Setting Research Priorities To Reduce Global Mortality from Childhood Diarrhoea by 2015

Olivier Fontaine and colleagues applied a priority-setting methodology to identify research priorities aimed at reducing global diarrhea mortality by 2015

Directing diarrhoeal disease research towards disease-burden reduction

Despite gains in controlling mortality relating to diarrhoeal disease, the burden of disease remains unacceptably high. To refocus health research to target disease-burden reduction as the goal of research in child health, the Child Health and Nutrition Research Initiative developed a systematic strategy to rank health research options. This priority-setting exercise included listing of 46 competitive research options in diarrhoeal disease and their critical and quantitative appraisal by 10 experts based on five criteria for research that reflect the ability of the research to be translated into interventions and achieved disease-burden reduction. These criteria included the answerability of the research questions, the efficacy and effectiveness of the intervention resulting from the research, the maximal potential for disease-burden reduction of the interventions derived from the research, the affordability, deliverability, and sustainability of the intervention supported by the research, and the overall effect of the research-derived intervention on equity. Experts scored each research option independently to delineate the best investments for diarrhoeal disease control in the developing world to reduce the burden of disease by 2015. Priority scores obtained for health policy and systems research obtained eight of the top 10 rankings in overall scores, indicating that current investments in health research are significantly different from those estimated to be the most effective in reducing the global burden of diarrhoeal disease by 2015

Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics

This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1 Mb in length in a representative population of 809 unrelated North Americans of European descent ranging in chronological age from 19–99 years old. These homozygous tracts made up a population average of 42 Mb of the genome corresponding to 1.6% of the entire genome, with each homozygous tract an average of 1.5 Mb in length. Runs of homozygosity are steadily decreasing in size and frequency as time progresses (linear regression, p<0.05). We also calculated inbreeding coefficients and showed a significant trend for population-wide increasing heterozygosity outside of linkage disequilibrium. We successfully replicated these associations in a demographically similar cohort comprised of a subgroup of 477 Baltimore Longitudinal Study of Aging participants. We also constructed statistical models showing predicted declining rates of autozygosity spanning the 20th century. These predictive models suggest a 14.0% decrease in the frequency of these runs of homozygosity and a 24.3% decrease in the percent of the genome in runs of homozygosity, as well as a 30.5% decrease in excess homozygosity based on the linkage pruned inbreeding coefficients. The trend for decreasing autozygosity due to panmixia and larger effective population sizes will likely affect the frequency of rare recessive genetic diseases in the future. Autozygosity has declined, and it seems it will continue doing so

Alma-Ata: Rebirth and revision 8 - Primary health care: making Alma-Ata a reality

The principles agreed at Alma-Ata 30 years ago apply just as much now as they did then. Health for all by the year 2000 was not achieved, and the Millennium Development Goals (MDGs) for 2015 will not be met in most low-income countries without substantial acceleration of primary health care. Factors have included insufficient political prioritisation of health, structural adjustment policies, poor governance, population growth, inadequate health systems, and scarce research and assessment on primary health care. We propose the following priorities for revitalising primary health care. Health-service infrastructure, including human resources and essential drugs, needs strengthening, and user fees should be removed for primary health-care services to improve use. A continuum of care for maternal, newborn, and child health services, including family planning, is needed. Evidence-based, integrated packages of community and primary curative and preventive care should be adapted to country contexts, assessed, and scaled up. Community participation and community health workers linked to strengthened primary-care facilities and first-referral services are needed. Furthermore, intersectoral action linking health and development is necessary, including that for better water, sanitation, nutrition, food security, and HIV control. Chronic diseases, mental health, and child development should be addressed. Progress should be measured and accountability assured. We prioritise research questions and suggest actions and measures for stakeholders both locally and globally, which are required to revitalise primary health care

Impact on emergency and elective hospital-based care in Scotland over the first 12 months of the pandemic: interrupted time-series analysis of national lockdowns

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This analysis is part of the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) study. EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE – The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through the Scottish Government DG Health and Social Care. SAS and AS are also supported by the COVID-19 Longitudinal Health and Wellbeing National Core Study, funded by the Medical Research Council (MC_PC_20030). SVK acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2) and the Scottish Government Chief Scientist Office (SPHSU17). JM is partly funded by the National Institute for Health Research Applied Research Collaboration West (NIHR ARC West).Objectives COVID-19 has resulted in the greatest disruption to National Health Service (NHS) care in its over 70-year history. Building on our previous work, we assessed the ongoing impact of pandemic-related disruption on provision of emergency and elective hospital-based care across Scotland over the first year of the pandemic. Design We undertook interrupted time-series analyses to evaluate the impact of ongoing pandemic-related disruption on hospital NHS care provision at national level and across demographics and clinical specialties spanning the period 29 March 2020?28 March 2021. Setting Scotland, UK. Participants Patients receiving hospital care from NHS Scotland. Main outcome measures We used the percentage change of accident and emergency attendances, and emergency and planned hospital admissions during the pandemic compared to the average admission rate for equivalent weeks in 2018-2019. Results As restrictions were gradually lifted in Scotland after the first lockdown, hospital-based admissions increased approaching pre-pandemic levels. Subsequent tightening of restrictions in September 2020 were associated with a change in slope of relative weekly admissions rate: -1.98% (-2.38, -1.58) in accident and emergency attendance, -1.36% (-1.68, -1.04) in emergency admissions and -2.31% (-2.95, -1.66) in planned admissions. A similar pattern was seen across sex, socioeconomic status and most age groups, except children (0-14 years) where accident and emergency attendance, and emergency admissions were persistently low over the study period. Conclusions We found substantial disruption to urgent and planned inpatient healthcare provision in hospitals across NHS Scotland. There is the need for urgent policy responses to address continuing unmet health needs and to ensure resilience in the context of future pandemics.Publisher PDFPeer reviewe

Estimation of the national disease burden of influenza-associated severe acute respiratory illness in Kenya and Guatemala : a novel methodology

Background: Knowing the national disease burden of severe influenza in low-income countries can inform policy decisions around influenza treatment and prevention. We present a novel methodology using locally generated data for estimating this burden. Methods and Findings: This method begins with calculating the hospitalized severe acute respiratory illness (SARI) incidence for children <5 years old and persons ≥5 years old from population-based surveillance in one province. This base rate of SARI is then adjusted for each province based on the prevalence of risk factors and healthcare-seeking behavior. The percentage of SARI with influenza virus detected is determined from provincial-level sentinel surveillance and applied to the adjusted provincial rates of hospitalized SARI. Healthcare-seeking data from healthcare utilization surveys is used to estimate non-hospitalized influenza-associated SARI. Rates of hospitalized and non-hospitalized influenza-associated SARI are applied to census data to calculate the national number of cases. The method was field-tested in Kenya, and validated in Guatemala, using data from August 2009–July 2011. In Kenya (2009 population 38.6 million persons), the annual number of hospitalized influenza-associated SARI cases ranged from 17,129–27,659 for children <5 years old (2.9–4.7 per 1,000 persons) and 6,882–7,836 for persons ≥5 years old (0.21–0.24 per 1,000 persons), depending on year and base rate used. In Guatemala (2011 population 14.7 million persons), the annual number of hospitalized cases of influenza-associated pneumonia ranged from 1,065–2,259 (0.5–1.0 per 1,000 persons) among children <5 years old and 779–2,252 cases (0.1–0.2 per 1,000 persons) for persons ≥5 years old, depending on year and base rate used. In both countries, the number of non-hospitalized influenza-associated cases was several-fold higher than the hospitalized cases. Conclusions: Influenza virus was associated with a substantial amount of severe disease in Kenya and Guatemala. This method can be performed in most low and lower-middle income countries

A cleaner burning biomass-fuelled cookstove intervention to prevent pneumonia in children under 5 years old in rural Malawi (the Cooking and Pneumonia Study): a cluster randomised controlled trial

Medical Research Council, UK Department for International Development, and Wellcome Trust

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in &gt;100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P &lt; 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD

Global, regional, and national estimates of pneumonia morbidity and mortality in children younger than 5 years between 2000 and 2015: a systematic analysis

Background: Global child mortality reduced substantially during the Millennium Development Goal period (2000–15). We aimed to estimate morbidity, mortality, and prevalence of risk factors for child pneumonia at the global, regional, and national level for developing countries for the Millennium Development Goal period. Methods: We estimated the incidence, number of hospital admissions, and in-hospital mortality due to all-cause clinical pneumonia in children younger than 5 years in developing countries at 5-year intervals during the Millennium Development Goal period (2000–15) using data from a systematic review and Poisson regression. We estimated the incidence and number of cases of clinical pneumonia, and the pneumonia burden attributable to HIV for 132 developing countries using a risk-factor-based model that used Demographic and Health Survey data on prevalence of the various risk factors for child pneumonia. We also estimated pneumonia mortality in young children using data from multicause models based on vital registration and verbal autopsy. Findings: Globally, the number of episodes of clinical pneumonia in young children decreased by 22% from 178 million (95% uncertainty interval [UI] 110–289) in 2000 to 138 million (86–226) in 2015. In 2015, India, Nigeria, Indonesia, Pakistan, and China contributed to more than 54% of all global pneumonia cases, with 32% of the global burden from India alone. Between 2000 and 2015, the burden of clinical pneumonia attributable to HIV decreased by 45%. Between 2000 and 2015, global hospital admissions for child pneumonia increased by 2·9 times with a more rapid increase observed in the WHO South-East Asia Region than the African Region. Pneumonia deaths in this age group decreased from 1·7 million (95% UI 1·7–2·0) in 2000 to 0·9 million (0·8–1·1) in 2015. In 2015, 49% of global pneumonia deaths occurred in India, Nigeria, Pakistan, Democratic Republic of the Congo, and Ethiopia collectively. All key risk factors for child pneumonia (non-exclusive breastfeeding, crowding, malnutrition, indoor air pollution, incomplete immunisation, and paediatric HIV), with the exception of low birthweight, decreased across all regions between 2000 and 2015. Interpretation: Globally, the incidence of child pneumonia decreased by 30% and mortality decreased by 51% during the Millennium Development Goal period. These reductions are consistent with the decrease in the prevalence of some of the key risk factors for pneumonia, increasing socioeconomic development and preventive interventions, improved access to care, and quality of care in hospitals. However, intersectoral action is required to improve socioeconomic conditions and increase coverage of interventions targeting risk factors for child pneumonia to accelerate decline in pneumonia mortality and achieve the Sustainable Development Goals for health by 2030. Funding: Bill &amp; Melinda Gates Foundation