Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Study of genetic heterogeneity of deafness by next-generation sequencing

Surdez e perda auditiva são termos utilizados para designar distúrbios da audição, o tipo de deficiência sensorial mais frequente em humanos e decorrente de alterações genéticas em cerca de 50% dos casos. A heterogeneidade de lócus, de alelos e de manifestações fenotípicas na surdez é impressionante. O lócus DFNB1, que contém os genes GJB2 e GJB6, é responsável por cerca de 40% dos casos de surdez não-sindrômica de origem genética, porém, variantes patogênicas em cerca de 150 genes são descritas como causa de surdez, que pode ser sindrômica ou não-sindrômica. Por permitirem o sequenciamento simultâneo de diversos genes em uma mesma análise, as técnicas de sequenciamento de nova geração têm sido empregadas para o diagnóstico molecular de condições geneticamente heterogêneas, incluindo a surdez. O objetivo desse estudo foi contribuir para o estudo da heterogeneidade genética da surdez por meio do sequenciamento de nova geração de um painel com 99 genes relacionados à perda auditiva. Indivíduos não aparentados de 91 famílias brasileiras, com provável causa genética de surdez, foram avaliados com o intuito de identificar as causas moleculares da surdez, detectar novas variantes e promover aconselhamento genético das famílias participantes do estudo. Variantes provavelmente causais foram detectadas em 41 dos 91 probandos analisados (45,1%), dos quais 34 (37,4%) apresentaram variantes patogênicas ou provavelmente patogênicas. Nos outros 7 casos, foram detectadas variantes de efeito desconhecido com elevado potencial de explicar a perda auditiva dos probandos. As taxas de detecção nos casos de provável surdez sindrômica foram de 44,4% no grupo com suspeita de síndrome de Waardenburg (4 de 9 casos) e de 61,5% no grupo com suspeita de síndrome de Usher (8 de 13 casos). Nos casos de surdez não-sindrômica, as taxas de detecção foram de 53,9% no grupo com provável surdez autossômica dominante, 35,1% no grupo com provável surdez autossômica recessiva e de 45,0 % no grupo com mais de um mecanismo de herança possível. Das 43 variantes classificadas como patogênicas ou provavelmente patogênicas detectadas nesse estudo, 15 nunca haviam sido descritas. Contribuições científicas importantes foram obtidas com a identificação de uma nova variante de perda de função no gene CEACAM16 como causa de surdez não-sindrômica autossômica recessiva e com a confirmação de uma variante no gene MYO3A como causa de surdez não-sindrômica autossômica dominante recém-descrita em famílias brasileiras. Os resultados obtidos permitiram concluir que o sequenciamento de nova geração de paineis multigênicos é uma estratégia eficaz para o estudo da heterogeneidade genética da surdez, contribuindo para a detecção de novas variantes, ampliando o conhecimento científico a respeito dos genes analisados, e para o aconselhamento genético dos indivíduos estudados e seus familiaresDeafness and hearing loss are terms used to describe hearing disorders, the most common type of sensory impairment in humans, which occurs due to genetic alterations in about 50% of cases. The heterogeneity of locus, alleles and phenotypic manifestations of deafness is striking. The DFNB1 locus, which contains the genes GJB2 and GJB6, is responsible for about 40% of cases of non-syndromic genetic hearing loss, but pathogenic variants in near 150 genes are described as causing deafness, which may be syndromic or non-syndromic. By allowing the simultaneous sequencing of several genes in the same analysis, next-generation sequencing techniques have been employed for the molecular diagnosis of genetically heterogeneous conditions, including deafness. The aim of this study was to contribute to the study of the genetic heterogeneity of deafness employing the next-generation sequencing of a panel with 99 genes related to hearing loss. Individuals from 91 unrelated Brazilian families, with a probable genetic cause for deafness, were evaluated with the purpose of identifying the molecular causes of deafness, to detect new variants and to provide genetic counseling to the families enrolled in the study. Probably causal variants were detected in 41 of the 91 probands analyzed (45.1%), of which 34 (37.4%) had pathogenic or likely pathogenic variants. In the other 7 cases, variants of unknown significance with high potential to explain the hearing loss were detected. Detection rates in cases of probable syndromic deafness were 44.4% in the group with suspected Waardenburg syndrome (4 of 9 cases) and 61.5% in the group with suspected Usher syndrome (8 of 13 cases). In cases of non-syndromic deafness, detection rates were 53.9% in the group with probable autosomal dominant inheritance, 35.1% in the group with probable autosomal recessive inheritance and 45.0% in the group with more than one possible mechanism of inheritance. Among the 43 variants classified as pathogenic or probably pathogenic detected in this study, 15 had never been described. Important scientific contributions were obtained such as the identification of a novel loss-of-function variant in the CEACAM16 gene as causing autosomal recessive non-syndromic deafness and the confirmation of a recently described variant in the MYO3A gene as causing autosomal dominant non-syndromic deafness in Brazilian families. The results obtained allowed us to conclude that next-generation sequencing of multigenic panels is an effective strategy for the study of the genetic heterogeneity of deafness, contributing to the detection of new variants, expanding scientific knowledge about the genes analyzed, and also to the genetic counseling of the individuals studied and their relative

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London