Considerações sobre o uso de evidências científicas em tempos de pandemia: o caso da COVID-19

Making better use of available evidence on drugs and non-pharmacological therapies in the context of the COVID-19 pandemic is critical to minimizing suffering and saving lives. This debate aimed to present considerations about the concept of evidence, the hierarchy of evidence and the types of scientific evidence, seeking application in the context of the COVID-19 pandemic, with regard to the use of therapies for prevention and treatment of the disease. Initially, we made a brief introduction on the topic, highlighting the existence of doubts regarding the use of various drugs, as well as whether those available to combat other diseases can be safe and effective in the treatment of COVID-19. Then, we present some definitions about evidence, reinforcing that an exact definition depends on the context in which it will be used, and may even have a broad or restrictive connotation. Next, we mention that the evidence is classified in a hierarchical order, illustrated by means of a pyramid, according to the design of the study employed, one of the important markers to define the quality of the evidence. Emphasis is given to the evidence from the expert opinion, which is based on beliefs built on the basis of theory and non-systematic learning. Soon after, we resorted to basic concepts about three types of scientific evidence (direct, indirect and preliminary evidence) to explain the divergences between expert opinions. We conclude with comments and reflections on the need to define reasonably acceptable criteria for the use of evidence, for now available, in times of a pandemic, such as COVID-19.Fazer o melhor uso das evidências disponíveis sobre medicamentos e terapias não farmacológicas no contexto da pandemia da COVID-19 é fundamental para minimizar os sofrimentos e salvar vidas. Este debate objetivou apresentar considerações sobre o conceito de evidência, hierarquia das evidências e os tipos de evidências científicas, buscando aplicação no contexto da pandemia da COVID-19, no que tange ao uso de terapias para prevenção e tratamento da doença. Inicialmente, fizemos uma breve introdução sobre o tema, destacando a existência de dúvidas quanto ao uso de vários medicamentos, bem como se aqueles disponíveis para combater outras doenças podem ser seguros e eficazes no tratamento da COVID-19. Em seguida, apresentamos algumas definições sobre evidência, reforçando que uma definição exata dependa do contexto em que será usada, podendo, inclusive, ter uma conotação abrangente ou restritiva. Na sequência, mencionamos que as evidências são classificadas em uma ordem hierárquica, ilustrada por meio de uma pirâmide, conforme o desenho do estudo empregado, um dos marcadores importantes para definir a qualidade da evidência. É dado um destaque a evidência advinda da opinião de especialista, a qual está fundamentada em crenças construídas com base em teoria e aprendizagem não sistemática. Logo a seguir, recorremos a conceitos básicos sobre três tipos de evidências científicas (evidências diretas, indiretas e preliminares) para explicar as divergências entre opiniões de especialistas. Concluímos com comentários e reflexões sobre a necessidade de definir critérios razoavelmente aceitáveis para uso de evidências, por ora disponíveis, em tempos de pandemia, a exemplo da COVID-19

Evolución y elementos-clave del sistema de farmacovigilancia de Brasil: una revisión de alcance a partir de la creación de la Agencia Nacional de Vigilancia Sanitaria

Esta revisão de escopo objetiva descrever e caracterizar o sistema de farmacovigilância do Brasil (SINAF) e averiguar o atendimento aos requisitos mínimos propostos pela Organização Mundial da Saúde para um desempenho funcional de sistemas nacionais dessa natureza. A estratégia de pesquisa bibliográfica utilizou recomendações do STARLITE e termos de busca nas bases de dados MEDLINE/PubMed, Google, Imprensa Nacional e website da Agência Nacional de Vigilância Sanitária (Anvisa), compreendendo o período entre 1999, ano de criação da Anvisa, e março de 2016. Foram incluídas 47 (4,4%) publicações, de um total de 1.068 identificadas, prevalecendo, nesta ordem: 14 normas jurídicas (29,8%), 13 (27,6%) documentos técnicos e 10 (21,3%) artigos científicos. Os estudos e documentos técnicos analisados compreenderam a criação, em âmbito federal, da primeira unidade técnica de farmacovigilância do sistema de notificação de eventos adversos, o Centro Nacional de Monitorização e a Câmara Técnica de Medicamentos. A taxa de notificação de eventos adversos a medicamentos no Brasil correspondeu, em 2013, a 36 notificações/1 milhão de habitantes, bastante inferior à meta proposta na literatura internacional, que sugere 300 notificações/1 milhão de habitantes. Este estudo identificou aspectos estruturais e funcionais que podem comprometer o desempenho do SINAF, como a falta de legislação que institua oficialmente o próprio sistema e suas finalidades.This scoping review aims to describe and characterize the Brazilian pharmacovigilance system Brazil (SINAF) and verify to what extent it meets the minimum requirements proposed by the World Health Organization for the functional performance of this type of national system. The literature search strategy used STARLITE recommendations and search terms in MEDLINE/PubMed, Google, the Brazilian National Press, and the website of the Brazilian Health Regulatory Agency (Anvisa), from 1999, when Anvisa was created, to March 2016. The review included 47 publications (4.4%), out of a total of 1,068 identified, in the following order: 14 legal provisions (29.8%), 13 (27.6%) technical documents, and 10 (21.3%) scientific articles. The studies and technical documents covered the creation of the first pharmacovigilance technical unit at the federal level, the reporting system for adverse events, the National Monitoring Center, and the Technical Chambers on Medications. The reporting rate for adverse drug events in Brazil in 2013 was 36 reports per million inhabitants, considerably lower than the target proposed in the international literature, which suggests 300 reports per million inhabitants. This study identified structural and functional aspects that can compromise the performance of SINAF, such as lack of legislation officially establishing the system itself and its objectives.Esta revisión de alcance tiene como objetivo describir y caracterizar el sistema de farmacovigilancia de Brasil (SINAF) y constatar su adscripción a los requisitos mínimos propuestos por la Organización Mundial de la Salud, respecto al desempeño funcional de los sistemas nacionales de esta naturaleza. La estrategia de investigación bibliográfica utilizó recomendaciones del STARLITE y términos de búsqueda en las bases de datos MEDLINE/PubMed, Google, Imprenta Nacional de Brasil y de la página web de la Agencia Nacional de Vigilancia Sanitaria (Anvisa), comprendiendo el período entre 1999, año de creación de la Anvisa, y marzo de 2016. Se incluyeron 47 (4,4%) publicaciones, de un total de 1.068 identificadas, predominando por este orden: 14 normas jurídicas (29,8%), 13 (27,6%) documentos técnicos y 10 (21,3%) artículos científicos. Los estudios y documentos técnicos analizados incluyeron la creación, en el ámbito federal, de la primera unidad técnica de farmacovigilancia del sistema de notificación de eventos adversos, el Centro Nacional de Monitoreo y la Cámara Técnica de Medicamentos. La tasa de notificación de eventos adversos en medicamentos dentro de Brasil correspondió, en 2013, a 36 notificaciones/1 millón de habitantes, bastante inferior a la meta propuesta en la literatura internacional, que sugiere 300 notificaciones/1 millón de habitantes. Este estudio identificó aspectos estructurales y funcionales que pueden comprometer el desempeño del SINAF, como la falta de legislación que instituya oficialmente al propio sistema y sus finalidades

Recommendation of ICD-10 codes for surveillance of adverse drug reactions and drug intoxication

Propor uma lista-referência de códigos da Classificação Internacional de Doenças e Problemas Relacionados à Saúde (CID-10) para a vigilância de reações adversas e intoxicações a medicamentos, denominados de eventos adversos. A elaboração da lista-referência percorreu quatro fases: definição dos códigos, validação e duas de caracterização da lista. As associações entre variáveis foram avaliadas por qui-quadrado de Pearson e análise de correspondência múltipla. Foram identificados 691 códigos relacionados com reação adversa a medicamentos (52,1%) e intoxicação medicamentosa (47,9%). Um total de 687 (99,4%) e 511 (73,9%) códigos foram validados na 1ª e 2ª validação, respectivamente. Há diferenças estatisticamente significativas (p < 0,05) entre reações adversas e intoxicação medicamentosa nas variáveis utilizadas para a caracterização da lista-referência. A associação entre medicamento e admissão hospitalar e óbito foi estatisticamente significativa quando estratificada por tipo de evento adverso (p < 0,001). Na análise de correspondência múltipla identificou-se três agrupamentos de códigos em que há associações entre as categorias de resposta das variáveis estudadas. A lista-referência pode ser uma ferramenta útil nas ações de farmacovigilância no Brasil.ICD-10 is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD), a medical classification list by the World Health Organization. It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases. Associations between variables were evaluated using Pearson’s chi-squared test and multiple correspondence analysis. Six hundred and ninety-one (691) codes were identified related to adverse drug reactions (52.1%) and drug poisoning (47.9%). A total of 687 (99.4%) and 511 (73.9%) codes were validated in 1st and 2nd validation, respectively. There were statistically significant differences (p <0.05) between adverse reactions and drug poisoning in the variables used to characterize the reference list. The association between drug and hospital admission and death was statistically significant when stratified by type of adverse event (p <0.001). Three groupings of codes were identified in multiple correspondence analysis where there are associations between categories of response assessed. The reference list can be a useful tool in pharmacovigilance actions in Brazil

Viral epidemiology of respiratory infections among children at a tertiary hospital in Southern Brazil

Introduction: This study reports the pediatric epidemiology of respiratory syncytial virus (RSV), infl uenza (IF), parainfl uenza (PIV), and adenovirus (ADV) at Hospital de Clínicas de Porto Alegre. Methods: Cases of infection, hospitalizations in intensive care units (ICUs), nosocomial infections, and lethality rates were collected from 2007 to 2010. Results: RSV accounted for most nosocomial infections. Intensive care units admission rates for ADV and RSV infections were highest in 2007 and 2010. During 2008-2009, H1N1 and ADV had the highest ICU admission rates. ADV had the highest fatality rate during 2007-2009. Conclusions: Each virus exhibited distinct behavior, causing hospitalization, outbreaks, or lethality

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause specifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient defi ciencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading fi ve risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden