Objectives To assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the impact of potential publication bias in trials of reboxetine. Design Systematic review and meta-analysis including unpublished data. Data sources Bibliographic databases (Medline, Embase, PsycINFO, BIOSIS, and Cochrane Library), clinical trial registries, trial results databases, and regulatory authority websites up until February 2009, as well as unpublished data from the manufacturer of reboxetine (Pfizer, Berlin). Eligibility criteria Double blind, randomised, controlled trials of acute treatment (six weeks or more) with reboxetine versus placebo or SSRIs in adults with major depression. Outcome measures Remission and response rates (benefit outcomes), as well as rates of patients with at least one adverse event and withdrawals owing to adverse events (harm outcomes). Data extraction and data synthesis The procedures for data extraction and assessment of risk of bias were always conducted by one person and checked by another. If feasible, data were pooled by meta-analyses (random effects model). Publication bias was measured by comparing results of published and unpublished trials. Results We analysed 13 acute treatment trials that were placebo controlled, SSRI controlled, or both, which included 4098 patients. Data on 74% (3033/4098) of these patients were unpublished. In the reboxetine versus placebo comparison, no significant differences in remission rates were shown (odds ratio 1.17, 95% confidence interval 0.91 to 1.51; P=0.216). Substantial heterogeneity (I 2 =67.3%) was shown in the meta-analysis of the eight trials that investigated response rates for reboxetine versus placebo. A sensitivity analysis that excluded a small inpatient trial showed no significant difference in response rates between patients receiving reboxetine and those receiving placebo (OR 1.24, 95% CI 0.98 to 1.56; P=0.071; I 2 =42.1%). Reboxetine was inferior to SSRIs (fluoxetine, paroxetine, and citalopram) for remission rates (OR 0.80, 95% CI 0.67 to 0.96; P=0.015) and response rates (OR 0.80, 95% CI 0.67 to 0.95; P=0.01). Reboxetine was inferior to placebo for both harm outcomes (P<0.001 for both), and to fluoxetine for withdrawals owing to adverse events (OR 1.79, 95% CI

MD; for the DEDAS InvestigatorsBackground and Purpose-Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke. Methods-DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 g/kg and 125 g/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined. Results-Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: nϭ8; 90 g/kg: nϭ14; 125 g/kg: nϭ15 g/kg desmoteplase. In the target population (nϭ25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 g/kg desmoteplase (Pϭ0.022). Conclusions-Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 g/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).

Ultrasonic perfusion imaging predicts size and localization of acute stroke. It is unclear whether irreversibly damaged tissue can be differentiated from tissue at risk. Thirty-four patients (ischemic stroke <12 h) were included (Phase Inversion Harmonic Perfusion Imaging; bolus kinetic; fitted model function). Three patterns of perfusion were defined in 14 prespecified regions of interest (ROI): ‘normal', ‘hypoperfusion', and ‘no perfusion'. Clinical status was assessed using the National Institutes of Health Stroke Scale (NIHSS) (at baseline and at days 2 to 4). Cranial Computed Tomography (CCT) (days 2 to 4) displayed final infarction. The pattern ‘hypoperfusion’ (ROIs presumably representing tissue at risk) was tested twofold: (i) Functional impairment by correlating their number with baseline NIHSS. (ii) Viability by correlating their recruitment rate to infarction with clinical course (ΔNIHSS days 2 to 4). In addition, various predictive values were assessed. Twenty-seven patients were eligible for analysis. The sum of ROIs with ‘no perfusion’ and ‘hypoperfusion’ correlated highest with baseline NIHSS ( ρ = 0.78, P < 0.001). Recruitment of hypoperfused ROIs to infarction highly correlated with clinical course ( ρ = 0.79, P < 0.001). Clinical course dichotomized the patients into subgroups A ('stable', ΔNIHSS ≥ −3) and B ('improved', ΔNIHSS ≤ −4). In A, sensitivity and specificity for hypo- and nonperfused tissue being eventually infarcted were 96% and 88% positive predictive value, PPV 89%, negative predictive value, NPV 96%). In B, sensitivity and specificity for nonperfused tissue eventually being infarcted were 81% and 99% (PPV 99%, NPV 84%). Different perfusion patterns (hypoperfusion, no perfusion) and dysfunctional but viable tissue at risk can be reliably detected by ultrasonic perfusion imaging. This method may give Supplementary information in cases illegible for perfusion-weighted magnetic resonance imaging (PW-MRI).