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Abstract 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)

Abstract 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.

Abstract 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.

Summary: 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.

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

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

Abstract 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

Abstract Objective To compare levels of immunity in children recovering from severe acute malnutrition (cases) against those of community controls (controls). Results At baseline children recovering from severe acute malnutrition had lower, mid upper arm circumference (122 mm for cases and 135 mm for controls; p

MicroRNAs (miRNAs) undergo high levels of regulation in skeletal muscle development and control skeletal muscle mass, function and metabolism over the lifespan. More recently, the role of long non-coding RNAs (lncRNAs) in skeletal muscle regulation has started to emerge. Following up on our recent study describing the expression pattern and putative roles of 768 miRNAs in the quadriceps muscle of mice at early life stages, we used a high-throughput miRNA qPCR-based array to assess the expression of the same miRNAs in 28-month old male mouse quadriceps muscle. In addition, we report the expression patterns of lncRNAs playing a putative role in muscle development and adaptation from growth to old age. Twelve miRNAs were significantly downregulated in 28-month old muscle when compared with 12-week old muscle. Ten of them clustered at the Dlk1-Dio3 locus, known as ‘Callipyge,’ which is associated with muscle development and hypertrophy. This collective downregulation was paralleled by decreases in the expression levels of the maternally expressed imprinted LncRNA coding genes Meg3 and Rian stemming from the same chromosomal region. In contrast, the paternally expressed imprinted Dlk1-Dio3 locus members Rtl1, Dio3, and Dlk1 and the muscle related lncRNAs lncMyoD1, Neat_v1, Neat_v2, and Malat1 underwent significant changes during growth, but their expression levels were not altered past the age of 12 weeks, suggesting roles limited to hyperplasia and early hypertrophy. In conclusion, collective muscle miRNA expression gradually decreases over the lifespan and a cluster of miRNAs and maternally expressed lncRNAs stemming from the Callipyge locus is significantly dysregulated in aging muscle. The Dlk1-Dio3 locus therefore represents a potential new mechanism for age-related muscle decline.

BACKGROUND:Ready-to-use therapeutic food (RUTF) is used to treat children suffering from severe acute malnutrition (SAM). Standard RUTF uses milk as the primary protein source, which makes the product expensive, and given the high worldwide SAM burden, having a less expensive effective alternative is a public health priority. OBJECTIVE:The objective of this study was to evaluate whether newly developed amino acid-enriched milk-free RUTF (FSMS-RUTF) or amino acid-enriched low-milk RUTF (MSMS-RUTF) treatment could replenish plasma amino acids to levels comparable to those following standard peanut-milk RUTF (PM-RUTF) treatment and to improve understanding of the effects of treatment on anthropometric measurements. A secondary analysis was performed to test the noninferiority hypothesis of plasma essential amino acid (EAA) levels. METHODS:Plasma EAA levels were measured in a nonblinded, 3-arm, parallel-group simple randomized controlled trial conducted in Malawi to examine the efficacy of FSMS-RUTF, MSMS-RUTF and PM-RUTF in the treatment of SAM in 2 groups of children aged 6-23 and 24-59 months (mo). Sample size calculations were performed based on the previous our study. A noninferiority margin was set at -25% of the PM-RUTF arm at discharge. RESULTS:The relative values of the differences (95% CI) in plasma EAA levels between PM-RUTF treatment and FSMS-RUTF and MSMS-RUTF treatments at discharge were -7.9% (-18.6, 2.8) and 9.8% (0.2, 19.5), respectively, in children aged 6-23 mo, while in those aged 24-59 mo, the difference values were 17.8% (1.6, 34.1) and 13.6% (-2.8, 29.9), respectively. CONCLUSION:At discharge, the plasma EAA concentrations in 6-59-mo-old SAM children treated with FSMS-RUTF and MSMS-RUTF were not less than those of children treated with PM-RUTF. These findings indicate that treatment with either of the 3 RUTFs was associated with adequate protein synthesis and that all the formulations provided sufficient functional metabolites of plasma amino acids to support nutritional recovery from SAM.

BACKGROUND:Children with moderate acute malnutrition (MAM) have an increased risk of mortality, infections and impaired physical and cognitive development compared to well-nourished children. In parts of Ethiopia not considered chronically food insecure there are no supplementary feeding programmes (SFPs) for treating MAM. The short-term outcomes of children who have MAM in such areas are not currently described, and there remains an urgent need for evidence-based policy recommendations. METHODS:We defined MAM as mid-upper arm circumference (MUAC) of ≥11.0 cm and

Paluku Bahwere, Kate Sadler, Steve CollinsValid International, Oxford, United KingdomObjective: A prospective descriptive study to assess acceptability and effectiveness of a locally made ready-to-use therapeutic food (RUTF) in HIV-infected chronically sick adults (CSA) with mid-upper-arm circumference (MUAC)