ).

Efferent inhibition strength is a physiological correlate of hyperacusis in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is a developmental disability that is poorly understood. ASD can influence communication, social interaction, and behavior. Children with ASD often have sensory hypersensitivities, including auditory hypersensitivity (hyperacusis). In adults with hyperacusis who are otherwise neurotypical, the medial olivocochlear (MOC) efferent reflex is stronger than usual. In children with ASD, the MOC reflex has been measured, but without also assessing hyperacusis. We assessed the MOC reflex in children with ASD by measuring the strength of MOC-induced inhibition of transient-evoked otoacoustic emissions (TEOAEs), a noninvasive physiological measure that reflects cochlear amplification. MOC activity was evoked by contralateral noise. Hyperacusis was assessed subjectively on the basis of the children's symptoms. We found a significant correlation between hyperacusis scores and MOC strength in children with ASD. When children were divided into ASD-with-severe-hyperacusis (ASDs), ASD-with-not-severe-hyperacusis (ASDns), and neurotypical (NT) groups, the last two groups had similar hyperacusis and MOC reflexes, whereas the ASDs group, on average, had hyperacusis and MOC reflexes that were approximately twice as strong. The MOC inhibition of TEOAEs averaged larger at all frequencies in the ASDs compared with ASDns and NT groups. The results suggest that the MOC reflex can be used to estimate hyperacusis in children with ASD and might be used to validate future questionnaires to assess hyperacusis. Our results also provide evidence that strong MOC reflexes in children with ASD are associated with hyperacusis and that hyperacusis is a comorbid condition and is not a necessary, integral part of the abnormal neural processing associated with ASD.NEW & NOTEWORTHY Children with autism spectrum disorder (ASD) are a heterogeneous group, some with hyperacusis and some without. Our research shows that hyperacusis can be estimated in children with ASD by using medial olivocochlear (MOC) reflex measurements. By establishing that an objective measure correlates with attributes of hyperacusis, our results enable future work to enable subtyping of children with ASD to provide improved individualized treatments to at-risk children and those without adequate language to describe their hyperacusis symptoms.

'Sometimes they fail to keep their faith in us': community health worker perceptions of structural barriers to quality of care and community utilisation of services in Bangladesh.

Community health workers (CHWs) have strong potential to extend health and nutrition services to underserved populations. However, CHWs face complex challenges when working within weak health systems and among communities with limited abilities to access and utilise CHW services. It is crucial to understand these challenges to improve programme support mechanisms. This study describes the results of qualitative investigations into CHW perceptions of barriers to quality of care among two groups of workers implementing community case management of acute respiratory infection, diarrhoea and severe acute malnutrition in southern Bangladesh. We explored systemic barriers to service delivery, pertaining to communities and health systems, which limited the usefulness and effectiveness of CHW services. Focus group discussions (n = 10) were conducted in March 2010. Discussions were analysed for themes related to CHWs' work challenges. Findings highlight several perceived barriers to effective service provision, including community poverty constraining uptake of recommended practices, irregular supplies of medicine from the health facility and poor quality of care for CHW referrals sent there. This study further documents interactions between demand-side and supply-side constraints including the influence of health system resource constraints on community trust in CHW services, and the influence of community resource constraints on the utilisation and effectiveness of CHW services. By documenting service delivery challenges from the perspective of the frontline workers themselves, this article contributes evidence to help identify appropriate support mechanisms for these workers, in order to develop scalable and sustainable CHW programmes in countries with under-resourced public health care infrastructure.

Comparison of the effectiveness of a milk-free soy-maize-sorghum-based ready-to-use therapeutic food to standard ready-to-use therapeutic food with 25% milk in nutrition management of severely acutely malnourished Zambian children: an equivalence non-blinded cluster randomised controlled trial.

Community-based Management of Acute Malnutrition using ready-to-use therapeutic food (RUTF) has revolutionised the treatment of severe acute malnutrition (SAM). However, 25% milk content in standard peanut-based RUTF (P-RUTF) makes it too expensive. The effectiveness of milk-free RUTF has not been reported hitherto. This non-blinded, parallel group, cluster randomised, controlled, equivalence trial that compares the effectiveness of a milk-free soy-maize-sorghum-based RUTF (SMS-RUTF) with P-RUTF in treatment of children with SAM, closes the gap. A statistician randomly assigned health centres (HC) either to the SMS-RUTF (n = 12; 824 enrolled) or P-RUTF (n = 12; 1103 enrolled) arms. All SAM children admitted at the participating HCs were enrolled. All the outcomes were measured at individual level. Recovery rate was the primary outcome. The recovery rates for SMS-RUTF and P-RUTF were 53.3% and 60.8% for the intention-to-treat (ITT) analysis and 77.9% and 81.8% for per protocol (PP) analyses, respectively. The corresponding adjusted risk difference (ARD) and 95% confidence interval, were -7.6% (-14.9, 0.6%) and -3.5% (-9,6., 2.7%) for ITT (P = 0.034) and PP analyses (P = 0.257), respectively. An unanticipated interaction (interaction P < 0.001 for ITT analyses and 0.0683 for PP analyses) between the study arm and age group was observed. The ARDs were -10.0 (-17.7 to -2.3)% for ITT (P = 0.013) and -4.7 (-10.0 to 0.7) for PP (P = 0.083) analyses for the <24 months age group and 2.1 (-10.3,14.6)% for ITT (P = 0.726) and -0.6 (-16.1, 14.5) for PP (P = 0.939) for the ≥24 months age group. In conclusion, the study did not confirm our hypothesis of equivalence between SMS-RUTF and P-RUTF in SAM management.

Effectiveness of milk whey protein-based ready-to-use therapeutic food in treatment of severe acute malnutrition in Malawian under-5 children: a randomised, double-blind, controlled non-inferiority clinical trial.

The cost of ready-to-use therapeutic food (RUTF) used in community-based management of acute malnutrition has been a major obstacle to the scale up of this important child survival strategy. The current standard recipe for RUTF [peanut-based RUTF (P-RUTF)] is made from peanut paste, milk powder, oil, sugar, and minerals and vitamins. Milk powder forms about 30% of the ingredients and may represent over half the cost of the final product. The quality of whey protein concentrates 34% (WPC34) is similar to that of dried skimmed milk (DSM) used in the standard recipe and can be 25-33% cheaper. This blinded, parallel group, randomised, controlled non-inferiority clinical trial tested the effectiveness in treating severe acute malnutrition (SAM) of a new RUTF formulation WPC-RUTF in which WPC34 was used to replace DSM. Average weight gain (non-inferiority margin Δ = -1.2 g kg(-1) day(-1) ) and recovery rate (Δ = -10%) were the primary outcomes, and length of stay (LOS) was the secondary outcome (Δ = +14 days). Both per-protocol (PP) and intention-to-treat (ITT) analyses showed that WPC-RUTF was not inferior to P-RUTF for recovery rate [difference and its 95% confidence interval (CI) of 0.5% (95% CI -2.7, 3.7) in PP analysis and 0.6% (95% CI -5.2, 6.3) in ITT analysis] for average weight gain [0.2 (-0.5; 0.9) for both analyses] and LOS [-1.6 days (95% CI, -4.6, 1.4 days) in PP analysis and -1.9 days (95% CI, -4.6, 0.8 days) for ITT analysis]. In conclusion, whey protein-based RUTF is an effective cheaper alternative to the standard milk-based RUTF for the treatment of SAM.

Quality of care for severe acute malnutrition delivered by community health workers in southern Bangladesh.

This study assessed the quality of care provided by community health workers (CHWs) in managing cases of severe acute malnutrition (SAM) according to a treatment algorithm. A mixed methods approach was employed to provide perspectives on different aspects of quality of care, including technical competence and acceptability to caretakers. CHWs screened children at community level using a mid-upper arm circumference measurement, and treated cases without medical complications. Fifty-five case management observations were conducted using a quality of care checklist, with 89.1% (95% confidence interval: 77.8-95.9%) of CHWs achieving 90% error-free case management or higher. Caretakers perceived CHWs' services as acceptable and valuable, with doorstep delivery of services promoting early presentation in this remote area of Bangladesh. Integration of the treatment of SAM into community-based health and nutrition programs appears to be feasible and effective. In this setting, well-trained and supervised CHWs were able to effectively manage cases of SAM. These findings suggest the feasibility of further decentralization of treatment from current delivery models for community-based management of acute malnutrition.

Nutrition of School-Aged Children and Adolescents in Europe and Central Asia Region: A Literature and Survey Review.

BACKGROUND: Middle childhood and adolescence are critical times for the growth, development, and establishment of healthy eating habits. The Europe and Central Asia (ECA) region has been through economic and nutrition transitions over the past 20 years, which are likely to have affected the nutritional status of this group. OBJECTIVE: This review aimed to collate data on the nutritional status and dietary patterns of school-aged children (SAC) and adolescents (5-19 years) across the ECA region in order to inform policy and programming decisions. METHODS: A systematic search of the literature in Pubmed, Cochrane, and ScienceDirect databases was conducted (April 2019), complemented by a systematic review of nationally representative surveys. Inclusion criteria were any data on micronutrient deficiencies, overweight, stunting, wasting, thinness, or dietary patterns in SAC and adolescents in the 21 UNICEF-defined countries of ECA, published since the year 2000. RESULTS: Results included 134 published papers and 6 sources of survey data. The majority of studies were conducted in Turkey (56%), with all other countries having fewer than 10 studies each; 8 countries in the region having no studies on this age group at all. The most significant nutrition issue was overweight and obesity. Micronutrient deficiencies, particularly anemia, emerge as a further challenge. Dietary patterns were worse in urban areas and boys. CONCLUSIONS: The findings of this review suggest that there are 3 critical areas that need immediate attention: the promotion of healthy diets and physical activity to address high levels of overweight/obesity, anemia prevention efforts, and addressing the considerable data gaps for SAC and adolescent nutrition.

Growth and Body Composition 5 y After Treatment for Severe Acute Malnutrition: A 5-y Prospective Matched Cohort Study in Ethiopian Children.

BACKGROUND: Short-term anthropometric outcomes are well documented for children treated for severe acute malnutrition (SAM). However, anthropometric recovery may not indicate restoration of healthy body composition. OBJECTIVES: This study aimed to evaluate long-term associations of SAM with growth and body composition of children 5 y after discharge from community-based management of acute malnutrition (CMAM). METHODS: We conducted a 5-y prospective cohort study, enrolling children aged 6 to 59 mo discharged from CMAM (post-SAM) (n = 203) and nonmalnourished matched controls (n = 202) from Jimma Zone, Ethiopia in 2013. Anthropometry and body composition (bioelectrical impedance) were assessed. Multiple linear regression models tested differences in height-for-age (HAZ), weight-for-age (WAZ), and body mass index-for-age (BAZ) z-scores; height-adjusted fat-free mass index (FFMI); and FM index (FMI) between groups. RESULTS: Post-SAM children had higher stunting prevalence than controls at discharge (82.2% compared with 36.0%; P < 0.001), 1 y (80.2% compared with 53.7%; P < 0.001), and 5 y postdischarge (74.2% compared with 40.8%; P < 0.001). Post-SAM children remained 5 cm shorter throughout follow-up, indicating no HAZ catch-up. No catch-up in WAZ or BAZ was observed. Post-SAM children had lower hip (-2.05 cm; 95% CI: -2.73, -1.36), waist (-0.92 cm; CI: -1.59, -0.23) and mid-upper arm (-0.64 cm; CI: -0.90, -0.42) circumferences and lower-limb length (-1.57 cm; 95% CI: -2.21, -0.94) at 5 y postdischarge. They had larger waist-hip (0.02 cm; 95% CI: 0.008, 0.033) and waist-height (0.013 cm; 95% CI: 0.004, 0.021) ratios, and persistent deficits in FFMI at discharge and 6 mo and 5 y postdischarge (P < 0.001 for all). No difference was detected in head circumference, sitting height, or FMI. CONCLUSIONS: Five y after SAM treatment, children maintained deficits in HAZ, WAZ, BAZ, and FFMI, with preservation of FMI, sitting height, and head circumference at the expense of lower-limb length, indicating a "thrifty growth" pattern. Research is urgently needed to identify effective clinical and public health interventions to mitigate these consequences of malnutrition.

Does greater workload lead to reduced quality of preventive and curative care among community health workers in Bangladesh?

BACKGROUND: Community health workers (CHWs) perform a range of important tasks; however, limited evidence is available regarding the association between their workload and the quality of care they provide. OBJECTIVE: To analyze the quality of preventive and curative care provided by two groups of CHWs with different workloads in southern Bangladesh. METHODS: One group of CHWs provided preventive care in addition to implementing community case management (CCM) of acute respiratory infection and diarrhea, and another group additionally treated severe acute malnutrition (SAM). Preventive care was measured by case management observation at a routine household visit. Curative care was measured by case scenarios. Qualitative methods were used to contextualize CHWs' performance by examining their perceptions of challenges related to their workload. A total of 338 CHWs were assessed. RESULTS: CHWs managing cases of SAM worked significantly more hours than the other group (16.7 +/- 6.9 hours compared with 13.3 +/- 4.6 hours weekly, p < .001) but maintained quality of care on curative and preventive work tasks. Effectively treating cases of SAM appeared to motivate CHWs. CONCLUSIONS: This was one of the first trials adding the treatment of SAM to a CHW workload and suggests that adding SAM to a well-trained and supervised CHW's workload, including preventive and curative tasks, does not necessarily yield lower quality of care. However, increased workloads had consequences for CHWs' domestic life, and further increases in workload may not be possible without additional incentives.

Nutrition status and morbidity of Ethiopian children after recovery from severe acute malnutrition: Prospective matched cohort study.

After recovery, children with severe acute malnutrition (SAM) remain vulnerable to sub-optimal growth and malnutrition relapse. Although there is an increased interest in understanding these problems, data are scarce, and contextual factors can cause variability. We prospectively followed a cohort of Ethiopian children (215 post-SAM cases and 215 non-wasted controls), monthly for one year. The post-SAM cases were: age 6-59 months at admission into the community management of acute malnutrition (CMAM) program and being successfully discharged from CMAM (MUAC>11.0cm, weight gain of 20%, absence of oedema and clinically stable for two consecutive weeks). The controls were apparently healthy children from same village who had no history of an episode of AM and were matched 1:1 to a post-SAM child by age and sex. The primary outcomes were: cumulative incidence of acute malnutrition; growth trajectory; cumulative incidence of reported common morbidities, and cumulative proportion and incidence of deaths. The burden of common morbidities was higher among post-SAM than controls; post-SAM children had more frequent illness episodes (Incidence Rate Ratio of any illness 1.39, 95% CI: 1.14, 1.71; p<0.001). The prevalence of SAM was consistently higher among post-SAM cases than the control group, having a 14 times higher risk of developing SAM (Incidence Rate Ratio: 14.1; 95% CI: 3.5, 122.5; p<0.001). The divergence in weight and growth trajectory remained the same during the study period. Our results advocate for the design of post-discharge interventions that aim to prevent the reoccurrence of acute malnutrition, reduce morbidity and promote catch-up growth. Research is needed to define the appropriate package of post-discharge interventions.

Clinician education unlikely effective for guideline-adherent medication prescription in low back pain: systematic review and meta-analysis of RCTs.

BACKGROUND: Effectiveness of implementing interventions to optimise guideline-recommended medical prescription in low back pain is not well established. METHODS: A systematic review and random-effects meta-analyses for dichotomous outcomes with a Paule-Mandel estimator. Five databases and reference lists were searched from inception to 4th August 2021. Randomised controlled/clinical trials in adults with low back pain to optimise medication prescription were included. Cochrane Risk of Bias 2 tool and GRADE were implemented. The review was registered prospectively with PROSPERO (CRD42020219767). FINDINGS: Of 3352 unique records identified in the search, seven studies were included and five were eligible for meta-analysis (N=11339 participants). Six of seven studies incorporated clinician education, three studies included audit/feedback components and one study implemented changes in medical records systems. Via meta-analysis, we estimated a non-significant odds-ratio of 0·94 (95% CI (0·77; 1.16), I² = 0%; n=5 studies, GRADE: low) in favour of the intervention group. The main finding was robust to sensitivity analyses. INTERPRETATION: There is low quality evidence that existing interventions to optimise medication prescription or usage in back pain had no impact. Peer-to-peer education alone does not appear to lead to behaviour change. Organisational and policy interventions may be more effective. FUNDING: This work was supported by internal institutional funding only.

Attempting to Separate Placebo Effects from Exercise in Chronic Pain: A Systematic Review and Meta-analysis.

BACKGROUND: Pain is the most disabling characteristic of musculoskeletal disorders, and while exercise is promoted as an important treatment modality for chronic musculoskeletal conditions, the relative contribution of the specific effects of exercise training, placebo effects and non-specific effects such as natural history are not clear. The aim of this systematic review and meta-analysis was to determine the relative contribution of these factors to better understand the true effect of exercise training for reducing pain in chronic primary musculoskeletal pain conditions. DESIGN: Systematic review with meta-analysis DATA SOURCES: MEDLINE, CINAHL, SPORTDiscus, EMBASE and CENTRAL from inception to February 2021. Reference lists of prior systematic reviews. ELIGIBILITY CRITERIA: Randomised controlled trials of interventions that used exercise training compared to placebo, true control or usual care in adults with chronic primary musculoskeletal pain. The review was registered prospectively with PROSPERO (CRD42019141096). RESULTS: We identified 79 eligible trials for quantitative analysis. Pairwise meta-analysis showed very low-quality evidence (GRADE criteria) that exercise training was not more effective than placebo (g [95% CI]: 0.94 [- 0.17, 2.06], P = 0.098, I2 = 92.46%, studies: n = 4). Exercise training was more effective than true, no intervention controls (g [95% CI]: 0.99 [0.66, 1.32], P < 0.001, I2 = 92.43%, studies: n = 42), usual care controls (g [95% CI]: 0.64 [0.44, 0.83], P < 0.001, I2 = 76.52%, studies: n = 33), and when all controls combined (g [95% CI]: 0.84 [0.64, 1.04], P < 0.001, I2 = 90.02%, studies: n = 79). CONCLUSIONS: There is very low-quality evidence that exercise training is not more effective than non-exercise placebo treatments in chronic pain. Exercise training and the associated clinical encounter are more effective than true control or standard medical care for reductions in pain for adults with chronic musculoskeletal pain, with very low quality of evidence based on GRADE criteria.

Selection and use of US Title II food aid products in programming contexts.

BACKGROUND: Food aid provided by the United States has saved lives for almost two centuries. Delivering the right products is important, but of equal concern are the ways in which products are delivered and to whom. OBJECTIVE: The study addresses how food products are currently used, whether interventions are appropriate to achieve nutrition objectives, and whether nutrition targets could be met more cost-effectively with a different mix of products or programs. METHODS: The team conducted consultations with a broad range of stakeholders. A survey of Title II implementing partners was conducted, focusing on procurement and logistics, and uses of FBFs and other foods. Input of implementing partners, civil society, and donor organizations was obtained through individual consultations, international and small group meetings. More than 400 individuals accessed the project's website. The project convened a panel of experts in food technology and science, food policy, law, industry, medicine, development and humanitarian work, and the maritime industry, and held regular joint meetings with USDA and USAID. The draft report was widely disseminated and posted on the website. RESULTS AND CONCLUSIONS: There is wide variation in the quantities of fortified blended foods provided to target populations. Most of these foods are used in health/nutrition programs, but they are also used in general family rations or as an incentive or pay. Clearer programming guidance and improved decision tools are needed to match products to nutrition goals, and programs should consider delivering nutrients across a basket of commodities, not single products. The evidence base for the effectiveness and cost-effectiveness of specific foods and programs needs to be strengthened and should be supported by FFP Research is needed to provide guidance on nutrition support for HIV/AIDS. Additional investments are needed in effective behavior change communication.

Amino acid-enriched plant-based RUTF treatment was not inferior to peanut-milk RUTF treatment in restoring plasma amino acid levels among patients with oedematous or non-oedematous malnutrition.

Ready-to-use therapeutic food (RUTF) with adequate quality protein is used to treat children with oedematous and non-oedematous severe acute malnutrition (SAM). The plasma amino acid (AA) profile reflects the protein nutritional status; hence, its assessment during SAM treatment is useful in evaluating AA delivery from RUTFs. The objective was to evaluate the plasma AAs during the treatment of oedematous and non-oedematous SAM in community-based management of acute malnutrition (CMAM) using amino acid-enriched plant-based RUTFs with 10% milk (MSMS-RUTF) or without milk (FSMS-RUTF) compared to peanut milk RUTF (PM-RUTF). Plasma AA was measured in a non-blinded, 3-arm, parallel-group, simple randomized controlled trial conducted in Malawi. The RUTFs used for SAM were FSMS-RUTF, MSMS-RUTF or PM-RUTF. A non-inferiority hypothesis was tested to compare plasma AA levels from patients treated with FSMS-RUTF or MSMS-RUTF with those from patients treated with PM-RUTF at discharge. For both types of SAM, FSMS-RUTF and MSMS-RUTF treatments were non-inferior to the PM-RUTF treatment in restoration of the EAA and cystine except that for FSMS-RUTF, methionine and tryptophan partially satisfied the non-inferiority criteria in the oedematous group. Amino-acid-enriched milk-free plant-source-protein RUTF has the potential to restore all the EAA, but it is possible that enrichment with amino acids may require more methionine and tryptophan for oedematous children.

Response to Malnutrition Treatment in Low Weight-for-Age Children: Secondary Analyses of Children 6-59 Months in the ComPAS Cluster Randomized Controlled Trial.

Weight-for-age z-score (WAZ) is not currently an admission criterion to therapeutic feeding programs, and children with low WAZ at high risk of mortality may not be admitted. We conducted a secondary analysis of RCT data to assess response to treatment according to WAZ and mid-upper arm circumference (MUAC) and type of feeding protocol given: a simplified, combined protocol for severe and moderate acute malnutrition (SAM and MAM) vs. standard care that treats SAM and MAM, separately. Children with a moderately low MUAC (11.5-12.5 cm) and a severely low WAZ (<-3) respond similarly to treatment in terms of both weight and MUAC gain on either 2092 kJ (500 kcal)/day of therapeutic or supplementary food. Children with a severely low MUAC (<11.5 cm), with/without a severely low WAZ (<-3), have similar recovery with the combined protocol or standard treatment, though WAZ gain may be slower in the combined protocol. A limitation is this analysis was not powered for these sub-groups specifically. Adding WAZ < -3 as an admission criterion for therapeutic feeding programs admitting children with MUAC and/or oedema may help programs target high-risk children who can benefit from treatment. Future work should evaluate the optimal treatment protocol for children with a MUAC < 11.5 and/or WAZ < -3.0.