Long-term survivor mixture model with random effects: application to a multi-centre clinical trial of carcinoma

A mixture model incorporating long-term survivors has been adopted in the field of biostatistics where some individuals may never experience the failure event under study. The surviving fractions may be considered as cured. In most applications, the survival times are assumed to be independent. However, when the survival data are obtained from a multi-centre clinical trial, it is conceived that the environ mental conditions and facilities shared within clinic affects the proportion cured as well as the failure risk for the uncured individuals. It necessitates a long-term survivor mixture model with random effects. In this paper, the long-term survivor mixture model is extended for the analysis of multivariate failure time data using the generalized linear mixed model (GLMM) approach. The proposed model is applied to analyse a numerical data set from a multi-centre clinical trial of carcinoma as an illustration. Some simulation experiments are performed to assess the applicability of the model based on the average biases of the estimates formed. Copyright (C) 2001 John Wiley & Sons, Ltd.

Research output of Australian general practice: A comparison with medicine, surgery and public health

Objectives: To compare the productivity of Australian general practice in terms of research publications with the productivity of other medical disciplines. Design: A survey of Australian general practice, medicine, surgery and public health publications carried out by manual searching of specific journals and an electronic search of the US National Library of Medicine's PubMed database. Main outcome measures: The number of original research publications by Australian general practitioners, physicians, surgeons and public health physicians during 1999; the relative publication rate of Australian general practice, medicine, surgery and public health over the period 1990-1999. Results: Of original research articles published in 1999, GPs authored 65% (17/26) in Australian Family Physician and 3% (3/90) in the Medical Journal of Australia; physicians published 4% and 37%, respectively. The electronic search identified 54 research articles relating to Australian general practice published in 1999 in 21 different journals, only two of which were primary care journals. Over the period 1990-1999, there was a publication rate of one general practice [discipline] article per 1000 GPs in practice per year. Corresponding rates for medicine, surgery and public health were 105/1000, 61/1000 and 148/1000, respectively. Conclusions: There is considerable disparity between the level of research output of general practice and that of the disciplines of medicine, surgery and public health. If we are to have effective general practice research, we urgently need to develop research skills, a supportive infrastructure and a culture that nurtures research.

Increasing relevance of pharmacogenetics of drug metabolism in clinical practice

Much of the individual variation in drug response is due to genetic drug metabolic polymorphisms. Clinically relevant examples include acetylator status; cytochrome P450 2D6, 2C9 and 2C19 polymorphisms; and thiopurine methyltransferase deficiency. It is important to be aware of which drugs are subject to pharmacogenetic variability. In the future, population-based pharmacogenetic testing will allow more individualized drug treatment and will avoid the current empiricism.

Clinical supervision in four mental health professions: A review of the evidence

This paper examines a range of theoretical issues and the empirical evidence relating to clinical supervision in four mental health professions, namely clinical psychology, occupational therapy, social work, and speech pathology. Despite the widespread acceptance of the value of supervision among practitioners and the large quantity of literature on the topic, there is very little empirical evidence in this area. It is not clear whether supervision actually produces a change in clinician behaviour, nor whether it produces benefits in terms of client outcomes. To date, there is insufficient evidence to demonstrate which styles of supervision are most beneficial for particular types of staff, in terms of their level of experience or learning style. The data suggest that directive forms of supervision, rather than unstructured approaches, are preferred by relatively inexperienced practitioners, and that experienced clinicians also value direct supervision methods when learning new skills or dealing with complex or crisis situations. The available evidence suggests that supervisors typically receive little training in supervision methods. However, to date, we have little information to guide us as to the most effective ways of training supervisors. While acknowledging the urgent need for research, the paper concludes that supervision is likely to form a valuable component of professional development for mental health professionals.

Association of clinical, radiological and synovial immunopathological responses to anti-rheumatic treatment in rheumatoid arthritis

Objectives. To compare immunohistochemical scoring with clinical scoring and radiology for the assessment of rheumatoid arthritis (RA) disease activity, synovial tissue (ST) biopsied arthroscopically was assessed from 18 patients before and after commencement of disease-modifying anti-rheumatic drug (DMARD) therapy. Methods. Lymphocytes, macrophages, differentiated dendritic cells (DC), vascularity, tumour necrosis factor (TNF)alpha and interleukin-1 beta levels were scored. Clinical status was scored using the American College of Rheumatology (ACR) core set and serial radiographs were scored using the Larsen and Sharp methods. Histopathological evidence of activity included infiltration by lymphocytes, DC, macrophages. tissue vascularity, and expression of lining and sublining TNF alpha. These indices co-varied across the set of ST biopsies and were combined as a synovial activity score for each biopsy. Results. The change in synovial activity with treatment correlated with the ACR clinical response and with decreased radiological progression by the Larsen score, The ACR response to DMARD therapy. the change in synovial activity score and the slowing of radiological progression were each greatest in patients with high initial synovial vascularity. Conclusions. The data demonstrate an association between clinical, radiological and synovial immunopathological responses to anti-rheumatic treatment in RA. High ST vascularity may predict favourable clinical and radiological responses to treatment.