PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury

BACKGROUND: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). METHODS: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). RESULTS: The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [-9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. CONCLUSIONS: DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01799941, registered on 25 February 2013

Genes, social transmission, but not maternal effects influence responses of wild Japanese macaques (Macaca fuscata) to novel-object and novel-food tests

Using long-term maternal pedigree data, microsatellite analysis, and behavioral tests, we examined whether personality differences in wild Japanese macaques (Macaca fuscata) are associated with additive genetic effects, maternal influences, or belonging to a particular social group. Behaviors elicited by novel-object tests were defined by a component related to caution around novel-objects (Ob-PC1) and behaviors elicited by novel food-tests were defined by correlated components related to consummatory responses (Fo-PC1) and caution around novel foods (Fo-PC2). The repeatability of Ob-PC1 was modest and not significant; the repeatabilities of Fo-PC1 and Fo-PC2 were moderate and significant. Linear mixed effects models found that sex, age, sex × age, provisioning, trial number, date, time of day, season, and distance to the closest monkey were not related to personality. Linear mixed effects models of females older than 2 years found that high rank was associated with greater caution around novel objects. Linear models were used to determine whether sex, age, group membership, maternal kinship, or relatedness had independent effects on the personality similarity of dyads. These analyses found that pairs of macaques that lived in the same group were less similar in their caution around novel objects, more closely related pairs of macaques were more similar in their tendency to eat novel food, and that pairs of macaques in the same group were more similar in how cautious they were around novel foods. Together, these findings suggest that personality in this population of wild monkeys was driven by rank, genetic effects, and group effects, the latter possibly including the need to exploit different niches in the environment

Lasers and lights for the treatment of striae distensae

Striae distensae (SD) or “stretch marks” are a common and well-recognized dermatologic entity affecting patients of all ages, genders, and ethnicities. The treatment of SD has long been plagued by disappointing outcomes and remains a frustrating entity for both physicians and patients. While striae may become less conspicuous over time, they rarely resolve without intervention. Inspired by the success of lasers for the treatment of scars and rhytides, these devices have been applied to the treatment of SD in the hopes of achieving similar efficacy