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

A quadruple blind, randomised controlled trial of gargling agents in reducing intraoral viral load among hospitalised COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial

Objectives: 1- To compare the effectiveness of 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline and a novel solution Neem extract (Azardirachta indica) in reducing intra-oral viral load in COVID-19 positive patients. 2- To determine the salivary cytokine profiles of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL- 17 among COVID-19 patients subjected to 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline or Neem extract (Azardirachta indica) based gargles.Trial design: This will be a parallel group, quadruple blind-randomised controlled pilot trial with an add on laboratory based study.Participants: A non-probability, purposive sampling technique will be followed to identify participants for this study. The clinical trial will be carried out at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. The viral PCR tests will be done at main AKUH clinical laboratories whereas the immunological tests (cytokine analysis) will be done at the Juma research laboratory of AKUH. The inclusion criteria are laboratory-confirmed COVID-19 positive patients, male or female, in the age range of 18-65 years, with mild to moderate disease, already admitted to the AKUH. Subjects with low Glasgow coma score, with a history of radiotherapy or chemotherapy, who are more than 7 days past the onset of COVID- 19 symptoms, or intubated or edentulous patients will be excluded. Patients who are being treated with any form of oral or parenteral antiviral therapy will be excluded, as well as patients with known pre-existing chronic mucosal lesions such as lichen planus.Intervention and comparator: Group A (n=10) patients on 10 ml gargle and nasal lavage using 0.2% Povidone-Iodine (Betadiene® by Aviro Health Inc./ Pyodine® by Brooks Pharma Inc.) for 20-30 seconds, thrice daily for 6 days. Group B (n=10) patients will be subjected to 10 ml gargle and nasal lavage using 1% Hydrogen peroxide (HP® by Karachi Chemicals Products Inc./ ActiveOxy® by Boumatic Inc.) for 20-30 seconds, thrice daily for 6 days. Group C will comprised of (n=10) subjects on 10ml gargle and nasal lavage using Neem extract solution (Azardirachta indica) formulated by Karachi University (chemistry department laboratories) for 20-30 seconds, thrice daily for 6 days. Group D (n=10) patients will use 2% hypertonic saline (Plabottle® by Otsuka Inc.) gargle and nasal lavage for a similar time period. Group E (n=10) will serve as positive controls. These will be given simple distilled water gargles and nasal lavage for 20-30 seconds, thrice daily for six days. For nasal lavage, a special douche syringe will be provided to each participant. Its use will be thoroughly explained by the data collection officer. After each use, the patient is asked not to eat, drink, or rinse their mouth for the next 30 minutes.Main outcomes: The primary outcome is the reduction in the intra-oral viral load confirmed with real time quantitative PCR.Randomisation: The assignment to the study group/ allocation will be done using the sealed envelope method under the supervision of Clinical Trial Unit (CTU) of Aga Khan University, Karachi, Pakistan. The patients will be randomised to their respective study group (1:1:1:1:1 allocation ratio) immediately after the eligibility assessment and consent administration is done.Blinding (masking): The study will be quadruple-blinded. Patients, intervention provider, outcome assessor and the data collection officer will be blinded. The groups will be labelled as A, B, C, D or E. The codes of the intervention will be kept in lock & key at the CTU and will only be revealed at the end of study or if the study is terminated prematurely.Numbers to be randomised (sample size): As there is no prior work on this research question, so no assumptions for the sample size calculation could be made. The present study will serve as a pilot trial. We intend to study 50 patients in five study groups with 10 patients in each study group. For details, please refer to Fig. 1 for details.Trial status: Protocol version is 7.0, approved by the department and institutional ethics committees and clinical trial unit of the university hospital. Recruitment is planned to start as soon as the funding is sanctioned. The total duration of the study is expected to be 6 months i.e. August 2020-January 2021.Trial registration: This study protocol was registered at www.clinicaltrials.gov on 10 April 2020 NCT04341688 .Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). Fig. 1 Flow diagram of study-participants\u27 timeline

Knowledge, attitudes and practices of physicians and dentists on medication-related osteonecrosis of the jaw: A cross-sectional survey

Background Bisphosphonate medication can cause osteonecrosis of the jaw, which is an uncommon but serious complication. This survey explores the knowledge, attitudes and practices of dentists and physicians regarding medication-related osteonecrosis of the jaw (MRONJ).Methods A cross-sectional study was conducted among physicians and dentists of Pakistan\u27s secondary and tertiary care hospitals between March and June 2021. Data were collected through a web-based questionnaire distributed among the eligible clinicians involved in prescribing bisphosphonates to patients or management of osteonecrosis. SPSS Statistics 23.0 was used for the data analysis. The frequencies and proportions of the descriptive variables were reported.Results A response rate of 29% was achieved. Only six dentists (n = 6/61; 9.8%) were aware that mammalian target of rapamycin inhibitors could lead to osteonecrosis. Only one-third (n = 9/26; 34.6%) of physicians informed their patients about the possible side effects of bisphosphonates. The most commonly identified risk factor among them was the duration of the drug (n = 77/87; 88.5%) and the least identified was gender (n = 34/87; 39.0%).Conclusions Our study revealed insufficient knowledge among the respondents about the recently updated established guidelines available on MRONJ. The majority of physicians don\u27t refer patients to dentists before prescribing bisphosphonates and other associated medication

Magneto-Transport and Enhanced Spin-Polarized Photo Response in Solution-Processed Vertically Aligned Zn_0.9Ni_0.1O Nanowires

In this study, we grew pristine and Ni-doped vertically aligned zinc oxide nanowires (NWs) on a glass substrate. Both the doped and pristine NWs displayed dominant 002 peaks, confirming their vertical alignment. The Ni-doped NWs exhibited a leftward shift compared to the pristine NWs. TEM measurements confirmed the high crystallinity of individual NWs, with a d-spacing of ~0.267 nm along the c-axis. Ni-doped NWs had a higher density, indicating increased nucleation sites due to nickel doping. Doped NW films on glass showed enhanced absorbance in the visible region, suggesting the creation of sub-gap defect levels from nickel doping. Magnetization vs. magnetic field measurements revealed a small hysteresis loop, indicative of soft ferromagnetic behavior. Current transient plots demonstrated an increase in current with an applied magnetic field. Two-terminal devices exhibited a photo response that intensified with magnetic field application. This increase was attributed to parallel grain alignment, resulting in enhanced carrier concentration and photo response. In the dark, transport properties displayed negative magnetoresistance behavior. This magneto-transport effect and enhanced photo response (under an LED at ~395 nm) were attributed to giant magnetoresistance (GMR) in the aligned NWs. The observed behavior arose from reduced carrier scattering, improved transport properties, and parallel spin alignment in the magnetic field

Exergy, advance exergy, and exergo-environmental based assessment of alkanol amine- and piperazine-based solvents for natural gas purification

Purification of Natural gas is vital for utilizing it as a source of energy harvesting for the world. Amine-based chemical absorption technique is the most utilized in the gas field for the purification of gas that ensures the purity of the sweet gas stream with the elimination of carbon dioxide. However, it is considered an energy -intensive process to deal with considerable energy loss and environmental damage to the ecosystem. Five cases have been developed in this study based on various blends comprising mono and tertiary amines in combination with piperazine with a focus on the use of Aqueous Monodiethanolamine (Aq. MDEA), Aqueous Monoethanolamine (Aq. MEA) and piperazine (Pz) for the CO2 sequestration from the sour natural gas extracted from the remote location located in the province of Baluchistan in Pakistan. The use of exergy, advanced exergy, and exergo environment for optimizing and selecting a suitable solvent combination that may result in an effective separation process has been proposed. Five cases have been developed based on various blends such as mono and tertiary amines combined with piperazine. From the results of all the studied scenarios, Case IV, based on the combination of Aqueous monoethanolamine and piperazine, provides reduced exergy destruction of 2551.7 KW. It was observed that the maximum removal of CO2 around 99.87 wt% is achieved in case IV. In addition, advance exergy analysis also highlights that case-IV has a venue of 25% exergy destruction avoidable, which would further enhance its performance. Nevertheless, still, case-IV has 75% exergy destruction un-avoidable. The environmental factors show that Case-IV has a reduced exergy destruction factor of 0.96, a highly environmentally benign choice as a solvent with a high value of 1.03, and case-IV has the higher operational stability and higher exergy efficiency with an exergy stability value of 0.40. Therefore, monoethanolamine combined with piperazine to be an effective and efficient solvent blend that could be an energy-effective approach for sweetening the natural gas

Tumor Necrosis Factor-Alpha Gene Promoter Region Polymorphism and the Risk of Coronary Heart Disease

Background. Tumor necrosis factor-alpha (TNF-) gene polymorphisms have been implicated in the manifestation of atherosclerosis. Controversy exists regarding the link between the cytokine's variant genotype and CHD among different ethnic groups. There have been fewer studies on the TNF-gene −1031T>C and −863C>A polymorphisms in relation to CHD. Therefore, the current study was designed to investigate the association of the TNF-gene −1031T>C and −863C>A polymorphisms with CHD in a Pakistani population. Methods. Patients with CHD ( = 310) and healthy individuals ( = 310) were enrolled in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. A significant difference was observed in the −863C>A polymorphism between patients with CHD and control subjects ( < 0.0001). CHD risk was positively associated with the variant allele −863A ( < 0.0001) in the study subjects. There was no significant link between the −1031T>C polymorphism and CHD risk in the study population. Haplotypes A-T and A-C of the TNF-alpha gene loci at −863 and −1031 showed higher frequency in the patient group compared with controls ( < 0.05). Conclusion. The TNF-−863C>A gene polymorphism was associated with the pathogenesis of CHD while the −1031T>C polymorphism did not show any link with the disease in a Pakistani population

An updated systematic review on toothbrush contamination: An overlooked oral health concern among general population

Objectives: The present systematic review was conducted to give an overview of toothbrush contamination among the general population and the factors affecting toothbrush contamination with an evidence-based approach. Data/sources: Medline (Pub Med), CINAHL Plus, Cochrane Library and Dentistry and Oral Health Sciences Source were searched for the results after applying the search strategy from January 2012 to May 2022, following inclusion and exclusion criteria. The data were collected using a self-made data collection form on study characteristics, population attributes and the main features, including the study\u27s outcomes. The methodological quality of the included studies was independently evaluated based on the Joanna Briggs Institute\u27s (JBI) critical appraisal checklist for cross-sectional studies and the Risk of Biasness Tool-1 (Rob-1) for randomized controlled trials (RCTs). A descriptive analysis of the included studies was done using SWiM guidelines. The impact of charcoal and non-charcoal brushes on toothbrush disinfection was quantitatively analysed using a forest plot. Study selection: Of the 687 studies screened by title and abstract, 27 articles were selected for full-text evaluation using the EndNote reference program (Ver. X9.2). From these, 15 qualified and were included in the systematic review. Among the selected studies, eight were RCTs, six were cross-sectional studies, and the remaining one was an in vitro experimental study. Conclusions: The toothbrush becomes contaminated even after its first usage, and the contamination level rises with continued use. There are a number of factors that lead to the contamination of brushes, such as increased humidity brought on by a plastic cover or a toilet setting. Charcoal brushes show significant efficacy as compared to regular bristles in reducing toothbrush contamination; however, more RCTs are needed to further assess its efficacy. Nevertheless, rinsing with chlorhexidine mouthwash after daily brushing shows favourable result