RESEARCH DESIGN AND METHOD: We reviewed a number of published articles from 2002 to 2016 to find out the appropriate management of diabetes mellitus. The paramount parameters of the selected studies include the insulin type & its dose, type of diabetes, duration and comparison of different insulin protocols. In addition, various newly developed approaches for insulin delivery with potential output have also been evaluated.

RESULTS: A great variability was observed in managing diabetes mellitus through insulin therapy and the important controlling factors found for this therapy include; dose titration, duration of insulin use, type of insulin used and combination therapy of different insulin.

METHOD: Terms of "Vortioxetine" OR "LuAA21004" AND "anxiety" OR "fear" OR "panic" OR "phobia" were searched. A total of two phase II and five phase III clinical trials were found.

RESULTS: Vortioxetine was overall superior to placebo in terms of the mean change from baseline in HAM-A total score at week 8 with the pool effect size of -2.95, 95% CIs, -4.37 to -1.53, p<0.01. The patients who received 5 mg of Vortioxetine had higher response rate when compared to placebo (pooled odds ratio=1.4, 95% CI = 1.08 to 1.82, p=0.01). However, the pooled odds ratio of the HAMA remission rate was not statistically significant for both Vortioxetine and placebo (pooled odds ratio= 1.06, 95% CI = 0.86 to 1.30, p=0.62). Although the discontinuation due to adverse effects was higher in Vortioxetine than placebo group (pooled OR= 1.55, 95% CI = 1.04 to 2.31, P= 0.037), the lack of efficacy (pooled OR= 0.39, 95% CI = 0.27 to 0.57, P<0.01) was higher in placebo than Vortioxetine group. Most of the adverse effects were mild and moderate. Overall, Vortioxetine displayed a good safety and tolerability profile.

OBJECTIVE: To establish whether tranexamic acid compared with placebo increased the prevalence or number of remote cerebral DWIHLs within 2 weeks of ICH onset.

DESIGN, SETTING, AND PARTICIPANTS: This prospective nested magnetic resonance imaging (MRI) substudy of a randomized clinical trial (RCT) recruited participants from the multicenter, double-blind, placebo-controlled, phase 3 RCT (Tranexamic Acid for Hyperacute Primary Intracerebral Hemorrhage [TICH-2]) from July 1, 2015, to September 30, 2017, and conducted follow-up to 90 days after participants were randomized to either the tranexamic acid or placebo group. Participants had acute spontaneous ICH and included TICH-2 participants who provided consent to undergo additional MRI scans for the MRI substudy and those who had clinical MRI data that were compatible with the brain MRI protocol of the substudy. Data analyses were performed on an intention-to-treat basis on January 20, 2020.

INTERVENTIONS: The tranexamic acid group received 1 g in 100-mL intravenous bolus loading dose, followed by 1 g in 250-mL infusion within 8 hours of ICH onset. The placebo group received 0.9% saline within 8 hours of ICH onset. Brain MRI scans, including DWI, were performed within 2 weeks.

MAIN OUTCOMES AND MEASURES: Prevalence and number of remote DWIHLs were compared between the treatment groups using binary logistic regression adjusted for baseline covariates.

RESULTS: A total of 219 participants (mean [SD] age, 65.1 [13.8] years; 126 men [57.5%]) who had brain MRI data were included. Of these participants, 96 (43.8%) were randomized to receive tranexamic acid and 123 (56.2%) were randomized to receive placebo. No baseline differences in demographic characteristics and clinical or imaging features were found between the groups. There was no increase for the tranexamic acid group compared with the placebo group in DWIHL prevalence (20 of 96 [20.8%] vs 28 of 123 [22.8%]; odds ratio [OR], 0.71; 95% CI, 0.33-1.53; P = .39) or mean (SD) number of DWIHLs (1.75 [1.45] vs 1.81 [1.71]; mean difference [MD], -0.08; 95% CI, -0.36 to 0.20; P = .59). In an exploratory analysis, participants who were randomized within 3 hours of ICH onset or those with chronic infarcts appeared less likely to have DWIHLs if they received tranexamic acid. Participants with probable cerebral amyloid angiopathy appeared more likely to have DWIHLs if they received tranexamic acid.

CONCLUSIONS AND RELEVANCE: This substudy of an RCT found no evidence of increased prevalence or number of remote DWIHLs after tranexamic acid treatment in acute ICH. These findings provide reassurance for ongoing and future trials that tranexamic acid for acute ICH is unlikely to induce cerebral ischemic events.