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

Program of Research and Education in Aerospace Structures

Since its inception in January 2003, the program has provided support for 1 research professor and a total of 10 Graduate Research Scholar Assistants of these all 10 have completed their MS degree program. The program has generated 10 MS thesis. Final report lists papers presented in seminars for the period January 1, 2003 through June 30, 2005

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

Religion, Genetics, and the Evolving American Experiment with Bioethics

Bioethics is an experiment in culture. As controversial new biological and medical technologies arise, the “public,” with all its institutional and ideological diversity in tow, responds – often in a cacophony of conflicting policy prescriptions. The resulting chaos thus requires a special class of professionals – the bioethicists – to determine the “appropriate” position, i.e. which research and practices should be allowed, funded and released to the public, and which should be condemned or even criminalized. In theory, the appropriate policies are determined and enacted, the appropriate research and practices go forward, and the public accepts and applauds the wisdom of biomedical elites. The reality is far messier. Over the past thirty years, bioethics – a field established to resolve conflict – has itself become a source of conflict and dispute. As such, this paper focuses on religion and genetics to chart the evolution of the American experiment with bioethics. The history reveals two primary trends: the “rationalization” of bioethics in the 1970s and 80s; and the corresponding conservative “Christian” backlash beginning in the 1990s. Additionally, the focus on controversial genetic research highlights the growing politicization of bioethics and Presidential bioethical committees as well as the use of bioethical issues in political elections. Finally, the first decade of the current millennium provides yet another twist: the growing importance of non-traditional or “radical” bioethics and more “liberal” Christian positions

Liquid-infiltrated photonic crystals: Ohmic dissipation and broadening of modes

The pronounced light-matter interactions in photonic crystals make them interesting as opto-fludic "building blocks" for lab-on-a-chip applications. We show how conducting electrolytes cause dissipation and smearing of the density-of-states, thus altering decay dynamics of excited bio-molecules dissolved in the electrolyte. Likewise, we find spatial damping of propagating modes, of the order dB/cm, for naturally occurring electrolytes such as drinking water or physiological salt water.Comment: 9 pages including 2 figure

Making a Case for Case-Based Teaching in Data Literacy

Building on a study conducted by the authors, this article provides strategies for teaching data literacy and outlines the case-based teaching method as an effective way of developing data-literate teachers

Asking, Learning, Seeking Out : An Exploration of Data Literacy for Teaching

The current study explored preservice and inservice teachers’ perspectives on data literacy for teaching. Semi-structured interviews were employed with 12 teacher candidates in elementary and special education. The findings revealed participants’ misconceptions regarding formative and summative data; their understanding of the value of formative data; perceptions of challenges related to data literacy for teaching including time, making sense of data, and reliability and validity; and candidates’ preferences for authentic data literacy instruction

Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily generalized tonic-clonic seizures: Pooled results from three Phase III studies

AbstractPurposeSecondarily generalized tonic-clonic seizures (SGTCS) are among the most devastating types of seizures, contributing to increased morbidity and mortality. Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle 2A (SV2A), has been shown to be useful for the adjunctive treatment of focal seizures. We sought to determine its specific efficacy in treating SGTCS.MethodsData were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1⿿2 antiepileptic drugs (AEDs) who received placebo or BRV 50⿿200mg/day without titration over a 12-week treatment period. We report efficacy and safety/tolerability data for the BRV therapeutic dose range (50⿿200 mg/day) in patients with focal seizures including baseline SGTCS.ResultsPatients (efficacy population, N=409) had been diagnosed with epilepsy for a mean±standard deviation duration of 22.2±13.1years. Baseline median SGTCS frequency was 3.0 per 28days. The majority (293, 71.6%) had failed ⿥2 AEDs prior to study enrollment. The median percent reduction from baseline in SGTCS frequency/28days was: placebo, 33.3%; BRV 50mg/day, 66.6% (p<0.001); BRV 100mg/day, 61.2% (p=0.002); and BRV 200mg/day, 82.1% (p<0.001). The ⿥50% responder rate for SGTCS was: placebo, 33.0%; BRV 50mg/day, 61.3% (p=0.003); BRV 100mg/day, 55.0% (p<0.001); and BRV 200mg/day, 64.0% (p<0.001). Freedom from SGTCS was achieved by: placebo, 14.8%; BRV 50mg/day, 22.6%; BRV 100mg/day, 31.0%; and BRV 200mg/day, 36.0% of patients. Time to first SGTCS during the treatment period was longer in patients receiving BRV than placebo (26days vs 8days, hazard ratio 0.55, p<0.001). In the SGTCS safety population (N=487), treatment-emergent adverse events (TEAEs) were reported by 60.6% of patients receiving placebo vs 65.0% of patients receiving BRV ⿥50mg/day. Serious TEAEs were reported by 3.1% placebo vs 3.9% BRV ⿥50mg/day. Discontinuations due to TEAEs were 3.9% placebo vs 6.3% BRV ⿥50mg/day.ConclusionsIn patients with drug-resistant focal seizures, adjunctive BRV is effective in reducing the frequency of SGTCS. Almost one-third (30.4%) of patients were rendered completely free of SGTCS during the 12-week treatment period when taking BRV ⿥50mg/day. BRV was well tolerated, with a TEAE profile consistent with that of the overall study population

“Paper Machine” for Molecular Diagnostics

Clinical tests based on primer-initiated amplification of specific nucleic acid sequences achieve high levels of sensitivity and specificity. Despite these desirable characteristics, these tests have not reached their full potential because their complexity and expense limit their usefulness to centralized laboratories. This paper describes a device that integrates sample preparation and loop-mediated isothermal amplification (LAMP) with end point detection using a hand-held UV source and camera phone. The prototype device integrates paper microfluidics (to enable fluid handling) and a multilayer structure, or a “paper machine”, that allows a central patterned paper strip to slide in and out of fluidic path and thus allows introduction of sample, wash buffers, amplification master mix, and detection reagents with minimal pipetting, in a hand-held, disposable device intended for point-of-care use in resource-limited environments. This device creates a dynamic seal that prevents evaporation during incubation at 65 °C for 1 h. This interval is sufficient to allow a LAMP reaction for the Escherichia coli malB gene to proceed with an analytical sensitivity of 1 double-stranded DNA target copy. Starting with human plasma spiked with whole, live E. coli cells, this paper demonstrates full integration of sample preparation with LAMP amplification and end point detection with a limit of detection of 5 cells. Further, it shows that the method used to prepare sample enables concentration of DNA from sample volumes commonly available from fingerstick blood draw.Chemistry and Chemical Biolog