netgsa: Fast computation and interactive visualization for topology-based pathway enrichment analysis.

Existing software tools for topology-based pathway enrichment analysis are either computationally inefficient, have undesirable statistical power, or require expert knowledge to leverage the methods' capabilities. To address these limitations, we have overhauled NetGSA, an existing topology-based method, to provide a computationally-efficient user-friendly tool that offers interactive visualization. Pathway enrichment analysis for thousands of genes can be performed in minutes on a personal computer without sacrificing statistical power. The new software also removes the need for expert knowledge by directly curating gene-gene interaction information from multiple external databases. Lastly, by utilizing the capabilities of Cytoscape, the new software also offers interactive and intuitive network visualization.

Time to Treatment Intensification After Monotherapy Failure and Its Association With Subsequent Glycemic Control Among 93,515 Patients With Type 2 Diabetes.

OBJECTIVE: The goal of this study was to evaluate the association between the timing of treatment intensification and subsequent glycemic control among patients with type 2 diabetes in whom monotherapy fails. RESEARCH DESIGN AND METHODS: This retrospective analysis of the U.K. Clinical Practice Research Datalink database focused on patients with type 2 diabetes and one or more HbA1c measurements ≥7% (≥53 mmol/mol) after ≥3 months of metformin or sulfonylurea monotherapy (first measurement meeting these criteria was taken as the study index date). Baseline (6 months before the index date) characteristics were stratified by time from the index date to intensification (early: <12 months; intermediate: 12 to <24 months; late: 24 to <36 months). Intensification was defined as initiating after the index date one or more noninsulin antidiabetes medication in addition to metformin or a sulfonylurea. Association between time to intensification and subsequent glycemic control (first HbA1c <7% [<53 mmol/mol] after intensification) was evaluated using Kaplan-Meier analyses and Cox proportional hazard models that accounted for baseline differences. RESULTS: Of the 93,515 patients who met the study criteria (mean age 60 years; ∼59% male; 80% taking metformin), 23,761 (25%) intensified <12 months after the index date; 11,908 (13%) intensified after 12 to <24 months; and 7,146 (8%) intensified after 24 to <36 months. Patients who intensified treatment ≥36 months after the index date (n = 9,638 [10%]) and those with no evidence of treatment intensification during the observable follow-up period (n = 41,062 [44%]) were not included in further analyses. The median times from intensification to control were 20.0, 24.1, and 25.7 months, respectively, for the early, intermediate, and late intensification cohorts. After adjustment for baseline differences, the likelihood of attaining glycemic control was 22% and 28% lower for patients in the intermediate and late intensification groups, respectively, compared with those intensifying early (P < 0.0001). CONCLUSIONS: Earlier treatment intensification is associated with shorter time to subsequent glycemic control, independent of whether patients initiate first-line treatment with metformin or a sulfonylurea.

Health Care Resource Utilization and Costs Associated with Transitioning to 3-month Paliperidone Palmitate Among US Veterans.

PURPOSE: The aim of this article was to describe and compare treatment patterns, health care resource utilization (HRU), and health care costs before and after transition in veterans with schizophrenia who were transitioned from paliperidone palmitate given once monthly (PP1M) to paliperidone palmitate given every 3 months (PP3M) according to prescribing-information guidelines. METHODS: This retrospective, longitudinal study was conducted using electronic health records data from the Veterans Health Administration (VHA). Veterans were eligible for inclusion if they were aged 18years or older, had ≥1 dispensation of PP3M, were enrolled with VHA benefits for ≥24 months prior to transition to PP3M, had ≥1 schizophrenia diagnosis, were transitioned to PP3M according to prescribing-information guidelines (operationalized as no gap in PP1M treatment of >45days during the 4 months prior to PP3M transition, with the same dosage in the last 2 PP1M dispensations), and had appropriate dose conversion. Treatment patterns, HRU, and costs 6 months pre and post PP3M transition were described and compared using the McNemar test and the Wilcoxon signed rank test. FINDINGS: Of the 277 veterans identified, the majority were men (92.8%); the median age was 56.5years. Among 197 veterans who had at least 6 months of follow-up pre and post PP3M transition, oral antipsychotic use was significantly decreased (from 49.7% to 43.1%; P = 0.0326). Additionally, the mean number of days spent in an inpatient setting (41.4vs 21.6; P = 0.0164), the mean number of outpatient visits per patient (31.0vs 25.6; P < 0.0001), and the mean total health care costs ($27,745vs $23,772; P = 0.0050) were significantly decreased. IMPLICATIONS: After transitioning to PP3M treatment, veterans had significantly reduced use of oral antipsychotics, HRU, and costs. Although generalizability may be limited due to the veteran population and to those who transitioned according to PP3M prescribing guidelines, future studies in other patient populations may be used to extend these conclusions.