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.
Subject(s)
COVID-19 , Thromboembolism , Humans , Brazil/epidemiology , COVID-19 Serotherapy , Adrenal Cortex Hormones , OxygenABSTRACT
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.
ABSTRACT
OBJECTIVE: 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.
OBJETIVOS: 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.
Subject(s)
COVID-19 Drug Treatment , COVID-19 , Thromboembolism , Adrenal Cortex Hormones/therapeutic use , Anti-Bacterial Agents , Antibodies, Monoclonal, Humanized , Brazil , COVID-19/therapy , Humans , Immunization, Passive , Oxygen , COVID-19 SerotherapyABSTRACT
BACKGROUND: Heart failure (HF) is a growing problem for healthcare systems worldwide. Sodium and fluid restriction are non-pharmacological treatments recommended for patients with HF by several guidelines over the years, even without consensus. OBJECTIVE: To evaluate the effects of sodium and fluid restriction in patients with HF. METHODS: We searched MEDLINE, Embase, and Cochrane CENTRAL databases up to June 2020 and screened the reference lists of relevant articles. We included randomized controlled trials evaluating sodium and/or fluid restriction in patients with HF. We assessed three independent comparisons: (a) sodium restriction versus control; (b) fluid restriction versus control; and (c) sodium and fluid restriction versus control. Main outcomes of interest were all-cause mortality and hospitalization. Two independent reviewers selected studies and extracted data. We pooled the results using random-effects meta-analysis. We used the RoB 2.0 and the GRADE framework to assess risk of bias and quality of evidence. RESULTS: We included 16 studies totaling 3545 patients in our meta-analysis. Daily sodium intake was 1.5-2.4 g for the intervention group and >2.7 g for the control group, and daily fluid intake was 0.8-1.5 L for the intervention group and free oral fluid intake for the control group. Sodium restriction increased mortality (relative risk 1.92, 95% confidence interval 1.51 to 2.45, moderate quality of evidence) and hospitalization (relative risk 1.63, 1.11 to 2.40, low quality of evidence). Fluid restriction reduced mortality (relative risk 0.32, 0.13 to 0.82, low quality of evidence) and hospitalization (relative risk 0.46, 0.27 to 0.77, n = 331, low quality of evidence). The combination of sodium and fluid restriction did not significantly affect the risk of mortality (relative risk 0.92, 0.49 to 1.73, low quality of evidence) or the risk of hospitalization (relative risk 0.94, 0.75 to 1.19, low quality of evidence). CONCLUSION: The combination of sodium and fluid restriction in clinical trials resulted in a null effect although results in the opposite direction were observed for each intervention independently. Combined sodium and fluid restriction are usually recommended for patients with HF. Our findings of sodium restriction harm, risk of mortality and hospitalization are consistent with publications from several clinical trial and physiologic explanations. A well-designed clinical trial nested by an implementation study is urgent for definitive sodium range recommendation, specially considering the change of currently guidelines, pushing up the cut-off of sodium restriction range.
Subject(s)
Heart Failure , Sodium , Drinking , Fluid Therapy/methods , Heart Failure/therapy , Hospitalization , HumansABSTRACT
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.
Subject(s)
COVID-19 Drug Treatment , COVID-19 , Cardiology , Communicable Diseases , Emergency Medicine , Geriatrics , Azithromycin , Brazil , COVID-19/therapy , Community Medicine , Humans , Immunization, Passive , Outpatients , Vascular Surgical Procedures , COVID-19 SerotherapyABSTRACT
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.
Subject(s)
Humans , SARS-CoV-2/drug effects , COVID-19/drug therapy , Oxygen Inhalation Therapy , Thromboembolism/prevention & control , Immunization, Passive , Adrenal Cortex Hormones/therapeutic use , Lopinavir/therapeutic use , Health Planning Guidelines , Hydroxychloroquine , Anti-Bacterial Agents/therapeutic useABSTRACT
Over the last decade, there has been a 10-fold increase in the number of published systematic reviews of prevalence. In meta-analyses of prevalence, the summary estimate represents an average prevalence from included studies. This estimate is truly informative only if there is no substantial heterogeneity among the different contexts being pooled. In systematic reviews, heterogeneity is usually explored with I-squared statistic (I2 ), but this statistic does not directly inform us about the distribution of effects and frequently systematic reviewers and readers misinterpret this result. In a sample of 134 meta-analyses of prevalence, the median I2 was 96.9% (IQR 90.5-98.7). We observed larger I2 in meta-analysis with higher number of studies and extreme pooled estimates (defined as <10% or >90%). Studies with high I2 values were more likely to have conducted a sensitivity analysis, including subgroup analysis but only three (2%) systematic reviews reported prediction intervals. We observed that meta-analyses of prevalence often present high I2 values. However, the number of studies included in the meta-analysis and the point estimate can be associated with the I2 value, and a high I2 value is not always synonymous with high heterogeneity. In meta-analyses of prevalence, I2 statistics may not be discriminative and should be interpreted with caution, avoiding arbitrary thresholds. To discuss heterogeneity, reviewers should focus on the description of the expected range of estimates, which can be done using prediction intervals and planned sensitivity analysis.
Subject(s)
Systematic Reviews as Topic , PrevalenceABSTRACT
PURPOSE: Reviewing systematically the randomized controlled trials (RCTs) that evaluated aerobic exercisealone vs. usual care in exercise tolerance, functional capacity, and quality of life (QoL) in patients withpre-dialysis. METHODS: Searches in the MEDLINE, Cochrane CENTRAL, EMBASE, PEDro, and LILACS databases untilFebruary 2021 included RCTs that evaluated the effects of aerobic exercise on peak VO2, functional capacity,lower limb muscle strength, and QoL. The random effect meta-analysis model was used andreported as mean difference (MD) and 95% confidence interval (CI), risk of bias through RoB2.0 and thequality of evidence by GRADE. RESULTS: 10 RCTs, with 365 patients. Aerobic exercise increased 2.07 ml/kg/min (95% CI = 1.16 to 2.98; I2= 24%, QoE moderate) at peak VO2; 77.78m (95% CI= 33.27 to 122.30; I2= 44.5%, QoE moderate) in the 6MWT and 7.65 repetitions (95% CI= 5.73 to 9.58; I2= 0 %; QoE moderate) in STS-30 versus usual care. In QoL, studies reported improvements in the questionnaire scores.Eu.2 = 24%, QoE moderado) no pico de VO2; 77,78 m (IC95% = 33,27-122,30; Eu.2 = 44,5%, QoE moderado) nas repetições 6MWT e 7,65 (IC95% = 5,73-9,58; Eu.2 = 0%; QoE moderado) em STS-30". CONCLUSION: Aerobic exercise increases VO2 peak, functional capacity and lower limb muscle strength in patients with pre-dialysis. Effects on QoL appear to be beneficial.IMPLICATIONS FOR REHABILITATIONAerobic exercise should be encouraged in the rehabilitation of patients at any stage of chronic kidney disease.Aerobic exercise promotes improved exercise tolerance, functional capacity, and muscle strength of the lower limbs.There is some evidence to show it is beneficial to improve the quality of life.
Subject(s)
Exercise , Renal Insufficiency, Chronic , Dialysis , Exercise Therapy , Exercise Tolerance , Humans , Quality of Life , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/therapyABSTRACT
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.
ABSTRACT
BACKGROUND: Single group data present unique challenges for synthesises of evidence. Proportional meta-analysis is becoming an increasingly common technique employed for the synthesis of single group data. Proportional meta-analysis shares many similarities with the conduct and reporting of comparative, or pairwise, meta-analysis. While robust and comprehensive methods exist detailing how researchers can conduct a meta-analysis that compares two (or more) groups against a common intervention, there is a scarcity of methodological guidance available to assist synthesisers of evidence in the conduct, interpretation, and importance of proportional meta-analysis in systematic reviews. MAIN BODY: This paper presents an overview targeted to synthesisers of evidence and systematic review authors that details the methods, importance, and interpretation of a proportional meta-analysis. We provide worked examples of how proportional meta-analyses have been conducted in research syntheses previously and consider the methods, statistical considerations, and presentation of this technique. CONCLUSION: This overview is designed to serve as practical guidance for synthesisers of evidence in the conduct of proportional meta-analyses.
Subject(s)
Research Design , Research Personnel , Humans , Systematic Reviews as TopicABSTRACT
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.
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.
Subject(s)
Brain Death , Critical Care , Brain , Humans , Respiration, Artificial , Tissue DonorsABSTRACT
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.
Subject(s)
Humans , Brain Death , Critical Care , Respiration, Artificial , Tissue Donors , BrainABSTRACT
CONTEXT: Risk of cancer is a major concern in the development of drugs for the treatment of obesity and diabetes. In randomized controlled trials (RCTs) of the Liraglutide Clinical Development Program, subjects treated with a glucagon-like peptide-1 receptor agonist (GLP-1RA) had a higher absolute number of breast cancer events. OBJECTIVE: To assess whether patients treated with GLP-1RAs had a higher risk of breast neoplasms. DATA SOURCES: We searched MEDLINE, Embase, Web of Science, and CENTRAL from July 31, 2019 to February 8, 2020. STUDY SELECTION: Reviewers assessed abstracts and full-text articles for RCTs of GLP-1RAs in adults with excessive weight and/or diabetes and a minimum follow-up of 24 weeks. DATA EXTRACTION: Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). DATA SYNTHESIS: We included 52 trials, of which 50 reported breast cancer events and 11 reported benign breast neoplasms. Overall methodological quality was high. Among 48 267 subjects treated with GLP-1RAs, 130 developed breast cancer compared with 107 of 40 755 controls (relative risk [RR], 0.98; 95% confidence interval [CI], 0.76-1.26). Subset analyses according to follow-up, participant/investigator blinding, and type of GLP-1RA did not reveal any differences. The risk of benign breast neoplasms also did not differ between groups (RR, 0.99; 95% CI, 0.48-2.01). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. CONCLUSIONS: Treatment with GLP-1RAs for obesity and diabetes does not increase the risk of breast neoplasms.
Subject(s)
Breast Neoplasms/chemically induced , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/adverse effects , Adult , Breast Neoplasms/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Exenatide/adverse effects , Female , Humans , Liraglutide/adverse effects , Obesity/drug therapy , Obesity/epidemiology , Risk , Risk FactorsABSTRACT
OBJECTIVE: To contribute to updating the recommendations for brain-dead potential organ donor management. METHOD: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, joined a task force formed by the General Coordination Office of the National Transplant System/Brazilian Ministry of Health (CGSNT-MS), the Brazilian Association of Intensive Care Medicine (AMIB), the Brazilian Association of Organ Transplantation (ABTO), and the Brazilian Research in Intensive Care Network (BRICNet). The questions were developed within the scope of the 2011 Brazilian Guidelines for Management of Adult Potential Multiple-Organ Deceased Donors. The topics were divided into mechanical ventilation, hemodynamic support, endocrine-metabolic management, infection, body temperature, blood transfusion, and use of checklists. The outcomes considered for decision-making were cardiac arrest, number of organs recovered or transplanted per donor, and graft function/survival. Rapid systematic reviews were conducted, and the quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Two expert panels were held in November 2016 and February 2017 to classify the recommendations. A systematic review update was performed in June 2020, and the recommendations were reviewed through a Delphi process with the panelists between June and July 2020. RESULTS: A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong (lung-protective ventilation strategy, vasopressors and combining arginine vasopressin to control blood pressure, antidiuretic hormones to control polyuria, serum potassium and magnesium control, and antibiotic use), 11 as weak (alveolar recruitment maneuvers, low-dose dopamine, low-dose corticosteroids, thyroid hormones, glycemic and serum sodium control, nutritional support, body temperature control or hypothermia, red blood cell transfusion, and goal-directed protocols), and 1 was considered a good clinical practice (volemic expansion). CONCLUSION: Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak. The observed lack of robust evidence on the topic highlights the importance of the present guideline to improve the management of brain-dead potential organ donors.
ABSTRACT
OBJECTIVE: To systematically review evidence comparing the effect of low-dose versus high-dose ACE inhibitors (ACEIs) on all-cause and cardiovascular mortality and hospitalisation, functional capacity and side effects in patients with heart failure (HF). METHODS: We searched PubMed, Embase, Cochrane CENTRAL and LILACS up to January 2019. We included randomised controlled trials (RCTs) comparing low-dose versus high-dose ACEIs in adults with HF with reduced left ventricular ejection fraction (HFrEF). Study selection and data extraction were performed by two independent reviewers. Risk of bias was assessed with RoB 2.0, and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). We conducted random effects meta-analysis and trial sequential analysis. RESULTS: We included eight RCTs (5829 patients with HF). In comparison with low-dose ACEIs, high-dose ACEIs showed a non-significant effect on all-cause mortality (8 RCTs, n=5828, relative risk (RR) 0.95, 95% CI 0.88 to 1.02; moderate quality of evidence), cardiovascular mortality (6 RCTs, n=4048, RR 0.93, 95% CI 0.85 to 1.01; moderate quality of evidence), all-cause hospitalisation (5 RCTs, n=5394, RR 0.95, 95% CI 0.82 to 1.10; moderate quality of evidence) and cardiovascular hospitalisation (4 RCTs, n=5242, RR 0.98, 95% CI 0.83 to 1.17; low quality of evidence). High-dose ACEI increased functional capacity (4 studies, n=555, standardised mean difference 0.38, 95% CI 0.20 to 0.55; low quality of evidence) and the risk of hypotension (4 RCTs, n=3783, RR 1.64, 95% CI 1.30 to 2.05; moderate quality of evidence). High-dose ACEI had no effect on dizziness (3 RCTs, n=4994, RR 1.37, 95% CI 0.97 to 1.93; low quality of evidence), but decreased the risk of cough (4 RCTs, n=5146, RR 0.85, 95% CI 0.73 to 0.98; moderate quality of evidence). CONCLUSIONS: The magnitude of benefit of using high dose versus low to intermediate doses of ACEIs might be less than traditionally suggested in clinical guidelines. These findings might help clinicians address the complex task of HF management in a more rational and timely fashion, saving efforts to implement strategies with the greatest net clinical benefit.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Heart Failure/drug therapy , Stroke Volume/drug effects , Ventricular Function, Left/drug effects , Aged , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Female , Functional Status , Heart Disease Risk Factors , Heart Failure/diagnosis , Heart Failure/mortality , Heart Failure/physiopathology , Humans , Male , Middle Aged , Recovery of Function , Risk Assessment , Treatment OutcomeABSTRACT
OBJECTIVES: The objective of the study is to identify items and domains applicable for the quality assessment of prevalence studies. STUDY DESIGN AND SETTING: We searched databases and the gray literature to identify tools or guides about the quality assessment of prevalence studies. After study selection, we abstracted questions applicable for prevalence studies and classified into at least one of the following domains: 'population and setting', 'condition measurement', 'statistics', and 'other'. PROSPERO registration:CRD42018088437. RESULTS: We included 30 tools: eight (26.7%) specifically designed to appraise prevalence studies and 22 (73.3%) adaptable for this purpose. We identified 12 unique items in the domain "population and setting", 16 in the domain "condition measurement", and 14 in the domain "statistics". Of those, 25 (59.5%) were identified in the eight specific tools. Regarding the domain "other", we identified 77 unique items, mainly related to manuscript writing and reporting (n = 48, 62.3%); of those, 24 (31.2%) were identified in the eight specific tools and 53 (68.8%) in the additional 22 nonspecific tools. CONCLUSION: We provide a comprehensive set of items classified by domains that can guide the appraisal of prevalence studies, conduction of primary prevalence studies, and update or development of tools to evaluate prevalence studies.
Subject(s)
Bias , Cross-Sectional Studies/standardsABSTRACT
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.
Subject(s)
Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , COVID-19 , Humans , PandemicsABSTRACT
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. 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. 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. 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.
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. 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. 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. 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
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics/prevention & control , Betacoronavirus/drug effects , Heparin/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Ritonavir/therapeutic use , Oseltamivir/therapeutic use , Lopinavir/therapeutic use , Aminoquinolines/therapeutic use , Anti-Bacterial Agents/therapeutic useABSTRACT
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.
Subject(s)
Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Pandemics , COVID-19ABSTRACT
BACKGROUND: There is a notable lack of methodological and reporting guidance for systematic reviews of prevalence data. This information void has the potential to result in reviews that are inconsistent and inadequate to inform healthcare policy and decision making. The aim of this meta-epidemiological study is to describe the methodology of recently published prevalence systematic reviews. METHODS: We searched MEDLINE (via PubMed) from February 2017 to February 2018 for systematic reviews of prevalence studies. We included systematic reviews assessing the prevalence of any clinical condition using patients as the unit of measurement and we summarized data related to reporting and methodology of the reviews. RESULTS: A total of 235 systematic reviews of prevalence were analyzed. The median number of authors was 5 (interquartile range [IQR] 4-7), the median number of databases searched was 4 (3-6) and the median number of studies included in each review was 24 (IQR 15-41.5). Search strategies were presented for 68% of reviews. Forty five percent of reviews received external funding, and 24% did not provide funding information. Twenty three percent of included reviews had published or registered the systematic review protocol. Reporting guidelines were used in 72% of reviews. The quality of included studies was assessed in 80% of reviews. Nine reviews assessed the overall quality of evidence (4 using GRADE). Meta-analysis was conducted in 65% of reviews; 1% used Bayesian methods. Random effect meta-analysis was used in 94% of reviews; among them, 75% did not report the variance estimator used. Among the reviews with meta-analysis, 70% did not report how data was transformed; 59% percent conducted subgroup analysis, 38% conducted meta-regression and 2% estimated prediction interval; I2 was estimated in 95% of analysis. Publication bias was examined in 48%. The most common software used was STATA (55%). CONCLUSIONS: Our results indicate that there are significant inconsistencies regarding how these reviews are conducted. Many of these differences arose in the assessment of methodological quality and the formal synthesis of comparable data. This variability indicates the need for clearer reporting standards and consensus on methodological guidance for systematic reviews of prevalence data.
