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

Table_1_Opium abuse and stroke in Iran: A systematic review and meta-analysis.docx

IntroductionOpium dependence is a significant health concern in low and middle-income countries, leading to a considerable number of deaths annually. Opium has several detrimental effects on its consumers. Data regarding the impact of opium on stroke are controversial. The objective of this study is to evaluate the association between opium dependence and stroke.MethodsI conducted a systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the association between opium dependence and stroke. Following the extraction of qualitative findings from included studies, a meta-analysis was performed to assess the pooled estimate of odds ratios (ORs).ResultsEight and four studies were included in qualitative and quantitative synthesis, respectively. Opium dependence increases the hazard of stroke mortality. Also, opium increases the odds of ischemic stroke by 127% (pooled OR = 2.27, 95% CI: 1.47–3.07).ConclusionOpium not only merely increases the odds of being diagnosed with ischemic stroke but also leads to a notable increase in the mortality rate following stroke.</p

Congenital Bladder and Urethral Agenesis: Two Case Reports and Management

Background. Agenesis of the bladder and urethra is a rare congenital anomaly, with a very few living cases reported in the literature so far. Case Presentation. We are reporting two female patients (3 and 6 years old) with bladder and urethral agenesis who presented with urinary incontinence. In both patients, magnetic resonant imaging (MRI) revealed a case of bladder and urethral agenesis with normal ureters draining into the vagina. Patients underwent a neobladder and conduit creation surgery. The neobladder was constructed from the whole cecum and a part of the ascending colon, followed by an anastomose of the ureters into the neobladder in a nonrefluxing fashion; the appendix was used simultaneously as a continent catheterizable conduit. The two patients attained urinary continence postoperatively. Conclusion. We reported two cases of bladder agenesis, and for the first time, we have performed neobladder creation surgery using the cecum and ascending colon. One-year follow-up did not reveal any complications

The Novel Coronavirus Disease (COVID-19): A PRISMA Systematic Review and Meta-Analysis of Clinical and Paraclinical Characteristics

An outbreak of pneumonia, caused by a novel coronavirus (SARS-CoV-2), was identified in China in December 2019. This virus expanded worldwide, causing global concern. Although clinical, laboratory, and imaging features of COVID-19 are characterized in some observational studies, we undertook a systematic review and meta-analysis to assess the frequency of these features. We did a systematic review and meta-analysis using three databases to identify clinical, laboratory, and computerized tomography (CT) scanning features of rRT-PCR confirmed cases of COVID-19. Data for 3420 patients from 30 observational studies were included. Overall, the results showed that fever (84.2%, 95% CI 82.6-85.7), cough (62%, 95% CI 60-64), and fatigue (39.4%, 95% CI 37.2-41.6%) are the most prevalent symptoms in COVID-19 patients. Increased CRP level, decreased lymphocyte count, and increased D-dimer level were the most common laboratory findings. Among COVID-19 patients, 92% had a positive CT finding, most prevalently ground-glass opacification (GGO) (60%, 95% CI 58-62) and peripheral distribution opacification (64%, 95% CI 60-69). These results demonstrate the clinical, paraclinical, and imaging features of COVID-19

Efficacy of Oral Administration of Allium sativum Powder “Garlic Extract” on Lipid Profile, Inflammation, and Cardiovascular Indices among Hemodialysis Patients

Background. Inflammation plays a prominent role in the deteriorating cardiovascular risk of hemodialysis patients. Utilization of herbal remedies, especially garlic extract, in these patients has resulted in promising improvement in lipid profile, inflammation, and cardiovascular markers. Purpose. In this survey, we aimed to determine the effects of oral administration of Allium sativum powder on lipid profile, inflammation, and cardiovascular markers among hemodialysis patients. Methods. In this interventional double-blinded randomized crossover study, 70 patients were enrolled and assigned in two groups. Each group received 300 mg of garlic powder BID or placebo for eight weeks; after a six-week wash-out period, the agents were switched between two groups so that the group who received garlic powder in the first eight weeks received placebo for the second eight weeks, and vice versa. Venous blood samples were obtained in baseline, wash-out period, and at the end of study. Following obtaining laboratory data, BUN, creatinine, Na, K, Ca, Ph, homocysteine, and lipid profile were compared. Results. No significant differences were shown at baselines of outcomes between the garlic and placebo group (p value>0.05). However, there was a significant decrease in absolute values of OXLDL (mean placebo = 979.63, mean garlic = 676.54; p value<0.001) and HCY (mean placebo = 36.54, mean garlic = 27.78; p value<0.001). In addition, significant treatment differences were seen in change values of Ca (placebo = 1.17, garlic = 0.21; p value = 0.006), TG (placebo = −6.71, garlic = -24.14; p value = 0.014), OXLDL (placebo = −281.30, garlic = -699.78; p value<0.001), and HCY (placebo = −0.24, garlic = −6.68; p value<0.001). Conclusion. In this study, Allium sativum powder demonstrated efficacy in lipid profile improvement and renal protective effects among hemodialysis patients

Oxidative balance score and risk of cancer: a systematic review and meta-analysis of observational studies

Abstract Background The oxidative balance score (OBS) has been utilized to assess the overall pro- and antioxidant exposure status in various chronic diseases. The current meta-analysis was carried out to pool the association between OBS and the risk of cancer. Methods We systematically searched the Web of Science, PubMed, Scopus, Embase, and Google Scholar up to August 2023. All observational studies which evaluated the association of OBS with the risk of cancers were included. There was no time of publication or language restrictions. Heterogeneity between studies was assessed using the Chi-square-based Q-test and the I2. A random-effects model meta-analysis was conducted to estimate the pooled effect sizes. Possible sources of heterogeneity were explored by subgroup and meta-regression analysis. Results Totally, 15 studies (9 case–control and 6 cohorts) were eligible for meta-analysis. Random effect model meta-analysis of case–control studies showed that higher OBS significantly decreases the odds of cancers (pooled OR: 0.64, 95% CI: 0.54, 0.74). In the cohort studies, the association of OBS with the risk of cancers was not significant (pooled HR: 0.97, 95% CI: 0.80,1.18). The subgroup analysis showed that cancer type and gender were the potential sources of heterogeneity. Conclusion Our results show an inverse and significant association between higher OBS and odds of colorectal cancers in case–control and cohort studies. In the case of prostate cancer in cohort studies, our results did not align with the hypothesis. Considering the importance of diet and antioxidant balance in the conditions of malignancy, it is suggested to conduct more comprehensive studies with standard measurement methods to obtain conclusive results

Therapeutic and Preventive Effects of Olea europaea Extract on Indomethacin-Induced Small Intestinal Injury Model in Rats

Background. Olea europaea (known as olive fruit) has anti-inflammatory and antioxidant activities and many potential health benefits including gastric inflammation reduction has been shown previously. This study aimed to investigate the preventive and therapeutic effects of O. europaea extract on the early histological changes in indomethacin-induced small intestinal injury model with the plasma D-lactate concentration being measured as a tool for determination of intestinal permeability. Methods. In this experimental study, two separate protective and therapeutic protocols were designed. In both experiments, male Wistar rats were randomly divided into 4 groups and either pretreated with 0, 100, 200, or 400 mg/kg/day of O. europaea extract or received the treatment after administration of indomethacin. Their small intestines were examined to compare the histological changes. The intestinal injury severity was evaluated according to the presence of eosinophils, plasma cell infiltration, edema, congestion, and hyperplasia of the crypt using a histological scoring system. Also, measured were the presence of neutrophils, decreased villus length-to-crypt depth ratio, and destructed villus architecture. The plasma concentration of D-lactate was measured as well. Results. The therapeutic use of O. europaea decreased the eosinophil, edema, congestion, and crypt hyperplasia scores compared to the control group. Although no significant difference was seen between groups of the preventive experiment in plasma cell infiltration score, villus length-to-crypt depth ratio, neutrophil infiltration, and percentage of destructed villus architecture, treatment with O. europaea caused a reduction in edema, eosinophil, congestion, and crypt hyperplasia score. In both experiments, no significant difference was seen between groups for villus length-to-crypt depth ratio, neutrophil infiltration, and percentage of destructed villus architecture. Plasma D-lactate concentration was decreased in all O. europaea-treated groups compared to the control group in the therapeutic and preventive experiments (p<0.01, one-way ANOVA followed by the Dunnett test). Conclusion. O. europaea extract can be used to decrease some side effects of indomethacin on intestinal tissue and enhances the gastrointestinal function. O. europaea extract could be considered as a potential herbal supplement in the treatment of intestinal morphological injuries

Epidemic size, trend and spatiotemporal mapping of SARS-CoV-2 using geographical information system in Alborz Province, Iran

Abstract Background The first confirmed cases of COVID-19 in Iran were reported in Qom city. Subsequently, the neighboring provinces and gradually all 31 provinces of Iran were involved. This study aimed to investigate the case fatility rate, basic reproductive number in different period of epidemic, projection of daily and cumulative incidence cases and also spatiotemporal mapping of SARS-CoV-2 in Alborz province, Iran. Methods A confirmed case of COVID-19 infection was defined as a case with a positive result of viral nucleic acid testing in respiratory specimens. Serial interval (SI) was fitted by gamma distribution and considered the likelihood-based R0 using a branching process with Poisson likelihood. Seven days average of cases, deaths, doubling times and CFRs used to draw smooth charts. kernel density tool in Arc GIS (Esri) software has been employed to compute hot spot area of the study site. Results The maximum-likelihood value of R0 was 2.88 (95%, CI: 2.57–3.23) in the early 14 days of epidemic. The case fatility rate for Alborz province (Iran) on March 10, was 8.33% (95%, CI:6.3–11), and by April 20, it had an increasing trend and reached 12.9% (95%,CI:11.5–14.4). The doubling time has been increasing from about two days and then reached about 97 days on April 20, 2020, which shows the slowdown in the spread rate of the disease. Also, from March 26 to April 2, 2020 the whole Geographical area of Karj city was almost affected by SARS-CoV-2. Conclusions The R0 of COVID-19 in Alborz province was substantially high at the beginning of the epidemic, but with preventive measures and public education and GIS based monitoring of the cases,it has been reduced to 1.19 within two months. This reduction highpoints the attainment of preventive measures in place, however we must be ready for any second epidemic waves during the next months