Global, regional, and national burden of epilepsy, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Epilepsy is one of the most common serious neurological disorders and affects individuals of all ages across the globe. The aim of this study is to provide estimates of the epilepsy burden on the global, regional, and national levels for 1990–2021. Methods: Using well established Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) methodology, we quantified the prevalence of active idiopathic (epilepsy of genetic or unknown origin) and secondary epilepsy (epilepsy due to an underlying abnormality of the brain structure or chemistry), as well as incidence, death, and disability-adjusted life-years (DALYs) by age, sex, and location (globally, 21 GBD regions and seven super-regions, World Bank country income levels, Socio-demographic Index [SDI], and 204 countries) and their trends from 1990 to 2021. Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy, largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs). Findings: In 2021, there were 51·7 million (95% UI 44·9–58·9) people with epilepsy (idiopathic and secondary combined) globally, with an age-standardised prevalence of 658 per 100 000 (569–748). Idiopathic epilepsy had an age-standardised prevalence of 307 per 100 000 (235–389) globally, with 24·2 million (18·5–30·7) prevalent cases, and secondary epilepsy had a global age-standardised prevalence of 350 per 100 000 (322–380). In 2021, 0·7% of the population had active epilepsy (0·3% attributed to idiopathic epilepsy and 0·4% to secondary epilepsy), and the age-standardised global prevalence of epilepsy from idiopathic and secondary epilepsy combined increased from 1990 to 2021 by 10·8% (1·1–21·3), mainly due to corresponding changes in secondary epilepsy. However, age-standardised death and DALY rates of idiopathic epilepsy reduced from 1990 to 2021 (decline of 15·8% [8·8–22·8] and 14·5% [4·2–24·2], respectively). There were three-fold to four-fold geographical differences in the burden of active idiopathic epilepsy, with the bulk of the burden residing in low-income to middle-income countries: 82·1% (81·1–83·4) of incident, 80·4% prevalent (79·7–82·7), 84·7% (83·7–85·1) fatal epilepsy, and 87·9% (86·2–89·2) epilepsy DALYs. Interpretation: Although the global trends in idiopathic epilepsy deaths and DALY rates have improved in the preceding decades, in 2021 there were almost 52 million people with active epilepsy (24 million from idiopathic epilepsy and 28 million from secondary epilepsy), with the bulk of the burden (>80%) residing in low-income to middle-income countries. Better treatment and prevention of epilepsy are required, along with further research on risk factors of idiopathic epilepsy, good-quality long-term epilepsy surveillance studies, and exploration of the possible effect of stigma and cultural differences in seeking medical attention for epilepsy. Funding: Bill and Melinda Gates Foundatio

Global, regional, and national stillbirths at 20 weeks' gestation or longer in 204 countries and territories, 1990–2021: findings from the Global Burden of Disease Study 2021

Background: Stillbirth is a devastating and often avoidable adverse pregnancy outcome. Monitoring stillbirth levels and trends—in a comprehensive manner that leaves no one uncounted—is imperative for continuing progress in pregnancy loss reduction. This analysis, completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, methodically accounted for different stillbirth definitions with the aim of comprehensively estimating all stillbirths at 20 weeks or longer for 204 countries and territories from 1990 to 2021. Methods: We extracted data on stillbirths from 11 412 sources across 185 of 204 countries and territories, including 234 surveys, 231 published studies, 1633 vital statistics reports, and 10 585 unique location-year combinations from vital registration systems. Our final dataset comprised 11 different definitions, which were adjusted to match two gestational age thresholds: 20 weeks or longer (reference) and 28 weeks or longer (for comparisons). We modelled the ratio of stillbirth rate to neonatal mortality rate with spatiotemporal Gaussian process regression for each location and year, and then used final GBD 2021 assessments of fertility and all-cause neonatal mortality to calculate total stillbirths. Secondary analyses evaluated the number of stillbirths missed with the more restrictive gestational age definition, trends in stillbirths as a function of Socio-demographic Index, and progress in reducing stillbirths relative to neonatal deaths. Findings: In 2021, the global stillbirth rate was 23·0 (95% uncertainty interval [UI] 19·7–27·2) per 1000 births (stillbirths plus livebirths) at 20 weeks' gestation or longer, compared to 16·1 (13·9–19·0) per 1000 births at 28 weeks' gestation or longer. The global neonatal mortality rate in 2021 was 17·1 (14·8–19·9) per 1000 livebirths, corresponding to 2·19 million (1·90–2·55) neonatal deaths. The estimated number of stillbirths occurring at 20 weeks' gestation or longer decreased from 5·08 million (95% UI 4·07–6·35) in 1990 to 3·04 million (2·61–3·62) in 2021, corresponding to a 39·8% (31·8–48·0) reduction, which lagged behind a global improvement in neonatal deaths of 45·6% (36·3–53·1) for the same period (down from 4·03 million [3·86–4·22] neonatal deaths in 1990). Stillbirths in south Asia and sub-Saharan Africa comprised 77·4% (2·35 million of 3·04 million) of the global total, an increase from 60·3% (3·07 million of 5·08 million) in 1990. In 2021, 0·926 million (0·792–1·10) stillbirths, corresponding to 30·5% of the global total (3·04 million), occurred between 20 weeks' gestation and 28 weeks' gestation, with substantial variation at the country level. Interpretation: Despite the gradual global decline in stillbirths between 1990 and 2021, the overall number of stillbirths remains substantially high. Counting all stillbirths is paramount to progress, as nearly a third—close to 1 million in total—are left uncounted at the 28 weeks or longer threshold. Our findings draw attention to the differential progress in reducing stillbirths, with a high burden concentrated in countries with low development status. Scarce data availability and poor data quality constrain our capacity to precisely account for stillbirths in many locations. Addressing inequities in universal maternal health coverage, strengthening the quality of maternal health care, and improving the robustness of data systems are urgently needed to reduce the global burden of stillbirths. Funding: Bill & Melinda Gates Foundation

Global, regional, and national age-sex-specific burden of diarrhoeal diseases, their risk factors, and aetiologies, 1990–2021, for 204 countries and territories: a systematic analysis for the Global Burden of Disease Study 2021

Background: Diarrhoeal diseases claim more than 1 million lives annually and are a leading cause of death in children younger than 5 years. Comprehensive global estimates of the diarrhoeal disease burden for specific age groups of children younger than 5 years are scarce, and the burden in children older than 5 years and in adults is also understudied. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to assess the burden of, and trends in, diarrhoeal diseases overall and attributable to 13 pathogens, as well as the contributions of associated risk factors, in children and adults in 204 countries and territories from 1990 to 2021. Methods: We used the Cause of Death Ensemble modelling strategy to analyse vital registration data, verbal autopsy data, mortality surveillance data, and minimally invasive tissue sampling data. We used DisMod-MR (version 2.1), a Bayesian meta-regression tool, to analyse incidence and prevalence data identified via systematic reviews, population-based surveys, and claims and inpatient data. We calculated diarrhoeal disability-adjusted life-years (DALYs) as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for each location, year, and age–sex group. For aetiology estimation, we used a counterfactual approach to quantify population-attributable fractions (PAFs). Additionally, we estimated the diarrhoeal disease burden attributable to the independent effects of risk factors using the comparative risk assessment framework. Findings: In 2021, diarrhoeal diseases caused an estimated 1·17 million (95% uncertainty interval 0·793–1·62) deaths globally, representing a 60·3% (50·6–69·0) decrease since 1990 (2·93 million [2·31–3·73] deaths). The most pronounced decline was in children younger than 5 years, with a 79·2% (72·4–84·6) decrease in diarrhoeal deaths. Global YLLs also decreased substantially, from 186 million (147–221) in 1990 to 51·4 million (39·9–65·9) in 2021. In 2021, an estimated 59·0 million (47·2–73·2) DALYs were attributable to diarrhoeal diseases globally, with 30·9 million (23·1–42·0) of these affecting children younger than 5 years. Leading risk factors for diarrhoeal DALYs included low birthweight and short gestation in the neonatal age groups, child growth failure in children aged between 1–5 months and 2–4 years, and unsafe water and poor sanitation in older children and adults. We estimated that the removal of all evaluated diarrhoeal risk factors would reduce global DALYs from 59·0 million (47·2–73·2) to 4·99 million (1·99–10·0) among all ages combined. Globally in 2021, rotavirus was the predominant cause of diarrhoeal deaths across all ages, with a PAF of 15·2% (11·4–20·1), followed by norovirus at 10·6% (2·3–17·0) and Cryptosporidium spp at 10·2% (7·03–14·3). In children younger than 5 years, the fatal PAF of rotavirus was 35·2% (28·7–43·0), followed by Shigella spp at 24·0% (15·2–37·9) and adenovirus at 23·8% (14·8–36·3). Other pathogens with a fatal PAF greater than 10% in children younger than 5 years included Cryptosporidium spp, typical enteropathogenic Escherichia coli, and enterotoxigenic E coli producing heat-stable toxin. Interpretation: The substantial decline in the global burden of diarrhoeal diseases since 1990, particularly in children younger than 5 years, supports the effectiveness of health interventions such as oral rehydration therapy, enhanced water, sanitation, and hygiene (WASH) infrastructure, and the introduction and scale-up of rotavirus vaccination. Targeted interventions and preventive measures against key risk factors and pathogens could further reduce this burden. Continued investment in the development and distribution of vaccines for leading pathogens remains crucial. Funding: Bill & Melinda Gates Foundation.</p

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding: Bill & Melinda Gates Foundation.</p

Global Burden of Cardiovascular Diseases and Risks, 1990-2022

No description supplied</p

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

BackgroundFuture trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050.MethodsUsing forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline.FindingsIn the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]).InterpretationGlobally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions.FundingBill & Melinda Gates Foundation.</p