Ralitza Gueorguieva

Bio: Ralitza Gueorguieva is an academic researcher from Yale University. The author has contributed to research in topics: Placebo & Randomized controlled trial. The author has an hindex of 53, co-authored 210 publications receiving 13013 citations. Previous affiliations of Ralitza Gueorguieva include Emory University & Veterans Health Administration.

Move over ANOVA: progress in analyzing repeated-measures data and its reflection in papers published in the Archives of General Psychiatry.

Abstract: Background The analysis of repeated-measures data presents challenges to investigators and is a topic for ongoing discussion in the Archives of General Psychiatry. Traditional methods of statistical analysis (end-point analysis and univariate and multivariate repeated-measures analysis of variance [rANOVA and rMANOVA, respectively]) have known disadvantages. More sophisticated mixed-effects models provide flexibility, and recently developed software makes them available to researchers. Objectives To review methods for repeated-measures analysis and discuss advantages and potential misuses of mixed-effects models. Also, to assess the extent of the shift from traditional to mixed-effects approaches in published reports in the Archives of General Psychiatry . Data Sources The Archives of General Psychiatry from 1989 through 2001, and the Department of Veterans Affairs Cooperative Study 425. Study Selection Studies with a repeated-measures design, at least 2 groups, and a continuous response variable. Data Extraction The first author ranked the studies according to the most advanced statistical method used in the following order: mixed-effects model, rMANOVA, rANOVA, and end-point analysis. Data Synthesis The use of mixed-effects models has substantially increased during the last 10 years. In 2001, 30% of clinical trials reported in the Archives of General Psychiatry used mixed-effects analysis. Conclusions Repeated-measures ANOVAs continue to be used widely for the analysis of repeated-measures data, despite risks to interpretation. Mixed-effects models use all available data, can properly account for correlation between repeated measurements on the same subject, have greater flexibility to model time effects, and can handle missing data more appropriately. Their flexibility makes them the preferred choice for the analysis of repeated-measures data.

Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression.

Abstract: Background Measurement of cortical γ-aminobutyric acid (GABA) and glutamate concentrations is possible using proton magnetic resonance spectroscopy. An initial report, using this technique, suggested that occipital cortex GABA concentrations are reduced in patients with major depressive disorder (MDD) relative to healthy comparison subjects. Objectives To replicate the GABA findings in a larger sample of MDD patients, to examine the clinical correlates of the GABA reductions in these subjects, and to examine other critical metabolite levels. Design Study for association. Setting Academic clinical research program. Participants The GABA measurements were made on 38 healthy control subjects and 33 depressed subjects. Interventions Occipital cortex metabolite levels were measured using proton magnetic resonance spectroscopy. Main Outcome Measures The levels of occipital cortex GABA, glutamate, N -acetylaspartate, aspartate, creatine, and choline-containing compounds, along with several measures of tissue composition, were compared between the 2 groups. Results Depressed subjects had significantly lower occipital cortex GABA concentrations compared with healthy controls ( P = .01). In addition, mean glutamate levels were significantly increased in depressed subjects compared with healthy controls ( P P = .009) and the percentage of white matter ( P = .04) in the voxel were also observed. An examination of a combined database including subjects from the original study suggests that GABA and glutamate concentrations differ among MDD subtypes. Conclusions The study replicates the findings of decreased GABA concentrations in the occipital cortex of subjects with MDD. It also demonstrates that there is a change in the ratio of excitatory-inhibitory neurotransmitter levels in the cortex of depressed subjects that may be related to altered brain function. Last, the combined data set suggests that magnetic resonance spectroscopy GABA measures may serve as a biological marker for a subtype of MDD.

The Design and Analysis of Experiments

Abstract: THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Abstract: Context Existing therapies for major depression have a lag of onset of action of several weeks, resulting in considerable morbidity. Exploring pharmacological strategies that have rapid onset of antidepressant effects within a few days and that are sustained would have an enormous impact on patient care. Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Objective To determine whether a rapid antidepressant effect can be achieved with an antagonist at theN-methyl-D-aspartate receptor in subjects with major depression. Design A randomized, placebo-controlled, double-blind crossover study from November 2004 to September 2005. Setting Mood Disorders Research Unit at the National Institute of Mental Health. Patients Eighteen subjects withDSM-IVmajor depression (treatment resistant). Interventions After a 2-week drug-free period, subjects were given an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days, a week apart. Subjects were rated at baseline and at 40, 80, 110, and 230 minutes and 1, 2, 3, and 7 days postinfusion. Main Outcome Measure Changes in scores on the primary efficacy measure, the 21-item Hamilton Depression Rating Scale. Results Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection, which remained significant throughout the following week. The effect size for the drug difference was very large (d = 1.46 [95% confidence interval, 0.91-2.01]) after 24 hours and moderate to large (d = 0.68 [95% confidence interval, 0.13-1.23]) after 1 week. Of the 17 subjects treated with ketamine, 71% met response and 29% met remission criteria the day following ketamine infusion. Thirty-five percent of subjects maintained response for at least 1 week. Conclusions Robust and rapid antidepressant effects resulted from a single intravenous dose of anN-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week. Trial Registration clinicaltrials.gov Identifier:NCT00088699.