Equity weights in the allocation of health care: the rank-dependent QALY model

This paper introduces the rank-dependent quality-adjusted life-years (QALY) model, a new method to aggregate QALYs in economic evaluations of health care. The rank-dependent QALY model permits the formalization of influential concepts of equity in the allocation of health care, such as the fair innings approach, and it includes as special cases many of the social welfare functions that have been proposed in the literature. An important advantage of the rank-dependent QALY model is that it offers a straightforward procedure to estimate equity weights for QALYs. We characterize the rank-dependent QALY model and argue that its central condition has normative appeal. (C) 2003 Elsevier B.V. All rights reserved.

Assessment of arginine 97 and lysine 72 as determinants of substrate specificity in cytochrome P450 2C9 (CYP2C9)

CYP2C9 is distinguished by a preference for substrates bearing a negative charge at physiological pH. Previous studies have suggested that CYP2C9 residues R97 and K72 may play roles in determining preference for anionic substrates by interaction at the active site or in the access channel. The aim of the present study was to assess the role of these two residues in determining substrate selectivity. R97 and K72 were substituted with negative, uncharged polar and hydrophobic residues using a degenerate polymerase chain reaction-directed strategy. Wild-type and mutant enzymes were expressed in bicistronic format with human cytochrome P450 reductase in Escherichia coli. Mutation of R97 led to a loss of holoenzyme expression for R97A, R97V, R97L, R97T, and R97E mutants. Low levels of hemoprotein were detected for R97Q, R97K, R97I, and R97P mutants. Significant apoenzyme was observed, suggesting that heme insertion or protein stability was compromised in R97 mutants. These observations are consistent with a structural role for R97 in addition to any role in substrate binding. By contrast, all K72 mutants examined (K72E, K72Q, K72V, and K72L) could be expressed as hemoprotein at levels comparable to wild-type. Type I binding spectra were obtained with wildtype and K72 mutants using diclofenac and ibuprofen. Mutation of K72 had little or no effect on the interaction with these substrates, arguing against a critical role in determining substrate specificity. Thus, neither residue appears to play a role in determining substrate specificity, but a structural role for R97 can be proposed consistent with recently published crystallographic data for CYP2C9 and CYP2C5.

Identifying the energy gap: Magnitude and determinants of 5-year weight gain in midage women

Objective: The aims of this study were to estimate average yearly weight gain in midage women and to identify the determinants of weight gain and gaining weight at double the average rate. Research Methods and Procedures: The study sample comprised 8071 participants (45 to 55 years old) in the Australian Longitudinal Study on Women's Health who completed mailed surveys in 1996, 1998, and 2001. Results: On average, the women gained almost 0.5 kg per year [average 2.42 kg (95% confidence interval, 2.29 to 2.54) over 5 years]. In multivariate analyses, variables associated with energy balance (physical activity, sitting time, and energy intake), as well as quitting smoking, menopause/hysterectomy, and baseline BMI category were significantly associated with weight gain, but other behavioral and demographic characteristics were not. After adjustment for all of the other biological and behavioral variables, the odds of gaining weight at about twice the average rate (> 5 kg over 5 years) were highest for women who quit smoking (odds ratio = 2.94; 95% confidence interval, 2.17, 3.96). There were also independent relationships between the odds of gaining > 5 kg and lower levels of habitual physical activity, more time spent sitting, energy intake (but only in women with BMI > 25 at baseline), menopause transition, and hysterectomy. Discussion: The average weight gain equates with an energy imbalance of only about 10 kcal or 40 kJ per day, which suggests that small sustained changes in the modifiable behavioral variables could prevent further weight gain.

Early practical experience and the social responsiveness of clinical education: Systematic review

Objectives To find how early experience in clinical and community settings (early experience) affects medical education, and identify strengths and limitations of the available evidence. Design A systematic review rating, by consensus, the strength and importance of outcomes reported in the decade 1992-2001. Data sources Bibliographical databases and journals were searched for publications on the topic, reviewed under the auspices of the recently formed Best Evidence Medical Education (BEME) collaboration. Selection of studies All empirical studies (verifiable, observational data) were included, whatever their design, method, or language of publication. Results Early experience was most commonly provided in community settings, aiming to recruit primary care practitioners for underserved populations. It increased the popularity of primary care residencies, albeit among self selected students. It fostered self awareness and empathic attitudes towards ill people, boosted students' confidence, motivated them, gave them satisfaction, and helped them develop a professional identity. By helping develop interpersonal skills, it made entering clerkships a less stressful experience. Early experience helped students learn about professional roles and responsibilities, healthcare systems, and health needs of a population. It made biomedical, behavioural, and social sciences more relevant and easier to learn. It motivated and rewarded teachers and patients and enriched curriculums. In some countries,junior students provided preventive health care directly to underserved populations. Conclusion Early experience helps medical students learn, helps them develop appropriate attitudes towards their studies and future practice, and orientates medical curriculums towards society's needs. Experimental evidence of its benefit is unlikely to be forthcoming and yet more medical schools are likely to provide it. Effort could usefully be concentrated on evaluating the methods and outcomes of early experience provided within non-experimental research designs, and using that evaluation to improve the quality of curriculums.

Promoting physical activity in Australian general practices: a randomised trial of health promotion advice versus hypertension management

A randomised controlled trial was conducted to determine if physicians' advice to promote physical activity to patients was more effective if the advice was tailored to the management of hypertension, compared with more general health promotion advice. Participants included inactive 40- to 70-year-old patients visiting the physicians' during study recruitment period. Physicians provided verbal physical activity advice and written materials, both tailored to either general health promotion messages or specifically as a means for treating or managing hypertension. Seventy-five physicians and 98% (767/780) of screened eligible patients participated in the study. Differences between intervention and control groups self-reported physical activity were assessed over 6 months. Follow-up response rates were 92 and 84% at the 2- and 6-month assessments. There were no consistent, significant differences between groups at the 2- or 6-month assessments. Thus, neither intervention strategy resulted in significant changes in patients self-reported physical activity, regardless of the whether the advice was tailored to hypertension management or general health promotion advice. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Being fit and looking healthy: Young women's and men's constructions of health and fitness

We drew on Foucault's notion of 'practices of the self' to examine how young people take up, negotiate, and resist the imperatives of a public health discourse concerned with the relationships between health, fitness, and the body. We did this through a discussion of the ways young women and men talk about their own and others' bodies, in the context of a number of in-depth interviews conducted for the Life Activity Project, a study of the place and meaning of physical activity in young people's lives, funded by an Australian Research Council Grant. We found that the young women and men in the study engaged the health/fitness discourse very differently: for the young men, health conflated with fitness as an embodied capacity to do physical work; and for the young women, health was a much more difficult and complex project associated with managing and monitoring practices associated with eating and exercise to maintain an 'appropriate' body shape.

Conceptions of health held by Aboriginal, Torres Strait Islander and Papua New Guinea health care students

Health is considered to be a fundamental human right. Concurrently health is assumed to be a global social goal (Bloom, 1987) yet many third-world countries and some sub-populations within developed countries do not enjoy a healthy existence. The research reported in this paper examined the conceptions of health, conceptions of illness and health practices for a group of Aboriginal, Torres Strait Islander, and Papua New Guinea university students studying health science courses. Results found three conceptions of health and three conceptions of illness that showed these students held traditional/cultural and Western beliefs about health and health practices. These findings may contribute to the development of health care courses that are more specific to how these students understand health. This may also serve to improve the educational status of Aboriginal and Torres Strait Islander people and potentially improve the health status within these communities (author abstract)