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

Effect of accumulated vs continuous exercise on excess post-exercise oxygen consumption

Background: A continuous aerobic exercise program is an effective method of improving calorie consumption on the metabolism of skeletal muscle. However, studies report that accumulated exercise of 30 minutes divided into three sessions of 10 minutes is as effective as one continuous exercise session for 30 minutes. As yet, no study has compared the excess post-exercise oxygen consumption associated with accumulated exercise and continuous exercise over these timeframes. Objective: The primary purpose of this study was to compare the excess post-exercise oxygen consumption associated with performing continuous exercise for 30 minutes and three sessions of accumulated exercise for 10 minutes at the same intensity of 60% VO2max. Method: Posters about the study were posted on the February 2019 Konkuk university homepage and bulletin board, and a total of 34 college students (males, n=18; females, n=16) volunteered to participate. Using a balanced repeated-measures crossover design, the subjects randomly took two exercises: continuous exercise (1 x 30 minutes) or accumulated exercise (3 x 10 minutes), and the washout period between the two exercises was a week. All exercises were performed using an ergometer at 60% maximal oxygen consumption. Oxygen consumption and heart rate were monitored and measured during exercise and after exercise. Lipid profile and lactate acid were measured at rest, exercise end, exercise end plus 30 minutes, and exercise end plus 60 minutes. IBM SPSS Statistics 23 was used to perform a paired t-test, and the statistically significant difference was set at <.05. Results: Excess post-exercise oxygen consumption parameters (e.g., total oxygen consumption, total calorie, and summation of heart rate) were higher in accumulated exercise than in continuous exercise (p<.05). No significant difference in the calorie during exercise between CEx and AEx (p = .140). No significant difference was observed in the lipid profile between accumulated exercise and continuous exercise (p>.05). No significant differences were observed at rest, exercise end plus 30 minutes, exercise end plus 60 minutes in lactic acid in the blood (p <.05). However, at exercise end, it was significantly higher in the accumulated exercise (p<.01). Conclusions: This study confirmed that after equalizing energy expenditure for continuous exercise and accumulated exercise in participants in their 20s, accumulated exercise results in higher excess post-exercise oxygen consumption than continuous exercise. The data suggests that accumulated exercise may be more effective in reducing body fat than continuous exercise for a given amount of energy expenditure. [Ethiop.J. Health Dev. 2020;34(Special issue-3):84-90] Keywords: Continuous exercise, accumulated exercise, excess post-exercise oxygen consumptio

Agoraphobia and Follicle-Stimulating Hormone Levels between Tamoxifen and Goserelin versus Tamoxifen Alone in Premenopausal Hormone Receptor-Positive Breast Cancer: A 12-Month Prospective Randomized Study

Objective: Tamoxifen is an estrogen receptor antagonist used to prevent recurrence of breast cancer, which may provoke depression and anxiety and increase follicle-stimulating hormone (FSH) to patients. We compared anxiety and depression symptoms and FSH levels who received conventional tamoxifen alone and combination treatment of goserelin, a gonadotropin-releasing hormone (GnRH) analogue, with tamoxifen. Methods: Sixty-four premenopausal women with hormone receptor-positive early-stage breast cancer were included and were assigned randomly to receive either tamoxifen and goserelin combination or tamoxifen alone for 12 months. The participants were evaluated blindly using the Hamilton Depression and Anxiety Rating Scale, the Beck Depression Rating Scale, and the Albany Panic and Phobia Questionnaire (APPQ). Blood FSH levels were assessed at baseline, 6 and 12 months. Results: A significant time×group difference was detected in the agoraphobia trends subscale of the APPQ and in FSH levels. The combination group showed significantly less increases in agoraphobia subscale of APPQ and greater decreases in FSH level than those in the tamoxifen-alone group from baseline to 12 months of treatment. No significant differences for age, tumor grade, body mass index, or family history were found at baseline between the two groups. Conclusion: Our results suggest that the combination treatment of tamoxifen and goserelin resulted in less agoraphobia than tamoxifen alone in premenopausal women with breast cancer, which may associated with FSH suppression of goserelin

Anti-inflammatory effects of Radix Gentianae Macrophyllae (Qinjiao), Rhizoma Coptidis (Huanglian) and Citri Unshiu Pericarpium (Wenzhou migan) in animal models

<p>Abstract</p> <p>Background</p> <p>KHU14, an ethanolic extract of <it>Radix Gentianae Macrophyllae </it>(<it>Qinjiao</it>), <it>Rhizoma Coptidis </it>(<it>Huanglian</it>) and <it>Citri Unshiu Pericarpium </it>(<it>Wenzhou migan</it>) was tested for its anti-inflammatory effects.</p> <p>Methods</p> <p>Three out of 20 herbs were found to have anti-inflammatory effects. The formulation of these herbs, i.e. KHU14 was tested for croton oil-induced ear edema, carrageenan-induced paw edema, acetic acid-induced capillary permeability, cotton pellet and delayed type hypersensitivity.</p> <p>Results</p> <p>KHU14 exhibited anti-inflammatory effects in animal models of acute and chronic inflammation. The anti-inflammatory activity of KHU14 observed was comparable to that of celecoxib. KHU14 inhibited the production of NO and PGE₂in LPS/IFN-gamma-stimulated peritoneal macrophages, and reduced edema and the amount of infiltrated cells in animal models.</p> <p>Conclusion</p> <p>KHU14 exhibited anti-inflammatory effects as demonstrated in typical immunological tests for anti-inflammation <it>in vitro </it>and <it>in vivo</it>.</p

Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08–3.29), bradycardia (aOR: 2.09, 95% CI: 1.24–3.53), and hypotension (aOR: 1.67, 95% CI: 1.03–2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin

Hypoxic Pilates Intervention for Obesity: A Randomized Controlled Trial

This study examined the effect of Pilates training under hypoxia, a novel treatment method, for obesity. Thirty-two Korean women with obesity (age: 34&ndash;60 (47.5 &plusmn; 7.5) years) were randomly assigned to control (CON; n = 10), normoxic Pilates training (NPTG; n = 10), and hypoxic Pilates training groups (HPTG; n = 12). The NPTG and HPTG performed 50 min of Pilates training using a tubing band for 12 weeks (3 days/week) in their respective environmental conditions (NPTG: normoxic condition, inspired oxygen fraction (FiO2) = 20.9%; HPTG: moderate hypoxic condition, FiO2 = 14.5%). The CON maintained their daily lifestyle without intervention. All subjects underwent body composition, blood pressure, arterial stiffness, vascular endothelial function, cardiometabolic biomarker, hemorheological function, and aerobic performance measurements before and after the intervention. The HPTG showed a significant improvement in diastolic blood pressure, total cholesterol and triglyceride concentrations, flow-mediated dilation, and erythrocyte deformability and aggregation (all p &lt; 0.05) compared with the CON and NPTG. However, compared with the CON and NPTG, the HPTG did not show improvement in other parameters. Hypoxic Pilates intervention is a novel and successful method for promoting endothelial and hemorheological functions in women with obesity

Suppressive Effects of Flavonoids on Macrophage-Associated Adipocyte Inflammation in a Differentiated Murine Preadipocyte 3T3-L1 Cells Co-Cultured with a Murine Macrophage RAW264.7 Cells

The suppressive effects of flavonoids on macrophage-associated adipocyte inflammation in a differentiated murine preadipocyte cell line (3T3-L1) co-cultured with a murine macrophage cell line (RAW264.7) were evaluated. Extracellular lipid accumulation was investigated via Oil Red O staining. The expression levels of adipogenesis- and inflammation-associated proteins, including CCAAT/enhancer-binding protein (C/EBP)-&alpha;, inducible nitric oxide synthase (iNOS), C/EBP&beta;, peroxisome proliferator-activated receptor &gamma; (PPAR&gamma;), and cyclooxygenase-2 (COX-2), were determined via Western blotting. Proinflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1) and interleukin-6 (IL-6), were assessed using enzyme-linked immunosorbent assay kits. We found that silybin, formononetin, and diosmetin inhibited lipid accumulation and production of proinflammatory cytokines in the co-cultures of 3T3-L1 and RAW264.7 cells. Moreover, they inhibited the protein expression of PPAR&gamma;, C/EBP&alpha;, COX-2, C/EBP&beta;, and iNOS in the co-cultures of 3T3-L1 and RAW264.7 cells. These data support that silybin, formononetin, and diosmetin inhibit macrophage-associated adipocyte inflammation and lipid accumulation

Simple and Efficient Spherical Crystallization of Clopidogrel Bisulfate Form-I via Anti-Solvent Crystallization Method

Clopidogrel bisulfate (CLP) form-I crystals are irregular, rectangular-shaped crystals. Because of their poor compressibility, flowability and their strong surface tension, manufacturers apply spherical crystallization methods to produce CLP form-I spherical agglomerates with a uniform particle size distribution. Consequently, manufacturers primarily synthesize CLP form-I crystal salts utilizing very complex methods, which produces form-I spherical agglomerates by means of spherical crystallization. In this study, spherical crystals of CLP Form-I were directly prepared from CLP Form-II, the most stable polymorph at room temperature, by using ethanol as solvent and a mixture of isopropyl alcohol (IPA)/n-Hexane (Hex) as an anti-solvent. To provide systematic inputs for the development of spherical agglomerates of optimal morphology, size, particle size distribution (PSD), and polymorphic form, processing parameters such as anti-solvent type, a mixture of IPA/Hex, pure Hex, or pure acetone; stirring speeds of 500, 600, 700, or 800 rpm; and temperatures ranging from 25 to 40 &deg;C were explored. The effects of these parameters on spherical crystallization and polymorphic form were studied in terms of supersaturation, a driving force for polymorphic transformation, and the crystallization solution. Notably, our method does not require a large volume of anti-solvent which is the main complication of conventional anti-solvent crystallization methods