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

Effects of e-cigarettes versus nicotine replacement therapy on short-term smoking abstinence when delivered at a community pharmacy.

E-cigarettes (EC) are now the most popular quit aid in England but their effectiveness for cessation if offered at a pharmacy has not been tested. Here we test the effectiveness of offering an e-cigarette with and without nicotine replacement therapy (NRT) on 4-6-week quit rates in adult smokers seeking support from a community pharmacy. A between subject, six-week, prospective, cohort design. 115 smokers (female = 74; age = 46.37,  = 13.56) chose either an EC, EC + NRT or NRT alone, alongside standard behavioural support. Smokers opting for an EC alone or an EC + NRT were more likely to report complete abstinence from smoking at 4-6 weeks (62.2% and 61.5% respectively) compared to NRT alone (34.8%). An EC intervention was significantly more effective for smoking cessation than NRT in this community pharmacy. The results for e-cigarettes appear positive but with the caveat that participants chose their own products which may have introduced bias

Percutaneous mitral heart valve repair--MitraClip.

Mitral regurgitation (MR) is the most common cardiac valvular disease in the United States. Approximately 4 million people have severe MR and roughly 250,000 new diagnoses of MR are made each year. Mitral valve surgery is the only treatment that prevents progression of heart failure and provides sustained symptomatic relief. Mitral valve repair is preferred over replacement for the treatment of MR because of freedom from anticoagulation, reduced long-term morbidity, reduced perioperative mortality, improved survival, and better preservation of left ventricular function compared with valve replacement. A large proportion of patients in need of valve repair or replacement do not undergo such procedures because of a perceived unacceptable perioperative risk. Percutaneous catheter-based methods for valvular pathology that parallel surgical principles for valve repair have been developed over the last few years and have been proposed as an alternate measure in high-risk patients. The MitraClip (Abbott Labs) device is one such therapy and is the subject of this review

Experimental investigations on mechanical properties of multi-layered structure fabricated by GMAW-based WAAM of SS316L

In the present study, the Gas metal arc welding (GMAW) based Wire-arc additive manufacturing (WAAM) process was used to fabricate a multi-layered structure at opti-mized process parameters on SS316L using metal wire of SS316L. The multi-layered structure’s microstructure, macrostructure, and mechanical properties (tensile test, impact test, microhardness, and fractography) were examined at three locations at the top, middle, and bottom sides of the structure. Macrostructure at different zones has confirmed an appropriate bonding between the two layers, complete fusion without oxidation, and free from defects and unwanted geometries. Microstructure results have observed a colony of columnar dendrites in the bottom zone, coarser grains with vertical growth along with the residual ferrite in the middle zone, and vertical dendritic structure with residual ferrite in skeletal shape in the top zone. Results of all tensile properties for top, middle and bottom zone developed by the WAAM process fall in the range values of wrought SS 316 L. The microhardness values were shown a consistent behavior across the built structure in all three zones. The obtained average value for the impact test has shown better strength than commercially used wrought SS 316 L. The results of fractured tensile and fracture impact test specimens revealed many dimples, which suggests a good ductility of the as -built structure. Thus, the obtained results have shown that the built structure using the GMAW-based WAAM process matches the standards for industrial applications. (C) 2022 The Author(s). Published by Elsevier B.V.The authors would like to thank ORSP, PDEU, for sponsoringthe research project in the SRP scheme via project number ORSP/R&amp;D/SRP/2021/010. Authors would also like toacknowledge project funded by Department of Science and Technology (DST), India (SR/FTP/ETA-19/08) for providing GMAW machining setupTThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</p

Meta-analysis Comparing Combined Use of Eicosapentaenoic Acid and Statin to Statin Alone

Role of omega-3-Fatty acids, especially eicosapentaenoic acid (EPA), in reducing cardiovascular events is not clear. We conducted a meta-analysis including trial sequential analysis (TSA) of all available randomized controlled trials (RCTs) assessing the impact of EPA + statin on cardiovascular risk reduction. The aim is to appraise cardiovascular risk reduction with EPA and statin taken together. A comprehensive search of PubMed and EMBASE databases was conducted for all RCTs that compared EPA + Statin versus statin alone and included outcomes related to cardiovascular health. We calculated a comprehensive odds ratio (ORs) and 95% confidence intervals (CIs) using a random-effects model. We included 5 RCTs totaling 27,415 patients. Our results demonstrated that EPA + statin resulted in 18% reduction in the incidence of MACE (OR = 0.78; 95% CI: 0.65 to 0.93, I = 54%, p value \u3c0.01) and 30% reduction in myocardial infarction (MI) (OR = 0.71; 95% CI: 0.61 to 0.82, I = 0% p value \u3c0.01) as compared with statin alone. With respect to MACE, the number needed to treat was 49. The statistical significance for reduction in the incidence of MACE with EPA+ statin was further augmented with trial sequential analysis. However, combined therapy of EPA + statin demonstrated no significant association on incidence of stroke when compared with statin alone or all-cause mortality. In conclusion, this meta-analysis demonstrated that EPA significantly reduced the incidence of MACE when combined with statin therapy, which is mainly driven by a significant reduction in myocardial infarction. 2

Maps & Legends

Lost in the Stacks podcast #3Podcast version of February 26th, 2010, broadcast of Lost in the Stacks. Hosted by Ameet Doshi and Charlie Bennett. Produced by Kyle Tait. Includes interviews with Ethan Kaempf (Georgia Tech student), Lisa Jackson & Muthukumar Subrahmanyam (from the Georgia Tech Center for Geographic Information Systems), and Jay Forrest (Spatial data librarian at the Georgia Tech Library)

Frequency of Cardiovascular Events and In-hospital Mortality With Opioid Overdose Hospitalizations

The United States is in the kernel of cataclysmic opioid misuse epidemic with over 33,000 deaths per year from both prescription and illegal opioids use. One of the most common pernicious effects of opioids is on the cardiovascular system. The purpose of this analysis was to determine the incidence of opioid overdose associated cardiovascular events and its impact on short-term outcomes. This was a retrospective, observational study which utilized data from the National Inpatient Sample from January 2005 to September 2015 using International Classifications of Disease, Ninth Revision, Clinical Modification diagnosis codes to identify patients with opioid overdose and associated cardiovascular outcomes. Cardiovascular events were mainly divided into the following 3 parts: Ischemic Events (ischemic stroke and myocardial infarction), acute heart failure, and arrhythmias. The primary outcome of this study was incidence of any cardiovascular event. This study analyzed a total of 430,459 patients hospitalized with opioid overdose, out of which 36,837 (8.6%) had at least 1 cardiovascular event. In all the opioid overdose hospitalizations, 13,979 (3.2%) developed ischemic events, 3,074 (0.7%) developed acute heart failure, and 22,444 (5.2%) developed arrhythmia. Opioid overdose patients with new-onset cardiovascular events had higher odds for in-hospital mortality (odds ratio 4.55; 95% confidence interval 4.11 to 5.04, p \u3c0.001) as compared to patients without cardiovascular events in the multivariable-adjusted model. This study group also demonstrated longer length of stay and higher cost of hospitalization associated with opioid overdose and associated cardiovascular outcome. In conclusion, opioid overdose is associated with higher rates of cardiovascular events, particularly ischemic events and cardiac arrhythmias. These adverse events eventually lead to higher mortality rates and more resource utilization

Predictors of coronary artery disease in patients with Behçet\u27s disease.

BACKGROUND: Behçet\u27s disease (BD) is a multisystem vasculitis of unknown etiology. We aimed to determine the prevalence and predictors of coronary artery disease (CAD) in patients with BD. METHODS: All adult patients diagnosed with BD from the National Inpatient Sample database using the International Classification of Diseases 9th revision (ICD-9 code 136.1) during 2009-2010 were included in the analysis. We analyzed the demographics, traditional risk factors, prevalence, and predictors of CAD in patients with BD using ICD-9 codes. RESULTS: The prevalence of BD among adults was 0.006% (n = 2,540) of all in-hospital admissions in the USA. The mean age was 43.9 years, with women (45 years) being older than men (40 years) (p \u3c 0.001). Traditional risk factors prevalent in our study were hypertension (35%), hyperlipidemia (17.4%), diabetes mellitus (13.8%), smoking (13.1%), and obesity (7.2%). The prevalence of CAD was 12.1%. Hypertension (OR = 2.20, p = 0.03) and hyperlipidemia (OR = 2.34, p = 0.02) were found to be independent predictors of CAD in a multimodel regression analysis. CONCLUSION: In patients with BD, traditional risk factors associated with CAD were similar to what is expected in the overall population. However, the young age of patients with CAD in this population suggests an accelerated course of atherosclerosis in BD

Discharge Navigator: Implementation and Cross-Sectional Evaluation of a Digital Decision Tool for Social Resources upon Emergency Department Discharge

Introduction: Many patients have unaddressed social needs that significantly impact their health, yet navigating the landscape of available resources and eligibility requirements is complex for both patients and clinicians. &nbsp;Methods: Using an iterative design-thinking approach, our multidisciplinary team built, tested, and deployed a digital decision tool called “Discharge Navigator” (edrive.ucsf.edu/dcnav) that helps emergency clinicians identify targeted social resources for patients upon discharge from the acute care setting. The tool uses each patient’s clinical and demographic information to tailor recommended community resources, providing the clinician with action items, pandemic restrictions, and patient handouts for relevant resources in five languages. We implemented two modules at our urban, academic, Level I trauma center. &nbsp;Results: Over the 10-week period following product launch, between 4-81 on-shift emergency clinicians used our tool each week. Anonymously surveyed clinicians (n = 53) reported a significant increase in awareness of homelessness resources (33% pre to 70% post, P&lt;0.0001) and substance use resources (17% to 65%, P&lt;0.0001); confidence in accessing resources (22% to 74%, P&lt;0.0001); knowledge of eligibility criteria (13% to 75%, P&lt;0.0001); and ability to refer patients always or most of the time (11% to 43%, P&lt;0.0001). The average likelihood to recommend the tool was 7.8 of 10. &nbsp;Conclusion: Our design process and low-cost tool may be replicated at other institutions to improve knowledge and referrals to local community resources.&nbsp