Testing the nonclinical Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm with an established anti-seizure medication: Levetiracetam case study.

Levetiracetam (LEV), a well-established anti-seizure medication (ASM), was launched before the original ICH S7B nonclinical guidance assessing QT prolongation potential and the introduction of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm. No information was available on its effects on cardiac channels. The goal of this work was to "pressure test" the CiPA approach with LEV and check the concordance of nonclinical core and follow-up S7B assays with clinical and post-marketing data.

Evaluation of the Effectiveness of the Risk Minimization Measures of Sodium Oxybate in the European Union.

Background: Sodium oxybate (Xyrem), approved by the European Medicines Agency (EMA) for narcolepsy with cataplexy, is only available through risk mitigation programs due to potential adverse effects including respiratory and central nervous system depression, neuropsychiatric events, and misuse.

Objective: We report findings from a survey evaluating effectiveness of the European Union Xyrem Risk Management Plan (RMP).

Patients And Methods: A cross-sectional, online, multiple-choice survey was distributed to randomly selected healthcare professionals (HCPs) from six European countries (April 2016-May 2018).

Long-term compliance, safety, and tolerability of sodium oxybate treatment in patients with narcolepsy type 1: a postauthorization, noninterventional surveillance study.

Study Objectives: To evaluate adherence to sodium oxybate prescribing information for indication and dosage, patients' compliance with instructions for use, safety/tolerability in routine clinical practice, and abuse potential.

Methods: A postauthorization, noninterventional surveillance study (NCT00244465) in patients who were prescribed sodium oxybate according to current practice by sleep disorders specialists. Patients were monitored for ≤18 months.

Safety of cetirizine in pregnancy.

Managing symptoms of allergic rhinitis (AR) and urticaria in pregnant women is important to reduce complications and negative outcomes. The objective of this study was to provide information on the pregnancy outcomes of women exposed to the antihistamine cetirizine (CTZ). The UCB Pharma Patient Safety Database was searched for pregnancies up to 28 February 2015.

Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re-evaluation of an established drug.

Several noncardiac drugs have been linked to cardiac safety concerns, highlighting the importance of post-marketing surveillance and continued evaluation of the benefit-risk of long-established drugs. Here, we examine the risk of QT prolongation and/or torsade de pointes (TdP) associated with the use of hydroxyzine, a first generation sedating antihistamine. We have used a combined methodological approach to re-evaluate the cardiac safety profile of hydroxyzine, including: (1) a full review of the sponsor pharmacovigilance safety database to examine real-world data on the risk of QT prolongation and/or TdP associated with hydroxyzine use and (2) nonclinical electrophysiological studies to examine concentration-dependent effects of hydroxyzine on a range of human cardiac ion channels.

Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies.

Objective: To evaluate efficacy, tolerability, and safety of adjunctive brivaracetam (BRV) in patients with Unverricht-Lundborg disease (EPM1).

Methods: Two prospective, multicenter, double-blind, phase III trials (N01187/NCT00357669; N01236/NCT00368251) in patients (≥16 years) with genetically ascertained EPM1, showing moderate-severe myoclonus (action myoclonus score ≥30/160), randomized (1:1:1) to twice-daily BRV (N01187: 50 or 150 mg/day; N01236: 5 or 150 mg/day), or placebo. Both studies comprised a baseline period (2 weeks), 2-week up-titration period, 12-week stable-dose maintenance period, and down-titration or entry into long-term follow-up study.

Levetiracetam in a broad population of patients with refractory epilepsy: interim results of the international SKATE trial.

Objective: To prospectively assess the safety and efficacy of levetiracetam in patients with uncontrolled focal epilepsy, in a common practice-based setting.

Patients And Methods: In this phase IV, open-label, 16-week community-based study, adult patients with focal seizures initially received levetiracetam 1,000 mg/day. Throughout the study, the dose was adjusted in increments of 1,000 mg (maximum 3,000 mg/day) to achieve seizure control and maintain tolerability.

Prevalence of activated protein C resistance and analysis of clinical profile in thromboembolic patients. A Belgian prospective study.

Objectives: To assess the prevalence of activated protein C resistance (APC-R) among healthy subjects and thromboembolic patients and to determine the clinical characteristics associated with APC-R.

Design: A prospective study.

Setting: One academic medical centre.

Acquired activated protein C resistance in pregnancy.

Pregnancy induces several haemostatic perturbations. Some authors described possible acquired activated protein C resistance (APCR) during normal pregnancy. We wanted to test this possibility and to evaluate if this acquired APCR might contribute to the known increased tendency to thrombosis associated with pregnancy.

Large increase in plasmatic 11-dehydro-TxB2 levels due to oral contraceptives.

Coagulation factors, 11-dehydro-TxB2 (metabolite of TxA2) and 6-keto-PGF1 alpha (metabolite of PGI2) levels in 87 women who were treated for 9 months with oral contraceptives (OC) containing low doses of oestrogens and progestogens (Triquilar, Trinovum or Cilest) were investigated. In plasma, increases in F I, II, VII, VIII-c and 11-dehydro-TxB2 levels, but no modification of 6-keto-PGF1 alpha were observed. In urine, FPA concentration rose, but no change occurred in 11-dehydro-TxB2 and 6-keto-PGF1 alpha levels.

Comparison of anti-Helicobacter (Campylobacter) pylori IgG antibodies between different areas of Belgium.

We have collected sera from 4053 patients of different parts of Belgium. Sera were randomly selected whatever the kind of pathology. Anti-Helicobacter (Campylobacter) pylori IgG were determined with an ELISA technique using whole formalized bacteria.

Rapid double-sandwich enzyme-linked immunosorbent assay for detection of human immunoglobulin M anti-Toxoplasma gondii antibodies.

The double-sandwich enzyme-linked immunosorbent assay has been compared with the indirect fluorescence assay for the detection of immunoglobulin M antibodies against Toxoplasma gondii in humans. Incubation times have been shortened, permitting the test to be completed within 2 h. The double-sandwich enzyme-linked immunosorbent assay is confirmed to be more sensitive and more specific than the immunofluorescence assay.