Muhammad Arshad

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

BACKGROUND: Combating viral hepatitis is part of the UN Sustainable Development Goals (SDGs), and WHO has put forth hepatitis B elimination targets in its Global Health Sector Strategy on Viral Hepatitis (WHO-GHSS) and Interim Guidance for Country Validation of Viral Hepatitis Elimination (WHO Interim Guidance). We estimated the global, regional, and national prevalence of hepatitis B virus (HBV), as well as mortality and disability-adjusted life-years (DALYs) due to HBV, as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. This included estimates for 194 WHO member states, for which we compared our estimates to WHO elimination targets. METHODS: The primary data sources were population-based serosurveys, claims and hospital discharges, cancer registries, vital registration systems, and published case series. We estimated chronic HBV infection and the burden of HBV-related diseases, defined as an aggregate of cirrhosis due to hepatitis B, liver cancer due to hepatitis B, and acute hepatitis B. We used DisMod-MR 2.1, a Bayesian mixed-effects meta-regression tool, to estimate the prevalence of chronic HBV infection, cirrhosis, and aetiological proportions of cirrhosis. We used mortality-to-incidence ratios modelled with spatiotemporal Gaussian process regression to estimate the incidence of liver cancer. We used the Cause of Death Ensemble modelling (CODEm) model, a tool that selects models and covariates on the basis of out-of-sample performance, to estimate mortality due to cirrhosis, liver cancer, and acute hepatitis B. FINDINGS: In 2019, the estimated global, all-age prevalence of chronic HBV infection was 4·1% (95% uncertainty interval [UI] 3·7 to 4·5), corresponding to 316 million (284 to 351) infected people. There was a 31·3% (29·0 to 33·9) decline in all-age prevalence between 1990 and 2019, with a more marked decline of 76·8% (76·2 to 77·5) in prevalence in children younger than 5 years. HBV-related diseases resulted in 555 000 global deaths (487 000 to 630 000) in 2019. The number of HBV-related deaths increased between 1990 and 2019 (by 5·9% [-5·6 to 19·2]) and between 2015 and 2019 (by 2·9% [-5·9 to 11·3]). By contrast, all-age and age-standardised death rates due to HBV-related diseases decreased during these periods. We compared estimates for 2019 in 194 WHO locations to WHO-GHSS 2020 targets, and found that four countries achieved a 10% reduction in deaths, 15 countries achieved a 30% reduction in new cases, and 147 countries achieved a 1% prevalence in children younger than 5 years. As of 2019, 68 of 194 countries had already achieved the 2030 target proposed in WHO Interim Guidance of an all-age HBV-related death rate of four per 100 000. INTERPRETATION: The prevalence of chronic HBV infection declined over time, particularly in children younger than 5 years, since the introduction of hepatitis B vaccination. HBV-related death rates also decreased, but HBV-related death counts increased as a result of population growth, ageing, and cohort effects. By 2019, many countries had met the interim seroprevalence target for children younger than 5 years, but few countries had met the WHO-GHSS interim targets for deaths and new cases. Progress according to all indicators must be accelerated to meet 2030 targets, and there are marked disparities in burden and progress across the world. HBV interventions, such as vaccination, testing, and treatment, must be strategically supported and scaled up to achieve elimination. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. METHODS: For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. FINDINGS: The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0·603 (0·400-1·00) standard drinks per day, and the NDE varied between 0·002 (0-0) and 1·75 (0·698-4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0-0·403) to 1·87 (0·500-3·30) standard drinks per day and an NDE that ranged between 0·193 (0-0·900) and 6·94 (3·40-8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3-65·4) were aged 15-39 years and 76·9% (73·0-81·3) were male. INTERPRETATION: There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. METHODS: Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. FINDINGS: There were 1·19 million (95% UI 1·11-1·28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5-65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8-57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9-15·6] per 100 000 person-years) and middle SDI (13·6 [12·6-14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9-25·2) DALYs to the global burden of disease, of which 2·7% (1·9-3·6) came from YLDs and 97·3% (96·4-98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. INTERPRETATION: Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. FUNDING: Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute.

BACKGROUND: Understanding health trends and estimating the burden of disease at the national and subnational levels helps policy makers track progress and identify disparities in overall health performance. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides comprehensive estimates for Pakistan. Comparison of health indicators since 1990 provides valuable insights about Pakistan's ability to strengthen its health-care system, reduce inequalities, improve female and child health outcomes, achieve universal health coverage, and meet the UN Sustainable Development Goals. We present estimates of the burden of disease, injuries, and risk factors for Pakistan provinces and territories from 1990 to 2019 based on GBD 2019 to improve health and health outcomes in the country. METHODS: We used methods and data inputs from GBD 2019 to estimate socio-demographic index, total fertility rate, cause-specific deaths, years of life lost, years lived with disability, disability-adjusted life-years, healthy life expectancy, and risk factors for 286 causes of death and 369 causes of non-fatal health loss in Pakistan and its four provinces and three territories from 1990 to 2019. To generate estimates for Pakistan at the national and subnational levels, we used 68 location-years of data to estimate Pakistan-specific demographic indicators, 316 location-years of data for Pakistan-specific causes of death, 579 location-years of data for Pakistan-specific non-fatal outcomes, 296 location-years of data for Pakistan-specific risk factors, and 3089 location-years of data for Pakistan-specific covariates. FINDINGS: Life expectancy for both sexes in Pakistan increased nationally from 61·1 (95% uncertainty interval [UI] 60·0-62·1) years in 1990 to 65·9 (63·8-67·8) years in 2019; however, these gains were not uniform across the provinces and federal territories. Pakistan saw a narrowing of the difference in healthy life expectancy between the sexes from 1990 to 2019, as health gains for women occurred at faster rates than for men. For women, life expectancy increased by 8·2% (95% UI 6·3-13·8) between 1990 and 2019, whereas the male life expectancy increased by 7·6% (3·5-11·8). Neonatal disorders, followed by ischaemic heart disease, stroke, diarrhoeal diseases, and lower respiratory infections were the leading causes of all-age premature mortality in 2019. Child and maternal malnutrition, air pollution, high systolic blood pressure, dietary risks, and tobacco consumption were the leading all-age risk factors for death and disability-adjusted life-years at the national level in 2019. Five non-communicable diseases-ischaemic heart disease, stroke, congenital defects, cirrhosis, and chronic kidney disease-were among the ten leading causes of years of life lost in Pakistan. Burden varied by socio-demographic index. Notably, Balochistan and Khyber Pakhtunkhwa had the lowest observed gains in life expectancy. Dietary iron deficiency was the leading cause of years lived with disability for both men and women in 1990 and 2019. Low birthweight and short gestation and particulate matter pollution were the leading contributors to overall disease burden in both 1990 and 2019 despite moderate improvements, with a 23·5% (95% UI 3·8-39·2) and 27·6% (14·3-38·6) reduction in age-standardised attributable DALY rates during the study period. INTERPRETATION: Our study shows that progress has been made on reducing Pakistan's disease burden since 1990, but geographical, age, and sex disparities persist. Equitable investment in the health system, as well as the prioritisation of high-impact policy interventions and programmes, are needed to save lives and improve health outcomes. Pakistan is facing several domestic and foreign challenges-the Taliban's return to power in Afghanistan, political turmoil, catastrophic flooding, the COVID-19 pandemic-that will shape the trajectory of the country's health and development. Pakistan must address the burden of infectious disease and curb rising rates of non-communicable diseases. Prioritising these three areas will enhance Pakistan's ability to achieve universal health coverage, meet its Sustainable Development Goals, and improve the overall health outcomes. FUNDING: Bill & Melinda Gates Foundation. TRANSLATION: For the Urdu translation of the abstract see Supplementary Materials section.