A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care

Mass deworming for improving health and cognition of children in endemic helminth areas: A systematic review and individual participant data network meta‐analysis

Background: Soil transmitted (or intestinal) helminths and schistosomes affect millions of children worldwide. Objectives: To use individual participant data network meta-analysis (NMA) to explore the effects of different types and frequency of deworming drugs on anaemia, cognition and growth across potential effect modifiers. Search Methods: We developed a search strategy with an information scientist to search MEDLINE, CINAHL, LILACS, Embase, the Cochrane Library, Econlit, Internet Documents in Economics Access Service (IDEAS), Public Affairs Information Service (PAIS), Social Services Abstracts, Global Health CABI and CAB Abstracts up to March 27, 2018. We also searched grey literature, websites, contacted authors and screened references of relevant systematic reviews. Selection Criteria: We included randomised and quasirandomised deworming trials in children for deworming compared to placebo or other interventions with data on baseline infection. Data Collection and Analysis: We conducted NMA with individual participant data (IPD), using a frequentist approach for random-effects NMA. The covariates were: age, sex, weight, height, haemoglobin and infection intensity. The effect estimate chosen was the mean difference for the continuous outcome of interest. Results: We received data from 19 randomized controlled trials with 31,945 participants. Overall risk of bias was low. There were no statistically significant subgroup effects across any of the potential effect modifiers. However, analyses showed that there may be greater effects on weight for moderate to heavily infected children (very low certainty evidence). Authors' Conclusions: This analysis reinforces the case against mass deworming at a population-level, finding little effect on nutritional status or cognition. However, children with heavier intensity infections may benefit more. We urge the global community to adopt calls to make data available in open repositories to facilitate IPD analyses such as this, which aim to assess effects for the most vulnerable individuals

PRIME-IPD SERIES Part 1. The PRIME-IPD tool promoted verification and standardization of study datasets retrieved for IPD meta-analysis

OBJECTIVES: We describe a systematic approach to preparing data in the conduct of Individual Participant Data (IPD) analysis. STUDY DESIGN AND SETTING: A guidance paper proposing methods for preparing individual participant data for meta-analysis from multiple study sources, developed by consultation of relevant guidance and experts in IPD. We present an example of how these steps were applied in checking data for our own IPD meta analysis (IPD-MA). RESULTS: We propose five steps of Processing, Replication, Imputation, Merging, and Evaluation to prepare individual participant data for meta-analysis (PRIME-IPD). Using our own IPD-MA as an exemplar, we found that this approach identified missing variables and potential inconsistencies in the data, facilitated the standardization of indicators across studies, confirmed that the correct data were received from investigators, and resulted in a single, verified dataset for IPD-MA. CONCLUSION: The PRIME-IPD approach can assist researchers to systematically prepare, manage and conduct important quality checks on IPD from multiple studies for meta-analyses. Further testing of this framework in IPD-MA would be useful to refine these steps

Mass deworming for improving health and cognition of children in endemic helminth areas: A systematic review and individual participant data network meta‐analysis

BackgroundSoil transmitted (or intestinal) helminths and schistosomes affect millions of children worldwide.ObjectivesTo use individual participant data network meta‐analysis (NMA) to explore the effects of different types and frequency of deworming drugs on anaemia, cognition and growth across potential effect modifiers.Search MethodsWe developed a search strategy with an information scientist to search MEDLINE, CINAHL, LILACS, Embase, the Cochrane Library, Econlit, Internet Documents in Economics Access Service (IDEAS), Public Affairs Information Service (PAIS), Social Services Abstracts, Global Health CABI and CAB Abstracts up to March 27, 2018. We also searched grey literature, websites, contacted authors and screened references of relevant systematic reviews.Selection CriteriaWe included randomised and quasirandomised deworming trials in children for deworming compared to placebo or other interventions with data on baseline infection.Data Collection and AnalysisWe conducted NMA with individual participant data (IPD), using a frequentist approach for random‐effects NMA. The covariates were: age, sex, weight, height, haemoglobin and infection intensity. The effect estimate chosen was the mean difference for the continuous outcome of interest.ResultsWe received data from 19 randomized controlled trials with 31,945 participants. Overall risk of bias was low. There were no statistically significant subgroup effects across any of the potential effect modifiers. However, analyses showed that there may be greater effects on weight for moderate to heavily infected children (very low certainty evidence).Authors' ConclusionsThis analysis reinforces the case against mass deworming at a population‐level, finding little effect on nutritional status or cognition. However, children with heavier intensity infections may benefit more. We urge the global community to adopt calls to make data available in open repositories to facilitate IPD analyses such as this, which aim to assess effects for the most vulnerable individuals.</div

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Acknowledgements: The authors thank the expert group for their time and effort in this priority–setting exercise, and the contribution of anonymous reviewers to the final version of this report. We acknowledge inputs from Dr Diane Morof from Centers for Disease Control and Prevention, USA. Funding: This work was supported by Save the Children.Peer reviewedPublisher PD

The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level Results From the Global Burden of Disease Study 2015

Akinyemiju T, Abera S, Ahmed M, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level Results From the Global Burden of Disease Study 2015. JAMA ONCOLOGY. 2017;3(12):1683-1691.IMPORTANCE Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. OBJECTIVE To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an " other" group that encompasses residual causes. DESIGN, SETTINGS, AND PARTICIPANTS Mortalitywas estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. MAIN OUTCOMES AND MEASURES Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. RESULTS There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and -8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. CONCLUSIONS AND RELEVANCE Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts

Setting research priorities to improve global newborn health and prevent stillbirths by 2025.

BACKGROUND: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. METHODS: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. RESULTS: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. CONCLUSION: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Background In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. Methods We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

Global and national Burden of diseases and injuries among children and adolescents between 1990 and 2013

Importance The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce. Objective To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study. Evidence Review Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates. Findings Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world’s deaths from neonatal encephalopathy. Half of the world’s diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia. Conclusions and Relevance Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed