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

Curse or Blessing?: The internationalization process of Born Globals in times of COVID-19 : A Swedish Perspective

There has been an increase in research on the internationalization of so-called born-globalfirms. However, this research primarily focused on the internationalization process duringcalmer times. So far, little attention has been paid to internationalization during times of crisis.Especially for the recently happened COVID-19 crisis, research on the implications for bornglobal internationalization has been neglected. Nonetheless, born-global firms face manyliabilities in their internationalization processes, even getting more severe in times of crisis.This study aims to fill the existing knowledge gap by examining the internationalization ofSwedish born-global firms and their challenges due to COVID-19. Finally, we seek to makerecommendations for firms and entrepreneurs on how to cope with those hurdles.This research was conducted using qualitative semi-structured interviews with the founders orco-founders of six Swedish companies that fit the specifics of a born-global firm.The empirical findings show that all firms internationalize quickly abroad by using variousstrategies. While some follow relatively gradual approaches, others internationalize withintheir home regions or globally from the beginning. Also, the firms faced challenges due toilliquid customers, funding issues, or impeded networking. On the other hand, many companiescould discover new opportunities due to the crisis that supported their survival in abroadmarkets. Herewith the digital infrastructure and being online was distinctive. Eventually, it waspossible to conclude supportive behavioral patterns for entrepreneurs and firms when facingcrises.

“What are the odds?”: A rare clinical syndrome from a rare vascular condition caused by a commonly used medication

Objective: Describe a case of a patient developing Balint\u27s syndrome from bilateral parieto-occiptal ischemic infarcts secondary to reversible cerebral vasoconstriction syndrome (RCVS) after sumatriptan use. Background: Sumatriptan is a commonly prescribed anti-migraine medication which has 5HT 1B & 1D agonistic properties. Injudicious use of sumatriptan can lead to intracranial vasoconstriction with disastrous outcomes as exemplified in our patient. Design/Methods: Case-study Results: 29-years old female with a remote history of headaches presented with severe headaches and acute encephalopathy. MRI revealed bilateral parieto-occipital infarcts. Autoimmune workup and cerebrospinal fluid analysis were unremarkable. Catheter angiography revealed moderate diffuse spasm of the basilar, bilateral intracranial internal carotid, and proximal middle cerebral arteries (MCA). Use of intra-arterial nicardipine during the angiography procedure was limited due to patient\u27s baseline hypotension. Verapamil was started along with fludrocortisone. Her progress was followed by serial transcranial-doppler which revealed resolution of MCA vasospasm. After clinical improvement with verapamil, she admitted taking 300-mg sumatriptan over a 5-day period prior to the onset of her encephalopathy. In addition, her neurological exam demonstrated clinical signs of optic ataxia and simultagnosia, consistent with Balint\u27s syndrome due to the location of the stroke Conclusions: On reviewing the literature, only two cases of RCVS have been reported with sumatriptan use. Our patient possesses a high educational value due to the presence of a rare clinical syndrome of Balint\u27s, from an unusual vascular pathology of RCVS, which was likely secondary from a medication with vasoconstrictive properties. RCVS commonly causes a “thunderclap” headache but in severe cases, can also be associated with ischemic or hemorrhagic infarction, encephalopathy, and seizures. Location of the ischemic infarcts in the bilateral parietal region enabled our patient to possess a mysterious clinical syndrome of simultagnosia and optic ataxia which was first described in 1909. The only sign missing in our patient from the classical Balint syndrome was ocular apraxia

Factors associated with outpatient follow-up in stroke clinic after discharge from a comprehensive stroke center

Objective: To identify factors associated with failed follow-up in stroke clinic after discharge from the Hospital. Background: Outpatient follow-up after a stroke is crucial for decreasing hospital readmissions, managing complications secondary to stroke, and preventing future stroke. Poor stroke follow-up rates have prompted further investigation at our comprehensive stroke center. Design/Methods: A retrospective analysis was conducted on patients discharged with a diagnosis of acute ischemic stroke or TIA from July 1, 2016 to Dec 31,2016. Patients who expired or were enrolled in hospice by discharge were excluded. Chi-squared tests and two sample t-tests tests were performed to assess the associations of 90-day followup visit with patient demographics, clinical factors and discharge variables. Multivariate analysis was performed on variables with p value \u3c0.10. Results: In this 6 month period, 384 patients were identified, of which only 45% (174) followed up in the stroke clinic by 90 days. Differences were significant for insurance carrier [commercial (55%) vs Medicare (28%) and Medicaid (31%); p\u3c0.001)], appointment scheduled at discharge (54% vs 32%, p\u3c0.001), primary service [neurology (49%) vs medicine (13%); p\u3c0.001)], mRS [less than 4 (52-58%) vs 4 (34%) vs 5 (0%); p=0.01], ambulatory status [independent (52%) vs assistance (44%) vs non-ambulatory; p=0.003], transition of care call [called-confirmed (79%) vs called-unreachable vs no documented call (41%)] and discharge disposition [Home (52%) vs acute care facility (38%) vs other (35%); p=0.006]. Insurance carrier, ambulation, transition of care call and appointment at discharge statuses remained significant in the multivariate analysis. Conclusions: Multiple factors can predict clinic follow-up in stroke patients. These factors can be used to identify patients at risk of not completing stroke preventative services, to structure stroke discharge clinics, and proactively improve stroke follow-up rates