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

2- 4-Acetyl-5-(biphenyl-4-yl)-4,5-dihydro-1,3,4-oxadiazol-2-yl phenyl acetate

In the title molecule, C(24)H(20)N(2)O(4), the five-membered oxadiazole ring is nearly planar (r.m.s. deviation = 0.053 angstrom) and the phenyl ring of the biphenyl unit attached to it forms a dihedral angle of 73.2 (1)degrees; the other phenyl ring is close to coplanar with the oxadiazole ring [dihedral angle = 6.2 (2)degrees]

Biphenyl-4-carbaldehyde azine

The complete molecule of the title compound, C(26)H(20)N(2), is generated by crystallographic inversion symmetry. The terminal phenyl ring is twisted by 19.2 (1)degrees with respect to the adjacent phenylene ring

N-Acetyl-2-hydroxy-N'-[methoxy(1-methylindol-2-yl)methyl]benzohydrazide

In the crystal structure of the title Schiff-base, C(20)H(21)N(3)O(4), the amino group forms an N-H⋯O hydrogen bond to the acetyl group of an adjacent mol-ecule, forming a zigzag chain. The 2-hydr-oxy group is inter-nally hydrogen bonded to the amido group though an O-H⋯O hydrogen bond

Di-n-butyl-ammonium 2-(3,5-di-tert-butyl-4-hydroxy-benzyl-sulfan-yl)nicotinate

The asymmetric unit of the title compound, C(8)H(20)N(+)·C(21)H(26)NO(3)S(-), contains two indpendent ion pairs which are disposed about a psuedo-inversion center, generating an ammonium-carboxylate N-H⋯O hydrogen-bonded four-component cluster. In the crystal structure, adjacent clusters are linked by hydr-oxy-carboxylate O-H⋯O hydrogen bonds, forming a chain

Anaemia and iron deficiency anaemia among aboriginal schoolchildren in rural Peninsular Malaysia: an update on a continuing problem

A cross-sectional study to determine the current prevalence of anaemia and iron deficiency anaemia (IDA) and to investigate the possible risk factors for IDA was carried out on 241 aboriginal schoolchildren (120 boys, 121 girls) aged 7-12 years and living in remote areas in Pos Betau, Pahang, Malaysia. Haemoglobin (Hb) level was measured and serum iron status was assessed by serum ferritin (SF), serum iron (S1) and total iron binding capacity measurements. Socioeconomic data were collected using pre-tested questionnaires. All children were screened for intestinal parasitic infections. Overall, 48.5 (95 CI 42.3-54.8) of children were anaemic (Hb < 12 g/dl). The prevalence of IDA was 34 (95 CI 28.3-40.2), which accounted for 70.1 of the anaemia cases. The prevalence of IDA was significantly higher in females than males. Low levels of mothers' education and low household income were identified as risk factors for IDA. Severe trichuriasis also found to be associated with low SF and St. Logistic regression confirmed tow levels of mothers' education and gender as significant risk factors for IDA. Improvement of socioeconomic status and health education together with periodic mass deworming should be included in public health strategies for the control and prevention of anaemia and IDA in this population. (c) 2008 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved

Susceptibility of Aedes albopictus skuse (Diptera: Culicidae) to permethrin in Kuala Lumpur, Malaysia

Background: Insects control using insecticides is used extensively and intensively in vector control programs in many countries including Malaysia. Because of this, mosquito species have been found to develop various levels of resistance towards these insecticides, leading to failure in vector control activities. Objectives: We determined permethrin resistance status in laboratory susceptible, permethrin-selected, and field strains of Aedes albopictus. Methods: The susceptibility status of laboratory susceptible strain, permethrin-selected strain, and four field strains of Aedes albopictus collected from Kuala Lumpur were determined using three standard laboratory tests, WHO larval bioassay, WHO adult mosquito bioassay, and microassay of mixed function oxidases (MFOs). Results: The LC50 values of permethrin-selected strain and field strains obtained from the WHO larval bioassay were almost two times higher (0.38-0.44 mg/L) than the LC50 value of the laboratory strain (0.20 mg/L). In the WHO adult bioassay, the susceptibility of permethrin-exposed of both permethrin-selected strain, and field strains (LT50 = 19.39 to 20.65 min) were reduced for 1.31 to 1.72 times after been exposed to the synergist, piperonyl butoxide (PBO) prior to permethrin. Complete mortalities were also recorded in both permethrin-exposed and PBO + permethrin-exposed Ae. albopictus of all strains, twenty-four hours post-exposure. For the MFOs enzyme microassay, a significant difference (p <0.05) in the mean absorbance of elevated oxidase activity at 630 nm was observed between all strains of both the non-exposed and PBO-exposed Ae. albopictus. Strong and significant positive correlations were also observed between LT50 values of permethrin-exposed and PBO + permethrinexposed with oxidase level in Ae. albopictus tested (r = 0.943; p <0.05). Conclusion: These results indicate the association of oxidase activity with permethrin resistance development in Ae. albopictus