Sustained multiplicity in everyday cholesterol reduction: repertoires and practices in talk about 'healthy living'.

This article is concerned with talk about and the practices of healthy living in relation to cholesterol reduction. It draws on qualitative interviews with 89 people who are current or former users of either cholesterol-lowering functional foods or statins for cardiovascular risk reduction. Focusing on data about everyday activities including food preparation, shopping and exercise, we illustrate four repertoires that feature in talk about cholesterol reduction (health, pleasure, sociality and pragmatism). Using Gilbert and Mulkay's notion of a 'reconciliation device', we suggest ways in which apparently contradictory repertoires are combined (for example, through talk about moderation) or kept apart. We suggest that, in contrast to the interactiveness of the repertoires of health and pleasure, a pragmatic repertoire concerning food provisioning, storage and cooking as well as the realities of exercise, appears distinct from talk about health and is relatively inert. Finally we consider the implications of these discursive patterns for daily practices. Our data suggest there is little emphasis on coherence in people's practices and illustrate the significance of temporal, spatial and social distribution in allowing people to pursue different priorities in their everyday lives. Rather than the calculated trade-offs of earlier medical sociology we draw on Mol to foreground the possibility of sustained multiplicity in daily practices.

Negotiating the practical ethics of 'self-tracking' in intimate relationships: Looking for care in healthy living.

In this paper, we offer insights into practices of tracking as part of healthy living through talk about home blood pressure and weight from adults living in the UK. Drawing on theoretical resources from feminist ethics of care and Science and Technology Studies on care as socio-material practice, we build on interest in the relational dimensions of tracking and the potential for intimate surveillance and care using monitoring technologies. Our cases offer not only new perspectives in a field that has often focused on fitness tracking but also help go beyond a narrow focus on surveillance, showing how surveillance and care may be intertwined in the everyday negotiation of health-related tracking and other 'health practices' in family life. Using the diversity in our relatively large sample, and reflecting on the different types of interview completed, we highlight the varied ways in which adults engage with tracking blood pressure and weight (or body mass index) in the context of established relationships. The combination of attentiveness and appeals to responsibility for maintaining health as something owed to a partner can make tracking a very ethically sensitive area. In this paper we emphasise that reciprocity is one important way in which couples make tracking feel more like care. Tracking together or discussing it can take couples in this direction even if the actual practice remains somewhat difficult. On the other hand, responsiveness to someone else's feelings, including a desire to avoid the topic altogether, or avoid weight as a specific parameter, might all help move towards more caring tracking. We therefore develop a more sustained account of care in relation to tracking than in previous work, and a novel account of tracking as a (potential) care practice between adult partners.

Healthcare practitioner views and experiences of patients self-monitoring blood pressure: a vignette study.

BACKGROUND: Home self-monitoring of blood pressure is widely used in primary care to assist in the diagnosis of hypertension, as well as to improve clinical outcomes and support adherence to medication. The National Institute for Health and Care Excellence (NICE) care pathways for hypertension recommend specific guidelines, although they lack detail on supporting patients to self-monitor. AIM: To elicit primary care practitioners' experiences of managing patients' home blood pressure self-monitoring, across surgeries located in different socioeconomic areas. DESIGN & SETTING: A qualitative focus group study was conducted with a total of 21 primary care professionals. METHOD: Participants were GPs and practice nurses (PNs), purposively recruited from surgeries in areas of low and high deprivation, according to the English indices of multiple deprivation. Six vignettes were developed featuring data from interviews with people who self-monitor and these were used in five focus groups. Results were thematically analysed. RESULTS: Themes derived in the thematic analysis largely reflected topics covered by the vignettes. These included: advice on purchase of a device; supporting home monitoring; mitigating patient anxiety experienced as a result of home monitoring; valuing patients' data; and effect of socioeconomic factors. CONCLUSION: The work provides an account of methods used by primary care practitioners in the management of home blood pressure self-monitoring, where guidance may be lacking and primary care practitioners act on their own judgement. Findings complement recent policy documentation, which recognises the need to adopt new ways of working to empower patients (for example, additional support from healthcare assistants), but lacks detail on how this should be done.

Structure-function relationships for the selective inhibition of human 3ß-hydroxysteroid dehydrogenase type 1 by a novel androgen analog.

3ß-Hydroxysteroid dehydrogenase type 1 (3ß-HSD1) is selectively expressed in human placenta, mammary glands and breast tumors in women. Human 3ß-HSD2 is selectively expressed in adrenal glands and ovaries. Based on AutoDock 3 and 4 results, we have exploited key differences in the amino acid sequences of 3ß-HSD1 (Ser194, Arg195) and 3ß-HSD2 (Gly194, Pro195) by designing a selective inhibitor of 3ß-HSD1. 2,16-Dicyano-4,5-epoxy-androstane-3,17-dione (16-cyano-17-keto-trilostane or DiCN-AND) was synthesized in a 4-step procedure from androstenedione. In purified 3ß-HSD inhibition studies, DiCN-AND competitively inhibited 3ß- HSD1 with Ki=4.7µM and noncompetitively inhibited 3ß-HSD2 with a 6.5-fold higher Ki=30.7µM. We previously reported similar isoenzyme-specific inhibition profiles for trilostane. Based on our docking results, we created, expressed and purified the chimeric S194G-1 mutant of 3ß-HSD1. Trilostane inhibited S194G-1 (Ki=0.67µM) with a noncompetitive mode compared to its 6.7-fold higher affinity, competitive inhibition of 3ß-HSD1 (Ki=0.10µM). DiCN-AND inhibited S194G-1 with a 6.3-fold higher Ki (29.5µM) than measured for 3ß-HSD1 (Ki=4.7µM) but with the same competitive mode for both enzyme species. Since DiCN-AND noncompetitively inhibits 3ß-HSD2, which has the Gly194 and Pro195 of 3ß-HSD2 in place of the Ser194 and Arg195 in 3ß-HSD1, this suggests that Arg195 alone in 3ß-HSD1 or S194G-1 is required to bind DiCN-AND in the substrate binding site (competitive inhibition). However, both Ser194 and Arg195 are required to bind trilostane in the 3ß-HSD1 substrate site based on its noncompetitive inhibition of S194G-1 and 3ß-HSD2. In support of this hypothesis, DiCN-AND inhibited our chimeric R195P-1 mutant noncompetitively with a Ki=41.3µM (similar to the 3ß-HSD2 inhibition profile). Since DiCN-AND competitively inhibited S194G-1 that still contains R195 but noncompetitively inhibited R195P-1 that still contains S194, our data provides strong evidence that the Arg195 being mutated to Pro195 (as present in 3ß-HSD2) shifts the inhibition mode from competitive to noncompetitive in 3ß-HSD1. This supports the key role of Arg195 in 3ß-HSD1 for the high affinity, competitive binding of the trilostane analogs. Our new structure/function information for the design of targeted 3ß-HSD1 inhibitors may lead to important new treatments for the prevention of spontaneous premature birth.

The drugs don't sell: DIY heart health and the over-the-counter statin experience.

This paper draws on a study of over-the-counter statins to provide a critical account of the figure of the 'pharmaceutical consumer' as a key actor in the pharmaceuticalisation literature. A low dose statin, promising to reduce cardiovascular risk, was reclassified to allow sale in pharmacies in the UK in 2004. We analysed professional and policy debates about the new product, promotional and sales information, and interviews with consumers and potential consumers conducted between 2008 and 2011, to consider the different consumer identities invoked by these diverse actors. While policymakers constructed an image of 'the citizen-consumer' who would take responsibility for heart health through exercising the choice to purchase a drug that was effectively rationed on the NHS and medical professionals raised concerns about 'a flawed consumer' who was likely to misuse the product, both these groups assumed that there would be a market for the drug. By contrast, those who bought the product or potentially fell within its target market might appear as 'health consumers', seeking out and paying for different food and lifestyle products and services, including those targeting high cholesterol. However, they were reluctant 'pharmaceutical consumers' who either preferred to take medication on the advice of a doctor, or sought to minimize medicine use. In comparison to previous studies, our analysis builds understanding of individual consumers in a market, rather than collective action for access to drugs (or, less commonly, compensation for adverse effects). Where some theories of pharmaceuticalisation have presented consumers as creating pressure for expanding markets, our data suggests that sociologists should be cautious about assuming there will be demand for new pharmaceutical products, especially those aimed at prevention or asymptomatic conditions, even in burgeoning health markets.

The management of enthusiasm: motives and expectations in cardiovascular medicine.

Debates about appropriate action in medicine often turn on finding the right emotional orientation to new developments. In this article enthusiasm emerges as a key term in a professional 'vocabulary of motive' around innovation, complicating current sociological interest in expectations. The negative associations that adhere to this word among clinical researchers indicate awareness with the difficulty of managing hype and public hopes, but analysis of its use by cardiologists over the past two decades also reveals tension around more specific professional dangers, including 'credulity' and inappropriate activism. An emphasis on clinical trials offers one resolution, but additional narrative strategies can be identified when discussing when to start such trials here illustrated for stem cells for cardiac repair. In particular, while some suggest delaying trials until there is good knowledge of mechanism gained in the laboratory, others support early clinical research through gestures of therapeutic and epistemic modesty.

Genetic unexceptionalism: clinician accounts of genetic testing for familial hypercholesterolaemia.

This paper considers the implications of genetic testing in the case of familial hypercholesterolaemia, drawing on twenty semi-structured interviews with general practitioners (family doctors in primary care), nurses and specialists in hospital clinics (secondary care) in the UK. Though these professionals appear aware of and interested in the genetic component of the condition, and DNA testing is underway in at least some centres, their accounts suggest that the genetic test is not having a major impact on clinical work. Instead we find that professionals report that they generally rely on other information when making a diagnosis, especially cholesterol levels understood as a key risk factor, while the results of DNA tests, if used, come late in a much longer series of clinical investigations, judgements and interventions. In addition to elaborating professional views of genetic testing, the research provides a way of understanding other studies that describe lay people as not necessarily privileging genetic explanations of familial hypercholesterolaemia.

Arguing about the evidence: readers, writers and inscription devices in coronary heart disease risk assessment.

This paper examines the history of tools developed to assess an individual's risk of coronary heart disease. A close reading of the tools themselves is combined with an analysis of debates published in medical journals such as the British Medical Journal (BMJ) and The Lancet. These literary conversations between scientists and doctors reveal complex negotiations about the form and meaning of medical technologies that have yet to become fully 'stable'. Early tools were promoted as a response to the high cost of cholesterol-lowering drugs (statins), but came to embody broader attempts to shape medical practice. These include the promotion of what has been understood as evidence-based medicine and regulation by political and professional actors, as well as the spread of 'risk thinking' more generally. Despite having a central place in recent British guidelines and policy, there is a surprising variety of tools in circulation, and ongoing uncertainty about their use and value.