Prediction of the Lethal Outcome of Acute Recurrent Cerebral Ischemic Hemispheric Stroke.

Background and objectives. Stroke-induced mortality is the third most common cause of death in developed countries. Intense interest has focused on the recurrent ischemic stroke, which rate makes up 30% during first 5 years after first-ever stroke. This work aims to develop criteria for the prediction of acute recurrent cerebral ischemic hemispheric stroke (RCIHS) outcome on the basis of comprehensive baseline clinical, laboratory, and neuroimaging examinations. Materials and Methods. One hundred thirty-six patients (71 males and 65 females, median age 74 (65; 78)) with acute RCIHS were enrolled in the study. All patients underwent a detailed clinical and neurological examination using National Institutes of Health Stroke Scale (NIHSS), computed tomography of the brain, hematological, and biochemical investigations. In order to detect the dependent and independent risk factors of the lethal outcome of the acute period of RCIHS, univariable and multivariable regression analysis were conducted. A receiver operating characteristic (ROC) analysis with the calculation of sensitivity and specificity was performed to determine the prediction variables. Results. Twenty-five patients died. The independent predictors of the lethal outcome of acute RCIHS were: Baseline NIHSS score (OR 95% CІ 1.33 (1.08-1.64), p = 0.0003), septum pellucidum displacement (OR 95% CI 1.53 (1.17-2.00), p = 0.0021), glucose serum level (OR 95% CI 1.28 (1.09-1.50), p = 0.0022), neutrophil-to-lymphocyte ratio (OR 95% CI 1.11 (1.00-1.21), p = 0.0303). The mathematical model, which included these variables was developed and it could determine the prognosis of lethal outcome of the acute RCIHS with an accuracy of 86.8% (AUC = 0.88 ± 0.04 (0.88-0.93), p < 0.0001).

Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial.

BACKGROUND: Many patients with Parkinson's disease have motor fluctuations despite treatment with available drugs. Tozadenant (SYN115) is an oral, selective adenosine A2A receptor antagonist that improves motor function in animal models of Parkinson's disease. We aimed to assess the safety and efficacy of tozadenant as an adjunct to levodopa in patients with Parkinson's disease who have motor fluctuations on levodopa. METHODS: We did an international, multicentre, phase 2b, randomised, double-blind, placebo-controlled, parallel-group, dose-finding clinical trial of tozadenant in levodopa-treated patients with Parkinson's disease who had motor fluctuations (at least 2·5 h off-time per day). Eligible patients were randomly assigned via a computer-generated randomisation schedule to receive tozadenant 60, 120, 180, or 240 mg or matching placebo twice daily for 12 weeks. All study management, site personnel, and patients were masked to treatment assignment. The primary outcome was change from baseline to week 12 in hours per day spent in the off-state (assessed from Parkinson's disease diaries completed by patients). This study is registered at ClinicalTrials.gov, number NCT01283594. FINDINGS: Of 420 randomised patients (mean age 63·3 [SD 8·3] years; mean duration of Parkinson's disease 8·7 [4·7] years), 403 provided post-baseline diary data and 337 completed study treatment. Compared with placebo, mean daily off-time was significantly reduced in the combined tozadenant 120 mg twice-daily and 180 mg twice-daily group (-1·1 h, 95% CI -1·8 to -0·5; p=0·0006), the tozadenant 120 mg twice-daily group (-1·1 h, -1·8 to -0·4; p=0.0039), and the tozadenant 180 mg twice-daily group (-1·2 h, -1·9 to -0·4; p=0·0039). The most common adverse events in these groups were dyskinesia (seven [8%] of 84 patients in the placebo group, 13 [16%] of 82 in the 120 mg twice-daily group, and 17 [20%] of 85 in the 180 mg twice-daily group), nausea (three [4%], 9 [11%], and ten [12%]), and dizziness (one [1%], four [5%], and 11 [13%]). Tozadenant 60 mg twice daily was not associated with a significant reduction in off-time, and tozadenant 240 mg twice daily was associated with an increased rate of discontinuation because of adverse events (17 [20%] of 84 patients). INTERPRETATION: Tozadenant at 120 or 180 mg twice daily was generally well tolerated and was effective at reducing off-time. Further investigation of tozadenant treatment in phase 3 trials is warranted. FUNDING: Biotie Therapies.