Modeling the impact of child vaccination (5-11 y) on overall COVID-19 related hospitalizations and mortality in a context of omicron variant predominance and different vaccination coverage paces in Brazil.

Background: Developing countries have experienced significant COVID-19 disease burden. With the emergence of new variants, particularly omicron, the disease burden in children has increased. When the first COVID-19 vaccine was approved for use in children aged 5-11 years of age, very few countries recommended vaccination due to limited risk-benefit evidence for vaccination of this population. In Brazil, ranking second in the global COVID-19 death toll, the childhood COVID-19 disease burden increased significantly in early 2022. This prompted a risk-benefit assessment of the introduction and scaling-up of COVID-19 vaccination of children. Methods: To estimate the potential impact of vaccinating children aged 5-11 years with mRNA-based COVID-19 vaccine in the context of omicron dominance, we developed a discrete-time SEIR-like model stratified in age groups, considering a three-month time horizon. We considered three scenarios: No vaccination, slow, and maximum vaccination paces. In each scenario, we estimated the potential reduction in total COVID-19 cases, hospitalizations, deaths, hospitalization costs, and potential years of life lost, considering the absence of vaccination as the base-case scenario. Findings: We estimated that vaccinating at a maximum pace could prevent, between mid-January and April 2022, about 26,000 COVID-19 hospitalizations, and 4200 deaths in all age groups; of which 5400 hospitalizations and 410 deaths in children aged 5-11 years. Continuing vaccination at a slow/current pace would prevent 1450 deaths and 9700 COVID-19 hospitalizations in all age groups in this same time period; of which 180 deaths and 2390 hospitalizations in children only. Interpretation: Maximum vaccination of children results in a significant reduction of COVID-19 hospitalizations and deaths and should be enforced in developing countries with significant disease incidence in children. Funding: This manuscript was funded by the Brazilian Council for Scientific and Technology Development (CNPq - Process # 402834/2020-8).

Modelling the impact of school reopening and contact tracing strategies on Covid-19 dynamics in different epidemiologic settings in Brazil.

We simulate the impact of school reopening during the COVID-19 pandemic in three major urban centers in Brazil to identify the epidemiological indicators and the best timing for the return of in-school activities and the effect of contact tracing as a mitigation measure. Our goal is to offer guidelines for evidence-based policymaking. We implement an extended SEIR model stratified by age and considering contact networks in different settings - school, home, work, and community, in which the infection transmission rate is affected by various intervention measures. After fitting epidemiological and demographic data, we simulate scenarios with increasing school transmission due to school reopening, and also estimate the number of hospitalization and deaths averted by the implementation of contact tracing. Reopening schools results in a non-linear increase in reported COVID-19 cases and deaths, which is highly dependent on infection and disease incidence at the time of reopening. When contact tracing and quarantining are restricted to school and home settings, a large number of daily tests is required to produce significant effects in reducing the total number of hospitalizations and deaths. Policymakers should carefully consider the epidemiological context and timing regarding the implementation of school closure and return of in-person school activities. While contact tracing strategies prevent new infections within school environments, they alone are not sufficient to avoid significant impacts on community transmission.

Modelling optimal vaccination strategies against COVID-19 in a context of Gamma variant predominance in Brazil.

INTRODUCTION: Brazil experienced moments of collapse in its health system throughout 2021, driven by the emergence of variants of concern (VOC) combined with an inefficient initial vaccination strategy against Covid-19. OBJECTIVES: To support decision-makers in formulating COVID-19 immunization policy in the context of limited vaccine availability and evolving variants over time, we evaluate optimal strategies for Covid-19 vaccination in Brazil in 2021, when vaccination was rolled out during Gamma variant predominance. METHODS: Using a discrete-time epidemic model we estimate Covid-19 deaths averted, considering the currently Covid-19 vaccine products and doses available in Brazil; vaccine coverage by target population; and vaccine effectiveness estimates. We evaluated a 5-month time horizon, from early August to the end of December 2021. Optimal vaccination strategies compared the outcomes in terms of averted deaths when varying dose intervals from 8 to 12 weeks, and choosing the minimum coverage levels per age group required prior to expanding vaccination to younger target populations. We also estimated dose availability required over time to allow the implementation of optimal strategies. RESULTS: To maximize the number of averted deaths, vaccine coverage of at least 80 % should be reached in older age groups before starting vaccination into subsequent younger age groups. When evaluating varying dose intervals for AZD1222, reducing the dose interval from 12 to 8 weeks for the primary schedule would result in fewer COVID-19 deaths, but this can only be implemented if accompanied by an increase in vaccine supply of at least 50 % over the coming six-months in Brazil. CONCLUSION: Covid-19 immunization strategies should be tailored to local vaccine product availability and supply over time, circulating variants of concern, and vaccine coverage in target population groups. Modelling can provide valuable and timely evidence to support the implementation of vaccination strategies considering the local context, yet following international and regional technical evidence-based guidance.

Automation of a tertiary hospital pharmacy drug dispensing system in a lower-middle-income country: A case study and preliminary results.

Background: An increase in the use of automated systems has optimised the drug dispensing process in hospitals. Methods: This case study describes the implementation of automated drug dispensing system and presents the preliminary results of automated pharmaceutical dispensing with robots (PillPick® and BoxPicker®, ©Swisslog Healthcare) at Hospital Sírio-Libanês, a private tertiary hospital in Brazil. Results: During the study period, between 2013 (pre-automation) and 2017 (post-automation) the number total of medication errors has not changed post-automation, but there was significant reduction in error in the dispensing phase with a relative risk of 0.84 (95% confidence interval: 0.70-0.99) withal a reduction in the numbers of returned items, breakages, and loss of medications, although that delivery times have increased.. Conclusion: The study results suggest that the use of robotic systems in the central pharmacy may improve hospital pharmacy management and generate only a few errors in dispensing pharmaceuticals.

Vitamin C-based regimens for sepsis and septic shock: Systematic review and meta-analysis of randomized clinical trials.

PURPOSE: to critically appraise and synthesize the evidence on the effects of vitamin C-based regimens for patients with sepsis or septic shock. METHODS: a broad search was performed on May 2021 to identify randomized clinical trials (RCTs) assessing vitamin C-based regimens as adjuvant therapy for adults with sepsis or septic shock. We used the Cochrane Risk of Bias table to assess the methodological quality of the included RCTs and the GRADE approach to evaluate the evidence certainty. RESULTS: We included 20 RCTs (2124 participants). Evidence from low to very low certainty showed that vitamin C compared to placebo may reduce all-cause mortality up to 28 days (relative risk [RR] 0.60, 95% confidence interval (CI) 0.45 to 0.80, 4 RCTs, 335 participants). Considering the other comparisons (vitamin C alone or combined with thiamine and/or hydrocortisone, compared to placebo, standard care or hydrocortisone), there were a little to no difference or very uncertain evidence for adverse events, SOFA score, ICU length of stay, acute kidney injury, mechanical ventilation- and vasoactive drugs-free days up to 28 days. CONCLUSION: Further RCTs with higher methodological quality, an increased number of participants and assessing clinically relevant outcomes are needed to provide better decision-making guidance. PROSPERO REGISTER: CRD42021251786.

Telehealth Strategies to Support Referral Management to Secondary Care in Brazil: A Cost-Effectiveness Analysis.

OBJECTIVES: This study aimed to assess the cost-effectiveness of a remotely operated referral management system (RORMS) compared with a conventional referral management system (CRMS) in Brazil. METHODS: This is a model-based cost-effectiveness analysis under the perspective of the Unified Healthcare System (Sistema Único de Saúde [SUS]) in Brazil. A Markov microsimulation model was developed to compare costs and referral outcomes of the RORMS and the CRMS. Model consisted of 4 states representative of sequential stepwise assessments of referral suitability, 3 states representative of referral outcomes, and 1 exit model state. Target population represented cases being referred from primary healthcare units to specialized care in SUS. Model inputs related to costs and effectiveness in the RORMS arm were obtained from the data set of a RORMS between July and December 2019. Model inputs for the CRMS model arm were obtained from administrative data sets of 2 Brazilian localities for the year 2019. Relative effect size of RORMS in comparison with CRMS in SUS was obtained from published studies. Effectiveness outcome was unnecessary referrals averted. The incremental cost-effectiveness ratio was calculated for the base case. Probabilistic sensitivity analysis was conducted. RESULTS: In the base-case analyses, RORMS dominated CRMS, with expected cost-savings from $50.42 to $80.62 per unnecessary referral averted. RORMS was the dominant strategy in 83.7% of 100 000 simulations in the probabilistic sensitivity analysis. In 16.2% of simulations, incremental cost-effectiveness ratio was between $0 and $222 per unnecessary referral averted. CONCLUSIONS: Model-based simulations indicate that the RORMS is likely to be cost saving in comparison with the CRMS.

Micro-Costing of a Remotely Operated Referral Management System to Secondary Care in the Unified Health System in Brazil.

Referral of cases from primary to secondary care in the Brazilian public healthcare system is one of the most important issues to be tackled. Telehealth strategies have been shown effective in avoiding unnecessary referrals. The objective of this study was to estimate cost per referred case by a remotely operated referral management system to further inform the decision making on the topic. Analysis of cost by applying time-driven activity-based costing. Cost analyses included comparisons between medical specialties, localities for which referrals were being conducted, and periods of time. Cost per referred case across localities ranged from R$ 5.70 to R$ 8.29. Cost per referred case across medical specialties ranged from R$ 1.85 to R$ 8.56. Strategies to optimize the management of referral cases to specialized care in public healthcare systems are still needed. Telehealth strategies may be advantageous, with cost estimates across localities ranging from R$ 5.70 to R$ 8.29, with additional observed variability related to the type of medical specialty.

Micro-Costing of a Remotely Operated Referral Management System to Secondary Care in the Unified Health System in Brazil / Microcusteio de um Sistema de Regulação Remoto para o Cuidado Especializado no Sistema Único de Saúde no Brasil

Abstract Referral of cases from primary to secondary care in the Brazilian public healthcare system is one of the most important issues to be tackled. Telehealth strategies have been shown effective in avoiding unnecessary referrals. The objective of this study was to estimate cost per referred case by a remotely operated referral management system to further inform the decision making on the topic. Analysis of cost by applying time-driven activity-based costing. Cost analyses included comparisons between medical specialties, localities for which referrals were being conducted, and periods of time. Cost per referred case across localities ranged from R$ 5.70 to R$ 8.29. Cost per referred case across medical specialties ranged from R$ 1.85 to R$ 8.56. Strategies to optimize the management of referral cases to specialized care in public healthcare systems are still needed. Telehealth strategies may be advantageous, with cost estimates across localities ranging from R$ 5.70 to R$ 8.29, with additional observed variability related to the type of medical specialty.

Resumo O encaminhamento de casos da atenção primária para a secundária no Sistema Único Brasileiro é uma das questões mais importantes a ser enfrentada. As estratégias de telessaúde têm se mostrado eficazes para evitar encaminhamentos desnecessários. O objetivo deste estudo foi estimar o custo por caso encaminhado por meio de um sistema de gerenciamento de referenciamentos operado remotamente para subsidiar a tomada de decisão sobre o tema. Análise de custo por meio da aplicação de custeio baseado em atividades orientado pelo tempo (time-driven activity-based costing ou TDABC). As análises de custo incluíram comparações entre especialidades médicas, localidades para as quais os encaminhamentos estavam sendo conduzidos e períodos de tempo. O custo por referenciamento em todas as localidades variou entre R$ 5,70 a R$ 8,29. O custo por referenciamento nas especialidades médicas variou entre R$ 1,85 a R$ 8,56. Estratégias para otimizar a gestão dos referenciamentos para a atenção especializada nos sistemas públicos de saúde ainda são necessárias. As estratégias de telessaúde podem ser vantajosas, com estimativas de custo entre as localidades variando entre R$ 5,70 a R$ 8,29, com variabilidade adicional observada relacionada ao tipo de especialidade médica.

Efficacy and safety of therapeutic use of cannabis derivatives and their synthetic analogs: Overview of systematic reviews.

The debate on the use of cannabinoids for therapeutic purposes is constantly on the rise. This overview aimed to map the evidence on the therapeutic effects of cannabis derivatives and their synthetic analogs. Systematic reviews (SRs) of randomized trials were identified through a comprehensive search in several databases, and their methodological quality were evaluated with AMSTAR-2. The results for main outcomes are presented, prioritizing those from updated and better quality SRs. Finally, 68 SRs, addressing 37 different health conditions, were included. The methodological quality was high for eight SRs. The evidence certainty (GRADE) for the effects of cannabinoids is not high for any of the outcomes identified. Evidence certainty was moderate for the following: (a) cannabidiol appears to be beneficial for quality of life but increases the risk of adverse events in ulcerative colitis; (b) cannabinoids in general appear to have no clinically important benefit for chronic non-oncologic pain, spasticity-related pain in multiple sclerosis, or for acute post-operative pain; (c) cannabinoids in general appear to have a benefit in reducing chemotherapy-related nausea and vomiting. For all other outcomes from remaining comparisons, the evidence certainty was low, very low, or not evaluated, which prevents recommendations for or against their routine use.

Frequency, signs and symptoms, and criteria adopted for long COVID-19: A systematic review.

AIMS: To identify, systematically evaluate and summarise the best available evidence on the frequency of long COVID-19 (post-acute COVID-19 syndrome), its clinical manifestations, and the criteria used for diagnosis. METHODS: Systematic review conducted with a comprehensive search including formal databases, COVID-19 or SARS-CoV-2 data sources, grey literature, and manual search. We considered for inclusion clinical trials, observational longitudinal comparative and non-comparative studies, cross-sectional, before-and-after, and case series. We assessed the methodological quality by specific tools based on the study designs. We presented the results as a narrative synthesis regarding the frequency and duration of long COVID-19, signs and symptoms, criteria used for diagnosis, and potential risk factors. RESULTS: We included 25 observational studies with moderate to high methodological quality, considering 5440 participants. The frequency of long COVID-19 ranged from 4.7% to 80%, and the most prevalent signs/symptoms were chest pain (up to 89%), fatigue (up to 65%), dyspnea (up to 61%), and cough and sputum production (up to 59%). Temporal criteria used to define long COVID-19 varied from 3 to 24 weeks after acute phase or hospital discharge. Potentially associated risk factors were old age, female sex, severe clinical status, a high number of comorbidities, hospital admission, and oxygen supplementation at the acute phase. However, limitations related to study designs added uncertainty to this finding. None of the studies assessed the duration of signs/symptoms. CONCLUSION: The frequency of long COVID-19 reached up to 80% over the studies included and occurred between 3 and 24 weeks after acute phase or hospital discharge. Chest pain, fatigue, dyspnea, and cough were the most reported clinical manifestations attributed to the condition. Based on these systematic review findings, there is an urgent need to understand this emerging, complex and challenging medical condition. Proposals for diagnostic criteria and standard terminology are welcome.

Qualidade metodológica das avaliações econômicas de antineoplásicos submetidas à Agência Nacional de Saúde Suplementar (ANS) na atualização do rol 2020 ­ Estudo de avaliação crítica / Methodological quality of economic assessments of antineoplastics submitted to Supplementary Health Agency in the update of the 2020 list ­ Critical assessment study

Objetivo: Descrever e analisar criticamente as avaliações econômicas de medicamentos antineoplásicos submetidas à Agência Nacional de Saúde Suplementar (ANS) durante o processo de atualização do rol de procedimentos em saúde 2020. Métodos: Estudo transversal de análise crítica dos estudos de avaliação econômica integrantes da documentação submetida à ANS com o objetivo de incorporação no rol de procedimentos. A avaliação da qualidade metodológica foi realizada por meio da ferramenta Methodology Checklist 6: Economic Evaluations Version 3.0 da Scottish Intercollegiate Guidelines Network. Resultados: Foram incluídas 49 avaliações econômicas: 22 estudos de custo-efetividade, 10 estudos de custo-utilidade, três estudos de custo-minimização e 14 estudos de custo-efetividade e custo-utilidade. A qualidade metodológica foi considerada, na maior parte (88%), como aceitável ou de baixa qualidade. Conclusão: Estudos de avaliação econômica são fundamentais no processo decisório de incorporação de tecnologias na saúde suplementar. Esta análise crítica sugere que a qualidade dos estudos econômicos apresentados dentro das propostas de incorporação de antineoplásicos durante o processo de atualização do rol 2020 da ANS foi limitada. Inconsistências metodológicas e falta de um relato transparente reduzem a validade e a aplicabilidade dos achados na tomada de decisão.

Objective: To describe and critically appraise the economic evaluations of antineoplastic drugs submitted to the ANS during the process of updating its 2020' list of procedures. Methods: Cross-sectional study of critical analysis of the economic evaluation studies included in the documentation submitted to the ANS with the aim of incorporating them into the list of procedures. The methodological quality assessment was carried out using the Methodology Checklist 6: Economic Evaluations Version 3.0 of the Scottish Intercollegiate Guidelines Network. Results: Overall, 49 economic evaluations were included: 22 cost-effectiveness studies, 10 cost-utility studies, three cost-minimization studies and 14 mixed economic studies. Methodological quality was mostly considered as acceptable or low quality. Conclusion: Economic evaluation studies are fundamental in the decision-making process of incorporating technologies into supplementary health care. This critical appraisal suggests that the quality of the economic studies presented within the proposals to incorporate antineoplastics during the process of updating the ANS 2020 roll was limited. Methodological inconsistencies and lack of transparent reporting reduce the validity and applicability of findings for decision-making

Delays and Disruptions in Cancer Health Care Due to COVID-19 Pandemic: Systematic Review.

PURPOSE: There has been noteworthy concern about the impact of COVID-19 pandemic on health services including the management of cancer. In addition to being considered at higher risk for worse outcomes from COVID-19, people with cancer may also experience disruptions or delays in health services. This systematic review aimed to identify the delays and disruptions to cancer services globally. METHODS: This is a systematic review with a comprehensive search including specific and general databases. We considered any observational longitudinal and cross-sectional study design. The selection, data extraction, and methodological assessment were performed by two independent reviewers. The methodological quality of the studies was assessed by specific tools. The delays and disruptions identified were categorized, and their frequency was presented. RESULTS: Among the 62 studies identified, none exhibited high methodological quality. The most frequent determinants for disruptions were provider- or system-related, mainly because of the reduction in service availability. The studies identified 38 different categories of delays and disruptions with impact on treatment, diagnosis, or general health service. Delays or disruptions most investigated included reduction in routine activity of cancer services and number of cancer surgeries; delay in radiotherapy; and delay, reschedule, or cancellation of outpatient visits. Interruptions and disruptions largely affected facilities (up to 77.5%), supply chain (up to 79%), and personnel availability (up to 60%). CONCLUSION: The remarkable frequency of delays and disruptions in health care mostly related to the reduction of the COVID-19 burden unintentionally posed a major risk on cancer care worldwide. Strategies can be proposed not only to mitigate the main delays and disruptions but also to standardize their measurement and reporting. As a high number of publications continuously are being published, it is critical to harmonize the upcoming reports and constantly update this review.

Technical Procedures for Preparation and Administration of Platelet-Rich Plasma and Related Products: A Scoping Review.

INTRODUCTION: Platelet-rich plasma is widely used for different types of clinical situations, but universal standardization of procedures for its preparation is still lacking. METHODS: Scoping review of comparative studies that have assessed at least two alternatives in one or more stages of preparation, storage and/or administration of PRP or its related products. A systematic search was conducted in MEDLINE, Embase, and LILACS. Two authors screened references independently. Data extraction was performed iteratively, and results were presented for each included comparison. RESULTS: Thirty-nine studies were included after assessing full texts, focusing on the comparison of PRP to a related product, types of anticoagulants, centrifugation protocols, commercial kits, processing time, methods for activation, and application concomitantly to other substances. Only laboratory outcomes were assessed, as platelet, leukocyte and growth factor concentrations. CONCLUSION: Results showed great variability related to methods employed in different stages of PRP processing, which may explain the variability observed in clinical trials assessing the efficacy of PRP for different clinical situations.

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.

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

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

Eficácia, segurança e aspectos regulatórios dos medicamentos órfãos para doenças raras: o caso Zolgensma® / Efficacy, safety and regulatory aspects of orphan drugs for rare diseases: Zolgensma®'s case study

Objetivo: discutir o processo regulatório de medicamentos para doenças raras no Brasil, com base no caso Zolgensma®, e avaliar criticamente as evidências disponíveis até o momento sobre a eficácia e a segurança do Zolgensma® no tratamento da atrofia muscular espinhal (AME). Metodologia: estudo descritivo realizado no Núcleo de Avaliação de Tecnologias em Saúde do Hospital Sírio-Libanês (NATS-HSL) em junho de 2019. Resultados: em abril de 2019, o uso do Zolgensma® para AME foi regulamentado nos Estados Unidos com base em dois estudos clínicos abertos (sem mascaramento), sem grupo comparador paralelo (e, portanto, não randomizados). Essas limitações metodológicas aumentam a incerteza nos resultados encontrados. A Agência Nacional de Vigilância Sanitária (Anvisa) aprovou estratégias para regulamentar o processo e os prazos de análise das submissões de registro de novos medicamentos para doenças raras, caso do Zolgensma®. Conclusão: faz-se necessário ampliar o debate em torno do processo de regulamentação e de incorporação de medicamentos órfãos para doenças raras no Brasil. O debate deve incluir as evidências relacionadas aos efeitos ­ benefícios e riscos ­ desses medicamentos, e maior clareza nos critérios para concessão de registro e recomendação de incorporação em sistemas de saúde. (AU).

Objective: to discuss the regulatory process of drugs for rare diseases in Brazil, based on the Zolgensma® case, and to critically evaluate the evidence so far available on the efficacy and safety of Zolgensma® for treating spinal muscular atrophy (SMA). Methods: descriptive study conducted at the Health Technology Assessment Center of the Sírio Libanês Hospital (NATS-HSL) in June 2019. Results: in April 2019, the use of Zolgensma® for SMA was regulated in the United States based on two open-lable (unmasked), non-comparative (and therefore non-randomized) studies. These methodological limitations increase the uncertainty related to study results. The National Agency of Sanitary Surveillance (Anvisa) has approved strategies to regulate the process and specific deadlines for completing the appraisal process of new medicines for rare diseases, such as Zolgensma®. Conclusion: it is necessary to broaden the debate about the process of regulation and incorporation of orphan drugs for rare diseases in Brazil. This debate should include evidence related to the effects (benefits and risks) of these drugs, and greater transparency of the criteria indispensable for granting registration and recommendation of incorporation into health systems. (AU).

Objetivo: analizar el proceso de fármacos reguladores para enfermedades raras en Brasil, con base en el caso Zolgensma, y para evaluar críticamente la evidencia disponible hasta el momento sobre la eficacia y seguridad de Zolgensma® nel tratamiento de atrofia muscular espinal (AME). Métodos: estudio descriptivo realizado en el Centro de Evaluación de Tecnología de Salud del Hospital Sírio-Libanês (NATS-HSL) en junio de 2019. Resultados: en abril de 2019, el uso de Zolgensma® para la AME se reguló en los Estados Unidos basado en dos estudios abiertos (no enmascarados), no comparativos (y por lo tanto no aleatorios). Estas limitaciones metodológicas aumentan la incertidumbre en los resultados encontrados. La Agencia Nacional de Vigilancia Sanitaria en Brasil (Anvisa) ha aprobado estrategias para regular el proceso y los plazos de análisis de las solicitudes de registro de nuevos fármacos para enfermedades raras, el caso de Zolgensma. Conclusión: es necesario ampliar el debate sobre el proceso de regulación e incorporación de medicamentos huérfanos para enfermedades raras en Brasil. Este debate debe incluir evidencia relacionada con los efectos (beneficios y riesgos) de estos medicamentos y una mayor transparencia en los criterios para otorgar el registro y la recomendación de incorporación a los sistemas de salud. (AU).

Electronic Version of the EQ-5D Quality-of-Life Questionnaire: Adaptation to a Brazilian Population Sample.

OBJECTIVES: To assess the measurement equivalence of the original paper version of an adapted tablet version of the EuroQol five-dimensional questionnaire (EQ-5D). METHODS: A randomly selected sample of 509 individuals aged 18 to 64 years from the general population responded to the EQ-5D at two time points separated by a minimum interval of 24 hours and were allocated to one of the following groups: test-retest group (tablet-tablet) or crossover group (paper-tablet and tablet-paper). Agreement between methods was determined using the intraclass correlation coefficient (ICC) and the κ coefficient. RESULTS: In the crossover group, the following ICC values were obtained: 0.76 (confidence interval [CI] 0.58-0.89) for EQ-5D scores and 0.77 (CI 0.68-0.84) for visual analogue scale in subjects responding first to the tablet version; 0.83 (CI 0.75-0.89) for EQ-5D scores and 0.75 (CI 0.67-0.85) for visual analogue scale in subjects responding first to the paper version. In the test-retest group, the ICC was 0.85 (CI 0.73-0.91) for EQ-5D scores and 0.79 (CI 0.66-0.87) for visual analogue scale. The κ values were higher than 0.69 in this group. The internal consistencies of the paper and tablet methods were similar. CONCLUSIONS: The paper and tablet versions of the EQ-5D are equivalent. Test-retest and crossover agreement was high and the acceptability of the methods was similar among individuals.

Health-related quality of life in Brazil: normative data for the SF-36 in a general population sample in the south of the country.

The objective of this study was to provide normative SF-36 scores in a general population sample in Brazil and to describe differences in mean scores according to socio-demographic characteristics. The SF-36 questionnaire was distributed to a randomly selected sample of the general population of Porto Alegre in the State of Rio Grande do Sul. The response rate was 68% and 755 subjects were included (38% male, 62% female). Lower health status was revealed among females in the 30 to 44 year age bracket, from the lower income class, with less education and self-reported chronic medical conditions. The results and percentiles of scores of the SF-36 are reported as normative data for the general population. The SF-36 was an acceptable and practical instrument for measuring health-related quality of life in a sample of Brazilians. The results of this study can be useful for researchers using the SF-36 questionnaire in other groups to compare the scores with normative data. The SF-36 may prove a valuable tool for discovering vulnerable groups in epidemiological studies due to the ability to discriminate between different population subgroups.