ABSTRACT BACKGROUND: Radiation therapy (RT) is a standard treatment for non-metastatic breast cancer and is associated with acute and late toxicities. Intensity-modulated RT (IMRT) may decrease toxicity and is convenient for patients. OBJECTIVES: To assess the efficacy and safety of IMRT in women with early stage breast cancer. DESIGN AND SETTING: Systematic review study; Multi-institutional centers. METHODS: Seven databases were searched. Randomized controlled trials (RCT) comparing IMRT with any “non-IMRT” strategies were included. Primary outcomes were local control and acute toxicity. Cochrane Handbook was use to plan and conduct the review, and PRISMA 2020 was used to report results. RESULTS: Five RCT involving 2,556 women (n = 1,283 IMRT; n = 1,274 control arm) were included. Baseline characteristics were similar between trials and arms. Local relapse-free survival rates were not different (hazard-ratio [HR] 0.62; 95%confidence interval [CI] -0.38 to 1.62; P > 0.05); however, IMRT reduced the overall acute toxicity (RR 0.69, 95%CI 0.58 to 0.82; P < 0.00001) and acute moist desquamation (risk-ratio [RR] 0.71, 95%CI 0.60 to 0.82; P < 0.00001). Lymphedema and pneumonitis rates, and survival outcomes were not affected by IMRT. The 2-year telangiectasia rate was decreased with IMRT (RR 0.66, 95%CI 0.47 to 0.93; P = 0.02); however, edema, pain, pigmentation, or fibrosis remained unaffected. IMRT did not improve cosmesis. CONCLUSIONS: IMRT improved acute toxicity and lowered telangiectasia rates, without affecting oncological and aesthetic outcomes. SYSTEMATIC REVIEW REGISTRATION: This review was registered at Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD010420. https://doi.org/10.1002/14651858.CD010420. BACKGROUND (RT nonmetastatic non metastatic toxicities Intensitymodulated Intensity modulated (IMRT patients OBJECTIVES SETTING study Multiinstitutional Multi institutional centers METHODS searched (RCT nonIMRT “non-IMRT included 202 results RESULTS 2556 2 556 2,55 1283 1 283 1,28 1274 274 1,27 arm arms relapsefree relapse free hazardratio hazard ratio HR [HR 0.62 062 0 62 95confidence confidence 95 CI [CI 0.38 038 38 -0.3 1.62 162 0.05 005 05 0.05) however RR 069 69 0.69 95CI 058 58 0.5 0.82 082 82 0.00001 000001 00001 riskratio risk [RR 071 71 0.71 060 60 0.6 0.00001. . 2year year 066 66 0.66 047 47 0.4 0.93 093 93 0.02 002 02 0.02) edema pain pigmentation unaffected cosmesis CONCLUSIONS REGISTRATION 2013 3 Art No. No CD010420 CD https//doi.org/10.1002/14651858.CD010420. httpsdoiorg10100214651858CD010420 httpsdoiorgCD https //doi.org/10.1002/14651858.CD010420. doi org 10 1002 14651858 https://doi.org/10.1002/14651858.CD010420 20 255 55 2,5 128 28 1,2 127 27 06 6 9 0.3 03 -0. 1.6 16 0.0 00 5 0. 0.8 08 8 0.0000 00000 0000 07 7 0.7 04 4 0.9 09 201 CD01042 https//doi.org/10.1002/14651858.CD010420 httpsdoiorg httpsdoiorg10100214651858CD01042 doiorg10100214651858CD010420 doiorgCD //doi.org/10.1002/14651858.CD010420 100 1465185 https://doi.org/10.1002/14651858.CD01042 25 2, 12 1, -0 1. 0.000 000 CD0104 https//doi.org/10.1002/14651858.CD01042 httpsdoiorg10100214651858CD0104 doiorg doiorg10100214651858CD01042 //doi.org/10.1002/14651858.CD01042 146518 https://doi.org/10.1002/14651858.CD0104 - 0.00 CD010 https//doi.org/10.1002/14651858.CD0104 httpsdoiorg10100214651858CD010 doiorg10100214651858CD0104 //doi.org/10.1002/14651858.CD0104 14651 https://doi.org/10.1002/14651858.CD010 CD01 https//doi.org/10.1002/14651858.CD010 httpsdoiorg10100214651858CD01 doiorg10100214651858CD010 //doi.org/10.1002/14651858.CD010 1465 https://doi.org/10.1002/14651858.CD01 CD0 https//doi.org/10.1002/14651858.CD01 httpsdoiorg10100214651858CD0 doiorg10100214651858CD01 //doi.org/10.1002/14651858.CD01 146 https://doi.org/10.1002/14651858.CD0 https//doi.org/10.1002/14651858.CD0 httpsdoiorg10100214651858CD doiorg10100214651858CD0 //doi.org/10.1002/14651858.CD0 14 https://doi.org/10.1002/14651858.CD https//doi.org/10.1002/14651858.CD doiorg10100214651858CD //doi.org/10.1002/14651858.CD

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

SUMMARY 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 METHODS metaresearch meta research RESULTS 8 considered Notably 793 79 3 79.3 65/82 6582 65 (65/82 707 70 7 70.7 58/82. 5882 58/82 . 58 (58/82) 785 78 5 78.5 51/65 5165 51 (51/65 drugfavorable 308 30 30.8 20/65 2065 20 (20/65 95 19/20 1920 19 (19/20 688 68 68.8 11/16 1116 11 16 (11/16 188 18 18.8 3/16 316 (3/16 667 66 66.7 2/3 23 2 (2/3 81.0% 810 81 0 (81.0% 47/58, 4758 47/58 , 47 47/58) 63.3% 633 63 (63.3% 14/22. 1422 14/22 14 22 14/22) 134 13 4 13.4 11/82 1182 (11/82 374 37 37.4 31/82 3182 31 (31/82 CONCLUSIONS common conclusion 79. 65/8 658 6 (65/8 70. 588 58/8 (58/82 78. 51/6 516 (51/6 30. 20/6 206 (20/6 9 19/2 192 1 (19/2 68. 11/1 111 (11/1 18. 3/1 (3/1 66. 2/ (2/ 81.0 (81.0 475 47/5 63.3 (63.3 142 14/2 13. 11/8 118 (11/8 37. 31/8 318 (31/8 65/ (65/ 58/ (58/8 51/ (51/ 20/ (20/ 19/ (19/ 11/ (11/ 3/ (3/ (2 81. (81. 47/ 63. (63. 14/ 31/ (31/ (65 (58/ (51 (20 (19 (11 (3 ( (81 (63 (31 (6 (58 (5 (1 (8

SUMMARY OBJECTIVE: The aim of this study was to identify the frequency of Cochrane systematic reviews and Cochrane systematic reviews protocols using (or planning to use) the risk of bias 2.0 tool to assess the risk of bias of the included randomized clinical trials. STUDY DESIGN: This is a meta-research study. METHODS: We included Cochrane systematic reviews or Cochrane systematic reviews protocols that planned to include randomized clinical trials. We assessed the Cochrane Database of Systematic Reviews and screened for issues published after the launch of risk of bias 2.0 tool (2019–2022). Two independent investigators performed the study selection and data extraction. RESULTS: We analyzed 440 Cochrane systematic reviews and 536 Cochrane systematic reviews protocols. Overall, 4.8% of the Cochrane systematic reviews and 28.5% of the Cochrane systematic reviews protocols used or planned to use risk of bias 2.0 tool. Although low, adherence is increasing over time. In 2019, 0% of Cochrane systematic reviews used risk of bias 2.0 tool, compared to 24.1% in 2022. In Cochrane systematic reviews protocols, adherence increased from 6.9% in 2019 to 41.5% in 2022. A total of 274 (62.1%) Cochrane systematic reviews had their protocols published before 2018; only one used risk of bias 2.0 tool and reported the change of versions in the “Differences between protocol and revision” section. CONCLUSION: The Cochrane's risk of bias 2.0 tool has low adherence among Cochrane protocols and systematic reviews. Further efforts are necessary to facilitate the implementation of this new tool. OBJECTIVE 20 2 0 2. trials DESIGN metaresearch meta research METHODS 2019–2022. 20192022 2019–2022 . 2022 (2019–2022) extraction RESULTS 44 53 Overall 48 4 8 4.8 285 28 5 28.5 time 241 24 1 24.1 69 6 9 6.9 201 415 41 41.5 27 62.1% 621 62 (62.1% 2018 Differences revision section CONCLUSION Cochranes s 2019202 2019–202 202 (2019–2022 4. 28. 24. 6. 41. 62.1 (62.1 201920 2019–20 (2019–202 62. (62. 20192 2019–2 (2019–20 (62 2019– (2019–2 (6 (2019– ( (2019 (201 (20 (2

ABSTRACT BACKGROUND: Imaging tests are important for diagnosis during the management of pulmonary nodules; however, biopsy is required to confirm the malignancy. OBJECTIVES: To compare the effects of different techniques used for the biopsy of a pulmonary nodule. DESIGN AND SETTING: Systematic review and meta-analysis were conducted using Cochrane methodology in São Paulo, São Paulo, Brazil. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) on minimally invasive techniques, including tomography-guided percutaneous biopsy (PERCUT), transbronchial biopsies with fluoroscopy (FLUOR), endobronchial ultrasound (EBUSR), and electromagnetic navigation (NAVIG). The primary outcomes were diagnostic yield, major adverse events, and need for another approach. RESULTS: Seven RCTs were included (913 participants; 39.2% female, mean age: 59.28 years). Little to no increase was observed in PERCUT over FLUOR (P = 0.84), PERCUT over EBUSR (P = 0.32), and EBUSR over NAVIG (P = 0.17), whereas a slight increase was observed in NAVIG over FLUOR (P = 0.17); however, the evidence was uncertain. EBUSR may increase the diagnostic yield over FLUOR (P = 0.34). PERCUT showed little to no increase in all bronchoscopic techniques, with uncertain evidence (P = 0.02). CONCLUSION: No biopsy method is definitively superior to others. The preferred approach must consider availability, accessibility, and cost, as safety and diagnostic yield do not differ. Further RCTs planned, conducted, and reported with methodological rigor and transparency are needed, and additional studies should assess cost and the correlation between nodule size and location, as well as their association with biopsy results. SYSTEMATIC REVIEW REGISTRATION: PROSPERO database, CRD42018092367 -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=92367. BACKGROUND nodules however malignancy OBJECTIVES SETTING metaanalysis meta analysis Paulo Brazil METHODS (RCTs tomographyguided tomography guided PERCUT, , (PERCUT) FLUOR, (FLUOR) EBUSR, (EBUSR) NAVIG. . (NAVIG) events RESULTS 913 (91 participants 392 39 2 39.2 female age 5928 59 28 59.2 years. years years) P 0.84, 084 0.84 0 84 0.84) 0.32, 032 0.32 32 0.32) 0.17, 017 0.17 17 0.17) 0.34. 034 0.34 34 0.34) 0.02. 002 0.02 02 0.02) CONCLUSION others availability accessibility differ planned needed location results REGISTRATION database CRD CRD4201809236 https//www.crd.york.ac.uk/PROSPERO/display_record.phpRecordID=92367. httpswwwcrdyorkacukPROSPEROdisplayrecordphpRecordID92367 httpswwwcrdyorkacukPROSPEROdisplayrecordphpRecordID https //www.crd.york.ac.uk/PROSPERO/display_record.php RecordID=92367. www crd york ac uk display record php RecordID 92367 -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=92367 (PERCUT (FLUOR (EBUSR (NAVIG 91 (9 3 39. 592 5 59. 08 0.8 8 03 0.3 01 0.1 1 00 0.0 CRD420180923 phpRecordID https//www.crd.york.ac.uk/PROSPERO/display_record.phpRecordID=92367 httpswwwcrdyorkacukPROSPEROdisplayrecordphpRecordID9236 wwwcrdyorkacukPROSPEROdisplayrecordphp RecordID92367 RecordID=92367 9236 -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=9236 9 ( 0. CRD42018092 https//www.crd.york.ac.uk/PROSPERO/display_record.phpRecordID=9236 httpswwwcrdyorkacukPROSPEROdisplayrecordphpRecordID923 RecordID9236 RecordID=9236 923 -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=923 CRD4201809 https//www.crd.york.ac.uk/PROSPERO/display_record.phpRecordID=923 httpswwwcrdyorkacukPROSPEROdisplayrecordphpRecordID92 RecordID923 RecordID=923 92 -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=92 CRD420180 https//www.crd.york.ac.uk/PROSPERO/display_record.phpRecordID=92 httpswwwcrdyorkacukPROSPEROdisplayrecordphpRecordID9 RecordID92 RecordID=92 -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=9 CRD42018 https//www.crd.york.ac.uk/PROSPERO/display_record.phpRecordID=9 RecordID9 RecordID=9 -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID= CRD4201 https//www.crd.york.ac.uk/PROSPERO/display_record.phpRecordID= RecordID= -https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID CRD420 https//www.crd.york.ac.uk/PROSPERO/display_record.phpRecordID CRD42 CRD4

Health professionals are encouraged to attend a residency period of two to seven years after graduating. The typical demands of this in-service training modality have been associated with reduced sleep quality, decreased exercise frequency, and detachment from family and social relationships, leading to an increased diagnosis of anxiety, depression, and burnout syndrome. Therefore, conducting a scoping review to identify strategies aimed at promoting mental health and wellbeing among residents from different health areas is essential to support any forthcoming preventive action.

Resumo O encaminhamento de casos da atenção primária para a secundária no Sistema Único Brasileiro é uma das questões mais importantes a ser enfrentada. As estratégias de telessaúde têm se mostrado eficazes para evitar encaminhamentos desnecessários. O objetivo deste estudo foi estimar o custo por caso encaminhado por meio de um sistema de gerenciamento de referenciamentos operado remotamente para subsidiar a tomada de decisão sobre o tema. Análise de custo por meio da aplicação de custeio baseado em atividades orientado pelo tempo (time-driven activity-based costing ou TDABC). As análises de custo incluíram comparações entre especialidades médicas, localidades para as quais os encaminhamentos estavam sendo conduzidos e períodos de tempo. O custo por referenciamento em todas as localidades variou entre R$ 5,70 a R$ 8,29. O custo por referenciamento nas especialidades médicas variou entre R$ 1,85 a R$ 8,56. Estratégias para otimizar a gestão dos referenciamentos para a atenção especializada nos sistemas públicos de saúde ainda são necessárias. As estratégias de telessaúde podem ser vantajosas, com estimativas de custo entre as localidades variando entre R$ 5,70 a R$ 8,29, com variabilidade adicional observada relacionada ao tipo de especialidade médica.

Abstract Referral of cases from primary to secondary care in the Brazilian public healthcare system is one of the most important issues to be tackled. Telehealth strategies have been shown effective in avoiding unnecessary referrals. The objective of this study was to estimate cost per referred case by a remotely operated referral management system to further inform the decision making on the topic. Analysis of cost by applying time-driven activity-based costing. Cost analyses included comparisons between medical specialties, localities for which referrals were being conducted, and periods of time. Cost per referred case across localities ranged from R$ 5.70 to R$ 8.29. Cost per referred case across medical specialties ranged from R$ 1.85 to R$ 8.56. Strategies to optimize the management of referral cases to specialized care in public healthcare systems are still needed. Telehealth strategies may be advantageous, with cost estimates across localities ranging from R$ 5.70 to R$ 8.29, with additional observed variability related to the type of medical specialty.

Resumo O encaminhamento de casos da atenção primária para a secundária no Sistema Único Brasileiro é uma das questões mais importantes a ser enfrentada. As estratégias de telessaúde têm se mostrado eficazes para evitar encaminhamentos desnecessários. O objetivo deste estudo foi estimar o custo por caso encaminhado por meio de um sistema de gerenciamento de referenciamentos operado remotamente para subsidiar a tomada de decisão sobre o tema. Análise de custo por meio da aplicação de custeio baseado em atividades orientado pelo tempo (time-driven activity-based costing ou TDABC). As análises de custo incluíram comparações entre especialidades médicas, localidades para as quais os encaminhamentos estavam sendo conduzidos e períodos de tempo. O custo por referenciamento em todas as localidades variou entre R$ 5,70 a R$ 8,29. O custo por referenciamento nas especialidades médicas variou entre R$ 1,85 a R$ 8,56. Estratégias para otimizar a gestão dos referenciamentos para a atenção especializada nos sistemas públicos de saúde ainda são necessárias. As estratégias de telessaúde podem ser vantajosas, com estimativas de custo entre as localidades variando entre R$ 5,70 a R$ 8,29, com variabilidade adicional observada relacionada ao tipo de especialidade médica.

Abstract Referral of cases from primary to secondary care in the Brazilian public healthcare system is one of the most important issues to be tackled. Telehealth strategies have been shown effective in avoiding unnecessary referrals. The objective of this study was to estimate cost per referred case by a remotely operated referral management system to further inform the decision making on the topic. Analysis of cost by applying time-driven activity-based costing. Cost analyses included comparisons between medical specialties, localities for which referrals were being conducted, and periods of time. Cost per referred case across localities ranged from R$ 5.70 to R$ 8.29. Cost per referred case across medical specialties ranged from R$ 1.85 to R$ 8.56. Strategies to optimize the management of referral cases to specialized care in public healthcare systems are still needed. Telehealth strategies may be advantageous, with cost estimates across localities ranging from R$ 5.70 to R$ 8.29, with additional observed variability related to the type of medical specialty.

ABSTRACT 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.

Resumo Objetivo Nós realizamos uma revisão sistemática para avaliar a efetividade e a segurança do Tribulus terrestris no tratamento da disfunção sexual feminina (DSF). Fontes de dados Nós realizados uma busca eletrônica irrestrita nas seguintes bases de dados: MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, PsycINFO, WHO-ICTR, Clinicaltrials.gov, e OpenGrey. Seleção dos estudos Nós incluímos todos os ensaios clínico randomizados (ECR) que comparou T. terrestris com controles ativos/inativos. Após o processo de seleção, conduzido por 2 revisores, 5 ECRs (n = 279 participantes) foram incluídos. Extração de dados O processo de extração de dados foi realizado por dois revisores, utilizando-se um formulário de extração de dados pré-estabelecido. Síntese de dados Devido à falta de dados disponíveis e à heterogeneidade clínica entre os estudos incluídos, nós não realizamos meta-análises. O risco de viés foi avaliado pela tabela de risco de viés da Cochrane e, a certeza do corpo da evidência foi avaliada pelo Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Resultados Após 1 a três 3 meses de tratamento, mulheres na pré e pós-menopausa randomizadas ao T. terrestris tiveram um aumento significante nos escores de função sexual. O grupo com 3 meses de tratamento com T. terrestris exibiu um aumento significante dos níveis séricos de testosterona emmulheres pré-menopausa. Não houve relato de eventos adversos graves, e nenhum estudo avaliou qualidade de vida das participantes. A certeza da evidência foi considerada muito baixa, o que significa que existe pouca certeza na estimativa dos efeitos e que é provável que futuros estudos mudem estas estimativas. Conclusão Mais ECRs são importantes para apoiar ou refutar o uso do T. terrestris. A decisão de usar essa intervenção deve ser compartilhada com pacientes, e as incertezas sobre seus efeitos devem ser discutidas durante o processo de decisão clínica.

Abstract Objective We performed a systematic review to assess the effectiveness and safety of Tribulus terrestris to treat female sexual dysfunction (FSD). Data sources We performed unrestricted electronic searches in the MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, PsycINFO,WHO-ICTR, Clinicaltrials.gov and OpenGrey databases. Selection of studies We included any randomized controlled trials (RCTs) that compared T. terrestris versus inactive/active interventions. After the selection process, conducted by two reviewers, 5 RCTs (n = 279 participants) were included. Data collection Data extraction was performed by two reviewers with a preestablished data collection formulary. Data synthesis Due to lack of data and clinical heterogeneity, we could not perform meta-analyses. The risk of bias was assessed by the Cochrane Risk of Bias (RoB) tool, and the certainty of evidence was assessed with Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Results After 1 to 3 months of treatment, premenopausal and postmenopausal women randomized to T. terrestris had a significant increase in sexual function scores. Three months of treatment with T. terrestris showed a significant increase in the serum testosterone levels of premenopausal women. There was no report of serious adverse events, and none of the studies assessed health-related quality of life. The certainty of the evidence was very low, whichmeans that we have very little confidence in the effect estimates, and future studies are likely to change these estimates. Conclusion MoreRCTs are needed to supportor refute the use of T. terrestris. The decision to use this intervention should be shared with the patients, and the uncertainties around its effects should be discussed in the clinical decision-making process. Number of Protocol registration in PROSPERO database: CRD42019121130

RESUMO Introdução: Há diversas terapias sendo utilizadas, consideradas ou propostas para o tratamento da COVID-19, muitas carecendo de apropriada avaliação de efetividade e segurança. O propósito deste documento é fornecer recomendações baseadas nas evidências científicas disponíveis e em sua interpretação transparente, para subsidiar decisões sobre o tratamento farmacológico da COVID-19 no Brasil. Métodos: Um grupo de 27 especialistas e metodologistas integraram a força-tarefa formada pela Associação de Medicina Intensiva Brasileira (AMIB), pela Sociedade Brasileira de Infectologia (SBI) e pela Sociedade Brasileira de Pneumologia e Tisiologia (SBPT). Foram realizadas revisões sistemáticas rápidas, atualizadas até 28 de abril de 2020. A qualidade das evidências e a elaboração das recomendações seguiram o sistema GRADE. As recomendações foram elaboradas nos dias 5, 8 e 13 de maio de 2020. Resultados: Foram geradas 11 recomendações, embasadas em evidência de nível baixo ou muito baixo. Não há indicação para uso de rotina de hidroxicloroquina, cloroquina, azitromicina, lopinavir/ritonavir, corticosteroides ou tocilizumabe no tratamento da COVID-19. Heparina deve ser utilizada em doses profiláticas no paciente hospitalizado, mas não deve ser realizada anticoagulação na ausência de indicação clínica específica. Antibacterianos e oseltamivir devem ser considerados somente nos pacientes em suspeita de coinfecção bacteriana ou por influenza, respectivamente. Conclusão: Até o momento, não há intervenções farmacológicas com efetividade e segurança comprovada que justifiquem seu uso de rotina no tratamento da COVID-19, devendo os pacientes serem tratados preferencialmente no contexto de pesquisa clínica. As recomendações serão revisadas continuamente, de forma a capturar a geração de novas evidências.

ABSTRACT Introduction: Different therapies are currently used, considered, or proposed for the treatment of COVID-19; for many of those therapies, no appropriate assessment of effectiveness and safety was performed. This document aims to provide scientifically available evidence-based information in a transparent interpretation, to subsidize decisions related to the pharmacological therapy of COVID-19 in Brazil. Methods: A group of 27 experts and methodologists integrated a task-force formed by professionals from the Brazilian Association of Intensive Care Medicine (Associação de Medicina Intensiva Brasileira - AMIB), the Brazilian Society of Infectious Diseases (Sociedad Brasileira de Infectologia - SBI) and the Brazilian Society of Pulmonology and Tisiology (Sociedade Brasileira de Pneumologia e Tisiologia - SBPT). Rapid systematic reviews, updated on April 28, 2020, were conducted. The assessment of the quality of evidence and the development of recommendations followed the GRADE system. The recommendations were written on May 5, 8, and 13, 2020. Results: Eleven recommendations were issued based on low or very-low level evidence. We do not recommend the routine use of hydroxychloroquine, chloroquine, azithromycin, lopinavir/ritonavir, corticosteroids, or tocilizumab for the treatment of COVID-19. Prophylactic heparin should be used in hospitalized patients, however, no anticoagulation should be provided for patients without a specific clinical indication. Antibiotics and oseltamivir should only be considered for patients with suspected bacterial or influenza coinfection, respectively. Conclusion: So far no pharmacological intervention was proven effective and safe to warrant its use in the routine treatment of COVID-19 patients; therefore such patients should ideally be treated in the context of clinical trials. The recommendations herein provided will be revised continuously aiming to capture newly generated evidence.

Resumo Foi realizada revisão sistemática para comparar a efetividade e a segurança de exercícios versus não exercícios em pacientes assintomáticos com aneurisma de aorta. Usamos os termos MeSH aortic aneurysm e exercise para as bases MEDLINE, Embase, CENTRAL, LILACS, PeDRO, CINAHL, clinicaltrials.gov, International Clinical Trials Registry Platform (ICTRP) e OpenGrey. Foram obtidas 1.189 referências. Cinco ensaios clínicos foram incluídos. Não houve morte ou rotura associada ao exercício. Além disso, este não reduziu a velocidade de crescimento do aneurisma em 12 semanas a 12 meses [diferença de médias (DM) −0,05; intervalo de confiança de 95% (IC95%) −0,13 a 0,03]. Seis semanas de exercícios pré-operatórios reduziram complicações clínicas renais e cardíacas (razão de risco 0,54; IC95% 0,31–0,93) e a permanência em unidade de terapia intensiva (DM −1,00; IC95% −1,26 a −0,74). Caminhadas nos períodos pré e pós-operatório reduziram a permanência hospitalar. A evidência foi classificada como de muito baixa qualidade.

Abstract We conducted a systematic review to compare the effectiveness and safety of exercise versus no exercise for patients with asymptomatic aortic aneurysm. We followed the guidelines set out in the Cochrane systematic review handbook. We searched Medline, Embase, CENTRAL, LILACS, PeDRO, CINAHL, clinicaltrials.gov, ICTRP, and OpenGrey using the MeSH terms “aortic aneurysm” and “exercise”. 1189 references were identified. Five clinical trials were included. No exercise-related deaths or aortic ruptures occurred in these trials. Exercise did not reduce the aneurysm expansion rate at 12 weeks to 12 months (mean difference [MD], −0.05; 95% confidence interval [CI], −0.13 to 0.03). Six weeks of preoperative exercise reduced severe renal and cardiac complications (risk ratio, 0.54; 95% CI, 0.31–0.93) and the length of intensive care unit stay (MD, −1.00; 95% CI, −1.26 to −0.74). Preoperative and postoperative forward walking reduced the length of hospital stay (MD, −0.69; 95% CI, −1.24 to −0.14). The evidence was graded as ‘very low’ level.

ABSTRACT BACKGROUND: Age-related macular degeneration (AMD) is the third largest cause of blindness worldwide, accounting for 8.7% of all cases. A considerable number of preventive or therapeutic interventions have been used for AMD. OBJECTIVE: This study presents a critical view of the interventions that have been assessed through Cochrane systematic reviews. DESIGN AND SETTING: Review of systematic reviews, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). METHODS: Review of Cochrane systematic reviews about interventions for AMD. RESULTS: The 18 systematic reviews included assessed the effects of surgical techniques, laser/photo/radiotherapy, intravitreal injections, systemic drugs and phytotherapy/vitamins/supplements. CONCLUSION: The Cochrane systematic reviews found evidence that use of bevacizumab, ranibizumab, pegaptanib, laser photocoagulation, photodynamic therapy and multivitamin compounds may present some benefits for treating AMD. There was insufficient evidence for supporting the use of macular translocation, submacular surgery, steroid implantation, radiotherapy, intravitreal aflibercept, interferon alfa, statins or omega-3 fatty acids for treating AMD; or the use of multivitamin antioxidant vitamins or mineral supplementation for preventing AMD. Future randomized controlled trials are imperative to reduce the uncertainty in several clinical questions regarding AMD.

ABSTRACT BACKGROUND: Irritable bowel syndrome (IBS) is a clinical disorder associated with high socioeconomic burden. Despite its importance, management of IBS remains difficult and several interventions have been hypothesized as beneficial for this condition. This study identified and summarized all Cochrane systematic reviews (SRs) about the effects of interventions for managing IBS patients. DESIGN AND SETTING: Review of systematic reviews, carried out in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). METHODS: Review of Cochrane SRs addressing interventions for IBS. RESULTS: We included six SRs assessing acupuncture, bulking agents, antispasmodics, antidepressants, herbal medicines, homeopathy, hypnotherapy and psychological therapy for IBS. The certainty of evidence ranged from unknown to moderate, mainly due to imprecision in the estimates and high risk of bias from the primary studies included. There was moderate certainty of evidence that acupuncture had no important benefit regarding improvement of symptoms and quality of life, compared with sham acupuncture. There was also very low certainty of evidence that homeopathic asafoetida, used alone or in association with nux, was better than placebo regarding self-reported overall improvement. CONCLUSION: There was moderate certainty of evidence that acupuncture had no important benefit regarding improvement of symptoms and quality of life. Further well-designed and well-conducted randomized clinical trials are needed in order to reduce the uncertainties regarding the most commonly used interventions for patients with IBS.

ABSTRACT CONTEXT AND OBJECTIVE: Insomnia is a frequent complaint that generates more than five million visits to doctors per year in the United States. This study summarizes all Cochrane systematic reviews (SRs) that evaluated interventions to treat insomnia. DESIGN AND SETTING: Review of SRs, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP). METHODS: A sensitive search was carried out in the Cochrane Database of Systematic Reviews to identify Cochrane SRs that assessed the effects of any type of intervention for people with insomnia. The results, main characteristics of the SRs and the certainty of the evidence obtained from them were synthesized and discussed. RESULTS: Seven SRs were included. They addressed the benefits and harm of acupuncture (n = 1), behavioral interventions (n = 1), music (n = 1), pharmacotherapy (n = 2), phototherapy (n = 1) and physical exercise (n = 1). The certainty of the evidence ranged from moderate to very low. CONCLUSION: Acupuncture, music, physical exercise, paroxetine, doxepin, trimipramine and trazodone seem to present some benefit for patients with insomnia. However, the uncertainty around these results means that no robust and definitive recommendations for clinical practice can be made until the benefits and harms from each intervention for patients with insomnia have been confirmed through further studies.