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...

Summary 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,...

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3•5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.

The formation of precise connections between retina and LGN involves the activity-dependent elimination of some synapses, with strengthening and retention of others. Here we show that the MHC Class I (MHCI) molecule H2-Db is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-Kb and H2-Db (KbDb−/−) despite intact retinal activity and basal synaptic transmission, the developmentally-regulated decrease in functional convergence of retinal ganglion cell synaptic inputs to LGN neurons fails and eye-specific layers do not form. Neuronal expression of just H2-Db in KbDb−/− mice rescues both synapse elimination and eye specific segregation despite a compromised immune system. When patterns of stimulation mimicking endogenous retinal waves are used to probe synaptic learning rules at retinogeniculate synapses, LTP is intact but LTD is impaired in KbDb−/− mice. This change is due to an increase in Ca2+ permeable AMPA receptors. Restoring H2-Db to KbDb−/− neurons renders AMPA receptors Ca2+ impermeable and rescues LTD. These observations reveal an MHCI mediated link between developmental synapse pruning and balanced synaptic learning rules enabling both LTD and LTP, and demonstrate a direct requirement for H2-Db in functional and structural synapse pruning in CNS neurons.

Key Points Question What is the current burden of neurological disorders in the US by states, and what are the temporal trends (from 1990 to 2017)? Findings Systematic analysis of the Global Burden of Disease study shows that, in 2017, the 3 most burdensome neurological disorders in the US were stroke, Alzheimer disease and other dementias, and migraine. The burden of individual neurological disorders varied moderately to widely by states (a 1.2-fold to 7.5-fold difference), and the absolute numbers of incident, prevalent, and fatal cases and disability-adjusted life-years of neurological disorders (except for traumatic brain injury incidence; spinal cord injury prevalence; meningitis prevalence, deaths, and disability-adjusted life-years; and encephalitis disability-adjusted life-years) across all US states increased from 1990 to 2017. Meaning A large and increasing number of people have various neurological disorders in the US, with significant variation in the burden of and trends in neurological disorders across the US states, and the reasons for these geographic variations need to be explored further.

Recovery from stroke engages mechanisms of neural plasticity. Here we examine a role for MHC Class I (MHCI) H2-Kb and H2-Db, and PirB receptor. These molecules restrict synaptic plasticity and motor learning in the healthy brain. Stroke elevates not only neuronal expression of H2-Kb and H2-Db, but also PirB and downstream signaling. KbDb KO or PirB KO mice have smaller infarcts and enhanced motor recovery. KO hippocampal organotypic slices, which lack an intact peripheral immune response, have less cell death after in vitro ischemia. In PirB KO mice, corticospinal projections from motor cortex are enhanced and the reactive astrocytic response is dampened following MCAO. Thus molecules that function in the immune system act not only to limit synaptic plasticity in healthy neurons, but also to exacerbate brain injury following ischemia. These results suggest novel therapies for stroke by targeting MHCI and PirB.

Background Vision loss is an important public health issue in China, but a detailed understanding of national and regional trends in its prevalence and causes, which could inform health policy, has not been available. This study aimed to assess the prevalence, causes, and regional distribution of vision impairment and blindness in China in 1990 and 2019.Methods Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used to estimate the prevalence of moderate and severe vision impairment and blindness in China and compare with other Group of 20 (G20) countries. We used GBD methodology to systematically analyse all available demographic and epidemiological data at the provincial level in China. We compared the age-standardised prevalences across provinces, and the changes in proportion of vision loss attributable to various eye diseases in 1990 and 2019. We used two different counterfactual scenarios with respect to population structure and age-specific prevalence to assess the contribution of population growth and ageing to trends in vision loss. FindingsIn 2019, the age-standardised prevalence was 2•57% (uncertainty interval [UI] 2•28-2•86) for moderate vision impairment, 0•25% (0•22-0•29) for severe vision impairment, and 0•48% (0•43-0•54) for blindness in China, which were all below the global average, but the prevalence of moderate and severe vision impairment had increased more rapidly than in other G20 countries from 1990 to 2019. The prevalence of vision loss increased with age, and the main causes of vision loss varied across age groups. The leading causes of vision impairment in China were uncorrected refractive error, cataract, and macular degeneration in both 1990 and 2019 in the overall population. From 1990 to 2019, the number of people with moderate vision impairment increased by 133•67% (from 19•65 to 45•92 million), those with severe vision impairment increased by 147•14% (from 1•89 to 4•67 million), and those with blindness increased by 64•35% (from 5•29 to 8•69 million); in each case, 20•16% of the increase could be explained by population growth. The contributions to these changes by population ageing were 87•22% for moderate vision impairment, 116•06% for severe vision impairment, and 99•22% for blindness, and the contributions by age-specific prevalence were 26•29% for moderate vision impairment, 10•91% for severe vision impairment, and -55•04% for blindness. The prevalence and specific causes of vision loss differed across provinces.Interpretation Although a comprehensive national policy to prevent blindness is in place, public awareness of visual health needs improving, and reducing the prevalence of moderate and severe vision impairment should be prioritised in future work.

During critical periods of development, the brain easily changes in response to environmental stimuli, but this neural plasticity declines by adulthood. By acutely disrupting paired immunoglobulin-like receptor B(PirB) function at specific ages, we show that PirB actively represses neural plasticity throughout life. We disrupted PirB function either by genetically introducing a conditional PirB allele into mice or by minipump infusion of a soluble PirB ectodomain (sPirB) into mouse visual cortex. We found that neural plasticity, as measured by depriving mice of vision in one eye and testing ocular dominance, was enhanced by this treatment both during the critical period and when PirB function was disrupted in adulthood. Acute blockade of PirB triggered the formation of new functional synapses, as indicated by increases in miniature excitatory postsynaptic current (mEPSC) frequency and spine density on dendrites of layer 5 pyramidal neurons. In addition, recovery from amblyopia— the decline in visual acuity and spine density resulting from long-term monocular deprivation— was possible after a 1-week infusion of sPirB after the deprivation period. Thus, neural plasticity in adult visual cortex is actively repressed and can be enhanced by blocking PirB function.