The II Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19 Joint Guidelines of the Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia and Sociedade Brasileira de Reumatologia / II Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19 Diretriz conjunta da Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia e Sociedade Brasileira de Reumatologia

ABSTRACT Objective: To update the recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. Methods: Experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. Results: Twenty-one recommendations were generated, including strong recommendations for the use of corticosteroids in patients using supplemental oxygen and conditional recommendations for the use of tocilizumab and baricitinib for patients on supplemental oxygen or on noninvasive ventilation and anticoagulants to prevent thromboembolism. Due to suspension of use authorization, it was not possible to make recommendations regarding the use of casirivimab + imdevimab. Strong recommendations against the use of azithromycin in patients without suspected bacterial infection, hydroxychloroquine, convalescent plasma, colchicine, and lopinavir + ritonavir and conditional recommendations against the use of ivermectin and remdesivir were made. Conclusion: New recommendations for the treatment of hospitalized patients with COVID-19 were generated, such as those for tocilizumab and baricitinib. Corticosteroids and prophylaxis for thromboembolism are still recommended, the latter with conditional recommendation. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and to promote resource economy.

RESUMO Objetivo: Atualizar as recomendações para embasar as decisões para o tratamento farmacológico de pacientes hospitalizados com COVID-19 no Brasil. Métodos: A elaboração desta diretriz foi feita por especialistas, incluindo representantes do Ministério da Saúde e metodologistas. O método utilizado para o desenvolvimento rápido de diretrizes baseou-se na adoção e/ou adaptação de diretrizes internacionais existentes (GRADE ADOLOPMENT) e contou com o apoio da plataforma e-COVID-19 RecMap. A qualidade das evidências e a elaboração das recomendações seguiram o método GRADE. Resultados: Chegaram-se a 21 recomendações, incluindo recomendações fortes quanto ao uso de corticosteroides em pacientes em uso de oxigênio suplementar e recomendações condicionais para o uso de tocilizumabe e baricitinibe, em pacientes com oxigênio suplementar ou ventilação não invasiva, e de anticoagulantes, para prevenção de tromboembolismo. Devido à suspensão da autorização de uso, não foi possível fazer recomendações para o tratamento com casirivimabe + imdevimabe. Foram feitas recomendações fortes contra o uso de azitromicina em pacientes sem suspeita de infecção bacteriana, hidroxicloroquina, plasma convalescente, colchicina e lopinavir + ritonavir, além de recomendações condicionais contra o uso de ivermectina e rendesivir. Conclusão: Foram criadas novas recomendações para o tratamento de pacientes hospitalizados com COVID-19, como as recomendações de tocilizumabe e baricitinibe. Ainda são recomendados corticosteroides e profilaxia contra tromboembolismo, esta em caráter condicional. Vários medicamentos foram considerados ineficazes e não devem ser usados, no intuito de proporcionar o melhor tratamento segundo os princípios da medicina baseada em evidências e promover a economia de recursos.

Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19: Diretriz conjunta da Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia e Sociedade Brasileira de Reumatologia / Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19: Joint guideline of Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia, Sociedade Brasileira de Reumatologia

Há diversas terapias sendo utilizadas ou propostas para a COVID-19, muitas carecendo de apropriada avaliação de efetividade e segurança. O propósito deste documento é elaborar recomendações para subsidiar decisões sobre o tratamento farmacológico de pacientes hospitalizados com COVID-19 no Brasil. Métodos: Um grupo de 27 membros, formado por especialistas, representantes do Ministério da Saúde e metodologistas, integra essa diretriz. Foi utilizado o método de elaboração de diretrizes rápidas, tomando por base a adoção e/ou a adaptação de recomendações a partir de diretrizes internacionais existentes (GRADE ADOLOPMENT), apoiadas pela plataforma e-COVID-19 RecMap. A qualidade das evidências e a elaboração das recomendações seguiram o método GRADE. Resultados: Foram geradas 16 recomendações. Entre elas, estão recomendações fortes para o uso de corticosteroides em pacientes em uso de oxigênio suplementar, para o uso de anticoagulantes em doses de profilaxia para tromboembolismo e para não uso de antibacterianos nos pacientes sem suspeita de infecção bacteriana. Não foi possível fazer uma recomendação quanto à utilização do tocilizumabe em pacientes hospitalizados com COVID-19 em uso de oxigênio, pelas incertezas na disponibilidade e de acesso ao medicamento. Foi feita recomendação para não usar azitromicina, casirivimabe + imdevimabe, cloroquina, colchicina, hidroxicloroquina, ivermectina, lopinavir/ ritonavir, plasma convalescente e rendesivir. Conclusão: Até o momento, poucas terapias se provaram efetivas no tratamento do paciente hospitalizado com COVID-19, sendo recomendados apenas corticosteroides e profilaxia para tromboembolismo. Diversos medicamentos foram considerados ineficazes, devendo ser descartados, de forma a oferecer o melhor tratamento pelos princípios da medicina baseada em evidências e promover economia de recursos não eficazes.

Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. Methods: A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. Results: Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made. Conclusion: To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.

Brazilian guidelines for the treatment of outpatients with suspected or confirmed COVID-19. A joint guideline of the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Medical Association (AMB), Brazilian Society of Angiology and Vascular Surgery (SBACV), Brazilian Society of Geriatrics and Gerontology (SBGG), Brazilian Society of Infectious Diseases (SBI), Brazilian Society of Family and Community Medicine (SBFMC), and Brazilian Thoracic Society (SBPT)

ABSTRACT Background Several therapies have been used or proposed for the treatment of COVID-19, although their effectiveness and safety have not been properly evaluated. The purpose of this document is to provide recommendations to support decisions about the drug treatment of outpatients with COVID-19 in Brazil. Methods A panel consisting of experts from different clinical fields, representatives of the Brazilian Ministry of Health, and methodologists (37 members in total) was responsible for preparing these guidelines. A rapid guideline development method was used, based on the adoption and/or adaptation of recommendations from existing international guidelines combined with additional structured searches for primary studies and new recommendations whenever necessary (GRADE-ADOLOPMENT). The rating of quality of evidence and the drafting of recommendations followed the GRADE method. Results Ten technologies were evaluated, and 10 recommendations were prepared. Recommendations were made against the use of anticoagulants, azithromycin, budesonide, colchicine, corticosteroids, hydroxychloroquine/chloroquine alone or combined with azithromycin, ivermectin, nitazoxanide, and convalescent plasma. It was not possible to make a recommendation regarding the use of monoclonal antibodies in outpatients, as their benefit is uncertain and their cost is high, with limitations of availability and implementation. Conclusion To date, few therapies have demonstrated effectiveness in the treatment of outpatients with COVID-19. Recommendations are restricted to what should not be used, in order to provide the best treatment according to the principles of evidence-based medicine and to promote resource savings by aboiding ineffective treatments.

Diretrizes brasileiras para o manejo de potenciais doadores de órgãos em morte encefálica. Uma força-tarefa composta por Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network e Coordenação Geral do Sistema Nacional de Transplantes / Brazilian guidelines for the management of brain-dead potential organ donors. The task force of the Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network, and the General Coordination of the National Transplant System

RESUMO Objetivo: Fornecer recomendações para nortear o manejo clínico do potencial doador em morte encefálica. Métodos: O presente documento foi formulado em dois painéis compostos por uma força tarefa integrada por 27 especialistas de diferentes áreas que responderam a questões dirigidas aos seguintes temas: ventilação mecânica, hemodinâmica, suporte endócrino-metabólico, infecção, temperatura corporal, transfusão sanguínea, e uso de checklists. Os desfechos considerados foram: parada cardíaca, número de órgãos retirados ou transplantados e função/sobrevida dos órgãos transplantados. A qualidade das evidências das recomendações foi avaliada pelo sistema Grading of Recommendations Assessment, Development, and Evaluation. Resultados: Foram geradas 19 recomendações a partir do painel de especialistas. Dessas, 7 foram classificadas como fortes, 11 fracas e uma foi considerada boa prática clínica. Conclusão: Apesar da concordância entre os membros do painel em relação à maior parte das recomendações, o grau de recomendação é fraco em sua maioria.

Abstract Objective: To contribute to updating the recommendations for brain-dead potential organ donor management. Methods: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, answered questions related to the following topics were divided into mechanical ventilation, hemodynamics, endocrine-metabolic management, infection, body temperature, blood transfusion, and checklists use. The outcomes considered were cardiac arrests, number of organs removed or transplanted as well as function / survival of transplanted organs. The quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system to classify the recommendations. Results: A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong, 11 as weak and 1 was considered a good clinical practice. Conclusion: Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak.

Diretrizes para o tratamento farmacológico da COVID-19. Consenso da Associação de Medicina Intensiva Brasileira, da Sociedade Brasileira de Infectologia e da Sociedade Brasileira de Pneumologia e Tisiologia / Guidelines for the pharmacological treatment of COVID-19. The task-force/consensus guideline of the Brazilian Association of Intensive Care Medicine, the Brazilian Society of Infectious Diseases and the Brazilian Society of Pulmonology and Tisiology

RESUMO Introdução: Há diversas terapias sendo utilizadas, consideradas ou propostas para o tratamento da COVID-19, muitas carecendo de apropriada avaliação de efetividade e segurança. O propósito deste documento é fornecer recomendações baseadas nas evidências científicas disponíveis e em sua interpretação transparente, para subsidiar decisões sobre o tratamento farmacológico da COVID-19 no Brasil. Métodos: Um grupo de 27 especialistas e metodologistas integraram a força-tarefa formada pela Associação de Medicina Intensiva Brasileira (AMIB), pela Sociedade Brasileira de Infectologia (SBI) e pela Sociedade Brasileira de Pneumologia e Tisiologia (SBPT). Foram realizadas revisões sistemáticas rápidas, atualizadas até 28 de abril de 2020. A qualidade das evidências e a elaboração das recomendações seguiram o sistema GRADE. As recomendações foram elaboradas nos dias 5, 8 e 13 de maio de 2020. Resultados: Foram geradas 11 recomendações, embasadas em evidência de nível baixo ou muito baixo. Não há indicação para uso de rotina de hidroxicloroquina, cloroquina, azitromicina, lopinavir/ritonavir, corticosteroides ou tocilizumabe no tratamento da COVID-19. Heparina deve ser utilizada em doses profiláticas no paciente hospitalizado, mas não deve ser realizada anticoagulação na ausência de indicação clínica específica. Antibacterianos e oseltamivir devem ser considerados somente nos pacientes em suspeita de coinfecção bacteriana ou por influenza, respectivamente. Conclusão: Até o momento, não há intervenções farmacológicas com efetividade e segurança comprovada que justifiquem seu uso de rotina no tratamento da COVID-19, devendo os pacientes serem tratados preferencialmente no contexto de pesquisa clínica. As recomendações serão revisadas continuamente, de forma a capturar a geração de novas evidências.

ABSTRACT Introduction: Different therapies are currently used, considered, or proposed for the treatment of COVID-19; for many of those therapies, no appropriate assessment of effectiveness and safety was performed. This document aims to provide scientifically available evidence-based information in a transparent interpretation, to subsidize decisions related to the pharmacological therapy of COVID-19 in Brazil. Methods: A group of 27 experts and methodologists integrated a task-force formed by professionals from the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB), the Brazilian Society of Infectious Diseases (Sociedad Brasileira de Infectologia - SBI) and the Brazilian Society of Pulmonology and Tisiology (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT). Rapid systematic reviews, updated on April 28, 2020, were conducted. The assessment of the quality of evidence and the development of recommendations followed the GRADE system. The recommendations were written on May 5, 8, and 13, 2020. Results: Eleven recommendations were issued based on low or very-low level evidence. We do not recommend the routine use of hydroxychloroquine, chloroquine, azithromycin, lopinavir/ritonavir, corticosteroids, or tocilizumab for the treatment of COVID-19. Prophylactic heparin should be used in hospitalized patients, however, no anticoagulation should be provided for patients without a specific clinical indication. Antibiotics and oseltamivir should only be considered for patients with suspected bacterial or influenza coinfection, respectively. Conclusion: So far no pharmacological intervention was proven effective and safe to warrant its use in the routine treatment of COVID-19 patients; therefore such patients should ideally be treated in the context of clinical trials. The recommendations herein provided will be revised continuously aiming to capture newly generated evidence.

Comparison of Cardiac and Vascular Parameters in Powerlifters and Long-Distance Runners: Comparative Cross-Sectional Study / Comparação de Parâmetros Cardíacos e Vasculares em Powerlifters e Corredores de Longa Distância: Um Estudo Transversal Comparativo

Abstract Background: Cardiac remodeling is a specific response to exercise training and time exposure. We hypothesized that athletes engaging for long periods in high-intensity strength training show heart and/or vascular damage. Objective: To compare cardiac characteristics (structure and function) and vascular function (flow-mediated dilation [FMD] and peripheral vascular resistance [PVR]) in powerlifters and long-distance runners. Methods: We evaluated 40 high-performance athletes (powerlifters [PG], n = 16; runners [RG], n = 24) and assessed heart structure and function (echocardiography), systolic and diastolic blood pressure (SBP/DBP), FMD, PVR, maximum force (squat, bench press, and deadlift), and maximal oxygen uptake (spirometry). A Student's t Test for independent samples and Pearson's linear correlation were used (p < 0.05). Results: PG showed higher SBP/DBP (p < 0.001); greater interventricular septum thickness (p < 0.001), posterior wall thickness (p < 0.001) and LV mass (p < 0.001). After adjusting LV mass by body surface area (BSA), no difference was observed. As for diastolic function, LV diastolic volume, wave E, wave e', and E/e' ratio were similar for both groups. However, LA volume (p = 0.016) and BSA-adjusted LA volume were lower in PG (p < 0.001). Systolic function (end-systolic volume and ejection fraction), and FMD were similar in both groups. However, higher PVR in PG was observed (p = 0.014). We found a correlation between the main cardiovascular changes and total weight lifted in PG. Conclusions: Cardiovascular adaptations are dependent on training modality and the borderline structural cardiac changes are not accompanied by impaired function in powerlifters. However, a mild increase in blood pressure seems to be related to PVR rather than endothelial function.

Resumo Fundamento: Remodelamento cardíaco é uma resposta específica ao tempo e modalidade de treinamento. Nós hipotetizamos que atletas de treinamento de força de alta intensidade, por longo tempo, mostram dano à estrutura cardíaca e/ou vascular. Objetivo: Comparar as características cardíacas (estrutura e funcionalidade) e função vascular (dilatação fluxo-mediada, FMD e resistência vascular periférica, PVR) em powerlifters e corredores. Métodos: Nós avaliamos 40 atletas de alto-desempenho (powerlifters [PG], n = 16; corredores [RG], n = 24). Mensuramos estrutura e funcionalidade cardíaca (ecocardiografia), pressão arterial (SBP/DBP), FMD, PVR, força máxima (agachamento, supino e levantamento terra) e consumo máximo de oxigênio (ergoespirometria). Foi utilizado teste T de Student e correlação linear de Pearson (p < 0,05). Resultados: PG mostrou maior SBP/DBP (p < 0,001), espessura de septo interventricular (p < 0,001), parede posterior (p < 0,001) e massa do VE (p < 0,001); após ajuste pela superfície corporal (BSA), não houve diferença na massa do VE. O volume do VE, onda E, onda e', e a razão E/e' foram similares entre os grupos. O volume do AE (p = 0,016), mesmo ajustado pela BSA (p < 0,001) foi menor no PG. A função sistólica (volume sistólico final e fração de ejeção) e FMD foram similares nos grupos. Contudo, foi observada maior PVR no PG (p = 0,014). Houve uma correlação direta entre as alterações cardíacas e a carga total levantada no PG. Conclusões: As adaptações cardiovasculares são dependentes da modalidade e os valores encontrados na estrutura do coração não são acompanhados por prejuízo na funcionalidade. Entretanto, um leve aumento na pressão arterial pode estar associado com maior PVR e não com a função endotelial.

Effects of high-intensity inspiratory muscle training associated with aerobic exercise in patients undergoing cabg: randomized clinical trial

Abstract Objective: Evaluate the interaction between high-intensity inspiratory muscle training (IMT) and aerobic exercise on physical capacity, respiratory muscle strength, peripheral muscle strength, and quality of life of patients who underwent coronary artery bypass grafting (CABG). Methods: Twenty-four patients underwent CABG were randomized into two groups. During 36 sessions, one group received IMT associated with aerobic exercise and the other group received only aerobic exercise. Primary outcome was the distance in the six-minute walk distance (6MWD) test. Secondary outcomes included respiratory muscle strength, peripheral muscle strength, and quality of life. Measures were taken at the baseline, at the 12th session, the 24th session, and 36th session. Results: Baseline characteristics were similar between the groups. There was no statistically significant difference between the two groups in any outcome [6MWD - P=0.935; peak oxygen consumption (PeakVO2) - P=0.853; maximal inspiratory pressure (MIP) - P=0.243; maximal expiratory pressure (MEP) - P=0.268; sitting-rising test (SRT) - P=0.212], but there was interaction in MIP (P=0.000) and all outcomes improved in the two groups (6MWD - P=0.000; PeakVO2 - P=0.000; MIP - P=0.000; MEP - P=0.000; SRT - P=0.000). Conclusion: There was an improvement of all outcomes in both groups, but IMT was not able to provide additional benefits. The use of this combination should be used with caution to not generate higher costs in the rehabilitation process of these patients.

Methodological quality of randomized clinical trials of respiratory physiotherapy in coronary artery bypass grafting patients in the intensive care unit: a systematic review

Abstract Objective: To assess methodological quality of the randomized controlled trials of physiotherapy in patients undergoing coronary artery bypass grafting in the intensive care unit. Methods: The studies published until May 2015, in MEDLINE, Cochrane and PEDro were included. The primary outcome extracted was proper filling of the Cochrane Collaboration's tool's items and the secondary was suitability to the requirements of the CONSORT Statement and its extension. Results: From 807 studies identified, 39 were included. Most at CONSORT items showed a better adequacy after the statement's publication. Studies with positive outcomes presented better methodological quality. Conclusion: The methodological quality of the studies has been improving over the years. However, many aspects can still be better designed.

Electrical stimulation and electromagnetic field use in patients with diabetic neuropathy: systematic review and meta-analysis

BACKGROUND: Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus, and pharmacological therapies are ineffective in many patients. Therefore, other treatment modalities should be considered, including electrical stimulation and electromagnetic fields. OBJECTIVES: The research objective was to evaluate the effect of treatment with electrical stimulation and electromagnetic fields on pain and sensitivity in patients with painful diabetic neuropathy compared with placebo or another intervention. METHOD: We searched the following electronic databases (from inception to April 2012): MEDLINE (accessed by PubMed), LILACS, Physiotherapy Evidence Database (PEDro), EMBASE and Cochrane CENTRAL. We included randomized trials that compared electrical stimulation or electromagnetic fields with control groups in which the objective was to assess pain and sensitivity in patients with PDN. Two reviewers independently extracted the data. A random-effects model was used for the main analysis. RESULTS: The search retrieved 1336 articles, of which 12 studies were included. Reductions in the mean pain score were significantly greater in the TENS (transcutaneous electrical nerve stimulation) group than in the placebo group [-0.44 (95% CI: -0.79 to -0.09; I2: 0%)]. There was no improvement in pain relief when electromagnetic fields were compared with the control group [-0.69 (95% CI: -1.86 to 0.48; I2: 63%)]. CONCLUSIONS: We found that TENS improved pain relief in patients with diabetic neuropathy, while no such improvement was observed with the use of electromagnetic field treatment. Due to the methodological differences between the studies, a meta-analysis for the outcome of sensitivity could not be performed. .