BRIVEST: A 'real-world' observational, single-centre study investigating the efficacy, safety and tolerability of Brivaracetam.

OBJECTIVE: Via measures of efficacy, tolerability, and safety, this open-label, single-center study assessed the overall effectiveness of Brivaracetam (BRV) for the treatment of epilepsy in the context of 'real-world' clinical practice. METHODS: Unselected consecutive patients were recruited and stratified into 3 cohorts with either fully prospective, fully retrospective or mixed data collection, dependent on whether their BRV prescriptions were historical, current, or pending. Prospective data were obtained at baseline, 3 and 6 months, and at 6-month intervals thereafter, from patient interviews and seizure diaries, and retrospective data from medical records. Efficacy variables were derived from seizure-related changes, and tolerability and safety variables from reported treatment-emergent adverse events (TEAEs), BRV withdrawal, and changes to questionnaire scores. Additionally, we investigated treatment outcomes for those with previous levetiracetam (LEV) use, a history of psychiatric comorbidity, a learning disability, and of older age. RESULTS: One hundred and nine patients (58.7% female, mean age 42 years, range: 18 to 72) were included, 59 with prospective follow-up for a minimum of 6 (47 patients, excluding those who withdrew) and a maximum of 24 months (2 patients). Of the full cohort, 87.2% had drug-resistant epilepsy. Retention: At the study end, the median treatment duration was 384 days (range: 6 to 1514 days), and BRV retention was 68.8%. Kaplan-Meier survival functions predicted retention rates of 74.0% and 70.0% at 6 and 12 months respectively. EFFICACY: At the last follow-up, there was a ≥ 50% responder rate of 30.8%, with 12.1% seizure-free. Seizure frequency categories improved in 31.4% of patients, remained the same in 44.2%, and worsened in 24.4%. Monthly tonic-clonic seizure frequency had significantly decreased, and of those reporting these seizures, 58.3% showed reductions and 25.0% showed complete tonic-clonic seizure freedom. TOLERABILITY: 91.7% of patients reported at least 1 TEAE, with fatigue (30.3%), irritability (29.4%), and depression/low mood (28.4%) as the most common. Only 58.4% of all TEAEs were persistent. Brivaracetam discontinuation due to side effects occurred in 27.5% of the cohort. Depression and anxiety scores remained stable over time, and quality-of-life scores improved. Subgroups: Measures of BRV efficacy and tolerability did not differ according to previous LEV exposure. Tolerability profiles of those with learning disabilities, histories of psychiatric comorbidities, and older age did not greatly differ from the rest of the cohort. Of note, specific history of depression predicted the reporting of suicidal ideation. CONCLUSION: The BRIVEST study provides real-world evidence of the effectiveness of BRV, suggesting that neither drug-resistant epilepsy nor previous LEV failure should preclude its use. Furthermore, BRV appears to be well-tolerated, even among those from vulnerable patient populations.

No Effect of Musical Training on Frequency Selectivity Estimated Using Three Methods.

It is widely believed that the frequency selectivity of the auditory system is largely determined by processes occurring in the cochlea. If so, musical training would not be expected to influence frequency selectivity. Consistent with this, auditory filter shapes for low center frequencies do not differ for musicians and nonmusicians. However, it has been reported that psychophysical tuning curves (PTCs) at 4000 Hz were sharper for musicians than for nonmusicians. This study explored the origin of the discrepancy across studies. Frequency selectivity was estimated for musicians and nonmusicians using three methods: fast PTCs with a masker that swept in frequency, "traditional" PTCs obtained using several fixed masker center frequencies, and the notched-noise method. The signal frequency was 4000 Hz. The data were fitted assuming that each side of the auditory filter had the shape of a rounded-exponential function. The sharpness of the auditory filters, estimated as the Q10 values, did not differ significantly between musicians and nonmusicians for any of the methods, but detection efficiency tended to be higher for the musicians. This is consistent with the idea that musicianship influences auditory proficiency but does not influence the peripheral processes that determine the frequency selectivity of the auditory system.