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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors

Thymidylate synthase (TS) has been an attention-grabbing area of research for the treatment of cancers due to their role in DNA biosynthesis. In the present study, we have synthesised a library of thiazolidinedione-1,3,4-oxadiazole hybrids as TS inhibitors. All the synthesised hybrids followed Lipinski and Veber rules which indicated good drug likeness properties upon oral administration. Among the synthesised hybrids, compound 9 and 10 displayed 4.5 and 4.4 folds activity of 5-Fluorouracil, respectively against MCF-7 cell line whereas 3.1 and 2.5 folds cytotoxicity against HCT-116 cell line. Furthermore, compound 9 and 10 also inhibited TS enzyme with IC50 = 1.67 and 2.21 µM, respectively. Finally, the docking studies of 9 and 10 were found to be consistent with in vitro TS results. From these studies, compound 9 and 10 has the potential to be developed as TS inhibitors

Synthesis, crystal structure and Hirschfeld surface analyses of an alkyl amine based salt, [C5H16N2][ZnCl4] and its enzyme inhibition activity

A novel ionic zinc salt based on alkyl amine is reported. The structure of the studied salt is established by crystal X-ray crystallography, FT-IR and NMR spectroscopy. Furthermore, Hirschfeld surface analyses of the studied salt have also been carried out. In addition, reported salt shows significant enzyme inhibition activity against acetylcholinesterase

Sandwich Composite Panel from Spent Mushroom Substrate Fiber and Empty Fruit Bunch Fiber for Potential Green Thermal Insulation

Massive generation of natural waste fiber from agricultural industries followed by improper disposal management might result in a detrimental effect on our ecosystem contributing to various types of environmental pollution. With the growing significance of climate change, an effort is being undertaken by utilizing natural waste fiber into eco-friendly insulation panels to reduce the environmental impact of buildings. In this research, a composite panel was developed from spent mushroom substrate (SMS) and empty fruit bunch (EFB) fibers via a sandwich technique. Five samples were made, each with a different fiber ratio (100 SMS: 0 EFB, 80 SMS: 20 EFB, 60 SMS: 40 EFB, 40 SMS: 60 EFB, and 0 SMS: 100 EFB) at density 0.8 g/cm3. Fourier transformation infrared (FTIR) Soxhlet extraction followed by thermogravimetric analysis (TGA) indicated that the SMS and EFB fibers were relevant for fabrication into a composite panel for thermal insulation. Thermal conductivity, thermal resistance, and thermal diffusivity values for these five composite samples were 0.231 to 0.31 W/(mK), 0.0194 to 0.0260 m2K/W, and 0.2665 to 0.3855 mm2/s, respectively. The flexural strength of the composite was at the range 15.61 to 23.62 MPa. These research findings suggest that the fabrication of a sandwich composite panel from SMS and EFB fiber is a promising alternative way to utilize natural waste fiber

Removal of Patent Blue Dye Using <i>Ananas comosus</i>-Derived Biochar: Equilibrium, Kinetics, and Phytotoxicity Studies

Patent Blue (PB) dye removal from an aqueous medium was investigated using pineapple fruit peel biochar (PFPB). The presence of functional groups and surface characteristics of PFPB was studied using Fourier transform infrared spectra (FTIR) and scanning electron microscopy (SEM). A study was conducted to assess the pH effect, contact time, concentration of dye, biochar dose, speed of agitation, and temperature on removal of PB (Patent Blue) dye from an aqueous medium by PFPB. The highest 95% elimination of PB dye was reported at pH 2 by PFPB with 600 mg/L concentration of PB dye. Equilibrium studies divulged the favorable adsorption that followed the Langmuir isotherm with a monolayer uptake potential of 10.29 mg/g. Findings of kinetics disclosed that adsorption results were properly explained by the pseudo second-order model. The adsorption phenomenon was exothermic and spontaneous, as observed by thermodynamic variables. PFPB reflected a 37% uptake capacity of PB dye for up to five consecutive cycles in the adsorption and desorption study. A phytotoxicity study exhibited that PFPB-treated PB dye solution enhanced the growth of seedlings and biochemical constituents of lentils. The findings of the present study indicate the immense potential of pineapple fruit peel biochar for anionic dye removal from wastewater systems. Thus, pineapple fruit peel biochar can be utilized as a promising green sorbent for the elimination of Patent Blue dye in industrial effluents, as it is widely available and converts wastewater into reusable assets

Synthesis and characterization of pharmacologically active 18-membered tetraamide macrocyclic complexes of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II): <i>In vitro</i> antimicrobial, anticancer screening, DNA interaction and docking studies

<p>The macrocyclic ligand, 2, 4: 11, 13-Dinaphthyl-1, 5, 10, 14 tetraazacyclooctadecane-6, 9, 15, 18-tetraone, (L) obtained from condensation of 1, 8-diaminonaphthalene and succinic acid, was used to synthesize the complexes of the type, [MLCl₂] [M = Mn(II), Co(II), Ni(II), Cu(II) and Zn(II)] and characterized by spectroscopic techniques. The calf-thymus DNA interaction and CD studies indicated relatively greater binding ability for Cu(II) complex via groove binding. The <i>in vitro</i> cytotoxicity toward the cell line HeLa and MCF-7 has been evaluated by MTT assay. Therefore, Cu(II) complex seems as a superlative candidate offering a probable alternative to traditional chemotherapeutic agents.</p

Isolation, Identification, Spectral Studies and X-ray Crystal Structures of Two Compounds from Bixa orellana, DFT Calculations and DNA Binding Studies

4,6-Diacetylresorcinol (1) and 3-O-methylellagic acid dihydrate (2), both biologically significant compounds, were extracted from Bixa orellana and studied using IR, 1H, and 13C NMR, and UV-vis spectroscopic techniques. X-ray crystallographic techniques were also used to establish the molecular structure of the isolated compounds 1 and 2. Geometric parameters, vibrational frequencies, and gauge including atomic orbital (GIAO) 1H and 13C NMR of 1 and 2 in the ground state were computed by the density functional theory (DFT) using B3LYP/6-311G(d,p) basis set backing up experimental studies and established the correct structure of isolated compounds. The parameters obtained from the combined DFT, and X-ray diffraction studies are mutually agreed to establish correct structures of 1 and 2. In addition, an electrostatic potential map and HOMOLUMO energy gap were made using the DFT calculation to determine the distribution of energy and the chemical reactivity region of the isolated compounds. The current study also provides further insights into the interaction of compound 2 with ct-DNA using numerous biophysical and in silico techniques. Moreover, in silico studies indicate that compound 2 binds to the DNA in the minor groove. Lipinski’s rule of five revealed a higher tendency of compound 2 towards drug-likeness. The bioavailability and synthetic accessibility score for compound 2 was found to be 0.55 and 3.21, suggesting that compound 2 could serve as an effective therapeutic candidate

Natural Clay as a Low-Cost Adsorbent for Crystal Violet Dye Removal and Antimicrobial Activity

This investigation aimed at evaluating the efficiency of micro and nanoclays as a low-cost material for the removal of crystal violet (CV) dye from an aqueous solution. The impacts of various factors (contact time, pH, adsorbent dosage, temperature, initial dye concentration) on the adsorption process have been taken into consideration. Six micro and nanoclay samples were obtained by treating clay materials collected from different locations in the Albaha region, Saudi Arabia. Out of the six tested micro and nanoclays materials, two (NCQ1 and NCQ3) were selected based on the highest adsorption efficiency for complete experimentation. The morphology and structure of the selected micro and nanoclay adsorbents were characterized by various techniques: SEM-EDX, FTIR, XRF, XRD, and ICP-MS. The XRF showed that the main oxides of both nanoclays were SiO2, Al2O3, Fe2O3, K2O, CaO, and MgO, and the rest were impurities. All the parameters affecting the adsorption of CV dye were optimized in a batch system, and the optimized working conditions were an equilibrium time of 120 min, a dose of 30 mg, a temperature of 25 °C, and an initial CV concentration of 400 mg/L. The equilibrium data were tested using nonlinear isotherm and kinetic models, which showed that the Freundlich isotherm and pseudo-second-order kinetics gave the best fit with the experimental data, indicating a physico-chemical interaction occurred between the CV dye and both selected micro and nanoclay surfaces. The maximum adsorption capacities of NCQ1 and NCQ3 adsorbents were 206.73 and 203.66 mg/g, respectively, at 25 °C. The thermodynamic factors revealed that the CV dye adsorption of both micro and nanoclays was spontaneous and showed an exothermic process. Therefore, the examined natural micro and nanoclays adsorbents are promising effective adsorbents for the elimination of CV dye from an aqueous environment