Animal models for bone tissue engineering and modelling disease

Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches

Offering statins to a population attending health checks with a 10-year cardiovascular disease risk between 10% and 20.

BACKGROUND: In 2014 the UK National Institute for Health and Care Excellence recommended reducing the threshold for offering statin therapy to patients from a 10-year modelled risk of cardiovascular disease (CVD) of 20% to 10%. AIM: To describe the response of patients in UK primary care with a CVD risk between 10% and 20% to an invitation to attend a consultation to discuss statins. DESIGN AND SETTING: Review of electronic medical records at one GP practice in the East of England. METHOD: We invited all patients who had attended an NHS Health Check at the practice, had a QRisk(®) score between 10% and 20%, and were not prescribed statins to attend designated clinics in the practice to discuss starting statins. We reviewed the medical records to identify those who had attended the clinics and those who had chosen to start a statin. RESULTS: Of 410 patients invited, 100 (24.4%) patients attended the designated clinics and 45 (11%) chose to start a statin. Those who chose to start a statin were older and with a higher QRisk(®) than those who did not. Among those who attended, individuals who started a statin had a higher QRisk(®) than those who did not and were more likely to be current or ex-smokers. CONCLUSIONS: The proportion choosing to start a statin was substantially lower than previously estimated. Large population-based studies with long-term follow-up are needed to assess the impact on health and workload of this change in guidance.JU-S is funded by a National Institute of Health Research Clinical Lectureship. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/ijcp.1274

Promoting the consumer voice : the role of Healthwatch Salford's Enter and View programme

The daily business of running a care home means that, outside of regulatory inspections, assessing and improving the user experience can often be forgotten. Healthwatch Salford discuss their process of gaining constructive feedback using their innovative Enter and View programm

The associations between the response efficacy and objective and subjective change in physical activity and diet in the Information and Risk Modification trial.

OBJECTIVES: Many health promotion campaigns and interventions focussing on improving health-related behaviours have been based on targeting response efficacy. This is based on the assumption that response efficacy is an important modifiable determinant of behaviour change. This study aimed to quantify the association between response efficacy and objective and subjective measures of physical activity and diet. STUDY DESIGN: Prospective cohort analysis of data from a randomised controlled trial. METHODS: A total of 953 participants were assessed for response efficacy at baseline and 12 weeks following randomisation to interventions to increase physical activity and improve diet. Subjective measures were collected via a self-report questionnaire that included two questions used to derive the Cambridge Index of physical activity and questions about daily or weekly fruit and vegetable, whole grain, meat and fish intake, based on the dietary guidelines to lower cardiovascular risk. Objective measures were quantified using accelerometers and plasma carotenoids. RESULTS: The mean change in response efficacy for physical activity was +0.5 (standard deviation [SD] 2.0) and for diet was +0.5 (SD 2.1).There were no clinically or statistically significant associations between baseline or change in response efficacy and objective and subjective measures of physical activity or objective measures of diet. There was a small statistically significant association between baseline response efficacy and change in self-reported wholegrain consumption, but this is unlikely to be clinically significant. CONCLUSIONS: Response efficacy is not a fundamental determinant of diet and physical activity and should not be the main focus of interventions targeting these behaviours

Women's views on screening for Type 2 diabetes after gestational diabetes: a systematic review, qualitative synthesis and recommendations for increasing uptake.

AIM: Many women do not attend recommended glucose testing following a pregnancy affected by gestational diabetes (GDM). We aimed to synthesize the literature regarding the views and experiences of women with a history of GDM on postpartum glucose testing, focusing on barriers and facilitators to attendance. METHODS: We systematically identified qualitative studies that examine women's experiences following GDM relating to glucose testing (diabetes screening) or experience of interventions to promote uptake of testing. We conducted a thematic synthesis to develop descriptive and then analytical themes, then developed recommendations to increase uptake based on the findings. We evaluated the quality of each study and the confidence that we had in the recommendations using published checklists. RESULTS: We included 16 articles after screening 23 160 citations and 129 full texts. We identified four themes of influences relating to the healthcare system and personal factors that affected both ability and motivation to attend: relationship with health care, logistics of appointments and tests, family-related practicalities and concern about diabetes. We developed 10 recommendations addressing diabetes risk information and education, and changes to healthcare systems to promote increased attendance at screening in this population, most with high or moderate confidence. CONCLUSIONS: We have identified a need to improve women's understanding about Type 2 diabetes and GDM, and to adjust healthcare provision during and after pregnancy to decrease barriers and increase motivation for testing. Encouraging higher uptake by incorporating these recommendations into practice will enable earlier management of diabetes and improve long-term outcomes.R.D. is funded by a PhD studentship from the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR; SPCR-S-S102). This paper presents independent research funded by the NIHR SPCR. The views expressed are those of the author(s) and not necessarily those of the NIHR, the NHS or the Department of Health. R.W. is funded by an NIHR Academic Clinical Fellowship. S.G. is supported by the Medical Research Council (MC_UU_12015/4). S.G. is an NIHR Senior Investigator. The University of Cambridge has received salary support in respect of S.G. from the NHS in the East of England through the Clinical Academic Reserve. J.U-S. is funded by a Cancer Research UK Cancer Prevention Fellowship (C55650/A21464)

Change in cardio-protective medication and health-related quality of life after diagnosis of screen-detected diabetes: Results from the ADDITION-Cambridge cohort.

AIMS: Establishing a balance between the benefits and harms of treatment is important among individuals with screen-detected diabetes, for whom the burden of treatment might be higher than the burden of the disease. We described the association between cardio-protective medication and health-related quality of life (HRQoL) among individuals with screen-detected diabetes. METHODS: 867 participants with screen-detected diabetes underwent clinical measurements at diagnosis, one and five years. General HRQoL (EQ5D) was measured at baseline, one- and five-years, and diabetes-specific HRQoL (ADDQoL-AWI) and health status (SF-36) at one and five years. Multivariable linear regression was used to quantify the association between change in HRQoL and change in cardio-protective medication. RESULTS: The median (IQR) number of prescribed cardio-protective agents was 2 (1 to 3) at diagnosis, 3 (2 to 4) at one year and 4 (3 to 5) at five years. Change in cardio-protective medication was not associated with change in HRQoL from diagnosis to one year. From one year to five years, change in cardio-protective agents was not associated with change in the SF-36 mental health score. One additional agent was associated with an increase in the SF-36 physical health score (2.1; 95%CI 0.4, 3.8) and an increase in the EQ-5D (0.05; 95%CI 0.02, 0.08). Conversely, one additional agent was associated with a decrease in the ADDQoL-AWI (-0.32; 95%CI -0.51, -0.13), compared to no change. CONCLUSIONS: We found little evidence that increases in the number of cardio-protective medications impacted negatively on HRQoL among individuals with screen-detected diabetes over five years.ADDITION-Cambridge was supported by the Wellcome Trust (grant reference No G061895) the Medical Research Council (grant reference no: G0001164), National Health Service R&D support funding (including the Primary Care Research and Diabetes Research Networks), and the National Institute for Health Research. We received an unrestricted grant from University of Aarhus, Denmark, to support the ADDITION-Cambridge trial. Bio-Rad provided equipment to undertake capillary glucose screening by HbA1c in general practice. The Primary Care Research Unit is supported by NIHR Research funds. SJG receives support from the Department of Health NIHR Programme Grant funding scheme (RP-PG-0606-1259). This article presents independent research funded by the NIHR under the Programme Grants for Applied Research programme (RP-PG-0606-1259]. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.diabres.2015.04.01

Risk prediction models for colorectal cancer in people with symptoms: a systematic review.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related death in Europe and the United States. Detecting the disease at an early stage improves outcomes. Risk prediction models which combine multiple risk factors and symptoms have the potential to improve timely diagnosis. The aim of this review is to systematically identify and compare the performance of models that predict the risk of primary CRC among symptomatic individuals. We searched Medline and EMBASE to identify primary research studies reporting, validating or assessing the impact of models. For inclusion, models needed to assess a combination of risk factors that included symptoms, present data on model performance, and be applicable to the general population. Screening of studies for inclusion and data extraction were completed independently by at least two researchers. Twelve thousand eight hundred eight papers were identified from the literature search and three through citation searching. 18 papers describing 15 risk models were included. Nine were developed in primary care populations and six in secondary care. Four had good discrimination (AUROC > 0.8) in external validation studies, and sensitivity and specificity ranged from 0.25 and 0.99 to 0.99 and 0.46 depending on the cut-off chosen. Models with good discrimination have been developed in both primary and secondary care populations. Most contain variables that are easily obtainable in a single consultation, but further research is needed to assess clinical utility before they are incorporated into practice.JUS is funded by a National Institute of Health Research (NIHR) Clinica

Metabolomics dataset of PPAR-pan treated rat liver

This article contains mass spectrometry (MS) data investigating small molecule changes as an effect of a triple peroxisome proliferator-activated receptor (PPAR-pan) agonist GW625019 in the liver as described in the manuscript (Ament et al., 2016) [1]. Samples were measured using gas chromatography-mass spectrometry (GC–MS) for total fatty acid content, and liquid chromatography-mass spectrometry (LC–MS) to measure intact lipids, carnitines and selected aqueous metabolites and eicosanoids. Data files comprise of Excel (Microsoft, WA, USA) spreadsheets of identified metabolites and their area ratio values for total fatty acids, carnitines, aqueous metabolites, and eicosanoids where the intensity of the analytes were normalised to the intensity of the internal standard. In the case of open profiling intact lipid data, the Excel file contains area ratio values of retention time and mass to charge ratio pairs; again, the area ratio values were calculated by normalising to the intensity of the internal standard. It should be noted that several metabolic changes are potentially indirect (secondary, tertiary and ensuing changes)

'Dressage Is Full of Queens!' Masculinity, Sexuality and Equestrian Sport

Attitudes towards sexuality are changing and levels of cultural homophobia decreasing, yet there remain very few openly gay men within sport. As a proving ground for heteromasculinity, sport has traditionally been a hostile environment for gay men. This article is based on an ethnographic study within a sporting subworld in which gay men do appear to be accepted: equestrian sport. Drawing on inclusive masculinity theory, equestrian sport is shown to offer an unusually tolerant environment for gay men in which heterosexual men of all ages demonstrate low levels of homophobia. Inclusive masculinity theory is a useful framework for exploring the changing nature of masculinities and this study demonstrates that gay men are becoming increasingly visible and accepted within once unreceptive locales, such as sport and rural communities. However, this more tolerant attitude is purchased at the expense of a subordinated feminine Other, perpetuating the dominance of men within competitive sport. © The Author(s) 2012