No abstract

Objective-To assess a non-invasive test for endothelial dysfunction, an important early event in the atherogenic process. Methods-Using high resolution ultrasound, the accuracy of detecting small changes in vessel diameter was assessed using phantom "arteries", and the same equipment was then used to measure flow mediated dilatation in the brachial artery of 40 healthy adults aged 22-51 years, studied on four occasions; intervals between scans were 1-2 days, 1-2 weeks, and 2-4 months. Results-Differences between pairs of phantom "arteries" with diameters 0-1-0'2 mm apart were correctly estimated in 162 of 264 cases (61%); no measurement by any of four independent observers was > 041 mm in error, and the mean error was 0*04 mm. For in vivo scans, the overall coefficient of variation for flow mediated dilatation was 1-8% (1.6% for women, 1-9% for men, P = 0.18). In 34/40 subjects (85%), all values for flow mediated dilatation were within 2-5% of the overall mean for each subject. A nested analysis of variance showed the expected between patient variability, and also significant day to day variation, but little between weeks or months. Using these data to generate power function analyses, we calculated that for individuals, an improvement in flow mediated dilatation of 4-8% is significantly greater than natural variability. In clinical trials, a mean improvement in flow mediated dilatation of at least 2% would usually be required to detect a treatment benefit, with much larger subject numbers needed for a parallel group compared to a crossover trial design. Conclusions-Vascular responses to endothelium dependent and independent stimuli in systemic arteries can be studied non-invasively in man. Subjects should be studied on at least two occasions before and after any intervention, to optimise the chance of showing a significant effect from any potentially beneficial therapy. (Br Heart J 1995;74:247-253).

Gibbs sampling has enormous potential for analysing complex data sets. However, routine use of Gibbs sampling has been hampered by the lack of general purpose software for its implementation. Until now all applications have involved writing one-off computer code in low or intermediate level languages such as C or Fortran. We describe some general purpose software that we are currently developing for implementing Gibbs sampling: BUGS (Bayesian inference using Gibbs sampling). The BUGS system comprises three components: first, a natural language for specifying complex models; second, an 'expert system' for deciding appropriate methods for obtaining samples required by the Gibbs sampler; third, a sampling module containing numerical routines to perform the sampling. S objects are used for data input and output. BUGS is written in Modula-2 and runs under both DOS and UNIX.

SummaryMany clinicians remain unsure of the relevance of measuring quality of life to their clinical practice.In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article-the first of three on measuring quality of life-reviews the instruments available and their application in screening programmes, audit, health care research, and clinical trials. Using the appropriate instrument is essential if outcome measures are to be valid and clinically meaningful.Interest in measuring quality of life in relation to health care has increased in recent years.' 2 The purpose is to provide more accurate assessments of individuals' or populations' health and of the benefits and harm that may result from health care. The term quality of life misleadingly suggests an abstract and philosophical approach, but most approaches used in medical contexts do not attempt to include more general notions such as life satisfaction or living standards and tend rather to concentrate on aspects of personal experience that might be related to health and health care. Some of the commonly used synonyms for quality of life more accurately convey the content and purpose of measures-health related quality of life, subjective health status, functional status. This is the first of three papers intended to review measurement issues surrounding the use of the growing number of questionnaires and interview based instruments designed to assess health related quality of life.

The design, analysis, and interpretation of studies using measures of quality of life vary according to the context of use. In this paper we are primarily concerned with quality of life measures in clinical trials but our comments are relevant in other contexts. DesignApart from the usual considerations of good study design, particular issues in studies measuring quality of life are the choice of dimensions and the selection of instruments to measure these dimensions. There are also several practical considerations.