Reducing dementia risk by targeting modifiable risk factors in mid-life: study protocol for the Innovative midlife intervention for dementia deterrence (In-MINDD) randomised controlled feasibility trial

Background Dementia prevalence is increasing as populations live longer, with no cure and the costs of caring exceeding many other conditions. There is increasing evidence for modifiable risk factors which, if addressed in mid-life, can reduce the risk of developing dementia in later life. These include physical inactivity, low cognitive activity, mid-life obesity, high blood pressure, and high cholesterol. This study aims to assess the acceptability and feasibility and impact of giving those in mid-life, aged between 40 and 60 years, an individualised dementia risk modification score and profile and access to personalised on-line health information and goal setting in order to support the behaviour change required to reduce such dementia risk. A secondary aim is to understand participants’ and practitioners’ views of dementia prevention and explore the acceptability and integration of the Innovative Midlife Intervention for Dementia Deterrence (In-MINDD) intervention into daily life and routine practice. Methods/design In-MINDD is a multi-centre, primary care-based, single-blinded randomised controlled feasibility trial currently being conducted in four European countries (France, Ireland, the Netherlands and the UK). Participants are being recruited from participating general practices. Inclusion criteria will include age between 40 and 60 years; at least one modifiable risk factor for dementia risk (including diabetes, hypertension, obesity, renal dysfunction, current smoker, raised cholesterol, coronary heart disease, current or previous history of depression, self-reported sedentary lifestyle, and self-reported low cognitive activity) access to the Internet. Primary outcome measure will be a change in dementia risk modification score over the timescale of the trial (6 months). A qualitative process evaluation will interview a sample of participants and practitioners about their views on the acceptability and feasibility of the trial and the links between modifiable risk factors and dementia prevention. This work will be underpinned by Normalisation Process Theory. Discussion This study will explore the feasibility and acceptability of a risk profiler and on-line support environment to help individuals in mid-life assess their risk of developing dementia in later life and to take steps to alleviate that risk by tackling health-related behaviour change. Testing the intervention in a robust and theoretically informed manner will inform the development of a future, full-scale randomised controlled trial

Can we spot deleterious ageing in two waves of data? The Lothian Birth Cohort 1936 from ages 70 to 73

‘Younger ’ old age (the late 60s through early 70s) is, for many, a period of stability of lifestyle and considerable freedom to pursue leisure activities. Despite the stability that many enjoy, the mortality rate is about 2 % per year in western nations. This increases to about 5 % by age 80. It would be useful to know if those most vulnerable can be identified through patterns of deleterious ageing, and especially if this could be accomplished with just two waves of data. The Lothian Birth Cohort 1936 was surveyed on a host of individual difference variables including cognition, personality, biomarkers of physical health, and activities at ages 70 and 73 years. Overall, the group showed the expected basic stability in mean levels for these variables, but some individuals had died and others did show substantial changes that could be considered statistically reliable. These presumably reliable changes were at least as likely to be positive (reflecting improved condition/ability) as negative (reflecting decline/ageing). Moreover, limitations in the estimated reliabilities of the measures meant that most of the observed changes could not be considered reliable. The changes clustered only weakly around general health to predict death over the next approximately two years. We concluded that two waves of longitudinal data were not sufficient to assess meaningful patterns of ageing, despite often being used to do so

Nursing and midwifery students' perception of learning enablers and gains in the first semester of their BSc programmes: A cross sectional study

Background: The student experience in the first year of university is fundamental to successful adaption to the higher education environment and this experience is essential when designing or reviewing curricula. Objectives: The aim of this study was to explore students' perceptions of their learning gains to identify factors that support student learning and identify elements that need improvement if specific learning needs are to be met. Design: A cross sectional descriptive study. Setting: A large urban university in Ireland that provides undergraduate nursing and midwifery degree programmes. Participants and Methods: The study was conducted using the Student Assessment of Learning Gains (SALG) questionnaire. This instrument consists of a series of closed questions which explore perceived student gains in skills, cognitions and attitudes. The questionnaire was adapted for a semester rather than a module evaluation. The tool also includes a series of open questions inviting students to comment in each section. Results: Students (n = 206) positively evaluated teaching and learning approaches used. The greatest enablers of learning were clinical skills laboratory small group teaching and support followed by online learning materials and multiple choice formative assessment questions. They reported gains in knowledge, generic skills development and an increase in confidence and enthusiasm for their chosen career. Conclusion: The feedback gained in this study provides valuable knowledge about the elements that support nursing and midwifery students learning and highlights areas that require attention. This is particularly useful for faculty who are involved in curriculum review and enhancement and in student engagement and retention

Bone marrow lesions and magnetic resonanceImaging–detected structural abnormalities in patients with midfoot pain and osteoarthritis: A cross-sectional study

To compare magnetic resonance imaging (MRI)–detected structural abnormalities in patients withsymptomatic midfoot osteoarthritis (OA), patients with persistent midfoot pain, and asymptomatic controls, and toexplore the association between MRI features, pain, and foot-related disability. One hundred seven adults consisting of 50 patients with symptomatic and radiographically confirmedmidfoot OA, 22 adults with persistent midfoot pain but absence of radiographic OA, and 35 asymptomatic adultsunderwent 3T MRI of the midfoot and clinical assessment. MRIs were read for the presence and severity of abnormal-ities (bone marrow lesions [BMLs], subchondral cysts, osteophytes, joint space narrowing [JSN], effusion-synovitis,tenosynovitis, and enthesopathy) using the Foot Osteoarthritis MRI Score. Pain and foot-related disability wereassessed with the Manchester Foot Pain and Disability Index. The severity sum score of BMLs in the midfoot was greater in patients with midfoot pain and no signs ofOA on radiography compared to controls (P= 0.007), with a pattern of involvement in the cuneiform–metatarsal jointssimilar to that in patients with midfoot OA. In univariable models, BMLs (ρ= 0.307), JSN (ρ= 0.423), and subchondralcysts (ρ= 0.302) were positively associated with pain (P< 0.01). In multivariable models, MRI abnormalities were notassociated with pain and disability when adjusted for covariates. In individuals with persistent midfoot pain but no signs of OA on radiography, MRIfindings suggestedan underrecognized prevalence of OA, particularly in the second and third cuneiform–metatarsal joints, where BMLpatterns were consistent with previously recognized sites of elevated mechanical loading. Joint abnormalities werenot strongly associated with pain or foot-related disability

8-modified-2\u27-deoxyadenosine analogues induce delayed polymerization arrest during HIV-1 reverse transcription

The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV-1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix &alpha;H in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2&prime;-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2&prime;-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication.<br /

Feasibility cluster randomised controlled trial of a within-consultation intervention to reduce antibiotic prescribing for children presenting to primary care with acute respiratory tract infection and cough

Objective To investigate recruitment and retention, data collection methods and the acceptability of a ‘within-consultation’ complex intervention designed to reduce antibiotic prescribing. Design Primary care feasibility cluster randomised controlled trial. Setting 32 general practices in South West England recruiting children from October 2014 to April 2015. Participants Children (aged 3 months to <12 years) with acute cough and respiratory tract infection (RTI). Intervention A web-based clinician-focussed clinical rule to predict risk of future hospitalisation and a printed leaflet with individualised child health information for carers, safety-netting advice and a treatment decision record. Controls Usual practice, with clinicians recording data on symptoms, signs and treatment decisions. Results Of 542 children invited, 501 (92.4%) consented to participate, a month ahead of schedule. Antibiotic prescribing data were collected for all children, follow-up data for 495 (98.8%) and the National Health Service resource use data for 494 (98.6%). The overall antibiotic prescribing rates for children’s RTIs were 25% and 15.8% (p=0.018) in intervention and control groups, respectively. We found evidence of postrandomisation differential recruitment: the number of children recruited to the intervention arm was higher (292 vs 209); over half were recruited by prescribing nurses compared with less than a third in the control arm; children in the intervention arm were younger (median age 2 vs 3 years controls, p=0.03) and appeared to be more unwell than those in the control arm with higher respiratory rates (p<0.0001), wheeze prevalence (p=0.007) and global illness severity scores assessed by carers (p=0.045) and clinicians (p=0.01). Interviews with clinicians confirmed preferential recruitment of less unwell children to the trial, more so in the control arm. Conclusion Differential recruitment may explain the paradoxical antibiotic prescribing rates. Future cluster level studies should consider designs which remove the need for individual consent postrandomisation and embed the intervention within electronic primary care records

Training the next generation of clinical researchers: Evaluation of a graduate podiatrist research internship in rheumatology

Background: The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors. Methods: Nine new graduates completed the internship programme (July 2006-June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes. Results: Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent 'Jewel in the Crown' award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees. Seven important themes arose from the qualitative phases: perceptions of the internship pre-application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme. Conclusions: The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales

Designing and Developing Core Physiology Learning Outcomes for Pre-registration Nursing Education Curriculum

Physiology is a key element of ‘bioscience’ education within pre-registration nursing programmes, but there is a lack of clarity on what is included. Physiology and bioscience content and delivery is highly varied across both higher education institutions and the related programmes in the UK. Despite evidence highlighting concerns over nurses lack of bioscience knowledge and unsafe practice, there is no universally agreed curriculum with detailed outcomes of minimum levels of knowledge to support nurses in practice and patient care. This study aimed to inform the construction of discipline specific physiology learning outcomes to clarify relevant physiological topics required in pre-registration nursing. Initially, 360 learning outcomes were identified from various sources. Using a modified Delphi approach, an expert panel from the Bioscience in Nurse Education group reviewed and modified the list to 195 proposed outcomes. These were circulated to Universities in the UK who teach Nursing (n=65). Outcomes which had 80% consensus were automatically included to the next round with others recommended with modification (response rate 22%). The panel reviewed the modifications and 182 outcomes were circulated in the second questionnaire (response rate 23%) and further panel review resulting in 177 outcomes agreed. These learning outcomes do not suggest how they should be delivered but gives the basic level required for qualification as a nurse commensurate with the Nursing and Midwifery Council new standards for the 'future nurse'

Clinical effectiveness and cost-effectiveness of a multifaceted podiatry intervention for falls prevention in older people : a multicentre cohort randomised controlled trial (the REducing Falls with ORthoses and a Multifaceted podiatry intervention trial)

BACKGROUND: Falls are a serious cause of morbidity and cost to individuals and society. Evidence suggests that foot problems and inappropriate footwear may increase the risk of falling. Podiatric interventions could help reduce falls; however, there is limited evidence regarding their clinical effectiveness and cost-effectiveness. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of a multifaceted podiatry intervention for preventing falls in community-dwelling older people at risk of falling, relative to usual care. DESIGN: A pragmatic, multicentred, cohort randomised controlled trial with an economic evaluation and qualitative study. SETTING: Nine NHS trusts in the UK and one site in Ireland. PARTICIPANTS: In total, 1010 participants aged ≥ 65 years were randomised (intervention, n = 493; usual care, n = 517) via a secure, remote service. Blinding was not possible. INTERVENTIONS: All participants received a falls prevention leaflet and routine care from their podiatrist and general practitioner. The intervention also consisted of footwear advice, footwear provision if required, foot orthoses and foot- and ankle-strengthening exercises. MAIN OUTCOME MEASURES: The primary outcome was the incidence rate of falls per participant in the 12 months following randomisation. The secondary outcomes included the proportion of fallers and multiple fallers, time to first fall, fear of falling, fracture rate, health-related quality of life (HRQoL) and cost-effectiveness. RESULTS: The primary analysis consisted of 484 (98.2%) intervention and 507 (98.1%) usual-care participants. There was a non-statistically significant reduction in the incidence rate of falls in the intervention group [adjusted incidence rate ratio 0.88, 95% confidence interval (CI) 0.73 to 1.05; p = 0.16]. The proportion of participants experiencing a fall was lower (50% vs. 55%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00; p = 0.05). No differences were observed in key secondary outcomes. No serious, unexpected and related adverse events were reported. The intervention costs £252.17 more per participant (95% CI -£69.48 to £589.38) than usual care, was marginally more beneficial in terms of HRQoL measured via the EuroQoL-5 Dimensions [mean quality-adjusted life-year (QALY) difference 0.0129, 95% CI -0.0050 to 0.0314 QALYs] and had a 65% probability of being cost-effective at the National Institute for Health and Care Excellence threshold of £30,000 per QALY gained. The intervention was generally acceptable to podiatrists and trial participants. LIMITATIONS: Owing to the difficulty in calculating a sample size for a count outcome, the sample size was based on detecting a difference in the proportion of participants experiencing at least one fall, and not the primary outcome. We are therefore unable to confirm if the trial was sufficiently powered for the primary outcome. The findings are not generalisable to patients who are not receiving podiatry care. CONCLUSIONS: The intervention was safe and potentially effective. Although the primary outcome measure did not reach significance, a lower fall rate was observed in the intervention group. The reduction in the proportion of older adults who experienced a fall was of borderline statistical significance. The economic evaluation suggests that the intervention could be cost-effective. FUTURE WORK: Further research could examine whether or not the intervention could be delivered in group sessions, by physiotherapists, or in high-risk patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN68240461. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 24. See the NIHR Journals Library website for further project information