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BACKGROUND: Accurate assessments of current and future fertility-including overall trends and changing population age structures across countries and regions-are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios. METHODS: To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10-54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values-a metric assessing gain in forecasting accuracy-by comparing predicted versus observed ASFRs from the past 15 years (2007-21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline. FINDINGS: During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63-5·06) to 2·23 (2·09-2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137-147), declining to 129 million (121-138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1-canonically considered replacement-level fertility-in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7-29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59-2·08) in 2050 and 1·59 (1·25-1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the worlds livebirths in 2100, to 41·3% (39·6-43·1) in 2050 and 54·3% (47·1-59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions-decreasing, for example, in south Asia from 24·8% (23·7-25·8) in 2021 to 16·7% (14·3-19·1) in 2050 and 7·1% (4·4-10·1) in 2100-but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40-1·92) in 2050 and 1·62 (1·35-1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction. INTERPRETATION: Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Future 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. METHODS: Using 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. FINDINGS: In 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]). INTERPRETATION: Globally, 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. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. METHODS: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk-outcome pairs. Pairs were included on the basis of data-driven determination of a risk-outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk-outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk-outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimates distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. FINDINGS: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7-9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4-9·2]), smoking (5·7% [4·7-6·8]), low birthweight and short gestation (5·6% [4·8-6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8-6·0]). For younger demographics (ie, those aged 0-4 years and 5-14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9-27·7]) and environmental and occupational risks (decrease of 22·0% [15·5-28·8]), coupled with a 49·4% (42·3-56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9-21·7] for high BMI and 7·9% [3·3-12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6-1·9) for high BMI and 1·3% (1·1-1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4-78·8) for child growth failure and 66·3% (60·2-72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). INTERPRETATION: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: This study presents estimates for type 2 diabetes mellitus (T2DM) burden and attributable risk factors in Iran from 1990-2019, using data from the 2019 Global Burden of Disease study. METHODS: This study reports prevalence, incidence, death, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) of T2DM in Iran, by sex, age, and province, from 1990 to 2019. We also present the T2DM burden attributable to risk factors. Results are reported in absolute number and age-standardized rates. RESULTS: Overall, the burden of T2DM had increased greatly since 1990. In 2019, the T2DM incidence and prevalence cases were 291,482 (a 374% increase) and 5,035,012 (a 417% increase) respectively. Moreover, the number of death and DALYs were 14,191 (a 488% increase) and 716,457 (a 417% increase) respectively. DALYs and YLDs in women were consistently higher than men were, whereas women experienced slower increases in YLLs from 1990 to 2019. The age-standardized DALYs rate increased for all Iranian provinces during study period. High body-mass index, ambient particulate matter pollution, and low physical activity remained the three major attributable risk factors in all provinces in 2019. CONCLUSION: T2DM constitutes a major health burden in Iran. The remarkable upsurge in the T2DM burden represents an ongoing challenge, given the rapidly aging population in Iran. Thus, integrated and multi-sectoral actions that decrease exposure to risk factors and improve the prevention and early diagnosis are needed.

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, Alzheimers 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.

INTRODUCTION: Socio-economic and political events of recent years have caused a significant increase in immigrants attempting to illegally cross the United States (US)-Mexico border. While a 30-foot border wall separates the US and Mexico, immigrants from around the world have used this location as their point of entry to the US. These border crossings have led to a dramatic increase in major trauma resulting in increased inpatient resource utilization and the need for comprehensive hospital services. The aim of this study was to describe the nationality of injured immigrants admitted to a Trauma Center serving a segment of the US-Mexico border wall and to report their ultimate destinations after discharge. METHODS: We performed a retrospective review of patients admitted to an academic, Level 1 Trauma Center after injury at the US-Mexico border wall from 2021 to 2022. Demographic information was obtained from the trauma registry. The electronic medical record was searched to identify each patients self-reported country of origin. Patients nationality was then stratified by region of the world to understand geographic representation of border injury admissions. RESULTS: We identified 597 patients injured while crossing the US-Mexico border wall representing 38 different countries. The mean age of patients was 32.2±10.4 years and 446 (75%) were male. Most patients (405, 67.8%) were Mexican, followed by 23 (3.9%) patients from Peru, 17 (2.8%) patients from India, 14 (2.3%) patients from El Salvador, 13 (2.2%) patients from Cuba and 12 (2.0%) patients from Jamaica. When considering regions of the world other than Mexico, patients were most commonly from Africa, South America and Central America. CONCLUSION: The increased volume of trauma associated with the US-Mexico border wall is a humanitarian and health crisis.(1) The diverse national origin of patients admitted after injury from border wall falls has shed new light on the social and interpreter services needed to care for these border injury patients and the challenges that exist in their post-discharge care.

Background: Central Asia is known to face various ecological challenges that constitutes major risk factors for Parkinson's disease (PD). This study examines the burden of PD in Central Asia, a region where data on neurological disorders is notably sparse. Methods: Building on the latest Global Burden of Disease Study (GBD 2021), this study investigates the Years of Life Lost (YLLs), Years Lived with Disability (YLDs), and Disability-Adjusted Life Years (DALYs) associated with PD in Central Asia and its countries from 1990 to 2021. The authors calculated average annual percent change (AAPC) to analyze trends, and compared individual country estimates to global figures. Additionally, incorporating data from the World Bank, both Bayesian hierarchical and non-hierarchical frequentist regression models were employed to assess their impact on DALYs. Results: The DALYs varied across the study period, primarily driven by YLLs. While YLLs showed a uniform trend, YLDs were mostly incremental. Kazakhstan had the highest estimates across all metrics and was the only country aligned with global patterns. Age- and sex-specific estimates revealed substantial variations, with notably high figures found in male subjects from Tajikistan. The YLLs, YLDs, and DALYs for Kazakhstan, Uzbekistan, and Turkmenistan saw a significant increase in AAPCs. In contrast, Kyrgyzstan and Tajikistan saw declines, likely attributable to civic conflict and inter-country differences in population structure. Further comparison of DALY trends revealed significant deviations for all countries from the global pattern. Conclusion: This study showed an overall increase in PD burden from 1990 to 2021. These findings underscore the need for targeted strategies to reduce PD burden, with a particular focus on Kazakhstan. Integrating historical information is crucial for discussing the plausible mechanisms in studies sourced from the GBD. [ABSTRACT FROM AUTHOR]

Background: Gallbladder and biliary tract cancer (GBTC) is a significant health burden in China, exacerbated by the rising prevalence of high body mass index (BMI). Understanding the trends and factors contributing to mortality and disability associated with GBTC is crucial for targeted public health interventions. Methods: We utilized data from the Global Burden of Disease (GBD) Study to assess the burden of GBTC attributable to high BMI in China from 1990 to 2021. Age-standardized rates of deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) were analyzed. Joinpoint regression and decomposition analyses were conducted to evaluate trends and identify contributing factors, including aging, population growth, and epidemiological changes. Gender-specific differences were also assessed. Results: In 2021, GBTC deaths attributable to high BMI in China reached 4,053, with males experiencing a higher overall burden than females, particularly in older age groups. While females showed a higher mortality and overall burden in the 60 to 79 age range, this trend reversed in older age brackets, with males experiencing steeper increases in mortality and disability-related indicators beyond age 80. The age-standardized DALYs rate mirrored this pattern, with higher rates in males in advanced age groups. From 1990 to 2021, China saw a steady increase in GBTC burden attributable to high BMI, contrasting with a global decline. Joinpoint analysis indicated marked rises in mortality and DALYs rates after 2005, especially in males. Decomposition analysis identified population growth and aging as major drivers of increased deaths, while epidemiological changes primarily contributed to rising DALYs, with a stronger impact observed in males. Conclusions: The burden of GBTC attributable to high BMI in China has increased substantially over the last three decades, driven by population growth, aging, and epidemiological shifts. The trends highlight a growing gender disparity, with males experiencing a greater rise in mortality and disability. Public health strategies targeting obesity and metabolic risk factors are critical to mitigating the increasing GBTC burden. [ABSTRACT FROM AUTHOR]

Background: Giardia lamblia is an intestinal protozoan estimated to cause ~200 million symptomatic infections annually, mainly in children in low- and middle-income countries associated with intestinal damage, increased permeability, and malabsorption. Methods and results: We describe here the epidemiology, incidence, clinical characteristics, and risk factors of acute gastroenteritis episodes (AGE) with G. lamblia detection (GAGE) using a birth cohort of 443 Nicaraguan children followed weekly until 36 months of life. From June 2017 to July 2021, 1385 AGE samples were tested by qPCR. G. lamblia was detected in 104 (7.5%) of AGE episodes. In all, 69 (15.6%) children experienced at least one GAGE episode, and 25 of them (36.2%) experienced more than one episode. The incidence rate of the first episode of GAGE was 6.8/100 child-years (95% CI, 4.5–9.1). During GAGE, bloody stools, vomiting, and fever were uncommon, and children were less likely to be treated at a primary care clinic, suggesting that GAGE is typically mild and most cases did not receive medical attention, which could facilitate higher parasite loads with increased possibilities of establishing chronic carriage. GAGE was more common in children 12–24 months of age (13.9/100 child-years [95% CI, 10.7–17.1]) as compared to other age groups. In our birth-cohort, children living in a home with an indoor toilet (aHR, 0.52 [95%CI, 0.29–0.92]), and being breastfed in the first year of life (aHR: 0.10 [95%IC, 0.02, 0.57]) had a lower incidence of GAGE. In contrast, being breastfed for ≤ 6 months was associated with a higher incidence if the children were living in houses without indoor toilets and earthen floors (HR, 7.79 [95% CI, 2.07, 29.3]). Conclusion: Taken together, GAGE is more frequent under poor household conditions. However, breastfeeding significantly reduces the incidence of GAGE in those children. Author summary: G. lamblia is an intestinal protozoan having mixed associations with acute gastroenteritis, yet positive associations with impaired child growth. G. lamblia infects millions of people worldwide annually and is more prevalent in children residing in low- and middle-income countries, making it an important target for prevention and control efforts. Although G. lamblia carriage is widespread, its epidemiology, natural history, genetic diversity, host genetic susceptibility factors, and post-infectious sequelae in children are still under investigation. As no human vaccine is available, understanding its risk factors in an endemic country is the first step for reducing the burden and mitigating its sequelae. In a birth cohort in León, Nicaragua, we found that children living in households with poor sanitation conditions are at higher risk of AGE with G. lamblia detection (GAGE), but prolonged duration of breastfeeding despite these conditions may reduce the risk in these children. The study highlights the importance of breastfeeding and the need to better understand how G. lamblia contributes to the global burden of disease in children, and the mechanisms of host protection to guide future interventions. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to be a critical public health concern in India, predominantly driven by complex interplays of ecological, climatic, and socioeconomic factors. Methods: This study aimed to assess the association between climatic variables (temperature and precipitation) and malaria incidence across India from 2010 to 2019, utilizing data from the Global Historical Weather and Climate Data for climate metrics and the Global Burden of Disease Study for malaria incidence rates. Generalized Linear Mixed Models (GLMMs) with a Poisson distribution were employed to analyze the data, adjusting for socio-economic status, as indexed by the Human Development Index (HDI). Results: The results indicated a declining trend in both the number of malaria cases and age-specific incidence rates (ASIR) over the study period. In 2010, India reported approximately 20.7 million cases with an ASIR of 1688.86 per 100,000 population, which significantly reduced to 9.8 million cases and an ASIR of 700.80 by 2019. High malaria incidence was consistently observed in the states of Jharkhand and Odisha, whereas Sikkim reported the lowest numbers. Statistical analysis identified significant associations between malaria incidence and both temperature deviations and precipitation levels, with variations also linked to HDI, suggesting better detection and reporting capabilities in more developed areas. Conclusion: The study underscores the critical interactions between climatic variables and socio-economic factors in shaping the trends of malaria incidence across India. These findings highlight the necessity for adaptive, localized public health strategies that integrate environmental monitoring with socio-economic data to efficiently predict and manage malaria outbreaks. [ABSTRACT FROM AUTHOR]

Background: While TB-related mortality in the US declined four-fold from 1990 to 2019, country-level estimates of TB burden obscure within-state racial heterogeneity and changes in TB burden over time. In sixteen US Southern States and Washington DC, the effects of health inequities engendered by Jim-Crow laws enacted from the late 1800s to the 1960s have not been evaluated for TB-related mortality. We, therefore, sought to compare TB mortality rates and annualized rate of change (AROC) between 1990 and 2019 in former Jim-Crow vs. non-Jim-Crow states to help guide response efforts and inform resource prioritization to improve racial equity. Methods: We evaluated whether TB-related mortality varied over time, from 1990 to 2019, between states that have a history of enacting Jim-Crow laws vs. states with no such history using estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). TB mortality per 100,000 population and bootstrap 95% uncertainty intervals (UIs) were modeled using the Cause of Death Ensemble model (CODEm) framework with varying combinations of predictive covariates. For changes over time, we present age-standardized AROC as the percent difference in the natural logarithm of the rate in 1990 and 2019 divided by 30 (i.e., 100*[ln(2019 Rate/1990 Rate)/(30)) and the corresponding 95% UIs. Results: TB-related mortality in all US states declined between 1990 and 2019. From 1990 to 2019, most former Jim-Crow states had higher mortality rates than states that did not enact Jim-Crow laws. The most significant decline in TB mortality was in Washington DC, with a six-fold decline from 2.69 (2.46–2.96) per 100,000 population in 1990 to 0.45(0.37–0.55) in 2019, corresponding to an AROC of -0.83% (-0.86;-0.79). The lowest decline was in Iowa, from 0.30 (0.27–0.33) to 0.09 (0.07–0.11) (AROC: -0.70% (-0.76; -0.63)). Eleven of the 16 states and Washington DC in the third tertile of TB mortality rate in 1990 (range 0.81–2.69) had a history of Jim-Crow laws, whereas none of the 17 states in the first tertile (range 0.30–0.51) had such history. Conversely, mortality decreased relatively slowly in former Jim-Crow states than in non-Jim-Crow states. Conclusions: Even though the 1964 Civil Rights Act dismantled Jim-Crow statutes, racial inequities in TB burden experienced by past generations may still be felt in subsequent generations. Understanding the role of structural racism at the intersection of science and medicine shows the complex ways historical laws, such as Jim-Crow laws, continue to negatively impact health outcomes and warn of future dangers, such as COVID-19, to avoid. [ABSTRACT FROM AUTHOR]

Objective: This study aims to systematically evaluate the burden of low back pain(LBP) in the middle-aged population across global regions and between genders, assess the major risk factors and their impacts, and project the burden to 2050, providing a scientific basis for global preventive actions. Methods: This study utilized The Global Burden of Disease(GBD) 2021 database. First, we integrated the population data of the 45–49, 50–54, and 55–59 age groups provided by the GBD using a weighted average method to calculate the Disability-adjusted life years(DALYs) rate for the middle-aged population aged 45 to 59 years. Subsequently, we analyzed the trends in the burden of LBP globally and across regions from 1990 to 2021, with a focus on stratified data by country, risk factors (e.g., high BMI), and gender. Finally, we employed the Bayesian Age-Period-Cohort(BAPC) model to predict future trends in LBP burden from 2021 to 2050. Results: Globally, from 1990 to 2021, the DALY rate for the 45–59 age group with LBP decreased from 875.45(95%UI: 534.57-1340.68) per 100,000 people to 747.92 (450.55-1,161.66), with an EAPC of -0.46 (95%UI: -0.50 to -0.43). Despite the decline in DALY rates, the total number of DALYs due to LBP increased from 5,515,080.64 (95%UI: 3,367,626.11–8,445,931.67) in 1990 to 9,816,401.64 (95%UI: 5,913,142.33–15,249,187.03) in 2021, a rise of 4,301,321. High Socio-Demographic Index (SDI) regions were the most affected, with a DALY rate of 933.03 (95%UI: 557.90–1,420.60) per 100,000 in 2021. Among risk factors, high BMI showed the most significant increase, with DALY rates rising from 153.64 (95%UI: 15.94–334.63) per 100,000 in 1990 to 209.09 (95%UI: 22.16–452.58) in 2021, and an EAPC of 1.08 (95%UI: 1.02 to 1.14). Gender differences revealed a DALY rate of 705.39 (95%UI: 431.21–1,078.96) per 100,000 for males and 803.62 (95%UI: 471.69–1,266.63) per 100,000 for females in 2021. Projections based on the BAPC model suggest that by 2050, global DALYs due to LBP will increase to 11,626,643.07, with females expected to account for 6,725,763.24 and males for 4,900,879.84, indicating a greater burden for females. Conclusion: This study highlights the global burden and trends of LBP in the middle-aged population. Although the DALY rate for the 45–59 age group decreased from 1990 to 2021, the total number of DALYs increased significantly due to population aging. In this context, the burden of LBP in low-middle SDI regions has remained largely unchanged and remains substantial, while high-SDI regions, despite some decline, continue to bear the highest overall burden. High BMI continues to contribute significantly to the rising LBP burden, particularly in middle-aged populations, and demands urgent attention. Gender differences indicate that females bear a greater LBP burden than males, with the gap widening over time. Effective preventive and intervention measures are urgently needed to mitigate the future burden of LBP. [ABSTRACT FROM AUTHOR]

Background: The zoonotic infectious diseases of poverty (zIDPs) are a group of diseases contributing to global poverty, with significant impacts on a substantial population. This study aims to describe the global, regional, and national burden of zIDPs—schistosomiasis, cystic echinococcosis, cysticercosis, and food-borne trematodiases (FBTs)—to support policy making and resource allocation for their control and elimination. Methods: Data of zIDPs from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 were retrieved from 1990 to 2021. The age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year (DALY) rate were described and the estimated annual percentage changes (EAPCs) were calculated to quantify their burden and temporal trends. Spearman correlation analysis was conducted to examine the relationship between age-standardized rates and Socio-demographic Index (SDI). Results: In 2021, these zIDPs exhibited a certain level of ASPRs and age-standardized DALY rates, while maintaining relatively low ASMRs. Noticeably, schistosomiasis presented the highest ASPR of 1914.299 (95% UI: 1378.920, 2510.853 per 100,000 population) and an age-standardized DALY rate of 21.895 (95% UI: 12.937, 37.278 per 100,000 population) among the zIDPs. The tapestry of burden—woven predominantly through low and lower-middle SDI regions—stretched across Africa, Latin America, and parts of Asia. From 1990 to 2021, a kaleidoscopic shift was observed globally as ASPRs, ASMRs, and age-standardized DALY rates declined significantly, as reflected by the EAPC values. Negative correlations were observed between the ASPRs, ASMRs, age-standardized DALY rates of schistosomiasis (r value = − 0.610, − 0.622 and − 0.610), cystic echinococcosis (− 0.676 of ASMR, − 0.550 of age-standardized DALYs), cysticercosis (− 0.420, − 0.797 and − 0.591) and the SDI. In contrast, a slight positive correlation was noted between the ASPR, age-standardized DALY rates of FBTs and SDI with r value of 0.221 and 0.213, respectively. Conclusion: The burden of zIDPs declined across almost all endemic regions from 1990 to 2021, yet still predominated in low and low-middle SDI regions. Substantial challenges exist to achieve the goal of control and elimination of zIDPs, and integrated approaches based on One Health need to be strengthened to improve health outcomes. [ABSTRACT FROM AUTHOR]

Larynx cancer poses a significant public health challenge in China, with rising incidence and mortality rates over the past decades. Understanding the long-term trends and underlying factors is crucial for effective intervention and policy formulation. Data were utilized from the global burden of disease (GBD) Study 2021 to analyze the incidence, prevalence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) due to larynx cancer in China from 1990 to 2021. Joinpoint regression analysis identified key changes in trends, while age-period-cohort (APC) analysis and decomposition analysis quantified the contributions of aging, epidemiological changes, and population growth to these trends. Our study found a significant increase in the incidence and prevalence of larynx cancer in China, particularly among males. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for males were substantially higher than those for females. Decomposition analysis revealed that aging was the primary driver of increasing incidence and mortality rates, while epidemiological changes had a mitigating effect. Joinpoint analysis identified periods of rapid urbanization and economic growth as key turning points for increased incidence. Bayesian APC models projected a continued upward trend in incidence rates up to 2030. The rising burden of larynx cancer in China underscores the need for targeted public health interventions, including smoking cessation programs, environmental pollution control, and early detection strategies. Addressing gender disparities and implementing effective prevention measures are crucial to mitigating the impact of larynx cancer in China. [ABSTRACT FROM AUTHOR]

Background: This study aims to analyze the historical trends of inflammatory bowel disease (IBD) burden in the elderly from 1990 to 2021 and forecast future trends up to 2051. Methods: Data from the Global Burden of Disease Study 2021 were utilized. Age-standardized rates (ASR) for incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated. Estimated annual percentage changes (EAPCs) were computed to quantify temporal trends. A Bayesian Age-Period-Cohort model was employed to project future trends. Results: From 1990 to 2021, the global number of elderly IBD increased from 573,500 to 1,278,190. The age-standardized incidence rate (ASIR) rose from 8.01 to 8.77 per 100,000, while the age-standardized prevalence rate (ASPR) slightly decreased from 118.14 to 117.29 per 100,000. Death number increased from 14,400 to 33,490, but the age-standardized mortality rate decreased from 3.21 to 2.84 per 100,000. DALYs increased from 324,100 to 683,750, with the age-standardized DALYs rate declining from 68.78 to 60.88 per 100,000. Significant geographical variations were observed, with high Socio-demographic Index regions showing the highest burden. Projections suggest that by 2051, elderly IBD prevalence number may reach 2,316,000, with ASIR and ASPR potentially rising after 2035 and 2042, respectively. Deaths and DALYs are projected to increase to 75,000 and 1,401,000 respectively, despite continued declines in ASRs. Conclusion: The absolute burden of IBD in the elderly population is projected to increase substantially by 2051, despite decreasing ASRs. These findings underscore the need for tailored healthcare strategies and resource allocation to address the growing challenge of elderly IBD globally. [ABSTRACT FROM AUTHOR]

Introduction: Migraine is a prevalent neurological disorder characterized by recurrent attacks, leading to a substantial global disease burden. Recent observational studies have reported the onset and worsening of migraine following COVID-19 infection and vaccination. However, traditional observational study designs have limitations in controlling for confounding factors, potentially resulting in biased and inconsistent conclusions. To address this, we applied Mendelian randomization (MR) to investigate the causal relationship between COVID-19 infection and vaccination with migraine. Methods: This study utilized summary-level genome-wide association study (GWAS) data from the GWAS catalog and FinnGen database to evaluate the effects of varying degrees of COVID-19 infection and vaccination on migraine. We employed inverse variance weighted (IVW) fixed-effect and random-effect models as the primary methods for MR analysis, with MR-Egger and other approaches as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept regression, and MR-PRESSO, were conducted to ensure robustness of the results. Results: Our MR analysis revealed no significant causal association between COVID-19 infection and migraine. However, a significant causal association was found between COVID-19 vaccination and migraine (beta = 0.071, P = 0.034). The results were confirmed through a series of sensitivity tests, demonstrating the robustness of the findings. Discussion: This study provides novel evidence of a significant causal link between COVID-19 vaccination and migraine, while no such association was observed with COVID-19 infection. These findings may have important implications for clinical practice, particularly in planning treatment adjustments and optimizing patient care for individuals with migraines in the context of COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Introduction: Currently, neurological diseases has surpassed cardiovascular diseases as the primary cause of global disease burden. Among these, headache disorders are the most prevalent and have emerged as the main cause of disability in people under 50 years old in recent years. Since the release of GBD 2021, there has been no comprehensive systematic exposition on the burden of headache among individuals under 50 years old and a forecast for future burdens. This study aims to quantify the global, regional, and national burden of headache disorders among people under 50 from 1992 to 2021 and to predict future trends in order to provide policy makers with precise and effective epidemiological evidence. Methods: This study extracted the incidence, prevalence, and DALYs data related to headache disorders in the 5–50 age group from the GBD 2021. After age-standardizing the data, we used joinpoint regression analysis and health inequity analysis to analyze the burden and temporal trend of headache disorders and predicted the future disease burden and changes based on the age-period-cohort model. Results: By 2021, the case number of global incidence, prevalence and DALYs have increased by 35, 39, and 41%, respectively, over the past 30 years. The incidence and prevalence of tension-type headache (TTH) are significantly higher than those of migraine, but migraine causes greater health burdens. The burden is higher for female than for male. In terms of age, youth aged 25–29 years had the highest incidence in 2021, with an age-standardized rate (ASR) of 13,454.64 (95%CI, 9,546.96–18,361.36) per 100,000 population. Nationally, the highest ASR of incidence and prevalence are found in Norway, and the most damaging to health is found in Belgium. Among the five sociodemographic index (SDI) categories, the middle SDI has the highest number of cases (190 million in 2021). It is worth noting that the forecast shows that by 2046 the three indicators will reach 680 million, 2.33 billion, and 41 million, respectively, indicating that the burden of headache disorders in this age group will continue to persist. Conclusion: Globally, the burden of headache disorders in people under 50 years of age remains significant and has not improved over the past 30 years, especially in regions with high SDI. Headache problems will continue to pose a serious public health challenge for this age group for some time to come. This study reveals the burden and distribution of headache disorders in this age group, providing important basis for governments and policymakers to accurately and effectively allocate health care resources, strengthen prevention and management strategies, and respond to this global health problem. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the burden of disease due to noncommunicable diseases (NCDs) between 1990 and 2021 in Brazil. In addition, this study compared mortality from NCDs with mortality from all causes and COVID-19, analysed NCD mortality trends and projections for 2030, and analysed NCD mortality rates and risk factors attributed to these deaths among the 27 states of Brazil. Ecological studies. This study used the Global Burden of Disease study (GBD) database from 1990 to 2021. Premature deaths from four NCDs (neoplasms, cardiovascular disease, chronic respiratory diseases and diabetes mellitus) were analysed. The following metrics were used to analyse the burden of NCDs in Brazil: absolute number of deaths, proportional mortality, mortality rate, years of life lost due to premature death (YLL), years lived with disabilities (YLD) and disability-adjusted years of life lost due to premature death (DALY). For comparison between the years studied and states, age-standardised rates were used. Finding from this study showed that there was increase in the proportion of premature deaths due to NCDs between 1990 and 2019 (29.4 % in 1990, 30.8 % in 2019), and a reduction in 2021 (24.7 %). The mortality rates, DALY and YLL from NCDs declined between 1990 and 2019 (−37.7 %, −34.5 % and −38.3 %, respectively); however, a stability in mortality rates, DALY, YLD, YLL was observed between 2019 and 2021 (−0.1 %, 0.7 %, −0.1 % and 0.8 %, respectively). Between 1990 and 2021, there was a decline in mortality rates, DALY and YLL for most states and an increase in YLD rates. However, results suggest that the Sustainable Development Goal (SDG) for the reduction in mortality from NCDs by one-third by 2030 will not be achieved. The main risk factors associated with premature death from NCDs in 2021 were high blood pressure, tobacco use, dietary risks, high body mass index (BMI) and high blood glucose levels. The correlation between sociodemographic index and percentage change in mortality rates was significant for the following total NCDs, cardiovascular disease, chronic respiratory disease, diabetes and neoplasms. The current study highlights the importance of deaths from NCDs in Brazil and the worsening of mortality rates since 2016, as a result of austerity measures and the COVID-19 pandemic, which compromises the achievement of the SDG reduced mortality targets for NCDs. There was a reduction in risk factors for NCDs, mainly behavioural, although metabolic risk factors are of great concern and require new strategies to promote health, prevention and comprehensive care. [ABSTRACT FROM AUTHOR]

To analyze the occurrence of leprosy in Brazil and its states between 1990 and 2019, according to Global Burden of Disease (GBD) estimates, and its correlation with development status. A descriptive and analytical ecological epidemiological study. Rates of incidence, prevalence, and years lived with disability (YLD) due to leprosy, standardized by age, per 100,000 inhabitants, were analyzed. The trend analysis consisted of the joinpoint regression model and the average annual percentage change. The correlation between the incidence rate and the sociodemographic index (SDI) was investigated (Spearman test) at a 5% significance level. Incidence, prevalence and YLD rates were presented by country's states, sex, and age. There was an average percentage decrease of −1.1% per year (P < 0.001) in the incidence rate in the country and, between 1990 and 2019, a decline from 4.8 to 3.5 per 100,000 inhabitants; prevalence from 26.1 to 22.2, and YLD from 1.1 to 1.0. The incidence rate was higher among men and the elderly. Maranhão (7.0 in 1990; 4.2 in 2019), Alagoas (6.6 in 1990; 4.1 in 2019), Acre (6.1 in 1990; 4.0 in 2019), Mato Grosso (5.2 in 1990 and 3.7 in 2019), and Mato Grosso do Sul (4.8 in 1990 and 3.7 in 2019) presented the highest incidence rates. A negative correlation was observed between SDI levels and leprosy incidence rates in 1990 (R = −0.71; P < 0.0001) and 2019 (R = −0.81; P < 0.0001). Despite the decrease in the rates of leprosy incidence, prevalence, and YLDs over the analyzed period, Brazil has a long way towards achieving its eradication. The greater burden of the disease in males stands out. The estimated risk of the disease was higher in the states with the lowest SDI levels. Therefore, interventions must consider the heterogeneity of the disease burden geographically and between sociodemographic groups. [ABSTRACT FROM AUTHOR]

This study aimed to comprehensively evaluate Mexico's health system performance from 1990 to 2019 utilising the Health Access and Quality Index (HAQI) as a primary indicator. A retrospective ecological analysis was performed using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) study and the National Population Council (CONAPO). HAQI values for 1990, 2000, 2010, 2015, and 2019 were examined for each state in Mexico and three age groups (young, working, and post-working). Additionally, the marginalisation index was employed to assess inequalities in the HAQI distribution across states. The concentration index of the HAQI for each year was estimated, and the efficiency of states in producing the HAQI was evaluated using a data envelopment approach. Through the analysis of national and subnational data, results indicated an overall improvement in healthcare access and quality during the study period. Although differences in the HAQI value related to state marginalisation decreased from 1990 to 2015, by 2019, the inequality had returned to a level comparable to 2000. Efficiency in producing health (HAQI values) exhibited substantial heterogeneity and fluctuations in the ranking order over time. States such as Nuevo León consistently performed well, while others, such as Guerrero, Chihuahua, Mexico City, and Puebla, consistently underperformed. The findings from this study emphasise the necessity for nuanced strategies to address healthcare disparities and enhance the overall system performance. The study provides valuable insights for ongoing discussions about the future of Mexico's healthcare system, aiming to inform evidence-based policy decisions and improve the nationwide delivery of healthcare services. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on the countries of Latin America and the Caribbean. This study aims to summarise key findings from the Global Burden of Disease (GBD) 2021 in the region. We also explore disparities in burden rates and the relationship with the Socio-demographic Index (SDI). A cross-sectional analysis of GBD 2021 results was conducted. We obtained the disability-adjusted life years (DALYs) due to COVID-19 for 20 countries, analysing number- and age-adjusted rates. Spearman's correlation (r h o) and 95% confidence intervals (CIs) assessed the SDI–DALY rates relationship. COVID-19 was the leading cause disease burden in the region, with 20,437,321 DALYs in 2020 and 31,525,824 in 2021. Premature mortality (years of life lost) accounted for over 95%. Disparities existed across sexes, age groups, and countries, with Bolivia and Peru having the highest rates. A significant 2021 correlation was found (r h o = −0.55, 95% CI: -0.90 to 0.19; P = 0.013) but not in 2020 (r h o = −0.40, 95% CI: -0.75 to 0.05; P = 0.078). COVID-19 posed a significant burden in Latin America and the Caribbean, emphasising the need for targeted interventions, especially in socioeconomically disadvantaged regions. [ABSTRACT FROM AUTHOR]

Cardiometabolic disorders contribute to the global burden of cardiovascular diseases. Emerging sphingolipid metabolites like sphingosine‐1‐phosphate (S1P) and its receptors, S1PRs, present a dynamic signalling axis significantly impacting cardiac homeostasis. S1P's intricate mechanisms extend to its transportation in the bloodstream by two specific carriers: high‐density lipoprotein particles and albumin. This intricate transport system ensures the accessibility of S1P to distant target tissues, influencing several physiological processes critical for cardiovascular health. This review delves into the diverse functions of S1P and S1PRs in both physiological and pathophysiological conditions of the heart. Emphasis is placed on their diverse roles in modulating cardiac health, spanning from cardiac contractility, angiogenesis, inflammation, atherosclerosis and myocardial infarction. The intricate interplays involving S1P and its receptors are analysed concerning different cardiac cell types, shedding light on their respective roles in different heart diseases. We also review the therapeutic applications of targeting S1P/S1PRs in cardiac diseases, considering existing drugs like Fingolimod, as well as the prospects and challenges in developing novel therapies that selectively modulate S1PRs. [ABSTRACT FROM AUTHOR]

The article "Trends in substance use disorder mortality in the United States and worldwide, 1990–2021" discusses the significant impact of substance use disorder (SUD) on global health, with alcohol use disorder being the largest contributor to SUD worldwide. Opioids are the most common drug associated with SUD mortality, accounting for approximately 70% of deaths globally. The study reveals an increase in SUD mortality in the USA, particularly attributed to opioids and psychostimulants, while worldwide trends show a tendency towards declines. The findings underscore the need for public health prevention efforts to address the growing epidemic of substance use and associated mortality in the USA. [Extracted from the article]

Mosquito‐borne diseases contribute substantially to the global burden of disease, and are strongly influenced by environmental conditions. Ongoing and rapid environmental change necessitates improved understanding of the response of mosquito‐borne diseases to environmental factors like temperature, and novel approaches to mapping and monitoring risk. Recent development of trait‐based mechanistic models has improved understanding of the temperature dependence of transmission, but model predictions remain challenging to validate in the field. Using West Nile virus (WNV) as a case study, we illustrate the use of a novel remote sensing‐based approach to mapping temperature‐dependent mosquito and viral traits at high spatial resolution and across the diurnal cycle. We validate the approach using mosquito and WNV surveillance data controlling for other key factors in the ecology of WNV, finding strong agreement between temperature‐dependent traits and field‐based metrics of risk. Moreover, we find that WNV infection rate in mosquitos exhibits a unimodal relationship with temperature, peaking at ~24.6–25.2°C, in the middle of the 95% credible interval of optimal temperature for transmission of WNV predicted by trait‐based mechanistic models. This study represents one of the highest resolution validations of trait‐based model predictions, and illustrates the utility of a novel remote sensing approach to predicting mosquito‐borne disease risk. [ABSTRACT FROM AUTHOR]

Kidney diseases have become a global epidemic with significant public health impact. Chronic kidney disease (CKD) is set to become the fifth largest cause of death by 2040, with major impacts on low-resource countries. This review is based on a recent report of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) which uncovered gaps in key vehicles of kidney care delivery assessed using World Health Organization building blocks for health systems (financing, services delivery, workforce, access to essential medicines, health information systems and leadership/governance). High-income countries had more centres for kidney replacement therapies (KRT), higher KRT access, higher allocation of public funds to KRT, larger workforces, more health information systems, and higher government recognition of CKD and KRT as health priorities than low-income nations. Evidence identified from the current ISN-GKHA initiative should serve as template for generating and advancing policies and partnerships to address the global burden of kidney disease. The results provide opportunities for kidney health policymakers, nephrology leaders and organizations to initiate consultations to identify strategies for improving care delivery and access in equitable, resource-sensitive manners. Policies to increase use of public funding for kidney care, lower the cost of KRT and increase workforces should be a high priority in low-resource nations, while strategies that expand access to kidney care and maintain current status of care should be prioritized in high-income countries. In all countries, the perspectives of people with CKD should be exhaustively explored to identify core kidney care priorities. [ABSTRACT FROM AUTHOR]

Background: Information about the chikungunya disease burden by age groups and geographic distribution is necessary to guide appropriate control measures. With this, we conducted a systematic review and meta-analysis to estimate the disease burden of chikungunya fever in India. Material and Methods: We conducted this systematic review according to the Cochrane Collaboration guidelines. We retrieved relevant articles from PubMed and a free online search. Two investigators screened titles and abstracts and extracted data from the relevant articles. Our primary outcome is the proportion of laboratory-confirmed Chikungunya fever among clinically suspected patients. We used a random effect model to estimate the pooled proportion of Chikungunya fever. Result: A total of 20 articles were included in the quantitative syntheses. The pooled proportion of laboratory-confirmed chikungunya fever from 20 studies estimated using the random effects model is 24% (95%CI: 15-34%). We found the pooled proportion in the southern region was 35% (95%CI: 4-66%), 28% (95%CI: 3-58%) in the western region, 24% (95%CI: 1-48%) in the eastern region, 20% (95%CI: 12-29%) in the northern region, and 4% (95%CI: 1-6%) in North-eastern region. Conclusion: This review emphasizes the need to strengthen the surveillance of disease burden using multiple diagnostic tests and the need for an appropriate molecular diagnostic for early detection of the chikungunya virus. [ABSTRACT FROM AUTHOR]

This study provides a comprehensive analysis of global, continental, and national trends in the prevalence and mortality of prostate cancer (PC), breast cancer (BC), and thyroid cancer (TC). Utilizing 2021 Global Burden of Diseases (GBD2021) data, prevalence and death rates for 2021 were examined, with temporal trends from 1990 to 2021 analyzed via Joinpoint regression. Annual percentage change (APC) and average APC (AAPC) were calculated with 95% CI. Distributive inequalities were quantified using the slope index of inequality and concentration index. In 2021, PC, BC, and TC showed higher global age-standardized prevalence rates (ASPR) in Europe and America compared to Africa and Asia, while higher age-standardized death rates (ASDR) for PC and BC were noted in Africa. Over the study period, significant global increases in ASPR were observed for PC (AAPC = 0.78, 95% CI: 0.67 to 0.89), BC (AAPC = 0.31, 95% CI: 0.24 to 0.37), and TC (AAPC = 1.42, 95% CI: 1.31 to 1.52). Conversely, ASDR significantly decreased for PC (AAPC = -0.83, 95% CI: -0.92 to -0.74), BC (AAPC = -0.48, 95% CI: -0.56 to -0.39), and TC (AAPC = -0.23, 95% CI: -0.29 to -0.17). Variations were observed across continents and time periods, affecting 204 countries and territories. Higher Social Development Index (SDI) levels were associated with a more pronounced burden of these cancers. The findings highlight significant global heterogeneity in prevalence, death rates, and temporal trends of endocrine cancers, with important implications for epidemiology and public health policies. [ABSTRACT FROM AUTHOR]

The article "Rocking Continuous Renal Replacement Therapy Management in Children and Young Adults With Sepsis: Impact of Hemodynamic Support on Outcomes" published in Critical Care Medicine discusses the use of continuous renal replacement therapy (CRRT) in children and young adults with sepsis to enhance kidney function recovery and overall outcomes. The study analyzed data from the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry, focusing on factors associated with Major Adverse Kidney Events at 90 days from CRRT initiation. Patients with sepsis had higher mortality rates, longer CRRT duration, and fewer ventilator-free days compared to those without sepsis, highlighting the challenges and outcomes associated with sepsis-associated acute kidney injury. [Extracted from the article]

Background: The disability-adjusted life year (DALY), a key metric for health resource allocation, encompasses morbidity through disability weights. Widely used in tuberculosis cost-effectiveness analysis (CEAs), DALYs play a significant role in informing intervention adopt/reject decisions. This study reviews the values and consistency of disability weights applied in tuberculosis-related CEAs. Methods: We conducted a systematic review using the Tufts CEA database, updated to July 2023 with searches in Embase, Scopus and PubMed. Eligible studies needed to have included a cost-per-DALY ratio, and additionally either evaluated a tuberculosis (TB) intervention or included tuberculosis-related weights. We considered all tuberculosis health states: with/without human immunodeficiency virus (HIV) coinfection, TB treatments and treatment side effects. Data were screened and extracted independently by combinations of two authors. Findings: A total of 105 studies spanning 2002–2023 across 50 countries (mainly low- and middle-income countries) were extracted. Disability weights were sourced primarily from the Global Burden of Disease (GBD; 100/165; 61%), with 17 non-GBD studies additionally referenced, along with primary derivation. Inconsistencies in the utilisation of weights were evident: of the 100 usages of GBD-sourced weights, only in 47 instances (47%) had the weight value been explicitly specified with an appropriate up-to-date reference cited (constituting 28% of all weight usages, 47/165). Sensitivity analyses on weight values had been conducted in 30% of studies (31/105). Twelve studies did not clearly specify weights or their sources; nine further calculated DALYs without morbidity. The review suggests methodological gaps in current approaches for representing important aspects of TB, including TB–HIV coinfection, treatment, drug-resistance, extrapulmonary TB and psychological impacts. We propose a set of best practice recommendations. Interpretation: There is a need for increased rigour in the application, sensitivity testing and reporting of TB disability weights. Furthermore, there appears a desire among researchers to reflect elements of the tuberculosis experience beyond those allowed for by GBD disability weights. [ABSTRACT FROM AUTHOR]

Objective: Motor neuron disease (MND) is a group of neurological diseases, the majority being amyotrophic lateral sclerosis (ALS), with varying clinical presentations across demographics. Clinical trial enrollment reflecting global disease burden improves understanding of diverse presentations and aids personalized therapy development. We assessed the sex, racial, and ethnic composition of MND/ALS clinical trial participants relative to global disease burdens. Methods: We searched 'motor neuron disease OR amyotrophic lateral sclerosis' on ClinicalTrials.gov from 02/2000–04/2024. We extracted trial (start year, study site, sponsor location, phase, masking, intervention) and demographic data (sex, race, ethnicity) from randomized interventional studies. We obtained sex-based MND/ALS disease burden estimates from the Global Burden of Disease database. For females, we calculated pooled participation-to-prevalence ratio (PPR) with 95% confidence intervals (CIs), with PPR of 0.8–1.2 indicating adequate enrollment. We used Kruskal–Wallis tests to compare demographic groups across trial characteristics. Results: Of 85 trials, females comprised 37.47% (n = 5011) of 13,372 participants; the pooled female PPR was 0.97 (95% CI: 0.77–1.16). Of 41 trials (9340 participants) reporting race, 121 (1.30%) participants were Black or African American, 16 (0.17%) American Indian or Alaskan Native, and 6 (0.06%) Native Hawaiian or Other Pacific Islander. 24 trials (595 participants) reported ethnicity, with a minority of Hispanic participants (n = 153; 2.57%). Conclusions: MND/ALS clinical trials had adequate female enrollment relative to global disease burdens. Race and ethnicity data were underreported. However, there were enrollment disparities of racial and ethnic groups. Increased trial leadership diversity, equitable enrollment policies, and addressing barriers to participation could improve enrollment diversity. [ABSTRACT FROM AUTHOR]

Background: For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialised tools are used. Three tools have been proven useful to personalise drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging. Methods: In these Guidelines, we provide an in-depth review of pharmacokinetics, pharmacodynamics, and pharmacogenetics for 45 antipsychotics. Over 30 international experts in psychiatry selected studies that have measured drug concentrations in the blood (TDM), gene polymorphisms of enzymes involved in drug metabolism, or receptor/transporter occupancies in the brain (positron emission tomography (PET)). Results: Study results strongly support the use of TDM and the cytochrome P450 (CYP) genotyping and/or phenotyping to guide drug therapies. Evidence-based target ranges are available for titrating drug doses that are often supported by PET findings. Conclusion: All three tools discussed in these Guidelines are essential for drug treatment. TDM goes well beyond typical indications such as unclear compliance and polypharmacy. Despite its enormous potential to optimise treatment effects, minimise side effects and ultimately reduce the global burden of diseases, personalised drug treatment has not yet become the standard of care in psychiatry. [ABSTRACT FROM AUTHOR]

Aim: Elevated body mass index (BMI) presents a significant public health challenge in the United States, contributing to considerable morbidity, mortality and economic burden. This study investigates the health burden of overweight and obesity in the United States from 1990 to 2021, leveraging the Global Burden of Disease data set to analyse trends, disparities and potential determinants of high BMI‐related health outcomes. Materials and Methods: Our study focused on the United States, analysing trends in disability‐adjusted life years (DALY) and deaths attributable to high BMI, defined as a BMI of 25 kg/m2 or higher for adults. Statistical analyses included estimated annual percentage change (EAPC) in age‐standardized DALY rates and age‐standardized death rates. Pearson correlation was performed between EAPCs and the socio‐demographic index (SDI), with significance set at p < 0.05. Results: From 1990 to 2021, age‐standardized DALY rates attributable to high BMI increased by 24.9%, whereas the age‐standardized death rates increased by 5.2%. Age disparities showed DALYs peaking at 60–64 years for males and 65–69 years for females, with deaths peaking at 65–69 years for males and 90–94 years for females. A strong negative correlation was found between the EAPC in age‐standardized DALY and death rates and the SDI. Conclusions: Overweight and obesity significantly impact public health in the United States, especially among older adults and lower socio‐demographic regions. Comprehensive public health strategies integrating behavioural, technological and environmental interventions are crucial. Future research should focus on longitudinal studies, personalized interventions and policy‐driven approaches to address the multifaceted influences on high BMI. [ABSTRACT FROM AUTHOR]

Gynecological diseases ranked second among new cases of noncommunicable diseases in women of reproductive age in 1990 and 2019 globally. The aim of this study was to estimate the disease burden of gynecological diseases and describe their trends in women of all ages from 1990 to 2019. Using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), authors examined the incidence, disability-adjusted life years, and deaths from gynecological diseases by age in 204 countries and territories worldwide from 1990 to 2019. Analyses were conducted in 2022. Globally, the age-standardized incidence rate and age-standardized disability-adjusted life year rate (ASDR) of gynecological diseases decreased by –0.176% and –0.245%, respectively from 1990 to 2019. Low socioeconomic development index countries had the highest age-standardized incidence rate and ASDR in 2019. The age-specific incidence rate of gynecological diseases in women aged 15–29 years increased from 1990 to 2019, and the 20–24-year age group increased the greatest by 0.21%. Polycystic ovary syndrome and other types of benign disorders contributed to the major increase. Although the disease burden of gynecological diseases decreased slightly between 1990 and 2019 globally, it remained highest in low socioeconomic development index countries. The disease burden in 20–24-year age group exhibited the fastest growth, with polycystic ovary syndrome and other types of benign disorders playing a significant role. Urgent and effective measures should be taken to target different age groups, types of gynecological disease, and regions with high disease burdens. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) is a malignant tumour with poor prognosis and high mortality, and high fasting plasma glucose (HFPG) is considered to be one of its important risk factors. Methods: PC disease burden data were obtained from the Global Burden of Disease Study 2021 (GBD 2021) database. Annual percent change (APC), average APC (AAPC), and 95% confidence interval (95% CI) were analysed using joinpoint linkpoint regression models to assess the trend of PC burden of disease between 1990 and 2021. An age-period-cohort model was used to estimate the independent effects of age, period, and cohort on PC burden, and data on PC mortality attributable to HFPG in China from 2022 to 2032 were analysed on the basis of a Bayesian age-period-cohort model projection. Results: The number of Pc deaths due to HFPG continue to rise in China from 1990 to 2021, with age-standardised mortality (ASMR) and age-standardised disability-adjusted life-year rates with increasing AAPC values of 1.12% (95% CI, 0.73-1.52) and 1.00% (95% CI, 0.63-1.37), respectively. Throughout the study, we found that the overall level of PC disease burden was significantly higher in men than that in women. In age-period-cohort analyses, the age effect of PC showed an increasing and then decreasing trend, the period effect showed an overall increasing trend during the study period, and the cohort effect showed an overall slow decreasing trend. In addition, the BAPC model predicted that ASMR is expected to decline significantly in both men and women from 2022 to 2032. Conclusions: It was found that PC attributable to HFPG was generally on the rise in China from 1990 to 2021 and has been on the decline in recent years, and projections suggest that the country's future PC disease burden will continue to show a downward trend. Age and period of birth are the main factors affecting the disease burden, especially in men and older age groups. Early prevention, regular screening, and research into the pathogenesis of PC have, therefore, become particularly important. [ABSTRACT FROM AUTHOR]

BACKGROUND Hypertension affects 25%–30% of the world population. Hydrochlorothiazide (HCTZ) is among the most used and cheapest medications but was in 2018 labeled with a warning stating the increased risk of nonmelanoma skin cancer (NMSC). This study describes geographical differences in the association between HCTZ and NMSC from the perspective of hypertensive heart disease (HHD). METHODS We conducted a systematic literature search (PubMed, Embase, Clinicaltrial.gov, and Clinicaltrial.eu) using PICO/PECO acronyms, including case–control, cohort, and randomized controlled trials. We constructed a rate ratio of disability-adjusted life years (DALY) for HHD/NMSC in the global burden of disease (GBD) regions. RESULTS No increased risk of NMSC with the use of HCTZ was found in Taiwan, India, and Brazil. A small (hazard ratio (HR)/odds ratio (OR) ≤1.5) but significantly increased risk was seen in Canada, the United States, and Korea. An increased risk (1.5< HR/OR ≤2.5) in Iceland, Spain, and Japan and a highly increased risk (HR/OR >2.5) in the United Kingdom, Denmark, the Netherlands, and Australia. HHD is associated with a more than tenfold DALY rate compared with NMSC in 13 of 21 GBD regions, corresponding to 77.2% of the global population. In none of these 13 regions was there an increased risk of HCTZ-associated NMSC. CONCLUSIONS Despite limited information from many countries, our data point to large geographical differences in the association between HCTZ and NMSC. In all GBD regions, except Australasia, HHD constitutes a more than fivefold DALY rate compared to NMSC. This disproportionate risk should be considered before avoiding HCTZ from the antihypertensive treatment. [ABSTRACT FROM AUTHOR]

Introduction: Development of an effective vaccine against tuberculosis is a critical step towards reducing the global burden of disease. A therapeutic vaccine might also reduce the high rate of TB recurrence and help address the challenges of drug-resistant strains. ID93+GLA-SE is a candidate subunit vaccine that will soon be evaluated in a phase 2b efficacy trial for prevention of recurrent TB among patients undergoing TB treatment. ID93+GLA-SE vaccination was shown to elicit robust CD4+ T cell and IgG antibody responses among recently treated TB patients in the TBVPX-203 Phase 2a study (NCT02465216), but the mechanisms underlying these responses are not well understood. Methods: In this study we used specimens from TBVPX-203 participants to describe the changes in peripheral blood gene expression that occur after ID93 +GLA-SE vaccination. Results: Analyses revealed several distinct modules of co-varying genes that were either up- or down-regulated after vaccination, including genes associated with innate immune pathways at 3 days post-vaccination and genes associated with lymphocyte expansion and B cell activation at 7 days post-vaccination. Notably, the regulation of these gene modules was affected by the dose schedule and by participant sex, and early innate gene signatures were correlated with the ID93-specific CD4+ T cell response. Discussion: The results provide insight into the complex interplay of the innate and adaptive arms of the immune system in developing responses to vaccination with ID93+GLA-SE and demonstrate how dosing and schedule can affect vaccine responses. [ABSTRACT FROM AUTHOR]

Background: Anemia is a significant global health issue, impacting 1.92 billion people and ranking as a leading cause of disability. It is marked by low hemoglobin levels, which hinder oxygen delivery to vital organs and result from causes such as nutritional deficiencies and chronic diseases. Despite some progress, anemia remains a major concern in Southeast Asia, including Vietnam. Although the country has reduced its anemia rates, the progress is insufficient to achieve the WHO’s 2030 targets for anemia reduction among women of reproductive age. This study explores anemia trends and socio-economic determinants in Vietnam, with a focus on age and gender differences, to inform targeted interventions and policy development. Methods: This study used the Global Burden of Diseases, Injuries, and Risk Factors (GBD) dataset to explore the burden of anemia and its causes in Vietnam from 1990 to 2021. The GBD study provides data on anemia prevalence and years lived with disability (YLD) by age, sex, and 37 causes across 204 countries and territories. Further, this study employed a regression model to examine how the anemia burden (i.e., prevalence rate and YLD rate) relates to socio-economic factors such as the Human Development Index (HDI), gender disparities in human development achievement, and gender-based inequalities in reproductive health, empowerment, and economic status in Vietnam over this period. Results: In 1990, there were 16.30 million anemia cases in Vietnam, decreasing slightly to 16.05 million by 2021. Male prevalence dropped from 34.90 to 26.58%, while female prevalence increased from 65.10 to 73.42%. Iron deficiency was the main cause, affecting 68.35% of cases in 1990 and 68.84% in 2021, with 24.96% in males and 75.04% in females in 2021. While anemia has decreased among infants, young children, and adolescents due to improved healthcare, it has increased among middle-aged and older adults, especially females. Regression analysis shows that higher human development and gender equality reduce anemia prevalence and disability, whereas gender inequality worsens the issue. Conclusions: The study underscores that anemia remains a major health concern in Vietnam, marked by significant gender and age disparities. Despite a decrease in overall anemia rates and the effectiveness of specific interventions like iron-folic acid supplementation, females, particularly those of reproductive age and older adults, continue to face higher rates. Socio-economic improvements, including higher income and better human development, are linked to lower anemia rates, though the impact differs by gender. The persistent gender disparity and the shift in burden to older adults highlight the need for more comprehensive, gender-sensitive interventions. Future efforts should integrate nutritional support with broader socio-economic enhancements to effectively address anemia and improve public health in Vietnam. [ABSTRACT FROM AUTHOR]

Background: High levels of low-density lipoprotein cholesterol (LDL-C) can lead to the occurrence and development of atherosclerosis, which is one of the important risk factors for ischemic stroke (IS). However, details regarding the evolution of the IS burden attributable to high LDL-C in China has not been available. The objective of this study was to examine the changes over time, from 1990 to 2019, in the burden of IS attributed to high levels of LDL-C in China and to estimate the individual impacts of age, period, and cohort on the burden of IS associated with high LDL-C. Methods: Detailed data on IS burden attributable to high LDL-C from 1990 to 2019 in China were extracted from the Global Burden of Disease (GBD) Study 2019. The numbers and age-standardized rates of IS-related mortality and disability-adjusted life years (DALYs) attributable to high LDL-C were assessed by age and sex. The annual percentage change (APC) and average annual percentage change (AAPC) in the burden of IS due to high LDL-C were analyzed using Joinpoint regression model. The age-period-cohort analysis was carried out to assess the individual impacts of age, period, and cohort on the trends over time of mortality and DALY rate. Results: The number of IS-related deaths and DALYs due to high LDL-C in China were 182.7 thousand and 4.43 million in 2019, respectively, both more than double the corresponding numbers reported in 1990. However, despite these increased, the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) remained unchanged. In 2019, men under 84 years of age had higher death and under 79 years of age had higher DALYs than women. However, above these ages, the gender disparities were reversed. Furthermore, age-specific rates of death, as well as DALY of IS attributable to high LDL-C in 2019 increased with age for both women and men, except for death in adults over 95 years old; and were greater in men than in women. From 1990 to 2019, males consistently had a higher ASMR and ASDR than females in China. During 1990–2019, the ASMR in women slightly decreased before 1997, sharply increased from 1997 to 2004, and then continuously decreased from 2004 to 2019, with an overall AAPC value of -0.4% (95% CI -0.8%, -0.0%). However, for the ASMR of men in China, the overall trend is upward and the AAPC is 0.5%(95% CI 0.1%, 0.8%). The ASDR in women and men had the similar trend as the ASMR over the time, with an AAPC of -0.4% (95% CI -0.7%, -0.1%) and 0.3% (95% CI 0.1%, 0.5%), respectively. The age-period-cohort analysis indicated a rise in period effects and a decline in cohort effects on mortality and DALY rate associated with IS caused by high LDL-C in both genders. Age effect on mortality rates from IS due to high LDL-C showed an exponential increased with age in all women and men except for the 60–69 age group and over 95 age group. The age relative risk of IS DALY rate due to high LDL-C increased with age in both genders except for 65–74 age group and over 95 age group. Conclusions: From 1990 to 2019, the burden of IS caused by high LDL-C in China significantly increased among both sexes combined and among men, while significantly decreased among women. Elderly have a substantial burden of IS attributable to high LDL-C. Therefore, effective and tailored strategies based on gender and age for IS primary prevention and management of IS and high LDL-C are urgently needed in China. [ABSTRACT FROM AUTHOR]

Background: Cirrhosis comprises a significant health challenge in the Middle East and North African (MENA) region impacting healthcare systems and communities. This study sought to investigate trends in the burden of cirrhosis and other chronic liver disease, different etiologies, deaths, and the disability burden utilizing data from the Global Burden of Disease (GBD) database. Methods: Analyzing epidemiological trends from 1990 to 2021 across 21 MENA countries, this research utilized data on age-standardized incidence rates (ASIR), age-standardized death rates, and age-standardized disability-adjusted life years (DALYs) to evaluate the burden of cirrhosis and other chronic liver disease. The study also examined national variations and sociodemographic relationships. Results: The study identified a 114.9% increase in cirrhosis and other chronic liver disease incidence within the MENA region between 1990 and 2021, with 7,344,030 incident cases reported in 2021. The ASIR showed a steeper rise in females (9.6%) compared to males (7.0%). Etiology-specific analysis revealed an increase in the ASIR for MASLD related cirrhosis and other chronic liver disease by 22.2%, while those due to alcohol as well as hepatitis B and C decreased by 28.1%, 59.3%, and 30%, respectively. Despite the rising incidence, overall age-standardized death rates across all etiologies decreased by 54.3%, with DALYs showing a 51.4% decrease during the same period. Country-specific trends varied significantly, with Oman recording the highest annual ASIR increase (0.64%), and Qatar observing the most substantial annual reduction in age-standardized death rates (-2.88%). Conclusion: The study highlights evolving trends in cirrhosis and other chronic liver disease within the MENA region, emphasizing the necessity for comprehensive, etiology, and gender-specific interventions. Despite an increasing incidence, the observed improvements in mortality rates and age-standardized disability burden indicate progress in public health efforts to mitigate cirrhosis's impact. These findings point to the complex nature of cirrhosis outcomes and the urgent need for tailored strategies to manage its increasing burden effectively. [ABSTRACT FROM AUTHOR]

The article explores the association between pesticide exposure and allergic asthma exacerbations, focusing on non-occupational pesticide exposure as a potential risk factor. A nationwide database study in France found that patients hospitalized for allergic asthma had higher exposure to pesticides compared to those with non-allergic asthma. The study suggests that higher pesticide exposure may contribute to hospital stays for allergic asthma, particularly in urban residents, highlighting the need for further research on personalized strategies for asthma prevention and management. [Extracted from the article]

Introduction: Congenital anomalies are one of the major causes of the global burden of diseases, and low- and middle-income countries (LMICs) are disproportionately affected. This review assesses the prenatal and postnatal screening methods and compares the prevalence of major congenital anomalies in LMICs. Methodology: We conducted a systematic search in MEDLINE/PubMed, CINAHL, Cochrane databases of systematic reviews, clinical trials.gov for relevant studies using Medical Subject Headings and keywords. We categorized the studies into different systems and screening methods depending on the time the tests were conducted (prenatal or postnatal). The studies were then subjected to detailed descriptive analysis. Results: A total of 59 studies were selected for analysis; these focused on screening methods for congenital anomalies and compared their prevalence with regards to different systems. The most common screening techniques both prenatal and postnatal included antenatal ultrasound, fetal echocardiography, pulse oximetry, and clinical examination. The most common congenital abnormalities involved the central nervous system (neural tube defects) and musculoskeletal (clubfoot), followed by gastrointestinal (omphalocele and gastroschisis) and cardiovascular (structural heart defect). Overall, different systems had varying prevalences of different birth defects, ranging from 0.28 to 8.5%. In contrast, the prevalence of musculoskeletal system disorders varied from 1.01% to 3.96%, in the cardiovascular system from 0.57% to 10.4%, and in the urogenital group from 0.83% to 5.9%. Conclusion: The review highlights the lack of screening programs and studies, especially in the primary and secondary care settings in LMICs, and limited studies do indicate a high burden of various congenital anomalies. There is a need for guidelines and programs in global maternal and child health programs to include timely screening and management of common birth defects in LMICs. [ABSTRACT FROM AUTHOR]

The incidence of thyroid cancer (TC) is increasing annually worldwide, with a growing burden. This study aims to analyze temporal trends in the burden of TC by age and sex in China and globally from 1990 to 2021, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates, and to predict future trends. We obtained data on TC in China and globally from 1990 to 2021 from the Global Burden of Disease (GBD) database. Using the Joinpoint regression model, we calculated and analyzed the trends in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). Specifically, we estimated the annual percent change (APC), the average annual percent change (AAPC), and the corresponding 95% confidence intervals (95% CI) for each metric. Additionally, we conducted a decomposition analysis to investigate the impact of aging, population growth, and epidemiological factors on the incidence and mortality rates of TC. Furthermore, the autoregressive integrated moving average (ARIMA) model was employed to predict the burden of TC from 2022 to 2036. From 1990 to 2021, the ASIR for TC in China increased from 1.249 (95% uncertainty interval [UI]: 1.009–1.473) per 100,000 to 2.473 (95% UI: 1.993–3.088) per 100,000. Conversely, the ASMR decreased from 0.473 (95% UI: 0.403–0.550) per 100,000 to 0.387 (95% UI: 0.307–0.472) per 100,000. Both males and females demonstrated an upward trajectory in ASIR. However, while the ASMR for females decreased, that for males showed an overall increase despite a decline in the last decade. The age of peak onset for TC ranged from 30 to 79 years, whereas the age of peak mortality was between 50 and 89 years. The analysis using the AAPC indicates that the growth in the ASIR (AAPC = 2.242, 95% CI: 2.112–2.371) and ASPR (AAPC = 2.975, 95% CI: 2.833–3.117) in China exceeds the global rate. Furthermore, the reduction in ASMR (AAPC = -0.651, 95% CI: -0.824 - -0.479) and ASDR (AAPC = -0.590, 95% CI: -0.787 - -0.392) in China is also more pronounced than globally. Decomposition analysis indicates that the increasing TC burden in China is primarily driven by population aging, whereas globally, population growth plays a more significant role. Projections based on predictive models suggest that from 2021 to 2036, the ASIR for both China and the global population is expected to continue rising, while the ASMR is anticipated to decline further. The incidence rates of TC in China and globally have shown a continuous upward trend, which is expected to persist over the next 15 years. Additionally, although the number of male TC cases is relatively lower compared to females, the overall ASMR and ASDR for males have shown an upward trend, despite a slight decline in recent years. This highlights the need to enhance prevention, diagnosis, and treatment measures, and to develop differentiated screening and treatment strategies based on age and sex. [ABSTRACT FROM AUTHOR]

Background: Estimation of global diabetes burden in adolescents and young adults (10–24 years) from 1990 to 2021. Methods: Data were extracted from the 2021 Global Burden of Disease Study. Joinpoint regression analysis was employed to examine trends over the past 30 years, frontier analysis identified regions with potential for improvement, and the slope index of inequality and the relative concentration index were used to assess health inequalities. Results: From 1990 to 2021, the age-standardized prevalence rates (ASPR) and age-standardized disability-adjusted life years rates (ASDR) of diabetes in adolescents and young adults increased globally, while age-standardized death rates (ASMR) remained stable. Oceania bore the highest burden regionally, East Asia experienced the fastest rise in ASPR and ASDR, and High-income Asia Pacific saw the most significant decrease in ASMR. Among 204 countries, Marshall Island and Hait reported the highest ASPR, ASDR, and ASMR in 2021. Health inequality analysis confirmed that the burden was concentrated in countries with lower Socio-Demographic Index (SDI). Frontier analysis showed that ASMR and ASDR were negatively correlated with SDI, with Yemen and Honduras, which have lower socio-demographic indices, exhibiting more smaller overall differences from frontier boundaries. Conclusions: The analysis revealed a sharp increase in the global ASPR and ASDR of diabetes in adolescents and young adults. Additionally, the disease burden is typically concentrated in countries with lower SDI, highlighting an urgent need for governments to develop flexible health policies to mitigate the escalating threat of diabetes in this demographic. [ABSTRACT FROM AUTHOR]

The article discusses the 25in25 initiative, a project aimed at reducing mortality due to heart failure by 25% in the next 25 years. The initiative focuses on early diagnosis, treatment, and prevention of heart failure, with the goal of saving over 10,000 lives annually. By collaborating with various organizations and implementing a Fast-Track Communities approach, the initiative seeks to make heart failure a national priority and improve outcomes for patients with heart failure. The project is currently in a pilot phase in the UK, with plans to expand nationally and internationally in the future. [Extracted from the article]

The article explores the use of abrocitinib in treating refractory chronic spontaneous urticaria (CSU) through a case series. Patients with inadequate responses to omalizumab were treated with abrocitinib, resulting in significant improvements in clinical outcomes. Abrocitinib, a JAK1 inhibitor, showed promise as a new treatment option for patients with refractory CSU. The study highlights the potential of abrocitinib in managing CSU and suggests further research to establish its long-term safety and efficacy. [Extracted from the article]

Background: Among the crises engulfing the world is the symbiotic rise of ultra-processed foods (UPFs) and plastics. Together, this co-dependent duo generates substantial profits for agri-food and petrochemical industries at high costs for people and planet. Cheap, lightweight and highly functional, plastics have ideal properties that enable business models to create demand for low-cost, mass-produced and hyper-palatable UPFs among populations worldwide, hungry, or not. Evidence linking UPF consumption to deterioration in diet quality and higher risk of chronic diseases is well-established and growing rapidly. At the same time, the issue of plastic food contact chemicals (FCCs) is receiving increasing attention among the human health community, as is the generation and dispersion of micro- and nanoplastics. Main body: In this commentary, we explore how the lifecycles and shared economic benefits of UPFs and plastics interact to co-produce a range of direct and indirect harms. We caution that the chemical dimension of these harms is underappreciated, with thousands of plastic FCCs known to migrate into foodstuffs. Some of these are hazardous and have been detected in humans and the broader environment, while many are yet to be adequately tested. We question whether policies on both UPF and plastic chemicals are fit for purpose when production and consumption of these products is adding to the chronic chemical exposures that plausibly contribute to the increasing global burden of non-communicable diseases. Conclusions: In the context of ongoing negotiations for a legally binding global treaty to end plastics pollution, and rapidly growing concern about the burgeoning share of UPFs in diets worldwide, we ask: What steps are needed to call time on this toxic relationship? [ABSTRACT FROM AUTHOR]

Background: Hepatitis B remains a significant global health concern with widespread communicability. Nevertheless, data on its burden and trends in children and adolescents were limited. We aim to evaluate the global, regional, and national trends of total burden related to hepatitis B in children and adolescents aged 0–19 years from 1990 to 2021. Methods: The age-standardized incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated by the Global Burden of Disease (GBD) study from 1990 to 2021. These indicators were stratified by sex, age, socio-demographic index (SDI), and disease stage. We calculated the correlation between them and SDI. The temporal trends were examined using the annual average percentage change (AAPC) and joinpoint regression. Results: The global age-standardized incidence of hepatitis B in children and adolescents decreased from 1385.20 per 100,000 population in 1990 to 418.68 per 100,000 population in 2021, with an AAPC of -3.76%. Similarly, age-standardized DALYs decreased from 70.78 per 100,000 population to 36.31 per 100,000 population, with an AAPC of -2.13%. The age-standardized prevalence (AAPC − 3.53%) and mortality (AAPC − 2.09%) of hepatitis B also decreased significantly. From 1990 to 2021, the age-standardized incidence and prevalence among males exhibited a higher trend compared to females, although both declined over time. These two indicators also decreased across all age subgroups, with consistently higher rates observed in the 15–19 age group compared to other age groups. The burden of hepatitis B demonstrated a notable reduction in countries with high-middle SDI, while it was highest in countries with low SDI. In 2021, Central sub-Saharan Africa and West sub-Saharan Africa reported the highest age-standardized incidence. For age-standardized DALYs, South Asia was the only region to experience an increase (AAPC 1.09%), while East Asia showed the largest decline (AAPC − 7.58%). Alcohol and drug use remained important risk factors for DALYs among people aged 15–19 years. Furthermore, the impact of drug use on disease burden was increasing, particularly in high-SDI countries. Conclusions: The global burden and trends of hepatitis B decreased significantly in children and adolescents, exhibiting regional and national variations. Management of alcohol and drug use remains a major challenge for people aged 15–19 years. [ABSTRACT FROM AUTHOR]

Background: Soil-transmitted helminth (STH) infections can cause a significant disease burden. It is estimated that 1.5 billion people worldwide are infected with STHs, primarily in tropical and subtropical regions. This study aimed to assess the distribution of the global burden and trend of STH infections from 1990 to 2021. Methods: We retrieved data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 on the age-standardized rates (ASRs) of prevalence and disability-adjusted life-years (DALYs) of STH infections for all age groups in 204 countries and territories from 1990 to 2021. The ASRs of prevalence and DALYs by age, gender, and socio-demographic index (SDI) were calculated to quantify the spatial distribution and temporal trend. Spearman correlation analysis was used to examine the relationship between ASR and SDI. Results: In 2021, there were an estimated 642.72 million cases and 1.38 million DALYs caused by STH infections worldwide. The age-standardized prevalence rate (ASPR) of STH infections was 8429.89 [95% uncertainty interval (UI): 7697.23, 9362.18 ] per 100,000 population globally. The ASPR of STH infections varied across 21 geographic regions in 2021, being mainly prevalent in most African and Latin American locations. The prevalence was higher in the groups of 5–19 years, especially the group of 5–9 years with the ASPR of 16,263 (95% UI: 14,877.06, 18,003.49) and ASR of DALYs of 40.69 (95% UI: 25.98, 60.91) per 100,000. The ASPR of STH infections showed an obvious decreasing trend worldwide (estimated annual percent change = − 4.03, 95% confidence interval: − 4.13, − 3.93) with variations in different species infections during the study years. At the regional level, the ASR of STH infections prevalence (r = − 0.8807, P < 0.0001) and DALYs (r = − 0.9069, P < 0.0001) were negatively correlated with SDI. Conclusions: STH infections remain a public health problem in 2021, particularly in regions such as the middle parts of Africa and Americas, and in the 5–19 age populations. The reduction in the rate of prevalence and the loss of DALYs are negatively correlated with the increase in SDI. Enhancing political commitment, providing accurate preventive chemotherapy, and advancing techniques for surveillance and mapping systems are essential to achieve the target of ending STH infections as a public health problem by 2030. [ABSTRACT FROM AUTHOR]