Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Strategies for reducing maternal mortality: getting on with what works

Observational findings achieved during the past two decades suggest that the intestinal microbiota may contribute to the metabolic health of the human host and, when aberrant, to the pathogenesis of various common metabolic disorders including obesity, type 2 diabetes, non-alcoholic liver disease, cardio-metabolic diseases and malnutrition. However, to gain a mechanistic understanding of how the gut microbiota affects host metabolism, research is moving from descriptive microbiota census analyses to cause-and-effect studies. Joint analyses of high-throughput human multi-omics data, including metagenomics and metabolomics data, together with measures of host physiology and mechanistic experiments in humans, animals and cells hold potential as initial steps in the identification of potential molecular mechanisms behind reported associations. In this Review, we discuss the current knowledge on how gut microbiota and derived microbial compounds may link to metabolism of the healthy host or to the pathogenesis of common metabolic diseases. We highlight examples of microbiota-targeted interventions aiming to optimize metabolic health, and we provide perspectives for future basic and translational investigations within the nascent and promising research field. In this Review, Fan and Pedersen discuss how the gut microbiota and derived microbial compounds may contribute to human metabolic health and to the pathogenesis of common metabolic diseases, and highlight examples of microbiota-targeted interventions aiming to optimize metabolic health.

Gut microbiota in human metabolic health and disease.

Hypertension 66 (20.3%) 24 (24.2%) 30 (16.3%) NS Diabetes 20 (6.2%) 7 (7.1%) 10 (5.4%) NS Excess weight 78 (24%) 27 (27.3%) 44 (23.9%) NS Smokers 64 (19.7%) 17 (17.2%) 35 (19.0%) NS Age >50 years 137 (42.2%) 54 (54.5%) 67 (36.4%) <0.02 Kidney disease 7 (2.2%) 1 (1%) 5 (2.7%) NS Family history, DM 102 (31.4%) 28 (28.3%) 66 (35.9%) NS

Conflict of interest statement. None declared.

We set out to determine the impact of washing hands with soap on the risk of diarrhoeal diseases in the community with a systematic review with random effects meta-analysis Our data sources were studies linking handwashing with diarrhoeal diseases Seven intervention studies, six case-control, two cross-sectional, and two cohort studies were located from electronic databases, hand searching, and the authors' collections The pooled relative risk of diarrhoeal disease associated with not washing hands from the intervention trials was 188 (95% CI 131-268), implying that handwashing could reduce diarrhoea risk by 47% When all studies, when only those of high quality, and when only those studies specifically mentioning soap were pooled, risk reduction ranged from 42-44% The risks of severe intestinal infections and of shigellosis were associated with reductions of 48% and 59%, respectively In the absence of adequate mortality studies, we extrapolate the potential number of diarrhoea deaths that could be averted by handwashing at about a million (11 million, lower estimate 05 million, upper estimate 14 million) Results may be affected by the poor quality of many of the studies and may be inflated by publication bias On current evidence, washing hands with soap can reduce the risk of diarrhoeal diseases by 42-47% and interventions to promote handwashing might save a million lives More and better-designed trials are needed to measure the impact of washing hands on diarrhoea and acute respiratory infections in developing countries

Effect of washing hands with soap on diarrhoea risk in the community: a systematic review

MALNUTRITION, WITH ITS 2 CONSTITUENTS of protein–energy malnutrition and micronutrient deficiencies, continues to be a major health burden in developing countries. It is globally the most important risk factor for illness and death, with hundreds of millions of pregnant women and young children particularly affected. Apart from marasmus and kwashiorkor (the 2 forms of protein– energy malnutrition), deficiencies in iron, iodine, vitamin A and zinc are the main manifestations of malnutrition in developing countries. In these communities, a high prevalence of poor diet and infectious disease regularly unites into a vicious circle. Although treatment protocols for severe malnutrition have in recent years become more efficient, most patients (especially in rural areas) have little or no access to formal health services and are never seen in such settings. Interventions to prevent protein– energy malnutrition range from promoting breast-feeding to food supplementation schemes, whereas micronutrient deficiencies would best be addressed through food-based strategies such as dietary diversification through home gardens and small livestock. The fortification of salt with iodine has been a global success story, but other micronutrient supplementation schemes have yet to reach vulnerable populations sufficiently. To be effective, all such interventions require accompanying nutrition-education campaigns and health interventions. To achieve the hunger- and malnutrition-related Millennium Development Goals, we need to address poverty, which is clearly associated with the insecure supply of food and nutrition.

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Malnutrition and health in developing countries

Methylene blue has intrinsic antimalarial activity and it can act as a chloroquine sensitizer. In addition, methylene blue must be considered for preventing methemoglobinemia, a serious complication of malarial anemia. As an antiparasitic agent, methylene blue is pleiotropic: it interferes with hemoglobin and heme metabolism in digestive organelles, and it is a selective inhibitor of Plasmodium falciparum glutathione reductase. The latter effect results in glutathione depletion which sensitizes the parasite for chloroquine action. At the Centre de Recherche en Sante de Nouna in Burkina Faso, we study the combination of chloroquine with methylene blue (BlueCQ) as a possible medication for malaria in endemic regions. A pilot study with glucose-6-phosphate dehydrogenase-sufficient adult patients has been conducted recently.

https://www.tandfonline.com/doi/pdf/10.1179/135100003225002899

Methylene blue as an antimalarial agent.

Determinants of utilisation of maternal care services after the reduction of user fees: A case study from rural Burkina Faso

OBJECTIVE: The aim of the study was to quantify the effect of risk factors for childhood mortality in a typical rural setting in sub- Saharan Africa. METHODS: We performed a survival analysis of births within a population under demographic surveillance from 1992 to 1999 based on data from a demographic surveillance system in 39 villages around Nouna, western Burkina Faso, with a total population of about 30 000. All children born alive in the period 1 January 1993 to 31 December 1999 in the study area (n = 10 122) followed-up until 31 December 1999 were included. All-cause childhood mortality was used as outcome variable. FINDINGS: Within the observation time, 1340 deaths were recorded. In a Cox regression model a simultaneous estimation of hazard rate ratios showed death of the mother and being a twin as the strongest risk factors for mortality. For both, the risk was most pronounced in infancy. Further factors associated with mortality include age of the mother, birth spacing, season of birth, village, ethnic group, and distance to the nearest health centre. Finally, there was an overall decrease in childhood mortality over the years 1993-99. CONCLUSION: The study supports the multi-causation of childhood deaths in rural West Africa during the 1990s and supports the overall trend, as observed in other studies, of decreasing childhood mortality in these populations. The observed correlation between the factors highlights the need for multivariate analysis to disentangle the separate effects. These findings illustrate the need for more comprehensive improvement of prenatal and postnatal care in rural sub-Saharan Africa.

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Risk factors of infant and child mortality in rural Burkina Faso

The literature on health care seeking behaviour in sub-Saharan Africa for children suffering from malaria is quite extensive. This literature, however, is predominately quantitative and, inevitably, fails to explore how the local concepts of illness may affect people's choices. Understanding local concepts of illness and their influence on health care-seeking behaviour can complement existing knowledge and lead to the development of more effective malaria control interventions. In a rural area of Burkina Faso, four local concepts of illness resembling the biomedical picture of malaria were described according to symptoms, aetiology, and treatment. Data were collected through eight focus group discussions, 17 semi-structured interviews with key informants, and through the analysis of 100 verbal autopsy questionnaires of children under-five diagnosed with malaria. Sumaya, dusukun yelema, kono, and djoliban were identified as the four main local illness concepts resembling respectively uncomplicated malaria, respiratory distress syndrome, cerebral malaria, and severe anaemia. The local disease categorization was found to affect both treatment and provider choice. While sumaya is usually treated by a mix of traditional and modern methods, dusukun yelema and kono are preferably treated by traditional healers, and djoliban is preferably treated in modern health facilities. Besides the conceptualization of illness, poverty was found to be another important influencing factor of health care-seeking behaviour. The findings complement previous evidence on health care-seeking behaviour, by showing how local concepts of illness strongly influence treatment and choice of provider. Local concepts of illness need to be considered when developing specific malaria control programmes.

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Olaf Müller

Papers

Malnutrition and health in developing countries

Methylene blue as an antimalarial agent.

Determinants of utilisation of maternal care services after the reduction of user fees: A case study from rural Burkina Faso

Risk factors of infant and child mortality in rural Burkina Faso

Malaria in rural Burkina Faso: local illness concepts, patterns of traditional treatment and influence on health-seeking behaviour.