Effectiveness and safety of tocilizumab for COVID-19: a systematic review and meta-analysis of randomized clinical trials

ABSTRACT BACKGROUND: Tocilizumab is an anti-human interleukin 6 receptor monoclonal antibody that has been used to treat coronavirus disease 2019 (COVID-19). However, there is no consensus on its efficacy for the treatment of COVID-19. OBJECTIVE: To evaluate the effectiveness and safety of tocilizumab for treating COVID-19. DESIGN AND SETTING: Systematic Review of randomized controlled trials (RCTs), Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil. METHODS: We searched MEDLINE via PubMed, EMBASE, CENTRAL, and IBECS for RCTs published up to March 2021. Two authors selected studies and assessed the risk of bias and the certainty of the evidence following Cochrane Recommendations. RESULTS: Eight RCTs with 6,139 participants were included. We were not able to find differences between using tocilizumab compared to standard care on mortality in hospitalized patients with COVID-19 (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.84 to 1.13; 8 trials; 5,950 participants; low-certainty evidence). However, hospitalized patients under tocilizumab plus standard care treatment seemed to present a significantly lower risk of needing mechanical ventilation (risk ratio = 0.78; 95% CI 0.64−0.94 moderate-certainty of evidence). CONCLUSIONS: To date, the best evidence available shows no difference between using tocilizumab plus standard care compared to standard care alone for reducing mortality in patients with COVID-19. However, as a finding with a practical implication, the use of tocilizumab in association to standard care probably reduces the risk of progressing to mechanical ventilation in those patients. REGISTRATION: osf.io/qe4fs.

Economic burden of respiratory syncytial and parainfluenza viruses in children of upper-middle-income countries: a systematic review

Abstract Objective: To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries. Methods: The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757. Results: No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed. Conclusion: The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.

Efetividade e segurança do treinamento muscular respiratório na apneia obstrutiva do sono: protocolo de uma revisão sistemática / Effectiveness and safety of respiratory muscle training in obstructive sleep apnea: systematic review protocol

Introdução: A apneia obstrutiva do sono (AOS) é o distúrbio respiratório do sono mais comum. O treino muscular respiratório tem surgido como uma intervenção promissora para a melhora dos sintomas e com boa adesão, porém muito ainda se tem discutido sobre sua efetividade e segurança. Objetivo: Avaliar a efetividade e segurança do TMR no tratamento de pacientes com AOS. Métodos: Para tanto, realizaremos uma revisão sistemática de ensaios clínicos randomizados (ECR). O protocolo do estudo foi registrado na Plataforma Prospero (CRD42018096980). Incluiremos indivíduos de idade superior ou igual a 18 anos, com diagnóstico de AOS, em uso ou não de pressão positiva nas vias aéreas. Excluiremos estudos com pacientes diagnosticados com lesão da medula espinhal ou doenças neuromusculares. As buscas serão realizadas nas bases de dados: Medical Literature Analysis and Retrieval System Online (Medline) via Pubmed, Excerpta Medica dataBASE (Embase) via Elsevier, Cochrane Central Register of Controlled Trials (Central) via Cochrane Library, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) via Portal da Biblioteca Virtual em Saúde e Physiotherapy Evidence Database (PEDro), sem restrições de idioma ou ano de publicação. Avaliaremos o rigor metodológico dos estudos incluídos e a certeza da evidência dos principais desfechos da revisão sistemática utilizando a ferramenta Risco de Viés 2.0 da Cochrane e a abordagem Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectivamente. A seleção dos estudos, extração de dados, avaliação do viés dos estudos incluídos e avaliação da certeza da evidência serão realizados por dois pesquisadores independentes. Resultados esperados: Espera-se que os resultados desta revisão forneçam informações úteis para a tomada de decisão clínica, exponham lacunas de conhecimento, assim como forneçam um bom embasamento para futuros ECR de alta qualidade sobre o assunto.

Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/ meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular, pulmonary and renal)

Abstract Sjogren's Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients.

Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sjögren syndrome: results of an epidemiologic systematic review/ meta-analysis and a consensus guideline from the Brazilian society of rheumatology (hepatic, gastrointestinal and pancreatic)

Abstract Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.

SARS-CoV-2 and arbovirus infection: a rapid systematic review

ABSTRACT BACKGROUND: The numbers of cases of arboviral diseases have increased in tropical and subtropical regions while the coronavirus disease (COVID-19) pandemic overwhelms healthcare systems worldwide. The clinical manifestations of arboviral diseases, especially dengue fever, can be very similar to COVID-19, and misdiagnoses are still a reality. In the meantime, outcomes for patients and healthcare systems in situations of possible syndemic have not yet been clarified. OBJECTIVE: We set out to conduct a systematic review to understand and summarize the evidence relating to clinical manifestations, disease severity and prognoses among patients coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and arboviruses. METHODS: We conducted a rapid systematic review with meta-analysis, on prospective and retrospective cohorts, case-control studies and case series of patients with confirmed diagnoses of SARS-CoV-2 and arboviral infection. We followed the Cochrane Handbook recommendations. We searched EMBASE, MEDLINE, Cochrane Library, LILACS, Scopus and Web of Science to identify published, ongoing and unpublished studies. We planned to extract data and assess the risk of bias and the certainty of evidence of the studies included, using the Quality in Prognosis Studies tool and the Grading of Recommendations Assessment. RESULTS: We were able to retrieve 2,407 citations using the search strategy, but none of the studies fulfilled the inclusion criteria. CONCLUSION: The clinical presentations, disease severity and prognoses of patients coinfected with SARS-CoV-2 and arboviruses remain unclear. Further prospective studies are necessary in order to provide useful information for clinical decision-making processes. Protocol registration number in the PROSPERO database: CRD42020183460

COVID-19 and patients with immune-mediated inflammatory diseases undergoing pharmacological treatments: a rapid living systematic review

ABSTRACT BACKGROUND: Patients with immune-mediated inflammatory diseases (IMID) are at increased risk of infection. OBJECTIVE: To assess whether patients undergoing pharmacological treatment for IMID present higher risk of worse outcomes when diagnosed with COVID-19. DESIGN AND SETTING: Rapid systematic review conducted in the medical school of the Federal University of São Paulo (SP), Brazil. METHODS: We searched CENTRAL, MEDLINE, EMBASE, LILACS, SCOPUS, Web of Science, L·OVE, ClinicalTrials.gov and WHO-ICTRP for studies evaluating patients diagnosed with COVID-19 who were undergoing pharmacological treatment for IMID. Two authors selected studies, extracted data and assessed risk of bias and certainty of evidence, following the Cochrane recommendations. RESULTS: We identified 1,498 references, from which one cohort study was included. This compared patients with and without rheumatic diseases (RD) who all had been diagnosed with COVID-19. Those with RD seemed to have higher chances of hospitalization and mortality, but no statistical difference was detected between the groups: hospitalization: odds ratio (OR) 1.17; 95% confidence interval (CI) 0.6 to 2.29; mortality rate: OR 1.53; 95% CI 0.33 to 7.11 (very low certainty of evidence). Patients with RD were three times more likely to require admission to intensive care units (ICUs), with invasive mechanical ventilation (IMV), than those without RD: OR 3.72; 95% CI 1.35 to 10.26 (for both outcomes; very low certainty of evidence). CONCLUSION: Patients undergoing pharmacological treatment for IMID seem to present higher chances of requiring admission to ICUs, with IMV. Additional high-quality studies are needed to analyze the effects of different treatments for IMID.

Clinical and socioeconomic characteristics of older adults with COVID-19: A protocol for a rapid systematic review

SUMMARY The aim of this rapid systematic review is to analyze the prevalence of clinical, socioeconomic, and demographic characteristics, laboratory and imaging findings, diagnostic tests, and treatment information of older adults with COVID-19. To conduct this systematic review, the Cochrane Handbook recommendations will be followed. Patients aged 60 years or older with a confirmed diagnosis of SARS-CoV-2 infection will be included. A comprehensive literature search will be performed in the following databases: MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILACS), Spanish Bibliographic Index on Health Sciences (IBECS) and Epistemonikos COVID-19 L·OVE platform. No language restrictions will be applied. To assess the methodological quality of the included studies and the certainty of the evidence, the Newcastle-Ottawa Scale, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used. The meta-analysis will be performed using R software. We believe this rapid systematic review will be able to summarize the currently available evidence on clinical, socioeconomic characteristics, and management of COVID-19 in older adults. Therefore, it will help implement adequate strategies to fight the pandemic and assist in understanding the clinical profile of older patients with COVID-19, providing data with due scientific support upon which to base future choices of procedures and interventions.

RESUMO O objetivo desta rápida revisão sistemática é analisar a prevalência de características clínicas, socioeconômicas e demográficas, achados laboratoriais e de imagem, testes de diagnóstico e informações de tratamento de idosos com COVID-19. Para conduzir esta revisão sistemática, serão seguidas as recomendações do Manual Cochrane. Pacientes com 60 anos ou mais com diagnóstico confirmado de infecção por Sars-CoV-2 serão incluídos. Uma pesquisa bibliográfica abrangente será realizada nas seguintes bases de dados: Medline via PubMed, Embase, Cochrane Central Register of Controlled Trials (Central), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Índice Bibliográfico Espanhol em Ciências da Saúde (Ibecs) e Epistemonikos Plataforma COVID-19 L · OVE. Nenhuma restrição de idioma será aplicada. Para avaliar a qualidade metodológica e a certeza das evidências dos estudos incluídos, serão utilizadas a Escala Newcastle-Ottawa e a abordagem Grading of Recommendations Assessment, Development and Evaluation (Grade). A meta-análise será realizada no software R. Acreditamos que esta revisão sistemática rápida será capaz de resumir as evidências atualmente disponíveis sobre as características clínicas, socioeconômicas e sobre o manejo de idosos com COVID-19. Portanto, ajudará a implementar estratégias adequadas para combater a pandemia e ajudará a entender o perfil clínico de pacientes idosos com COVID-19, fornecendo dados com o devido apoio científico sobre o qual basear futuras escolhas de procedimentos e intervenções.

What do Cochrane systematic reviews say about telemedicine for healthcare?

ABSTRACT BACKGROUND: Telemedicine has emerged as a tool for overcoming the challenges of healthcare systems and is likely to become increasingly viable, since information and communication technologies have become more sophisticated and user-friendly. OBJECTIVE: We aimed to identify all Cochrane systematic reviews (CSRs) on telemedicine within healthcare and to summarize the current evidence regarding its use. DESIGN AND SETTING: Review of CSRs, developed at the Discipline of Emergency and Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo. METHODS: We searched for studies that compared use of telemedicine with conventional treatment or management of diseases within healthcare. Diagnostic telemedicine studies or studies using automatic text, voice-text or even self-managed care were excluded. The main characteristics and the certainty of evidence were synthetized and critically discussed by all authors. RESULTS: We included 10 CSRs that investigated a broad range of diseases. There is still insufficient evidence to determine what types of telemedicine interventions are effective, for which patients and in which settings, and whether such interventions can be used as a replacement for the standard treatment. Harm relating to telemedicine technologies needs to be better investigated and addressed. CONCLUSION: Telemedicine might be an excellent way to facilitate access to treatment, monitoring and dissemination of important clinical knowledge. However, given the recognition of systematic reviews as the best evidence resource available for decision-making, further randomized controlled trials with stricter methods are necessary to reduce the uncertainties in evidence-based use of telemedicine.

Consumption of antihypertensive drugs dispensed under the pharmacy benefit management program

Pharmacy benefit management (PBM) programs provide attractive discounts for drug purchase, a relevant measure to address costs, mainly of drugs for the treatment of chronic diseases. This study investigated whether PBM may be used as a tool to provide information about the use of antihypertensive medications when they are purchased. The profile of medicines taken to treat high blood pressure by large IT company employees and their dependents was evaluated from January to December 2009. The mean rate of drug boxes purchased to control hypertension was 9.4 ± 10.0 in 2009. Men purchased more drugs than women. The number of drugs purchased for the treatment of hypertension was lower than expected in all age groups except for individuals aged 54-58 and >59 years. Among men, the purchase of drugs to treat hypertension was higher than expected in the 24-28, 34-38 and 54-58 age groups. Among women, results matched expectations, except for the age group 34-38 years, in which purchase was lower than expected. Individuals in the age group 0-18 years were found to consume antihypertensive drugs. Although the PBM system may be used to identify drugs purchased by users, it does not ensure patient adherence to recommended drug treatment to control hypertension.

O objetivo do Programa de Benefícios em Medicamentos (PBM) é proporcionar descontos atraentes para aquisição de medicamentos, um fator relevante para o custo, principalmente no tratamento de doenças crônicas. O objetivo deste estudo é comprovar se o PBM pode ser utilizado como ferramenta para o fornecimento de informações sobre o consumo de medicamentos antihipertensivos através da aquisição dos mesmos. Foi realizada análise do perfil de medicamentos adquiridos para o tratamento de hipertensão arterial sistêmica por funcionários e seus dependentes de uma empresa de grande porte na área de tecnologia de informação (TI) no período compreendido entre janeiro a dezembro de 2009. A taxa de aquisição média de medicamentos para o controle da hipertensão foi de 9,4±10,0 embalagens durante o ano de 2009. Os homens consumiram mais caixas de medicamentos que as mulheres. O número de caixas de medicamentos adquiridas para o tratamento da hipertensão arterial foi abaixo do esperado em todas as faixas de idade, exceto para 54-58 e >59 anos. Entre os homens, a aquisição de caixas de medicamentos para o tratamento da hipertensão arterial foi maior que o esperado nas seguintes faixas de idade: 24-28, 34-38 e 54-58 anos. Entre as mulheres, a aquisição de caixas de medicamentos anti-hipertensivos foi dentro do esperado, exceto para aquelas com idade compreendida entre 34-38 anos que foi abaixo do esperado. Observou-se a existência de consumo de fármacos antihipertensivos na faixa etária de 0-18 anos. Embora o sistema de PBM permita identificar a aquisição de medicamentos anti-hipertensivos por seus usuários, não garante que os pacientes estejam aderidos à terapia medicamentosa recomendada para o controle da hipertensão.