Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

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

The effectiveness of positive treatment on distress tolerance and rumination in patients with chronic hypertension

Background and Aim: It is necessary to identify psychological treatments effective in improving the mental health of patients with chronic blood pressure, so the aim of this study was to determine the effectiveness of positive therapy on the tolerance of distress and rumination in patients with chronic blood pressure Methods: The present research was a quasi-experimental type of pre-test-post-test with a control group. The statistical population of the present study was all patients with high blood pressure who referred to the specialized and super-specialized center of Imam Khomeini Hospital in 2021. Among the qualified people who volunteered to participate in the research, 30 people were selected by available sampling method and randomly placed in two experimental and control groups (15 people in each group). The experimental group participated in nine 90-minute sessions of positive therapy training based on Marrero et al.'s (2016) therapy package, but the control group did not receive therapy. Data collection tools included Simons and Gaher (2005) distress tolerance scale and Nolen Hoeksema and Morrow (1991) rumination scale. Data were analyzed using SPSS version 24 software and multivariate analysis of covariance at a significance level of α=0.05. Results: The results showed that positive treatment significantly increased distress tolerance (F=75.29, P<0.001) and decreased rumination (F=24.73, P<0.001) in patients with chronic hypertension. Conclusion: The results emphasize the importance of positive therapy in patients with chronic hypertension and providing new horizons in clinical interventions. Therefore, positive therapy can be used as a complementary treatment to create a positive and appropriate change in patients with chronic hypertension

Factors Associated With Neurological Manifestations in Patients With COVID-19: Neurological Manifestations of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) is the most terrible pandemic of a respiratory disease that we had in the past century. Most existing studies explore different manifestations in COVID-19. Few recent studies have described neurological manifestations of patients with COVID-19 but their associations with age, laboratory findings, and mortality rates have not been explored well.Methods: This case-control study includes 263 patients with COVID-19 without neurological symptoms (control group) and all patients with COVID-19 with the central nervous system symptoms (n = 460, case group) hospitalized between February 2020 and April 2020. Data on demographic factors, medical history, symptoms, and laboratory tests, all are extracted from medical records.Results: Out of 723 patients with confirmed SARS-CoV-2 infection, 460 (63.6%) were identified to have at least one neurological manifestation. The mean ages of patients with and without neurological manifestation were 60.6 ± 18.0 and 60.8 ± 15.7 years, respectively. The most common symptoms were myalgia (41%), headache (20.3%), and loss of consciousness (LOC) (16.5%). Women were more likely to develop a neurological manifestation (P = 0.001). Moreover, smoking history was significantly more in patients with neurological manifestations (P = 0.03). Also, we compared two groups in terms of tracheal intubation. The need for tracheal intubation was 19% and 12% in patients with and without neurological manifestations, respectively. Furthermore, the prevalence of intensive care unit (ICU) admission was 28% and 24% in patients with COVID-19, with and without neurological manifestations, respectively. Some of the neurological manifestations such as LOC, limbs weakness, and seizure might need more ICU admission and tracheal intubation. The frequency of comorbidities and the laboratory test results were almost similar between the two groups.Conclusion: Myalgia, headache, and LOC were the most common neurological manifestations and their distributions varied depending on age. Only a few neurological manifestations were related to mortality and morbidity rates, while some of them occurred in mild cases

Factors Associated With Neurological Manifestations in Patients With COVID-19

Background: The coronavirus disease 2019 (COVID-19) is the most terrible pandemic of a respiratory disease that we had in the past century. Most existing studies explore different manifestations in COVID-19. Few recent studies have described neurological manifestations of patients with COVID-19 but their associations with age, laboratory findings, and mortality rates have not been explored well. Methods: This case-control study includes 263 patients with COVID-19 without neurological symptoms (control group) and all patients with COVID-19 with the central nervous system symptoms (n=460, case group) hospitalized between February 2020 and April 2020. Data on demographic factors, medical history, symptoms, and laboratory tests, all are extracted from medical records. Results: Out of 723 patients with confirmed SARS-CoV-2 infection, 460 (63.6%) were identified to have at least one neurological manifestation. The mean ages of patients with and without neurological manifestation were 60.6±18.0 and 60.8±15.7 years, respectively. The most common symptoms were myalgia (41%), headache (20.3%), and loss of consciousness (LOC) (16.5%). Women were more likely to develop a neurological manifestation (P = 0.001). Moreover, smoking history was significantly more in patients with neurological manifestations (P=0.03). Also, we compared two groups in terms of tracheal intubation. The need for tracheal intubation was 19% and 12% in patients with and without neurological manifestations, respectively. Furthermore, the prevalence of intensive care unit (ICU) admission was 28% and 24% in patients with COVID-19, with and without neurological manifestations, respectively. Some of the neurological manifestations such as LOC, limbs weakness, and seizure might need more ICU admission and tracheal intubation. The frequency of comorbidities and the laboratory test results were almost similar between the two groups. Conclusion: Myalgia, headache, and LOC were the most common neurological manifestations and their distributions varied depending on age. Only a few neurological manifestations were related to mortality and morbidity rates, while some of them occurred in mild cases

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundRegular, 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.MethodsThe 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.FindingsThe 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.InterpretationLong-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