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

Background: Despite a substantial reduction in the use of solid fuels for cooking worldwide, exposure to household air pollution (HAP) remains a leading global risk factor, contributing considerably to the burden of disease. We present a comprehensive analysis of spatial patterns and temporal trends in exposure and attributable disease from 1990 to 2021, featuring substantial methodological updates compared with previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study, including improved exposure estimations accounting for specific fuel types. Methods: We estimated HAP exposure and trends and attributable burden for cataract, chronic obstructive pulmonary disease, ischaemic heart disease, lower respiratory infections, tracheal cancer, bronchus cancer, lung cancer, stroke, type 2 diabetes, and causes mediated via adverse reproductive outcomes for 204 countries and territories from 1990 to 2021. We first estimated the mean fuel type-specific concentrations (in μg/m3) of fine particulate matter (PM2·5) pollution to which individuals using solid fuels for cooking were exposed, categorised by fuel type, location, year, age, and sex. Using a systematic review of the epidemiological literature and a newly developed meta-regression tool (meta-regression: Bayesian, regularised, trimmed), we derived disease-specific, non-parametric exposure–response curves to estimate relative risk as a function of PM2·5 concentration. We combined our exposure estimates and relative risks to estimate population attributable fractions and attributable burden for each cause by sex, age, location, and year. Findings: In 2021, 2·67 billion (95% uncertainty interval [UI] 2·63–2·71) people, 33·8% (95% UI 33·2–34·3) of the global population, were exposed to HAP from all sources at a mean concentration of 84·2 μg/m3. Although these figures show a notable reduction in the percentage of the global population exposed in 1990 (56·7%, 56·4–57·1), in absolute terms, there has been only a decline of 0·35 billion (10%) from the 3·02 billion people exposed to HAP in 1990. In 2021, 111 million (95% UI 75·1–164) global disability-adjusted life-years (DALYs) were attributable to HAP, accounting for 3·9% (95% UI 2·6–5·7) of all DALYs. The rate of global, HAP-attributable DALYs in 2021 was 1500·3 (95% UI 1028·4–2195·6) age-standardised DALYs per 100 000 population, a decline of 63·8% since 1990, when HAP-attributable DALYs comprised 4147·7 (3101·4–5104·6) age-standardised DALYs per 100 000 population. HAP-attributable burden remained highest in sub-Saharan Africa and south Asia, with 4044·1 (3103·4–5219·7) and 3213·5 (2165·4–4409·4) age-standardised DALYs per 100 000 population, respectively. The rate of HAP-attributable DALYs was higher for males (1530·5, 1023·4–2263·6) than for females (1318·5, 866·1–1977·2). Approximately one-third of the HAP-attributable burden (518·1, 410·1–641·7) was mediated via short gestation and low birthweight. Decomposition of trends and drivers behind changes in the HAP-attributable burden highlighted that declines in exposures were counteracted by population growth in most regions of the world, especially sub-Saharan Africa. Interpretation: Although the burden attributable to HAP has decreased considerably, HAP remains a substantial risk factor, especially in sub-Saharan Africa and south Asia. Our comprehensive estimates of HAP exposure and attributable burden offer a robust and reliable resource for health policy makers and practitioners to precisely target and tailor health interventions. Given the persistent and substantial impact of HAP in many regions and countries, it is imperative to accelerate efforts to transition under-resourced communities to cleaner household energy sources. Such initiatives are crucial for mitigating health risks and promoting sustainable development, ultimately improving the quality of life and health outcomes for millions of people. Funding: Bill & Melinda Gates Foundation

Microbial Pathogenesis and Pathophysiology of Alzheimer's Disease: A Systematic Assessment of Microorganisms' Implications in the Neurodegenerative Disease

Microbial infections have been linked to the pathogenesis and pathophysiology of Alzheimer's disease (AD) and other neurodegenerative diseases. The present study aimed to synthesise and assess global evidence of microbial pathogenesis and pathophysiology in AD (MPP-AD) and associated neurodegenerative conditions using integrated science mapping and content analytics to explore the associated research landscape. Relevant MPP-AD documents were retrieved from Web of Science and Scopus according to PRISMA principles and analysed for productivity/trend linked to authors/countries, thematic conceptual framework, and international collaborative networks. A total of 258 documents published from 136 sources to 39.42 average citations/document were obtained on MPP-AD. The co-authors per document were 7.6, and the collaboration index was 5.71. The annual research outputs increased tremendously in the last 6 years from 2014 to 2019, accounting for 66% compared with records in the early years from 1982 to 1990 (16%). The USA (n = 71, freq. = 30.34%), United Kingdom (n = 32, freq. = 13.68%) and China (n = 27, 11.54%) ranked in first three positions in term of country's productivity. Four major international collaboration clusters were found in MPP-AD research. The country collaboration network in MPP-AD was characteristic of sparse interaction and acquaintanceship (density = 0.11, diameter = 4). Overall, international collaboration is globally inadequate [centralisation statistics: degree (40.5%), closeness (4%), betweenness (23%), and eigenvector (76.7%)] against the robust authors' collaboration index of 5.71 in MPP-AD research. Furthermore, four conceptual thematic frameworks (CTF) namely, CTF#1, roles of microbial/microbiome infection and dysbiosis in cognitive dysfunctions; CTF#2, bacterial infection specific roles in dementia; CTF#3, the use of yeast as a model system for studying MPP-AD and remediation therapy; and CFT#4, flow cytometry elucidation of amyloid-beta and aggregation in Saccharomyces cerevisiae model. Finally, aetiology-based mechanisms of MPP-AD, namely, gut microbiota, bacterial infection, and viral infection, were comprehensively discussed. This study provides an overview of MPP-AD and serves as a stepping stone for future preparedness in MPP-AD-related research.</jats:p

Modulation of some markers of erectile dysfunction and malonaldehyde levels in isolated rat penile tissue with unripe and ripe plantain peels: identification of the constituents of the plants using HPLC

Context: Plantain fruit pulp has been used as a natural remedy to manage erectile dysfunction (ED) in traditional medicine. However, the potency of the peel has not been examined with respect to ED management. Objective: This study investigated and compared the inhibitory potential of unripe (UPP) and ripe (RPP) plantain peels on some enzymes associated with ED and Fe2+-induced oxidative stress in albino rat penile homogenate in vitro. Materials and method: Aqueous extract of the peels was prepared and the effect on phosphodiesterase-5 (PDE-5), arginase, acetylcholinesterase (AChE), angiotensin-I converting enzyme (ACE) and Fe2+-induced malonyladehyde in isolated albino rat penile homogenate were investigated. Phenolic constituents of the peels powder were characterized using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Result: Extract from UPP had higher PDE-5 (IC50 = 3.10 μg/mL), arginase (IC50 = 0.96 μg/mL), AChE (IC50 = 6.30 μg/mL) and ACE (IC50 = 0.41 μg/mL) inhibitory ability compared with RPP (PDE-5, IC50 = 4.33 μg/mL; arginase, IC50 = 1.34 μg/mL; AChE, IC50 = 8.64 μg/mL; ACE, IC50 = 0.63 μg/mL). The extract from UPP also had higher inhibition of Fe2+-induced lipid peroxidation. HPLC-DAD analysis revealed that gallic and caffeic acids, rutin, quercitrin and quercetin were abundant in UPP, while catechin, kaempferol, chlorogenic and ellagic acids were the dominant phenolic compounds in RPP. Discussion and conclusion: Inhibition of enzymes associated with ED and lipid peroxidation could be linked with the phenolic compounds. However, UPP appeared to be more potent

Global, regional, and national prevalence of kidney failure with replacement therapy and associated aetiologies, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023

Background Kidney failure with replacement therapy (KFRT) such as dialysis or transplantation represents a severe stage of chronic kidney disease (CKD) and poses a major global health burden. Although many CKD cases are diagnosed in the earlier stages, the greatest risk occurs when CKD progresses to KFRT. Despite its considerable financial and imposing impact on public health, there is a notable gap in international policies addressing CKD and KFRT. To bridge this gap and help policy makers and health systems effectively tackle the public health challenge of KFRT, a better understanding of the disease burden is essential. Thus, this analysis aims to provide a detailed overview of the global prevalence of KFRT and its associated aetiologies with estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2023. Methods This study defined KFRT as individuals on maintenance dialysis for 90 days or more or those who have undergone a kidney transplant, aligning with the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Renal registries served as the primary data sources. Prevalence and underlying aetiology estimates (type 1 diabetes, type 2 diabetes, hypertension, glomerulonephritis, and other causes) were generated with DisMod-MR 2.1, an epidemiological Bayesian mixed-effects meta-regression modelling tool. Both all-age and age-standardised estimates were reported and accompanied with 95% uncertainty intervals (UIs). Findings In 2023, the number of global cases of KFRT was 4·59 million (95% UI 4·17–5·08) for both sexes and all ages, with an age-standardised prevalence of 50·7 (46·1–56·0) per 100 000 population. Over the past three decades, there has been a steady increase in KFRT prevalence globally. The highest prevalence was found in the GBD high-income regions, while the lowest was observed in sub-Saharan Africa. KFRT prevalence was generally higher in countries classified within the World Bank's high-income and upper-middle-income groups, while lower prevalence was more common in countries within the World Bank's low-income and lower-middle-income groups. Additionally, a pronounced sex disparity was identified, where male dialysis and transplant prevalence estimates were consistently higher than those for females in most countries. Type 2 diabetes and hypertension were among the leading associated aetiologies of KFRT globally. From 1990 to 2023, the all-age and age-standardised prevalence estimates across the ascribed aetiologies increased for KFRT, with the largest increases associated with type 2 diabetes and hypertension. Interpretation KFRT affects approximately 5 million people globally, with high treatment and mortality costs. Our study unveiled considerable geographical variation in KFRT prevalence, which should be seen as indicators of health-care system opportunities. As the prevalence of the leading aetiologies of KFRT—type 2 diabetes and hypertension—continues to rise, there is a crucial need to prioritise the development and implementation of cost-effective strategies aimed at preventing CKD and its progression to KFRT, particularly in low-resource settings. These preventive efforts must happen in tandem with efforts to expand capacity for dialysis and transplant services. Funding Gates Foundation

Global, regional, and national burden of stroke and its risk factors, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Up-to-date estimates of stroke burden and attributable risks and their trends at global, regional, and national levels are essential for evidence-based health care, prevention, and resource allocation planning. We aimed to provide such estimates for the period 1990–2021. Methods: We estimated incidence, prevalence, death, and disability-adjusted life-year (DALY) counts and age-standardised rates per 100 000 people per year for overall stroke, ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage, for 204 countries and territories from 1990 to 2021. We also calculated burden of stroke attributable to 23 risk factors and six risk clusters (air pollution, tobacco smoking, behavioural, dietary, environmental, and metabolic risks) at the global and regional levels (21 GBD regions and Socio-demographic Index [SDI] quintiles), using the standard GBD methodology. 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 2021, stroke was the third most common GBD level 3 cause of death (7·3 million [95% UI 6·6–7·8] deaths; 10·7% [9·8–11·3] of all deaths) after ischaemic heart disease and COVID-19, and the fourth most common cause of DALYs (160·5 million [147·8–171·6] DALYs; 5·6% [5·0–6·1] of all DALYs). In 2021, there were 93·8 million (89·0–99·3) prevalent and 11·9 million (10·7–13·2) incident strokes. We found disparities in stroke burden and risk factors by GBD region, country or territory, and SDI, as well as a stagnation in the reduction of incidence from 2015 onwards, and even some increases in the stroke incidence, death, prevalence, and DALY rates in southeast Asia, east Asia, and Oceania, countries with lower SDI, and people younger than 70 years. Globally, ischaemic stroke constituted 65·3% (62·4–67·7), intracerebral haemorrhage constituted 28·8% (28·3–28·8), and subarachnoid haemorrhage constituted 5·8% (5·7–6·0) of incident strokes. There were substantial increases in DALYs attributable to high BMI (88·2% [53·4–117·7]), high ambient temperature (72·4% [51·1 to 179·5]), high fasting plasma glucose (32·1% [26·7–38·1]), diet high in sugar-sweetened beverages (23·4% [12·7–35·7]), low physical activity (11·3% [1·8–34·9]), high systolic blood pressure (6·7% [2·5–11·6]), lead exposure (6·5% [4·5–11·2]), and diet low in omega-6 polyunsaturated fatty acids (5·3% [0·5–10·5]). Interpretation: Stroke burden has increased from 1990 to 2021, and the contribution of several risk factors has also increased. Effective, accessible, and affordable measures to improve stroke surveillance, prevention (with the emphasis on blood pressure, lifestyle, and environmental factors), acute care, and rehabilitation need to be urgently implemented across all countries to reduce stroke burden. Funding: Bill & Melinda Gates Foundation

Global, regional, and national prevalence of child and adolescent overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021

Background Despite the well documented consequences of obesity during childhood and adolescence and future risks of excess body mass on non-communicable diseases in adulthood, coordinated global action on excess body mass in early life is still insufficient. Inconsistent measurement and reporting are a barrier to specific targets, resource allocation, and interventions. In this Article we report current estimates of overweight and obesity across childhood and adolescence, progress over time, and forecasts to inform specific actions. Methods Using established methodology from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021, we modelled overweight and obesity across childhood and adolescence from 1990 to 2021, and then forecasted to 2050. Primary data for our models included 1321 unique measured and self-reported anthropometric data sources from 180 countries and territories from survey microdata, reports, and published literature. These data were used to estimate age-standardised global, regional, and national overweight prevalence and obesity prevalence (separately) for children and young adolescents (aged 5–14 years, typically in school and cared for by child health services) and older adolescents (aged 15–24 years, increasingly out of school and cared for by adult services) by sex for 204 countries and territories from 1990 to 2021. Prevalence estimates from 1990 to 2021 were generated using spatiotemporal Gaussian process regression models, which leveraged temporal and spatial correlation in epidemiological trends to ensure comparability of results across time and geography. Prevalence forecasts from 2022 to 2050 were generated using a generalised ensemble modelling approach assuming continuation of current trends. For every age-sex-location population across time (1990–2050), we estimated obesity (vs overweight) predominance using the log ratio of obesity percentage to overweight percentage. Findings Between 1990 and 2021, the combined prevalence of overweight and obesity in children and adolescents doubled, and that of obesity alone tripled. By 2021, 93·1 million (95% uncertainty interval 89·6–96·6) individuals aged 5–14 years and 80·6 million (78·2–83·3) aged 15–24 years had obesity. At the super-region level in 2021, the prevalence of overweight and of obesity was highest in north Africa and the Middle East (eg, United Arab Emirates and Kuwait), and the greatest increase from 1990 to 2021 was seen in southeast Asia, east Asia, and Oceania (eg, Taiwan [province of China], Maldives, and China). By 2021, for females in both age groups, many countries in Australasia (eg, Australia) and in high-income North America (eg, Canada) had already transitioned to obesity predominance, as had males and females in a number of countries in north Africa and the Middle East (eg, United Arab Emirates and Qatar) and Oceania (eg, Cook Islands and American Samoa). From 2022 to 2050, global increases in overweight (not obesity) prevalence are forecasted to stabilise, yet the increase in the absolute proportion of the global population with obesity is forecasted to be greater than between 1990 and 2021, with substantial increases forecast between 2022 and 2030, which continue between 2031 and 2050. By 2050, super-region obesity prevalence is forecasted to remain highest in north Africa and the Middle East (eg, United Arab Emirates and Kuwait), and forecasted increases in obesity are still expected to be largest across southeast Asia, east Asia, and Oceania (eg, Timor-Leste and North Korea), but also in south Asia (eg, Nepal and Bangladesh). Compared with those aged 15–24 years, in most super-regions (except Latin America and the Caribbean and the high-income super-region) a greater proportion of those aged 5–14 years are forecasted to have obesity than overweight by 2050. Globally, 15·6% (12·7–17·2) of those aged 5–14 years are forecasted to have obesity by 2050 (186 million [141–221]), compared with 14·2% (11·4–15·7) of those aged 15–24 years (175 million [136–203]). We forecasted that by 2050, there will be more young males (aged 5–14 years) living with obesity (16·5% [13·3–18·3]) than overweight (12·9% [12·2–13·6]); while for females (aged 5–24 years) and older males (aged 15–24 years), overweight will remain more prevalent than obesity. At a regional level, the following populations are forecast to have transitioned to obesity (vs overweight) predominance before 2041–50: children and adolescents (males and females aged 5–24 years) in north Africa and the Middle East and Tropical Latin America; males aged 5–14 years in east Asia, central and southern sub-Saharan Africa, and central Latin America; females aged 5–14 years in Australasia; females aged 15–24 years in Australasia, high-income North America, and southern sub-Saharan Africa; and males aged 15–24 years in high-income North America. Interpretation Both overweight and obesity increased substantially in every world region between 1990 and 2021, suggesting that current approaches to curbing increases in overweight and obesity have failed a generation of children and adolescents. Beyond 2021, overweight during childhood and adolescence is forecast to stabilise due to further increases in the population who have obesity. Increases in obesity are expected to continue for all populations in all world regions. Because substantial change is forecasted to occur between 2022 and 2030, immediate actions are needed to address this public health crisis. Funding Bill & Melinda Gates Foundation and Australian National Health and Medical Research Council