Advanced therapy with mesenchymal stromal cells for knee osteoarthritis: Systematic review and meta-analysis of randomized controlled trials.

Background: Advanced cell therapies emerged as promising candidates for treatment of knee articular diseases, but robust evidence regarding their clinical applicability is still lacking. Objective: To assess the efficacy and safety of advanced mesenchymal stromal cells (MSC) therapy for knee osteoarthritis (OA) and chondral lesions. Methods: Systematic review of randomized controlled trials conducted in accordance with Cochrane Handbook and reported following PRISMA checklist. GRADE approach was used for assessing the evidence certainty. Results: 25 randomized controlled trials that enrolled 1048 participants were included. Meta-analyses data showed that, compared to viscosupplementation (VS), advanced MSC therapy resulted in a 1.91 lower pain VAS score (95 % CI -3.23 to -0.59; p < 0.00001) for the treatment of knee OA after 12 months. Compared to placebo, the difference was 0.99 lower pain VAS points (95 % CI -1.94 to -0.03; p = 0.76). According to the GRADE approach, the evidence was very uncertain for both comparisons. By excluding studies with high risk of bias, there was a similar size of effect (VAS MD -1.54, 95 % CI -2.09 to -0.98; p = 0.70) with improved (moderate) certainty of evidence, suggesting that MSC therapy probably reduces pain slightly better than VS. Regarding serious adverse events, there was no difference from advanced MSC therapy to placebo or to VS, with very uncertain evidence. Conclusion: Advanced MSC therapy resulted in lower pain compared to placebo or VS for the treatment of knee OA after 12 months, with no difference in adverse events. However, the evidence was considered uncertain. The Translational Potential of this Article: Currently, there is a lack of studies with good methodological structure aiming to evaluate the real clinical impact of advanced cell therapy for knee OA. The present study was well structured and conducted, with Risk of Bias, GRADE certainty assessment and sensitivity analysis. It explores the translational aspect of the benefits and safety of MSC compared with placebo and gold-standard therapy to give practitioners and researchers support to expand this therapy in their practice. PROSPERO registration number: CRD42020158173. Access at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=158173.

Methodological and reporting quality of systematic reviews on aesthetics and reconstructive breast surgery: A meta-research.

OBJECTIVE: To evaluate the methodological and reporting quality of systematic reviews (SR) of randomized controlled trials on esthetics and reconstructive breast surgery. METHODS: Meta-research study with a broad search strategy was developed to retrieve all relevant systematic reviews. We evaluated the methodological and reporting guidance adopted by these reviews and assessed their adequacy to items from AMSTAR-2 (methodological quality) and PRISMA 2020 (reporting quality). The protocol of this study was prospectively published in: https://osf.io/preprints/osf/ucpgd. RESULTS: After the selection process, 15 SR were included; eight (60%) referred the use of a methodological guide and five (33.3%) invertedly referred PRISMA as the methodological guide. Reporting guidelines were referred by none of the included systematic review. The median adequacy to PRISMA-2020 items was 42.9% (Q1 - 38.1%/Q3 - 95.2%) and to AMSTAR-2 items was 33.3% (Q1 - 23.3%/Q3 - 93.3%) which reflects overall low reporting and methodological quality of included SR. The overall confidence in the results using AMSTAR-2 framework was critically low in 73.3% of included SR. Although a small number of SR were included, a high correlation between the methodological and reporting quality was observed (Spearmean rho = 0.96, 95% bias-corrected confidence interval = 0.84 to 0.99). CONCLUSION: Methodological and reposting quality of SR of randomized clinical trials on esthetic or reconstructive breast surgery is poor. Half of the authors referred to the use of valid guidance to plan and conduct their reviews and none of them referred the use of a guidance for reporting their results.

Supporting evidence-based judicial decisions on health care in Brazil: an experience report / Apoio técnico-científico à tomada de decisão judicial em saúde no Brasil: um relato de experiência / Apoyo técnico-científico a la toma de decisiones judiciales en salud en Brasil: un relato de experiencia

Objective: The main objective of this study is to report on the implementation and results of the "Supporting Health-Related Judicial Decisions in Brazil" project conducted at the Health Technology Assessment Center, Hospital Sírio-Libanês through the "Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde", in Brazil. Methods: This study is an experience report of a project conducted at the Health Technology Assessment Center, Hospital Sírio-Libanês. Results: The activities of the project occurred in 2023 and included two online training courses on primary studies and systematic reviews, 11 one-day workshops with technical-scientific content for members of the Technical Support Centers for the Judiciary (NATJus), 40 online technical-scientific consultations for magistrates on a digital platform, 11 technical-scientific reports addressing the most legally claimed technologies in Brazil; two methodological tools, a national forum (hybrid event), 10 chat-based mentorships for NATJus members; and the maintenance of an open-access blog, by publishing news on relevant topics on law and health. Discussion and conclusion: This project has contributed to the improvement of the judicial decision-making process by providing a range of activities aimed at aiding the prioritization of health technologies that are clearly effective and safe over those that are ineffective, harmful, or have uncertain effects.

Objetivo: O objetivo principal deste estudo é relatar a implementação e os resultados do projeto "Apoio técnico-científico à tomada de decisão judicial em Saúde no Brasil" realizado no Hospital Sírio-Libanês por meio do "Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde". Métodos: Este estudo é um relato de experiência de um projeto realizado no Núcleo de Avaliação de Tecnologias em Saúde do Hospital Sírio-Libanês. Resultados: As atividades do projeto ocorreram em 2023 e incluíram dois cursos de formação online sobre estudos primários e revisões sistemáticas, 11 oficinas de um dia com conteúdo técnico-científico para membros dos Núcleos de Apoio Técnico ao Judiciário (NATJus), 40 consultas on-line técnico-científicas para magistrados em plataforma digital, 11 relatórios técnico-científicos abordando as tecnologias mais reivindicadas judicialmente no Brasil; duas ferramentas metodológicas, um fórum nacional (evento híbrido), 10 mentorias via chat para membros do NATJus; e a manutenção de um blog de acesso aberto, com publicação de notícias sobre temas relevantes de direito e saúde. Discussão e conclusão: Este projeto contribuiu para a melhoria do processo de tomada de decisão judicial, fornecendo uma série de atividades destinadas a ajudar na priorização de tecnologias de saúde que sejam claramente eficazes e seguras em detrimento daquelas que são ineficazes, prejudiciais ou têm efeitos incertos.

Objetivo: El objetivo principal de este estudio es informar sobre la implementación y los resultados del proyecto "Apoyo a las Decisiones Judiciales Relacionadas con la Salud en Brasil" realizado en el Centro de Tecnología en Salud del Hospital Sírio-Libanês a través del "Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde", en Brasil. Métodos: Este estudio es un informe de experiencia de un proyecto realizado en el Centro de Tecnología en Salud del Hospital Sírio-Libanês. Resultados: Las actividades del proyecto ocurrieron en 2023 e incluyeron dos cursos de capacitación en línea sobre estudios primarios y revisiones sistemáticas, 11 talleres de un día de contenido técnico-científico para miembros de los Centros de Apoyo Técnico al Poder Judicial (NATJus), 40 consultas técnico-científicas en línea para magistrados en plataforma digital, 11 informes técnico-científicos que abordan las tecnologías más reclamadas legalmente en Brasil; dos herramientas metodológicas, un foro nacional (evento híbrido), 10 mentorías basadas en chat para miembros de NATJus; y el mantenimiento de un blog de acceso abierto, mediante la publicación de noticias sobre temas relevantes en derecho y salud. Discusión y conclusión: Este proyecto ha contribuido a mejorar el proceso de toma de decisiones judiciales proporcionando actividades para priorizar las tecnologías sanitarias claramente eficaces y seguras frente a aquellas que son ineficaces, nocivas o de efectos inciertos.

Primary outcomes and characteristics of clinical trial registries (up to October 2021) on COVID-19 vaccines.

OBJECTIVES: To analyse the general and primary outcome-related characteristics of clinical trials protocols on COVID-19 vaccines. STUDY DESIGN AND SETTING: A meta-research study. A search for clinical trial protocols on COVID-19 vaccines was conducted on the ClinicalTrials.gov platform. We considered all protocols of comparative trials registered up to October 26, 2021. RESULTS: Two hundred and eighty-two trials were analysed. The median expected trial duration was 445 days (interquartile range [IQR] = 225), and the median target sample size was 420 participants (IQR = 1638). A retrospective registry (after the start date) was observed for 42.55% of the trials. Randomization procedures were planned by 84.75% and full-blinding procedures by 34.75% of the 282 trials. Most trials were labelled as active or still recruiting, and 14 trials (5%) were completed. None of the 14 trials labelled as completed on our search date had results available. Industry funding was reported by 198 trials (70.2%). Most studies declared more than one primary outcome, usually a safety or immunogenicity outcome, and 59 studies (20.9%) had at least one primary efficacy outcome. The description of the primary efficacy outcomes was limited in most cases, referred to as a non-specified 'efficacy' outcome (18.6%) or described as 'COVID-19 cases' (32.2%). CONCLUSION: the primary outcomes of clinical trials on COVID-19 vaccines are poorly described, and the registers provide insufficient information about them. The registry was retrospectively fulfilled for many trials, which may lead to bias and research waste. Outcomes were generically described and did not provide transparent information for replication in practice, further trials or meta-analyses.

Work-related musculoskeletal disorders in dockworkers. Systematic review and meta-analysis.

BACKGROUND: Dockworkers are exposed to physical overloads that can contribute to the development of musculoskeletal disorders, leading to functional disability and absenteeism. OBJECTIVE: to map, critically appraise, and synthesize the available evidence on the prevalence of musculoskeletal diseases associated with port occupational activities. METHODS: A comprehensive search was conducted in structured and unstructured databases in August 2023, with no date or language restriction, to identify observational studies evaluating the prevalence of musculoskeletal disorders in dockworkers' occupational activity. The risk of bias was assessed using validated tools based on the included study designs. Data from studies were pooled in meta-analyses. The certainty of the evidence was assessed using the GRADE approach. RESULTS: We identified 12 analytical cross-sectional studies involving 7821 participants in ports of five countries. Most studies (75%) had a moderate methodological quality according to the Joanna Briggs Institute tool. Considering the overall worker categories and any musculoskeletal disorders, the meta-analysis showed a prevalence of 58% (95% Confidence Interval [95% CI] 37% to 78%), with degenerative spinal diseases 42% (95% CI -0.6% to 91%) and low back pain 36% (95% CI 21% to 50%) being the most prevalent conditions. Symptoms were predominantly in foremen and stevedores. The certainty of the evidence was very low. CONCLUSIONS: Musculoskeletal disorders seem prevalent among dockworkers, mainly degenerative spinal diseases and low back pain. Studies with greater methodological consistency are still needed to validate these hypotheses and assist in decision-making for implementing preventive and informational policies in maritime port management organizations. PROSPERO registry CRD42021257677.

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.

What is an "ongoing" clinical trial? An analysis of different sources revealed heterogeneous definitions of when a clinical trial starts and ends: a meta-research study

ABSTRACT BACKGROUND: Although the concept of an "ongoing study" seems self-explanatory, it is difficult to determine whether a trial is underway. OBJECTIVE: To analyze the definitions of "ongoing clinical trial" across different clinical trial registries, methodological guidelines, and other sources. DESIGN AND SETTING: This meta-research study was conducted at the Universidade Federal de São Paulo (UNIFESP), Brazil. METHODS: We performed a cross-sectional analysis of relevant clinical trial registry databases, methodological guidelines for conducting systematic reviews, and other sources that would define or regulate clinical trials. RESULTS: We identified various heterogeneous definitions used by eligible sources at both the start and end of a clinical trial. The starting criteria used were as follows: when the team is planning the protocol, when permission is given to conduct the study, or when the first participant is enrolled. Some sources used the time at which the last outcome data was collected as a criterion to determine the end of the trial. The International Committee of Medical Journal Editors stated that a study is still "ongoing" during the analysis process. Several sources use a vague definition or present no clear criteria for defining the start or end of a study. CONCLUSION: The concept of "ongoing clinical trials" lacks a transparent and homogeneous definition across relevant sources. A consensus on this concept is important to facilitate the evaluation of available evidence and conduct research synthesis. Further efforts are necessary to determine the best definition for the start and end of a clinical trial.

An evidence-informed policymaking (EIPM) competency profile for the Brazilian Health System developed through consensus: process and outcomes.

BACKGROUND: Evidence-informed policymaking (EIPM) requires a set of individual and organizational knowledge, skills and attitudes that should be articulated with background factors and needs. In this regard, the development of an EIPM competency profile is important to support the diagnosis, planning and implementation of EIPM. PURPOSE: To present the process and outcomes of the development of an EIPM competency profile by an expert committee, to be applied in different contexts of the Brazilian Health System. METHODS: A committee of experts in EIPM shared different views, experiences and opinions to develop an EIPM competency profile for Brazil. In six consensus workshops mediated by facilitators, the committee defined from macro problems to key actions and performances essential for the competency profile. The development steps consisted of: (1) Constitution of the committee, including researchers, professionals with practical experience, managers, and educators; (2) Development of a rapid review on EIPM competency profiles; (3) Agreement on commitments and responsibilities in the processes; (4) Identification and definition of macro problems relating to the scope of the competency profile; and (5) Outlining of general and specific capacities, to be incorporated into the competency profile, categorized by key actions. RESULTS: The development of the EIPM competency profile was guided by the following macro problems: (1) lack of systematic and transparent decision-making processes in health policy management; (2) underdeveloped institutional capacity for knowledge management and translation; and (3) incipient use of scientific evidence in the formulation and implementation of health policies. A general framework of key actions and performances of the EIPM Competency Profile for Brazil was developed, including 42 specific and general key actions distributed by area of activity (Health Management, Scientific Research, Civil Society, Knowledge Translation, and Cross-sectional areas). CONCLUSIONS: The competency profile presented in this article can be used in different contexts as a key tool for the institutionalization of EIPM.

What is an "ongoing" clinical trial? An analysis of different sources revealed heterogeneous definitions of when a clinical trial starts and ends: a meta-research study.

BACKGROUND: Although the concept of an "ongoing study" seems self-explanatory, it is difficult to determine whether a trial is underway. OBJECTIVE: To analyze the definitions of "ongoing clinical trial" across different clinical trial registries, methodological guidelines, and other sources. DESIGN AND SETTING: This meta-research study was conducted at the Universidade Federal de São Paulo (UNIFESP), Brazil. METHODS: We performed a cross-sectional analysis of relevant clinical trial registry databases, methodological guidelines for conducting systematic reviews, and other sources that would define or regulate clinical trials. RESULTS: We identified various heterogeneous definitions used by eligible sources at both the start and end of a clinical trial. The starting criteria used were as follows: when the team is planning the protocol, when permission is given to conduct the study, or when the first participant is enrolled. Some sources used the time at which the last outcome data was collected as a criterion to determine the end of the trial. The International Committee of Medical Journal Editors stated that a study is still "ongoing" during the analysis process. Several sources use a vague definition or present no clear criteria for defining the start or end of a study. CONCLUSION: The concept of "ongoing clinical trials" lacks a transparent and homogeneous definition across relevant sources. A consensus on this concept is important to facilitate the evaluation of available evidence and conduct research synthesis. Further efforts are necessary to determine the best definition for the start and end of a clinical trial.

Strategies for communicating scientific evidence on healthcare to managers and the population: a scoping review.

BACKGROUND: Health evidence needs to be communicated and disseminated in a manner that is clearly understood by decision-makers. As an inherent component of health knowledge translation, communicating results of scientific studies, effects of interventions and health risk estimates, in addition to understanding key concepts of clinical epidemiology and interpreting evidence, represent a set of essential instruments to reduce the gap between science and practice. The advancement of digital and social media has reshaped the concept of health communication, introducing new, direct and powerful communication platforms and gateways between researchers and the public. The objective of this scoping review was to identify strategies for communicating scientific evidence in healthcare to managers and/or population. METHODS: We searched Cochrane Library, Embase®, MEDLINE® and other six electronic databases, in addition to grey literature, relevant websites from related organizations for studies, documents or reports published from 2000, addressing any strategy for communicating scientific evidence on healthcare to managers and/or population. RESULTS: Our search identified 24 598 unique records, of which 80 met the inclusion criteria and addressed 78 strategies. Most strategies focused on risk and benefit communication in health, were presented by textual format and had been implemented and somehow evaluated. Among the strategies evaluated and appearing to yield some benefit are (i) risk/benefit communication: natural frequencies instead of percentages, absolute risk instead relative risk and number needed to treat, numerical instead nominal communication, mortality instead survival; negative or loss content appear to be more effective than positive or gain content; (ii) evidence synthesis: plain languages summaries to communicate the results of Cochrane reviews to the community were perceived as more reliable, easier to find and understand, and better to support decisions than the original summaries; (iii) teaching/learning: the Informed Health Choices resources seem to be effective for improving critical thinking skills. CONCLUSION: Our findings contribute to both the knowledge translation process by identifying communication strategies with potential for immediate implementation and to future research by recognizing the need to evaluate the clinical and social impact of other strategies to support evidence-informed policies. Trial registration protocol is prospectively available in MedArxiv (doi.org/10.1101/2021.11.04.21265922).

A scoping review of graphene-based biomaterials for in vivo bone tissue engineering.

The growing demand for more efficient materials for medical applications brought together two previously distinct fields: medicine and engineering. Regenerative medicine has evolved with the engineering contributions to improve materials and devices for medical use. In this regard, graphene is one of the most promising materials for bone tissue engineering and its potential for bone repair has been studied by several research groups. The aim of this study is to conduct a scoping review including articles published in the last 12 years (from 2010 to 2022) that have used graphene and its derivatives (graphene oxide and reduced graphene) in preclinical studies for bone tissue regeneration, searching in PubMed/MEDLINE, Embase, Web of Science, Cochrane Central, and clinicaltrials.gov (to confirm no study has started with clinical trial). Boolean searches were performed using the defined key words "bone" and "graphene", and manuscript abstracts were uploaded to Rayyan, a web-tool for systematic and scoping reviews. This scoping review was conducted based on Joanna Briggs Institute Manual for Scoping Reviews and the report follows the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews (PRISMA-ScR) statement. After the search protocol and application of the inclusion criteria, 77 studies were selected and evaluated by five blinded researchers. Most of the selected studies used composite materials associated with graphene and its derivatives to natural and synthetic polymers, bioglass, and others. Although a variety of graphene materials were analyzed in these studies, they all concluded that graphene, its derivatives, and its composites improve bone repair processes by increasing osteoconductivity, osteoinductivity, new bone formation, and angiogenesis. Thus, this systematic review opens up new opportunities for the development of novel strategies for bone tissue engineering with graphene.

Alemtuzumab for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS therapies focus on treating and preventing exacerbations, and avoiding the progression of disability. At present, there is no treatment that is capable of safely and effectively reaching these objectives. Clinical trials suggest that alemtuzumab, a humanized monoclonal antibody, could be a promising option for MS. OBJECTIVES: To evaluate the benefits and harms of alemtuzumab alone or associated with other treatments in people with any form of MS. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 21 June 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in adults with any subtype of MS comparing alemtuzumab alone or associated with other medications versus placebo; another active drug; or alemtuzumab in another dose, regimen, or duration. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our co-primary outcomes were 1. relapse-free survival, 2. sustained disease progression, and 3. number of participants experiencing at least one adverse event. Our secondary outcomes were 4. participants free of clinical disability, 5. quality of life, 6. change in disability, 7. fatigue, 8. new or enlarging lesions on resonance imaging, and 9. dropouts. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included three RCTs (1713 participants) comparing intravenous alemtuzumab versus subcutaneous interferon beta-1a for relapsing-remitting MS. Participants were treatment-naive (two studies) or had experienced at least one relapse after interferon or glatiramer (one study). Alemtuzumab was given at doses of 12 mg/day or 24 mg/day for five days at months 0 and 12, or 24 mg/day for three days at months 12 and 24. Participants in the interferon beta-1a group received 44 µg three times weekly. Alemtuzumab 12 mg: 1. may improve relapse-free survival at 36 months (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.18 to 0.53; 1 study, 221 participants; low-certainty evidence); 2. may improve sustained disease progression-free survival at 36 months (HR 0.25, 95% CI 0.11 to 0.56; 1 study, 223 participants; low-certainty evidence); 3. may make little to no difference on the proportion of participants with at least one adverse event at 36 months (risk ratio [RR] 1.00, 95% CI 0.98 to 1.02; 1 study, 224 participants; low-certainty evidence), although the proportion of participants with at least one adverse event was high with both drugs; 4. may slightly reduce disability at 36 months (mean difference [MD] -0.70, 95% CI -1.04 to -0.36; 1 study, 223 participants; low-certainty evidence). The evidence is very uncertain regarding the risk of dropouts at 36 months (RR 0.81, 95% CI 0.57 to 1.14; 1 study, 224 participants; very low-certainty evidence). Alemtuzumab 24 mg: 1. may improve relapse-free survival at 36 months (HR 0.21, 95% CI 0.11 to 0.40; 1 study, 221 participants; low-certainty evidence); 2. may improve sustained disease progression-free survival at 36 months (HR 0.33, 95% CI 0.16 to 0.69; 1 study, 221 participants; low-certainty evidence); 3. may make little to no difference on the proportion of participants with at least one adverse event at 36 months (RR 0.99, 95% CI 0.97 to 1.02; 1 study, 215 participants; low-certainty evidence), although the proportion of participants with at least one adverse event was high with both drugs; 4. may slightly reduce disability at 36 months (MD -0.83, 95% CI -1.16 to -0.50; 1 study, 221 participants; low-certainty evidence); 5. may reduce the risk of dropouts at 36 months (RR 0.08, 95% CI 0.01 to 0.57; 1 study, 215 participants; low-certainty evidence). For quality of life, fatigue, and participants free of clinical disease activity, the studies either did not consider these outcomes or they used different measuring tools to those planned in this review. AUTHORS' CONCLUSIONS: Compared with interferon beta-1a, alemtuzumab may improve relapse-free survival and sustained disease progression-free survival, and make little to no difference on the proportion of participants with at least one adverse event for people with relapsing-remitting MS at 36 months. The certainty of the evidence for these results was very low to low.

Minimally invasive interventions for biopsy of malignancy-suspected pulmonary nodules: a systematic review and meta-analysis.

BACKGROUND: Imaging tests are important for diagnosis during the management of pulmonary nodules; however, biopsy is required to confirm the malignancy. OBJECTIVES: To compare the effects of different techniques used for the biopsy of a pulmonary nodule. DESIGN AND SETTING: Systematic review and meta-analysis were conducted using Cochrane methodology in São Paulo, São Paulo, Brazil. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) on minimally invasive techniques, including tomography-guided percutaneous biopsy (PERCUT), transbronchial biopsies with fluoroscopy (FLUOR), endobronchial ultrasound (EBUSR), and electromagnetic navigation (NAVIG). The primary outcomes were diagnostic yield, major adverse events, and need for another approach. RESULTS: Seven RCTs were included (913 participants; 39.2% female, mean age: 59.28 years). Little to no increase was observed in PERCUT over FLUOR (P = 0.84), PERCUT over EBUSR (P = 0.32), and EBUSR over NAVIG (P = 0.17), whereas a slight increase was observed in NAVIG over FLUOR (P = 0.17); however, the evidence was uncertain. EBUSR may increase the diagnostic yield over FLUOR (P = 0.34). PERCUT showed little to no increase in all bronchoscopic techniques, with uncertain evidence (P = 0.02). CONCLUSION: No biopsy method is definitively superior to others. The preferred approach must consider availability, accessibility, and cost, as safety and diagnostic yield do not differ. Further RCTs planned, conducted, and reported with methodological rigor and transparency are needed, and additional studies should assess cost and the correlation between nodule size and location, as well as their association with biopsy results. SYSTEMATIC REVIEW REGISTRATION: PROSPERO database, CRD42018092367 -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=92367.

Skin-sparing mastectomy for the treatment of breast cancer.

BACKGROUND: Skin-sparing mastectomy (SSM) is a surgical technique that aims to maximize skin preservation, facilitate breast reconstruction, and improve cosmetic outcomes. Despite its use in clinical practice, the benefits and harms related to SSM are not well established. OBJECTIVES: To assess the effectiveness and safety of skin-sparing mastectomy for the treatment of breast cancer. SEARCH METHODS: We searched Cochrane Breast Cancer's Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov on 9 August 2019. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-randomized or non-randomized studies (cohort and case-control) comparing SSM to conventional mastectomy for treating ductal carcinoma in situ (DCIS) or invasive breast cancer. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome was overall survival. Secondary outcomes were local recurrence free-survival, adverse events (including overall complications, breast reconstruction loss, skin necrosis, infection and hemorrhage), cosmetic results, and quality of life. We performed a descriptive analysis and meta-analysis of the data. MAIN RESULTS: We found no RCTs or quasi-RCTs. We included two prospective cohort studies and twelve retrospective cohort studies. These studies included 12,211 participants involving 12,283 surgeries (3183 SSM and 9100 conventional mastectomies). It was not possible to perform a meta-analysis for overall survival and local recurrence free-survival due to clinical heterogeneity across studies and a lack of data to calculate hazard ratios (HR).  Based on one study, the evidence suggests that SSM may not reduce overall survival for participants with DCIS tumors (HR 0.41, 95% CI 0.17 to 1.02; P = 0.06; 399 participants; very low-certainty evidence) or for participants with invasive carcinoma (HR 0.81, 95% CI 0.48 to 1.38; P = 0.44; 907 participants; very low-certainty evidence). For local recurrence-free survival, meta-analysis was not possible, due to high risk of bias in nine of the ten studies that measured this outcome. Informal visual examination of effect sizes from nine studies suggested the size of the HR may be similar between groups. Based on one study that adjusted for confounders, SSM may not reduce local recurrence-free survival (HR 0.82, 95% CI 0.47 to 1.42; P = 0.48; 5690 participants; very low-certainty evidence).  The effect of SSM on overall complications is unclear (RR 1.55, 95% CI 0.97 to 2.46; P = 0.07, I2 = 88%; 4 studies, 677 participants; very low-certainty evidence). Skin-sparing mastectomy may not reduce the risk of breast reconstruction loss (RR 1.79, 95% CI 0.31 to 10.35; P = 0.52; 3 studies, 475 participants; very low-certainty evidence), skin necrosis (RR 1.15, 95% CI 0.62 to 2.12; P = 0.22, I2 = 33%; 4 studies, 677 participants; very low-certainty evidence), local infection (RR 2.04, 95% CI 0.03 to 142.71; P = 0.74, I2 = 88%; 2 studies, 371 participants; very low-certainty evidence), nor hemorrhage (RR 1.23, 95% CI 0.47 to 3.27; P = 0.67, I2 = 0%; 4 studies, 677 participants; very low-certainty evidence). We downgraded the certainty of the evidence due to the risk of bias, imprecision, and inconsistency among the studies. There were no data available on the following outcomes: systemic surgical complications, local complications, explantation of implant/expander, hematoma, seroma, rehospitalization, skin necrosis with revisional surgery, and capsular contracture of the implant. It was not possible to perform a meta-analysis for cosmetic and quality of life outcomes due to a lack of data. One study performed an evaluation of aesthetic outcome after SSM: 77.7% of participants with immediate breast reconstruction had an overall aesthetic result of excellent or good versus 87% of participants with delayed breast reconstruction. AUTHORS' CONCLUSIONS: Based on very low-certainty evidence from observational studies, it was not possible to draw definitive conclusions on the effectiveness and safety of SSM for breast cancer treatment. The decision for this technique of breast surgery for treatment of DCIS or invasive breast cancer must be individualized and shared between the physician and the patient while considering the potential risks and benefits of available surgical options.

Most Cochrane systematic reviews and protocols did not adhere to the Cochrane's risk of bias 2.0 tool

SUMMARY OBJECTIVE: The aim of this study was to identify the frequency of Cochrane systematic reviews and Cochrane systematic reviews protocols using (or planning to use) the risk of bias 2.0 tool to assess the risk of bias of the included randomized clinical trials. STUDY DESIGN: This is a meta-research study. METHODS: We included Cochrane systematic reviews or Cochrane systematic reviews protocols that planned to include randomized clinical trials. We assessed the Cochrane Database of Systematic Reviews and screened for issues published after the launch of risk of bias 2.0 tool (2019-2022). Two independent investigators performed the study selection and data extraction. RESULTS: We analyzed 440 Cochrane systematic reviews and 536 Cochrane systematic reviews protocols. Overall, 4.8% of the Cochrane systematic reviews and 28.5% of the Cochrane systematic reviews protocols used or planned to use risk of bias 2.0 tool. Although low, adherence is increasing over time. In 2019, 0% of Cochrane systematic reviews used risk of bias 2.0 tool, compared to 24.1% in 2022. In Cochrane systematic reviews protocols, adherence increased from 6.9% in 2019 to 41.5% in 2022. A total of 274 (62.1%) Cochrane systematic reviews had their protocols published before 2018; only one used risk of bias 2.0 tool and reported the change of versions in the "Differences between protocol and revision" section. CONCLUSION: The Cochrane's risk of bias 2.0 tool has low adherence among Cochrane protocols and systematic reviews. Further efforts are necessary to facilitate the implementation of this new tool.

Competency profiles for evidence-informed policy-making (EIPM): a rapid review.

BACKGROUND: Evidence-informed policy-making (EIPM) requires a set of individual and organizational capacities, linked with background factors and needs. The identification of essential knowledge, skills and attitudes for EIPM can support the development of competency profiles and their application in different contexts. PURPOSE: To identify elements of competency (knowledge, skills and attitudes) for EIPM, according to different professional profiles (researcher, health professional, decision-maker and citizen). METHODS: Rapid umbrella review. A structured search was conducted and later updated in two comprehensive repositories (BVSalud and PubMed). Review studies with distinctive designs were included, published from 2010 onwards, without language restrictions. Assessment of the methodological quality of the studies was not performed. A meta-aggregative narrative synthesis was used to report the findings. RESULTS: Ten reviews were included. A total of 37 elements of competency were identified, eight were categorized as knowledge, 19 as skills and 10 as attitudes. These elements were aggregated into four competency profiles: researcher, health professional, decision-maker and citizen. The competency profiles included different sets of EIPM-related knowledge, skills and attitudes. STRENGTHS AND LIMITATIONS: This study is innovative because it aggregates different profiles of competency from a practical perspective, favouring the application of its results in different contexts to support EIPM. Methodological limitations are related to the shortcuts adopted in this review: complementary searches of the grey literature were not performed, and the study selection and data extraction were not conducted in duplicate. FINAL CONSIDERATIONS: CONCLUSIONS AND IMPLICATIONS OF THE FINDINGS: EIPM requires the development of individual and organizational capacities. This rapid review contributes to the discussion on the institutionalization of EIPM in health systems. The competency profiles presented here can support discussions about the availability of capacity and the need for its development in different contexts.

Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage.

BACKGROUND: Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH. OBJECTIVES: To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 15 October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated erythromycin before endoscopy compared to any other treatment or no treatment/placebo before endoscopy in adults with acute UGIH. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. UGIH-related mortality and 2. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. visualisation of gastric mucosa, 3. non-serious adverse events, 4. rebleeding, 5. blood transfusion, and 5. rescue invasive intervention. We used GRADE criteria to assess the certainty of the evidence for each outcome.  MAIN RESULTS: We included 11 RCTs with 878 participants. The mean age ranged from 53.13 years to 64.5 years, and most participants were men (72.3%). One RCT included only non-variceal haemorrhage, one included only variceal haemorrhage, and eight included both aetiologies. We defined short-term outcomes as those occurring within one week of initial endoscopy. Erythromycin versus placebo Three RCTs (255 participants) compared erythromycin with placebo. There were no UGIH-related deaths. The evidence is very uncertain about the short-term effects of erythromycin compared with placebo on serious adverse events (risk difference (RD) -0.01, 95% confidence interval (CI) -0.04 to 0.02; 3 studies, 255 participants; very low certainty), all-cause mortality (RD 0.00, 95% CI -0.03 to 0.03; 3 studies, 255 participants; very low certainty), non-serious adverse events (RD 0.01, 95% CI -0.03 to 0.05; 3 studies, 255 participants; very low certainty), and rebleeding (risk ratio (RR) 0.63, 95% CI 0.13 to 2.90; 2 studies, 195 participants; very low certainty). Erythromycin may improve gastric mucosa visualisation (mean difference (MD) 3.63 points on 16-point ordinal scale, 95% CI 2.20 to 5.05; higher MD means better visualisation; 2 studies, 195 participants; low certainty). Erythromycin may also result in a slight reduction in blood transfusion (MD -0.44 standard units of blood, 95% CI -0.86 to -0.01; 3 studies, 255 participants; low certainty). Erythromycin plus nasogastric tube lavage versus no intervention/placebo plus nasogastric tube lavage Six RCTs (408 participants) compared erythromycin plus nasogastric tube lavage with no intervention/placebo plus nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin plus nasogastric tube lavage compared with no intervention/placebo plus nasogastric tube lavage on all-cause mortality (RD -0.02, 95% CI -0.08 to 0.03; 3 studies, 238 participants; very low certainty), visualisation of the gastric mucosa (standardised mean difference (SMD) 0.48 points on 10-point ordinal scale, 95% CI 0.10 to 0.85; higher SMD means better visualisation; 3 studies, 170 participants; very low certainty), non-serious adverse events (RD 0.00, 95% CI -0.05 to 0.05; 6 studies, 408 participants; very low certainty), rebleeding (RR 1.13, 95% CI 0.63 to 2.02; 1 study, 169 participants; very low certainty), and blood transfusion (MD -1.85 standard units of blood, 95% CI -4.34 to 0.64; 3 studies, 180 participants; very low certainty). Erythromycin versus nasogastric tube lavage Four RCTs (287 participants) compared erythromycin with nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin compared with nasogastric tube lavage on all-cause mortality (RD 0.02, 95% CI -0.05 to 0.08; 3 studies, 213 participants; very low certainty), visualisation of the gastric mucosa (RR 1.19, 95% CI 0.79 to 1.79; 2 studies, 198 participants; very low certainty), non-serious adverse events (RD -0.10, 95% CI -0.34 to 0.13; 3 studies, 213 participants; very low certainty), rebleeding (RR 0.77, 95% CI 0.40 to 1.49; 1 study, 169 participants; very low certainty), and blood transfusion (median 2 standard units of blood, interquartile range 0 to 4 in both groups; 1 study, 169 participants; very low certainty). Erythromycin plus nasogastric tube lavage versus metoclopramide plus nasogastric tube lavage One RCT (30 participants) compared erythromycin plus nasogastric tube lavage with metoclopramide plus nasogastric tube lavage. The evidence is very uncertain about the effects of erythromycin plus nasogastric tube lavage on all the reported outcomes (serious adverse events, visualisation of gastric mucosa, non-serious adverse events, and blood transfusion). AUTHORS' CONCLUSIONS: We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.

Most Cochrane systematic reviews and protocols did not adhere to the Cochrane's risk of bias 2.0 tool.

OBJECTIVE: The aim of this study was to identify the frequency of Cochrane systematic reviews and Cochrane systematic reviews protocols using (or planning to use) the risk of bias 2.0 tool to assess the risk of bias of the included randomized clinical trials. STUDY DESIGN: This is a meta-research study. METHODS: We included Cochrane systematic reviews or Cochrane systematic reviews protocols that planned to include randomized clinical trials. We assessed the Cochrane Database of Systematic Reviews and screened for issues published after the launch of risk of bias 2.0 tool (2019-2022). Two independent investigators performed the study selection and data extraction. RESULTS: We analyzed 440 Cochrane systematic reviews and 536 Cochrane systematic reviews protocols. Overall, 4.8% of the Cochrane systematic reviews and 28.5% of the Cochrane systematic reviews protocols used or planned to use risk of bias 2.0 tool. Although low, adherence is increasing over time. In 2019, 0% of Cochrane systematic reviews used risk of bias 2.0 tool, compared to 24.1% in 2022. In Cochrane systematic reviews protocols, adherence increased from 6.9% in 2019 to 41.5% in 2022. A total of 274 (62.1%) Cochrane systematic reviews had their protocols published before 2018; only one used risk of bias 2.0 tool and reported the change of versions in the "Differences between protocol and revision" section. CONCLUSION: The Cochrane's risk of bias 2.0 tool has low adherence among Cochrane protocols and systematic reviews. Further efforts are necessary to facilitate the implementation of this new tool.

Effects of preoperative magnetic resonance image on survival rates and surgical planning in breast cancer conservative surgery: randomized controlled trial (BREAST-MRI trial).

BACKGROUND: Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. METHODS: A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0-III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. RESULTS: 524 were randomized to preoperative MRI group (n = 257) or control group (n = 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR = 0.72; 95% CI 0.12-4.28; p = 0.7) and an OS of 95.3% in the MRI group versus 96.3% in the control group (HR = 1.37 95% CI 0.59-3.19; p = 0.8). Surgical management changed in 21 ipsilateral breasts in the MRI group; 21 (8.3%) had mastectomies versus one in the control group. No difference was found in reoperation rates, 22 (8.7%) in the MRI group versus 23 (8.7%) in the control group (RR = 1.002; 95% CI 0.57-1.75; p = 0.85). CONCLUSION: Preoperative MRI increased the mastectomy rates by 8%. The use of preoperative MRI did not influence local relapse-free survival, overall survival, or reoperation rates.

Supporting Decisions of the Brazilian Regulatory Agency for Supplementary Healthcare: A Case Study.

OBJECTIVES: This study aimed to report implementation and partial results of the project "Supporting the Brazilian regulatory agency for supplementary healthcare through health technology assessment actions" conducted at Hospital Sírio-Libanês, Brazil, from 2020 to 2023, through Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde, a Brazilian Ministry of Health initiative. METHODS: This was a case study conducted at Health Technology Center, Hospital Sírio-Libanês. RESULTS: From its inception, in 2020, to July 2022, the following activities and products were completed: 59 technical-methodological reports assessing the efficacy, safety, cost-effectiveness, and budget impact of technologies received by Agência Nacional de Saúde Suplementar (ANS) to compose its catalog of drugs products and services; 50 analyses of society contributions from public consultation; 34 methodological or clinical tutorial sessions to support ANS team; 2 templates to systematize the update process of ANS catalog; and one training course on systematic reviews and meta-analysis for ANS team. CONCLUSION: The project has contributed to increasing ANS autonomy in the health technology assessment, collaborating to efficiency in technologies offer to the users. By adopting and fostering evidence-based knowledge construction, the project reinforces its bridging role for supporting the consonance between public and supplementary healthcare sectors in Brazil.