Approximately 96% of patients with glioblastomas (GBM) have IDH1 wildtype GBMs, characterized by extremely poor prognosis, partly due to resistance to standard temozolomide treatment. O6-Methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a crucial prognostic biomarker for alkylating chemotherapy resistance in patients with GBM. However, MGMT methylation status identification methods, where the tumor tissue is often undersampled, are time consuming and expensive. Currently, presurgical noninvasive imaging methods are used to identify biomarkers to predict MGMT methylation status. We evaluated a novel radiomics-based eXtreme Gradient Boosting (XGBoost) model to identify MGMT promoter methylation status in patients with IDH1 wildtype GBM. This retrospective study enrolled 53 patients with pathologically proven GBM and tested MGMT methylation and IDH1 status. Radiomics features were extracted from multimodality MRI and tested by F-score analysis to identify important features to improve our model. We identified nine radiomics features that reached an area under the curve of 0.896, which outperformed other classifiers reported previously. These features could be important biomarkers for identifying MGMT methylation status in IDH1 wildtype GBM. The combination of radiomics feature extraction and F-core feature selection significantly improved the performance of the XGBoost model, which may have implications for patient stratification and therapeutic strategy in GBM.

The Bureau of Controlled Drugs at Ministry of Health, Executive Yuan in Taiwan All prescription data were divided into three 4 month periods: period I was when the flunitrazepam prescription was not controlled, period II represented the time when flunitrazepam was placed on Schedule III and when physicians were required to use a special duplicated prescription form and period III was when the TMU-WFH started to set a stricter control for the prescription of flunitrazepam. The results indicated that the number of flunitrazepam prescriptions during period III had decreased significantly compared with period I (P £ 0.05). Eventually, 45.7% of flunitrazepam-medicated patients were followed up monthly with a restriction of their flunitrazepam supply to no more than 14 days, 22.9% of patients were followed up fortnightly at clinics with a 14 day supply of flunitrazepam, 15.7% were followed up fortnightly with a 14 day restriction of flunitrazepam plus a non-flunitrazepan benzodiazepine supplement, 10.7% were referred to clinics within the Department of Psychiatry and 5% were switched from flunitrazepam to other drugs. Like most BZD, flunitrazepam produces five physiologic (anxiolytic, sedative, anticonvulsant, musclerelaxing and amnestic) functions. 1 Usually, there is no life-threatening outcome of overdose with flunitrazepam alone because it acts only on BZD GABA A (or simply benzodiazepine) receptors in the central nervous system. 1 However, flunitrazepam has the potential to be fatal if coadministered with alcohol, which acts directly on chloride ion channels. 1,5 Flunitrazepam readily dissolves and, once in solution, is colorless, odorless and tasteless. 5,6 Victims are vulnerable to sexual assault when flunitrazepam is administered in an alcoholic drink; therefore, flunitrazepam is widely abused as a drug in date rape or acquaintance rape scenarios. 3,7 Before 1 April 2000, all BZD were easily obtained from any drugstore in Taiwan. However, the Bureau of Controlled Drugs of Ministry of Health, Executive Yuan classified all BZD as Schedule IV drugs (Table 1), 8 with the exception of three BDZ (brotizolam, triazolam and flunitrazelam), which were specifically placed on Schedule III. 8 Of these three BZD, only flunitrazepam is available from the formulary in the Department of Pharmacy at Taipei Medical University-Wan Fang Hospital (TMU-WFH). Only 2 mg flunitrazepam pills are available at the TMU-WFH. According to Government policy, a prescribing physician needs to register with the Bureau for a prescribing license and fills out a duplicate prescription sheet when he/she prescribes any controlled drug on Schedules I-III. 8 To abide by the new policy of the Bureau of Controlled Drugs, the Committee of Controlled Drugs was founded at TMU-WFH in the summer of 2000. The Committee assumed the task of hospital-wide education and in-service training for physicians and related clinical disciplines (nurses, physicians' assistants, pharmacists etc.) about the classification of scheduled drugs (Table 1) and the regul...