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.

Network pharmacology analysis of Chandraprabha Vati: A new hope for the treatment of Metabolic Syndrome.

BACKGROUND: Drug research is increasingly using Network Pharmacology (NP) to tackle complex conditions like Metabolic Syndrome (MetS), which is characterized by obesity, hyperglycemia, and dyslipidemia. Single-action drugs are inadequate to treat MetS, which is marked by a range of complications including glucose intolerance, hyperlipidemia, mitochondrial dysfunction, and inflammation. OBJECTIVES: To analyze Chandraprabha vati using Network Pharmacology to assess its potential in alleviating MetS-related complications. MATERIAL AND METHODS: The genes related to MetS, inflammation, and the target genes of the CPV components were identified using network pharmacology tools like DisgNET and BindingDB. Followed by mapping of the CPV target genes with the genes implicated in MetS and inflammation to identify putative potential targets. Gene ontology, pathway enrichment analysis, and STRING database were employed for further exploration. Furthermore, drug-target-protein interactions network were visualized using Cytoscape 3.9.1. RESULTS: The results showed that out of the 225 target genes of the CPV components, 33 overlapping and 19 non-overlapping genes could be potential targets for MetS. Similarly, 14 overlapping and 7 non-overlapping genes could be potential targets for inflammation. The CPV bioactives target genes were found to be involved in lipid and insulin homeostasis via several pathways revealed by the pathway analysis. The importance of CPV in treating MetS was supported by GO enrichment data; this could be due to its potential to influence pathways linked to metabolism, ER stress, mitochondrial dysfunction, oxidative stress, and inflammation. CONCLUSIONS: These results offer a promising approach to developing treatment and repurposing CPV for complex conditions such as MetS.

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. Design: A retrospective cross-sectional study was conducted using data from a large geographically diverse hospital discharge database. Setting: 860 acute care hospitals in the United States. Participants: Patients 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. Relevance: The 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.

Clinical and Economic Outcomes of Intravenous Brivaracetam Compared With Levetiracetam for the Treatment of Seizures in United States Hospitals.

Background: Seizures are common among hospitalized patients. Levetiracetam (LEV), a synaptic vesicle protein 2A (SV2A) ligand, is a common intravenous (IV) anti-seizure medication option in hospitals. Brivaracetam (BRV), a selective SV2A ligand for treatment of focal seizures in patients ≥16 years, has greater binding affinity, higher lipophilicity, and faster brain entry than IV LEV. Differences in clinical outcomes and associated costs between IV BRV and IV LEV in treating hospitalized patients with seizure remain unknown. Objectives: To compare the clinical outcomes, costs, and healthcare resource utilization between patients with seizure treated with IV BRV and those with IV LEV within hospital setting. Design/Methods: A retrospective cohort analysis was performed using chargemaster data from 210 United States hospitals in Premier Healthcare Database. Adult patients (age ≥18 years) treated intravenously with LEV or BRV (with or without BZD) and a seizure discharge diagnosis between July 1, 2016 and December 31, 2019 were included. The cohorts were propensity score-matched 4:1 on baseline characteristics. Outcomes included intubation rates, intensive care unit (ICU) admission, length of stay (LOS), all-cause and seizure-related readmission, total hospitalization cost, and in-hospital mortality. A multivariable regression analysis was performed to determine the association between treatment and main outcomes adjusting for unbalanced confounders. Results: A total of 450 patients were analyzed (IV LEV, n = 360 vs. IV BRV, n = 90). Patients treated with IV BRV had lower crude prevalence of ICU admission (14.4 vs. 24.2%, P < 0.05), 30-day all-cause readmission (1.1 vs. 6.4%, P = 0.06), seizure-related 30-day readmission (0 vs. 4.2%, P < 0.05), similar mean total hospitalization costs ($13,715 vs. $13,419, P = 0.91), intubation (0 vs. 1.1%, P = 0.59), and in-hospital mortality (4.4 vs. 3.9%, P = 0.77). The adjusted odds for ICU admission (adjusted odds ratio [aOR] = 0.6; 95% confidence interval [CI]:0.31, 1.16; P = 0.13), 30-day all-cause readmission (aOR = 0.17; 95% CI:0.02, 1.24; P = 0.08), and in-hospital mortality (aOR = 1.15; 95% CI:0.37, 3.58, P = 0.81) were statistically similar between comparison groups. Conclusion: The use of IV BRV may provide an alternative to IV LEV for management of seizures in hospital setting due to lower or comparable prevalence of ICU admission, intubation, and 30-day seizure-related readmission. Additional studies with greater statistical power are needed to confirm these findings.

Efficacy, safety, and tolerability of microsphere adapalene vs. conventional adapalene for acne vulgaris.

BACKGROUND: The present study was undertaken to compare the efficacy, safety and tolerability of a new microsphere adapalene formulation and conventional adapalene in adult patients with mild to moderate acne vulgaris. MATERIALS AND METHODS: This prospective, randomized, assessor-blind, multi-centric (3 centres) comparative, post-marketing phase IV study was undertaken in 175 patients with mild to moderate acne after approval by respective Institutional review boards. Patients fulfilling selection criteria were randomly assigned to either microsphere adapalene gel or conventional adapalene gel both once daily in the evening for 12 weeks after obtaining their informed consent. Efficacy variables included success rate and percent lesion reduction from baseline. Safety and tolerability was assessed on the basis of physical examination and monitoring of treatment-emergent adverse events. RESULTS: Of the 175 patients (88 in microsphere and 87 in conventional) 21 were lost to follow-up and considered drop-outs. There was a significant decrease (P < 0.05) in mean inflammatory and non-inflammatory lesion and total lesion counts from 1st week onwards in both groups. A significantly lower number of microsphere treated patients (50%) reported a side effect (P < 0.05) as compared to 71.3% in conventional users. A highly significant decrease was observed in dryness and erythema (P < 0.01) in microsphere group compared to conventional. Eight patients in conventional group discontinued therapy due to severe irritation as compared to none in microsphere adapalene group. COMMENT: Therapy with microsphere adapalene provided a better tolerability with minimal irritation compared to conventional adapalene, without compromising efficacy and could be a better therapeutic option for acne.