Age-sex differences in the global burden of lower respiratory infections and risk factors, 1990-2019: results from the Global Burden of Disease Study 2019.

BACKGROUND: The global burden of lower respiratory infections (LRIs) and corresponding risk factors in children older than 5 years and adults has not been studied as comprehensively as it has been in children younger than 5 years. We assessed the burden and trends of LRIs and risk factors across all age groups by sex, for 204 countries and territories. METHODS: In this analysis of data for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we used clinician-diagnosed pneumonia or bronchiolitis as our case definition for LRIs. We included International Classification of Diseases 9th edition codes 079.6, 466-469, 470.0, 480-482.8, 483.0-483.9, 484.1-484.2, 484.6-484.7, and 487-489 and International Classification of Diseases 10th edition codes A48.1, A70, B97.4-B97.6, J09-J15.8, J16-J16.9, J20-J21.9, J91.0, P23.0-P23.4, and U04-U04.9. We used the Cause of Death Ensemble modelling strategy to analyse 23 109 site-years of vital registration data, 825 site-years of sample vital registration data, 1766 site-years of verbal autopsy data, and 681 site-years of mortality surveillance data. We used DisMod-MR 2.1, a Bayesian meta-regression tool, to analyse age-sex-specific incidence and prevalence data identified via systematic reviews of the literature, population-based survey data, and claims and inpatient data. Additionally, we estimated age-sex-specific LRI mortality that is attributable to the independent effects of 14 risk factors. FINDINGS: Globally, in 2019, we estimated that there were 257 million (95% uncertainty interval [UI] 240-275) LRI incident episodes in males and 232 million (217-248) in females. In the same year, LRIs accounted for 1·30 million (95% UI 1·18-1·42) male deaths and 1·20 million (1·07-1·33) female deaths. Age-standardised incidence and mortality rates were 1·17 times (95% UI 1·16-1·18) and 1·31 times (95% UI 1·23-1·41) greater in males than in females in 2019. Between 1990 and 2019, LRI incidence and mortality rates declined at different rates across age groups and an increase in LRI episodes and deaths was estimated among all adult age groups, with males aged 70 years and older having the highest increase in LRI episodes (126·0% [95% UI 121·4-131·1]) and deaths (100·0% [83·4-115·9]). During the same period, LRI episodes and deaths in children younger than 15 years were estimated to have decreased, and the greatest decline was observed for LRI deaths in males younger than 5 years (-70·7% [-77·2 to -61·8]). The leading risk factors for LRI mortality varied across age groups and sex. More than half of global LRI deaths in children younger than 5 years were attributable to child wasting (population attributable fraction [PAF] 53·0% [95% UI 37·7-61·8] in males and 56·4% [40·7-65·1] in females), and more than a quarter of LRI deaths among those aged 5-14 years were attributable to household air pollution (PAF 26·0% [95% UI 16·6-35·5] for males and PAF 25·8% [16·3-35·4] for females). PAFs of male LRI deaths attributed to smoking were 20·4% (95% UI 15·4-25·2) in those aged 15-49 years, 30·5% (24·1-36·9) in those aged 50-69 years, and 21·9% (16·8-27·3) in those aged 70 years and older. PAFs of female LRI deaths attributed to household air pollution were 21·1% (95% UI 14·5-27·9) in those aged 15-49 years and 18·2% (12·5-24·5) in those aged 50-69 years. For females aged 70 years and older, the leading risk factor, ambient particulate matter, was responsible for 11·7% (95% UI 8·2-15·8) of LRI deaths. INTERPRETATION: The patterns and progress in reducing the burden of LRIs and key risk factors for mortality varied across age groups and sexes. The progress seen in children younger than 5 years was clearly a result of targeted interventions, such as vaccination and reduction of exposure to risk factors. Similar interventions for other age groups could contribute to the achievement of multiple Sustainable Development Goals targets, including promoting wellbeing at all ages and reducing health inequalities. Interventions, including addressing risk factors such as child wasting, smoking, ambient particulate matter pollution, and household air pollution, would prevent deaths and reduce health disparities. FUNDING: Bill & Melinda Gates Foundation.

Burden of chronic kidney diseases and underlying causes in Zambia: evidence from the global burden of disease study 2019.

INTRODUCTION: Chronic kidney disease (CKD) has been a global public health problem and a major source of suffering and poor quality of life for those afflicted. Using data from the global burden of disease (GBD) study 2019, we estimated the magnitude of the burden of CKD as well as the underlying causes of CKD in the Zambian population. METHOD: The data used for this study were extracted from the GBD 2019 study. The GBD 2019 provides estimates of several metrics of disease burden including the commonly used disability-adjusted life year (DALYs) for over 369 diseases and injuries, and 87 risk factors and combinations of these in 204 countries and territories from 1990 to 2019. We estimated the burden of CKD as the number and rates (per 100,000 population) of DALYs, disaggregated by year, sex, and age group. We examined the underlying causes of CKD by estimating the population attributable fraction as the percentage contributions of risk factors to CKD DALY. RESULTS: The number of DALYs for CKD was estimated as 76.03 million (95% UI: 61.01 to 93.36) in 2019 compared to 39.42 million (95% UI: 33.09 to 45.90) in 1990, representing 93% increase whereas the DALYs rate per 100,000 population was estimated as 416.89 (95% UI: 334.53 to 511.93) in 2019 compared to 496.38 (95% UI: 416.55 to 577.87) in 1990, representing 16% reduction. CKD due to hypertension accounted for 18.7% of CKD DALYs and CKD due to diabetes (types 1 and 2) accounted for 22.7%, while CKD from glomerulonephritis accounted for the most DALYs at 33%. The age group most impacted from CKD were adolescents and young adults. CONCLUSION: The burden of CKD remains high in the Zambian population with diabetes, high blood pressure, and glomerulonephritis as important causes. The results highlight the need to develop a comprehensive action plan to prevent and treat kidney disease. Increasing the awareness of CKD among the public as well as adaptation of guidelines for treating patients with end stage kidney disease are important considerations.

The state of health in Pakistan and its provinces and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

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.

Ecological and socioeconomic factors associated with the human burden of environmentally mediated pathogens: a global analysis.

BACKGROUND: Billions of people living in poverty are at risk of environmentally mediated infectious diseases-that is, pathogens with environmental reservoirs that affect disease persistence and control and where environmental control of pathogens can reduce human risk. The complex ecology of these diseases creates a global health problem not easily solved with medical treatment alone. METHODS: We quantified the current global disease burden caused by environmentally mediated infectious diseases and used a structural equation model to explore environmental and socioeconomic factors associated with the human burden of environmentally mediated pathogens across all countries. FINDINGS: We found that around 80% (455 of 560) of WHO-tracked pathogen species known to infect humans are environmentally mediated, causing about 40% (129 488 of 359 341 disability-adjusted life years) of contemporary infectious disease burden (global loss of 130 million years of healthy life annually). The majority of this environmentally mediated disease burden occurs in tropical countries, and the poorest countries carry the highest burdens across all latitudes. We found weak associations between disease burden and biodiversity or agricultural land use at the global scale. In contrast, the proportion of people with rural poor livelihoods in a country was a strong proximate indicator of environmentally mediated infectious disease burden. Political stability and wealth were associated with improved sanitation, better health care, and lower proportions of rural poverty, indirectly resulting in lower burdens of environmentally mediated infections. Rarely, environmentally mediated pathogens can evolve into global pandemics (eg, HIV, COVID-19) affecting even the wealthiest communities. INTERPRETATION: The high and uneven burden of environmentally mediated infections highlights the need for innovative social and ecological interventions to complement biomedical advances in the pursuit of global health and sustainability goals. FUNDING: Bill & Melinda Gates Foundation, National Institutes of Health, National Science Foundation, Alfred P. Sloan Foundation, National Institute for Mathematical and Biological Synthesis, Stanford University, and the US Defense Advanced Research Projects Agency.

A global, regional, and national survey on burden and Quality of Care Index (QCI) of bladder cancer: The global burden of disease study 1990-2019.

INTRODUCTION: Bladder cancer (BCa) is the second most common genitourinary cancer and among the leading causes of cancer-related deaths. We aimed to assess BCa quality of care (QOC) utilizing a novel multi-variable quality of care index (QCI). MATERIALS AND METHODS: Data were retrieved from the Global Burden of Disease 1990-2019 database. QCI scores were calculated using four indices of prevalence-to-incidence ratio, Disability-Adjusted Life Years-to-prevalence ratio, mortality-to-incidence ratio, and Years of Life Lost-to-Years Lived with Disability ratio. We used principal component analysis to allocate 0-100 QCI scores based on region, age groups, year, and gender. RESULTS: Global burden of BCa is on the rise with 524,305 (95% UI 475,952-569,434) new BCa cases and 228,735 (95% UI 210743-243193) deaths in 2019, but age-standardized incidence and mortality rates did not increase. Global age-standardized QCI improved from 75.7% in 1990 to 80.9% in 2019. The European and African regions had the highest and lowest age-standardized QCI of 89.7% and 37.6%, respectively. Higher Socio-demographic index (SDI) quintiles had better QCI scores, ranging from 90.1% in high SDI to 30.2% in low SDI countries in 2019; however, 5-year QCI improvements from 2014 to 2019 were 0.0 for high and 4.7 for low SDI countries. CONCLUSION: The global QCI increased in the last 30 years, but the gender disparities remained relatively unchanged despite substantial improvements in several regions. Higher SDI quintiles had superior QOC and less gender- and age-based inequalities compared to lower SDI countries. We encourage countries to implement the learned lessons and improve their QOC shortcomings.

A framework for assessing the impact of disease treatment.

OBJECTIVES: To address ongoing pandemics and epidemics, policy makers need good data not only on the need for treatments but also on new interventions' impacts. We present a mathematical model of medicines' health consequences using disease surveillance data to inform health policy and scientific research that can be extended to address the current public health crisis. METHODS: The Global Health Impact index calculates the amount of mortality and morbidity averted by key medicines for malaria, TB, HIV/AIDS and several Neglected Tropical Diseases (NTDs) using data on outcomes in the absence of treatment, treatment effectiveness and access to needed treatment. Country-level data were extracted from data repositories maintained by the Global Burden of Disease study, Global Health Observatory, WHO, UNICEF and a review of the scientific literature. RESULTS: The index aggregates drug impact by country, disease, company and treatment regimen to identify the spatial and temporal patterns of treatment impact and can be extended across multiple diseases. Approximately 62 million life-years were saved by key drugs that target malaria, TB, HIV/AIDS and NTDs in our latest model year. Malaria and TB medicines together were responsible for alleviating 95% of this burden, while HIV/AIDS and NTD medicines contribute 4% and 1%, respectively. However, the burden of disease in the absence of treatment was nearly evenly distributed among malaria, TB and HIV/AIDS. CONCLUSIONS: A common framework that standardises health impact across diseases and their interventions can aid in identifying current shortcomings on a global scale.

The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01-4·94) deaths and 105 million (95·0-116) DALYs for both sexes combined, representing 44·4% (41·3-48·4) of all cancer deaths and 42·0% (39·1-45·6) of all DALYs. There were 2·88 million (2·60-3·18) risk-attributable cancer deaths in males (50·6% [47·8-54·1] of all male cancer deaths) and 1·58 million (1·36-1·84) risk-attributable cancer deaths in females (36·3% [32·5-41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6-28·4) and DALYs by 16·8% (8·8-25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9-42·8] and 33·3% [25·8-42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. FUNDING: Bill & Melinda Gates Foundation.

National Burden and Trend of Cancer in Ethiopia, 2010-2019: a systemic analysis for Global burden of disease study.

Over the last two decades, we have tracked the national burden of cancer and its trends in Ethiopia, providing estimates of incidence, death, and disability adjusted life years. In Ethiopia, there were an estimated 53,560 (95% UI 52,480-55,540) new incident cases, 39,480 deaths (95% UI 32,640-46,440), and 1.42 million (95% UI 1.16-1.68) DALYs of cancer 2019. Cancer incidence, death, and DALYs counts increased by 32% (95% UI 11-55%), 29% (95% UI 12-44%), and 19% (95% UI - 2 to 44%) between 2010 to 2019, respectively, while age-standardised incidence, death, and DALYs rates increased by 5% (95% UI - 7 to 18%), 2% (95% UI - 9 to 14%), and - 2% (95% UI - 15 to 12%) respectively. In 2019, the leading incidence cases were leukemia, cervical cancer, breast cancer, colon and rectum cancer, and stomach cancer, while leukemia, breast cancer, cervical cancer, and stomach cancer were the most common killer cancers in Ethiopia. According to the findings of this study, tobacco-related cancers such as pancreatic, kidney, and lung cancer have increased in Ethiopian females over the last decade, while genitourinary cancer has increased in Ethiopian males. Another significant finding was that infection-related cancers, such as stomach cancer and Hodgkin lymphoma, have been rapidly declining over the last decade.

The global, regional and national burden of stomach cancer and its attributable risk factors from 1990 to 2019.

We aimed to estimate the incidence, mortality, and disability-adjusted life-years (DALYs) of stomach cancer at the global, regional, and national levels. Stomach cancer resulted in 1.3 million (1.2-1.4 million) incident cases, 9.5 hundred thousand (8.7-10.4 hundred thousand) deaths, and 22.2 million (20.3-24.1 million) DALYs in 2019. The age-standardized incidence rate, death rate and DALY rate were 15.6 (14.1-17.2), 11.9 (10.8-12.8), and 268.4 (245.5-290.6) per 100,000 person-years, respectively. Between 1990 and 2019, the global age-standardized incidence rate, death rate, and DALY rate decreased by - 30.5% (- 36.7 to - 22.9), - 41.9% (- 47.2 to - 36.3), and - 45.6% (- 50.8 to - 39.8), respectively. In 2019, most of the global numbers of incidence, death and DALYs were higher among males than females. A considerable burden of stomach cancer was attributable to smoking and a high-sodium diet. Although the global age-standardized incidence and death rates have decreased, continued growth in absolute numbers in some regions, especially in East Asia, poses a major global public health challenge. To address this, public health responses should be tailored to fit each country's unique situation. Primary and secondary prevention strategies with increased effectiveness are required to reduce the incidence and mortality of stomach cancer, particularly in populations with a high disease burden.

Burden of non-communicable diseases among adolescents aged 10-24 years in the EU, 1990-2019: a systematic analysis of the Global Burden of Diseases Study 2019.

BACKGROUND: Disability and mortality burden of non-communicable diseases (NCDs) have risen worldwide; however, the NCD burden among adolescents remains poorly described in the EU. METHODS: Estimates were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Causes of NCDs were analysed at three different levels of the GBD 2019 hierarchy, for which mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were extracted. Estimates, with the 95% uncertainty intervals (UI), were retrieved for EU Member States from 1990 to 2019, three age subgroups (10-14 years, 15-19 years, and 20-24 years), and by sex. Spearman's correlation was conducted between DALY rates for NCDs and the Socio-demographic Index (SDI) of each EU Member State. FINDINGS: In 2019, NCDs accounted for 86·4% (95% uncertainty interval 83·5-88·8) of all YLDs and 38·8% (37·4-39·8) of total deaths in adolescents aged 10-24 years. For NCDs in this age group, neoplasms were the leading causes of both mortality (4·01 [95% uncertainty interval 3·62-4·25] per 100 000 population) and YLLs (281·78 [254·25-298·92] per 100 000 population), whereas mental disorders were the leading cause for YLDs (2039·36 [1432·56-2773·47] per 100 000 population) and DALYs (2040·59 [1433·96-2774·62] per 100 000 population) in all EU Member States, and in all studied age groups. In 2019, among adolescents aged 10-24 years, males had a higher mortality rate per 100 000 population due to NCDs than females (11·66 [11·04-12·28] vs 7·89 [7·53-8·23]), whereas females presented a higher DALY rate per 100 000 population due to NCDs (8003·25 [5812·78-10 701·59] vs 6083·91 [4576·63-7857·92]). From 1990 to 2019, mortality rate due to NCDs in adolescents aged 10-24 years substantially decreased (-40·41% [-43·00 to -37·61), and also the YLL rate considerably decreased (-40·56% [-43·16 to -37·74]), except for mental disorders (which increased by 32·18% [1·67 to 66·49]), whereas the YLD rate increased slightly (1·44% [0·09 to 2·79]). Positive correlations were observed between DALY rates and SDIs for substance use disorders (rs=0·58, p=0·0012) and skin and subcutaneous diseases (rs=0·45, p=0·017), whereas negative correlations were found between DALY rates and SDIs for cardiovascular diseases (rs=-0·46, p=0·015), neoplasms (rs=-0·57, p=0·0015), and sense organ diseases (rs=-0·61, p=0·0005). INTERPRETATION: NCD-related mortality has substantially declined among adolescents in the EU between 1990 and 2019, but the rising trend of YLL attributed to mental disorders and their YLD burden are concerning. Differences by sex, age group, and across EU Member States highlight the importance of preventive interventions and scaling up adolescent-responsive health-care systems, which should prioritise specific needs by sex, age, and location. FUNDING: Bill & Melinda Gates Foundation.

Measuring the availability of human resources for health and its relationship to universal health coverage for 204 countries and territories from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Human resources for health (HRH) include a range of occupations that aim to promote or improve human health. The UN Sustainable Development Goals (SDGs) and the WHO Health Workforce 2030 strategy have drawn attention to the importance of HRH for achieving policy priorities such as universal health coverage (UHC). Although previous research has found substantial global disparities in HRH, the absence of comparable cross-national estimates of existing workforces has hindered efforts to quantify workforce requirements to meet health system goals. We aimed to use comparable and standardised data sources to estimate HRH densities globally, and to examine the relationship between a subset of HRH cadres and UHC effective coverage performance. METHODS: Through the International Labour Organization and Global Health Data Exchange databases, we identified 1404 country-years of data from labour force surveys and 69 country-years of census data, with detailed microdata on health-related employment. From the WHO National Health Workforce Accounts, we identified 2950 country-years of data. We mapped data from all occupational coding systems to the International Standard Classification of Occupations 1988 (ISCO-88), allowing for standardised estimation of densities for 16 categories of health workers across the full time series. Using data from 1990 to 2019 for 196 of 204 countries and territories, covering seven Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) super-regions and 21 regions, we applied spatiotemporal Gaussian process regression (ST-GPR) to model HRH densities from 1990 to 2019 for all countries and territories. We used stochastic frontier meta-regression to model the relationship between the UHC effective coverage index and densities for the four categories of health workers enumerated in SDG indicator 3.c.1 pertaining to HRH: physicians, nurses and midwives, dentistry personnel, and pharmaceutical personnel. We identified minimum workforce density thresholds required to meet a specified target of 80 out of 100 on the UHC effective coverage index, and quantified national shortages with respect to those minimum thresholds. FINDINGS: We estimated that, in 2019, the world had 104·0 million (95% uncertainty interval 83·5-128·0) health workers, including 12·8 million (9·7-16·6) physicians, 29·8 million (23·3-37·7) nurses and midwives, 4·6 million (3·6-6·0) dentistry personnel, and 5·2 million (4·0-6·7) pharmaceutical personnel. We calculated a global physician density of 16·7 (12·6-21·6) per 10 000 population, and a nurse and midwife density of 38·6 (30·1-48·8) per 10 000 population. We found the GBD super-regions of sub-Saharan Africa, south Asia, and north Africa and the Middle East had the lowest HRH densities. To reach 80 out of 100 on the UHC effective coverage index, we estimated that, per 10 000 population, at least 20·7 physicians, 70·6 nurses and midwives, 8·2 dentistry personnel, and 9·4 pharmaceutical personnel would be needed. In total, the 2019 national health workforces fell short of these minimum thresholds by 6·4 million physicians, 30·6 million nurses and midwives, 3·3 million dentistry personnel, and 2·9 million pharmaceutical personnel. INTERPRETATION: Considerable expansion of the world's health workforce is needed to achieve high levels of UHC effective coverage. The largest shortages are in low-income settings, highlighting the need for increased financing and coordination to train, employ, and retain human resources in the health sector. Actual HRH shortages might be larger than estimated because minimum thresholds for each cadre of health workers are benchmarked on health systems that most efficiently translate human resources into UHC attainment. FUNDING: Bill & Melinda Gates Foundation.

Variation in the COVID-19 infection-fatality ratio by age, time, and geography during the pre-vaccine era: a systematic analysis.

BACKGROUND: The infection-fatality ratio (IFR) is a metric that quantifies the likelihood of an individual dying once infected with a pathogen. Understanding the determinants of IFR variation for COVID-19, the disease caused by the SARS-CoV-2 virus, has direct implications for mitigation efforts with respect to clinical practice, non-pharmaceutical interventions, and the prioritisation of risk groups for targeted vaccine delivery. The IFR is also a crucial parameter in COVID-19 dynamic transmission models, providing a way to convert a population's mortality rate into an estimate of infections. METHODS: We estimated age-specific and all-age IFR by matching seroprevalence surveys to total COVID-19 mortality rates in a population. The term total COVID-19 mortality refers to an estimate of the total number of deaths directly attributable to COVID-19. After applying exclusion criteria to 5131 seroprevalence surveys, the IFR analyses were informed by 2073 all-age surveys and 718 age-specific surveys (3012 age-specific observations). When seroprevalence was reported by age group, we split total COVID-19 mortality into corresponding age groups using a Bayesian hierarchical model to characterise the non-linear age pattern of reported deaths for a given location. To remove the impact of vaccines on the estimated IFR age pattern, we excluded age-specific observations of seroprevalence and deaths that occurred after vaccines were introduced in a location. We estimated age-specific IFR with a non-linear meta-regression and used the resulting age pattern to standardise all-age IFR observations to the global age distribution. All IFR observations were adjusted for baseline and waning antibody-test sensitivity. We then modelled age-standardised IFR as a function of time, geography, and an ensemble of 100 of the top-performing covariate sets. The covariates included seven clinical predictors (eg, age-standardised obesity prevalence) and two measures of health system performance. Final estimates for 190 countries and territories, as well as subnational locations in 11 countries and territories, were obtained by predicting age-standardised IFR conditional on covariates and reversing the age standardisation. FINDINGS: We report IFR estimates for April 15, 2020, to January 1, 2021, the period before the introduction of vaccines and widespread evolution of variants. We found substantial heterogeneity in the IFR by age, location, and time. Age-specific IFR estimates form a J shape, with the lowest IFR occurring at age 7 years (0·0023%, 95% uncertainty interval [UI] 0·0015-0·0039) and increasing exponentially through ages 30 years (0·0573%, 0·0418-0·0870), 60 years (1·0035%, 0·7002-1·5727), and 90 years (20·3292%, 14·6888-28·9754). The countries with the highest IFR on July 15, 2020, were Portugal (2·085%, 0·946-4·395), Monaco (1·778%, 1·265-2·915), Japan (1·750%, 1·302-2·690), Spain (1·710%, 0·991-2·718), and Greece (1·637%, 1·155-2·678). All-age IFR varied by a factor of more than 30 among 190 countries and territories. After age standardisation, the countries with the highest IFR on July 15, 2020, were Peru (0·911%, 0·636-1·538), Portugal (0·850%, 0·386-1·793), Oman (0·762%, 0·381-1·399), Spain (0·751%, 0·435-1·193), and Mexico (0·717%, 0·426-1·404). Subnational locations with high IFRs also included hotspots in the UK and southern and eastern states of the USA. Sub-Saharan African countries and Asian countries generally had the lowest all-age and age-standardised IFRs. Population age structure accounted for 74% of logit-scale variation in IFRs estimated for 39 in-sample countries on July 15, 2020. A post-hoc analysis showed that high rates of transmission in the care home population might account for higher IFRs in some locations. Among all countries and territories, we found that the median IFR decreased from 0·466% (interquartile range 0·223-0·840) to 0·314% (0·143-0·551) between April 15, 2020, and Jan 1, 2021. INTERPRETATION: Estimating the IFR for global populations helps to identify relative vulnerabilities to COVID-19. Information about how IFR varies by age, time, and location informs clinical practice and non-pharmaceutical interventions like physical distancing measures, and underpins vaccine risk stratification. IFR and mortality risk form a J shape with respect to age, which previous research, such as that by Glynn and Moss in 2020, has identified to be a common pattern among infectious diseases. Understanding the experience of a population with COVID-19 mortality requires consideration for local factors; IFRs varied by a factor of more than 30 among 190 countries and territories in this analysis. In particular, the presence of elevated age-standardised IFRs in countries with well resourced health-care systems indicates that factors beyond health-care capacity are important. Potential extenuating circumstances include outbreaks among care home residents, variable burdens of severe cases, and the population prevalence of comorbid conditions that increase the severity of COVID-19 disease. During the pre-vaccine period, the estimated 33% decrease in median IFR over 8 months suggests that treatment for COVID-19 has improved over time. Estimating IFR for the pre-vaccine era provides an important baseline for describing the progression of COVID-19 mortality patterns. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.

Prevalence, incidence, morbidity and mortality rates of COPD in Saudi Arabia: Trends in burden of COPD from 1990 to 2019.

BACKGROUND: The available data to determine the chronic obstructive pulmonary disease (COPD) burden in Saudi Arabia are scarce. Therefore, this study closely examines and tracks the trends of the COPD burden in Saudi Arabia from 1990 to 2019 using the dataset of the Global Burden of Disease (GBD) 2019. METHODS: This study used the GBD 2019 dataset to analyse the COPD prevalence, incidence, morbidity and mortality rates in the Saudi Arabian population from 1990 to 2019, stratified by sex and age. The age-standardised rate was used to determine the prevalence, incidence, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs) and deaths. RESULTS: In 2019, an estimated 434,560.64 people (95% Uncertainty Interval (UI) 396,011.72-473,596.71) had COPD in Saudi Arabia, corresponding to an increase of 329.82% compared with the number of diagnosed people in 1990 [101,104.05 (95% UI 91,334.4-111,223.91)]. The prevalence rate of COPD increased by 49%, from 1,381.26 (1,285.35-1,484.96) cases per 100,000 in 1990 to 2,053.04 (1918.06-2194.29) cases per 100,000 in 2019, and this trend was higher in males than females. The incidence rate of COPD in 2019 was 145.06 (136.62-154.76) new cases per 100,000, representing an increase of 43.4% from the 1990 incidence rate [101.18 (95.27-107.86)]. In 2019, the DALYs rate was 508.15 (95% UI 434.85-581.58) per 100,000 population. This was higher in males than females, with a 14.12% increase among males. In 2019, YLLs contributed to 63.6% of DALYs due to COPD. The death rate due to COPD was 19.6 (95% UI 15.94-23.39) deaths per 100 000 in 2019, indicating a decrease of 41.44% compared with the death rate in 1990 [33.55 deaths per 100 000 (95% UI 25.13-47.69)]. In 2019, COPD deaths accounted for 1.65% (1.39-1.88) of the total of deaths in Saudi Arabia and 57% of all deaths caused by chronic respiratory diseases. CONCLUSION: Over the period 1990-2019, the prevalence and incidence of COPD in Saudi Arabia have been steadily rising. Even though COPD morbidity and death rates have been decreasing, they remain higher in men and older age. The holistic assessment and interventions with careful attention to optimising the community-based primary care management, such as screening for early diagnosis, smoking cessation programs and pulmonary rehabilitation, are likely to be the most successful strategies to reduce the burden of COPD in Saudi Arabia.

COVID-19 Impact on Public Health, Environment, Human Psychology, Global Socioeconomy, and Education.

The end of the year 2019 was marked by the introduction of a third highly pathogenic coronavirus, after SARS-CoV (2003) and MERS-CoV (2012), in the human population which was officially declared a global pandemic by the World Health Organization (WHO) on March 11, 2020. Indeed, the pandemic of COVID-19 (Coronavirus Disease 19) has evolved at an unprecedented rate: after its emergence in Wuhan, the capital of the province of Hubei of the People's Republic of China, in December 2019, the total number of confirmed cases did not cease growing very quickly in the world. In this manuscript, we have provided an overview of the impact of COVID-19 on health, and we have proposed different nutrients suitable for infected patients to boost their immune systems. On the other hand, we have described the advantages and disadvantages of COVID-19 on the environment including the quality of water, air, waste management, and energy consumption, as well as the impact of this pandemic on human psychology, the educational system, and the global economy. In addition, we have tried to come up with some solutions to counter the negative repercussions of the pandemic.

Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic.

BACKGROUND: Before 2020, mental disorders were leading causes of the global health-related burden, with depressive and anxiety disorders being leading contributors to this burden. The emergence of the COVID-19 pandemic has created an environment where many determinants of poor mental health are exacerbated. The need for up-to-date information on the mental health impacts of COVID-19 in a way that informs health system responses is imperative. In this study, we aimed to quantify the impact of the COVID-19 pandemic on the prevalence and burden of major depressive disorder and anxiety disorders globally in 2020. METHODS: We conducted a systematic review of data reporting the prevalence of major depressive disorder and anxiety disorders during the COVID-19 pandemic and published between Jan 1, 2020, and Jan 29, 2021. We searched PubMed, Google Scholar, preprint servers, grey literature sources, and consulted experts. Eligible studies reported prevalence of depressive or anxiety disorders that were representative of the general population during the COVID-19 pandemic and had a pre-pandemic baseline. We used the assembled data in a meta-regression to estimate change in the prevalence of major depressive disorder and anxiety disorders between pre-pandemic and mid-pandemic (using periods as defined by each study) via COVID-19 impact indicators (human mobility, daily SARS-CoV-2 infection rate, and daily excess mortality rate). We then used this model to estimate the change from pre-pandemic prevalence (estimated using Disease Modelling Meta-Regression version 2.1 [known as DisMod-MR 2.1]) by age, sex, and location. We used final prevalence estimates and disability weights to estimate years lived with disability and disability-adjusted life-years (DALYs) for major depressive disorder and anxiety disorders. FINDINGS: We identified 5683 unique data sources, of which 48 met inclusion criteria (46 studies met criteria for major depressive disorder and 27 for anxiety disorders). Two COVID-19 impact indicators, specifically daily SARS-CoV-2 infection rates and reductions in human mobility, were associated with increased prevalence of major depressive disorder (regression coefficient [B] 0·9 [95% uncertainty interval 0·1 to 1·8; p=0·029] for human mobility, 18·1 [7·9 to 28·3; p=0·0005] for daily SARS-CoV-2 infection) and anxiety disorders (0·9 [0·1 to 1·7; p=0·022] and 13·8 [10·7 to 17·0; p<0·0001]. Females were affected more by the pandemic than males (B 0·1 [0·1 to 0·2; p=0·0001] for major depressive disorder, 0·1 [0·1 to 0·2; p=0·0001] for anxiety disorders) and younger age groups were more affected than older age groups (-0·007 [-0·009 to -0·006; p=0·0001] for major depressive disorder, -0·003 [-0·005 to -0·002; p=0·0001] for anxiety disorders). We estimated that the locations hit hardest by the pandemic in 2020, as measured with decreased human mobility and daily SARS-CoV-2 infection rate, had the greatest increases in prevalence of major depressive disorder and anxiety disorders. We estimated an additional 53·2 million (44·8 to 62·9) cases of major depressive disorder globally (an increase of 27·6% [25·1 to 30·3]) due to the COVID-19 pandemic, such that the total prevalence was 3152·9 cases (2722·5 to 3654·5) per 100 000 population. We also estimated an additional 76·2 million (64·3 to 90·6) cases of anxiety disorders globally (an increase of 25·6% [23·2 to 28·0]), such that the total prevalence was 4802·4 cases (4108·2 to 5588·6) per 100 000 population. Altogether, major depressive disorder caused 49·4 million (33·6 to 68·7) DALYs and anxiety disorders caused 44·5 million (30·2 to 62·5) DALYs globally in 2020. INTERPRETATION: This pandemic has created an increased urgency to strengthen mental health systems in most countries. Mitigation strategies could incorporate ways to promote mental wellbeing and target determinants of poor mental health and interventions to treat those with a mental disorder. Taking no action to address the burden of major depressive disorder and anxiety disorders should not be an option. FUNDING: Queensland Health, National Health and Medical Research Council, and the Bill and Melinda Gates Foundation.

Estimating the cause-specific relative risks of non-optimal temperature on daily mortality: a two-part modelling approach applied to the Global Burden of Disease Study.

BACKGROUND: Associations between high and low temperatures and increases in mortality and morbidity have been previously reported, yet no comprehensive assessment of disease burden has been done. Therefore, we aimed to estimate the global and regional burden due to non-optimal temperature exposure. METHODS: In part 1 of this study, we linked deaths to daily temperature estimates from the ERA5 reanalysis dataset. We modelled the cause-specific relative risks for 176 individual causes of death along daily temperature and 23 mean temperature zones using a two-dimensional spline within a Bayesian meta-regression framework. We then calculated the cause-specific and total temperature-attributable burden for the countries for which daily mortality data were available. In part 2, we applied cause-specific relative risks from part 1 to all locations globally. We combined exposure-response curves with daily gridded temperature and calculated the cause-specific burden based on the underlying burden of disease from the Global Burden of Diseases, Injuries, and Risk Factors Study, for the years 1990-2019. Uncertainty from all components of the modelling chain, including risks, temperature exposure, and theoretical minimum risk exposure levels, defined as the temperature of minimum mortality across all included causes, was propagated using posterior simulation of 1000 draws. FINDINGS: We included 64·9 million individual International Classification of Diseases-coded deaths from nine different countries, occurring between Jan 1, 1980, and Dec 31, 2016. 17 causes of death met the inclusion criteria. Ischaemic heart disease, stroke, cardiomyopathy and myocarditis, hypertensive heart disease, diabetes, chronic kidney disease, lower respiratory infection, and chronic obstructive pulmonary disease showed J-shaped relationships with daily temperature, whereas the risk of external causes (eg, homicide, suicide, drowning, and related to disasters, mechanical, transport, and other unintentional injuries) increased monotonically with temperature. The theoretical minimum risk exposure levels varied by location and year as a function of the underlying cause of death composition. Estimates for non-optimal temperature ranged from 7·98 deaths (95% uncertainty interval 7·10-8·85) per 100 000 and a population attributable fraction (PAF) of 1·2% (1·1-1·4) in Brazil to 35·1 deaths (29·9-40·3) per 100 000 and a PAF of 4·7% (4·3-5·1) in China. In 2019, the average cold-attributable mortality exceeded heat-attributable mortality in all countries for which data were available. Cold effects were most pronounced in China with PAFs of 4·3% (3·9-4·7) and attributable rates of 32·0 deaths (27·2-36·8) per 100 000 and in New Zealand with 3·4% (2·9-3·9) and 26·4 deaths (22·1-30·2). Heat effects were most pronounced in China with PAFs of 0·4% (0·3-0·6) and attributable rates of 3·25 deaths (2·39-4·24) per 100 000 and in Brazil with 0·4% (0·3-0·5) and 2·71 deaths (2·15-3·37). When applying our framework to all countries globally, we estimated that 1·69 million (1·52-1·83) deaths were attributable to non-optimal temperature globally in 2019. The highest heat-attributable burdens were observed in south and southeast Asia, sub-Saharan Africa, and North Africa and the Middle East, and the highest cold-attributable burdens in eastern and central Europe, and central Asia. INTERPRETATION: Acute heat and cold exposure can increase or decrease the risk of mortality for a diverse set of causes of death. Although in most regions cold effects dominate, locations with high prevailing temperatures can exhibit substantial heat effects far exceeding cold-attributable burden. Particularly, a high burden of external causes of death contributed to strong heat impacts, but cardiorespiratory diseases and metabolic diseases could also be substantial contributors. Changes in both exposures and the composition of causes of death drove changes in risk over time. Steady increases in exposure to the risk of high temperature are of increasing concern for health. FUNDING: Bill & Melinda Gates Foundation.

The burden and trend of gastric cancer and possible risk factors in five Asian countries from 1990 to 2019.

The burdens and trends of gastric cancer are poorly understood, especially in high-prevalence countries. Based on the Global Burden of Disease Study 2019, we analyzed the incidence, death, and possible risk factors of gastric cancer in five Asian countries, in relation to year, age, sex, and sociodemographic index. The annual percentage change was calculated to estimate the trends in age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR). The highest ASIR per 100,000 person-years in 2019 was in Mongolia [44 (95% uncertainty interval (UI), 34 to 55)], while the lowest was in the Democratic People's Republic of Korea (DPRK) [23 (95% UI, 19 to 29)]. The highest ASDR per 100,000 person-years was in Mongolia [46 (95% UI, 37 to 57)], while the lowest was in Japan [14 (95% UI, 12 to 15)]. Despite the increase in the absolute number of cases and deaths from 1990 to 2019, the ASIRs and ASDRs in all five countries decreased with time and improved sociodemographic index but increased with age. Smoking and a high-sodium diet were two possible risk factors for gastric cancer. In 2019, the proportion of age-standardized disability-adjusted life-years attributable to smoking was highest in Japan [23% (95% UI, 19 to 28%)], and the proportions attributable to a high-sodium diet were highest in China [8.8% (95% UI, 0.21 to 33%)], DPRK, and the Republic of Korea. There are substantial variations in the incidence and death of gastric cancer in the five studied Asian countries. This study may be crucial in helping policymakers to make better decisions and allocate appropriate resources.

Cost-effectiveness of Vitamin A supplementation among children in three sub-Saharan African countries: An individual-based simulation model using estimates from Global Burden of Disease 2019.

BACKGROUND: Vitamin A Supplementation (VAS) is a cost-effective intervention to decrease mortality associated with measles and diarrheal diseases among children aged 6-59 months in low-income countries. Recently, experts have suggested that other interventions like large-scale food fortification and increasing the coverage of measles vaccination might provide greater impact than VAS. In this study, we conducted a cost-effectiveness analysis of a VAS scale-up in three sub-Saharan African countries. METHODS: We developed an individual-based microsimulation using the Vivarium simulation framework to estimate the cost and effect of scaling up VAS from 2019 to 2023 in Nigeria, Kenya, and Burkina Faso, three countries with different levels of baseline coverage. We calibrated the model with disease and risk factor estimates from the Global Burden of Disease 2019 (GBD 2019). We obtained baseline coverage, intervention effects, and costs from a systematic review. After the model was validated against GBD inputs, we modeled an alternative scenario where we scaled-up VAS coverage from 2019 to a level that halved the exposure to lack of VAS in 2023. Based on the simulation outputs for DALYs averted and intervention cost, we determined estimates for the incremental cost-effectiveness ratio (ICER) in USD/DALY. FINDINGS: Our estimates for ICER are as follows: $860/DALY [95% UI; 320, 3530] in Nigeria, $550/DALY [240, 2230] in Kenya, and $220/DALY [80, 2470] in Burkina Faso. Examining the data for DALYs averted for the three countries over the time span, we found that the scale-up led to 21 [5, 56] DALYs averted per 100,000 person-years in Nigeria, 21 [5, 47] DALYs averted per 100,000 person-years in Kenya, and 14 [0, 37] DALYs averted per 100,000 person-years in Burkina Faso. CONCLUSIONS: VAS may no longer be as cost-effective in low-income regions as it has been previously. Updated estimates in GBD 2019 for the effect of Vitamin A Deficiency on causes of death are an additional driver of this lower estimate of cost-effectiveness.