Bmc Med
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Several quinoline and structurally related antimalarial drugs are associated with cardiovascular side effects, particularly hypotension and electrocardiographic QT interval prolongation. A prolonged QT interval is a sensitive but not specific risk marker for the development of Torsade de Pointes-a potentially lethal polymorphic ventricular tachyarrhythmia. The increasing use of quinoline and structurally related antimalarials in mass treatments to eliminate malaria rapidly highlights the need to review their cardiovascular safety profiles. ⋯ No serious cardiac adverse effects were recorded in malaria clinical trials of 35,548 participants who received quinoline and structurally related antimalarials with close follow-up including 18,436 individuals who underwent ECG evaluation. While these findings provide further evidence of the rarity of serious cardiovascular events after treatment with these drugs, they also underscore the need for continued strengthening of pharmacovigilance systems for robust detection of rare drug adverse events in real-world populations. A standardised approach to measurement and reporting of ECG data in malaria trials is also needed.
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Maternal gestational diabetes (GDM) is an established risk factor for large size at birth, but its influence on intrauterine fetal growth in different ethnic populations is less well understood. Here, we examine the joint associations of GDM and ethnicity with longitudinal fetal growth in South Asian and White European origin women. ⋯ In both ethnic groups, GDM is associated with early fetal size deviations prior to GDM diagnosis, highlighting the need for novel strategies to diagnose pregnancy hyperglycemia earlier than current methods. Our findings also suggest that ethnic-specific fetal growth criteria are important in identifying hyperglycemia-associated pathological effects.
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Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. ⋯ Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.
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Childhood malnutrition remains highly prevalent in low-income countries, and a 40% reduction in under-5 year stunting is WHO's top Global Target 2025. Disappointingly, meta-analyses of intensive nutrition interventions reveal that they generally have low efficacy at improving growth. Unhygienic environments also contribute to growth failure, but large WASH Benefits and SHINE trials of improved water, sanitation and hygiene (WASH) recently reported no benefits to child growth. ⋯ The large difference in growth between children in SES1A living in Western-type housing and SES1B children living in the village, and the very shallow gradient between SES1B and SES5, implies a very high SES threshold before stunting and underweight will be eliminated. This may help to explain the lack of efficacy of the recent WASH interventions and points to the need for what is termed 'Transformative WASH'. Good quality housing, with piped water into the home, may be key to eliminating malnutrition.
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Randomized Controlled Trial Multicenter Study
Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children.
The RTS,S/AS01E vaccine provides partial protection against malaria in African children, but immune responses have only been partially characterized and do not reliably predict protective efficacy. We aimed to evaluate comprehensively the immunogenicity of the vaccine at peak response, the factors affecting it, and the antibodies associated with protection against clinical malaria in young African children participating in the multicenter phase 3 trial for licensure. ⋯ Cytophilic IgG responses to the C-terminal and NANP repeat regions of CSP and anti-HBsAg antibodies induced by RTS,S/AS01E vaccination were associated with malaria protection. In contrast, higher malaria exposure at baseline and non-cytophilic IgG responses to CSP were associated with disease risk. Data provide new correlates of vaccine success and failure in African children and reveal key insights into the mode of action that can guide development of more efficacious next-generation vaccines.