Trakya University

About: Trakya University is a education organization based out in Edirne, Turkey. It is known for research contribution in the topics: Population & Medicine. The organization has 2727 authors who have published 5490 publications receiving 76048 citations. The organization is also known as: University of Thrace & Trakya Üniversitesi.

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial

Abstract: Summary Background Ramucirumab—an IgG1 vascular endothelial growth factor receptor 2 antagonist—plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov , NCT02426125 ; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. Findings Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5–13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3–4·8] vs 2·8 months [2·6–2·9]; HR 0·696 [95% CI 0·573–0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9–11·4) in the ramucirumab group versus 7·9 months (7·0–9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724–1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. Interpretation Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Funding Eli Lilly and Company.

The influence of methylene blue infusion on cytokine levels during severe sepsis.

Abstract: The aim of our study was to assess the effect of methylene blue infusion on plasma levels of cytokines in severe sepsis. In a prospective, randomized, double-blind, placebo-controlled study, patients received either methylene blue 0.5 mg.kg-1.h-1 (MB group, n = 15) or similar volume of isotonic saline (control group, n = 15) i.v. for 6 hours. Plasma concentrations of tumour necrosis factor-alpha, interleukin-1, interleukin-2 receptor, interleukin-6, interleukin-8 were measured by sensitive immunoassays at basal (15 min before start of the study), immediately after, and at 24 and 48 hours after methylene blue infusion. We evaluated haemodynamic parameters (mean arterial pressure, heart rate), blood gases, methaemoglobin levels, and biochemical parameters at the same time. Methylene blue administration had no significant effect on plasma cytokine levels, blood gases and biochemical parameters. When compared to placebo infusion in controls, methylene blue administration resulted in significantly higher mean arterial pressure (85 +/- 14 mmHg vs 74.1 +/- 10.3 mmHg; P < 0.01), and methaemoglobin levels (1.06 +/- 0.22% vs 0.9 +/- 0.05%; P < 0.05). Furthermore, comparison with baseline levels revealed significantly increased both mean arterial pressure (85 +/- 14 mmHg and 74.1 +/- 10.2 mmHg; P < 0.05) and methaemoglobin levels (1.06 +/- 0.22% and 0.88 +/- 0.06%; P < 0.05) in MB group. There was no difference in mortality rates between the groups. We found that methylene blue infusion did not change cytokine levels or outcome in severe sepsis. The administration of methylene blue, however, resulted in a transient increase in arterial pressure. Because of the limited size of the present study, and the short period of observation, our findings need to be confirmed by larger clinical trials of methylene blue infused in a dose-titrated manner.

Exploration of problematic Internet use and social interaction anxiety among Turkish pre-service teachers

Abstract: The current study investigated the relationship between problematic Internet use and social interaction anxiety among pre-service teachers. Participants were 1235 students attending teacher training programs at a Turkish state university. The ''Problematic Internet Use Scale'' and ''Social Interaction Anxiety Scale'' were used to collect the data. Independent-samples t-test and one-way ANOVA were conducted to examine the differences; and correlation and regression analyses were used to examine the relationships between variables. Findings revealed that male students' use of the Internet was more problematic compared to female students'. As the time spent on the Internet increased, so did the problematic Internet use levels. In addition, the problematic Internet use levels of students varied with regard to departments. A significant relationship was found between the level of problematic Internet use and social interaction anxiety, and social interaction anxiety was found to be among the predictors of problematic Internet use. Implications and suggestions for further research are provided.