Background:
Pharmacological and clinical evidence suggest that sulfonylurea (SU) medications may improve acute ischemic stroke (AIS) outcomes. The SHINE trial studied intensive vs standard blood sugar management in patients presenting with AIS and hyperglycemia. We investigated whether pre-existing SU use impacted functional outcomes in SHINE.
Methods:
SHINE data collection forms were reviewed to identify AIS patients taking SUs at the time of study enrollment. Our primary outcome compared the adjusted 90-day utility weighted modified Rankin Scale (UW-mRS) score in the SU and non-SU cohorts. The UW-mRS score was adjusted for age, baseline NIHSS, baseline glucose, and reperfusion therapy. Pre-specified analyses of the 90-day UW-mRS scores assessed for heterogeneity of SU effect across the following subgroups: age, stroke severity, reperfusion therapy, type of SU, and SHINE study arm.
Results:
In total, 1066 SHINE subjects with a final diagnosis of AIS were included (SU=248 [23.3%], non-SU=818 [76.7%]). Baseline demographics were generally similar (Table 1). Calculated 90-day mean UW-mRS score were higher in the non-SU group compared to the SU group: mean 0.617 ± 0.012 versus mean 0.566 ± 0.022 (Diff 0.051, 95% CI 0.001-0.1) without heterogeneity of treatment effect (Figure 1).
Conclusion:
Contrary to our hypothesis and published literature, our retrospective analysis of the SHINE trial demonstrated better functional outcomes in the non-SU cohort. This may be due to selection bias with inadequate controlling for baseline risk factors present in the SU cohort. Definitive prospective studies are required.
Background:
Recurrent glioblastoma multiforme (rGBM) has a grim prognosis with current therapies offering no survival benefit. Several combination therapies involving anti-VEGF agents have been studied with mixed results.
Methods:
A systematic search was performed using five electronic databases: PubMed, Scopus, ISI, Embase, and the Cochrane Library without language limitations. The primary outcome of interest was progression free survival (PFS). Secondary outcomes were overall survival (OS), objective response ratio (ORR), and grade ≥ 3 adveraxaxse events. Estimates for PFS, OS were calculated as random effects hazard ratio (HR) with 95% confidence intervals (CIs) using the generic inverse variance method. Estimates for ORR, grade ≥ 3 adverse events were calculated using a random-effects risk ratio (RR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method.
Results:
Thirteen studies met the inclusion criteria and a total of 1994 patients have been included in the analysis. There was no statistically significant improvement in PFS (HR 0.84; 95% CI (0.68, 1.03); I2=81%), OS (HR 0.99; 95% CI (0.88, 1.12); I2=0%), ORR (RR 1.36; 95% CI (0.96, 1.92); I2=61%) in the combination therapy group when compared to the control group. Significantly higher grade ≥3 adverse events (RR 1.30; 95% CI (1.14, 1.48); I2=47%) were seen in the combination therapy when compared to the control group.
Conclusion:
Our analysis showed that the use of combination therapy with anti-VEGF agents did not offer any benefit in PFS, OS, or ORR. In contrast, it had significantly higher grade 3-5 adverse events. Further studies are needed to identify effective therapies in rGBM that can improve survival.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.