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

Microfilaria in forearm swelling aspirate: An unusual finding

Filariasis is a major public health problem in tropical countries, including India. The disease is endemic all over India, especially in Uttar Pradesh, Bihar, Jharkhand, Andhra Pradesh, Orissa, Tamil Nadu, Kerala, and Gujarat. A majority of infected individuals in filarial endemic communities are asymptomatic. Adult worms live in the lymphatic vessels of the definitive host and microfilaria is released and circulates in the peripheral blood. Cases of microfilaremia have been reported from atypical sites such as thyroid, lymph node, pleural and pericardial fluid, breast lump, and bone marrow. We here present a case of microfilaria in the forearm swelling found on fine-needle aspiration cytology, which is an unusual finding

Cranial and extracranial presentations of schwannoma: Original study

Introduction: Schwannoma is a benign tumor that originates from the Schwann cells of the peripheral nerves. Schwannomas are usually a solitary, slow growing benign neoplasm, and well-encapsulated. The present study was carried out to know the cranial and extracranial presentations of schwannoma at various locations in the body. Materials and Methods: This was a retrospective and prospective study carried out for a period of 2 years, on patients who underwent excision of the tumor at different locations, which were diagnosed as schwannoma on microscopy. Cases were analyzed in detail regarding clinical history and other findings. Results: A total of 28 cases were diagnosed as schwannoma, among them 20 cases were located at cerebellopontine angle. Male:female ratio was 1:1.8. Youngest age group was 28 and eldest was 70 years in our study and the most common age group affected was between 30 and 40 years. Conclusion: Schwannoma should be considered as one of the differential diagnosis for swelling over the body as schwannoma can present extracranially also. Classical schwannoma was the most common and plexiform schwannoma was the least common variant in our study

Placental site nodule: A tumor like trophoblastic lesion - rare case report

Placental site nodule (PSN) is an uncommon, benign, generally asymptomatic lesion of trophoblastic origin, which may often be detected several months to years after the pregnancy from which it is resulted. This entity may have bizarre histologic findings and should be distinguished from other aggressive lesions like placental site trophoblastic tumor, epithelioid trophoblastic tumor and squamous cell carcinoma

Malignant melanoma of male breast with nodal metastasis

Malignant melanoma or melanocarcinoma arising from melanocytes is one of the most rapidly spreading malignant tumor of the skin can occur at all ages, but is a rare before puberty. Malignant melanoma is relatively common neoplasm that not long ago was considered almost uniformly deadly. The great preponderance of melanomas arises in the skin; other sites of origin include the oral and anogenital mucosal surfaces, esophagus, meninges and notably the eye. Breast is a very uncommon site for malignant melanoma; here, we present a case of malignant melanoma of male breast with nodal metastasis

Bilateral dermoid cyst of ovary

A dermoid cyst (also called as "mature teratoma") is a sac-like growth that may be present at birth. It contains structures such as hair, fluid, teeth or skin glands that can be found on or in the skin. In some cases, especially when in the ovary, it also contains thyroid or brain tissue. Ovarian dermoid cysts, which not uncommonly are found in both ovaries, can develop in a woman during her reproductive years. The word "teratoma" is derived from Greek work "teraton" meaning monster. It was initially used by Virchow in 1863. The term "dermoid cyst" was coined by Leblanc in 1831

Castleman′s disease: Hyaline vascular type

Castleman′s disease is a rare disease of lymph node with two identified forms, the hyaline vascular type and plasma cell type. It presents as localized or systemic lymphadenopathy or even as extranodal mass and may give rise to several differential diagnoses. Castleman′s disease represents a morphologically distinct form of lymph node hyperplasia rather than a neoplasm or a hamartoma. It occurs most commonly in adults but it can also affect children. Here we present a case of Castleman′s disease in a 22 year male patient involving right cervical lymphnode

Pilomatrixoma of right scapular region: Rare case report

Pilomatrixoma, a benign skin appendageal tumor, is seen commonly in head and neck. Pilomatrixoma also known as pilomatricoma or calcifying epithelioma of Malherbe. These lesions are typically found in the head and neck region, but also occur in the upper extremities and are rarely reported in other sites. Most cases of pilomatrixoma occur in children under the age of 7 and the condition is twice as common in females as in males. Pilomatrixomas are frequently misdiagnosed when the evaluation is based on clinical or radiographic examination alone. Therefore, the final diagnosis requires histopathological examination

Right atrial myxoma in a 65-year-old female: A rare presentation

Primary tumors of the heart are quite rare found in 0.04% of autopsies. In decreasing order of frequency, the benign tumors encountered in the heart are myxoma, lipoma, fibroelastoma, rhabdomyoma, hemangioma, and lymphangioma. Malignant tumors are still rare such as rhabdomyosarcoma, angiosarcoma, and malignant mesothelioma. Myxoma is the most common primary tumor of the heart comprising about 50% of all primary cardiac tumors. Majority of them occur in the age group of 30–60 years. Myxomas may be located in any cardiac chamber or the valves, but 90% of them are situated in the left atrium. We here present a case of myxoma in the 65-year-old female which is located in the right atrium

Spectrum of hematological disorders observed in one-hundred and ten consecutive bone marrow aspirations and biopsies

Introduction: The study was done to know the spectrum of hematological disorders. Materials and Methods: This was a retrospective and prospective study of bone marrow aspiration (BMA) and biopsies done on patients who were referred for bone marrow examination. Cases were analyzed in detail regarding clinical examination and other investigations. Results: BMA from 110 patients were analyzed. Nutritional anemia contributed highest number of cases among the nonhematological group. Out of nutritional anemia megaloblastic anemia was the most common disorder. Acute myeloid leukemia was the commonest malignant hematological disorder in the present study. Among 110 cases 56 cases were male and 54 were female patients with highest number of cases in the age group of 21-30 years. Conclusion : Although bone marrow examination is an invasive procedure this is well tolerated by patients. The examination helps in many cases to arrive at a final diagnosis within a short span of time