Handgrip strength in patients with acute decompensated heart failure: Accuracy as a predictor of malnutrition and prognostic value.

OBJECTIVES: The aim of this study was to determine whether handgrip strength (HGS) has diagnostic accuracy for malnutrition assessment and whether it is an independent predictor of 90-d mortality in patients with acute decompensated heart failure (ADHF). METHODS: This cohort study evaluated patients with ADHF within 36 h of hospital admission. Subjective global assessment and handgrip dynamometry were performed and the patients' medical records were analyzed. Mortality was monitored by phone contact and/or medical record search after 90 d. Diagnostic accuracy was tested with receiver operating characteristic (ROC) curves, and survival was tested in a Cox model. RESULTS: The sample consisted of 161 patients with ADHF who were predominantly male (62%) and older (77%), with a mean age of 68 y (60-75 y) and an ejection fraction of 37.7% ± 16.2%. According to subjective global assessment, 60% were suspected of malnourishment or were moderately or severely malnourished and these patients had lower HGS values than the well-nourished patients (P < 0.001). The ROC curve for HGS was sufficiently accurate to assess malnutrition (area under the curve [AUC] = 0.696; 95% confidence interval [CI], 0.614-0.779; P < 0.001) and had very good accuracy to predict severe malnutrition (AUC = 0.817; 95% CI, 0.711-0.923, P < 0.001). When analyzed by sex, HGS could only accurately detect malnutrition in men, although it could detect severe malnutrition in both men and women. During the 90-d follow-up period, there were 16 deaths (9.9%). An HGS cutoff value of 25.5 kg for men was considered significant for 90-d mortality (hazard ratio, 8.6; 95% CI, 1.1-70.9; P = 0.045). CONCLUSION: The results suggested that HGS is an independent indicator of malnutrition in patients with ADHF and can serve as a prognostic marker of 3-mo mortality in men.

Comportamento do mercado de trabalho brasileiro em duas recessões: análise do período 2015-2017 e da pandemia de Covid-19

Este estudo procura analisar os ajustes do mercado de trabalho em meio a essas duas retrações, tentando estabelecer similaridades e diferenças entre os ajustes observados nas crises anterior e mais recente. Para tanto, serão usados diversos indicadores de trabalho, construídos a partir da Pesquisa Nacional por Amostra de Domicílios (PNAD) Contínua, do Instituto Brasileiro de Geografia e Estatística (IBGE), do Cadastro Geral de Empregados e Desempregados (Caged), da Secretaria Especial de Previdência e Trabalho (SEPRT), e da Relação Anual de Informações Sociais (Rais), também produzida por essa secretaria.

Dietary Patterns in Secondary Prevention of Heart Failure: A Systematic Review.

BACKGROUND: Diet is an important factor in secondary prevention of heart failure (HF) but there is still no consensus as to which dietary model should be adopted by this population. This systematic review aims to clarify the relationship between dietary patterns and secondary prevention in HF. METHODS: We searched the Medline, Embase and Cochrane databases for studies with different dietary patterns and outcomes of secondary prevention in HF. No limitation was used in the search. RESULTS: 1119 articles were identified, 12 met the inclusion criteria. Studies with Dietary Approaches to Stop Hypertension (DASH), Mediterranean, Hyperproteic and Low-carb diets were found. The DASH pattern showed improvement in cardiac function, functional capacity, blood pressure, oxidative stress and mortality. The Mediterranean diet had a correlation with inflammation, quality of life and cardiac function but just on cross-sectional studies. Regarding the Hyperproteic and Low-carb diets only one study was found with each pattern and both were able to improve functional capacity in patients with HF. CONCLUSIONS: DASH pattern may have benefits in the secondary prevention of HF. The Mediterranean diet demonstrated positive correlation with factors of secondary prevention of HF but need more RCTs and cohort studies to confirm these effects. In addition, the Hyperproteic and Low-carb diets, despite the lack of studies, also demonstrated positive effects on the functional capacity in patients with HF.

Questões relevantes para a aprovação de medicamentos biossimilares / Relevant issues to biossimilars licensing

Medicamentos genéricos podem ser introduzidos a baixo custo no mercado quando a patente do medicamento inovador expira. Os resultados dos testes que demonstram a segurança e eficácia do produto inovador podem ser extrapolados para o genérico, simplificando sua aprovação. Este paradigma não pode ser aplicado aos biofármacos, grandes moléculas de difícil caracterização, onde pequenas alterações no processo de manufatura influenciam as propriedades biológicas e clínicas do produto e podem resultar em diferenças nos seus perfis de eficácia e segurança. Não sendo possível demonstrar a identidade entre biofármacos, eles não podem ser aprovados como simples genéricos e necessitam regulamentação específica. Neste trabalho foram feitos um levantamento bibliográfico das principais questões envolvidas na aprovação de versões similares de biofármacos e uma análise comparativa da situação regulatória nos principais mercados - EUA e União Europeia - a partir de legislação, projetos de lei, diretrizes e referências técnicas de suas agências regulatórias - FDA (Food and Drug Administration) e EMEA (European Medicines Agency), respectivamente, visando à discussão do caso brasileiro. A partir da legislação e diretrizes estudadas conclui-se que, apesar de Brasil, Europa e Estados Unidos estarem em estágios distintos de definição de sua estrutura regulatória para biossimilares, é possível identificar algumas semelhanças nas abordagens seguidas, como a necessidade de tratamento diferenciado para cada classe de produto (ou um enfoque caso a caso) e de um exercício de comparabilidade passo a passo, cujos resultados definirão a quantidade de dados e estudos clínicos e não clínicos necessários. Entretanto, questões como intercambialidade e substituição automática dos produtos de referência por biossimilares ainda não estão claramente definidas. Do ponto de vista sanitário, a Europa apresenta uma postura mais conservadora, enquanto que EUA e Brasil parecem estar construindo um arcabouço mais flexível. Ao lado das questões sanitárias, entretanto, destacam-se as questões econômicas, de grande importância na legislação dos EUA e Europa e não abordadas na regulamentação brasileira - o que pode trazer insegurança aos produtores interessados neste mercado.

When the patent of a drug expires, low cost generics may be introduced in market. Trial results that demonstrate the safety and efficacy of the reference product can be extrapolated to the generic, simplifying the approval process. This paradigm cannot be applied to biopharmaceutical products, large molecules difficult to be characterized. Minor changes in the production process can influence the biological and clinical properties of the product and result in differences in efficacy and safety profiles. It is not possible to demonstrate the identical nature of biopharmaceuticals arising from different manufacturing sources, so they cannot be approved as simple generics and need specific regulation. A bibliographical survey of the main issues involved in the approval of similar versions of biopharmaceuticals was performed as well as a comparative analysis of the regulatory situation in the largests pharmaceutical markets - U.S. and European Union - based on legislation, draft laws, guidelines and technical references issued by their regulatory agencies - FDA (Food and Drug Administration) and EMEA (European Medicines Agency), respectively, in order enlight the discussion now taking place in Brazil. Based on the laws and guidelines studied, it is concluded that, although Brazil, Europe and the United States are at different stages of setting their regulatory framework for biossimilars, it is possible to identify some similarities in approach, such as the need for different treatment for each product class (or a case by case focus) and a step by step comparison exercise, the results of which will define the amount of data and non-clinical and clinical studies required. However, issues such as interchangeability and automatic substitution of biossimilars for reference products are not yet clearly defined. From the sanitary point of view, Europe has a more conservative posture, while the U.S. and Brazil seem to be building a more flexible framework. Besides the health issues, however, we highlight the economic issues, of great importance in Europe and U.S. legislation, and not addressed in the Brazilian regulation - which can bring insecurity to producers interested in this market.

Relevant issues to biossimilars licensing.

When the patent of a drug expires, low cost generics may be introduced in market. Trial results that demonstrate the safety and efficacy of the reference product can be extrapolated to the generic, simplifying the approval process. This paradigm cannot be applied to biopharmaceutical products, large molecules difficult to be characterized. Minor changes in the production process can influence the biological and clinical properties of the product and result in differences in efficacy and safety profiles. It is not possible to demonstrate the identical nature of biopharmaceuticals arising from different manufacturing sources, so they cannot be approved as simple generics and need specific regulation. A bibliographical survey of the main issues involved in the approval of similar versions of biopharmaceuticals was performed as well as a comparative analysis of the regulatory situation in the largests pharmaceutical markets - U.S. and European Union - based on legislation, draft laws, guidelines and technical references issued by their regulatory agencies - FDA (Food and Drug Administration) and EMEA (European Medicines Agency), respectively, in order enlight the discussion now taking place in Brazil. Based on the laws and guidelines studied, it is concluded that, although Brazil, Europe and the United States are at different stages of setting their regulatory framework for biossimilars, it is possible to identify some similarities in approach, such as the need for different treatment for each product class (or a case by case focus) and a step by step comparison exercise, the results of which will define the amount of data and non-clinical and clinical studies required. However, issues such as interchangeability and automatic substitution of biossimilars for reference products are not yet clearly defined. From the sanitary point of view, Europe has a more conservative posture, while the U.S. and Brazil seem to be building a more flexible framework. Besides the health issues, however, we highlight the economic issues, of great importance in Europe and U.S. legislation, and not addressed in the Brazilian regulation - which can bring insecurity to producers interested in this market.