Effects of ambient heat exposure on risk of all-cause mortality in children younger than 5 years in Africa: a pooled time-series analysis.

BACKGROUND: Reducing child mortality is a Sustainable Development Goal, and climate change constitutes numerous challenges for Africa. Previous research has shown an association between leading causes of child mortality and climate change. However, few studies have examined these effects in detail. We aimed to explore the effects of ambient heat on neonate, post-neonate, and child mortality rates. METHODS: For this pooled time-series analysis, health data were obtained from the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) Health and Demographic Surveillance System. We included data from 29 settlements from 13 countries across Africa, collected via monthly surveys from Jan 1, 1993, to Dec 31, 2016. Climate data were obtained from ERA5, collected from Jan 1, 1991, to Dec 31, 2019. We pooled these data for monthly mean daily maximum wet bulb globe temperature (WBGT) and downscaled to geolocations. Due to data heaping, we pooled our health data on a monthly temporal scale and a spatial scale into six different climate regions (ie, Sahel [ie, Burkina Faso and northern Ghana], Guinea [ie, southern Ghana, Côte d'Ivoire, and Nigeria], Senegal and The Gambia, eastern Africa [ie, Kenya, Malawi, Tanzania, Mozambique, and Uganda], South Africa, and Ethiopia). Our outcomes were neonate (ie, younger than 28 days), post-neonate (ie, aged 28 days to 1 year), and child (ie, older than 1 year and younger than 5 years) mortality. To assess the association between WBGT and monthly all-cause mortality, we used a time-series regression with a quasi-Poisson, polynomial-distributed lag model. FINDINGS: Between Jan 1, 1993, and Dec 31, 2016, there were 44 909 deaths in children younger than 5 years across the 29 sites in the 13 African countries: 10 078 neonates, 14 141 post-neonates, and 20 690 children. We observed differences in the association of heat with neonate, post-neonate, and child mortality by study region. For example, for Ethiopia, the relative risk ratio of mortality at the 95th percentile compared with median heat exposure during the study period was 1·14 (95% CI 1·06-1·23) for neonates, 0·99 (0·90-1·07) for post-neonates, and 0·79 (0·73-0·87) for children. Across the whole year, there was a significant increase in the relative risk of increased mortality for children in eastern Africa (relative risk 1·27, 95% CI 1·19-1·36) and Senegal and The Gambia (1·11, 1·04-1·18). INTERPRETATION: Our results show that the influence of extreme heat on mortality risk in children younger than 5 years varies by age group, region, and season. Future research should explore potentially informative ways to measure subtleties of heat stress and the factors contributing to vulnerability. FUNDING: EU Horizons as part of the Heat Indicators for Global Health (HIGH) Horizons project.

Development and Verification of a Body Weight-Directed Disease Trial Model for Glucose Homeostasis.

Weight loss has been associated with improvement in insulin sensitivity. It is consequently a cornerstone in the management of type 2 diabetes mellitus (T2DM). However, the strictly quantitative relationship between weight loss, insulin sensitivity, and clinically relevant glucose homeostasis biomarkers as well as changes therein as T2DM progresses is not yet fully understood. Therefore, the objective of our research was to establish a body weight-directed disease trial model for glucose homeostasis. To that end, we conducted a model-based meta-analysis using time course data of body weight loss (following lifestyle change or surgical procedure) and corresponding improvement of insulin sensitivity expressed as the Matsuda index. Changes in body weight were best described by a sigmoidal Emax model, whereas changes in the Matsuda index were best described by a linear model with a slope of 3.49. Once developed and verified, the model-based meta-analysis was linked to a disease-drug trial model for T2DM previously developed by our group to characterize and predict the impact of weight loss on clinically relevant glucose homeostasis biomarkers. The joint model was then used to conduct clinical trial simulations, which showed that weight loss can greatly improve clinically relevant glucose homeostasis biomarkers in T2DM patients.