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Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61-1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64-1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09-0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.
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INTRODUCTION: Shorter courses of antimicrobials have been shown to be non-inferior to longer, "traditional" duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB. METHODS: This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days. PLANNED OUTCOMES: The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%. CONCLUSION: The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE).
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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.
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COVID-19 , Tromboembolia , Humanos , Brasil/epidemiologia , Soroterapia para COVID-19 , Corticosteroides , OxigênioRESUMO
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.
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[This corrects the article DOI: 10.1017/ash.2023.136.].
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Objective: Data are scarce regarding hospital infection control committees and compliance with infection prevention and control (IPC) recommendations in Brazil, a country of continental dimensions. We assessed the main characteristics of infection control committees (ICCs) on healthcare-associated infections (HAIs) in Brazilian hospitals. Methods: This cross-sectional study was conducted in ICCs of public and private hospitals distributed across all Brazilian regions. Data were collected directly from the ICC staff by completing an online questionnaire and during on-site visits through face-to-face interviews. Results: In total, 53 Brazilian hospitals were evaluated from October 2019 to December 2020. All hospitals had implemented the IPC core components in their programs. All centers had protocols for the prevention and control of ventilator-associated pneumonia as well as bloodstream, surgical site, and catheter-associated urinary tract infections. Most hospitals (80%) had no budget specifically allocated to the IPC program; 34% of the laundry staff had received specific IPC training; and only 7.5% of hospitals reported occupational infections in healthcare workers. Conclusions: In this sample, most ICCs complied with the minimum requirements for IPC programs. The main limitation regarding ICCs was the lack of financial support. The findings of this survey support the development of strategic plans to improve IPCs in Brazilian hospitals.
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BACKGROUND: Previous systematic reviews have identified no benefit of hydroxychloroquine and chloroquine in non-hospitalized COVID-19 patients. After publication of these reviews, the results of COPE, the largest randomized trial conducted to date, became available. OBJECTIVES: To conduct a systematic review and meta-analyses of randomized clinical trials (RCTs) to synthesize the evidence on the efficacy and safety of hydroxychloroquine and chloroquine for non-hospitalized COVID-19 patients compared to placebo or standard of care. METHODS: Searches were conducted in PubMed, Embase, The Cochrane Library, and ClinicalTrials.gov complemented by manual search. Pairwise meta-analyses, risk of bias, and evidence certainty assessments were conducted, including optimal information size analysis (OIS). A level of significance of 0.05 was adopted in the meta-analysis. PROSPERO: CRD42021265427. RESULTS: Eight RCTs with 3,219 participants were included. COVID-19 hospitalization and any adverse events rates were not significantly different between hydroxychloroquine (5.6% and 35.1%) and control (7.4% and 20.4%) (risk ratio, RR, 0.77, 95% confidence interval, CI, 0.57-1.04, I2: 0%; RR 1.78, 95%-CI 0.90; 3.52, I2: 93%, respectively). The OIS (7,880) was not reached for COVID-19 hospitalization, independently of the simulation for anticipated event rate and RR reduction estimate. CONCLUSION: Evidence of very low certainty showed lack of benefit with hydroxychloroquine in preventing COVID-19 hospitalizations. Despite being the systematic review with the largest number of participants included, the OIS, considering pre-vaccination response to infection, has not yet been reached.
FUNDAMENTO: Revisões sistemáticas anteriores não identificaram benefício do uso da hidroxicloroquina ou da cloroquina em pacientes com COVID-19 não hospitalizados. Após a publicação dessas revisões, os resultados do COPE, o maior ensaio clínico randomizado até hoje, tornaram-se disponíveis. OBJETIVOS: Conduzir uma revisão sistemática e metanálise de ensaios clínicos randomizados (ECRs) para sintetizar as evidências sobre a eficácia e a segurança da hidroxicloroquina e da cloroquina em pacientes com COVID-19 não hospitalizados em comparação a controle ou tratamento padrão. MÉTODOS: As buscas foram conduzidas nos bancos de dados PubMed, Embase, The Cochrane Library e ClinicalTrials.gov, e complementadas por busca manual. Foram realizadas metanálises diretas e avaliações de risco de viés e certeza da evidência, incluindo análise do tamanho ótimo da informação (OIS, optimal information size). Um nível de significância de 0,05 foi adotado na metanálise. PROSPERO: CRD42021265427. RESULTADOS: Oito ECRs com 3219 participantes foram incluídos. As taxas de internação por COVID-19 e de eventos adversos não foram significativamente diferentes entre hidroxicloroquina (5,6% e 5,1%) e controle (7,4% e 20,4%) [risco relativo (RR) 0,77, intervalo de confiança 95% (IC95%), 0,57-1,04, I2: 0%; RR 1,78, IC95% 0,90; 3,52, I2: 93%, respectivamente)]. O OIS (7880) não foi alcançado para hospitalização por COVID-19, independentemente da simulação para a taxa de evento e redução do RR estimados. CONCLUSÃO: A evidência de muito baixa qualidade indicou falta de benefício com hidroxicloroquina em prevenir internações por COVID-19. Apesar de ser a revisão sistemática com o maior número de participantes incluídos, o OIS, considerando a resposta à infecção anterior à vacinação, não foi atingido.
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COVID-19 , Humanos , Hidroxicloroquina/uso terapêutico , Tratamento Farmacológico da COVID-19 , Ensaios Clínicos Controlados Aleatórios como Assunto , Cloroquina/efeitos adversosRESUMO
BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.
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PURPOSE: To assess the association between acute disease severity and 1-year quality of life in patients discharged after hospitalisation due to coronavirus disease 2019 (COVID-19). METHODS: We conducted a prospective cohort study nested in 5 randomised clinical trials between March 2020 and March 2022 at 84 sites in Brazil. Adult post-hospitalisation COVID-19 patients were followed for 1 year. The primary outcome was the utility score of EuroQol five-dimension three-level (EQ-5D-3L). Secondary outcomes included all-cause mortality, major cardiovascular events, and new disabilities in instrumental activities of daily living. Adjusted generalised estimating equations were used to assess the association between outcomes and acute disease severity according to the highest level on a modified ordinal scale during hospital stay (2: no oxygen therapy; 3: oxygen by mask or nasal prongs; 4: high-flow nasal cannula oxygen therapy or non-invasive ventilation; 5: mechanical ventilation). RESULTS: 1508 COVID-19 survivors were enrolled. Primary outcome data were available for 1156 participants. At 1 year, compared with severity score 2, severity score 5 was associated with lower EQ-5D-3L utility scores (0.7 vs 0.84; adjusted difference, - 0.1 [95% CI - 0.15 to - 0.06]); and worse results for all-cause mortality (7.9% vs 1.2%; adjusted difference, 7.1% [95% CI 2.5%-11.8%]), major cardiovascular events (5.6% vs 2.3%; adjusted difference, 2.6% [95% CI 0.6%-4.6%]), and new disabilities (40.4% vs 23.5%; adjusted difference, 15.5% [95% CI 8.5%-22.5]). Severity scores 3 and 4 did not differ consistently from score 2. CONCLUSIONS: COVID-19 patients who needed mechanical ventilation during hospitalisation have lower 1-year quality of life than COVID-19 patients who did not need mechanical ventilation during hospitalisation.
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COVID-19 , Doenças Cardiovasculares , Adulto , Humanos , SARS-CoV-2 , Qualidade de Vida , Atividades Cotidianas , Estudos Prospectivos , Respiração Artificial , Hospitalização , Gravidade do PacienteRESUMO
OBJECTIVES: This study aimed to estimate the socioeconomic return from the value of lives saved by the protocol indicated by the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). ART was conducted through a multicenter randomized trial at 120 intensive care units from 9 countries, enrolling adults with moderate to severe acute respiratory distress syndrome. It investigated whether lung recruitment associated with positive end-expiratory pressure titration according to the best respiratory system compliance decreases 28-day mortality of patients compared with a conventional low-positive end-expiratory pressure strategy. METHODS: The value of lives saved was estimated by considering whether the trial findings were implemented in the eligible patient populations for 1 year, and then the social economic return was computed by subtracting the clinical trial costs from the gross benefit. The return was computed by subtracting the ART costs from its gross benefit. RESULTS: The ART net benefit is approximately 152 million dollars if it is implemented in 50% of eligible patients in Brazil under the baseline assumptions. For every dollar spent in the clinical trial, a return of 114 dollars was achieved in Brazil alone. If the trial findings are implemented in all eligible patients, then the trial return would be 229.5 dollars for every dollar invested with a net benefit of 304 million dollars. CONCLUSIONS: These findings highlight the substantial economic benefit of clinical trials on acute respiratory distress syndrome treatments for society. It also points out that the public return of clinical trials can be potentialized when the new trial findings are fully implemented on eligible patients.
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Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório , Adulto , Humanos , Respiração com Pressão Positiva/métodos , Pulmão , Síndrome do Desconforto Respiratório/terapia , Unidades de Terapia Intensiva , Custos e Análise de CustoRESUMO
Resumo Fundamento: Revisões sistemáticas anteriores não identificaram benefício do uso da hidroxicloroquina ou da cloroquina em pacientes com COVID-19 não hospitalizados. Após a publicação dessas revisões, os resultados do COPE, o maior ensaio clínico randomizado até hoje, tornaram-se disponíveis. Objetivos: Conduzir uma revisão sistemática e metanálise de ensaios clínicos randomizados (ECRs) para sintetizar as evidências sobre a eficácia e a segurança da hidroxicloroquina e da cloroquina em pacientes com COVID-19 não hospitalizados em comparação a controle ou tratamento padrão. Métodos: As buscas foram conduzidas nos bancos de dados PubMed, Embase, The Cochrane Library e ClinicalTrials.gov, e complementadas por busca manual. Foram realizadas metanálises diretas e avaliações de risco de viés e certeza da evidência, incluindo análise do tamanho ótimo da informação (OIS, optimal information size). Um nível de significância de 0,05 foi adotado na metanálise. PROSPERO: CRD42021265427. Resultados: Oito ECRs com 3219 participantes foram incluídos. As taxas de internação por COVID-19 e de eventos adversos não foram significativamente diferentes entre hidroxicloroquina (5,6% e 5,1%) e controle (7,4% e 20,4%) [risco relativo (RR) 0,77, intervalo de confiança 95% (IC95%), 0,57-1,04, I2: 0%; RR 1,78, IC95% 0,90; 3,52, I2: 93%, respectivamente)]. O OIS (7880) não foi alcançado para hospitalização por COVID-19, independentemente da simulação para a taxa de evento e redução do RR estimados. Conclusão: A evidência de muito baixa qualidade indicou falta de benefício com hidroxicloroquina em prevenir internações por COVID-19. Apesar de ser a revisão sistemática com o maior número de participantes incluídos, o OIS, considerando a resposta à infecção anterior à vacinação, não foi atingido.
Abstract Background: Previous systematic reviews have identified no benefit of hydroxychloroquine and chloroquine in non-hospitalized COVID-19 patients. After publication of these reviews, the results of COPE, the largest randomized trial conducted to date, became available. Objectives: To conduct a systematic review and meta-analyses of randomized clinical trials (RCTs) to synthesize the evidence on the efficacy and safety of hydroxychloroquine and chloroquine for non-hospitalized COVID-19 patients compared to placebo or standard of care. Methods: Searches were conducted in PubMed, Embase, The Cochrane Library, and ClinicalTrials.gov complemented by manual search. Pairwise meta-analyses, risk of bias, and evidence certainty assessments were conducted, including optimal information size analysis (OIS). A level of significance of 0.05 was adopted in the meta-analysis. PROSPERO: CRD42021265427. Results: Eight RCTs with 3,219 participants were included. COVID-19 hospitalization and any adverse events rates were not significantly different between hydroxychloroquine (5.6% and 35.1%) and control (7.4% and 20.4%) (risk ratio, RR, 0.77, 95% confidence interval, CI, 0.57-1.04, I2: 0%; RR 1.78, 95%-CI 0.90; 3.52, I2: 93%, respectively). The OIS (7,880) was not reached for COVID-19 hospitalization, independently of the simulation for anticipated event rate and RR reduction estimate. Conclusion: Evidence of very low certainty showed lack of benefit with hydroxychloroquine in preventing COVID-19 hospitalizations. Despite being the systematic review with the largest number of participants included, the OIS, considering pre-vaccination response to infection, has not yet been reached.
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RESUMO Objetivo: Descrever o IMPACTO-MR, um estudo brasileiro de plataforma nacional em unidades de terapia intensiva focado no impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Métodos: Descrevemos a plataforma IMPACTO-MR, seu desenvolvimento, critérios para seleção das unidades de terapia intensiva, caracterização da coleta de dados, objetivos e projetos de pesquisa futuros a serem realizados na plataforma. Resultados: Os dados principais foram coletados por meio do Epimed Monitor System® e consistiram em dados demográficos, dados de comorbidades, estado funcional, escores clínicos, diagnóstico de internação e diagnósticos secundários, dados laboratoriais, clínicos e microbiológicos e suporte de órgãos durante a internação na unidade de terapia intensiva, entre outros. De outubro de 2019 a dezembro de 2020, 33.983 pacientes de 51 unidades de terapia intensiva foram incluídos no banco de dados principal. Conclusão: A plataforma IMPACTO-MR é um banco de dados clínico brasileiro de unidades de terapia intensiva focado na pesquisa do impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Essa plataforma fornece dados para o desenvolvimento e pesquisa de unidades de terapia intensiva individuais e ensaios clínicos observacionais e prospectivos multicêntricos.
ABSTRACT Objective: To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria. Methods: We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform. Results: The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database. Conclusion: The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.
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RESUMO Objetivo: Descrever os efeitos do uso de soluções balanceadas nos desfechos de curto prazo de pacientes com traumatismo craniencefálico incluídos no estudo BaSICS. Métodos: Os pacientes foram randomizados para receber solução salina 0,9% ou solução balanceada durante a internação em unidade de terapia intensiva. O desfecho primário foi mortalidade em 90 dias, já os desfechos secundários foram dias de vida e sem internação em unidade de terapia intensiva aos 28 dias. O desfecho primário foi avaliado por regressão logística bayesiana. O desfecho secundário foi avaliado usando regressão beta-binomial inflada de zeros bayesiana. Resultados: Incluímos 483 pacientes (236 no braço de solução salina 0,9% e 247 no braço de solução balanceada). Foram incluídos 338 pacientes (70%) com pontuação na escala de coma de Glasgow ≤ 12. A probabilidade geral de que soluções balanceadas estivessem associadas a maior mortalidade em 90 dias foi de 0,98 (RC de 1,48; ICr95% 1,04 - 2,09). Esse aumento de mortalidade foi particularmente perceptível em pacientes com pontuação na escala de coma de Glasgow abaixo de 6 no momento da inclusão (probabilidade de dano de 0,99). Soluções balanceadas foram associadas a -1,64 dia de vida e sem internação em unidade de terapia intensiva aos 28 dias (ICr95% -3,32 - 0,00) com probabilidade de dano de 0,97. Conclusão: Houve alta probabilidade de que soluções balanceadas estivessem associadas a alta mortalidade em 90 dias, menos dias de vida e sem internação em unidade de terapia intensiva aos 28 dias. ClinicalTrials.gov:NCT02875873
ABSTRACT Objective: To describe the effects of balanced solution use on the short-term outcomes of patients with traumatic brain injury enrolled in BaSICS trial. Methods: Patients were randomized to receive either 0.9% saline or balanced solution during their intensive care unit stay. The primary endpoint was 90-day mortality, and the secondary outcomes were days alive and free of intensive care unit stay at 28 days. The primary endpoint was assessed using Bayesian logistic regression. The secondary endpoint was assessed using a Bayesian zero-inflated beta binomial regression. Results: We included 483 patients (236 in the 0.9% saline arm and 247 in the balanced solution arm). A total of 338 patients (70%) with a Glasgow coma scale score ≤ 12 were enrolled. The overall probability that balanced solutions were associated with higher 90-day mortality was 0.98 (OR 1.48; 95%CrI 1.04 - 2.09); this mortality increment was particularly noticeable in patients with a Glasgow coma scale score below 6 at enrollment (probability of harm of 0.99). Balanced solutions were associated with -1.64 days alive and free of intensive care unit at 28 days (95%CrI -3.32 - 0.00) with a probability of harm of 0.97. Conclusion: There was a high probability that balanced solutions were associated with high 90-day mortality and fewer days alive and free of intensive care units at 28 days. ClinicalTrials.gov:NCT02875873
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OBJECTIVE: To compare the lung mechanics and outcomes between COVID-19-associated acute respiratory distress syndrome and non-COVID-19-associated acute respiratory distress syndrome. METHODS: We combined data from two randomized trials in acute respiratory distress syndrome, one including only COVID-19 patients and the other including only patients without COVID-19, to determine whether COVID-19-associated acute respiratory distress syndrome is associated with higher 28-day mortality than non-COVID-19 acute respiratory distress syndrome and to examine the differences in lung mechanics between these two types of acute respiratory distress syndrome. RESULTS: A total of 299 patients with COVID-19-associated acute respiratory distress syndrome and 1,010 patients with non-COVID-19-associated acute respiratory distress syndrome were included in the main analysis. The results showed that non-COVID-19 patients used higher positive end-expiratory pressure (12.5cmH2O; SD 3.2 versus 11.7cmH2O SD 2.8; p < 0.001), were ventilated with lower tidal volumes (5.8mL/kg; SD 1.0 versus 6.5mL/kg; SD 1.2; p < 0.001) and had lower static respiratory compliance adjusted for ideal body weight (0.5mL/cmH2O/kg; SD 0.3 versus 0.6mL/cmH2O/kg; SD 0.3; p = 0.01). There was no difference between groups in 28-day mortality (52.3% versus 58.9%; p = 0.52) or mechanical ventilation duration in the first 28 days among survivors (13 [IQR 5 - 22] versus 12 [IQR 6 - 26], p = 0.46). CONCLUSION: This analysis showed that patients with non-COVID-19-associated acute respiratory distress syndrome have different lung mechanics but similar outcomes to COVID-19-associated acute respiratory distress syndrome patients. After propensity score matching, there was no difference in lung mechanics or outcomes between groups.
OBJETIVO: Comparar a mecânica pulmonar e os desfechos entre a síndrome do desconforto respiratório agudo associada à COVID-19 e a síndrome do desconforto respiratório agudo não associada à COVID-19. MÉTODOS: Combinamos dados de dois ensaios randomizados sobre a síndrome do desconforto respiratório agudo, um incluindo apenas pacientes com COVID-19 e o outro incluindo apenas pacientes sem COVID-19, para determinar se a síndrome do desconforto respiratório agudo associada à COVID-19 está associada à maior mortalidade aos 28 dias do que a síndrome do desconforto respiratório agudo não associada à COVID-19 e também examinar as diferenças na mecânica pulmonar entre esses dois tipos de síndrome do desconforto respiratório agudo. RESULTADOS: Foram incluídos na análise principal 299 pacientes com síndrome do desconforto respiratório agudo associada à COVID-19 e 1.010 pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19. Os resultados mostraram que os pacientes sem COVID-19 utilizaram pressão positiva expiratória final mais alta (12,5cmH2O; DP 3,2 versus 11,7cmH2O; DP 2,8; p < 0,001), foram ventilados com volumes correntes mais baixos (5,8mL/kg; DP 1,0 versus 6,5mL/kg; DP 1,2; p < 0,001) e apresentaram menor complacência respiratória estática ajustada para o peso ideal (0,5mL/cmH2O/kg; DP 0,3 versus 0,6mL/cmH2O/kg; DP 0,3; p = 0,01). Não houve diferença entre os grupos quanto à mortalidade aos 28 dias (52,3% versus 58,9%; p = 0,52) ou à duração da ventilação mecânica nos primeiros 28 dias entre os sobreviventes (13 [IQ 5 - 22] dias versus 12 [IQ 6 - 26] dias; p = 0,46). CONCLUSÃO: Esta análise mostrou que os pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19 têm mecânica pulmonar diferente, mas desfechos semelhantes aos dos pacientes com síndrome do desconforto respiratório agudo associada à COVID-19. Após pareamento por escore de propensão, não houve diferença na mecânica pulmonar e nem nos desfechos entre os grupos.
Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Pontuação de Propensão , COVID-19/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório/terapia , Pulmão , Respiração Artificial/métodos , Mecânica RespiratóriaRESUMO
RESUMO Objetivo: Comparar a mecânica pulmonar e os desfechos entre a síndrome do desconforto respiratório agudo associada à COVID-19 e a síndrome do desconforto respiratório agudo não associada à COVID-19. Métodos: Combinamos dados de dois ensaios randomizados sobre a síndrome do desconforto respiratório agudo, um incluindo apenas pacientes com COVID-19 e o outro incluindo apenas pacientes sem COVID-19, para determinar se a síndrome do desconforto respiratório agudo associada à COVID-19 está associada à maior mortalidade aos 28 dias do que a síndrome do desconforto respiratório agudo não associada à COVID-19 e também examinar as diferenças na mecânica pulmonar entre esses dois tipos de síndrome do desconforto respiratório agudo. Resultados: Foram incluídos na análise principal 299 pacientes com síndrome do desconforto respiratório agudo associada à COVID-19 e 1.010 pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19. Os resultados mostraram que os pacientes sem COVID-19 utilizaram pressão positiva expiratória final mais alta (12,5cmH2O; DP 3,2 versus 11,7cmH2O; DP 2,8; p < 0,001), foram ventilados com volumes correntes mais baixos (5,8mL/kg; DP 1,0 versus 6,5mL/kg; DP 1,2; p < 0,001) e apresentaram menor complacência respiratória estática ajustada para o peso ideal (0,5mL/cmH2O/kg; DP 0,3 versus 0,6mL/cmH2O/kg; DP 0,3; p = 0,01). Não houve diferença entre os grupos quanto à mortalidade aos 28 dias (52,3% versus 58,9%; p = 0,52) ou à duração da ventilação mecânica nos primeiros 28 dias entre os sobreviventes (13 [IQ 5 - 22] dias versus 12 [IQ 6 - 26] dias; p = 0,46). Conclusão: Esta análise mostrou que os pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19 têm mecânica pulmonar diferente, mas desfechos semelhantes aos dos pacientes com síndrome do desconforto respiratório agudo associada à COVID-19. Após pareamento por escore de propensão, não houve diferença na mecânica pulmonar e nem nos desfechos entre os grupos.
ABSTRACT Objective: To compare the lung mechanics and outcomes between COVID-19-associated acute respiratory distress syndrome and non-COVID-19-associated acute respiratory distress syndrome. Methods: We combined data from two randomized trials in acute respiratory distress syndrome, one including only COVID-19 patients and the other including only patients without COVID-19, to determine whether COVID-19-associated acute respiratory distress syndrome is associated with higher 28-day mortality than non-COVID-19 acute respiratory distress syndrome and to examine the differences in lung mechanics between these two types of acute respiratory distress syndrome. Results: A total of 299 patients with COVID-19-associated acute respiratory distress syndrome and 1,010 patients with non-COVID-19-associated acute respiratory distress syndrome were included in the main analysis. The results showed that non-COVID-19 patients used higher positive end-expiratory pressure (12.5cmH2O; SD 3.2 versus 11.7cmH2O SD 2.8; p < 0.001), were ventilated with lower tidal volumes (5.8mL/kg; SD 1.0 versus 6.5mL/kg; SD 1.2; p < 0.001) and had lower static respiratory compliance adjusted for ideal body weight (0.5mL/cmH2O/kg; SD 0.3 versus 0.6mL/cmH2O/kg; SD 0.3; p = 0.01). There was no difference between groups in 28-day mortality (52.3% versus 58.9%; p = 0.52) or mechanical ventilation duration in the first 28 days among survivors (13 [IQR 5 - 22] versus 12 [IQR 6 - 26], p = 0.46). Conclusion: This analysis showed that patients with non-COVID-19-associated acute respiratory distress syndrome have different lung mechanics but similar outcomes to COVID-19-associated acute respiratory distress syndrome patients. After propensity score matching, there was no difference in lung mechanics or outcomes between groups.
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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.
