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 Acute Aquatic High-Intensity Intermittent Exercise on Blood Pressure and Arterial Stiffness in Postmenopausal Women with Different ACE Genotypes

The present study investigated the effects of acute aquatic high-intensity intermittent jumping (HIIJ) on blood pressure (BP) and arterial stiffness in postmenopausal women with different angiotensin-converting enzyme genotypes (ACE). We recruited 12 postmenopausal women carrying the ACE deletion/deletion (DD) genotype and 61 carrying the insertion/insertion or insertion/deletion (II/ID) genotype. The participants performed 12 trials of 30 s, 75% heart rate reserve (HRR) jumping, and 60 s, 50% HRR recovery, and 3 trials of 40 s upper limb resistance exercises were performed as fast as possible. The heart rate (HR) and BP were measured before exercise, immediately, 10 min, and 45 min after exercise. The brachial-ankle pulse wave velocity (baPWV) was measured before and after exercise. The systolic blood pressure (SBP) of the DD genotype increased more significantly than those with the II/ID genotype post-exercise (30.8 ± 4.48 vs. 20.4 ± 2.00 mmHg, p = 0.038). The left and right sides of baPWV increased significantly after exercise (1444.8 ± 29.54 vs. 1473.4 ± 32.36 cm/s, p = 0.020; 1442.1 ± 30.34 vs. 1472.0 ± 33.09, p = 0.011), and there was no significant difference between the two groups. The HIIJ increased baPWV. The postmenopausal women with the DD genotype have a higher SBP increased post-exercise than those with II/ID genotype. These findings suggest that the aquatic exercise program has better effects in decreasing blood pressure in postmenopausal women with the II/ID genotype. Those with the DD genotype should pay attention to the risk of increasing blood pressure after aquatic HIIJ exercise

Impact of Extracorporeal Membrane Oxygenation Support on Clinical Outcome of Pediatric Patients with Acute Cardiopulmonary Failure: A Single-Center Experience

Background: Conventional therapy against acute pediatric cardiopulmonary failure (APCPF) caused by a variety of disease entities remains unsatisfactory with extremely high morbidity and mortality. For refractory APCPF, extracorporeal membrane oxygenation (ECMO) is one of the last resorts. Methods: In this study, the in-hospital outcomes of pediatric patients with refractory APCPF receiving ECMO support were reviewed. Results: Between August 2006 and May 2011, a single-center cohort study was performed in pediatric patients who required ECMO support due to cardiogenic shock or severe hypoxemia. A total of 22 patients with mean age of 7.0 ± 6.3 years received ECMO (male = 11; female = 11). The indications included acute fulminant myocarditis (AFM) (n = 6), congenital diaphragmatic hernia (CDH) (n = 3), acute respiratory distress syndrome (ARDS) (n = 6), enterovirus 71 (n = 3), viral sepsis (n = 2), refractory ventricular fibrillation due to long QT syndrome (n = 1), and pulmonary edema with brain herniation (n = 1). Eighteen patients received veno-arterial (VA) mode ECMO, while another four patients undertook the veno-venous (VV) mode. The duration of ECMO use and hospitalization were 6.1 ± 3.1 and 24.4 ± 19.4 days, respectively. The survival rate in patients with AFM was 100% (n = 6). Successful ECMO weaning with uneventful discharge from hospital was noted in 14 (63.6%) patients, whereas in-hospital mortality despite successful ECMO weaning occurred in 5 patients (22.7%). Failure in ECMO weaning and in-hospital death was noted in 3 patients (13.6%). Conclusions: ECMO resuscitation is an effective strategy in the clinical setting of APCPF

Retention Model of TaO/HfO x and TaO/AlO x RRAM with Self-Rectifying Switch Characteristics

Abstract A retention behavior model for self-rectifying TaO/HfO x - and TaO/AlO x -based resistive random-access memory (RRAM) is proposed. Trapping-type RRAM can have a high resistance state (HRS) and a low resistance state (LRS); the degradation in a LRS is usually more severe than that in a HRS, because the LRS during the SET process is limited by the internal resistor layer. However, if TaO/AlO x elements are stacked in layers, the LRS retention can be improved. The LRS retention time estimated by extrapolation method is more than 5 years at room temperature. Both TaO/HfO x - and TaO/AlO x -based RRAM structures have the same capping layer of TaO, and the activation energy levels of both types of structures are 0.38 eV. Moreover, the additional AlO x switching layer of a TaO/AlO x structure creates a higher O diffusion barrier that can substantially enhance retention, and the TaO/AlO x structure also shows a quite stable LRS under biased conditions

No correlation between body mass index and 30-day prognostic outcome in Asians with acute ST-elevation myocardial infarction undergoing primary coronary intervention

Background: This study investigated whether body mass index (BMI) was a risk factor predictive of 30-day prognostic outcome in Asians with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Material and methods: Data regarding the impact of BMI on the prognostic outcome in Asian populations after acute STEMI is scarce. A number of 925 STEMI patients were divided into three groups according to the BMI: normal weight (<25 kg/m2), overweight (≥25.0 to <30.0 kg/m2) and obese (≥30.0 kg/m2). Results: The obese group was significantly younger with significantly higher incidences of smoking and diabetes mellitus. The incidences of multi-vessel disease, final thrombolysis in myocardial infarction (TIMI)-3 flow, advanced Killip score, advance congestive heart failure, 30-day mortality and combined 30-day major adverse clinical outcome (MACO) did not differ among the three groups. Multiple regression analysis showed the age, unsuccessful reperfusion and lower left ventricular ejection fraction were most significant and independent predictor of 30-day mortality. Conclusion: BMI is not a predictor of 30-day prognostic outcome in Asians with STEMI undergoing primary PCI

Impact of chronic obstructive pulmonary disease on patient with acute myocardial infarction undergoing primary percutaneous coronary intervention

Background: This study reported the incidence and prognostic outcome of chronic obstructive lung disease (COPD) patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: Between January 2002 and May 2011, totally 1554 consecutive patients who experienced STEMI undergoing primary PCI were enrolled into the study. Results: Of the 1554 patients, 124 (9.7%) with diagnosis of COPD and 1430 (90.3%) without COPD were categorized into group 1 and group 2. Although no difference in in-hospital mortality was noted between the two groups (p = 0.726). However, the hospitalization duration was notably longer (p = 0.003), the incidences of recurrent MI and re-hospitalization for congestive heart failure were significantly higher in group 1 than in group 2 (all p < 0.02). Although Kaplan-Meier analysis demonstrated that the incidence of freedom from one-year major adverse clinical outcome (MACO) (defined as recurrent MI, re-admission for congestive heart failure was significantly lower in group 1 than group 2 (p = 0.012), multivariate Cox regression analysis showed COPD was not an independent predictor of MACO-free time after adjusting traditional risk factors. Conclusion: COPD was not an independent predictor of short-term and medium-term MACO in patients with STEMI undergoing primary PCI