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Severe acute malnutrition (SAM) constitutes a substantial burden in African hospitals. Despite adhering to international guidelines, high inpatient mortality rates persist and the underlying contributing factors remain poorly understood. We evaluated the 10-year trend (2011-2021) in clinical factors and outcomes among children with severe wasting and/or nutritional edema at Malawi's largest nutritional rehabilitation unit (NRU). This retrospective study analyzed trends in presentation and outcomes using generalized additive models. The association between clinical characteristics and mortality or readmission was examined and key features were also related to time to either mortality or discharge. 1497 children (53%, females) were included. Median age at admission (23 months, IQR 14, 34) or anthropometry (i.e., weight-for-age, height-for-age and weight-for-height) did not change over the 10-years. But the prevalence of edema decreased by 40% whereas dehydration, difficulty breathing, and pallor became more common. Yearly HIV testing increased but positive-detection remained around 11%. Reporting of complete vaccination dropped by 49%, and no reduction in 'watch' antibiotic usage was detected. Overall admissions declined but mortality remained around 23% [95%CI; 21, 25], and deaths occurred earlier (5.6 days [95%CI; 4.6, 6.9] in 2011 vs. 3.5 days [95%CI; 2.5, 4.7] in 2021; p<0.001). Duration of hospitalization was shortened and readmissions surged from 4.9% [95%CI; 3.3, 7.4] in 2011 to 25% [95%CI; 18, 33] in 2021 (p<0.001). Age, wasting, having both dehydration and diarrhea, or having vomiting, cough, or difficulty breathing were associated with mortality but these associations did not show any interaction over time. Over 10 years, mortality risk remained high among hospitalized children with SAM and coincided with worsened clinical presentation at admission and increased readmission. Longitudinal data from major NRUs can identify shifts in clinical profiles or outcomes, and this information can be leveraged to promote earlier care-seeking, improved risk stratification, and implementation of more patient-centered treatments.

Background Despite adherence to WHO guidelines, inpatient mortality among sick children admitted to hospital with complicated severe acute malnutrition (SAM) remains unacceptably high. Several studies have examined risk factors present at admission for mortality. However, risks may evolve during admission with medical and nutritional treatment or deterioration. Currently, no specific guidance exists for assessing daily treatment response. This study aimed to determine the prognostic value of monitoring clinical signs on a daily basis for assessing mortality risk during hospitalization in children with SAM. Methods This is a secondary analysis of data from a randomized trial (NCT02246296) among 843 hospitalized children with SAM. Daily clinical signs were prospectively collected during ward rounds. Multivariable extended Cox regression using backward feature selection was performed to identify daily clinical warning signs (CWS) associated with time to death within the first 21 days of hospitalization. Predictive models were subsequently developed, and their prognostic performance evaluated using Harrell’s concordance index (C-index) and time-dependent area under the curve (tAUC). Results Inpatient case fatality ratio was 16.3% ( n =127). The presence of the following CWS during daily assessment were found to be independent predictors of inpatient mortality: symptomatic hypoglycemia, reduced consciousness, chest indrawing, not able to complete feeds, nutritional edema, diarrhea, and fever. Daily risk scores computed using these 7 CWS together with MUAC<10.5cm at admission as additional CWS predict survival outcome of children with SAM with a C-index of 0.81 (95% CI 0.77–0.86). Moreover, counting signs among the top 5 CWS (reduced consciousness, symptomatic hypoglycemia, chest indrawing, not able to complete foods, and MUAC<10.5cm) provided a simpler tool with similar prognostic performance (C-index of 0.79; 95% CI 0.74–0.84). Having 1 or 2 of these CWS on any day during hospitalization was associated with a 3 or 11-fold increased mortality risk compared with no signs, respectively. Conclusions This study provides evidence for structured monitoring of daily CWS as recommended clinical practice as it improves prediction of inpatient mortality among sick children with complicated SAM. We propose a simple counting-tool to guide healthcare workers to assess treatment response for these children. Trial registration NCT02246296

Children with medically complicated severe acute malnutrition (SAM) have high risk of inpatient mortality. Diarrhea, carbohydrate malabsorption, and refeeding syndrome may contribute to early mortality and delayed recovery. We tested the hypothesis that a lactose-free, low-carbohydrate F75 milk would serve to limit these risks, thereby reducing the number of days in the stabilization phase. In a multicenter double-blind trial, hospitalized severely malnourished children were randomized to receive standard formula (F75) or isocaloric modified F75 (mF75) without lactose and with reduced carbohydrate. The primary endpoint was time to stabilization, as defined by the World Health Organization (WHO), with intention-to-treat analysis. Secondary outcomes included in-hospital mortality, diarrhea, and biochemical features of malabsorption and refeeding syndrome. The trial was registered at clinicaltrials.gov (NCT02246296). Four hundred eighteen and 425 severely malnourished children were randomized to F75 and mF75, respectively, with 516 (61%) enrolled in Kenya and 327 (39%) in Malawi. Children with a median age of 16 months were enrolled between 4 December 2014 and 24 December 2015. One hundred ninety-four (46%) children assigned to F75 and 188 (44%) to mF75 had diarrhea at admission. Median time to stabilization was 3 days (IQR 2-5 days), which was similar between randomized groups (0.23 [95% CI -0.13 to 0.60], P = 0.59). There was no evidence of effect modification by diarrhea at admission, age, edema, or HIV status. Thirty-six and 39 children died before stabilization in the F75 and in mF75 arm, respectively (P = 0.84). Cumulative days with diarrhea (P = 0.27), enteral (P = 0.42) or intravenous fluids (P = 0.19), other serious adverse events before stabilization, and serum and stool biochemistry at day 3 did not differ between groups. The main limitation was that the primary outcome of clinical stabilization was based on WHO guidelines, comprising clinical evidence of recovery from acute illness as well as metabolic stabilization evidenced by recovery of appetite. Empirically treating hospitalized severely malnourished children during the stabilization phase with lactose-free, reduced-carbohydrate milk formula did not improve clinical outcomes. The biochemical analyses suggest that the lactose-free formulae may still exceed a carbohydrate load threshold for intestinal absorption, which may limit their usefulness in the context of complicated SAM. ClinicalTrials.gov NCT02246296.

Governmental and non-governmental organisations in low-income countries have transitioned from paper data collection to electronic data collection at a slower pace than those in high-income countries due to limitations of funding, internet stability and trained personnel, among other reasons. This paper chronicles the process employed by one small non-governmental organisation in Malawi from the selection of a programme through implementation, describing challenges and successes along the way in order to facilitate the adoption process for NGOs in sub-Saharan Africa or other low-income countries. Upgrading the data collection system presented a daunting challenge. Despite the significant learning curve for the entire team, the implementation phase proceeded smoothly. Although staff remained apprehensive, they also understood the need for change and fully invested in the process. The benefits of electronic charting outweigh the struggles involved in learning a new system. Key elements of the process that supported success were active engagement of users at all points during the transition, selection of a programme that was well-suited for the size and needs of the NGO, and appropriate support from ancillary staff and outside experts.

Intestinal pathology in children with complicated severe acute malnutrition (SAM) persists despite standard management. Given the similarity with intestinal pathology in non-IgE mediated gastrointestinal food allergy and Crohn’s disease, we tested whether therapeutic feeds effective in treating these conditions may benefit children with complicated SAM. After initial clinical stabilisation, 95 children aged 6–23 months admitted at Queen Elizabeth Central Hospital, Blantyre, Malawi between January 1 st and December 31 st , 2016 were allocated randomly to either standard feeds, an elemental feed or a polymeric feed for 14 days. Change in faecal calprotectin as a marker of intestinal inflammation and the primary outcome was similar in each arm: elemental vs. standard 4.1 μg/mg stool/day (95% CI, −29.9, 38.15; P  = 0.81) and polymeric vs. standard 10 (−23.96, 43.91; P  = 0.56). Biomarkers of intestinal and systemic inflammation and mucosal integrity were highly abnormal in most children at baseline and abnormal values persisted in all three arms. The enteropathy in complicated SAM did not respond to either standard feeds or alternative therapeutic feeds administered for up to 14 days. A better understanding of the pathogenesis of the gut pathology in complicated SAM is an urgent priority to inform the development of improved therapeutic interventions.

IntroductionSevere acute malnutrition (SAM) and disability are major global health issues. Although they can cause and influence each other, data on their co-existence are sparse. We aimed to describe the prevalence and patterns of disability among a cohort of children with SAM.MethodsA longitudinal cohort study in Malawi followed SAM survivors up to 7 years postdischarge. Clinical and anthropometric profiles were compared with sibling and community controls. Disability at original admission was identified clinically; at 7-year follow-up a standardised screening tool called ‘the Washington Group Questionnaire’ was used.Results60/938 (6.4%) of admissions to SAM treatment had clinically obvious disability at admission. Post-treatment mortality was high, with only 11/60 (18%) surviving till 7-year follow-up. SAM children with a disability at admission had 6.99 (95% CI 3.49 to 14.02; p<0.001) greater risk of dying compared with children without disability. They were also older, less likely to be HIV positive or have oedema and more severely malnourished. Long-term survivors were more stunted, had less catch-up growth, smaller head circumference, weaker hand grip strength and poorer school achievement than non-disabled survivors.The Washington Group Questionnaire confirmed disability in all who had been identified clinically, and identified many who had not been previously flagged.ConclusionDisability is common among children affected by SAM. Those with disability-associated SAM have greatly increased risk of dying even if they survive the initial episode of malnutrition. Survivors have poorer growth, physical strength and school achievement. To enable all children to survive and thrive post-SAM, it is vital to focus more on those with disabilities. SAM treatment programmes should consider using not just clinical assessment but structured assessments to better identify at-risk individuals as well as understand the population of children for which they are developing services.

Background Children admitted to hospital with complicated severe malnutrition (CSM) have high mortality despite compliance with standard WHO management guidelines. Limited data suggests a relationship between intestinal dysfunction and poor prognosis in CSM, but this has not been explicitly studied. This study aimed to evaluate the role of intestinal disturbances in CSM mortality. Methods A case-control study nested within a randomized control trial was conducted among children hospitalized with CSM in Kenya and Malawi. Children who died (cases, n  = 68) were compared with those who were discharged, propensity matched to the cases on age, HIV and nutritional status (controls, n  = 68) on fecal metabolomics that targeted about 70 commonly measured metabolites, and enteropathy markers: fecal myeloperoxidase (MPO), fecal calprotectin, and circulating intestinal fatty acid binding protein (I-FABP). Results The fecal metabolomes of cases show specific reductions in amino acids, monosaccharides, and microbial fermentation products, when compared to controls. SCFA levels did not differ between groups. The overall fecal metabolomics signature moderately differentiates cases from controls (AUC = 0.72). Enteropathy markers do not differ between groups overall, although serum I-FABP is elevated in cases in a sensitivity analysis among non-edematous children. Integrative analysis with systemic data suggests an indirect role of intestinal inflammation in the causal path of mortality. Conclusions Intestinal disturbances appear to have an indirect association with acute mortality. Findings of the study improve our understanding of pathophysiological pathways underlying mortality of children with CSM. Plain Language Summary Malnourished children are at a high risk of dying when exposed to an acute illness. They often have symptoms like diarrhea that indicate their gut is not working properly. It is unclear whether these gut problems contribute to their deaths. Feces contain numerous small molecules processed by the gut that reflect gut health. We compare these fecal molecules between malnourished children who died during hospitalization to those who survived, and relate them to signs of inflammation in the body. We show that the fecal molecules are different between children who died and those who survived. These differences reveal that poor gut health could increase risk of death, potentially by perturbing the body’s defensive response to an acute illness. These findings underscore that treatment for ill severely malnourished children should focus on improving gut health. Wen et al. investigate associations between intestinal disturbances and mortality in children hospitalized with complicated severe malnutrition. Differences are seen in the fecal metabolome of children who die compared with those who are discharged, with integrative analyses suggesting an indirect role for intestinal inflammation in mortality.

Severe acute malnutrition (SAM) constitutes a substantial burden in African hospitals. Despite adhering to international guidelines, high inpatient mortality rates persist and the underlying contributing factors remain poorly understood. We evaluated the 10-year trend (2011-2021) in clinical factors and outcomes among children with severe wasting and/or nutritional edema at Malawi's largest nutritional rehabilitation unit (NRU). This retrospective study analyzed trends in presentation and outcomes using generalized additive models. The association between clinical characteristics and mortality or readmission was examined and key features were also related to time to either mortality or discharge. 1497 children (53%, females) were included. Median age at admission (23 months, IQR 14, 34) or anthropometry (i.e., weight-for-age, height-for-age and weight-for-height) did not change over the 10-years. But the prevalence of edema decreased by 40% whereas dehydration, difficulty breathing, and pallor became more common. Yearly HIV testing increased but positive-detection remained around 11%. Reporting of complete vaccination dropped by 49%, and no reduction in 'watch' antibiotic usage was detected. Overall admissions declined but mortality remained around 23% [95%CI; 21, 25], and deaths occurred earlier (5.6 days [95%CI; 4.6, 6.9] in 2011 vs. 3.5 days [95%CI; 2.5, 4.7] in 2021; p<0.001). Duration of hospitalization was shortened and readmissions surged from 4.9% [95%CI; 3.3, 7.4] in 2011 to 25% [95%CI; 18, 33] in 2021 (p<0.001). Age, wasting, having both dehydration and diarrhea, or having vomiting, cough, or difficulty breathing were associated with mortality but these associations did not show any interaction over time. Over 10 years, mortality risk remained high among hospitalized children with SAM and coincided with worsened clinical presentation at admission and increased readmission. Longitudinal data from major NRUs can identify shifts in clinical profiles or outcomes, and this information can be leveraged to promote earlier care-seeking, improved risk stratification, and implementation of more patient-centered treatments.

To assess differences in cognition functions and gross brain structure in children seven years after an episode of severe acute malnutrition (SAM), compared with other Malawian children. Prospective longitudinal cohort assessing school grade achieved and results of five computer-based (CANTAB) tests, covering three cognitive domains. A subset underwent brain MRI scans which were reviewed using a standardized checklist of gross abnormalities and compared with a reference population of Malawian children. Blantyre, Malawi.ParticipantsChildren discharged from SAM treatment in 2006 and 2007 (n 320; median age 9·3 years) were compared with controls: siblings closest in age to the SAM survivors and age/sex-matched community children. SAM survivors were significantly more likely to be in a lower grade at school than controls (adjusted OR = 0·4; 95 % CI 0·3, 0·6; P < 0·0001) and had consistently poorer scores in all CANTAB cognitive tests. Adjusting for HIV and socio-economic status diminished statistically significant differences. There were no significant differences in odds of brain abnormalities and sinusitis between SAM survivors (n 49) and reference children (OR = 1·11; 95 % CI 0·61, 2·03; P = 0·73). Despite apparent preservation in gross brain structure, persistent impaired school achievement is likely to be detrimental to individual attainment and economic well-being. Understanding the multifactorial causes of lower school achievement is therefore needed to design interventions for SAM survivors to thrive in adulthood. The cognitive and potential economic implications of SAM need further emphasis to better advocate for SAM prevention and early treatment.