What is the best size descriptor to use for pharmacokinetic studies in the obese?

The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution (V) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V. A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.

An examination of the needs of parents of hospitalized children: comparing parents' and staff's perceptions

The needs of parents of hospitalized children have received some attention in the health literature, but few studies have compared parents' perceptions of needs with staff's ideas about parents' needs. The aim of this Study was to examine differences between the perceptions of the needs of parents of hospitalized children held by staff - nurses, doctors and allied health staff, and parents in a 150-bed paediatric hospital in Sweden. The convenience sample comprised 132 staff - nurses, doctors and allied health stall and 115 parents of children admitted to all the wards except intensive care. Kristjansdottir's needs of parents of hospitalized children questionnaire (NPQ) was the instrument of choice and was modified slightly for use with staff. Results indicated significant differences in perceptions of the importance of different needs of parents, of how well they were being met in the hospital arid how much help the parents needed to have them filled. Differences between parents' and staff's perceptions of the importance of parental needs were found in areas relating to psychosocial needs, but in general, in that hospital, the needs were being adequately met. The main differences between staff's and parents' results were in the degree of independence shown by parents in requiring hell) to have their needs met. This demonstrates either that parents are much more independent than appraised by staff, or, that parents are sometimes unaware of the level of assistance available.

Revisiting the conceptualisation of politeness in English and Japanese

The issue of what in fact constitutes politeness remains a source of considerable debate amongst researchers. There is mounting evidence that although there may be common underlying elements, politeness is conceptualised differently across cultures. A comparison of the notions of politeness in English and teinei, reigi tadashii and keii hyoogen in Japanese indicates that these respective terms encompass somewhat different conceptual ranges. Politeness in English refers to showing consideration for others and demonstrating a polished self-presentation. In Japanese, on the other hand, it encompasses showing respect (with a strong nuance of vertical respect involved) and consideration towards the position and quality of character of others, and modesty about oneself While politeness in both English and Japanese involves showing one thinks well of others (other-oriented politeness) and showing one does not think too highly of oneself (self-oriented politeness), differences in the underlying conceptualisation of politeness give rise to different ways of expressing politeness. It is thus difficult to maintain the assumption that politeness can be defined in the same way across different cultures, although this does not necessarily preclude the identification of common elements of politeness across cultures. © Walter de Gruyter.

Constructing the architext: Georges Perec's life a user's manual

Mitchell critiques Georges Perec's Life a User's Manual, which articulates compellingly the confluence of literature and architecture studies that emerged in the late twentieth century. She argues the Perec's novel diverges from this tradition, for, rather than being a search for origins and true expression, Life a User's Manual denies the very possibility of originality. She adds that Perec's architext is de-constructive and ironic.

Excess in cardiovascular events on mondays: a meta-analysis analysis and prospective study

The aim of this paper was to summarise the reported excess in coronary events on Mondays, and examine the evidence for three competing explanations: stress, alcohol consumption, or registration errors. A review of the literature found 28 studies covering 16 countries and over 1.6 million coronary events. The overall Monday excess was small; in a population experiencing 100 coronary events per week there was one more event on Monday than other days. The excess was larger in men and in studies including sudden cardiac death or cardiac arrests. In a prospective study an increase in events on Mondays was associated with greater alcohol consumption, lower rainfall, and the month of January. The excess in coronary events on Mondays is a persistent phenomenon. The size of the effect varies widely between populations. There is some evidence of an association with alcohol consumption, but a definitive explanation remains elusive and is likely to remain so because of the smallness of the effect and the paucity of high quality data.