Multiparametric MRI as a Noninvasive Monitoring Tool for Children With Autoimmune Hepatitis.

Objectives: Autoimmune hepatitis (AIH) is a progressive liver disease managed with corticosteroids and immunosuppression and monitored using a combination of liver biochemistry and histology. However, liver biopsy is invasive with risk of pain and bleeding. The aim of the present study was to investigate the utility of noninvasive imaging with multiparametric magnetic resonance imaging (MRI) (mpMRI) to provide clinically useful information on the presence and extent of hepatic inflammation, potentially guiding immunosuppression.

Serum Lipid and Protein Changes in Healthy Dyslipidemic Subjects Given a Selective Inhibitor of p70 S6 Kinase-1.

The safety, pharmacokinetic, and pharmacodynamic effects of LY2584702, a selective inhibitor for p70 S6 serine/threonine protein kinase-1, were evaluated in healthy dyslipidemic volunteers. LY2584702 was tolerated well as a monotherapy and dose-dependently reduced low-density lipoprotein cholesterol and triglycerides by up to 60% and 50%, respectively, without significantly changing high-density lipoprotein cholesterol levels in plasma. LY2584702 also dose-dependently decreased factor V activity.

Pharmacokinetics and pharmacodynamics of the cathepsin S inhibitor, LY3000328, in healthy subjects.

Aim: The aim of this study was to assess the safety and tolerability, pharmacokinetics and pharmacodynamics of LY3000328 when administered as single escalating doses to healthy volunteers.

Methods: This was a phase 1, placebo-controlled, dose escalation study with LY3000328 in 21 healthy male volunteers. Subjects were administered escalating LY3000328 doses up to 300 mg with food in this single dose study.

Site versus centralized raters in a clinical depression trial: impact on patient selection and placebo response.

The use of centralized raters who are remotely linked to sites and interview patients via videoconferencing or teleconferencing has been suggested as a way to improve interrater reliability and interview quality. This study compared the effect of site-based and centralized ratings on patient selection and placebo response in subjects with major depressive disorder. Subjects in a 2-center placebo and active comparator controlled depression trial were interviewed twice at each of 3 time points: baseline, 1-week postbaseline, and end point--once by the site rater and once remotely via videoconference by a centralized rater.

Changes in brain function during administration of venlafaxine or placebo to normal subjects.

Previous research has demonstrated neurophysiologic effects of antidepressants in depressed subjects. We evaluated neurophysiologic effects of venlafaxine in normal subjects. Healthy adults (n=32) received a 1-week placebo lead-in followed by 4 weeks randomized double-blind treatment with venlafaxine IR 150 mg.

Optimizing the ability of the Hamilton Depression Rating Scale to discriminate across levels of severity and between antidepressants and placebos.

Efforts to improve the Hamilton Rating Scale for Depression (HRSD) have included shortening the scale by selecting the best performing items, lengthening the scale by assessing additional symptoms, modifying the format and scoring of existing items, and developing structured interview guides for administration. We defined item performance exclusively in terms of the ability of items to discriminate differences among levels of depressive severity which has not be used to guide any revisions of the HRSD conducted to date. Two techniques derived from item response theory were used to improve the ability of the HRSD to discriminate among individuals with different degrees of depressive severity.

An integrative approach to determine the best behavioral and biological markers of methylphenidate.

Aims: To distinguish the most sensitive markers of methylphenidate (MPH) effects on behavior and underlying biology using an integrated cognitive and brain function test battery.

Methods: A randomized placebo-controlled trial with 32 healthy adult males. Subjects were tested on MPH doses across 18 sessions with subjective mood, objective behavioral and biological endpoints.

Anchoring perceptions of clinical change on accurate recollection of the past: memory enhanced retrospective evaluation of treatment (MERET).

Objective: To evaluate patients' self-reports of treatment efficacy with and without self-prompted memory aids regarding their clinical experiences obtained prior to treatment initiation.

Design: Double-blind, placebo-controlled trial with variable expected duration placebo lead-in and washout.

Setting: Multisite (US) randomized clinical trial.

An examination of 26,168 Hamilton Depression Rating Scale scores administered via interactive voice response across 17 randomized clinical trials.

This article presents descriptive and psychometric data from 26,168 Hamilton Depression Rating Scale (HAM-D) scores administered via Interactive Voice Response (IVR) in 17 randomized clinical trials sponsored by 6 pharmaceutical companies. To provide evidence for construct validity, the IVR HAM-D scores before and after randomization are compared, and the change in the IVR HAM-D scores over time after randomization are examined. In addition, the evidence for the reliability of the IVR-administered HAM-D is presented.

Rating the raters: assessing the quality of Hamilton rating scale for depression clinical interviews in two industry-sponsored clinical drug trials.

Objective: The quality of clinical interviews conducted in industry-sponsored clinical drug trials is an important but frequently overlooked variable that may influence the outcome of a study. We evaluated the quality of Hamilton Rating Scale for Depression (HAM-D) clinical interviews performed at baseline in 2 similar multicenter, randomized, placebo-controlled depression trials sponsored by 2 pharmaceutical companies.

Methods: A total of 104 audiotaped HAM-D clinical interviews were evaluated by a blinded expert reviewer for interview quality using the Rater Applied Performance Scale (RAPS).

The dose-dependent effect of methylphenidate on performance, cognition and psychophysiology.

The effects of methylphenidate (MPH) on 32 healthy human male volunteers (aged 18 to 25 years, mean age=22.26) were examined using a within-subject design. Each participant attended six testing periods, held once per week.

Neurophysiologic correlates of side effects in normal subjects randomized to venlafaxine or placebo.

Adverse events reported in the context of medication administration may be due to pharmacodynamic and/or nonpharmacodynamic effects (eg, nocebo phenomena). Neurophysiological substrates of side effects may be examined in placebo-controlled antidepressant treatment trials. We explored the relationship between side effects and regional neurophysiologic changes in normal subjects receiving a 1-week placebo lead-in followed by 4 weeks randomized treatment with placebo (n = 15) or venlafaxine IR (n = 17).

An Item Response analysis of the Hamilton Depression Rating Scale using shared data from two pharmaceutical companies.

Although the Hamilton Depression Rating Scale (HAMD) remains the most widely used outcome measure in clinical trials of Major Depressive Disorder, the psychometric properties of the individual HAMD items have not been extensively studied. In the present paper, data from four separate clinical trials conducted independently by two pharmaceutical companies were analyzed to determine the relationship between scores on the individual HAMD items and overall depressive severity in an outpatient population. Option characteristic curves (the probability of scoring a particular option in relation to overall HAMD scores) were generated in order to illustrate the relationship between scoring patterns for each item and the range of total HAMD scores.

Assessing and interpreting treatment effects in longitudinal clinical trials with missing data.

Treatment effects are often evaluated by comparing change over time in outcome measures; however, valid analyses of longitudinal data can be problematic, particularly if some data are missing. For decades, the last observation carried forward (LOCF) approach has been a common method of handling missing data. Considerable advances in statistical methodology and our ability to implement those methods have been made in recent years.