Imaging associations enhance the understanding of ECG abnormalities in male Brazilian football players: findings from the B-Pro Foot ECG study.

OBJECTIVES: To evaluate the prevalence of abnormal ECG findings and their association with imaging results in male Brazilian football players. METHODS: The 'B-Pro Foot ECG' is a multicentre observational study conducted in 82 Brazilian professional clubs. It analysed 6125 players aged 15-35 years (2496 white, 2004 mixed-race and 1625 black individuals) who underwent cardiovascular screening from 2002 to 2023. All ECGs were reviewed by two experienced cardiologists in the athlete's care. Those with abnormal findings underwent further investigations, including a transthoracic echocardiogram (TTE). Cardiac magnetic resonance (CMR) was subsequently performed based on TTE findings or clinical suspicion. RESULTS: In total, 180 (3%) players had abnormal ECGs and 176 (98%) showed normal TTE results. Athletes aged 26-35 years had a higher prevalence of abnormal ECGs than younger athletes (15-25 years). Black players had a higher prevalence of T-wave inversion (TWI) in the inferior leads than white players (2.6% vs 1.4%; p=0.005), as well as in V5 (2.9%) and V6 (2.1%) compared with white (1.2% and 1.0%; p<0.001) and mixed-race (1.5% and 1.2%; p<0.05) players, respectively. TTE parameters were similar across ethnicities. However, four out of 75 players with inferolateral TWI showed abnormal TTEs and CMR findings consistent with cardiomyopathies. CMR also showed cardiomyopathies or myocarditis in four players with inferolateral TWI and normal TTEs. In total, nine (0.1%) athletes were diagnosed with cardiac diseases and were followed for 40±30 months, with no cardiac events documented. CONCLUSION: This study found a 3% prevalence of abnormal ECGs in male Brazilian football players. Inferolateral TWI was associated with cardiac pathologies confirmed by CMR, even in athletes with a normal TTE.

What Powers Trastuzumab's Cardiotoxicity? Decoding Mitochondrial-Related Gene Expression Through Integrative Review and Meta-Analysis in Cardiomyocytes.

Trastuzumab is a monoclonal antibody used in oncotherapy for HER2-positive tumors. However, as an adverse effect, trastuzumab elevates the risk of heart failure, implying the involvement of energy production and mitochondrial processes. Past studies with transcriptome analysis have offered insights on pathways related to trastuzumab safety and toxicity but limited study sizes hinder conclusive findings. Therefore, we meta-analyzed mitochondria-related gene expression data in trastuzumab-treated cardiomyocytes. We searched the transcriptome databases for trastuzumab-treated cardiomyocytes in the ArrayExpress, DDBJ Omics Archive, Gene Expression Omnibus, Google Scholar, PubMed, and Web of Science repositories. A subset of 1270 genes related to mitochondrial functions (biogenesis, organization, mitophagy, and autophagy) was selected from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology Resource databases to conduct the present meta-analysis using the Metagen package (Study register at PROSPERO: CRD42021270645). Three datasets met the inclusion criteria and 1243 genes were meta-analyzed. We observed 69 upregulated genes after trastuzumab treatment which were related mainly to autophagy (28 genes) and mitochondrial organization (28 genes). We also found 37 downregulated genes which were related mainly to mitochondrial biogenesis (11 genes) and mitochondrial organization (24 genes). The present meta-analysis indicates that trastuzumab therapy causes an unbalance in mitochondrial functions, which could, in part, help explain the development of heart failure and yields a list of potential molecular targets. These findings contribute to our understanding of the molecular mechanisms underlying the cardiotoxic effects of trastuzumab and may have implications for the development of targeted therapies to mitigate such effects.

Selective Internal Radiation Therapy Using Y-90 Resin Microspheres for Metastatic Colorectal Cancer: An Updated Systematic Review and Network Meta-Analysis.

INTRODUCTION: This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). METHODS: In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. RESULTS: Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. CONCLUSION: Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.

The role of colonoscopy in young patients with rectal bleeding: a systematic review and meta-analysis.

PURPOSE: Anal bleeding is a frequent complaint in the coloproctological practice. Although usually associated with common anorectal disorders, it may represent a sign of an occult colorectal carcinoma. Our purpose was to evaluate the accuracy of the colonoscopy for detection of neoplastic lesions in patients under 50 years of age with rectal bleeding. METHODS: This systematic review and meta-analysis searched publications in PubMed, Web of Science, and Cochrane Library databases up to August, 2023. Cross-sectional and case-control studies including patients under 50 years with rectal bleeding evaluated by colonoscopy were included. Primary outcome was prevalence of neoplastic lesions (adenomas and adenocarcinomas). Secondary outcomes were prevalence of those lesions according to age and anatomic location. The study was registered on PROSPERO (CRD42021257859) on July 5, 2021. RESULTS: Nine studies comprising 4162 patients were analyzed. A total of 398 patients with adenomas and 40 patients with adenocarcinoma were identified. Prevalence of neoplastic lesions (adenomas and carcinomas) was 10%. In patients under 40 years, the prevalence of neoplastic lesions was 7% (6% of adenomas, 1% of carcinomas). Among patients aged 40-50 years the prevalence was 15%, 14%, and 1%, respectively. Most lesions (71%) were located distally to splenic flexure. CONCLUSION: About 10% of patients under 50 years with anal bleeding will have a neoplastic lesion detected through colonoscopy. The greatest benefit of the procedure is observed between 40 and 50 years. Almost 30% of the neoplastic lesions were found in the proximal colon and could not be detected without the performance of a complete colonoscopy.

Thiazide diuretics alone or combined with potassium-sparing diuretics to treat hypertension: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension. METHODS: A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer. RESULTS: Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents. CONCLUSION: Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.

Efficacy of six exercise-based interventions for individuals undergoing hemodialysis: a network meta-analysis of randomized clinical trials.

BACKGROUND: Evidence comparing different exercise modalities in individuals undergoing hemodialysis remains incipient. Our aim was to conduct a systematic review and network meta-analysis of randomized clinical trials to compare and synthesize the efficacy of five different intradialytic exercise modalities and home-based training in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Studies were searched in PubMed/MEDLINE, Cochrane Library, Embase, Cinahl, and Scopus from their inception to 19 September 2022. We used traditional random-effects models and Bayesian network meta-analysis models. The risk of bias was assessed using the RoB v.2.0 tool, and the assessment of confidence in the results through the Confidence in Network Meta-Analysis (CINeMA) tool. RESULTS: Seventy-eight studies involving 3326 participants were included. Our network meta-analysis showed that combined training was the intervention with the best performance to increase VO2 peak [mean difference (MD) = 3.94 ml/kg/min; 95% credible interval (CrI), 2.38 to 5.76] and to reduce diastolic blood pressure (MD = -5.19 mmHg; 95%CrI, -9.35 to -0.96) compared to the usual care group. Inspiratory muscle training was the intervention that most improved the 6-minute walk test distance (MD = 70.97 m; 95%CrI, 18.09 to 129.87). C-reactive protein decreased in resistance training (MD = -2.6 mg/l; 95%CrI, -4.97 to -0.33) and aerobic training (MD = -1.4 mg/l; 95%CrI, -3.15 to -0.06). Kt/V improved in aerobic training (MD = 0.11; 95%CrI, 0.02 to 0.18), and SF-36 physical functioning outcomes improved in resistance training (MD = 10.66 points; 95%Crl, 1.91 to 20.22). No intradialytic exercise modality was superior to others or comparable with home-based training in improving the evaluated outcomes. Subgroup analysis revealed that exercise interventions >12 weeks improved functional capacity more than interventions ≤12 weeks, and that combined training reduces diastolic blood pressure only after 12 weeks of follow-up. Furthermore, our results suggest that moderate or moderate-to-vigorous intensity training leads to more pronounced improvements in functional capacity, whereas mild or mild-to-moderate intensity training does not have the same effect. In this review, most of the included studies were assessed as having some concern, which resulted in a low to very low level of confidence in the overall findings. CONCLUSIONS: Both intradialytic training and home-based training can promote benefits for individuals undergoing hemodialysis, with no evidence of the superiority of either training modality over the other.

Hospital Mortality from Myocardial Infarction in Latin America and the Caribbean: Systematic Review and Meta-Analysis. / Mortalidade Hospitalar Por Infarto do Miocárdio na América Latina e no Caribe: Revisão Sistemática e Metanálise.

BACKGROUND: Most cardiovascular deaths occur in low- and middle-income countries and myocardial infarction is one of the main life-threatening conditions. OBJECTIVE: We assessed all-cause in-hospital mortality in patients admitted for myocardial infarction (STEMI and NSTEMI) in Latin America and the Caribbean from 2000 onward. METHODS: We systematically searched in electronic bibliographic databases for cohort studies which reported in-hospital mortality due to STEMI and NSTEMI. A meta-analysis was performed and a p-value < 0.05 was considered significant. RESULTS: We identified 38 studies (29 STEMI, 3 NSTEMI and 6 both). Pooled STEMI in-hospital mortality was 9.9% (95% CI: 9.1 - 10.7). Heterogeneity was not trivial (I2 = 74% and prediction interval = 6.6 - 14.5). The percentage of reperfusion therapy and decade explain part of the heterogeneity (I2 = 54%). The higher the rate of reperfusion therapy, the lower the in-hospital mortality (coefficient = -0.009, 95% CI: -0.013 to -0.006, p<0.001). This mortality was higher in the first decade as compared with the second (coefficient = -0.14, 95% CI: -0.27 to -0.02, p=0.047). Pooled NSTEMI in-hospital mortality was 6.3% (95% CI: 5.4 - 7.4) and heterogeneity was null. CONCLUSION: Pooled STEMI in-hospital mortality in low- and middle-income countries was high in comparison with rates reported in high income countries. To improve these estimates, higher use of reperfusion therapy must be pursued. Pooled NSTEMI in-hospital mortality was similar to the ones found in high-income countries; however, it was based on few studies and most of them were carried out in two countries.

FUNDAMENTO: A maioria das mortes por doenças cardiovasculares ocorrem em países de renda baixa e média, e o infarto do miocárdio é uma das condições com maior risco de morte. OBJETIVOS: Avaliar a mortalidade hospitalar por todas as causas em pacientes admitidos por infarto do miocárdio (IAMCSST e IAMSSST) na América Latina e no Caribe no ano de 2000 em diante. MÉTODOS: Realizamos uma busca sistemática em bancos de dados eletrônicos por estudos do tipo coorte que relataram morte hospitalar por IAMCSST e IAMSSST. Foi realizada uma metanálise e um valor de p<0,05 foi considerado estatisticamente significativo. RESULTADOS: Identificamos 38 estudos (29 com pacientes com IAMCSST, 3 com IAMSSST e 6 com IAMCSST e IAMSSST). A mortalidade por IAMCSST agrupada foi de 9,9% (IC95%: 9,1 ­ 10,7). Observou-se importante heterogeneidade (I2 = 74% e o intervalo de predição foi de 6,6 ­ 14.5). A porcentagem de terapia de reperfusão e a década em que os estudos foram conduzidos explicam parte dessa heterogeneidade (I2 = 54%). Quanto maior a taxa de terapia de reperfusão, menor a mortalidade hospitalar (coeficiente = −0,009, IC95%: −0,013 a −0,006, p<0,001). A mortalidade foi maior na primeira década em comparação com a mortalidade na segunda década (coeficiente = −0,14, IC95%: −0,27 a −0,02, p=0,047). A mortalidade hospitalar por IAMSSST foi de 6,3% (IC95%: 5,4 ­ 7,4) e a heterogeneidade foi nula. CONCLUSÃO: A mortalidade por IAMCSST em países de renda baixa e média foi maior em comparação com as taxas relatadas em outros países. Para melhorar essas estimativas, deve-se buscar um maior uso de terapia de reperfusão. A mortalidade hospitalar por IAMSSST agrupada foi similar às taxas descritas em países de alta renda. Contudo, esse dado foi baseado em poucos estudos, cuja maioria foi conduzida em dois países.

Mortalidade Hospitalar Por Infarto do Miocárdio na América Latina e no Caribe: Revisão Sistemática e Metanálise / Hospital Mortality from Myocardial Infarction in Latin America and the Caribbean: Systematic Review and Meta-Analysis

Resumo Fundamento: A maioria das mortes por doenças cardiovasculares ocorrem em países de renda baixa e média, e o infarto do miocárdio é uma das condições com maior risco de morte. Objetivos: Avaliar a mortalidade hospitalar por todas as causas em pacientes admitidos por infarto do miocárdio (IAMCSST e IAMSSST) na América Latina e no Caribe no ano de 2000 em diante. Métodos: Realizamos uma busca sistemática em bancos de dados eletrônicos por estudos do tipo coorte que relataram morte hospitalar por IAMCSST e IAMSSST. Foi realizada uma metanálise e um valor de p<0,05 foi considerado estatisticamente significativo. Resultados: Identificamos 38 estudos (29 com pacientes com IAMCSST, 3 com IAMSSST e 6 com IAMCSST e IAMSSST). A mortalidade por IAMCSST agrupada foi de 9,9% (IC95%: 9,1 - 10,7). Observou-se importante heterogeneidade (I2 = 74% e o intervalo de predição foi de 6,6 - 14.5). A porcentagem de terapia de reperfusão e a década em que os estudos foram conduzidos explicam parte dessa heterogeneidade (I2 = 54%). Quanto maior a taxa de terapia de reperfusão, menor a mortalidade hospitalar (coeficiente = −0,009, IC95%: −0,013 a −0,006, p<0,001). A mortalidade foi maior na primeira década em comparação com a mortalidade na segunda década (coeficiente = −0,14, IC95%: −0,27 a −0,02, p=0,047). A mortalidade hospitalar por IAMSSST foi de 6,3% (IC95%: 5,4 - 7,4) e a heterogeneidade foi nula. Conclusão: A mortalidade por IAMCSST em países de renda baixa e média foi maior em comparação com as taxas relatadas em outros países. Para melhorar essas estimativas, deve-se buscar um maior uso de terapia de reperfusão. A mortalidade hospitalar por IAMSSST agrupada foi similar às taxas descritas em países de alta renda. Contudo, esse dado foi baseado em poucos estudos, cuja maioria foi conduzida em dois países.

Abstract Background: Most cardiovascular deaths occur in low- and middle-income countries and myocardial infarction is one of the main life-threatening conditions. Objective: We assessed all-cause in-hospital mortality in patients admitted for myocardial infarction (STEMI and NSTEMI) in Latin America and the Caribbean from 2000 onward. Methods: We systematically searched in electronic bibliographic databases for cohort studies which reported in-hospital mortality due to STEMI and NSTEMI. A meta-analysis was performed and a p-value < 0.05 was considered significant. Results: We identified 38 studies (29 STEMI, 3 NSTEMI and 6 both). Pooled STEMI in-hospital mortality was 9.9% (95% CI: 9.1 - 10.7). Heterogeneity was not trivial (I2 = 74% and prediction interval = 6.6 - 14.5). The percentage of reperfusion therapy and decade explain part of the heterogeneity (I2 = 54%). The higher the rate of reperfusion therapy, the lower the in-hospital mortality (coefficient = −0.009, 95% CI: −0.013 to −0.006, p<0.001). This mortality was higher in the first decade as compared with the second (coefficient = −0.14, 95% CI: −0.27 to −0.02, p=0.047). Pooled NSTEMI in-hospital mortality was 6.3% (95% CI: 5.4 - 7.4) and heterogeneity was null. Conclusion: Pooled STEMI in-hospital mortality in low- and middle-income countries was high in comparison with rates reported in high income countries. To improve these estimates, higher use of reperfusion therapy must be pursued. Pooled NSTEMI in-hospital mortality was similar to the ones found in high-income countries; however, it was based on few studies and most of them were carried out in two countries.

New approaches to the effectiveness of inhalation aromatherapy in controlling painful conditions: A systematic review with meta-analysis.

OBJECTIVE: Gather scientific evidence on the application of inhalation aromatherapy for pain relief and estimate the effect measure of this practice on pain reduction. METHODS: Searches were performed in 2021 in the Pubmed, Scopus, Web of Science, Cochrane, Science direct, Lilacs, Scielo databases. We selected 44 articles demonstrating the effect of aromatherapy on different painful conditions, of which 17 were inserted in the meta-analysis. The risk of bias was assessed according to Cochrane methodology. RESULTS: In 35 (79.55%) studies was observed a significant reduction in pain, especially pain labor and postoperative pain. Through the meta-analysis, it was found that inhalation aromatherapy reduces by up to -1.73 points of the visual analog scale (VAS), indicating that this practice contributes to the reduction of pain perception in different painful conditions. In addition, the meta-analysis indicated that the time after inhalation, the type of oil used and the type of pain treated are important variables that interfere with the magnitude of the effect. These effects are attributed to the ability of essential oils to modulate nerve control centers and neurotransmission systems involved in pain control. CONCLUSION: From the gathering of articles on aromatherapy, it can be noted that aromatherapy appears to be helpful in alleviating acute pain, however there is an imminent need to improve aromatherapy studies to reduce the risk of bias and increase the power of its clinical evidence. PROSPERO: CRD42019121665.

Citrus Extract as a Perspective for the Control of Dyslipidemia: A Systematic Review With Meta-Analysis From Animal Models to Human Studies.

This study aims to obtain scientific evidence on the use of Citrus to control dyslipidemia. The surveys were carried out in 2020 and updated in March 2021, in the PubMed, Scopus, LILACS, and SciELO databases, using the following descriptors: Citrus, dyslipidemias, hypercholesterolemia, hyperlipidemias, lipoproteins, and cholesterol. The risk of bias was assessed according to the Cochrane methodology for clinical trials and ARRIVE for preclinical trials. A meta-analysis was performed using the application of R software. A total of 958 articles were identified and 26 studies demonstrating the effectiveness of the Citrus genus in controlling dyslipidemia were selected, of which 25 were included in the meta-analysis. The effects of Citrus products on dyslipidemia appear consistently robust, acting to reduce total cholesterol, LDL, and triglycerides, in addition to increasing HDL. These effects are associated with the composition of the extracts, extremely rich in antioxidant, as flavonoids, and that act on biochemical targets involved in lipogenesis and beta-oxidation. The risk of bias over all of the included studies was considered critically low to moderate. The meta-analysis demonstrated results favorable to control dyslipidemia by Citrus products. On the other hand, high heterogeneity values were identified, weakening the evidence presented. From this study, one can suggest that Citrus species extracts are potential candidates for dyslipidemia control, but more studies are needed to increase the strength of this occurrence.

Thiazide diuretics alone or in combination with a potassium-sparing diuretic on blood pressure-lowering in patients with primary hypertension: protocol for a systematic review and network meta-analysis.

BACKGROUND: The use of thiazide (T) diuretics for the treatment of hypertension may be associated with adverse metabolic effects, which can be minimized by combining thiazides with potassium-sparing (PS) diuretics. The additional blood pressure (BP)-lowering effect provided by the addition of a PS diuretic is unclear. Due to a large number of drugs in the T diuretics class, and the possible difference between them, there is a need to identify the best available evidence for health decision-making. This systematic review with network meta-analysis aims to compare the antihypertensive efficacy of T diuretics alone or in combination with a PS diuretic in patients with primary hypertension, as well as the safety of such drugs through the measurement of drug-related adverse events. METHODS: A comprehensive electronic search will be conducted in six electronic bibliographic databases (PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, Scopus, Lilacs), a registration database ( ClinicalTrials.gov ), and Educational Resources Information Center (ERIC [ProQuest]), published from inception to the date of the search. The search will be updated towards the end of the review. A hand search of the reference sections of the included studies and cited studies will also be performed. In case of missing data, authors will be contacted by e-mail or academic social networking sites whenever possible. To be included in the review, studies must be double-blind randomized controlled trials evaluating T diuretics alone or in combination with PS diuretics in patients with primary hypertension. The primary outcome measure will be office BP. Ambulatory BP monitoring (ABPM), non-melanoma skin cancer, major adverse cardiovascular events, laboratory parameters, and the number of withdrawals will be included as secondary outcomes. The results will be quantitatively summarized using differences between the mean change from baseline or differences between means for quantitative outcomes and relative risk for dichotomous outcomes. Results will be presented as mean or relative risk with credible intervals through a league table. The treatments will also be ranked using the surface under the cumulative ranking curve method. The risk of bias will be assessed through the RoB 1.0 tool. DISCUSSION: To the best of our knowledge, this review will be the first to synthesize currently available evidence on the antihypertensive efficacy of different T diuretics alone or in combination with PS diuretics in adults with hypertension. The goals of hypertension treatment are to control high BP and to reduce associated cardiovascular morbidity and mortality, using the most appropriate therapy. Thiazides are widely used for pharmacological treatment due to their demonstrated effectiveness in reducing BP, favorable safety profile, and low cost. The results of this study will provide evidence regarding the best therapeutic strategies with T and PS diuretics, evidencing interventions with better antihypertensive efficacy and safety profile. TRIAL REGISTRATION: This systematic review and network meta-analysis was prospectively registered at the PROSPERO database ( CRD42018118492 ).

The effect of mobile health focused on diet and lifestyle on blood pressure: a systematic review and meta-analysis.

To determine the effect of mobile health (mHealth) focused on diet and lifestyle on blood pressure (BP). We performed a systematic review with meta-analysis using the mean difference (MD) of change from baseline as an effect measure. MEDLINE via PubMed, Cochrane Central, and EMBASE were reviewed until 6 May 2020. We included randomized controlled trials of adults who participated in mHealth focused on diet and lifestyle. Interventions were grouped according to the presence of health professional intervention (PI) (PI + mHealth or mHealth only). Eligible controls did not participate in mHealth and were classified as active comparator (PI) or no intervention (NI). Subgroup analyses were performed according to the presence of prior cardiovascular disease and hypertension status. We included 44 trials involving 24 692 participants. Mobile health interventions were superior to NI in reducing SBP in both situations: alone [MD = -1.8 mmHg; 95% confidence interval (CI): -3.6; 0.0] or with PI (MD = -5.3 mmHg; 95% CI: -7.5; -3.1), with a greater effect size in the latter group (P = 0.016). This benefit was not observed when the control was PI. DBP and SBP had consistent results. There was a marked effect of PI + mHealth vs. NI on the BP reduction among hypertensive participants. Current evidence shows that mHealth focused on diet and lifestyle can reduce BP, especially when implemented in hypertensive participants, and PI may provide additional benefit. PROSPERO ID CRD42019141475.

ABC2-SPH risk score for in-hospital mortality in COVID-19 patients: development, external validation and comparison with other available scores.

OBJECTIVES: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones. METHODS: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients. RESULTS: Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO2/FiO2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833-0.885]) and Spanish (0.894 [95% CI 0.870-0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). CONCLUSIONS: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.

Clinical characteristics and outcomes of patients hospitalized with COVID-19 in Brazil: Results from the Brazilian COVID-19 registry.

OBJECTIVES: To describe the clinical characteristics, laboratory results, imaging findings, and in-hospital outcomes of COVID-19 patients admitted to Brazilian hospitals. METHODS: A cohort study of laboratory-confirmed COVID-19 patients who were hospitalized from March 2020 to September 2020 in 25 hospitals. Data were collected from medical records using Research Electronic Data Capture (REDCap) tools. A multivariate Poisson regression model was used to assess the risk factors for in-hospital mortality. RESULTS: For a total of 2,054 patients (52.6% male; median age of 58 years), the in-hospital mortality was 22.0%; this rose to 47.6% for those treated in the intensive care unit (ICU). Hypertension (52.9%), diabetes (29.2%), and obesity (17.2%) were the most prevalent comorbidities. Overall, 32.5% required invasive mechanical ventilation, and 12.1% required kidney replacement therapy. Septic shock was observed in 15.0%, nosocomial infection in 13.1%, thromboembolism in 4.1%, and acute heart failure in 3.6%. Age >= 65 years, chronic kidney disease, hypertension, C-reactive protein ≥ 100mg/dL, platelet count < 100×109/L, oxygen saturation < 90%, the need for supplemental oxygen, and invasive mechanical ventilation at admission were independently associated with a higher risk of in-hospital mortality. The overall use of antimicrobials was 87.9%. CONCLUSIONS: This study reveals the characteristics and in-hospital outcomes of hospitalized patients with confirmed COVID-19 in Brazil. Certain easily assessed parameters at hospital admission were independently associated with a higher risk of death. The high frequency of antibiotic use points to an over-use of antimicrobials in COVID-19 patients.

First-line Treatment of Metastatic Renal Cell Carcinoma in the Immuno-oncology Era: Systematic Review and Network Meta-analysis.

Combination treatments with immuno-oncology (IO) agents and IO agents plus a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) have been approved for first-line treatment of patients with metastatic renal cell carcinoma (mRCC). No direct comparisons have been performed among these treatment options. We performed a systematic review and network meta-analysis to compare and rank the available regimens for first-line treatment in terms of survival benefit and efficacy. In accordance with the Preferred Reporting Items for Systematic Review statement, a systematic search of reported studies was performed in MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE up to May 31, 2019. Network meta-analysis models were adjusted using the Bayesian method. Four randomized clinical trials, with a total of 3758 patients, met the inclusion criteria. Considering systemic therapy, 1880 patients had received sunitinib and 550, 432, 442, and 454 patients had received ipilimumab plus nivolumab (ipi + nivo), pembrolizumab plus axitinib (pembro + axi), avelumab plus axitinib (avelu + axi), and atezolizumab plus bevacizumab (atezo + bev). No difference was found in overall survival between ipi + nivo and pembro + axi for the intention to treat population (hazard ratio [HR], 1.34; 95% credible interval [CrI], 0.92-1.97). No difference was found in progression-free survival among the treatments. The overall response rate (ORR) was superior with pembro + axi and avelu + axi compared with the ORR with the other treatments (atezo + bev vs. pembro + axi: HR, 0.66; 95% CrI, 0.52-0.84; ipi + nivo vs. pembro + axi: HR, 0.73; 95% CrI, 0.59-0.90; atezo + bev vs. avelu + axi: HR, 0.55; 95% CrI, 0.43-0.71; avelu + axi vs. ipi + nivo: HR, 1.66; 95% CrI, 1.31-2.12), with no differences across them (HR, 1.21; 95% CrI, 0.95-1.53). In the present indirect comparison, for an intention to treat population, we found no survival differences between pembro + axi and ipi + nivo. All treatments showed better progression-free survival compared with sunitinib that was similar among them. The combination of an IO agent (pembrolizumab or avelumab) and axitinib seemed to be the most effective therapy for the ORR.

Splenic flexure mobilization in sigmoid and rectal cancer resections: a meta-analysis of surgical outcomes. / Mobilização da flexura esplênica nas ressecções dos tumores de reto e sigmoide: meta-análise dos resultados cirúrgicos.

OBJECTIVE: to evaluate the influence of the splenic flexure mobilization for the main surgical outcomes of patients submitted to resection of sigmoid and rectal cancer. METHODS: we searched the MEDLINE, Cochrane Central Register of Controlled Trials and LILACS, using the terms "splenic flexure mobilization", "colorectal surgery", "rectal cancer", "anterior resection", "sigmoid colon cancer", and "sigmoid resection". The main outcome was anastomotic dehiscence. Other outcomes analyzed were mortality, bleeding, infection and general complications. We estimated the effect sizes by grouping data from six case-control studies (1,433 patients) published until January 2018. RESULTS: our meta-analysis showed that patients undergoing complete mobilization of the splenic flexure had a higher risk of anastomotic dehiscence (RR=2.27, 95%CI: 1.22-4.23) compared with those not submitted to this procedure. There was no difference between the groups in terms of mortality, bleeding, infection and general complications. CONCLUSION: splenic flexure mobilization is associated with a higher risk of anastomotic dehiscence in resections of sigmoid and rectal cancer. This surgical maneuver should be used with caution in the surgical management of sigmoid or rectal cancers.

OBJETIVO: avaliar a influência da mobilização da flexura esplênica nos principais resultados cirúrgicos de pacientes submetidos à ressecção de câncer do cólon sigmoide ou reto. MÉTODOS: os bancos de dados MEDLINE, Cochrane Central Register de Ensaios Controlados e LILACS foram pesquisados usando os termos "mobilização da flexura esplênica", "cirurgia colorretal", "câncer retal", "ressecção anterior", "câncer de cólon sigmoide", "ressecção de sigmoide". O desfecho principal foi a deiscência da anastomose. Outros desfechos analisados foram mortalidade, sangramento, infecção e complicações gerais. Os tamanhos dos efeitos foram estimados por meio do agrupamento dos dados de seis estudos de caso-controle (1.433 pacientes) publicados até janeiro de 2018. RESULTADOS: nossa meta-análise revelou que pacientes submetidos à mobilização completa da flexura esplênica tinham um risco maior de deiscência anastomótica (RR=2,27, IC95%: 1,22-4,23) em comparação àqueles não submetidos a esse procedimento. Nenhuma diferença pôde ser demonstrada entre os grupos em termos de mortalidade, sangramento, infecção e complicações gerais. CONCLUSÃO: a mobilização da flexura esplênica está associada a um maior risco de deiscência anastomótica nas ressecções de câncer de reto ou cólon sigmoide. Esta manobra cirúrgica deve ser utilizada com cautela no manejo cirúrgico dos tumores colorretais.

Different light-activation systems associated with dental bleaching: a systematic review and a network meta-analysis.

OBJECTIVES: A systematic review and a network meta-analysis were performed to answer the following research question: "Is there any light-activation protocol capable of improving color change efficacy when associated with an in-office bleaching gel in adults?" MATERIAL AND METHODS: A search was performed in PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and SIGLE without date and/or language restrictions in April 23, 2017 (updated on March 30, 2018). IADR abstracts (1990-2018), unpublished and ongoing trial registries, dissertations, and theses were also searched. Only randomized clinical trials conducted in adults that included at least one group treated with in-office dental bleaching with light activation were included. The risk of bias (RoB) was evaluated using the Cochrane Collaboration tool. A random-effects Bayesian-mixed treatment comparison (MTC) model was used to combine light-activated versus light-free in-office bleaching with direct light-free comparison trials. A meta-analysis with independent analysis (high- and low-concentrate hydrogen peroxide [HP]) was conducted for color change (∆E*, ∆SGU). RESULTS: After the removal of duplicates, title, and abstract screening, 28 studies remained. Nine were considered to be at a low RoB, five were at a high RoB, and the remaining were at an unclear RoB. The MTC analysis showed no significant difference in color change (ΔE* and ΔSGU) between light-activation protocols and light-free in-office bleaching, regardless of the HP concentration in the efficacy of the bleaching. CONCLUSION: No type of light-activated in-office bleaching was superior to light-free in-office bleaching for both high- and low-concentrate in-office bleaching gels (PROSPERO-CRD42017078743). CLINICAL RELEVANCE: Although many times dental professionals use "laser whitening" as a form of marketing, this study confirmed that no type of light-activation for in-office bleaching can improve the bleaching efficacy.

Mobilização da flexura esplênica nas ressecções dos tumores de reto e sigmoide: meta-análise dos resultados cirúrgicos / Splenic flexure mobilization in sigmoid and rectal cancer resections: a meta-analysis of surgical outcomes

RESUMO Objetivo: avaliar a influência da mobilização da flexura esplênica nos principais resultados cirúrgicos de pacientes submetidos à ressecção de câncer do cólon sigmoide ou reto. Métodos: os bancos de dados MEDLINE, Cochrane Central Register de Ensaios Controlados e LILACS foram pesquisados usando os termos "mobilização da flexura esplênica", "cirurgia colorretal", "câncer retal", "ressecção anterior", "câncer de cólon sigmoide", "ressecção de sigmoide". O desfecho principal foi a deiscência da anastomose. Outros desfechos analisados foram mortalidade, sangramento, infecção e complicações gerais. Os tamanhos dos efeitos foram estimados por meio do agrupamento dos dados de seis estudos de caso-controle (1.433 pacientes) publicados até janeiro de 2018. Resultados: nossa meta-análise revelou que pacientes submetidos à mobilização completa da flexura esplênica tinham um risco maior de deiscência anastomótica (RR=2,27, IC95%: 1,22-4,23) em comparação àqueles não submetidos a esse procedimento. Nenhuma diferença pôde ser demonstrada entre os grupos em termos de mortalidade, sangramento, infecção e complicações gerais. Conclusão: a mobilização da flexura esplênica está associada a um maior risco de deiscência anastomótica nas ressecções de câncer de reto ou cólon sigmoide. Esta manobra cirúrgica deve ser utilizada com cautela no manejo cirúrgico dos tumores colorretais.

ABSTRACT Objective: to evaluate the influence of the splenic flexure mobilization for the main surgical outcomes of patients submitted to resection of sigmoid and rectal cancer. Methods: we searched the MEDLINE, Cochrane Central Register of Controlled Trials and LILACS, using the terms "splenic flexure mobilization", "colorectal surgery", "rectal cancer", "anterior resection", "sigmoid colon cancer", and "sigmoid resection". The main outcome was anastomotic dehiscence. Other outcomes analyzed were mortality, bleeding, infection and general complications. We estimated the effect sizes by grouping data from six case-control studies (1,433 patients) published until January 2018. Results: our meta-analysis showed that patients undergoing complete mobilization of the splenic flexure had a higher risk of anastomotic dehiscence (RR=2.27, 95%CI: 1.22-4.23) compared with those not submitted to this procedure. There was no difference between the groups in terms of mortality, bleeding, infection and general complications. Conclusion: splenic flexure mobilization is associated with a higher risk of anastomotic dehiscence in resections of sigmoid and rectal cancer. This surgical maneuver should be used with caution in the surgical management of sigmoid or rectal cancers.

Bipolar Disorder Mixed Episodes: A Pragmatic Trial of a Public Health Treatment Effectiveness.

OBJECTIVES: To evaluate the effectiveness of an algorithm for the treatment of mixed episodes in bipolar disorder (BD) using the medications available under the Unified Health System (Sistema Único de Saúde) in Brazil. METHODS: The study included 107 individuals with BD in a current mixed episode, assessed biweekly for the outcomes of response and remission. The subjects were randomly assigned to start treatment with lithium, valproic acid, or carbamazepine, following a clinical protocol at a public outpatient clinic. Eligibility screening instruments, semistructured interview, and clinical psychiatric evaluation were used for diagnosis. To measure response and remission, the Hamilton Rating Scale for Depression and the Young Mania Rating Scale were used. A parameter of 50% or less in the symptom scales was used to define responses, as assessed by Kaplan-Meier time-event analysis. RESULTS: For the main outcome, response to treatment, all interventions proposed were proven to be effective, with no difference in response time for any of them. There was a lack of placebo control and blinding for intervention or outcomes. Individuals with mixed episodes in BD often face contradictory symptoms, and these inherent difficulties are the main obstacles to stabilize such a condition. CONCLUSIONS: The findings presented in this study show that the treatments available under the Unified Health System are able to reduce the overall burden of disease in terms of symptom reduction.

Association between PCOS and autoimmune thyroid disease: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder affecting women of reproductive age. PCOS has been associated with distinct metabolic and cardiovascular diseases and with autoimmune conditions, predominantly autoimmune thyroid disease (AITD). AITD has been reported in 18-40% of PCOS women, depending on PCOS diagnostic criteria and ethnicity. The aim of this systematic review and meta-analysis was to summarize the available evidence regarding the likelihood of women with PCOS also having AITD in comparison to a reference group of non-PCOS women. We systematically searched EMBASE and MEDLINE for non-interventional case control, cross-sectional, or cohort studies published until August 2017. The Ottawa-Newcastle Scale was used to assess the methodological quality of studies. Statistical meta-analysis was performed with R. Thirteen studies were selected for the present analysis, including 1,210 women diagnosed with PCOS and 987 healthy controls. AITD was observed in 26.03% and 9.72% of PCOS and control groups respectively. A significant association was detected between PCOS and chance of AITD (OR= 3.27, 95%CI 2.32-4.63). Notably, after geographical stratification, the higher risk of AITD in PCOS women persisted for Asians (OR= 4.56, 95%CI 2.47-8.43), Europeans (OR= 3.27, 95%CI 2.07-5.15), and South Americans (OR= 1.86, 95 %CI 1.05-3.29). AIDT is a frequent condition in PCOS patients, and might affect thyroid function. Thus, screening for thyroid function and thyroid-specific autoantibodies should be considered in patients with PCOS even in the absence of overt symptoms. This systematic review and meta-analysis is registered in PROSPERO under number CRD42017079676.