Impacto dos inibidores de SGLT2 na qualidade de vida em pacientes com insuficiência cardíaca: revisão sistemática

A insuficiência cardíaca é uma das principais causas de morbidade e mortalidade global, afetando cerca de 2 milhões de pessoas no Brasil anualmente. Os inibidores de SGLT2 surgem como uma opção terapêutica promissora para essa condição, devido à sua eficácia e capacidade de reduzir eventos adversos. Esta revisão sistemática com meta-análise investigou a eficácia desses medicamentos na qualidade de vida de pacientes com insuficiência cardíaca, independentemente da presença de diabetes mellitus tipo 2 ou fração de ejeção. O objetivo foi avaliar o impacto dos inibidores de SGLT2, considerando sua relevância emergente no tratamento da condição. Seguindo o protocolo PRISMA 2020, foram incluídos estudos publicados entre 2019 e 2024 no PubMed, com texto completo gratuito, usando os descritores 'SGLT2 inhibitors', 'heart failure' e 'hospitalization' no DeCS, com o operador booleano 'AND'. Dos 21.677 participantes, 10.840 (≅ 50,01%) receberam inibidores de SGLT2, resultando 1.444 eventos adversos (≅ 13,32%). No grupo placebo, com 10.837 participantes (≅ 49,99%), ocorreram 1.939 casos de desfechos (≅ 17,89%). A análise de risco relativo mostrou uma redução significativa nos eventos adversos no grupo de intervenção (RR: 0,74, IC 95% 0,70-0,79, p<0,01). Conclui-se que os inibidores de SGLT2 podem beneficiar pacientes com insuficiência cardíaca, independentemente da presença de diabetes ou fração de ejeção

Intoxicação medicamentosa nas regiões federativas do Brasil: Medical poisoning in the federal regions of Brazil

Estudo ecológico que analisou o perfil epidemiológico das intoxicações medicamentosas no Brasil e regiões federativas de 2011 a 2020, utilizando dados do Sistema de Informação de Agravos e Notificação (SINAN) do Departamento de Informática do Sistema Único de Saúde (DATASUS). As informações investigadas foram sexo, idade, raça/cor, escolaridade, circunstância, tipo de exposição e evolução. Mais da metade dos casos ocorreu na região Sudeste. As notificações foram mais frequentes nas mulheres (β 5253,8; IC95% 3164,9; 7342,7), pretas/pardas (β 3144,6; IC95% 1988,8; 4300,3), idade entre 20 e 39 anos (β 3029,8; IC95% 1862,5; 4197,1), 9 a 11 anos de estudo (β 2302,9; IC95% 1401,5; 3204,2), com exposição aguda e única (β 4371,1; IC95% 2548,4; 6193,7) e evolução sem sequelas (β 5348,1; IC95% 3187,4; 7688,7). Houve aumento de 38,8% nas tentativas de suicídio no Brasil entre 2011 e 2020, e tal sentido foi observado em todas as regiões do país. Tendência crescente dos casos foi observada nas mulheres, jovens, pretas/pardas, com maior grau de instrução e tendo como principal motivo a tentativa de suicídio. As exposições mais frequentes foram agudas e únicas e com evolução sem sequelas. A promoção de políticas públicas de redução do consumo e acesso aos medicamentos pode contribuir para diminuição dos casos

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

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

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

To which world regions does the valence–dominance model of social perception apply?

Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy, the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution.C.L. was supported by the Vienna Science and Technology Fund (WWTF VRG13-007); L.M.D. was supported by ERC 647910 (KINSHIP); D.I.B. and N.I. received funding from CONICET, Argentina; L.K., F.K. and Á. Putz were supported by the European Social Fund (EFOP-3.6.1.-16-2016-00004; ‘Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pécs’). K.U. and E. Vergauwe were supported by a grant from the Swiss National Science Foundation (PZ00P1_154911 to E. Vergauwe). T.G. is supported by the Social Sciences and Humanities Research Council of Canada (SSHRC). M.A.V. was supported by grants 2016-T1/SOC-1395 (Comunidad de Madrid) and PSI2017-85159-P (AEI/FEDER UE). K.B. was supported by a grant from the National Science Centre, Poland (number 2015/19/D/HS6/00641). J. Bonick and J.W.L. were supported by the Joep Lange Institute. G.B. was supported by the Slovak Research and Development Agency (APVV-17-0418). H.I.J. and E.S. were supported by a French National Research Agency ‘Investissements d’Avenir’ programme grant (ANR-15-IDEX-02). T.D.G. was supported by an Australian Government Research Training Program Scholarship. The Raipur Group is thankful to: (1) the University Grants Commission, New Delhi, India for the research grants received through its SAP-DRS (Phase-III) scheme sanctioned to the School of Studies in Life Science; and (2) the Center for Translational Chronobiology at the School of Studies in Life Science, PRSU, Raipur, India for providing logistical support. K. Ask was supported by a small grant from the Department of Psychology, University of Gothenburg. Y.Q. was supported by grants from the Beijing Natural Science Foundation (5184035) and CAS Key Laboratory of Behavioral Science, Institute of Psychology. N.A.C. was supported by the National Science Foundation Graduate Research Fellowship (R010138018). We acknowledge the following research assistants: J. Muriithi and J. Ngugi (United States International University Africa); E. Adamo, D. Cafaro, V. Ciambrone, F. Dolce and E. Tolomeo (Magna Græcia University of Catanzaro); E. De Stefano (University of Padova); S. A. Escobar Abadia (University of Lincoln); L. E. Grimstad (Norwegian School of Economics (NHH)); L. C. Zamora (Franklin and Marshall College); R. E. Liang and R. C. Lo (Universiti Tunku Abdul Rahman); A. Short and L. Allen (Massey University, New Zealand), A. Ateş, E. Güneş and S. Can Özdemir (Boğaziçi University); I. Pedersen and T. Roos (Åbo Akademi University); N. Paetz (Escuela de Comunicación Mónica Herrera); J. Green (University of Gothenburg); M. Krainz (University of Vienna, Austria); and B. Todorova (University of Vienna, Austria). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.https://www.nature.com/nathumbehav/am2023BiochemistryGeneticsMicrobiology and Plant Patholog

To which world regions does the valence–dominance model of social perception apply?

Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy, the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world