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

Exploring fatty acid derivatives from renewable resources as raw materials for coating applications

In the work presented herein, epoxy fatty acid derivatives were explored in the formation of thermosets for coating applications. The epoxy fatty acid derivatives were obtained from renewable resources such as birch tree bark and epoxidized linseed oil. The birch bark was used to isolate 9,10-epoxy-18-hydroxyoctadecanoic acid (EFA) and the epoxidized linseed oil was used to retrieve methyl stearate and 3 different epoxy methyl esters: epoxy methyl oleate/linoleate/linolenate (EMO/EMLO/EMLEN). The obtained epoxy fatty acid derivatives were used in resin formulations together with other reactants or in the synthesis of multifunctional oligomer resins using enzyme catalysis. All resins were cured using different polymerization techniques to form thermosets with a wide variety of properties.Multifunctional oligomer resin were synthesized using Candida Antarctica lipase-B (CALB) as enzyme. It was demonstrated that the synthesis was efficient and the oligomers were obtained from “one-pot” route. In addition, the selectivity of CALB was useful in preserving a variety of functional groups (epoxides, alkenes and thiols) in the final oligomers. The oligomers were cross-linked by either thiol-ene chemistry or cationic polymerization resulting in functional thermosets. It was further shown that surface properties of the cured thermosets could be changed by using post-functionalization.Pure fatty acid methyl esters cure into soft materials. An approach in increasing the thermal and mechanical properties was investigated. The 3 different epoxy functional methyl esters together with a furan-2,5-dicarboxylic acid derivative were investigated in the formation of thermosets. Glass transition temperature (Tg) below 0 °C and above 100 °C were obtained by varying the stoichiometric feed of the reactants.The thermal curing of EFA as a one-component system was investigated by model studies showing that a self-catalyzed process occur. EFA thermally cures into a thermoset without the need of an added catalyst. Furthermore, the thermoset showed adhesive properties.Crude mixture containing methyl stearate, EMO, EMLO and EMLEN obtained from epoxidized linseed oil were investigated as reactive diluent in coil-coatings. The mixture was also compared with commercially available reactive diluents such as fatty acid methyl esters (FAME) obtained from rapeseed oil. The results obtained showed that more fatty methyl esters could be incorporated in the final thermoset when using the epoxidized linseed oil fatty acid derivatives.Real-time Fourier-transform infrared spectroscopy (RT-FTIR) was used during most of the work presented in the thesis and proved to be a powerful tool in monitoring the different reactions and comparing relative reaction rates.I arbetet som presenteras i denna avhandling undersöktes epoxifettsyraderivat vid bildandet av härdplaster för ytmodifieringsapplikationer. Förnybara råvarorna björkbark och epoxiderad linolja andändes för att erhålla epoxifettsyraderivaten. Björkbarken användes för att isolera 9,10-epoxi-18-hydroxidekansyra (EFA) och epoxoderad linolja användes för att extrahera metylstearat och 3 olika epoximetylestrar: epoximetyl oleat/linoleat/linolenat (EMO/EMLO/EMLEN). Epoxifettsyraderivaten användes i olika hartsformuleringar tillammans med andra reaktanter eller vid syntes av multifunktionella oligomerhartser med hjälp av enzymatisk katalys. Med hjälp av olika polymerisationstekniker så härdades alla hartser till härdplaster med en mängd olika egenskaper.Multifunktionella oligomerhartser syntetiserades med hjälp av enzymet Candida Antarctica lipas-b (CALB). Syntesen visade sig vara effektiv och oligomererna erhölls från en sats. Dessutom var selektiviteten hos CALB användbar för att bevara en mängd olika funktionella grupper (epoxider, alkener och tioler) i de slutliga oligomererna. Tiol-ene kemi eller katjonisk polymerisation användes sedan för att härda oligomererna, vilket resulterade i funktionella härdplaster. Vidare visades att ytegenskaperna kunde ändras genom möjlighet till funktionalisering av härdplasterna.Mjuka material återfås då man härdar rena fettsyrametylestrar. Ett sätt att öka de termiska och mekaniska egenskaperna undersöktes. De tre olika epoxifunktionella metylestrarna tillsammans med furan-2,5-dicarboxylsyraderivat blandades i hartser och härdades. Genom att variera de stökiometriska förhållanderna av reaktanterna så erhölls glastemperaturer (Tg) under 0°C och över 100 °C.Undersökningen av termisk härdning av EFA som ett komponentssystem studerades genom modelstudier. Studierna visade att en självkatalyserad process sker då EFA värms upp. Detta leder således till att EFA kan termiskt härda utan behov av en tillsatt katalysator. Dessutom uppvisade härdplasten limegenskaper.Rå blandning innehållande metylstearate, EMO, EMLO och EMLEN som erhölls från epoxiderad linolja undersöktes som en reaktiv utspädare i spolbeläggningar. Blandningen jämfördes även med kommersiellt tillgängliga utspädare så som fettsyrametylestrar (FAME) erhållna från rapsolja. De erhållna resultaten påvisade att fler feta metylestrar kunde integreras i slutliga beläggningen när fettsyraderivat från epoxideradlinolja användes.Realtids Fourier-transform infrarödspektroskopi (RT-FTIR) användes under det mesta av arbetet som presenteras i denna avhandling. RT-FTIR visade sig vara ett kraftfullt vektyg för att övervaka de olika reaktionerna samt jämföra relativa reaktionshastigheter.QC 20190506</p

Exploring fatty acid derivatives from renewable resources as raw materials for coating applications

In the work presented herein, epoxy fatty acid derivatives were explored in the formation of thermosets for coating applications. The epoxy fatty acid derivatives were obtained from renewable resources such as birch tree bark and epoxidized linseed oil. The birch bark was used to isolate 9,10-epoxy-18-hydroxyoctadecanoic acid (EFA) and the epoxidized linseed oil was used to retrieve methyl stearate and 3 different epoxy methyl esters: epoxy methyl oleate/linoleate/linolenate (EMO/EMLO/EMLEN). The obtained epoxy fatty acid derivatives were used in resin formulations together with other reactants or in the synthesis of multifunctional oligomer resins using enzyme catalysis. All resins were cured using different polymerization techniques to form thermosets with a wide variety of properties.Multifunctional oligomer resin were synthesized using Candida Antarctica lipase-B (CALB) as enzyme. It was demonstrated that the synthesis was efficient and the oligomers were obtained from “one-pot” route. In addition, the selectivity of CALB was useful in preserving a variety of functional groups (epoxides, alkenes and thiols) in the final oligomers. The oligomers were cross-linked by either thiol-ene chemistry or cationic polymerization resulting in functional thermosets. It was further shown that surface properties of the cured thermosets could be changed by using post-functionalization.Pure fatty acid methyl esters cure into soft materials. An approach in increasing the thermal and mechanical properties was investigated. The 3 different epoxy functional methyl esters together with a furan-2,5-dicarboxylic acid derivative were investigated in the formation of thermosets. Glass transition temperature (Tg) below 0 °C and above 100 °C were obtained by varying the stoichiometric feed of the reactants.The thermal curing of EFA as a one-component system was investigated by model studies showing that a self-catalyzed process occur. EFA thermally cures into a thermoset without the need of an added catalyst. Furthermore, the thermoset showed adhesive properties.Crude mixture containing methyl stearate, EMO, EMLO and EMLEN obtained from epoxidized linseed oil were investigated as reactive diluent in coil-coatings. The mixture was also compared with commercially available reactive diluents such as fatty acid methyl esters (FAME) obtained from rapeseed oil. The results obtained showed that more fatty methyl esters could be incorporated in the final thermoset when using the epoxidized linseed oil fatty acid derivatives.Real-time Fourier-transform infrared spectroscopy (RT-FTIR) was used during most of the work presented in the thesis and proved to be a powerful tool in monitoring the different reactions and comparing relative reaction rates.I arbetet som presenteras i denna avhandling undersöktes epoxifettsyraderivat vid bildandet av härdplaster för ytmodifieringsapplikationer. Förnybara råvarorna björkbark och epoxiderad linolja andändes för att erhålla epoxifettsyraderivaten. Björkbarken användes för att isolera 9,10-epoxi-18-hydroxidekansyra (EFA) och epoxoderad linolja användes för att extrahera metylstearat och 3 olika epoximetylestrar: epoximetyl oleat/linoleat/linolenat (EMO/EMLO/EMLEN). Epoxifettsyraderivaten användes i olika hartsformuleringar tillammans med andra reaktanter eller vid syntes av multifunktionella oligomerhartser med hjälp av enzymatisk katalys. Med hjälp av olika polymerisationstekniker så härdades alla hartser till härdplaster med en mängd olika egenskaper.Multifunktionella oligomerhartser syntetiserades med hjälp av enzymet Candida Antarctica lipas-b (CALB). Syntesen visade sig vara effektiv och oligomererna erhölls från en sats. Dessutom var selektiviteten hos CALB användbar för att bevara en mängd olika funktionella grupper (epoxider, alkener och tioler) i de slutliga oligomererna. Tiol-ene kemi eller katjonisk polymerisation användes sedan för att härda oligomererna, vilket resulterade i funktionella härdplaster. Vidare visades att ytegenskaperna kunde ändras genom möjlighet till funktionalisering av härdplasterna.Mjuka material återfås då man härdar rena fettsyrametylestrar. Ett sätt att öka de termiska och mekaniska egenskaperna undersöktes. De tre olika epoxifunktionella metylestrarna tillsammans med furan-2,5-dicarboxylsyraderivat blandades i hartser och härdades. Genom att variera de stökiometriska förhållanderna av reaktanterna så erhölls glastemperaturer (Tg) under 0°C och över 100 °C.Undersökningen av termisk härdning av EFA som ett komponentssystem studerades genom modelstudier. Studierna visade att en självkatalyserad process sker då EFA värms upp. Detta leder således till att EFA kan termiskt härda utan behov av en tillsatt katalysator. Dessutom uppvisade härdplasten limegenskaper.Rå blandning innehållande metylstearate, EMO, EMLO och EMLEN som erhölls från epoxiderad linolja undersöktes som en reaktiv utspädare i spolbeläggningar. Blandningen jämfördes även med kommersiellt tillgängliga utspädare så som fettsyrametylestrar (FAME) erhållna från rapsolja. De erhållna resultaten påvisade att fler feta metylestrar kunde integreras i slutliga beläggningen när fettsyraderivat från epoxideradlinolja användes.Realtids Fourier-transform infrarödspektroskopi (RT-FTIR) användes under det mesta av arbetet som presenteras i denna avhandling. RT-FTIR visade sig vara ett kraftfullt vektyg för att övervaka de olika reaktionerna samt jämföra relativa reaktionshastigheter.QC 20190506</p

Exploring fatty acid derivatives from renewable resources as raw materials for coating applications

In the work presented herein, epoxy fatty acid derivatives were explored in the formation of thermosets for coating applications. The epoxy fatty acid derivatives were obtained from renewable resources such as birch tree bark and epoxidized linseed oil. The birch bark was used to isolate 9,10-epoxy-18-hydroxyoctadecanoic acid (EFA) and the epoxidized linseed oil was used to retrieve methyl stearate and 3 different epoxy methyl esters: epoxy methyl oleate/linoleate/linolenate (EMO/EMLO/EMLEN). The obtained epoxy fatty acid derivatives were used in resin formulations together with other reactants or in the synthesis of multifunctional oligomer resins using enzyme catalysis. All resins were cured using different polymerization techniques to form thermosets with a wide variety of properties.Multifunctional oligomer resin were synthesized using Candida Antarctica lipase-B (CALB) as enzyme. It was demonstrated that the synthesis was efficient and the oligomers were obtained from “one-pot” route. In addition, the selectivity of CALB was useful in preserving a variety of functional groups (epoxides, alkenes and thiols) in the final oligomers. The oligomers were cross-linked by either thiol-ene chemistry or cationic polymerization resulting in functional thermosets. It was further shown that surface properties of the cured thermosets could be changed by using post-functionalization.Pure fatty acid methyl esters cure into soft materials. An approach in increasing the thermal and mechanical properties was investigated. The 3 different epoxy functional methyl esters together with a furan-2,5-dicarboxylic acid derivative were investigated in the formation of thermosets. Glass transition temperature (Tg) below 0 °C and above 100 °C were obtained by varying the stoichiometric feed of the reactants.The thermal curing of EFA as a one-component system was investigated by model studies showing that a self-catalyzed process occur. EFA thermally cures into a thermoset without the need of an added catalyst. Furthermore, the thermoset showed adhesive properties.Crude mixture containing methyl stearate, EMO, EMLO and EMLEN obtained from epoxidized linseed oil were investigated as reactive diluent in coil-coatings. The mixture was also compared with commercially available reactive diluents such as fatty acid methyl esters (FAME) obtained from rapeseed oil. The results obtained showed that more fatty methyl esters could be incorporated in the final thermoset when using the epoxidized linseed oil fatty acid derivatives.Real-time Fourier-transform infrared spectroscopy (RT-FTIR) was used during most of the work presented in the thesis and proved to be a powerful tool in monitoring the different reactions and comparing relative reaction rates.I arbetet som presenteras i denna avhandling undersöktes epoxifettsyraderivat vid bildandet av härdplaster för ytmodifieringsapplikationer. Förnybara råvarorna björkbark och epoxiderad linolja andändes för att erhålla epoxifettsyraderivaten. Björkbarken användes för att isolera 9,10-epoxi-18-hydroxidekansyra (EFA) och epoxoderad linolja användes för att extrahera metylstearat och 3 olika epoximetylestrar: epoximetyl oleat/linoleat/linolenat (EMO/EMLO/EMLEN). Epoxifettsyraderivaten användes i olika hartsformuleringar tillammans med andra reaktanter eller vid syntes av multifunktionella oligomerhartser med hjälp av enzymatisk katalys. Med hjälp av olika polymerisationstekniker så härdades alla hartser till härdplaster med en mängd olika egenskaper.Multifunktionella oligomerhartser syntetiserades med hjälp av enzymet Candida Antarctica lipas-b (CALB). Syntesen visade sig vara effektiv och oligomererna erhölls från en sats. Dessutom var selektiviteten hos CALB användbar för att bevara en mängd olika funktionella grupper (epoxider, alkener och tioler) i de slutliga oligomererna. Tiol-ene kemi eller katjonisk polymerisation användes sedan för att härda oligomererna, vilket resulterade i funktionella härdplaster. Vidare visades att ytegenskaperna kunde ändras genom möjlighet till funktionalisering av härdplasterna.Mjuka material återfås då man härdar rena fettsyrametylestrar. Ett sätt att öka de termiska och mekaniska egenskaperna undersöktes. De tre olika epoxifunktionella metylestrarna tillsammans med furan-2,5-dicarboxylsyraderivat blandades i hartser och härdades. Genom att variera de stökiometriska förhållanderna av reaktanterna så erhölls glastemperaturer (Tg) under 0°C och över 100 °C.Undersökningen av termisk härdning av EFA som ett komponentssystem studerades genom modelstudier. Studierna visade att en självkatalyserad process sker då EFA värms upp. Detta leder således till att EFA kan termiskt härda utan behov av en tillsatt katalysator. Dessutom uppvisade härdplasten limegenskaper.Rå blandning innehållande metylstearate, EMO, EMLO och EMLEN som erhölls från epoxiderad linolja undersöktes som en reaktiv utspädare i spolbeläggningar. Blandningen jämfördes även med kommersiellt tillgängliga utspädare så som fettsyrametylestrar (FAME) erhållna från rapsolja. De erhållna resultaten påvisade att fler feta metylestrar kunde integreras i slutliga beläggningen när fettsyraderivat från epoxideradlinolja användes.Realtids Fourier-transform infrarödspektroskopi (RT-FTIR) användes under det mesta av arbetet som presenteras i denna avhandling. RT-FTIR visade sig vara ett kraftfullt vektyg för att övervaka de olika reaktionerna samt jämföra relativa reaktionshastigheter.QC 20190506</p

Biobased Cationically Polymerizable Epoxy Thermosets from Furan and Fatty Acid Derivatives

In the pursuit of environmentally friendly building blocks in polymer chemistry the utilization of biobased monomers is highly desired. In the present study, the biobased monomer 2,5-furandicarboxylic acid (FDCA) has been extended into epoxy thermosets. The study presents the synthesis of diallyl furan-2,5-dicarboxylate (DAFDC) followed by an epoxidation of the allyls to form diglycidyl furan-2,5-dicarboxylate (DGFDC). DGFDC was then copolymerized in both stoichiometric and off-stoichiometric ratios with epoxidized fatty methyl esters to form a range of thermosets. The cross-linking reaction was either thermally or UV-induced cationic polymerization utilizing onium salt initiators where the reactivity was studied by DSC and real-time fourier transform infrared analysis. Furthermore, the structure–property relationships of the final thermosets were determined by dynamic mechanical thermal analysis revealing a possibility to tune the properties over a wide range. In addition thermosets were made from diglycidyl Bisphenol-A (DGEBA) with epoxidized fatty methyl esters made for comparative purposes

Inter-rater reliability and concurrent validity of ROBINS-I: protocol for a cross-sectional study

Abstract Background The Cochrane Bias Methods Group recently developed the “Risk of Bias (ROB) in Non-randomized Studies of Interventions” (ROBINS-I) tool to assess ROB for non-randomized studies of interventions (NRSI). It is important to establish consistency in its application and interpretation across review teams. In addition, it is important to understand if specialized training and guidance will improve the reliability of the results of the assessments. Therefore, the objective of this cross-sectional study is to establish the inter-rater reliability (IRR), inter-consensus reliability (ICR), and concurrent validity of ROBINS-I. Furthermore, as this is a relatively new tool, it is important to understand the barriers to using this tool (e.g., time to conduct assessments and reach consensus—evaluator burden). Methods Reviewers from four participating centers will appraise the ROB of a sample of NRSI publications using the ROBINS-I tool in two stages. For IRR and ICR, two pairs of reviewers will assess the ROB for each NRSI publication. In the first stage, reviewers will assess the ROB without any formal guidance. In the second stage, reviewers will be provided customized training and guidance. At each stage, each pair of reviewers will resolve conflicts and arrive at a consensus. To calculate the IRR and ICR, we will use Gwet’s AC1 statistic. For concurrent validity, reviewers will appraise a sample of NRSI publications using both the New-castle Ottawa Scale (NOS) and ROBINS-I. We will analyze the concordance between the two tools for similar domains and for the overall judgments using Kendall’s tau coefficient. To measure the evaluator burden, we will assess the time taken to apply the ROBINS-I (without and with guidance), and the NOS. To assess the impact of customized training and guidance on the evaluator burden, we will use the generalized linear models. We will use Microsoft Excel and SAS 9.4 to manage and analyze study data, respectively. Discussion The quality of evidence from systematic reviews that include NRS depends partly on the study-level ROB assessments. The findings of this study will contribute to an improved understanding of the ROBINS-I tool and how best to use it

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BackgroundEstimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period.Methods22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution.FindingsGlobal all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations.InterpretationGlobal adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic