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

Synthesis and characterization of novel benzimidazole embedded 1,3,5-trisubstituted pyrazolines as antimicrobial agents

Efficient syntheses of some new substituted pyrazoline derivatives linked to substituted benzimidazole scaffold were performed by multistep reaction sequences. All the synthesized compounds were characterized using elemental analysis and spectral studies (IR, 1D/2D NMR techniques and mass spectrometry). The synthesized compounds were screened for their antimicrobial activity against selected Gram-positive and Gram-negative bacteria, and fungi strain. The compounds with halo substituted phenyl group at C5 of the 1-phenyl pyrazoline ring (15, 16 and 17) showed significant antibacterial activity. Among the screened compounds, 17 showed most potent inhibitory activity (MIC = 64 μg mL-1) against a bacterial strain. The tested compounds were found to be almost inactive against the fungal strain C. albicans, apart from pyrazoline-1-carbothiomide 21, which was moderately active

Ultrasound Assisted Synthesis and Antimicrobial Evaluation of Novel Thiophene Chalcone Derivatives

Abstract: A series of 10 novel 5-bromo-thiophene containing chalcone derivatives (SN1-SN10) were synthesized under ultrasonic irradiation in the presence of lithium hydroxide monohydrate (LiOH.H 2 O) as a catalyst, which provided the products in good yields after short reaction times under mild conditions. All the synthesized compounds were characterized by spectral data and evaluated for in vitro antibacterial and antifungal activities. Antibacterial and antifungal activities were tested using the agar diffusion method. From the screening studies it was observed that most of the compounds have shown moderate antibacterial and antifungal activities at 500 µg/mL and 100 μg/mL concentrations respectively. Test compounds SN4, SN6, SN7 and SN8 exhibited promising antibacterial activity at 500 µg/mL concentration against the standard ciprofloxacin, whereas all the tested compounds are less active against Candida albicans and moderately active against Aspergillus niger when compared to that of the standard fluconazole

Development and Validation of RP-HPLC Method for the Estimation of Voriconazole in Bulk and Pharmaceutical Dosage Form

Abstract: A simple, accurate and precise reverse phase HPLC method was developed for the estimation of Voriconazole in bulk and pharmaceutical dosage form. The drug was resolved on an enable C18G column (250 mm x 4.6 mm i.d, 5 µm particle size) used with photodiode array UVVisible detector using the mobile phase consisting of Acetonitrile and water in the ratio of 60:40V/V. The flow rate was 1 mL/min and the effluent was monitored at 256 nm. The retention time of the drug was 5.360 min. The linearity of the drug was found to be the concentration range 10-50 µg/mL. The method was found to be reproducible with relative standard deviation of <2%. The percentage recovery was 99.89-100.86%. The results of method have been validated according to ICH guidelines requirements. This method can be successfully employed for the quantitative analysis of Voriconazole in bulk and pharmaceutical dosage form

HRCT Chest Imaging in Pediatric, Adult, and Geriatric COVID-19 patients, with analysis of clinical presentation – A study conducted in Odisha COVID Hospital, KIMS, India

Background: Coronavirus Disease 2019 (COVID-19), a severe acute respiratory syndrome documented as a pandemic by WHO, known to affect patients of all ages.Purpose: The purpose of our study is to characterize the HRCT chest features of COVID-19 patients and analyze the imaging pattern inpediatric, adult and geriatric patients.Materials and Methods: A cohort study of 1208 laboratory-confirmed COVID-19 and HRCT positive patients were undertaken, between May 1, 2020 to July 31, 2020. Patients were divided into 3 groups: Pediatric patients (6 to 18 years), Adults (18 to 60 years) and Geriatric patients (older than 60 years). The demographic, clinical, laboratory and HRCT chest findings were assessed and analyzed between the three groups.Results: A total of 1208 patients with laboratory confirmed COVID-19 infections were assessed. There was a male predominance overall with statistical difference where males are more common affected in adults (86.6%) in compare to pediatric (71%) and geriatric patients (70%). Most of the patients were asymptomatic or had mild symptoms, fever was the most common clinical presentation in pediatric (46.5%), adults (44%) and geriatric patients (52.8%). Increased C-reactive protein was noted in all the three groups with p-value<0.05. Geriatric patients have higher CT positivity (97.1%) and CT severity (10.59±6.7) in comparison to pediatric (66.6%, 4.04±4.6) and adult patients (79.4%, 5.96±6.5). Bilateral and peripheral sub-pleural distribution of pulmonary opacities was the most common pattern seen in both adults and pediatric groups, 56.7% and 50% respectively while diffuse and peripheral distribution predominance in geriatrics (45%) Conclusion: Pediatric, adult and geriatric patients showed distinctive clinical and CT chest finding with pediatric patients have relatively milder symptoms with higher prevalence of negative CTs and lesser extension on imaging while geriatric patients have more symptoms with higher prevalence of positive CTs and more extensive involvement in comparison to adult patients. Keywords: COVID-19, pediatrics, adults, geriatrics, HRCT ches

One-pot multicomponent diastereoselective synthesis of novel dihydro-1<i>H</i>-furo[2,3-<i>c</i>]pyrazoles

<p>An efficient method was developed for the diastereoselective synthesis of novel fused dihydro-1<i>H</i>-furo[2,3-<i>c</i>]pyrazole by a one-pot, four-component reaction of β-keto ester, hydrazine, aromatic aldehyde, and pyridinium ylide in the presence of triethylamine under microwave irradiation in solvent-free conditions in good yields. The merits of this cascade Knoevenagel condensation/Michael addition/cyclization sequence include its high atom economy, good yields, and efficiency of producing three new bonds (two C–C and one C–O) and two stereocenters in a single operation.</p