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. / 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.

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.

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.

Cost-effectiveness of antimicrobial treatment for inpatients with carbapenem-resistant Klebsiella pneumoniae infection: a systematic review of economic evidence.

OBJECTIVES: The objective of this review was to evaluate the cost-effectiveness of antimicrobial therapy for patients with carbapenem-resistant Klebsiella pneumoniae infection. INTRODUCTION: Among the main multi-resistant microorganisms, carbapenem-resistant K. pneumoniae is responsible for the mortality of 40% of patients following 30 days of infection. Treatment for carbapenem-resistant K. pneumoniae infection entails the use of high-cost antimicrobials. Inappropriate use of antimicrobials can increase the cost of treatment fourfold. This review aimed to evaluate the cost-effectiveness of antimicrobial therapy treatment for patients with carbapenem-resistant K. pneumoniae infection to better inform decision making in hospital services. INCLUSION CRITERIA: The review included studies on participants 18 years or over with carbapenem-resistant K. pneumoniae infection who had undergone antimicrobial therapy in hospital and acute care services. Studies that compared the cost-effectiveness of different antimicrobial therapy for carbapenem-resistant K. pneumoniae infection were included. Outcome measures were cost per unit of effect expressed in clinical outcome units; this included cost per avoided death, cost per prevention of sepsis and cost per duration of stay. Economic studies with a cost-effectiveness design were considered, as well as modeling studies. METHODS: A three-step search strategy was utilized to locate studies published in English, Spanish or Portuguese, with no date restrictions. Two independent reviewers screened titles and abstracts and the full texts of potentially relevant studies for eligibility. Methodological quality was assessed by two independent reviewers using the JBI critical appraisal checklist for economic evaluations. Data were extracted from included studies using the standardized JBI data extraction tool. Data were synthesized using narrative, tables and the JBI Dominance Ranking Matrix. RESULTS: This review identified eight studies that evaluated the cost-effectiveness of different treatments for carbapenem-resistant K. pneumoniae infection. The results of this study demonstrated that there was no gold standard treatment for carbapenem-resistant K. pneumoniae infection, hence treatment was generally directed by colonization pressure and resistance profiles. Furthermore, due to the moderate quality and limited number of studies, there was high uncertainty of the values of the cost-effectiveness ratio. CONCLUSIONS: Ofloxacin appears to be the most cost-effective treatment; however, conclusions are limited due to the small number and low quality of studies.

Análise econômica do denosumabe e dos bisfosfonatos no tratamento de pacientes com metástase óssea / Economic analysis of denosumab and bisphosphonates for the treatment of patients with bone metastases

Introdução: Metástases ósseas são prevalentes em pacientes com câncer avançado e podem causar prejuízos significativos na qualidade de vida do doente. O tratamento consiste no controle da dor e na prevenção de Eventos Relacionados ao Esqueleto (ERE), complicações altamente limitantes e de impacto multidimensional. Na prevenção de ERE são utilizados bisfosfonatos e denosumabe, medicamentos de uso crônico e de alto custo, os quais requerem avaliações de custo-efetividade, sobretudo para auxiliar decisões que envolvem alocação de recursos públicos. Objetivo: Realizar análise econômica de medicamentos alvo-específicos usados no tratamento de pacientes com metástases ósseas. Método: Trata-se de uma Avaliação de Tecnologias em Saúde (ATS) em que se realizou Análise de Custo-Efetividade (ACE) e de impacto orçamentário (AIO), sob a perspectiva do Sistema Único de Saúde, com horizonte temporal de dois anos. Os dados relativos a custos foram provenientes de bases de dados nacionais. Informações relativas à efetividade, medida pela proporção de pacientes livres de ERE derivou-se de revisões sistemáticas. Na ACE, desenvolveram-se dois modelos de Markov, a saber: pacientes com câncer de mama, cujo tratamento foi baseado no uso de denosumabe, ácido zoledrônico ou pamidronato; e para Outros Tumores Sólidos (OTS), baseado no uso de denosumabe ou ácido zoledrônico. Nestes modelos, considerou-se quatro estados de saúde (com/sem ERE, novo ERE e morte). Resultados foram expressos em Razão de Custo- Efetividade Incremental (RCEI) e as incertezas foram testadas em análise de sensibilidade determinística e probabilística. Realizou-se AIO em cinco anos, considerando-se diferentes cenários de uso das terapias. Resultados: Na modelagem de Markov para mama, evidenciou-se que o pamidronato foi o tratamento mais custo-efetivo. As RCEI do ácido zoledrônico e do denosumabe em relação ao pamidronato foram, respectivamente, de R$ 5.935,60 e R$ 17.929,09 por ERE evitado. No modelo para OTS, a estratégia custo-efetiva foi o ácido zoledrônico. A RCEI do denosumabe em relação ao ácido zoledrônico foi de R$ 26.061,90 por ERE evitada. Em análise de sensibilidade, os resultados inicialmente encontrados foram mantidos, o que indica a robustez das análises. Na AIO, independentemente do tipo de tumor, o uso do ácido zoledrônico representou o cenário menos oneroso, em cinco anos. Conclusões: Para o Brasil, as ACE apontaram que o medicamento custo- efetivo para o tratamento de metástases ósseas no câncer de mama foi o pamidronato e para OTS foi o ácido zoledrônico. A incorporação do denosumabe resultaria em aumento substancial nos custos do tratamento, especialmente em longo prazo. Entretanto, para a tomada de decisão, devem-se considerar fatores para além de efetividade, segurança e custos, como aceitabilidade, valores e preferências dos pacientes, viabilidade e equidade.

Introduction: Bone metastases are prevalent among patients with advanced cancer and may result in significant decrease in quality of life. Its treatment consists of pain alleviation and prevention of Skeletal Related Events (SRE), highly debilitating complications with multidimensional impact. Bisphosphonates and denosumab are the treatment of choice to prevent SRE. Both are high cost medications of chronic use, which requires cost effectiveness analyses to support decision making in resource allocation. Objectives: To conduct an economic analysis of bone-targeted agents for the treatment of bone metastases secondary to solid tumors. Methods: A Health Technology Assessment (HTA) with Cost-Effectiveness Analysis (CEA) and Budget Impact Analysis (BIA) was performed from the Brazilian Unified Healthcare System, over a 2-year time horizon. Data were collected from different sources and included national databases for different categories of costs, and scientific articles for effectiveness, measured by the proportion of SRE-free patients. The CEA was based on two Markov models: For patients with breast cancer, in which the treatment was based on denosumab, zoledronic acid or pamidronate; and for Other Solid Tumors (OST), based on the use of denosumab and zoledronic acid. In these models, four health states (with/without SRE, new SRE, and death), and their transition probabilities were considered. Results were expressed by means of Incremental Cost-Effectiveness Ratios (ICER), and the uncertainties were tested in deterministic and probabilistic sensitivity analyses. A BIA in five years was conducted considering different scenarios. Results: In the Markov model for breast cancer, pamidronate was the cost-effective strategy. In the zoledronic acid/pamidronate and denosumab/pamidronate comparisons, ICERs of R$ 5,935.70 and R$ 17,929.09 per SRE avoided were observed. In the OST model, zoledronic acid was the cost-effective strategy, and the ICER of denosumab compared with zoledronic acid was R$ 26,061.44 per SRE avoided. Sensitivity analysis confirmed the robustness of the model, as results remained unchanged. In the BIA, regardless of tumor type, the least costly scenario in five years was the one in which all patients received zoledronic acid. Conclusion: Considering the Brazilian healthcare setting, the CEA showed that pamidronate for breast cancer and zoledronic acid for OST were the cost-effective strategies. Denosumab coverage would result in substantial increase in treatment costs. However, in the decision-making process, factors beyond effectiveness, safety and costs should be considered, for example, acceptability, patients values and preferences, feasibility and equity.

Cost-effectiveness of the antimicrobial treatment for inpatients infected with Klebsiella pneumoniae carbapenemase: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to evaluate the cost-effectiveness of antimicrobial therapy treatment for inpatients infected with Klebsiella pneumoniae carbapenemase.More specifically, the review question is: What is the best evidence on the cost-effectiveness of the antimicrobial treatment for inpatients infected with Klebsiella Pneumoniae Carbapenemase?"

Effects of dignity therapy on terminally ill patients: a systematic review / Efectos de la Terapia Dignidad Para Pacientes en Fase Final de Vida: Revisión Sistemática / Efeitos da terapia da dignidade para pacientes em fase final de vida: revisão sistemática

Abstract OBJECTIVE Analyzing the evidence of the effects of dignity therapy onterminally ill patients. METHOD A Systematic review of the literature conducted using the search strategy in six databases. Inclusion criteria were primary studies, excluding literature reviews (systematic or not) and conceptual articles. RESULTS Ten articles were analyzed regarding method, results and evidence level. Dignity therapy improved the sense of meaning andpurpose, will to live, utility, quality of life, dignity and family appreciationin studies with a higher level of evidence. The effects are not well established in relation to depression, anxiety, spirituality and physical symptoms. CONCLUSION Studies with a moderate to high level of evidence have shown increased sense of dignity, will to live and sense of purpose. Further studies should be developed to increase knowledge about dignity therapy.

Resumen OBJETIVO Analizar las evidencias acerca de los efectos de la terapia dignidad para pacientes en fase terminal de vida. MÉTODO Revisión sistemática de la literatura llevada a cabo en seis bases de datos en la estrategia de búsqueda. Los criterios de inclusión fueron estudios primarios, excluyéndose las revisiones de literatura (sistemáticas o no) y los artículos conceptuales. RESULTADOS Diez artículos fueron analizados en cuanto al método, los resultados y el nivel de evidencia. En los estudios con mayor nivel de evidencia, la terapida de la dignidad mejoró el sentido de significado, propósito, ganas de vivir, utilidad, calidad de vida, dignidad y estimación familiar. Los efectos no están bien planteados con respecto a la depresión, ansiedad, espiritualidad y los síntomas físicos. CONCLUSIÓN Los estudios de nivel de evidencia de moderado a alto demostraron incremento del sentido de dignidad, ganas de vivir y sentido de propósito. Se deben desarrollar más estudios a fin de ampliar el conocimiento acerca de la terapia de la dignidad.

Resumo OBJETIVO Analisar as evidências sobre os efeitos da terapia da dignidade para pacientes em fase terminal de vida. MÉTODO Revisão sistemática da literatura realizada em seis bases de dados na estratégia de busca. Os critérios de inclusão foram estudos primários, excluindo-se revisões da literatura (sistemáticas ou não) e artigos conceituais. RESULTADOS Dez artigos foram analisados quanto ao método, aos resultados e nível de evidência. Nos estudos com maior nível de evidência, a terapia da dignidade melhorou o senso de significado, propósito, vontade de viver, utilidade, qualidade de vida, dignidade e apreciação familiar.Os efeitos não estão bem estabelecidos em relação à depressão, ansiedade, espiritualidade e aos sintomas físicos. CONCLUSÃO Os estudos de nível de evidência de moderado a alto demonstraram aumento do senso de dignidade, vontade de viver e senso de propósito. Mais estudos devem ser desenvolvidos para ampliar o conhecimento sobre a terapia da dignidade.

Effects of dignity therapy on terminally ill patients: a systematic review.

OBJECTIVE: Analyzing the evidence of the effects of dignity therapy onterminally ill patients. METHOD: A Systematic review of the literature conducted using the search strategy in six databases. Inclusion criteria were primary studies, excluding literature reviews (systematic or not) and conceptual articles. RESULTS: Ten articles were analyzed regarding method, results and evidence level. Dignity therapy improved the sense of meaning andpurpose, will to live, utility, quality of life, dignity and family appreciationin studies with a higher level of evidence. The effects are not well established in relation to depression, anxiety, spirituality and physical symptoms. CONCLUSION: Studies with a moderate to high level of evidence have shown increased sense of dignity, will to live and sense of purpose. Further studies should be developed to increase knowledge about dignity therapy. OBJETIVO: Analisar as evidências sobre os efeitos da terapia da dignidade para pacientes em fase terminal de vida. MÉTODO: Revisão sistemática da literatura realizada em seis bases de dados na estratégia de busca. Os critérios de inclusão foram estudos primários, excluindo-se revisões da literatura (sistemáticas ou não) e artigos conceituais. RESULTADOS: Dez artigos foram analisados quanto ao método, aos resultados e nível de evidência. Nos estudos com maior nível de evidência, a terapia da dignidade melhorou o senso de significado, propósito, vontade de viver, utilidade, qualidade de vida, dignidade e apreciação familiar.Os efeitos não estão bem estabelecidos em relação à depressão, ansiedade, espiritualidade e aos sintomas físicos. CONCLUSÃO: Os estudos de nível de evidência de moderado a alto demonstraram aumento do senso de dignidade, vontade de viver e senso de propósito. Mais estudos devem ser desenvolvidos para ampliar o conhecimento sobre a terapia da dignidade.