Selective outcome reporting in randomized clinical trials using the third molar surgery model.

Selective outcome reporting (SOR) can threaten the validity of results found in clinical trials. Some studies in the literature have analyzed SOR in dentistry, but there is no study that has observed SOR in clinical trials in oral and maxillofacial surgery. Impacted third molar surgery is one of the most used models in clinical trials to study mainly analgesic and anti-inflammatory drug interventions. Our study aimed to evaluate the prevalence of SOR in publications employing the third molar extraction clinical trial model, and to verify whether there was an association between the statistical significance of outcomes and other characteristics that could lead to SOR. A systematic search was performed on the ClinicialTrials.gov platform for randomized clinical trial protocols, using the condition of third molar extraction. The corresponding published articles were sourced in PubMed, Scopus, and Embase databases, and compared with the registered protocols regarding the methodological data, in terms of: sample calculation, primary outcome identification, end-point periods, insertion of new outcomes in the publication, and results of outcomes. 358 protocol records were retrieved; 87 presented their corresponding articles. SOR was identified in 28.74% of the publications, and had a significant relationship with changes in the protocol, insertions of new outcomes, and discrepancies in the types of study. General risk of bias was found to be low. There were associations between SOR and the discrepancies in terms of the type of study, the choice of new outcome, and changes in the history of protocol records. The prevalence of SOR in clinical research using the third molar extraction surgery model is moderate. The quality of the scientific reporting of the results and, consequently, the certainty of evidence relating to the intervention tested can be overstated, increasing the chances of misinterpretation by health professionals.

Interpreting Meta-Analyses: A Guide to Funnel and Forest Plots.

Meta-analyses represent the best available medical evidence. Although a powerful tool, they are not without criticisms since any bias in the original studies are then compounded when they are pooled together for the meta-analysis. Funnel plots provide a useful graphical representation of the presence of bias, and forest plots represent the heterogeneity of findings within studies included in a meta-analysis. The purpose of this review is to help readers interpret these statistical tools to better understand the findings of a meta-analysis.

Prognostic role and clinical significance of tumor-infiltrating lymphocyte (TIL) and programmed death ligand 1 (PD-L1) expression in gastric cancer: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: This study intended to evaluate the prognostic effects of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in survival and their associations with clinicopathological characteristics in patients with gastric cancer. METHODS: PubMed, Scopus, ProQuest, Web of Science, and Ovid databases were searched to obtain the relevant studies. Eleven studies with 2298 patients were included in this study. RESULTS: Like the level of TILs, there were no significant associations between PD-L1 expression and TNM stage, lymph node metastasis, vascular invasion, and tumor location (All p values ≥ 0.05). Furthermore, there was no significant association between PD-L1 expression with overall survival (OS) (HR = 0.76, 95% CI: 0.55 to 1.05, p value = 0.10) and disease-free survival (DFS) (HR = 0.62, 95% CI: 0.10 to 3.68, p value = 0.59). In the assessment of TILs presence and survival association, the analysis showed no association between TILs presence and overall survival (OS) (HR = 0.95, 95% CI: 0.62 to 1.45). CONCLUSIONS: In conclusion, the study has revealed no prognostic effect of PD-L1 and TILs in gastric cancer patients.

Are most published research findings false in a continuous universe?

Diagnostic screening models for the interpretation of null hypothesis significance test (NHST) results have been influential in highlighting the effect of selective publication on the reproducibility of the published literature, leading to John Ioannidis' much-cited claim that most published research findings are false. These models, however, are typically based on the assumption that hypotheses are dichotomously true or false, without considering that effect sizes for different hypotheses are not the same. To address this limitation, we develop a simulation model that overcomes this by modeling effect sizes explicitly using different continuous distributions, while retaining other aspects of previous models such as publication bias and the pursuit of statistical significance. Our results show that the combination of selective publication, bias, low statistical power and unlikely hypotheses consistently leads to high proportions of false positives, irrespective of the effect size distribution assumed. Using continuous effect sizes also allows us to evaluate the degree of effect size overestimation and prevalence of estimates with the wrong sign in the literature, showing that the same factors that drive false-positive results also lead to errors in estimating effect size direction and magnitude. Nevertheless, the relative influence of these factors on different metrics varies depending on the distribution assumed for effect sizes. The model is made available as an R ShinyApp interface, allowing one to explore features of the literature in various scenarios.

Clinicopathological and prognostic significance of COX-2 in glioma patients: a meta-analysis.

BACKGROUND: In recent years, cyclooxygenase-2 (COX-2) has been identified as a cancer stem cell (CSC) marker in gliomas. Nevertheless, the clinical and prognostic significance of COX-2 in glioma patients remains controversial. OBJECTIVE: To evaluate the correlation of COX-2 with the prognosis in glioma patients. METHODS: Eligible studies on this subject were included, and pooled odd ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were estimated. Publication bias was assessed through funnel plots, and heterogeneity and sensitivity were analyzed as well. RESULTS: In the present study, 11 articles with a total of 641 patients were included. The high expression of COX-2 in glioma patients was negatively associated with overall survival (OS) (n = 11; HR = 2.26; 95%CI = 1.79-2.86), and the subgroup analysis showed no differences in OS between Asian (n = 5; HR = 2.16; 95%CI = 1.57-2.97) and non-Asian (n = 6; HR = 2.39; 95%CI = 1.69-3.38) glioma patients. The Begg funnel plots test indicated that there was no evident risk of publication bias in the meta-analysis. CONCLUSION: The present study suggests that COX-2 could be recommended as a useful pathological and prognostic biomarker in the clinical practice.

INTRODUçãO: Nos últimos anos, a ciclooxigenase-2 (COX-2) foi identificada como um marcador de células-tronco cancerígenas (CSC) em gliomas. No entanto, o significado clínico e prognóstico da COX-2 em pacientes com glioma permanece controverso. OBJETIVO: Avaliar a correlação da COX-2 com o prognóstico em pacientes com glioma. MéTODOS: Estudos elegíveis sobre este assunto foram incluídos e foram estimados odds ratios (ORs) e hazard ratios (HRs) com intervalos de confiança de 95% (IC 95%). O viés de publicação foi avaliado por meio de gráficos de funil, e a heterogeneidade e a sensibilidade também foram analisadas. RESULTADOS: No presente estudo foram incluídos 11 artigos com um total de 641 pacientes. A alta expressão de COX-2 em pacientes com glioma foi negativamente associada à sobrevida global (OS) (n = 11; HR = 2,26; IC 95% = 1,79-2,86), e a análise de subgrupo não mostrou diferenças na OS entre asiáticos (n = 5; HR = 2,16; IC 95% = 1,57­2,97) e não asiáticos (n = 6; HR = 2,39; IC 95% = 1,69­3,38) pacientes com glioma. O teste de gráficos de funil de Begg indicou que não havia risco evidente de viés de publicação na metanálise. CONCLUSãO: O presente estudo sugere que a COX-2 pode ser recomendada como um biomarcador patológico e prognóstico útil na prática clínica.

The importance of full text screening when judging eligibility criteria in a systematic review: a systematic survey / A importância da avaliação do texto completo ao julgar os critérios de elegibilidade em uma revisão sistemática: uma revisão de métodos

Aim: To evaluate if statistically significant results are more likely to be reported in title/abstracts compared to non-significant outcomes. Methods: In this methodological survey, we reanalyzed 59 observational studies from a previous systematic review. The PECO question was: Patient (P): children with primary teeth; Exposure (E): low birth weight and/or preterm; Comparison (C): normal birth weight and/or full-term; Outcome (O): dental caries. We analyzed the presence of key terms in the titles and abstracts, such as gestational age, preterm, full-term, birth weight, low/normal birth weight. Full texts were analyzed for "positive outcomes" (statistically significant association, p < 0.05 or 95% CI not crossing the null effect line) related to the association between the outcome and the exposure; and "negative outcomes" (when the outcome had statistically similar occurrence between the exposure and the comparison group). The odds ratio (OR) was calculated between the presence of key terms in titles/abstracts and the type of outcome (positive or negative). Results: Of 59 studies, 66% cited the key terms in titles/abstracts, and 75% reported negative outcomes. Studies with positive outcomes were more likely to report key terms in the titles/abstracts compared to studies with negative outcomes (OR: 4.5; 95% CI: 0.9-22.4; Chi-square test: p = 0.06). Studies with statistically significant outcomes, favoring the exposure or the comparison, were more likely to report these data in the titles/abstracts. Conclusion: When conducting a systematic review, the final decision related to the inclusion of a study must be based on a full-text level.

Objetivo: Avaliar se os resultados estatisticamente significativos são mais prováveis de serem relatados nos títulos/resumos dos artigos do que os resultados não significativos. Métodos: Neste levantamento metodológico, foram reanalisados 59 estudos observacionais de uma revisão sistemática anterior. A questão PECO foi: Paciente (P): crianças com dentes decíduos; Exposição (E): baixo peso ao nascer e/ou pré-termo; Comparação (C): peso normal ao nascer e/ou a termo; Resultado (O): cárie dentária. Foi analisada a presença de termos-chave nos títulos/resumos, como idade gestacional, pré-termo, a termo, peso ao nascer, baixo/peso normal ao nascer. Textos completos foram analisados para "desfechos positivos" (associação estatisticamente significativa, p < 0,05 ou IC 95% não cruzando a linha de efeito nulo) relacionados à associação entre o desfecho e a exposição; e "desfechos negativos" (quando o desfecho teve ocorrência estatisticamente semelhante entre a exposição e o grupo de comparação). Foi calculada a odds ratio (OR) entre a presença de termos-chave nos títulos/resumos e o tipo de resultado (positivo ou negativo). Resultados: Dos 59 estudos, 66% citaram os termos-chave nos títulos/resumos e 75% relataram resultados negativos. Estudos com resultados positivos foram mais propensos a relatar os termos-chave nos títulos/resumos em comparação com estudos com resultados negativos (OR: 4,5; IC 95%: 0,9-22,4; teste do qui-quadrado: p = 0,06). Estudos com significância estatística os desfechos, favorecendo a exposição ou a comparação, foram mais propensos a relatar esses dados nos títulos/resumos. Conclusão: Ao realizar uma revisão sistemática, a decisão final quanto à inclusão de um estudo deve ser baseada por meio da análise do texto completo.

Peri-abortion contraceptive counseling: A systematic review of randomized controlled trials.

OBJECTIVE: To assess the effects of peri-abortion contraceptive counseling interventions. METHODS: We performed a systematic review of randomized controlled trials (RCTs) that compared the effect of different types of peri-abortion contraceptive counseling interventions and were published as original papers in scientific journals. The literature search was performed in June 2021 in PubMed, Central Cochrane Library (CENTRAL), Scopus, and Google Scholar; without restrictions in language or publication date. Two independent authors identified studies that met the inclusion and exclusion criteria and extracted the data. The risk of bias was assessed using the Cochrane tool, and evidence certainty was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Whenever possible, meta-analyses were performed. The protocol was registered at PROSPERO (CRD42020187354). RESULTS: Eleven RCTs were eligible for inclusion (published from 2004 to 2017), from which nine compared enhanced versus standard counseling. Pooled estimates showed that, compared to standard counseling, enhanced counseling was associated with a higher incidence of effective contraceptive use (>3 months) (relative risk [RR], 1.12; 95% confidence interval [CI], 1.09-1.16), although no significant difference was found in the incidence of long-acting reversible contraceptive use (RR, 1.25; 95% CI, 0.68-2.29), contraceptive uptake (RR, 1.06; 95% CI, 0.98-1.15), and obstetric event occurrence (RR, 0.91; 95% CI, 0.57-1.47). Certainty of evidence was very low for all outcomes. In addition, two studies compared contraceptive counseling provided by physicians versus that provided by non-physicians, which did not show significant differences. CONCLUSIONS: Enhanced contraceptive counseling may favor effective contraceptive use but may not affect the rate of obstetric event occurrence. Also, the studies did not find a difference in the effects of counseling interventions given by different providers. Since evidence certainty was very low, future well-designed RCTs are needed to make informed decisions. REGISTRATION: The study protocol was registered at PROSPERO (CRD42020187354).

Riesgo de sesgo de publicación en intervenciones terapéuticas para la COVID-19

[RESUMEN]. En este artículo se describe el sesgo de publicación, sus causas más frecuentes, sus características, las herramientas regulatorias para evitarlo y algunas técnicas estadísticas para analizarlo. Se explican y aplican estas técnicas a tres intervenciones terapéuticas relacionadas con la enfermedad por el coronavirus 2019 (COVID-19, por su sigla en inglés): corticoides, ivermectina y tocilizumab; se detectó riesgo de sesgo de publicación para ivermectina y tocilizumab. Las revisiones sistemáticas y los metaanálisis son diseños de investigación secundaria que constituyen una referencia para guiar la toma de decisiones. Son propensos a distintos tipos de sesgo, que es una desviación sistemática en los resultados. Aun desarrollados con rigor metodológico, su validez puede verse amenazada por el sesgo de publicación. Este se define como el acto de ocultar o retrasar la publicación, retener datos surgidos de los estudios de investigación, o ambos. Hasta la mitad de los ensayos controlados que se realizan permanecen sin publicarse. Durante la pandemia por virus H1N1, el sesgo de publicación de estudios financiados por la industria llevó a recomendar y comprar en gran escala el fármaco oseltamivir que, luego se supo, no tenía efectos beneficiosos relevantes. Dos tercios del financiamiento de los estudios clínicos para COVID-19 provienen de la industria farmacéutica. En el contexto de la pandemia actual por COVID-19, se publican estudios a un ritmo acelerado, por lo que resulta de gran trascendencia conocer e identificar el sesgo de publicación. Para reducir el sesgo de publicación es necesario regular el registro y la publicación de ensayos clínicos, pero esto requiere una coordinación de los países y organismos internacionales. Es importante sospechar e intentar identificar el sesgo de publicación para la toma de decisiones.

[ABSTRACT]. This article describes publication bias, its most frequent causes, its characteristics, the regulatory tools to avoid it, and some statistical techniques to analyze it. These techniques are explained and applied to three therapeutic interventions related to the 2019 coronavirus disease (COVID-19): corticosteroids, ivermectin, and tocilizumab. Risk of publication bias was detected for ivermectin and tocilizumab. Systematic reviews and meta-analyses are secondary research designs that provide a reference to guide decision-making. They are prone to different types of bias, i.e., a systematic deviation in the results. Even if carried out with methodological rigor, their validity can be threatened by publication bias. This is defined as the act of concealing or delaying publication, withholding data arising from research studies, or both. Up to half of controlled trials remain unpublished. During the H1N1 virus pandemic, publication bias from industry-funded studies led to the recommendation and large-scale procurement of oseltamivir, a drug that later proved to have no relevant beneficial effects. Two-thirds of clinical trial funding for COVID-19 comes from the pharmaceutical industry. In the context of the COVID-19 pandemic, studies are published at an accelerated pace, making it very important to understand and identify publication bias. To reduce publication bias it is necessary to regulate the registration and publication of clinical trials, but this requires coordination among countries and international bodies. It is important to suspect and attempt to identify publication bias for decision making.

[RESUMO]. Este artigo descreve o viés de publicação, suas causas mais frequentes, suas características, as ferramentas regulatórias para evitá-lo e algumas técnicas estatísticas para analisá-lo. Essas técnicas são explicadas e aplicadas a três intervenções terapêuticas relacionadas à doença pelo coronavírus 2019 (COVID-19, na sigla em inglês): corticoides, ivermectina e tocilizumabe. Detectou-se risco de viés de publicação para ivermectina e tocilizumabe. As revisões sistemáticas e as meta-análises são delineamentos de pesquisa secundária que constituem uma referência para orientar a tomada de decisão. Estão propensas a diferentes tipos de viés, que é um desvio sistemático nos resultados. Mesmo tendo sido desenvolvidas com rigor metodológico, sua validade pode ser ameaçada pelo viés de publicação, que é definido como o ato de ocultar ou atrasar a publicação, reter dados de pesquisa ou ambos. Até metade dos estudos controlados realizados jamais são publicados. Durante a pandemia pelo vírus H1N1, o viés de publicação de estudos financiados pela indústria levou à recomendação e à compra, em grande escala, do medicamento oseltamivir que, mais tarde, ficou conhecido por não ter efeitos benéficos relevantes. Dois terços do financiamento para os ensaios clínicos referentes à COVID-19 vêm da indústria farmacêutica. No contexto da atual pandemia de COVID-19, os estudos vêm sendo publicados em ritmo acelerado; portanto, é fundamental conhecer e identificar o viés de publicação. Para reduzi-lo, é necessário regulamentar o registro e a publicação de ensaios clínicos, o que requer coordenação entre países e organismos internacionais. É importante suspeitar e tentar identificar o viés de publicação para a tomada de decisão.

Circulating MicroRNAs as Novel Potential Diagnostic Biomarkers for Osteosarcoma: A Systematic Review.

Osteosarcoma (OS) is a fast-progressing bone tumor with high incidence in children and adolescents. The main diagnostic methods for OS are imaging exams and biopsies. In spite of the several resources available for detecting the disease, establishing an early diagnosis is still difficult, resulting in worse prognosis and lower survival rates for patients with OS. The identification of novel biomarkers would be helpful, and recently, circulating microRNAs (miRNAs) have been pointed to as possible non-invasive biomarkers. In order to assess the effectiveness of miRNA research, we performed a systematic review to assess the potential role of circulating miRNAs as biomarkers for OS diagnosis. We performed a search in various databases-PubMed, LILACS (Literatura Latino-americana e do Caribe em Ciências da Saúde), VHL (Virtual Health Library), Elsevier, Web of Science, Gale Academic One File-using the terms: "Circulating microRNAs" OR "plasma microRNAs" OR "serum microRNAs" OR "blood microRNAs" OR "cell-free microRNAs" OR "exosome microRNAs" OR "extracellular vesicles microRNAs" OR "liquid biopsy" AND "osteosarcoma" AND "diagnostic". We found 35 eligible studies that were independently identified and had had their quality assessed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Despite the useful number of publications on this subject and the fact that several microRNAs showed excellent diagnostic performance for OS, the lack of consistency in results suggests that additional prospective studies are needed to confirm the role of circulating miRNAs as non-invasive biomarkers in OS.

High frequency of spin bias in controlled trials of cannabis derivatives and their synthetic analogues: A meta-epidemiologic study.

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.

Polysaccharides with Antitumor Effect in Breast Cancer: A Systematic Review of Non-Clinical Studies.

Purpose: To review the effects of polysaccharides and their proposed mechanisms of action in breast cancer experimental models. Data sources, selection, and extraction: Articles were selected by using PubMed, ScienceDirect, Scopus, and Medline, assessed from 1 May 2019 to 1 July 2020. The systematic review was registered in the International Prospective Register of Systematic Reviews (Prospero) under the number CRD42020169103. Results: Most of the studies explore algae polysaccharides (43.2%), followed by mushrooms (13.5%), plants (13.5%), fruits (10.8%), fungus (2.7%), bacteria, (2.7%), and sea animals (2.7%). A total of 8.1% investigated only in vitro models, 62.1% evaluated only in vivo models, and 29.7% evaluated in vitro and in vivo models. The mechanism of action involves apoptosis, inhibition of cellular proliferation, angiogenesis, and antimetastatic effects through multiple pathways. Conclusions: Findings included here support further investigations on the anti-tumor effect of polysaccharides. Some polysaccharides, such as fucoidan and ß-glucans, deserve detailed and structured studies aiming at translational research on breast tumors, since they are already used in the clinical practice of other proposals of human health.

The GRADE approach, Part 1: how to assess the certainty of the evidence. / Metodología GRADE, parte 1: cómo evaluar la certeza de la evidencia.

The certainty of the evidence for interventions is the certainty or confidence that the true effect is within a particular range or relative to a threshold. In the new pyramid of evidence, systematic reviews represent the magnifying glass through which this certainty is evaluated. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach arises in response to the existence of multiple evidence classification systems, and it offers a transparent and structured process to develop and present summaries of evidence considering its certainty and, in a second step, the strength of the recommendations that they inform. The GRADE process begins with an explicit question that includes all important and critical outcomes explicitly. The main domains used to assess the certainty of the evidence are risk of bias, inconsistency, indirectness of evidence, imprecision, and publication bias. The factors that can increase the certainty of the evidence are dose-response gradient, large magnitude of an effect, and effect of plausible residual confounding. Finally, the Summary of Findings tables summarize the process in a simplified way and with controlled language. This narrative reviews purpose is to address the GRADE approachs theoretical and practical underlying concepts in a simplified way and with practical examples.

La certeza de la evidencia para las intervenciones es la seguridad o confianza de que el verdadero efecto se encuentra dentro de un rango particular o en relación con un umbral. En la nueva pirámide de la evidencia, las revisiones sistemáticas representan la lupa a través de la cual se evalúa dicha certeza. La metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) surge como respuesta a la existencia de múltiples sistemas de clasificación de la evidencia y ofrece un proceso transparente y estructurado para desarrollar y presentar resúmenes de evidencia considerando la certeza de esta y, en un segundo paso, la fuerza de las recomendaciones que informan. El proceso GRADE comienza con una pregunta explícita, que incluye las especificaciones de todos los desenlaces importantes y críticos. Los principales dominios que se utilizan para valorar la certeza de la evidencia son: 1. El riesgo de sesgo, 2. La inconsistencia, 3. Evidencia indirecta, 4. Imprecisión, y 5. El sesgo de publicación. Los factores que pueden aumentar la certeza de la evidencia son: 1. Gradiente dosis respuesta, 2. Gran magnitud del efecto, 3. Efecto de los potenciales factores de confusión residual. Finalmente, las tablas de resumen de hallazgos (Summary of Findings) sintetizan el proceso de manera simplificada y con un lenguaje controlado. El objetivo general de esta revisión narrativa es abordar los principales conceptos básicos teóricos y prácticos de la metodología GRADE de manera simplificada y con ejemplos prácticos.

Resistance training to reduce resting blood pressure and increase muscle strength in users and non-users of anti-hypertensive medication: A meta-analysis.

Objective: The aim of this study was to conduct a systematic review with meta-analysis to analyze the effect of resistance training variables prescription on resting systolic (SBP) and diastolic blood pressure (DBP) and muscle strength changes. Methods: The search was conducted in the PubMed, Web of Science, and SPORTDiscus databases until August 2020 for randomized controlled trials with non-exercising control group. Results: In total, 36 studies qualified for inclusion in this meta-analysis. Eleven studies included users of antihypertensive medication, while the remaining 25 studies were conducted with non-users of antihypertensive medication. Resistance training only reduced SBP (-0.56 [-0.77 to -0.35]; P < .001) and DBP (-0.46 [-0.68 to -0.24]; P < .001) in anti-hypertensive medication users, with changes ranging from -6.1 to -2.8 mmHg for SBP and -4.6 to -1.6 mmHg for DBP. Muscle strength increased significantly in both users (0.76 [0.49 to 1.02]; P < .001) and non-users of antihypertensive medication (0.94 [0.71 to 1.16]; P < .001). Resistance training should be performed by users and non-users of antihypertensive medication for 8 to 16 weeks (2 to 3 days a week) and 8 to 12 non-failure repetitions. However, users should train with less load (60-80 vs 70-85% 1RM) and exercise sets (1-3 vs 2-4) than non-users of antihypertensive medication. Conclusion: Resistance training increases muscle strength and reduces resting SBP and DBP in individuals under BP pharmacological therapy, while in individuals who do not use antihypertensive drugs, resistance training only increases strength.

Accuracy of frozen section in intraoperative margin assessment for breast-conserving surgery: A systematic review and meta-analysis.

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.

Compreendendo o GRADE: PICO e qualidade dos estudos / Understanding GRADE system: PICO and study quality

A saúde baseada em evidências se refere ao uso criterioso do conhecimento científico existente, oriundo de pesquisas clínicas, utilizando metodologias específicas que garantam solidez e clareza nas informações a serem aplicadas na tomada de decisão clínica. Dessa forma, reduzem-se as incertezas no julgamento clínico. O objetivo deste artigo foi descrever a metodologia PICO e a qualidade dos estudos com base no sistema GRADE. (AU)

Evidence-based health refers to the judicious use of existing scientific knowledge from clinical research, using specific methodologies that ensure solidity and clarity to the information to be applied in clinical decision-making, thus reducing uncertainties in clinical judgment. The objective of this article is to describe PICO methodology and the quality of studies in the GRADE system. (AU)

Enhancing the Therapeutic Potential of Mesenchymal Stem Cells with Light-Emitting Diode: Implications and Molecular Mechanisms.

This study evaluated the effects of light-emitting diode (LED) on mesenchymal stem cells (MSCs). An electronic search was conducted in PubMed/MEDLINE, Scopus, and Web of Science database for articles published from 1980 to February 2020. Ten articles met the search criteria and were included in this review. The risk of bias was evaluated to report quality, safety, and environmental standards. MSCs were derived from adipose tissue, bone marrow, dental pulp, gingiva, and umbilical cord. Protocols for cellular irradiation used red and blue light spectrum with variations of the parameters. The LED has been shown to induce greater cellular viability, proliferation, differentiation, and secretion of growth factors. The set of information available leads to proposing a complex signaling cascade for the action of photobiomodulation, including angiogenic factors, singlet oxygen, mitogen-activated protein kinase/extracellular signal-regulated protein kinase, Janus kinase/signal transducer, and reactive oxygen species. In conclusion, although our results suggest that LED can boost MSCs, a nonuniformity in the experimental protocol, bias, and the limited number of studies reduces the power of systematic review. Further research is essential to find the optimal LED irradiation parameters to boost MSCs function and evaluate its impact in the clinical setting.

The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta­analysis.

OBJECTIVE: Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. METHODS: We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. RESULTS: Five eligible studies (four cohort studies and one case-control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60-1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39-0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). CONCLUSIONS: Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified.

Effect of low-level laser therapy on seminiferous epithelium: a systematic review of in vivo studies.

Laser therapy has proved effective in the treatment of different tissue injuries but little is known about its effect on the testis. The aim of this review was to synthesize research on the in vivo effect of low-level laser therapy on the seminiferous epithelium. A search was performed in the PubMed/Medline, Scopus, Web of Science, and LILACS databases. The initial search retrieved 354 references, and five articles that met the eligibility criteria were selected. In general, the studies showed that laser therapy exerted a positive effect on the germ cell population; however, there was considerable variation in the laser parameters, as well as in the experimental models and methods of tissue analysis used. In conclusion, further studies determining the biostimulation parameters of laser therapy in the testis are necessary in order to provide a basis for the possible application of this technique to the restoration of the human seminiferous epithelium and consequent treatment of some male reproductive disorders.

Peptides from Animal Origin: A Systematic Review on Biological Sources and Effects on Skin Wounds.

BACKGROUND: Skin wounds are closely correlated with opportunistic infections and sepsis risk. Due to the need of more efficient healing drugs, animal peptides are emerging as new molecular platforms to accelerate skin wound closure and to prevent and control bacterial infection. AIM: The aim of this study was to evaluate the preclinical evidence on the impact of animal peptides on skin wound healing. In addition, we carried out a critical analysis of the studies' methodological quality. Main Methods. This systematic review was performed according to the PRISMA guidelines, using a structured search on the PubMed-Medline, Scopus, and Web of Science platforms to retrieve studies published until August 25, 2020 at 3 : 00 pm. The studies included were limited to those that used animal models, investigated the effect of animal peptides with no association with other compounds on wound healing, and that were published in English. Bias analysis and methodological quality assessments were examined through the SYRCLE's RoB tool. RESULTS: Thirty studies were identified using the PRISMA workflow. In general, animal peptides were effective in accelerating skin wound healing, especially by increasing cellular proliferation, neoangiogenesis, colagenogenesis, and reepithelialization. Considering standardized methodological quality indicators, we identified a marked heterogeneity in research protocols and a high risk of bias associated with limited characterization of the experimental designs. CONCLUSION: Animal peptides show a remarkable healing potential with biotechnological relevance for regenerative medicine. However, rigorous experimental approaches are still required to clearly delimit the mechanisms underlying the healing effects and the risk-benefit ratio attributed to peptide-based treatments.