The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3•5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.

Accumulating evidences suggest that glutamate plays a key role in the proliferation and invasion of malignant glioblastoma (GBM) tumors. It has been shown that GBM cells release and exploit glutamate for proliferation and invasion through AMPA glutamate receptors. Additionally, amplification of the epidermal growth factor receptor (EGFR) gene occurs in 40-50% of GBM. Since, PI3K/Akt is considered one of the main intracellular pathways involved in EGFR activation, AKT functions could trigger EGFR signaling. Thus, we investigated whether EGFR-phospho-Akt pathway is involved on the glutamate inducing U-87MG human GBM cell line proliferation. For these purpose, we treated the U-87MG cell line with 5 to 200 mM of glutamate and assessed the number of viable cells by trypan blue dye exclusion test. An increase in cell number (50%) was found at 5 mM glutamate, while the addition of DNQX (500 microM), an antagonist of AMPA receptor, inhibited the effect of glutamate on the U87-MG cells proliferation. Also, at 5 mM glutamate we observed an increase on the EGFR and phospho-Akt contents evaluated by immunohistochemistry. Moreover, U-87MG cells treated with glutamate exhibited an increase about 2 times in the EGFR mRNA expression. While, in the presence of the anti-EGFR gefitinib (50 muM) or the PI3K inhibitor wortmannin (5 muM), the U-87MG proliferation was restored to control levels. Together, our data suggest that glutamate signaling mediated by AMPA receptor induces U-87MG human GBM cell line proliferation via EGFR-phospho-Akt pathway.

O objetivo foi estimar a prevalência de doenças respiratórias crônicas autorreferidas, a indicação, o acesso e o uso de medicamentos, bem como fontes de obtenção, na população adulta brasileira. Foram analisados dados de adultos com idade maior ou igual a 20 anos, provenientes da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos no Brasil (PNAUM), realizada entre setembro de 2013 e fevereiro de 2014. A prevalência de doenças respiratórias crônicas foi de 3% (IC95%: 2,7-3,3). Desses, 58,1% (IC95%: 51,8-64,0) tinham indicação de tratamento farmacológico. Daqueles com indicação de tratamento, 77,1% (IC95%: 71,0-82,8) estavam utilizando pelo menos um dos medicamentos indicados. O acesso total à terapia foi de 91,4% (IC95%: 79,9-96,6), sendo que mais da metade das pessoas com doenças respiratórias crônicas adquiria pelo menos um de seus medicamentos em farmácias comerciais (57,3%). A classe de medicamentos mais referida foi a associação beta-2 agonista de longa duração e corticosteroides sob a forma inalatória, cujo representante mais frequente foi a associação budesonida/formoterol (20,3%; IC95%: 16,0-25,4). De acordo com o nosso estudo, a prevalência de doenças respiratórias crônicas autorreferida foi inferior a trabalhos previamente publicados para a população brasileira. Verificou-se que quase metade da população que referiu doenças respiratórias crônicas não tinha indicação de tratamento farmacológico. Já aqueles com indicação, aproximadamente um quarto não utilizava os medicamentos no período do estudo e, para os que usavam, embora o acesso fosse elevado, precisavam pagar para adquirir seus tratamentos.

Background : Knowledge about COVID-19 in pregnancy is limited, and evidence on the impact of the infection during pregnancy and postpartum is still emerging. Aim : To analyze maternal morbidity and mortality due to severe acute respiratory infections (SARI), including COVID-19, in Brazil. Methods : National surveillance data from the SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe) was used to describe currently and recently pregnant women aged 10-49 years hospitalized for SARI from January through November, 2020. SARI cases were grouped into: COVID-19; influenza or other detected agent SARI; and SARI of unknown etiology. Characteristics, symptoms and outcomes were presented by SARI type and region. Binomial proportion and 95% confidence intervals (95% CI) for outcomes were obtained using the Clopper-Pearson method. Results : Of 945,460 SARI cases in the SIVEP-Gripe, we selected 11,074 women aged 10-49 who were pregnant (7,964) or recently pregnant (3,110). COVID-19 was confirmed in 49.4% cases; 1.7% had influenza or another etiological agent; and 48.9% had SARI of unknown etiology. The pardo race/ethnic group accounted for 50% of SARI cases. Hypertension/Other cardiovascular diseases, chronic respiratory diseases, diabetes, and obesity were the most common comorbidities. A total of 362 women with COVID-19 (6.6%; 95%CI 6.0-7.3) died. Mortality was 4.7% (2.2-8.8) among influenza patients, and 3.3% (2.9-3.8) among those with SARI of unknown etiology. The South-East, Northeast and North regions recorded the highest frequencies of mortality among COVID-19 patients. Conclusion : Mortality among pregnant and recently pregnant women with SARIs was elevated among those with COVID-19, particularly in regions where maternal mortality is already high.

Introduction: In Brazil, little is known about the trends of chronic respiratory diseases, which was estimated as the third leading cause of deaths in 2017 worldwide. Methods: We analyzed Global Burden of Disease (GBD) 2017 estimates for prevalence, incidence, mortality, disability-adjusted life years (DALY), a summary measure of years of life lost (YLLs) and years lived with disability (YLDs), and risk factors attributable to chronic respiratory diseases in Brazil from 1990 to 2017. Results: The overall estimates have decreased for all ages and both sexes, and for age-standardized rates. For age-adjusted prevalence, there was a 21% reduction, and nearly 16% reduction for incidence. There was a 42% reduction in mortality for both sexes, though the rate of deaths for men was 30% greater than the rate in women. The increase in the number of DALY was essentially due to the population growth and population ageing. We observed a 34% increase in the absolute number of DALY in Brazil over the study period. The majority of the DALY rates were due to Chronic Obstructive Pulmonary Disease (COPD). For all ages and both sexes, smoking was the main attributable risk factor. Conclusion: In Brazil, although mortality, prevalence and incidence for chronic respiratory diseases have decreased over the years, attention should be taken to the DALYs increase. Smoking remained as the main risk factor, despite the significant decrease of tobacco use, reinforcing the need for maintenance of policies and programs directed at its cessation.

Purpose: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region.Methods: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed.Results: We identified 125 data sources for DUR in nine LatAm countries. Thirtyeight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data.Conclusions: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medicationrelated problems that need further exploration.

Hypertensive disorders of pregnancy account for approximately 22% of all maternal deaths in Latin America and the Caribbean. Pharmacotherapies play an important role in preventing and reducing the occurrence of adverse outcomes. However, the patterns of medications used for treating women with hypertensive disorders of pregnancy (HDP) living in this country is unclear. A population-based birth cohort study including 4262 women was conducted to describe the pattern of use of cardiovascular agents and acetylsalicylic acid between women with and without HDP in the 2015 Pelotas (Brazil) Birth Cohort. The prevalence of maternal and perinatal outcomes in this population was also assessed. HDP were classified according to Ministry of Health recommendations. Medications were defined using the Anatomical Therapeutic Chemical Classification System and the substance name. In this cohort, 1336 (31.3%) of women had HDP. Gestational hypertension was present in 636 (47.6%) women, 409 (30.6%) had chronic hypertension, 191 (14.3%) pre-eclampsia, and 89 (6.7%) pre-eclampsia superimposed on chronic hypertension. Approximately 70% of women with HDP reported not using any cardiovascular medications. Methyldopa in monotherapy was the most frequent treatment (16%), regardless of the type of HDP. Omega-3 was the medication most frequently reported by women without HDP. Preterm delivery, caesarean section, low birth weight, and neonatal intensive care admissions were more prevalent in women with HDP. Patterns of use of methyldopa were in-line with the Brazilian guidelines as the first-line therapy for HDP. However, the large number of women with HDP not using medications to manage HDP requires further investigation.

Objetivo: Este estudo visou avaliar a adequação da prescrição de profilaxia de tromboembolismo venoso (TEV) após a implementação do protocolo. Métodos: Trata-se de um estudo antes e depois realizado em um hospital de cuidados terciários no Rio Grande do Sul, Brasil. Pacientes clínicos e cirúrgicos internados, com 18 anos ou mais, foram avaliados para o risco de TEV e, posteriormente, para adequação da tromboprofilaxia, de acordo com o risco. As avaliações ocorreram antes e depois de uma estratégia de implementação de protocolo, que consistiu em uma plataforma on-line para acessar o protocolo, uma postagem pública do diagrama do protocolo, alertas clínicos na sala de convívio médico, alertas de e-mail e alertas pop-up no sistema informatizado de prescrição médica. O Desfecho principal foi a adequação da prescrição de profilaxia do TEV de acordo com o protocolo. Resultados: Foram avaliados 429 pacientes para adequação da tromboprofilaxia (213 antes e 216 depois). A prevalência de adequação aumentou de 54% para 63% (pré e pós-intervenção, respectivamente) e após o ajuste por tipo de paciente e fase do estudo, a razão de prevalência atingiu (RP) = 1,20, intervalo de confiança de 95% (IC) 1,02-1,42. Conclusões: os resultados mostraram que a adequação geral da prescrição de tromboprofilaxia foi discretamente melhorada. Apesar desses resultados, este estudo fornece evidências, até o momento, de uma série de estratégias para implementar o protocolo em instituições privadas em países de renda média com uma equipe médica aberta, pois há poucas pesquisas investigando esse tipo de intervenção simples e pragmática. Descritores: Tromboembolismo venoso; Adesão as diretrizes; Prevenção; Tromboprofilaxia.