Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies

Introduction: This analysis was conducted to assess the tolerability, safety, and efficacy of brivaracetam (BRV) for adjunctive treatment of focal (partial-onset) seizures in patients aged ≥65 years. Methods: Safety/tolerability and efficacy data for patients aged ≥65 years were pooled from three randomized, double-blind, placebo-controlled, fixed-dose Phase III studies (NCT00490035, NCT00464269, and NCT01261325). Data were pooled by treatment group: placebo or the proposed therapeutic dose range of 50–200 mg/day: BRV 50, 100, 200 mg/day. Results: Thirty-two patients aged ≥65 years were randomized to placebo or BRV 50–200 mg/day. Of these, 30 patients (93.8%) completed their respective study. In the safety population (n = 32), 87.5% placebo- vs 73.3% BRV-treated patients reported treatment-emergent adverse events (TEAEs) during the treatment period; most commonly, headache (25.0% vs 12.5%), paresthesia (0% vs 12.5%), and somnolence (50.0% vs 12.5%) for placebo- vs BRV-treated patients, respectively. During the treatment period, drug-related TEAEs were reported by 62.5% of placebo- vs 53.3% of BRV-treated patients, and serious TEAEs (SAEs) were reported by 0% of placebo- and 4.2% of BRV-treated patients; there were no drug-related SAEs and no deaths. Three SAEs (placebo 1/8; BRV 2/24) and two deaths (placebo 1/8; BRV 1/24) occurred in the post-treatment period. In the efficacy population (n = 31), median percent reduction from baseline in focal seizure frequency/28 days was 14.0% for placebo vs 25.5%, 49.6%, and 74.9% for BRV 50, 100, and 200 mg/day, respectively. The ≥50% responder rate was 14.3% for placebo vs 25.0%, 50.0%, and 66.7% for BRV 50, 100, and 200 mg/day, respectively. Conclusions: Safety/tolerability and efficacy findings in this small subgroup of older patients treated with adjunctive BRV are consistent with those observed in the much larger overall pooled population. BRV may be a suitable adjunctive treatment for older patients with uncontrolled focal seizures. Further larger studies in this population are warranted

Comparison of efficacy of ketamine, midazolam and ketamine plus midazolam for prevention of shivering under spinal anaesthesia

Background: Ketamine and Midazolam have been reported to be effective for prevention and treatment of post-operative shivering following spinal anesthesia. The present study aimed at the comparison of i.v. ketamine, i.v. midazolam, midazolam and ketamine in combination, and placebo (saline) for the prevention of shivering in patients undergoing elective surgery under spinal anesthesia.Methods: This study was a double blinded, prospective, randomized controlled study of 120 cases between 18-60 years of age of either sex operated in the Uro-surgery department at KEM Hospital, Mumbai, after obtaining approval from institutional ethics committee and written informed consent from the patients.Results: Midazolam premedication reduces core body temperature by inhibiting tonic thermoregulatory vasoconstriction whereas, ketamine premedication increased core temperature.  Core temperature remained unchanged in combination of the drugs which suggests that the thermoregulatory effects of a benzodiazepine receptor agonist and competitive receptor antagonist of NMDA oppose each other.Conclusions: This study concludes that use of a combination of ketamine plus midazolam was significantly superior to ketamine alone for the prevention of shivering.

Editorial

No Abstrac

AI Radar Sensor: Creating Radar Depth Sounder Images Based on Generative Adversarial Network

This work is licensed under a Creative Commons Attribution 4.0 International License.Significant resources have been spent in collecting and storing large and heterogeneous radar datasets during expensive Arctic and Antarctic fieldwork. The vast majority of data available is unlabeled, and the labeling process is both time-consuming and expensive. One possible alternative to the labeling process is the use of synthetically generated data with artificial intelligence. Instead of labeling real images, we can generate synthetic data based on arbitrary labels. In this way, training data can be quickly augmented with additional images. In this research, we evaluated the performance of synthetically generated radar images based on modified cycle-consistent adversarial networks. We conducted several experiments to test the quality of the generated radar imagery. We also tested the quality of a state-of-the-art contour detection algorithm on synthetic data and different combinations of real and synthetic data. Our experiments show that synthetic radar images generated by generative adversarial network (GAN) can be used in combination with real images for data augmentation and training of deep neural networks. However, the synthetic images generated by GANs cannot be used solely for training a neural network (training on synthetic and testing on real) as they cannot simulate all of the radar characteristics such as noise or Doppler effects. To the best of our knowledge, this is the first work in creating radar sounder imagery based on generative adversarial network

Editorial

Education in Uganda and indeed in most of the developing world is regarded as theoretical and irrelevant to the realities of practical life. It is true that due to the increase in the number of higher education institutions, the number of graduates has also soared. Much as there are limited formal employment opportunities for thesefresh job seekers, the challenge is that many of them even lack the skills to perform the duties required of the few vacancies that exist in the job market – let alone the innovativeness to create their own

Classification of Native Vegetation of Oregon - 2019

This classification is an update of the 2004 classification of native vegetation of Oregon by Kagan, Christy, Murray and Titus. As before, this classification lists the native plant associations known to occur in Oregon, and includes both successional and climax vegetation types that were part of the presettlement landscape of Oregon and can still be found in the state. It serves as an index to the diversity, distribution and relative rarity of the state\u27s native plant associations, and as a guide to their literature. Published and unpublished reports supported by quantitative data were the primary sources for the classification. In order to accurately identify or describe a plant association, we recommend reading the written descriptions or keys presented in the references cited for each association. This update incorporates recent classification efforts and scholarship, removes a handful of associations that are no longer present in Oregon, and reconciles the 2004 classification with the United States National Vegetation Classification (USNVC) version 2.02 (2018). The USNVC is a hierarchical plant community classification designed to standardize vegetation classification in the United States (Jennings et al. 2009). It employs a nested system of six physiognomic ranks and two floristically-defined ranks. Only associations, the finest level of that classification are described here. This list includes some newly described or provisional associations not included in the USNVC, which do not have standard USNVC codes. Plant associations are listed by scientific name, followed by common name. Listings include the global and state rank of each association, a unique code linking to the National Vegetation Classification (USNVC), the Omernik based ecoregions in Oregon in which it occurs, and its distribution in other western states and provinces. Also included is a list of primary references in which the association was described. Sampling methods and concepts of species and associations differ greatly among researchers. Publications from other states or provinces in the Pacific Northwest are included for associations known to occur in, but not described from Oregon

Efficacy and tolerability of adjunctive brivaracetam in patients with prior antiepileptic drug exposure: A post-hoc study.

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV at enrollment were excluded from this analysis. Patients were categorized by their status of prior exposure to LEV, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LTG), to investigate any consistent trend towards reduced response in AED-exposed subgroups compared to AED-naïve subgroups, regardless of the mechanism of action. Study completion rates, percent reduction from baseline in focal seizure frequency over placebo, ≥50% responder rates, and tolerability were evaluated for each subgroup. A total of 1160 patients were investigated. Study completion rates were similar in the AED-exposed subgroups and AED-naïve subgroups. In subgroups with (531 patients) or without (629 patients) prior LEV exposure, ≥50% responder rates for each dose of BRV compared with placebo were generally higher among the LEV-naïve subgroups than the previously LEV-exposed subgroups. LEV-exposed subgroups receiving BRV doses ≥50mg/day showed greater ≥50% responder rates than those receiving placebo. Similar results were observed for CBZ, TPM, and LTG. Previous treatment failure with commonly prescribed AEDs (LEV, CBZ, TPM, or LTG) is associated with a reduced response to BRV irrespective of the mechanism of action. Hence, this post-hoc analysis indicates that previous treatment failure with LEV does not preclude the use of BRV in patients with epilepsy