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.
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.
BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification. FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. ; Funding: We thank the countless individuals who have contributed to the Global Burden of Disease (GBD) Study 2015 in various capacities. We specifically thank Jeffrey Eaton and John Stover. HW and CJLM received funding for this study from the Bill & Melinda Gates Foundation; the National Institute of Mental Health, National Institutes of Health (NIH; R01MH110163); and the National Institute on Aging, NIH (P30AG047845). LJAR acknowledges the support of Qatar National Research Fund (NPRP 04-924-3-251) who provided the main funding for generating the data provided to the GBD-Institute for Health Metrics and Evaluation effort. BPAQ acknowledges institutional support from PRONABEC (National Program of Scholarship and Educational Loan), provided by the Peruvian government. DB is supported by the Bill & Melinda Gates Foundation (grant number OPP1068048). JDN was supported in his contribution to this work by a Fellowship from Fundacao para a Ciencia e a Tecnologia, Portugal (SFRH/BPD/92934/2013). KD is supported by a Wellcome Trust Fellowship in Public Health and Tropical Medicine (grant number 099876). TF received financial support from the Swiss National Science Foundation (SNSF; project number P300P3-154634). AG acknowledges funding from Sistema Nacional de Investigadores de Panama-SNI. PJ is supported by Wellcome Trust-DBT India Alliance Clinical and Public Health Intermediate Fellowship. MK receives research support from the Academy of Finland, the Swedish Research Council, Alzheimerfonden, Alzheimer's Research & Prevention Foundation, Center for Innovative Medicine (CIMED) at Karolinska Institutet South Campus, AXA Research Fund, Wallenberg Clinical Scholars Award from the Knut och Alice Wallenbergs Foundation, and the Sheika Salama Bint Hamdan Al Nahyan Foundation. AK's work was supported by the Miguel Servet contract financed by the CP13/00150 and PI15/00862 projects, integrated into the National R&D&I and funded by the ISCIII (General Branch Evaluation and Promotion of Health Research), and the European Regional Development Fund (ERDF-FEDER). SML is funded by a National Institute for Health Research (NIHR) Clinician Scientist Fellowship (grant number NIHR/CS/010/014). HJL reports grants from the NIHR, EU Innovative Medicines Initiative, Centre for Strategic & International Studies, and WHO. WM is Program analyst, Population and Development, in the Peru Country Office of the United Nations Population Fund, which does not necessarily endorse this study. For UOM, funding from the German National Cohort Consortium (O1ER1511D) is gratefully acknowledged. KR reports grants from NIHR Oxford Biomedical Research Centre, NIHR Career Development Fellowship, and Oxford Martin School during the conduct of the study. GR acknowledges that work related to this paper has been done on the behalf of the GBD Genitourinary Disease Expert Group supported by the International Society of Nephrology (ISN). ISS reports grants from FAPESP (Brazilian public agency). RSS receives institutional support from Universidad de Ciencias Aplicadas y Ambientales, UDCA, Bogota Colombia. SS receives postdoctoral funding from the Fonds de la recherche en sante du Quebec (FRSQ), including its renewal. RTS was supported in part by grant number PROMETEOII/2015/021 from Generalitat Valenciana and the national grant PI14/00894 from ISCIII-FEDER. PY acknowledges support from Strategic Public Policy Research (HKU7003-SPPR-12).
Background: timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. Methods: for countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification. Findings: global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1–3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5–2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6–40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7–1·9 million) in 2005, to 1·2 million deaths (1·1–1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. Interpretation: scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. Funding Bill & Melinda Gates Foundation, and National Institute of Mental Health and National Institute on Aging, National Institutes of Health
Background Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. Methods For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification. Findings Global HIV incidence reached its peak in 1997, at 3.3 million new infections (95% uncertainty interval [UI] 3.1-3.4 million). Annual incidence has stayed relatively constant at about 2.6 million per year (range 2.5-2.8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38.8 million (95% UI 37.6-40.4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1.8 million deaths (95% UI 1.7-1.9 million) in 2005, to 1.2 million deaths (1.1-1.3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. Interpretation Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license
Publisher's version (útgefin grein) ; Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd. ; Research reported in this publication was supported by the Bill & Melinda Gates Foundation; the University of Melbourne; Queensland Department of Health, Australia; the National Health and Medical Research Council, Australia; Public Health England; the Norwegian Institute of Public Health; St Jude Children's Research Hospital; the Cardiovascular Medical Research and Education Fund; the National Institute on Ageing of the National Institutes of Health (award P30AG047845); and the National Institute of Mental Health of the National Institutes of Health (award R01MH110163). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. The authors alone are responsible for the views expressed in this Article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated, the National Health Service (NHS), the National Institute for Health Research (NIHR), the UK Department of Health and Social Care, or Public Health England; the United States Agency for International Development (USAID), the US Government, or MEASURE Evaluation; or the European Centre for Disease Prevention and Control (ECDC). This research used data from the Chile National Health Survey 2003, 2009-10, and 2016-17. The authors are grateful to the Ministry of Health, the survey copyright owner, for allowing them to have the database. All results of the study are those of the authors and in no way committed to the Ministry. The Costa Rican Longevity and Healthy Aging Study project is a longitudinal study by the University of Costa Rica's Centro Centroamericano de Poblacion and Instituto de Investigaciones en Salud, in collaboration with the University of California at Berkeley. The original pre-1945 cohort was funded by the Wellcome Trust (grant 072406), and the 1945-55 Retirement Cohort was funded by the US National Institute on Aging (grant R01AG031716). The principal investigators are Luis Rosero-Bixby and William H Dow and co-principal investigators are Xinia Fernandez and Gilbert Brenes. The accuracy of the authors' statistical analysis and the findings they report are not the responsibility of ECDC. ECDC is not responsible for conclusions or opinions drawn from the data provided. ECDC is not responsible for the correctness of the data and for data management, data merging and data collation after provision of the data. ECDC shall not be held liable for improper or incorrect use of the data. The Health Behaviour in School-Aged Children (HBSC) study is an international study carried out in collaboration with WHO/EURO. The international coordinator of the 1997-98, 2001-02, 2005-06, and 2009-10 surveys was Candace Currie and the databank manager for the 1997-98 survey was Bente Wold, whereas for the following surveys Oddrun Samdal was the databank manager. A list of principal investigators in each country can be found on the HBSC website. Data used in this paper come from the 2009-10 Ghana Socioeconomic Panel Study Survey, which is a nationally representative survey of more than 5000 households in Ghana. The survey is a joint effort undertaken by the Institute of Statistical, Social and Economic Research (ISSER) at the University of Ghana and the Economic Growth Centre (EGC) at Yale University. It was funded by EGC. ISSER and the EGC are not responsible for the estimations reported by the analysts. The Palestinian Central Bureau of Statistics granted the researchers access to relevant data in accordance with license number SLN2014-3-170, after subjecting data to processing aiming to preserve the confidentiality of individual data in accordance with the General Statistics Law, 2000. The researchers are solely responsible for the conclusions and inferences drawn upon available data. Data for this research was provided by MEASURE Evaluation, funded by USAID. The authors thank the Russia Longitudinal Monitoring Survey, conducted by the National Research University Higher School of Economics and ZAO Demoscope together with Carolina Population Center, University of North Carolina at Chapel Hill and the Institute of Sociology, Russia Academy of Sciences for making data available. This paper uses data from the Bhutan 2014 STEPS survey, implemented by the Ministry of Health with the support of WHO; the Kuwait 2006 and 2014 STEPS surveys, implemented by the Ministry of Health with the support of WHO; the Libya 2009 STEPS survey, implemented by the Secretariat of Health and Environment with the support of WHO; the Malawi 2009 STEPS survey, implemented by Ministry of Health with the support of WHO; and the Moldova 2013 STEPS survey, implemented by the Ministry of Health, the National Bureau of Statistics, and the National Center of Public Health with the support of WHO. This paper uses data from Survey of Health, Ageing and Retirement in Europe (SHARE) Waves 1 (DOI:10.6103/SHARE. w1.700), 2 (10.6103/SHARE.w2.700), 3 (10.6103/SHARE.w3.700), 4 (10.6103/SHARE.w4.700), 5 (10.6103/SHARE.w5.700), 6 (10.6103/SHARE.w6.700), and 7 (10.6103/SHARE.w7.700); see Borsch-Supan and colleagues (2013) for methodological details. The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193, COMPARE: CIT5-CT-2005-028857, SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N degrees 211909, SHARE-LEAP: GA N degrees 227822, SHARE M4: GA N degrees 261982) and Horizon 2020 (SHARE-DEV3: GA N degrees 676536, SERISS: GA N degrees 654221) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2, P01_AG005842, P01_AG08291, P30_AG12815, R21_AG025169, Y1-AG-4553-01, IAG_BSR06-11, OGHA_04-064, HHSN271201300071C), and from various national funding sources is gratefully acknowledged. This study has been realised using the data collected by the Swiss Household Panel, which is based at the Swiss Centre of Expertise in the Social Sciences. The project is financed by the Swiss National Science Foundation. The United States Aging, Demographics, and Memory Study is a supplement to the Health and Retirement Study (HRS), which is sponsored by the National Institute of Aging (grant number NIA U01AG009740). It was conducted jointly by Duke University and the University of Michigan. The HRS is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan. This paper uses data from Add Health, a program project designed by J Richard Udry, Peter S Bearman, and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due to Ronald R Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website. No direct support was received from grant P01-HD31921 for this analysis. The data reported here have been supplied by the United States Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government. Collection of data for the Mozambique National Survey on the Causes of Death 2007-08 was made possible by USAID under the terms of cooperative agreement GPO-A-00-08-000_D3-00. This manuscript is based on data collected and shared by the International Vaccine Institute (IVI) from an original study IVI conducted. L G Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Brazil; finance code 001) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, a Brazilian funding agency). I N Ackerman was supported by a Victorian Health and Medical Research Fellowship awarded by the Victorian Government. O O Adetokunboh acknowledges the South African Department of Science and Innovation and the National Research Foundation. A Agrawal acknowledges the Wellcome Trust DBT India Alliance Senior Fellowship. S M Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. M Ausloos, C Herteliu, and A Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. A Badawi is supported by the Public Health Agency of Canada. D A Bennett was supported by the NIHR Oxford Biomedical Research Centre. R Bourne acknowledges the Brien Holden Vision Institute, University of Heidelberg, Sightsavers, Fred Hollows Foundation, and Thea Foundation. G B Britton and I Moreno Velasquez were supported by the Sistema Nacional de Investigacion, SNI-SENACYT, Panama. R Buchbinder was supported by an Australian National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship. J J Carrero was supported by the Swedish Research Council (2019-01059). F Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. A R Chang was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK106515. V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundacao para a Ciencia e Tecnologia, IP, under the Norma Transitaria DL57/2016/CP1334/CT0006. A Douiri acknowledges support and funding from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South London at King's College Hospital NHS Foundation Trust and the Royal College of Physicians, and support from the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. B B Duncan acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. H E Erskine is the recipient of an Australian NHMRC Early Career Fellowship grant (APP1137969). A J Ferrari was supported by a NHMRC Early Career Fellowship grant (APP1121516). H E Erskine and A J Ferrari are employed by and A M Mantilla-Herrera and D F Santomauro affiliated with the Queensland Centre for Mental Health Research, which receives core funding from the Queensland Department of Health. M L Ferreira holds an NHMRC Research Fellowship. C Flohr was supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust. M Freitas acknowledges financial support from the EU (European Regional Development Fund [FEDER] funds through COMPETE POCI-01-0145-FEDER-029248) and National Funds (Fundacao para a Ciencia e Tecnologia) through project PTDC/NAN-MAT/29248/2017. A L S Guimaraes acknowledges support from CNPq. C Herteliu was partially supported by a grant co-funded by FEDER through Operational Competitiveness Program (project ID P_40_382). P Hoogar acknowledges Centre for Bio Cultural Studies, Directorate of Research, Manipal Academy of Higher Education and Centre for Holistic Development and Research, Kalaghatagi. F N Hugo acknowledges the Visiting Professorship, PRINT Program, CAPES Foundation, Brazil. B-F Hwang was supported by China Medical University (CMU107-Z-04), Taichung, Taiwan. S M S Islam was funded by a National Heart Foundation Senior Research Fellowship and supported by Deakin University. R Q Ivers was supported by a research fellowship from the National Health and Medical Research Council of Australia. M Jakovljevic acknowledges the Serbian part of this GBD-related contribution was co-funded through Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. P Jeemon was supported by a Clinical and Public Health intermediate fellowship (grant number IA/CPHI/14/1/501497) from the Wellcome Trust-Department of Biotechnology, India Alliance (2015-20). O John is a recipient of UIPA scholarship from University of New South Wales, Sydney. S V Katikireddi acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_12017/13, MC_UU_12017/15), and the Scottish Government Chief Scientist Office (SPHSU13, SPHSU15). C Kieling is a CNPq researcher and a UK Academy of Medical Sciences Newton Advanced Fellow. Y J Kim was supported by Research Management Office, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/00010). K Krishan is supported by UGC Centre of Advanced Study awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar was supported by K43 TW 010716 FIC/NIMH. B Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. J V Lazarus was supported by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III [ISCIII]/ESF, the EU [CP18/00074]). K J Looker thanks the NIHR Health Protection Research Unit in Evaluation of Interventions at the University of Bristol, in partnership with Public Health England, for research support. S Lorkowski was funded by the German Federal Ministry of Education and Research (nutriCARD, grant agreement number 01EA1808A). R A Lyons is supported by Health Data Research UK (HDR-9006), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. J J McGrath is supported by the Danish National Research Foundation (Niels Bohr Professorship), and the Queensland Health Department (via West Moreton HHS). P T N Memiah acknowledges support from CODESRIA. U O Mueller gratefully acknowledges funding by the German National Cohort Study BMBF grant number 01ER1801D. S Nomura acknowledges the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). A Ortiz was supported by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. S B Patten was supported by the Cuthbertson & Fischer Chair in Pediatric Mental Health at the University of Calgary. G C Patton was supported by an aNHMRC Senior Principal Research Fellowship. M R Phillips was supported in part by the National Natural Science Foundation of China (NSFC, number 81371502 and 81761128031). A Raggi, D Sattin, and S Schiavolin were supported by grants from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4-Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). P Rathi and B Unnikrishnan acknowledge Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal. A L P Ribeiro was supported by Brazilian National Research Council, CNPq, and the Minas Gerais State Research Agency, FAPEMIG. D C Ribeiro was supported by The Sir Charles Hercus Health Research Fellowship (#18/111) Health Research Council of New Zealand. D Ribeiro acknowledges financial support from the EU (FEDER funds through the Operational Competitiveness Program; POCI-01-0145-FEDER-029253). P S Sachdev acknowledges funding from the NHMRC of Australia Program Grant. A M Samy was supported by a fellowship from the Egyptian Fulbright Mission Program. M M Santric-Milicevic acknowledges the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract number 175087). R Sarmiento-Suarez received institutional support from Applied and Environmental Sciences University (Bogota, Colombia) and ISCIII (Madrid, Spain). A E Schutte received support from the South African National Research Foundation SARChI Initiative (GUN 86895) and Medical Research Council. S T S Skou is currently funded by a grant from Region Zealand (Exercise First) and a grant from the European Research Council under the EU's Horizon 2020 research and innovation program (grant agreement number 801790). J B Soriano is funded by Centro de Investigacion en Red de Enfermedades Respiratorias, ISCIII. R Tabares-Seisdedos was supported in part by the national grant PI17/00719 from ISCIII-FEDER. N Taveira was partially supported by the European & Developing Countries Clinical Trials Partnership, the EU (LIFE project, reference RIA2016MC-1615). S Tyrovolas was supported by the Foundation for Education and European Culture, the Sara Borrell postdoctoral programme (reference number CD15/00019 from ISCIII-FEDER). S B Zaman received a scholarship from the Australian Government research training programme in support of his academic career. ; "Peer Reviewed"
Memoria de Tesis doctoral presentada por Guillermo Asín Prieto, para obtener el doctorado (Mención en Ingeniería Eléctrica, Electrónica y de Automatización) por la Universidad Carlos III de Madrid (UC3M), realizada bajo la dirección de Juan Camilo Moreno Sastoche y José Luis Pons Rovira .-- 186 páginas. ; This doctoral thesis presents, after reviewing human gait, the main pathologies and conditions that affect it, and the different rehabilitation approaches with the corresponding neurophysiological implications, the research journey that leads to the development of the rehabilitation robotic tool, and the therapies that have been designed, within the framework of the European projects BioMot: Smart Wearable Robots with Bioinspired Sensory-Motor Skills and HANK: European advanced exoskeleton for rehabilitation of Acquired Brain Damage (ABD) and/or spinal cord injury's patients, and tested under the umbrella of the European project ASTONISH: Advancing Smart Optical Imaging and Sensing for Health and the national project ASSOCIATE: A comprehensive and wearable robotics based approach to the rehabilitation and assistance to people with stroke and spinal cord injury. Initially human gait is presented, characterizing it according to its stance and swing phases, and the spatiotemporal, kinetic and kinematic parameters, without neglecting the physiological parameters; followed by a review of the main pathologies or conditions that affect human gait: spinal cord injury, cerebral palsy, traumatic brain injury, neuromuscular impairments, osteoarticular diseases, aging, and stroke or cerebrovascular accident. Next, the robotic tool that is developed in this thesis is framed in the context of rehabilitation for stroke, based on its use in this widespread pathology, as it affects 13.7 million people every year, since there are about 80 million survivors, affecting all age ranges. In addition, 80 % of people affected by a stroke find also compromised their motor abilities, motivating the need to develop tools focused on the rehabilitation and recovery, as far as possible, of the independence lost due to the disease, with gait as a fundamental component of that independence. After reviewing gait and the characteristics of the pathology, an explanatory review is given for the three phases of therapy for gait rehabilitation: T1) preparatory training based on mobilization of the lower limb joints; T2) gait recovery; and T3) improvement of gait with the aim of recovering mobility for activities of daily living. This classification of the therapy phases is presented to frame the work of this thesis in phases T1 and T2. Motor recovery is based on motor learning, and thus, I provide a brief introduction to it, exposing its relationship with neuroplasticity, and establishing that, in order to enhance all types of learning, it is essential to establish a challenge, i.e., an acceptable difficulty, not only making the training less monotonous, but also enhancing retention. Motor learning, like all kinds of learning, requires the occurrence of neural plasticity. Neural plasticity can be described by these four factors: 1) evolution of neuronal representation for movements that require skill, which were latent before the injury; and recruitment of healthy areas that were used before the injury occurred, when the difficulty of the task was greater; 2) greater excitability of neurons and more efficiency of synaptic connections; 3) morphological changes associated with long-term potentiation and depression (LTP and LTD) phenomena; and 4) adaptation of cortical, subcortical and spinal networks that still function to the learned movement. There are different non-invasive methods that allow the evaluation of neuroplastic changes (Hoffman reflex, F-wave, motor evoked potentials, etc.), and since in this thesis the motor evoked potentials (MEPs) have been assessed, transcranial magnetic stimulation (TMS) is presented as the technique used to evoke potentials in the motor cortex associated with the muscle or muscles whose excitability is being evaluated, collected by means of superficial electromyography. The TMS technique allows to observe changes in corticospinal excitability before and after a treatment that potentially induces motor learning, being able also to evaluate if these changes are related to the treatment, as well as allowing to observe if they are long-lasting. In the literature review chapter, the differences between traditional rehabilitation approaches, and those robotic technology-aided are also introduced, showing that there is no clear winner in such a battle, but showing the advantage of robot-aided approaches, as they allow objectively measuring and help characterizing the recovery process. Once the robotic technology has been introduced as a rehabilitation technology, exoskeletons are presented as the most appropriate robotic technology involved in rehabilitative approaches for gait, and a review of the relevant existing devices, with their characteristics and limitations, is given to show the motivation of this work. The limitations presented by current devices are: they use pre-recorded patterns; they do not have visual feedback systems, or their feedback systems are too simple, not presenting the potential of a video game: entertainment and adherence to the treatment, allowing the difficulty to be modified. Some, on the other hand, are so complex that they demand a high cognitive effort for patients, or are even complex to configure and command, leading to the abandonment of the technology by both patients and therapists. In addition, most of them lack the ability to introduce randomness in the treatment, potentially leading to boredom of the patient, and ultimately abandonment of the therapy. Last but not least, the tasks are not adapted along the treatment to the capacities and the recovery of the subject. Therefore, the tool proposed in this thesis consists of the integration of a robotic ankle fixed to a platform, with a visual feedback comprised of a video game designed to train movements in the sagittal plane of the ankle: dorsiflexion and plantarflexion; with the subject sitting. The tool is capable of generating controlled torque patterns that disturb the trajectory followed by the subject, increasing the difficulty to collect the items on the screen. In addition, the magnitude of these disturbances depends on the performance during the task, increasing the difficulty when the performance is rising, managing to impose a continuous challenge, enhancing the adherence to the treatment as well as its effectiveness to promote the retention of what has been learned. After presenting the review of the literature, I present the development of the rehabilitation tool, describing the journey from the test of the control algorithms, to the development of the video game and design of the experimental protocol, through the adaptation of the control to the compliant actuator on which the tool is based, or tests first on a test bench and then with healthy subjects wearing the device. The first study presents the application of a bioinspired algorithm for autonomous learning, used in bipeds (providing them with the ability to learn to walk without prior knowledge of the task nor the environment, only knowing some points of the angular trajectory), to a six degrees of freedom actuated exoskeleton, with rigid actuators, in the sagittal plane, corresponding to the three main joints of the lower limb, i.e., hip, knee and ankle. This adaptation of the algorithm allows to modulate the rigidity of a rigid actuator with a simple implementation. The term tacit adaptability (TAd) was coined to refer to this control strategy. The third study extends the results to subjects on a treadmill, showing that the algorithm allows to absorb the deviations that the subject may have on the trajectory imposed by the controller of the robot. These studies have demonstrated the use of TAd with a position controller. For the development of the tool, its use is also tested with a torque controller, in order to modulate the amplitude of the applied torque. Then, the following chapter shows two protocols applicable to the T2 phase, just before starting free overground gait rehabilitation. The same robotic tool is used, varying the angle at which the subject's leg rests, to be used standing up. This study aims to explore the application of torque controllers to the rehabilitation robotic tool. In the first training, the robot applies a torque downwards, during the time equivalent to the swing phase, to force the subject to make a higher dorsiflexion torque to be able to follow a natural ankle angular trajectory profile. At the end of the training, during the final 15-20 % of time, the torque is removed. It is observed that the subjects have a greater dorsiflexion when the effect is removed, as well as a minor activation of the dorsiflexor muscles (in the absence of the force to be compensated), and tend to normalize the patterns over time. We also observe that when the torque downwards is removed, there is a trend to anticipate the maximum dorsiflexion peak angle in the swing phase, a trend that tends to disappear over time. In the second training, the robot exerts a torque upwards, similar to that exerted by the ground in the stance phase (ground reaction force), but at a lower magnitude, throughout the training. A lower activation is observed in the gastrocnemius medialis (plantarflexor muscle) than during a free walking over ground. This indicates that the reduced force made by the robot is similar to that experienced when wearing a body weight support. Next, the development of the visual feedback based on a video game is presented. The game consists of a gyrocopter whose position on the vertical axis can be modified by means of the dorsi and plantarflexion of the instrumented ankle (the horizontal axis advances automatically). The aim of the game is to collect the gas bottles that appear on the screen, following the optimal trajectory between bottles. The following study, whose objective is to demonstrate the feasibility of using the tool integrated by the robotic ankle fixed to the platform and the rehabilitation video game, prior to applying the TAd, exposes that applying a training without modulating, and modulating progressively and with a simple rule, the maximum torque applied by the robot, learning is promoted in healthy subjects, being greater the learning with the modulated approaches. Once the viability of the tool to promote motor learning in healthy subjects has been proven, the adaptation of TAd to MACCEPA, with a torque controller, is presented, giving rise to what we have dubbed as haptic adaptive feedback (HAF). This paradigm makes use of the performance in the task to modulate the maximum amplitude of the torque exerted by the robot, depending on the capabilities of the subject. In this way, the concept of challenge is maintained, without excessively exceeding the subject's capabilities, and adapting to the improvements in the execution of the task. The last study I present, corresponding to the development phase, presents the results when testing the feasibility of the final protocol with a healthy individual. For five consecutive days, the subject received a training with the robotic ankle consisting of playing the video game designed to encourage motor learning. We observed that the subject learned throughout the days, showing a significant reduction in the error when following the best trajectory between bottles, as well as a significant increase in the score, understood as the number of collected bottles. The study shows that the protocol is capable of generating learning in a healthy subject. The following chapter shows an extension of the previous study to a sample of ten healthy subjects, applicable to the T1 therapy phase. The subjects trained for three consecutive days. In addition, corticospinal excitability was recorded by means of TMS, focused on the tibialis anterior muscle, before starting the training on the first day, just after the training on the third (and last) day, 30 minutes later to see if the effects were maintained along time (LTP-like), and 24 hours after, to see long-lasting effects. An increase in both score and error was observed throughout the days. Likewise, a significant increase in the corticospinal excitability of the tibialis anterior was obtained, but not in the other two registered muscles: soleus (as a muscle involved in the task) and rectus femoris (as a proximal muscle, and, therefore, not involved in the task of dorsi/plantarflexion). The lack of significant changes in the soleus may be due to the fact that being a muscle whose action is in favor of gravity, it has been less potentiated. Another possible reason is that, because the tibialis anterior receives a higher density of corticospinal projections than the rest of the lower limb muscles, it needs a lower intensity to be recruited compared to the soleus. We extended this study in a case study with a pathological subject to test the feasibility of applying the protocol with patients. To do this, we modified the torque profile exerted by the robot so that it only forced dorsiflexion, preventing the patient from having to compensate for a movement of the robot downwards, focusing on training the dorsiflexor muscles. We observed a significant increase in the score in the task of the video game, as well as a significant decrease in the error, throughout the five days of the experiment. In the case of the patient, clinical scales were also recorded, observing improvements in resistance, speed, distance and transition time to standing position. Finally, the range of motion and speed of dorsi/plantarflexion were also recorded by means of an ad-hoc designed test, in which the subject was asked to move the foot up and down as quickly as possible to vertically move an onscreen ball to the limits of the screen. These metrics also shown improvements throughout the treatment. Nonetheless, these positive results cannot be extrapolated to the population of pathological subjects, as the effects of our training cannot be isolated from the rest of the patient's daily therapy; but it is concluded that it is a viable training for use in clinical scenarios. ; Esta tesis doctoral presenta, tras repasar la marcha humana, las principales patologías y condiciones que la afectan, y los distintos enfoques de rehabilitación con la correspondiente implicación neurofisiológica, el camino de investigación que desemboca en la herramienta robótica de rehabilitación y las terapias que se han desarrollado en el marco de los proyectos europeos BioMot: Smart Wearable Robots with Bioinspired Sensory-Motor Skills y HANK: European advanced exoskeleton for rehabilitation of Acquired Brain Damage (ABD) and/or spinal cord injury's patients, y probado bajo el paraguas del proyecto europeo ASTONISH: Advancing Smart Optical Imaging and Sensing for Health y el proyecto nacional ASSOCIATE: A comprehensive and wearable robotics based approach to the rehabilitation and assistance to people with stroke and spinal cord injury. Inicialmente se presenta la marcha humana, caracterizándola en arreglo a sus fases de apoyo y balanceo, y a los parámetros espaciotemporales, cinéticos y cinemáticos, sin dejar de lado los parámetros fisiológicos; para pasar a mostrar un repaso por las principales patologías o condiciones que afectan la marcha humana: lesión medular, parálisis cerebral, lesión cerebral traumática, deficiencias neuromusculares, enfermedades osteoarticulares, envejecimiento, e ictus o accidente cerebrovascular. A continuación, se enmarca la herramienta robótica que se desarrolla en esta tesis, en la rehabilitación para el ictus, fundamentando su uso en esta extendida patología debido a que afecta a 13,7 millones de personas cada a˜no, y a que hay unos 80 millones de supervivientes, afectando a todos los rangos de edad. Además, el 80 % de las personas afectadas por un accidente cerebrovascular ven asimismo comprometida su capacidad motora, motivando la necesidad de desarrollar herramientas enfocadas en la rehabilitación y recuperación, hasta donde sea posible, de la independencia perdida por motivo de la enfermedad, con la marcha como componente fundamental de esa independencia. Después de dar un repaso por la marcha y las características de la patología, se da un repaso explicativo por las tres fases de la terapia para rehabilitación de la marcha: T1) entrenamiento preparatorio basado en movilización de las articulaciones del miembro inferior; T2) recuperación de la marcha; y T3) mejora de la marcha con el objetivo de recuperar la movilidad para las actividades de la vida diaria. Se presenta esta clasificación de las fases para enmarcar el trabajo de esta tesis en las fases T1 y T2. Debido a que la recuperación motora se basa en el aprendizaje motor, se da una breve introducción al mismo exponiendo su relación con la neuroplasticidad, y estableciendo que, para potenciar todo tipo de aprendizaje, es capital establecer un reto, esto es, una dificultad asumible, y que no sólo hace que la tarea de entrenamiento sea menos monótona, sino que además potencia el proceso de retención del aprendizaje. El aprendizaje motor, como todo aprendizaje, para poder tener lugar, requiere que haya plasticidad neuronal. La plasticidad neuronal se puede describir por medio de estos cuatro factores: 1) evolución de la representación neuronal para movimientos que requieren habilidad, que estaban latentes antes de la lesión; y reclutamiento de áreas sanas y que se usaban antes de que la lesión ocurriera, cuando la dificultad de la tarea era mayor; 2) mayor excitabilidad de las neuronas y m´as eficacia de la conexión sináptica; 3) cambios morfológicos asociados a los fenómenos de potenciación y depresión a largo plazo (LTP y LTD de sus siglas en inglés, long term potentiation y long term depression respectivamente); y 4) adaptación de las redes corticales, subcorticales y espinales que aún funcionan al movimiento aprendido. Hay distintos métodos no invasivos que permiten evaluar los cambios neuroplásticos (reflejo de Hoffman, onda F, potenciales motores evocados, etc), y dado que en esta tesis se han usado los potenciales motores evocados(MEPs, de sus siglas en inglés, motor evoked potentials), se presenta la estimulación magnética transcraneal (TMS, de sus siglas en inglés, transcranial magnetic stimulation), como la técnica utilizada para evocar en la corteza motora asociada al músculo o a los músculos, cuya excitabilidad corticoespinal se desea evaluar, un potencial motor, recogido por medio de electromiografía superficial. La técnica de TMS permite observar cambios en la excitabilidad corticoespinal antes y después de un tratamiento que potencialmente induzca un aprendizaje motor, para poder evaluar si estos cambios están relacionados con el tratamiento, as´ı como permitiendo observar si son duraderos en el tiempo. En el capítulo de la revisión de la literatura se introducen también las diferencias entre los enfoques clásicos de rehabilitación, y los ayudados por las tecnologías robóticas, mostrando que no hay un claro ganador en tal batalla, pero manifestando la ventaja de la tecnología al permitir medir de manera objetiva y ayudar a caracterizar el proceso de recuperación. Una vez introducida la tecnología robótica como tecnología para la rehabilitación, se presentan los exoesqueletos como la tecnología robótica más adecuada implicada en los enfoques rehabilitadores para la marcha, y se da un repaso por los dispositivos existentes, con sus características y limitaciones, para mostrar la motivación de este trabajo. Las limitaciones que presentan los dispositivos actuales relevantes son que: utilizan patrones pre-grabados; no tienen sistemas de retroalimentación visual, o sus sistemas de retroalimentación son demasiados simples, no presentando el potencial de un video juego: entretenimiento y adherencia al tratamiento, permitiendo modificar la dificultad. Algunos, por otro lado, son tan complejos que demandan un esfuerzo cognitivo difícil para los pacientes, o incluso son complejos de configurar y comandar, llevando al abandono de la tecnología tanto por parte de pacientes como por parte de terapeutas. Además, la mayoría de ellos carecen de la capacidad de introducir aleatoriedad en el tratamiento, potencialmente desembocando en el aburrimiento del paciente, y en el abandono de la terapia en última instancia. Por último, pero no por ello menos importante, las tareas que proponen no se adaptan a lo largo del entrenamiento a las capacidades y recuperación del sujeto. Por ello, la herramienta que se propone en esta tesis consta de la integración de un tobillo robótico fijado a una plataforma, con una retroalimentación visual por medio de un video juego diseñado para entrenar los movimientos en el plano sagital del tobillo: dorsiflexión y plantarflexión; con el sujeto sentado. La herramienta es capaz de generar patrones de par controlados que perturban las trayectorias seguidas por el sujeto, dificultando la tarea de recoger los ítems en pantalla. Además, la magnitud de estas perturbaciones depende del rendimiento durante la tarea, incrementando la dificultad cuando el rendimiento va mejorando, consiguiendo imponer un reto continuo, potenciando la adherencia al tratamiento así como su eficacia para fomentar la retención de lo aprendido. Tras exponer la revisión de la literatura, se presenta el desarrollo de la herramienta de rehabilitación, recorriendo el camino desde la prueba de los algoritmos de control, hasta el desarrollo del video juego y diseño del protocolo experimental, pasando por la adecuación del control al actuador compliant en que se basa la herramienta, o las pruebas primero en banco de pruebas y después con sujetos sanos vistiendo el dispositivo. El primer estudio que se presenta consiste en aplicar un algoritmo, bioinspirado, de aprendizaje autónomo, utilizado en b´ıpedos (los cuales presentan la capacidad de aprender a caminar sin conocimiento previo de la tarea ni del entorno, únicamente conociendo algunos puntos de la trayectoria angular a realizar por las articulaciones), a un exoesqueleto con seis grados de libertad actuados, con actuadores rígidos, en el plano sagital, correspondiendo con las tres principales articulaciones del miembro inferior, esto es, cadera, rodilla y tobillo. Esta adaptación del algoritmo permite modular la rigidez de un actuador rígido con una implementación sencilla. Se acuñó el término adaptabilidad tácita (TAd, de sus siglas en inglés, tacit adaptability) para referirse a esta estrategia de control. El segundo estudio que se presenta tiene como objetivo aplicar el TAd a un actuador compliant: el MACCEPA (de sus siglas en inglés, mechanically adjustable compliance and controllable equilibrium position actuator). El MACCEPA es un actuador basado en un elemento elástico en serie, cuya pre-compresión puede variarse, ofreciendo distintos grados de rigidez. La ventaja de este actuador es que permite aplicar un control de par sin necesidad de un complejo sensor de par, conociendo la constante del elemento elástico y las posiciones del motor y del ángulo articular del sujeto. En el estudio, se presenta adaptación del TAd al MACCEPA, en el banco de pruebas, mostrando que, mediante este algoritmo, y sin modificar la pre-compresión del elemento elástico, se puede modular la rigidez del actuador tanto en condiciones estáticas como dinámicas, demostrando que el control puede adaptarse a las capacidades del sujeto, de manera automática y autónoma. El tercer estudio extiende los resultados a sujetos sobre la cinta de marcha, mostrando que el algoritmo permite absorber las desviaciones que pueda tener el sujeto sobre la trayectoria impuesta por el control del robot. Estos estudios han demostrado el uso del TAd con un control de posición. Para el desarrollo de la herramienta, se prueba también su uso con un control de par, para poder modular la magnitud del par aplicado. El siguiente capítulo muestra dos protocolos aplicables a la fase T2, justo antes de empezar un entrenamiento de marcha libre. Se utiliza la misma herramienta robótica, variando el ángulo en que reposa la pierna del sujeto, para poder ser utilizado en bipedestación. Este estudio tiene como objetivo explorar los controladores de par con la herramienta de rehabilitación robótica propuesta. El primero de los entrenamientos consiste en que el robot aplica un par negativo (hacia el suelo), durante el tiempo equivalente a la fase de balanceo, para forzar a que el sujeto haga un par de dorsiflexion superior al habitual para poder seguir una trayectoria angular de tobillo natural en caminata. Al final del entrenamiento, durante el 15 - 20 % final del tiempo, se quita el par negativo. Se observa que los sujetos tienen una dorsiflexión mayor al quitar el efecto, así como una activación menor de los músculos dorsiflexores (en ausencia de la fuerza a compensar), y tienden a normalizar los patrones a lo largo del tiempo. Observamos también que cuando se deja de aplicar el par, hay una tendencia a anticiparse al efectuar el pico máximo de dorsiflexión en la fase de balanceo, tendencia que va desapareciendo con el tiempo. En el segundo entrenamiento, el robot ejerce un par positivo, similar al ejercido por el suelo en la fase de apoyo, pero de una magnitud inferior, durante todo el entrenamiento. Se observa una activación inferior en el gastrocnemio medial (músculo plantarflexor) que durante una caminata normal sobre suelo. Esto indica que la fuerza reducida efectuada por el robot es similar a una caminata con un sistema de suspensión del peso. A continuación, se presenta el desarrollo de la realimentación visual a modo de videojuego. El juego consiste en un autogiro cuya posición en el eje vertical puede modificarse por medio de la dorsi y plantarflexión del tobillo instrumentado (el eje horizontal avanza de manera automática). El objetivo es recoger las botellas de gasolina que aparecen en la pantalla, siguiendo la trayectoria óptima entre botellas. El siguiente estudio, cuyo objetivo es demostrar la viabilidad de uso de la herramienta integrada por tobillo robótico fijado a la plataforma y el videojuego de rehabilitación, previo a aplicar el TAd, expone que aplicando un entrenamiento sin modular de ninguna manera, y modulando de manera progresiva y con una regla simple, el máximo par aplicado por el robot, se promueve aprendizaje en sujetos sanos, siendo mayor con los enfoques modulados. Una vez probada la viabilidad de la herramienta para fomentar el aprendizaje motor en sujetos sanos, se presenta la adaptación del TAd al MACCEPA, esta vez controlado en par, dando lugar a lo que hemos bautizado como retroalimentación adaptativa háptica (HAF, de sus siglas en inglés, haptic adaptive feedback). Este paradigma hace uso del rendimiento en la tarea para modular la máxima amplitud del par efectuado por el robot en cada momento en función de las capacidades del sujeto. De esta manera, se mantiene el concepto de reto, sin sobrepasar en exceso las capacidades del sujeto, y adecuándose según se producen mejoras en la ejecución de la tarea. El último estudio presentado, correspondiente a la fase de desarrollo, presenta los resultados a la hora de probar la viabilidad del protocolo final con un sujeto sano. A lo largo de cinco d´ıas consecutivos, el sujeto recibío el entrenamiento con el tobillo robótico consistente en jugar al videojuego diseñado para fomentar el aprendizaje motor. Se observó que el sujeto aprendía a lo largo de los días, mostrando reducción significativa en el error a la hora de seguir la mejor trayectoria entre botellas, así como aumento significativo en la puntuación, entendida como número de botellas recogidas. El estudio demuestra que el protocolo es capaz de generar aprendizaje en un sujeto sano. El siguiente capítulo muestra una ampliación del estudio previo a una muestra de diez sujetos sanos, aplicable a la fase de terapia T1. Los sujetos entrenaron a lo largo de tres días consecutivos. Además, se registró la excitabilidad corticoespinal por medio de TMS, enfocado en el tibial anterior, antes de empezar el entrenamiento el primer día, justo después del entrenamiento del tercer (y ´ultimo) día, media hora después para ver si los efectos se mantenían con el tiempo, y 24 horas después, para ver efectos a largo plazo. Se observó, a lo largo de los días, un incremento tanto en puntuación como en error. Así mismo, se obtuvo un incremento significativo en la excitabilidad corticoespinal del tibial anterior, pero no así de los otros dos músculos registrados: sóleo (como músculo involucrado en la tarea) y recto femoral (como músculo proximal, y, por tanto, no involucrado en la tarea de dorsi/plantarflexión). La falta de cambios significativos en el sóleo puede deberse a que al ser un músculo cuya acción es a favor de la gravedad, se haya visto menos potenciado. Otra posible razón es que, debido a que el tibial anterior recibe una mayor densidad de proyecciones corticoespinales que el resto de músculos del miembro inferior, necesite una intensidad inferior para ser reclutado en comparación con el sóleo. Se extendió este estudio con un caso de estudio con un sujeto patológico para probar la viabilidad de aplicación del protocolo con pacientes. Para ello, se modificó el par realizado por el robot para que sólo forzase dorsiflexión, evitando que el paciente tuviera que compensar un movimiento del robot hacia abajo, centrado en entrenar los músculos dorsiflexores. Se observó un incremento significativo en la puntuación en la tarea del videojuego, así como un decremento significativo del error, a lo largo de los cinco días de experimento. En el caso del paciente se registraron también escalas clínicas, observando mejoras en resistencia, velocidad, distancia recorrida y tiempo de transición a bipedestación. Por ´ultimo, también se registró el rango de movimiento y velocidad de dorsi/plantarflexión por medio de un test dise˜nado ad-hoc, en el que se pidío al sujeto que moviera el pie arriba y abajo lo más rápido posible para tocar con una bolita los extremos verticales de la pantalla. Se observó una mejora en esta métrica a lo largo del tratamiento. Aunque se ven mejoras, no puede extrapolarse este resultado a la población de sujetos patológicos, así como no se pueden aislar los efectos del juego del resto de la terapia diaria del paciente; pero se concluye que es un entrenamiento viable para su uso en entornos clínicos. ; The research presented in this thesis has been funded by the Commission of the European Union under the BioMot project - Smart Wearable Robots with Bioinspired Sensory-Motor Skills (Grant Agreement number IFP7-ICT - 611695); under HANK Project - European advanced exoskeleton for rehabilitation of Acquired Brain Damage (ABD) and/or spinal cord injury's patients (Grant Agreements number H2020-EU.2. - PRIORITY 'Industrial leadership' and H2020-EU.3. - PRIORITY 'Societal challenges' - 699796); also under the ASTONISH Project - Advancing Smart Optical Imaging and Sensing for Health (Grant Agreement number H2020-EU.2.1.1.7. - ECSEL - 692470); with financial support of Spanish Ministry of Economy and Competitiveness (MINECO) under the ASSOCIATE project - A comprehensive and wearable robotics based approach to the rehabilitation and assistance to people with stroke and spinal cord injury (Grant Agreement number 799158449-58449-45-514); and with grant RYC-2014-16613, also by Spanish Ministry of Economy and Competitiveness.
Das International Social Survey Programme (ISSP) ist ein länderübergreifendes, fortlaufendes Umfrageprogramm, das jährlich Erhebungen zu Themen durchführt, die für die Sozialwissenschaften wichtig sind. Das Programm begann 1984 mit vier Gründungsmitgliedern - Australien, Deutschland, Großbritannien und den Vereinigten Staaten - und ist inzwischen auf fast 50 Mitgliedsländer aus aller Welt angewachsen. Da die Umfragen auf Replikationen ausgelegt sind, können die Daten sowohl für länder- als auch für zeitübergreifende Vergleiche genutzt werden. Jedes ISSP-Modul konzentriert sich auf ein bestimmtes Thema, das in regelmäßigen Zeitabständen wiederholt wird. Details zur Durchführung der nationalen ISSP-Umfragen entnehmen Sie bitte der Dokumentation. Die vorliegende Studie konzentriert sich auf Fragen zu Umwelt, Klimawandel und Umweltschutz.
Für weitere Informationen zur Variablenliste siehe die Dokumentation (Codebook) des CSES Module 1-3 Harmonized Trend File. Informationen zum Inhalt können den Studiennummern ZA5179 CSES Module 1 Full Release, ZA5180 CSES Module 2 Full Release, und ZA5181 CSES Module 3 Full Release entnommen werden.
Für weitere Informationen zur Variablenliste siehe die Dokumentation (Codebook) des CSES Module 1-3 Harmonized Trend File.
Informationen zum Inhalt können den Studiennummern ZA5179 CSES Module 1 Full Release, ZA5180 CSES Module 2 Full Release, und ZA5181 CSES Module 3 Full Release entnommen werden.
BACKGROUND:Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. METHODS:Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0-100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target-1 billion more people benefiting from UHC by 2023-we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. FINDINGS:Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2-47·5) in 1990 to 60·3 (58·7-61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9-3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010-2019 relative to 1990-2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6-421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0-3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5-1040·3]) residing in south Asia. INTERPRETATION:The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people-the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close-or how far-all populations are in benefiting from UHC. FUNDING:Bill & Melinda Gates Foundation.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. Data for this research was provided by MEASURE Evaluation, funded by the United States Agency for International Development (USAID). Views expressed do not necessarily reflect those of USAID, the US Government, or MEASURE Evaluation. The Palestinian Central Bureau of Statistics granted the researchers access to relevant data in accordance with licence no. SLN2014-3-170, after subjecting data to processing aiming to preserve the confidentiality of individual data in accordance with the General Statistics Law-2000. The researchers are solely responsible for the conclusions and inferences drawn upon available data. ; Background Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing. ; Research reported in this publication was supported by the Bill & Melinda Gates Foundation, the University of Melbourne, Public Health England, the Norwegian Institute of Public Health, St. Jude Children's Research Hospital, the National Institute on Aging of the National Institutes of Health (award P30AG047845), and the National Institute of Mental Health of the National Institutes of Health (award R01MH110163). ; Peer reviewed
