Effectiveness and Safety of Adjunctive Cenobamate in People with Focal-Onset Epilepsy: Evidence from the First Interim Analysis of the BLESS Study.

INTRODUCTION: Despite new anti-seizure medications (ASMs) being introduced into clinical practice, about one-third of people with epilepsy do not reach seizure control. Cenobamate is a novel tetrazole-derived carbamate compound with a dual mechanism of action. In randomized controlled trials, adjunctive cenobamate reduced the frequency of focal seizures in people with uncontrolled epilepsy. Studies performed in real-world settings are useful to complement this evidence and better characterize the drug profile. METHODS: The Italian BLESS ("Cenobamate in Adults With Focal-Onset Seizures") study is an observational cohort study aimed to evaluate the effectiveness, tolerability, and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy in the context of real-world clinical practice. The study is ongoing and conducted at 50 centers in Italy. This first interim analysis includes participants enrolled until June 2023 and with 12-week outcome data available. RESULTS: Forty participants with a median age of 36.5 (interquartile range [IQR] 26.0-47.5) years were included. The median monthly seizure frequency at baseline was 6.0 (IQR 2.5-17.3) seizures and 31 (77.5%) participants had failed four or more ASMs before cenobamate. At 12 weeks from starting cenobamate, the median reduction in monthly seizure frequency was 52.8% (IQR 27.1-80.3%); 22 (55.0%) participants had a ≥ 50% reduction in baseline seizure frequency and six (15.0%) reached seizure freedom. The median number of concomitant ASMs decreased from 3 (IQR 2-3) at baseline to 2 (IQR 2-3) at 12 weeks and the proportion of patients treated with > 2 concomitant ASMs decreased from 52.5% to 40.0%. Seven (17.5%) patients reported a total of 12 adverse events, 11 of which were considered adverse drug reactions to cenobamate. CONCLUSION: In adults with uncontrolled focal seizures, the treatment with adjunctive cenobamate was well tolerated and was associated with improved seizure control and a reduction of the burden of concomitant ASMs. TRIAL REGISTRATION NUMBER: NCT05859854 (ClinicalTrials.gov Identifier).

Treatment persistence in patients with schizophrenia treated with lurasidone in Italian clinical practice.

BACKGROUND AND RATIONALE: Treatment persistence combines clinician and patient judgment of efficacy, tolerability and safety into a comprehensive measure of effectiveness and is defined as the act of continuing a treatment over time. Studies have reported poor treatment persistence to antipsychotic medications in patients with schizophrenia. This study evaluated treatment persistence to lurasidone (LUR) in patients with schizophrenia in a real-world Italian setting. METHODS: This was a retrospective observational study of patients with schizophrenia who started treatment with LUR ≥ 6 months before inclusion. Following informed consent, data were collected starting from the index date (start of LUR treatment) at all visits occurring as per clinical practice. The primary endpoint was treatment persistence during the first 6 months, defined as the time between index date and all-cause discontinuation. Patients treated with LUR > 180 days were considered persistent. As secondary endpoint, treatment persistence was evaluated for a period of ≥ 18 months. RESULTS: Forty-five patients were enrolled and 41 (91.11%) completed the study. Forty-one patients (91.11%) were included in the eligible population as they initiated LUR treatment ≥ 6 months before data collection. Patients were 43.0 ± 15.89 years old and 61% were female. Twenty-two patients (53.66%) started LUR treatment in a hospital setting and 19 (46.34%) in an outpatient setting. Based on Clinical Global Impression-Severity scale (CGI-S) at LUR initiation, 12 patients (29.27%) were severely ill, 17.07% markedly ill, 19.51% moderately ill, 2.44% mildly ill and 4.88% borderline mentally ill. Thirty-two patients (78.05%) were treatment persistent for ≥ 180 days. Among the 19 patients observed for ≥ 18 months, 11 (57.89%) were persistent for ≥ 18 months. Among the 22 study patients observed for < 18 months, 12 (54.54%) were persistent. An improvement in schizophrenia severity according to CGI-S was observed at inclusion (following LUR therapy) compared to the index date. Six patients (14.63%) experienced at least one adverse drug reaction: akathisia (7.32%), extrapyramidal disorder (4.88%), hyperprolactinemia (2.44%), restlessness (2.44%), and galactorrhea (2.44%). None were serious. CONCLUSIONS: Persistence to LUR in patients with schizophrenia was relatively high: 78% and 58% of patients were still on LUR after 6 and 18 months of treatment, respectively. This may reflect LUR's relatively favorable balance between efficacy and tolerability, as well as favorable patient satisfaction and acceptance.

Non-bullous Impetigo: Incidence, Prevalence, and Treatment in the Pediatric Primary Care Setting in Italy.

Impetigo is a common skin infection in children. The worldwide prevalence in children is estimated to be 12%, but this may be lower since high-income countries are under-represented. This research aims to evaluate the incidence, prevalence, and management of children with non-bullous impetigo (NBI) residing in Italy. This retrospective cohort study included children up to 14 years of age enrolled in the Pedianet database from January 2004 to June 2018. Events were identified searching ICD9-CM codes (684 and 694.3) and free text fields for a diagnosis of NBI reported during a primary care visit. Diagnoses were manually validated, and events registered within 30-days after the index date were considered follow-ups. Incidence (IR) and prevalence (PR) rates of NBI were stratified by sex, age group, and calendar year. Topical and systemic antibiotic treatments were grouped based on ATC codes. 15,136 NBI episodes occurred in a total cohort of 225,979 children. The overall IR of NBI was 9.5 per 1,000 person-years, and children aged 1-4 years had the highest IR (13.2 per 1,000 person-years). A significant decrease in NBI IR from 13 per 1,000 person-years in 2004 to 7.46 per 1,000 person-years in 2018 (p < 0.0001) was noted. Most of the episodes were treated; systemic antibiotics were preferred over topical. Conclusion: The prevalence of NBI in children in Italy is less than one third than the global estimate and the trend in time is decreasing. Over prescriptions of systemic antibiotics pose a threat to the diffusion of antimicrobial resistance.