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

Ultrasound-Determined Residual Gastric Volume after Clear-Fluid Ingestion in the Paediatric Population: Still a Debatable Issue

Background: Current fasting guidelines are often exceeded in clinical practice, resulting in stressful events during anaesthesia in children. This prospective study compares residual gastric volume after 1 versus 2 h of clear fluid ingestion in fasted children. METHODS: A total of 106 patients were enrolled in the study. Ultrasonography (USG) of gastric antrum (GA) was performed in the supine and right lateral decubitus (RLD) positions. All children fasted from solid food for 6 h. Blackcurrant flavoured drink (3 mL/kg) was given following the measurement of baseline (T0) USG of GA, with follow-ups after 1 (T1) and 2 (T2) hours post-ingestion. Residual gastric volume (RGV) was calculated from the cross-sectional area of GA using a standard formula. Parental satisfaction with their children’s behaviour concerning fasting time was recorded. Results: RGV was significantly higher at T1 compared to T2 (p < 0.001). No significant difference was seen between T0 and T2 (p = 0.30). Parental satisfaction was similar at T1 and T2 (p = 0.158). Conclusions: The RGV in paediatric patients after 1 h of clear fluid ingestion was significantly higher than after 2 h of ingestion. There was no difference observed in parental satisfaction concerning the two intervals of fluid fasting. RLD and supine positions can be used reliably to measure the RGV in children

CFA for C19-VHS-M.

IntroductionHealthcare workers play a crucial role in supporting COVID-19 vaccination as they are the most trusted source of information to the public population. Assessing the healthcare workers’ hesitancy towards COVID-19 vaccination is pertinent, however, there are limited validated tools to measure their hesitancy on COVID-19 vaccines. This study aims to adapt and validate the first COVID-19 hesitancy scale among healthcare workers in Malaysia.Materials and methodsThis study adapted and translated the Vaccine Hesitancy Scale (VHS) developed by the WHO SAGE Working Group. The scale underwent a sequential validation process, including back-back translation, content, face, and construct validity for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). The reliability was tested using internal consistency (Cronbach’s alpha composite reliability (CR) and average variance extracted (AVE)).ResultsThe data for EFA and CFA were completed by a separate sample of 125 and 300 HCWs, respectively. The EFA analysis of the C19-VHS-M scale was unidimensional with 10 items. A further CFA analysis revealed a uniform set of nine items with acceptable goodness fit indices (comparative fit index = 0.997, Tucker-Lewis index = 0.995, incremental fit index = 0.997, chi-squared/degree of freedom = 1.352, and root mean square error of approximation = 0.034). The Cronbach’s alpha, CR and AVE results were 0.953, 0.95 and 0.70, respectively.ConclusionsThe questionnaire was valid and reliable for use in the Malay language.</div

EFA for C19-VHS-M.

IntroductionHealthcare workers play a crucial role in supporting COVID-19 vaccination as they are the most trusted source of information to the public population. Assessing the healthcare workers’ hesitancy towards COVID-19 vaccination is pertinent, however, there are limited validated tools to measure their hesitancy on COVID-19 vaccines. This study aims to adapt and validate the first COVID-19 hesitancy scale among healthcare workers in Malaysia.Materials and methodsThis study adapted and translated the Vaccine Hesitancy Scale (VHS) developed by the WHO SAGE Working Group. The scale underwent a sequential validation process, including back-back translation, content, face, and construct validity for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). The reliability was tested using internal consistency (Cronbach’s alpha composite reliability (CR) and average variance extracted (AVE)).ResultsThe data for EFA and CFA were completed by a separate sample of 125 and 300 HCWs, respectively. The EFA analysis of the C19-VHS-M scale was unidimensional with 10 items. A further CFA analysis revealed a uniform set of nine items with acceptable goodness fit indices (comparative fit index = 0.997, Tucker-Lewis index = 0.995, incremental fit index = 0.997, chi-squared/degree of freedom = 1.352, and root mean square error of approximation = 0.034). The Cronbach’s alpha, CR and AVE results were 0.953, 0.95 and 0.70, respectively.ConclusionsThe questionnaire was valid and reliable for use in the Malay language.</div

Content and face validity for C19-VHS-M.

IntroductionHealthcare workers play a crucial role in supporting COVID-19 vaccination as they are the most trusted source of information to the public population. Assessing the healthcare workers’ hesitancy towards COVID-19 vaccination is pertinent, however, there are limited validated tools to measure their hesitancy on COVID-19 vaccines. This study aims to adapt and validate the first COVID-19 hesitancy scale among healthcare workers in Malaysia.Materials and methodsThis study adapted and translated the Vaccine Hesitancy Scale (VHS) developed by the WHO SAGE Working Group. The scale underwent a sequential validation process, including back-back translation, content, face, and construct validity for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). The reliability was tested using internal consistency (Cronbach’s alpha composite reliability (CR) and average variance extracted (AVE)).ResultsThe data for EFA and CFA were completed by a separate sample of 125 and 300 HCWs, respectively. The EFA analysis of the C19-VHS-M scale was unidimensional with 10 items. A further CFA analysis revealed a uniform set of nine items with acceptable goodness fit indices (comparative fit index = 0.997, Tucker-Lewis index = 0.995, incremental fit index = 0.997, chi-squared/degree of freedom = 1.352, and root mean square error of approximation = 0.034). The Cronbach’s alpha, CR and AVE results were 0.953, 0.95 and 0.70, respectively.ConclusionsThe questionnaire was valid and reliable for use in the Malay language.</div

Sociodemographic data of the participants.

IntroductionHealthcare workers play a crucial role in supporting COVID-19 vaccination as they are the most trusted source of information to the public population. Assessing the healthcare workers’ hesitancy towards COVID-19 vaccination is pertinent, however, there are limited validated tools to measure their hesitancy on COVID-19 vaccines. This study aims to adapt and validate the first COVID-19 hesitancy scale among healthcare workers in Malaysia.Materials and methodsThis study adapted and translated the Vaccine Hesitancy Scale (VHS) developed by the WHO SAGE Working Group. The scale underwent a sequential validation process, including back-back translation, content, face, and construct validity for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). The reliability was tested using internal consistency (Cronbach’s alpha composite reliability (CR) and average variance extracted (AVE)).ResultsThe data for EFA and CFA were completed by a separate sample of 125 and 300 HCWs, respectively. The EFA analysis of the C19-VHS-M scale was unidimensional with 10 items. A further CFA analysis revealed a uniform set of nine items with acceptable goodness fit indices (comparative fit index = 0.997, Tucker-Lewis index = 0.995, incremental fit index = 0.997, chi-squared/degree of freedom = 1.352, and root mean square error of approximation = 0.034). The Cronbach’s alpha, CR and AVE results were 0.953, 0.95 and 0.70, respectively.ConclusionsThe questionnaire was valid and reliable for use in the Malay language.</div

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