Effect of mivacurium 200 and 250 μg/kg in infants during isoflurane anesthesia: a randomized controlled trial [ISRCTN07742712]

BACKGROUND: Infants usually respond differently to a neuromuscular relaxant compared to children or adults. Isoflurane is commonly used as an anesthetic gas in infants. In an RCT design, we investigated whether a dose of mivacurium 250 μg/kg results in faster onset of action than 200 μg/kg in infants under isoflurane anesthesia. Spontaneous recovery times and cardiovascular response were also evaluated. METHODS: Twenty-four low surgical risk children, aged 6–24 months, undergoing an elective surgery and requiring tracheal intubation were selected. After anesthetic induction, patients randomly received an iv bolus dose of mivacurium 200 or 250 μg/kg. After maximal relaxation, the patient was intubated. Isoflurane was administered to maintain anesthetic level during the surgical procedure. Neuromuscular function was monitored by accelerometry (TOF-Guard) at the adductor pollicies. The first twitch (T) of the TOF and the T4/T1 were measured. The time-course of heart rate and systolic and diastolic blood pressure were analysed by transforming them into their respective areas under the curve. RESULTS: Mivacurium 250 μg/kg produced a maximal T block faster than 200 μg/kg, i.e. 2.4 ± 1.1 vs. 3.5 ± 1.4 min (p < 0.05). Spontaneous recovery times were similar in both groups. Heart rate was similar between doses while systolic and diastolic blood pressures were lower with the higher dose (p < 0.05). Flushing was observed in two cases, one in each group. CONCLUSIONS: The maximal effect of mivacurium 250 μg/kg, in infants under isoflurane anesthesia, was present one minute faster than 200 μg/kg. However, it produced a significant cardiovascular response

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Evolution and patterns of global health financing 1995-2014 : development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries

Background An adequate amount of prepaid resources for health is important to ensure access to health services and for the pursuit of universal health coverage. Previous studies on global health financing have described the relationship between economic development and health financing. In this study, we further explore global health financing trends and examine how the sources of funds used, types of services purchased, and development assistance for health disbursed change with economic development. We also identify countries that deviate from the trends. Methods We estimated national health spending by type of care and by source, including development assistance for health, based on a diverse set of data including programme reports, budget data, national estimates, and 964 National Health Accounts. These data represent health spending for 184 countries from 1995 through 2014. We converted these data into a common inflation-adjusted and purchasing power-adjusted currency, and used non-linear regression methods to model the relationship between health financing, time, and economic development. Findings Between 1995 and 2014, economic development was positively associated with total health spending and a shift away from a reliance on development assistance and out-of-pocket (OOP) towards government spending. The largest absolute increase in spending was in high-income countries, which increased to purchasing power-adjusted $5221 per capita based on an annual growth rate of 3.0$914 and $267 per capita in 2014, respectively. Spending in low-income countries grew nearly as fast, at 4.6$51 to $120 per capita. In 2014, 59.2$37.6 billion in 2016. Nonetheless, there is a great deal of variation revolving around these averages. 29 countries spend at least 50% more than expected per capita, based on their level of economic development alone, whereas 11 countries spend less than 50% their expected amount. Interpretation Health spending remains disparate, with low-income and lower-middle-income countries increasing spending in absolute terms the least, and relying heavily on OOP spending and development assistance. Moreover, tremendous variation shows that neither time nor economic development guarantee adequate prepaid health resources, which are vital for the pursuit of universal health coverage.Peer reviewe

Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000–2018

Background: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA. © 2022, The Author(s).Funding text 1: S Afzal acknowledges support of the Pakistan Society of Medical Infectious Diseases and King Edward Medical University to access the relevant data of HIV from various sources. T W Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia (FCT), I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB; FCT/MCTES (Ministério da Ciência, Tecnologia e Ensino Superior) through the project UIDB/50006/2020. K Deribe acknowledges support by the Wellcome Trust [grant number 201900/Z/16/Z] as part of his International Intermediate Fellowship. C Herteliu and A Pana are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. Claudiu Herteliu is partially supported by a grant of the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. Y J Kim acknowledges support by the Research Management Centre, Xiamen University Malaysia [No. XMUMRF/2020-C6/ITCM/0004]. S L Koulmane Laxminarayana acknowledges institutional support by the Manipal Academy of Higher Education. K Krishan acknowledges non-financial support from UGC Centre of Advanced Study, CAS II, Department of Anthropology, Panjab University, Chandigarh, India. M Kumar would like to acknowledge NIH/FIC K43 TW010716-04. I Landires is a member of the Sistema Nacional de Investigación (SNI), supported by the Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT), Panama. V Nuñez-Samudio is a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT). O O Odukoya was supported by the Fogarty International Center of the National Institutes of Health under the Award Number K43TW010704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Z Quazi Syed acknowledges support from JNMC, Datta Meghe Institute of Medical Sciences. A I Ribeiro was supported by National Funds through FCT, under the ‘Stimulus of Scientific Employment – Individual Support’ program within the contract CEECIND/02386/2018. A M Samy acknowledges the support from a fellowship of the Egyptian Fulbright Mission program and Ain Shams University. R Shrestha acknowledges support from NIDA K01 Award: K01DA051346. N Taveira acknowledges support from FCT and Aga Khan Development Network (AKDN) - Portugal Collaborative Research Network in Portuguese speaking countries in Africa (project reference: 332821690), and by the European & Developing Countries Clinical Trials Partnership (EDCTP), UE (project reference: RIA2016MC-1615). B Unnikrishnan acknowledges support from Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal. ; Funding text 2: LBD sub-Saharan Africa HIV Prevalence Collaborators S Afzal acknowledges support of the Pakistan Society of Medical Infectious Diseases and King Edward Medical University to access the relevant data of HIV from various sources. T W Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia (FCT), I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB; FCT/MCTES (Ministério da Ciência, Tecnologia e Ensino Superior) through the project UIDB/50006/2020. K Deribe acknowledges support by the Wellcome Trust [grant number 201900/Z/16/Z] as part of his International Intermediate Fellowship. C Herteliu and A Pana are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. Claudiu Herteliu is partially supported by a grant of the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. Y J Kim acknowledges support by the Research Management Centre, Xiamen University Malaysia [No. XMUMRF/2020-C6/ITCM/0004]. S L Koulmane Laxminarayana acknowledges institutional support by the Manipal Academy of Higher Education. K Krishan acknowledges non-financial support from UGC Centre of Advanced Study, CAS II, Department of Anthropology, Panjab University, Chandigarh, India. M Kumar would like to acknowledge NIH/FIC K43 TW010716-04. I Landires is a member of the Sistema Nacional de Investigación (SNI), supported by the Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT), Panama. V Nuñez-Samudio is a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT). O O Odukoya was supported by the Fogarty International Center of the National Institutes of Health under the Award Number K43TW010704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Z Quazi Syed acknowledges support from JNMC, Datta Meghe Institute of Medical Sciences. A I Ribeiro was supported by National Funds through FCT, under the ‘Stimulus of Scientific Employment – Individual Support’ program within the contract CEECIND/02386/2018. A M Samy acknowledges the support from a fellowship of the Egyptian Fulbright Mission program and Ain Shams University. R Shrestha acknowledges support from NIDA K01 Award: K01DA051346. N Taveira acknowledges support from FCT and Aga Khan Development Network (AKDN) - Portugal Collaborative Research Network in Portuguese speaking countries in Africa (project reference: 332821690), and by the European & Developing Countries Clinical Trials Partnership (EDCTP), UE (project reference: RIA2016MC-1615). B Unnikrishnan acknowledges support from Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal.; Funding text 3: This work was primarily supported by grant OPP1132415 from the Bill & Melinda Gates Foundation. The funder of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to publish. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. ; Funding text 4: S Afzal reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with the Pakistan society of Community Medicine & Public Health, the Pakistan Association of Medical Editors, and the Pakistan Society of Medical Infectious Diseases, all outside the submitted work. R Ancuceanu reports 5 payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Avvie, Sandoz, and B Braun, all outside the submitted work. T W Bärnighausen reports research grants from the European Union (Horizon 2020 and EIT Health), German Research Foundation (DFG), US National Institutes of Health, German Ministry of Education and Research, Alexander von Humboldt Foundation, Else-Kröner-Fresenius-Foundation, Wellcome Trust, Bill & Melinda Gates Foundation, KfW, UNAIDS, and WHO; consulting fees from KfW on the OSCAR initiative in Vietnam; participation on a Data Safety Monitoring Board or Advisory Board with the NIH-funded study “Healthy Options” (PIs: Smith Fawzi, Kaaya), Chair, Data Safety and Monitoring Board (DSMB), German National Committee on the “Future of Public Health Research and Education,” Chair of the scientific advisory board to the EDCTP Evaluation, Member of the UNAIDS Evaluation Expert Advisory Committee, National Institutes of Health Study Section Member on Population and Public Health Approaches to HIV/AIDS (PPAH), US National Academies of Sciences, Engineering, and Medicine’s Committee for the “Evaluation of Human Resources for Health in the Republic of Rwanda under the President’s Emergency Plan for AIDS Relief (PEPFAR),” University of Pennsylvania (UPenn) Population Aging Research Center (PARC) External Advisory Board Member; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as co-chair of the Global Health Hub Germany (which was initiated by the German Ministry of Health); all outside the submitted work. J das Neves reports grants or contracts from Ref. 13605 – Programa GÉNESE, Gilead Portugal (PGG/002/2016 – Programa GÉNESE, Gilead Portugal) outside the submitted work. L Dwyer-Lindgren reports support for the present manuscript from the Bill & Melinda Gates Foundation through grant OPP1132415. I Filip reports other financial or non-financial interests from Avicenna Medical and Clinical Research Institute, outside the submitted work. E Haeuser reports support for the present manuscript from the Bill & Melinda Gates Foundation through grant OPP1132415. C Herteliu reports grants from Romanian Ministry of Research Innovation and Digitalization, MCID, for project number ID-585-CTR-42-PFE-2021 (Jan 2022-Jun 2023) “Enhancing institutional performance through development of infrastructure and transdisciplinary research ecosystem within socio-economic domain – PERFECTIS,” from Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, for project number PN-III-P4-ID-PCCF-2016-0084 (Oct 2018-Sep 2022) “Understanding and modelling time-space patterns of psychology-related inequalities and polarization,” and project number PN-III-P2-2.1-SOL-2020-2-0351 (Jun 2020-Oct 2020) “Approaches within public health management in the context of COVID-19 pandemic,” and from the Ministry of Labour and Social Justice, Romania for project number “Agenda for skills Romania 2020-2025”; all outside the submitted work. J J Jozwiak reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Teva, Amgen, Synexus, Boehringer Ingelheim, Zentiva, and Sanofi as personal fees, all outside the submitted work. J Khubchandani reports other financial interests from Teva Pharmaceuticals, all outside the submitted work. K Krishnan reports other non-financial support from UGC Centre of Advanced Study, CAS II, Department of Anthropology, Panjab University, Chandigarh, India, outside the submitted work. H J Larson reports grants or contracts from the MacArthur Foundation and Merck to London School of Hygeine and Tropical Medicine, and from the Vaccine Confidence Fund to the University of Washington; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Center for Strategic and International Studies as payment to LSHTM for co-chairing HighLevel Panel and from GSK as personal payment for developing training sessions and lectures; leadership or fiduciary role in other board, society, committee or advocacy group, pair, with the ApiJect Advisory Board; all outside the submitted work. O O Odukoya reports support for the present manuscript from the Fogarty International Center of the National Institutes of Health under the Award Number K43TW010704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A Pans reports grants from Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, for project number PN-III-P4-ID-PCCF-2016-0084 (Oct 2018-Sep 2022) “Understanding and modelling time-space patterns of psychology-related inequalities and polarization,” and project number PN-III-P2-2.1-SOL-2020-2-0351 (Jun 2020-Oct 2020) “Approaches within public health management in the context of COVID-19 pandemic,” outside the submitted work. S R Pandi-Perumal reports royalties from Springer for editing services; stock or stock options in Somnogen Canada Inc as the President and Chief Executive Officer; all outside the submitted work. A Radfar reports other financial or non-financial interests from Avicenna Medical and Clinical Research Institute, outside the submitted work. A I Ribeiro reports grants or contracts from National Funds through FCT, under the ‘Stimulus of Scientific Employment – Individual Support’ program within the contract CEECIND/02386/2018, outside the submitted work. J M Ross reports support for the present manuscript from the Bill & Melinda Gates Foundation through grant OPP1132415; grants or contracts from National Institutes of Health and Firland Foundation as payments to their institution; consulting fees from United States Agency for International Development as personal payments, and from KNCV Tuberculosis Foundation as payments to their institution; all outside the submitted work. E Rubagotti reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Greenwich China Office and Unviersity Prince Mohammad VI, Morocco, all outside the submitted work. B Sartorius reports grants or contracts from DHSC – GRAM Project; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as a member of the GBD Scientific Council and a Member of WHO RGHS; all outside the submitted work. J A Singh reports consulting fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science LLC, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications, and the National Institutes of Health and the American College of Rheumatology; payment or honoraria for participating in the speakers bureau for Simply Speaking; support for attending meetings and/or travel from the steering committee of OMERACT, to attend their meeting every 2 years; participation on a Data Safety Monitoring Board or Advisory Board as an unpaid member of the FDA Arthritis Advisory Committee; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as a member of the steering committee of OMERACT, an international organization that develops measures for clinical trials and receives arm’s length funding from 12 pharmaceutical companies, with the Veterans Affairs Rheumatology Field Advisory Committee as Chair, and with the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis as a director and editor; stock or stock options in TPT Global Tech, Vaxart pharmaceuticals, Atyu Biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics Inc, Series Therapeutics, Tonix Pharmaceuticals, and Charlotte’s Web Holdings Inc. and previously owned stock options in Amarin, Viking, and Moderna pharmaceuticals; all outside the submitted work. N Taveira reports grants or contracts from FCT and Aga Khan Development Network (AKDN) – Portugal Collaborative Research Network in Portuguese speaking countries in Africa (Project reference: 332821690) and from European & Developing Countries Clinical Trials Partnership (EDCTP), UE (Project reference: RIA2016MC-1615), as payments made to their institution, all outside the submitted work

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future

Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015:a systematic analysis for the Global Burden of Disease Study 2015

Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores.Findings We generated 9.3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17.2 billion, 95% uncertainty interval [UI] 15.4-19.2 billion) and diarrhoeal diseases (2.39 billion, 2.30-2.50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2.36 billion (2.35-2.37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20-30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo.Interpretation Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. Copyright (C) The Author(s). Published by Elsevier Ltd.</p

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40.0% (95% uncertainty interval [UI] 39.4-40.7) to 50.3% (50.0-50.5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46.3% (95% UI 46.1-46.5) in 2017, compared with 28.7% (28.5-29.0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88.6% (95% UI 87.2-89.7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664-711) of the 1830 (1797-1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76.1% (95% UI 71.6-80.7) of countries from 2000 to 2017, and in 53.9% (50.6-59.6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe