A proof-of-concept study comparing tinnitus and neural connectivity changes following multisensory perceptual training with and without a low-dose of fluoxetine.

Background. This proof-of-concept study investigated a method of multisensory perceptual training for tinnitus, and whether a short, low-dose administration of fluoxetine enhanced training effects and changed neural connectivity.Methods. A double-blind, randomized placebo controlled design with 20 participants (17 male, 3 female, mean age = 57.1 years) involved 30 min daily computer-based, multisensory training (matching visual, auditory and tactile stimuli to perception of tinnitus) for 20 days, and random allocation to take 20 mg fluoxetine or placebo daily. Behavioral measures of tinnitus and correlations between pairs of a priori regions of interest (ROIs), obtained using resting-state functional magnetic resonance imaging (rs-fMRI), were performed before and after the training.Results. Significant changes in ratings of tinnitus loudness, annoyance, and problem were observed with training. No statistically significant changes in Tinnitus Functional Index, Tinnitus Handicap Inventory or Depression Anxiety Stress Scales were found with training. Fluoxetine did not alter any of the behavioural outcomes of training compared to placebo. Significant changes in connectivity between ROIs were identified with training; sensory and attention neural network ROI changes correlated with significant tinnitus rating changes. Rs-fMRI results suggested that the direction of functional connectivity changes between auditory and non-auditory networks, with training and fluoxetine, were opposite to the direction of those changes with multisensory training and placebo.Conclusions. Improvements in tinnitus measures were correlated with changes in sensory and attention networks. The results provide preliminary evidence for changes in rs-fMRI accompanying a multisensory training method in persons with tinnitus.

Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.

OBJECTIVES: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. METHODS: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. RESULTS: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). CONCLUSIONS: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.