Intravenous Brivaracetam in the Management of Acute Seizures in the Hospital Setting: A Scoping Review

Background Clinical considerations for drug treatment of acute seizures involve variables such as safety, tolerability, drug-drug interactions, dosage, route of administration, and alterations in pharmacokinetics because of critical illness. Therapy options that are easily and quickly administered without dilution, well tolerated, and effective are needed for the treatment of acute seizures. The objective of this review is to focus on the clinical considerations relating to the use of intravenous brivaracetam (IV BRV) for the treatment of acute seizures in the hospital, focusing on critically ill patients. Methods This was a scoping literature review of PubMed from inception to April 13, 2021, and search of the American Academy of Neurology (AAN) 2021 Annual Meeting website for English language publications/conference abstracts reporting the results of IV BRV use in hospitalized patients, particularly in the critical care setting. Outcomes of interest relating to the clinical pharmacology, safety, tolerability, efficacy, and effectiveness of IV BRV were reviewed and are discussed. Results Twelve studies were included for analysis. One study showed that plasma concentrations of IV BRV 15 min after the first dose were similar between patients receiving IV BRV as bolus or infusion. IV BRV was generally well tolerated in patients with acute seizures in the hospital setting, with a low incidence of individual TEAEs classified as behavioral disorders. IV BRV demonstrated efficacy and effectiveness and had a rapid onset, with clinical and electrophysiological improvement in seizures observed within minutes. Although outside of the approved label, findings from several studies suggest that IV BRV reduces seizures and is generally well tolerated in patients with status epilepticus. Conclusions IV BRV shows effectiveness, and is generally well tolerated in the management of acute seizures in hospitalized patients where rapid administration is needed, representing a clinically relevant antiseizure medication for potential use in the critical care setting

Student Perceptions of a Flipped Pharmacotherapy Course

Objective. To evaluate student perception of the flipped classroom redesign of a required pharmacotherapy course

Predictors of Gastrointestinal Bleeding Among Patients with Atrial Fibrillation After Initiating Dabigatran Therapy

To identify demographic and clinical risk factors associated with gastrointestinal (GI) bleeding among a large cohort of patients with atrial fibrillation (AF) who initiated dabigatran therapy for stroke prevention, and to describe patterns of subsequent anticoagulant use after occurrence of the GI bleeding event

Epidemiology and injectable antiseizure medication treatment patterns of seizure patients treated in United States hospitals

Objective This study aimed to examine the epidemiology of seizures, clinical outcomes, and antiseizure medication treatment patterns among seizure patients treated in United States hospitals.DesignA retrospective cross-sectional study was conducted using data from a large geographically diverse hospital discharge database.Setting860 acute care hospitals in the United States.ParticipantsPatients aged ≥18 years with an outpatient emergency department or inpatient visit between 1 July 2016–31 December 2019 were included. Intervention None. Main outcomes and measures Key outcomes included prevalence of seizure, seizure type, admission point of origin, intensive care unit admission, discharge status, and injectable antiseizure medication utilization. Seizures were identified by the International Classification of Disease, Tenth Revision, Clinical Modification diagnosis codes. Results Among 36,598,627 unique emergency department outpatients (72,372,464 outpatient visits) and 16,543,592 unique inpatients (24,923,489 inpatient admissions) analyzed, seizure was present in 2.1% of outpatients (1.87% of outpatient visits) and 4.9% of inpatients (4.8% of inpatient admissions). In overall seizure patients, 49.1% were unclassified, 4.4% had generalized onset, 2.9% had focal onset, and 42.8% were categorized as other (including 38.5% with convulsion). Among seizure-associated inpatient admissions, <1% were transferred directly from skilled nursing facility or other long-term care facilities but 22.7% were discharged to such facilities. Nearly a third (31%) of all inpatients were admitted to ICU. About 88.3% of patients with injectable ASM use had monotherapy, 4.6% had polytherapy with 1 day or multiple non-consecutive days of overlap, and 7.0% had polytherapy with ≥2 consecutive days of overlap. The percentage of patients with no step down to any oral ASM ranged between 34.0–57.0%. Conclusions Seizures affect a substantial number of hospital-based emergency department outpatient and inpatient encounters and are associated with poor clinical outcomes and significant healthcare burden. Concomitant use of injectable ASMs is uncommon and a high percentage of IV ASM users with a diagnosis of seizure had no step down to oral therapy.RelevanceThe study findings may inform clinicians and hospital decision makers about current clinical practice and burden of seizures and identify areas to improve overall outcomes for patients with seizures

Factors Driving Anticoagulant Selection in Patients With Atrial Fibrillation in the United States

With the introduction of novel oral anticoagulants (NOACs), the factors driving anticoagulant selection in atrial fibrillation (AF) in real-world practice are unclear. The goal was to examine whether and to what extent utilization has been driven by predictions of stroke risk (treatment benefit), bleeding risk (treatment harm), or prescription benefits’ coverage. We extracted a cohort of non-valvular AF patients initiating anticoagulation from Oct 2010-Dec 2012 from a large US database of commercial and Medicare supplement claims. Multivariable regression examined associations between ischemic stroke (CHA2DS2-VASc) and bleeding (ATRIA) risk scores and benefits’ generosity (proportion of costs covered by patients relative to total) with warfarin and NOAC selection and also between dabigatran and rivaroxaban. C-statistics and partial chi-square statistics were used to assess the variation explained. Of 70,498 patients initiating anticoagulation, 29.9% and 7.9% used dabigatran and rivaroxaban, respectively. Compared with warfarin, patients were less likely to receive a NOAC with high ischemic stroke risk (CHA2DS2-VASc ≥2) (Adjusted Relative Risk [aRR]: 0.75, 95% CI: 0.72-0.77) and high bleeding risk (ATRIA≥5) (aRR: 0.66, 95% CI: 0.64-0.69) but more likely with good benefits’ generosity (≤20% of costs borne by patient) (aRR: 2.03, 95% CI: 1.92-2.16). Prescription generosity explained almost twice the model variation as either risk score. Compared with dabigatran, patients were more likely to fill rivaroxaban with high bleeding risk (aRR: 1.16, 95% CI: 1.09-1.24). In conclusion, patients with higher bleeding and ischemic stroke risk were more likely to initiate warfarin, but generous benefits more strongly predicted NOAC usage and drove more selection

Perceptions of Tenure and Tenure Reform in Academic Pharmacy

Objectives. To determine the academic pharmacy community’s perceptions of and recommendations for tenure and tenure reform

Scoping Review of Rational Polytherapy in Patients with Drug-Resistant Epilepsy

There is a paucity of literature regarding the optimal selection of combination antiseizure medications (ASMs) for drug-resistant epilepsy (DRE). The aim of this scoping review is to evaluate current evidence related to rational polytherapy among adults with DRE. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-SCr) guidelines, PubMed, ProQuest, CINAHL, and Cochrane databases were searched using DRE- and polytherapy-related keywords. The exclusion criteria applied included: non-English; non-human studies; non-research studies; participants less than 18 years; status epilepticus; ASM monotherapy; and certain ASMs. In Covidence, two researchers independently reviewed articles for inclusion at each phase, with a third resolving conflicts. Data were extracted, with quality appraisal using the Mixed Methods Appraisal Tool (MMAT). Of the 6477 studies imported for screening, 33 studies were included. Clinical, humanistic, and economic outcomes were reported by 26, 12, and one study, respectively. Common efficacy-related clinical outcomes included ≥50% reduction in seizure frequency (n = 14), seizure freedom (n = 14), and percent reduction in seizure frequency (n = 8). Common humanistic outcomes included quality of life (n = 4), medication adherence (n = 2), sleep-related outcomes (n = 2), and physician and patient global assessments (n = 2). The economic study reported quality-adjusted life years. The median MMAT score was 80 (range: 60-100). Two studies referenced the standard definition of DRE, whereas five studies did not specifically define DRE. Gaps in the literature include limited generalizability, minimal reports in pregnancy, and lack of optimal ASM combinations, among others. Strengths of the evidence include addressing a variety of outcomes. Inconsistent definitions of DRE, small sample sizes, and heterogeneity among studies limit the ability to draw meaningful conclusions. Optimal combinations of ASMs for rational polytherapy for DRE is unclear