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Biomedical subjects

Gillian M Raab

Publications and source records attributed to Gillian M Raab.

4 recordsLinked to original sources

Cytotoxic assays for screening anticancer agents.

In the process of identifying potential anticancer agents, the ability of a new agent is tested for cytotoxic activity against a panel of standard cancer cell lines. The National Cancer Institute (NCI) present the cytotoxic profile for each agent as a set of estimates of the dose required to inhibit the growth of each cell line. The NCI estimates are obtained from a linear interpolation method applied to the dose-response curves. In this paper non-linear fits are proposed as an alternative to interpolation. This is illustrated with data from two agents recently submitted to NCI for potential anticancer activity. Fitting of individual non-linear curves proved difficult, but a non-linear mixed model applied to the full set of cell lines overcame most of the problems. Two non-linear functional forms were fitted using random effect models by both maximum likelihood and a full Bayesian approach. Model-based toxicity estimates have some advantages over those obtained from interpolation. They provide standard errors for toxicity estimates and other derived quantities, allow model comparisons. Examples of each are illustrated.

Antineoplastic Agents↗

Addressing the efficacy of dihydrocodeine versus methadone as an alternative maintenance treatment for opiate dependence: A randomized controlled trial.

AIM: The aim of this study is to define the efficacy of dihydrocodeine as an alternative to methadone in the maintenance treatment of opiate dependence. DESIGN: A pragmatic open-label randomized controlled study of patients recommended for opiate maintenance treatment to test equivalence of the two treatment options with follow-up continuing for up to 42 months after recruitment. SETTING: Assessment at either Edinburgh's Community Drug Problem Service or at two general practitioner practices with specialist drug community psychiatric nurses, then with shared care follow-up. PARTICIPANTS: Two hundred and thirty-five subjects (168 male, 67 female) with opiate dependence syndrome were recruited. Subjects selected were suitable for opiate maintenance treatment. Routine treatment was offered throughout. INTERVENTION: Patients were randomized to receive either methadone mixture 1 mg/ml or dihydrocodeine, 30 mg or 60 mg tablets. MEASUREMENTS: The primary outcome measure was retention in treatment. Eight secondary outcomes included total illicit opiate use, reported crime, physical health, mental health, injecting drug use, overdoses, selling drugs and being in education or work. Measures were compared over 42 months follow-up. FINDINGS: There was no difference in groups for retention in treatment at follow-up and there was improvement in all secondary outcomes from baseline. No significant difference in outcomes was found between randomized groups over time. Compliance with randomized treatment differed by randomized group and was affected by experiences in custody during follow-up. Those randomized to dihydrocodeine were more likely to switch treatments. CONCLUSIONS: These results, combined with existing clinical experience, provide evidence that dihydrocodeine is a viable alternative to methadone as a maintenance treatment for opiate dependence. Indirect comparisons with other studies show dihydrocodeine (and methadone) to be superior to placebo.

Administration, Oral↗

Randomization inference for balanced cluster-randomized trials.

This paper discusses the choice of randomization tests for inferences from cluster-randomized trials that have been designed to ensure a balanced allocation of clusters to treatments. Methods for covariate-adjusted randomization tests are reviewed and their application to balanced cluster-randomized trials discussed. Two cluster-randomized trials with balanced designs are used to illustrate the choices that can be made in selecting a randomization test, and methods for obtaining confidence intervals for treatment effects are illustrated. The balance imposed by the randomization in these trials makes adjustment for covariates less beneficial than for an unbalanced design. However, the adjusted analyses do not appear generally to have worse properties than the unadjusted ones, and may provide protection against any imbalance that has not been controlled for in the design. The only case when adjustment for covariates may result in worse precision is when a large number of cluster-level covariates are included in the analysis. An expression is provided that allows the size of this effect to be calculated for any given set of cluster-level covariates.

Cluster Analysis↗

Limits of teacher delivered sex education: interim behavioural outcomes from randomised trial.

OBJECTIVE: To determine whether a theoretically based sex education programme for adolescents (SHARE) delivered by teachers reduced unsafe sexual intercourse compared with current practice. DESIGN: Cluster randomised trial with follow up two years after baseline (six months after intervention). A process evaluation investigated the delivery of sex education and broader features of each school. SETTING: Twenty five secondary schools in east Scotland. PARTICIPANTS: 8430 pupils aged 13-15 years; 7616 completed the baseline questionnaire and 5854 completed the two year follow up questionnaire. INTERVENTION: SHARE programme (intervention group) versus existing sex education (control programme). MAIN OUTCOME MEASURES: Self reported exposure to sexually transmitted disease, use of condoms and contraceptives at first and most recent sexual intercourse, and unwanted pregnancies. RESULTS: When the intervention group was compared with the conventional sex education group in an intention to treat analysis there were no differences in sexual activity or sexual risk taking by the age of 16 years. However, those in the intervention group reported less regret of first sexual intercourse with most recent partner (young men 9.9% difference, 95% confidence interval -18.7 to -1.0; young women 7.7% difference, -16.6 to 1.2). Pupils evaluated the intervention programme more positively, and their knowledge of sexual health improved. Lack of behavioural effect could not be linked to differential quality of delivery of intervention. CONCLUSIONS: Compared with conventional sex education this specially designed intervention did not reduce sexual risk taking in adolescents.

Adolescent↗