Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

Comparative resource utilization and costs for patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with clopidogrel or prasugrel

Purpose. Results of a study of bleeding events and other inhospital outcomes with the use of clopidogrel versus prasugrel in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) are reported. Methods. Demographic and clinical data on adults hospitalized for ACS, managed with PCI, and treated with clopidogrel or prasugrel during a two-year period were extracted from a large hospital claims database. Bleeding rates, hospital length of stay (LOS), and total hospital costs during the index hospitalization were evaluated. Results. The study sample consisted of 75,297 patients who received clopidogrel and 9,477 who received prasugrel. The unadjusted bleeding rates were 5.7% with clopidogrel use and 3.2% with prasugrel use (p < 0.0001). After propensity score stratification to adjust for selection bias, rates of bleeding events were not significantly different between clopidogrel- and prasugrel-treated patients (odds ratio, 0.90; 95% confidence interval [CI], 0.80-1.02; p = 0.0949). The adjusted mean S.D. hospital LOS was 0.22 day lower (95% CI, 0.15-0.28; p < 0.001) with the use of prasugrel versus clopidogrel, and adjusted total mean hospital costs were $375 less for prasugrel-treated patients (p = 0.003). Conclusion. After adjustments for demographic and clinical characteristics, rates of inhospital bleeding in patients who received prasugrel and those who received clopidogrel were not significantly different. The adjusted analyses showed that the mean hospital LOS was shorter and total mean hospital costs were lower for patients treated with prasugrel