Modifiable risk factors for bone health & fragility fractures.

Osteoporosis is an ageing disorder characterised by poor microstructural architecture of the bone and an increase in the risk of fragility fractures, which often leads to hospitalisation and eventually a loss of mobility and independence. By 2050, it is estimated that more than 30 million people in Europe will be affected by bone diseases, and European hospitalisation alone can approximately cost up to 3.5 billion euros each year [1]. Although inherited variation in bone mineral density (BMD) is pre-determined by up to 85% [2], there is a window of opportunity to optimise BMD and reduce fracture risk through key modifiable lifestyle factors during the life course. An optimal diet rich in micronutrients, such as calcium, vitamin D, and potassium, has long been considered an important modifiable component of bone health, which is attributed to their direct roles within bone metabolism. Recently, there has been emerging evidence to suggest that protein and even an adequate intake of fruit and vegetables may also play an important role in improving BMD [3,4]. Maintaining a physically active lifestyle is not only protective from non-communicable diseases such as cardiovascular disease but it also has been shown to lessen the risk of fractures later in life, thereby making it an imperative modifiable factor for bone health, particularly as it also supports peak bone mass attainment during childhood/adolescence and can facilitate the maintenance of bone mass throughout adulthood [5]. Other key lifestyle factors that could be potentially modified to reduce the risk of osteoporosis or osteoporotic fractures later in life include smoking status, alcohol intake, and body composition [6]. Therefore, the principle aim of this review is to highlight the recent evidence pertaining to modifiable lifestyle factors that contribute to optimal bone health and the prevention of fragility fractures in later life.

A mixed methods case study investigating how randomised controlled trials (RCTs) are reported, understood and interpreted in practice.

BACKGROUND: While randomised controlled trials (RCTs) provide high-quality evidence to guide practice, much routine care is not based upon available RCTs. This disconnect between evidence and practice is not sufficiently well understood. This case study explores this relationship using a novel approach. Better understanding may improve trial design, conduct, reporting and implementation, helping patients benefit from the best available evidence. METHODS: We employed a case-study approach, comprising mixed methods to examine the case of interest: the primary outcome paper of a surgical RCT (the TIME trial). Letters and editorials citing the TIME trial's primary report underwent qualitative thematic analysis, and the RCT was critically appraised using validated tools. These analyses were compared to provide insight into how the TIME trial findings were interpreted and appraised by the clinical community. RESULTS: 23 letters and editorials were studied. Most authorship included at least one academic (20/23) and one surgeon (21/23). Authors identified wide-ranging issues including confounding variables or outcome selection. Clear descriptions of bias or generalisability were lacking. Structured appraisal identified risks of bias. Non-RCT evidence was less critically appraised. Authors reached varying conclusions about the trial without consistent justification. Authors discussed aspects of internal and external validity covered by appraisal tools but did not use these methodological terms in their articles. CONCLUSIONS: This novel method for examining interpretation of an RCT in the clinical community showed that published responses identified limited issues with trial design. Responses did not provide coherent rationales for accepting (or not) trial results. Findings may suggest that authors lacked skills in appraisal of RCT design and conduct. Multiple case studies with cross-case analysis of other trials are needed.

Evidence into practice: protocol for a new mixed-methods approach to explore the relationship between trials evidence and clinical practice through systematic identification and analysis of articles citing randomised controlled trials.

INTRODUCTION: Randomised controlled trials (RCTs) provide high-quality evidence to inform practice. However, much routine care is not based on available RCT evidence. Understanding this disconnect may improve trial design, reporting and implementation. Published literature commenting on RCTs may yield relevant insights. This protocol presents a new approach examining how researchers understand, contextualise and use evidence from RCTs, through analysis of letters, editorials and discussion pieces citing individual RCTs. Surgical case studies will illustrate its ability to identify wide-ranging factors influencing application of trials evidence. METHODS AND ANALYSIS: In-depth study of published literature will explore written responses to RCTs. After purposefully selecting individual RCTs, we will systematically identify all citing articles covered in Web of Science and Scopus. Editorials, discussions and letters will be included. These are considered most likely to provide critiques and opinions about index RCTs. Original articles and reviews will be excluded. Clinical specialty, RCT design, outcomes and bibliographical data will be collected for RCTs and citing articles. Citing articles will be thematically analysed using the constant comparison technique to explore author understanding, contextualisation and relationship to clinical practice for the index trial. Coding will include generic issues relevant to all RCTs, such as sample size or blinding, and features specific to surgery, such as learning curve. Index trial quality will be examined using validated tools. Results will be combined to create a broad overview of the understanding and use of RCT evidence. ETHICS AND DISSEMINATION: This study involves secondary use of existing articles and does not require ethical approval. Pilot work will establish its feasibility and inform progression to larger scale utilisation across a broad range of RCTs. Findings will be published in a peer-reviewed journal and presented at surgical and methodological conferences. Results will guide future work on trial design to optimise implementation of results.

Coded talk, scripted omissions: the micropolitics of AIDS talk in an affected community in South Africa.

In this ethnographic article, we explore the character of local discourse about AIDS in an affected township community in South Africa, describing the "indirection" that characterized communication about suspected cases of AIDS. Through a case study of one affected family, the article first explores the diverse ways in which people came to "know" that specific cases of illness were AIDS related, and how this "knowledge" was communicated. We consider why communication was indirect and coded, arguing that this reflected nota "denial" of its presence in this community but, rather, a complex group of overlapping concerns far from unique to AIDS: first, a normative injunction on naming potentially fatal conditions; second, an interest in pursuing different therapeutic options and the need to maintain hope of recovery; and third, a wish to avoid the "disrespect" entailed in referring directly to the nature of the problem in a context where, discursively, stigma was still present. The coded and indirect character of HIV/AIDS-related talk underlines the importance of ethnographic inquiry in understanding community responses to this epidemic, demonstrating that the subtleties entailed by verbal silence and elision should not be interpreted naively as collective "denial" but rather be grounded within existing patterns of responses to dangerous sickness.

Strategies for skeletal health in the elderly.

Osteoporosis is a common disease in the elderly, and the fractures that result from this disorder affect 40 % of women and 14 % of men over the age of 50 years. The risk of fracture relates to bone mineral density and the risk of falling, among other factors. Low bone mineral density in the elderly can result from either low peak bone mass or accelerated bone loss, or a combination of the two. Nutritional factors play a role in both the attainment of peak bone mass and in the rate of age-related bone loss. The main determinants of peak bone mass are genetic factors, early-life nutrition, diet and exercise. Of the nutritional factors Ca, and particularly milk, are the most important contributors to peak bone mass. Some of these factors may interact; for example, a low dietary Ca in addition to an unfavourable vitamin D receptor gene polymorphism may result in low peak bone mass. The age-related changes in bone mass may also have a genetic basis, but deficiency of oestrogen is a major contributor. In addition, undernutrition is common in the elderly, and lack of dietary protein contributes both to impaired bone mineral conservation and increased propensity to fall. There is a decreased ability of the intestine to adapt to a low-Ca diet with increasing age. Other dietary factors include vitamin K, Zn and fruit and vegetables. Adequate nutritional status, particularly of Ca and vitamin D, is essential for the successful pharmaceutical treatment of osteoporosis. Thus, strategies for enhancing skeletal health in the elderly must begin in early childhood, and continue throughout life.

Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia.

OBJECTIVES: To assess the cost effectiveness of strategies to screen for and treat familial hypercholesterolaemia. DESIGN: Cost effectiveness analysis. A care pathway for each patient was delineated and the associated probabilities, benefits, and costs were calculated. PARTICIPANTS: Simulated population aged 16-54 years in England and Wales. INTERVENTIONS: Identification and treatment of patients with familial hypercholesterolaemia by universal screening, opportunistic screening in primary care, screening of people admitted to hospital with premature myocardial infarction, or tracing family members of affected patients. MAIN OUTCOME MEASURE: Cost effectiveness calculated as cost per life year gained (extension of life expectancy resulting from intervention) including estimated costs of screening and treatment. RESULTS: Tracing of family members was the most cost effective strategy (3097 pounds sterling (euros 5066, $4479) per life year gained) as 2.6 individuals need to be screened to identify one case at a cost of 133 pounds sterling per case detected. If the genetic mutation was known within the family then the cost per life year gained (4914 pounds sterling ) was only slightly increased by genetic confirmation of the diagnosis. Universal population screening was least cost effective (13 029 pounds sterling per life year gained) as 1365 individuals need to be screened at a cost of 9754 pounds sterling per case detected. For each strategy it was more cost effective to screen younger people and women. Targeted strategies were more expensive per person screened, but the cost per case detected was lower. Population screening of 16 year olds only was as cost effective as family tracing (2777 pounds sterling with a clinical confirmation). CONCLUSIONS: Screening family members of people with familial hypercholesterolaemia is the most cost effective option for detecting cases across the whole population.