Prospective multicenter study of continuous tonic-clonic seizure monitoring on Apple Watch in epilepsy monitoring units and ambulatory environments.

Objective: Evaluate the performance of a custom application developed for tonic-clonic seizure (TCS) monitoring on a consumer-wearable (Apple Watch) device.

Methods: Participants with a history of convulsive epileptic seizures were recruited for either Epilepsy Monitoring Unit (EMU) or ambulatory (AMB) monitoring; participants without epilepsy (normal controls [NC]) were also enrolled in the AMB group. Both EMU and AMB participants wore an Apple Watch with a research app that continuously recorded accelerometer and photoplethysmography (PPG) signals, and ran a fixed-and-frozen tonic-clonic seizure detection algorithm during the testing period.

Effect of Chemical Modification on Molecular Ordering in Polydiketopyrrolopyrrole Copolymers: From Liquid Crystalline to Crystalline.

The chemical architecture of conjugated polymers is often designed by contemplating and understanding the consequences of structural changes on electronic properties at the molecular level. However, even minor changes to the chemical structure of a polymer can significantly influence the packing arrangement, which also influences the electronic properties of the bulk material. Here, we investigate the molecular arrangement in the ordered state at room temperature of a series of three different polydiketopyrrolopyrroles (PDPPs) in bulk and oriented thin films in detail by wide-angle X-ray scattering and by atomic force microscopy.

Posttraumatic Epilepsy and Dementia Risk.

Importance: Although both head injury and epilepsy are associated with long-term dementia risk, posttraumatic epilepsy (PTE) has only been evaluated in association with short-term cognitive outcomes.

Objective: To investigate associations of PTE with dementia risk.

Design, Setting, And Participants: The Atherosclerosis Risk in Communities (ARIC) study initially enrolled participants from 1987 to 1989 and this prospective cohort study uses data through December 31, 2019, with a median follow-up of 25 years.

Cognitive and psychiatric adverse events during adjunctive cenobamate treatment in phase 2 and phase 3 clinical studies.

Objective: Cognitive and psychiatric adverse events in patients with epilepsy are important determinants of therapeutic outcomes and patient quality of life. We assessed the relationship between adjunctive cenobamate treatment and selected cognitive and psychiatric treatment-emergent adverse events (TEAEs) in adults with uncontrolled focal epilepsy.

Methods: This was a retrospective analysis of pooled populations of patients with focal epilepsy from two phase 2, randomized, double-blind clinical trials; two open-label extensions (OLEs) of those trials; and a long-term, open-label, phase 3 safety study.

Sublingual lorazepam as rescue therapy for seizure emergencies in adults.

Objective: Limited acute home treatments are available for patients with prolonged (>5 minutes) or repetitive (≥2 in 24 hours) seizures. While this early seizure treatment may reduce the need for emergency care, intermittent intranasal benzodiazepine formulations are expensive and rectal diazepam administration is often socially unacceptable. We determined whether caregivers could use sublingual lorazepam oral concentrate solution effectively as acute treatment for adults with prolonged and repetitive seizures.

Seizure Rescue Therapies: Comparing Approved and Commonly Used Benzodiazepine Formulations.

Acute seizure therapies given out of the hospital are important for interrupting acute repetitive and prolonged seizures and preventing hospitalization. These vary in their administration routes, indications for children and adults, pharmacologic profiles, and efficacy. We reviewed and compared the uses of current formulations available to treat acute seizures, including newly released intranasal (IN) benzodiazepines and older formulations which are widely used for interrupting seizures.

Failure to use new breakthrough treatments for epilepsy.

Despite the approval of ~20 additional antiseizure medications (ASMs) since the 1980s, one-third of epilepsy patients experience seizures despite therapy. Drug-resistant epilepsy (DRE) is associated with cognitive and psychiatric comorbidities, socioeconomic impairment, injuries, and a 9.3-13.

Dose Adjustment of Concomitant Antiseizure Medications During Cenobamate Treatment: Expert Opinion Consensus Recommendations.

Introduction: Our objective was to provide expert consensus recommendations to improve treatment tolerability through dose adjustments of concomitant antiseizure medications (ASMs) during addition of cenobamate to existing ASM therapy in adult patients with uncontrolled focal seizures.

Methods: A panel of seven epileptologists experienced in the use of ASMs, including cenobamate, used a modified Delphi process to reach consensus. The panelists discussed tolerability issues with concomitant ASMs during cenobamate titration and practical strategies for dose adjustments that may prevent or mitigate adverse effects.

Future opportunities for research in rescue treatments.

Clinical studies of rescue medications for seizure clusters are limited and are designed to satisfy regulatory requirements, which may not fully consider the needs of the diverse patient population that experiences seizure clusters or utilize rescue medication. The purpose of this narrative review is to examine the factors that contribute to, or may influence the quality of, seizure cluster research with a goal of improving clinical practice. We address five areas of unmet needs and provide advice for how they could enhance future trials of seizure cluster treatments.

Long-term Efficacy and Safety From an Open-Label Extension of Adjunctive Cenobamate in Patients With Uncontrolled Focal Seizures.

Background And Objectives: To evaluate long-term efficacy (percent seizure frequency reduction and responder rates), safety, and tolerability of adjunctive cenobamate (CNB) in an open-label extension (OLE) of the randomized, double-blind, placebo-controlled study.

Methods: Patients (aged 18-70 years) with uncontrolled focal seizures despite treatment with 1-3 antiseizure medications who completed the 18-week double-blind study (n = 360) could enter the OLE, where they underwent a 2-week blinded conversion to CNB (target dose, 300 mg/d; min/max, 50/400 mg/d).

Results: Three hundred fifty-five patients were included in the OLE safety population (265 originally randomized to CNB, 90 originally randomized to placebo), and 354 were included in the OLE modified intent-to-treat population.

Efficacy of cenobamate for uncontrolled focal seizures in patients with previous epilepsy-related surgery: Post hoc analysis of a phase 3, multicenter, open-label study.

Objective: This post hoc analysis of 10 US study sites from a long-term open-label phase 3 study of adjunctive cenobamate evaluated the efficacy of cenobamate in patients with prior epilepsy-related surgery.

Methods: Patients with uncontrolled focal seizures despite taking stable doses of 1-3 concomitant antiseizure medications (ASMs) received increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) at 2-week intervals over 12 weeks (target dose, 200 mg/day).

Seizure triggers identified postictally using a smart watch reporting system.

Persons with epilepsy (PWE) often report that seizure triggers can influence the occurrence and timing of seizures. Some previous studies of seizure triggers have relied on retrospective daily seizure diaries or surveys pertaining to all past seizures, recent and/or remote, in respondents. To assess the characteristics of seizure triggers at the granularity of individual seizures, we used a seizure-tracking app, called EpiWatch, on a smart watch system (Apple Watch and iPhone) in a national study of PWE.

Association of Head Injury With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Cohort.

Background And Objectives: Late-onset epilepsy (LOE; i.e., epilepsy starting in later adulthood) affects a significant number of individuals.

Efficacy of cenobamate for uncontrolled focal seizures: Post hoc analysis of a Phase 3, multicenter, open-label study.

Objective: To report long-term post hoc efficacy and safety data from 10 US study sites from an open-label Phase 3 study of adjunctive cenobamate (NCT02535091).

Methods: Patients with uncontrolled focal seizures taking stable doses of 1-3 antiseizure medications (ASMs) were administered increasing daily doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals (target dose = 200 mg/day).

Post hoc analysis of a phase 3, multicenter, open-label study of cenobamate for treatment of uncontrolled focal seizures: Effects of dose adjustments of concomitant antiseizure medications.

Objective: To report post hoc results on how adjustments to baseline antiseizure medications (ASMs) in a subset of study sites (10 US sites) from a long-term, open-label phase 3 study of adjunctive cenobamate affected tolerability, efficacy, and retention.

Methods: Patients with uncontrolled focal seizures taking stable doses of one to three ASMs were administered increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals (target dose = 200 mg/day).

Highly Efficient Doping of Conjugated Polymers Using Multielectron Acceptor Salts.

Chemical doping is a vital tool for tuning electronic properties of conjugated polymers. Most single electron acceptors used for p-doping necessitate high dopant concentrations to achieve good electrical conductivity. However, high-molar doping ratios hamper doping efficiency.

Practical guidance for the management of adults receiving adjunctive cenobamate for the treatment of focal epilepsy-expert opinion.

Clinical trial results have demonstrated that adjunctive cenobamate (CNB) substantially decreases seizure frequency in adults with uncontrolled focal onset seizures with an acceptable and well-identified safety profile. This manuscript summarizes an expert panel's recommendations regarding optimized CNB treatment of epilepsies with focal onset seizures. Cenobamate, when slowly titrated to the target maintenance dose, represents an effective new antiseizure medication (ASM) with a comparatively high rate of seizure freedom relative to existing treatment options.

Mortality in Patients With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.

Background And Objectives: To determine the risk of mortality and causes of death in persons with late-onset epilepsy (LOE) compared to those without epilepsy in a community-based sample, adjusting for demographics and comorbid conditions.

Methods: This is an analysis of the prospective Atherosclerosis Risk in Communities study, initiated in 1987-1989 among 15,792 mostly Black and White men and women in 4 US communities. We used Centers for Medicare & Medicaid Services fee-for-service claims codes to identify cases of incident epilepsy starting at or after age 67.

Long-term safety of adjunctive cenobamate in patients with uncontrolled focal seizures: Open-label extension of a randomized clinical study.

Objective: This study was undertaken to examine long-term (up to 7.8 years) retention rate, safety, and tolerability of the antiseizure medication (ASM) cenobamate as adjunctive treatment in the open-label extension (OLE) of study YKP3089C013 (C013; ClinicalTrials.gov: NCT01397968).

A multivariable prediction model of a major treatment response for focal-onset seizures: A post-hoc analysis of Phase III trials of perampanel.

Objective: Although 50 % reduction in seizure frequency is a common efficacy endpoint in clinical trials of antiepileptic drugs (AEDs), 75 % or greater reductions may be required to improve patients' health-related quality of life. Identification of clinical factors that are associated with high responder rates may help to inform clinicians on which patients may optimally benefit from treatment. We evaluated potential predictive factors for achieving major treatment responses (≥75 % reduction in seizure frequency per 28 days from study baseline) in patients with drug-resistant focal-onset seizures, with/without focal to bilateral tonic-clonic (FBTC) seizures in perampanel trials designed for regulatory approval.

Cenobamate treatment of focal-onset seizures: Quality of life and outcome during up to eight years of treatment.

A large proportion of patients with focal-onset epilepsy have frequent seizures despite treatment with newer anti-seizure medications (ASMs). We describe our experience optimizing cenobamate treatment for 49 patients treated at one center for up to eight years. We assessed the influence of treatment response on measurements of quality of life (QOLIE).

Dementia in late-onset epilepsy: The Atherosclerosis Risk in Communities study.

Objective: To determine the risk of dementia after the development of late-onset epilepsy.

Methods: We used data from the Atherosclerosis Risk in Communities (ARIC) cohort study, which started in 1987 to 1989 with 15,792 mostly Black and White men and women from 4 US communities. We identified late-onset epilepsy (LOE; seizures starting at age 67 or later) from linked Medicare claims data.

HOMO-HOMO Electron Transfer: An Elegant Strategy for p-Type Doping of Polymer Semiconductors toward Thermoelectric Applications.

Unlike the conventional p-doping of organic semiconductors (OSCs) using acceptors, here, an efficient doping concept for diketopyrrolopyrrole-based polymer PDPP[T] -EDOT (OSC-1) is presented using an oxidized p-type semiconductor, Spiro-OMeTAD(TFSI) (OSC-2), exploiting electron transfer from HOMO to HOMO . A shift of work function toward the HOMO upon doping is confirmed by ultraviolet photoelectron spectroscopy (UPS). Detailed X-ray photoelectron spectroscopy (XPS) and UV-vis-NIR absorption studies confirm HOMO to HOMO electron transfer.