Behavioral and transcriptomic effects of a novel cannabinoid on a rat valproic acid model of autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social communication, restricted interests, repetitive behavior and irritability. Exposure to valproic acid (VPA) during pregnancy has been shown to increase the risk of autism in children and has led to the development of the in-utero VPA rat model that elicits neurodevelopmental autistic-like features. Offspring exhibit behavioral and neurobiological alterations modelling ASD symptoms.

Long-term efficacy and safety of three times weekly dosing regimen of glatiramer acetate in relapsing multiple sclerosis patients: Seven-year results of the Glatiramer Acetate Low-frequency Administration (GALA) open-label extension study.

Objective: Describe the long-term outcomes of early-start (ES) and delayed-start (DS) glatiramer acetate 40 mg/mL treatment three times weekly (GA40) for up to seven years in the Glatiramer Acetate Low-frequency Administration (GALA) study in patients with relapsing multiple sclerosis (RMS).

Methods: Patients were evaluated every three to six months. The primary efficacy endpoint was annualized relapse rate (ARR); additional endpoints were exploratory or post hoc.

Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia.

Objective: To evaluate the long-term safety and efficacy of deutetrabenazine in patients with tardive dyskinesia (TD).

Method: Patients with TD who completed the 12 week, phase 3, placebo-controlled trials were eligible to enter this open-label, single-arm study. The open-label study consisted of a 6 week dose-escalation phase and a long-term maintenance phase (clinic visits at Weeks 4, 6 and 15, and every 13 weeks until Week 106).

The MSOAC approach to developing performance outcomes to measure and monitor multiple sclerosis disability.

Background: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability.

Objectives: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials.

Methods: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials.

Comparative utility of disability progression measures in PPMS: Analysis of the PROMiSe data set.

Objective: To assess the comparative utility of disability progression measures in primary progressive MS (PPMS) using the PROMiSe trial data set.

Methods: Data for patients randomized to placebo (n = 316) in the PROMiSe trial were included in this analysis. Disability was assessed using change in single (Expanded Disability Status Scale [EDSS], timed 25-foot walk [T25FW], and 9-hole peg test [9HPT]) and composite disability measures (EDSS/T25FW, EDSS/9HPT, and EDSS/T25FW/9HPT).

Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial.

Background: Tardive dyskinesia results from exposure to dopamine receptor antagonists, such as typical and atypical antipsychotics. If clinically appropriate, clinicians often manage this disorder by lowering the dose of, or discontinuing, the causative drug. There is a significant unmet need for a treatment option that does not disrupt treatment regimens for underlying psychiatric illnesses.

Randomized controlled trial of deutetrabenazine for tardive dyskinesia: The ARM-TD study.

Objective: To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD).

Methods: One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) score of ≥6 assessed by blinded central video rating, stable psychiatric illness, and stable psychoactive medication treatment.

Time course of glatiramer acetate efficacy in patients with RRMS in the GALA study.

Objective: To determine the time to efficacy onset of glatiramer acetate (GA) 40 mg/mL 3-times-weekly formulation (GA40).

Methods: This post hoc analysis of data from the 1-year, double-blind, placebo-controlled phase of the Glatiramer Acetate Low-Frequency Administration study (NCT01067521) of GA40 in patients with relapsing-remitting MS (RRMS) sought to determine the timing of efficacy onset using a novel data-censoring approach.

Results: Compared with placebo-treated patients, those receiving GA40 exhibited a >30% reduction in the accumulated annualized relapse rate (ARR) within 2 months of initiating treatment and generally sustained this treatment difference during the 1-year study.

Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate in relapsing-remitting multiple sclerosis patients: 3-year results of the Glatiramer Acetate Low-Frequency Administration open-label extension study.

Background: The 1-year placebo-controlled (PC) phase of the Glatiramer Acetate Low-Frequency Administration (GALA) study showed that glatiramer acetate 40 mg/mL three times weekly (GA40) significantly reduced annualized relapse rate (ARR) and magnetic resonance imaging (MRI) activity in patients with relapsing-remitting multiple sclerosis. Patients completing the PC phase were invited to an open-label (OL) extension.

Objective: To evaluate the effects of early start (ES) and delayed start (DS) of GA40 over 3 years.

The Effect of Three Times a Week Glatiramer Acetate on Cerebral T1 Hypointense Lesions in Relapsing-Remitting Multiple Sclerosis.

Background And Purpose: Two definitions of T1 hypointense (T1H) lesions can be derived from pre-contrast images: those that may or may not have a corresponding gadolinium-enhancing correlate on post-contrast images (T1H total), and those that are simultaneously non-gadolinium-enhancing on post-contrast scans (T1H non-enhancing). To determine the differences in lesion evolution between these two T1H definitions, we examined the effect of glatiramer acetate 40 mg/mL three times weekly subcutaneous injection (GA40) on the number of new or enlarging T1H total and T1H non-enhancing lesions in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: The Phase III GALA study randomized 1404 RRMS subjects 2:1 to receive GA40 or placebo for 12 months.

Determining agreement using rater characteristics.

When evaluating the usefulness of clinical information for the diagnosis of disease, multiple raters provide a diagnosis for the same set of data. These ratings provide important insights into the performance of the diagnosis, determining the accuracy of each rater's diagnosis compared to the truth standard and the level of agreement among the raters. We demonstrate that the intraclass correlation coefficient (ICC) is dependent on the sensitivities and specificities of the raters involved in the study.

Discordance between non-HDL-cholesterol and LDL-particle measurements: results from the Multi-Ethnic Study of Atherosclerosis.

Background: Cardiovascular risk assessment incorporates measurement of atherogenic lipids such as non-HDL cholesterol (non-HDL-C). It remains uncertain under which circumstances atherogenic lipoprotein enumeration such as LDL particle number (LDL-P) differs from simultaneously acquired non-HDL-C.

Methods: Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) were deemed LDL-P > non-HDL-C discordant if they exhibited higher LDL-P than expected for simultaneously measured non-HDL-C, given the observed distribution of both in MESA.

Amyloid deposition detected with florbetapir F 18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals.

The objective of this study was to evaluate the relationship of amyloid burden, as assessed by florbetapir F 18 ((18)F-AV-45) amyloid positron emission tomography, and cognition in healthy older control (HC) subjects. Seventy-eight HC subjects were assessed with a brief cognitive test battery and positron emission tomography (PET) imaging with (18)F-AV-45. A standard uptake value ratio was computed for mean data from 6 cortical regions using a whole cerebellum reference region.

Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study.

Objectives: Florbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline.

Methods: A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment.