Purpose Mutation in isocitrate dehydrogenase 1 (IDH1) at R132 (IDH1R132MUT) is frequent in low-grade diffuse gliomas and, within glioblastoma (GBM), has been proposed as a marker for GBMs that arise by transformation from lower-grade gliomas, regardless of clinical history. To determine how GBMs arising with IDH1R132MUT differ from other GBMs, we undertook a comprehensive comparison of patients presenting clinically with primary GBM as a function of IDH1R132 mutation status. Patients and Methods In all, 618 treatment-naive primary GBMs and 235 lower-grade diffuse gliomas were sequenced for IDH1R132 and analyzed for demographic, radiographic, anatomic, histologic, genomic, epigenetic, and transcriptional characteristics. Results Investigation revealed a constellation of features that distinguishes IDH1R132MUT GBMs from other GBMs (including frontal location and lesser extent of contrast enhancement and necrosis), relates them to lower-grade IDH1R132MUT gliomas, and supports the concept that IDH1R132MUT gliomas arise from a neural precursor population that is spatially and temporally restricted in the brain. The observed patterns of DNA sequence, methylation, and copy number alterations support a model of ordered molecular evolution of IDH1R132MUT GBM in which the appearance of mutant IDH1 protein is an initial event, followed by production of p53 mutant protein, and finally by copy number alterations of PTEN and EGFR. Conclusion Although histologically similar, GBMs arising with and without IDH1R132MUT appear to represent distinct disease entities that arise from separate cell types of origin as the result of largely nonoverlapping sets of molecular events. Optimal clinical management should account for the distinction between these GBM disease subtypes.

Objective A growing body of evidence suggests that testing for influenza virus alone is more appropriate than multiplex respiratory viral panel (RVP) testing for general populations of patients with respiratory tract infections. We aimed to decrease the proportion of RVPs out of total respiratory viral testing ordered during influenza season. Methods We implemented two consecutive interventions: reflex testing for RVPs only after a negative influenza test, and noninterruptive clinical decision support (CDS) including modifications of the computerized physician order entry search behavior and cost display. We conducted an interrupted time series of RVPs and influenza polymerase chain reaction tests pre- and postintervention, and performed a mixed-effects logistic regression analysis with a primary outcome of proportion of RVPs out of total respiratory viral tests. The primary predictor was the intervention period, and covariates included the provider, clinical setting, associated diagnoses, and influenza incidence. Results From March 2013 to April 2019, there were 24,294 RVPs and 26,012 influenza tests (n = 50,306). Odds of ordering an RVP decreased during the reflex testing period (odds ratio: 0.432, 95% confidence interval: 0.397–0.469), and decreased more dramatically during the noninterruptive CDS period (odds ratio: 0.291, 95% confidence interval: 0.259–0.327). Discussion The odds of ordering an RVP were 71% less with the noninterruptive CDS intervention, which projected 4,773 fewer RVPs compared with baseline. Assuming a cost equal to Medicare reimbursement rates for RVPs and influenza tests, this would generate an estimated averted cost of $1,259,474 per year. Conclusion Noninterruptive CDS interventions are effective in reducing unnecessary and expensive testing, and avoid typical pitfalls such as alert fatigue.

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