Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults With Focal Epilepsy: A Phase 2b Randomized Clinical Trial.

Importance: Many patients with focal epilepsy experience seizures despite treatment with currently available antiseizure medications (ASMs) and may benefit from novel therapeutics.

Objective: To evaluate the efficacy and safety of XEN1101, a novel small-molecule selective Kv7.2/Kv7.

Pathophysiology of duodenal ulcer disease.

: Before the discovery of Helicobacter pylori infection some 12 years ago, three major disturbances in gastric physiology had been identified in patients with duodenal ulcer disease. These abnormalities were: impaired acid inhibition of gastrin release from the antral mucosa, increased basal and stimulated acid secretion by the body of the stomach and increased acid load in the duodenum. Some of these abnormalities in gastric function can now be explained by the effects of H.

Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus.

Background: Patients with concomitant diabetes mellitus (DM) and prior stroke (PS) were excluded from European approval of alteplase in stroke. We examined the influence of DM and PS on the outcomes of patients who received thrombolytic therapy (T; data from Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register) compared to nonthrombolyzed controls (C; data from Virtual International Stroke Trials Archive).

Methods: We selected ischemic stroke patients on whom we held data on age, baseline NIH Stroke Scale score (NIHSS), and 90-day modified Rankin Scale score (mRS).

Home time is extended in patients with ischemic stroke who receive thrombolytic therapy: a validation study of home time as an outcome measure.

Background And Purpose: "Home time" (HT) refers to the number of days over the first 90 after stroke onset that a patient spends residing in their own home or a relative's home versus any institutional care. It is an accessible and objective parameter, free from subjective bias, with potential as an outcome measure in acute stroke trials. We sought to validate HT and assess treatment responsiveness using independent data.

Thrombolysis in very elderly people: controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive.

Objective: To assess effect of age on response to alteplase in acute ischaemic stroke.

Design: Adjusted controlled comparison of outcomes between non-randomised patients who did or did not undergo thrombolysis. Analysis used Cochran-Mantel-Haenszel test and proportional odds logistic regression analysis.

Influence of age on outcome from thrombolysis in acute stroke: a controlled comparison in patients from the Virtual International Stroke Trials Archive (VISTA).

Background And Purpose: Thrombolysis for acute ischemic stroke in patients aged > 80 years is not approved in some countries due to limited trial data in the very elderly. We compared outcomes between thrombolysed and nonthrombolysed (control) patients from neuroprotection trials to assess any influence of age on response. Method-Among patients with ischemic stroke of known age, pretreatment severity (baseline National Institutes of Health Scale Score), and 90-day outcome (modified Rankin Scale score; National Institutes of Health Scale score), we compared the distribution of modified Rankin score in thrombolysed patients with control subjects by Cochran-Mantel-Haenszel test and then logistic regression after adjustment for age and baseline National Institutes of Health Scale score.

Thrombolysis is associated with consistent functional improvement across baseline stroke severity: a comparison of outcomes in patients from the Virtual International Stroke Trials Archive (VISTA).

Background And Purpose: Baseline stroke severity predicts outcomes among thrombolysed patients. The baseline National Institutes of Health Stroke Scale (NIHSS) thresholds are sometimes used to select patients for thrombolysis, clinical trial enrollment, or both. Using data lodged with Virtual International Stroke Trials Archive, we compared adjusted outcomes between thrombolysed and nonthrombolysed patients enrolled in neuroprotection trials (1998-2007) to assess the influence of various levels of baseline NIHSS.

Comparison of outcomes following thrombolytic therapy among patients with prior stroke and diabetes in the Virtual International Stroke Trials Archive (VISTA).

Objective: The use of alteplase in patients who have had a prior stroke and concomitant diabetes is not approved in Europe. To examine the influence of diabetes and prior stroke on outcomes, we compared data on thrombolysed patients with nonthrombolysed comparators.

Research Design And Methods: We selected patients with ischemic stroke on whom we had data on age, pretreatment baseline National Institutes of Health Stroke Scale (b-NIHSS), and 90-day outcome measures (functional modified Rankin score [mRS]) and neurological measures [NIHSS]) in the Virtual International Stroke Trials Archive.

Mismatch-based delayed thrombolysis: a meta-analysis.

Background And Purpose: Clinical benefit from thrombolysis is reduced as stroke onset to treatment time increases. The use of "mismatch" imaging to identify patients for delayed treatment has face validity and has been used in case series and clinical trials. We undertook a meta-analysis of relevant trials to examine whether present evidence supports delayed thrombolysis among patients selected according to mismatch criteria.

The Virtual International Stroke Trials Archive.

Background And Purpose: Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses.

Halving effort in acute stroke trials.

The expense and substantial effort required to conduct multicenter acute stroke trials are potentially limiting factors for progress in this field. To facilitate future work, we need to expand on collaborative approaches to learn from existing trial data sets, for example, using the Virtual International Stroke Trials Archive. Using these networks, we can identify ways of reducing future effort in trials.

A randomised, controlled pilot study to investigate the potential benefit of intervention with insulin in hyperglycaemic acute ischaemic stroke patients.

Background: Hyperglycaemia on presentation with acute ischaemic stroke (AIS) is associated with poor outcome, but intervention is unproven. We investigated the safety and tolerability of one method of glycaemic control.

Methods: Patients within 24 h of AIS and plasma glucose 8-20 mmol/l were randomised to receive either rigorous glycaemic control (RC) or standard management (SM) for 48 h.

NXY-059 for acute ischemic stroke.

Background: NXY-059 is a free-radical-trapping agent that is neuroprotective in animal models of stroke. We tested whether it would reduce disability in humans after acute ischemic stroke.

Methods: We conducted a randomized, double-blind, placebo-controlled trial involving 1722 patients with acute ischemic stroke who were randomly assigned to receive a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours after the onset of the stroke.

The prognostic significance of visible infarction on computed tomography following lacunar stroke: results of a long-term follow-up study.

Background And Purpose: Substantial variability in functional outcome and relatively few factors predictive of death or degree of recovery have been observed in patients with lacunar stroke. Such indicators are of great use in the selection of optimal rehabilitation strategies after stroke. Although computed tomography (CT) of patients with a clinical diagnosis of lacunar stroke performed within the first 10 days shows evidence of cerebral infarction in 50% to 60%, the prognostic significance of a visible ischemic lesion on CT is unclear.

Proton pump inhibitors reduce the bioavailability of dietary vitamin C.

Background: The gastric juice concentration of vitamin C is reduced in subjects with elevated intragastric pH. This is probably because of the fact that the vitamin is unstable at non-acidic pH and undergoes irreversible denaturation.

Aim: To determine whether elevation of intragastric pH reduces the bioavailability of dietary vitamin C.

The AMPA antagonist ZK 200775 in patients with acute ischaemic stroke: a double-blind, multicentre, placebo-controlled safety and tolerability study.

Background And Purpose: ZK 200775 is a selective competitive AMPA receptor antagonist. It has demonstrated neuroprotective efficacy in experimental models of stroke and tolerability in healthy volunteers. We tested the safety and tolerability of ZK 200775 in patients with acute ischaemic stroke.

Effect of perindopril on cerebral vasomotor reactivity in patients with lacunar infarction.

Background And Purpose: There is growing evidence that pharmacologic interference with the renin-angiotensin system may reduce risk of stroke, although the mechanism is unclear. Impaired reactivity of cerebral vessels has recently been recognized as a risk factor for stroke. We examined the effect of the angiotensin-converting enzyme (ACE) inhibitor perindopril on cerebral vasomotor reactivity to acetazolamide in patients with lacunar cerebral infarction.

Bioequivalence and other unresolved issues in generic drug substitution.

Background: Substitution of generic drugs for brand-name products is highly controversial and often is met with suspicion by health care providers and patients. Historically, the debate has focused on the issue of bioequivalence, and clinical practice has identified a number of drug classes for which generic substitution should be approached with caution. Current bioequivalence requirements are based on a measure of average bioequivalence; however, there are fears that use of this measure may be inappropriate in the case of a drug with a narrow or wide therapeutic range or high intrasubject or intersubject variability.

Outcomes from a nurse-led clinic for adolescents with epilepsy.

Purpose: Epilepsy is the commonest serious neurological condition to affect adolescents. We established a nurse-led clinic for young people with suspected or diagnosed epilepsy. Outcomes in all patients referred during the first 4 years after its inception are reported.

Management of acute stroke.

Acute stroke is a medical emergency. The outcome is influenced by the rapidity and quality of initial care, which is best delivered by specialists with appropriate facilities, including 24 h access to computed tomography. Stroke management requires attention to simple details and has been summarised in clinical guidelines.

Vigabatrin, but not gabapentin or topiramate, produces concentration-related effects on enzymes and intermediates of the GABA shunt in rat brain and retina.

Purpose: The antiepileptic drug (AED) vigabatrin (VGB), which exerts its pharmacologic effects on the gamma-aminobutyric acid (GABA) system, causes concentric visual field constriction in >40% of exposed adults. This may be a class effect of all agents with GABA-related mechanisms of action. We compared the concentration-related effects of VGB in rat brain and eye with those of gabapentin (GBP) and topiramate (TPM), both of which have been reported to elevate brain GABA concentrations in humans.

UK-279,276, a neutrophil inhibitory glycoprotein, in acute stroke: tolerability and pharmacokinetics.

Background And Purpose: UK-279,276, a recombinant glycoprotein, binds selectively to the CD11b/CD18 integrin on neutrophils and has the potential to modulate the neuroinflammation associated with acute stroke. After preclinical evidence of neuroprotection, UK-279,276 has entered clinical development. The purposes of this study were to evaluate the safety and tolerability of UK-279,276 and to examine its pharmacokinetics and pharmacodynamics (binding to neutrophil CD11b) in patients with acute stroke.

Low triglyceride, not low cholesterol concentration, independently predicts poor outcome following acute stroke.

Background: Recent data have shown an unexpected association between poor outcome after acute stroke and lower serum cholesterol. Triglyceride concentration has been linked to coronary heart disease and stroke; however, there are currently no data on the relationship between triglyceride and stroke outcome. Such information may yield further mechanistic information on the relationship between lipids and stroke outcome.

Differential expression of multidrug resistance genes in naïve rat brain.

The multidrug resistance (mdr1) gene family encodes the efflux transporter P-glycoprotein (P-gp) which contributes to the functionality of the blood-brain barrier. We have characterised the regional expression of mdr1 genes in nai;ve rat brain. Adult male Sprague-Dawley rats (n=6) were sacrificed and their brains rapidly removed.