Biomedical subjects

A Gamst

Publications and source records attributed to A Gamst.

3 recordsLinked to original sources

PubMed2000

Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study.

CONTEXT: Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women. OBJECTIVE: To determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD. DESIGN: The Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999. SETTING: Thirty-two study sites in the United States. PARTICIPANTS: A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy. INTERVENTIONS: Participants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial. MAIN OUTCOME MEASURES: The primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up. RESULTS: The CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01). CONCLUSIONS: Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.

Aged↗

PubMed1999

Two-sample continual reassessment method.

We discuss an extension of the continual reassessment method (CRM) for use in phase I dose-finding studies. The extension enables the method to be applied to two groups of patients to determine the appropriate dose levels for each group. The method takes the specification of a simple relationship between the dose-toxicity curves for the two groups and runs the CRM on the bivariate model using maximum likelihood. We prove consistency of the method under fairly weak conditions and provide several simulations to give an idea how the method works in practice. We also undertake an evaluation of its performance by considering three possible situations: The first is the two-sample CRM, which directly uses a working model for the relationship between the two groups, carrying out a single trial using this method; the second situation carries out single trials for each of the two groups separately using the original (one-sample) CRM. The third situation is the case where such heterogeneity is ignored and the two groups are pooled into a single group, again using the original (one-sample) CRM. Simulations are carried out under a large class of model misspecifications, both of the dose-toxicity relationships and of the functional form linking the groups, and are backed up by asymptotic results. Our conclusions match intuition: The first scheme gives the most favorable results when the two groups are different but share some features. When the groups are very different, the second scheme performs similarly to the first for finite sample sizes while having some advantages in terms of asymptotic efficiency. The third, as expected, gives the best results in the absence of patient heterogeneity. The two-sample method appears particularly advantageous when there may not be enough subjects in one of the subgroups for it to be feasible to carry out two trials.

Clinical Trials, Phase I as Topic↗

PubMed1996

Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients.

The nonnucleoside reverse transcriptase inhibitor nevirapine rapidly selects for mutant human immunodeficiency virus (HIV) in vivo. The most common mutation occurs at amino acid residue 181 in patients receiving monotherapy. After the initiation of nevirapine therapy, plasma and peripheral blood mononuclear cell samples were collected at frequent intervals and assayed for HIV RNA levels and the proportion of virus containing a mutation at residue 181. HIV RNA levels remained stable for the first 24 h after initiation of therapy and rapidly declined between 1 and 7 days. There was a consistent maximum decrease of 2 log10 HIV RNA copies per ml of plasma (range, 1.96 to 2.43) from baseline after 2 weeks in all monotherapy subjects. The estimated median half-life of HIV RNA was 1.11 days (range, 0.63 to 1.61). After 14 days of therapy, HIV RNA levels began to increase and 181 mutant virus was detected. The estimated doubling time of the emerging virus population ranged from 1.80 to 5.73 days. Viral DNA in peripheral blood mononuclear cells turned over from wild type to the mutant with a mutation at residue 181 significantly more slowly than did HIV RNA in plasma. In two subjects, the calculated prevalence of the 181 mutant virus prior to treatment was 7 and 133 per 10,000 copies of plasma HIV RNA.

Clinical Trials as Topic↗