Tranexamic acid is an antifibrinolytic agent widely used in several surgical procedures to reduce intraoperative bleeding. Intraoperative bleeding is a crucial problem for the ear surgeon, as it prevents good visualization of the surgical field. The aim of this work was to analyze the relevant literature about the use of tranexamic acid in ear surgery. A literature search was conducted in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, across 3 databases (Medline, Cochrane, and Google Scholar), with the terms \"tranexamic acid,\" and \"ear,\" and \"surgery.\" Three prospective, randomized, and double-blind clinical trials met the inclusion criteria. Studies were not able to be pooled because of heterogeneity in material, methods of delivery and evaluation, and procedures used. Despite these limitations, all 3 papers found a significant reduction in intraoperative bleeding, allowing a better visualization of the operating field. Despite the scarcity of published trials, tranexamic acid is safe and seems to be useful in reducing intraoperative bleeding in ear surgery, thus improving operative field visualization.

The risks and benefits of bedaquiline (BDQ) for treatment of drug-resistant tuberculosis (DR-TB) have not been firmly established. We aimed to assess the safety and efficacy of BDQ-containing regimens for the treatment of DR-TB as evidenced in available randomized controlled trials (RCTs). In this systematic review and meta-analysis, five databases (i.e., ClinicalTrials.gov, Cochrane CENTRAL, PubMed, ScienceDirect, and SinoMed) were searched. RCTs among DR-TB patients that had a control arm were eligible. The safety endpoints were all-cause mortality and serious adverse effects (SAEs). Efficacy outcomes were sputum culture conversion rate at 8-12 weeks and 24-26 weeks, treatment success, and time to culture conversion. A total of 476 records were screened; 18 met the eligibility criteria. The pooled analysis included 2520 participants (55.8% received BDQ-containing regimens, n = 1408). Pooled safety outcomes showed no significant reduction in all-cause mortality (relative risk [RR] [95%confidence interval (CI)] = 0.94 [0.41-2.20]) or SAEs (RR [95%CI] = 0.91 [0.67-1.23]) in the BDQ-regimen group. Pooled efficacy outcomes showed significantly superior culture conversion rates at 8-12 weeks (RR [95%CI] = 1.35 [1.10-1.65]) and 24-26 weeks (RR [95%CI] = 1.25 [1.15-1.36]), more treatment success (RR [95%CI] = 1.30 [1.17-1.44]), and a 17-day reduction in the time to culture conversion (standardized mean difference [SMD] [95%CI] = -17.46 [-34.82 to -0.11]) in the BDQ-regimen group (reference: non-BDQ regimen). Overall, BDQ regimens showed significant treatment effect against DR-TB but did not reduce mortality or SAEs.

BACKGROUND: The association between opioid use and the risk of ventricular arrhythmias (VA) is poorly understood.
OBJECTIVE: The objective of this study was to synthesize the evidence on the risk of VA associated with opioid use.
METHODS: We systematically searched the Cochrane Library, Embase, MEDLINE, and CINAHL databases in July 2022. Risk of bias was assessed using the Cochrane risk for bias tool for randomized controlled trials (RCTs) and ROBINS-I for observational studies. Certainty of evidence was assessed using GRADE.
RESULTS: We included 15 studies (12 observational, 2 post hoc analyses of RCTs, 1 RCT). Most studies focused on opioid use for maintenance therapy (n = 9), comparing methadone to buprenorphine (n = 13), and reported QTc prolongation (n = 13). Six observational studies had a critical risk of bias, and one RCT was at high risk of bias. Two studies could not be included in the meta-analysis as they reported a different outcome and studied an opioid antagonist. Meta-analysis of 13 studies indicated that the use of methadone was associated with an increased risk of VA compared to the use of buprenorphine, morphine, placebo, or levacetylmethadol (risk ratio [RR], 2.39; 95% CI, 1.31-4.35; I2 = 60%). The pooled estimate varied greatly between observational studies (RR, 2.12; 95% CI, 1.15-3.91; I2 = 62%) and RCTs (RR, 14.09; 95% CI, 1.52-130.61; I2 = 0%), but both indicated an increased risk.
CONCLUSIONS: In this systematic review and meta-analysis, we found that methadone use is associated with more than twice the risk of VA compared to comparators. However, our findings should be interpreted cautiously given the limited quality of the available evidence.

OBJECTIVE: To systematically review and meta-analyse the efficacy of resistance training on quality of life (QOL), fatigue, physical function, and muscular strength in people diagnosed with cancer undergoing chemotherapy.
METHODS: Electronic databases PubMed, Cochrane Central, CINAHL, SCOPUS and Web of Science were systematically searched for randomised controlled trials (RCTs) that compared the effects of resistance training to control on QOL, fatigue, physical function, and lower-body and upper-body muscular strength in adults undergoing chemotherapy. Standardised mean differences (SMDs) were pooled using a random effects model. Risk of bias was assess using the risk of bias tool for randomised trials (RoB 2).
RESULTS: Seven RCTs encompassing 561 participants were included. The pooled results of seven RCTs showed that resistance training during chemotherapy significantly improved lower-body strength (n = 555, SMD 0.33, 95% CI 0.12 to 0.53, moderate-quality evidence, I2 = 23%) compared to control. There was no evidence for an effect of resistance training on QOL (n = 373, SMD 0.13, 95% CI -0.15 to 0.42, low-quality evidence, I2 = 0%), fatigue (n = 373, SMD -0.08, 95% CI -0.37 to 0.22, low-quality evidence, I2 = 20%), physical function (n = 198, SMD 0.61, 95% CI -0.73 to 1.95, very low-quality evidence, I2 = 83%), or upper-body strength (n = 413, SMD 0.37, 95% CI -0.07 to 0.80, very low-quality evidence, I2 = 69%).
CONCLUSIONS: Resistance training may improve lower-body strength in patients undergoing chemotherapy treatment compared to control.

Hypoxic-ischaemic encephalopathy (HIE) is a major cause of mortality and neurodevelopmental disability, especially in low-income countries. While therapeutic hypothermia has been shown to reduce morbidity and mortality in infants with HIE, some clinical trials in low-income countries have reported an increase in the risk of mortality. We conducted a systematic review and meta-analysis of all randomized and quasi-randomized controlled trials conducted in low-income and lower-middle-income countries that compared cooling therapy with standard care for HIE. Our primary outcome was composite of neonatal mortality and neurodevelopmental disability at 6 months or beyond. The review was registered with PROSPERO (CRD42022352728). Our review included 11 randomized controlled trials with 1324 infants with HIE. The composite of death or disability at 6 months or beyond was lower in therapeutic hypothermia group (RR 0.78, 95% CI 0.66-0.92, I2 = 85%). Neonatal mortality rate did not differ significantly between cooling therapy and standard care (RR 0.92, 95% CI 0.76-1.13, I2 = 61%). Additionally, the cooled group exhibited significantly lower rates of neurodevelopmental disability at or beyond 6 months (RR 0.34, 95%CI 0.22-0.52, I2 = 0%). Our analysis found that neonatal mortality rate did not differ between cooled and noncooled infants in low- and lower-middle-income countries. Cooling may have a beneficial effect on neurodevelopmental disability and the composite of death or disability at 6 months or beyond.

BACKGROUND: Dexamethasone is associated with increased blood glucose levels that could impact patient outcomes or management. This study aimed to synthesize the available evidence regarding the impact of an intraoperative single dose of dexamethasone on blood glucose levels.
METHODS: We searched CENTRAL, MEDLINE, and clinicaltrials.gov for randomized controlled trials (RCTs) comparing a single intraoperative dose of dexamethasone to control in adult patients who underwent noncardiac surgery. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the review was registered in PROSPERO (CRD42023420562). Data were pooled using a random-effects model. We reported pooled dichotomous data using odds ratios (OR) and continuous data using the mean difference (MD), reporting 95% confidence intervals (95% CIs), and corresponding P-values for both. Confidence in the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. As primary outcomes we assessed maximum blood glucose levels measurement and variation from baseline within 24 hours of surgery; blood glucose levels measurement and variation from baseline at 2, 4, 8, 12, and 24 hours after dexamethasone administration. As secondary outcomes, we evaluated insulin requirements and hyperglycemic events.
RESULTS: We included 23 RCTs, enrolling 11,154 participants overall. Dexamethasone was associated with a significant increment in blood glucose levels compared to control at all timepoints. The results showed an increase compared to control of 0.37 mmol L-1 (6.7 mg dL-1) at 2 hours (95% CI, 0.16-0.58 mmol L-1 or 2.9-10.5 mg dL-1), 0.97 mmol L-1 (17.5 mg dL-1) at 4 hours (95% CI, 0.67-1.25 mmol L-1 or 12.1-22.5 mg dL-1), 0.96 mmol L-1 (17.3 mg dL-1) at 8 hours (95% CI, 0.55-1.36 mmol L-1 or 9.9-24.5 mg dL-1), 0.90 mmol L-1 (16.2 mg dL-1) at 12 hours (95% CI, 0.62-1.19 mmol L-1 or 11.2-21.4 mg dL-1) and 0.59 mmol L-1 (10.6 mg dL-1) at 24 hours (95% CI, 0.22-0.96 mmol L-1 or 4.0-17.3 mg dL-1). No difference was found between subgroups regarding diabetic status (patients with diabetes versus patients without diabetes) in all the outcomes except 2 (maximum blood glucose levels variation within 24 hours and variation at 4 hours) and dexamethasone dose (4-5 mg vs 8-10 mg) in all the outcomes except 2 (blood glucose levels at 24 hours and hyperglycemic events).
CONCLUSIONS: Mean blood glucose levels rise between 0.37 and 1.63 mmol L-1 (6.7 and 29.4 mg dL-1) within 24 hours after a single dose of dexamethasone administered at induction of anesthesia compared to control, but in most patients this difference will not be clinically relevant.

BACKGROUND: The perioperative use of dexamethasone in diabetic patients remains controversial due to concerns related to infection and adverse events. This study aimed to determine whether clinical evidence supports withholding dexamethasone in diabetic patients due to concern for infection risk. We hypothesized that there is no difference in infectious outcomes between dexamethasone-treated patients and controls.
METHODS: A literature search was performed on November 22, 2022 to identify randomized, placebo-controlled trials investigating short-course (<72 hours), perioperative dexamethasone that explicitly included diabetic patients and measured at least 1 clinical outcome. Pertinent studies were independently searched in PubMed, Embase, and Cochrane. Authors for all identified studies were contacted with the aim of performing quantitative subgroup analyses of diabetic patients. The primary end point was surgical site infection and the secondary end point was a composite of adverse events. Qualitative remarks were reported based on the total available data and a quality assessment tool. Meta-analyses were performed using inverse variance with random effects. Heterogeneity was assessed via standard χ2 and I2 tests.
RESULTS: Sixteen unique studies were included, 5 of which were analyzed quantitatively. Of the 2592 diabetic patients, 2344 (1184 randomized to dexamethasone and 1160 to placebo) were analyzed in at least 1 quantitative outcome. Quantitative analysis showed that the use of perioperative dexamethasone had no effect on the risk of surgical site infections (log odds ratio [LOR], -0.10, 95%; 95% confidence interval [CI], -0.64 to 0.44) while significantly reducing the risk of composite adverse events (LOR, -0.33; 95% CI, -0.62 to -0.05). Qualitative analysis reinforced these findings, demonstrating noninferior to superior results across all clinical outcomes. There was high heterogeneity between the included studies.
CONCLUSIONS: Current evidence suggests perioperative dexamethasone may be given to diabetic patients without increasing the risk of infectious complications. Prospective investigations aimed at optimizing dose, frequency, and timing are needed, as well as studies aimed explicitly at exploring the use of dexamethasone in patients with poorly controlled diabetes.

BACKGROUND: Cardiovascular disease (CVD) remains the foremost cause of mortality globally. Taurine, an amino acid, holds promise for cardiovascular health through mechanisms such as calcium regulation, blood pressure reduction, and antioxidant and anti-inflammatory effects. Despite these potential benefits, previous studies have yielded inconsistent results. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the existing evidence on the quantitative effects of taurine on hemodynamic parameters and cardiac function grading, which are indicative of overall cardiovascular health and performance.
METHODS: We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, from their inception to January 2, 2024. Our analysis focused on key cardiovascular outcomes, such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) Functional Classification. Meta-regression was applied to explore dose-dependent relationships based on the total taurine dose administered during the treatment period. A subgroup analysis, stratified according to the baseline disease status of patients, was also conducted.
RESULTS: The analysis included a pooled sample of 808 participants from 20 randomized controlled trials. Taurine demonstrated a significant reduction in HR (weighted mean difference [WMD] = -3.579 bpm, 95% confidence interval [CI] = -6.044 to -1.114, p = 0.004), SBP (WMD = -3.999 mm Hg, 95% CI = -7.293 to -0.706, p = 0.017), DBP (WMD: -1.435 mm Hg, 95% CI: -2.484 to -0.386, p = 0.007), NYHA (WMD: -0.403, 95% CI: -0.522 to -0.283, p < 0.001), and a significant increase in LVEF (WMD: 4.981%, 95% CI: 1.556 to 8.407, p = 0.004). Meta-regression indicated a dose-dependent reduction in HR (coefficient = -0.0150 per g, p = 0.333), SBP (coefficient = -0.0239 per g, p = 0.113), DBP (coefficient = -0.0089 per g, p = 0.110), and NYHA (coefficient = -0.0016 per g, p = 0.111), and a positive correlation with LVEF (coefficient = 0.0285 per g, p = 0.308). No significant adverse effects were observed compared to controls. In subgroup analysis, taurine significantly improved HR in heart failure patients and healthy individuals. Taurine significantly reduced SBP in healthy individuals, heart failure patients, and those with other diseases, while significantly lowered DBP in hypertensive patients It notably increased LVEF in heart failure patients and improved NYHA functional class in both heart failure patients and those with other diseases.
CONCLUSIONS: Taurine showed noteworthy effects in preventing hypertension and enhancing cardiac function. Individuals prone to CVDs may find it advantageous to include taurine in their daily regimen.

OBJECTIVE: Sphingosine 1-phosphate receptor modulators (S1PRMs) are an effective treatment for ulcerative colitis (UC). This review summarizes all available randomized trial data on the efficacy and safety of S1PRM therapy.
METHODS: Multiple publication databases were systematically searched for randomized control trials (RCTs) of adults with moderate to severe UC treated with S1PRMs. Random effects meta-analysis was performed. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool, and the overall quality of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.
RESULTS: We identified 7 RCTs (1737 patients) involving the use of S1PRMs for moderate to severe UC. During induction, S1PRM therapy was efficacious when compared with placebo for clinical remission [RR: 2.65 (95% CI: 2.00, 3.53)], clinical response [RR: 1.68 (95% CI: 1.48, 1.91)], endoscopic improvement [RR: 2.17 (95% CI: 1.76, 2.68)], endoscopic normalization [RR: 2.56 (95% CI: 1.58, 3.83)], mucosal healing [RR: 2.88 (95% CI: 1.94, 4.26)], and histologic remission [RR: 2.42 (95% CI: 1.60, 3.66)]. Similar results were seen throughout the maintenance peroid, although fewer data were available to pool; notably, both sustained [RR: 3.57 (95% CI: 1.23, 10.35)] and steroid-free [RR: 2.92 (95% CI: 1.35, 6.33)] remission were significantly increased by S1PRM. There were no significant differences in adverse events [RR: 1.02 (95% CI: 0.90, 1.15)] and infections [RR: 1.15 (95% CI: 0.82, 1.60)] between S1PRM and placebo.
CONCLUSIONS: Pooling of RCT data confirms that S1PRM therapy is both effective and safe for patients with moderate to severe UC.

BACKGROUND: Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation.
METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs.
RESULTS: The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, I2 = 49.6%). The subgroup dose-response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400-1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% CI: 0.85 to 0.99, I2 = 55.7%, number needed to treat [NNT]: 36), trials duration < 4 months (RR: 0.81, 95% CI: 0.67 to 0.97, I2 = 48.8%, NNT: 16), summer-sparing seasons (RR: 0.85, 95% CI: 0.74 to 0.98, I2 = 55.8%, NNT: 26), and winter-dominant seasons (RR: 0.79, 95% CI: 0.71 to 0.89, I2 = 9.7%, NNT: 10).
CONCLUSIONS: Vitamin D supplementation may slightly prevent ARIs when taken daily at doses between 400 and 1200 IU/d during spring, autumn, or winter, which should be further examined in future clinical trials.