Not just old and sick - the 'will to health' in later life

The end of the ‘Golden Age’ of welfare capitalism in the 1970s was the prelude to a period of greater individualisation within societies and was accompanied by an increase in the importance of consumption as a way of organising social relations. During the same period there was also an expansion in the discourses aimed at enhancing the government of the autonomous self. One such discourse operates around what has been termed the ‘will to health’: it suggests that health has become a required goal for individual behaviour and has become synonymous with health itself. The generational groups whose lifecourses were most exposed to these changes are now approaching later life. We explore the extent to which social transformations related to risk, consumption and individualisation are reflected in the construction of later-life identities around health and ageing. We examine how the growth in health-related ‘technologies of the self’ have fostered a distinction between natural and normal ageing, wherein the former is associated with coming to terms with physical decline and the latter associated with maintaining norms of self-care aimed at delaying such decline. Finally, we consider anti-ageing medicine as a developing arena for the construction of later-life identities and discuss the implications of the social changes for researching later life

Handling of Missing Outcome Data in Traumatic Brain Injury Research: A Systematic Review.

Traumatic brain injury (TBI) research commonly measures long-term functional outcome, but studies often suffer from missing data as patients are lost to follow-up. This review assesses the extent and handling of missing outcome data in the TBI literature and provides a practical guide for future research. Relevant electronic databases were searched from January 1, 2012 to October 27, 2017 for TBI studies that used the Glasgow Outcome Scale or Glasgow Outcome Scale-Extended (GOS/GOSE) as an outcome measure. Studies were screened and data extracted in line with Cochrane guidance. A total of 195 studies, 21 interventional, 174 observational, with 104,688 patients were included. Using the reported follow-up rates in a mixed model, on average 91% of patients were predicted to return to follow-up at 6 months post-injury, 84% at 1 year, and 69% at 2 years. However, 36% of studies provided insufficient information to determine the number of subjects at each time-point. Of 139 studies that did report missing outcome data, only 50% attempted to identify why data were missing, with just 4 reporting their assumption on the "missingness mechanism." The handling of missing data was heterogeneous, with the most common method being its exclusion from analysis. These results confirm substantial variability in the standard of reporting and handling of missing outcome data in TBI research. We conclude that practical guidance is needed to facilitate meaningful and accurate study interpretation, and therefore propose a framework for the handling of missing outcome data in future TBI research.The work of HFL, AIRM, DN, EWS, DKM and LW was supported in the context of CENTERTBI (www.center-tbi.eu) by the Fp7 program of the EU (602150). VFJN was supported by an Academy of Medical Sciences / The Health Foundation Clinician Scientist Fellowship. SR was supported by a National Institute of Health Research (NIHR) Academic Clinical Fellowship. The research was supported by the NIHR Biomedical Research Centre based as the Cambridge University Hospitals NHS Foundation Trust and University of Cambridge

Modelling neurofibromatosis type 1 tibial dysplasia and its treatment with lovastatin

<p>Abstract</p> <p>Background</p> <p>Bowing and/or pseudarthrosis of the tibia is a known severe complication of neurofibromatosis type 1 (NF1). Mice with conditionally inactivated neurofibromin (Nf1) in the developing limbs and cranium (Nf1Prx1) show bowing of the tibia caused by decreased bone mineralisation and increased bone vascularisation. However, in contrast to NF1 patients, spontaneous fractures do not occur in Nf1Prx1 mice probably due to the relatively low mechanical load. We studied bone healing in a cortical bone injury model in Nf1Prx1 mice as a model for NF1-associated bone disease. Taking advantage of this experimental model we explore effects of systemically applied lovastatin, a cholesterol-lowering drug, on the Nf1 deficient bone repair.</p> <p>Methods</p> <p>Cortical injury was induced bilaterally in the <it>tuberositas tibiae </it>in Nf1Prx1 mutant mice and littermate controls according to a method described previously. Paraffin as well as methacrylate sections were analysed from each animal. We divided 24 sex-matched mutant mice into a lovastatin-treated and an untreated group. The lovastatin-treated mice received 0.15 mg activated lovastatin by daily gavage. The bone repair process was analysed at three consecutive time points post injury, using histological methods, micro computed tomography measurements and <it>in situ </it>hybridisation. At each experimental time point, three lovastatin-treated mutant mice, three untreated mutant mice and three untreated control mice were analysed. The animal group humanely killed on day 14 post injury was expanded to six treated and six untreated mutant mice as well as six control mice.</p> <p>Results</p> <p>Bone injury repair is a complex process, which requires the concerted effort of numerous cell types. It is initiated by an inflammatory response, which stimulates fibroblasts from the surrounding connective tissue to proliferate and fill in the injury site with a provisional extracellular matrix. In parallel, mesenchymal progenitor cells from the periost are recruited into the injury site to become osteoblasts. In Nf1Prx1 mice bone repair is delayed and characterised by the excessive formation and the persistence of fibro-cartilaginous tissue and impaired extracellular matrix mineralisation. Correspondingly, expression of Runx2 is downregulated. High-dose systemic lovastatin treatment restores Runx2 expression and accelerates new bone formation, thus improving cortical bone repair in Nf1Prx1 tibia. The bone anabolic effects correlate with a reduction of the mitogen activated protein kinase pathway hyper-activation in Nf1-deficient cells.</p> <p>Conclusion</p> <p>Our data suggest the potential usefulness of lovastatin, a drug approved by the US Food and Drug Administration in 1987 for the treatment of hypercholesteraemia, in the treatment of Nf1-related fracture healing abnormalities. The experimental model presented here constitutes a valuable tool for the pre-clinical stage testing of candidate drugs, targeting Nf1-associated bone dysplasia.</p

Development and validation of a risk model for predicting adverse drug reactions in older people during hospital stay: Brighton Adverse Drug Reactions Risk (BADRI) model

BACKGROUND: Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model. METHODS: We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset). RESULTS: Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively. CONCLUSIONS: We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported

A randomized controlled trial reporting functional outcomes of cognitive-behavioural therapy in medication‑treated adults with ADHD and comorbid psychopathology

Studies assessing psychological treatment of attention deficit hyperactivity disorder (ADHD) in adults are increasingly reported. However, functional outcomes are often neglected in favour of symptom outcomes. We investigated functional outcomes in 95 adults with ADHD who were already treated with medication and randomized to receive treatment as usual (TAU/MED) or psychological treatment (CBT/MED) using a cognitive–behavioural programme, R&R2ADHD, which employs both group and individual modalities. RATE-S functional outcomes associated with ADHD symptoms, social functioning, emotional control and antisocial behaviour were given at baseline, end of treatment and three-month follow-up. The Total composite score of these scales is associated with life satisfaction. In addition, independent evaluator ratings of clinicians who were blind to treatment arm were obtained on the Clinical Global Impression scale at each time point. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater functional improvement on all scales. Post-group treatment effects were maintained at follow-up with the exception of emotional control and the Total composite scales, which continued to improve. The largest treatment effect was for the RATE-S Total composite scale, associated with life satisfaction. CGI significantly correlated with all outcomes except for social functioning scale at follow-up. The study provides further evidence for the effectiveness of R&R2ADHD and demonstrates the importance of measuring functional outcomes. The key mechanism associated with improved functional outcomes is likely to be behavioural control

Scents of Adolescence: The Maturation of the Olfactory Phenotype in a Free-Ranging Mammal

Olfaction is an important sensory modality for mate recognition in many mammal species. Odorants provide information about the health status, genotype, dominance status and/or reproductive status. How and when odor profiles change during sexual maturation is, however often unclear, particularly in free-ranging mammals. Here, we investigated whether the wing sac odorant of male greater sac-winged bats (Saccopteryx bilineata, Emballonuridae) differs between young and adults, and thus offers information about sexual maturity to potential mating partners. Using gas chromatography – mass spectrometry, we found differences in the odorants of young and adult males prior and during, but not after the mating period. The wing sac odorant of adult males consists of several substances, such as Pyrocoll, 2,6,10-trimethyl-3-oxo-6,10-dodecadienolide, and a so far unidentified substance; all being absent in the odor profiles of juveniles prior to the mating season. During the mating season, these substances are present in most of the juvenile odorants, but still at lower quantities compared to the wing sac odorants of adults. These results suggest that the wing sac odorant of males encodes information about age and/or sexual maturity. Although female S. bilineata start to reproduce at the age of half a year, most males of the same age postpone the sexual maturation of their olfactory phenotype until after the first mating season

Energy expenditure during egg laying is equal for early and late breeding free-living female great tits

In many bird populations, variation in the timing of reproduction exists but it is not obvious how this variation is maintained as timing has substantial fitness consequences. Daily energy expenditure (DEE) during the egg laying period increases with decreasing temperatures and thus perhaps only females that can produce eggs at low energetic cost will lay early in the season, at low temperatures. We tested whether late laying females have a higher daily energy expenditure during egg laying than early laying females in 43 great tits (Parus major), by comparing on the same day the DEE of early females late in their laying sequence with DEE of late females early in their egg laying sequence. We also validated the assumption that there are no within female differences in DEE within the egg laying sequence. We found a negative effect of temperature and a positive effect of female body mass on DEE but no evidence for differences in DEE between early and late laying females. However, costs incurred during egg laying may have carry-over effects later in the breeding cycle and if such carry-over effects differ for early and late laying females this could contribute to the maintenance of phenotypic variation in laying dates

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Physicians' intentions and use of three patient decision aids

<p>Abstract</p> <p>Background</p> <p>Decision aids are evidence based tools that assist patients in making informed values-based choices and supplement the patient-clinician interaction. While there is evidence to show that decision aids improve key indicators of patients' decision quality, relatively little is known about physicians' acceptance of decision aids or factors that influence their decision to use them. The purpose of this study was to describe physicians' perceptions of three decision aids, their expressed intent to use them, and their subsequent use of them.</p> <p>Methods</p> <p>We conducted a cross-sectional survey of random samples of Canadian respirologists, family physicians, and geriatricians. Three decision aids representing a range of health decisions were evaluated. The survey elicited physicians' opinions on the characteristics of the decision aid and their willingness to use it. Physicians who indicated a strong likelihood of using the decision aid were contacted three months later regarding their actual use of the decision aid.</p> <p>Results</p> <p>Of the 580 eligible physicians, 47% (n = 270) returned completed questionnaires. More than 85% of the respondents felt the decision aid was well developed and that it presented the essential information for decision making in an understandable, balanced, and unbiased manner. A majority of respondents (>80%) also felt that the decision aid would guide patients in a logical way, preparing them to participate in decision making and to reach a decision. Fewer physicians (<60%) felt the decision aid would improve the quality of patient visits or be easily implemented into practice and very few (27%) felt that the decision aid would save time. Physicians' intentions to use the decision aid were related to their comfort with offering it to patients, the decision aid topic, and the perceived ease of implementing it into practice. While 54% of the surveyed physicians indicated they would use the decision aid, less than a third followed through with this intention.</p> <p>Conclusion</p> <p>Despite strong support for the format, content, and quality of patient decision aids, and physicians' stated intentions to adopt them into clinical practice, most did not use them within three months of completing the survey. There is a wide gap between intention and behaviour. Further research is required to study the determinants of this intention-behaviour gap and to develop interventions aimed at barriers to physicians' use of decision aids.</p