Effects of topical timolol for the prevention of radiation-induced dermatitis in breast cancer: a pilot triple-blind, placebo-controlled trial.

INTRODUCTION: Radiation therapy is one of the standard methods in the treatment of breast cancer. Radiotherapy-induced dermatitis (RID) is a common complication of radiotherapy (RT) resulting in less tolerance in RT and even discontinuation of treatment. Timolol is a ß-adrenergic receptor antagonist that presents the best wound healing effects on both chronic and incurable wound healing. Topical forms of timolol could be effective in the prevention of RID due to the role of ß-adrenergic receptors in skin cells and keratinocyte migration, as well as the anti-inflammatory effect of timolol. However, no placebo-controlled randomized trial is available to confirm its role. The current trial aimed to evaluate the efficacy of topical timolol 0.5% (w/w) on the RID severity and patients' quality of life (QOL). METHOD: Patients aged older than 18 years with positive histology confirmed the diagnosis of invasive and localized breast cancer were included. Patients were randomized based on the random number table to receive each of the interventions of timolol 0.5% (w/w) or placebo topical gels from the first day of initiation of RT and for 6 weeks, a thin layer of gel twice daily. Patients were asked to use a thin layer of gel for at least two hours before and after radiation therapy. Primary outcomes were acute radiation dermatitis (ARD) grade using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale and severity of desquamation based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Secondary outcomes were QOL based on Skindex16 (SD-16), maximum grade of ARD, and time of initial RD occurrence. RESULTS: A total of 64 female patients with an age range of 33 to 79 years were included. The means (SD) of age were 53.88 (11.02) and 54.88 (12.48) in the control and timolol groups, respectively. Considering the RTOG/EORTC and CTCAE scores the difference between groups was insignificant (P-Value = 0.182 and P-Value = 0.182, respectively). In addition, the mean (SD) of time of initial RID occurrence in placebo and timolol groups were 4.09 (0.588) and 4.53 (0.983) weeks, respectively (P-Value = 0.035). The maximum grade of RID over time was significantly lower in the timolol group. During the study period, 75.0% of patients in placebo groups had grade 2 of ARD while in the timolol group it was 31.3% (P-Value = 0.002). QoL was not significantly different between groups (P-Value = 0.148). CONCLUSION: Although the topical formulation of timolol, 0.5% (w/w), was found to reduce the average maximum grade of ARD and increase the mean (SD) time of initial RID occurrence, it showed no effect on ARD, severity, and QOL. However, future clinical trials should be performed to assess timolol gel formulation in larger study populations. TRIAL REGISTRATION: https://irct.ir/ IRCT20190810044500N11 (17/03/2021).

Effect of livergol on the improvement of fatty liver in patients with cancer undergoing irinotecan- and oxaliplatin-based chemotherapy regimen.

BACKGROUND: The aim of this study was to determine the effect of Livergol on the improvement of fatty liver in patients with cancer undergoing irinotecan- and oxaliplatin-based chemotherapy regimen. MATERIALS AND METHODS: This was an add-on nonrandomized clinical trial study on thirty selected eligible cancer patients undergoing irinotecan (8 patients) and oxaliplatin (22 patients) with diagnosed fatty liver disease-based liver ultrasonography, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Patients in each group received Livergol at a dose of 140 mg daily for 1 month. ALT and AST levels as well as grade of fatty liver were evaluated before and after intervention. RESULTS: In the oxaliplatin/Livergol group, 40% and 44.4% of patients who were in Grade 2 and 3 before intervention were altered to Grades 1 and 2, respectively (P = 0.005), and in irinotecan/Livergol group, the mentioned percentages were 80% and 66.7% (P = 0.014). The mean levels of ALT and AST enzymes were decreased in both groups after tacking Livergol; however, the observed decreases were not significantly different between groups. CONCLUSION: It was concluded that the adding of Livergol to oxaliplatin and irinotecan regimens significantly improved the fatty liver of patients and none of them was superior.

Prevalence of Cannabis Lifetime Use in Iranian High School and College Students: A Systematic Review, Meta-Analyses, and Meta-Regression.

Cannabis is the most widely used substance in the world. This study aimed to estimate the prevalence of cannabis lifetime use (CLU) in high school and college students of Iran and also to determine factors related to changes in prevalence. A systematic review of literature on cannabis use in Iran was conducted according to MOOSE guideline. Domestic scientific databases, PubMed/Medline, ISI Web of Knowledge, and Google Scholar, relevant reference lists, and relevant journals were searched up to April, 2014. Prevalences were calculated using the variance stabilizing double arcsine transformation and confidence intervals (CIs) estimated using the Wilson method. Heterogeneity was assessed by Cochran's Q statistic and I(2) index and causes of heterogeneity were evaluated using meta-regression model. In electronic database search, 4,000 citations were retrieved, producing a total of 33 studies. CLU was reported with a random effects pooled prevalence of 4.0% (95% CI = 3.0% to 5.0%). In subgroups of high school and college students, prevalences were 5.0% (95% CI = 3.0% to -7.0%) and 2.0% (95% CI = 2.0% to -3.0%), respectively. Meta-regression model indicated that prevalence is higher in college students (ß = 0.089, p < .001), male gender (ß = 0.017, p < .001), and is lower in studies with sampling versus census studies (ß = -0.096, p < .001). This study reported that prevalence of CLU in Iranian students are lower than industrialized countries. In addition, gender, level of education, and methods of sampling are highly associated with changes in the prevalence of CLU across provinces.