Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

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 developm nt 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. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017

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

Histone Modification on Parathyroid Tumors: A Review of Epigenetics

Parathyroid tumors are very prevalent conditions among endocrine tumors, being the second most common behind thyroid tumors. Secondary hyperplasia can occur beyond benign and malignant neoplasia in parathyroid glands. Adenomas are the leading cause of hyperparathyroidism, while carcinomas represent less than 1% of the cases. Tumor suppressor gene mutations such as MEN1 and CDC73 were demonstrated to be involved in tumor development in both familiar and sporadic types; however, the epigenetic features of the parathyroid tumors are still a little-explored subject. We present a review of epigenetic mechanisms related to parathyroid tumors, emphasizing advances in histone modification and its perspective of becoming a promising area in parathyroid tumor research

Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized, Controlled Trial

Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to determine whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. Twenty-one individuals diagnosed with metabolic syndrome were randomly assigned for caloric restriction (CR; n = 11, diet of 5941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, diet of 8409 ± 2360 KJ per day) and followed for 27 days. Like CR, PR promoted weight loss due to a reduction in adiposity, which was associated with reductions in blood glucose, lipid levels, and blood pressure. More strikingly, both CR and PR improved insulin sensitivity by 62.3% and 93.2%, respectively, after treatment. Fecal microbiome diversity was not affected by the interventions. Adipose tissue bulk RNA-Seq data revealed minor changes elicited by the interventions. After PR, terms related to leukocyte proliferation were enriched among the upregulated genes. Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has more significant potential to be used as adjuvant therapy for people with metabolic syndrome

Diverse anthropogenic disturbances shift Amazon forests along a structural spectrum

Amazon forests are being degraded by myriad anthropogenic disturbances, altering ecosystem and climate function. We analyzed the effects of a range of land-use and climate-change disturbances on fine-scale canopy structure using a large database of profiling canopy lidar collected from disturbed and mature Amazon forest plots. At most of the disturbed sites, surveys were conducted 10–30 years after disturbance, with many exhibiting signs of recovery. Structural impacts differed in magnitude more than in character among disturbance types, producing a gradient of impacts. Structural changes were highly coordinated in a manner consistent across disturbance types, indicating commonalities in regeneration pathways. At the most severely affected site – burned igapó (seasonally flooded forest) – no signs of canopy regeneration were observed, indicating a sustained alteration of microclimates and consequently greater vulnerability to transitioning to a more open-canopy, savanna-like state. Notably, disturbances rarely shifted forests beyond the natural background of structural variation within mature plots, highlighting the similarities between anthropogenic and natural disturbance regimes, and indicating a degree of resilience among Amazon forests. Studying diverse disturbance types within an integrated analytical framework builds capacity to predict the risk of degradation-driven forest transitions.Fil: Smith, Marielle N.. Bangor University; Reino Unido. Michigan State University; Estados UnidosFil: Stark, Scott C.. Michigan State University; Estados UnidosFil: Taylor, Tyeen C.. University of Michigan; Estados UnidosFil: Schietti, Juliana. Universidade Federal Do Amazonas; Brasil. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: de Almeida, Danilo Roberti Alves. Universidade de Sao Paulo; BrasilFil: Aragón, Susan. Universidade Federal Do Oeste Do Pará; BrasilFil: Torralvo, Kelly. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Lima, Albertina P.. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: de Oliveira, Gabriel. University Of South Alabama; Estados UnidosFil: de Assis, Rafael Leandro. University of Oslo; Noruega. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Leitold, Veronika. University of Maryland; Estados UnidosFil: Pontes-Lopes, Aline. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Scoles, Ricardo. Universidade Federal Do Oeste Do Pará; BrasilFil: de Sousa Vieira, Luciana Cristina. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Resende, Angelica Faria. Universidade de Sao Paulo; BrasilFil: Coppola, Alysha I.. ETH Zurich. Geological Institute Biogeosciences; SuizaFil: Brandão, Diego Oliveira. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: de Athaydes Silva Junior, João. Universidade Federal do Pará; BrasilFil: Lobato, Laura F.. Universidade Federal Do Oeste Do Pará; BrasilFil: Freitas, Wagner. Universidade Federal Do Oeste Do Pará; BrasilFil: Almeida, Daniel. Universidade Federal Do Oeste Do Pará; BrasilFil: Souza, Mendell S.. Universidade Federal Do Oeste Do Pará; BrasilFil: Minor, David M.. University of Maryland; Estados UnidosFil: Villegas, Juan Camilo. Universidad de Antioquia; ColombiaFil: Law, Darin J.. University of Arizona; Estados UnidosFil: Gonçalves, Nathan. Michigan State University; Estados UnidosFil: da Rocha, Daniel Gomes. The Mamirauá Sustainable Development Institute; Brasil. University of California at Davis; Estados UnidosFil: Guedes, Marcelino Carneiro. Ministerio da Agricultura Pecuaria e Abastecimento de Brasil. Empresa Brasileira de Pesquisa Agropecuaria; BrasilFil: Tonini, Hélio. Embrapa Pecuária Sul; BrasilFil: da Silva, Kátia Emídio. Ministerio da Agricultura Pecuaria e Abastecimento de Brasil. Empresa Brasileira de Pesquisa Agropecuaria; BrasilFil: van Haren, Joost. University of Arizona; Estados UnidosFil: Rosa, Diogo Martins. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: do Valle, Dalton Freitas. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Cordeiro, Carlos Leandro. Instituto Internacional Para Sustentabilidade; BrasilFil: de Lima, Nicolas Zaslavsky. Universidade Federal Do Oeste Do Pará; BrasilFil: Shao, Gang. Michigan State University; Estados Unidos. Purdue University Libraries And School Of Information Studies; Estados UnidosFil: Menor, Imma Oliveras. University of Oxford; Reino UnidoFil: Conti, Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Florentino, Ana Paula. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Montti, Lía. Universidad Nacional de Mar del Plata; ArgentinaFil: Aragão, Luiz. Instituto Nacional de Pesquisas Espaciais; BrasilFil: McMahon, Sean M.. Smithsonian Environmental Research Center; Estados UnidosFil: Parker, Geoffrey G.. Smithsonian Environmental Research Center; Estados UnidosFil: Breshears, David D.. University of Arizona; Estados UnidosFil: Da Costa, Antonio Carlos Lola. Universidade Federal do Pará; BrasilFil: Magnusson, William E.. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Mesquita, Rita. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Camargo, José Luís C.. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: de Oliveira, Raimundo C.. Embrapa Amazônia Oriental; BrasilFil: de Camargo, Plinio B.. Universidade de Sao Paulo; BrasilFil: Saleska, Scott R.. University of Arizona; Estados UnidosFil: Nelson, Bruce Walker. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; Brasi

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software