Search

Sandra Kalil Bussadori,1 Lara Jassiski Motta,1 Anna Carolina Ratto Tempestini Horliana,1 Elaine Marcílio Santos,1,2 Ana Luiza Cabrera Martimbianco2 1Postgraduate Program in Biophotonics Applied to Health Sciences, University Nove De Julho (UNINOVE), São Paulo, Brazil; 2Postgraduate Program in Health and Environment, Universidade Metropolitana De Santos (UNIMES), Santos, Sao Paulo, BrazilCorrespondence: Sandra Kalil BussadoriPostgraduate Program in Biophotonics Applied to Health Sciences, University Nove De Julho (UNINOVE), Rua Vergueiro, 239/245, São Paulo, SP CEP 01504-000, BrazilTel/Fax +55 (11) 3385-9222Email sandra.skb@gmail.comAbstract: Bruxism, specifically sleep bruxism (SB), is a worldwide discussed topic in the literature; however, there is insufficient evidence to define and support a standard approach for the treatment of SB. The purpose of this overview was to map the evidence from systematic reviews (SR), examining the effects of interventions to improve chronic pain related to bruxism. The methodological quality of SRs was assessed using the AMSTAR-2 tool. We conducted a comprehensive literature search in April 2020, in the following databases: Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, LILACS, BBO, and Epistemonikos. Nine SRs with critically low to high methodological quality were included. Considering the main findings, botulinum toxin type A (BTX-A) showed a significant pain and sleep bruxism frequency reduction when compared to placebo or conventional treatment (behavioral therapy, occlusal splints, and drugs), after 6 and 12 months. Occlusal splints combined to muscle massage showed some benefit in pain reduction. There was no difference in pain and bruxism frequency between biofeedback therapy and an inactive control group. Regarding drug therapy, there is no difference when amitriptyline, bromocriptine, clonidine, propranolol, and levodopa were compared to placebo. In conclusion, there is some evidence to support the use of occlusal splints plus massage, and BTX-A to reduce chronic pain related to SB. No evidence was provided to support the recommendation of biofeedback therapy and drug therapy. There is still a need for more methodologically rigorous randomized clinical trials (RCT) to be conducted on the efficacy and safety of different therapies for SB.Keywords: sleep bruxism, pain management, evidence-based dentistry

Objective: The objective of this study was to describe and critically appraise the conclusions of randomized clinical trials assessing monoclonal antibodies sponsored by the pharmaceutical industry., Methods: This is a meta-research study on conclusions' characteristics of randomized clinical trials with monoclonal antibodies as interventions sponsored by the pharmaceutical industry., Results: A total of 82 publications were considered. Notably, 79.3% (65/82) of the trials were fully funded by the pharmaceutical industry, and sponsors had data and publishing rights in 70.7% (58/82). Among the fully sponsored studies, 78.5% (51/65) presented conclusions with a drug-favorable direction of the effect, and 30.8% (20/65) made some recommendations for clinical practice, of which 95% (19/20) were favorable to the drug. In relation to the partially funded studies, drug-favorable direction of effect was present in 68.8% (11/16) of conclusions, and 18.8% (3/16) recommended the drug for the practice, in which 66.7% (2/3) favored the drug. Positive direction of effect was more present in trials in which the sponsor owned data and publication (81.0%; 47/58), compared to trials where the funder did not (63.3%; 14/22). Only 13.4% (11/82) of included studies recognize the uncertainty in the estimates in the conclusions, and 37.4% (31/82) had a statement regarding the need for future studies., Conclusions: Most of the included randomized clinical trials on monoclonal antibodies funded by the industry concluded a drug-favorable direction of effect. Recommendations for practice were common, while recognition of uncertainty and statements regarding the need for future studies were less frequently present in the conclusion.

Objective: several clinical trials have been published in recent years to investigate the potential benefits of physical exercise for women with breast cancer. This meta-epidemiological study aimed to map and critically assess the methodological quality of systematic reviews on physical activity for breast cancer patients., Methods: a meta-epidemiological study including systematic reviews of randomized clinical trials that evaluated the effects of physical exercise on breast cancer patients. The search was performed in MEDLINE. The methodological quality was assessed using the AMSTAR-2 tool. We collected additional information regarding included systematic review search details., Results: we included 57 systematic reviews published between 2006 and 2021, including only randomized clinical trials on the effects of any physical activity on breast cancer patients. The results showed that 58% of the included reviews were classified as low or critically low quality. Only 10% presented high methodological quality, and 32% were classified as moderate. Furthermore, complete search strategies were presented in 54,4% of the reviews, and 59,6% fully described the search date; 61,4% presented data and/or language restrictions, and 52,6% conducted additional hand searches., Conclusion: The findings of this study showed the methodological frailty of most systematic reviews on the effects of physical exercises on breast cancer patients. Caution is needed on the part of health professionals, managers and policymakers in health, patients and the general population when interpreting the applicability of this evidence, and it is suggested to perform systematic reviews of high methodological quality to assist decision-making., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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&#95;record.php?RecordID=158173., Competing Interests: The authors declare that they have no conflicts of interest related to this study., (© 2024 The Authors.)

Objective: To evaluate the efficacy and safety of nonpharmacological topical interventions for treating breastfeeding nipple pain. Methods: Randomized clinical trials (RCTs) assessing lactating women suffering from breastfeeding painful nipples were included. Primary outcomes were pain, healing process, and adverse events. A comprehensive search was conducted on June 02, 2023, without date or language restrictions. Methodological quality was assessed using the Cochrane risk of bias tool and the certainty of the evidence, the GRADE approach. Results: Nineteen RCTs with unclear to high risk of bias were included. There was uncertain evidence regarding the effects of photobiomodulation versus placebo on pain reduction (mean difference [MD] -0.15; 95% confidence interval [95% CI] -1 0.49 to 1.19; 139 participants, 2 RCTs). There are uncertainties concerning the effects of lanolin versus breast milk on pain (MD -1.80; 95% CI -2.43 to -1.17; 1 RCT; 180 participants), wound healing (MD 0.10; 95% CI -0.26 to -0.46; 1 RCT; 180 participants), and any adverse events (zero events in both groups). Similar effects were observed by the other interventions assessed. Conclusion: The evidence of nonpharmacological topical interventions for painful nipples is imprecise, and future RCTs with higher methodological quality are needed to support recommendations. Considering the accessibility and low cost of these alternative treatments, the findings of this evidence synthesis could support clinical decision-making and guide future research. PROSPERO CRD42020170320.

Objectives: To assess to what extent the overall quality of evidence indicates changes to observe intervention effect estimates when new data become available., Methods: We conducted a meta-epidemiological study. We obtained evidence from meta-analyses of randomized trials of Cochrane reviews addressing the same health-care question that was updated with inclusion of additional data between January 2016 and May 2021. We extracted the reported effect estimates with 95% confidence intervals (CIs) from meta-analyses and corresponding GRADE (Grading of Recommendations Assessment, Development, and Evaluation) assessments of any intervention comparison for the primary outcome in the first and the last updated review version. We considered the reported overall quality (certainty) of evidence (CoE) and specific evidence limitations (no, serious or very serious for risk of bias, imprecision, inconsistency, and/or indirectness). We assessed the change in pooled effect estimates between the original and updated evidence using the ratio of odds ratio (ROR), absolute ratio of odds ratio (aROR), ratio of standard errors (RoSE), direction of effects, and level of statistical significance., Results: High CoE without limitations characterized 19.3% (n = 29) out of 150 included original Cochrane reviews. The update with additional data did not systematically change the effect estimates (mean ROR 1.00; 95% CI 0.99-1.02), which deviated 1.06-fold from the older estimates (median aROR; interquartile range [IQR]: 1.01-1.15), gained precision (median RoSE 0.87; IQR 0.76-1.00), and maintained the same direction with the same level of statistical significance in 93% (27 of 29) of cases. Lower CoE with limitations characterized 121 original reviews and graded as moderate CoE in 30.0% (45 of 150), low CoE in 32.0% (48 of 150), and very low CoE in 18.7% (28 of 150) reviews. Their update had larger absolute deviations (median aROR 1.12 to 1.33) and larger gains in precision (median RoSE 0.78-0.86) without clear and consistent differences between these categories of CoE. Changes in effect direction or statistical significance were also more common in the lower quality evidence, again with a similar extent across categories (without change in 75.6%, 64.6%, and 75.0% for moderate, low, very low CoE). As limitations increased, effect estimates deviated more (aROR 1.05 with zero, 1.11 with one, 1.25 with two, 1.24 with three limitations) and changes in direction or significance became more frequent (93.2% stable with no limitations, 74.5% with one, 68.2% with two, and 61.5% with three limitations)., Conclusion: High-quality evidence without methodological deficiencies is trustworthy and stable, providing reliable intervention effect estimates when updated with new data. Evidence of moderate and lower quality may be equally prone to being unstable and cannot indicate if available effect estimates are true, exaggerated, or underestimated., Competing Interests: Declaration of competing interest I.H.: has one-year consulting contract for research projects at the Medical University of South Carolina, Charleston, SC, USA. D.N.: declares having led/coauthored/coauthoring Cochrane Reviews and conducted GRADE assessments as part of completing some of these reviews. He also declares having been part of the Cochrane Convenes initiative organized by Cochrane to consider the issue of misinformation, its impact on the health evidence ecosystem and solutions to address it. L.G.H.’s Institution (RC2NB) is supported by Foundation Clinical Neuroimmunology and Neuroscience Basel. There are no competing interests for any other author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Clinical trials on tyrosine kinase inhibitors (TKI) treatment have shown an improvement in overall and progression-free survival in patients with advanced differentiated thyroid cancer. However, it is necessary to evaluate these studies to assess methodological biases and inconsistencies that may impact the effects., Objective: To map and assess the methodological quality of randomized clinical trials (RCTs) regarding randomization, allocation concealment, blinding, and selective reporting bias., Methods: RCTs assessing the efficacy and safety of TKI for the treatment of advanced differentiated thyroid cancer were included. The search was performed in the MEDLINE database. The included RCTs were assessed for the adequacy of the methodological steps, as recommended by the Cochrane Risk of Bias tool., Results: Nine studies were analyzed, of which 77.7% were classified as low risk of bias regarding selective reporting and 33.3% as high risk of reporting bias. The mean time between protocol registration and study publication was approximately 5.11 years. Moreover, 66.7% were classified as low risk of bias for randomization and allocation concealment, and 33.3% did not specify the randomization process and allocation concealment in a way that would allow the identification of occurrences of bias. Concerning blinding of participants and outcome assessors, 77.8% of the RCTs reported adequate blinding and were classified as having a low risk of bias, 11.1% had a high risk of bias, and 11.1% had insufficient information and were classified as having unclear risk of bias. Regarding the blinding of the outcome assessors, 33.3% did the blinding correctly, 11.1% did not blind, and 55.6% did not provide enough information., Conclusion: Overall, the assessed RCTs were predominantly at low risk of bias. The critical evaluation of these studies is essential to have confidence in the treatment estimated effect that will support clinical decision-making and provide information to preclude future clinical study flaws., (© 2024 Wiley Periodicals LLC.)

Background: Systematic reviews of Randomized Controlled Trials (RCTs) are considered high-level evidence to support a decision on therapeutic interventions, and their methodological quality is essential to provide reliable and applicable results., Objective: This meta-epidemiological study aimed to map and critically appraise systematic reviews assessing treatments for vesiculobullous skin diseases., Methods: We conducted a comprehensive search strategy on MEDLINE (via Pubmed) in December 2022 without restrictions to find systematic reviews evaluating pharmacological interventions for vesiculobullous skin diseases. The methodological quality was assessed using the AMSTAR-2 tool, and additional information was extracted. We identified nine systematic reviews published between 2002 and 2021, seven assessing pemphigus., Results: According to the AMSTAR-2 tool, 55.6% were classified as critically low quality, 22.2% as moderate quality, 11.1% as low and 11.1% as high quality. No review assessed the certainty of the evidence (GRADE); 86% of pemphigus reviews had at least two overlapping RCTs. There were some limitations regarding methodological flaws and the AMSTAR-2 tool use CONCLUSIONS: These findings reveal a frail methodological quality of systematic reviews about vesiculobullous diseases treatment that may impact the results. Therefore, methodological rigor is mandatory for future systematic reviews to avoid duplication of effort and increase the certainty of the evidence supporting decision-making., (Copyright © 2023. Published by Elsevier España, S.L.U.)

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.

Managing tibial fractures requires substantial health resources, which costs the health system. This study aimed to describe the costs of photobiomodulation (PBM) with LEDs in the healing process of soft tissue lesions associated with tibial fracture compared to a placebo. Economic analysis was performed based on a randomized controlled clinical trial, with a simulation of the cost-effectiveness and incremental cost model. Adults (n = 27) hospitalized with tibia fracture awaiting definitive surgery were randomized into two distinct groups: the PBM Group (n = 13) and the Control Group with simulated phototherapy (n = 14). To simulate the cost-effectiveness and incremental cost model, the outcome was the evolution of wound resolution by the BATES-JENSEN scale and time of wound resolution in days. The total cost of treatment for the Control group was R$21,164.56, and a difference of R$7,527.10 more was observed when compared to the treatment of the PBM group. The proposed intervention did not present incremental cost since the difference in the costs to reduce measures between the groups was smaller for the PBM group. When analyzing the ICER (Incremental cost-effectiveness ratio), it would be possible to save R$3,500.98 with PBM and decrease by 2.15 points in the daily average on the BATES-JENSEN scale. It is concluded, therefore, that PBM can be a supportive therapy of clinical and economic interest in a hospital setting., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Neto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Severe coronavirus disease 2019 (COVID-19) can cause thrombotic events that lead to severe complications or death. Antiplatelet agents, such as acetylsalicylic acid, have been shown to effectively reduce thrombotic events in other diseases: they could influence the course of COVID-19 in general., Objectives: To assess the efficacy and safety of antiplatelets given with standard care compared to no treatment or standard care (with/without placebo) for adults with COVID-19., Search Methods: We searched the Cochrane COVID-19 Study Register (which comprises MEDLINE (PubMed), Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv, CENTRAL), Web of Science, WHO COVID-19 Global literature on coronavirus disease and the Epistemonikos COVID-19 L*OVE Platform to identify completed and ongoing studies without language restrictions to December 2022., Selection Criteria: We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating antiplatelet agents for the treatment of COVID-19 in adults with COVID-19, irrespective of disease severity, gender or ethnicity., Data Collection and Analysis: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (RoB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the outcomes., Main Results: Antiplatelets plus standard care versus standard care (with/without placebo) Adults with a confirmed diagnosis of moderate to severe COVID-19 We included four studies (17,541 participants) that recruited hospitalised people with a confirmed diagnosis of moderate to severe COVID-19. A total of 8964 participants were analysed in the antiplatelet arm (either with cyclooxygenase inhibitors or P2Y12 inhibitors) and 8577 participants in the control arm. Most people were older than 50 years and had comorbidities such as hypertension, lung disease or diabetes. The studies were conducted in high- to lower middle-income countries prior to wide-scale vaccination programmes. Antiplatelets compared to standard care: - probably result in little to no difference in 28-day mortality (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.85 to 1.05; 3 studies, 17,249 participants; moderate-certainty evidence). In absolute terms, this means that for every 177 deaths per 1000 people not receiving antiplatelets, there were 168 deaths per 1000 people who did receive the intervention (95% CI 151 to 186 per 1000 people); - probably result in little to no difference in worsening (new need for invasive mechanical ventilation or death up to day 28) (RR 0.95, 95% CI 0.90 to 1.01; 2 studies, 15,266 participants; moderate-certainty evidence); - probably result in little to no difference in improvement (participants discharged alive up to day 28) (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 15,454 participants; moderate-certainty evidence); - probably result in a slight reduction of thrombotic events at longest follow-up (RR 0.90, 95% CI 0.80 to 1.02; 4 studies, 17,518 participants; moderate-certainty evidence); - may result in a slight increase in serious adverse events at longest follow-up (Peto odds ratio (OR) 1.57, 95% CI 0.48 to 5.14; 1 study, 1815 participants; low-certainty evidence), but non-serious adverse events during study treatment were not reported; - probably increase the occurrence of major bleeding events at longest follow-up (Peto OR 1.68, 95% CI 1.29 to 2.19; 4 studies, 17,527 participants; moderate-certainty evidence). Adults with a confirmed diagnosis of asymptomatic SARS-CoV-2 infection or mild COVID-19 We included two RCTs allocating participants, of whom 4209 had confirmed mild COVID-19 and were not hospitalised. A total of 2109 participants were analysed in the antiplatelet arm (treated with acetylsalicylic acid) and 2100 participants in the control arm. No study included people with asymptomatic SARS-CoV-2 infection. Antiplatelets compared to standard care: - may result in little to no difference in all-cause mortality at day 45 (Peto OR 1.00, 95% CI 0.45 to 2.22; 2 studies, 4209 participants; low-certainty evidence); - may slightly decrease the incidence of new thrombotic events up to day 45 (Peto OR 0.37, 95% CI 0.09 to 1.46; 2 studies, 4209 participants; low-certainty evidence); - may make little or no difference to the incidence of serious adverse events up to day 45 (Peto OR 1.00, 95% CI 0.60 to 1.64; 1 study, 3881 participants; low-certainty evidence), but non-serious adverse events were not reported. The evidence is very uncertain about the effect of antiplatelets on the following outcomes (compared to standard care plus placebo): - admission to hospital or death up to day 45 (Peto OR 0.79, 95% CI 0.57 to 1.10; 2 studies, 4209 participants; very low-certainty evidence); - major bleeding events up to longest follow-up (no event occurred in 328 participants; very low-certainty evidence). Quality of life and adverse events during study treatment were not reported., Authors' Conclusions: In people with confirmed or suspected COVID-19 and moderate to severe disease, we found moderate-certainty evidence that antiplatelets probably result in little to no difference in 28-day mortality, clinical worsening or improvement, but probably result in a slight reduction in thrombotic events. They probably increase the occurrence of major bleeding events. Low-certainty evidence suggests that antiplatelets may result in a slight increase in serious adverse events. In people with confirmed COVID-19 and mild symptoms, we found low-certainty evidence that antiplatelets may result in little to no difference in 45-day mortality and serious adverse events, and may slightly reduce thrombotic events. The effects on the combined outcome admission to hospital or death up to day 45 and major bleeding events are very uncertain. Quality of life was not reported. Included studies were conducted in high- to lower middle-income settings using antiplatelets prior to vaccination roll-outs. We identified a lack of evidence concerning quality of life assessments, adverse events and people with asymptomatic infection. The 14 ongoing and three completed, unpublished RCTs that we identified in trial registries address similar settings and research questions as in the current body of evidence. We expect to incorporate the findings of these studies in future versions of this review., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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.

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)., (© 2023. The Author(s).)

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., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Rationale & Objective: Infections are an important cause of mortality among patients receiving maintenance hemodialysis. Staphylococcus aureus is a frequent etiological agent, and previous nasal colonization is a risk factor for infection. Repeated antimicrobial decolonization reduces infection in this population but can induce antibiotic resistance. We compared photodynamic therapy, a promising bactericidal treatment that does not induce resistance, to mupirocin treatment among nasal carriers of S aureus., Study Design: Randomized controlled pilot study., Setting & Participants: 34 patients receiving maintenance hemodialysis who had nasal carriage of S aureus., Interventions: Patients were randomly assigned to decolonization with a single application of photodynamic therapy (wavelength of 660nm, 400mW/cm 2 , 300 seconds, methylene blue 0.01%) or with a topical mupirocin regimen (twice a day for 5 days)., Outcome: Nasal swabs were collected at time 0 (when the carrier state was identified), directly after treatment completion, 1 month after treatment, and 3 months after treatment. Bacterial isolates were subjected to proteomic analysis to identify the species present, and antimicrobial susceptibility was characterized., Results: All 17 participants randomized to photodynamic therapy and 13 of 17 (77%) randomized to mupirocin were adherent to treatment. Directly after treatment was completed, 12 participants receiving photodynamic therapy (71%) and 13 participants treated with mupirocin (77%) had cultures that were negative for S aureus (risk ratio, 0.92 [95% CI, 0.61-1.38]; P=0.9). Of the patients who had negative cultures directly after completion of photodynamic therapy, 67% were recolonized within 3 months. There were no adverse events in the photodynamic therapy group., Limitations: Testing was restricted to assessing nasal colonization; infectious complications were not assessed., Conclusions: Photodynamic therapy is a feasible approach to treating nasal carriage of S aureus. Future larger studies should be conducted to determine whether photodynamic therapy is equivalent to the standard of care with mupirocin., Funding: Government grant (National Council for Scientific and Technological Development process 3146682020-9)., Trial Registration: Registered at ClinicalTrials.gov with study number NCT04047914., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

This study evaluated the efficacy and safety of multiwavelength photobiomodulation (MPBM) in healing soft tissue injuries associated with tibial and/or ankle fractures. Participants were randomized into the MPBM or control group. Primary outcome was wound healing, measured by the Bates-Jensen scale. Assessments were performed daily. Twenty-seven hospitalized adults were included. MPBM showed an improvement in the daily mean Bates-Jensen scale (MPBM 32.1 vs. control 34.2; p = 0.029), daily mean pain score change (MPBM 0.5 vs. control 0.2; p = 0.04) and occurrence of infection at the site of the external fixator pins (MPBM 15.3% vs. control 57.1%; p = 0.02). MPBM group also showed faster-wound resolution (MPBM 13.1 vs. control 23.1 days). Subgroup analysis showed improvement in the MPBM group among less severe patients on the Bates-Jensen scale (MPBM 27.4 vs. control 34.7; p = 0.0081) and mean time for wound resolution (MPBM 7.0 vs. control 14.6 days; p = 0.03). MPBM appears safe and effective in reducing wound resolution time, infection in the surgical pin sites, reported pain and time before definitive surgery., (© 2023 Wiley-VCH GmbH.)

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., (Copyright © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

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.

Pregnancy in chronic kidney disease (CKD) women is relatively rare, and the less risky choice of hemodialysis is unknown. The objective of this systematic review was to identify, systematically evaluate and summarize the available evidence on the efficacy and safety of hemodialysis strategies for pregnant CKD women. Sensitive search strategies were applied to six databases without data or language restrictions. Comparative (randomized and non-randomized) studies were prioritized. Two reviewers independently selected, extracted, and critically evaluated data from studies. The risk of bias assessment was performed using the ROBINS-I tool, considering the study design (non-randomized comparative observational studies). The certainty of the evidence was assessed using the GRADE approach. From 7210 references identified, six retrospective cohort studies were included (576 women). The effects of intensive hemodialysis (over 20 h/week) are uncertain for maternal and neonatal mortality (Peto odds ratio [OR] 0.85; 95% confidence interval [95% CI] 0.26-2.80), miscarriage (Peto OR 0, 38; 95% CI 0.12-1.23), stillbirths (Peto OR 0, 56; 95% CI 0.13-2.31), preterm birth (Peto OR 0.87; 95% CI 0.33-2.28), low birth weight (Peto OR 0.71; 95% CI 0.20-2.50) and congenital anomalies rates. The certainty of the evidence was very low due to studies methodological limitations and effect estimates imprecision. The uncertainty about intensive versus conventional hemodialysis effects for pregnant women with CKD and the imprecision in the estimated effects precludes any recommendation. The strategy choice must consider treatment availability, costs, and maternal social aspects until future studies provide more reliable evidence. PROSPERO CRD42021259237., (© 2022 Wiley Periodicals LLC.)

Importance: Numerous studies have been published assessing the effects of resistance muscle training to mitigate menopausal symptoms, given the endocrine muscle function and its metabolic regulation. Therefore, mapping and synthesizing high-quality studies are necessary to help clinical decisions., Objective: The aim of this study was to assess the effects (benefits and harms) of resistance muscle training for postmenopausal women., Evidence Review: Electronic searches were conducted in MEDLINE (via PubMed), EMBASE, CENTRAL, PEDro, LILACS, and SPORTDiscus up to December 2021. Two independent reviewers selected the retrieved references and extracted relevant data from included studies. The methodological quality (risk of bias) using the Cochrane Risk of Bias table and the certainty of the evidence (GRADE approach) were assessed., Findings: Twelve randomized clinical trials (n = 452) with unclear to high risk of bias were identified. Compared with no exercise, resistance training (up to 16 weeks) seems to promote an improvement in functional capacity (mean difference [MD], 2.90 points; 95% CI, 0.60-5.20) and bone mineral density (MD, 0.10; 95% CI, 0.10-0.10) and a reduction in the hot flash frequency (13/29 vs 1/29; risk ratio, 13.0; 95% CI, 1.82-93.01) and fat mass (MD, -3.15; 95% CI, -6.68 to 0.38), and no differences were observed between groups regarding abdominal circumference and body mass index. When compared with aerobic exercises, resistance training may result in a reduction of hot flash frequency (7/18 vs 14/18; risk ratio, 0.50; 95% CI, 0.27-0.94) and fat mass (MD, -7.80; 95% CI, -14.02 to -1.58) and no difference in the quality of life and body mass index. Regarding safety, no serious adverse events were reported. Based on the GRADE approach, the certainty of this evidence was graded as very low to low, leading to imprecisely estimated effects., Conclusions and Relevance: Resistance muscle training seems to improve postmenopausal symptoms and functional capacity. Given the low to very low certainty of the evidence, further randomized clinical trials with higher methodological quality and better reports are still needed. As an implication for clinical practice, health professionals should consider individualized aspects such as the previous history of exercise practice, physical capacity, and adaptation period., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2022 by The North American Menopause Society.)

Aims: to map and synthesize the results from studies that assessed whether individuals diagnosed with cerebral palsy (CP) have abnormal masseter and temporal muscles activation during the masticatory cycle., Methods: Six databases were searched for comparative observational studies assessing masticatory muscles activation in individuals with CP through electromyography analysis. Methodological quality was evaluated using the Joanna Briggs Critical Appraisal Checklist. Outcome data were combined in meta-analysis using the Review Manager software., Results: We included five cross-sectional studies with an overall low risk of bias. Meta-analyses showed no difference between CP and healthy individuals regarding maximum voluntary isometric contraction: right masseter (Standard mean difference [SMD] - 0.95; 95% CI -2.03 to 0.13); left masseter (SMD -0.92; 95% CI -1.93 to 0.09); right temporal (SMD -0.72; 95% CI -1.63 to 0.18); and left temporal (SMD -0.68; 95% CI -1.76 to 0.40). Electrical activity amplitude in the inactive period was superior in the CP group, and maximum bite pressure presented higher values in the control group (Mean difference [MD] - 17.38; CI 95% -26.62 to -10.15)., Conclusions: Based on observational studies with a lower level of evidence, individuals with CP seem to present difficulties activating masticatory muscles. Future prospective cohort studies with rigorous methodology are still necessary to support these findings. PROSPERO register CRD42020208444.

Purpose: to critically appraise and synthesize the evidence on the effects of vitamin C-based regimens for patients with sepsis or septic shock., Methods: a broad search was performed on May 2021 to identify randomized clinical trials (RCTs) assessing vitamin C-based regimens as adjuvant therapy for adults with sepsis or septic shock. We used the Cochrane Risk of Bias table to assess the methodological quality of the included RCTs and the GRADE approach to evaluate the evidence certainty., Results: We included 20 RCTs (2124 participants). Evidence from low to very low certainty showed that vitamin C compared to placebo may reduce all-cause mortality up to 28 days (relative risk [RR] 0.60, 95% confidence interval (CI) 0.45 to 0.80, 4 RCTs, 335 participants). Considering the other comparisons (vitamin C alone or combined with thiamine and/or hydrocortisone, compared to placebo, standard care or hydrocortisone), there were a little to no difference or very uncertain evidence for adverse events, SOFA score, ICU length of stay, acute kidney injury, mechanical ventilation- and vasoactive drugs-free days up to 28 days., Conclusion: Further RCTs with higher methodological quality, an increased number of participants and assessing clinically relevant outcomes are needed to provide better decision-making guidance., Prospero Register: CRD42021251786., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to map and synthesize evidence on the adequacy of dietary calcium intake and dairy products in Brazilian preschoolers and schoolchildren., Data Source: Evidence searches were performed in the MEDLINE (via PubMed) and Latin American and Caribbean Health Sciences Literature (LILACS; via BVS) databases, with no restriction on date or language of publication. Experimental or observational studies that evaluated healthy Brazilian children between 2 and 12 incomplete years old were included., Data Synthesis: A total of 18 studies were included. Seven of 11 studies of 11 studies (63.6%) identified mean values of dietary calcium intake below the age recommendation, especially in schoolchildren, with the progression of the age group. Among preschoolers, studies with direct weighing of food showed higher mean values of dietary calcium ingested compared to those with dietary recall. Children attending public daycare centers on a part-time basis tended to have inadequate calcium intake. The consumption of milk and dairy products was lower among older children, especially schoolchildren., Conclusions: Inadequate dietary calcium intake seems to be prevalent in Brazil during childhood, especially among schoolchildren. Therefore, the evaluation of milk and dairy products intake must be considered in order to desgn appropriate corrective actions.

Objective: To identify, critically evaluate and synthesize the evidence obtained from systematic reviews on the association between genetic polymorphisms and osteoarthritis (OA) development., Methods: Considering gene polymorphisms associated with OA susceptibility (risk or protection), a comprehensive search was conducted in the following databases, without date or language restrictions: MEDLINE, via Pubmed; Embase, via Elsevier; Cochrane Database of Systematic Reviews, via Wiley; Biblioteca Virtual em Saúde. Gray literature was also searched through the OpenGrey database. The AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews) was used to assess the methodological quality of the included systematic reviews., Results: We included 14 systematic reviews of case-control studies comparing individuals with a radiographic diagnosis of all OA types and healthy controls, all submitted to the genetic examination of different polymorphisms in candidate genes. Meta-analyses showed a protective effect against knee and hand OA associated with GDF-5 gene (odds ratio [OR] 0.90, 95% confidence interval (CI) 0.85-0.95), and knee OA with ESRα gene (OR 0.63, 95% CI 1.26-1.97). SMAD3 gene was associated with knee and hip OA risk (OR 1.21. 95% CI 1.07-1.38) and MMP-1 gene was associated with temporomandibular OA (OR 1.58. 95% CI 1.26-1.97)., Conclusion: Based on low-quality to critically-low-quality systematic reviews, some gene polymorphisms seem to be associated with risk or protection for OA. Further high-quality studies are needed to validate these hypotheses, contribute to disease understanding, and possibly help the decision-making related to early diagnosis and treatment options for OA. PROSPERO register CRD42021234231., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

The aim of this study was to identify, systematically assess and summarise the available evidence about the efficacy and safety of intravenous home antibiotic therapy. In this systematic review, we considered studies of adults with any kind of infection and recommended intravenous antibiotic therapy. We included studies comparing therapy given at the patient's home versus any other setting (other levels of healthcare services or sites). We performed wide and sensitive literature searches with strategies adjusted for each of the electronic databases, including CINAHL, ClinicalTrials.gov, Cochrane Library, Embase, Epistemonikos, Health System Evidence, LILACS, MEDLINE and grey literature (OpenGrey). We used the Cochrane risk-of-bias and GRADE tools to evaluate the risk of bias and the certainty of evidence. At least two reviewers, working independently, selected the studies, extracted data and critically evaluated the evidence. We performed random-effects meta-analyses where possible. From 20 099 references initially identified, we included 6 randomised controlled trials (RCTs) with 616 participants. We considered the certainty of the body of evidence as low to very low regarding infection resolution after 6 weeks, risk of adverse events, mortality and clinical status. Based on six RCTs with considerable risk of bias, this systematic review found low or very low evidence about the advantages of intravenous antibiotic therapy at home. The imprecision of the results does not allow us to recommend or contraindicate the use of this strategy in clinical practice. [PROSPERO register: this review protocol was prospectively submitted at the PROSPERO register base at 31 January 2021 (submission no. 42021234454)]., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The purpose of this study was to evaluate the efficacy and safety of photobiomodulation as an adjuvant treatment for primary headache. A systematic review of randomized clinical trials was performed. For such, electronic searches were performed in the MEDLINE, Embase, Cochrane Library, LILACS, PEDro, PsycInfo, Clinicaltrials.gov., and WHO/ICTRP databases, with no restrictions imposed regarding language or year of publication. We included studies that assessed any photobiomodulation therapy as an adjuvant treatment for primary headache compared to sham treatment, no treatment, or another intervention. The methodological assessment was conducted using the Cochrane Risk of Bias tool. The certainty of the evidence was classified using the GRADE approach. Four randomized clinical trials were included. Most of the included studies had an overall high risk of bias. Compared to sham treatment, photobiomodulation had a clinically important effect on pain in individuals with primary headache. Despite the benefits reported for other outcomes, the estimates were imprecise, and the certainty of the evidence was graded as low. These findings are considered insufficient to support the use of photobiomodulation in the treatment of primary headache. Randomized clinical trials, with higher methodological quality, are needed to enhance the reliability of the estimated effects.

Background: To investigate the efficacy and safety of interventions for early stage pericoronitis., Methods: We searched for randomized controlled trials (RCTs) in databases from inception to July 2020, without language restriction. RCTs assessing adolescents and adults were included., Results: Seven RCT with clinical diversity were included, so, it was not possible to conduct meta-analyses. Individual study data showed an improvement in oral health quality of life in favor of topical benzydamine versus diclofenac capsule (Mean difference (MD) -1.10, 95% Confidence interval (CI) -1.85 to -0.35), and no difference between topical benzydamine and flurbiprofen capsule (MD -0.55 95% CI -1.18 to 0.0). There was no difference between diclofenac and flurbiprofen capsules (MD 0.55, 95% CI -0.29 to 1.39). An imprecise estimate of effects was found for all outcomes, considering (i) oral versus topic pharmacological treatment, (ii) different oral pharmacological treatments, (iii) pharmacological treatment associated with laser versus placebo laser, (iv) pharmacological treatment associated with different mouthwashes, and (v) conventional treatment associated to antimicrobial photodynamic therapy versus conventional treatment, with low to very low certainty of evidence., Conclusions: Until future well-designed studies can be conducted, the clinical decision for early stage pericoronitis should be guided by individual characteristics, settings and financial aspects.

Background: This systematic review aimed to assess the effectiveness and safety of aPDT for the treatment of halitosis., Methods: Search strategies were conducted in October 2021 without language or data restrictions, on the following databases: MEDLINE, EMBASE, CENTRAL, LILACS and BBO, as well as a manual search. Randomized clinical trials (RCTs) with parallel design were considered for inclusion, assessing individuals (adolescents and adults) with a clinical diagnosis of halitosis treated with photodynamic therapy (aPDT). Primary outcomes assessed were halitosis measurements, adverse events and quality of life. The risk of bias for each included study was evaluated with the Cochrane Risk of Bias tool and the certainty of the body of the evidence was assessed with the GRADe approach., Results: Six RCTs (total of 225 participants) were included and due to clinical diversities it was not possible to group the outcome data in meta-analyses. Based on very low-certainty evidence (GRADE) the results showed that, when compared to tongue scraper, aPDT seems to promote a little to no difference in reducing halitosis and in the microbiological analysis. No adverse events were reported. Considering aPDT combined with tongue scraper, better outcome results were observed when compared to tongue scraper alone., Conclusions: Based on very low-certainty evidence, the findings of this review are uncertain about the effects of aPDT for halitosis control. Further RCTs with higher number of participants and long term assessments need to be conducted to support the use of this intervention. The protocol was registered in the PROSPERO database (number: CRD42020215319) on 19 November 2020-retrospectively registered.

The debate on the use of cannabinoids for therapeutic purposes is constantly on the rise. This overview aimed to map the evidence on the therapeutic effects of cannabis derivatives and their synthetic analogs. Systematic reviews (SRs) of randomized trials were identified through a comprehensive search in several databases, and their methodological quality were evaluated with AMSTAR-2. The results for main outcomes are presented, prioritizing those from updated and better quality SRs. Finally, 68 SRs, addressing 37 different health conditions, were included. The methodological quality was high for eight SRs. The evidence certainty (GRADE) for the effects of cannabinoids is not high for any of the outcomes identified. Evidence certainty was moderate for the following: (a) cannabidiol appears to be beneficial for quality of life but increases the risk of adverse events in ulcerative colitis; (b) cannabinoids in general appear to have no clinically important benefit for chronic non-oncologic pain, spasticity-related pain in multiple sclerosis, or for acute post-operative pain; (c) cannabinoids in general appear to have a benefit in reducing chemotherapy-related nausea and vomiting. For all other outcomes from remaining comparisons, the evidence certainty was low, very low, or not evaluated, which prevents recommendations for or against their routine use., (© 2021 John Wiley & Sons Ltd.)

Introduction: Muscle disorders caused by cerebral palsy (CP) can affect oral function. The treatment for masticatory muscle spasticity is important to minimize muscle hyperactivity and preclude oral damages., Objectives: To evaluate the efficacy and safety of non-surgical interventions for the treatment of masticatory muscle spasticity in CP patients., Methods: A comprehensive search was performed in the following databases: MEDLINE, Embase, Cochrane Library, LILACS, BBO, PEDro, Clinicaltrials.gov and WHO/ICTRP, without date and language restrictions. Randomized controlled trials (RCT) evaluating non-surgical interventions were considered. Primary outcomes such as masticatory function and adverse events were planned to be assessed. The risk of bias assessment was performed using the Cochrane risk of bias tool. The certainty of the evidence was assessed using the GRADE approach., Results: Three RCT assessing the effects of botulinum toxin, functional masticatory training and neuromuscular electrostimulation (NMES) were included. Evidence with a very low certainty showed: (i) no difference between botulinum toxin and placebo regarding maximum chewing strength, chewing efficiency and global oral health scale; (ii) improvement in masticatory function in favor of functional masticatory training versus conventional exercises, and (iii) in favor of strengthening exercises plus NMES versus placebo., Conclusions: There was insufficient evidence to support the use of botulinum toxin and masticatory muscle strengthening programs alone and associated with NMES for the treatment of masticatory muscle in patients with PC. The clinical decision must be individualized, and further studies are needed to support or refute the use of different non-surgical interventions for PC. PROSPERO register number CRD42020209761., Competing Interests: Declarations of competing interest The author declare no conflicts of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: The purpose of this systematic review was to investigate and synthesize the effects (benefits and harms) of electrical stimulation (EE), alone or in association with other interventions, compared with sham and other interventions, for the treatment of neurogenic bladder dysfunction in myelomeningocele., Methods: This systematic review was conducted following the methodological recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and registered at PROSPERO (CRD42020200425). A search was performed in the following electronic databases: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, LILACS, and PEDro. Randomized clinical trials (RCTs) that assessed any EE in children diagnosed with myelomeningocele and neurogenic bladder and/or urinary incontinence were included and reported., Results: When comparing EE versus sham groups, some estimated effects showed a wide confidence interval, probably due to the small sample size of the included studies. This indicates an imprecision in these findings. Regarding the safety of this intervention and safety of the lower urinary tract, no adverse events resulting from EE were reported. All the included studies have evaluated the efficacy of EE compared with sham, but different EE parameters and electrode positions among studies make it impossible to perform a meta-analysis., Conclusions: Based on very low certainty evidence, the findings of this systematic review suggested no difference between EE and sham to improve urinary incontinence in children with myelomeningocele. However, the small sample size and the imprecision arising from the wide confidence intervals must be considered. Future RCTs following a rigorous methodology, as recommended by the CONSORT statement, should be conducted to support the use of this intervention in clinical practice., (© 2021 Wiley Periodicals LLC.)

Cochrane devolves most editorial governance of the Cochrane Database of Systematic Reviews (CDSR), including title prioritization, protocol registration, peer-review, editorial oversight and subsequent review deposition, to specific Cochrane Review Group (CRG) editorial boards. Current Cochrane policy stipulates authors of reviews who are also members of the supporting CRG declare this non-financial conflict of interest and confirm no involvement in the review editorial process. The aim of this cross-sectional analysis was to assess adherence to Cochrane's editorial conflict of interest policy. All 260 published Cochrane reviews (CR) in issues 1 to 6 from 2019 of the CDSR were reviewed. A total of 133 (51.2%, 133/260) of CRs had at least one author that was also listed as an editor in the CRG. Of these, only five (3.8%, 5/133) appropriately declared the conflict according to Cochrane policy. In 6.5% (17/133) CRs, the contact author had a leading editorial position within the CRG and in only four of 17 was this declared according to Cochrane policy. No CR with the contact author who also had a leading editorial position described methods to prevent any potential issues related to this scenario during the editorial process in accordance with Cochrane policy. We propose a specific form to improve the transparency and reliability of editorial conflict of interest reporting in CRs. The suggested form can be adapted to other contexts., (© 2021 John Wiley & Sons Ltd.)

Type 2 Diabetes Mellitus (DM) is the most common form of diabetes. The initial treatment of type 2 DM consists of the adoption of healthy lifestyle habits together with several classes of hypoglycemic agents. However, these medications are not always able to reduce the blood glucose levels in all patients. Therefore, creatine supplementation has emerged as a new putative candidate for type 2 DM treatment. This systematic review aimed to investigate the effects (benefits and harms) of creatine supplementation in patients with type 2 diabetes through a systematic review. The studies were searched in MEDLINE, EMBASE, LILACS, CENTRAL, SPORTDiscus, and CINAHL databases, without date or language restrictions. Methodological quality was assessed using the Cochrane risk-of-bias table. The certainty of the evidence was classified using the Grading of Recommendations Assessment, Development and Evaluation approach. Three randomized controlled trials (RCTs) were included (87 participants). Overall, the methodological quality was classified as unclear to a high risk of bias. Each trial compared creatine supplementation with a different control group (placebo, metformin, and glibenclamide). Creatine supplementation seems to be effective in decreasing glycemic levels and glycosylated hemoglobin concentrations compared to placebo. No difference was observed compared to metformin or glibenclamide with creatine, and all treatments were able to reduce blood glucose levels. No major adverse effects were observed. Based on the low certainty of evidence, creatine supplementation was shown to be a hypoglycemic intervention for patients with type 2 diabetes, without major adverse events reported. However, well- designed RCTs with larger sample sizes and long-term outcomes are needed to support this evidence., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To investigate the frequency and perform a qualitative analysis of spin bias in publications of controlled trials assessing the therapeutic use of cannabis derivatives and their synthetic analogues., Study Design and Setting: Meta-epidemiologic study carried out at the Universidade Federal de São Paulo, Brazil., Results: A total of 65 publications with at least one efficacy primary outcome were considered. The results analysis for the primary outcome indicated statistically significant effects in 44.6% (29/65) of the publications, and 70.7% (45/65) of the conclusions were considered favorable to the intervention. Among the 36 publications that found statistically nonsignificant results for the primary outcome, 44.4% (16/36) presented conclusions favorable to or recommending the intervention, which represents spin bias according to the definition adopted in this study. Qualitative analysis of the 16 studies with spin bias showed selective outcomes reporting (elevating secondary outcomes that had positive results or reporting only subgroup results), deviations from the planned statistical analysis, and failure to consider or report uncertainty in the estimates of treatment effects., Conclusion: The frequency of spin bias among publications of controlled trials with statistically nonsignificant results assessing the therapeutic use of cannabis derivatives and their synthetic analogues reached 44.4%. When not observed by readers, such deviation can lead to misconduct in clinical practice through the adoption of interventions that are not effective or whose effectiveness is uncertain., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Ankyloglossia (tongue-tie) is an anomaly characterised by an abnormally short, thick or small lingual frenulum that restricts tongue movements. This condition is considered one of the factors that can interfere with breast feeding by diminishing the ability of the newborn to latch adequately. According to the Brazilian Health Ministry, the prevalence of this anomaly among newborns is 3%-16%. Frenectomy is the most suitable surgical procedure for the treatment of ankyloglossia. The aim of this study is to compare the performance of electrocautery and high-power diode laser as forms of frenectomy., Methods and Analysis: The proposed study will be a randomised, controlled, blind clinical trial involving the participation of healthy infants 0-3 months of age with breastfeeding difficulty and a diagnosis of tongue-tie with an indication for lingual frenectomy. The guardians will receive clarifications regarding the procedures and will authorise the participation of the infants by signing a statement of informed consent. A non-blinded researcher will perform the screening and procedures and a blinded researcher will perform the postoperative evaluations. Fifty-six infants will be randomly allocated into two groups (n=28): the electrocautery group or the high-power laser group. The preparation of the patients, asepsis and infection control procedures will rigorously follow biosafety norms. For both groups, patient histories will be taken, clinical evaluations will be performed and a standardised photograph of the lingual frenulum will be taken before surgery. The Bristol Tongue Assessment Tool will be used. We will evaluate pain in the mother during breast feeding before, immediately after, and 15 days after surgery., Ethics and Dissemination: This protocol was submitted to the Research Ethics Committee of Nove de Julho University, having been given a favourable opinion (Number: 4387769). Results will be submitted to international peer-reviewed journals and presented at international conferences., Trial Registration Number: NCT04487418., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The development of severe coronavirus disease 2019 (COVID-19) and poor clinical outcomes are associated with hyperinflammation and a complex dysregulation of the immune response. Colchicine is an anti-inflammatory medicine and is thought to improve disease outcomes in COVID-19 through a wide range of anti-inflammatory mechanisms. Patients and healthcare systems need more and better treatment options for COVID-19 and a thorough understanding of the current body of evidence., Objectives: To assess the effectiveness and safety of Colchicine as a treatment option for COVID-19 in comparison to an active comparator, placebo, or standard care alone in any setting, and to maintain the currency of the evidence, using a living systematic review approach., Search Methods: We searched the Cochrane COVID-19 Study Register (comprising CENTRAL, MEDLINE (PubMed), Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv), Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index), and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 21 May 2021., Selection Criteria: We included randomised controlled trials evaluating colchicine for the treatment of people with COVID-19, irrespective of disease severity, age, sex, or ethnicity. We excluded studies investigating the prophylactic effects of colchicine for people without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but at high risk of SARS-CoV-2 exposure., Data Collection and Analysis: We followed standard Cochrane methodology. We used the Cochrane risk of bias tool (ROB 2) to assess bias in included studies and GRADE to rate the certainty of evidence for the following prioritised outcome categories considering people with moderate or severe COVID-19: all-cause mortality, worsening and improvement of clinical status, quality of life, adverse events, and serious adverse events and for people with asymptomatic infection or mild disease: all-cause mortality, admission to hospital or death, symptom resolution, duration to symptom resolution, quality of life, adverse events, serious adverse events., Main Results: We included three RCTs with 11,525 hospitalised participants (8002 male) and one RCT with 4488 (2067 male) non-hospitalised participants. Mean age of people treated in hospital was about 64 years, and was 55 years in the study with non-hospitalised participants. Further, we identified 17 ongoing studies and 11 studies completed or terminated, but without published results. Colchicine plus standard care versus standard care (plus/minus placebo) Treatment of hospitalised people with moderate to severe COVID-19 All-cause mortality: colchicine plus standard care probably results in little to no difference in all-cause mortality up to 28 days compared to standard care alone (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.93 to 1.08; 2 RCTs, 11,445 participants; moderate-certainty evidence). Worsening of clinical status: colchicine plus standard care probably results in little to no difference in worsening of clinical status assessed as new need for invasive mechanical ventilation or death compared to standard care alone (RR 1.02, 95% CI 0.96 to 1.09; 2 RCTs, 10,916 participants; moderate-certainty evidence). Improvement of clinical status: colchicine plus standard care probably results in little to no difference in improvement of clinical status, assessed as number of participants discharged alive up to day 28 without clinical deterioration or death compared to standard care alone (RR 0.99, 95% CI 0.96 to 1.01; 1 RCT, 11,340 participants; moderate-certainty evidence). Quality of life, including fatigue and neurological status: we identified no studies reporting this outcome. Adverse events: the evidence is very uncertain about the effect of colchicine on adverse events compared to placebo (RR 1.00, 95% CI 0.56 to 1.78; 1 RCT, 72 participants; very low-certainty evidence). Serious adverse events: the evidence is very uncertain about the effect of colchicine plus standard care on serious adverse events compared to standard care alone (0 events observed in 1 RCT of 105 participants; very low-certainty evidence). Treatment of non-hospitalised people with asymptomatic SARS-CoV-2 infection or mild COVID-19 All-cause mortality: the evidence is uncertain about the effect of colchicine on all-cause mortality at 28 days (Peto odds ratio (OR) 0.57, 95% CI 0.20 to 1.62; 1 RCT, 4488 participants; low-certainty evidence). Admission to hospital or death within 28 days: colchicine probably slightly reduces the need for hospitalisation or death within 28 days compared to placebo (RR 0.80, 95% CI 0.62 to 1.03; 1 RCT, 4488 participants; moderate-certainty evidence). Symptom resolution: we identified no studies reporting this outcome. Quality of life, including fatigue and neurological status: we identified no studies reporting this outcome. Adverse events: the evidence is uncertain about the effect of colchicine on adverse events compared to placebo . Results are from one RCT reporting treatment-related events only in 4412 participants (low-certainty evidence). Serious adverse events: colchicine probably slightly reduces serious adverse events (RR 0.78, 95% CI 0.61 to 1.00; 1 RCT, 4412 participants; moderate-certainty evidence). Colchicine versus another active treatment (e.g. corticosteroids, anti-viral drugs, monoclonal antibodies) No studies evaluated this comparison. Different formulations, doses, or schedules of colchicine No studies assessed this., Authors' Conclusions: Based on the current evidence, in people hospitalised with moderate to severe COVID-19 the use of colchicine probably has little to no influence on mortality or clinical progression in comparison to placebo or standard care alone. We do not know whether colchicine increases the risk of (serious) adverse events. We are uncertain about the evidence of the effect of colchicine on all-cause mortality for people with asymptomatic infection or mild disease. However, colchicine probably results in a slight reduction of hospital admissions or deaths within 28 days, and the rate of serious adverse events compared with placebo. None of the studies reported data on quality of life or compared the benefits and harms of colchicine versus other drugs, or different dosages of colchicine. We identified 17 ongoing and 11 completed but not published RCTs, which we expect to incorporate in future versions of this review as their results become available. Editorial note: due to the living approach of this work, we monitor newly published results of RCTs on colchicine on a weekly basis and will update the review when the evidence or our certainty in the evidence changes., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Attention deficit hyperactivity disorder (ADHD) is one of the most frequent childhood psychiatric problems., Objective: The objective of this study was to identify, synthesize the results, and critically evaluate all Cochrane systematic reviews (SRs) on the pharmacological interventions for children and adolescents (up to age 18) diagnosed with ADHD., Methods: The search was performed in the Cochrane Database of Systematic Reviews (via Wiley) in July 2020., Results: The search strategy resulted in four SRs of high methodological quality, analyzing 51 randomized clinical trials (9,013 participants). Compared to placebo, treatment with tricyclic antidepressants (TCAs) (desipramine), amphetamine, and methylphenidate showed improvement in symptoms such as difficulty concentrating, impulsivity, and hyperactivity in the short term (up to 6 months). There was an increase in the occurrence of adverse events, such as reduced appetite, difficulty sleeping, and abdominal pain. Insufficient evidence was found to support the effects of supplementation with polyunsaturated fatty acids., Conclusions: The use of TCAs, amphetamine, and methylphenidate in children and adolescents with ADHD seems to present positive effects and higher rates of minor adverse events when compared to placebo., Competing Interests: Disclosure: The authors report no conflicts of interest.

Objectives: Assess the effects of different routes of prophylactic oxytocin administration for preventing blood loss at caesarean section (CS)., Design: Systematic review and meta-analysis., Methods: Medline, EMBASE, CINAHL, Cochrane Library, BVS, SciELO and Global Index Medicus were searched through 24 May 2020 for randomised controlled trials (RCTs) comparing different routes of prophylactic oxytocin administration during CS. Study selection, data extraction and quality assessment were conducted by two investigators independently. We pooled results in fixed effects meta-analyses and calculated average risk ratio (RR), mean difference (MD) and 95% CI. We used GRADE to assess the overall quality of evidence for each outcome., Results: Three trials (180 women) were included in the review. All studies compared intramyometrial (IMY) versus intravenous oxytocin in women having prelabour CS. IMY compared with intravenous oxytocin administration may result in little or no difference in the incidence of postpartum haemorrhage (RR 0.14, 95% CI 0.01 to 2.70; N=100 participants; 1 RCT), hypotension (RR 1.00, 95% CI 0.29 to 3.45; N=40; 1 RCT), headache (RR 3.00, 95% CI 0.13 to 69.52; N=40; 1 RCT) or facial flushing (RR 0.50, 95% CI 0.05 to 5.08; N=40; 1 RCT); IMY oxytocin may reduce nausea/vomiting (RR 0.13, 95% CI 0.02 to 0.69; N=140; 2 RCTs). We are very uncertain about the effect IMY versus intravenous oxytocin on the need for additional uterotonics (RR 0.82; 95% CI 0.25 to 2.69; N=140; 2 RCTs). IMY oxytocin may reduce blood loss slightly (MD -57.40 mL, 95% CI -101.71 to -13.09; N=40; 1 RCT)., Conclusions: There is limited, low to very low certainty evidence on the effects of IMY versus intravenous oxytocin at CS for preventing blood loss. The evidence is insufficient to support choosing one route over another. More trials, including studies that assess intramuscular oxytocin administration, are needed on this relevant question., Prospero Registration Number: CRD42020186797., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Numerous systematic reviews on coronavirus disease-19 (COVID-19) treatment have been developed to provide syntheses of the large volume of primary studies. However, the methodological quality of most of these reviews is questionable and the results provided may therefore present bias., Objective: To investigate how many systematic reviews on the therapeutic or preventive options for COVID-19 assessed the certainty of the evidence through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Methods: We conducted a sensitive search in MEDLINE (via PubMed) and included all systematic reviews that assessed any intervention for COVID-19. The systematic reviews included were examined to identify any planned and/or actual assessment using the GRADE approach (or absence thereof) regarding the certainty of the evidence., Results: We included 177 systematic reviews and found that only 37 (21%; 37/177) assessed and reported the certainty of the evidence using the GRADE approach. This number reduced to 27 (16.2%; 27/167) when Cochrane reviews (n = 10), in which an evaluation using GRADE is mandatory, were excluded., Conclusion: Most of the systematic reviews on interventions relating to COVID-19 omitted assessment of the certainty of the evidence. This is a critical methodological omission that must not be overlooked in further research, so as to improve the impact and usefulness of syntheses relating to COVID-19.

Context: Caffeine is 1 of the most popular supplements consumed by athletes, and the evidence for improving soccer performance remains limited., Objective: To investigate and update the effects (benefits and harms) of caffeine to improve performance on soccer players., Data Sources: Electronic search in Medline (via PubMed), CENTRAL, Embase, SPORTDiscus, and LILACS, from inception to March 28, 2020., Study Selection: Randomized clinical trials (RCTs) assessing the effects of caffeine on the performance of soccer players., Study Design: Systematic review with meta-analysis., Level of Evidence: Level 1., Data Extraction: Data extraction was conducted independently by 2 authors using a piloted form. We assessed methodological quality (Cochrane risk-of-bias [RoB] table) and the certainty of the evidence (GRADE [Grading of Recommendations Assessment, Development and Evaluation] approach)., Results: Sixteen RCTs were included. Overall methodological quality was classified as unclear to low risk of bias. When assessing aerobic endurance, meta-analyses did not demonstrate the differences between caffeine and placebo (mean difference [MD], 44.9 m; 95% confidence interval [CI], -77.7 to 167.6). Similarly, no difference was observed during time to fatigue test (MD, 169.8 seconds; 95% CI, -71.8 to 411.6). Considering anaerobic power, meta-analyses also did not find differences for vertical jump (MD, 1.01 cm; 95% CI, -0.68 to 2.69) and repeated sprint tests (MD, -0.02 seconds; 95% CI, -0.09 to 0.04), as well as reaction time agility test (MD, 0.02 seconds; 95% CI, -0.01 to 0.04) and rating of perceived exertion (MD, 0.16 points; 95% CI, -0.55 to 0.87). Regarding safety, a few minor adverse events were reported. Based on the GRADE approach, the certainty of this evidence was classified as very low to low., Conclusion: We found no significant improvement in soccer-related performance with caffeine compared with placebo or no intervention. However, caffeine appears to be safe.

Introduction: Patients with Parkinson's disease (PD) present a variety of oral disease that can be worsened by xerostomia and sialorrhea. The patients' physical limitations, for example rigidity and tremor, add to the difficulty of oral care by the general dental surgeon. The objective of the present review was to organize a list of evidence-based recommendations for the oral care of patients with PD., Methods: A systematic review of the literature was carried out by specialists who selected the relevant papers and created a list of recommendations based upon the literature., Results: Fourteen papers (data reported in 16 articles) were included in this review. Patients with PD had reduced quality of oral health and hygiene, and high prevalence of gingival recession, periodontal disease, dental calculus, tooth decay, tooth mobility and loss, drooling, xerostomia, dysphagia and temporomandibular disorders. Most studies offered class IV evidence, while one paper had class II evidence., Conclusion: Patients with PD present poor oral health with conditions that are mostly preventable.

Background and Objectives: It is well established that tumor-free margin is an important factor for reducing local recurrence and reoperation rates. This systematic review with meta-analysis of frozen section intraoperative margin assessment aims to evaluate the accuracy, and reoperation and survival rates, and to establish its importance in breast-conserving surgery., Methods: A thorough review was conducted in all online publication-databases for the related literature up to March 2020. MeSH terms used: "Breast Cancer", "Segmental Mastectomy" and "Frozen Section". We included the studies that evaluated accuracy of frozen section, reoperation and survival rates. To ensure quality of the included articles, the QUADAS-2 tool (adapted) was employed. The assessment of publication bias by graphical and statistical methods was performed using the funnel plot and the Egger's test. The review protocol was registered in PROSPERO (CRD42019125682)., Results: Nineteen studies were deemed suitable, with a total of 6,769 cases. The reoperation rate on average was 5.9%. Sensitivity was 0.81, with a Confidence Interval of 0.79-0.83, p = 0.0000, I2 = 95.1%, and specificity was 0.97, with a Confidence Interval of 0.97-0.98, p = 0.0000, I-2 = 90.8%, for 17 studies and 5,615 cases. Accuracy was 0.98. Twelve studies described local recurrence and the highest cumulative recurrence rate in 3 years was 7.5%. The quality of the included studies based on the QUADAS-2 tool showed a low risk of bias. There is no publication bias (p = 0.32) and the funnel plot showed symmetry., Conclusion: Frozen section is a reliable procedure with high accuracy, sensitivity and specificity in intraoperative margin assessment of breast-conserving surgery. Therefore, this modality of margin assessment could be useful in reducing reoperation rates., Competing Interests: No authors have competing interests.

A review of systematic reviews (SRs) and a critical appraisal study was conducted at Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp). The objectives of this review are (1) to identify all published SRs comparing the effectiveness and safety of carotid endarterectomy (CEA) versus carotid artery stenting (CAS) for carotid artery stenosis, (2) to assess their methodological quality and (3) to compare the primary studies contained in each SR. We included 17 SRs published between 2005 and 2017. None of the SRs fulfilled all items of AMSTAR-2. The overall confidence in the results was graded as critically low for 16 SRs (94%) and low for 1 SR (6%). Five items were judged inadequate in all SRs: reference to a published protocol, explanation to the selection of study design, comprehensive search of the literature, methods for statistical combination of findings and consideration of the risk of bias on the results of meta-analysis. In total, 15 randomised clinical trials (RCTs) were included at least in one SR. The number of included RCTs in each SR was inconsistent (4 to 15) and was not related to the year of publication of the SR. Our study found redundant and low methodological quality SR comparing CAS versus CEA for carotid stenosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Delays and disruptions in health systems because of the COVID-19 pandemic were identified by a previous systematic review from our group. For improving the knowledge about the pandemic consequences for cancer care, this article aims to identify the effects of mitigation strategies developed to reduce the impact of such delays and disruptions., Methods: Systematic review with a comprehensive search including formal databases, cancer and COVID-19 data sources, gray literature, and manual search. We considered clinical trials, observational longitudinal studies, cross-sectional studies, before-and-after studies, case series, and case studies. The selection, data extraction, and methodological assessment were performed by two independent reviewers. The methodological quality of the included studies was assessed by specific tools. The mitigation strategies identified were described in detail and their effects were summarized narratively., Results: Of 6,692 references reviewed, 28 were deemed eligible, and 9 studies with low to moderate methodological quality were included. Five multiple strategies and four single strategies were reported, and the possible effects of mitigating delays and disruptions in cancer care because of COVID-19 are inconsistent. The only comparative study reported a 48.7% reduction observed in the number of outpatient visits to the hospital accompanied by a small reduction in imaging and an improvement in radiation treatments after the implementation of a multiple organizational strategy., Conclusion: The findings emphasize the infrequency of measuring and reporting mitigation strategies that specifically address patients' outcomes and thus a scarcity of high-quality evidence to inform program development. This review reinforces the need of adopting standardized measurement methods to monitor the impact of the mitigation strategies proposed to reduce the effects of delays and disruptions in cancer health care because of COVID-19.