Nutritional treatment of children 6-59 months with severely low weight-for-age z-score: a study protocol for a 3-arm randomized controlled trial.

BACKGROUND: Admission criteria that treat children with low mid-upper-arm circumference (MUAC), and low weight-for-height z-score (WHZ) are not aligned with the evidence on which children are at risk of mortality. An analysis of community-based cohort data from Senegal found that a combination of weight-for-age (WAZ) and MUAC criteria identified all children at risk of near-term death associated with severe anthropometric deficits. This study will address whether children with WAZ <-3 but MUAC ≥125 mm benefit from therapeutic feeding with ready-to-use therapeutic foods (RUTF) and whether a simplified protocol is non-inferior to the weight-based standard protocol. METHODS: This is a prospective individually randomized controlled 3-arm trial conducted in the Nara health district in Mali. Children aged 6-59 months presenting with MUAC ≥125 mm and WAZ <-3 will be randomized to (1) control group receiving no treatment, (2) simplified treatment receiving 1 sachet of RUTF daily until WAZ ≥-3 for 2 visits, (3) standard treatment receiving RUTF according to WHZ category: (a) WHZ <-3 receive 200 kcal/kg/day until WHZ ≥-2 for 2 visits, (b) WHZ ≥-3 but <-2 receive 1 sachet daily until WHZ ≥-2 for 2 visits or (c) WHZ ≥-2 receive no treatment. All children will be followed up first fortnightly for 12 weeks and then monthly until 6 months post-enrolment. The primary endpoint will be measured at 2 months with the primary outcome being WAZ as a continuous measure. Other outcomes include other anthropometric measurements and a secondary endpoint will be observed at 6 months. A total of 1397 children will be recruited including 209 in the control and 594 in both the simplified and standard arms. The sample size should enable us to conclude on the superiority of the simplified treatment compared to no treatment and on the non-inferiority of the simplified treatment versus standard treatment with a margin of non-inferiority of 0.2 WAZ. DISCUSSION: This trial aims to generate new evidence on the benefit of treating children with WAZ <-3 but MUAC ≥125 mm in order to guide the choice of admission criteria to malnutrition treatment and build evidence on the most efficient treatment protocol. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov: NCT05248516 on February 21, 2022.

Spontaneous memory strategies in a videogame simulating everyday memory tasks.

People can use different internal strategies to manage their daily tasks, but systematic research on these strategies and their significance for actual performance is still quite sparse. Here we examined self-reported internal strategy use with a 10-block version of the videogame EPELI (Executive Performance in Everyday LIving) in a group of 202 neurotypical adults of 18-50 years of age. In the game, participants perform lists of everyday tasks from memory while navigating in a virtual apartment. Open-ended strategy reports were collected after each EPELI task block, and for comparison also after an EPELI Instruction Recall task and a Word List Learning task assessing episodic memory. On average, 45% of the participants reported using some strategy in EPELI, the most common types being grouping (e.g., performing the tasks room by room), utilising a familiar action schema, and condensing information (e.g., memorising only keywords). Our pre-registered hypothesis on the beneficial effect of self-initiated strategy use gained support, as strategy users showed better performance on EPELI as compared with no strategy users. One of the strategies, grouping, was identified as a clearly effective strategy type. Block-by-block transitions suggested gradual stabilisation of strategy use over the 10 EPELI blocks. The proneness to use strategies showed a weak but reliable association between EPELI and Word List Learning. Overall, the present results highlight the importance of internal strategy use for understanding individual differences in memory performance, as well as the potential benefit for internal strategy employment when faced with everyday memory tasks.

Vitamin B12 Status before and after Outpatient Treatment of Severe Acute Malnutrition in Children Aged 6-59 Months: A Sub-Study of a Randomized Controlled Trial in Burkina Faso.

Severe acute malnutrition (SAM) is treated with ready-to-use therapeutic foods (RUTF) containing a vitamin-mineral premix. Yet little is known about micronutrient status in children with SAM before and after treatment. We aimed to investigate vitamin B12 status in children with uncomplicated SAM, aged 6-59 months in Burkina Faso, before and after treatment with a standard or a reduced dose of RUTF. Blood samples were collected at admission and discharge. Serum B12 was determined with microbiological assay and serum methylmalonic acid (MMA) and total homocysteine (tHcy) were analyzed with gas chromatography-tandem mass spectrometry. B12 status was classified using the combined indicator (3cB12). Among 374 children, the median [interquartile range] age was 11.0 [7.7-16.9] months, and 85.8% were breastfed. Marked or severe B12 deficiency, as judged by 3cB12, decreased from 32% to 9% between admission and discharge (p < 0.05). No differences in B12 status following treatment with either standard (n = 194) or reduced (n = 180) doses of RUTF were observed. Breastfed children showed a lower B12 status (3cB12) than non-breastfed ones (-1.10 vs -0.18, p < 0.001 at admission; -0.44 vs 0.19; p < 0.001 at discharge). In conclusion, treatment of SAM with RUTF improved children's B12 status but did not fully correct B12 deficiency.

The bioelectrical impedance analysis (BIA) international database: aims, scope, and call for data.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a technique widely used for estimating body composition and health-related parameters. The technology is relatively simple, quick, and non-invasive, and is currently used globally in diverse settings, including private clinicians' offices, sports and health clubs, and hospitals, and across a spectrum of age, body weight, and disease states. BIA parameters can be used to estimate body composition (fat, fat-free mass, total-body water and its compartments). Moreover, raw measurements including resistance, reactance, phase angle, and impedance vector length can also be used to track health-related markers, including hydration and malnutrition, and disease-prognostic, athletic and general health status. Body composition shows profound variability in association with age, sex, race and ethnicity, geographic ancestry, lifestyle, and health status. To advance understanding of this variability, we propose to develop a large and diverse multi-country dataset of BIA raw measures and derived body components. The aim of this paper is to describe the 'BIA International Database' project and encourage researchers to join the consortium. METHODS: The Exercise and Health Laboratory of the Faculty of Human Kinetics, University of Lisbon has agreed to host the database using an online portal. At present, the database contains 277,922 measures from individuals ranging from 11 months to 102 years, along with additional data on these participants. CONCLUSION: The BIA International Database represents a key resource for research on body composition.

Assessment of goal-directed behavior and prospective memory in adult ADHD with an online 3D videogame simulating everyday tasks.

The diagnosis of ADHD is based on real-life attentional-executive deficits, but they are harder to detect in adults than in children and objective quantitative measures reflecting these everyday problems are lacking. We developed an online version of EPELI 3D videogame for naturalistic and scalable assessment of goal-directed action and prospective memory in adult ADHD. In EPELI, participants perform instructed everyday chores in a virtual apartment from memory. Our pre-registered hypothesis predicted weaker EPELI performances in adult ADHD compared to controls. The sample comprised 112 adults with ADHD and 255 neurotypical controls comparable in age (mean 31, SD = 8 years), gender distribution (71% females) and educational level. Using web-browser, the participants performed EPELI and other cognitive tasks, including Conner's Continuous Performance Test (CPT). They also filled out questionnaires probing everyday executive performance and kept a 5-day diary of everyday prospective memory errors. Self-reported strategy use in the EPELI game was also examined. The ADHD participants' self-ratings indicated clearly more everyday executive problems than in the controls. Differences in the EPELI game were mostly seen in the ADHD participants' higher rates of task-irrelevant actions. Gender differences and a group × gender interaction was found in the number of correctly performed tasks, indicating poorer performance particularly in ADHD males. Discriminant validity of EPELI was similar to CPT. Strategy use strongly predicted EPELI performance in both groups. The results demonstrate the feasibility of EPELI for online assessment and highlight the role of impulsivity as a distinctive everyday life problem in adult ADHD.

Post-Recovery Relapse of Children Treated with a Simplified, Combined Nutrition Treatment Protocol in Mali: A Prospective Cohort Study.

The present study aimed to determine the 6-month incidence of relapse and associated factors among children who recovered from acute malnutrition (AM) following mid-upper arm circumference (MUAC)-based simplified combined treatment using the ComPAS protocol. A prospective cohort of 420 children who had reached a MUAC ≥ 125 mm for two consecutive measures was monitored between December 2020 and October 2021. Children were seen at home fortnightly for 6 months. The overall 6-month cumulative incidence of relapse [95%CI] into MUAC < 125 mm and/or edema was 26.1% [21.7; 30.8] and 1.7% [0.6; 3.6] to MUAC < 115 mm and/or edema. Relapse was similar among children initially admitted to treatment with a MUAC < 115 mm and/or oedema and among those with a MUAC ≥ 115 mm but <125 mm. Relapse was predicted by lower anthropometry both at admission to and discharge from treatment, and a higher number of illness episodes per month of follow-up. Having a vaccination card, using an improved water source, having agriculture as the main source of income, and increases in caregiver workload during follow-up all protected from relapse. Children discharged as recovered from AM remain at risk of relapsing into AM. To achieve reduction in relapse, recovery criteria may need to be revised and post-discharge strategies tested.

Assessment of goal-directed behavior with the 3D videogame EPELI: Psychometric features in a web-based adult sample.

EPELI (Executive Performance in Everyday LIving) is a recently developed gaming tool for objective assessment of goal-directed behavior and prospective memory (PM) in everyday contexts. This pre-registered study examined psychometric features of a new EPELI adult online version, modified from the original child version and further developed for self-administered web-based testing at home. A sample of 255 healthy adults completed EPELI where their task was to perform household chores instructed by a virtual character. The participants also filled out PM-related questionnaires and a diary and performed two conventional PM tasks and an intelligence test. We expected that the more "life-like" EPELI task would show stronger associations with conventional PM questionnaires and diary-based everyday PM reports than traditional PM tasks would do. This hypothesis did not receive support. Although EPELI was rated as more similar to everyday tasks, performance in it was not associated with the questionnaires and the diary. However, there were associations between time-monitoring behavior in EPELI and the traditional PM tasks. Taken together, online adult-EPELI was found to be a reliable method with high ecological face validity, but its convergent validity requires further research.

Factors associated with acute malnutrition among children aged 6-59 months in Haiti, Burkina Faso and Madagascar: A pooled analysis.

BACKGROUND: Acute malnutrition is one of the main causes of morbidity and mortality among children under 5 years worldwide, and Action Contre la Faim (ACF) aims to address its causes and consequences. To better tailor humanitarian programs, ACF conducts standardized contextual studies called Link NCAs (Nutrition Causal Analysis), to identify factors associated with severe acute malnutrition (SAM) and moderate acute malnutrition (MAM). Data from three Link NCAs performed in 2018 and 2019 in Haiti, Burkina Faso and Madagascar were used to explore the prevalence of malnutrition by different indicators and associated risk factors among children aged 6-59 months. METHODS: Cross-sectional data, collected via household surveys applying two-stage cluster sampling, were pooled to build a sample of 1,356 children. Recommended anthropometric thresholds were used to define SAM (Weight-for-Height Z-score (WHZ) <-3 or Mid-upper Arm Circumference (MUAC) <115 mm and/or presence oedema), MAM (-3≤WHZ<-2 or 115≤MUAC<125 mm) and global acute malnutrition GAM (SAM or MAM) among children. Multivariate analyses for each anthropometric indicator were performed using logistic mixed models and adjusting for potential confounders. RESULTS: The prevalence of acute malnutrition was the highest in Madagascar. The risk of having GAM and MAM varied across countries, while the risk of having SAM varied across clusters. Being male, suffering from diarrhea, and having unwashed face and hands, were significantly associated with GAM by WHZ with adjusted odds ratio of 1.9 [95%Confidence interval (CI):1.1-3.2], 1.7 (95%CI: 1.0-3.1) and 1.9 (95%CI: 1.0-3.6) respectively. These factors were also associated with MAM by WHZ. None of the studied factors was significantly associated with SAM, which could be due to a small sample size. CONCLUSION: These results obtained from a large sample contribute to the evidence of the factors associated with undernutrition in children aged 6-59 months. Further research with larger sample sizes is needed to confirm these results.

Effectiveness of Acute Malnutrition Treatment at Health Center and Community Levels with a Simplified, Combined Protocol in Mali: An Observational Cohort Study.

A simplified, combined protocol was created that admits children with a mid-upper-arm circumference (MUAC) of <125 mm or edema to malnutrition treatment with ready-to-use therapeutic food (RUTF) that involves prescribing two daily RUTF sachets to children with MUAC < 115 mm or edema and one daily sachet to those with 115 mm ≤ MUAC < 125 mm. This treatment was previously shown to result in non-inferior programmatic outcomes compared with standard treatment. We aimed at observing its effectiveness in a routine setting at scale, including via delivery by community health workers (CHWs). A total of 27,800 children were admitted to the simplified, combined treatment. Treatment resulted in a 92% overall recovery, with a mean length of stay of 40 days and a mean RUTF consumption of 62 sachets per child treated. Among children admitted with MUAC < 115 mm or edema, 87% recovered with a mean length of stay of 55 days and consuming an average of 96 RUTF sachets. The recovery in all sub-groups studied exceeded 85%. Treatment by CHWs resulted in a similar (94%) recovery to treatment by formal healthcare workers (92%). The simplified, combined protocol resulted in high recovery and low RUTF consumption per child treated and can safely be adopted by CHWs to provide treatment at the community level.

Predictors of time to recovery and non-response during outpatient treatment of severe acute malnutrition.

BACKGROUND: Every year, over 4 million children are treated for severe acute malnutrition with varying program performance. This study sought to explore the predictors of time to recovery from and non-response to outpatient treatment of SAM. METHODS: Children with weight-for-height z-score (WHZ) <-3 and/or mid-upper arm circumference (MUAC) <115 mm, without medical complications were enrolled in a trial (called MANGO) from outpatient clinics in Burkina Faso. Treatment included a weekly ration of ready-to-use therapeutic foods. Recovery was declared with WHZ ≥-2 and/or MUAC ≥125 mm, for two weeks without illness. Children not recovered by 16 weeks were considered as non-response to treatment. Predictors studied included admission characteristics, morbidity and compliance during treatment and household characteristics. Cox proportional hazard models were fitted and restricted mean time to recovery calculated. Logistic regression was used to analyse non-response to treatment. RESULTS: Fifty-five percent of children recovered and mean time to recovery was eight weeks while 13% ended as non-response to treatment. Independent predictors of longer time to recovery or non-response included low age, being admitted with WHZ <-3, no illness nor anaemia at admission, illness episodes during treatment, skipped or missed visits, low maternal age and not practising open defecation. Eighty-four percent of children had at least one and 59% at least two illness episodes during treatment. This increased treatment duration by 1 to 4 weeks. Thirty-five percent of children missed at least one treatment visit. One missed visit predicted 3 weeks longer and two or more missed visits 5 weeks longer treatment duration. CONCLUSIONS: Both longer time to recovery and higher non-response to treatment seem most strongly associated with illness episodes and missed visits during treatment. This indicates that prevention of illnesses would be key to shortening the treatment duration and that there is a need to seek ways to facilitate adherence.

Simplifying and optimising management of acute malnutrition in children aged 6 to 59 months: study protocol for a 3 arms community-based individually randomised controlled trial in decentralised Niger.

BACKGROUND: Simplified approaches of acute malnutrition (AM) treatment have been conducted over the past 5 years intending to unify processes and increase coverage among children aged 6 to 59 months without medical complication. The Optimsing treatment for Acute Malnutrition (OptiMA) and the Combined Protocol for Acute Malnutrition Study (ComPAS) are mid-upper arm circumference (MUAC)-based approaches treating children with MUAC < 125 mm or oedema with one sole product-ready-to-use therapeutic food-at a gradually tapered doses. This trial aims to compare the OptiMA and ComPAS strategies to the standard nutritional protocol of Niger assessed by a favourable outcome in the treatment of uncomplicated AM at 6 months post-randomisation and in terms of recovery rate after treatment of uncomplicated SAM (WHZ < - 3 or MUAC < 115mm or oedema) and among the most vulnerable children (MUAC < 115mm or oedema). METHODS: A non-inferiority individually randomised controlled clinical trial was conducted at the primary health centres level and in the community in the Zinder region in Niger in March 2021. Participants are children aged 6-59 months attending outpatient health centres with MUAC < 125mm or oedema without medical complications. All participants are followed for 6 months. Simplified strategies propose a gradual reduction of RUTF according to MUAC and weight in OptiMA and MUAC only in ComPAS. Favourable outcome is compositely defined at 6 months post-inclusion as being alive, not acutely malnourished by the definition applied at inclusion and without any additional episode of AM throughout the 6-month observation period. Recovery is defined throughout the 6 months post-randomisation by a minimum of 4-week duration of treatment, an axillary temperature < 37.5°C, an absence of bipedal oedema and a MUAC ≥ 125 mm for two consecutive weeks. The sample size calculation required 567 children per arm for the main objective, 295 and 384 children per arm for the secondary objectives among SAM and MUAC < 115 mm children, respectively. Per-protocol and intention-to-treat analyses will be conducted for each outcome. DISCUSSION: This trial is intending to generate much-needed evidence on various simplified and optimised AM treatment approaches and to participate in reaching a consensus on such nutrition protocols. TRIAL REGISTRATION: ClinicalTrials.gov NCT04698070 . Registered on January 6, 2021.

Availability, use, and consumption practices of ready-to-use therapeutic foods prescribed to children with uncomplicated severe acute malnutrition aged 6-59 months during outpatient treatment in Burkina Faso.

Ready-to-use-therapeutic-foods (RUTF) was designed for the nutritional management of children with uncomplicated severe acute malnutrition (SAM) treated as outpatients. However, to our knowledge, no study has evaluated the availability, use and consumption of RUTF within the beneficiary household in programs and in the context of a reduction in the dose of RUTF. This study, assessed the effect of a reduction in RUTF dose on the availability, use, consumption, and perceptions of caregivers on RUTF prescribed to 516 children treated for SAM, aged 6-59 months in Burkina Faso. Children received a weekly dose of RUTF according to their treatment arm until recovery. Data were collected by structured individual in-depth interviews, with caregivers one month and two months post-admission. Differences between children receiving reduced RUTF (intervention arm) and those receiving standard RUTF (control arm) were assessed by Poisson, logistic, and ordered logistic regression model. RUTF was available for the whole week in 95% in intervention arm compared to about 98% in control arm (p > 0.05). Starting from week 3 onwards, children in intervention arm consumed an average of 9 sachets of RUTF per week compared to 15 sachets in control arm (p < 0.001) and 5% of children in intervention arm reported leftover compared to 11% in control arm (p < 0.05). About 40% of children in intervention arm consumed RUTF at least 3-times per day compared to 82% in control arm (p < 0.001). The amount of RUTF prescribed was perceived as sufficient in 93% by caregivers in intervention arm against 97% in control arm (p > 0.05). In conclusion, reducing the dose of RUTF did not affect the availability of RUTF during treatment but did reduce leftover and the frequency of consumption of RUTF.

Complementary feeding practices and associated factors of dietary diversity among uncomplicated severe acute malnourished children aged 6-23 months in Burkina Faso.

Nutritional treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF). With treatment provided at community level, children could have access to other foods, and a reduction in the dose of RUTF could further increase dietary diversity during treatment. We assessed the dietary diversity score (DDS), the minimum dietary diversity (MDD), the minimum meal frequency (MMF) and the minimum acceptable diet (MAD) of 459 infants and young children aged 6-23 months being treated for SAM with different doses of RUTF. We also investigated the factors associated with DDS. Dietary intake was estimated using a single 24-h multipass dietary recall, 1 month after starting treatment, from December 2016 to August 2018. The DDS was calculated on the basis of eight food groups. Differences between children receiving the reduced RUTF and the standard RUTF dose and factors associated with DDS were assessed by Poisson and logistic regression models. RUTF dose was not associated with DDS (4.07 ± 1.25 for reduced RUTF and 4.01 ± 1.26 for standard RUTF; P = 0.77). Food groups most consumed by children were grains, roots or tubers (96%) and legumes and nuts (72%). Eggs consumption was low (3%). DDS was positively associated with child's age, mother's education, household wealth index, urban residence and rainy season. The present findings show that children with SAM consumed a variety of foods during treatment in addition to the RUTF ration prescribed to them. Reducing the dose of RUTF during SAM treatment did not impact DDS.

Economic evaluation of a reduced dosage of ready-to-use therapeutic foods to treat uncomplicated severe acute malnourished children aged 6-59 months in Burkina Faso.

Ready-to-use therapeutic foods (RUTF) used to treat children with severe acute malnutrition (SAM) are costly, and the prescribed dosage has not been optimized. The MANGO trial, implemented by Action Contre la Faim in Burkina Faso, proved the non-inferiority of a reduced RUTF dosage in community-based treatment of uncomplicated SAM. We performed a cost-minimization analysis to assess the economic impact of transitioning from the standard to the reduced RUTF dose. We used a decision-analytic model to simulate a cohort of 399 children/arm, aged 6-59 months and receiving SAM treatment. We adopted a societal perspective: direct medical costs (drugs, materials and staff time), non-medical costs (caregiver expenses) and indirect costs (productivity loss) in 2017 international US dollar were included. Data were collected through interviews with 35 caregivers and 20 informants selected through deliberate sampling and the review trial financial documents. The overall treatment cost for 399 children/arm was $36,550 with the standard and $30,411 with the reduced dose, leading to $6,140 (16.8%) in cost savings ($15.43 saved/child treated). The cost/consultation was $11.6 and $9.6 in the standard and reduced arms, respectively, with RUTF accounting for 56.2% and 47.0% of the total. The savings/child treated was $11.4 in a scenario simulating the Burkinabè routine SAM treatment outside clinical trial settings. The reduced RUTF dose tested in the MANGO trial resulted in significant cost savings for SAM treatment. These results are useful for decision makers to estimate potential economic gains from an optimized SAM treatment protocol in Burkina Faso and similar contexts.

Adequacy of Nutrient Intakes of Severely and Acutely Malnourished Children Treated with Different Doses of Ready-To-Use Therapeutic Food in Burkina Faso.

BACKGROUND: Ready-to-use therapeutic foods (RUTF) are designed to cover the daily nutrient requirements of children with severe acute malnutrition (SAM). However, with the transfer of uncomplicated SAM care from the hospital environment to the community level, children will be able to consume complementary and family foods (CFF) in addition to RUTF, and this might decrease the quantity of RUTF needed for recovery. OBJECTIVES: Using an individually randomized clinical trial, we investigated the effects of a reduced RUTF dose on the daily energy and macronutrient intakes, the proportion of energy coming from CFF, and the mean probability of adequacy (MPA) of intake in 11 micronutrients of 516 children aged 6-59 mo who were treated for SAM in Burkina Faso. METHODS: The data were collected using a single 24-h multipass dietary recall, 1 mo after starting treatment, from December 2016 to August 2018, repeated on a subsample of 66 children. Differences between children receiving the reduced RUTF (intervention arm) and those receiving standard RUTF (control arm) were assessed by linear mixed models. RESULTS: Daily energy intake was lower (P < 0.01) in the intervention arm (mean ± SD 1321 ± 339 kcal) than in the control arm (1467 ± 319 kcal). CFF contributed to 40% of the daily energy intake in the intervention and 35% in the control arm. The MPA for 11 micronutrients was 0.89 ± 0.1 in the intervention arm and 0.95 ± 0.07 in the control arm (P = 0.06). CONCLUSIONS: Reducing the dose of RUTF during SAM treatment had a negative impact on daily energy intake of the children. Despite this, children covered their recommended energy intake. The energy intake coming from CFF was similar between arms, suggesting that children's feeding practices did not change due to the reduction in RUTF in this context. This trial was registered at the IRSCTN registry as ISRCTN50039021.

Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 µmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 µg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 µmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 µg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.

Body composition during outpatient treatment of severe acute malnutrition: Results from a randomised trial testing different doses of ready-to-use therapeutic foods.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) prescribed based on body weight and administered at home. Treatment performance is typically monitored through weight gain. We previously reported that a reduced dose of RUTF resulted in weight gain velocity similar to standard dose. Here we investigate the change in body composition of children treated for SAM and compare it to community controls, and describe the effect of a reduced RUTF dose on body composition at recovery. METHODS: Body composition was measured via bio-electrical impedance analysis at admission and recovery among a sub-group of children with SAM participating in a clinical trial and receiving a reduced or a standard dose of RUTF. Non-malnourished children were measured to represent community controls. Linear mixed regression models were fitted. RESULTS: We obtained body composition data from 452 children at admission, 259 at recovery and 97 community controls. During SAM treatment the average weight increased by 1.20 kg of which 0.55 kg (45%) was fat-free mass (FFM) and 0.67 kg (55%) was fat mass (FM). At recovery, children treated for SAM had 1.27 kg lower weight, 0.38 kg lower FFM, and 0.90 kg lower FM compared to community controls. However, their fat-free mass index (FFMI) was not different from community controls (Δ0.2 kg/m2; 95% CI -0.1, 0.4). No differences were observed in FFM, FM or fat mass index (FMI) between the study arms at recovery. However, FFMI was 0.35 kg/m2 higher at recovery with the reduced compared to standard dose (p = 0.007) due to slightly lower height (Δ0.22 cm; p = 0.25) and higher FFM (Δ0.11 kg; p = 0.078) in the reduced dose group. CONCLUSIONS: Almost half of the weight gain during SAM treatment was FFM. Compared to community controls, children recovered from SAM had a lower FM while their height-adjusted FFM was similar. There was no evidence of a differential effect of a reduced RUTF dose on the tissue accretion of treated children when compared to standard treatment.

Impact of reduced dose of ready-to-use therapeutic foods in children with uncomplicated severe acute malnutrition: A randomised non-inferiority trial in Burkina Faso.

BACKGROUND: Children with uncomplicated severe acute malnutrition (SAM) are treated at home with ready-to-use therapeutic foods (RUTFs). The current RUTF dose is prescribed according to the weight of the child to fulfil 100% of their nutritional needs until discharge. However, there is doubt concerning the dose, as it seems to be shared, resulting in suboptimal cost-efficiency of SAM treatment. We investigated the efficacy of a reduced RUTF dose in community-based treatment of uncomplicated SAM. METHODS AND FINDINGS: We undertook a randomised trial testing the non-inferiority of weight gain velocity of children with SAM receiving (a) a standard RUTF dose for two weeks, followed by a reduced dose thereafter (reduced), compared with (b) a standard RUTF dose throughout the treatment (standard). A mean difference of 0.0 g/kg/day was expected, with a non-inferiority margin fixed at -0.5 g/kg/day. Linear and logistic mixed regression analyses were performed, with study site and team as random effects. Between October 2016 and July 2018, 801 children with uncomplicated SAM aged 6-59 months were enrolled from 10 community health centres in Burkina Faso. At admission, the mean age (± standard deviation [SD]) was 13.4 months (±8.7), 49% were male, and the mean weight was 6.2 kg (±1.3). The mean weight gain velocity from admission to discharge was 3.4 g/kg/day and did not differ between study arms (Δ 0.0 g/kg/day; 95% CI -0.4 to 0.4; p = 0.92) confirming non-inferiority (p = 0.013). However, after two weeks, the weight gain velocity was significantly lower in the reduced dose with a mean of 2.3 g/kg/day compared with 2.7 g/kg/day in the standard dose (Δ -0.4 g/kg/day; 95% CI -0.8 to -0.02; p = 0.041). The length of stay (LoS) was not different (p = 0.73) between groups with a median of 56 days (interquartile range [IQR] 35-91) in both arms. No differences were found between reduced and standard arm in recovery (52.7% and 55.4%; p = 0.45), referral (19.2% and 20.1%; p = 0.80), defaulter (12.2% and 8.5%; p = 0.088), non-response (12.7% and 12.5%; p = 0.95), and relapse (2.4% and 1.8%; p = 0.69) rates, respectively. However, the reduced RUTF dose had a small 0.2 mm/week (95% CI 0.04 to 0.4; p = 0.015) negative effect on height gain velocity with a mean height gain of 2.6 mm/week with reduced and 2.8 mm/week with standard RUTF dose. The impact was more pronounced in children under 12 months of age (interaction, p = 0.019) who gained 2.8 mm/week with reduced and 3.1 mm/week with standard dose (Δ -0.4 mm/week; 95% CI -0.6 to -0.2; p < 0.001). Limitations include not blinding participants to the RUTF dose received and excluding all children with negative appetite test. The results are generalisable for relatively food secure contexts with a young SAM population. CONCLUSIONS: Reducing the RUTF dose provided to children with SAM after two weeks of treatment did not reduce overall weight or mid-upper arm circumference (MUAC) gain velocity nor affect recovery or lengthen treatment time. However, it led to a small but significant negative effect on linear growth, especially among the youngest. The potential effect of reducing the RUTF dose in a routine program on treatment outcomes should be evaluated before scaling up. TRIAL REGISTRATION: ISRCTN registry ISRCTN50039021.

Heme Iron Intake, Dietary Antioxidant Capacity, and Risk of Colorectal Adenomas in a Large Cohort Study of French Women.

BACKGROUND: Nitrosylated and non-nitrosylated heme iron from red processed and nonprocessed meat have been associated with increased colorectal carcinogenesis. Mechanisms include oxidative processes. It has been hypothesized that dietary antioxidants could counteract the effects of heme iron. We investigated the relationships between heme iron intake and the risk of colorectal adenomas, and a potential interaction with the dietary antioxidant capacity, in the E3N prospective cohort study. METHODS: The study included 17,397 women, who underwent at least one colonoscopy. Among them, 1,409 were diagnosed with at least one first colorectal adenoma during the 103,253 person-years of follow-up. Dietary intake was measured by a semiquantitative food history questionnaire. HR estimates and 95% confidence intervals (CI) were obtained from Cox proportional hazards models, adjusted for potential confounders. RESULTS: Heme iron intake was positively associated with colorectal and colon adenoma risks [HR for the fourth vs. first quartile: HR4 = 1.36 (1.13-1.65), Ptrend = 0.001 and HR4 = 1.49; 95% CI, 1.19-1.87; Ptrend = 0.0003, respectively]. Nonnitrosylated and nitrosylated heme iron intakes were, respectively, associated with advanced distal and proximal adenoma risks. There was a dose-effect relationship between the heme iron to total dietary antioxidant capacity ratio and colorectal adenoma risk. CONCLUSION: In this prospective cohort study, the association between heme iron and colorectal adenoma risk was found to depend on site, nitrosylation or not, and the ratio with the NEAC. IMPACT: These results emphasize the need for a global assessment of diet when considering nutritional prevention of colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 25(4); 640-7. ©2016 AACR.