Definition and reporting of composite outcomes are often inadequate in randomized clinical trials on pharmacological interventions for coronary artery disease.

OBJECTIVES: To estimate the frequency and critically appraise the use and reporting of composite outcomes in randomized clinical trials on pharmacological interventions for coronary artery disease. STUDY DESIGN AND SETTING: A metaresearch study. A search strategy was developed to retrieve references from MEDLINE. We considered articles, published from 1st January 2020, to December 31, 2021, reporting results of clinical primary outcomes from randomized clinical trials which assessed pharmacological interventions, used alone or in combination, for the treatment or secondary prevention (previous coronary event) of coronary artery disease. RESULTS: From the 34 included studies, 28 (82.35%) had a primary composite outcome. Thirteen unique composite primary outcomes were used with the most frequent being "cardiovascular death, myocardial infarction, stroke" (12/28, 42.86%). The term major adverse cardiac events was used for five distinct composite primary outcomes. A combination of 12 different components resulted in the 28 primary composite outcomes, with stroke being the most frequent component present in 96.43% (27/28) of the primary composite outcomes. From the included studies, 60.71% (17/28) reported the estimates for each individual component and the direction of the effect was consistent between all components and the composite outcomes in 58.82% (10/17) of them. Additionally, no included study discussed potential limitations and/or related advantages of the composite outcomes. CONCLUSION: In randomized clinical trials on pharmacological interventions for coronary artery disease, composite outcomes are frequently used, but the definition of their components is very heterogeneous. The estimate for individual components within the composite outcome is often not fully reported, which prevents a complete analysis of their adequacy for clinical practice. The term major adverse cardiac events was used inconsistently and to refer to different set of components, which can also be misleading and confusing.

Functional orthopedic treatment for anterior open bite in children. A systematic review of randomized clinical trials.

PURPOSE: This systematic review aimed to assess the effects of orthopedic functional appliances for anterior open bite (AOB) in primary or mixed dentition children. METHODS: A search for randomized controlled trials (RCT) was conducted in November 2020 in electronic databases with no data or language restrictions. Primary outcomes were skeletal cephalometric variables and adverse events. We used the Cochrane risk-of-bias tool to assess methodological quality and the GRADE approach to assess the certainty of the evidence. RESULTS: We identified five RCTs (220 participants). Very low certainty evidence showed an improvement in overbite (mean difference [MD] 3.60; 95% confidence interval [CI] 2.63-4.57) and in the angulation of the upper incisors to the palatal plane (MD 3.70; 95% CI 0.85-6.55) with Frankel's functional regulator, compared to no treatment. There was no difference in the measured cephalometric variables when comparing removable palatal crib to fixed palatal crib, bonded spurs, and chin cup. When comparing removable versus magnetic bite blocks, a beneficial effect was observed in overbite, overjet, skeletal anteroposterior angular measurements, and skeletal vertical linear measures in the magnetic group. No adverse events were reported. CONCLUSION: There was insufficient evidence to infer the effects of these treatments for AOB, and high-quality RCTs are needed to increase the estimated effects. PROSPERO REGISTER: CRD42020175634, prospectively registered (05 July 2020).

Moderately hypofractionated post-operative radiation therapy for breast cancer: Systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: We provide a critical assessment regarding current evidence for the use of moderately hypofractionated irradiation for patients with breast cancer. The aim of the study was to summarize the available evidence regarding outcomes after moderately hypofractionated compared with conventional radiation doses in the post-operative treatment of patients with breast cancer. MATERIAL AND METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS databases were searched until March 25, 2021. All randomized phase 3 clinical trials that compared moderately hypofractionated with conventional radiation doses in the post-operative treatment of patients with breast cancer were selected. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. RESULTS: Eight clinical trials satisfied the eligibility criteria and were the focus of the analysis. A total of 12,139 breast cancer patients was randomly assigned for moderately hypofractionated compared with conventional irradiation. Meta-analysis of the trials regarding local recurrence, loco-regional recurrence, disease-free survival, and overall survival outcomes did not demonstrate any significant difference between moderately hypofractionated irradiation and conventional radiation doses groups. The rate of severe side effects was low in both groups; acute and late side effects and cosmesis were similar or even tended to be lower after moderately hypofractionated than after conventional irradiation. CONCLUSIONS: Moderately hypofractionated is at least as effective and safe as conventional radiation irradiation regimens and should be considered as a treatment option for most, if not all, breast cancer patients.

Timing of oxytocin administration to prevent post-partum hemorrhage in women delivered by cesarean section: A systematic review and metanalysis.

BACKGROUND: There is no consensus on the best timing for prophylactic oxytocin administration during cesarean section (CS) to prevent post-partum hemorrhage (PPH). OBJECTIVES: Assess the effects of administrating prophylactic oxytocin at different times during CS. METHODS: We searched nine databases to identify relevant randomized controlled trials (RCT). We pooled results and calculated average risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI). We used GRADE to assess the overall evidence certainty. RESULTS: We screened 13,389 references and included four trials. We found no statistically significant differences between oxytocin given before versus after fetal delivery on PPH (RR 0.60, 95%CI 0.15-2.47; 1 RCT, N = 300) or nausea/vomiting (RR 1.21, 95%CI 0.69-2.13; 1 RCT, N = 300). There was a significant reduction in the need for additional uterotonics when oxytocin was given immediately before uterine incision versus after fetal delivery (RR 0.37, 95%CI 0.18-0.73; I2 = 0%; 2 RCTs; N = 301). Oxytocin given before fetal delivery significantly reduced intra-operative blood loss (MD -146.77mL, 95%CI -168.10 to -125.43; I2 = 0%; 3 RCTs, N = 601) but did not change the incidence of blood transfusion (RR 0.50, 95%CI 0.13-1.95; I2 = 0%; 2 RCTs, N = 301) or hysterectomy (RR 3.00; 95%CI 0.12-72.77; I2 = 0%; 2 RCTs, N = 301). One trial (N = 100) compared prophylactic oxytocin before versus after placental separation and found no significant differences on PPH, additional uterotonics, or nausea/vomiting. CONCLUSIONS: In women having pre-labor CS, there is limited evidence indicating no significant differences between prophylactic oxytocin given before versus after fetal delivery on PPH, nausea/vomiting, blood transfusion, or hysterectomy. Earlier oxytocin administration may reduce the volume of blood loss and need for additional uterotonics. There is very limited evidence suggesting no significant differences between prophylactic oxytocin given before versus after placental separation on PPH, need for additional uterotonic, or nausea/vomiting. The overall certainty of the evidence was mostly low or very low due to imprecision. Protocol: CRD42020186797.

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.

Busca em bases de dados eletrônicas da área da saúde: por onde começar / Search in databases area electronics health: where to start

Introdução: Com o crescimento contínuo das informações disponíveis na área da saúde, é fundamental que o profissional da saúde desenvolva habilidades e competências para realizar buscas de evidências cientificas. Objetivo: Apresentar as principais bases da área da saúde e os mecanismos de busca específicos para cada uma delas. Métodos: Estudo descritivo desenvolvido na Disciplina de Medicina Baseada em Evidências da Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp). Resultados: Este estudo apresentou os quatro passos do processo de busca em uma base de dados científica da área da saúde: (1) identificação da pergunta estruturada por meio dos acrônimos PICO/PECO, (2) escolha da base de dados (3) escolha e uso dos descritores em saúde apropriados para cada base (DeCS/MeSH/EMTREE) e (4) escolha e uso dos operadores booleanos (AND/OR/AND NOT). Conclusão: O processo de elaboração de uma estratégia de busca para bases de dados da área da saúde pode ser estruturado em quatro passos iniciais, que vão da identificação da pergunta estruturada ao uso dos operadores booleanos. Apropriar-se destes passos é fundamental para conseguir elaborar uma estratégia de busca adequada, capaz de recuperar os estudos de interesse e que abordem realmente a pergunta proposta.

Evidências de revisões sistemáticas Cochrane sobre o tratamento da gota / Evidence of Revisions Cochrane systematic reviews gout treatment

Contexto: A gota é uma doença articular metabólica inflamatória, caracterizada pelo acúmulo de cristais de monourato de sódio no líquido sinovial das articulações e em outros tecidos. Objetivo: apresentar as evidências de revisões sistemáticas Cochrane sobre efetividade e segurança de intervenções disponíveis para o manejo da gota. Métodos: Foram identificadas revisões sistemáticas a partir de busca na Biblioteca Cochrane. Dois autores avaliaram as revisões quanto aos critérios de elegibilidade das revisões encontradas e apresentaram síntese de seus achados. Resultados: Foram incluídas 13 revisões sistemáticas Cochrane (6 para gota aguda e 7 para gota crônica) que avaliaram intervenções medicamentosas sistêmicas e locais (tópica e intra-articular) e mudanças no estilo de vida. A confiança no corpo final das evidências encontradas variou de desconhecida a moderada entre os desfechos considerados. Os principais resultados mostraram que anti-inflamatórios não esteroidais (AINE) convencionais são tão efetivos quanto AINE inibidores da ciclo-oxigenase-2 e corticoides para controle da dor em pacientes com gota aguda. Para gota crônica, o alopurinol parece ser semelhante ao febuxostate e a benzbromarona na prevenção de crises de gota. Conclusão: Nenhum dos achados das revisões forneceu evidência de alta certeza sobre os efeitos das intervenções para gota, ou seja, estudos futuros podem, com variada probabilidade, modificar a estimativa que conhecemos hoje para os efeitos das intervenções avaliadas.

O que as revisões sistemáticas Cochrane dizem sobre o uso das 10 novas práticas de medicina integrativa incorporadas ao Sistema Único de Saúde / What systematic reviews allows the doctor to use the 10 new practices of integrated medicine to the Unified Health System

Contexto: O Ministério da Saúde do Brasil anunciou, em março de 2018, uma expansão das políticas para práticas integrativas em saúde dentro do Sistema Único de Saúde (SUS), incorporando 10 novos tipos de práticas integrativas à lista de procedimentos disponíveis no sistema público de saúde brasileiro. Objetivo: Identificar, sintetizar e avaliar criticamente evidências de revisões sistemáticas Cochrane sobre as novas práticas de medicina integrativa inseridas no SUS. Métodos: Revisão de revisões sistemáticas conduzida pela Disciplina de Medicina Baseada em Evidências, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), sobre as seguintes intervenções: apiterapia, aromaterapia, bioenergética, constelação familiar, terapia de florais, cromoterapia, geoterapia, hipnoterapia, imposição de mãos e ozonioterapia. Resultados: Foram incluídas 16 revisões sistemáticas: 4 sobre apiterapia, 4 sobre aromaterapia, 6 sobre hipnoterapia e 2 sobre ozonioterapia. Não foram encontradas revisões sistemáticas Cochrane referentes aos temas bioenergética, constelação familiar, cromoterapia, geoterapia, terapia de florais ou imposição de mãos. A única evidência de alta qualidade encontrada nessas revisões foi sobre o potencial benefício da apiterapia, especificamente para o uso de curativos de mel para cura parcial de feridas por queimadura, para redução de tosse entre crianças com tosse aguda e para prevenção de reações alérgicas a picadas de insetos. Conclusão: Exceto por alguns usos específicos da apiterapia (mel para lesões por queimadura e para tosse aguda e do veneno de abelhas para reações alérgicas às picadas de insetos), o uso das 10 práticas integrativas recentemente incorporadas ao SUS não é embasado por evidências de revisões sistemáticas Cochrane.

Modafinil for poststroke patients: A systematic review.

INTRODUCTION: Stroke is a major cause of death and disability worldwide. The use of modafinil, a wakefulness-promoting agent, is hypothesised to benefit stroke patients. METHODS: We performed a systematic review in accordance with the Cochrane Handbook for Systematic Reviews of Interventions recommendations to assess the efficacy and safety of modafinil in poststroke patients. We prospectively registered the review protocol in PROSPERO (CRD42017078465) and reported the systematic review following the PRISMA statement. RESULTS: Two published studies (77 participants) and one ongoing randomised controlled trial, with limited methodological quality, assessed the effects of modafinil (200 mg or 400 mg) for adults from 14 days poststroke up to 3 months poststroke and fulfilled our inclusion criteria. The clinical and methodological variability between studies precluded meta-analyses. Overall, these studies showed some benefit of modafinil for fatigue, but no benefit for disability, cognition, and for subscores of stroke-specific quality of life. Data for adverse events were scarce and mortality was not considered by studies. Due to very low quality related to the evidence, we are uncertain about the effects of modafinil for all outcomes assessed by our systematic review. CONCLUSION: Based on two small randomised controlled trial, which provided very low quality evidence, the effects (benefits and harms) of modafinil for stroke patients are unclear and do not support its routinely use in clinical practice for this clinical situation. Number of Protocol registration in PROSPERO database: CRD42017078465 (available from http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017078465).