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

Persistent, Poorly Responsive Immune Thrombocytopenia Secondary to Asymptomatic COVID-19 Infection in a Child

Immune thrombocytopenic purpura (ITP) secondary to asymptomatic COVID-19 infection, especially in children, is not reported. Furthermore, persistent, treatment-resistant ITP secondary to COVID-19 is not reported. We report a previously healthy 14-year-old Asian boy who developed secondary ITP following an asymptomatic COVID-19 infection and is having a relapsing and remitting cause with poor response to immunosuppressants even after 21 months following the diagnosis. This case emphasizes the importance of testing for COVID-19 in newly diagnosed ITP patients and the need for follow-up platelet counts in patients who recover from COVID-19 as it may follow into developing secondary ITP yet being asymptomatic until you present with a bleeding complication of ITP. The poor response to standard immunosuppression warrants more understanding of the pathophysiology of persistently low platelets following COVID-19 infection. Long-term sequelae of the disease highlight the importance of getting vaccinated for COVID-19 despite COVID-19 being no longer a global emergency

Body iron status of children and adolescents with transfusion dependent β-thalassaemia: trends of serum ferritin and associations of optimal body iron control

Abstract Objective This cross sectional study aims to describe the body iron status, trends of serum ferritin and associations of optimal body iron control in patients aged below 16 years with transfusion dependent β-thalassaemia attending Paediatric and Adolescent Thalassaemia Centres of the Colombo North Teaching Hospital of Sri Lanka. Results Out of 54 children, 51% were males and a majority were aged 11–16 years; 83% had β-thalassaemia major while 13% had HbE β-thalassaemia. Mean serum ferritin was 1778(± 1458) µg/l and 29% had optimal serum ferritin (below 1000 µg/l). Trend of mean serum ferritin over time showed gradual decline between 2011 and 2017 and longitudinal trend of individual patients at yearly intervals showed gradual rise until 5 years of age and plateauing thereafter. All except two patients were receiving iron chelator medication of which the most commonly used was oral deferasirox (92%). The most common iron-related complications were short stature (24.1%) and pubertal delay (42.8% of > 14 years). None of the patients had hypothyroidism, hypoparathyroidism or diabetes. Optimal serum ferritin levels were significantly associated with the diagnosis of thalassaemia at a later age (23.6 vs 9.0 months) and higher family income (OR-4.81;95%CI 1.17–19.67) however was not associated with the age of the patient or duration of transfusion

Hypoglycaemia and fits in a thyrotoxic man

We report prolonged severe hypoglycaemia with raised serum insulin levels in a Sri Lankan man with recently diagnosed Graves disease being treated with carbimazole. We diagnosed insulin autoimmune syndrome on the basis of raised anti-insulin antibody levels, and this diagnosis was supported by the subsequent course of the illness. The patient recovered completely after carbimazole was replaced with propylthiouracil and he was treated with dextrose infusions, frequent high-carbohydrate meals and a course of prednisolone

Glycaemic control and avenues for improvement among people with type 2 diabetes mellitus from rural Sri Lanka – a retrospective cohort study

10.1016/j.lansea.2023.100169The Lancet Regional Health - Southeast Asia100169-10016

Psychological morbidity among children with transfusion dependent β-thalassaemia and their parents in Sri Lanka.

BACKGROUND:Thalassaemia is a chronic disease which requires lifelong treatment in a majority. Despite recent advances in the medical care, minimal attempts are made to improve psychological health in these patients. In this study, we aim to describe the psychological morbidity in patients with transfusion dependent β-thalassaemia and their mothers in Sri Lanka. METHODS:This case control study was conducted in the three largest thalassaemia centres of Sri Lanka. All patients with transfusion dependent β-thalassaemia aged 4-18 years were recruited as cases whilst a randomly selected group of children without chronic diseases were recruited as controls. Psychological morbidity of children was assessed using the Strengths and Difficulties Questionnaire and depressive symptoms of mothers was assessed by the Centre for Epidemiological Studies Depression Scale. RESULTS:288 transfusion dependent β-thalassaemia patients and equal number of controls were recruited. Abnormal emotional, conduct, hyperactivity and peer relationship symptom scores were reported by 18%, 17%, 9% and 14% of patients with thalassaemia respectively. Prevalences of abnormal psychological symptom scores in all domains were significantly higher among patients compared to controls. Abnormal conduct symptoms were significantly more prevalent among patients with HbE β-thalassaemia and those with suboptimal pretransfusion haemoglobin levels, lower transfusion volumes, hypothyroidism and undernutrition. Short stature was associated with abnormal emotional and hyperactivity scores. Depressive symptoms were significantly higher among mothers of patients with thalassaemia. Higher depressive symptom scores in mothers were significantly associated with abnormal emotional, conduct and peer relationship symptom scores in children. CONCLUSIONS:A higher proportion of patients with transfusion dependent β-thalassaemia had abnormal psychological symptom scores. Abnormal conduct symptoms were more prevalent among patients with HbE β-thalassaemia, those who were inadequately transfused and having hypothyroidism and undernutrition. Mothers of the children with transfusion dependent β-thalassaemia had significantly higher depressive symptoms which were significantly associated with psychological symptoms among children

MOESM1 of Body iron status of children and adolescents with transfusion dependent β-thalassaemia: trends of serum ferritin and associations of optimal body iron control

Additional file 1: Table S1. Clinical and socio-demographic characteristics of the study population

Identification of patients with type 2 diabetes with non-alcoholic fatty liver disease who are at increased risk of progressing to advanced fibrosis: a cross-sectional study

10.1136/bmjopen-2022-063959BMJ Open131e063959-e06395