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Children who receive therapeutic feeding for wasting treatment but do not reach the anthropometric definitions of recovery (usually within 12-16 weeks) are categorised as 'non-responders' and considered as treatment failures. We conducted a pooled analysis to explore the growth trajectories of non-responders and the appropriateness of the definition of 'non-response'. We pooled 14 studies of children aged 6-59 months receiving treatment for wasting. We included children classified by their studies as recovered or as non-responders. Observing the pooled data of non-responders' mid-upper arm circumference (MUAC), weight, weight-for-age z-score, weight-for-height z-score and daily weight gain rate, we found that the first quartile differentiated those who did not grow at all versus those that demonstrated some growth. We therefore defined 'low growth non-responders' as < 25th percentile anthropometric gain between admission and exit using the non-responders' pooled study data, and 'high growth non-responders' as ≥ 25th percentile gain. We plotted the growth trajectories of MUAC-, weight- and height-related indices of the recovered, high growth and low growth non-responder groups over time using mixed effects generalised additive models. We compared age, sex and anthropometric characteristics of the three groups and explored predictors of non-response category using a multivariate multinomial logistic regression model. For all outcomes, the high growth non-responders started with a worse anthropometric status compared to those who recovered, but then tracked along a near-parallel growth trajectory. The low growth non-responders showed limited growth throughout treatment. High growth non-responders are better viewed as 'delayed responders' and may need to be kept longer under treatment to recover and reduce the risks from early discharge. Low growth non-responders are the true treatment failures and should be referred for further investigations as quickly as possible. In conclusion, non-responders are not a homogenous group; ~75% of them respond well to treatment and ~25% are treatment failures., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: IT currently serves on the editorial board of PLOS Global Public Health. All other co-authors declare no competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Acute malnutrition (AM) causes large loss of life and disability in children in Africa. Researchers are testing innovative approaches to increase efficiency of treatment programs. This paper presents results of a cost-effectiveness analysis of one such program in the Democratic Republic of the Congo (DRC) based on a secondary analysis of a randomized controlled trial Optimizing Treatment for Acute Malnutrition (OptiMA), conducted in DRC in 2018-20. 896 children aged 6-59 months with a mid-upper arm circumference (MUAC) <125 mm or with oedema were treated and followed for six months. Cost-effectiveness of OptiMA using ready-to-use therapeutic food (RUTF) at a tapered dose was compared with the standard national program in which severe cases (SAM) received RUTF proportional to weight, and moderate cases (MAM) were referred to another clinic for a fixed dose regimen of ready-to-use supplementary food. Cost analysis from provider perspective used data collected during the trial and from administrative records. Statistical differences were derived using t-tests. The mean cost per enrolled child under OptiMA was $123 [95%CI: 114-132], not statistically different from the standard group ($127 [95%CI: 118-136], p=0.549), while treatment success (i.e. recovery to MUAC > 125mm and no relapse for 6 months) under OptiMA was 9 percentage points higher (72% vs 63%, p=0.004). Among children with SAM at enrollment, there was no significant difference in treatment success between OptiMA and standard (70% vs 62%, p=0.12) but OptiMA's mean cost per enrolled child was 23% lower ($128 vs $166, p<0.0001). OptiMA was more effective at preventing progression to SAM among those enrolled with MAM (5% vs 16%, p<0.0001) with an incremental cost-effectiveness ratio (ICER) of $234 per progression to SAM prevented. Overall, OptiMA had significantly better outcomes and was no more expensive than standard care. Its adoption could enable more children to be successfully treated in contexts where therapeutic food products are scarce., (© The Author(s) 2024. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Background: In the treatment of acute malnutrition (AM), non-response is considered a treatment failure for not meeting recovery criteria within a therapeutic window of 12-16 weeks, but this category of children is misunderstood. As current research emphasizes ways to simplify and optimize treatment protocols, non-response emerges as a new issue to enhance program efficiency., Methods: A prospective cohort study was conducted from 2019 to 2020 at two health centres in Mirriah, Niger among children aged 6-59 months with uncomplicated AM treated under the Optimising treatment for Acute MAlnutrition (OptiMA) protocol. Children who did not meet recovery criteria by 12 weeks (mid-upper arm circumference (MUAC) ≥125 mm without oedema for two consecutive weeks) were classified as non-responders. Non-responders received a home visit six-months post-discharge. Logistic regression was used to analyze factors associated with non-responders compared with children who recovered., Results: Of the 1,112 children enrolled, 909 recovered and 139 were non-responders, of which 127 (80.6%) had significant MUAC gain (mean: +9.6 mm, sd = 5.1) at discharge. Girls (adjusted hazard ratio (aHR) = 2.07, 95% CI 1.33-3.25), children <12 months of age (aHr = 4.23, 95% CI 2.02-9.67), those with a MUAC <115 mm (aHR = 11.1, 95% CI 7.23-17.4) or severe stunting (aHR = 2.5, 1.38-4.83) at admission and a negative or flat MUAC trajectory between admission and week 4 (aHR = 4.66, 95% CI 2.54-9.13) were more likely to be non-responders. The nutritional status of non-responders had generally improved 6 months after discharge, but only 40% had achieved MUAC ≥125 mm., Conclusion: Non-responders are not a homogeneous group; while most children ultimately show significant nutritional improvement, rapid hospital referral is crucial for those not gaining MUAC early in treatment. As efforts to expand MUAC-based programming progress, adapting exit criterion and/or providing additional food supplementation with smaller daily ration for children with risk factors discussed here may help improve programme efficiency without adding to the cost of treatment., Competing Interests: KP serves on the Social Purposes Advisory Commission of Nutriset, a main producer of lipid-based nutrient supplement products. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Daures, Hien, Cazes, Alitanou, Saillet, Séri, Aly, Maidadji, Sanoussi, Mahamadou, Altmann, Phelan, Becquet and Shepherd.)

Introduction: Globally, access to treatment for severe and moderate acute malnutrition is very low, in part because different protocols and products are used in separate programs. New approaches, defining acute malnutrition (AM) as mid-upper arm circumference (MUAC) < 125 mm or oedema, are being investigated to compare effectiveness to current programs. Optimizing Malnutrition treatment (OptiMA) is one such strategy that treats AM with one product - ready-to-use therapeutic food, or RUTF - at reduced dosage as the child improves., Methods: This study aimed to determine whether OptiMA achieved effectiveness benchmarks established in the Nigerien National Nutrition protocol. A prospective cohort study of children in the rural Mirriah district evaluated outcomes among children 6-59 months with uncomplicated AM treated under OptiMA. In a parallel, unconnected program in one of the two trial sites, all non-malnourished children 6-23 months of age were provided small quantity lipid-based nutritional supplements (SQ-LNS). A multivariate logistic regression identified factors associated with hospitalization., Results: From July-December 2019, 1,105 children were included for analysis. Prior to treatment, 39.3% of children received SQ-LNS. Recovery, non-response, and mortality rates were 82.3%, 12.6%, and 0.7%, respectively, and the hospitalization rate was 15.1%. Children who received SQ-LNS before an episode of AM were 43% less likely to be hospitalized (ORa=0.57; 0.39-0.85, p = 0.004)., Discussion: OptiMA had acceptable recovery compared to the Nigerien reference but non-response was high. Children who received SQ-LNS before treatment under OptiMA were less likely to be hospitalized, showing potential health benefits of combining simplified treatment protocols with food-based prevention in an area with a high burden of malnutrition such as rural Niger., Competing Interests: KP serves on the Social Purposes Advisory Commission of Nutriset, a main producer of lipid-based nutrient supplement products. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Phelan, Seri, Daures, Yao, Alitanou, Aly, Maidadji, Sanoussi, Mahamadou, Cazes, Moh, Becquet and Shepherd.)

Background: Current standard management of severe acute malnutrition uses ready-to-use therapeutic food (RUTF) at a single weight-based calculation resulting in an increasing amount of RUTF provided to the family as the child's weight increases during recovery. Using RUTF at a gradually reduced dosage as the child recovers could reduce costs while achieving similar growth response., Methods: We conducted an open-label, non-inferiority, randomised controlled trial in the Democratic Republic of the Congo. Children aged 6-59 months with a mid-upper-arm circumference (MUAC) of less than 115 mm or a weight-for-height z-score (WHZ) of less than -3 or bipedal oedema and without medical complication were randomly assigned (1:1 ratio) using a specially developed software and random blocks (size was kept confidential), to either the current standard treatment (increasing the RUTF amount with increasing weight) or the OptiMA strategy (decreasing the RUTF dose with increasing weight and MUAC). The main endpoint was proportion of children who achieved recovery over the 6 months follow up period, as defined as meeting the following criteria for two consecutive weeks after a minimum of 4 weeks' treatment: axillary temperature less than 37.5 °C, no bipedal oedema, and anthropometric improvement (either MUAC 125 mm or greater or WHZ -1.5 or higher). We performed analyses on the intention-to-treat (ITT) (all children) and per-protocol populations (participants who had a minimum prescription of 4 weeks' RUTF, received at least 90% of the total amount of RUTF they were supposed to receive as per the protocol, and had a maximum interval of 6 weeks between any two visits in the 6-month follow-up). The non-inferiority margin was 10%. This trial is registered at ClinicalTrials.gov, and is now closed NCT03751475., Findings: Between July 22, 2019, and January 20, 2020, 491 children were randomly assigned, of whom 482 were analysed (240 in the standard group and 242 in the OptiMA group). In the ITT analysis, 234 (98%) children in the standard group and 231 (96%) children in OptiMA recovered (difference 2.0%, 95% CI -2.0% to 6.4%). In the PP analysis, 234 (98%) children in the standard group and 228 (97%) in OptiMA recovered (difference 1.3%, 95% CI -2.3% to 5.1%). Sensitivity analyses applying the same anthropometric recovery criteria to each group also showed non-inferiority of the OptiMA strategy in ITT and PP analysis., Interpretation: This non-inferiority trial treating uncomplicated children with MUAC of less than 115 mm or a WHZ of less than -3 or bipedal oedema with decreasing RUTF dose as MUAC and weight increase demonstrated non-inferiority compared to the standard protocol in a highly food-insecure context in the Democratic Republic of the Congo. These findings add evidence on the safety of RUTF dose reduction with significant RUTF cost savings., Funding: Innocent Foundation and European Civil Protection and Humanitarian Aid Operations., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: K.P. serves on the Social Purposes Advisory Commission of Nutriset, a main producer of lipid-based nutrient supplement products. All other authors declare no competing interests., (© 2023 The Authors.)

Background: Global access to acute malnutrition treatment is low. Different programmes using different nutritional products manage cases of severe acute malnutrition and moderate acute malnutrition separately. We aimed to assess whether integrating severe acute malnutrition and moderate acute malnutrition treatment into one programme, using a single nutritional product and reducing the dose as the child improves, could achieve similar or higher individual efficacy, increase coverage, and minimise costs compared with the current programmes., Methods: We conducted an open-label, non-inferiority, randomised controlled trial in the Democratic Republic of the Congo. Acutely malnourished children aged 6-59 months with a mid-upper-arm circumference (MUAC) of less than 125 mm or oedema were randomly assigned (1:1), using specially developed software and random blocks (size was kept confidential), to either the current standard strategy (one programme for severe acute malnutrition using ready-to-use therapeutic food [RUTF] at an increasing dose as weight increased, another for moderate acute malnutrition using a fixed dose of ready-to-use supplementary food [RUSF]) or the OptiMA strategy (a single programme for both severe acute malnutrition and moderate acute malnutrition using RUTF at a decreasing dose as MUAC and weight increased). The primary endpoint was a favourable outcome at 6 months, defined as being alive, not acutely malnourished as per the definition applied at inclusion, and with no further episodes of acute malnutrition throughout the 6-month observation period; the endpoint was analysed in the intention-to-treat (all children) and per-protocol populations (participants who had a minimum prescription of 4 weeks' RUTF, received at least 90% of the total amount of RUTF they were supposed to receive as per the protocol, or were prescribed RUSF rations for a minimum of 4 weeks [ie, minimum of 28 RUSF sachets], and had a maximum interval of 6 weeks between any two visits in the 6-month follow-up). The non-inferiority analysis (margin 10%) was to be followed by a superiority analysis (margin 0%) if non-inferiority was concluded. This trial is registered at ClinicalTrials.gov, NCT03751475, and is now closed., Findings: Between July 22 and Dec 6, 2019, 912 children were randomly assigned; after 16 were excluded, 896 were analysed (446 in the standard group and 450 in the OptiMA group). In the intention-to-treat analysis, 282 (63%) of 446 children in the standard group and 325 (72%) of 450 children in the OptiMA group had a favourable outcome (difference -9·0%, 95% CI -15·9 to -2·0). In the per protocol analysis, 161 (61%) of 264 children in the standard group and 291 (74%) of 392 children in the OptiMA group had a favourable outcome (-13·2%, -21·6 to -4·9)., Interpretation: In this non-inferiority trial treating children with MUAC of less than 125 mm or oedema, decreasing RUTF dose according to MUAC and weight increase proved to be a superior strategy to the standard protocol in the Democratic Republic of the Congo. These results demonstrate the safety and benefits of an approach that could substantially increase access to treatment for millions of children with acute malnutrition in sub-Saharan Africa., Funding: Innocent Foundation and European Civil Protection and Humanitarian Aid Operations., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests KP serves on the Social Purposes Advisory Commission of Nutriset, a main producer of lipid-based nutrient supplement products. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022. The Author(s).)

Introduction: Acute malnutrition (AM) is a continuum condition, arbitrarily divided into moderate and severe AM (SAM) categories, funded and managed in separate programmes under different protocols. Optimising acute MAlnutrition (OptiMA) treatment aims to simplify and optimise AM management by treating children with mid-upper arm circumference (MUAC) <125 mm or oedema with one product-ready-to-use therapeutic food-at a gradually tapered dose. Our main objective was to compare the OptiMA strategy with the standard nutritional protocol in children 6-59 months presenting with MUAC <125 mm or oedema without additional complications, as well as in children classified as uncomplicated SAM (ie, MUAC <115 mm or weight-for-height Z-score (WHZ) <-3 or with oedema)., Methods and Analysis: This study was a non-inferiority, individually randomised controlled clinical trial conducted at community level in the Democratic Republic of Congo. Children 6-59 months presenting with MUAC <125 mm or WHZ <-3 or with bipedal oedema and without medical complication were included after signed informed consent in outpatient health facilities. All participants were followed for 6 months. Success in both arms was defined at 6 months post inclusion as being alive, not acutely malnourished per the definition applied at inclusion and without an additional episode of AM throughout the 6-month observation period. Recovery among children with uncomplicated SAM was the main secondary outcome. For the primary objective, 890 participants were needed, and 480 children with SAM were needed for the main secondary objective. We will perform non-inferiority analyses in per-protocol and intention-to-treat basis for both outcomes., Ethics and Dissemination: Ethics approvals were obtained from the National Health Ethics Committee of the Democratic Republic of Congo and from the Ethics Evaluation Committee of Inserm, the French National Institute for Health and Medical Research (Paris, France). We will submit results for publication to a peer-reviewed journal and disseminate findings in international and national conferences and meetings., Trial Registration Number: NCT03751475. Registered 19 September 2018, https://clinicaltrials.gov/ct2/show/NCT03751475., Competing Interests: Competing interests: KP serves on the Social Purposes Advisory Commission of Nutriset, a main producer of lipid-based nutrient supplement products., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The Optimising treatment for acute MAlnutrition (OptiMA) strategy trains mothers to use mid upper arm circumference (MUAC) bracelets for screening and targets treatment to children with MUAC < 125 mm or oedema with one therapeutic food at a gradually reduced dose. This study seeks to determine whether OptiMA conforms to SPHERE standards (recovery rate > 75 %). A single-arm proof-of-concept trial was conducted in 2017 in Yako district, Burkina Faso including children aged 6-59 months in outpatient health centres with MUAC < 125 mm or oedema. Outcomes were stratified by MUAC category at admission. Multivariate survival analysis was carried out to identify variables predictive of recovery. Among 4958 children included, 824 (16·6 %) were admitted with MUAC < 115 mm or oedema, 1070 (21·6 %) with MUAC 115-119 mm and 3064 (61·8 %) with MUAC 120-124 mm. The new dosage was correctly implemented at all visits for 75·9 % of children. Global recovery was 86·3 (95 % CI 85·4, 87·2) % and 70·5 (95 % CI 67·5, 73·5) % for children admitted with MUAC < 115 mm or oedema. Average therapeutic food consumption was 60·8 sachets per child treated. Recovery was positively associated with mothers trained to use MUAC prior to child's admission (adjusted hazard ratio 1·09; 95 % CI 1·01, 1·19). OptiMA was successfully implemented at the scale of an entire district under 'real-life' conditions. Programme outcomes exceeded SPHERE standards, but further study is needed to determine if increasing therapeutic food dosages for the most severely malnourished will improve recovery.

Introduction: Liver abscess is a serious and an uncommon pediatric disease., Objective and Method: Description of 20 pediatric patients with liver abscess admitted in "Ricardo Gutierrez" Children's Hospital, a Tertiary Reference Center of Buenos Aires, between 2009 and 2015., Results: The hospitalization rate was 35/100.000 admissions. Median age was 5 years old, male/female ratio 4/1. Five patients (25%) had predisposing factors. Median days at diagnosis were 12., Features: Fever 100%, prolonged fever 60%, abdominal pain 50%. The majority had leukocytosis and elevated CRP (median 160 mg/L). Liver enzymes were elevated in only 40% of patients. Ultrasonography detected 90%. A single abscess was observed in 60%; localized at right hepatic lobe, 65%. Purulent material was positive in 12/17 (70%) and bacteremia was present in 3/20 (15%). Wide empirical antibiotic therapy was used. Treatment shift was needed in four patients. The median days of intravenous antibiotics were 30 and the median of total treatment were 53. Surgical procedures were performed in 13/20 (65%)., Conclusion: Community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) was the most frequent pathogen, especially in healthy children that associated skin or respiratory illness. Appropriate antibiotic treatment and eventual drainage allows good outcome without sequela or deaths.

Saint Louis encephalitis is transmitted by Culex mosquitoes. In Argentina sporadic cases are registered. Symptomatic illness is unusual in children. We present a case of meningoencephalitis caused by an uncommon viral infection. The clinical signs and symptoms are unusual for pediatric patients and the bilateral thalamic compromise showed on magnetic resonance has not been described previously. An 8-year-old girl consulted due to fever, behavior disorders and ataxia. Clonus and neck stiffness were detected at physical exam. Cerebrospinal fluid revealed mononuclear leukocytosis; bilateral ischemic compromise was observed in thalamus by magnetic resonance. Saint Louis virus was confirmed by serology: serum and cerebrospinal fluid IgM were positive during the acute phase of the disease and serum IgG was positive four weeks later. Most of the signs and symptoms of the disease were resolved, however mild behavior disorders were observed as acute sequelae up to 45 days after hospital discharge., (Sociedad Argentina de Pediatría.)

The objectives of this study were to investigate the social behavior, interrelations, cohesion, efficiency and team formation of the crew during 60 days of isolation and confinement, to make a critical comparison of a variety of test methods used for this purpose and to formulate recommendations for their applications in selection, training and support for future studies of this kind. The study consisted of three phases: (1) the pre-isolation period, in which initial individual and group assessment were made to understand the motivation, characteristics, and styles of the crew members, the state of the crew, and to make a prognosis for the behavior of the group and its members, (2) the isolation period, with tests and observations to follow and analyze behavior and group dynamics of the crew, and to detect manifestations of stress, and (3) the post-isolation period with final assessment and debriefing. During these three periods individual and group tests were carried out. Direct methods, questionnaires and tests, as well as indirect methods, observations of behavior, were used. These had cognitive, affective-emotional and social components; they were quantitative, qualitative or a combination. Before isolation the crew members expressed strong confidence in the team and in their own personal capability. The leadership of the Commander seemed uncontested. Crew functioning during this period was conflict-free, but was structured in a rather rigid and defensive way (isolation of affects, denial of anxiety). Apparently, the members strongly needed to present a good image image of themselves. The relatively short period of the experiment, and the absence of real risk suggested that the crew would be able to maintain their cohesion, but in a real spaceflight situation this behavior could be inadequate and even dangerous. The pre-isolation prognosis for crew behavior during isolation was validated to a large extent. During isolation there were no clear manifestations of stress. Nevertheless, the confinement and isolation were experienced as the major stress factors. The crew members described themselves as a heterogeneous but harmonious group that was successful in their mission. In fact, the team maintained its cohesion by opposing external authority, using management as a scapegoat. Occasionally, in times of crisis, they also criticized ground crew. The Commander supported this attitude. Strongly differences in personality and behavior were noted. Analysis of the sociometric data showed that the asserted harmony was more apparent than real. It is questionable whether the group cohesion would have persisted in a life threatening crisis or even in a prolongation of the experiment. The most reliable instruments for this type of survey seem to be: group methods, non-obstructive tests, indirect instruments, and qualitative tools. The least reliable are: strictly quantitative methods, self-evaluations, standard debriefing techniques, since these reinforced in most cases subjects' defenses in an unconscious avoidance of criticism. Several recommendations were made for the organization, definition of objectives, experiment selection, crew selection, roles of external management and personnel. In particular, it is felt to be necessary to explain the aims of the mission to the subjects, to give clear and complete information, to establish confident and cooperative relations with the crew. It is essential to allow dialogue, to take opinions and suggestions of the crew seriously, and to establish clear rules of confidentiality.