Durable suppression of seizures in a preclinical model of KCNT1 genetic epilepsy with divalent small interfering RNA.

Objective: Gain-of-function variants in the KCNT1 gene, which encodes a sodium-activated potassium ion channel, drive severe early onset developmental epileptic encephalopathies including epilepsy of infancy with migrating focal seizures and sleep-related hypermotor epilepsy. No therapy provides more than sporadic or incremental improvement. Here, we report suppression of seizures in a genetic mouse model of KCNT1 epilepsy by reducing Kcnt1 transcript with divalent small interfering RNA (siRNA), an emerging variant of oligonucleotide technology developed for the central nervous system.

Dose-dependent reduction of somatic expansions but not Htt aggregates by di-valent siRNA-mediated silencing of MSH3 in HdhQ111 mice.

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the HTT gene. In addition to germline CAG expansions, somatic repeat expansions in neurons also contribute to HD pathogenesis. The DNA mismatch repair gene, MSH3, identified as a genetic modifier of HD onset and progression, promotes somatic CAG expansions, and thus presents a potential therapeutic target.

Examining the case for direct contracting: A multistakeholder case study.

Background: Employers and pharmacies are challenged by a complex system for prescription payment. Cost plus direct contracts for prescriptions and bundled services may yield benefits.

Objectives: This study aimed to (1) explore direct contracting using multistakeholder interviews, (2) compare employer costs and employee copays for 6 months of prescription charges under their pharmacy benefit manager (PBM) with projected costs under a pharmacy direct contract, (3) project pharmacy revenue, costs, and net profit had these prescriptions been processed through the direct contract, and (4) assess employee satisfaction under the direct contract.

Retrospective analysis of drug therapy problems identified with a telephonic appointment-based model of medication synchronization.

Objectives: To describe the drug therapy problems (DTPs) identified for patients enrolled in an Appointment Based Model (ABM) for medication synchronization, describe the pharmacist-delivered clinical interventions, and assess what patient characteristics are associated with the number of DTPs identified.

Methods: A cross-sectional chart review of 1 month of pharmacist notes for telephone ABM encounters at one independent community pharmacy in the Midwest U.S.